KR19990072826A - A process for producing enteric-coated pancreatin granules - Google Patents

A process for producing enteric-coated pancreatin granules Download PDF

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KR19990072826A
KR19990072826A KR19990005822A KR19990005822A KR19990072826A KR 19990072826 A KR19990072826 A KR 19990072826A KR 19990005822 A KR19990005822 A KR 19990005822A KR 19990005822 A KR19990005822 A KR 19990005822A KR 19990072826 A KR19990072826 A KR 19990072826A
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method
pancreatin
coating
granules
enteric
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KR19990005822A
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박동우
전홍렬
이경희
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우재영
일양약품 주식회사
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/5021Organic macromolecular compounds
    • A61K9/5026Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/465Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/47Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/48Hydrolases (3) acting on peptide bonds (3.4)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1629Organic macromolecular compounds
    • A61K9/1635Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1629Organic macromolecular compounds
    • A61K9/1652Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2072Pills, 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
    • A61K9/2077Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A61K9/2081Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/5021Organic macromolecular compounds
    • A61K9/5036Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/5021Organic macromolecular compounds
    • A61K9/5052Proteins, e.g. albumin

Abstract

본 발명은 판크레아틴을 씨드(seed)로 하여 저온에서 1차 코팅한 다음, 필요에 따라 2차 코팅을 실시하여 타정압에 안정하며 장내효소활성이 우수한 판크레아틴 장용코팅 과립을 제조하는 방법에 관한 것이다. The invention plate a primary coating at low temperature to the creatine as a seed (seed), and then subjected to a secondary coating as needed stability to the other static-pressure and a method for the intestinal enzyme activity produced excellent pancreatin enteric-coated granules will be.

Description

판크레아틴 장용코팅과립의 제조방법{A PROCESS FOR PRODUCING ENTERIC-COATED PANCREATIN GRANULES} Production method of pancreatin enteric-coated granules {A PROCESS FOR PRODUCING ENTERIC-COATED PANCREATIN GRANULES}

본 발명은 산성의 pH에서 안정하며 우수한 타정성을 갖고 타정시 안정한 미세 장용 판크레아틴코팅과립의 제조방법에 관한 것이다. The present invention is stable at the pH of the acid, and has excellent stability on the other tableting the production method of a stable fine pancreatin enteric-coated granules.

판크레아틴은 소나 돼지 등의 포유류의 췌장에서 분리해낸 아밀라제, 프로테아제, 리파제의 활성을 가진 소화효소로 낭포성섬유증, 췌장염, 췌장소화효소결핍증등의 치료제로 알려져 있다. Pancreatin has been known as a therapeutic agent, such as amylase, protease, cystic fibrosis to the digestive enzymes with the activity of the lipase, pancreatitis, pancreatic digestive enzyme deficiency came up away from the pancreas of mammals such as cows and pigs. 췌장에서 생성된 췌장효소는 십이지장으로 분비되는데 이때 pH는 중성 내지 약알칼리성이다. The pancreatic enzyme production in the pancreas are secreted into the duodenum there is this time the pH is neutral to slightly alkaline. 분비된 췌장효소는 이러한 pH 조건하에서만 활성화되며 소장 상부에서의 소화작용도 정상적으로 진행될 수 있다. The pancreatic enzyme secretion is activated only under these pH conditions it can be carried out normally even digestion in the small intestine of the upper. 췌장기능부전으로 인해 외부로부터 섭취되는 판크레아틴은 위장을 거쳐야 하는데 이때 위산과 펩신에 의해 비가역적으로 불활성화 되고 만다. Due to pancreatic insufficiency pancreatin being ingested from outside Manda ratio is irreversible activated fire by gastric acid and pepsin this time to go through the stomach. 산성조건하에서는 보통 10 내지 40%의 낮은 활성을 나타내는데 그 중 리파제가 특히 많은 영향을 받는다. Under acidic conditions is that of the lipase to indicate the low activity of the usual 10 to 40% subject to particularly great influence. 그러므로, 경구로 투여된 효소는 위장에서 불활성화 되어지는 것을 막기 위해 적당한 보호막이 필요하다. Thus, the enzyme administered orally, it is necessary a suitable protective film to prevent the light which is active in the stomach.

최적의 보호막으로는 장용코팅이 필수적인데, 판크레아틴제제에 적용되는 장용코팅의 종류는 크게 2가지로 나뉜다. The optimum protection film is the enteric coating is necessary, the type of enteric coating applied to the pancreatin preparation is divided largely into two. 첫 번째는 국내시장에서 많이 사용되고 있는 방법으로 판크레아틴을 적당한 부형제와 혼합, 타정한 뒤 이를 장용코팅하는 기술이다. The first is a technique that is often used enteric coating them after how the pancreatin mixed with suitable excipients, tableting as in the domestic market. 판크레아틴은 단일성분으로 보다는 복합소화효소제로 많이 사용되고 있는데 이러한 형태의 제제는 위에서부터 약효를 발현해야하는 성분까지 장용코팅을 함으로써 그 약리작용이 충분히 발휘되지 못하는 불합리한 면이 있다. Pancreatin there is widely used as a digestive enzyme complex, rather than a single component of this type has the formulation unreasonable surface does not fully exhibit its pharmacological action by the enteric coating to the component must express the drug from the top.

두 번째는 판크레아틴과 적당한 부형제, 결합제 및 유기용매를 혼합, 조립하여 얻은 과립을 구형의 입자로 압착, 건조하여 장용코팅(미국특허 제5,302,400호 및 미국특허 제5,260,074호)하는 방법이다. The second is a method of pancreatin and mixed with a suitable excipient, binding agent and organic solvent, the granules obtained by the granulation compression of spherical particles, and dried to enteric-coated (5.3024 million U.S. Patent No. 5,260,074 and U.S. Patent No. No.). 미국특허 제4,079,125호에 소개된 기술로 판크레아틴을 적당한 결합제, 안정화제, 붕해제 및 유기용매와 혼합하여 조립, Marumerizer compaction으로 비드(bead)를 성형하여 이를 장용코팅한다든가 판크레아틴분말을 활택제와 혼합, 롤러 컴팩트(Roller compact), 음각 컴팩트(Concave compact), 양각 컴팩트(Convex compact) 등을 이용 구형 플레이트로 압착한 후 분쇄, 체과하여 유기용매를 사용하지 않고 장용코팅하는 코팅기술이다. Lubricating the United States Patent No. 4,079,125 suitable for Pancreatin a technology introduced to the call agent, a stabilizer, a disintegrant and a pancreatin powder deunga by molding a bead (bead) in the assembly, Marumerizer compaction is mixed with an organic solvent and this enteric coat the with mixing, compact roller (roller compact), intaglio compact (concave compact), after compression and the like embossed compact (Convex compact) using a rectangular plate grinding, to chegwa without using an organic solvent, a technique of coating an enteric coating. 이러한 기술은 조립과정중 용매사용으로 인해 또는 압착과정시 생긴 열에 의해 효소의 활성이 떨어지는 문제점과 생산에 적용시 여러 단계의 공정으로 인한 비효율성이 지적되어 왔다. This technique has the inefficiency due to the different stages of the process, when applied to a lowered production and activity of the enzyme caused by heat during assembly due to the solvent or compression process used in the process is pointed. 장용코팅한 과립을 정제에 적용시 타정압에 안정하려면 코팅과립의 입자가 미세해야 하는데 이는 입자가 미세해야 타정압이 분산되어 장용코팅이 부서지지(brittle)않고 성형되기 때문이다. To stabilize the other positive pressure when applying the granules in the enteric-coated tablets to have fine particles of the granular coating This is because the particles are other fine be static pressure dispersion enteric coating is not broken (brittle) without molding. 그러나, 기존의 방법은 과립의 입자가 미세하지 않거나 불균일해서 안정한 코팅과립을 기대하기엔 미흡한 방법이다. However, the conventional method is insufficient method hagien expect a stable coated granules to uneven or the particles of the coarse granules.

따라서, 판크레아틴을 나정 또는 위용성코팅만으로도 위용부, 장용부로 구획이 가능한 정제 즉, 복합제제에 사용할 때 유리하고 직타성이 뛰어나며 타정압에 안정한 장용코팅과립의 발명이 요구되었다. Thus, the plate is glass and the other straight inertia excellent this invention were required for stable enteric-coated granules in the static pressure when creatine uncoated tablet or gastric coating that is only a possible purification partitioned by grandeur unit, enteric, used in the combined preparation. 이에 본 발명자들은 코팅기제로서 각종 고분자와 천연물추출원료의 개발을 기초로 위내 환경에서 효소가 불활성화되지 않고 장에서 신속히 붕해되며 타정압에 안정한 미세장용코팅 방법을 발견하기에 이르렀다. The present inventors have found that the enzyme in the stomach and the environment based on the development of a variety of polymeric and natural product extract material as a coating base rapidly disintegrate in the field without being inactivated, leading to the discovery of stable fine enteric-coating method to the other static-pressure.

본 발명은 판크레아틴을 저온하에 부유시키면서 고속으로 코팅액을 분무하고, 필요에 따라 형성된 미세 코팅과립을 저온하에 부유시키면서 고속으로 1차 코팅액과 동일하거나 상이한 코팅액으로 재분무하여 과립을 생성함을 특징으로 하는 판크레아틴 장용코팅과립의 제조방법을 제공한다. The invention is characterized by spraying a coating solution at a high speed, while floating the pancreatin under low temperature, and the need to create a fine coated granules suspended while by spraying the same with the first coating fluid at a high speed, or material with a different coating solution for granulation under a low-temperature formed in accordance with the pancreatin provides a process for the preparation of enteric-coated granules.

본 발명의 방법에서 1차 및 2차 코팅에 사용되는 코팅기제로는 옥수수단백추출물과 이를 인위적으로 가공한 유사물질, 알긴산나트륨, 알긴산, 메타크릴산-아크릴산에틸공중합체류, 쉘락류, 카보폴류(카보머 (R) , 카복시비닐폴리머), 하이드록시프로필메칠셀룰로오스프탈레이트류, 하이드록시프로필메칠셀룰로오스 아세테이트숙시네이트, 하이드록시프로필메칠 아세테이트숙시네이트, 카르복시메칠셀룰로오스, 셀룰로오스아세테이트프탈레이트류, 하이드록시프로필셀룰로오스류, 에칠셀룰로오스류, 메칠셀룰로오스류, 폴리비닐아세테이트프탈레이트, 대두단백 또는 소맥단백 또는 이를 인위적으로 가공한 유사물질, 키틴 또는 키틴산 또는 이를 인위적으로 가공한 유사물질, 한천, 카라기난(Carrageenan), 펙틴(Pectin), 구아 검(Guar gum), 로우커스트 검(Locu Coating agent used in the primary and secondary coating in the method of the present invention is corn protein extract and a this processing artificially similar products, alginic acid, sodium alginate, methacrylic acid-ethyl acrylate copolymers, shell rakryu, carbonyl polryu (Cabo Murray (R), carboxyvinyl polymer), hydroxypropyl methyl cellulose phthalates, hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl acetate succinate, carboxymethylcellulose, cellulose acetate phthalates, hydroxypropyl celluloses, echil celluloses, methyl celluloses, polyvinyl acetate phthalate, soy protein or wheat protein, or it artificially processed into a similar substance, chitin or chitin acid or this processing, artificially-like substances, agar, carrageenan (carrageenan), pectin (pectin ), guar gum (guar gum), low-Cust gum (Locu st bean gum), 잔탄검(Xanthan gum), 젤란 검(Gellan gum), 아라비아 검(Arabic gum), 탄소수 6~12개의 중쇄 지방산류 등을 단독으로 또는 둘 이상 혼합하여 사용할 수 있다. st bean gum), xanthan gum (Xanthan gum), gellan gum (Gellan gum), gum arabic (Arabic gum), at least alone, or both, or the like having a carbon number of 6 to 12 of the heavy chain fatty acids can be used as a mixture.

각층의 코팅액 제조를 위한 기제의 사용량은 판크레아틴 사용량을 기준으로 하여 1 내지 250 중량%이며, 바람직하게는 50 내지 180 중량%이다. The amount of the base for the coating solution prepared for each layer is 1 to 250% by weight based on the Pancreatin amount, preferably from 50 to 180% by weight.

본 발명의 코팅에서 사용되는 가소제는 폴리에틸렌글리콜류, 글리세린지방산에스테르류, 소르비탄 지방산 에스테르류, 프로필렌글리콜, 글리세린, 구연산트리에틸, 트리아세틴, 세틸알코올, 스테아릴알코올 등으로 이를 단독 또는 둘 이상 혼합하여 사용할 수 있으며 가소제의 사용량은 판크레아틴 사용량을 기준으로 하여 1 내지 50 중량%이며, 바람직하게는 5 내지 30 중량%이다. Plasticizers used in the coatings of the present invention are polyethylene glycols, glycerine fatty acid esters, sorbitan fatty acid esters, mixture of at least them alone or both of propylene glycol, glycerin, triethyl citrate, triacetin, cetyl alcohol, stearyl alcohol, etc. to be used and the amount of the plasticizer is 1 to 50% by weight based on the pancreatin amount, preferably 5 to 30% by weight.

상기 코팅기제 및 가소제의 사용량 범위를 벗어난 경우 코팅과립의 붕해가 늦어져 신속한 약효발현을 기대할수 없거나 위액에서 안정한 코팅막을 얻을수 없게되어 효소활성을 보장할 수 없게 된다. If out of the amount range of the coating base and a plasticizer is not able to expect a rapid efficacy expression becomes delayed disintegration of the coated granules, or get a stable coating film on the gastric juice, it is impossible to ensure the enzyme activity.

본 코팅에 사용된 용매로는 물, 알콜, 아세톤, 아세토니트릴, 메칠렌클로라이드, 에테르, 헥산, 클로르포름, 1,4-디옥산, 테트라하이드로푸란, 디메틸설폭사이드, 에칠아세테이트, 메칠아세테이트 또는 이들의 혼합물을 포함한다. With the solvent used in the coating are water, alcohols, acetone, acetonitrile, methylene chloride, ether, hexane, chloroform, 1,4-dioxane, tetrahydrofuran, dimethylsulfoxide, echil acetate, methyl acetate, or their of a mixture.

코팅에 사용된 장치는 일명 "유동층조립기" (Fluid bed), 또는 이와 유사한 장치로서 본 발명에서는 유동층조립기 SFC-MINI(Freund Co. Japan)를 사용하였으나 이와 유사한 장치로도 상기 제제에 대한 제조가 가능하다. The apparatus used in the coating are sometimes referred to as "fluidized bed granulator" (Fluid bed), or in a similar device in the present invention, but using a fluid bed granulator SFC-MINI (Freund Co. Japan) is also a similar device that can be manufactured for the formulations Do.

장치의 제조 조건은 유입공기의 온도는 35 내지 70℃의 범위이고 단계별 장치내 과립의 온도는 모두 25℃이상이 되어야 흡습과 과립끼리의 응집을 막을 수 있다. Production conditions of the device can the temperature of the temperature within the range of 35 to 70 ℃ a step-by-step device granules of the incoming air are all be at least 25 ℃ prevent agglomeration between the granules and moisture.

그러나 모든 공정은 장치내 과립의 온도가 25℃ 내지 60℃의 범위를 유지하는 것이 바람직하다. However, all of the process it is preferred that the temperature of the apparatus granules keep a range of 25 ℃ to 60 ℃. 왜냐하면 그 이상의 온도에서는 공정중 효소의 역가가 감소될 수 있기 때문이다. Because the higher temperature, because it can be the activity of the enzyme decreased in the process.

하기 실시예로 본 발명에 따른 판크레아틴의 장용피제를 위한 조성 및 그의 제조공정을 구체적으로 예시한다. The following Examples specifically exemplified a composition and its preparation process for the enteric pije of pancreatin in accordance with the present invention to.

실시예 1 Example 1

1차코팅Seed :코팅액 :2차코팅Seed :코팅액 : The primary coating Seed: coating: Secondary Coating Seed: coating: 판크레아틴HPMC 2208물폴리에틸렌글리콜 60001차 미세코팅과립Eudragit (R) L 30D (물분산형)물프로필렌글리콜 Pancreatin HPMC 2208 Water Polyethylene glycol 60001 car fine granules coated with Eudragit (R) L 30D (mulbun acid type), water-propylene glycol 300g15g300㎖2g300g1,320㎖(고형분으로서 400g)500㎖40g 300g15g300㎖2g300g1,320㎖ (solids content 400g) 500㎖40g

(a) 1차 미세 코팅과립의 제조 (A) 1 primary production of fine-coated granules

판크레아틴 분말을 유동층조립기(SFC-MINI)에서 부유시키면서 상기의 코팅액을 분사시키면서 코팅하였다. While floating the pancreatin powder in a fluidized bed granulator (SFC-MINI) it was coated while spraying the above-mentioned coating solution. 유동층조립기의 장치내 PRODUCT의 온도는 25℃ 내지 60℃의 범위를 벗어나지 않게 하였다. The temperature of the fluidized bed granulator PRODUCT the apparatus was not within the scope of 25 ℃ to 60 ℃.

(b) 2차 코팅과립의 제조 (B) 2 primary production of coated granules

(a)의 미세 코팅과립을 유동층조립기에서 부유시키면서 상기의 Eudragit (R) L 30D 와 가소제로 구성된 코팅액을 분사하여 코팅하였다. while floating the fine granules coated in (a) was coated in a fluid bed granulator by spraying a coating solution consisting of the Eudragit (R) L 30D and plasticizers. 유동층조립기의 작동조건은 상기의 범위내에서 하였으며 유동층조립기의 장치내 과립의 온도는 25℃ 내지 60℃의 범위를 벗어나지 않게 하였다. Operating conditions of the fluid bed granulator was in the range of the temperature was not within the fluid bed granulator apparatus granules departing from the scope of 25 ℃ to 60 ℃. 2차 코팅기제는 경우에 따라 Kollicoat MAE 30 DP로 변경하여 코팅할 수 있다. Secondary coating base is in some cases may be coated to change the Kollicoat MAE 30 DP.

실시예 2 Example 2

1차코팅Seed :코팅액 :2차코팅Seed :코팅액 : The primary coating Seed: coating: Secondary Coating Seed: coating: 판크레아틴알긴산 나트륨물글리세린1차 미세코팅과립Zein-DP (R) (옥수수단백추출물)셸락80%에탄올프로필렌 글리콜글리세린 Pancreatin sodium alginate water glycerin primary coating fine granules Zein-DP (R) (corn protein extract) of 80% shellac in ethanol, propylene glycol glycerol 300g3g300㎖3g300g150g30g1,200㎖6g12g 300g3g300㎖3g300g150g30g1,200㎖6g12g

실시예 1에 기술된 바와 동일한 방식으로 상기의 성분을 사용하여 1차코팅, 2차코팅을 하여 제조하였다. Carried out using the above components in the same manner as described in Example 1 was prepared by the primary coating, the secondary coating.

실시예 3 Example 3

1차코팅Seed :코팅액 :2차코팅Seed :코팅액 : The primary coating Seed: coating: Secondary Coating Seed: coating: 판크레아틴HPMC 2910물글리세린1차코팅과립HPMCP80%에탄올글리세린지방산에스테르 Pancreatin HPMC 2910 water glycerin primary coated granules HPMCP80% ethanol, glycerol fatty acid ester 300g10g200㎖2g300g400g4,000㎖30g 300g10g200㎖2g300g400g4,000㎖30g

실시예 1에 기술된 바와 동일한 방식으로 상기의 성분을 사용하여 1차코팅, 2차코팅을 하여 제조하였다. Carried out using the above components in the same manner as described in Example 1 was prepared by the primary coating, the secondary coating. 1차코팅기제는 경우에 따라 HPC로 변경하여 코팅할 수 있다. In some cases, the primary coating base may be coated to change the HPC.

실시예 4 Example 4

1차코팅Seed :코팅액 :2차코팅Seed :코팅액 : The primary coating Seed: coating: Secondary Coating Seed: coating: 판크레아틴HPC물글리세린1차 미세코팅과립폴리비닐아세테이트프탈레이트물프로필렌글리콜 Pancreatin HPC water glycerin primary fine granules coated polyvinyl acetate phthalate water-propylene glycol 300g10g200㎖4g300g450g4,000㎖10g 300g10g200㎖4g300g450g4,000㎖10g

실시예 1에 기술된 바와 동일한 방식으로 상기의 성분을 사용하여 1차코팅, 2차코팅을 하여 제조하였다. Carried out using the above components in the same manner as described in Example 1 was prepared by the primary coating, the secondary coating.

실시예 5 Example 5

Seed :코팅액 : Seed: coating: 판크레아틴HPMCP80%에탄올글리세린지방산에스테르 Pancreatin HPMCP80% ethanol, glycerol fatty acid ester 300g400g4,000㎖30g 300g400g4,000㎖30g

실시예 1에 기술된 바와 동일한 방식으로 상기의 성분을 사용하여 단층코팅을 하였다. Was performed for single-layer coating by using the components of the in the same way as described in Example 1.

실시예 6 Example 6

Seed :코팅액 : Seed: coating: 판크레아틴Eudragit (R) L 30D물구연산트리에틸 Pancreatin Eudragit (R) L 30D water triethyl citrate 300g1,485㎖(고형분으로서 450g)300㎖30g 300g1,485㎖ (solids content 450g) 300㎖30g

실시예 1에 기술된 바와 동일한 방식으로 상기의 성분을 사용하여 단층코팅을 하였다. Was performed for single-layer coating by using the components of the in the same way as described in Example 1. 상기의 코팅기제는 경우에 따라 Kollicoat MAE 30 DP로 변경하여 코팅할 수 있다. The above coating base may be coated, or change to Kollicoat MAE 30 DP in some cases. 단층코팅의 경우 초기 분무속도를 늘려 조기에 입자를 만드는 것이 코팅액에 의한 역가의 저하를 방지할 수 있다. For a single layer coating to make the particles prematurely increasing the initial spray rate it is possible to prevent a decrease in the activity due to the coating liquid.

실험실시예 1 For one hour lab

상기의 실시예 1 내지 8의 코팅과립의 입자분포를 측정하였고 이의 결과는 하기 표 1에 나타낸 바와 같다. We measured the particle size distribution of the coated granules of Examples 1 to 8 the results thereof are shown in Table 1 below.

판크레아틴 코팅과립의 입도분포(%) The particle size distribution of the coated pancreatin granules (%)

메쉬크기(mm) Mesh Size (mm)
20 (0.84) 20 (0.84) 30 (0.59) 30 (0.59) 40 (0.42) 40 (0.42) 50 (0.297) 50 (0.297)
실시예 1실시예 2실시예 3실시예 4실시예 5실시예 6 Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 7.49.59.311.74.89.0 7.49.59.311.74.89.0 50.547.645.844.152.254.7 50.547.645.844.152.254.7 38.634.437.340.038.630.5 38.634.437.340.038.630.5 3.58.57.64.24.45.8 3.58.57.64.24.45.8

표 1의 결과로 30 내지 40메쉬에 코팅과립이 80%이상 분포하는 균질한 코팅과립을 얻을 수 있었다. As a result of Table 1 was obtained a homogeneous coated granules to coat the granules is 80% or more is distributed in 30 to 40 mesh.

실험실시예 2 For example, when two laboratories

상기의 실시예 1 내지 6의 판크레아틴 코팅과립을 유럽약전 판크레아틴의 정량법에 따라 리파제 활성, 아밀라제 활성, 프로테아제 활성을 측정하여 판크레아틴 원료의 결과와 비교하였고 이의 결과는 하기 표 2에 기재된 바와 같다. As the above-mentioned Examples 1 to 6 pancreatin coated granules described in lipase activity, amylase activity, protease to determine the activity was compared to the results of pancreatin raw results thereof are in Table 2 in accordance with the assay method of the European Pharmacopoeia pancreatin .

판크레아틴의 정량시험결과 Quantitative test results of pancreatin

코팅과립중판크레아틴양 (%) Coated granules middle plate creatine amount (%) 효소활성 (U/mg) Enzyme activity (U / mg)
리파제 활성 Lipase activity 아밀라제 활성 Amylase activity 프로테아제 활성 Protease activity
원 료 Raw material 73.1 73.1 80.5 80.5 6.1 6.1
실시예 1 Example 1 38.4 38.4 28.3 28.3 31.5 31.5 2.4 2.4
실시예 2 Example 2 59.1 59.1 43.3 43.3 47.0 47.0 3.6 3.6
실시예 3 Example 3 39.5 39.5 28.9 28.9 32.0 32.0 2.4 2.4
실시예 4 Example 4 37.7 37.7 27.4 27.4 30.9 30.9 2.3 2.3
실시예 5 Example 5 41.1 41.1 30.3 30.3 33.8 33.8 2.6 2.6
실시예 6 Example 6 38.5 38.5 28.2 28.2 31.3 31.3 2.3 2.3

표 2에서 실시예 1∼6의 효소역가는 전체 코팅과립중 코팅기제와 가소제를 제외한 판크레아틴의 역가(이론값)과 거의 일치하였다. Table 2 Examples 1 to 6 was almost consistent with the enzymes except for thin coatings, granule coating base and a plasticizer of the reverse activity of pancreatin (theoretical value) at. 그러므로 본 발명자들은 코팅공정 중 판크레아틴의 효소역가가 저하되지 않음을 알 수 있었다. Therefore, the present inventors it was found that the enzyme activity of pancreatin of the coating process not degradation.

실험실시예 3 For example, when three laboratories

장용코팅 과립의 메쉬크기에 따른 타정압의 영향을 살펴보고자 상기의 실시예 1 내지 6 코팅과립을 크기별로 2종을 선택하여 직타하여 얻은 정제를 용출시험하였다. Examine the effects of other positive pressure according to the mesh size of the enteric-coated granules were obtained by the dissolution test for tablets jikta to the above embodiments 1 to 6 coated granules to select two or by size. 이때 부형제로는 미결정셀룰로오스를 사용하였으며 전체 정제중 장용코팅과립의 양은 50%로 하였다. The excipients include microcrystalline cellulose was used in the amount was 50% of the enteric-coated granules of the total tablet. 용출시험장치 1을 이용하여 pH 2.0 및 pH 3.0의 인공위액 800㎖에서 60분 동안 100rpm으로 교반한다. Using a dissolution test apparatus 1 and the mixture was to 100rpm for 60 minutes in artificial gastric juice of pH 2.0 and pH 3.0 800㎖. 이를 인공장액(pH 6.0 인산완충액)으로 옮겨 용출시험장치 2로 30분동안 100rpm으로 교반한 후, 이 용출액 적량을 취해 리파제 활성을 시험한다. It examines the artificial intestinal fluid (pH 6.0 phosphate buffer) was stirred with 100rpm for 30 minutes in a dissolution test apparatus 2 moves, the eluent lipase activity takes a suitable amount. 결과는 하기 표 3에 기재된 바와 같다. Results are described in Table 3 below.

판크레아틴의 용출시험결과 Dissolution test results of pancreatin

pH 2.0의 인공위액을 사용한 경우 If using artificial gastric juice of pH 2.0 pH 3.0의 인공위액을 사용한 경우 If using artificial gastric juice of pH 3.0
리파제 활성(U/mg) Lipase activity (U / mg) Tolerance(%) Tolerance (%) 리파제 활성(U/mg) Lipase activity (U / mg) Tolerance(%) Tolerance (%)
실시예 1 Example 1 20-30 mesh 20-30 mesh 23.8 23.8 84.1 84.1 26.1 26.1 92.2 92.2
30-40 mesh 30-40 mesh 24.7 24.7 87.3 87.3 27.4 27.4 96.8 96.8
실시예 2 Example 2 20-30 mesh 20-30 mesh 15.0 15.0 34.6 34.6 18.5 18.5 42.7 42.7
30-40 mesh 30-40 mesh 18.0 18.0 41.6 41.6 19.1 19.1 44.1 44.1
실시예 3 Example 3 20-30 mesh 20-30 mesh 24.1 24.1 83.4 83.4 26.5 26.5 91.7 91.7
30-40 mesh 30-40 mesh 25.0 25.0 86.5 86.5 27.5 27.5 95.2 95.2
실시예 4 Example 4 20-30 mesh 20-30 mesh 23.2 23.2 84.7 84.7 24.5 24.5 89.4 89.4
30-40 mesh 30-40 mesh 24.5 24.5 89.4 89.4 26.2 26.2 95.6 95.6
실시예 5 Example 5 20-30 mesh 20-30 mesh 24.9 24.9 82.2 82.2 27.2 27.2 89.8 89.8
30-40 mesh 30-40 mesh 26.5 26.5 87.5 87.5 28.7 28.7 94.7 94.7
실시예 6 Example 6 20-30 mesh 20-30 mesh 22.8 22.8 80.9 80.9 25.1 25.1 89.0 89.0
30-40 mesh 30-40 mesh 24.8 24.8 87.9 87.9 26.8 26.8 95.0 95.0

표 3의 결과로 판크레아틴의 장용코팅과립은 산성조건하에서 충분히 보호막으로서의 역할을 할 수 있으며 코팅과립의 크기에 따라 영향 받는다는 것을 알 수 있었다. Enteric-coated granules of pancreatin as a result of Table 3 can serve sufficiently as a protective layer under an acidic condition, and it was found that maven influenced by the size of the coated granules.

본 발명의 판크레아틴의 장용코팅과립은 타정압에 의하여 거의 코팅층이 깨어지지 않았다. Enteric-coated granules of a pancreatin according to the present invention, was almost the coating layer is broken by the static pressure at the other. 내산성시험에서 입자가 큰 코팅과립은 작은 입자의 코팅과립에 비해 역가의 저하가 많았다. Large granular particles coated in acid resistance test were compared to the potency of the coated granules of small particle degradation. 이는 코팅입자가 작을수록 타정압을 분산시키거나 흡수하여 코팅층이 깨어짐을 방지하는 것으로 예측된다. This is to reduce or absorb the other static pressure distribution the smaller the coated particles is expected that a coating layer is to prevent cracking.

실험실시예4 For example, when the laboratory 4

판크레아틴장용과립을 직타하였을 때 부형제의 영향(코팅과립의 깨어짐)을 알아보고자 미결정셀룰로오스를 부형제로 사용하여 직타한 후 용출시험을 하였다. Pancreatin after jikta when the enteric granules to examine the effect of excipient (cracking of the coated granules) jikta using microcrystalline cellulose as an excipient was the dissolution test. 사용된 판크레아틴장용과립의 입자는 30-40mesh의 크기였으며 정제중의 양은 각각 25%,50%,75%,90%로 하였으며 판크레아틴장용과립의 정제 중 절대량은 동일하였다. The pancreatin particle of enteric granules used was 25% was in the size of the tablet The amount 30-40mesh respectively, 50%, 75% and 90% of the absolute amount of the purification of pancreatin enteric granules was the same.

판크레아틴의 용출시험결과 Dissolution test results of pancreatin

pH 2.0의 인공위액을 사용한 경우 If using artificial gastric juice of pH 2.0 pH 3.0의 인공위액을 사용한 경우 If using artificial gastric juice of pH 3.0
판크레아틴코팅 과립의 함량(%) The content of the coated pancreatin granules (%) 리파제 활성(U/mg) Lipase activity (U / mg) Tolerance(%) Tolerance (%) 리파제 활성(U/mg) Lipase activity (U / mg) Tolerance(%) Tolerance (%)
실시예 1 Example 1 25 25 26.1 26.1 92.2 92.2 27.9 27.9 98.6 98.6
50 50 24.7 24.7 87.3 87.3 27.4 27.4 96.8 96.8
75 75 21.2 21.2 74.9 74.9 24.4 24.4 86.2 86.2
90 90 18.3 18.3 64.7 64.7 21.0 21.0 74.2 74.2
실시예 2 Example 2 25 25 20.4 20.4 47.1 47.1 21.3 21.3 49.2 49.2
50 50 18.0 18.0 41.6 41.6 19.1 19.1 44.1 44.1
75 75 14.2 14.2 32.8 32.8 16.7 16.7 38.6 38.6
90 90 10.5 10.5 24.2 24.2 13.5 13.5 31.2 31.2
실시예 3 Example 3 25 25 26.8 26.8 92.7 92.7 28.2 28.2 97.6 97.6
50 50 25.0 25.0 86.5 86.5 27.5 27.5 95.2 95.2
75 75 22.7 22.7 78.5 78.5 25.1 25.1 86.9 86.9
90 90 19.4 19.4 67.1 67.1 21.0 21.0 72.7 72.7
실시예 4 Example 4 25 25 26.0 26.0 94.9 94.9 27.0 27.0 98.5 98.5
50 50 24.5 24.5 89.4 89.4 26.2 26.2 95.6 95.6
75 75 21.7 21.7 79.2 79.2 23.9 23.9 87.2 87.2
90 90 19.2 19.2 70.1 70.1 20.7 20.7 75.5 75.5
실시예 5 Example 5 25 25 28.6 28.6 94.4 94.4 29.3 29.3 96.7 96.7
50 50 26.5 26.5 87.5 87.5 28.7 28.7 94.7 94.7
75 75 23.2 23.2 76.6 76.6 26.4 26.4 87.1 87.1
90 90 20.0 20.0 66.0 66.0 23.1 23.1 76.2 76.2
실시예 6 Example 6 25 25 26.9 26.9 95.4 95.4 27.9 27.9 98.9 98.9
50 50 24.8 24.8 87.9 87.9 26.8 26.8 95.0 95.0
75 75 21.5 21.5 76.2 76.2 24.0 24.0 85.1 85.1
90 90 18.7 18.7 66.3 66.3 21.2 21.2 75.2 75.2

표4의 결과로 본 발명자들은 판크레아틴장용과립을 부형제와 함께 직타하였을 때 부형제의 비율이 너무 적은 경우 타정압에대한 완충제로서의 역할을 할수없으므로 코팅층이 깨어지는 것을 확인할 수 있었다. The present inventors as a result of the Table 4 are when jikta the pancreatin enteric granules with excipients, if the proportion of the excipient is too small because it is not possible to serve as a buffer for the other static pressure was confirmed that a coating layer is broken.

이상의 실험 결과에 비추어 본 발명에 따라서 제조된 판크레아틴장용코팅과립은 입자가 미세하여 타정압에 대해 안정성이 우수하고 또한 본 발명에 따라 제조된 정제의 판크레아틴 장내 활성이 원료 그 자체와 비교하여 거의 대등한 수준에 있어 본 발명은 산업적으로 매우 유용하다 할 것이다. According to the invention the produced pancreatin enteric-coated granules in light of the above experimental results, the particles in the fine and the other stability is excellent for a constant pressure and also pancreatin enteric activity of the produced tablets according to the invention compared to the material itself virtually It presents in a comparable level invention to be industrially very useful.

Claims (11)

  1. 판크레아틴을 저온하에 부유시키면서 고속으로 코팅액으로 분무하여 코팅과립을 생성함을 특징으로 하는 판크레아틴 장용코팅과립의 제조방법. Pancreatin enteric-coated granules while the method of producing a rich pancreatin under low temperature and high speed by spraying with the coating solution, characterized in that the generation of coated granules.
  2. 제1항에 있어서, 생성된 코팅과립을 저온하에 부유시키면서 고속으로 1차 코팅액과 동일하거나 상이한 코팅액으로 재분무하는 단계를 추가로 수행하는 방법. The method of claim 1, while floating the resulting coated granules under low temperature To equal to the first coating liquid at a high speed, or performed by adding the step of re-spraying with a different coating solution.
  3. 제1항에 있어서, 코팅기제가 옥수수단백추출물, 알긴산나트륨, 알긴산, 메타크릴산-아크릴산에틸공중합체류, 쉘락류, 카보폴류, 하이드록시프로필메칠셀룰로오스프탈레이트류, 하이드록시프로필메칠셀룰로오스 아세테이트숙시네이트, 하이드록시프로필메칠 아세테이트숙시네이트, 카르복시메칠셀룰로오스, 셀룰로오스아세테이트프탈레이트류, 하이드록시프로필셀룰로오스류, 에칠셀룰로오스류, 메칠셀룰로오스류, 폴리비닐아세테이트프탈레이트, 대두단백, 소맥단백, 키틴, 키틴산, 한천, 카라기난, 펙틴, 구아 검, 로우커스트 검, 잔탄검, 젤란 검, 아라비아 검, 탄소수 6~12개의 중쇄 지방산류 및 이의 혼합물로 이루어진 그룹중에서 선택되는 방법. The method of claim 1 wherein the coating agent corn protein extract, alginic acid, sodium alginate, methacrylic acid-ethyl acrylate copolymers, shell rakryu, carbonyl polryu, hydroxypropyl methyl cellulose phthalates, hydroxypropyl methyl cellulose acetate succinate, hydroxy hydroxypropyl methyl acetate succinate, carboxymethylcellulose, cellulose acetate phthalates, hydroxypropyl celluloses, echil celluloses, methyl celluloses, polyvinyl acetate phthalate, soy protein, wheat protein, chitin, chitin acid, agar, carrageenan, pectin, guar gum, low Cust gum, xanthan gum, gellan gum, gum arabic, is selected from the group consisting of the 12 heavy chain fatty acid having 6 to acids, and mixtures thereof.
  4. 제1항에 있어서, 코팅액중의 가소제가 폴리에틸렌글리콜, 글리세린지방산에스테르, 프로필렌글리콜, 소르비탄 지방산 에스테르류, 글리세린, 구연산트리에틸, 트리아세틴, 세틸알코올, 스테아릴알코올 및 이의 혼합물로 이루어진 그룹중에서 선택되는 방법. According to claim 1, selected from the of the coating liquid plasticizer, polyethylene glycol, glycerol fatty acid ester, propylene glycol, sorbitan fatty acid esters, glycerin, triethyl citrate, triacetin, cetyl alcohol, stearyl alcohol, and the group consisting of a mixture thereof how.
  5. 제1항에 있어서, 가소제의 함량이 판크레아틴 사용량의 1 내지 50 중량%인 방법. The method of claim 1, wherein the content of the plasticizer is 1 to 50% by weight of pancreatin usage.
  6. 제1항에 있어서, 판크레아틴의 함량이 과립의 1 내지 95 중량%인 방법. The method of claim 1, wherein the plate method content of 1 to 95% by weight of the granules of creatine.
  7. 제1항에 있어서, 코팅기제의 함량이 판크레아틴 사용량의 1 내지 250 중량%인 방법. The method of claim 1, wherein 1 to 250% by weight The method of the content of the coating base pancreatin usage.
  8. 제 1항에 있어서, 코팅액중의 용매가 물, 알콜, 아세톤, 아세토니트릴, 메칠렌클로라이드, 에테르, 헥산, 클로르포름, 1,4-디옥산, 테트라하이드로푸란, 디메틸설폭사이드, 에칠아세테이트, 메칠아세테이트 및 이의 혼합물로 이루어진 그룹중에서 선택되는 방법. The method of claim 1, wherein the solvent in the coating liquid, water, alcohols, acetone, acetonitrile, methylene chloride, ether, hexane, chloroform, 1,4-dioxane, tetrahydrofuran, dimethylsulfoxide, echil acetate, methyl It is selected from the group consisting of acetate, and mixtures thereof.
  9. 제 1항 내지 7항중 어느 한 항에 있어서, 모든 조작을 20℃ 내지 70℃범위에서 실시하는 방법. According to claim 1 to 7 wherein any one of a method of carrying out all operations at 20 ℃ to 70 ℃ range.
  10. 제 1항에 있어서 사용된 장치가 유동층조립기(Fluid bed coater) 또는 CF-Granulater를 사용하는 방법. The method of the device is using a fluidized bed granulator (Fluid bed coater) or CF-Granulater use according to claim 1.
  11. 제 1항의 판크레아틴 코팅과립을 정제의 총 중량중 5내지 80%의 양으로 약제학적으로 허용되는 부형제와 혼합하고 이 혼합물을 타정함을 특징으로 하는 판크레아틴코팅과립을 함유하는 정제의 제조방법. Claim 1 pancreatin coating method for producing a tablet of the total weight of the tablet granule mixture as excipients a pharmaceutically acceptable an amount of 5 to 80% and containing pancreatin coated granules, characterized by tenderness other the mixture.
KR19990005822A 1998-02-26 1999-02-22 A process for producing enteric-coated pancreatin granules KR19990072826A (en)

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Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6632429B1 (en) 1999-12-17 2003-10-14 Joan M. Fallon Methods for treating pervasive development disorders
US20070053895A1 (en) 2000-08-14 2007-03-08 Fallon Joan M Method of treating and diagnosing parkinsons disease and related dysautonomic disorders
CA2419726A1 (en) 2000-09-07 2003-02-14 Tokyo Gas Company Limited Preparations for diagnosing extrapancreatic secretory function
DE10053416A1 (en) 2000-10-27 2002-05-08 Bsh Bosch Siemens Hausgeraete Process for machine cleaning textiles or solid objects
KR20030060105A (en) * 2000-11-15 2003-07-12 유란드 인터내셔날 에스.피.아. Microsphere of pancreatic enzymes with high stability and production method thereof
US8030002B2 (en) 2000-11-16 2011-10-04 Curemark Llc Methods for diagnosing pervasive development disorders, dysautonomia and other neurological conditions
JP4592041B2 (en) * 2000-11-24 2010-12-01 株式会社Nrlファーマ Preparation and use of novel foods to improve the quality of life
JP4494712B2 (en) * 2002-11-12 2010-06-30 大日本住友製薬株式会社 Multiple unit type sustained release preparation
GB0320020D0 (en) 2003-08-27 2003-10-01 Mw Encap Ltd Improved formulation for providing an enteric coating material
CN1933850B (en) 2004-03-22 2011-01-12 索尔瓦药物有限公司 Oral pharmaceutical compositions of lipase-containing products, in particular of pancreatin, containing surfactants
WO2005097082A1 (en) * 2004-03-31 2005-10-20 Bpsi Holdings, Inc. Enteric coatings for orally ingestible substrates
KR101199196B1 (en) * 2005-07-25 2012-11-07 (주)다산메디켐 Manufacturing method for spheric granule of pancreatin
JP5284092B2 (en) * 2005-08-15 2013-09-11 アボット ラボラトリーズ ゲゼルシャフト ミット ベシュレンクテル ハフツングAbbott Laboratories GmbH Pancreatin micro pellet cores suitable for enteric coating
RU2440101C2 (en) * 2005-08-15 2012-01-20 Зольвай Фармасьютиклз Гмбх Controlled release pharmaceutical compositions unstable in medicinal acid medium
US9198871B2 (en) 2005-08-15 2015-12-01 Abbott Products Gmbh Delayed release pancreatin compositions
US20080058282A1 (en) 2005-08-30 2008-03-06 Fallon Joan M Use of lactulose in the treatment of autism
DE102006001554A1 (en) * 2006-01-05 2007-07-12 Ipc Process-Center Gmbh & Co. Micro pellets for the production of pet food pellets
US10072256B2 (en) 2006-05-22 2018-09-11 Abbott Products Gmbh Process for separating and determining the viral load in a pancreatin sample
ES2560527T3 (en) * 2007-02-20 2016-02-19 Allergan Pharmaceuticals International Limited stable compositions of digestive enzymes
WO2009109856A3 (en) 2008-03-07 2010-03-25 Axcan Pharma Inc. Method for detecting infectious parvovirus in pharmaceutical preparations
US8658163B2 (en) 2008-03-13 2014-02-25 Curemark Llc Compositions and use thereof for treating symptoms of preeclampsia
US8084025B2 (en) 2008-04-18 2011-12-27 Curemark Llc Method for the treatment of the symptoms of drug and alcohol addiction
US9320780B2 (en) 2008-06-26 2016-04-26 Curemark Llc Methods and compositions for the treatment of symptoms of Williams Syndrome
US20100092447A1 (en) 2008-10-03 2010-04-15 Fallon Joan M Methods and compositions for the treatment of symptoms of prion diseases
EP2947100A1 (en) 2009-01-06 2015-11-25 Curelon LLC Oral compositions for the treatment or the prevention of infections by E. Coli
EP3064217B1 (en) 2009-01-06 2018-04-18 Galenagen, LLC Compositions comprising protease, amylase and lipase for use in the treatment of staphylococcus aureus infections
US9056050B2 (en) 2009-04-13 2015-06-16 Curemark Llc Enzyme delivery systems and methods of preparation and use
EP2295039B1 (en) 2009-08-28 2013-12-11 Nordmark Arzneimittel GmbH & Co.KG Method of preparing pancreatin pellets, in particular pancreatin micropellets, and pancreatin pellets prepared thereby
WO2011050135A1 (en) 2009-10-21 2011-04-28 Curemark Llc Methods and compositions for the prevention and treatment of influenza
US20110183032A1 (en) 2010-01-15 2011-07-28 Kemin Industries, Inc. Stomach-proected Alpha-amylase to Improve the Utilization of Diet Energy and Growth Performance of Animals
WO2011114224A1 (en) * 2010-03-19 2011-09-22 Axcan Pharma Inc. Gastro-resistant enzyme pharmaceutical compositions
EP2616048A4 (en) * 2010-11-19 2014-04-02 Curemark Llc Preparation and use of combination enzyme and gastrointestinal modulator delivery systems
EP2701733A4 (en) 2011-04-21 2014-12-31 Curemark Llc Compounds for the treatment of neuropsychiatric disorders
WO2013021359A1 (en) 2011-08-08 2013-02-14 Aptalis Pharma Ltd. Method for dissolution testing of solid compositions containing digestive enzymes
JP6304234B2 (en) * 2013-03-08 2018-04-04 ライオン株式会社 Coating composition, the coating formulations and a method of manufacturing the same

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