WO2014017833A1 - Formulation composite pour administration orale comprenant de la metformine et de la rosuvastatine - Google Patents

Formulation composite pour administration orale comprenant de la metformine et de la rosuvastatine Download PDF

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Publication number
WO2014017833A1
WO2014017833A1 PCT/KR2013/006637 KR2013006637W WO2014017833A1 WO 2014017833 A1 WO2014017833 A1 WO 2014017833A1 KR 2013006637 W KR2013006637 W KR 2013006637W WO 2014017833 A1 WO2014017833 A1 WO 2014017833A1
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Prior art keywords
coating layer
composite formulation
rosuvastatin
metformin
weight
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Ceased
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PCT/KR2013/006637
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English (en)
Inventor
Jin Cheul Kim
Ki Woo Jeong
Jae Ho Kim
Yong Il Kim
Jae Hyun Park
Jong Soo Woo
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Hanmi Pharmaceutical Co Ltd
Hanmi Pharmaceutical Industries Co Ltd
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Hanmi Pharmaceutical Co Ltd
Hanmi Pharmaceutical Industries Co Ltd
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Publication of WO2014017833A1 publication Critical patent/WO2014017833A1/fr
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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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • 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
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • 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
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

  • the present invention relates to a composite formulation for oral administration comprising metformin and rosuvastatin.
  • Metformin a biguanide-based antidiabetic agent
  • NIDDM non-insulin dependent diabetes mellitus
  • a glycemic control mechanism is irrelevant to insulin secretion, and it is known that such a mechanism activates a glucose transporter in the liver.
  • Metformin induces weight loss in diabetic patients, decreases the level of blood triglycerides and low density lipoprotein, and increases the level of high density lipoprotein.
  • metformin can be used as a primary drug for a non-insulin dependent diabetic patient having an insulin resistance.
  • metformin is commercially available on the market in the form of hydrochloride tablets as Glucophage ® (Merck).
  • the Glucophage ® tablet contains 250 mg, 500 mg, or 1,000 mg of metformin hydrochloride, and its administration is carried out within a range that does not exceed 2,550 mg, a maximum demand volume in consideration of both aspects of effectiveness and tolerance.
  • a side effect associated with taking metformin is a decrease of appetite, abdominal distension, nausea, diarrhea, and the like that occur in 20 to 30% of the patients who take metformin. Most side effects often clear up after 2 to 3 weeks of taking metformin transiently. However, it is preferable to stop taking metformin when diarrhea and serious abdominal distension does not clear up. In rare cases, taking metformin may cause a skin rash, hives, and the like.
  • the side effects may be avoided by decreasing the minimal dose and/or continuous dose or using a sustained release formulation capable of reducing the number of administration.
  • a conventional metformin sustained release formlation is prepared by using a polymer material or performing controlled release depending on osmotic pressure.
  • Korean Patent No. 1043816 discloses a metformin sustained release tablet using metformin, a selected hydrophobic sustained release carrier and a water-swellable polymer, in which the drug release rate is controlled by water swelling caused by a water-swellable polymer and by blocking of water permeation induced by a hydrophobic polymer.
  • Korean Patent No. 1043816 discloses a metformin sustained release tablet using metformin, a selected hydrophobic sustained release carrier and a water-swellable polymer, in which the drug release rate is controlled by water swelling caused by a water-swellable polymer and by blocking of water permeation induced by a hydrophobic polymer.
  • 0772980 discloses a sustained release formulation of metformin for oral administration containing natural gums and polyethylene oxide, which is a hydrophilic polymer, as a sustained release carrier, which is capable of maintaining a consistent blood concentration of metformin by restricting the release rate of metformin having high water solubility when being administered orally.
  • HMG-CoA reductase inhibitor such as rosuvastatin calcium salts is a 3 -hydroxy lactone ring or the corresponding ring-opened dihydroxy open acid, and is often referred to as "statin".
  • statin a single-drug therapy using statin has been used to maintain a cholesterol level within the normal range.
  • Statin suppresses a HMG-CoA reductase, which controls the rate of cholesterol production in the body, resulting in a delay in the production of cholesterol, or promotes an improvement in liver function of removing blood LDL cholesterol, and thereby reducing the level of cholesterol, and thus can be used to treat dyslipidemia and hypercholesterolemia.
  • statin when they have dyslipidemia and hypercholesterolemia. Accordingly, in case of developing a composite formulation comprising metformin and statin, which are often prescribed together, it is possible to substitute the co-administration, and thus can improve patient compliance. Also, taking the composite formulation is financially advantageous as compared with the case of taking each of the single drugs together.
  • the present inventors have conducted a thorough investigation to prepare a composite formulation for oral administration comprising metformin and rosuvastatin having excellent storage stability, and as a result, the inventors have found that it is possible to prevent physical contact between said drugs by coating metformin with a coating layer comprising a functional coating material, and then coating metformin with a coating layer comprising an alkalizing agent and rosuvastatin.
  • the formulation comprises metformin or a pharmaceutically acceptable salt thereof and rosuvastatin or a pharmaceutically acceptable salt thereof.
  • a composite formulation for oral administration comprising:
  • sustained release core comprising metformin or a pharmaceutically acceptable salt thereof and a release-controlling agent
  • a second coating layer formed on a surface of the first coating layer which comprises rosuvastatin or a pharmaceutically acceptable salt thereof and an alkalizing agent.
  • a method for preparing the composite formulation for oral administration which comprises the steps of:
  • a second coating layer on a surface of the first coating layer, which comprises rosuvastatin or a pharmaceutically acceptable salt thereof and an alkalizing agent.
  • FIGS. 1 and 2 are graphs showing the changes in rosuvastatin assays of the formulations prepared in Comparative Examples and Examples, respectively, under accelerated storage conditions;
  • FIG. 3 is a graph showing a dissolution rate of metformin depending on an assay of ethylcellulose (EC) in the coating of the formulations prepared in Comparative Examples and Examples.
  • the present invention provides a composite formulation for oral administration comprising: 1) a sustained release core comprising metformin or a pharmaceutically acceptable salt thereof and a release-controlling agent; 2) a first coating layer formed on a surface of the core, which comprises a functional coating material; and 3) a second coating layer formed on a surface of the first coating layer, which comprises rosuvastatin or a pharmaceutically acceptable salt thereof and an alkalizing agent.
  • Sustained release core comprising metformin or a pharmaceutically acceptable salt thereof
  • the sustained release core comprises metformin or a pharmaceutically acceptable salt thereof and a release-controlling agent.
  • the sustained release core comprises, as a first pharmacologically active material, metformin or a pharmaceutically acceptable salt thereof, preferably metformin hydrochloride.
  • the composite formulation may comprise metformin or a pharmaceutically acceptable salt thereof in an amount of 250 mg to 1000 mg, preferably
  • the sustained release core may comprise a release-controlling agent that is a swelling polymer, which is selected from the group consisting of hydroxypropyl methylcellulose, hydroxyethyl cellulose, methylcellulose, ethylcellulose, polyethylene oxide, guar gum, locust bean gum, and a mixture thereof, preferably hydroxypropyl methylcellulose.
  • a release-controlling agent that is a swelling polymer, which is selected from the group consisting of hydroxypropyl methylcellulose, hydroxyethyl cellulose, methylcellulose, ethylcellulose, polyethylene oxide, guar gum, locust bean gum, and a mixture thereof, preferably hydroxypropyl methylcellulose.
  • the release-controlling agent may be employed in an amount of 25 to 65% by weight, preferably 35 to 55 % by weight, based on the total weight of the core.
  • the sustained release core according to the present invention is preferably in the form of tablet, and the sustained release core in the form of tablet may be prepared by mixing metformin or a pharmaceutically acceptable salt thereof, a release-controlling agent and other pharmaceutically acceptable excipients, granulating and tableting the mixture.
  • metformin hydrochloride, hydroxypropyl methylcellulose, lactose, and polyvinylpyrrolidone are mixed; a certain amount of purified water is added and mixed; and then the mixture is dried to prepare a granular material. Subsequently, a lubricant is added to the granular material to enhance lubricating properties for a certain period of time, and then a certain compression pressure is applied to prepare a sustained release core.
  • the first coating layer is a coating layer applied onto a surface of the sustained release core which functions to minimize the production of rosuvastatin-related materials produced by the interaction between metformin and rovasutatin by avoiding physical contact of metformin and rovasutatin and to prevent migration of water, which is contained in a release-controlling agent comprised in the metformin sustained release core, into rosuvastatin.
  • the first coating layer comprises a functional (hydrophobic) coating material.
  • the first coating layer comprising a functional coating material is formed between the sustained release core comprising metformin and a second coating layer comprising rosuvastatin, i.e., on the surface of the sustained release core, so that it can prevent a decrease in the rosuvastatin assay during a storage period.
  • the functional coating material which can be used in the present invention may be selected from the group consisting of ethyl cellulose, cellulose acetate, (meth)acrylic acid copolymer (Eudragit), and a mixture thereof, preferably ethyl cellulose.
  • the functional coating material may be employed in an amount of from 16 to less than 48 % by weight, preferably 16 to 32 % by weight, based on the total weight of the first coating layer.
  • the functional coating material e.g., ethyl cellulose
  • the functional coating material may not be able to cover the whole area of the sustained release core, and thus, the assay of rosuvastatin may be reduced over a certain time period.
  • the functional coating material is used in an amount of 48 % by weight or more, drug release is delayed, and with more excessive amount used, more delay in drug release is expected.
  • the first coating layer may further comprise a general coating material known in the art, e.g., hydroxypropyl methylcellulose, hydroxypropyl cellulose, and polyvinyl alcohol in addition to the functional coating material. Moreover, if necessary, it may further comprise a pharmaceutically acceptable additive.
  • a pharmaceutically acceptable additive include a disintegrant, a diluent, a stabilizer, a binder, and a lubricant.
  • the first coating layer may be formed by applying a coating solution on to a surface of the sustained release core, which is prepared by dispersing or dissolving the functional coating material in water, ethanol, or a mixed solvent thereof, preferably a mixed solvent of water and ethanol,
  • the first coating layer may be applied on to the surface of the sustained release core in an amount of 2 parts by weight or more and preferably 4 parts to 10 parts by weight, based on 100 parts by weight of the sustained release core.
  • Second coating layer (rosuvastatin coating layer)
  • a second coating layer comprises, as a second pharmacologically active ingredient, rosuvastatin or a pharmaceutically acceptable salt thereof and an alkalizing agent.
  • rosuvastatin or the pharmaceutically acceptable salt thereof in accordance with the present invention rosuvastatin calcium is preferred, and may be employed in an amount of 1 mg to 50 mg, preferably 5 to 40 mg per unit dosage form, but not limited thereto.
  • the second coating layer comprises an alkalizing agent that suppresses the production of lactone which is the main degradation product of rosuvastatin.
  • the alkalizing agent may be selected from the group consisting of magnesium carbonate (MgC0 3 ), magnesium hydroxide (Mg(OH) 2 ), sodium bicarbonate (NaHC0 3 ), calcium carbonate (CaC0 3 ), and a mixture thereof.
  • the alkalizing agent may be employed in an amount of 2 to 8 % by weight, preferably 4 to 8 % by weight, based on the total weight of the second coating layer.
  • the alkalizing agent When the alkalizing agent is employed in an amount of more than 8 % by weight, no further suppressing effect against the production of the lactone can be achieved, but a relative assay of the coating material is reduced, so that the adhesion rate of the second coating layer is decreased.
  • the second coating layer may further comprise a general coating material such as polyethylene glycol, polyvinyl alcohol (PVA), polyvinyl alcohol-polyethylene glycol graft polymer, or a mixture thereof.
  • a general coating material such as polyethylene glycol, polyvinyl alcohol (PVA), polyvinyl alcohol-polyethylene glycol graft polymer, or a mixture thereof.
  • Said polyethylene glycol, polyvinyl alcohol, polyvinyl alcohol-polyethylene glycol graft polymer or the mixture thereof may be employed in an amount of 25 to 85% by weight, preferably 25 to 80% by weight, based on the total weight of the second coating layer.
  • the second coating layer may be prepared by dispersing or dissolving rosuvastatin or a pharmaceutically acceptable salt thereof, polyethylene glycol, polyvinyl alcohol (PVA), polyvinyl alcohol-polyethylene glycol graft polymer or a mixture thereof, and an alkalizing agent in water, ethanol, or a mixture thereof, and then applying the coating thus obtained onto the surface of the first coating layer.
  • PVA polyvinyl alcohol
  • an alkalizing agent in water, ethanol, or a mixture thereof
  • the second coating layer may be applied on to the surface of the first coating layer in an amount of 3 parts to 30 parts by weight, preferably 5 parts to 20 parts by weight, based on 100 parts by weight of the sustained release core.
  • the present invention provides a method for preparing a composite formulation for oral administration, which comprises the steps of: 1) preparing a sustained release core including metformin or a pharmaceutically acceptable salt thereof and a release-controlling agent; 2) forming a first coating layer on a surface of the core, which comprises a functional coating material; and 3) forming a second coating layer on the first coating layer, which comprises rosuvastatin or a pharmaceutically acceptable salt thereof and an alkalizing agent.
  • the present invention provides a method for preparing a composite formulation for oral administration, which comprises the steps of: 1) preparing a sustained release core by using metformin or a pharmaceutically acceptable salt thereof and a release-controlling agent according to a conventional method for preparing a tablet; 2) forming a first coating layer by applying a coating solution prepared by dissolving a functional coating material in a suitable solvent for enteric coating (e.g., a mixed solvent of ethanol and water) on to a surface of the sustained release core, and then drying; and 3) forming a second coating layer by applying a coating solution prepared by dissolving a coating material such as polyethylene glycol, polyvinyl alcohol-polyethylene glycol graft polymer, or a mixture thereof, an alkalizing agent, and rosuvastatin or a pharmaceutically acceptable salt thereof, along with any pharmaceutically acceptable additives in a suitable solvent (e.g., a mixed solvent of ethanol and water) on to the surface of the first coating layer and then drying.
  • the composite formulation for oral administration prepared in accordance with the method of the present invention can maintain the assay of rosuvastatin of 90% or more, which is the requirement set forth in International Conference on Harmonisation (ICH) Guideline, after being stored under accelerated storage conditions of 40 °C and 75% relative humidity for 6 months.
  • the composite formulation for oral administration has excellent storage stability and drug release rate, so that it can be effectively used as a composite formulation.
  • the composite formulation for oral administration of the present invention comprises two pharmacologically active components, i.e., metformin and rosuvastatin, in one tablet, and thus can be used to treat dyslipidemia and hypercholesteremia in a diabetic patient at the same time. Accordingly, the composite formulation for oral administration can reduce inconvenience that a patient takes two tablets separately and significantly improve patient compliance.
  • Step 1 Metformin sustained release core
  • Metformin hydrochloride, hydroxypropyl methylcellulose HPMC 2208 (Shin-Etsu Chemical), lactose, and polyvinyl pyrrolidone PVP K30 (BASF, Germany) were first admixed according to the composition listed in the Table 1 below. Subsequently, a certain amount of purified water was added thereto, and the mixture was mixed, and dried to obtain a granular product. Magnesium stearate was added to the prepared mixture, the mixture was modified to enhance its slip properties for 5 minutes, and then a compression pressure of 10 kN was applied to prepare a sustained release tablet.
  • Step 3 Rosuvastatin drug coating
  • Rosuvastatin calcium, polyvinyl alcohol-polyethylene glycol graft polymer (Kollicoat ® IR, BASF, Germany), magnesium carbonate and Povidone K30 (BASF, Germany) were admixed in a mixed solvent of ethanol and water according to the composition listed in Table 3 below.
  • the mixture was secondarily coated on the surface of the sustained release tablet coated with functional barrier prepared in Step 2 above using a coater (SEJONG, SFC-30), and then dried to prepare the composite formulation of the present invention.
  • SEJONG, SFC-30 a coater
  • the supply air temperature was controlled to be 45 °C and product temperature was controlled to be 30 °C.
  • the tablet was dried for 30 minutes to remove remaining ethanol and water.
  • composition of rosuvastatin drug coating Component Assay (mg)
  • Hydroxypropyl methylcelluose HPMC 2910 (Shin-Etsu, Japan), polyethylene glycol PEG 6000 (SANYO Chem., Japan), and polyvinyl pyrrolidone PVP K-30 (BASF, Germany) were admixed along with ethyl cellulose, cellulose acetate (Eastmal, USA), (meth)acrylic acid copolymer (Evonik, Germany), polyvinyl alcohol (Astro, USA), or white sugar (CJ, Korea) in a mixed solvent of ethanol and water according to a composition listed in Table 4 below.
  • the procedures of Example 1 were repeated, except that a functional barrier coated tablet was prepared by coating with the mixture by using a coater (SEJONG, SFC-30), to prepare a sustained release tablet.
  • Rosuvastatin calcium, polyvinyl alcohol-polyethylene glycol graft polymer (Kollicoat IR, BASF, Germany), and Povidone K30 (BASF, Germany) were admixed along with magnesium hydroxide (Ilyang pharmaceutical Co., LTD, Korea), sodium bicarbonate (Duksan Company, Korea) or calcium carbonate (Sankyo, Japan) in a mixed solvent of ethanol and water according to the composition listed in Table 5 below.
  • the procedures of Example 1 were repeated, except that the composite formulation of the present invention was prepared by secondarily coating the mixture on the sustained release tablet coated with the functional barrier prepared in Step 2 using a coater (SEJONG, SFC-30) and then drying, to prepare a sustained release tablet.
  • Examples 8 to 10 and Comparative Examples 6 to 8 Preparation of sustained release tablet coated with rosuvastatin using different amounts of alkalizing agents
  • a sustained release tablet was prepared by using the same method as Example 1 , except that in the rosuvastatin drug coating described in Step 3 of Example 1 , the assay of magnesium carbonate (BASF, Germany) was changed as listed in the following Table 6 to prepare the complex formulation. [Table 6]
  • Comparative Example 9 Preparation of sustained release tablet comprising metformin The procedures of Step 1 of Example 1 were repeated to prepare a sustained release tablet comprising metformin, and then a coating comprising rosuvastatin was formed as described in Step 3 of Example 1 without a functional barrier coating to prepare the sustained release tablet.
  • Example 7 The procedures of Example 1 were repeated, except that the composition of the functional barrier coating as listed in Table 7 below was used, to prepare a sustained release tablet. [Table 7]
  • Experimental Example 1 Stability of rosuvastatin according to the presence of a functional barrier coating layer
  • the formulations prepared in Comparative Examples 9 and 10 were packaged in a high density polyethylene (HDPE) bottle, and then stored under accelerated conditions of 50 °C and 75% relative humidity. After 1, 3, and 6 months of storage, the samples were taken and tested with reference to a standard and test method of Suvast (Hanmi Pharm. Co., Ltd.) that is a rosuvastatin control formulation. Specifically, 100 mg of a rosuvastatin sample was added to a 500 ml-flask and then shaken to mix thoroughly.
  • the dissolution test was performed using 900 mL of the second liquid (artificial intestinal secretion) in accordance with the dissolution test of the Korean Pharmacopoeia as a solution at 37 °C by using the Second Method (paddle method) used in dissolution test according to the Korean Pharmacopoeia.
  • Time-based dissolution solutions were collected after dissolution was initiated, and then metformin was analyzed with a high-performance liquid chromatography to measure a dissolution rate. The results are shown in Table 10 (unit: %) and FIG. 3. [Table 10]
  • the preferable amount of the EC in the functional barrier coating layer was in the range of 16 to 32% for securing an assay stability of rosuvastatin by blocking water and also for not affecting on metformin drug release.
  • Experimental Example 4 Stability of rosuvastatin depending on the type of a coating material of functional barrier coating layer
  • the assay of rosuvastatin was confirmed according to the same method as Experimental Example 1 by using the formulations prepared in Examples 3 and 4 and Comparative Examples 3 and 4. The results are shown in Table 1 1 (unit: %).

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Abstract

La présente invention concerne une formulation composite destinée à une administration orale comprenant de la metformine et de la rosuvastatine, ainsi qu'un procédé de préparation de celle-ci. La formulation composite selon l'invention présente d'excellents effets sur la prévention et le traitement de la dyslipidémie et de l'hypercholestérolémie et présente une excellente stabilité de stockage, et peut ainsi être utilisée efficacement pour le traitement de la dyslipidémie et de l'hypercholestérolémie chez un patient diabétique.
PCT/KR2013/006637 2012-07-24 2013-07-24 Formulation composite pour administration orale comprenant de la metformine et de la rosuvastatine Ceased WO2014017833A1 (fr)

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KR1020120080347A KR20140013436A (ko) 2012-07-24 2012-07-24 메트포르민 및 로수바스타틴을 포함하는 경구용 복합 제제
KR10-2012-0080347 2012-07-24

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CN104523650A (zh) * 2014-12-20 2015-04-22 山东新时代药业有限公司 一种含有瑞舒伐他汀钙的胶囊
CN106659690A (zh) * 2014-06-30 2017-05-10 韩美药品株式会社 包括含有活性成分的膜包衣层的复合制剂
RU2721406C1 (ru) * 2016-11-15 2020-05-19 ЭлДжи КЕМ, ЛТД. Лекарственный комплекс для лечения диабета 2 типа и диабетической дислипидемии

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR112016030731A2 (pt) * 2014-06-30 2017-08-22 Hanmi Pharm Ind Co Ltd Preparação de compósito, e, método de preparação de uma preparação de compósito
MY181172A (en) * 2014-06-30 2020-12-21 Hanmi Pharm Ind Co Ltd Composite preparation comprising active ingredient-containing film coating layer
KR101526825B1 (ko) * 2014-12-23 2015-06-08 주식회사 한독 당뇨병 치료용 약제학적 조성물
KR102687535B1 (ko) * 2018-07-06 2024-07-24 한미약품 주식회사 무정형의 다파글리플로진 l-프롤린을 포함하는 약학적 제제 및 이의 제조방법

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050013863A1 (en) * 2003-07-18 2005-01-20 Depomed, Inc., A Corporation Of The State Of California Dual drug dosage forms with improved separation of drugs
US20060240095A1 (en) * 2003-08-22 2006-10-26 Jean-Louis Junien Pharmaceutical composition comprising a combination of metformin and a statin
US20100330150A1 (en) * 2009-05-01 2010-12-30 Gopi Venkatesh Orally Disintegrating Tablet Compositions Comprising Combinations of High and Low-Dose Drugs
WO2011081493A2 (fr) * 2009-12-30 2011-07-07 Bcworld Pharm. Co., Ltd. Composition pharmaceutique comprenant de la metformine et de la rosuvastatine
US20110217374A1 (en) * 2009-10-09 2011-09-08 Yungjin Pharm. Co., Ltd. pharmaceutical composition simultaneously having rapid-acting property and long-acting property

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050013863A1 (en) * 2003-07-18 2005-01-20 Depomed, Inc., A Corporation Of The State Of California Dual drug dosage forms with improved separation of drugs
US20060240095A1 (en) * 2003-08-22 2006-10-26 Jean-Louis Junien Pharmaceutical composition comprising a combination of metformin and a statin
US20100330150A1 (en) * 2009-05-01 2010-12-30 Gopi Venkatesh Orally Disintegrating Tablet Compositions Comprising Combinations of High and Low-Dose Drugs
US20110217374A1 (en) * 2009-10-09 2011-09-08 Yungjin Pharm. Co., Ltd. pharmaceutical composition simultaneously having rapid-acting property and long-acting property
WO2011081493A2 (fr) * 2009-12-30 2011-07-07 Bcworld Pharm. Co., Ltd. Composition pharmaceutique comprenant de la metformine et de la rosuvastatine

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CN106659690A (zh) * 2014-06-30 2017-05-10 韩美药品株式会社 包括含有活性成分的膜包衣层的复合制剂
CN106659692A (zh) * 2014-06-30 2017-05-10 韩美药品株式会社 包括含有活性成分的膜包衣层的复合制剂
EP3162363A4 (fr) * 2014-06-30 2018-01-03 Hanmi Pharm. Co., Ltd. Préparation composite comprenant une couche de revêtement par film contenant un principe actif
EP3150201A4 (fr) * 2014-06-30 2018-01-03 Hanmi Pharm. Co., Ltd. Preparation composite comprenant une couche de revêtement pelliculaire contenant un inhibiteur de la 5-alpha-réductase, et procédé pour produire la préparation composite
CN106659690B (zh) * 2014-06-30 2020-08-18 韩美药品株式会社 包括含有活性成分的膜包衣层的复合制剂
CN106659692B (zh) * 2014-06-30 2020-08-18 韩美药品株式会社 包括含有活性成分的膜包衣层的复合制剂
CN104523650A (zh) * 2014-12-20 2015-04-22 山东新时代药业有限公司 一种含有瑞舒伐他汀钙的胶囊
CN104523650B (zh) * 2014-12-20 2017-04-12 山东新时代药业有限公司 一种含有瑞舒伐他汀钙的胶囊
RU2721406C1 (ru) * 2016-11-15 2020-05-19 ЭлДжи КЕМ, ЛТД. Лекарственный комплекс для лечения диабета 2 типа и диабетической дислипидемии

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AR092356A1 (es) 2015-04-15
UY34931A (es) 2013-09-02
TW201408283A (zh) 2014-03-01
TWI573587B (zh) 2017-03-11

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