KR20140118412A - Slow release pharmaceutical composition having Eperisone as active ingredient - Google Patents
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- 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
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- 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
- A61K47/38—Cellulose; Derivatives thereof
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
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- 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
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- 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
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- 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
- A61K9/2009—Inorganic compounds
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- 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
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- 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
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
Abstract
Description
본 발명은 활성 성분으로 에페리손을 함유하는 서방성 제제 조성물에 관한 것이다. 더욱 상세하게는 에페리손과 산성화제를 포함하는 에페리손 의약 조성물에 방출 조절제로서 하이드록시프로필메틸셀룰로오스(HPMC) 및 방출 조절 고분자를 첨가시킨 에페리손을 함유하는 서방성 제제 조성물에 관한 것이다. 본 발명의 서방성 제제 내의 에페리손 의약 조성물은 에페리손에 산성화제를 첨가시킨 저장 및 pH 환경 변화에 안정한 에페리손 의약 조성물로서 상기 에페리손 의약 조성물을 위장관 내에서 pH 변화에 안정하게 지속적으로 에페리손 활성 성분을 방출시킬 수 있는 서방성 제제 조성물에 관한 것이다.
The present invention relates to a sustained release pharmaceutical composition containing eperisone as an active ingredient. More particularly, the present invention relates to a sustained-release pharmaceutical composition containing eperisone in which hydroxypropyl methylcellulose (HPMC) and a release-controlling polymer are added as a release-controlling agent to eperisone pharmaceutical compositions containing eperisone and an acidifying agent. The epherzone pharmaceutical composition in the sustained-release preparation of the present invention is an epherissone pharmaceutical composition which is stable to storage and pH change by adding an acidifying agent to epherison. The epherison pharmaceutical composition is continuously and continuously adjusted to pH change in the gastrointestinal tract, To a sustained release pharmaceutical composition capable of releasing an active ingredient.
에페리손(Eperisone)은 하기 화학식 1로 표시되는 근골격계 평활근 및 혈관계 평활근에 이완제로 작용하여 근골격계 질환에 수반되는 동통성 근육연축을 비롯한 신경계 질환에 의한 경직성 마비의 치료에 사용되는 약물이며 혈액 내 반감기가 짧아서 현재로서는 1일 용량 50∼150mg을 1일 3회 복용하는 제품이 시판되고 있다.
Eperisone is a drug used as a relaxing agent for musculoskeletal smooth muscle and vascular smooth muscle of the following formula (1), and is used for the treatment of a rigid paralysis caused by neurological diseases including painful muscle spasm accompanied by musculoskeletal diseases. At present, a product that takes 50-150 mg daily dose three times a day is on the market.
[화학식 1][Chemical Formula 1]
상기와 같은 화학 구조를 지닌 에페리손은 알칼리 환경에서 피페리딘 고리가 쉽게 개환될 수 있는 이유로 pH 안정성에 문제가 있다. 또한 상기 약물을 제제화하여 보관 시에도 경시 변화에 따른 저장 안정성의 문제가 있었던 것이다.
Eperisone having such a chemical structure has a problem in pH stability because the piperidine ring can be easily opened in an alkaline environment. In addition, there was a problem of storage stability due to changes over time even when the medicines were prepared and stored.
따라서 이러한 pH 안정성 및 저장 안정성의 개선을 위해 에페리손 조성물의 개발이 진행되어왔고 특히 에페리손에 산성 pH 조절제를 첨가시킨 서방성 의약 조성물이 개시되어 왔다.
Therefore, development of an epherrison composition has been advanced to improve the pH stability and storage stability, and a sustained-release pharmaceutical composition in which an acidic pH regulator is added to epherison has been disclosed.
대한민국 특허등록 제10-1156054호 '안정한 에페리손 함유 서방성 의약 조성물'에서는 카보머, 시트르산 등의 특정 종류의 산성화제를 포함시켜 pH 5.6 이하 범위로 제제화 함으로써 제제의 장기 보관 안정성과 위장관내에서 장시간 체류해야 하는 서방성 제제의 특성상 pH 변화 등의 극한 환경에서도 용출 특성의 변화없이 주성분 분해를 억제할 수 있는 에페리손 서방성 의약 조성물을 개시하고 있다.
Korean Patent Registration No. 10-1156054 'Stable eperrissone-containing sustained-release pharmaceutical composition' contains a specific type of acidifying agent such as carbomer and citric acid and is formulated in a pH range of 5.6 or less to provide long-term storage stability of the preparation, Discloses a sustained-release pharmaceutical composition of effervescence capable of inhibiting the decomposition of the main component without changing the elution characteristics even in an extreme environment such as a pH change due to the characteristics of the sustained-release preparation to be retained.
또한 상기 특허문헌에서는 산성 pH 조절제 또는 물에 현탁, 용해, 팽윤 또는 혼화되었을 때 pH 5.0 이하를 나타내는 부형제 중에서 선택된 산성화제를 포함하며, 0.5%(W/V) 수성용액으로 제조했을 때의 산도가 pH 0.5∼5.6인 것을 특징으로 하는 안정한 에페리손 함유 서방성 의약조성물을 개시하고 있으며 이때 사용되는 산성 pH 조절제로서는 알긴산, 아세트산, 포름산, 아디프산, 에데트산, 푸마르산, 젖산, 말산, 말레산, 팔미트산, 프로피온산, 소르빈산, 스테아르산, 주석산, 아스코르빈산, 에리소르빈산, 시트르산, 옥살산, 숙신산, 톨루엔설폰산, 메탄설폰산, 질산, 염산, 인산 및 황산으로 이루어진 그룹 중에서 선택된 1종 이상을 개시하고 있다.
In addition, the patent literature discloses acidic pH adjusting agents or acidifying agents selected from excipients which exhibit a pH of less than 5.0 when suspended, dissolved, swollen or miscible in water, and the acidity when prepared in a 0.5% (w / v) wherein the acidic pH controlling agent is selected from the group consisting of alginic acid, acetic acid, formic acid, adipic acid, edetic acid, fumaric acid, lactic acid, malic acid, maleic acid, At least one member selected from the group consisting of hydrochloric acid, hydrobromic acid, phosphoric acid, maleic acid, palmitic acid, propionic acid, sorbic acid, stearic acid, tartaric acid, ascorbic acid, erosorbic acid, citric acid, oxalic acid, succinic acid, toluenesulfonic acid, methanesulfonic acid, Lt; / RTI >
한편으로는 에페리손 함유 서방형 제제의 개발도 진행되고 있는 바, 대한민국 공개특허공보 10-2012-52080호 '에페리손 함유 서방정 및 이의 제조방법'에서는 에페리손에 폴리비닐아세테이트, 비닐피롤리돈-비닐아세테이트 공중합체 및 하이드록시프로필메틸셀룰로스를 포함한 서방정 형태의 조성물이 개시되어 있다.
On the other hand, the development of a sustained-release preparation containing epsilon is also under way. Korean Patent Laid-Open Publication No. 10-2012-52080 entitled " Epsilon-containing sustained release tablet and its preparation method ", discloses that polyphenylacetate, Vinyl acetate copolymer and hydroxypropylmethylcellulose is disclosed.
그러나 다양한 환경에 장시간 노출되어도 에페리손 염산염의 안정성에 문제가 없는 저장 및 pH 안정성이 개선된 에페리손 의약 조성물의 개발은 충분치 않은 바, 이러한 에페리손 염산염의 안정성 저하 문제로 에페리손 방출을 지연시켜 서방성 제형으로서의 완전한 개발이 어려웠던 것이다.
However, development of a pharmaceutical composition of eferissone improved in storage stability and pH stability which does not cause any problem in the stability of eferrizone hydrochloride even after prolonged exposure to various environments is not sufficient. As a result of such a problem of lowering the stability of eferrizone hydrochloride, It was difficult to completely develop it as a sexual preparation.
이에 본 발명자들은 본 출원과 동일자로 출원된 '저장 및 pH 안정성이 개선된 에페리손 의약 조성물'에서 에페리손의 저장 및 pH 안정성을 개선시키기 위해 에페리손에 D-글루카르산, D-글루코아스코르브산, 글루콘산, D-글루쿠론산, 글루코노락톤, 글루쿠로노락톤, 글루탐산, 이타콘산, 카페인산, 글리시리진산, 에탄술폰산, 벤젠술폰산, 데하이드로아스코르브산, 살리실산, 살리실술폰산, 몰식자산, 니코틴산 또는 클로로겐산에서 선택된 1종 이상의 산을 산성화제로 첨가하고 에페리손과 산성화제 간의 안정적 조성을 형성하기 위해 폴리비닐피롤리돈을 결합제로 첨가시킨 에페리손 의약 조성물을 특허 출원하여 개시한 바 있다.
Therefore, the inventors of the present application filed a patent application entitled " Ephrisson medicinal composition with improved storage and pH stability " filed in the same name as the present application, to improve the storage and pH stability of eferissone in Dessellone with D-glucuronic acid, D- Glucuronic acid, ethanesulfonic acid, benzenesulfonic acid, dehydroascorbic acid, salicylic acid, salicylsulfonic acid, gallic acid, glutaric acid, gluconic acid, gluconic acid, gluconic acid, gluconic acid, gluconic acid, gluconolactone, glucuronolactone, glutamic acid, itaconic acid, caffeic acid, Patent application for a pharmaceutical composition of epherrison in which polyvinylpyrrolidone is added as a binding agent in order to add at least one acid selected from nicotinic acid or chlorogenic acid as an acidifying agent and to form a stable composition between epherison and an acidic agent has been filed and patented.
한편, 통상 시판되고 있는 에페리손은 1일 3회 용량으로 복용하게 제조되고 있으나 에페리손 제제와 병용 처방되는 비-스테로이드성 소염진통제(NSAID)의 경우 통상 1일 2회 용량으로 복용하게 되어있는 바 상호간 투여 회수가 일치하지 않음에 따라 병용 처방시 환자들의 복약 순응도가 낮아지는 경향이 있어 1일 2회 용량으로 복용할 수 있는 에페리손 서방성 제제의 개발이 더욱 요구되어 왔던 것이다.
On the other hand, the commercially available eperisone is prepared to be taken at a dose of three times a day, but in the case of a non-steroidal anti-inflammatory analgesic (NSAID) prescribed in combination with an eperisone preparation, Because of the inconsistency of reciprocal doses, patients' compliance with the prescription of medication tends to be lowered. Therefore, it has been demanded to develop an ephedrine sustained release preparation which can be taken twice a day.
따라서 본 발명자들은 본 발명자들이 이미 개발한 에페리손에 산성화제와 폴리비닐피롤리돈 결합제를 첨가시킨 에페리손 의약 조성물에 방출 조절제로서 하이드록시프로필메틸셀룰로오스(HPMC)와 방출 조절 고분자를 첨가시킨 에페리손을 함유하는 서방성 제제 조성물을 개발함으로써 본 발명을 완성하게 된 것이다.
Therefore, the inventors of the present invention have found that the present inventors have found that the present invention can provide a pharmaceutical composition containing an acidic agent and a polyvinylpyrrolidone, The present invention has been completed.
본 발명이 해결하고자 하는 과제는 1일 2회 용량으로 복용 가능한 서방출 특성을 갖는 에페리손 함유 서방성 제제를 개발코자 한 것으로, 본 발명자들이 이미 개발한 에페리손에 산성화제와 결합제를 첨가시킨 에페리손 의약 조성물에 방출 조절제로서 하이드록시프로필메틸셀룰로오스(HPMC)와 방출 조절 고분자를 첨가시킨 에페리손을 함유하는 서방성 제제 조성물을 개발코자 한 것이다.
SUMMARY OF THE INVENTION The object of the present invention is to develop a sustained-release preparation containing epsilon with a sustained-release property which can be taken twice a day, and the present inventors have developed an ephesolone having an acidifying agent and a binder It is intended to develop a sustained release pharmaceutical composition containing epherrisone in which hydroxypropylmethylcellulose (HPMC) and a release-controlling polymer are added as a release modifying agent to a lysone drug composition.
본 발명의 목적은 저장 및 pH 안정성을 지닌 에페리손 의약 조성물 50∼90 중량%; 방출 조절제로서 하이드록시프로필메틸셀룰로오스(HPMC) 1∼20 중량%; 및 방출 조절 고분자 5∼45 중량%;를 포함하는 활성 성분으로 에페리손을 함유하는 서방성 제제 조성물을 제공하는 것이다.
The object of the present invention is to provide a pharmaceutical composition comprising 50 to 90% by weight of an epherzone pharmaceutical composition having storage and pH stability; 1 to 20% by weight of hydroxypropylmethylcellulose (HPMC) as a release modifier; And 5 to 45% by weight of a release modifying polymer; wherein the sustained release pharmaceutical composition comprises eperisone as an active ingredient.
이때 상기 저장 및 pH 안정성을 지닌 에페리손 의약 조성물은 에페리손 또는 그의 약제학적으로 허용 가능한 염 20∼60 중량%; D-글루카르산, D-글루코아스코르브산, 글루콘산, D-글루쿠론산, 글루코노락톤, 글루쿠로노락톤, 글루탐산, 이타콘산, 카페인산, 글리시리진산, 에탄술폰산, 벤젠술폰산, 데하이드로아스코르브산, 살리실산, 살리실술폰산, 몰식자산, 니코틴산 또는 클로로겐산에서 선택된 1종 이상의 산성화제 1∼30 중량%; 결합제로서 결합제 0.5∼8 중량%; 및 희석제 10∼80 중량%;를 포함함을 특징으로 한다.
Wherein the pharmaceutical composition of the present invention having storage and pH stability comprises 20 to 60% by weight of eperisone or a pharmaceutically acceptable salt thereof; Glucuronic acid, gluconic acid, itaconic acid, caffeic acid, glycyrrhetinic acid, ethanesulfonic acid, benzenesulfonic acid, dehydroaromatic acid, 1 to 30% by weight of at least one acidic agent selected from ascorbic acid, salicylic acid, salicylsulfonic acid, gallic acid, nicotinic acid or chlorogenic acid; 0.5 to 8% by weight of a binder as a binder; And 10 to 80% by weight of a diluent.
또한 상기 방출 조절제로서 하이드록시프로필메틸셀룰로오스(HPMC)는 점도가 6∼10,000 cps 범위인 것을 특징으로 한다.
Also, hydroxypropyl methylcellulose (HPMC) as the release modifier has a viscosity of 6 to 10,000 cps.
한편 상기 방출 조절 고분자는 미결정셀룰로오스, 전분, 크로스포비돈, 저치환도 히드록시프로필셀룰로오스, 전분글리콘산나트륨, 크로스카멜로오스나트륨, 카르복시메틸셀룰로오스 칼슘 또는 마그네슘알루미늄실리케이트 중에서 선택된 1종 이상임을 특징으로 한다.
Meanwhile, the release-controlling polymer may be at least one selected from the group consisting of microcrystalline cellulose, starch, crospovidone, low-substituted hydroxypropylcellulose, sodium starch glyconate, croscarmellose sodium, carboxymethylcellulose calcium or magnesium aluminum silicate .
또한 상기 활성 성분으로 에페리손을 함유하는 서방성 제제 조성물은 pH 1.2의 완충액 내에서 용출 초기 60분 이내 전체 함량의 30∼55 중량%, 3시간 이내 55∼85 중량%, 그리고 5시간 이내 85 중량% 이상 용출됨을 특징으로 한다.
In addition, the sustained release pharmaceutical composition containing the active ingredient, eperisone, is contained in a buffer solution having a pH of 1.2 within a range of 30 to 55% by weight, within a period of 3 hours to 55 to 85% by weight, % Or more.
한편 본 발명의 또 다른 목적은 속방출층으로 상기 저장 및 pH 안정성을 지닌 에페리손 의약 조성물을 사용하고 서방출층으로 상기 활성 성분으로 에페리손을 함유하는 서방성 제제 조성물을 사용한 이중층 형태의 에페리손 함유 서방정을 제공하는 것이다.
It is another object of the present invention to provide a pharmaceutical composition comprising the effervescent pharmaceutical composition having the storage and pH stability as the immediate release layer and the double layered epsilon using the sustained release pharmaceutical composition containing the epelizone as the active ingredient as the release layer Containing sustained-release tablet.
한편 본 발명의 또 다른 목적은 상기 활성 성분으로 에페리손을 함유하는 서방성 제제 조성물에 추가적으로 비-스테로이드성 소염진통제(NSAID)를 포함하는 에페리손 복합제제를 제공하는 것이다.
Yet another object of the present invention is to provide an effer- sison combination preparation comprising a non-steroidal anti-inflammatory analgesic (NSAID) in addition to the sustained-release composition containing eperisone as the active ingredient.
이때 상기 비-스테로이드성 소염진통제(NSAID)는 셀레콕시브, 아세클로페낙, 디클로페낙, 이부프로펜, 덱시부프로펜, 록소프로펜, 잘토프로펜, 케토프로펜, 멜록시캄, 나프록센, 에토돌락, 나부메톤, 펠비낙, 니메설리드 중에서 선택된 1종 이상임을 특징으로 한다.
Wherein the nonsteroidal anti-inflammatory analgesic (NSAID) is selected from the group consisting of celecoxib, aceclofenac, diclofenac, ibuprofen, dexibuprofen, loxoprofen, Methane, felbinac, and nimesulide.
본 발명의 효과는 1일 2회 용량으로 복용 가능한 서방출 특성을 갖는 에페리손 함유 서방성 제제를 제공하기 위한 것으로, 에페리손에 산성화제와 폴리비닐피롤리돈 결합제를 첨가시킨 에페리손 의약 조성물에 방출 조절제로서 하이드록시프로필메틸셀룰로오스(HPMC)와 방출 조절 고분자를 첨가시킨 에페리손을 함유하는 서방성 제제 조성물을 제공하는 것이다.
The effect of the present invention is to provide a sustained-release preparation containing epsilon with a sustained-release property which can be taken twice a day, and is characterized in that an effer- sison pharmaceutical composition comprising an acidifying agent and a polyvinylpyrrolidone- (HPMC) as a release modifier and eperisone to which a release-controlling polymer is added.
도 1은 본 발명의 제조실시예 1에서 제조된 시료의 패들법에 의한 시간별 용출율을 도시한 그래프이다.FIG. 1 is a graph showing the dissolution rate by time of the paddle method of the sample prepared in Production Example 1 of the present invention.
본 발명은 저장 및 pH 안정성을 지닌 에페리손 의약 조성물 50∼90 중량%; 방출 조절제로서 하이드록시프로필메틸셀룰로오스(HPMC) 1∼20 중량%; 및 방출 조절 고분자 5∼45 중량%;를 포함하는 활성 성분으로 에페리손을 함유하는 서방성 제제 조성물에 관한 것이다.
The present invention relates to a pharmaceutical composition comprising 50 to 90% by weight of an epherzone pharmaceutical composition having storage and pH stability; 1 to 20% by weight of hydroxypropylmethylcellulose (HPMC) as a release modifier; And 5 to 45% by weight of a release modifying polymer; and effervescence as an active ingredient.
이때 서방성 제제 내의 에페리손 의약 조성물은 에페리손에 산성화제를 첨가시킨 저장 및 pH 환경 변화에 안정한 에페리손 의약 조성물로서 상기 에페리손 의약 조성물을 위장관 내에서 pH 변화에 안정하게 지속적으로 에페리손 활성 성분을 방출시킬 수 있는 서방성 제제 조성물에 관한 것이다.
Wherein the pharmaceutical composition of eperisone in the sustained-release preparation is an eperisone pharmaceutical composition which is stable to storage and pH changes by adding an acidifying agent to eperisone, wherein the eperisone pharmaceutical composition is continuously and stably applied to the pH change in the gastrointestinal tract, To a sustained release formulation composition.
이하 본 발명을 더욱 상세히 설명한다.
Hereinafter, the present invention will be described in more detail.
본 발명의 서방성 제제 조성물 내에 사용되는 저장 및 pH 안정성을 지닌 에페리손 의약 조성물은 에페리손 또는 그의 약제학적으로 허용 가능한 염 20∼60 중량%; D-글루카르산, D-글루코아스코르브산, 글루콘산, D-글루쿠론산, 글루코노락톤, 글루쿠로노락톤, 글루탐산, 이타콘산, 카페인산, 글리시리진산, 에탄술폰산, 벤젠술폰산, 데하이드로아스코르브산, 살리실산, 살리실술폰산, 몰식자산, 니코틴산 또는 클로로겐산에서 선택된 1종 이상의 산성화제 1∼30 중량%; 결합제 0.5∼8 중량%; 및 희석제 10∼80 중량%;를 포함하는 것이다.
The effervescent pharmaceutical composition having storage and pH stability used in the sustained release pharmaceutical composition of the present invention comprises 20 to 60% by weight of eperisone or a pharmaceutically acceptable salt thereof; Glucuronic acid, gluconic acid, itaconic acid, caffeic acid, glycyrrhetinic acid, ethanesulfonic acid, benzenesulfonic acid, dehydroaromatic acid, 1 to 30% by weight of at least one acidic agent selected from ascorbic acid, salicylic acid, salicylsulfonic acid, gallic acid, nicotinic acid or chlorogenic acid; 0.5 to 8% by weight binder; And 10 to 80% by weight of a diluent.
상기 저장 및 pH 안정성을 지닌 에페리손 의약 조성물 내에 사용되는 희석제로서는 미결정셀룰로오스, 유당 수화물, 무수 유당, 전분, 덱스트로즈, 설탕, 말티톨, 인산수소칼슘 또는 만니톨에서 선택된 1종 이상을 들 수 있다.
Examples of the diluent used in the effervescence pharmaceutical composition having storage and pH stability include at least one selected from microcrystalline cellulose, lactose hydrate, lactose anhydrous, starch, dextrose, sugar, maltitol, calcium hydrogen phosphate or mannitol.
또한 상기 산성화제로서는 D-글루쿠론산(D-glucuronic acid), 글루코노락톤(gluconolactone) 또는 글루쿠로노락톤(glucuronolactone)에서 선택된 1종 이상이 바람직하다.
The acidifying agent is preferably at least one selected from the group consisting of D-glucuronic acid, gluconolactone, and glucuronolactone.
한편 상기 산성화제의 함량은 상기 에페리손 의약조성물의 1.0%(w/v) 수용성 용액의 pH를 2.0∼5.5로 조정시킬 수 있는 양이다.
On the other hand, the content of the acidifying agent is an amount capable of adjusting the pH of the 1.0% (w / v) aqueous solution of the drug composition of efferissone to 2.0 to 5.5.
또한 본 발명의 서방성 제제 조성물에 사용되는 방출 조절제로서 하이드록시프로필메틸셀룰로오스(HPMC)는 점도가 6∼10,000 cps 범위인 것으로 이때 점도가 10,000 cps를 초과하면 약물의 용출이 낮아지는 문제가 있다.
Also, hydroxypropylmethylcellulose (HPMC) as a release modifier used in the sustained release pharmaceutical composition of the present invention has a viscosity ranging from 6 to 10,000 cps, and when the viscosity exceeds 10,000 cps, the elution of the drug is lowered.
또한 본 발명의 서방성 제제 조성물에 사용되는 방출 조절 고분자는 미결정셀룰로오스, 전분, 크로스포비돈, 저치환도 히드록시프로필셀룰로오스, 전분글리콘산나트륨, 크로스카멜로오스나트륨, 카르복시메틸셀룰로오스 칼슘 또는 마그네슘알루미늄실리케이트 중에서 선택된 1종 이상이며 상기 방출 조절 고분자는 방출 조절제로 사용하는 하이드록시프로필메틸셀룰로오스(HPMC)와 서로 혼합하여 사용함으로써 저장 및 pH 안정성을 지닌 에페리손 의약 조성물의 방출을 더욱 안정적으로 조절할 수 있게 한다.
In addition, the release-controlling polymer used in the sustained release pharmaceutical composition of the present invention may contain microcrystalline cellulose, starch, crospovidone, low-substituted hydroxypropyl cellulose, sodium starch glycolate, , And the release-controlling polymer is mixed with hydroxypropylmethylcellulose (HPMC) used as a release controlling agent, whereby the release of the efferissone pharmaceutical composition having storage stability and pH stability can be more stably controlled .
또한 본 발명의 활성성분인 에페리손은 염산염 형태가 바람직하고, 1회 투여 용량 내 함유된 염산 에페리손의 함량은 75∼150mg가 바람직하다.
In addition, the active ingredient of the present invention is preferably a hydrochloride form, and the content of eperissone hydrochloride contained in a single dose is preferably 75 to 150 mg.
또한 상기 활성 성분으로 에페리손을 함유하는 서방성 제제 조성물은 pH 1.2의 완충액 내에서 용출 초기 60분 이내 전체 함량의 30∼55 중량%, 3시간 이내 55∼85 중량%, 그리고 5시간 이내 85 중량% 이상 용출됨을 특징으로 한다.
In addition, the sustained release pharmaceutical composition containing the active ingredient, eperisone, is contained in a buffer solution having a pH of 1.2 within a range of 30 to 55% by weight, within a period of 3 hours to 55 to 85% by weight, % Or more.
한편 본 발명의 또 다른 목적은 속방출층으로 상기 저장 및 pH 안정성을 지닌 에페리손 의약 조성물을 사용하고 서방출층으로 상기 활성 성분으로 에페리손을 함유하는 서방성 제제 조성물을 사용한 이중층 형태의 에페리손 함유 서방정을 제공하는 것이다.
It is another object of the present invention to provide a pharmaceutical composition comprising the effervescent pharmaceutical composition having the storage and pH stability as the immediate release layer and the double layered epsilon using the sustained release pharmaceutical composition containing the epelizone as the active ingredient as the release layer Containing sustained-release tablet.
이때 속방출층은 60분 이내에 활성성분의 85 중량% 이상 용출되는 특성을 지니며 이러한 2개 층의 결합을 통한 2중층 형태의 에페리손 함유 서방정을 제조함으로써 더욱 편리하게 1일 2회 용량으로 복용 가능케 한다.
At this time, the rapid-release layer has a characteristic of eluting at least 85% by weight of the active ingredient within 60 minutes, and it is more convenient to prepare the double-layered efferissone-containing sustained release through binding of these two layers, It is possible.
한편 본 발명은 상기 활성 성분으로 에페리손을 함유하는 서방성 제제 조성물에 추가적으로 비-스테로이드성 소염진통제(NSAID)를 포함하는 에페리손 복합제제를 제공하는 것이다.
The present invention also provides an effer- sison combination preparation comprising a non-steroidal anti-inflammatory analgesic (NSAID) in addition to a sustained-release composition containing eperisone as the active ingredient.
본 발명의 에페리손을 함유하는 서방성 제제 조성물은 추가적으로 비-스테로이드성 소염진통제(NSAID)를 포함할 수 있으며, 예를 들면 셀레콕시브, 아세클로페낙, 디클로페낙, 이부프로펜, 덱시부프로펜, 록소프로펜, 잘토프로펜, 케토프로펜, 멜록시캄, 나프록센, 에토돌락, 나부메톤, 펠비낙, 니메설리드 중에서 선택된 1종 이상을 열거할 수 있다.
The sustained release pharmaceutical composition containing the effervesons of the present invention may additionally comprise a non-steroidal anti-inflammatory analgesic (NSAID), such as celecoxib, aceclofenac, diclofenac, ibuprofen, dexibupropene, At least one selected from the group consisting of fenugreek, penicillin, zotto-propene, ketoprofen, meloxicam, naproxen, etodolac, nabumetone, felbinac and nimesulide.
본 발명의 1일 2회 용량으로 복용 가능한 에페리손을 함유하는 서방성 제제 조성물과 1일 2회 복용하는 비-스테로이드성 소염진통제를 병용 투여하면 환자들의 복용 편리성을 증진시켜 복약 순응도를 더욱 향상시킬 수 있다.
The combination of the sustained release pharmaceutical composition containing eperisone and the non-steroidal anti-inflammatory analgesic, which can be taken twice a day according to the present invention, and the twice-a-day non-steroidal anti-inflammatory analgesic improves the convenience of taking the patients and improves the compliance .
본 발명의 에페리손을 함유하는 서방성 제제 조성물은 각각의 조성 성분을 혼합시킨 후 통상적인 직타법이나 습식법, 건식법 등을 통해 제조할 수 있으며 일반적인 과립 비드 펠렛 정제 캡슐 환제 뿐 아니라 이들의 다층정, 코팅정, 유핵정, 매트릭스 형태로 제형화할 수 있다.
The sustained release pharmaceutical composition containing the effervescent of the present invention can be prepared by mixing the respective components and then preparing the composition through conventional direct method, wet method, dry method, and the like. In addition to general granule bead pellet tablet capsule pills, A tablet, a coated tablet, a press-coated tablet, or a matrix.
이하 본 발명을 제조실시예, 제조비교예 및 실시예를 통하여 더욱 상세히 설명한다. 그러나 본 발명의 실시예들로 본 발명의 범위를 한정하는 것은 아니다.
Hereinafter, the present invention will be described in more detail through Production Examples, Production Comparative Examples and Examples. However, the scope of the present invention is not limited to the embodiments of the present invention.
(제조실시예 1) 본 발명의 활성 성분으로 에페리손을 함유하는 서방성 제제 조성물의 제조
(Production Example 1) Production of sustained release pharmaceutical composition containing eperisone as an active ingredient of the present invention
(단계 1)
(Step 1)
염산에페리손 100g, 산성화제로서 글루쿠론산 20g, 희석제로서 유당 수화물 175g을 정량하여 24 메쉬체에 사과한 후 투입하여 5분간 혼합하였다. 결합제로서 폴리비닐피롤리돈(PVP K30) 5g을 이소프로판올 50ml에 녹여 결합액을 만든 후 상기 혼합물로 에페리손 의약 조성물 300g을 제조하였다.
100 g of perisone in hydrochloric acid, 20 g of glucuronic acid as an acidifying agent and 175 g of lactose hydrate as a diluent were weighed and added to a 24-mesh sieve, followed by mixing and mixing for 5 minutes. 5 g of polyvinylpyrrolidone (PVP K30) as a binder was dissolved in 50 ml of isopropanol to prepare a binding solution, and 300 g of the pharmaceutical composition of eperisone was prepared from the mixture.
(단계 2)
(Step 2)
상기 단계 1에서 제조된 조성물 225g에 하이드록시프로필메틸셀룰로오스(HPMC) 36g과 방출 조절 고분자로서 미결정셀룰로오스 30g, 폴리비닐피롤리돈 5g 및 소량의 물을 첨가하여 5분간 혼합시킨 후 과립물을 오븐에서 50℃ 조건으로 1시간 동안 건조한 후 20 메쉬체를 이용하여 정립하여 과립물을 제조하였으며 활택제로서 탤크 및 스테아르산마그네슘 각 2g을 투입하여 비닐백에서 3분간 혼합하고, 이 혼합물을 타정기에서 압축하여 1정당 염산에페리손 75mg이 함유된 300mg 정제 1000개를 제조하였다. 최종 활성 성분으로 에페리손을 함유하는 서방성 제제의 성분 함량은 1정 당 염산에페리손 75mg, 글루쿠론산 15mg, 유당 수화물 131.25mg, 폴리비닐피롤리돈 8.75mg, HPMC 36mg, 미결정셀룰로오스 30mg 이었다.
36 g of hydroxypropylmethylcellulose (HPMC), 30 g of microcrystalline cellulose as a release controlling polymer, 5 g of polyvinylpyrrolidone and a small amount of water were added to 225 g of the composition prepared in the step 1, and the mixture was stirred for 5 minutes. Dried at 50 DEG C for 1 hour, and then sieved using a 20 mesh sieve to prepare granules. Two grams of talc and magnesium stearate were added as a lubricant and mixed in a vinyl bag for 3 minutes. The mixture was compressed in a tablet machine One thousand 300 mg tablets containing 75 mg of perisone in one hydrochloric acid were prepared. The components of the sustained-release preparation containing eperisone as the final active ingredient were 75 mg of perisone, 15 mg of glucuronic acid, 131.25 mg of lactose, 8.75 mg of polyvinylpyrrolidone, 36 mg of HPMC and 30 mg of microcrystalline cellulose in 1 g of hydrochloric acid per tablet .
(제조실시예 2) 본 발명의 활성 성분으로 에페리손을 함유하는 서방성 제제 조성물의 제조
(Preparation Example 2) Preparation of a sustained release pharmaceutical composition containing eperisone as an active ingredient of the present invention
제조실시예 1에서 방출 조절 고분자로서 미결정셀룰로오스 30g 대신에 저치환도히드록시프로필셀룰로오스 30g을 사용한 것을 제외하고는 제조실시에 1과 동일한 방법으로 제조하였다. 최종 활성 성분으로 에페리손을 함유하는 서방성 제제의 성분 함량은 1정 당 염산에페리손 75mg, 글루쿠론산 15mg, 유당 수화물 131.25mg, 폴리비닐피롤리돈 8.75mg, HPMC 36mg, 저치환도히드록시프로필셀룰로오스 30mg 이었다.
Production Example 1 was repeated except that 30 g of low substituted hydroxypropylcellulose was used instead of 30 g of microcrystalline cellulose as a release modifying polymer. As a final active ingredient, the sustained-release preparation containing eperisone was prepared by adding peritoneal hydrochloric acid 75 mg of perisone, 15 mg of glucuronic acid, 131.25 mg of lactose, 8.75 mg of polyvinylpyrrolidone, 36 mg of HPMC, And 30 mg of hydroxypropylcellulose.
(제조실시예 3) 본 발명의 활성 성분으로 에페리손을 함유하는 서방성 제제 조성물의 제조
(Preparation Example 3) Preparation of a sustained release pharmaceutical composition containing eperisone as an active ingredient of the present invention
제조실시예 1에서 방출 조절 고분자로서 미결정셀룰로오스 30g 대신에 전분글리콜산나트륨 30g을 사용한 것을 제외하고는 제조실시에 1과 동일한 방법으로 제조하였다. 최종 활성 성분으로 에페리손을 함유하는 서방성 제제의 성분 함량은 1정 당 염산에페리손 75mg, 글루쿠론산 15mg, 유당 수화물 131.25mg, 폴리비닐피롤리돈 8.75mg, HPMC 36mg, 전분글리콜산나트륨 30mg 이었다.
Production Example 1 was repeated except that 30 g of sodium starch glycolate was used instead of 30 g of microcrystalline cellulose as a release modifying polymer. As a final active ingredient, the sustained-release preparation containing eperisone was prepared by adding peritoneal hydrochloric acid 75 mg of perisone, 15 mg of glucuronic acid, 131.25 mg of lactose, 8.75 mg of polyvinylpyrrolidone, 36 mg of HPMC, sodium starch glycolate Respectively.
(제조비교예 1) HPMC의 성분 제외
(Production Comparative Example 1) Exclusion of components of HPMC
제조실시예 1에서 첨가된 HPMC를 첨가하지 않은 대신에 방출 조절 고분자 미결정셀룰로오스의 함량을 30g 대신에 66g으로 증가시켜 제조실시에 1과 동일한 방법으로 제조하였다. 최종 활성 성분으로 에페리손을 함유하는 서방성 제제의 성분 함량은 1정 당 염산에페리손 75mg, 글루쿠론산 15mg, 유당 수화물 131.25mg, 폴리비닐피롤리돈 8.75mg, 미결정셀룰로오스 66mg 이었다.
Production Example 1 was replaced by the same method as in Production Example 1 except that the content of the release-controlling polymer microcrystalline cellulose was increased to 66 g instead of 30 g, instead of the addition of HPMC added. The components of the sustained-release preparation containing eperisone as the final active ingredient were 75 mg of perisone hydrochloride, 15 mg of glucuronic acid, 131.25 mg of lactose monohydrate, 8.75 mg of polyvinylpyrrolidone and 66 mg of microcrystalline cellulose in 1 g of hydrochloric acid per tablet.
(제조비교예 2) 방출 조절 고분자 성분 제외
(Preparation Comparative Example 2) Excluding the emission modulating polymer component
제조실시예 1에서 첨가된 방출 조절 고분자 미결정셀룰로오스를 첨가하지 않은 대신에 HMPC의 함량을 36g 대신에 66g으로 증가시켜 제조실시에 1과 동일한 방법으로 제조하였다. 최종 활성 성분으로 에페리손을 함유하는 서방성 제제의 성분 함량은 1정 당 염산에페리손 75mg, 글루쿠론산 15mg, 유당 수화물 131.25mg, 폴리비닐피롤리돈 8.75mg, HPMC 66mg 이었다.
The content of HMPC was increased to 66 g instead of 36 g instead of the addition of the release-controlling polymer microcrystalline cellulose added in Production Example 1, and the same procedure as in Production Example 1 was carried out. As a final active ingredient, the sustained release preparation containing eperisone contained 75 mg of perisone hydrochloride, 15 mg of glucuronic acid, 131.25 mg of lactose, 8.75 mg of polyvinylpyrrolidone, and 66 mg of HPMC in a hydrochloric acid solution per tablet.
(제조비교예 3) 에페리손 의약 조성물 내 산성화제 성분 제외
(Preparation Comparative Example 3) Except for the acidifying agent component in the pharmaceutical composition of eperisone
제조실시예 1 단계 1에서 에페리손 의약 조성물을 제조하는 단계에서 산성화제로 사용된 글루쿠론산 20g을 첨가하지 않고 대신에 희석제 유당 수화물의 함량을 195g으로 증가시켜 에페리손 의약 조성물을 제조하였다. 상기 수득된 에페리손 의약 조성물 225g을 제조실시예 1 단계 2에 첨가하여 제조실시예 1과 동일한 방법으로 제조하였다. 최종 활성 성분으로 에페리손을 함유하는 서방성 제제의 성분 함량은 1정 당 염산에페리손 75mg, 유당 수화물 146.25mg, 폴리비닐피롤리돈 8.75mg, HPMC 36mg, 미결정셀룰로오스 30mg 이었다.
Production Example 1 In step 1, the pharmaceutical composition of eperisone was prepared by increasing the content of diluent lactose hydrate to 195 g instead of adding 20 g of glucuronic acid used as an acidifier in the step of preparing the eperisone pharmaceutical composition. 225 g of the above-obtained drug product of ephrissone was added to the preparation example 1 step 2, and the same procedure as in preparation example 1 was carried out. As a final active ingredient, the sustained release preparation containing eperisone contained 75 mg of perisone hydrochloride, 146.25 mg of lactose hydrate, 8.75 mg of polyvinylpyrrolidone, 36 mg of HPMC and 30 mg of microcrystalline cellulose in hydrochloric acid per tablet.
(실시예) 용출 시험(패들법)
(Example) Elution test (paddle method)
상기 제조실시예 1 내지 3, 제조비교예 1 내지 3에서 제조된 서방형 제제 시료 1정을 37℃에서 pH 1.2 완충액에 넣어 패들법으로 50rpm의 조건에서 용출시험을 시행하였다. 각 시점에서 5mL를 채취하여 여과한 후 UV-스펙트로포토미터 흡광도측정법(261nm)으로 에페리손 염산염의 함량을 측정하여 그 누적 용출율을 표 1에 나타내었다. 또한 도 1은 제조실시예 1에서 제조된 시료의 용출 그래프를 나타낸 것이다.
One sample of the sustained release pharmaceutical preparation prepared in Preparation Examples 1 to 3 and Comparative Preparation Examples 1 to 3 was placed in a pH 1.2 buffer solution at 37 占 폚 and subjected to a dissolution test at 50 rpm in a paddle method. After collecting 5 mL at each time point, the content of efferissin hydrochloride was measured by a UV-spectrophotometer absorbance measurement method (261 nm), and the cumulative dissolution rate is shown in Table 1. Fig. 1 also shows a dissolution graph of the sample prepared in Production Example 1. Fig.
상기 표 1의 결과로부터 알 수 있는 바와 같이, 본 발명의 제조실시예 1 내지 3에서 제조된 서방성 제제(1정당 염산에페리손 75mg 함유)의 경우, 초기 60분에 전체 함량의 36 내지 42%를 방출하였고 180분에 74 내지 80%, 300분에 95% 이상의 용출율을 나타내고 있어 안정된 용출패턴을 보여주고 있다.
As can be seen from the results of the above Table 1, in the case of the sustained-release preparation (containing 75 mg of Perisson in one hydrochloric acid per unit) prepared in Production Examples 1 to 3 of the present invention, %, A dissolution rate of 74 to 80% at 180 minutes, and 95% or more at 300 minutes, showing a stable elution pattern.
반면 본 발명의 제조비교예 1 내지 3에서 제조된 제제(1정당 염산에페리손 75mg 함유)의 경우, 초기 60분에 전체 함량의 25 내지 99%를 방출하였고 180분에 46 내지 99%, 300분에 58 내지 100% 의 용출율을 나타내어 안정하지 않고 변화가 큰 용출패턴을 나타내고 있다.
On the other hand, in the case of the preparations prepared in Comparative Preparation Examples 1 to 3 of the present invention (containing 75 mg of perissone in hydrochloric acid per unit), 25 to 99% of the total content was released in the initial 60 minutes, and 46 to 99% Min., Showing a dissolution rate of 58 to 100%, which is not stable and shows a large change in the elution pattern.
따라서 본 발명의 방법에 따라 제조된 에페리손을 함유하는 서방성 제제 조성물의 경우 제조비교예에 의해 제조된 서방성 제제 조성물에 비해 안정되고 일정한 용출 패턴의 차이를 나타냄을 확인한 것이다.
Thus, it was confirmed that the sustained release pharmaceutical composition containing the effer- sison prepared according to the method of the present invention exhibited a stable and constant difference in elution pattern compared to the sustained-release pharmaceutical composition prepared by the comparative example.
본 발명의 방법에 따라 제조된 에페리손을 함유하는 서방성 제제 조성물의 경우 위에서 체류하는 시간 뿐 아니라 소장을 통과하는 시간 동안에도 정제의 붕해가 완전히 이루어지지 않고 정제 내에 약물을 계속 함유한 상태로 이동하게 된다. 즉 위내에서 체류하는 동안에 활성성분인 에페리손이 일부만 방출되고, 그 잔량은 붕해되지 않은 정제 내에 남아 소장을 통과하면서 서서히 방출되는 양상을 나타내게 된다.
In the case of the sustained-release pharmaceutical composition containing the effer- sison prepared according to the method of the present invention, the disintegration of the tablets is not completely completed not only at the time of residence but also during the passage through the small intestine, . That is, during the stay in the stomach, only a part of the active ingredient, epelizone, is released, and the remaining amount remains in the disintegrating tablet and gradually emits while passing through the small intestine.
따라서 소장 내부의 높은 pH 환경에서도 에페리손이 화학적 안정성을 유지하도록 정제 내부의 pH 환경을 낮게 유지할 필요가 있다. 이러한 기술적 요구에 따라 본 발명에서는 산성화제를 첨가함으로써 pH 6.8의 완충액 중에서 에페리손의 분해산물이 현저히 낮게 생성됨을 확인할 수 있다.Therefore, it is necessary to keep the pH environment inside the tablet low in order to maintain the chemical stability of eperisone even in the high pH environment inside the small intestine. According to this technical requirement, it is confirmed that, in the present invention, by adding an acidifying agent, decomposition products of ephrisson are remarkably lowered in a buffer solution of pH 6.8.
Claims (8)
50 to 90% by weight of efferissone pharmaceutical composition having storage and pH stability; 1 to 20% by weight of hydroxypropylmethylcellulose (HPMC) as a release modifier; And 5 to 45% by weight of a release modifying polymer; and effervescence as an active ingredient.
The pharmaceutical composition according to claim 1, wherein the storage and pH-stable epherzone pharmaceutical composition comprises 20 to 60% by weight of epherison or a pharmaceutically acceptable salt thereof; Glucuronic acid, gluconic acid, itaconic acid, caffeic acid, glycyrrhetinic acid, ethanesulfonic acid, benzenesulfonic acid, dehydroaromatic acid, 1 to 30% by weight of at least one acidic agent selected from ascorbic acid, salicylic acid, salicylsulfonic acid, gallic acid, nicotinic acid or chlorogenic acid; 0.5 to 8% by weight binder; And 10 to 80% by weight of a diluent; wherein the sustained-release pharmaceutical composition comprises eperisone as an active ingredient.
The sustained release pharmaceutical composition of claim 1, wherein the release modifying agent is hydroxypropyl methylcellulose (HPMC) having a viscosity ranging from 6 to 10,000 cps.
The composition of claim 1, wherein the release modifying polymer is selected from the group consisting of microcrystalline cellulose, starch, crospovidone, low substituted hydroxypropyl cellulose, sodium starch glyconate, croscarmellose sodium, carboxymethylcellulose calcium or magnesium aluminum silicate Wherein the active ingredient is effervescent. ≪ RTI ID = 0.0 > 8. < / RTI >
The sustained release pharmaceutical composition according to claim 1, wherein the sustained release pharmaceutical composition containing eperisone as the active ingredient is contained in a buffer solution of pH 1.2 in an amount of 30 to 55% by weight, within a period of 3 hours to 55 to 85% by weight, Wherein the active ingredient is eluted at least 85 wt% within 5 hours.
A double-layered effer- sison-containing sustained-release tablet using the sustained-release layer as the release layer and the sustained release formulation composition containing the ephedrine as the active ingredient of claim 1, using the ephedlison pharmaceutical composition having the above storage and pH stability.
An epherrine conjugate formulation comprising in addition to a sustained release pharmaceutical composition containing epherrison as an active ingredient of claim 1, a non-steroidal anti-inflammatory analgesic (NSAID).
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| KR20160105662A (en) | 2015-02-27 | 2016-09-07 | 대원제약주식회사 | Pharmaceutical composition comprising eperison and pelubiprofen |
| KR20200117138A (en) * | 2019-04-03 | 2020-10-14 | 위더스제약주식회사 | Eperisone-containing pharmaceutical having improved storage-stability |
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| WO2018044020A1 (en) * | 2016-08-29 | 2018-03-08 | 초당약품공업 주식회사 | Method for preparing eperisone sustained release microsphere, and composite preparation of eperisone sustained release microsphere and aceclofenac |
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| WO2010103544A2 (en) * | 2009-03-09 | 2010-09-16 | Dinesh Shantilal Patel | A novel sustained release composition of compounds selected from the class of centrally acting muscle relaxants |
| EP2486918A4 (en) * | 2009-10-09 | 2014-02-26 | Yungjin Pharmaceutical Co Ltd | Pharmaceutical composition with both immediate and extended release characteristics |
| KR101156054B1 (en) * | 2011-09-05 | 2012-06-20 | 주식회사 네비팜 | A stable and control-released pharmaceutical composition comprising eperisone |
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| KR20160105662A (en) | 2015-02-27 | 2016-09-07 | 대원제약주식회사 | Pharmaceutical composition comprising eperison and pelubiprofen |
| WO2016137266A3 (en) * | 2015-02-27 | 2016-10-20 | 대원제약주식회사 | Pharmaceutical composition containing eperisone and pelubiprofen |
| KR20200117138A (en) * | 2019-04-03 | 2020-10-14 | 위더스제약주식회사 | Eperisone-containing pharmaceutical having improved storage-stability |
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