BRPI0804150A2 - process for obtaining chitosan derivatives, chitosan derivatives, photoprotective chitosan derivatives, pharmaceutical composition, cosmetic composition and use - Google Patents

Abstract

The present invention patent relates to processes for obtaining chitosan derivatives, and the molecules derived from these processes may have photoprotective ability for cosmetic, pharmaceutical and / or biomedical, veterinary and biomaterials application.

Description

"PROCESS FOR OBTAINING CHITOSANA DERIVATIVES, CHITOSANA DERIVATIVES, CHITOSANA DERIVATIVES PHOTOPROTECTOR COMPATIBILITY, PHARMACEUTICAL COMPOSITION, COSMETIC COMPOSITION AND USE"

Application field

The present invention patent relates to processes for obtaining chitosan derivatives, wherein the molecules originated by these processes have photoprotective ability for cosmetic, pharmaceutical and / or biomedical, veterinary and biomaterials application.

State of the Art

With the depletion of the ozone layer in recent years, the ultraviolet radiation (UV) levels reaching the troposphere have increased significantly, resulting in an increased incidence of skin cancer and photo-aging [GRUIJL, F. R. Skin cancer and solar radiation. Eur. J. Cancer, v. 35, (14), p.2003-2009; 1999].

The population is more aware that exposure to UV radiation may cause skin lesions such as photoaging and carcinogenesis [DOMLOGE, N.; BAUZA, E .; CUCUMEL.K .; PEYRONEL, D .; DAL FARRA, C; Artemia Extract: In Search of Broader Sun Protection. Cosmetics & Toiletries, Ed. Port., Sao Paulo, v. 14, pp. 60-67, 2001]. Despite this awareness, approximately 70% (seventy percent) of Brazilians expose themselves to the unprotected sun (Sociedade Brasileira de Dermatologia).

The National Cancer Institute (INCA) predicted 116,640 new cases of skin cancer for the year 2006. Of these, 55,480 cases would be in men and 61,160 cases in women. The estimated risk for these values is 61 new cases per 100,000 men and 65 per 100,000 women. During the National Skin Cancer Prevention Campaign, held in December 2004 by the Brazilian Society of Dermatology, over 33,000 people were treated throughout Brazil, of which almost 3,000 had skin cancer, or 8.4% of all care. . In 2006, this same campaign, also held in December, recorded 41,751 calls. Of the people attended, 9.5% had the disease. A worrying index pointed out by the campaign is the percentage of Brazilians still exposed to the sun without protection: 67.6%. Percentage of men who claimed not to protect themselves from the sun was 76.7% and women was 62.0%. Among the patients who sought care, 16.5% had a case of skin cancer in the family.

The Brazilian Society of Dermatology (SBD) has recorded that in the early nineties, for every eighty cases of cancer diagnosed, one was identified as skin cancer. By the end of the same decade, every seventeen cases of cancer, one was identified as skin.

Biologically reactive solar radiation to the skin is limited by UVC radiation, with wavelengths between 200 and 280 nm, UVB (280-320 nm) and UVA (320-400 nm). The extent of biological events caused by solar radiation on the skin is determined by the dose and duration of exposure; the exposed skin area; and genetic predisposition of the individual [(INAL, EM; KAHRAMAN, A.; KÕKEN, T. Benefit Effects of Quercetin on Oxidative Stress Induced by Ultraviolet A. Clinical and Experimental Dermatology, V.26, n.6 p. 536-539, 2001 ) and (SALIOU, C.; KITAZAWA, M.; McLAUGHLIN, L.; YANG, JP; LODGE, JKTETSUKA, T.; IWASAKI, K.; CILLARD, J.; OKAMOTO, T.; PACKER, L. AntioxidantsModulate Acute Solar Ultraviolet Radiation-Induced NF-KAPPA-B Activation in a Human Keratinocyte Cell Line, Free Radical Biology and Medicine; v.26; No. 1-2; pp. 174-183, 1999)].

Acute effects of sun exposure include sunburn and drug-induced phototoxic reactions. Chronic effects include photoaging and skin cancer [GUZZO, C. A .; LAZARUS, G. S .; WERTH, V.P. Dermatological Pharmacology In: - Goodman & Gilman. The Pharmacological Bases of Therapeutics.9 ° ed., Rio de Janeiro: Guanabara, p. 1182-1193, 1996].

As research on actinic damage becomes increasingly conclusive, revealing the serious risks of photoaging and skin cancer associated with sun exposure, there is a greater demand for developing long-acting, broad-spectrum photoprotective products, including UVB and IR (infrared) solar, proven responsible for the harmful effects of the sun on the skin. In addition, the increasing use of sunscreens, not only in prolonged sun exposure, but also daily, motivated by consumer awareness, has intensified the emergence of sunscreens with high SPF [AZZELLINI, SC, Photoprotective Potentiating Agents. , Cosmetics and Toiletries (Ed. Port), v.7, jul / ago, p.34-7, 1995] .The Sunscreen Factor (SPF) is a numerical value that correlates the time required for a given dose. ultraviolet exposure causes a noticeable erythema to appear on the protected skin compared to the time required for the erythema to appear on identical conditions in the unprotected skin of the same individual. Thus, it can be stated that the higher the SPF value used, the longer the resistance of the skin exposed to UV radiation to the appearance of solar erythema. Valordo SPF naturally depends on the types and concentration of sunscreens present in the formulation, but the increase in SPF does not occur linearly in relation to the increase of sunscreen concentrations [AZZELLINI, S. C, Photoprotective Potentiating Agents, Cosmetics and Toiletries (Ed. Port ), v.7, Jul / Aug, p.34-7, 1995]. There are examples of formulations that did not show growth in SPF with increasing sunscreen levels. From this it was concluded that saturation is reached at a certain level and that through increasing the filter concentration, SPF does not increase significantly [Wünsch, T., Dr. High Performance UV Filter Synergistic Effects, Cosmetics and Toiletries (Ed. Port), v. 13, Jan / Feb, p. 54-7, 2001].

As more sunscreens are added at higher levels, the cost of products increases dramatically, along with the potential for irritation and skin sensitivity. This has become even more important with the explosive increase in the use of sunscreens in children; which leads to the paradox of trying to develop more effective sunscreens with less irritation power [SHAATH, N. A .; WORLDWIDE, K .; FARES, H.M .; KLEIN, K. Chemical Photodegradation of Sun Protectors: Solvent Considerations, Cosmetic and Toiletries (Ed. Port), v.4, Jul / ago, p. 32-6, 1992].

The effectiveness of a sunscreen depends not only on the types and quantities of filters involved, but also on the characteristics of the final product, and it is of crucial importance to choose the appropriate components of the formulation, including vehicles, emulsifiers, adjuvants, among others [AZZELLINI, S. C , Photoprotective Potentiating Agents, Cosmetics andToiletries (Ed. Port), v.7, Jul / Aug, p.34-7, 1995].

Therefore, it is clear that many other factors must be considered when formulating sunscreen products, including thickness, uniformity and film forming capacity [SHAATH, N. A.; WORLDWIDE, K .; FARES, H.M .; KLEIN, K. Chemical Photodegradation of Solar Protectors: Solvent Considerations, Cosmetic and Toiletries (Ed.Port), v.4, Jul / ago, p. 32-6, 1992].

Regular use of a sunscreen minimizes the harmful effects induced by solar radiation. This protector must be effective, photostable and safe. Since, researchers have shown, using a duct tape and HPLC methods, that ethylhexyl methoxycinnamate and benzophenone-3 penetrate the horny stratum [(HANSON, KM Bright Skin: Solar Filters, Oxygen Reagent Species, and Photon Fluorescence Microscopy). Double: In: CONGRESSIFSCC, 23, Orlando FL, 2004, Abstracts, USA, Cosmetics and Toiletries (Port.), 2004, v.16, p.52-54)].

The effect and effectiveness (degree of protection) of solar filter preparations are characterized by their Sun Protection Factor. The photostability of a filter depends on how much it is able to release absorbed energy into the environment in the form of heat rather than radiation. Finally, sunscreen's active ingredients must not have adverse effects on humans and the environment [OSTERWALDER, U; HERZOG, B. Designing Broad-Spectrum UV Absorbers. Cosmetics & Toiletries, Carol Stream, v.119, no. 9, p.61-68,2004].

Another parameter of great importance in obtaining effective sunscreens is the use of preparations that ensure uniform application in it, ie, that have good spreadability. Finally, the maintenance of thixotropic properties and thermal stability of photoprotectors that tend to remain for long periods exposed to the sun should be considered, with loss of original viscosity or compromising formulation formulation [AZZELLINI, S. C, Photoprotective Potentiating Agents. , Cosmetics and Toiletries (Ed. Port), v.7, Jul / Aug, p.34-7, 1995].

There are film-forming agents that, although devoid of photoprotector-intrinsic effect, determine the performance increase of formulations containing filtrosolar. In addition to facilitating the spreadability of photoprotective formulations, it avoids irregularities in their application and, consequently, the lack of uniformity in the skin surface [AZZELLINI, S. C, Photoprotective Potentiating Agents, Cosmetics and Toiletries (Ed. Port), v.7, Jul / Aug, pp. 34-7, 1995].

Recently copolymers have been developed that combine desilicone resins with organic esters of lauric acid and isostearyl acid, which potentiate the effect of photoprotectors by their ability to form water resistant films, and have extreme skin affinity and very low toxicity [AZZELLINI, S. C , Protective Potentiating Agents, Cosmetics and Toiletries (Ed. Port), v.7, Jul / Aug, p.34-7, 1995].

JP 6183928 is a hair and skin-tightening cosmetic product containing vinyl copolymers such as 2- [2'-hydroxy-5 '- (methacryloyloxy-ethyl) -phenyl] -benzo-triazole polymer, This cosmetic product protects against UV damage or irritation.

As also developed by MAILLAN et al. (2005), chromophorous actives associated with polymeric bases to be applied to hair [(MAILLAN, P .; GRIP, A .; SIT, F .; JERMANN, R .; WESTENFELDER, H. UV and Brightness Improvement, Cosmetics & Toiletries (Ed. Port.), v. 17, p. 72-75,2005)].

Given the above, it is desirable that new photoprotective molecules have a broad absorption spectrum to UVB, UVA and IR radiation, and at the same time, are nontoxic and safe, ie, they guarantee their non-absorption and have low or no potential. irritation and skin sensitivity.

In the work developed by the INOLEX CHEMICAL COMPANY team (1998), it was found that specific polyesters have been shown to be useful in retaining sunscreen actives in the outer layers of the skin's corneal extract (EC). It was possible to optimize the retention of photoprotective actives in the EC by controlling the specific structural aspects of the polyester monomers.

High molecular weight polymers with large number of cross chains were the characteristics of the polyesters that had the greatest effect on the retention of octyl methoxycinnamate and oxybenzone in the horn extract. This can minimize the risk of skin irritation and at the same time increase the efficiency and effectiveness of photoprotective actives [SMITH, D .; O'CONNOR, A .; SIEGFRIED, R.Polyesters as Topic Release System, Cosmetics and Toiletries (Ed.Port.), V. 10, Sep / Oct, p.51-59, 1998].

US 5403944 has disclosed the invention of a UV-absorbing polymer-dimerganopolysiloxane which does not penetrate the skin stratocornum due to the large molar mass of that polymer.

Both YOU and SEO document US 2004137041 (2004) and the work of YAGI and collaborators (1992) explored the filmogenic property, that is, the film-forming ability because of the polymeric-molecular arrangement, and this characteristic ensured stability. spectrophotometric profile of the filters, as the molecule could have the UV radiation filtering means attached to the basic polymer structure [CHEN, Y .; DUO, Y.; LUO, Y .; TAN, H. Cinnamyl modification research of chitosan and chitin, Gaofenzi Cailiao Kexue Yu Gongcheng, v. 21, no. 3, p.286-289, 2005 apudSciFinder Scholar]. The polymer formed by chains containing a chromophor becomes photostable, and has a good safety profile due to its large molecular size. Property reported by MAILLAN et al. (2005) in which he associated benzyl chromophoromalonate molecules to polysiloxane chains [MAILLAN, P .; GRIP, A .; SIT, F .; JERMANN, R.; WESTENFELDER, H. UV Hair Protection and Brightness Improvement, Cosmetics & Toiletries (Ed. Port.), V. 17, p. 72-75, 2005] and also in RICHARD Patent FR2756288 (1996); H. and LEDUC, M. where they synthesized desiloxane derivatives with cinamides, benzylidenomalonamides and benzylidenomalonate and found that these derivatives were photostable and with excellent UV radiation absorption. The polymer can potentiate the effect of UV absorbing action, increasing the value of the Sun Protection Factor. This feature was observed in FR 2860155 by SEYLER AND CANDAU (2005) in which they developed a photoprotective formulation containing an active and segmented polymers for skin protection. They found that the polymer enhances the protection factor. According to MAILLAN et al. (2005), the distribution and loading of UV chromophores in siloxane chains are optimized to enhance UV protection. Besides avoiding the "window effect", which are flaws in the uniformity of the film, as detected in hydroalcoholic lotions, which, by evaporation of alcohol, ends up compromising the quality of the protective film [RANGEL, V. L. B.; CORRÊA, M. A. Photoprotection. Cosmetics & Toilletries (Port.), V.14, p.88-95, 2002]. O'NEILL (1984) studied the effect of film irregularity on the efficacy of photoprotectors and found that the non-uniform distribution of chromophore actives in it can lead to large discrepancies between what is clinically observed and what is predicted for its efficacy [O'NEILL, JJ Effect of Film Irregularities on Suncreen Efficacy, Journal of Pharmaceutical Sciences, v. 73, no. 7, p.888-891.1984].

EP 1281390 discloses the combined use of latex particle adjuvants to increase the Sun Protection Factor index and / or the UVA protection ability of cosmetics or dermatological compositions.

Recently researchers have shown that commercially available solar filter formulations provide percutaneous absorption of the photoprotective actives, for example ethylhexyl methoxycinnamate and benzophenone-3. Tests were performed using tape and high efficiency liquid chromatography spectrometric methods. (HPLC) [(VARVARESOU, A. Percutaneous Absorption of Organic Sunscreens. Journal of Cosmetic Dermatology, v. 5, p. 53-57,2006); (HANSON, KM. Bright Skin: Solar Filters, Oxygen Reagent Species and Double Photon Fluorescence Microscopy. In: CONGRESS IFSCC, 23, Orlando FL.2004, Abstracts, USA, Cosmetics and Toiletries, Sao Paulo, 2004, v.16 , p.52-54); (JANJUA, NR; MOGENSEN, B.; ANDERSSON, AM; PETERSEN, JH; HENRIKSEN, M.; SKAKKEBAEK, NE; WULF, HC SystemicAbsorption of the Sunscreens Benzophenone-3, Octyl-Methoxycinnamate, and 3- (4-Methyl- Benzylidene) Camphor After Whole-Body Topical Application and Reproductive Hormone Levels in Humans, Journal of Investigative Dermatology, v.123, No. 1, pp. 57-61, 2004); (JIANG, R.; ROBERTS, MS; COLLINS, MD; BENSON, HAE Absorption of sunscreens across human skin: an evaluation of commercial products for children and adults. British Journal of Clinical Pharmacology - BJCP, v. 48, n.4, p. 635-637, 1999); (Hayden, C.G.J; ROBERTS, M.S.; BENSON, H.A.E. Systemic absorption of sunscreen after topicalapplication. The Lancet, v. 350, no. 20, pp. 863-864, 1997)].

In US 3864473 (1975) the synthesis of polymeric derivatives with the function of sunscreens was reported [CIAUDELLI, J. P. RAMSEY, N. J. Substantive polymeric sunscreen composition US Pat 3864473, 4 Feb. 1975. 4p.]. The same occurred in EP0123368 (1984) which developed polymeric photoprotectors [CHO, J. R .; JOHNSON, S.C. Polymeric sunscreens EP Pat 0123368.31 out. 1984].

According to research by SANDFORD et al. (1989) and RINAUDO ecolaboradores (1992), one of the characteristics and properties of the various physical forms of biopolymer, in the chitosan case, is its ability to form flexible, resistant, permeable, easily moldable and highly adherent film. negative surfaces. These are interesting characteristics for the formulation of a photoprotective film [(SANDFORD, PA "Chitosan: commercial uses and potential applications". In: SKJAK-BRAEK, S.; ANTHONSEN, T .; SANDFORD, PA. Editors. Chitin and Chitosan: Sources, Chemistry, Biochemistry, Physical Properties and Applications, New York: Elsevier Applied Science, pp. 51-70, 1989)] and RINAUDO & DOMARD (1992) [(RINAUDO, M.; DOMARD, A. Solution properties of chitosan. In: BRINE.CJ; SANDFORD, PA; ZIKAKIS, JP, editors, Advances in Chitin and Chitosan, New Jersey: Elsevier Applied Science; pp. 71-86, 1992)]. According to RANGEL AND CORRÊA (2002), the aspects that should be considered in obtaining Sun Protection Factor values are: film uniformity, film thickness, non-transparent film, minimal interaction with the active chromophores (filters) and, the heavier and more uniform. the more effective the movie will be the protection [RANGEL, VLBI; CORRÊA, M. A. Photoprotection. Cosmetics & Toilletries (Port.), V.14, p.88-95, 2002]. Therefore, the chitosan molar mass: 3,800 to 2,000,000 Daltons, made up of a series of polymers, is interesting for sunscreens because it makes the product safe while minimizing the risk of the active ingredient being absorbed percutaneously.

Document DE 10145111 studied the use of chitosan in the stabilization of cosmetics and / or dermatological preparations at a concentration of 0.5% with good results. These preparations are developed in the form of emulsions: O / W, W / O, W / O / W and / or O / W / O, ie dispersions: hydro, oil, hydrogels or oleogels.

The application of chitosan and its derivatives in dermocosmetics and their evaluation as moisturizers has already been studied by LIU et al. (1999). They have studied the hygroscopic capacity and water retention mechanism of N-succinyl-chitosan in the skin. [LIU, Y .; WANG, J .; ZHANG, J. Skin moisturizers and evaluation of their properties. Riyong Huaxue Gongye, v.5, p.52-54, 1999. apud SciFinder Scholar, 2005].

In the work of YUAN and WEI (2004) a new contact lens based on chitosan / gelatin composite was developed. They report that prepared chitosan / gelatin composite films are more permeable, transparent, flexible than biocompatible films and can potentially be used as contact lens material [YUAN, S. X .; WEI, T.T. New Contact Lens Basedon Chitosan / Gelatin Composites. Journal of Bioactive and Compatible Polymers, v.19, p.467-479, 2004].

These films can be obtained by crosslinking reaction [MONTEIRO, O.A.C .; AIROLDI, C. Some studies of chitosan-glutaraldehydeinteraction crosslinking in a homogeneous system. International Journal of Biological Macromolecules, v. 26, p. 119-128, 1999] or by compositing, as already described by YUAN and WEI (2004) [YUAN, S. X .; WEI, T.T. New Contact Lens Basedon Chitosan / Gelatin Composites. Journal of Bioactive and Compatible Polymers, v.19, p.467-479, 2004], or by forming biofiber blends, which can be obtained by mixing the chemically modified polymer with other polymers, for example, cellulose and silk fibroin, or with any other biopolymer, may be a mixture thereof, as described by HIRANO et al. (2002). [HIRANO, S .; NAKAHIRA, T .; ZHANG, M .; NAKAGAWA, M .; YOSHIKAWA, M.; MIDORIKAWA, T. Wep-spun blend biofibers of cellulose-silk fibroin and cellulose-chitin-silk fibroin. Carbohydrate Polymers. v. 47, p. 121-124, 2002].

US 6242099 has disclosed the development of dequitin microcapsules or chitin derivatives or polyhydroxylated polyamines or one of their salts involving hydrophobic substances which are prepared to form a hydrophobic phase emulsion of the aqueous phase containing an anionic surfactant capable of causing chitosan insolubility. or derivatives thereof or polyhydroxylated polyamides, by mixing the chitosan emulsion or chitosan derivatives or organic salt of polyhydroxylated polyamines for the purpose of coacervating chitosan or derivatives thereof and are applicable in cosmetic compositions including photoprotectors.

US 20020128310 has disclosed a medical composition and its use in the production of selective topical formulations with UV-absorbing absorption function or for use in formulations such as antiviral, antifungal, or anti-inflammatory purposes. The described composition comprises a cationic, hydrophilic and amine-containing polymer, preferably groups consisting of natural chitosan and cationic derivatives thereof, cationic polyethylene compounds, DEAE-4; or polynitine, with others, preferably derived from groups consisting of anionic amino ethylene compounds, tetraazacycloalkane-N, N, N, N-tetraacetic acids and polymeric derivatives of porphyrins or an endogenous compound. The cationic chitosan derivatives are preferably from groups consisting of chitosan carbanic acid, chitosan chloride, 6-0-carboxymethylchitosan, 6-O-dihydropropylchitosan, 6-O-hydroxyethylchitosan, 6-0-sulfatoquitosan, A / -sulfatoquitosan and / V- carboxybutylchitosan.

US 20040192646 discloses an invention of functional derivatives comprising chitin and / or chitosan. Invention in which a carbohydrate has been incorporated into the polymer chain, a photo-reactive functional group, an amphoteric group such as polyoxyethylene alkyl ether and a glycosaminoglycan. Due to this incorporation, polymer solubility at neutral pH, crosslinking ability, high wetting capacity and antithrombotic property occurred. The photo-reactive functional groups acquired by chemical modifications in chitosan according to the invention with amino groups or hydroxyl groups derived from cyclic unsaturated compounds as well as asbenzophenones, cinnamic acids, azides, diolefins and bis-anthracene, are preferably those having carbonylazides, sulfonylazide groups. and azidaaromatic.

EP 0879592 is an invention of a photoprotective formulation containing (a) oil, (b) emulsifier, (c) chitosan and (d) weak UV filter.

In addition, the use of cationic biopolymer as water repellent for the composition of the photoprotective agent is claimed.

FR 2860155 deals with a photoprotective composition containing an active and segmented skin protection polymers, where the polymer strengthens the protection factor.

In the work developed by the HENKEL team (Brazil, Germany and the United Kingdom), the action of multifunctional ingredients in the cosmetic formulation was studied, in this case, filmogenic agents, such as chitosan glycolate (1.0% solution). Tests were performed to determine the resistance to water rinse of two identical formulations except one containing 1.0% chitosan degiicolate (equivalent to 10% of its solution). Prior to water treatment the difference in SPF was not considered significant (SPF 8 active cream / SPF 7 active cream). However, after 20 minutes of water immersion and SPF re-determination, there was a significant difference, as chitosan comgiicolate cream showed SPF 6 versus SPF 4 for placebo cream (33% difference) [LEONARD, M .; JACKWERTH, B .; KAWA, R .; CARMINI, M. Synergistic Effects on Photoprotection Systems, Cosmetics and Toiletries (Ediç.Port.), V. 10, Sep / Oct, pp. 63-9, 1998].

Another possible formulation, according to BR 9902912, is the use of chitosan microspheres and their derivatives in the microencapsulation of pharmacologically active substances and plant extracts.

In this case, it can be extended to this invention by making it from microspheres, nanoparticles or nanocapsules of the encapsulated chromophore active photoprotectors film as described in EP274961 and FR 2659554. Also, as described in the work of Perugini Ecolaboradores [PERUGINI , P.; SIMEONI, S .; SCALIA, S .; GENTA, I .; MODENA, T.; CONTI, B .; PAVANETTO, F. Effect of nanoparticle encapsulation on the potential of the sunscreen agent, 2-ethylhexyl-p-methoxycinnamate, International Journal of Pharmaceutics, v. 246, pp. 37-45, 2002].

Given the above, chitosan is a biopolymer with great development potential, generating different types of materials with varied functions, including specific biological activities. As changes in structure, chitin and / or chitosan have found applications in the pharmaceutical, cosmetic, food and diagnostic fields [(OGAWA, M., MAGALHÃES NETO, EO, VI Brazilian Fisheries Engineering Congress, 91-105, 1989). ); (ORNUM, J. V. "Deacetylated chitin used as adsorbents in the production of clarified pineapple syrup" Infofish Int., 6, 48-52, 1992)]. As examples are given. wound dressings, contact lenses, hemostatic agents, drug delivery system, serum cholesterol lowering agent and others [MELLO, K. G. P. C; Synthesis and physicochemical evaluations of chemically modified chitosans by the insertion of succinic anhydride radicals. São Paulo, 2005. 89p. - Master's Dissertation - Faculty of Pharmaceutical Sciences, University of São Paulo].

Chitin is easily obtained as a by-product of the fishing industry, and its annual production is estimated to be approximately as much as dacelulose. Chitosan is a biodegradable, hydrophilic, odorless, non-toxic, biocompatible, and enzymatically biodegradable aminopolysaccharide obtained from alkaline acetylation ([ROBERTS, G., A., I.; et al., Chitin Chemistry, London: Macmillan., 1992) and (LEE, ST; M1, F.L; SHEN, YJ; SHYU, SS; Equilibrium andkinetic studies of copper (II) ion uptake by chitosan-tripolyphosphate chelating resin., Polymer, 42, p.1879 - 1892, 2001). Their chemical structure is formed by the p- (1,4) -2-amino 2-deoxy-D-glucose (GlcN) and B- (1-4) -2-acetamide 2-deoxy-D-glucose (GlcNac) polymers with the presence of amino groups and hydroxyl groups derived by chitin n-deacetylation Proportion of GlcNac units relative to GlcN is defined as biopolymer degree of acetylation (GA) and differentiates chitosin (GA> 0.5) from chitosan (GA <0 However, this value is only an approximation, the difference being also based on the solubility of the biopolymer in acidic medium, in which chitosan is soluble. unlike chitin, which is insoluble [LE DUNG, P .; MILAS, M.; RINAUDO, M .; DESBRIÈRES, J. Water soluble derivatives obtained by controlledchemical modifications of chitosan. Carbohydrate Polymers, v. 24, no. 3, p. 209-214.1994); (KURITA, K .; NISHIMURA, SI; ISHII, S.; TOMITA, K .; TADA, T .; SHIMODA, K. Characteristic properties of squid chitin. In: BRINE, CJ; SANDFORD, PA; ZIKAKIS, JP, eds Advances in Chitin and Chitosan London, New York: Elsevier Applied Science, 1992. pp. 188-195 [Proceedings from the Sth International Conference on Chitin and Chitosan, New Jersey, 1991)]. When chitin deacetylation is complete, another class of polymer is obtained, polyglycosamine (polyhydroxylated polyamide) [(GRANDMONTAGNE, B .; MARCHIO, F. Microcapsulesmade from chitin derivatives containing a hydrophobic substance, in particular to sunscreen, and process for the preparation of such microcapsules (USPat. 6242099, 2001, 9p.)].

Chitosan is a cationic polysaccharide, that is, positively charged at pH <6.0. The free amino groups (NH2) present in chitosan make the chitosan insoluble at pH> 6.0 and in most organic solvents. These groups when protonated give the matrix polycationic characteristics (NH3 +) becoming soluble at pH <6.0. In this way, positively charged chitosan will interact with negatively charged surfaces such as hair and skin. The bioadhesive capacity of chitosan is therefore the main factor of its cosmetic field employer. In addition, it is a moisturizing and moisturizing agent, forming a transparent protective layer that aids skin and hair hydration. It works as a viscosity donor in amphoteric / nonionic shampoos. It is an excellent hair conditioning conditioner, forms protein films and substrates and can encapsulate fragrances, pigments and active ingredients. Insoluble in most solvents except organic acids such as acetic, formic, succinic and lactic. Its use is restricted due to insolubility in water, high viscosity and tendency to coagulate in high pH proteins [MELLO, K. G. P. C; Synthesis and physicochemical evaluations of chitosan-chemically modified by the insertion of succinic anhydride radicals. São Paulo, 2005. 89p. - Master's Dissertation - Faculty of Pharmaceutical Sciences, University of São Paulo]. Some pharmaceutical applications of chitosan are limited by solubility because it is insoluble empH (ideal condition for physiological enzymes to exert their activity) [(KUBOTA, N .; TASTUMOTO, N .; SANO, T; TOYA, K .; Carbohydr Res., V.324, p.268, 2000.); (SILVA, H.S.R.C; dos SANTOS, K.S.R.R., FERREIRA, E.I.Quitoana: Water-Soluble Derivatives, Pharmaceutical Applications, and Advances. Quím.Nova, Vol. 29, No. 4, 776-785, 2006)].

Because it is a natural polymer, the molar mass of different chitosan samples is inconsistent. Many values can be obtained depending on the sample procedure and the types of treatment that were used to obtain it. To reduce the discrepancies in the molar mass ranges obtained, the chitosan samples were classified according to the molar mass distribution: low, medium and high [MELLO, K. G. P. C; Synthesis and physicochemical evaluations of chemically modified chitosans by insertion of succinic anhydride radicals. São Paulo, 2005. 89p. - Master Thesis - Faculty of Pharmaceutical Sciences, University of São Paulo].

Chitosan classification: low molar mass (on average) 100,000 g / mol, medium molar chitosan (on average) 500,000 g / mol and high molar chitosan (on average) 1,000,000 g / mol [DEE, J. D .; RHODE, O .; WACHTER, R.Chitosan-Multi-functional marine polymer. Cosmetics and Toiletries, Carol Stream, v.116, n. 2, 39-42, 2001); (MELLO, K G. P. C; Synthesis and physicochemical evaluations of chemically modified chitosans by insertion of succinic radicals. São Paulo, 2005. 89 p. - Master's Dissertation - Faculty of Pharmaceutical Sciences of the University of São Paulo)].

The size of the polymer chain and its molar mass also interfere with sample solubility. Due to the high molar mass and its linear structure, aquitosan confers viscosity to solutions in small acid concentration at 2.0-3.0% concentration and a pseudoplastic behavior exhibiting a decrease in viscosity as shear stress increases. The risk of chitosan solutions increases as the sample concentration increases, the temperature decreases and the degree of acetylation increases [(SINGLA, AK; CHAWLA, M. Chitosan: some pharmaceutical and biological aspects. An update. Journal of Pharmacy and Pharmacology. v. 53; pp. 1047-1067, 2001); (MELLO, K. G. P. C; Synthesis and physicochemical evaluations of chemically modified chitosans by insertion of anhydridosuccinic radicals. São Paulo, 2005. 89 p. - Master's Dissertation - Faculty of Pharmaceutical Sciences of the University of São Paulo)].

Low acetylation degrees lead to higher water solubility derivatives, ie, it is considered that in polysaccharide the solubility increases proportionally with the increase of free amino groups present in the molecule [SINGLA, A.K .; CHAWLA, M. Chitosan: somepharmaceutical and biological aspects-an update. Journal of Pharmacy and Pharmacology. v. 53; P. 1047-1067, 2001].

Moreover, the greater the amount of amino groups in the polysaccharide structure, the greater the amount of drug molecules to be inserted into the polymer chain [SILVA, H. S. R. C; dos SANTOS, K. S. C.R., FERREIRA, E. I. Chitosan: Water Soluble Derivatives, Pharmaceutical Applications and Advances. Chem. Nova, vol. 29, no. 4,776-785, 2006]. However, a technique has been developed for obtaining water-soluble chitosan by reacting chitosan with succinic anhydride, thereby obtaining succinylated chitosan [(MELLO, KGP C; BERNUSSO, LC; PITOMBO, NMR; POLAKIEWICZ, B.Synthesis and Physicochemical Characterization of Chemically Modified Chitosanby Succinic Anhydride, Brazilian Archives of Biology and Technology, v. 49, no. 4, p.665 - 668, 2006); (YAMAGUCHI, R .; ARAI, Y .; ITOH, T. Preparation of partially N-succinylated chitosans and their cross-linked gels. Carbohydrate Research, v.88, pp. 172-175, 1981)].

Chitosan / V-succinylated derivatives have different physicochemical characteristics compared to the original chitosan [YAMAGUCHI, R., ARAI, Y., ITOH, T., HIRANO, S .; "Preparation of Partial N-succinylated chitosans and their cross-linked gels". Carbohydate Research, v. 88, p. 172-175, 1981].

Chemical modification is known to be one of the proposed methods for improving the functional properties of proteins and other compounds for processing in the food industry [(LI-CHANG, et al Covalent attachment of wheat to gluten for nutritional improvement. J. Agric. Food Chem ., v. 27, p.822-877, 1979); (MATHEIS, G .; WHITAKER, J.R. Chemical phosphorylation offood protein: in overview and a prospectus. J.Agric. Food Chem., V.32, p.699-705.1984); (EL-ADAWY, T. A. Functional properties and nutritional quality of acetylated and succinylated mung bean protein isolate. Food Chem., Amsterdam, v.70, p.83-91,2000)].

Chemical modifications in the structure of chitosan have been widely studied for opening possibilities for new applications [DUNG, P., MILA, M., RINAUDO, M., DESBRIÈRES, J .; "Water soluble derivatives by controlled Chemical Modifications of Chitosan". Carbohydrate Polymers, 24, 209 - 214, 1994] .MELLO, KGP C and collaborators (2006) based on the work of YAMAGUCHI and collaborators (1981) obtained the soluble chitosan in medium, but with modifications in the obtaining process, such as reagents. , solvents and reaction time [(MELLO, KGP C; BERNUSSO, LC; PITOMBO, NMR; POLAKIEWICZ, B. Synthesis and PhysicochemicalCharacterization of Chemically Modified Chitosan by Succinic Anhydride, BrazilianArchives of Biology and Technology, v. 49, no. 4, p 665-668, 2006); (YAMAGUCHI, R .; ARAI, Y .; ITOH, T. Preparation of partially N-succinylated chitosans and their cross-linked gels. Carbohydrate Research, v.88, pp. 172-175, 1981)].

According to MELLO, K. G. P. C (2005), the addition of succinic radicals in different concentrations to the amino group of chitosan generates carboxyamides. These give the polymer water solubility and electrolyte characteristics due to the presence of a long alkyl chain, having at the end a highly hydrophilic carboxylate group removed from the hydrophobic sites of the molecule [MELLO, K. G. P.C; Synthesis and physicochemical evaluations of chemically modified chitosans by insertion of succinic anhydride radicals. São Paulo, 2005. 89p. -Master Dissertation - Faculty of Pharmaceutical Sciences, University of São Paulo].

The presence of primary amino groups in the C2 'carbon of the chitosan polymeric chain allows selective chemical modifications through typical derivations of this functional group, enabling the synthesis of chitosan derivatives with potential commercial uses [NIFANTEV, N. E; CHERNETSKII, V.N., MENDELEV Chem. J., v. 41, p. 96-100, 1998].

The structure of the A / acylation and / or AZ-alkylation (R) chitosan biopolymer on the amino group of the polymeric chain is represented by the following formula:

<formula> formula see original document page 16 </formula>

The most commonly used reactions to obtain chitosan derivatives are the partial acylation reactions of the polymer amino groups with acidic anhydrides or with carboxylic acid halides. As well as Schiff's base formation reactions with aldehydes such as glutaraldehyde, formaldehyde and glyoxal. These aldehydes form a reticulum with chitosan and thus increase molecular weight, resulting in increased viscosity. This technique also allows the binding of chitosan to other aldeidoses used in perfumery and in the food industry, giving chitosan proper fixation of aromas and fragrances [(BORGOGNONI, CFMicroencapsulation by d-limonene freeze-drying in maltodextrin and chitosanamodified] São Paulo, 2005 105p - Master's Dissertation - Faculty of Pharmaceutical Sciences, University of São Paulo); (GUERRIERO, MFB; BERNUSSO, L. C; HONDA, API; POLAKIEWICZ, B. Development and characterization of a thickening base with fragrance-fixing power to be incorporated into the cosmetic formulation. In: 20th Brazilian Congress of Cosmetology, 2006, São Paulo , Cosmetics & Toiletries. (Ed. Port), Sao Paulo: Tecnopress Editorae Advertising Ltda, 2006, v.18. P.68-68); (MELLO, K. G. P. C; Physicochemical synthesis and evaluations of chemically modified chitosans by the insertion of succinic anhydride radicals. São Paulo, 2005. 89p. - Master's Dissertation - Faculty of Pharmaceutical Sciences of the University of São Paulo)].

In US 3879376 (1975), VANLERBERGHE et al. Presented a method of chitosan derivative process and cosmetic composition. In this patent the process of obtaining comprises the acitosis of those with saturated or unsaturated organic diacid anhydrides. The ratio employed was 0.3 mmol to 2.0 mo of saturated anhydride per amino group equivalent present in the chitosan polymer, or 1.0 to 2.0 mmol of amino group unsaturated anhydride (GlcN) present in chitosan. In other analyzed studies stoichiometric calculations appear in the range of 0.7 nm to 1.5 nm of hydrochloride by (GlcN).

HIRANO et al. (1979) studied obtaining gels derived from the chitosan / V-acylation reaction with carboxylic anhydrides in a water / acetic acid / methanol mixture. Other new groups of gels may be formed by chitosan reaction with aldehydes [HIRANO, S .; MATSUDA, N .; MIURA, O .; IWAKI, H. Add N-arylidenechitosan gels. Carbohydrate Research, v. 71, p. 339-343,1979].

FUJI et al. (1980), GRANT et al. (1990) studied chitosan modification by incorporation of the acyl group through a long chain acyl chloride polymer reaction [(ZONG, Z., KIMURA, Y .; TAKAHASHI, M YAMANE, H. Characterization of Chemical and Solid Statestructures of Acylated Chitosans (Polymer, Vol. 41, pp. 899-906, 2000); (FUJII, S.; KUMAGAI, H., NODA, M. Carbohydr. Res., V. 83, p. 389, 1980); (GRANT, S. BLAIR, H.S., MCKAY, G. Polym Commun, v. 31, p. 267, 1990)]. HALL et al. (1980) and YALPANI et al. (1984) studied the reaction of V-alkylation of thaitosan [(HALL, LD, YALPANI, MJ J Chem Soe, Chem Commun, p. 1153,1980), (YALPANI, M. HALL, LD Macromolecules, V. 17, pp. 272, 1984)]. HIRANO Ecolaborators (1976) and MOORE and collaborators (1981) studied the N-acylation reaction of chitosan [(HIRANO, S .; OHE, Y, ON, H.Carbohydr. Res. V. 47, p.315, 1976) ; (MOORE, G.K., GOERGE, A.F. Int. J Biol Macromol, v. 3, p.292,1981)].

YAMAGUCHI and co-workers (1981) have developed Î ± -acyl chitosan, β-alkylidene chitosan gels and medium-water soluble chitosan salts [YAMAGUCHI, R .; ARAI, Y .; ITOH, T. Preparation of partially N-succinylatedchitosans and their cross-linked gels. Carbohydrate Research, v.88, p. 172-175.1981].

HIRANO et al. (1981) synthesized N-carboxylacylated chitosan derivatives using anhydrides in acetic acid and methanol, and obtained water-soluble derivatives [(HIRANO, S .; MORIYASU, T .; Carbohydr. Res.1981, 92, 319.); (YAMAGUCHI, R .; ARAI, Y .; ITOH, T .; HIRANO, S; Carbohydr.

Res. 1981, 88, 172); (HIRANO, S .; HAYAKI, K .; HIROCHI, K .; Carbohydr. Res.1992, 225, 175); (SILVA, H.S.R.C; dos SANTOS, K.S.R.R., FERREIRA, E.I.Quitoana: Water-Soluble Derivatives, Pharmaceutical Applications, and Advances. Quím.Nova, Vol. 29, No. 4, 776-785, 2006)].

MUZZARELLI et al. (1982) studied the A / -carboxyalkylation reaction of chitosan [MUZZARELLI, R. A.A .; TANFANI, F. Puree Appl Chem, v.54, p. 2141, 1982]. GRANT et al. (1989) studied the chitosan O-acylation reaction [GRANT, S .; BLAIR, H.S .; MCKAY, G. Makromol Chem, v.190, p. 2279, 1989].

MUZZARELLI et al. (1989) reported the production of N-carboxybutyl chitosan using levulinic acid [(MUZZARELLI, R.; WECHY, M.; FILIPPINI, O .; LOUGH, C.; Carbohydr. Polym. 1989, 11, 307); (SILVA, HSR C; dos SANTOS, KSCR, FERREIRA, EI Chitosan: Water Soluble Derivatives, Pharmaceutical Applications and Advances. Quim. Nova, vol. 29, no. 4,776-785, 2006)]. HIRANO et al. (1992) studied derivatives A -carboxymethylchitosan t -acylates by random reaction with carboxylic anhydrides.Synthesized the derivatives with the incorporation of the Î ± -acyl groups: acetyl, propionyl, butyryl, pentanoyl, hexanoyl, octanoyl, decanoyl, lauryl, palmitoyl, benzoyl, succinyl phthaloyl [HIRANO, S .; HAYASHI, K .; HIROCHI, K. Some / V-acyl derivatives of O-carboxymethylchitosan. Carbohydrate Research, v.225, p. 175-178, 1992].

LE DUNG et al. (1994) obtained water-soluble derivatives in homogeneous conditions using low acetylation chitosans (12.5% and 11%). The obtained derivatives, quartenary salts of chitosan and N-carboxymethylchitosan, were soluble over the whole pH range [(LE DUNG, P.; MILAS, M .; RINAUDO, M .; DESBRIÈRES, J .; Carbohydr. Polym. , 1994, 24,209); (SILVA, H.S.R.C; dos SANTOS, K.S.R.R., FERREIRA, E.I. Chitosan: Water-Soluble Derivatives, Pharmaceutical Applications, and Advances. Quím. Nova, vol.29, no. 4, 776-785, 2006)].

PIZZA et al. (1999) showed that the hydrolysis of chitosanavia chitosanases is a function of pH and temperature, being pH 5.8 and 54 ° C ideal conditions for hydrolysis of chitosan evaluated [(PIZZA, FAT; SILOTO, AP; CARVALHO, CV; FRANCO , TT; Braz J. Chem. Eng. 1999, 16, 85.); (SILVA, H.S. R. C; dos SANTOS, K. S. C.R., FERREIRA, E. I. Chitosan: Water-Soluble Derivatives, Pharmaceutical Applications, and Advances. Quim. Nova, Vol. 29, No. 4,776-785, 2006)].

SASHIWA and SHIGEMASA (1999) proposed to obtain several water-soluble chitosan derivatives. These include N-alkyl and N-acyl chitosan derivatives such as succinylchitosan and maleylchitosan. N-acylated derivatives are obtained in the presence of cyclic anhydrides [(SASHIWA, H.; SHIGEMASA, y .; Carbohydr. Polym. 1999, 39, 127); (SILVA, HSR C; dosSANTOS, KSCR, FERREIRA, EI Chitosan: Water-Soluble Derivatives, Pharmaceutical Applications and Advances. Quim. Nova, Vol. 29, No. 4, 776-785, 2006)]. ZONG et al. (2000) studied chemical characterization and solid state of acetylated chitosan structures. In this work, chitosan derivatives were synthesized by reaction of the polymer with acid chloride, in this case hexanoyl, decanoyl and lauryl. Obtaining Substituted A-Acyl and O-Acyl Compounds [ZONG, Z .; KIMURA, Y .; TAKAHASHI, M .; YAMANE, H.Characterization of chemical and solid state structures of acylated chitosans. Polymer, vol. 41, p. 899 - 906, 2000]. RINAUDO et al. (2001) also described obtaining water-soluble N-carboxybutylchitosan and 5-methylpyrrolidine-chitosan. N-carboxybutyl chitosan was produced using chitosan [(RINAUDO, M.; DESBRIERES, J .; LE DUNG, P.; THUY BINH, P.; DONG, N. T .; Carbohydr. Polym. 2001, 46, 339); (SILVA, H. S. R. O; dos SANTOS, K. S. C.R., FERREIRA, E.I. Quasana: Water-Soluble Derivatives, Pharmaceutical Applications and Advances. Quím.Nova, vol. 29, no. 4, 776-785, 2006)].

BAUMANN and FAUST (2001) described the synthesis of water-soluble chitosan derivatives, such as O-sulfo, A / -sulfo and / V-carboxymethylchitosan, where chitosan 1.0 g (6 mmol based on monomeric residue) was solubilized. 100 ml of 5% lithium chloride solution in formaldehyde. The derivatives A / -sulfoe A / -carboxymethylchitosan were obtained sequentially. Initially, partial hydrolysis of chitosan with HCI was performed [(BAUMANN, H .; FAUST, V.; Carbohydr. Res., 331, 43, 2001); (SILVA, H. S. R. O; dos SANTOS, K. S. C.R., FERREIRA, E. I. Chitosan: Water-Soluble Derivatives, Pharmaceutical Applications and Advances. Quim. Nova, Vol. 29, No. 4, 776-785, 2006)].

JIA et al. (2001) reported the production of water-soluble chitosan ammonium salts with antibacterial activity. Salt production occurred when the amino group of chitosan reacted with an aldehyde to form an imine, or Schiff base. This intermediate reacted with methyliodide to form the chitosan quartenary salt [(JIA, Z .; SHEN, D .; XU, W .; Carbohydr. Res. 333.1, 2001); (SILVA, H.S.R.C; dos SANTOS, K.S.R.R., FERREIRA, E.I. Chitosan: Water-Soluble Derivatives, Pharmaceutical Applications and Advances. Quim. Nova, Vol. 29, No. 4, 776-785, 2006)].

XIE et al. (2001) have been able to insert maleic acid into hydroxypropyl chitosan and carboxymethyl chitosan to produce water-soluble derivatives. [(XIE, W .; XU, P .; LIU, Q .; Bioorg. Med. Chem. Lett., 11, 1699, 2001) ; (SILVA, H. S.R. C; dos SANTOS, K. S. C.R., FERREIRA, E.I. Chitosan: Water-Soluble Derivatives, Pharmaceutical Applications, and Advances. Quim. Nova, Vol. 29, No. 4,776-785, 2006)].

AGULLÓ et al. (2001) obtained water-soluble N-methylenephosphonic chitosan, which is also described in the literature. Its achievement was accomplished using phosphoric acid and formaldehyde. [(HERAS, A.; RODRIGUES, NM; RAMOS, VM; AGULLO, E .; Carbohydr. Polym. 2001, 44.1); (RAMOS, VM; RODRIGUES, NM; RODRIGUES, MS; HERAS, A. AGULLO, Carbohydr, Polym 2003, 51, 425); RAMOS, V.M .; RODRIGUES, N.M .; DÍAZ, M. F. RODRIGUES, M.S .; HERAS, A .; AGULLÓ.E .; Carbohydr. Polym 2003, 52, 39); (SILVA, HSR C; dos SANTOS, KSCR, FERREIRA, EI Chitosan: Water-Soluble Derivatives, Pharmaceutical Applications and Advances. Quim. Nova, vol.29, n. 4, 776-785, 2006)] .

HIRANO et al. (2002) studied water-soluble A / -acyl fat derivatives of chitosan and aqueous alkaline acid solutions. In this study the derivatives were obtained by reaction of the acid comanhydrides polymer, in the case of acetic, propionic, butyric, pentanoic, hexanoic, octanic, decanoic, lauric, myristic, palmitic and stearic acids [HIRANO, S .; YAMAGUCHI, Y .; KAMIYA, M. Novel N-saturated-fatty-acyl derivatives ofchitosan soluble in water and in aqueous acid and alkaline solutions. CarbohydratePolymers, Vol. 48, p. 203-207, 2002].

HIRANO et al. (2003) studied chitosan derivatives obtained by Schiff's base reaction, that is, formation of porosaldehyde chitosan imine in order to study the formation of biofibers with incorporation of fragrances [HIRANO, S .; HAYASHI, H. Some fragrant fibers and yams based onchitosan. Carbohydrate Polymers, v. 54, p. 131-136, 2003].

HIRANO et al. (2003) developed pH-soluble chitosan. 0.48 g (3 mmol based on monomeric residue) dequitosan was solubilized in 60 ml of 2% aqueous acetic acid solution and, after complete polymer dissolution, 60 ml of methanol was added. To this was added 1.5 g (15 mmol) of succinic anhydride and the system was stirred for 10 min at 50 ° C and then for 24 hours at room temperature [HIRANO, S.; MORIYASU, T. Some novel / V- (carboxyacyl) chitosan filaments. Carbohydr. Poly., V. 245-248, 2003].

MUZZARELI et al. (2003) developed soluble chitosan empH 10.0 through the formation of the carbamate ion after addition of NH4HC03 [(MUZZARELLI, RAA; TOSI, G .; FRANCESGANGELI, O; MUZZARELLI, C.; Carbohydr. Res., 338, 2247, 2003); (SILVA, H.S.R.C; dos SANTOS, K.S.R.R., FERREIRA, E.I. Chitosan: Water-Soluble Derivatives, Pharmaceutical Applications and Advances. Quim. Nova, Vol. 29, No. 4, 776-785, 2006)].

SILVA, H. S. R. C. et al. (2003) and SANTOS et al. (2003) described obtaining a higher replacement carboxybutylchitosan than described in the literature. In these works, chitosan was first purified and characterized according to the methodology proposed by CANELLA eGARCIA (2001) [(CANELLA, KMND; GARCIA, RB; Quim. Nova 2001, 24, 13); (SILVA, HSR C; dos SANTOS, KSCR, FERREIRA, EI Chitosan: Water Soluble Derivatives, Pharmaceutical Applications and Advances (Quim. Nova, vol.29, no. 4, 776-785, 2006); (SILVA, H.S.R.C; dos SANTOS, K.S.R.C., FAGUNDES F.P.; GARCIA, R.B .; FERREIRA, E. I. Brazilian Journal of Pharmaceutical Sciences, 2003, 39, suppl. 3, 87); (dos SANTOS, K. S. C.R.; COSTA SILVA, H.S. R .; FERREIRA, E. I .; Book of Abstracts of the 26th Meeting of the Brazilian Chemical Society, Poços de Caldas, Brazil, 2003)].

MELLO et al. (2005) based on the work of YAMAGUCHI and co-workers (1981) obtained basic pH-soluble chitosan, but commodities in the process of obtaining such as reagents, solvents and reaction time [(MELLO, KGP C; Synthesis and ratings physicochemical dequitosans chemically modified by the insertion of anhydridosuccinic radicals São Paulo, 2005. 89p - Master's Dissertation - Faculty of Pharmaceutical Sciences of the University of São Paulo); (MELLO, KGP C; BERNUSSO, LC; PITOMBO, NMR; POLAKIEWICZ, B. Synthesis and Physicochemical Characterization of Chemically Modified Chitosan by Succinic Anhydride, Brazilian Archives of Biology and Technology, v. 49, no. 4, pp. 665 - 668,2006 )].

FR 2859726 discloses a method of producing chitin and chitosan derivatives comprising crushing the shell skeletons of crustaceans and cephalopods in the presence of a strong base 0.1 to 20% g / g of water and subsequently of an organic acid 0.1 to 20% g / g water.

WO 2007013717 documented the obtaining of high quality water soluble chitosanoligosaccharide as well as the composition and method for obtaining it. The method is based on the ultrafiltration membrane separation process according to the 30kDa, 10kDa, 3kDa and 1kDa molar mass.

In the work of BERNUSSO, L. C. (2007) the equivalent of 0.025 moles of saturated anhydride was used, in this case succinic anhydride per amino dopolymer group 60% GD (degree of deacetylation) and 0.024 moles of the same anhydride to62% GD. Also, the equivalent of 0.010 mmol of unsaturated anhydride was used, in this case p-methoxy-frans cinnamic anhydride or 4-methoxybenzoic anhydride per 60% GD polymer amino group and 0.009 mo of the same 62% GD opolymer anhydride. US 3879376 indicated the use of 1.0 to 2.0 mo of unsaturated anhydride [BERNUSSO, L. C. Synthesis and characterization of the library of rutin and chitosan-derived molecules with potential photoprotectant. São Paulo, 2007. - Master's Dissertation - Faculty of Pharmaceutical Sciences, University of São Paulo].

The liposolubility of chitosan has also been studied as, for example, the Î ± -acyl fatty and Î ± -alkyl fatty derivatives.

In the work of HIRANO, S. (1971), selective A / -acetylation of amino groups with carboxylic anhydrides in methanol resulting in 2- (2-carboxybenzamido) -2-deoxy-αD-glycopyranose or 2-carboxybenzamido-chitosan (CAS) was investigated. 31505-42-7). Under acetylation conditions, this compound resulted in 1,3,4,6-tetra-0-acetyl-2-deoxy-2-phthalimido-αD-glycopyranose, which again with methanol containing refluxing hydrochloric acid results in 2-deoxy-2-yl. phthalimido-β-D-glycopyranose or 2-phthalimido chitosan or β-phthaloyl chitosan (CAS 135364-79-3).

In the work of BERNUSSO, LC (2007), 2- (2-carboxybenzamido) -2-deoxy-ar-D-glycopyranose or 2-carboxybenzamido-chitosan (CAS 31505-42-7) was synthesized under different conditions than HIRANO, S. (1971) synthesized.

In other work by HIRANO, S. and MORIYASU, T. (1981), syntheses of A / - derivatives (carboxyacyl) were reported, which were prepared by reaction of thatitosan with some dicarboxylic anhydrides resulting in intramolecular modifications [HIRANO, S .; MORIYASU, T.N- (Carboxyacyl) chitosans.Carbohydrate Research, v. 92, p. 323-327, 1981].

In the work of NISHIMURA, S. I. et al. (1991) the synthesis of (1-4) -2-deoxy-2-phthalimido-R-D-glycopyranose, the same as N-phthaloylchitosan, has been reported. The solubility of this compound has been demonstrated in organic solvents such as: N, α-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), dimethylacetamide (DMac) and pyridine [NISHIMURA, S. I .; KOHGO, O .; ISHII, S.; KURITA, K .; MOCHIDA, K .; KUZUHARA, H. New trends in bioactive chitosanderivatives: use of "standardized intermediates" with excellent solubility in commonorganic solvents. In: BRINE, C. J .; SANDFORD, P. A .; ZIKAKIS, J. P. Advances in Chitin and Chitosan. London and New York: Elsevier Applied Science, 1991, p. 533-542].

The same result found in the work of NISHIMURA, SI and co-workers (1991) is in the work of KURITA, K. et al. (1991). In this work, the synthesis of chitosan-derived compounds such as α-phthaloyl chitosan and α / phthaloyl chitosan was reported. acetylated. The β-phthaloylchitosan molecule has been shown to be soluble in polar organic compounds such as DMSO and pyridine. Acetylated A-β-phthaloyl chitosan has been found to be very soluble, dissolving in low boiling compounds such as chloroform and dichloromethane [(KURITA, K .; KAMIYA, M .; Solubilization of a RigidPolysaccharide: Controlled Partial Acetylation of Chitosan to Develop Solubility (Carbohydrate Polymers, v. 16, pp. 83-92, 1991); (KURITA, K .; NISHIMURA, SI; ISHII, S.; TOMITA, K .; TADA, T .; SHIMODA, K. Characteristic properties of squidchitin. In: BRINE, CJ; SANDFORD, PA; ZIKAKIS, JP, eds. Advances in Chitinand Chitosan, London, New York: Elsevier Applied Science, 1992. pp. 188-195 (Proceedings from the 5th International Conference on Chitin and Chitosan, New Jersey, 1991])].

ZONG et al. (2000) studied the chemical characterization and solid state of acetylated chitosan structures. In this work, chitosan derivatives were synthesized by reaction of the polymer with acid chloride, in this case hexanoyl, decanoyl and lauryl. Obtaining substituted-V-acyl and O-acyl group compounds [ZONG, Z .; KIMURA, Y .; TAKAHASHI, M .; YAMANE, H.Characterization of chemical and solid state structures of acylated chitosans. Polymer, vol. 41, p. 899 - 906, 2000].

In another work by KURITA, K. (2001) the synthesis of / V-phthaloyl chitosan also obtaining a DMSO-soluble compound [KURITA, K .; Controlledfunctionalization of the polysaccharide chitin. Progress in Polymer Science, v.26, p.1921-1971, 2001],

In the work of BAUMANN, H. and FAUST, V. (2001) also reported the synthesis of 87% yield A / -phthaloylchitosan [BAUMANN, H .; FAUST, V.Concepts for improved regioselective placement of O-sulfo, A / -sulfo, / V-acetyl, andA / -carboxymethyl groups in chitosan derivatives. Carbohydrate Research, Vol. 331, p.43-57, 2001].

In the work of WU, Y. et al. (2003), the spectrophotometric UV-Vis absorption activities of the N-phthaloylchitosan compound were studied and activity was obtained in the UV region with a peak absorption of 330 nm [WU, Y .; DONG, Y .; ZHOU, H .; RUAN, Y .; WANG, H .; ZHAO, Y. Studies on the Critical Phase-Transition Behavior of Cholesteric N-Phthaloyl Chitosan / Dimethyl Sulfoxide Solutions by Five Techniques. Journal of Applied Polymer Science, v. 90, p. 583-586, 2003],

WO 2003020235 has reported the stabilization of oxidation and UV radiation sensitive actives with dialkyl naphthalates in cosmetic and dermatological formulations.

DE 3912122 of CLAUSEN (1990) disclosed the development of a chitin and chitosan derivative with UV-absorbing groups in the molecule. The UVB absorbing group in this case is p-methoxy cinnamoyl. Thus, the developed molecules are: p-methoxy cinnamoyl chitin and p-methoxy cinnamoyl chitosan (CAS not defined) by the process of obtaining: 115.3 g of 3,4,5-trimethoxybenzoyl chloride were added. in 300 ml_MeS03H and stirred for more than 3 hours for 20.3 g of chitin in 150 ml MeS03H and stirred for 2 hours at 0 ° C under a temperature of -3 ° to 0 ° C. The methodology resulted in 39.6g (3,4,5-trimethoxybenzoyl) -chitine with a viscosity of 12 ml / g, with 1.9 degree disubstitution, and UV absorption in the region of 240-320 nm.

CHEN et al. (2005) studied the ultraviolet (UV) absorbing capacity of the natural chitosan polymer with incorporation of the cinamoyl group into the polymer chain. They prepared chitosan cinnamate and chitin ecinamate with infrared confirmed structures. The results demonstrated excellent UV absorption capacity [CHEN, Y .; DUO, Y .; LUO, Y .; TAN, H. Cinnamyl modification research of chitosan andchitin, Gaofenzi Cailiao Kexue Yu Gongcheng, v. 21, no. 3, p.286-289, 2005. apudSciFinder Scholar].

WU et al. (2005), through regioselective modifications, studied some acetylated chitosan derivatives, such as O-cinnamoyl chitosan, with substitution degree ranging from 0.8 to 2.0 and the / V-alkyl-O-fatty acids. di-cinnamoyl chitosan with different C2 -C12 alkyl chain sizes [WU, Y .; SEO, T.; MAEDA, S .; SASAKI, T .; IRIE, S .; SAKURAI, K. Circular dichroism induced by thehelical conformations of acylated chitosan derivatives bearing cinnamatechromophores. Journal of Polymer Science, Part B: Polymer Physics, v. 43, no. 11, p.1354-1364, 2005].

In the work of HUANG, R. et al. (2006) the N-succinyl-O- (p-methoxy-frans-cinnamoyl) -chitosan molecule was synthesized and spectrophotometric experiments were performed to confirm its application as a photoprotector [HUANG, R. ; MENDIS, E .; RAJAPAKSE, N .; KIM, S. K. Strongelectronic charge as an important factor for anticancer activity ofchitooligosaccharides (COS). Life Sciences, v. 78, p. 2399 - 2408, 2006].

In the work of TSAI, B. H. et al. (2006), the synthesis of crosslinked and photon-resorbing chitosan copolymer derivatives (photocopolymer) was demonstrated by the compolyethylene glycol photopolymerization reaction [TSAI, B .; LIN, C; LIN, J. Synthesis and Property Evaluations of Photocrosslinkable Chitosan Derivative and its Photocopolymerization with Poly (ethylene glycol). Journal of Applied Polymer Science, v. 100, p. 1794-1801,2006].

In the work of BERNUSSO, LC (2007), p-methoxy cinnamoyl chitosan or A / - (p-methoxy-frans cinnamyl) chitosan was synthesized under different conditions of the synthesis process of DE 3912122 by CLAUSEN, T. et al. (1990), [BERNUSSO, L. C; Synthesis and library characterization of rutin and chitosan-derived molecules with photoprotective potential. São Paulo, 2007. -Master Dissertation - Faculty of Pharmaceutical Sciences, University of São Paulo].

In the work of BERNUSSO, L. C. (2007) the italic derivatives of chitosan 60 and 62% GD as 2-carboxybenzamido-chitosan and 2-phthalimido-chitosan or A / -phthalyl chitosan were synthesized and spectrophotometrically characterized. These compounds showed UV absorption. The 2-carboxybenzamido-chitosan molecule showed peak absorption at 239 and 277 nm (UVC) and A / -phthaloyl chitosan peaked at 294 nm (UVB). In addition, N- (p-methoxy-trans-cinnamoyl) -chitosan and A / -succinyl-chitosan were synthesized.

Of these the first showed UV absorption in the UVB region with peaks at 306.5nm; the second, in the UVC region with 294nm and 2777nm absorption peaks. [BERNUSSO, L. C; Synthesis and library characterization of rutin and chitosan-derived molecules with photoprotective potential. São Paulo, 2007. -Master Dissertation - Faculty of Pharmaceutical Sciences, University of São Paulo].

Goals

Based on the above and aiming to solve and overcome the problems presented, a new process of obtaining chitosan derivatives was developed, presenting the following characteristics: faster preparation;

- low cost because it employs less amount of anhydride reagent - high purity of the obtained derivative, since there is less salt formed in the reaction.

From the obtained derivative, photoprotective chitosan derivatives were developed with the following characteristics:

- good photostability;

- good effectiveness (degree of protection);

- good thermal stability;

broad spectrum absorption of UVB and / or UVA and / or UVC radiation;

- good lipo and water solubility;

safe to the environment.

Brief Description of the Invention

The present invention is a novel process for obtaining chitosan derivatives which comprises the reaction by N-acylation or N-alkylation of chitosan, having deacetylation degree ranging from 10% to 90%, with comanhydrides ranging from 1: 1 to 1: 4 w / w in presence of prototype or aprotype organic solvent in one or more steps; and after the reaction of achitosan with anhydrides, the process also presents a step of pH adjustment of the solution obtained for the range between 5.0 and 8.0 for the synthesized derivatives in the prototype.

Additionally, the invention contemplates the chitosan derivatives obtained from such a process, as well as the pharmaceutical and cosmetic composition containing the derivatives obtained and their use in the areas of pharmaceutical, cosmetic, veterinary and / or biomaterials.

Detailed Description of the Invention

The chitosan monomer is represented by the following structural formula: The process for obtaining chitosan derivatives is based on the chemical synthesis of chitosan-derived polymeric molecules with anhydrides. The chemical reaction between the chitosan biopolymer with anhydrides results in a biopolymer with soluble capacity at slightly acidic, neutral and basic pHs and optimization of the preparation technique resulting in less addition of anhydrides, acid and bases. This is possible because the following polymeric variables are taken into account: Degalactillation Degree (GD) and Chitosan Molar Mass, which lead to particular molarity conditions of the reagent to be added in the major reaction.

According to the average degree of acetylation (GA) or average degree of acetylation (GD), which is the average parameter to characterize the average content of chitosan A / -acetyl-D-glycosamine units, several chitosans can be obtained, varying thus their physicochemical properties, such as solubility, pKa and viscosity [(SINGLA, A, K.; CHAWLA, M .; J. Pharm.Pharmacol. 2001, 53, 1047); (SILVA, H.S.R.C; dos SANTOS, K.S.R.R., FERREIRA, E.I. Chitosan: Water-Soluble Derivatives, Pharmaceutical Applications and Advances. Quim. Nova, Vol. 29, No. 4, 776-785, 2006)].

The present invention is a novel process for obtaining chitosan derivatives comprising the reaction by Î ± V-acylation or Î ± -alkylation of chitosan, having deacetylation degree ranging from 10% to 90%, comanhydrides ranging from 1: 1 to 1: 4 w / w in the presence of prototype or aprotypeorganic solvent in one or more steps; and after the reaction of tositosan with anhydrides, the process also presents, for the synthesized derivatives in a prototype medium, the pH adjustment step of the solution obtained for the range between 5.0 and 8.0.

According to the invention, the anhydride may be from 2 carbon atoms to 18 carbon atoms. Examples of the reaction employable anhydrides include acetic, propionic, butyric, pentanoic, hexanoic, octanoic, decanoic, lauric, palmitic, benzoic, succinic, phthalic, oleic, cinnamic, p-methoxy-cinnamic, caffeic, benzophenic anhydrides. ), salicylic, p-aminobenzoic and their synthetic derivatives, phenylpropenoic, o-hydroxybenzoic, anthranylate, avobenzonic, octocrylene, triazole, gallic acid and its derivatives, urocanic acid, 2-phenylglutaric acid and its derivatives, synthetic derivatives of camphor benzylidene, or their mixtures or derivatives thereof, preferably, anhydrides are used: succinic, phthalic, p-methoxkrans-cinnamic and / or mixtures thereof.

Preferably, the degree of deacetylation of chitosan is 60% and 62%, and the chitosan: anhydride ratio is shown in Table 1 below:

<table> table see original document page 29 </column> </row> <table>

TABLE 1

The process of obtaining chitosan derivatives is characterized by the following steps:

(i) dissolving chitosan in appropriate medium;

(ii) reaction of chitosan with one or more anhydrides in the presence of prototype or aprotype organic solvent;

(iii) stirring and resting the solution obtained in step (ii);

(iv) increasing the pH of the solution from 5.0 to 8.0 for derivatives synthesized in a prototype medium;

(v) filtering the precipitate obtained in step (iv);

(vi) resuspension in water of the precipitate obtained in a prototype medium in

(v) adjusting the solution to the desired pH; or precipitated drying obtained in step (v).

The means for dissolving chitosan may be chosen from acetic acid, hydrochloric acid, glyoxylic acid, formic acid, succinic acid, tactical acid or mixtures thereof; preferably acetic acid and lactic acid. The prototype organic solvent used can be chosen from methanol, ethanol, propanol, butanol or mixtures thereof; preferably ethanol. As for the aprotypeorganic solvent used, it can be chosen from dimethylformamide (DMF), pyridine, methane sulfonic acid (MeSO3H).

According to the invention, step (iv) of the reaction described above occurs by the addition of sodium carbonate, sodium hydroxide or mixtures thereof, preferably sodium carbonate and / or sodium hydroxide.

The process for obtaining chitosan derivatives optionally presents the reaction between chitosan molecules with grouping carriers that modify the solubility of the molecule. The group that makes the molecule more water soluble may be chosen from hydroxyl, succinic or phthalic group or mixtures thereof; preferably succinic. The group that makes the molecule more fat soluble can be chosen from: phthalic, group of saturated fatty acids, unsaturated, animal or vegetable origin that present C4 - C18, preferably lauric or oleic acid.

According to the process of obtaining the resulting chitosan derivatives, synthesized in a prototype medium, they may be in mildly acidic, basic, neutral or solid form as film or as hydrogels.

In a particular form, the invention relates to a process for obtaining a basic and / or neutral solution containing chitosan derivatives synthesized in a prototype, comprising the following steps:

(i) reaction of chitosan with anhydride;

(ii) stirring and resting the solution obtained in (i);

(iii) adding sodium carbonate and / or sodium hydroxide to raise the pH of the solution to between 6.0 and 7.0;

(iv) filtering the precipitate obtained in step (iii);

(v) solubilizing the precipitate obtained in step (iv) in water at the desired concentration;

(vi) adding dilute sodium hydroxide to adjust pH to neutral or basic.

The invention also relates to a process for obtaining an acid solution containing chitosan derivatives synthesized in a prototype medium, comprising the following steps:

(i) reaction of chitosan with anhydride;

(ii) stirring and resting the solution obtained in (i), (iii) adding sodium carbonate and / or sodium hydroxide to raise the pH of the solution to between 6.0 and 7.0;

(iv) filtering the precipitate obtained in step (iii);

(v) solubilizing the precipitate obtained in step (iv) in water at the desired concentration;

(vi) adding dilute sodium hydroxide to adjust pH to neutral;

(vii) adding acetic acid and / or dilute lactic acid to adjust the pH to slightly acidic.

The present invention is further directed to the process of obtaining synthesized dehydrosan derivatives in solid form, comprising the following steps:

(i) reaction of chitosan with anhydride;

(ii) stirring and resting the solution obtained in (i);

(iii) adding sodium carbonate and / or sodium hydroxide to raise the pH of the solution to between 6.0 and 7.0;

(iv) filtering the precipitate obtained in step (iii);

(v) drying the precipitate obtained in step (iv).

The structure of the chitosan biopolymer derivatives in this work with A / acylation and / or A / alkylation (R) photoprotective activity on the amino polymeric chain group is represented by the following formula:

<formula> formula see original document page 31 </formula>

The molecular structure of 2-carboxybenzamido-chitosan or 2- (2-carboxybenzamido) -2-deoxy-α-D-glycopyranose is as follows:

<formula> formula see original document page 31 </formula> The molecular structure of 2-phthalimido chitosan or A / phthaloyl chitosan is as follows:

<formula> formula see original document page 32 </formula>

The molecular structure of Î ± -succinyl- / β- (p-methoxy-frans-cinnamoyl) -chitosan is as follows:

<formula> formula see original document page 32 </formula>

The molecular structure of β-2-carboxybenzamido- β- (p-methoxy-frans-cinnamoyl) -chitosan is as follows:

<formula> formula see original document page 32 </formula>

The molecular structure of A? -2-carboxybenzamido-O- (p-methoxy-trans-cinnamoyl) -chitosan is given below: <formula> formula see original document page 33 </formula>

According to the invention, chitosan derivatives can be obtained by acetylation process, by crosslinking these polymers (using glucutaraldehyde) or by enzymatic reaction.

The invention further contemplates the chitosan derivatives obtained by the above processes as well as the echmetic pharmaceutical compositions containing them.

Derivatives according to the invention may be: 2-carboxybenzamido-chitosan, N- (p-methoxy-frap7S-cinnamoyl) -chitosan, N-phthaloyl-chitosan, N-succinyl-A / - ( p-methoxy-trans-cinnamoyl) -chitosan, N-2-carboxybenzamido-A / - (p-methoxy-frans-cinnamoyl) -chitosan, N-2-carboxybenzamido-0- (p-methoxy-trans-cinnamyl) ) -chitosan and A / -succinyl chitosan.

The invention further contemplates photoprotective derivatives which may be: p-methoxy-frans-cinnamoyl chitosan, 2-carboxybenzamido-chitosan, N-phthaloyl-chitosan, A / -succinyl-A / - (p-methoxy-trans-cinnamyl) - chitosan, Î ± -2-carboxybenzamido-β- (p-methoxy-frans-cinnamoyl) -chitosan and Î ± -2-carboxybenzamido-0- (p-methoxy-Î ± -synnamyl) -chitosan.

According to the invention, the pharmaceutical composition comprises one or more chitosan derivatives, in a suitable pharmaceutically acceptable carrier, and additives known to the person skilled in the art; being the appropriate vehicle for both hydrophilic, lipophilic, or amphoteric usotopic. The pharmaceutical composition consists of formulations of liquid and / or stone soaps, lotions, creams, moisturizers, moisturizers and sunscreens, and may be used for hair and / or skin treatment. Cosmetic compositions contain chitosan derivatives obtained in vehicles. acceptable and appropriate, in addition to additives known to the skilled artisan. In addition to a suitable carrier, the composition may contain aqueous solvents, lipophilic solvents, thickening agents, polymers, surfactants, solid oils (grease or lanolin, for example), moisturizing agents, humectants, preservatives, pH modifiers, colorants, flavorants, antioxidants and vitamins.

Compositions used for hair treatment may be, for example, shampoo, conditioner, lotion and gel formulations to be applied before or after washing as well as after dyeing or bleaching, or after straightening or perming hair. It can also be used in makeup products such as lipsticks, bases, rhyme, eyeshadows, eyeliner or masks and blushers.

Chitosan derivatives can be applied to composites or blends, biofibers or membranes with other UV absorbing polymers or not. Polysilicone-15 (dimethylcodiethylbenzalmalonate), or polycrylamide methyl benzylidene camphor (N - {(2 and 4) [2-oxoborn-3-ylidene] methyl} benzyl} acrylamide polymer), or cellulose derivatives, or derivatives of descending fibroin, or animal protein derivatives, or vegetable protein derivatives thereof; preferably polysilicone-15.

Chitosan derivatives may be applied to gels or hydrogels with other UV absorbing polymers or not. Polysilicone-15 (dimethylcodiethylbenzalmalonate), or methyl benzylidene camphor (N - {(2 and 4) [2-oxoborn-3-ylidene] methyl} benzyl} acrylamide polymer), or cellulose derivatives, or derivatives of sucrose, or silk fibroin derivatives, or animal protein derivatives, or vegetable protein derivatives, their mixtures preferably sucrose derivatives.

Chitosan derivatives may be applied in capsules, microcapsules or nanocapsules. They may be used in conjunction with other UV absorbing and / or antioxidant molecules and / or vitamins. Of the UV-absorbing molecules, oil-soluble (fat-soluble) actives may be used as examples: p-methoxy-frans cinnamic ester, p-aminobenzoic ester, estersalicylic acid, benzylidenocanfor ester and derivatives, benzophenones and derivatives, dibenzoylmethanes, benzylphenylacrylates, benzylphenylacrylates, triazines or mixtures thereof.

Preferably, octyl methoxycinnamate, octyl dimethyl PABA, octylsalicylate, homomentyl salicylate, 4-methylbenzylidenocamphor, 3-benzophenone, butyl methoxydibenzoylmethane, octocrylene, menthylantranylate, triazone are employed. Antioxidants can be chosen from: flavonoids and their derivatives, terpenes and their derivatives (alpha-tocopherol, beta-carotene, lycopene). Vitamins can be chosen from: vitamin E (alpha-tocopherol), vitamin C (ascorbic acid) and their derivatives.

Chitosan derivatives may also have intrinsic fragrance synthesized polymer. This characteristic results from specific reactions of incorporation of aromatic groups to the polymeric chain. Therefore, the molecule (raw material) has, besides its photoprotective capacity, the option of exhaling perfume.

These compositions of the invention fall within the medical and / or pharmaceutical and / or veterinary and / or cosmetic fields especially for their activity in absorbing ultraviolet radiation, combating photooxidative damage to the skin, skin aging and / or skin cancer. In combating the photo-oxidative damage of the cornea acting as an eye drop or the like, suitable for people with hypersensitivity to the sun as well as in postoperative cases where UV radiation protection is necessary, as well as in cases of cataract prevention. Also, when combined with any substance with synergistic actions with regard to its antioxidant, anti-aging and photoprotective activity, such as applications on gels, hydrogels, composites and biofiber blends or membranes.

These compositions of the invention fall within the area of polymer formulation especially for their film-forming and surface coating property, adding to this the photoprotective and antioxidant capacity.

Thus leading to an increase in the life of the protected polymer.

The invention further relates to the use of chitosan derivatives using chitosan derivatives obtained in the pharmaceutical, cosmetic, veterinary and biomaterial fields, and such derivatives may have photoprotective properties.

The following are examples for further clarification of the invention, but should not be taken for purposes of limiting the invention.

Reference Methodologies

• VANLERBERGHE, G; SEBAG, H. Chitosan derivative, method of making the same and cosmetic composition containing the same. US Pat 3879376, May 22, 1975. 9p.

In US 3879376 (1975), VANLERBERGHE et al. Presented chitosan derivative process method and cosmetic composition. In this patent the process of obtaining comprises acylating the tositosan with saturated or unsaturated organic diacid anhydrides. The ratio employed was 0.3 mmol to 2.0 mmol of saturated anhydride per amino group equivalent present in the chitosan polymer, or 1.0 to 2.0 mmol of amino group unsaturated anhydride (GlcN) present in chitosan. In other analyzed studies stoichiometric calculations appear in the range of 0.7 nm to 1.5 nm of hydrochloride by (GlcN).

• YAMAGUCHI, R .; ARAI, Y .; ITOH, T. Preparation of partially N-succinylatedchitosans and their cross-linked gels. Carbohydrate Research, v.88, p. 172-175,1981

• YAMAGUCHI and collaborators (1981) developed A / -acyl chitosan gels, A / -alkylidenosquitosans and basic-soluble chitosan salts. In this work a stoichiometric calculation of 14.6 mmol anhydride by (GlcN) was used.

• MELLO, K. G. P. C; Synthesis and physicochemical evaluations of chitosan-chemically modified by the insertion of succinic anhydride radicals. São Paulo, 2005. 89 p. - Master's Dissertation - Faculty of Pharmaceutical Sciences, University of São Paulo

In this work the stoichiometric calculation of 1.0 mol of anhydride per (GlcN) was used, and this relationship proved to be insufficient to occupy all amino groups, thus obtaining an insoluble product in pHneutral.

Process:

Four samples of 10.0 g chitosan were dissolved in 3.0% aqueous acetic acid solution (300mL). After complete dissolution and under constant stirring 1000mL of ethanol was added. Then 2.5 was slowly added to each sample; 5.0; 10.0 and 30.0g by mass of succinic anhydride dissolved directly in the reaction medium. Three hours of mechanical emagitator stirring and 12 hours of rest followed, then the samples precipitated to pH 10.0 and then the samples were vacuum filtered. The precipitate was washed with ethanol / ether, filtered and vacuum dried again to constant weight. Thus, sodium β-succinyl chitosan was obtained CAS: 125692-28-6EDUARDO, M. F .; Rheological and Physical-Chemical Evaluation of Chocolate and Chocolate Chocolate, São Paulo, 2004. 105 p. - Master Thesis - Pharmaceutical Sciences Faculty of the University of São Paulo.

It follows the methodology of MELLO, K. G. P. C (2005) by adding dialysis at the end of the process for the purification of the synthesized molecule, as this was at pH 10.0. The reaction product was subjected to dialysis to remove sodium salts in order to obtain a product with pH = 7.0.

Modified Processes:

EXAMPLE # 1:

In this example the polymer variables are considered, for example, the degree of deacetylation (GD) and its molar mass (kD). These two variables lead to a study of the molarity conditions of the reagent to be added in the reaction medium. It was obtained in the work of BERNUSSO, LC (2007) when compared with VANLERBERGHE document US 3879376, the equivalent of 0.025 moles of saturated anhydride was used, in this case succinic anhydride per polymer group 60% GD (degree of deacetylation) and 0.024 moles of the same anhydride to 62% GD. Also, the equivalent of 0.010 mmol of unsaturated anhydride, in this case p-methoxy-rarts cinnamic anhydride or 4-methoxybenzoic anhydride per 60% GD polymer amino group and 0.009 mmol of the same anhydride for the 62% GD polymer, was used. In US 3879376, the use of 1.0 to 2.0 mmol of unsaturated anhydride was indicated [BERNUSSO, L. C; Synthesis and library characterization of molecules derived from rutin and photoprotective chitosan. São Paulo, 2007. - Master's Dissertation - Faculty of Pharmaceutical Sciences, University of São Paulo].

EXAMPLE # 2:

Obtaining the molecule / V-succinyl chitosan or Chitosan A / succinamide CAS78809-92-4

In a glass flask under magnetic stirring was placed 1.0 g (6 mmol based on monomeric residue) of 60% GD chitosan, as well as with 62% GD; dissolved in 20 mL of 5.0% acetic acid. After complete dissolution of the tositosan, 65 ml of ethanol was added and then the deamidation reaction was initiated by the addition of succinic anhydride at a ratio of 1: 1.5 w / w, ie 1.0 g (6 mmol based on the residue). chitosan monomer) and 1.5 g (15 mmol succinic anhydride) corresponding to 25 mmol of anhydride per amino acid present in the 60% GD chitosan polymer and corresponding to 24.2 mmol of amino acid anhydrous equivalent present in chitosan 62% GD. After 2.0 hours of stirring, the material was allowed to stand for 10 hours and then the pH of the solution was raised to approximately 4.0 with Na2 CO3 and completed with droplets of 50% NaOH to pH = 7.0; as well as pH can be adjusted only by the addition of 50% NaOH droplets. Thus, the obtained precipitate was funneled with filter paper and when semi-wet resuspended with distilled water / Milliq at the desired concentration. Before supplementing with water, the pH is adjusted to the desired pH. Also, the semi-wet precipitate obtained after funnel filtration with filter paper can be dried under reduced pressure (desiccator) at room temperature to constant weight.

The active begins to solubilize from pH 6.5 to 7.0 with little base addition (low molarity). Addition of the basifying agent should be followed by agitation of the system for better homogenization. This technique is specific for the preparation of solutions in different active concentrations with the desired pH and the minimum salt formed. With this technique, the solubility of the raw material is obtained from the pH around 7,0. Thus, there is no need to dialysis the polymer to remove sodium acetate or sodium succinate salts, which causes loss of the polymer. A proof of this is the plate test, where an aliquot of the dissolved polymer is placed and taken to the drying oven. This methodology allows the formation of a translucent polymer film obtained in the plate, which is not possible with other methodologies.

To obtain solutions with pH <7.0, for example pH 6.0, the pH is corrected with the acidulant after reaching pH 7.0 (solubility point). For this, drops of acidic solutions, for example low molar acetic or lactic acid, may be added to the solution under constant stirring to a minimum pH of 6.0.

In addition to the above; Different degrees of solubility of these compounds to pharmaceutical pharmaceutical vehicles may also be synthesized for their use in various formulations, such as lotions, creams and shampoos. Solubility is modified according to the insertion of groups that leave the most water-soluble molecule, such as succinic and / or phthalic group; or fat-soluble, such as fatty acid-derived groups, such as lauric and oleic.

EXAMPLE No. 3:

Obtaining the molecule 2-carboxybenzamido-chitosan or 2- (2-carboxybenzamido) -2-deoxy-q-D-glycopyranose. CAS 31505-42-7

This methodology was modified from the work of MELLO, K. G. P. C. Ecolaboradores (2006); LEMIEUX, R. U. and collaborators (1976); VANLERBERGHE, G. and collaborators (1975); HIRANO, S. (1971). In a glass flask under magnetic stirring 2.0 g (12 mmol based on the monomeric residue) of 60% GD chitosan as well as 62% GD dissolved in 40 mL of 5.0% acetic acid were placed. After complete dissolution of chitosan, 130 mL of ethanol was added and then the amidation reaction was initiated by the addition of 5.52g (37.2mmol) of phthalic anhydride, ie at a ratio of 1: 2.7 w / w. p, corresponding to 31 mmol of anhydride per amino equivalent present in the 60% GD chitosan polymer and corresponding to 30 mmol of anhydride per amino equivalent present in the chitosan 62% GD polymer. After 3.0 hours of stirring, the material was left to stand for 12 hours and then the pH of the solution was raised to = 7.0 with few 50% NaOH depletion. In view of this, it was filtered, dried at room temperature and dried to constant weight [(MELLO, KGP C; BERNUSSO, LC; PITOMBO, NMR; POLAKIEWICZ, B. Synthesis and Physicochemical Characterization of Chitosan by Succinic Anhydride, Brazilian Archives of Biology and Technology, v. 49, no. 4, pp. 665-668, 2006); (LEMIEUX, R.U .; TAKEDA, T .;

CHUNG, B.Y. Synthesis of 2-amino-2-deoxy-α-D-glucopyranosides. Properties anduse of 2-deoxy-2-phthalimidoglycosyl halides. ACS Symposium Series (1976), 39 {Synth. Methods Carbohydr., Symp.), 90-115 apud SciFinder Scholar®, 2006); (VANLERBERGHE, G; SEBAG, H. Chitosan derivative, method of making the cosmetic composition containing the same. US Pat 3879376, 22 Apr.1975 9p.);

(HIRANO, S. Some phthaloyl derivatives of 2-amino-2-deoxy-D-glucopyranose. Carbohydrate Research, v. 16, p.229-231, 1971)].

EXAMPLE # 4:

reference:

DE 3912122 of CLAUSEN (1990) disclosed the development of a chitin and chitosan derivative with UV-absorbing groups in the molecule. The UVB absorbing group in this case is p-methoxy cinnamoyl. Thus, the developed molecules are: p-methoxy cinnamoyl chitin and p-methoxy cinnamoyl chitosan (CAS not defined) by the process of obtaining: 115.3 g of 3,4,5-trimethoxybenzoyl chloride were added. in 300 ml_MeS03H and stirred for more than 3 hours for 20.3 g of chitin in 150 ml MeS03H and stirred for 2 hours at 0 ° C under a temperature of -3 ° to 0 ° C. The methodology resulted in 39.6 g (3,4,5-trimethoxybenzoyl) -chitine with a viscosity of 12 ml / g, with 1.9 degree disubstitution, and UV absorption in the region of 240-320 nm.

This technique makes use of acid chlorides for the synthesis of the polymer derivative, as well as in CIAUDELLI, JPRAMSEY, NJ (1975) US 3864473 which also makes preferential use of chlorides, bromides, fluorides and iodides as halocarbonic groups for synthesis. Polymeric Derivatives [CIAUDELLI, JP RAMSEY, NJ Substantive polymericsunscreen composition US Pat 3864473, 4 Feb. 1975. 4p.].

Modified Process:

Obtaining the N- (p-methoxy-trans-cinnamoyl) -guitosan molecule or chitosan p-methoxy-trans-cinamide CAS (undefined)

This methodology was modified from the works of CLAUSEN, T. ecolaboradores (1990); CIAUDELLI, J. P. RAMSEY, N. J. (1975); CHO, J.R., JOHNSON, S.C. (1984); MELLO, K. G. P. C. and colleagues (2006); HIRANO, S. (1971); VANLERBERGHE, G. et al. (1975). In a glass flask with magnetic stirring was placed 1.0 g (6 mmol based on the monomeric residue) of 60% GD chitosan as well as 62% GD dissolved in 20 mL 5.0% acetic acid. After complete dissolution of the chitosan 65 mL of ethanol was added and then the amidation reaction was initiated by the addition of p-methoxy-frans cinnamic anhydride in the ratio of 1: 1.92 w / w, ie 1, 0 g (6 mmol with basene chitosan monomeric residue) and 1.92 g (5.43 mmol of p-methoxy-trans-cinnamic anhydride) corresponding to 9.05 mmol of anhydride per aminopresent equivalent in 60% chitosan polymer GD is 8.76 mmol of anhydrous equivalent per amino acid present in the 62% GD chitosan polymer. After 2.0 hours of stirring, the material was allowed to stand for 10 hours and then the pH of the solution was raised to 7.0 with a few drops of 50% NaOH. Thereafter, it was filtered, dried at room temperature in the desiccator to constant weight [(MELLO, KGP C; BERNUSSO, LC; PITOMBO, NMR; POLAKIEWICZ, B. Syhthesisand Physicochemical Characterization of Chemically Modified Chitosan by SuccinicAnhydride, Brazilian Archives of Biology and Technology , v. 49, no. 4, pp. 665-668,2006); (CLAUSEN, T .; GÜTHER; LENZ, H.R .; MARESCH, G. UV-Strahlenabsorbierende Chitosan und Chitinderivate, Verfahren zu deren Herstellung unddiese Verbindungen enthaltendes kosmetisches Mittel. DE 3912122 25 Oct. 1990.8p.); (CIAUDELLI, J.P. RAMSEY, N.J. Substantive polymeric sunscreencomposition US Pat 3864473, Feb. 4, 1975. 4p.); (CHO, J.R .; JOHNSON, S.C. Polymeric sunscreens EP Pat 0123368, 31 Oct. 1984); (VANLERBERGHE, G; SEBAG, H. Chitosan derivative, method of making the same and cosmetic composition containing the same. US Pat 3879376, 22 Apr.1975. 9p.); (HIRANO, S.Some phthaloyl derivatives of 2-amino-2-deoxy-D-glucopyranose. Carbohydrate Research, v. 16, p.229-231, 1971)].

EXAMPLE No. 5:

Obtaining the p-methoxy-frans cinnamic anhydride molecule or 4-methoxybenzoic anhydride CAS 794-94-5

This methodology was adapted from the work of SIMPSON & ISRAELSTAM (1949).

A mixture of p-methoxy frans cinnamic acid 30g (168.3 mmol) and 50ml anhydridoacetic acid (528 mmol) was refluxed for 2 hours at 50 ° C. A drop of H2 SO4 was instilled into the reaction medium. After synthesis, the crystals were filtered on the Buchner funnel and washed with acetic acid to crystallize them.

Left to dry in the desiccator to constant weight. Yield = 50% [SIMPSON, J.D.M .; ISRAELSTAM, S.S. The reaction between cinnamic acid and certain phenols. Journal of the South African Chemical Institute, v.2, p.165-71, 1949, cited SciFinder Scholar, February 2, 2006].

Obtainment of A / -phthaloyl chitosan or 2-phthalimido-chitosan molecule CAS 135364-79-3

This methodology was adapted from the works of TSAI, B.H. ecolaboradores (2006); WU, Y. et al. (2003); Lemieux, R. U. co-workers (1976); VANLERBERGHE, G. et al. (1975); HIRANO, S. (1971). In a glass flask under magnetic stirring were placed 2.5 g (15 mmol based on monomeric residue) of 60% GD chitosan, as well as for 62% GD, dissolved in 50 mL stirring DMF, nitrogen atmosphere and 80 ° C. temperature for 01 hour. After this procedure, 2.76 g (46.5 mmol) of phthalic anhydride were added under stirring with nitrogen atmosphere and 130 ° C temperature for 08 hours. The one corresponding to 31 mmol per amino equivalent anhydride present in the 60% GD chitosan polymer and the one corresponding to 30 mmol of an amino equivalent per amino acid present in the chitosan62% GD polymer. After this reaction, to the material was added ice water to precipitate the product. The reaction medium was neutralized and the product was filtered and washed several times with water and ethanol. The filtrate was dried at room temperature in the desiccator to constant weight [(TSAI, B.; LIN, C; LIN; J. Synthesis and Property Evaluations of Photocrosslinkable Chitosan Derivative and its Photocopolymerization with Poly (ethylene glycol). Journal of Applied Polymer Science, v. 100, pp 1794-1801,2006); (LEMIEUX, RU; TAKEDA, T.; CHUNG, BY Synthesis of 2-amino-2-deoxy-BD-glucopyranosides. Properties and use of 2-deoxy-2-phthalimidoglycosyl halides.ACS Symposium Series (1976), 39 (Synth Methods Carbohydr., Symp.), 90-115 (SciFinder Scholar®, 2006); (VANLERBERGHE, G; SEBAG, H. Chitosanderivative, Method of Making the Same and Cosmetic Composition Containing Them. US Pat 3879376, 22 Apr.1975. 9p.); (HIRANO, S. Some phthaloyl derivativesof 2-amino-2-deoxy-D-glucopyranose. Carbohydrate Research, v. 16, p.229-231.1971)].

EXAMPLE # 6:

Obtaining the molecule? V-2-carboxybenzamido-O- (p-methoxy-frans-cinnamoyl) -chitosan.

This methodology was adapted from the work of WU et al. (2005), KURITA et al. (2001) and KURITA et al. (2002), BAUMANN et al. (2001), BRUICE (2001) and SOLOMONS and FRYHLE (2001).

In this case, it is necessary to incorporate groups in the polymeric chain by acid chloride esterification reaction, protecting the primary aminogroups by forming a salt with methyl sulfonic acid (MeS03H) and followed by an amidation reaction in / V Α-dimethylacetamide (DMAc). According to the work of WU and collaborators (2005). In this case: esterification reaction using p-methoxy-trans-cinnamic acid chloride (p-methoxy-trans-cinnamoyl chloride) and subsequent amidation reaction with phthalic anhydride, or esterification reaction with phthaloyl chloride and subsequent amidation reaction with p-methoxy-trans-cinnamic anhydride.

In a glass flask under magnetic stirring was placed 1.0 g (6 mmol based on the monomeric residue) of 60% GD chitosan as well as with 62% GD dissolved in 10 mL of methyl sulfonic acid, the mixture was stirred at room temperature. 20 ° C until the polymer was completely dissolved.

Then, the p-methoxy cinnamoyl chloride solution (3 equivalents per chitosan amino group was gradually added at low temperature.) The mixture was stirred for a further 30 min so that the cinnamoyl chloride was completely dissolved, and the reaction proceeded for three hours. at room temperature and overnight at -27 DEG C. The precipitate of the product was washed with water and filtered and further washed with distilled water and 200 ml of 1.4% ammonium hydroxide. The product was reacted several times with water, methanol and ether and the product was dried in 20 ml of 5.0% acetic acid. After the 3.0 hours of stirring, the material was allowed to stand for 12 hours and then the pH of the solution was raised to ~ 7.0. with a few drops of 50% NaOH, which was filtered, dried at room temperature in the desiccator to constant weight

Another method: a method that employs the Amide Synthesis Reaction from Esters (Ammonolysis) indicated in the literature of BRUICE (2001) and deSOLOMONS and FRYHLE (2001). It is a transesterification in neutral compH medium. In this case, the 2-carboxybenzamido-chitosan molecule reacts with methyl p-methoxy-trans-cinnamate under neutral pH conditions and distillation of the alcohol formed is used to accelerate the reaction. This is a very slow transesterification reaction.

In the method described by Kurita et al. (2001) and Kurita ecolaboradores (2002), regioselectivity was applied to protect the amino groups of chitosan with italic groups. For this, they protect the amino group chitosan with italic anhydride. The reaction proceeds in N / A / dimethylformamide, resulting in O-phthaloylation and N-phthaloylation. The extent of O-phthaloylation was dependent on the reaction time and temperature. O-phthalic groups may be removed completely under appropriate reaction conditions with triphenylmethylation. They also selectively removed the O-phthalic groups by methoxide transesterification to result in β-phthaloyl chitosan (2-phthalimido-chitosan).

In the work of BAUMANN et al (2001), a strategy for shaping the regioselectivity of O-sulfo, V-sulfo, A / -acetyl and A / -carboxymethyl groups in chitosan derivatives was studied. In one case, they used α-phthaloyl chitosan or (2-phthalimido-chitosan) as an intermediate group to give a high degree of desulfonation. To this end, they synthesized 2-Î ± -phthaloyl chitosan or (2-phthalimido-chitosan) to protect the primary amino group (NH2). They performed the synthesis 3,6-Di-O-sulfonation and, finally, the removal of the phthalic group by hydrated hydrazine, with minimal interference on the C-6. [(WU, Y .; SEO, T .; MAEDA, S. ; SASAKI, T .; IRIE, S.; SAKURAI, K. Circular dichroism induced by helical conformations of acylatedchitosan derivatives bearing chromophores. Journal of Polymer Science, Part B: Polymer Physics, v. 43, no. 11, p. (1364, 2005) (KURITA, K.; Controlledfunctionalization of the polysaccharide chitin. Progress in Polymer Science, v.26, p.1921-1971, 2001); (KURITA, K .; IKEDA, H .; YOSHIDA, Y .; SHIMOJOH, M.; HARATA, M. Chemoselective Protection of the Amino Groups of Chitosan by Controlled Phthaloylation: Facile Preparation of a Useful Precursor for Chemical Modifications. , No. 1, pp. 1-4, 2002) (BAUMANN, H.; FAUST, V. Concepts for improved regioselective placement of O-sulfo, A / -sulfo, A / -acetyl, andA / -carboxymethyl groups in chitosan derivatives (Carbohydrate Research, Vol. 331, p.43-57, 2001); (BRUICE, PY Organic Chemistry. 4th ed. Sao Paulo: PearsonPrentice Hall, 2006, 704p); (SOLOMONS, G .; FRYHLE, C. Organic Chemistry. 7.Rio de Janeiro: LTC Editora, 2001. v.1 , p.505-511; v.2, p.353-358)].

Analytical test for identification and structural determination of dequitosan derivatives

Infrared Analysis

Infrared (IR) spectroscopy: Bomem MB 100 apparatus, KBr pellets, 4cm "1 resolution, 21 scans / mim, wavelength frequency (400 - 4000cm" 1) and transmittance (%).

Analyzes of the starting polymer 62% deacetylated chitosan (GD) as well as the chitosan derivatives: A / succinyl chitosan 62% (GD), V-phthaloyl chitosan 62% (GD), 2- carboxybenzamido chitosan 62% (GD) and N- (p-methoxy-frans cinnamoyl) chitosan 62% (GD).

Samples of chitosan and its synthesized derivatives, before being subjected to the IV assay, were subjected to dialysis and lyophilization.

Figure 1 shows the Infrared spectrum of the freeze-dried 62% GD chitosan.

The infrared spectrum of the "freeze-dried" 62% (GD) chitosan molecule showed the following bands: stretch at 3619 cm -1 (OH); stretch at 2928 cm ~ 1 (C-H) asymmetry of aliphatics; 1634cm -1 stretch of (C = 0) amide I; 1558cm -1 strain of (N-H) amine primary; symmetrical deformation at 1405cm'1 of CH3; 1385cm-1 deformation (C = 0-NH) and amide group CH2; axial deformation 1077cm-1 of (CN); angular deformation 1027cm-1 of (COC); 600 -700cm-1 angular deformation outside of the plane (NH).

The molecular structure of 2-carboxybenzamido-chitosan is as follows:

<formula> formula see original document page 45 </formula>

Figure 2 shows the Infrared spectrum of α / β-succinyl chitosan62% (GD).

The infrared spectrum of the dialyzed and lyophilized 62% GD succinyl-chitosan molecule had the following bands: stretch at 3430 cm -1 (OH); stretch at 2926 cm -1 of (CH) asymmetry; stretch at 1725 cm -1 of (C = 0) carboxylic acid; 1655 cm -1 deformation (N-H) of amide; increase in creep intensity by 1560cm "1 of (N-H) primary amine; weak formation intensity increase by 1406cm" 1 doCH3; 1383cm-1 strain (C = 0-NH) and the CH2 group; angular strain at 1029cm-1 (C-O-C).

The molecular structure of / V-succinyl chitosan is shown below:

<formula> formula see original document page 45 </formula> Figure 3 shows the 2-carboxybenzamido-chitosan (GD) Infrared spectrum.

The infrared spectrum of the "dialyzed and lyophilized" 2-carboxybenzamido-chitosan62% GD molecule had the following bands: stretch at 3423cm-1de (OH); stretch at 2927cm-1 (CH) asymmetry of aromatics; stretch at 1773-1772 (C = O) carboxylic acid of italic acid; 1646cm-1 stretch of (C = 0) amide I; 1582cm-1 strain of (N-H) amine primary; symmetrical axial deformation at 1560cm "1 of (C = 0) 2" shy deformation at 1443cm "1 of CH3; symmetrical axial deformation at 1385cm" 1 of (C = 0) 2 "

The molecular structure of 2-phthalimido chitosan or Î ± -phthaloyl chitosan is as follows:

<formula> formula see original document page 46 </formula>

Figure 4 shows the Infrared spectrum of Δ-phthaloyl chitosan62% (GD).

The infrared spectrum of the "dialyzed and lyophilized" A-phthaloyl chitosan or 2-phthalimido-chitosan molecule showed the following bands: 3448cm-1de (OH) Stretch; 2926cm-1 Stretch of (CH) Aromatic ; 1777 stretch of (C = 0) phthalimido; 1711 cm -1 stretch (C = 0) of phthalimido; 969 - 1111 cm -1 stretch (pyranose); 720cm "1 stretch of aromatic.

The molecular structure of A / - (p-methoxy-frans-cinnamoyl) -chitosan is given below: <formula> formula see original document page 47 </formula>

Figure 5 shows the Infrared spectrum of 62% A / - (p-methoxy-frans-cinnamoyl) -chitosan (GD).

The infrared spectrum of the "dialyzed and lyophilized" A / - (β-methoxy-fr [7s-cinnamoyl) -chitosan molecule 62% GD showed the following bands: stretch at 3436cm-1de (OH); stretch at 2926cm-1 of (CH) aromatics; 1635 cm -1 stretch of (C = 0) amide I; 1563 cm -1 stretch of (N-H) primary amine; 1563 cm -1 stretch (C = C) of the aromatic ring; 1417cm -1 stretch of (C = C) aromatic ring; 1383cm -1 stretch of (C = C) aromatic ring; 1029cm'1 deformation of (C-O-C); 656 - 618cm "1 deformation of (C-H) vinyl vibration group.

1H NMR Analysis

1 H NMR analysis was performed with the 62% deacetylated chitosan (GD) samples as well as the chitosan derivatives: Î ± -succinyl chitosan62% (GD), A7-phthaloyl chitosan 62% (GD), 2- carboxybenzamido-chitosan 62% (GD) and A / - (p-methoxy-frans-cinnamoyl) -chitosan 62% (GD) which were previously subjected to dialysis and lyophilization. Have been solubilized with the appropriate solvents:

Figure 6 shows the 1H-NMR spectrum of? V-succinyl chitosan CAS78809-92-4

1H-NMR (DzO) 81.9 (s, H- (CH3), J 0.03 Hz), 2.6; 3.3-3.6; 4.5 (m, H- (C-1-6), J 2.75 Hz), 2.4 (s, H - (-COCH2 CH2 COO), J 1.3 Hz).

Figure 7 shows the 1 H-NMR spectrum of 2-carboxybenzamido chitosan or -2r (2-carboxybenzamido) -2? Jeoxy-g-D-glycopyranose. CAS 31505-42-7.

1H-NMR (D20) δ 2.0 (s, H-8), 3.2 - 3.3 (m, H-2 '), 3.7 - 4.1 (m, H-2, H-3) H-4, H-5, H-6), 4.7 - 5.2 (d, H-1), 7.6 - 8.2 (m, H- (Ar)). 1 H NMR spectrum of β-phthaloyl chitosan or 2-phthalimido chitosan CAS 135364-79-3.

1H-NMR (DMSO-c / 6) 81.29 (s, 6H- (methylene)), J 1.04 Hz), 1.34 (t, 6H- (methylene), J 1.04 Hz), 2, 26 (s, 2H- (carbonyl adjunct methylene)), J 0.35 Hz), 4.01 (m, 2H- (oxygen adjunct methylene)), J 1.25Hz), 1.34 (d, N - (Ar)), J 1.04Hz), 2.50 (d, N- (Ar)), J 5.03Hz), 2.9 - 5.2 (m, N- (Ar)), J 8.18 Hz), 7.22 - 7.95 (m, N- (Ar)), J18.42Hz).

Figure 9 shows the 1 H-NMR spectrum of N- (pn) and \ ox \ trans-cinnamoyl) -chitosan or chitosan p-methoxy-frans cinamide CAS (undefined) 1 H-NMR (D20) 52.0 ( s, H-8), 3.2 - 3.3 (m, H-2 '), 3.7 - 4.1 (m, H-2, H-3, H-4, H-5, H -6), 4.7 - 5.2 (d, H-1), 3.7 (s, -OCH 3), 6.05-6.15 (d, a-CH), 6.73-6, 80 (d, H- (Ar)), 7.30-7.5 (d, & -CH).

Analysis of Determination of the Maximum UV Absorption of Molecules by UV Spectrophotometric Scanning and Determination of Substance Molar Absorption (£ max) -

The determination of the maximum A in the UV absorbance spectrum, range from 400nm to 200nm for verification of the ultraviolet radiation absorption profile, was performed on the UV-1203, UV-VIS spectrophotometer SHIMADZUCORPORATION equipment. Samples of 62% deacetylated chitosan (GD) as well as chitosan derivatives: A / succinyl chitosan 62% (GD), A / phthaloyl chitosan62% (GD), 2-carboxybenzamido-chitosan 62% ( GD) and Î ± - (β-methoxy-frans-cinnamoyl) -chitosan 62% (GD) subjected to the spectrophotometric assay were dialyzed eliophilized a priori.

Table 2 below shows the values obtained from the application of the formula Molar absorptivity (emax):

<table> table see original document page 48 </column> </row> <table> <table> table see original document page 49 </column> </row> <table>

TABLE 2

Figure 10 shows the determination of A max in the UV absorbance spectrum in the range 200nm to 400nm of chitosan molecule 60 and 62% GD (A max = 278.0 and 241.0nm; acid medium).

Figure 11 shows the determination of A max in the UV absorbance spectrum in the 200nm to 400nm range of 2-carboxybenzamido-chitosan 60% GD molecules (A max = 276.5 nm and 239.5 nm; acidic medium) and 2-carboxybenzamido -chitosan 62% GD (λ max = 275.5 nm and 241.5 nm; acid medium).

Figure 12 shows the determination of A max in the UV absorbance spectrum in the 200nm to 400nm range of the 2-phthalimido-chitosan60% GD molecule (A max = 294.5 nm; solvent: DMSO).

Figure 13 shows the determination of the A max in the UV absorbance spectrum in the range 200nm to 400nm of the molecule V- (p-methoxy-frans-cinnamoyl) -chitosan 62% GD (A max = 306.5 nm; acid medium ).

Claims (27)

1. A process for obtaining chitosan derivatives comprising the reaction by A / acylation or A / alkylation of chitosan, with deacetylation ranging from 10% to 90%, with anhydrides ranging from 1: 1 to 1: 4. w / w in the presence of organic solvent prototype or aprotype in one or more steps; After the reaction of the tositosan and / or its derivatives with the anhydrides, the process also presents, for the derivatives synthesized in a prototype medium, the pH adjustment step obtained from the solution between 5.0 and 8.0. Process for obtaining chitosan derivatives according to claim 1, characterized in that the anhydride is carboxylic acid anhydride from 2 carbon atoms to 18 carbon atoms. Process for obtaining chitosan derivatives according to claim 2, characterized in that the anhydride may be chosen from anhydridosacetic, propionic, butyric, pentanoic, hexanoic, octanic, decanoic, lauric, palmitic, benzoic, succinic, phthalic, oleic, cinnamic, p-methoxy-cinnamic, caffeic, benzophenic (diphenyl ketone), salicylic, p-aminobenzoic and their synthetic derivatives, phenylpropenoic, o-hydroxybenzoic, anthranylate, avobenzonic, octocrylene, triazole, gallic acid and its derivatives, aciduronic acid, 2-acid phenylglutaric derivatives thereof, synthetic derivatives of benzylidene camphor, or mixtures thereof or derivatives thereof. Process for obtaining chitosan derivatives according to claim 1 or 3, characterized in that the anhydride is preferably succinic, phthalic, p-methoxy-frans cinnamic and / or mixtures thereof. Process for obtaining chitosan derivatives according to claim 1, characterized in that the degree of deacetylation of chitosan is preferably 60% and 62%. Process for obtaining chitosan derivatives according to claims 1 and 3, characterized in that the chitosan: succinic anhydride ratio is preferably 1: 1.5. Process for obtaining chitosan derivatives according to claims 1 and 3, characterized in that the chitosan: phthalic anhydride ratio is preferably 1: 2.7 or 1: 1.1. Process for obtaining chitosan derivatives according to claims 1 and 3, characterized in that the chitosan: p-methoxkrans-cinnamic anhydride ratio is preferably 1: 1.92. Process for obtaining chitosan derivatives according to claim 1, characterized in that it comprises the following steps: (i) dissolving chitosan in an appropriate medium, (ii) reacting chitosan with one or more anhydrides in the presence of prototype or aprotype organic solvent; (iii) stirring and resting the solution obtained in step (ii), (iv) raising the pH of the solution to a range of 5.0 to 8.0 for derivatives synthesized in a prototype medium, (v) filtering the precipitate obtained in (iv) resuspension in water of the precipitate obtained in a prototype medium at (v) and adjusting the solution to the desired pH; or drying the precipitate obtained in step (v). Process for obtaining chitosan derivatives according to claim 9, characterized in that step (iv) occurs by the addition of sodium carbonate, sodium hydroxide or mixtures thereof; preferably sodium carbonate and / or sodium hydroxide. Process for obtaining chitosan derivatives according to claim 9, characterized in that the chitosan derivatives obtained, synthesized in a prototype medium, are in the form of a slightly acidic, basic, neutral or solid solution. Process for obtaining chitosan derivatives according to claims 1 or 9, characterized in that, optionally, chitosan molecules are cleaved with grouping compounds that modify the solubility of the molecule. Process for obtaining chitosan derivatives according to claim 12, characterized in that the grouping which makes the molecule more water soluble can be chosen from: hydroxyl, succinic group or mixtures thereof; preferably succinic. Process for obtaining chitosan derivatives according to claim 12, characterized in that the grouping which makes the molecule more fat soluble can be chosen from: italics, group of saturated, unsaturated, animal or vegetable acid acids which have C4 - C18, preferably lauric or oleic acid. Process for obtaining chitosan derivatives according to claim 1, characterized in that the derivatives can be obtained by the process of desynthesis of Î ± -acyl fatty acids and Î ± -alkyl fatty acids, crosslinking of these polymers or by enzymatic reaction. 16. Chitosan derivatives characterized in that they obtain the second claims 1 to 15. Chitosan derivatives according to claim 16, characterized in that the fat may be 2-carboxybenzamido-chitosan, A / - (p-methoxy-frans-cinnamoyl) -chitosan, A / -phthaloyl-chitosan, A / -succinyl-A / - (p-methoxy-trans-cinnamoyl) -chitosan, N-2-carboxybenzamido-A / - (p-methoxy-frans-cinnamoyl) -chitosan, N-2-carboxybenzamido-O- (p-methoxy-trans) (cinnamoyl) chitosan and / V-succinyl chitosan. Chitosan derivatives according to claim 16, characterized in that the factor may be Î ± -succinyl chitosan. 19. Photoprotective chitosan derivatives according to claims 16 and 17, characterized in that they may be p-methoxy-frans-cinnamoyl-chitosan, 2-carboxybenzamido-chitosan, A / -phthaloyl-chitosan, N-succinyl-A / - (p-methoxy-trans-cinnamoyl) -chitosan, N-2-carboxybenzamido- / V- (p-methoxy-frans cinnamoyl) -chitosan and N-2-carboxybenzamido-0- (p-methoxy-fransam) cinnamoyl) chitosan. Pharmaceutical composition comprising one or more compounds obtained according to claims 1 to 15 in suitable pharmaceutically acceptable carriers and additives known to the man of the art. Pharmaceutical composition according to Claim 20, characterized in that it has a suitable carrier for topical use, either hydrophilic, quantolipophilic, or amphoteric. Pharmaceutical composition according to Claim 20, characterized in that it can be presented by formulating liquid soaps and / or stones, lotions, creams, moisturizers, humectants and sunscreens. Pharmaceutical composition according to Claim 20, characterized in that it is intended for hair and / or skin treatment. Cosmetic composition, characterized in that it comprises one or more compounds obtained according to claims 1 to 15, in an acceptable and appropriate vehicle, and additives known to the person skilled in the art. Cosmetic composition according to Claim 24, characterized in that it may contain, in addition to an appropriate carrier, aqueous solvents, lipophilic solvents, thickening agents, polymers, surfactants, solid oils, moisturizing agents, humectants, preservatives, pH modifiers, colorants, flavorants, antioxidants. and vitamins. Cosmetic composition according to claim 24, characterized in that it is intended for hair and / or skin treatment. Use of chitosan derivatives characterized by the use of compounds obtained according to claims 1 to 15 in pharmaceutical, cosmetic, veterinary and / or biomaterial applications and may have photoprotective properties.