WO2024201238A1 - Compositions filmogènes avec du chitosane et du chitosane carboxyméthylé - Google Patents

Compositions filmogènes avec du chitosane et du chitosane carboxyméthylé Download PDF

Info

Publication number
WO2024201238A1
WO2024201238A1 PCT/IB2024/052763 IB2024052763W WO2024201238A1 WO 2024201238 A1 WO2024201238 A1 WO 2024201238A1 IB 2024052763 W IB2024052763 W IB 2024052763W WO 2024201238 A1 WO2024201238 A1 WO 2024201238A1
Authority
WO
WIPO (PCT)
Prior art keywords
chitosan
acid
soluble
film
melanin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IB2024/052763
Other languages
English (en)
Inventor
Edmund Franklen ANDERSON
Eden STEVEN
Fransiska NA
Kiman KAREL
Kresentia Adela PUTRITAMA
Clare EVANGELINE
Yovita Yunita ANGKAWIJAYA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pt Hermetia Bio Sejahtera
Original Assignee
Pt Hermetia Bio Sejahtera
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pt Hermetia Bio Sejahtera filed Critical Pt Hermetia Bio Sejahtera
Publication of WO2024201238A1 publication Critical patent/WO2024201238A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/736—Chitin; Chitosan; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/006—Antidandruff preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/59—Mixtures
    • A61K2800/592—Mixtures of compounds complementing their respective functions

Definitions

  • the present invention relates to film-forming compositions with chitosan as a film-forming compound.
  • Such compositions can be used topically, e.g., on skin or hair, for both cosmetic and therapeutic purposes.
  • Chitosan is a natural polymer with random distribution of p-(l,4)-linked-D- glucosamine and N-acetyl-D-glucosamine, and can be obtained by deacetylation of chitin, for example by treating chitin in a strong alkali solution. Chitin can be obtained from crustaceans or insects. Chitin is insoluble in water and weak acid solution, whereas the chitosan is soluble in weak acid solutions such as lactic acid and acetic acid solutions. Chitosan can form gels and films which are desirable for compositions for topical use where chitosan can be used as the structural matrix of the composition and the film formed by such compositions.
  • Chitosan has other properties which are desirable in topical applications, such as being biologically active having for example anti-microbial properties due to its polycationic structure. Chitosan also acts as a humectant and moisturizing agent and is reported to have UV-absorption capability. Chitosan can also be obtained from insects and is biodegradable, which is an advantage for the overall sustainability of products using chitosan.
  • compositions including chitosan are known in the art, for example WO2016164903A1 which discloses an aqueous gel of chitosan for use in surgery where the gel is to be applied to control bleeding and has a viscosity suitable for film adhesion and effective application.
  • WO2014126370A1 discloses a pharmaceutical composition for wound healing where chitosan is used as a film forming substance of the composition which then forms a film upon application and continuously deliver active pharmaceutical ingredients to the wound area.
  • EP0879592A2 describes a sunscreen composition where chitosan is used as the stabilizing agent.
  • chitosan is also biologically active, being for example anti-microbial.
  • the bioactivity of chitosan in topical applications is however limited by its poor skin-absorption and poor solubility at skin conditions.
  • compositions having chitosan as a film-forming component will form a film on the area to which it is applied, thereby isolating the area from the surroundings.
  • the film may serve to create an environment promoting for example wound healing.
  • the film adhering to the area of application provides a continual contact between the ingredients of the film and the area of application and thus improves delivery of effective ingredients of the composition to the area of application. To achieve these effects the films' ability to adhere and ensure continual contact once applied is important.
  • the films are subjected to strains and frictions, wearing on the film which may crack or disengage from the area of application.
  • the film formed by chitosan will typically be suitably strong to handle the strains in topical use, but it may be too strong, which can be unconformable for the user who may experience the film as being restrictive or can lead to the film disengaging from the skin. A user who experiences the film as being unconformable is less likely to continue use of the composition.
  • UV light can cause short-term problems such as inflammation (sunburn) and longterm problems such as scar tissue discoloration.
  • short-term problems such as inflammation (sunburn)
  • longterm problems such as scar tissue discoloration.
  • an object of the invention is to provide a water and chitosan- based film-forming composition having improved bioactivity.
  • a further object is to provide a water and chitosan-based film-forming composition with an improved film, especially one which is more comfortable for the user.
  • a further object of the present invention is to provide water and chitosan-based film-forming compositions for topical use combining the benefits of chitosan with increased radiation protection.
  • a still further object of the invention is to provide such composition using naturally derived ingredients.
  • Yet another object of the invention is to provide such compositions using ingredients which improve the sustainability of the composition.
  • a film-forming composition for topical use comprising: chitosan and/or a salt thereof, acid soluble carboxymethylated chitosan, abbreviated CMC, and/or salt thereof, which acid soluble CMC is soluble at pH 5 or lower, and an aqueous acid solution.
  • CMC carboxymethylated chitosan
  • chitosan has certain advantages over film-forming compositions using chitosan alone, since CMC is more effective in terms of bioactivity as it is more effectively delivered to the area on which the composition is applied compared to chitosan.
  • CMC is soluble at skin conditions and is thus more readily delivered to for example bacteria, promoting the anti-bacterial effect.
  • the inventors found that CMC showed improved absorption on human skin compared to chitosan. Additionally, CMC was found to provide advantageous mechanical properties to the film.
  • CMC is however both a more costly material compared to chitosan and attempts to add CMC to chitosan compositions revealed that not all CMC were compatible with the acid solutions used to dissolve chitosan. This was tested by mixing CMC and chitosan in a film-forming composition where it was found immiscible even at small ratios of CMC to chitosan.
  • the inventors have found that by using an acid soluble CMC, a homogenous composition of chitosan, acid soluble CMC, water, and acid can be achieved. Further, by including the acid soluble CMC, the bioactivity, e.g., antimicrobial effect, is improved beyond that of a composition using chitosan alone, absorption of the composition is improved, and the resulting film is less rigid, providing at least in part the advantages of the CMC to the composition.
  • carboxymethylated chitosan is a chitosan having carboxymethyl groups (-CH2COOH) substituted on the hydroxyl and/or amino groups of the chitosan molecule.
  • CMC can have varying degrees of substitution.
  • acid soluble CMC refers to a CMC which is soluble at pH 5 or lower, e.g. in a pH range of 2 to 5. Soluble in context of acid soluble CMC is to be understood as soluble at least up to a 5 w/w%, e.g.
  • the aqueous solution may be a lactic acid solution.
  • the pH level of the lactic acid solution can be adjusted by adding NaOH.
  • the inventors have surprisingly found that the acid solubility of CMC can be varied.
  • the inventors have found that the degree of substitution on the amino groups may be a first factor that changes the acid solubility of CMC.
  • CMC with more than 50% substitution of the amino groups by carboxymethyl groups is referred to as fully carboxymethylated chitosan and fully carboxymethylated chitosan is commonly not soluble in acidic solutions of pH 5 or lower, as shown in Example VIII below.
  • CMC comprising carboxymethyl substitutions in the range of 20% - 50% of the amino groups is acid soluble at pH 5 or lower.
  • the acid soluble carboxymethylated chitosan may be chitosan, where 20% to 50%, e.g. 25% to 35%, of the amino groups carry carboxymethyl groups.
  • CMC is commonly known to comprise sodium residues from the preparation of chitosan to CMC.
  • the acid soluble CMC prepared with the disclosed method has shown to be substantially free from Na-residues.
  • the degree of substitution i.e. the first factor and the absence of Na-residues i.e. second factor may be observed using FT-IR spectroscopy using the ISO STANDARD 19702:2015.
  • carboxymethyl groups (-CH2COOH) on the N-site may be observed by FT-IR spectroscopy at a wavenumber of substantially 1580 cm' 1 .
  • the acid soluble CMC according to the disclosure may have a reduced transmittance in the range of 3% to 8%, preferably 4% to 7%, even more preferred substantially 5% at a wavenumber of substantially 1580 cm 1 compared to the chitosan from which it was derived and measured by FT-IR Spectroscopy using the ISO STANDARD 19702:2015, wherein the chitosan and the acid soluble CMC are normalized to their common peak at substantially 2865 cm 4 .
  • the acid soluble CMC according to the disclosure may have a reduced transmittance in the range of 1% to 3% at a wavenumber of substantially 1743 cm 1 compared to the chitosan from which it was derived and measured by FT-IR Spectroscopy using the ISO STANDARD 19702:2015, wherein the chitosan and the acid soluble CMC are normalized to their common peak at substantially 2865 cm ⁇ 1 .
  • An exemplary FTIR spectrum is shown in Fig. 12.
  • the acid soluble CMC have been found to form a homogenous composition with the chitosan and aqueous acid solution, allowing the incorporation of acid soluble CMC in the composition.
  • the acid soluble CMC may be obtained by incubation of chitosan in an isopropanol, followed by incubation with an alkali hydroxide followed by addition of haloacetic acid, as will be described in greater detail below.
  • the aqueous acid solution comprises an acid.
  • the acid may constitute 0.5 to 5 % with respect to the total weight of the composition.
  • the acid is selected from the group of lactic acid, acetic acid, citric acid, and gluconic acid or combinations thereof, preferably the acid is lactic acid.
  • the acid is needed both to dissolve the chitosan and to reach the desired pH for topical applications. Lactic acid is preferred as it is also beneficial for skin applications being an alpha hydroxy acid.
  • the acid soluble CMC may be obtained by incubation of chitosan in an isopropanol, followed by incubation with an alkali hydroxide followed by addition of monochloroacetic acid.
  • film -forming as used herein is understood to mean a composition which following application leaves a film as the water of the composition evaporates and/or is absorbed.
  • the aqueous acid solution forms the major component of the composition, and the major component of the aqueous acid solution is water.
  • water may constitute at least 50 w/w% of the composition, even at least 75 w/w%.
  • Topical use is to be understood as uses on the surface of the body such as the skin and/or hair.
  • the composition may be applied to the skin as an ointment or mask such as a gel mask. It may alternatively and/or additionally be applied to the hair in form of a gel, a tonic and/or a pomade.
  • the film-forming composition may further comprise a preserving agent, such as ethanol, sodium benzoate, potassium sorbate or mixtures thereof.
  • a preserving agent such as ethanol, sodium benzoate, potassium sorbate or mixtures thereof.
  • Ethanol has the benefit of acting as a preserving agent and improves the shelf life of the composition.
  • Ethanol also has the benefit of acting as an astringent to help clean the skin.
  • Ethanol may constitute 1 to 10 w/w%, 2 to 5 w/w%, 2.5 to 3.5 w/w% of the composition.
  • the film-forming composition may further comprise a chelating agent, such as Ethylenediaminetetraacetic acid, abbreviated EDTA, or gluconic acid.
  • EDTA has the benefit of acting as a preservative against bacteria, yeast, and mould.
  • EDTA also has the benefit of acting as a chelating agent to bind trace contaminants.
  • EDTA may constitute 0.05 to 0.3 w/w%, e.g. 0.075 to 0.25 w/w%, or 0.05 to 0.2 w/w%, preferably substantially 0.2 w/w% of the composition or substantially 0.1 w/w% of the composition.
  • the EDTA is preferably disodium EDTA.
  • the combination of chitosan and acid soluble CMC constitutes 0.2 to 4 w/w% of the composition, preferably 1.5 to 3 w/w%, more preferably 1.75 to 2.75 w/w%.
  • Chitosan and acid soluble CMC in these ranges has shown to provide a film with the preferred properties.
  • chitosan and acid soluble CMC constitute between 1.5 to 3 w/w % of the composition due to the hardness of the film in embodiments with >3 w/w% of chitosan and acid soluble CMC.
  • the chitosan and acid soluble CMC constitute substantially 2.5 w/w% of the composition.
  • the acid soluble CMC constitutes 0.01 to 2 w/w% of the composition, preferably 0.02 to 1.5 w/w%, more preferably 0.02 to 1 w/w%.
  • the chitosan constitutes 0.4 to 3.5 w/w %, preferably 1.5 to 3 w/w %, more preferably 1.7 to 2.7 w/w %.
  • acid soluble CMC constitutes 0.01 to 2 w/w% and chitosan constitutes 0.4 to 3.5 w/w%, preferably 0.02 to 1.5 w/w% and 1.5 to 3 w/w% respectively, more preferably 0.02 to 1 w/w% and 1.7 to 2.7 w/w%, respectively.
  • the combination of acid soluble CMC and chitosan has shown to provide films with the preferred properties. Embodiments with a larger amount of chitosan compared to acid soluble CMC has the benefit of being more cost-effective while still providing the effects of the acid soluble CMC such as reduced strength of the film and improved absorption and thus bioactivity.
  • Some embodiments have a larger amount of acid soluble CMC compared to chitosan.
  • some embodiments of the filmforming composition comprise 0.9 w/w% acid soluble CMC and 0.1 w/w % chitosan.
  • acid soluble CMC and chitosan constitute substantially equal parts of the film-forming composition such as the embodiments constituting 1 w/w % acid soluble CMC and 1 w/w % chitosan.
  • acid soluble CMC is present in a smaller amount than chitosan.
  • the composition comprises a thickener and a co-sol- vent.
  • the co-solvent is selected from glycerine, propylene glycol, sorbitol or combinations thereof.
  • the thickener provides a desired viscosity of compositions. Some thickeners may also provide benefits such as reducing adhesion of the film to the skin. A film adhering too strongly is not desirable.
  • the co-solvent facilitates incorporation of the thickener into the composition to provide a homogenous composition. Thickeners can be difficult to mix into the composition without co-solvent. The co-solvent also acts as a plasticizer improving flexibility of the film.
  • the thickener is a natural gum.
  • the natural gum may be a natural gum from the group comprising Xanthan gum, guar gum, and konjac gum.
  • the thickener may constitute 0.05 to 4 w/w% of the composition.
  • the amount of thickener is adjusted according to the viscosity desired for a specific application. Ointments to be applied to the skin are generally more viscous than tonics to be applied to the hair/scalp, while pomades or gel-masks are typically even more viscous than ointments.
  • the thickener preferably constitutes 0.3 to 3 w/w%, more preferably 0.4 to 1.6 w/w% of the composition.
  • the thickener is a guar gum.
  • guar gum When using guar gum as the thickener it is preferably present in the above amount in the composition, e.g. guar gum may constitute 0.5 to 1.25 w/w% of the composition.
  • Guar gum has the benefit of homogenizing well with the solutions of acid soluble CMC and chitosan. Guar gum also has the benefit of reducing adhesion of the film to the skin and being a naturally derived ingredient.
  • the thickener may additionally or alternatively be a cellulose ether, e.g. hydroxypropyl methyl cellulose, HPMC.
  • a cellulose ether e.g. hydroxypropyl methyl cellulose, HPMC.
  • the thickener When the thickener is HPMC, the thickener may constitute 0.05 to 0.5 w/w%, e.g. 0.1 to 0.15 w/w% of the composition.
  • the co-solvent may constitute 0.5 to 10 w/w% of the composition, preferably 0.7 to 5 w/w%, more preferably 1 to 4 w/w%.
  • the co-solvent is glycerine.
  • glycerine When using glycerine as the co-solvent it is preferably present in the above amount in the composition. Glycerine provides good integration of the guar gum in the composition and increase flexibility of the film.
  • the acid soluble CMC, chitosan, thickener, and cosolvent constitute 0.01 to 2 w/w%, 0.4 to 3.5 w/w%, 0.25 to 4 w/w%, and 0.5 to 10 w/w% of the composition respectively.
  • the acid soluble CMC, chitosan, thickener, and co-solvent constitute 0.02 to 1.5 w/w%, 1.5 to 3 w/w%, 0.3 to 3 w/w%, and 0.7 to 5 w/w% of the composition respectively.
  • the acid soluble CMC, chitosan, thickener, and co-solvent constitute 0.02 to 1 w/w%, 1.7 to 2.7 w/w%, 0.4 to 1.6 w/w%, and 1 to 4 w/w% of the composition respectively.
  • These embodiments may further comprise soluble melanin as will be described in greater detail below.
  • the soluble melanin is soluble in water.
  • the composition further comprises soluble melanin.
  • the soluble melanin may be obtained by a method comprising:
  • the hydroxide is ammonium hydroxide
  • the peroxide is hydrogen peroxide
  • the soluble melanin may be prepared using the following steps:
  • the soluble melanin is prepared using the following additional steps after drying the melanin mixture at 60 °C overnight:
  • Melanin is a naturally occurring dark pigment which, among other beneficial properties, absorbs UV light. By having melanin in the composition, the radiation protection offered by the composition is increased. However, melanin is poorly soluble in the acidic solution needed to dissolve chitosan. When adding soluble melanin powder or aqueous solutions of soluble melanin to the aqueous solutions of chitosan, acid soluble CMC or a mixture of chitosan and acid soluble CMC, the inventors found that the melanin could not be dissolved resulting in a non-homogenous mixture with visible melanin particulates, which is not suitable for topical use.
  • soluble melanin can be added to compositions further comprising the thickener and the co-solvent and form a homogenous mixture.
  • soluble melanin is used to denote melanin which is soluble in water at least up to 100 mg/mL.
  • Embodiments containing soluble melanin may be produced by a further aspect of the invention, providing a method for producing a composition fortopical use, the method comprising the steps of:
  • aqueous solution of soluble melanin has a melanin concentration of 50 mg/mL or less, e.g. 45 mg/mL, 40 mg/mL, 35 mg/mL, 30 mg/mL, 25 mg/mL, 20 mg/mL, 15 mg/mL, 10 mg/mL, 10 mg/mL, 5 mg/mL, 4 mg/mL, or 1 mg/mL.
  • the inventors have found than when the soluble melanin is added as a dilute aqueous solution to a mixture comprising thickener and co-solvent, the composition is homogenous without particulates of melanin.
  • the thickener is preferably guar gum or HPMC.
  • the co-solvent is selected from glycerine, propylene glycol, sorbitol or combinations thereof, it is preferably glycerine.
  • the soluble melanin solution is preferably added to a mixture comprising chitosan, acid soluble CMC, thickener, and co-solvent.
  • Acid soluble CMC and chitosan may be mixed by adding an acid soluble CMC solution to a chitosan solution.
  • Acid soluble CMC may be dissolved in water, such as distilled water, to provide an acid soluble CMC solution.
  • Chitosan is dissolved in an aqueous acid solution, such as a lactic acid solution, to provide a chitosan solution.
  • Acid soluble CMC and chitosan may alternatively be mixed by mixing acid soluble CMC powder with chitosan powder and afterwards adding an aqueous acid solution. This solution may be an aqueous lactic acid solution.
  • the soluble melanin is contained in an amount of less than 10000 ppm, preferably less than 1000 ppm, more preferably less than 500 ppm.
  • the composition has a pH-value in the range of 4 - 6, preferably in the range of 4.5 - 5.5, more preferably substantially 5.
  • the optimal pH value of the skin is approximately between 4.7 and 5.75, and by having a composition in substantially the same pH-range, the film-forming composition is capable of being applied to the skin without substantially changing the preferred pH of the skin.
  • the chitosan and/orthe acid soluble CMC is obtained from Hermetia illucens.
  • Hermetia illucens is also known as Black Solider Fly, abbreviated BSF, and is a source of chitin raw material which is considered especially advantageous to use as the source of chitosan and acid soluble CMC.
  • BSF can be produced efficiently, compared to other sources of chitin such as crustaceans, as it can be reared in a space efficient and controlled environment, reducing the environmental impact of production.
  • Crustacean-derived chitin may have a higher risk of residual contamination of toxins and pollutants due to their growth habitat increasingly being polluted, whereas BSF can be reared on land in a controlled environment.
  • BSF can be grown using organic waste material as the nutritional substrate which also contributes to reducing the environmental impact of production.
  • chitin from BSF is allergy-friendly compared to crustacean based chitin which may be unsuitable for user with allergy to crustaceans. Chitin is found in BSF larvae, BSF pupae and BSF imagoes and can be extracted by, for example, pressing one or more of these to separate protein and fat from the solid chitinous fraction.
  • the chitinous fraction can then be purified to chitin, which purification may include an acid treatment to remove minerals, mainly calcium carbonate, a deproteinization step using an alkaline or enzymatic treatment to remove residual protein substance.
  • the resulting chitin raw material can then be treated with a strong alkali solution, e.g. 15 M sodium hydroxide, to deacetylate the chitin yielding chitosan.
  • a strong alkali solution e.g. 15 M sodium hydroxide
  • This removal of acetyl groups from chitin structure provides the chitosan which is polycationic and as a result, chitosan has antimicrobial properties.
  • the chitosan can be further purified by dissolution in acid, e.g. acetic acid, followed precipitation by pH adjustment. As previously described, the chitosan can then be further processed into acid soluble CMC.
  • the melanin used in some embodiments may also be obtained from BSF where it is found in the exoskeleton and can be extracted by treating with strong alkali.
  • the acid soluble CMC is produced by a method comprising the steps of: i) mixing and incubating chitosan with a solvent to obtain a first mixture, the solvent being selected from isopropanol, acetone, butanol, methanol, and ethanol, preferably isopropanol; ii) mixing and incubating the first mixture obtained in step i) with an aqueous solution of NaOH and/or KOH, preferably NaOH, to obtain a second mixture; iii) mixing and incubating the second mixture obtained in step ii) with a halo- acetic acid to obtain a third mixture, the haloacetic acid being selected from monochloroacetic acid, bromoacetic acid, and iodoacetic acid, preferably monochloroacetic acid; and iv) isolating acid soluble CMC from the third mixture obtained in step iii).
  • the CMC obtained by such a method is soluble at pH 5 or lower, e.g. in a pH range of 2 to 5, and can be used in the film-forming composition according to the invention.
  • the ratio of chitosan to solvent (chitosa solvent) in step i) is in the range 0.5:10 to 2:10 by weight, e.g. 1:10 by weight or 1:8 by weight.
  • Step i) preferably comprises incubating for 10 to 30 minutes, more preferably 15 to 25 minutes.
  • the incubation temperature in step i) may be room temperature, i.e. 15 to 30 °C.
  • the aqueous solution used in step ii) has a concentration of NaOH and/or KOH in the range of 40 to 60 w/w%.
  • the ratio of chitosan to alkali hydroxide (NaOH and/or KOH) in step i) is in the range 0.75:1 to 1.25:1 by weight, preferably 1:1 by weight (chitosa alkali hydroxide).
  • Step ii) preferably comprises incubating for 30 to 60 minutes, more preferably 40 to 50 minutes.
  • the incubation temperature in step ii) may be room temperature, i.e. 15 to 30 °C.
  • the ratio of chitosan to haloacetic acid (chitosa haloacetic acid) in step iii) is 1:6 or more, such as 1:7 or 1:8.
  • Haloacetic acid is thus used in step iii) in excess of chitosan by at least a factor 6.
  • incubation in step iii) is performed at a temperature below 80 °C, such as about 60 °C.
  • Step iii) preferably comprises incubating for 2 to 4 hours, preferably 2.5 to 3.5 hours.
  • the ratios of chitosan to reagents/solvents described above are weight ratios and refer to the amount of ingredient without solvents if a solvent is present.
  • the amount of chitosan is dry chitosan powder, and the amount of alkali hydroxide does not include the water in which it is dissolved.
  • the isolation of acid soluble CMC in step iv), can be achieved by filtration and washing. Vacuum filtration is suitable and ethanol is a suitable washing agent. After the acid soluble CMC is isolated, it can be dried, for example at 40 °C.
  • the acid soluble CMC is obtained by a method comprising the steps of i) mixing chitosan with isopropanol at a ratio in the range 0.5:10 to 2:10 by weight (chitosa isopropanol), more preferably 1:10 by weight, and incubating at 15 to 30 °C for 15 to 25 minutes to obtain the first mixture; ii) mixing the first mixture obtained in step i) with a 40 to 60 w/w% aqueous NaOH solution at chitosan to NaOH ratio in the range 0.75:1 to 1.25:1 by weight, preferably 1:1 by weight, and incubating at room temperature for 40 to 50 minutes to obtain the second mixture; iii) mixing the second mixture obtained in step ii) with monochloroacetic acid, at a ratio of 1:6 or more and incubating at a temperature below 80 °C to obtain the third mixture; and iv) isolating the acid soluble CMC from the third mixture by
  • the acid soluble CMC is obtained by a method comprising the steps of i) mixing chitosan with isopropanol at a ratio in the range 0.5:10 to 2:10 by weight (chitosamisopropanol), more preferably 1:8 by weight, and incubating at 15 to 30 °C for 15 to 25 minutes, preferably substantially 20 minutes, to obtain the first mixture; ii) mixing the first mixture obtained in step i) with a NaOH solution, where the NaOH solution comprises NaOH in the range of 30 to 60 w/w%, e.g.
  • the chitosan to NaOH ratio is in the range 0.2:1 to 1.25:1 by weight, preferably 0.75:1 to 1:1 by weight, and incubating at room temperature for 30 to 50 minutes, preferably 40 minutes, to obtain the second mixture; iii) mixing the second mixture obtained in step ii) with monochloroacetic acid at a ratio of 1:6 of second mixture to monochloroacetic acid and incubating at a temperature below 80 °C to obtain the third mixture; and iv) isolating the acid soluble CMC from the third mixture by filtration.
  • the film-forming composition according to the first aspect of the invention and the embodiments described above may be used fortreatment of a skin condition.
  • step iii) an incubation temperature in the range of 30 °C and 60 °C has shown to be advantageous.
  • One potential advantage is increased acid solubility of the acid soluble CMC.
  • step iii) the second mixture and the monochloroacetic acid may be mixed at a ratio of 1:7, 1:8, 1:9, or 1:10 of second mixture to monochloroacetic acid.
  • the inventors have found that the above method to obtain acid soluble CMC uses approximately 50 mL isopropanol, 12.5 mL of Sodium Hydroxide Solution (40 w/w% in water), and 30 grams of monochloroacetic acid per 5 grams of chitosan, compared to methods for obtaining fully carboxymethylated CMC i.e. neutral-soluble CMC where approximately 115 mL isopropanol, 25.5 mL Sodium Hydroxide Solution (40 w/w% in water) and 9 grams of monochloroacetic acid per 5 gram of chitosan is used.
  • the reduced total amount of solvent used per gram chitosan for producing acid soluble CMC compared to fully carboxymethylated chitosan has the advantage of being a more efficient and more environmentally friendly procedure by using a lower total volume of solvents per gram chitosan.
  • the skin condition is selected from wounds, insect bites, a fungal infection such as Tinea, bacterial infections, dandruff, inflammatory skin conditions (dermatitis) such as Pityriasis alba or eczema, and psoriasis.
  • the film formed by the composition may serve to promote wound healing and insect bites. It may also provide relief for insect bites, reducing itchiness and i nflammation.
  • the composition may be used to treat eczema or rash.
  • chitosan and acid soluble CMC makes it particularly suitable for treatment of bacterial or fungal infections.
  • exemplary applications for fungal infections are dandruff and Tinea (athletes foot, ringworm).
  • compositions according to the invention comprises further ingredients, such as pharmaceutically active substances, antioxidants, natural surfactants, vitamins and/or flavouring agents in an amount of 0.1 to 10 w/w% of the total composition.
  • Pharmaceutically active substances include antibiotics, disinfectants, and anti-inflammatory agents.
  • Antioxidants include tocopherols, lecithin, ascorbic acid.
  • Natural surfactants include lauryl glucoside, decyl glucoside, and coco glucoside.
  • Vitamins include retinol, tocopherols, biotin, folic acid, niacinamide, and pan- thenol.
  • Fig. 1 shows three samples of a film-forming composition according to the invention described in Example IV which is seen to form clear homogenous mixtures without particulates.
  • Fig. 2 shows two mixtures of a chitosan solution and a solution of commercially available CMC, at a ratio of 1:3 (left) and at a ratio of 19:1 (right) as described in Example I. Both mixtures are seen to be cloudy due to insoluble particulates of CMC.
  • Fig. 3 shows an attempt to add soluble melanin powder to 2.5% acid soluble CMC solution as described in Example III.
  • Fig. 4A shows three samples of 2.5 w/w% chitosan solution with lOOppm melanin described in Example III. From left to right: 100 ppm melanin by addition of 2mg/mL soluble melanin, 100 ppm melanin by addition of 3mg/mL soluble melanin, 100 ppm melanin by addition of 4mg/mL soluble melanin.
  • Fig. 4B shows five samples of a composition of 1.25 w/w% chitosan and 1.25 w/w% acid soluble CMC with soluble melanin, described in Example III. From left to right: 100 ppm melanin by addition of 2mg/mL soluble melanin, 100 ppm melanin by addition of 3mg/mL soluble melanin, 100 ppm melanin by addition of 4mg/mL soluble melanin, 100 ppm melanin by addition of 5mg/mL soluble melanin, 100 ppm melanin by addition of lOmg/mL soluble melanin.
  • Fig. 4C shows five samples of a 2.5 w/w% acid soluble CMC solution with soluble melanin described in Example III . From left to right: 100 ppm melanin by addition of 2mg/mL soluble melanin, 100 ppm melanin by addition of 3mg/mL soluble melanin, 100 ppm melanin by addition of 4mg/mL soluble melanin, 100 ppm melanin by addition of 5mg/mL soluble melanin, 100 ppm melanin by addition of lOmg/mL soluble melanin.
  • Fig. 5A shows five samples of a comparative composition with melanin.
  • the composition comprises 2.5 w/w% chitosan, 0.5 w/w% guar gum, 1.25 w/w% glycerine, 0.1 w/w% disodium EDTA and 3w/w% ethanol and soluble melanin.
  • Fig. 5B shows five samples of a composition according to the invention with melanin as described in Example IV.
  • the composition comprises 2.5 w/w% acid soluble CIVIC and chitosan in a 1:2 ratio, 0.5 w/w% guar gum, 1.25 w/w% glycerine, 0.1 w/w% disodium EDTA and 3w/w% ethanol and soluble melanin.
  • Fig. 5C shows five samples of a composition according to the invention with melanin as described in Example IV.
  • the composition comprises 2.5 w/w% acid soluble CIVIC and chitosan in a 1:1 ratio, 0.5 w/w% guar gum, 1.25 w/w% glycerine, 0.1 w/w% disodium EDTA and 3w/w% ethanol and soluble melanin.
  • Fig. 5D shows five samples of a composition according to the invention with melanin as described in Example IV.
  • the composition comprises 2.5 w/w% acid soluble CIVIC and chitosan in a 2:1 ratio, 0.5 w/w% guar gum, 1.25 w/w% glycerine, 0.1 w/w% disodium EDTA and 3w/w% ethanol and soluble melanin.
  • Fig. 5E shows five samples of a comparative composition described in Example IV.
  • the composition comprises 2.5 w/w% acid soluble CMC, 0.5 w/w% guar gum, 1.25 w/w% glycerine, 0.1 w/w% disodium EDTA and 3w/w% ethanol and soluble melanin.
  • Fig. 6A shows data from stress-strain tests of films by a composition wherein the composition comprises 2.5 w/w% chitosan as described in Example VI.
  • Fig. 6B shows data from stress-strain tests of films formed by composition according to the invention, wherein the composition comprises 2 w/w% chitosan and 0.5 w/w% acid soluble CIVIC as described in Example VI.
  • Fig. 6C shows data from stress-strain tests of films formed by a composition according to the invention, wherein the composition comprises 1.5 w/w% chitosan and 1 w/w% acid soluble CIVIC as described in Example VI.
  • Fig. 6D shows data from stress-strain tests of films formed by a film-forming composition according to the invention, wherein the composition comprises 1 w/w% chitosan and 1.5 w/w% acid soluble CIVIC as described in Example VI.
  • Fig. 6E shows data from stress-strain tests of films formed by a composition according to the invention, wherein the composition comprises 0.5 w/w% chitosan and 2 w/w% acid soluble CIVIC as described in Example VI.
  • Fig. 6F shows data from stress-strain tests of films formed by comparative composition, wherein the composition comprises 2.5 w/w% acid soluble CIVIC as described in Example VI.
  • Fig. 7 shows the results of the absorption test described in Example V.
  • Fig, 8 shows the results of the absorption test described in Example V
  • Fig. 9 shows the results of the absorption test described in Example V.
  • Figs. 10 and 11 show the results of dissolving the acid-soluble CIVIC and a commercially available CIVIC at various pH levels, as described in Example VIII.
  • Fig. 12 shows FTIR spectra of chitosan, the acid soluble CIVIC according to this invention, and commercially available fully carboxymethylated chitosan.
  • chitosan acid soluble CMC and melanin was obtained from Black Soldier Fly (BSF).
  • BSF Black Soldier Fly
  • the chitosan was obtained by deacetylating chitin from BSF using a strong sodium hydroxide solution as previously described.
  • Chitosan was mixed with isopropanol at a ratio of 1:10 (by weight) and incubated at room temperature for 20 minutes.
  • the chitosan mixture was then mixed with NaOH (40 w/w% solution in water) at a ratio of 1:1 (chitosa NaOH) and incubated at room temperature for 45 minutes.
  • chitosan mixture was then mixed with monochloroacetic acid (MCA) at a ratio of 1:6 (chitosa MCA).
  • MCA monochloroacetic acid
  • an "acid soluble CMC solution” refers to a solution of acid soluble CMC in water and a “chitosan solution” refers to a solution of chitosan in aqueous lactic acid.
  • soluble melanin was prepared using the following steps:
  • Chitosan solution was mixed with insoluble CMC solution at a 1:3 ratio in which the insoluble CMC clearly precipitated.
  • concentrations of insoluble CMC specifically a 19:1 ratio of chitosan solution to insoluble CMC solution, particles of CMC were still observed as can be seen in Fig. 2.
  • the left sample shows a solution with a 1:3 ratio of chitosan to insoluble CMC.
  • the right sample shows a solution with 19:1 ratio of chitosan to insoluble CMC. In both cases chitosan and the insoluble CMC did not homogenize.
  • insoluble CMC solutions were prepared in 0.1%, 0.2%, 0.4%, 0.6%, 0.8%, 1% concentrations, respectively.
  • the lowest ratio of insoluble CMC to chitosan mixture made was 0.2 g of 0.1% insoluble CMC to 5g of chitosan solution, in which small particles of insoluble CMC was still visible, which concluded the poor miscibility of insoluble CMC solution and chitosan solution.
  • Example VIII The solubility of the "insoluble CMC" at various pH is further described in Example VIII, where it is compared to the acid soluble CMC.
  • Acid soluble CMC solution and chitosan solution were shown to be miscible at the tested ratios ranging from 1:3 chitosa acid soluble CMC to 3:1 chitosa acid soluble CMC.
  • Soluble melanin was mixed with acid soluble CMC and chitosan solutions.
  • the acid soluble CMC solution was 2.5 w/w% acid soluble CMC dissolved in distilled water
  • the chitosan solution was 2.5 w/w% chitosan dissolved in a 1% lactic acid solution.
  • Soluble melanin solutions at 2mg/mL, 3mg/mL, 4mg/mL, 5mg/mL, and lOmg/mL in water were prepared. Each melanin solution was mixed into separate solutions of 1:3 acid soluble CMC:chitosan, 1:1 acid soluble CMC:chitosan, and 3:1 acid soluble CMC:chitosan solutions, respectively, resulting in a total of 15 individual mixes each at 100 ppm soluble melanin. Soluble melanin at the starting concentration of 2mg/mL and above refused to homogenize well in CMC:CA solution (1:3), (1:1) and (3:1). When increasing the amount of acid soluble CMC, greater quantities of soluble melanin seemed to precipitate out from the chitosan solution.
  • Fig. 4B the results of the series of the five 1:1 acid soluble CMC:chi- tosan solution is shown in Fig. 4B, with 2mg/mL, 3mg/mL, 4mg/mL, 5mg/mL, lOmg/mL from left to right.
  • the chitosan and acid soluble CMC forms a homogenous mixture, but melanin precipitate.
  • the melanin precipitates are indicated by circles in the figure 4B.
  • the prepared melanin solutions were also added to the pure chitosan solution and to the pure acid soluble CMC solution, also to a target of 100 ppm melanin.
  • soluble melanin solutions In pure chitosan solution i.e., in the total absence of acid soluble CMC, soluble melanin solutions of 2 mg/mL and above showed better miscibility, as is shown in Fig. 4A, showing left to right the results of melanin being added as the 2 mg/mL, 3 mg/mL and 4 mg/mL solutions respectively. As can be seen, the chitosan solution and soluble melanin showed good miscibility with no particulates after the addition of melanin at all three concentrations.
  • melanin precipitates were formed with all the tested melanin solutions and was not miscible as is shown in Fig. 4C.
  • the melanin precipitates are indicated by circles in the figure.
  • Water-based, film-forming compositions were prepared according to the following recipe:
  • compositions were prepared with various ratios of chitosan to acid soluble CMC but consistently at a total amount of 2.5 w/w% chitosan and/or acid soluble CMC across all samples.
  • the five acid soluble CMC:Chitosan ratios were: 0:1, 1:2; 1:1, 2:1, and 1:0.
  • the ratio of chitosan to acid soluble CMC varied from pure chitosan to pure acid soluble CMC.
  • soluble melanin solutions in water were prepared at 2 mg/mL, 3 mg/mL, 4 mg/mL, 5 mg/mL, and 6 mg/mL.
  • Fig. 5A-5E where each column is separate melanin solutions increasing from left to right.
  • Fig. 5A is the pure chitosan (0:1)
  • Fig. 5B is the 1:2
  • Fig. 5C is the 1:1
  • Fig. 5D is the 2:1
  • Fig. 5E is the pure acid soluble CMC (1:0).
  • the black vertical line is located between samples using the 3 mg/mL (left) and 4 mg/mL (right).
  • the melanin was found to be miscible at all ratios of acid soluble CMC to chitosan at the addition of melanin in 2 mg/mL and 3 mg/mL. At the addition of 4mg/mL melanin solution and above, melanin was found to be not miscible, as indicated by the circles. Air bubbles, 20a - 20b, visible in some samples were caused by the mixing procedure and are not particulates.
  • the test was repeated using the 2 mg/ml melanin solution but in composition at acid soluble CMC:chitosan ratios of 1:1, 3:1 and 1:3.
  • the acid soluble CMC powder and chitosan powder were initially dissolved separately in water and 1% lactic acid solutions and then mixed with the remaining ingredients of the composition. Melanin was miscible in all three samples as show in Fig. 1 showing the acid soluble CMC:chitosan ratios 1:1, 3:1, and 1:3 from left to right.
  • the pH of the composition was in the range 5 to 5.5.
  • Fig. 1 and Fig. 5B-D show that chitosan and acid soluble CMC are miscible compared to the chitosan and insoluble CMC mixture shown in Fig. 2 which is not miscible.
  • melanin could be mixed into the composition comprising guar gum and glycerine using a soluble melanin solution at 3 mg/mL or less as shown in Fig. 1 and Fig. 5A-E. This in comparison to Fig. 4B-C where melanin was not miscible in the solutions of acid soluble CMC combined with chitosan and pure acid soluble CMC.
  • Sample 000 2.5 w/w% chitosan, 0.5 w/w% guar gum, 1.25 w/w% glycerine, 0.1% disodium EDTA, 3 w/w% ethanol in a 1% lactic acid solution.
  • Sample 010 1 w/w% acid soluble CMC, 1.5 w/w% chitosan, 0.5 w/w% guar gum, 1.25 w/w% glycerine, 0.1% disodium EDTA, 3 w/w% ethanol in a 1% lactic acid solution.
  • Sample 020 2 w/w% acid soluble CMC, 0.5 w/w% chitosan, 0.5 w/w% guar gum, 1.25 w/w% glycerine, 0.1% disodium EDTA, 3 w/w% ethanol in a 1% lactic acid solution.
  • the inventors conducted an absorption simulation on a dried Kanebo Plas cleaning cloth the results of which are shown in Fig. 8. A droplet of the composition was added to the cloth. It was observed that diffusion was more rapid with increased acid soluble CMC content with visible difference between the three samples after 2 minutes. After 6 minutes sample 020 was completely absorbed by the cloth, whereas samples 000 and 010 both showed signs of a watery surface on top of the cloth. This indicates that adding acid soluble CMC enhances absorption rate.
  • Fig. 8 show pictures from the absorption test on a Kanebo Plas cloth. Absorption was observed at the time of application of the composition on the cloth and again at 2 minutes, 4 minutes, and 6 minutes after application of the composition.
  • the top row shows sample 000.
  • the middle row shows the test of sample 010.
  • the bottom row shows the test of sample 020. From left to right, the columns show the compositions at application, 2 minutes, 4 minutes, and 6 minutes after application.
  • compositions containing acid soluble CMC is better absorbed by the skin compared to the composition without acid soluble CMC, and that the presence of acid soluble CMC is favourable for delivering bioactive material through the skin, while chitosan acts as a better film forming material to protect the skin from exposure to unwanted material.
  • Example VI Strain tests
  • Sample 000 2.5 w/w% chitosan, 0.5 w/w% guar gum, 1.25 w/w% glycerine, 0.1% disodium EDTA, 3 w/w% ethanol in a 1% lactic acid solution. The results are shown in Fig. 6A.
  • Sample 005 0.5 w/w% acid soluble CMC, 2 w/w% chitosan, 0.5 w/w% guar gum, 1.25 w/w% glycerine, 0.1% disodium EDTA, 3 w/w% ethanol in a 1% lactic acid solution.
  • the results are shown in Fig. 6B.
  • Sample 010 1 w/w% acid soluble CMC, 1.5 w/w% chitosan, 0.5 w/w% guar gum, 1.25 w/w% glycerine, 0.1% disodium EDTA, 3 w/w% ethanol in a 1% lactic acid solution.
  • the results are shown in Fig. 6C.
  • Sample 015 1.5 w/w% acid soluble CMC, 1.0 w/w% chitosan, 0.5 w/w% guar gum, 1.25 w/w% glycerine, 0.1% disodium EDTA, 3 w/w% ethanol in a 1% lactic acid solution. The results are shown in Fig. 6D.
  • Sample 020 2 w/w% acid soluble CMC, 0.5 w/w% chitosan, 0.5 w/w% guar gum, 1.25 w/w% glycerine, 0.1% disodium EDTA, 3 w/w% ethanol in a 1% lactic acid solution.
  • the results are shown in Fig. 6E.
  • Sample 025 2.5 w/w% acid soluble CMC, 0.5 w/w% guar gum, 1.25 w/w% glycerine, 0.1% disodium EDTA, 3 w/w% ethanol in a 1% lactic acid solution. The results are shown in Fig. 6F.
  • the tests were performed under temperature and humidity control at 27 °C and 65% relative humidity. Each sample was strained until failure. The tests were performed using a Hongjin HY-UT-5PC Tensile Testing Machine applying a strain rate at 10 mm/min. All samples had the same dimensions.
  • samples containing both acid soluble CMC and chitosan were less stiff, i.e. lower stress-strain relationship (slope in data of Figs. 6A- 6F), compared to samples containing only acid soluble CMC and samples containing only chitosan.
  • the strain tests in figs. 6A-6F show that the films comprising only chitosan are stiffer than films comprising both acid soluble CMC and chitosan.
  • the compositions comprising both acid soluble CMC and chitosan also tended to form thinner films compared to compositions without acid soluble CMC.
  • the thick films of chitosan tended to adhere to strongly to skin and being restrictive on the skin, which can be irritating for the user and thus contribute to the user removing the composition too early.
  • This example shows describes the results of using compositions according to the invention.
  • a subject applied a composition to split lips and bug bites once daily for 2 days (lip) and 3 days (bug bite).
  • Lips A small layer on the skin of the lips was observed and stinging due to the split lip was removed fast.
  • Bug bite itchiness and inflammation were reduced immediately.
  • the composition used consisted of 2.4% chitosan, 0.1% acid soluble CMC, 75 ppm melanin, 1% lactic acid, 0.5% guargum, 1.25% glycerine, 10% ethanol and water for the rest.
  • a subject applied a composition to Tinea (ringworm) between their toes for a total of 3 weeks; once a day for 6 days and twice a week for another 2 weeks. Cracks from Tinea bleeding were removed to a great extent with a minor amount of dead skin remaining on day 6.
  • the composition was the same as in the first case.
  • a subject applied a composition to eczema/rash for 6 days twice a day.
  • the composition was the same as in the first two cases. After 6 days of usage, no eczema/rash was observable.
  • the composition used consisted of 1.9% chitosan, 0.1% acid soluble CMC, 75 ppm melanin, 1% lactic acid, 1% guar gum, 2.5 % glycerine, 10% ethanol, lavender oil, peppermint oil, and water for the rest. No dandruff, was observable after use and scalp itchiness was removed.
  • a subject applied the composition used in the first case but which further included 0.1% disodium EDTA, to eczema on their feet and to scratched and inflamed skin for 1 week twice a day. After 3 days of usage, skin was no longer itchy. After 1 week, the dark ring around the eczema vanished, the skin surface was no longer inflamed, and the scratches had closed completely.
  • a subject applied the composition used in the fifth case to scratched skin for 2 days twice a day. After 2 days, redness disappeared and the open wound had closed a little bit more.
  • the composition consisted of 2.1% chitosan, 0.1% acid soluble CMC, 800 ppm melanin, 1% lactic acid, 0.8% guar gum, 2% glycerine, 10% ethanol, 0.1 % disodium EDTA and water for the rest.
  • Fig. lOa-k shows the samples with acid-soluble CMC, where Fig. 10a is pH 2, Fig. 10b is pH 3, Fig. 10c is pH 4, Fig. lOd is pH 5, Fig. lOe is pH 6, Fig. lOf is pH 7, Fig. 10g is pH 8, Fig. lOh is pH 9, Fig. lOi is pH 10, Fig. lOj is pH 11, and Fig. 10k is pH 12.
  • Fig. lla-k shows the samples with "insoluble CMC", where Fig. 11a is pH 2, Fig. lib is pH 3, Fig. 11c is pH 4, Fig. lid is pH 5, Fig. lie is pH 6, Fig. Ilf is pH 7, Fig. 11g is pH 8, Fig. llh is pH 9, Fig. Hi is pH 10, Fig. llj is pH 11, and Fig. Ilk is pH 12.
  • Example IX FT-IR Spectroscopy
  • FT-IR Spectroscopy was performed on chitosan obtained from
  • the data from the three analysed samples have been normalized to a peak at approximately 2865 cm 1 due to the invariance in chitosan and CMC samples at this peak.
  • a signature of carboxymethylation is the substitution of carboxymethyl groups (-CH2COOH) on the amino groups at a wavenumber of approximately 1580 cm 1 and shown at 30a in Fig. 12.
  • the chitosan, the acid soluble CMC, and the commercially available fully carboxymethylated CMC show transmittance of 0.941 a.u., 0.902 a.u., and 0.808 a.u., respectively, at the wavenumber 1580 cm' 1 .
  • the substitution degree of the acid soluble CMC referred to A.S. CMC, was calculated by:
  • the peak at approximately 1407 cm' 1 , 30b indicates the presence of -COONa i.e. residues of sodium.
  • Sodium residues seem to be present in the commercially available CMC and it is presently contemplated that sodium residues may influ- ence acid solubility.
  • the acid soluble CMC lacks the peak at -1407 cm 1 and shows a peak at approximately 1743 cm' 1 , 30C, indicating the presence of -COOH rather than -COONa, suggesting a sodium free CMC.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Cosmetics (AREA)

Abstract

La présente invention concerne des compositions filmogènes comprenant du chitosane et du chitosane carboxyméthylé soluble dans l'acide, lesdites compositions étant destinées à une utilisation topique dans des applications cosmétiques et thérapeutiques.
PCT/IB2024/052763 2023-03-27 2024-03-22 Compositions filmogènes avec du chitosane et du chitosane carboxyméthylé Ceased WO2024201238A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DKPA202370151 2023-03-27
DKPA202370151 2023-03-27

Publications (1)

Publication Number Publication Date
WO2024201238A1 true WO2024201238A1 (fr) 2024-10-03

Family

ID=90717704

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2024/052763 Ceased WO2024201238A1 (fr) 2023-03-27 2024-03-22 Compositions filmogènes avec du chitosane et du chitosane carboxyméthylé

Country Status (1)

Country Link
WO (1) WO2024201238A1 (fr)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0879592A2 (fr) 1997-04-17 1998-11-25 Henkel Kommanditgesellschaft auf Aktien Compositions de protection solaire
CN103120642A (zh) * 2012-12-20 2013-05-29 贵州扬生医用器材有限公司 一种用于皮肤疾患的凝胶及其制备方法
WO2014126370A1 (fr) 2013-02-13 2014-08-21 Dong-A Pharmaceutical Co.,Ltd Composition pharmaceutique formant une pellicule pour cicatriser les plaies, et méthode de préparation associée
WO2016164903A1 (fr) 2015-04-10 2016-10-13 Hemcon Medical Technologies, Inc. Gel de chitosane bioadhésif destiné à réguler les saignements et à favoriser la guérison par la réduction des cicatrices sans cacher ou gêner l'accès a un champ chirurgical
WO2018202456A1 (fr) * 2017-05-03 2018-11-08 Ricerfarma S.R.L. Compositions topiques conçues pour maintenir et restaurer l'homéostasie de l'eau de la peau
CN110386996A (zh) * 2018-04-19 2019-10-29 中国海洋大学 一种羧甲基壳聚糖的均相合成方法
CN111228579A (zh) * 2020-01-21 2020-06-05 赛克赛斯生物科技股份有限公司 可注射水凝胶及其制备方法和应用以及关节润滑剂

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0879592A2 (fr) 1997-04-17 1998-11-25 Henkel Kommanditgesellschaft auf Aktien Compositions de protection solaire
CN103120642A (zh) * 2012-12-20 2013-05-29 贵州扬生医用器材有限公司 一种用于皮肤疾患的凝胶及其制备方法
WO2014126370A1 (fr) 2013-02-13 2014-08-21 Dong-A Pharmaceutical Co.,Ltd Composition pharmaceutique formant une pellicule pour cicatriser les plaies, et méthode de préparation associée
WO2016164903A1 (fr) 2015-04-10 2016-10-13 Hemcon Medical Technologies, Inc. Gel de chitosane bioadhésif destiné à réguler les saignements et à favoriser la guérison par la réduction des cicatrices sans cacher ou gêner l'accès a un champ chirurgical
WO2018202456A1 (fr) * 2017-05-03 2018-11-08 Ricerfarma S.R.L. Compositions topiques conçues pour maintenir et restaurer l'homéostasie de l'eau de la peau
CN110386996A (zh) * 2018-04-19 2019-10-29 中国海洋大学 一种羧甲基壳聚糖的均相合成方法
CN111228579A (zh) * 2020-01-21 2020-06-05 赛克赛斯生物科技股份有限公司 可注射水凝胶及其制备方法和应用以及关节润滑剂

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DUMONT VITOR C ET AL: "Chitosan and carboxymethyl-chitosan capping ligands: Effects on the nucleation and growth of hydroxyapatite nanoparticles for producing biocomposite membranes", MATERIALS SCIENCE AND ENGINEERING C, ELSEVIER SCIENCE S.A, CH, vol. 59, 14 October 2015 (2015-10-14), pages 265 - 277, XP029329638, ISSN: 0928-4931, DOI: 10.1016/J.MSEC.2015.10.018 *
TAO XU ET AL: "Synthesis, characteristic and antibacterial activity of N,N,N-trimethyl chitosan and its carboxymethyl derivatives", CARBOHYDRATE POLYMERS, vol. 81, no. 4, 1 July 2010 (2010-07-01), pages 931 - 936, XP055140601, ISSN: 0144-8617, DOI: 10.1016/j.carbpol.2010.04.008 *

Similar Documents

Publication Publication Date Title
CN101977589B (zh) 皮肤病学使用的壳聚糖凝胶、其制备方法及其用途
DE60307603T2 (de) Zellwandderivate aus biomasse und herstellung davon
AU2008238445B2 (en) Extract of Trigonella foenum-graecum
EP3017808B1 (fr) Gel d'acide hyaluronique hydrosoluble et procédé pour le produire
EP1696971B1 (fr) Pansements pour plaies a action therapeutique, leur production et leur utilisation
Karami et al. Chitosan-based emulgel and xerogel film containing Thymus pubescens essential oil as a potential wound dressing
EP2937101A1 (fr) Composition semi-fluide pour lubrification, rétention d'humidité, désinfection, stérilisation et procédé utilisant celle-ci
ES2857273T3 (es) Formulación esterilizada por calor que comprende quitosán y proceso para preparación de la misma
Wani et al. Chitosan and Aloe vera: Two gifts of nature
CN108158995A (zh) 一种含有壳聚糖的妇科用抗菌泡沫剂及其制备方法
CA2897518A1 (fr) Composition dermatologique topique comportant un peptide antimicrobien cationique couple a un lipide et de l'acide hyaluronique.
AU2011296641B2 (en) Antifungal composition
EP0949919B1 (fr) Procede de stabilisation de compositions d'acide ascorbique levogyre (laa) et de laa stable
EP3574022A1 (fr) Acide hyaluronique réticulé avec des agents de réticulation naturels ou semi-synthétiques
WO2024201238A1 (fr) Compositions filmogènes avec du chitosane et du chitosane carboxyméthylé
CN1377698A (zh) 纳米芦荟妇洁护理露及其制备方法
CN111905030A (zh) 一种阴道健康护理凝胶及其制备方法和应用
EP2440179B1 (fr) Compositions à base d'oligosaccharides de chitosane
Ewii et al. A Comparative Study on the Physicochemical Characterization of Chitosan Obtained from Seafood in Uyo Metropolis, Nigeria.
Yusan et al. Anti-bacterial activity of chitosan nanoparticles gel from crab shell waste (Portunus pelagicus) against Staphylococcus aureus and Escherichia coli bacteria
CN116327654B (zh) 具有天然防腐性能的组合物及制备方法与应用
KR20020012465A (ko) 키토산 및 알긴산을 이용한 천연고분자 항균비누 및 그의제조 방법
CN118872696B (zh) 一种基于芦荟提取物的抑菌组合物及其制备方法
RU2709102C2 (ru) Состав и технология получения присыпки ранозаживляющего действия
WO1993022370A1 (fr) Derives d'acide undecylenique avec des macromolecules hydrophiles et utilisations en cosmetique ou en pharmacie

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24716468

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 24716468

Country of ref document: EP

Kind code of ref document: A1