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WO2015198258A1 - Comprimé dispersible comprenant de l'acide ursodésoxycholique ou ses sels - Google Patents

Comprimé dispersible comprenant de l'acide ursodésoxycholique ou ses sels Download PDF

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Publication number
WO2015198258A1
WO2015198258A1 PCT/IB2015/054773 IB2015054773W WO2015198258A1 WO 2015198258 A1 WO2015198258 A1 WO 2015198258A1 IB 2015054773 W IB2015054773 W IB 2015054773W WO 2015198258 A1 WO2015198258 A1 WO 2015198258A1
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WO
WIPO (PCT)
Prior art keywords
ursodiol
pharmaceutically acceptable
dispersible tablet
tablet composition
tablets
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IB2015/054773
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English (en)
Inventor
Krishnamurthy TOPPALADODDI
Pradeep SHIVAKUMAR
Chaturvedi AKSHAY KANT
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.)
Shilpa Medicare Ltd
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Shilpa Medicare Ltd
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 Shilpa Medicare Ltd filed Critical Shilpa Medicare Ltd
Publication of WO2015198258A1 publication Critical patent/WO2015198258A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches

Definitions

  • the invention relates to a dispersible tablet composition
  • a dispersible tablet composition comprising a therapeutically effective amount of Ursodiol or its pharmaceutically acceptable salts thereof, with one or more pharmaceutically acceptable excipients, having disintegration time of less than 2 minutes in a dispersion medium.
  • the invention also relates to a process of preparing a dispersible tablet composition comprising a therapeutically effective amount of Ursodiol or its pharmaceutically acceptable salts thereof, with one or more pharmaceutically acceptable excipients, having disintegration time of less than 2 minutes in a dispersion medium.
  • the invention further, relates to provide a method of administering the medicament in a liquid administration form containing Ursodiol, for the treatment of Primary biliary cirrhosis in adults and geriatrics, and cholestatic hepatic diseases in infants and children.
  • PBC Primary biliary cirrhosis
  • bile is an autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts of the liver, with the intralobular ducts (Canals of Hering) affected early in the disease.
  • Canals of Hering affected early in the disease.
  • bile builds up in the liver (cholestasis) and over time damages the tissue. This can lead to scarring, fibrosis and cirrhosis. It was previously thought to be a rare disease, but more recent studies have shown that it may affect up to 1 in 3,000 people; the sex ratio is at least 9: 1 (female to male).
  • Raoul Poupon et al in US4859660 covers a method of treating primary biliary cirrhosis which comprises administering an effective amount of ursodeoxycholic acid (Ursodiol) to a patient suffering from primary biliary cirrhosis.
  • Urodiol ursodeoxycholic acid
  • Ursodeoxycholic acid is a known compound that has been used for the dissolving treatment of cholesterolic biliary lithiasis, and Raoul Poupon et al in US4859660 taught the use of Ursodiol for the treatment of primary biliary cirrhosis, and the treatment is based on the hypothesis that the symptomatology and the extent of the disease are not immunological, but are due to the toxicity of the biliary acids synthesized by the liver. These acids are involved in the lipids metabolism. The biliary acids are involved in a closed cycle of elimination by the bile and reabsorption by the intestine. When administered chronically, ursodeoxycholic acid, which is non-toxic, substitutes itself for these biliary acids which allows the elimination from the body.
  • Ursodeoxycholic acid is normally present as a minor fraction of the total bile acids in humans (about 5%). Following oral administration, the majority of Ursodeoxycholic acid is absorbed by passive diffusion and its absorption is incomplete. Once absorbed, Ursodeoxycholic acid undergoes hepatic extraction to 5 the extent of about 50% in the absence of liver disease. As the severity of liver disease increases, the extent of extraction decreases. In the liver, Ursodeoxycholic acid is conjugated with glycine or taurine, then secreted into bile. These conjugates of Ursodeoxycholic acid are absorbed in the small intestine by passive and active mechanisms.
  • the conjugates can also be deconjugated in the ileum by intestinal enzymes, leading to the formation of free ursodiol that can be reabsorbed and reconjugated in the liver.
  • Non-absorbed ursodiol passes into the colon where it is mostly 7-dehydroxylated to lithocholic acid.
  • Some Ursodeoxycholic acid is epimerized to chenodiol (CDCA) via a 7-oxo intermediate. Chenodiol also undergoes 7-dehydroxylation to form lithocholic acid. These metabolites are poorly soluble and excreted in the feces.
  • lithocholic acid A small portion of lithocholic acid is reabsorbed, conjugated in the liver with glycine, or taurine and sulfated at the 3 position.
  • the resulting sulfated lithocholic acid conjugates are excreted in bile and then lost in feces.
  • Ursodeoxycholic acid is marketed in France as DELURSAN ® 250mg tablets or RUSOLVAN ® 200mg capsules. After administration of 13 to 15 mg/kg/day of ursodeoxycholic acid to patients for 2 years, the total concentration of serum bile acids was unaltered; the percentage of patients having pruritus fell from 53 to 8%; the patients' blood bilirubin concentration became less than 34 ⁇ ; the serum alkaline phosphatase, transaminase and y-glutamyl transferase activities decreased in all the patients; and the levels of prothrombin, albumin, y-globulins and immunoglobulins M were unaltered. Results obtained during the last 5 years confirm previous results. With increased numbers of patients, it can be shown that the therapeutic effect increases with time and with no adverse effects.
  • UDCA possesses a defined role in treating patients with cholestatic liver diseases.
  • UDCA has been used in clinical practice for more than 20 years and is marketed either as oral tablets or oral capsules with different strengths typically ranging from 50 mg, 150 mg and 300 mg tablets as well as 250 mg capsules.
  • JP 6209441 covers a long acting preparation of UDCA conciting of different kinds of granules, viz a rapid release granule agent and a slow release granule agent.
  • GB 2036558 covers a UDCA formulation that releases the active principle over a prolonged period of time that is buildup of UDCA that releases immediately and UDCA with a delayed or retarded release.
  • WO2008/1130234 covers an immediate release oral pharmaceutical formulation in the form of a multiparticulate comprising between 400 to 3000 mg ursodeoxycholic acid or its pharmaceutically acceptable salt, in a monodose container and comprising a single type of particles that contain a core with said ursodeoxycholic acid, and a coating.
  • EP0599282 covers a controlled release pharmaceutical compositions for Ursodeoxycholic acid containing microgranules, wherein microgranules are prepared by extrusion-spheronization technique.
  • EP1317925 covers a taste masked microgranules for the oral administration of
  • Ursodeoxycholic acid which consists of plasticiser and copolymer of (meth) acrylic acid having a molecular weight ranging between 100,000 and 850,000.
  • EP0524395 covers a sustained release pharmaceutical compositions of Ursodeoxycholic acid containing agar, one or more substances suitable for gel formation and a basic buffer.
  • EP0625353 covers a slow-release pharmaceutical composition containing a bile acid as active ingredient and comprising at least one bioadhesive substance and at least one high specific gravity substance, and provided in the form of 0.5-2 mrn diameter coated particles or of tablets, characterized by having an aliquot enteric coated with gastro-resistant substances and the remainder non-enteric coated.
  • EP0508312 covers a controlled release pharmaceutical formulations for oral use coated by an entero-soluble gastro-resistant film containing therapeutically effective amounts of a mixture of bile acids and their salts with alkali metals or organic bases.
  • US5262172 covers a granular, microencapsulated bile acid composition for the treatment of bile acid deficiency of a mammal comprising, by weight per weight percentages based on the total weight of the composition:
  • an additional buffering agent selected from the group consisting of sodium carbonate (anhydrous), sodium bicarbonate, potassium carbonate, potassium bicarbonate, tromethamine, diethanolamine and triethanolamine;
  • a disintegrant selected from the group consisting of starch and modified starches, microcrystalline cellulose and propylene glycol alginate
  • WO2013/057741 covers a pharmaceutical composition of Ursodeoxycholic acid, wherein the composition comprises micronized Ursodeoxycholic acid having a particle size of dgo less than 25 microns and one or more pharmaceutically acceptable excipients.
  • EP0640344 covers a medicament in a liquid administration form containing ursodeoxycholic acid as the active agent, particularly for the treatment of cholestatic hepatic diseases in infants, characterized in that the liquid to be taken is a suspension prepared accompanied by the addition of a swelling and/or thickening agent, which contains the active agent mainly in a finely crystalline form as the disperse phase and only in a much smaller proportion dissolved in the aqueous dispersant.
  • the dose requirement in patients is up to 1-2 grams daily, the currently available treatments imply that the patients will need to swallow 4-8 tablets or alternatively 4 to 8 capsules daily and hence presently available dosage strengths are not optimal for this high dose treatment.
  • the currently available tablet and capsule formulations are already bulky and higher dose formulations are becoming very difficult to swallow, especially for Bed ridden patients and geriatrics, children and infants. Since, UDCA is extremely bitter-tasting and causes in most patients esophageal reflux, nausea and/or vomiting, the currently available Immediate Release tablets and capsules. Hence, substantial taste masking of the bitter taste of the drug formulation is a prerequisite.
  • a suitably taste-masked dispersible tablet comprising Ursodiol or its salts thereof, with one or more pharmaceutically acceptable excipients, having fast disintegration time in a dispersion medium, rapid onset of action and comparable bioavailability to that of commercially available Ursodiol tablets and capsules.
  • a dispersible tablet composition comprising a therapeutically effective amount of Ursodiol or its pharmaceutically acceptable salts thereof, with one or more pharmaceutically acceptable excipients, having disintegration time of less than 2 minutes in a dispersion medium.
  • It is yet an object of the present invention to provide a wet granulation process of preparing dispersible tablet composition comprising a therapeutically effective amount of Ursodiol or its pharmaceutically acceptable salts thereof, with one or more pharmaceutically acceptable excipients, having disintegration time of less than 2 minutes in a dispersion medium.
  • aspects of the present invention describes a dispersible tablet composition
  • a dispersible tablet composition comprising Ursodiol or its pharmaceutically acceptable salts thereof, with one or more pharmaceutically acceptable excipients, having ideal disintegration time and also palatable taste for masking bitter taste of Ursodiol.
  • the pharmaceutically acceptable excipients are selected from the group consisting of diluents, binders, disintegrants, wetting agents, Lubricants, glidants, sweeteners, flavouring agents and combinations thereof.
  • therapeutically effective amount means the amount of drug that when administered to a mammal for treating a state, disorder or condition, is sufficient to effect such treatment.
  • the “therapeutically effective amount” will vary depending on the compound, the disease and its severity and the age, weight, physical condition and responsiveness of the mammal to be treated.
  • the term "diluents” is intended to mean inert substances used as fillers to create the desired bulk, flow properties, and compression characteristics in the preparation of tablets and capsules.
  • Such compounds include, by way of example and without limitation, dibasic calcium phosphate, kaolin, sucrose, mannitol, microcrystalline cellulose, powdered cellulose, precipitated calcium carbonate, sorbitol, starch, Lactose monohydrate, Lactose anhydrous and combinations thereof and other such diluents known to those of ordinary skill in the art.
  • binders means excipients which are used to bring adhesion of powder particles in tablet granulations
  • binders include without limitation, acacia alginic acid, tragacanth, carboxymethylcellulose sodium, poly (vinylpyrrolidone), compressible sugar (e.g. NuTab), ethylcellulose, gelatin, liquid glucose, methylcellulose, Povidone and Pregelatinized starch, combinations thereof and other binder excipients known to those of ordinary skill in the art.
  • disintegrants is intended to mean excipients used in solid dosage forms to promote the disruption of the solid mass into smaller particles which are more readily dispersed or dissolved.
  • exemplary disintegrants include, by way of example and without limitation, Crospovidone, Sodium starch glycolate, Crosscarmellose sodium, starches such as com starch, potato starch, pregelatinized and modified starched thereof and other disintegrants known to those of ordinary skill in the art.
  • glidants is intended to mean excipients used in tablet formulations to improve flow-properties during tablet compression and to produce an anti-caking effect.
  • Such compounds include, by way of example and without limitation, include colloidal silica, calcium silicate, magnesium silicate, silicon hydrogel, cornstarch, talc, combinations thereof and other such glidants known to those of ordinary skill in the art.
  • lubricants is intended to mean excipients used in tablet formulations to reduce friction during tablet compression. Such excipients include, by way of example and without limitation, calcium stearate, magnesium stearate, mineral oil, stearic acid, zinc stearate, combinations thereof and other lubricants known to those of ordinary skill in the art.
  • sweetening agent is intended to mean excipients used to impart sweetness to a tablet containing bitter drugs.
  • excipients include, by way of example and without limitation, aspartame, dextrose, glycerin, mannitol, saccharin sodium, sorbitol, sucrose, fructose and other such materials known to those of ordinary skill in the art.
  • wetting agents are intended to mean excipients used to aid in attaining intimate contact between solid particles and liquids.
  • exemplary wetting agents include, by way of example and without limitation, Sodium lauryl sulfate, gelatin, casein, lecithin (phosphatides), gum acacia, cholesterol, tragacanth, stearic acid, benzalkonium chloride, calcium stearate, glycerol monostearate, etostearyl alcohol, cetomacrogol, emulsifying wax, sorbitan esters, polyoxyethylene alkyl ethers (e.g., macrogol ethers such as cetomacrogol 1000), polyoxyethylene castor oil derivatives, polyoxyethylene, sorbitan fatty acid esters, (e.g., TWEEN.TM.s), and other wetting agents known to those of ordinary skill in the art.
  • macrogol ethers such as cetomacrogol 1000
  • polyoxyethylene castor oil derivatives polyoxyethylene,
  • Flavoring agents are intended to mean excipients used in the formulation to improve the flavor or give a pleasant taste to the formulation. Flavoring agents are mostly restricted to the formulations in which are intended to be released in the mouth or for Dispersible tablets or chewable tablets. Exemplary Flavoring agents include, by way of example and without limitation, Mint flavour and Banana flavour, and other flavoring agents known to those of ordinary skill in the art.
  • Ursodiol or “Ursodeoxycholic acid” are intended to mean Ursodiol or its pharmaceutically acceptable salts thereof.
  • a taste masked dispersible tablet composition comprising a therapeutically effective amount of Ursodiol or its pharmaceutically acceptable salts thereof, with one or more pharmaceutically acceptable excipients, having disintegration time of less than 2 minutes in a dispersion medium selected from water, orange juice, carbonated water and breast milk.
  • the taste masking of the bitter taste of the drug is partly and/or substantially masked by the incorporation of conventional sweetening agents and flavoring agents in the dispersible tablets.
  • a dispersible tablet composition comprising a therapeutically effective amount of Ursodiol or its pharmaceutically acceptable salts thereof, with one or more pharmaceutically acceptable excipients, having disintegration time of less than 2 minutes in a dispersion medium.
  • dispersible tablet composition comprising a therapeutically effective amount of Ursodiol or its pharmaceutically acceptable salts thereof, with one or more pharmaceutically acceptable excipients, having disintegration time of less than 2 minutes in a dispersion medium, wherein the composition is prepared by wet granulation, direct compression and dry granulation.
  • a process of preparing a dispersible tablet composition comprising a therapeutically effective amount of Ursodiol, wherein the process comprising:
  • step (c) Granulate step (a) material with the binder solution of step (b).
  • step (d) Dry the wet granules of step (c) to achieve LOD in the range of 0.5-1.5%w/w;
  • step (e) Sifting the dried granules of step (d) through an appropriate sieve;
  • step (f) milling the dried granules which are sieve retentions of step (e);
  • step (j) Blend the material of step (e) and (f) with sifted materials of steps (g) and (h) in a blender.
  • step (k) Blend the material of step (i) with sifted Lubricant of step (j) in a blender.
  • step (k) The final Lubricated blend of step (k) is compressed into tablets with appropriate tablet tooling.
  • sweetening agents and flavoring agents can be incorporated in many ways as known to those of ordinary skill in the art.
  • the incorporation of these excipients may be Intragranular and/or Extragranular portions of the invention compositions.
  • a dispersible tablet composition comprising a therapeutically effective amount of Ursodiol or its pharmaceutically acceptable salts thereof, wherein the Ursodeoxycholic acid is between 50 to 500 mg.
  • compositions of Ursodiol dispersible tablets wherein the Ursodiol or its pharmaceutically acceptable salts thereof, in the form of micronized particles having a particle size of d 9 o less than 90 microns.
  • a particular embodiments of the present invention describes API particle size for the invention compositions of Ursodiol dispersible tablets, wherein the Ursodiol or its pharmaceutically acceptable salts thereof, in the form of micronized particles having a particle size of dgo less than 25 microns.
  • a dispersible tablet composition comprising a therapeutically effective amount of Ursodiol, Microcrystalline cellulose, Lactose monohydrate, Povidone, Crospovidone, Colloidal silicon dioxide, Magnesium stearate, Aspartame, Mint flavor and Banana flavor, having disintegration time of less than 2 minutes in a dispersion medium.
  • dispersible tablet must be protected from the ambient humidity.
  • the dispersible tablets should not be divided or chewed.
  • the quality of the packaging is critical to guarantee the conservation of the product.
  • Dispersible tablets are usually packed in blisters (Aluminium/PVC) or strips (aluminium). Dispersible tablets must be used immediately after removal from the blister packaging. According to present invention dissolution profiling of dispersible tablets to be followed according to the Dissolution Method for Ursodiol tablets USP.
  • the advantages provided by the invention is a dispersible tablet composition dispersible tablets composition comprising a therapeutically effective amount of Ursodiol or its pharmaceutically acceptable salts thereof, has the following advantages over conventional dosage forms:
  • Dispersble tablets remain solid until administration. This aids the stability of pharmaceutically active agent, the dose accuracy, and storage of the tablets.
  • Dispersble tablets are easy to dispense and they require minimal manipulation by health professionals and parents prior to use which minimises the risk of errors.
  • Dispersble tablets require a small amount of water for administration.
  • the present invention describes a dispersible medium for preparing the liquid medicament for the Ursodiol dispersible tablet composition, wherein the dispersible medium selected from water, orange juice, carbonated water and breast milk.
  • the volume of dispersion medium for preparing liquid medicament is about 50 ml to 100 ml of water, 250 ml of orange Juice and may also be administered using carbonated water (SODA).
  • SODA carbonated water
  • the present invention describes a preparation of the liquid medicament for the Ursodiol dispersible tablet composition, wherein the dispersible medium is 50ml of water. In one of the embodiments of the present invention, describes a preparation of the liquid medicament for the Ursodiol dispersible tablet composition, wherein the dispersible medium is breast milk for administering to infants.
  • the present invention describes a method of administering the medicament in a liquid administration form containing Ursodiol, for the treatment of Primary biliary cirrhosis in adults and geriatrics, and cholestatic hepatic diseases in infants and children.
  • step 4 Drymix the material of step 1&2 in rapid mixer granulator and granulated with binder solution of step 3.
  • step 7 Blend the material of step 7 and step 6 for 10 minutes in double cone blender.
  • step 11 Compress the lubricated final blend of step 11 using appropriate tablet tooling.
  • Tablet tooling and In-process tablet characteristics are tabulated below.
  • Time intervals 5, 10, 15, 30, 45 and 60 minutes.
  • Example 1 Ursodiol dispersible tablet composition and manufacturing process.
  • step 4 Drymix the material of step no.l & 2 in rapid mixer granulator, and granulated with binder solution of step 3.
  • step no. 7 & 8 Blend the material of step no. 7 & 8 to the material of step no. 6 for 10 minutes in double cone blender.

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  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une composition de comprimé dispersible comprenant une quantité thérapeutiquement efficace de l'ursodiol, ou de ses sels pharmaceutiquement acceptables, avec un ou plusieurs excipients pharmaceutiquement acceptables, présentant un temps de désintégration inférieur à 2 minutes dans un milieu de dispersion. L'invention concerne, en outre, un procédé d'administration du médicament dans une forme d'administration liquide, contenant de l'ursodiol, pour le traitement de la cirrhose biliaire primaire chez les adultes et les personnes âgées et de maladies hépatiques cholestatiques chez les nourrissons et les enfants.
PCT/IB2015/054773 2014-06-28 2015-06-25 Comprimé dispersible comprenant de l'acide ursodésoxycholique ou ses sels Ceased WO2015198258A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN3159/CHE/2014 2014-06-28
IN3159CH2014 2014-06-28

Publications (1)

Publication Number Publication Date
WO2015198258A1 true WO2015198258A1 (fr) 2015-12-30

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PCT/IB2015/054773 Ceased WO2015198258A1 (fr) 2014-06-28 2015-06-25 Comprimé dispersible comprenant de l'acide ursodésoxycholique ou ses sels

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114504580A (zh) * 2021-12-28 2022-05-17 湖南醇健制药科技有限公司 一种大批量制备熊去氧胆酸制剂的方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006048895A1 (fr) * 2004-11-08 2006-05-11 Rubicon Research Pvt. Ltd. Revetement pharmaceutique aqueux
CN101028274A (zh) * 2006-03-03 2007-09-05 北京奇源益德药物研究所 治疗肝胆疾病的熊去氧胆酸制剂及其制备方法
WO2008062475A2 (fr) * 2006-10-26 2008-05-29 Cadila Healthcare Limited Compositions pharmaceutiques d'ursodiol
WO2008130234A1 (fr) * 2007-04-19 2008-10-30 Disphar International B.V. Composition à dose élevée d'acide ursodésoxycholique
WO2013057741A2 (fr) * 2011-10-21 2013-04-25 Genovo Development Services Limited Compositions pharmaceutiques d'acide ursodésoxycholique
KR101401628B1 (ko) * 2012-12-24 2014-06-02 삼성제약공업주식회사 간기능 개선용 정제 및 그 제조 방법

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006048895A1 (fr) * 2004-11-08 2006-05-11 Rubicon Research Pvt. Ltd. Revetement pharmaceutique aqueux
CN101028274A (zh) * 2006-03-03 2007-09-05 北京奇源益德药物研究所 治疗肝胆疾病的熊去氧胆酸制剂及其制备方法
WO2008062475A2 (fr) * 2006-10-26 2008-05-29 Cadila Healthcare Limited Compositions pharmaceutiques d'ursodiol
WO2008130234A1 (fr) * 2007-04-19 2008-10-30 Disphar International B.V. Composition à dose élevée d'acide ursodésoxycholique
WO2013057741A2 (fr) * 2011-10-21 2013-04-25 Genovo Development Services Limited Compositions pharmaceutiques d'acide ursodésoxycholique
KR101401628B1 (ko) * 2012-12-24 2014-06-02 삼성제약공업주식회사 간기능 개선용 정제 및 그 제조 방법

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114504580A (zh) * 2021-12-28 2022-05-17 湖南醇健制药科技有限公司 一种大批量制备熊去氧胆酸制剂的方法
CN114504580B (zh) * 2021-12-28 2024-04-16 湖南醇健制药科技有限公司 一种大批量制备熊去氧胆酸制剂的方法

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