| 摘要 |
Processes are described for producing solid or semi-solid compositions, in particular solid oral compositions for pharmaceutical use, comprising treating an enzyme or enzyme-mixture with lipase-activity and a surfactant-component at defined process parameters. Said processes are suited for diminishing undesired biological contamination, e.g. viral contamination, of the said enzyme or enzyme-mixture while maintaining its desired biological activities, e.g. enzymatic activities. The process is suitable for industrial use. Also described are solid or semi-solid compositions comprising an enzyme or enzyme-mixture having lipase activity, a surfactant-component and a polymeric additive, optionally comprising further auxiliaries. Said compositions can preferably be obtained by the processes as described herein. Further described are pharmaceutical compositions comprising the solid or semi-solid compositions as described herein. |
| 主权项 |
1. A process for the preparation of a solid or semi-solid composition, comprising processing a mixture, comprising
(a) 40-75% by weight of pancreatin and/or a pancreatin-containing mixture of digestive enzymes derived from a mammal; (b) 10-50% by weight of a surfactant-component comprising
(i) at least one surfactant selected from polyethylene glycol-fatty acid monoesters: polyethylene glycol-fatty acid diesters; polyethylene glycol glycerol fatty acid esters; ethylene glycol alkyl ethers; polyethylene glycol glycerol fatty acid esters; polyethylene glycol alkyl ethers; oligoethylene glycol alkyl ethers; polyethylene glycol sterol ethers; polyethylene glycol sorbitan fatty acid esters; sugar esters; D-α-tocopheryl polyethylene glycol 1000 succinate; fatty acid amidoalkylbetaines with C2-C22 fatty acids; lecithin, lysolecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylglycerol, lysophosphatidylinositol, lysophosphatidic acid, lysophosphatidylserine, and mixtures of any of the foregoing,(ii) optionally at least one co-surfactant selected from partial esters of glycerol, propylene glycol and/or polyglycerols with aliphatic carboxylic acids; esters of ethyl diglycol with aliphatic carboxylic acids; partial ethers of glycerol, propylene glycol, and/or polyglycerols with aliphatic alcohols; ethers of ethyl diglycol with aliphatic alcohols, mono or diesters of oligoethylene glycols with aliphatic carboxylic (fatty) acids and mixtures of any of the foregoing, and(iii) optionally a lipophilic phase, selected from diglycerides of aliphatic carboxylic acids, triglycerides of aliphatic carboxylic acids and mixtures of any of the foregoing; (c) 0-25% by weight of one or more pharmaceutically acceptable auxiliary agent(s), and (d) 0-35% by weight of a polymeric additive selected from hydrophilic polymers with a melting points or glass transition temperatures of 50-160° C.;and wherein the % by weight of components (a), (b), (c) and (d) are weight to weight of the mixture for preparing a solid composition and add to 100% by weight for said mixture in each case;by a method selected from melt granulation, melt pelletization and melt extrusion, in each case at a product temperature of 90-130° C. and for a time period of not less than 30 sec. and not exceeding 45 min. |
