WO2001001993A1 - A formulation of glucosamine sulphate - Google Patents
A formulation of glucosamine sulphate Download PDFInfo
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- WO2001001993A1 WO2001001993A1 PCT/CH1999/000291 CH9900291W WO0101993A1 WO 2001001993 A1 WO2001001993 A1 WO 2001001993A1 CH 9900291 W CH9900291 W CH 9900291W WO 0101993 A1 WO0101993 A1 WO 0101993A1
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- glucosamine sulphate
- formulation
- formulation according
- acid
- mixed salt
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Classifications
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- 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
- A61K31/7008—Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
Definitions
- the present invention relates to a formulation of glucosamine sulphate or a mixed salt thereof in accordance with the preamble of claim 1.
- Glucosamine sulphate is a well-known substance for the treatment of rheumatic fever, pains resulting from arthrosis and arthritis and generally of all pathological conditions originating from metabolic disorders of the osteo-articular tissue
- D-Glucosamine as the active pharmaceutical compound, used in the form of a salt formed by mixing the amine with sulphuric acid, is known to combine favourable pharmaco-kinetics with its anti-inflammatory effect (for ref., cp. e g.
- glucosamine sulphate has several drawbacks which render the storage of a pharmaceutical composition thereof problematic. Solid Glucosamine sulphate is highly hygroscopic and its amino group oxidises readily. Up to now glucosamine sulphate only exists in the form of coated tablets, ampules or capsules and thus is protected from contact to oxygen In addition, the dosage of glucosamine sulphate required for treatment is considerable. The patient has to swallow three times a day 1-2 of the currently available pills, comprimates or capsules, each one comprising roughly 250 mg glucosamino sulphate.
- glucosamine sulphate In contrast, parentally applied pharmaceutical compositions of glucosamine sulphate allow to provide more than a day's dose by a single injection, though they have the disadvantage that they need to be applied by a physician and that they require local anesthesia. Thus achieving a storage-stable formulation of glucosamine sulphate is a prerequesite for therapeutic compliance.
- US-4642340 describes formation of a crystalline mixed salt of glucosamine sulphate with an alkali halide, namely sodium chloride. Formation of a mixed salt increases the chemical stability at ambient temperature and renders the glucosamine sulphate less hygroscopic.
- EP-214642 describes an improved method for formation of a mixed salt of glucosamine sulphate with alkali halides. Specifically it describes preparation of a mixed salt with potassium chloride.
- the potassium salt has the advantage of avoiding the disfavourable adiuretic effect of sodium chloride which is particularly detrimental in case of patients with cardio-vascular disease.
- the mixed salt is essentially stable over 30 days at 75% rH/20°C.
- EP-444000 describes the stabilisation of an oral dosage form of glucosamine sulphate by providing ascorbic acid as an anti-oxidant in an amount being of at least V* of that of glucosamine sulphate.
- Calcium carbonate is required as a desiccant. It compensates both for the hygroscopic nature of the glucosamine sulphate and for that of the ascorbic acid, especially in its conventional dry powder form.
- reducing agents such as ascorbic acid may be prone to slow oxidation and discoloration during storage.
- a formulation of glucosamine sulphate or a mixed salt thereof shows improved storage-stability by comprising a fruit acid .
- Fruit acid' (ace to Rompp Chemie Lexikon, ed J Falbe, M Regitz, Thieme Verlag, Stuttgart New York 1990) is a common generic term for bio-compatible carboxylic acids naturally occuring in fruits Examples are citric acid, tartric acid, glutaric, lactic, malic or gluconic acid Fruit acids are common additives in nutrition, food chemists also refer to them as ,food acids' and use them for preservation or flavoring of nutritionals They may naturally occur in a wide concentration range.
- citric or malic acid are abundant both in fruits and vegetables, whereas some as glutaric acid are naturally only occuring in certain vegetables in larger amounts
- the majority of fruit acids is found in what is considered a fruit (tables in Food chemistry, H D Belitz, W Grosch, Springer Verlag 1987), namely a seed (the zygote) surrounded by a shell or peel
- This definition includes vegetables, corns, fruits, etc
- fruits are citrus fruits
- Fruit acids in accordance with the present invention are all aliphatic, carboxylic organic acids satisfying the above mentioned definition
- the term aliphatic encompasses linear and/or branched as well as ali- and/or heterocyclic saturated compounds Besides the carboxylic groups they may bear other unsaturated functional groups
- the fruit acids have linear saturated C-chains
- all carboxylic organic acids having unsaturated C-chains such as ascorbic acid are excluded Therefore fruit acids employed in the present invention do not display the reactivity typical for olefinic bonds and are therefore more stable upon storage Whilst not intending to provide a complete theory for the stabilizing effect of the fruit acid, fruit acids encompassed by the definition of the present invention are strongly acidifying (tartric acid pK a f.
- ambient humidity may temporarily hydratize or dissolve microscopic domains in that formulation
- a pH in the range of pH 3-4, preferably of at least pH 3, is then favourable in order to prevent oxidation of the glucosamine sulphate and is not yet detrimental to the compound itself
- the fruit acid forms a mixed salt with glucosamine sulphate upon transient humidification
- the fruit acids in accordance with the present invention are readily water soluble and are therefore ideally suited for those oral dosage forms that need to be dissolved in water prior to consumption.
- a formulation in accordance with the present invention may also be stored as a liquid or a dispersion of a solid in a pasty, oily or viscous medium, e g. a solution destined for parenteral injection, a soft drink, a lotion for cutaneous application or a viscous suspension destined for oral intake
- a formulation in accordance with the present invention may also be stored as a liquid or a dispersion of a solid in a pasty, oily or viscous medium, e g. a solution destined for parenteral injection, a soft drink, a lotion for cutaneous application or a viscous suspension destined for oral intake
- fruit acids in accordance with the present invention are hydroxylated Hydroxylated fruit acids are more readily water-soluble and are more acidic, as judged by their pk a ⁇ values, due to the polarizing effect of the hydroxy groups This latter effect is most pronounced in case of the alpha-carbon atom (with regard to a carboxylic group) carrying a hydroxy group Furthermore, their multiple polar groups render them effective chelating agents for metal ions which may otherwise serve as catalysts for oxidation reactions or may induce precipitation of other compounds upon dissolving the formulation in water
- the weight ratio between the solid glucosamine sulphate or a mixed salt thereof and the fruit acid in the solid formulation is in the range of between 0 2.1 to 5 1, preferably in the range of 0 2 1 to 2 1, and most preferably in the range of between 0 5 1 0 to 1 1 0 Since always only one or two carboxyl groups per molecule contribute to the initial strong acidity, a large
- the fruit acid in accordance with the present invention has at least two carboxylic groups, since this increases the overall buffer capacity of a formulation comprising that fruit acid, renders it more acidic due to the polarizing effect of a second carbonyl moiety and renders it a more effective chelating agent
- the prefered fruit acid in accordance with the present invention is citric acid, due to its pharmaco ⁇
- the fruit acid is pure, crystalline citric acid as specified in the European Pharmacopeia
- the fruit acid is anhydrous, crystalline citric acid .
- Anhydrous' refers to a water content of crystalline citric acid of or of less than 0 5% as specified in the European Pharmacopeia This ensures minimal hygroscopicity and maximum stability of the citric acid in a storage-stable formulation with glucosamine sulphate or a
- Both the monohydrate and anhydrous crystalline citric acid have well-defined crystal geometries and are stable when stored at standard relative humidity
- the monohydrate is modifying at a temperature beyond 75°C, whereas the anhydrous form remains solid and chemically stable up to 153°C.
- the mixed salt of glucosamine sulphate employed in a formulation according to the present invention is either glucosamine sulphate 2 KCl or glucosamine sulphate HC1.
- the manufacture of a mixed salt of glucosamine sulphate having inorganic ions such as K + as cation is well-known in the art and has the advantage of reducing hygroscopicity as compared to the bare glucosamine sulphate, a variety of halide salts can be employed in the manufacture of a mixed salt of glucosamine sulphate.
- a formulation in accordance with the present invention employing a mixed salt of glucosamine sulphate combines the advantageous, stabilizing effect of the mixed salt and of the fruit acid.
- a potassium or hydro chloride mixed salt is preferable to a sodium salt due to the adverse adiuretic effect of the latter, especially for patients with cardio-vascular disease.
- a formulation in accordance with the present invention comprises an anti-oxidant, preferably up to 5% (w/w)
- the formulation comprises an additional protective agent against oxidation acting synergistically with the fruit acid.
- the formulation in accordance with the present invention is a solid, homogenous mixture. It has the appearance of a powder or granules, suitable for being used in oral dosage forms such as tablets, pills, comprimates or capsules
- the isolated glucosamine sulphate requires an ambient relativ humidity not greater than 30%, preferably not more than 10% and even more preferably not greater than 8% after or while preparing the formulation in accordance with the present invention
- An ultra-brief wetting step in a flow or spray dryer may be included in the manufacture of a specific dosage form of the formulation
- solid' refers to standard conditions
- solid stands for solids as defined in Rompp Chemie Lexikon, Eds J Falbe, Dr Regitz, 9 edition, Georg Thieme Verlag, Stuttgart, New York 1990, S 1334
- a solid formulation according to the present invention is characterized in that the production method comprises the step of spraying a mixture, comprising at least glucosamine sulphate or a mixed salt thereof and a fruit acid, preferably citric acid, with water in a spray dryer prior to drying the complete formulation to a water content of less than 1 5% (W/W)
- the granulation step in a spray dryer provides transiently the humidity to the mixture
- Glucosamine sulphate effervescent tablets with lemon flavour total weight 4 5g
- D-glucosamine sulphate di-potassium chloride is mixed with the acidic ingredients, the colorants and the flavor additives in a mixed-flow spray dryer, addition of sprayed water leads to formation of granules
- the basic ingredients are mixed alike Both granular pre-mixes are joined and mixed in the mixed-flow spray dryer
- the composition thus obtained is compressed to biplanar tabletts of 25 mm diameter (thickness 6 mm) on a high-speed tabletting machine
- a tube made of non-transparent PET is used for packaging the tablets in lots of twenty
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Abstract
A storage-stable formulation of glucosamine sulphate or a mixed salt thereof, comprising a fruit acid. In a prefered embodiment, the fruit acid, preferably citric acid, is provided in an amount roughly equal to glucosamine sulphate.
Description
A formulation of glucosamine sulphate.
The present invention relates to a formulation of glucosamine sulphate or a mixed salt thereof in accordance with the preamble of claim 1. Glucosamine sulphate is a well-known substance for the treatment of rheumatic fever, pains resulting from arthrosis and arthritis and generally of all pathological conditions originating from metabolic disorders of the osteo-articular tissue D-Glucosamine as the active pharmaceutical compound, used in the form of a salt formed by mixing the amine with sulphuric acid, is known to combine favourable pharmaco-kinetics with its anti-inflammatory effect (for ref., cp. e g. Setnikar et al., ,Pharmacokinetics of Glucosamine in the Dog and in Man', Arz- neimittelforschung, April 1986, 36(4), pp.729-735) . Methods for industrial synthesis of glucosamine sulphate are described in US 3683076 and CH 525861.
However, glucosamine sulphate has several drawbacks which render the storage of a pharmaceutical composition thereof problematic. Solid Glucosamine sulphate is highly hygroscopic and its amino group oxidises readily. Up to now glucosamine sulphate only exists in the form of coated tablets, ampules or capsules and thus is protected from contact to oxygen In addition, the dosage of glucosamine sulphate required for treatment is considerable. The patient has to swallow three times a day 1-2 of the currently available pills, comprimates or capsules, each one comprising roughly 250 mg glucosamino sulphate. In contrast, parentally applied pharmaceutical compositions of glucosamine sulphate allow to provide more than a day's dose by a single injection, though they have the disadvantage that they need to be applied by a physician and that they require local anesthesia.
Thus achieving a storage-stable formulation of glucosamine sulphate is a prerequesite for therapeutic compliance.
US-4642340 describes formation of a crystalline mixed salt of glucosamine sulphate with an alkali halide, namely sodium chloride. Formation of a mixed salt increases the chemical stability at ambient temperature and renders the glucosamine sulphate less hygroscopic.
EP-214642 describes an improved method for formation of a mixed salt of glucosamine sulphate with alkali halides. Specifically it describes preparation of a mixed salt with potassium chloride. The potassium salt has the advantage of avoiding the disfavourable adiuretic effect of sodium chloride which is particularly detrimental in case of patients with cardio-vascular disease. The mixed salt is essentially stable over 30 days at 75% rH/20°C.
It is known that anti-oxidants such as sodium hyposulfite block the oxidation of the amino function. EP-444000 describes the stabilisation of an oral dosage form of glucosamine sulphate by providing ascorbic acid as an anti-oxidant in an amount being of at least V* of that of glucosamine sulphate. Calcium carbonate is required as a desiccant. It compensates both for the hygroscopic nature of the glucosamine sulphate and for that of the ascorbic acid, especially in its conventional dry powder form. However, reducing agents such as ascorbic acid may be prone to slow oxidation and discoloration during storage.
It is an object of the present invention to overcome the drawbacks of the prior art. In particular, it is an object of the present invention to improve the storage-stability of formulations comprising glucosamine sulphate or a mixed salt thereof. In particular, it is a further object to provide a pharma-
ceutical composition destined for oral intake which comprises a one-day-dose of glucosamine sulphate This objects are solved with the features on the independent claim 1
Surprisingly it is found that a formulation of glucosamine sulphate or a mixed salt thereof shows improved storage-stability by comprising a fruit acid .
, Fruit acid' (ace to Rompp Chemie Lexikon, ed J Falbe, M Regitz, Thieme Verlag, Stuttgart New York 1990) is a common generic term for bio-compatible carboxylic acids naturally occuring in fruits Examples are citric acid, tartric acid, glutaric, lactic, malic or gluconic acid Fruit acids are common additives in nutrition, food chemists also refer to them as ,food acids' and use them for preservation or flavoring of nutritionals They may naturally occur in a wide concentration range. Some such as citric or malic acid are abundant both in fruits and vegetables, whereas some as glutaric acid are naturally only occuring in certain vegetables in larger amounts The majority of fruit acids is found in what is considered a fruit (tables in Food chemistry, H D Belitz, W Grosch, Springer Verlag 1987), namely a seed (the zygote) surrounded by a shell or peel This definition includes vegetables, corns, fruits, etc In a prefered embodiment fruits are citrus fruits
Fruit acids in accordance with the present invention are all aliphatic, carboxylic organic acids satisfying the above mentioned definition In the context of the present invention, the term aliphatic encompasses linear and/or branched as well as ali- and/or heterocyclic saturated compounds Besides the carboxylic groups they may bear other unsaturated functional groups In a prefered embodiment the fruit acids have linear saturated C-chains Thus all carboxylic organic acids having unsaturated C-chains such as ascorbic acid are excluded Therefore fruit acids employed in the present invention do not display the reactivity typical for olefinic bonds and are therefore more stable upon storage
Whilst not intending to provide a complete theory for the stabilizing effect of the fruit acid, fruit acids encompassed by the definition of the present invention are strongly acidifying (tartric acid pKaf. 2 9, citric acid pKαι 3.1 as compared to ascorbic acid p u 4.1). The pH of an aequeous solution is an important parameter for oxidation reactions, as is well known to chemists The electrochemical potential, as expressed by the Equation of Nernst, can be a function of the concentration of H+ or HjO* , respectively. In a solid formulation according to the present invention, ambient humidity may temporarily hydratize or dissolve microscopic domains in that formulation A pH in the range of pH 3-4, preferably of at least pH 3, is then favourable in order to prevent oxidation of the glucosamine sulphate and is not yet detrimental to the compound itself It is also conceivable that the fruit acid forms a mixed salt with glucosamine sulphate upon transient humidification The fruit acids in accordance with the present invention are readily water soluble and are therefore ideally suited for those oral dosage forms that need to be dissolved in water prior to consumption. However, a formulation in accordance with the present invention may also be stored as a liquid or a dispersion of a solid in a pasty, oily or viscous medium, e g. a solution destined for parenteral injection, a soft drink, a lotion for cutaneous application or a viscous suspension destined for oral intake
In a prefered embodiment, fruit acids in accordance with the present invention are hydroxylated Hydroxylated fruit acids are more readily water-soluble and are more acidic, as judged by their pkaι values, due to the polarizing effect of the hydroxy groups This latter effect is most pronounced in case of the alpha-carbon atom (with regard to a carboxylic group) carrying a hydroxy group Furthermore, their multiple polar groups render them effective chelating agents for metal ions which may otherwise serve as catalysts for oxidation reactions or may induce precipitation of other compounds upon dissolving the formulation in water
In a prefered embodiment of the invention the weight ratio between the solid glucosamine sulphate or a mixed salt thereof and the fruit acid in the solid formulation is in the range of between 0 2.1 to 5 1, preferably in the range of 0 2 1 to 2 1, and most preferably in the range of between 0 5 1 0 to 1 1 0 Since always only one or two carboxyl groups per molecule contribute to the initial strong acidity, a large amount of fruit acid provides sufficient buffer capacity and ensures maintenance of a pH in the order of 3-4, preferably around 3
Preferably the fruit acid in accordance with the present invention has at least two carboxylic groups, since this increases the overall buffer capacity of a formulation comprising that fruit acid, renders it more acidic due to the polarizing effect of a second carbonyl moiety and renders it a more effective chelating agent
The prefered fruit acid in accordance with the present invention is citric acid, due to its pharmaco¬
logical compliance, its excellent solubility (62g/l) in water , its strong acidity (pKaι 3 1 ) and its
chelating properties
Preferably, the fruit acid is pure, crystalline citric acid as specified in the European Pharmacopeia
In an even more prefered embodiment of the present invention, the fruit acid is anhydrous, crystalline citric acid .Anhydrous' refers to a water content of crystalline citric acid of or of less than 0 5% as specified in the European Pharmacopeia This ensures minimal hygroscopicity and maximum stability of the citric acid in a storage-stable formulation with glucosamine sulphate or a
mixed salt thereof Both the monohydrate and anhydrous crystalline citric acid have well-defined crystal geometries and are stable when stored at standard relative humidity The monohydrate is
modifying at a temperature beyond 75°C, whereas the anhydrous form remains solid and chemically stable up to 153°C.
In a prefered embodiment of the present invention, the mixed salt of glucosamine sulphate employed in a formulation according to the present invention is either glucosamine sulphate 2 KCl or glucosamine sulphate HC1. As outlined in the prior art, the manufacture of a mixed salt of glucosamine sulphate having inorganic ions such as K+ as cation is well-known in the art and has the advantage of reducing hygroscopicity as compared to the bare glucosamine sulphate, a variety of halide salts can be employed in the manufacture of a mixed salt of glucosamine sulphate. A formulation in accordance with the present invention employing a mixed salt of glucosamine sulphate combines the advantageous, stabilizing effect of the mixed salt and of the fruit acid. However, a potassium or hydro chloride mixed salt is preferable to a sodium salt due to the adverse adiuretic effect of the latter, especially for patients with cardio-vascular disease.
In another prefered embodiment, a formulation in accordance with the present invention comprises an anti-oxidant, preferably up to 5% (w/w) Thus the formulation comprises an additional protective agent against oxidation acting synergistically with the fruit acid.
In a preferred embodiment, the formulation in accordance with the present invention is a solid, homogenous mixture. It has the appearance of a powder or granules, suitable for being used in oral dosage forms such as tablets, pills, comprimates or capsules In the context of the present invention, the isolated glucosamine sulphate requires an ambient relativ humidity not greater than 30%, preferably not more than 10% and even more preferably not greater than 8% after or while preparing the formulation in accordance with the present invention An ultra-brief wetting step in a flow or
spray dryer may be included in the manufacture of a specific dosage form of the formulation In contrast, with regard to the final, storage-stable formulation, , solid' refers to standard conditions
The term "solid" stands for solids as defined in Rompp Chemie Lexikon, Eds J Falbe, Dr Regitz, 9 edition, Georg Thieme Verlag, Stuttgart, New York 1990, S 1334
In another prefered embodiment, a solid formulation according to the present invention is characterized in that the production method comprises the step of spraying a mixture, comprising at least glucosamine sulphate or a mixed salt thereof and a fruit acid, preferably citric acid, with water in a spray dryer prior to drying the complete formulation to a water content of less than 1 5% (W/W) The granulation step in a spray dryer (fluid bed granulator) provides transiently the humidity to the mixture
Example 1
Glucosamine sulphate effervescent tablets with lemon flavour, total weight 4 5g
Recommended daily dosage -750 mg D-glucosamine sulphate
D-glucosamine sulphate di-potassium chloride is mixed with the acidic ingredients, the colorants and the flavor additives in a mixed-flow spray dryer, addition of sprayed water leads to formation of granules In parallel, the basic ingredients are mixed alike Both granular pre-mixes are joined and mixed in the mixed-flow spray dryer The composition thus obtained is compressed to biplanar tabletts of 25 mm diameter (thickness 6 mm) on a high-speed tabletting machine A tube made of non-transparent PET is used for packaging the tablets in lots of twenty
D-glucosamine sulphate ' 2KC1 750mg
Citric acid 1662 5mg
Maltodex 270mg
Sorbitol powder 13 5mg
Saccharine 15mg
Sodium carbonate 0-50 1124mg
Colourant 30mg
Lemon flavor 635mg
Example 2
Glucosamine effervescent tablets with orange flavour, total weight 6.5g
Recommended daily dosage 1500mg D-glucosamine sulphate
The manufacture of the tabletts is identical to the procedure as described in example 1. D-glucosamine sulphateΗCl 1500mg
Citric acid 1933mg
Maltodex 390mg
Sorbitol powder 19.5mg
Saccharine 15mg
Sodium carbonate 0-13 1517.5mg
Colourant 5mg
Aromes 1120mg
Claims
1. A formulation of glucosamine sulphate or a mixed salt thereof, characterized in that it comprises a fruit acid for the improvement of the storage stability.
2. A formulation according to claim 1, characterized in that the fruit acid is hydroxylated.
3. A formulation according to claim 1 or 2, characterized in that the weight ratio between the glucosamine sulphate or a mixed salt thereof and said fruit acid is in the range of between 0.2 : 1 to 5:1, preferably in the range of between 0.2: 1 to 2:1.
4. A formulation according to claim 3 , characterized in that the weight ratio between the glucosamine sulphate or a mixed salt thereof and said fruit acid is in the range of between 0.5: 1 to 1:1.
5. A formulation according to one of the preceding claims , characterized in that the fruit acid has at least two carboxylic groups.
6. A formulation according to one of the preceding claims, characterized in that the fruit acid is citric acid.
7. A formulation according to one of the preceding claims , characterized in that the fruit acid is crystalline citric acid.
8. A formulation according to one of the preceding claims, characterized in that the fruit acid is anhydrous, crystalline citric acid.
9. A formulation according to one of the preceding claims, characterized in that the mixed salt is a glucosamine sulphate hydrochloride.
10. A formulation according to one of the preceding claims, characterized in that the mixed salt is a glucosamine sulphate potassium chloride.
11. A formulation according to one of the preceding claims, characterized in that the formulation comprises an anti-oxidant.
12. A formulation according to one of the preceding claims, characterized in that it is a solid formulation.
13. A formulation according to claim 12, characterized in that the production method comprises the step of spraying a mixture, comprising at least glucosamine sulphate or a mixed salt thereof and a fruit acid, preferably citric acid, with water in a spray dryer prior to drying the complete formulation to a water content of equal or less than 1.5% (W W) preferably equal or less than 0.5% (W/W).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CH1999/000291 WO2001001993A1 (en) | 1999-07-02 | 1999-07-02 | A formulation of glucosamine sulphate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CH1999/000291 WO2001001993A1 (en) | 1999-07-02 | 1999-07-02 | A formulation of glucosamine sulphate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2001001993A1 true WO2001001993A1 (en) | 2001-01-11 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CH1999/000291 WO2001001993A1 (en) | 1999-07-02 | 1999-07-02 | A formulation of glucosamine sulphate |
Country Status (1)
| Country | Link |
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| WO (1) | WO2001001993A1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002011894A1 (en) | 2000-08-09 | 2002-02-14 | Innovata Biomed Limited | Diaphragm |
| EP1461045A2 (en) * | 2001-12-07 | 2004-09-29 | Cargill, Incorporated | Glucosamine organic acid adducts |
| CN102276663A (en) * | 2011-05-30 | 2011-12-14 | 南京工业大学 | Preparation method of glucosamine sulfate |
| CN105193760A (en) * | 2015-10-08 | 2015-12-30 | 北京康力基生物科技有限公司 | High-content glucosamine sulfate tablet and preparation method |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6236306A (en) * | 1985-08-12 | 1987-02-17 | Taiyo Kagaku Kk | Skin-beautifying cosmetic |
| EP0444000A2 (en) * | 1990-02-22 | 1991-08-28 | Health Maintenance Programs, Inc. | Storage-stable glucosamine sulphate oral dosage forms and methods for their manufacture |
| DE19735868A1 (en) * | 1996-08-19 | 1998-02-26 | Rotta Research B V Amsterdam | Glucosamine sulphate preparation in stable crystalline form |
| WO1998046217A1 (en) * | 1997-04-16 | 1998-10-22 | Yu Ruey J | Molecular complex and control-release of alpha hydroxyacids |
| US5902801A (en) * | 1998-05-22 | 1999-05-11 | Jame Fine Chemicals, Inc. | Glucosamine sulfate metal chloride compositions and process of preparing same |
-
1999
- 1999-07-02 WO PCT/CH1999/000291 patent/WO2001001993A1/en active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6236306A (en) * | 1985-08-12 | 1987-02-17 | Taiyo Kagaku Kk | Skin-beautifying cosmetic |
| EP0444000A2 (en) * | 1990-02-22 | 1991-08-28 | Health Maintenance Programs, Inc. | Storage-stable glucosamine sulphate oral dosage forms and methods for their manufacture |
| DE19735868A1 (en) * | 1996-08-19 | 1998-02-26 | Rotta Research B V Amsterdam | Glucosamine sulphate preparation in stable crystalline form |
| WO1998046217A1 (en) * | 1997-04-16 | 1998-10-22 | Yu Ruey J | Molecular complex and control-release of alpha hydroxyacids |
| US5902801A (en) * | 1998-05-22 | 1999-05-11 | Jame Fine Chemicals, Inc. | Glucosamine sulfate metal chloride compositions and process of preparing same |
Non-Patent Citations (2)
| Title |
|---|
| CHEMICAL ABSTRACTS, vol. 107, no. 6, 10 August 1987, Columbus, Ohio, US; abstract no. 46060, XP002130451 * |
| PATENT ABSTRACTS OF JAPAN vol. 1999, no. 09 30 July 1999 (1999-07-30) * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002011894A1 (en) | 2000-08-09 | 2002-02-14 | Innovata Biomed Limited | Diaphragm |
| EP1461045A2 (en) * | 2001-12-07 | 2004-09-29 | Cargill, Incorporated | Glucosamine organic acid adducts |
| EP1461045A4 (en) * | 2001-12-07 | 2005-10-19 | Cargill Inc | Glucosamine organic acid adducts |
| CN102276663A (en) * | 2011-05-30 | 2011-12-14 | 南京工业大学 | Preparation method of glucosamine sulfate |
| CN102276663B (en) * | 2011-05-30 | 2013-09-25 | 南京工业大学 | Preparation method of glucosamine sulfate |
| CN105193760A (en) * | 2015-10-08 | 2015-12-30 | 北京康力基生物科技有限公司 | High-content glucosamine sulfate tablet and preparation method |
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