EP1067967A1 - Composition de medicament contenant de la pravastatine sodique - Google Patents
Composition de medicament contenant de la pravastatine sodiqueInfo
- Publication number
- EP1067967A1 EP1067967A1 EP99912138A EP99912138A EP1067967A1 EP 1067967 A1 EP1067967 A1 EP 1067967A1 EP 99912138 A EP99912138 A EP 99912138A EP 99912138 A EP99912138 A EP 99912138A EP 1067967 A1 EP1067967 A1 EP 1067967A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- drug composition
- cellulose
- composition according
- sodium pravastatin
- amount
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/225—Polycarboxylic acids
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
Definitions
- the present invention relates to a drug composition containing sodium pravastatin and more particularly, to the drug composition containing further ⁇ -cyclodextrin as stabilizer for sodium pravastatin, thus enhancing the stability of sodium pravastatin which is unstable at high humidity and temperature.
- Hyperlipidemia is a symptom characterized by high levels of lipids (cholesterol, neutral lipid, phospholipid, free fatty acid, etc.) in the plasma, and is associated with a number of serious disorders, notably arteriosclerosis, hypertension, ischemic heart disease, pancreatitis, etc.
- sodium pravastatin among these drugs is known to be useful in the treatment of hyperlipidemia, since it serves to inhibit the activity of hydroxylmethyl glutaryl CoA reductase, which results in suppressing the synthesis of cholesterol.
- Sodium pravastatin generates its lactones and several isomers at high humidity and temperature.
- the conventional method has adopted its manufacturing process using some commonly available excipients such as lactose, silicon dioxide, sodium cross-camellose, micro-crystallized cellulose and polyvinyl pyrrolidone.
- the general drug composition contains sodium pravastatin, lactose, micro-crystallized cellulose, polyvinyl pyrrolidone, sodium cross-camellose and magnesium stearate (VIDAL, p.568(1997), ELISOR; VIDAL, pp.l750-1751(1997), VASTEN 20mg; ROTE LISTE 58 038(1996), PRAVASTIN 5mg/10mg/20mg).
- the drug composition consisting of the above excipient is rapidly degraded at high humidity and temperature.
- ⁇ - cyclodextrin may encloses molecules with a low-molecular weight which may block any substances at the surrounding environment.
- it is an object of this invention to provide a drug composition comprising sodium pravastatin, excipient, binder, lubricants, disintegrator and ⁇ -cyclodextrin, whereby enhancing the stability of sodium pravastatin which is unstable at high humidity and temperature.
- Fig. la is a graph which shows the stability of drug composition prepared according to example 1 and comparative example 1 at 40 ° C .
- Fig. lb is a graph which shows the stability of drug composition prepared according to example 1 and comparative example 1 at 50 ° C .
- Fig. lc is a graph which shows the stability of drug composition prepared according to example 1 and comparative example 1 at 60 ° C .
- Fig. Id is a graph which shows the stability of drug composition prepared according to example 1 and comparative example 1 at 70 ° C .
- Fig. 2a is a graph which shows the stability of drug composition prepared according to example 2 and comparative example 2 at 40 ° C .
- Fig. 2b is a graph which shows the stability of drug composition prepared according to example 1 and comparative example 1 at 50 ° C .
- Fig. 2c is a graph which shows the stability of drug composition prepared according to example 1 and comparative example 1 at 60 ° C .
- Fig. 2d is a graph which shows the stability of drug composition prepared according to example 1 and comparative example 1 at 70 ° C .
- Fig. 3a is a graph which shows the stability of drug composition prepared according to example 3 and comparative example 3 at 40 ° C .
- Fig. 3b is a graph which shows the stability of drug composition prepared according to example 3 and comparative example 3 at 50 ° C .
- Fig. 3c is a graph which shows the stability of drug composition prepared according to example 3 and comparative example 3 at 60 ° C .
- Fig. 3d is a graph which shows the stability of drug composition prepared according to example 3 and comparative example 3 at 70 ° C .
- Fig. 4a is a graph which shows the stability of drug composition prepared according to example 4 and comparative example 4 at 40 ° C .
- Fig. 4b is a graph which shows the stability of drug composition prepared according to example 4 and comparative example 4 at 50 ° C .
- Fig. 4c is a graph which shows the stability of drug composition prepared according to example 4 and comparative example 4 at 60 ° C .
- Fig. 4d is a graph which shows the stability of drug composition prepared according to example 4 and comparative example 4 at 70 ° C .
- Fig. 5a is a graph which shows the stability of drug composition 4 prepared according to example 5 and comparative example 5 at 40 °C .
- Fig. 5b is a graph which shows the stability of drug composition prepared according to example 5 and comparative example 5 at 50 ° C .
- Fig. 5c is a graph which shows the stability of drug composition 5 prepared according to example 5 and comparative example 5 at 60 °C .
- Fig. 5d is a graph which shows the stability of drug composition prepared according to example 5 and comparative example 5 at 70 ° C .
- Fig. 6a is a graph which shows the stability of drug composition prepared according to example 1 and comparative example 1 under accelerated l o condition (40 ° C / 75 % R.H.) at 40 ° C .
- Fig. 6b is a graph which shows the stability of drug composition prepared according to example 2 and comparative example 2 under accelerated condition (40 ° C/75% R.H.) at 40 ° C .
- Fig. 6c is a graph which shows the stability of drug composition 15 prepared according to example 3 and comparative example 3 under accelerated condition (40 ° C/75% R.H.) at 40 ° C .
- Fig. 6d is a graph which shows the stability of drug composition prepared according to example 4 and comparative example 4 under accelerated condition (40 " C / 75% R.H.) at 40 ° C .
- Fig. 6e is a graph which shows the stability of drug composition prepared according to example 5 and comparative example 5 under accelerated condition (40 ° C/75% R.H.) at 40 ° C .
- Fig. 7a is a graph which shows the stability of drug composition prepared in example 1 and A tabletTM at 40 ° C .
- Fig. 7b is a graph which shows the stability of drug composition prepared in example 1 and A tabletTM at 50 ° C .
- Fig. 7c is a graph which shows the stability of drug composition prepared in example 1 and A tabletTM at 60 ° C . 5
- Fig. 7d is a graph which shows the stability of drug composition prepared in example 1 and A tabletTM at 70 ° C .
- This invention is characterized by a drug composition
- a drug composition comprising sodium pravastatin as active ingredient and ⁇ -cyclodextrin as stabilizer as well as excipient, binder, disintegrator and lubricant.
- This invention pertains to the drug composition containing sodium pravastatin as active ingredient which has better stability in the mechanism that ⁇ -cyclodextrin encloses some molecules with a low-molecular weight to block any substances at the surrounding environment, thus preventing the rapid degradation of the drug composition at high temperature and humidity.
- the drug composition of this invention comprises the following ingredients: sodium pravastatin as active ingredient; ⁇ -cyclodextrin as stabilizer; excipient such as lactose, starch and micro-crystallized cellulose; binder such as hydroxypropyl cellulose, non-crystallized cellulose, hydroxypropyl methyl cellulose and dextrin; disintegrator such as low- substituted hydoxypropyl cellulose and sodium cross-camellose; and lubricant such as magnesium stearate, talc and stearic acid.
- the amount of sodium pravastatin as active ingredient is advantageously in the range of 2 to 50wt% in proportion to the total drug composition, preferably in the range of 2 to 30wt%, at such levels, the drug composition serves to inhibit the activity of hydroxylmethyl glutaryl CoA reductase which results in suppressing the synthesis of cholesterol. If the amount of sodium pravastatin is less than 2wt%, a drug compliance is reduced due to increased weight of tablet; however, in case of exceeding 50wt%, a dose adjustment of each patient becomes difficult.
- the sodium pravastatin is apt to form its lactones and several kinds of isomers at high humidity and temperature
- ⁇ -cyclodextrin is added to the drug composition of this invention as a stabilizer so as to prevent such structural transformations.
- the addition of ⁇ -cyclodextrin as a stabilizer according to this invention contributes to production of a drug composition with better stability at high humidity and temperature.
- the amount of -cyclodextrin is advantageously in the range of 50 to 5,000 weight parts in proportion to 100 weight parts of sodium pravastatin, preferably in the range of 100 to 3,000 weight parts. If the amount of ⁇ -cyclodextrin is less than 50 weight parts, insufficiently stabilized sodium pravastatin, is degraded at high humidity and temperature; in case of exceeding 5,000 weight parts, the formulation becomes difficult.
- the drug composition of this invention contains some additives such as excipient, binder, disintegrator and lubricant.
- the excipient of this invention is at least one selected from the group consisting of corn starch, potato starch, wheat starch, lactose, white sugar, glucose, fructose, D-mannitol, precipitated calcium carbonate, micro- crystallized cellulose, dextrin and methyl cellulose; it is preferred that the amount of excipient is in the range of 5-90wt% to the total drug composition.
- the binder of this invention is at least one selected from the group consisting of gelatin, methyl cellulose, non-crystallized cellulose, hydroxy cellulose, hydroxymethyl cellulose, glycerin, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, dextrin and polyvinyl alcohol; it is preferred 7 that the amount of binder is in the range of 2.5-35wt% to the total drug composition.
- the disintegrator of this invention is at least one selected from the group consisting of hydroxypropyl methyl cellulose, hydroxypropyl starch, polyvinyl pyrrolidone, ethyl cellulose and low-substituted hydoxypropyl cellulose; it is preferred that the amount of disintegrator is in the range of 0.5-
- the lubricant of this invention is at least one selected from the group consisting of stearic acid, magnesium stearate, talc, fluidized paraffin and rigid anhydrous silic acid; it is preferred that the amount of lubricant is in the range of 0.25-5wt% to the total drug composition. Also, some edible dye may be added to the drug composition depending on the objective of this invention.
- the drug composition comprising the aforementioned ingredients is prepared as follows: First, sodium pravastatin and ⁇ -cyclodextrin are ground in an appropriate container for tens of minutes, followed by the addition of one or more excipients. Then, for the purpose of use, the mixture is under wet granulation in the presence of a solution containing one or more binders and solvent (water, isopropanol, dichloromethane, etc.) and dried. As an alternative procedure, one or more lubricants and/ or binders are added to the mixture of sodium pravastatin and ⁇ -cyclodextrin and under drying granulation using a rolling compactor.
- the drug composition of this invention is prepared with the addition of one or more disintegrators, lubricants or binders, if deemed necessary.
- the drug composition of this invention prepared as mentioned above, comprising sodium pravastatin as an active ingredient and ⁇ - cyclodextrin as stabilizer is mixed with some pharmaceutically acceptable 8 carriers to formulate a variety of dosage forms (e.g., tablet, capsule, powder, granule and pill) in the pharmaceutical field.
- dosage forms e.g., tablet, capsule, powder, granule and pill
- the examples of the carriers according to this invention include some pharmaceutically applicable carrier such as binder, lubricant, disintegrator, excipient, stabilizer and conspergative agent.
- the concurrent use of an antacid and enteric coated tablet and granule are recommended. It is recommended that the drug composition of this invention be orally administered as a desirable route (ABPI Compendium of Data Sheets, VIDAL, ROTE LISTE, Physicians' Desk Reference).
- a dose of the active ingredient varies depending on its absorption rate, inactivation rate and excretion rate, and other variations such as age, sex and conditions of patients, severity of disease, etc.
- the regimen of the drug composition is recommended as follows: a) the usual dose of the drug composition for adult is 10-40mg per day before bedtime with initial dose of 10-20mg once daily (ABPI Compendium of Data Sheets, pp.1780- 1782(1995-1996), LIPOSTAT TABLETS). The usual dose for adult is 10-40mg and in the case of the elderly patients, the usual dose is given at the dose of less than 20mg (Physicians' Desk Reference, pp.732-735(1995), PRAVACHOL).
- Another initial dose is lOmg once per day with a maximum dose of 40mg in the evening (VIDAL, p.568(1997), ELISOR; pp.l750-1751(1997) VASTEN), while the initial dose is 5-10mg once daily with a maximum dose of 40mg (ROTE LISTE, 58 038(1996), PRAVASIN 5mg/10mg/20mg). Based on the cited references, therefore, it is preferred that the drug composition of this invention is administered at a dose of 5-40mg once daily in the evening or before bedtime.
- the drug 9 composition comprising sodium pravastatin as active ingredient and ⁇ -cyclodextrin as stabilizer, so formulated, for enclosing the active ingredient.
- the drug composition containing ⁇ -cyclodextrin shows excellent stability at high temperature and humidity (Fig. la-7d).
- Magnesium stearate 0.9mg A mixture of sodium pravastatin and ⁇ -cyclodextrin was ground in a reactor for 20 mins. With the addition of lactose, the reacting solution was well mixed and agglomerated in an aqueous solution of a binder solution (hydroxypropyl cellulose solution). The solution was dried in an oven at 30- 10
- a mixture of sodium pravastatin and ⁇ -cyclodextrin was ground in a reactor for 20 mins.
- the reacting solution was well mixed and agglomerated in an aqueous solution of a binder solution (hydroxypropyl cellulose solution).
- the solution was dried in an oven at 30-40 ° C and sized with a sieve of No. 20.
- the mixture was well mixed for its tableting process.
- a mixture of sodium pravastatin and ⁇ -cyclodextrin was ground in a 11 reactor for 20 mins.
- lactose, rigid anhydrous silicic acid and magnesium stearate 0.mg
- the reacting solution was well mixed and subjected to rolling compactor, finally preparing dried granules.
- low-substituted hydroxypropyl cellulose and magnesium stearate the mixture was well mixed for its tableting process.
- a mixture of sodium pravastatin and ⁇ -cyclodextrin was ground in a reactor for 20 mins.
- lactose and corn starch (14.0mg)
- the reacting solution was well mixed and agglomerated in an aqueous solution of a binder solution (dextrin) containing dyes (red-dye # 3 and blue-dye #1 aluminium lake), followed by drying in oven at 30-40 ° C .
- a binder solution containing dyes (red-dye # 3 and blue-dye #1 aluminium lake
- Magnesium stearate 1.6mg A mixture of sodium pravastatin and ⁇ -cyclodextrin was ground in a reactor for 20 mins. With the addition of lactose and potato starch, the reacting solution was well mixed and agglomerated in an aqueous solution of a binder solution (polyvinyl alcohol), followed by drying in oven at 30-40 °C . With the addition of magnesium stearate, the mixture was well mixed for its tableting process.
- a binder solution polyvinyl alcohol
- a mixture of sodium pravastatin and lactose was well mixed and agglomerated in an aqueous solution of a binder solution (hydroxypropyl cellulose), followed by drying in oven at 30-40 ° C . Then, the dried preparation was sized with a sieve of No. 20. With the addition of low-substituted hydroxypropyl cellulose and magnesium stearate, the mixture was well mixed for its tableting process.
- a binder solution hydroxypropyl cellulose
- a mixture of sodium pravastatin, lactose and corn starch was well mixed and agglomerated in an aqueous solution of a binder solution (hydroxypropyl cellulose), followed by drying in oven at 30-40 ° C . Then, the dried preparation was sized with a sieve of No. 20. With the addition of low- substituted hydroxypropyl cellulose and magnesium stearate, the mixture was well mixed for its tableting process.
- a binder solution hydroxypropyl cellulose
- Magnesium stearate 1.6mg
- sodium pravastatin, lactose and corn starch half of the content
- the reacting solution was well mixed and agglomerated in an aqueous solution of a binder solution (dextrin) containing dyes (red-dye # 3 and blue-dye #1 aluminium lake), followed by drying in oven at 30-40 ° C .
- a binder solution containing dyes (red-dye # 3 and blue-dye #1 aluminium lake)
- the reacting solution was well mixed and agglomerated in an aqueous solution of a binder solution (polyvinyl alcohol), followed by drying in oven at 30-40 ° C .
- a binder solution polyvinyl alcohol
- magnesium stearate With the addition of magnesium stearate, the mixture was well mixed for its tableting process.
- Test l In order to confirm the effect of this invention, final preparations were tested under rigorous temperature condition (40, 50, 60 and 70 ° C) with regard to an alteration of content and degraded products by using the following machine, and the results are shown in Table a-le and Fig. la-5d: 15
- the pharmaceutical composition of this invention comprising sodium pravastatin as active ingredient and ⁇ -cyclodextrin as stabilizer, has excellent stability at high humidity and temperature so that it prohibits the sodium pravastatin from decomposing rapidly, and may employ the existing machine in mass production, thereby improving the aspects of economics such as the additional cost for production.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Emergency Medicine (AREA)
- Nanotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Diabetes (AREA)
- Crystallography & Structural Chemistry (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
La présente invention concerne une composition de médicament contenant de la pravastatine sodique et, plus particulièrement, la composition de médicament contenant également de la cyclodextrine β en tant que stabilisant de la pravastatine sodique, améliorant ainsi la stabilité de la pravastatine sodique, laquelle est instable à une humidité et à une température élevées.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR9811172 | 1998-03-31 | ||
KR1019980011172A KR100281521B1 (ko) | 1998-03-31 | 1998-03-31 | 프라바스타틴나트륨이 함유된 약제 조성물 |
PCT/KR1999/000157 WO1999049896A1 (fr) | 1998-03-31 | 1999-03-31 | Composition de medicament contenant de la pravastatine sodique |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1067967A1 true EP1067967A1 (fr) | 2001-01-17 |
Family
ID=19535615
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP99912138A Withdrawn EP1067967A1 (fr) | 1998-03-31 | 1999-03-31 | Composition de medicament contenant de la pravastatine sodique |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP1067967A1 (fr) |
JP (1) | JP2003517432A (fr) |
KR (1) | KR100281521B1 (fr) |
CN (1) | CN1298311A (fr) |
AU (1) | AU3057099A (fr) |
CA (1) | CA2326603A1 (fr) |
WO (1) | WO1999049896A1 (fr) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4658306B2 (ja) * | 2000-10-18 | 2011-03-23 | ナガセ医薬品株式会社 | 錠剤用医薬組成物 |
WO2003055991A1 (fr) * | 2001-12-21 | 2003-07-10 | Rigshospitalet | Mobilisation de gametes et amelioration de la competence de developpement chez les mammiferes au moyen de l'inhibition de la biosynthese des sterols de novo et/ou de l'activation de la sortie des sterols |
WO2003080026A1 (fr) * | 2002-03-22 | 2003-10-02 | Ranbaxy Laboratories Limited | Systeme d'administration de medicaments a liberation controlee de pravastatine |
US20060229277A1 (en) * | 2005-04-08 | 2006-10-12 | Orbus Pharma, Inc. | Stabilized pharmaceutical compositions comprising an HMG-CoA reductase inhibitor |
EP1940391A4 (fr) * | 2005-08-05 | 2010-01-20 | Orbus Pharma Inc | Compositions pharmaceutiques a liberation prolongee, stabilisees, comprenant un inhibiteur de l'hmg-coa reductase |
US7879821B2 (en) * | 2006-01-26 | 2011-02-01 | University Of Medicine And Dentistry Of New Jersey | Method for modulating inflammatory responses by altering plasma lipid levels |
BG934U1 (bg) * | 2006-12-14 | 2007-11-30 | "Софарма" Ад | Състав за твърда лекарствена форма, съдържащ правастатин |
GB0713707D0 (en) * | 2007-07-13 | 2007-08-22 | Generics Uk Ltd | Stable compositions |
CN101580466B (zh) * | 2008-05-12 | 2012-04-04 | 上海天伟生物制药有限公司 | 一种萘维太定的钠盐的制备方法 |
JP4890657B1 (ja) * | 2011-06-03 | 2012-03-07 | 小野薬品工業株式会社 | リマプロストとβ−シクロデキストリンを含有する錠剤 |
JP2013147488A (ja) * | 2011-12-21 | 2013-08-01 | Taisho Pharmaceutical Co Ltd | 固形製剤 |
JP6088872B2 (ja) * | 2013-03-22 | 2017-03-01 | サラヤ株式会社 | ラクトン型ソホロリピッドの分解が抑制されたソホロリピッド粉末 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3223232C2 (de) * | 1982-06-22 | 1984-04-05 | Wolfgang Dipl.-Phys. Dr.-Ing. 4800 Bielefeld Lindemann | Vorschubeinrichtung an einer mit einem umlaufenden Werkzeug versehenen Maschine, wie Schäl- oder Richtmaschine, für stangenförmiges Material, wie Wellen, Draht, Rohre o.dgl. |
DD232198A1 (de) * | 1984-07-13 | 1986-01-22 | Jenapharm Veb | Verfahren zur herstellung von festen komprimaten |
US5030447A (en) * | 1988-03-31 | 1991-07-09 | E. R. Squibb & Sons, Inc. | Pharmaceutical compositions having good stability |
TW224049B (fr) * | 1991-12-31 | 1994-05-21 | Sunkyong Ind Ltd |
-
1998
- 1998-03-31 KR KR1019980011172A patent/KR100281521B1/ko not_active IP Right Cessation
-
1999
- 1999-03-31 WO PCT/KR1999/000157 patent/WO1999049896A1/fr not_active Application Discontinuation
- 1999-03-31 CA CA002326603A patent/CA2326603A1/fr not_active Abandoned
- 1999-03-31 JP JP2000540858A patent/JP2003517432A/ja active Pending
- 1999-03-31 EP EP99912138A patent/EP1067967A1/fr not_active Withdrawn
- 1999-03-31 CN CN99805551A patent/CN1298311A/zh active Pending
- 1999-03-31 AU AU30570/99A patent/AU3057099A/en not_active Abandoned
Non-Patent Citations (1)
Title |
---|
See references of WO9949896A1 * |
Also Published As
Publication number | Publication date |
---|---|
JP2003517432A (ja) | 2003-05-27 |
KR19990076302A (ko) | 1999-10-15 |
AU3057099A (en) | 1999-10-18 |
CA2326603A1 (fr) | 1999-10-07 |
WO1999049896A1 (fr) | 1999-10-07 |
CN1298311A (zh) | 2001-06-06 |
KR100281521B1 (ko) | 2001-02-15 |
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