WO2004096202A1 - Pharmaceutical formulation comprising anti-obesity agent and acidulant - Google Patents
Pharmaceutical formulation comprising anti-obesity agent and acidulant Download PDFInfo
- Publication number
- WO2004096202A1 WO2004096202A1 PCT/GB2004/001808 GB2004001808W WO2004096202A1 WO 2004096202 A1 WO2004096202 A1 WO 2004096202A1 GB 2004001808 W GB2004001808 W GB 2004001808W WO 2004096202 A1 WO2004096202 A1 WO 2004096202A1
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- WIPO (PCT)
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- pharmaceutical formulation
- sibutramine
- acidulant
- acid
- formulation according
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
Abstract
A pharmaceutical formulation comprising an anti-obesity agent, such as sibutramine, and at least one acidulant, such as fumaric acid, together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
Description
PHARMACEUTICAL FORMULATIONS
The present invention relates to pharmaceutical formulations comprising an anti- obesity agent useful in the management and treatment of obesity and related conditions.
Obesity can be defined as a condition occurring as a result of environmental, emotional and / or familial factors that have as the lowest common denominator an abnormal energy balance, usually resulting from excessive caloric intake and inadequate caloric loss. In simple terms, obesity exists when there is excess energy stored as body fat. In man, moderate obesity is present when fat accounts for more than 25% of ideal weight. The upper limit in females is about 30%. Difference in racial background and socioeconomic status appear to influence body fat, but it is often difficult to accurately distinguish the individual effects that each of the factors have.
Obesity is the most prevalent and serious nutritional disease among western countries. Approximately 300,000 deaths a year are currently associated with overweight and obesity. Obesity affects many organ systems and is a risk factor for gastrooesophageal reflux disease, nonalcoholic fatty liver disease, cholelithiasis, and colon cancer. Chronic obesity is also associated with various cardiovascular disorders, including diabetes, dyslipidemia and hypertension. Medication for the treatment of obesity act through one or more of three mechanisms:
1. Appetite suppression (eg. treatment with sibutramine, orlistat or the like); .
2. Increased metabolic activity;
3. Decreased absorption of caloric load.
Pharmacotherapy with anti-obesity agents is an important management strategy, in conjunction with lifestyle interventions.
For mild to moderate obesity, medications can be beneficial. Two medications approved by USFDA for long term obesity management are sibutramine and orlistat. Both drugs are reported to modestly reduce weight.
Orlistat, N-formyl-L-leucine (lS)-l-[[(2S,3S)-3-hexyl-4-oxo-2- oxetanyl]methyl]dodecyl ester, has the following structural formula
Orlistat is a pancreatic lipase inhibitor and as such is useful as an anti-obesity agent. Sibutramine, N- { 1 -[ 1 -(4-chlorophenyl)cyclobutyl]-3-methylbutyl} -N,N-dimethyl- amine, has the following structural formula
Sibutramine is an orally administered agent for the treatment of obesity and chemically the active ingredient is a racemic mixture of its enantiomers. Sibutramine is a serotonin - norepinephrine reuptake inhibitor indicated for the management of obesity in conjunction with a reduced calorie diet. For example, sibutramine produces its therapeutic effects by norepinephrine serotonin and dopamine reuptake inhibition. Sibutramine is an orally administered agent that primarily acts to promote a sense of satiety; this is the result of serotonin (5-hydroxytryptamine) and noradrenaline reuptake inhibition effected by the drug. Sibutramine also has a moderate effect on energy expenditure by attenuating the decrease in energy output during rest. Increased satiety (i.e. decreased energy intake) combined with increased physical activity (i.e. increased energy output), which is encouraged during therapy, should lead to an overall decrease in body weight. Sibutramine is a centrally acting agent that dose-dependently inliibits serotonin and noradrenaline reuptake. The effect of sibutramine is largely attributable to its active primary and secondary amine metabolites. The pharmacological activity of sibutramine does not appear to be a result of increased serotonin
release; this differentiates it from the actions of dexfenfluramme, which predominantly releases serotonin, and dexamphetamine, which predominantly releases dopamine and noradrenaline. Hence, the pharmacological mechanisms by which sibutramine exerts its weight loss effect are likely due to a combination of reduced appetite, feelings of satiety, and possibly the induction of themiogenesis. It's efficacy for inducing an initial-weight loss and the subsequent maintenance of the weight loss is well proven in short- and long-term clinical trials. Sibutramine is thus an established and well-proven agent for obesity, is available for use and should be considered effective in the management of patients requiring pharmacotherapy as part of the multi-modal approach to weight-loss.
The literature reports formulations of sibutramine hydrochloride and orlistat for use in the treatment of obesity and related conditions. For example, prior art sibutramine hydrochloride formulations are described in US 6162831, US 6426096, WO 01/34140, WO 01/00187, WO 01/00205 and BG106180.
More particularly, BG106180 describes pharmaceutical compositions of sibutramine hydrochloride and orlistat for the treatment of co-morbid conditions associated with obesity in a human in need of such treatment, which comprises administration to the human a therapeutically effective amount of the drug.
WO 01/00187, WO 01/00205, US 6162831 and US 6426096 describe pharmaceutical compositions of sibutramine hydrochloride alone or with other active agents for the treatment of obesity and related disorders.
WO01/34140 describes pharmaceutical formulations comprising sibutramine hydrochloride and a bulking agent for the treatment of obesity and related disorders. The bulking agent not only works as the excipient and / or aid in the formulation but also helps to have a synergistic action with the drug. This is because, when the bulk-forming agent is taken with water, this swells in a patient's stomach, giving rise to a sense of satiety and thus reducing food intake and acting as an anti-obesity agent.
Despite a large number of known formulations of sibutramine hydrochloride, for example as discussed above, there continues to exist a need for improved stable formulations of an anti-obesity agent, such as sibutramine and orlistat. To this end, it has surprisingly been found that use of sibutramine or orlistat as the free base, with acidulants (to prepare salt in situ) provides good therapeutic effect for treatment of obesity and related disorders.
Additionally, the free base is more stable compared to prior art salts, such as the hydrochloride salt, with respect to accelerated conditions of temperature and humidity.
According to the present invention, therefore, there is provided a pharmaceutical formulation comprising an anti-obesity agent, and at least one acidulant, together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
Suitably, an anti-obesity agent for use in a pharmaceutical formulation according to the present invention is selected from the group consisting of sibutramine, orlistat, pharmaceutically acceptable salts, solvates or physiologically functional derivatives thereof. h a preferred embodiment according to the present invention, there is provided a pharmaceutical formulation which is prepared from an admixture of an anti-obesity agent, present as the free base, and at least one acidulant, together with a pharmaceutically acceptable carrier, diluent or excipient therefor. Preferably, the anti-obesity agent comprises sibutramine or orlistat, especially sibutramine. In this way a salt of the anti-obesity agent and the acidulant, such as for example sibutramine fumarate, is formed in situ in the formulation.
There is further provided by the present invention, therefore, a pharmaceutical formulation which comprises an anti-obesity agent present in salt form, wherein said salt is formed from said anti-obesity agent and an acidulant, together with a pharmaceutically acceptable carrier, diluent or excipient therefor. Preferably, the anti-obesity agent comprises sibutramine or orlistat, especially sibutramine, as referred to above.
The acidulant employed in a pharmaceutical formulation according to the present invention is suitably selected to react with an anti-obesity agent, such as sibutramine or orlistat, when present as the free base, thereby forming a salt of the anti-obesity agent with the acidulant. This resulting salt form of the anti-obesity agent is stable and is substantially equivalent to prior art hydrochloride salts of anti-obesity agents, such as sibutramine hydrochloride, in terms of in vitro performance of respective formulations thereof.
An acidulant as present in a pharmaceutical formulation according to the present invention is suitably selected from the group consisting of acetic acid, citric acid anhydrous, citric acid monohydrate, fumaric acid, DL-malic acid, L-malic acid, phosphoric acid, sorbic acid, DL-tartaric acid, L-tartaric acid, succinic acid and the like. Most preferred is fumaric acid and analogues thereof.
Pharmaceutical formulations according to the present invention are preferably in the form of capsules, but it is possible to use other preparations, such as tablets, oral solution, or
the like. Suitably, 5-50 mg of an anti-obesity agent, as present in a formulation according to the present invention, when administered once daily generally provides effective therapy for obesity and related disorders.
In particular, the present invention provides capsule formulations comprising at least one anti-obesity agent together with at least one acidulant. A preferred anti-obesity agent for use in a capsule fonnulation according to the present invention is sibutramine, or analogues thereof, and substantially as hereinbefore described the acidulant is suitably selected from the group consisting of acetic acid, citric acid anhydrous, citric acid monohydrate, fumaric acid, DL-malic acid, L-malic acid, phosphoric acid, sorbic acid, DL-tartaric acid, L-tartaric acid, succinic acid and the like. Most preferred is fumaric acid and analogues thereof.
Suitably, a diluent or bulking agent is present in a capsule formulation according to the present invention and typically can provide an increase in capsule size. The artisan can utilize known methods to select the diluent, which provides good flow, better compressibility and good homogeneity as required for pharmaceutical usage. A preferred diluent is lactose or microcrystalline cellulose. Various forms of lactose are appropriate for such formulations, including anhydrous, hydrous and spray dried forms. The most desired form of lactose for use according to the present invention can be selected based on desired dissolution, content uniformity, flowability and disintegration time. The artisan can use known techniques to achieve the desired physical properties.
The artisan may further select appropriate dry binders and disintegrants using known methods. Most preferably, dry binders and disintegrants are starch and microcrystalline cellulose; however, other appropriate dry binders and disintegrants may be selected.
Further suitable binders for use in capsule formulations according to the present invention include a hydroalcoholic solution, an aqueous binder or a non-aqueous binder. A particular binder described in the Examples is isopropyl alcohol together with methylene chloride.
A capsule formulation according to the present invention may also include a hydrophobic lubricant and a suitable glidant. The artisan can select an appropriate lubricant and glidant in combination to impart good flowability to the blend to enable filling into the capsule shells. Suitable agents include talc, colloidal silicon dioxide and derivatives thereof, fatty acids and salts of fatty acids, mineral oil, and hydro genated vegetable oils. An example
of a suitable fatty acid material is stearic acid or its magnesium salt. The most preferred combination is colloidal silicon dioxide and magnesium stearate.
The present invention further comprises a process of preparing a pharmaceutical formulation substantially as herein before described, which process comprises providing an anti-obesity agent substantially as hereinbefore described, and at least one acidulant substantially as hereinbefore described, together with one or more pharmaceutically acceptable carriers, diluents or excipients therefor, in a pharmaceutical formulation. More particularly, a process of preparing a pharmaceutical formulation substantially as herein before described comprises mixing an anti-obesity agent, typically sibutramine, present as the free base, with a portion of acidulant, and at least one pharmaceutically acceptable carrier, diluent or excipient therefor, to obtain a dry mix, dissolving the remaining portion of acidulant in substantially purified water to obtain an aqueous acidulant solution, granulating the dry mix with the aqueous acidulant solution, to obtain a mass of required consistency, drying, sizing and filtering the resulting granules, and filling the granules in an appropriate capsule size.
There is also provided by the present invention sibutramine fumarate suitable for use in a pharmaceutical formulation substantially as hereinbefore described.
There is also provided by the present invention sibutramine fumarate, for use in the manufacture of a medicament for the treatment of obesity and related conditions.
There is also provided by the present invention, use of sibutramine free base, together with an acidulant substantially as hereinbefore described, for the manufacture of a medicament for the treatment of obesity and related conditions.
There is still further provided by the present invention a method of treating obesity and related conditions, which method comprises administering to a patient in need of such treatment sibutramine fumarate, or a pharmaceutical formulation, substantially as hereinbefore described.
The present invention will now be further illustrated by the following examples, which do not limit the scope of the invention in anyway.
Example 1
Procedure: Sibutramine was mixed with a portion of fumaric acid, lactose and microcrystalline cellulose in a suitable mixer for five minutes. The remaining portion of fumaric acid was dissolved in purified water. The dry mix was granulated with fumaric acid solution until a mass of suitable consistency was obtained. The granules were dried to obtain a desired LOD and were sized. The granules were then filled into appropriate capsule sizes.
Example 2
Procedure: Sibutramine was mixed with a portion of fumaric acid, lactose and microcrystalline cellulose in a suitable mixer for five minutes. The remaining portion of fumaric acid was dissolved in purified water. The dry mix was granulated with fumaric acid
solution until a mass of suitable consistency was obtained. The granules were dried to obtain a desired LOD and were sized. The granules were then filled into appropriate capsule sizes.
Example 3
Procedure: Sibutramine was mixed with a portion of fumaric acid, lactose and microcrystalline cellulose in a suitable mixer for five minutes. The remaining portion of fumaric acid was dissolved in purified water. The dry mix was granulated with fumaric acid solution until a mass of suitable consistency was obtained. The granules were dried to obtain a desired LOD and were sized. The granules were then filled into appropriate capsule sizes.
Example 4
Sibutramine Capsules 12.556 mg:
Label Claim: Each Capsule Contains:
Sibutramine Base .... 12.556mg
(equivalent to Sibutramine Hydrochloride Monohydrate ... 15 mg )
Approved colours used in empty capsule.
Batch Size: 1,00,000 capsules ( 22 Kg )
* Sibutramine (Base) to be taken on 100% assay on as such basis, weight per capsule to be adjusted by reducing microcrystalline cellulose accordingly.
Sibutramine (Base) manufactured by Cipla Ltd to be used.
(Calculations:
Sibutramine Base Mol. Wt : 279.86
Sibutramine hydrochloride Monohydrate Mol. Wt : 334.33
12.556 mg of Sibutramine Base is equivalent to 15 mg of Sibutramine hydrochloride
Monohydrate)
Example 5
Sibutramine Capsules 8.37 mg:
Label Claim: Each Capsule Contains:
Sibutramine Base .... 8.37 mg
(equivalent to Sibutramine Hydrochloride Monohydrate ... 10 mg)
Approved colours used in empty capsule.
Batch Size: 1,00,000 capsules ( 22 Kg )
*Sibutramine (Base) to be taken on 100% assay on as such basis, weight per capsule to be adjusted by reducing microcrystalline cellulose accordingly.
Sibutramine (Base) manufactured by Cipla Ltd to be used.
(Calculations:
Sibutramine Base Mol. Wt : 279.86
Sibutramine hydrochloride Monohydrate Mol. Wt : 334.33
8.37 mg of Sibutramine Base is equivalent to 10 mg of Sibutramine hydrochloride
Monohydrate)
Example 6
Sibutramine Capsules 4.185 mg:
Label Claim: Each Capsule Contains:
Sibutramine Base .... 4.185 mg
(equivalent to Sibutramine Hydrochloride Monohydrate ... 5 mg)
Approved colours used in empty capsule.
Batch Size: 1,00,000 capsules ( 11 Kg )
*Sibutramine (Base) to be taken on 100% assay on as such basis, weight per capsule to be adjusted by reducing microcrystalline cellulose accordingly.
Sibutramine (Base) manufactured by Cipla Ltd to be used.
(Calculations:
Sibutramine Base Mol. Wt : 279.86
Sibutramine hydrochloride Monohydrate Mol. Wt : 334.33
4.185 mg of Sibutramine Base is equivalent to 5 mg of Sibutramine hydrochloride
Monohydrate)
Example of DC Formula of Sibutramine base
Procedure: Sibutramine was mixed with fumaric acid, lactose and microcrystalline cellulose in a suitable mixer/blender for five minutes. The granules were filled in appropriate capsule sizes.
While the present invention is described above in connection with preferred or illustrative embodiments, these embodiments are not intended to be exhaustive or limiting of the invention. Rather, the invention is intended to cover all alternatives, modifications and equivalents included within its spirit and scope, as defined by the appended claims.
Claims
1. A pharmaceutical formulation comprising an anti-obesity agent, and at least one acidulant, together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
2. A pharmaceutical formulation according to claim 1, wherein said anti-obesity agent is selected from the group consisting of sibutramine, orlistat, pharmaceutically acceptable salts, solvates or physiologically functional derivatives thereof.
3. A pharmaceutical formulation according to claim 2, wherein said anti-obesity agent is sibutramine.
4. A pharmaceutical formulation which is prepared from an admixture of an anti-obesity agent, present as the free base, and at least one acidulant, together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
5. A pharmaceutical formulation according to claim 4, wherein the anti-obesity agent comprises sibutramine or orlistat free base.
6. A pharmaceutical formulation according to claim 5, wherein said anti-obesity agent is sibutramine free base.
7. A pharmaceutical formulation which comprises an anti-obesity agent present in salt form, wherein said salt is formed from said anti-obesity agent and an acidulant, together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
8. A pharmaceutical formulation according to claim 7, wherein said anti-obesity agent is sibutramine or orlistat.
9. A pharmaceutical formulation according to claim 8, wherein said anti-obesity agent is sibutramine.
10. A pharmaceutical formulation according to any of claims 1 to 9, wherein said acidulant is selected from the group consisting of acetic acid, citric acid anhydrous, citric acid monohydrate, fumaric acid, DL-malic acid, L-malic acid, phosphoric acid, sorbic acid, DL- tartaric acid, L-tartaric acid and succinic acid.
11. A pharmaceutical formulation according to claim 10, wherein said acidulant is fumaric acid.
12. A pharmaceutical formulation according to claim 10, wherein said acidulant is succinic acid.
13. A pharmaceutical formulation according to any of claims 1 to 12, which is an oral preparation for the treatment of obesity and related conditions.
14. A pharmaceutical formulation according to claim 13, which is a capsule or tablet formulation.
15. A pharmaceutical formulation according to claim 14, which is a capsule.
16. A pharmaceutical formulation according to any of claims 1 to 15, wherein said diluent comprises lactose and / or microcrystalline cellulose.
17. A pharmaceutical formulation according to any of claims 1 to 16, which further comprises a glidant.
18. A pharmaceutical formulation according to claim 17, wherein said glidant is selected from the group consisting of talc, colloidal silicon dioxide and derivatives thereof, fatty acids and salts of fatty acids, mineral oil, and hydrogenated vegetable oils.
19. A pharmaceutical formulation according to claim 18, wherein said glidant comprises colloidal silicon dioxide and magnesium stearate.
20. A process of preparing a pharmaceutical formulation according to any of claims 1 to 19, which process comprises providing said anti-obesity agent and said at least one acidulant, together with said one or more pharmaceutically acceptable carriers, diluents or excipients therefor, in a pharmaceutical formulation according to any of claims 1 to 19.
21. A process according to claim 20, which comprises mixing said anti-obesity agent, present as the free base, with a portion of said acidulant, and at least one pharmaceutically acceptable carrier, diluent or excipient therefor, to obtain a dry mix, dissolving the remaining portion of acidulant in substantially purified water to obtain an aqueous acidulant solution, granulating the dry mix with said aqueous acidulant solution, to obtain a mass of required consistency, drying, sizing and filtering the resulting granules, and filling the granules in an appropriate capsule size.
22. Sibutramine fumarate.
23. A pharmaceutical formulation comprises sibutramine fumarate, together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
24. Sibutramine fumarate, for use in the manufacture of a medicament for the treatment of obesity and related conditions.
25. Use of sibutramine free base, together with an acidulant, for the manufacture of a medicament for the treatment of obesity and related conditions.
26. Use according to claim 25, wherein said acidulant is selected from the group consisting of acetic acid, citric acid anhydrous, citric acid monohydrate, fumaric acid, DL- malic acid, L-malic acid, phosphoric acid, sorbic acid, DL-tartaric acid, L-tartaric acid and succinic acid.
27. Use according to claim 26, wherein said acidulant is fumaric acid.
28. Use according to claim 26, wherein said acidulant is succinic acid.
29. A method of treating obesity and related conditions, which method comprises administering to a patient in need of such treatment a therapeutically effective amount of sibutramine fumarate according to claim 22, or a pharmaceutical formulation according to any of claims 1 to 19, or 23.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP04729915A EP1622600A1 (en) | 2003-04-28 | 2004-04-28 | Pharmaceutical formulation comprising anti-obesity agent and acidulant |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN421/MUM/2003 | 2003-04-28 | ||
| IN421MU2003 | 2003-04-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2004096202A1 true WO2004096202A1 (en) | 2004-11-11 |
Family
ID=33397670
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB2004/001808 WO2004096202A1 (en) | 2003-04-28 | 2004-04-28 | Pharmaceutical formulation comprising anti-obesity agent and acidulant |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP1622600A1 (en) |
| WO (1) | WO2004096202A1 (en) |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006090999A1 (en) * | 2005-02-22 | 2006-08-31 | Ckd Bio Corp | Anhydrous sibutramine malates and preparation method thereof |
| KR100627687B1 (en) | 2005-04-20 | 2006-09-25 | 주식회사 씨티씨바이오 | Composition containing sibutramine free base and manufacturing method thereof |
| WO2006112649A1 (en) * | 2005-04-20 | 2006-10-26 | Ctc Bio, Inc. | Pharmaceutical composition containing sibutramine free base and manufacturing method thereof |
| WO2007007971A1 (en) * | 2005-07-12 | 2007-01-18 | Yuhan Corporation | Pharmaceutical compositions comprising sibutramine |
| WO2007040306A1 (en) * | 2005-08-31 | 2007-04-12 | Daewoong Pharmaceutical Co., Ltd. | A solid dispersion comprising sibutramine and surfactants, and a preparation method thereof |
| KR100763105B1 (en) * | 2006-09-07 | 2007-10-04 | 코오롱제약주식회사 | Sibutramine composition of the powders and granules type having improved solubility, its pharmaceutical preparation and method |
| KR100814384B1 (en) * | 2006-02-10 | 2008-03-18 | 대화제약 주식회사 | Pharmaceutical composition containing sibutramine salt, and manufacturing method thereof |
| US20080200536A1 (en) * | 2005-08-17 | 2008-08-21 | Boram Pharm.Co., Ltd | Pharmaceutical Formulation with High Stability and Dissolution and Manufacturing Process |
| WO2010082216A2 (en) * | 2008-12-08 | 2010-07-22 | Matrix Laboratories Ltd | Novel salts of sibutramine and their crystal forms |
| US7989500B2 (en) | 2006-09-15 | 2011-08-02 | Reviva Pharmaceuticals, Inc. | Synthesis, methods of using, and compositions of cycloalkylmethylamines |
| WO2013102195A1 (en) | 2011-12-30 | 2013-07-04 | Reviva Pharmaceuticals, Inc. | Compositions, synthesis, and methods of using phenylcycloalkylmethylamine derivatives |
| US8604244B2 (en) | 2010-07-02 | 2013-12-10 | Reviva Pharmaceuticals, Inc. | Compositions, synthesis, and methods of using cycloalkylmethylamine derivatives |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2561583C2 (en) * | 2013-07-10 | 2015-08-27 | Компания с ограниченной ответственностью ПРОМОМЕД | Pharmaceutical composition for treating and/or preventing obesity related disorders, and method of treating and/or preventing obesity related disorders |
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- 2004-04-28 EP EP04729915A patent/EP1622600A1/en not_active Withdrawn
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| US6187820B1 (en) * | 1996-09-25 | 2001-02-13 | Knoll Aktiengesellschaft | Medical treatment to improve lipid levels |
| WO2000056323A1 (en) * | 1999-03-19 | 2000-09-28 | Knoll Gmbh | Treatment of certain cancers associated with weight gain |
| WO2001034140A1 (en) * | 1999-11-06 | 2001-05-17 | Abbott Gmbh & Co. Kg | Pharmaceutical formulation |
| US20020183554A1 (en) * | 2001-04-13 | 2002-12-05 | Senanayake Chris Hugh | Methods of preparing didesmethylsibutramine and other sibutramine derivatives |
Cited By (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006090999A1 (en) * | 2005-02-22 | 2006-08-31 | Ckd Bio Corp | Anhydrous sibutramine malates and preparation method thereof |
| KR100627687B1 (en) | 2005-04-20 | 2006-09-25 | 주식회사 씨티씨바이오 | Composition containing sibutramine free base and manufacturing method thereof |
| WO2006112649A1 (en) * | 2005-04-20 | 2006-10-26 | Ctc Bio, Inc. | Pharmaceutical composition containing sibutramine free base and manufacturing method thereof |
| WO2007007971A1 (en) * | 2005-07-12 | 2007-01-18 | Yuhan Corporation | Pharmaceutical compositions comprising sibutramine |
| KR100781882B1 (en) | 2005-07-12 | 2007-12-05 | 주식회사유한양행 | A pharmaceutical composition containing sibutramine |
| US20080200536A1 (en) * | 2005-08-17 | 2008-08-21 | Boram Pharm.Co., Ltd | Pharmaceutical Formulation with High Stability and Dissolution and Manufacturing Process |
| WO2007040306A1 (en) * | 2005-08-31 | 2007-04-12 | Daewoong Pharmaceutical Co., Ltd. | A solid dispersion comprising sibutramine and surfactants, and a preparation method thereof |
| KR100814384B1 (en) * | 2006-02-10 | 2008-03-18 | 대화제약 주식회사 | Pharmaceutical composition containing sibutramine salt, and manufacturing method thereof |
| KR100763105B1 (en) * | 2006-09-07 | 2007-10-04 | 코오롱제약주식회사 | Sibutramine composition of the powders and granules type having improved solubility, its pharmaceutical preparation and method |
| US7989500B2 (en) | 2006-09-15 | 2011-08-02 | Reviva Pharmaceuticals, Inc. | Synthesis, methods of using, and compositions of cycloalkylmethylamines |
| US8338632B2 (en) | 2006-09-15 | 2012-12-25 | Reviva Pharmaceuticals, Inc. | Cycloalkylmethylamines |
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| WO2010082216A2 (en) * | 2008-12-08 | 2010-07-22 | Matrix Laboratories Ltd | Novel salts of sibutramine and their crystal forms |
| WO2010082216A3 (en) * | 2008-12-08 | 2012-06-21 | Matrix Laboratories Ltd | Novel salts of sibutramine and their crystal forms |
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| US9096515B2 (en) | 2010-07-02 | 2015-08-04 | Reviva Pharmaceuticals, Inc. | Methods of using cycloalkylmethylamine derivatives |
| WO2013102195A1 (en) | 2011-12-30 | 2013-07-04 | Reviva Pharmaceuticals, Inc. | Compositions, synthesis, and methods of using phenylcycloalkylmethylamine derivatives |
| JP2018138566A (en) * | 2011-12-30 | 2018-09-06 | レビバ ファーマシューティカルズ，インコーポレイティド | Compositions, synthesis, and methods of using phenylcycloalkylmethylamine derivatives |
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| Publication number | Publication date |
|---|---|
| EP1622600A1 (en) | 2006-02-08 |
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