EP2190853A1 - Complexes medicamenteux acides de glucosamine exempts d'halogenure - Google Patents

Complexes medicamenteux acides de glucosamine exempts d'halogenure

Info

Publication number
EP2190853A1
EP2190853A1 EP07835861A EP07835861A EP2190853A1 EP 2190853 A1 EP2190853 A1 EP 2190853A1 EP 07835861 A EP07835861 A EP 07835861A EP 07835861 A EP07835861 A EP 07835861A EP 2190853 A1 EP2190853 A1 EP 2190853A1
Authority
EP
European Patent Office
Prior art keywords
complex
copolymers
homopolymers
glucosamine
water
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.)
Withdrawn
Application number
EP07835861A
Other languages
German (de)
English (en)
Other versions
EP2190853A4 (fr
Inventor
Vilas M. Chopdekar
Michael J. Torntore
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.)
Gluconova LLC
Original Assignee
Gluconova LLC
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 Gluconova LLC filed Critical Gluconova LLC
Publication of EP2190853A1 publication Critical patent/EP2190853A1/fr
Publication of EP2190853A4 publication Critical patent/EP2190853A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
    • C07H5/04—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to nitrogen
    • C07H5/06—Aminosugars
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Definitions

  • the invention relates to halide-free glucosamine complexes of acidic drugs and to methods for preparing such complexes.
  • Glucosamine is a well-known amino monosaccharide found in chitin, glycoproteins and glycosaminoglycans. Glucosamine is widely used for the treatment of rheumatic fever, arthritic and arthosic complaints, in the acute as well as chronic forms, as well as in the treatment of pathological conditions originating from metabolic disorders of the osteo-articular tissue. Although products in the marketplace are labeled as, or referred to as, "glucosamine", they are misnomers since such products consist of glucosamine hydrochloride or as unreacted mixtures of glucosamine hydrochloride and a complex such as potassium or sodium sulfate.
  • One drawback of many therapeutic drugs is their relative insolubility in the body after they have been administered to a patient. It would be most desirable if more soluble versions of therapeutic drugs could be made available.
  • Salts or mixtures of "glucosamine” or “glucosamine sulfate” and a therapeutic drug such as aspirin, ibuprofen, ketoprofen, etc. are known in the prior art, e.g., see U.S. Patent Publication 2002/0058642 Al; U.S. Patent 6,608,041 B2; U.S. Patent 6,291,527
  • glucosamine sulfate employed in such compositions are misnomers, inasmuch as such materials are actually glucosamine hydrochloride or mixed complexes of glucosamine hydrochloride and an alkali or alkaline earth metal sulfate.
  • the glucosamine employed in preparing the complexes of the invention is halide-free (i.e., the glucosamine has a purity of at least about 99 wt.% and a maximum halide content of about 0.01 wt.%) and as a result, the complexes of the invention will contain neither a halide nor any extraneous anions nor any extraneous cations (e.g., sodium, potassium, calcium, etc.).
  • the starting materials for preparing the complexes of the invention are halide-free glucosamine and a therapeutic drug having a pKa of less than 7.
  • Such drugs will contain at least one acid functionality, e.g., a carbonyl moiety, a carboxyl moiety and/or a sulfoxide moiety.
  • Glucosamine extracted from shellfish or prepared by a fermentation process, is only available in the form of its hydrochloride salt. If the glucosamine hydrochloride salt is neutralized with a base, e.g., NaOH, KOH, etc. in order to release the glucosamine, the resultant product will always contain a salt, i.e., NaCl or KCl, respectively, and it is not possible to separate the glucosamine from the salt since both the glucosamine and the salt are fully soluble in water.
  • a base e.g., NaOH, KOH, etc.
  • Free glucosamine be prepared by the method recited in Chem. Ber.. volume 75, page 1274. Such method involves the treatment of glucosamine hydrochloride with an ethanolic solution of a tertiary base such as triethylamine. Triethylamine hydrochloride is filtered off and the free glucosamine is then recovered from the reaction mixture.
  • triethylamine is a toxic material even in small quantities and the yield of the free glucosamine is quite low.
  • the free glucosamine still contains residual chloride.
  • a method for producing halide-free glucosamine with a very high degree of purity has now been discovered. Such method may be summarized as follows::
  • a glucosamine halide complex e.g., glucosamine hydrochloride, glucosamine hydroiodide, etc.
  • a glucosamine halide complex e.g., glucosamine hydrochloride, glucosamine hydroiodide, etc.
  • a glucosamine halide complex e.g., glucosamine hydrochloride, glucosamine hydroiodide, etc.
  • a glucosamine halide complex e.g., glucosamine hydrochloride, glucosamine hydroiodide, etc.
  • the insoluble halide-free glucosamine is separated from the Ci - C 4 alcohol solution of the lithium halide complex.
  • the reaction should be carried out at a temperature of about 15 to about 35°C; conveniently, the reaction may be carried out at ambient temperatures.
  • the Ci - C 4 alcohol may be, e.g., methanol, ethanol (preferably anhydrous), isopropanol, etc; the preferred alcohol comprises methanol.
  • the lithium base may be anhydrous lithium hydroxide, lithium hydroxide monohydrate, lithium methoxide, lithium ethoxide or lithium isopropoxide.
  • the preferred lithium base comprises anhydrous lithium hydroxide. It has been found that the presence of water in the reaction mixture reduces the yield of the halide-free glucosamine. Accordingly, it is preferred that the reaction be carried out under anhydrous conditions.
  • the lithium base is employed in an amount of about 1.0 to about 1.2 moles per mole of halide present in the glucosamine halide complex. Excess lithium base is unnecessarily wasteful and will reduce the yield of the halide-free glucosamine.
  • the alcohol is employed in an amount of about 1 to about 10 parts, preferably 3 to 6 parts, per part of lithium base.
  • the solid halide-free glucosamine is filtered off from the resultant alcohol solution of the lithium halide and washed with additional alcohol.
  • the halide-free glucosamine may then be dried under vacuum at a temperature of about 15 to about 30 0 C. The yield typically ranges from about 85 to about 90 %.
  • the halide-free glucosamine is quite pure. It will have a purity level of greater than about 99 wt.% and the halide content will be about 0.01 wt.% or less, e.g., 100 ppm or less and very often, the halide content will be less than 50 ppm and as low as 25 ppm. Based upon the residual halide content of the halide-free glucosamine, the lithium residue in the glucosamine will generally be about 20 ppm or less and very often, the lithium residue content will be less than 10 ppm
  • the halide-free glucosamine is quite hygroscopic and will decompose over a period of time if subjected to ambient temperature and/or to the atmosphere. Accordingly, it should be refrigerated in a closed container or preferably promptly used after recovery for conversion to the complexes of the invention as described below.
  • the halide-free glucosamine may be readily converted to the glucosamine-acidic drug complex of the invention by reacting the glucosamine with a therapeutic drug having at least one acidic functionality, i.e. a therapeutic drug having a pK* of less than 7.
  • the molar ratio of the halide-free glucosamine to the acidic drug in the complex is not critical and may be in the range of about 1 mole of glucosamine per mole of the drug up to about 15 moles of the glucosamine per mole of the drug. If the selected drug has more than one acidic functionality, the molar ratio of the glucosamine to the selected drug should be adjusted such that there will be about 1 to about IS moles of glucosamine employed per acidic functionality in the selected drug.
  • the reaction mixture will comprise the halide-free glucosamine, about 5 to about 30 parts, preferably 15 to 20 parts, of water (preferably purified water) per part of the glucosamine and the selected drug.
  • the resultant solutions may become too viscous to be properly agitated, particularly if the glucosamine-therapeutic drug complex is not isolated from the reaction mixture, but is stabilized by the addition of a polymer to the reaction mixture, as described below.
  • excessive amounts of water may lead to reduced yields if a water-miscible solvent is used to recover the complex and if freeze-drying is used to recover the complex, the freeze-drying process becomes more time-consuming and expensive because of the large amount of water to be removed from the reaction mixture.
  • the selected acidic drug is slowly added to the aqueous solution of the halide-free glucosamine while the aqueous solution is agitated, e.g. over a period of a few minutes, and the reaction mixture is further agitated for 5 to 120 minutes.
  • the reaction is typically conducted at a temperature of about 15 to about 4O 0 C.
  • the glucosamine- acidic drug complex of the invention may be recovered from the reaction mixture by freeze-drying or by adding a water-miscible solvent such as acetone to the reaction mixture such that the complex will precipitate from the reaction mixture and the complex is then recovered by conventional filtration methods.
  • the complex may then be dried by conventional methods, e.g., a stream of nitrogen, a vacuum oven at 30-50 0 C for a period of 1 to 10 hours, etc. It is preferred that the recovery of the halide-free glucosamine- acidic drug complex of the invention be carried out by a freeze-drying process as described in greater detail below.
  • halide-free glucosamine-acidic drug complexes of the invention may decompose over a period of time if they are exposed to ambient temperatures or the atmosphere. Therefore, it is preferred that the complex not be recovered from the reaction mixture as is, but converted to a stabilized form prior to recovery. Conversion of the complex to its stabilized form may be desirable even for those complexes that do not decompose upon exposure to ambient temperatures and/or the atmosphere, since the pharmaceutically acceptable polymers employed in stabilizing, i.e., coating, the complexes of the invention may provide extended-release properties when the complexes are administered to warm-blooded vertebrates in need of treatment.
  • Stabilization of the halide-free glucosamine-acidic drug complex is readily accomplished by adding a suitable pharmaceutically acceptable polymer to the reaction mixture prior to recovery of the complex.
  • the pharmaceutically acceptable polymer may be a water-soluble, water-dispersible and/or or a water-swellable homopolymer and/or copolymer.
  • the pharmaceutically acceptable polymer will be water-soluble.
  • the polymer will be employed in an amount of about 2 to about 70, preferably
  • Nonlimiting examples of commercially available pharmaceutically acceptable homopolymers and copolymers suitable for stabilizing the halide-free glucosamine- therapeutic drug complexes of the invention include the following: carboxypoly- methylene homopolymers and copolymers, i.e., vinyl polymers having active carboxyl groups such as high molecular weight homopolymers of acrylic acid crosslinked with allylsucrose or allylpentaerythritol and copolymers of acrylic acid modified by long chain (Cio - C30) alkyl acrylates and crosslinked with allylpentaerythritol - such polymers are commercially available and are marketed as Carbopol ® polymers; polyethylene glycol homopolymers and copolymers (e.g., polyethylene-co-lactic acid copolymers), particularly polyethylene glycol polymers having molecular weights in the range of about 2,000 to about 20,000, preferably 4,000 to 18,000; polypropylene glycol homo
  • the choice of particular homopolymers and/or copolymers for coating, i.e., stabilizing, the complex is not critical so long as the polymers are pharmaceutically acceptable, have the capability of coating, i.e., stabilizing, the complex without any adverse chemical reaction occurring between the selected polymer and the complex and the resultant coated complexes are stable, i.e., they will not undergo decomposition when exposed to ambient temperatures and/or the atmosphere.
  • the desired pharmaceutically acceptable polymer is added, preferably in increments, with stirring, to the aqueous halide-free glucosamine solution preferably prior to the addition of the acidic drug.
  • This step will generally take about 5 to about 15 minutes and is preferably conducted at a temperature of about 15 to about 40 0 C.
  • stirring is continued for an additional 5 to 120 minutes.
  • the acidic drug is slowly added to the reaction mixture, while maintaining the reaction mixture at a temperature of about 15 to 40 0 C.
  • the last step is the recovery of the polymer-coated, i.e., stabilized, complex from the reaction mixture.
  • the stabilized complex may be recovered from the reaction mixture by freeze-drying or by adding a water-miscible solvent, e.g., acetone, to the reaction mixture to cause the stabilized complex to precipitate out from the reaction mixture.
  • a water-miscible solvent e.g., acetone
  • the precipitate is then recovered by conventional filtration methods and it may be dried as described below.
  • the choice of stabilizing polymer and water-miscible solvent should be such that the polymer will not dissolve in, or otherwise react with, the solvent.
  • the complex of the invention is preferably recovered by removal of water from the reaction mixture by freeze-drying, a well-known technique for removing water from compositions.
  • freeze-drying is a time-consuming process, (a reaction mixture containing one liter of water will typically require 30-36 hours to remove about 97% of the water), it is preferred since the formation of decomposition products resulting from heating the reaction mixture or adding solvents to the reaction mixture can be avoided.
  • the freeze-drying process will generally be carried out at a reduced pressure and reduced temperature, e.g., a pressure of not greater than 500 milHTorre, preferably 300 to 100 milliTorre and at a temperature of about -60 to about -2O 0 C, preferably -50 to -4O 0 C.
  • the endpoint of the completion of the freeze-drying process may be determined by condensing and measuring the quantity of water removed during the freeze-drying process.
  • the time required for completion of the freeze-drying process will vary depending on factors such as pressure, temperature, quantity of reaction mixture to be free-dried, level of water to be tolerated in the stabilized halide-free glucosamine-drug complex, the thickness and surface area of the reaction mixture in the trays of the freeze- drying equipment, etc.
  • the stabilized complex is to be recovered by precipitation from the reaction mixture by addition of a water-miscible solvent such as acetone to the reaction mixture, generally about 2 to about 10 parts of solvent per part of reaction mixture will be required.
  • the stabilized complex After the stabilized complex has been recovered from the reaction mixture, it may be dried by conventional techniques, e.g., a stream of nitrogen, vacuum oven at a temperature of about 30 to about 50 0 C for 1 to 10 hours or more, etc.
  • the stabilization of the complexes of the invention may provide an additional advantage to warm-blooded vertebrates to whom such complexes are administered.
  • the stabilized, i.e., polymer-coated, versions of the complexes may provide extended release properties, i.e., the glucosamine-therapeutic drug complex may be released within the vertebrate over an extended period of time, thereby possibly resulting in a reduction of the frequency and the amount of the dosage that would otherwise be required to be administered to the vertebrate.
  • the therapeutic drug that is to be complexed with the halide-free glucosamine may be any therapeutic drug that exhibits an acidic pKa, i.e., a pK a of less than 7.0.
  • Such drugs will contain one or more acidic functionalities such as a carbonyl moiety, a carboxyl moiety, a sulfoxide moiety, etc.
  • the list of therapeutic drugs that fit such definition is quite voluminous.
  • Suitable therapeutic drugs containing at least one acidic functionality may be found in one or more of the following nonlimiting, representative classes of drugs: ⁇ - and ⁇ -Adrenergic Agonists; Narcotic and Non-Narcotic Analgesics; Anorexics; Antiallergics; Antianginals; Antiarrhythmics; Antiasthmatics; Antibiotics; Anti-coagulants; Anticonvulsants; Antidepressants; Antidiabetics; Antihistaminics; Antihypertensives; Nonsteroidal Anti-Inflammatories; Antimigraines; Antineoplastics; Antiparkinsonians; Antipsychotics; Antipyretics; Antispasmodics; Antithrombotics; Antiulceratives; Anxiolytics; Decongestants; Diuretics; Hepatoprotectants; Sedatives; and Vasodilators.
  • therapeutic drugs within the foregoing-listed classes will be suitable for preparing a complex with the halide-free glucosamine. Only those therapeutic drugs that are sufficiently acidic in nature to form such a complex with the halide-free glucosamine are suitable. As mentioned above, such therapeutic drugs will have a pK a of less than 7.0 and will contain at least one acid functionality, e.g. a carbonyl moiety, a carboxyl moiety, a sulfoxide moiety, etc.
  • Particularly suitable specific drugs within the foregoing classes include: acetaminophen, acetazolamide, ampicillin, ampiroxicam, aspirin, bromfenac, carprofen, celecoxib, cetirizine, chlorothiazide, chlorpropamide, ciprofloxacin, diazepam, diclofenac, ethacrynic acid, flufenamic acid, furosemide, ibuprofen, indomethacin, indoprofen, ketoprofen, levodopa, meclofenamic acid, methotrexate, methyldopa, naproxen, orazamide, penicillamine, pentobarbital, phenobarbital, phenytoin, piroxicam, propylthiouracil, protoprophyrin EX, rofecoxib, salicyclic acid, sulfadiazine, sulfapyridine, sulinda
  • a reaction vessel was equipped with a stirrer and a nitrogen blanket. To the reaction vessel were added 4.1 g (0.02 mole) of ibuprofen and 200 cc of pharmaceutical grade methanol. The mixture was stirred to obtain a solution and thereafter, 3.58 g (0.02 mole) of halide-free glucosamine were added to the reaction mixture. The reaction mixture was then stirred for 1 hour at 2S-30°C, resulting in a clear solution. The methanol was stripped off from the reaction mixture using a rotary evaporator at a temperature of 50 0 C. The resultant glucosamine-ibuprofen complex weighed 7 g.
  • a reaction vessel was set up with a stirrer and a warm water bath. Into the reaction vessel were added 1.79 g (0.01 mole) of halide-free glucosamine and the mixture was stirred at 25-35 0 C to obtain a clear solution. Thereafter, 3.57 g (0.01 mole) of indomethacin were added and the reaction mixture was stirred for 1 hour at 35-45 0 C. The reaction mixture was then freeze-di ⁇ ed at a pressure of about 200 milHTorre and a temperature of about -45°C. 3.8 g of a light yellow powder consisting of the glucosamine-indomethacin complex were obtained.
  • Example 2 was repeated using 8.6 g (0.05 mole) of halide-free glucosamine, 150 cc of purified water and 7.54 g (0.05 mole) of acetaminophen. 15 g of a white powder consisting of the glucosamine-acetaminophen complex were obtained.
  • Example 2 was repeated using 9.0 g (slight excess above 0.05 mole) of halide-free glucosamine, 150 cc of purified water and 9 g (0.05 mole) of acetylsalicyclic acid. 17.4 g of a white solid consisting of the glucosamine-acetylsalicyclic acid complex were obtained.
  • Example 2 was repeated using 1.79 g (0.01 mole) of halide-free glucosamine, 100 cc of purified water and 2.3 g (0.01 mole) of naproxen. 3.8 g of a white product consisting of the glucosamine-naproxen complex were obtained.
  • Example 2 was repeated using 1.79 g (0.01 mole) of halide-free glucosamine, 100 cc of purified water and 2.96 g (0.01 mole) of diclofenac. 4.0 g of an off-white powder consisting of the glucosamine-diclofenac complex were obtained.
  • Example 2 was repeated using 1.79 g (0.01 mole) of halide-free glucosamine, 50 cc of purified water and 0.28 g (0.01 mole) of diazepam. 0.43 g of a white solid consisting of the glucosamine-diazepam complex was obtained.
  • Example 1 was repeated using 3.6 g (0.02 mole) of halide-free glucosamine, 300 cc of pharmaceutical grade methanol and 5.04 g (0.02 mole) of phenytoin. 8 g (92% yield) of a white solid consisting of the glucosamine-phenytoin complex were obtained.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Dermatology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un complexe de glucosamine présentant une pureté d'au moins environ 99 % en poids et une teneur maximale en halogénure d'environ 0,01 % en poids, ainsi qu'un médicament thérapeutique présentant un pKa inférieur à 7. Le complexe selon l'invention est de préférence stabilisé par enrobage dudit complexe au moyen d'au moins un polymère pharmaceutiquement acceptable contenant un homopolymère et/ou copolymère hydrosoluble, immiscible dans l'eau et/ou dilatable dans l'eau. Les polymères appropriés comprennent : des homopolymères et des copolymères de carboxypolyméthylène ; des homopolymères et des copolymères de polyéthylène glycol, des homopolymères et des copolymères de povidone ; des homopolymères et des copolymères d'acide polyacrylique ; des homopolymères et des copolymères de polyacrylamide ; des polysaccharides ; et des mélanges d'au moins deux de ces polymères. Le complexe enrobé résultant est stable dans des conditions d'exposition à la température ambiante et/ou à l'air ambiant. Les médicaments thérapeutiques appropriés sont classés selon les catégories suivantes : agonistes adrénergiques α et β ; analgésiques narcotiques et non narcotiques ; anorexigènes ; antiallergiques ; antiangineux ; antiarythmisants ; antiasthmatiques ; antibiotiques ; anticoagulants ; anticonvulsifs ; antidépresseurs ; antidiabétiques ; antihistaminiques ; hypotenseurs ; des anti-inflammatoires non stéroïdiens ; antimigraineux ; anticancéreux ; antiparkinsoniens ; antipsychotiques ; antipyrétiques ; antispasmodiques ; antithrombotiques ; antiulcéreux ; anxiolytiques ; décongestionnants ; diurétiques ; hépatoprotecteurs ; sédatifs ; et vasodilatateurs.
EP07835861A 2007-06-22 2007-06-22 Complexes medicamenteux acides de glucosamine exempts d'halogenure Withdrawn EP2190853A4 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2007/014610 WO2009002297A1 (fr) 2007-06-22 2007-06-22 Complexes medicamenteux acides de glucosamine exempts d'halogenure

Publications (2)

Publication Number Publication Date
EP2190853A1 true EP2190853A1 (fr) 2010-06-02
EP2190853A4 EP2190853A4 (fr) 2011-08-31

Family

ID=40185904

Family Applications (1)

Application Number Title Priority Date Filing Date
EP07835861A Withdrawn EP2190853A4 (fr) 2007-06-22 2007-06-22 Complexes medicamenteux acides de glucosamine exempts d'halogenure

Country Status (3)

Country Link
EP (1) EP2190853A4 (fr)
CA (1) CA2690776A1 (fr)
WO (1) WO2009002297A1 (fr)

Families Citing this family (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT2413535E (pt) 2010-07-30 2013-01-25 Deutsche Telekom Ag Método para estimar o tipo da estrutura do grupo de imagens de uma pluralidade de fotogramas de vídeo numa sequência de vídeo
WO2014037832A2 (fr) 2012-09-06 2014-03-13 Mahesh Kandula Compositions et méthodes de traitement de l'épilepsie et de maladies neurologiques
WO2013168021A1 (fr) 2012-05-07 2013-11-14 Mahesh Kandula Compositions et méthodes pour le traitement des troubles neuromusculaires et des troubles neurodégénératifs
US9399634B2 (en) 2012-05-07 2016-07-26 Cellix Bio Private Limited Compositions and methods for the treatment of depression
WO2013167985A1 (fr) 2012-05-07 2013-11-14 Mahesh Kandula Compositions et méthodes de traitement de troubles neurologiques
WO2013168023A1 (fr) 2012-05-08 2013-11-14 Mahesh Kandula Compositions et méthodes pour le traitement de la maladie de parkinson
WO2013168003A1 (fr) * 2012-05-08 2013-11-14 Mahesh Kandula Compositions et méthodes de traitement de l'inflammation
WO2013167992A1 (fr) 2012-05-08 2013-11-14 Mahesh Kandula Compositions et méthodes de traitement de troubles inflammatoires
US9522884B2 (en) 2012-05-08 2016-12-20 Cellix Bio Private Limited Compositions and methods for the treatment of metabolic disorders
US9434704B2 (en) 2012-05-08 2016-09-06 Cellix Bio Private Limited Compositions and methods for the treatment of neurological degenerative disorders
WO2013168025A1 (fr) 2012-05-08 2013-11-14 Mahesh Kandula Compositions et méthodes de traitement des maladies de coagulation du sang
WO2013168002A1 (fr) 2012-05-10 2013-11-14 Mahesh Kandula Compositions et méthodes de traitement d'affections neurologiques
WO2013168012A1 (fr) 2012-05-10 2013-11-14 Mahesh Kandula Compositions et méthodes de traitement de troubles respiratoires
WO2013167997A2 (fr) 2012-05-10 2013-11-14 Mahesh Kandula Compositions et méthodes de traitement du syndrome métabolique
WO2013167999A2 (fr) 2012-05-10 2013-11-14 Mahesh Kandula Compositions et méthodes de traitement d'affections neurologiques
US9273061B2 (en) 2012-05-10 2016-03-01 Cellix Bio Private Limited Compositions and methods for the treatment of chronic pain
WO2013168000A1 (fr) 2012-05-10 2013-11-14 Mahesh Kandula Compositions et méthodes de traitement de la douleur sévère
WO2013168005A2 (fr) 2012-05-10 2013-11-14 Mahesh Kandula Compositions et méthodes de traitement du syndrome des jambes sans repos et de la fibromyalgie
WO2013168033A1 (fr) 2012-05-10 2013-11-14 Mahesh Kandula Compositions et methodes pour le traitement de maladies neurologiques
WO2013168004A2 (fr) 2012-05-10 2013-11-14 Mahesh Kandula Compositions et méthodes de traitement de la douleur fibromyalgique
WO2013168016A1 (fr) 2012-05-10 2013-11-14 Mahesh Kandula Compositions et méthodes de traitement du syndrome métabolique
US9321775B2 (en) 2012-05-10 2016-04-26 Cellix Bio Private Limited Compositions and methods for the treatment of moderate to severe pain
US9499527B2 (en) 2012-05-10 2016-11-22 Cellix Bio Private Limited Compositions and methods for the treatment of familial amyloid polyneuropathy
WO2013168015A1 (fr) 2012-05-10 2013-11-14 Mahesh Kandula Compositions et méthodes pour le traitement de l'asthme et de l'allergie
JP2015518854A (ja) 2012-05-23 2015-07-06 セリックスビオ プライヴェート リミテッド 多発性硬化症の治療のための組成物および方法
NZ701832A (en) 2012-05-23 2016-08-26 Cellix Bio Private Ltd Compositions and methods for treatment of inflammatory bowel disease
WO2013175344A2 (fr) 2012-05-23 2013-11-28 Mahesh Kandula Compositions et méthodes pour le traitement de la parodontite et de la polyarthrite rhumatoïde
WO2013175347A2 (fr) 2012-05-23 2013-11-28 Mahesh Kandula Compositions et méthodes pour le traitement de troubles respiratoires
AU2013264820A1 (en) 2012-05-23 2014-11-27 Cellixbio Private Limited Compositions and methods for treatment of mucositis
US9492409B2 (en) 2012-05-23 2016-11-15 Cellix Bio Private Limited Compositions and methods for the treatment of local pain
US9108942B1 (en) 2014-11-05 2015-08-18 Mahesh Kandula Compositions and methods for the treatment of moderate to severe pain
WO2014020480A2 (fr) 2012-08-03 2014-02-06 Mahesh Kandula Compositions et méthodes pour le traitement de la migraine et de maladies neurologiques
WO2014037833A2 (fr) 2012-09-06 2014-03-13 Mahesh Kandula Compositions et méthodes de traitement d'une inflammation et de troubles lipidiques
SG11201407325YA (en) 2012-09-08 2014-12-30 Cellix Bio Private Ltd Compositions and methods for treatment of inflammation and lipid disorders
CA2800056A1 (fr) 2012-12-24 2014-06-24 Nova Chemicals Corporation Compositions de melange de polyethylene
US9333187B1 (en) 2013-05-15 2016-05-10 Cellix Bio Private Limited Compositions and methods for the treatment of inflammatory bowel disease
SG11201509782TA (en) 2013-06-04 2015-12-30 Cellix Bio Private Ltd Compositions and methods for the treatment of diabetes and pre-diabetes
US9096537B1 (en) 2014-12-31 2015-08-04 Mahesh Kandula Compositions and methods for the treatment of mucositis
NZ736131A (en) 2014-09-26 2019-04-26 Cellix Bio Private Ltd Compositions and methods for the treatment of epilepsy and neurological disorders
ES2799309T3 (es) 2014-09-29 2020-12-16 Cellix Bio Private Ltd Compuestos y composiciones para el tratamiento de esclerosis múltiple
JP6564868B2 (ja) 2014-10-27 2019-08-21 セリックス バイオ プライヴェート リミテッドＣｅｌｌｉｘ Ｂｉｏ Ｐｒｉｖａｔｅ Ｌｉｍｉｔｅｄ 多発性硬化症の治療のための、フマル酸モノメチルエステルとピペラジン又はエチレンジアミンとの３つの成分の塩
US9150557B1 (en) 2014-11-05 2015-10-06 Cellix Bio Private Limited Compositions and methods for the treatment of hyperglycemia
US9290486B1 (en) 2014-11-05 2016-03-22 Cellix Bio Private Limited Compositions and methods for the treatment of epilepsy
US9284287B1 (en) 2014-11-05 2016-03-15 Cellix Bio Private Limited Compositions and methods for the suppression of carbonic anhydrase activity
US10208014B2 (en) 2014-11-05 2019-02-19 Cellix Bio Private Limited Compositions and methods for the treatment of neurological disorders
US9173877B1 (en) 2014-11-05 2015-11-03 Cellix Bio Private Limited Compositions and methods for the treatment of local pain
US9321716B1 (en) 2014-11-05 2016-04-26 Cellix Bio Private Limited Compositions and methods for the treatment of metabolic syndrome
US9175008B1 (en) 2014-11-05 2015-11-03 Cellix Bio Private Limited Prodrugs of anti-platelet agents
WO2016088132A1 (fr) 2014-12-01 2016-06-09 Cellix Bio Private Limited Compositions et méthodes pour le traitement de la sclérose en plaques
US9206111B1 (en) 2014-12-17 2015-12-08 Cellix Bio Private Limited Compositions and methods for the treatment of neurological diseases
SG11201705524SA (en) 2015-01-06 2017-08-30 Cellix Bio Private Ltd Compositions and methods for the treatment of inflammation and pain

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HUT59692A (en) * 1990-11-15 1992-06-29 Puetter Medice Chem Pharm Process for producing complexes containing s/+/-phenyl-alkanoic acids and aminosugars
JP2002510336A (ja) * 1998-04-11 2002-04-02 エレカッパ・ユウロテラピッチ・ソシエタ・ペル・アチオニ 水溶性ケトプロフェン塩を含有する薬学的調製物及びその使用方法
US6472380B1 (en) * 1999-11-24 2002-10-29 Jame Fine Chemicals, Inc. Glucosamine sulfate calcium chloride composition and processes for the preparation of glucosamine sulfate metal chlorides
CA2613631A1 (fr) * 2005-06-23 2007-01-04 Spherics, Inc. Formes de dosage ameliorees pour le traitement de troubles moteurs

Also Published As

Publication number Publication date
EP2190853A4 (fr) 2011-08-31
WO2009002297A1 (fr) 2008-12-31
CA2690776A1 (fr) 2008-12-31

Similar Documents

Publication Publication Date Title
WO2009002297A1 (fr) Complexes medicamenteux acides de glucosamine exempts d'halogenure
US20240293327A1 (en) Monolithic tablets based on carboxyl polymeric complexes for controlled drug release
Yilmaz Chitosan: a versatile biomaterial
EP0710653B1 (fr) Sels de la néfazodone ayant une vitesse de dissolution améliorée
MX351855B (es) Composicion farmaceutica para liberacion modificada.
US7622576B1 (en) Halide-free glucosamine base and method of preparation
JP2007153944A (ja) カチオン化ヒアルロン酸
CA3050150C (fr) Formulations de cannabidiol a liberation immediate
WO2009002299A1 (fr) Méthode de traitement de vertébrés à sang chaud au moyen de complexes médicamenteux acides de glucosamine exempts d'halogénure
JP6356923B2 (ja) 水溶性エステル化セルロースエーテル
US7662802B2 (en) Halide-free glucosamine-acidic drug complexes
EP1347986B1 (fr) Sels metalliques de sulfate de glucosamine cristallin et processus de preparation de ces sels
US20070259043A1 (en) Halide-free glucosamine-therapeutic drug salt compositions
AU2002217416A1 (en) Crystalline glucosamine sulphate metal salts
JP5043364B2 (ja) 多糖誘導体の製造方法
US7388001B1 (en) Halide-free glucosamine sulfate compositions and methods of preparation
US7388000B1 (en) Halide-free glucosamine phosphate compositions and methods of preparation
US20070248677A1 (en) Method for treating warm-blooded vertebrates with a salt of a halide-free glucosamine base and a therapeutic drug
US7662803B2 (en) Method for treating warm-blooded vertebrates with halide-free glucosamine-acidic drug complexes
JP2015160812A (ja) 崩壊剤
JP2009519313A5 (fr)
US5324717A (en) Therapeutical composition comprising hydrolyzed carboxylalkyl cellulose
Garud et al. APPLICATION OF THIOLATED CHITOSAN IN MUCOADHESIVE BUCCAL DRUG DELIVERY SYSTEM
IE68049B1 (en) Quaternary ammonium salts derived from chitosan
Thajeel et al. LOCALLY MADE CHITOSAN COVALENTLY LINKED TO INDOMETHACIN: A NOVEL APPROACH TO FORMULATE SUSTAINED RELEASE INDOMETHACIN CAPSULE IN BASRAH

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20100113

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC MT NL PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA HR MK RS

DAX Request for extension of the european patent (deleted)
A4 Supplementary search report drawn up and despatched

Effective date: 20110728

RIC1 Information provided on ipc code assigned before grant

Ipc: C07H 5/06 20060101AFI20110722BHEP

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20120228