WO2012008675A1 - Comprimé à libération prolongée contenant de la trimébutine - Google Patents

Comprimé à libération prolongée contenant de la trimébutine Download PDF

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Publication number
WO2012008675A1
WO2012008675A1 PCT/KR2011/001895 KR2011001895W WO2012008675A1 WO 2012008675 A1 WO2012008675 A1 WO 2012008675A1 KR 2011001895 W KR2011001895 W KR 2011001895W WO 2012008675 A1 WO2012008675 A1 WO 2012008675A1
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WO
WIPO (PCT)
Prior art keywords
weight
sustained
polyethylene oxide
release tablet
tablet
Prior art date
Application number
PCT/KR2011/001895
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English (en)
Korean (ko)
Inventor
어진
김창환
한창균
정현근
김양중
김종걸
박정기
Original Assignee
안국약품 주식회사
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.)
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Publication date
Application filed by 안국약품 주식회사 filed Critical 안국약품 주식회사
Priority to EA201390014A priority Critical patent/EA023139B1/ru
Publication of WO2012008675A1 publication Critical patent/WO2012008675A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • 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
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
    • 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

Definitions

  • the present invention relates to a trimebutin-containing sustained-release tablet, and more specifically, it consists of a two-layer structure of the upper layer and the lower layer adjacent to each other, wherein the upper layer and the lower layer include an active ingredient and a hydrophilic sustained-release polyethylene oxide, respectively, There is no problem such as hardness decrease or tableting disorder in the process, and further relates to a trimebutin-containing sustained-release tablet having an excellent dissolution pattern.
  • Trimebutine i.e. 3, 4, 5-trimethoxy benzoic acid 2- (dimethylamino) -2-phenylbutyl ester (3, 4, 5-trimethoxy benzoic acid-2-dimethyl amino-2-phenybutyl ester )
  • malate salts are known drugs that act on peripheral Encephalinergic receptors involved in digestion.
  • This trimebuterine is itself or in the form of a salt with maleic acid, and is used for the treatment of digestive problems such as abdominal pain, indigestion, nausea and vomiting, or irritable bowel syndrome and non-infectious gastrointestinal disorders such as constipation or diarrhea. , In the form of injections, suppositories, and suspensions for oral administration.
  • Trimebutin maleate tablets for oral administration include a core containing a carrier that enhances the release of an appropriate carrier and active ingredient, and a water-soluble temporary coating that is sufficiently effective to prevent disintegration of the core and premature release of the active ingredient.
  • Korean Patent No. 0483716 (Registration Date; 2005.04.08) has 30-60% by weight of trimebuterin or maleic acid trimerbutin, 20-40% by weight lactose, 0.1-10% by weight of calcium dihydrogen phosphate, povidone K Sustained-release tablet compositions of trimebuterine or trimebuterine maleate containing 0.1-30 wt% of lubricant, 5-25 wt% of Eudragit RL-PO as lubricants, excipients and sustained release agents are introduced.
  • trimebutin-containing sustained-release tablets have an inconvenience of being too large for patients to take since the weight of one tablet in excess of an excess sustained release mechanism is over 700 mg.
  • an object of the present invention is to solve the problems such as hardness decrease and tableting disorder, which are problems of the prior art in sustained-release tablets containing trimebuterin or salts thereof, the overall manufacturing process is simple and easy, and further, the bioavailability is It is to provide a trimebutin-containing sustained-release tablet which is the same as a conventional tablet but exhibits a more stable release pattern.
  • the weight of one tablet is designed not to exceed 500mg to improve the convenience of patients taking.
  • the release rate of the active ingredient is to maintain a constant zero-order reaction rate, while at the same time the bioavailability is to implement a sustained-release tablet at least the same as the conventional commercial product or superior to the conventional commercial product.
  • the trimebutin-containing sustained-release tablet according to the present invention is composed of an upper layer and a lower layer adjacent to each other and a film coating layer surrounding them, and includes 300 mg of maleic acid trimerbutin as an active ingredient in one tablet and has a weight of one tablet. 480-500 mg, the upper layer contains 100 to 110 parts by weight of trimeric acid maleate, 12 to 30 parts by weight of polyethylene oxide, and 6 to 20 parts by weight of hypromellose, and the lower layer contains 190 to 200 maleic acid trimerbutin. It is characterized in that the weight part, 25 to 55 parts by weight of polyethylene oxide, 10 to 35 parts by weight of hypromellose is included.
  • the trimetabutin-containing sustained-release tablet according to the present invention is 105 mg of maleic acid trimebuterin, 6.25-18.25 mg of hypromellose, 15-27 mg of polyethylene oxide, 22.75 mg of fumaric acid, 1.75 mg of hydroxypropyl cellulose, magnesium stearate
  • An upper layer composed of 7 mg and 1 mg of a coloring agent
  • Lower layer consisting of 195 mg of maleic acid trimebutin, 11.75 to 33.75 mg of hypromellose, 28 to 50 mg of polyethylene oxide, 42.25 mg of fumaric acid, 3.25 mg of hydroxypropyl cellulose, and 13 mg of magnesium stearate
  • trimebutin-containing sustained-release tablet according to the present invention exhibits the same pharmacological effect as conventional commercial tablets to be administered three or more times a day, even if administered twice a day, and at the same time, the weight of one tablet is reduced to 500 mg or less. Patients have high drug compliance.
  • the overall manufacturing process is easy by solving problems such as low hardness and tableting disorders that appear in the process of manufacturing a trimebuterin-containing tablet in the prior art, in particular, there is an effect suitable for mass production.
  • FIG. 1 is a perspective view of a sustained release tablet according to the present invention
  • Figure 2 is a graph showing the elution profile in distilled water for slow release tablets according to the present invention.
  • the trimebutin-containing sustained-release tablet according to the present invention contains 300 mg of maleic acid trimerbutin as an active ingredient in one tablet, and has a total weight of 480 to 500 mg, and includes an upper layer and a lower layer adjacent to each other and a film coating layer surrounding them.
  • the upper part contains 100 to 110 parts by weight of trimerbutane maleic acid, 12 to 30 parts by weight of polyethylene oxide, 6 to 20 parts by weight of hypromellose, and the lower layer is 190 to 200 parts by weight of maleic acid trimerbutin and 25 to 55 parts by weight of polyethylene oxide and 10 to 35 parts by weight of hypromellose are included.
  • hypomethylcellulose is an abbreviation of "hydroxypropyl methyl cellulose.”
  • the film coating layer is the same as a conventional coating layer, it is made of hypromellose and polyethylene glycol.
  • the weight of the film coating layer is preferably applied so as to about 2 to 3% with respect to the weight of the upper and lower layers.
  • Polyethylene oxide (polyethylene oxide) used as a sustained release base in the present invention is a hydrophilic material, and can play a significant role in miniaturizing the tablet size because it can significantly improve the viscosity even in a small amount compared to conventionally known sustained release bases. . It also has a very characteristic function of reducing tableting disorders such as sticking and improving the hardness of tablets.
  • the polyethylene oxide may be used POLYOX (trade name) sold by Colorcon (Colorcon), each having a different viscosity depending on the molecular weight, in the present invention, it is preferable to use a molecular weight of 300,000 to 7,000,000.
  • the present invention in order to form a double layer structure of the upper layer portion and the lower layer portion is compressed using a multilayer tablet press.
  • the sustained-release tablet according to the present invention is formed in a double layer structure of the upper layer and the lower layer, and thus can more safely and effectively control drug release as compared to the conventional single layer structure.
  • Tableting and coating Tableting the upper layer composition and the lower layer composition with a multi-layer tablet press to form an upper layer and a lower layer, and by applying a hypromellose and polyethylene glycol in a conventional manner to form a film coating layer by weight of one tablet This 500 mg sustained release tablet was prepared.
  • the upper layer and the lower layer is composed of a composition ratio as shown in Table 2 below to prepare a trimebutin-containing sustained-release tablet.
  • the upper layer and the lower layer is composed of a composition ratio as shown in Table 2 below to prepare a trimebutin-containing sustained-release tablet.
  • the maleic acid-containing sustained-release tablet according to the present invention exhibits a very ideal release pattern while maintaining a zero-order reaction rate for 8 hours after the dissolution test.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Emergency Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne un comprimé à libération prolongée contenant de la trimébutine, et plus particulièrement, un comprimé à libération prolongée contenant de la trimébutine qui présente deux couches supérieure et inférieure adjacentes formant une bicouche, chacune des couches supérieure et inférieure renfermant un principe actif ainsi qu'un polyoxyde d'éthylène comme agent hydrophile. Par ailleurs, le comprimé à libération prolongée contenant de la trimébutine ne rencontre pas de problèmes de dégradation de la dureté lors de la fabrication ou de restrictions lors de la de mise en comprimés, et présente un bon diagramme de dissolution.
PCT/KR2011/001895 2010-07-16 2011-03-18 Comprimé à libération prolongée contenant de la trimébutine WO2012008675A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EA201390014A EA023139B1 (ru) 2010-07-16 2011-03-18 Таблетка длительного высвобождения, содержащая тримебутин

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020100069014A KR101220829B1 (ko) 2010-07-16 2010-07-16 트리메부틴 함유 서방성 정제
KR10-2010-0069014 2010-07-16

Publications (1)

Publication Number Publication Date
WO2012008675A1 true WO2012008675A1 (fr) 2012-01-19

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ID=45469647

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2011/001895 WO2012008675A1 (fr) 2010-07-16 2011-03-18 Comprimé à libération prolongée contenant de la trimébutine

Country Status (3)

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KR (1) KR101220829B1 (fr)
EA (1) EA023139B1 (fr)
WO (1) WO2012008675A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101679140B1 (ko) 2015-03-10 2016-11-25 경희대학교 산학협력단 팔라듐 이온 특이적 dna 앱타머 및 이의 선별 방법

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2536254C1 (ru) * 2013-11-26 2014-12-20 Общество С Ограниченной Ответственностью "Валента-Интеллект" Таблетки-ретард с тримебутином
RU2706166C2 (ru) * 2017-11-20 2019-11-14 Общество С Ограниченной Ответственностью "Валента - Интеллект" Новые полиморфные формы тримебутина малеата, способ получения и применения
RU2770300C2 (ru) * 2019-10-17 2022-04-15 Общество С Ограниченной Ответственностью "Валента - Интеллект" Новые полиморфные формы тримебутина малеата, способ получения и применения
RU2770301C2 (ru) * 2019-10-17 2022-04-15 Общество С Ограниченной Ответственностью "Валента - Интеллект" Новые полиморфные формы тримебутина малеата, способ получения и применения

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998005320A1 (fr) * 1996-08-07 1998-02-12 Jouveinal Comprime de maleate de trimebutine pellicule
KR100483716B1 (ko) * 2002-06-26 2005-04-18 한국유나이티드제약 주식회사 트리메부틴 서방정의 조성물 및 그의 제조방법
JP2005232185A (ja) * 2003-03-06 2005-09-02 Astellas Pharma Inc 放出制御用医薬組成物およびその製造方法
US20090202634A1 (en) * 2008-01-25 2009-08-13 Grunenthal Gmbh Pharmaceutical dosage form
KR20100022219A (ko) * 2008-08-19 2010-03-02 한국콜마 주식회사 말레인산트리메부틴 서방정
KR20100037737A (ko) * 2008-10-02 2010-04-12 한국유나이티드제약 주식회사 용출률과 복용편의성이 향상된 트리메부틴 서방정

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998005320A1 (fr) * 1996-08-07 1998-02-12 Jouveinal Comprime de maleate de trimebutine pellicule
KR100483716B1 (ko) * 2002-06-26 2005-04-18 한국유나이티드제약 주식회사 트리메부틴 서방정의 조성물 및 그의 제조방법
JP2005232185A (ja) * 2003-03-06 2005-09-02 Astellas Pharma Inc 放出制御用医薬組成物およびその製造方法
US20090202634A1 (en) * 2008-01-25 2009-08-13 Grunenthal Gmbh Pharmaceutical dosage form
KR20100022219A (ko) * 2008-08-19 2010-03-02 한국콜마 주식회사 말레인산트리메부틴 서방정
KR20100037737A (ko) * 2008-10-02 2010-04-12 한국유나이티드제약 주식회사 용출률과 복용편의성이 향상된 트리메부틴 서방정

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101679140B1 (ko) 2015-03-10 2016-11-25 경희대학교 산학협력단 팔라듐 이온 특이적 dna 앱타머 및 이의 선별 방법

Also Published As

Publication number Publication date
EA023139B1 (ru) 2016-04-29
KR20120008262A (ko) 2012-01-30
KR101220829B1 (ko) 2013-01-10
EA201390014A1 (ru) 2013-12-30

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