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1. 发明授权

US4640834A Method of inactivating reproducible filterable pathogens in blood products as well as a method of producing blood products 失效
标题翻译：灭活血液制品中可再生可过滤病原体的方法以及生产血液制品的方法
公开(公告)号：US4640834A
公开(公告)日：1987-02-03
申请号：US705691
申请日：1985-02-26
申请人： Johann Eibl , Otto Schwarz , Fritz Elsinger , Gunter Wober , Anton Philapitsch , Yendra Linnau , Friedrich Dorner , Karl Trambauer , Wolfgang Frechinger
发明人： Johann Eibl , Otto Schwarz , Fritz Elsinger , Gunter Wober , Anton Philapitsch , Yendra Linnau , Friedrich Dorner , Karl Trambauer , Wolfgang Frechinger
IPC分类号： A61K39/395 , A61K35/14 , A61K35/16 , A61K38/16 , A61K38/48 , A61K38/55 , A61L2/00 , A61L2/04 , C12N9/68 , A61K37/465 , A61K37/48
CPC分类号： A61K35/16 , A61L2/0023
摘要： A method of inactivating viruses in blood products is described, wherein the blood products are heat-treated in a humid or in a solid state in the presence of inorganic or organic hydroxyl group-containing compounds having an H.sup.+ -dissociation constant of
摘要翻译：描述了一种在血液制品中灭活病毒的方法，其中血液制品在H + - 解离常数<10-11的无机或有机羟基化合物存在下，以潮湿或固态热处理浓度大于0.05（5重量％）且小于0.70（70重量％）。含羟基的化合物可以是水，甲醇，乙醇或甘露醇。温度可能高达121℃，热处理可能持续1秒至100小时。灭活方法可以用于产生选自酶，包括凝血因子，酶抑制剂，免疫球蛋白，白蛋白，纤溶酶原，纤维蛋白原，纤连蛋白或血浆的酶的血液制品，灭活破坏可能存在的任何可再现的可过滤病原体。

2. 发明授权

US5234685A Method of determining incompatibility-reaction-causing substances in blood products as well as a method of inactivating said incompatibility-reaction-causing substances 失效
标题翻译：测定血液制品中不相容反应物质的方法以及灭活所述不相容反应物质的方法
公开(公告)号：US5234685A
公开(公告)日：1993-08-10
申请号：US412999
申请日：1989-09-26
申请人： Johann Eibl , Yendra Linnau , Otto Schwarz
发明人： Johann Eibl , Yendra Linnau , Otto Schwarz
IPC分类号： A61K35/16 , A61K38/00 , C07K16/06
CPC分类号： C07K16/065 , A61K35/16 , A61K38/00
摘要： There is disclosed a method of determining the presence of incompatibility-reaction-causing substances in blood products. There is also disclosed a method of inactivating incompatibility-reaction-causing substances in blood products to be applied therapeutically and prophylactically. For this purpose, a fraction obtained from human or animal blood is treated with pancreas enzymes bound to water insoluble carrier material and, optionally, the fraction is subjected to further fractionation and concentration.
摘要翻译：公开了一种测定血液制品中不相容反应物质的存在的方法。还公开了一种使治疗和预防性应用的血液制品中不相容反应物质失活的方法。为此，从与人或动物血液获得的级分用与水不溶性载体材料结合的胰腺酶处理，并且任选地，将级分进一步分级和浓缩。

3. 发明授权

US4886758A Method of determining incompatibility-reaction-causing substances in blood products as well as a method of inactivating said incompatibility-reaction-causing substances 失效
标题翻译：测定血液制品中不相容反应物质的方法以及灭活所述不相容反应物质的方法
公开(公告)号：US4886758A
公开(公告)日：1989-12-12
申请号：US907652
申请日：1986-09-15
申请人： Johann Eibl , Yendra Linnau , Otto Schwarz
发明人： Johann Eibl , Yendra Linnau , Otto Schwarz
IPC分类号： A61K39/395 , A61K35/16 , A61K38/00 , A61K49/00 , C07K16/06 , G01N33/15
CPC分类号： A61K35/16 , C07K16/065 , A61K38/00
摘要： There is disclosed a method of determining the presence of incompatibility-reaction-causing substances in blood products. There is also disclosed a method of inactivating incompatibility-reaction-causing substances in blood products to be applied therapeutically and prophylactically. For this purpose, a fraction obtained from human or animal blood is treated with pancreas enzymes bound to water insoluble carrier material and, optionally, the fraction is subjected to further fractionation and concentration.
摘要翻译：公开了一种测定血液制品中不相容反应物质的存在的方法。还公开了一种使治疗和预防性应用的血液制品中不相容反应物质失活的方法。为此，从与人或动物血液获得的级分用与水不溶性载体材料结合的胰腺酶处理，并且任选地，将级分进一步分级和浓缩。

4. 发明授权

US5122373A Immunoglobulin-G-containing fraction 失效
$Immunoglobulin-G-containing fraction$
标题翻译：含有免疫球蛋白的G含量
公开(公告)号：US5122373A
公开(公告)日：1992-06-16
申请号：US569535
申请日：1990-08-20
申请人： Johann Eibl , Yendra Linnau , Otto Schwarz
发明人： Johann Eibl , Yendra Linnau , Otto Schwarz
IPC分类号： A61K39/395 , A61K38/00 , C07K16/06
CPC分类号： C07K16/065 , A61K38/00
摘要： An immunoglobulin-G-containing fraction from human or animal plasma comprising monomeric IgG molecules as well as at least 70% gammaglobulins, destined for intravenous application.The fraction has a low anticomplementary activity and is substantially free of vasoactive and leucopenically active as well as bronchospastic substances.
摘要翻译：来自人或动物血浆的含有免疫球蛋白G的级分包含单体IgG分子以及至少70％的用于静脉内应用的丙种球蛋白。所述级分具有低抗补体活性，并且基本上不含血管活性和有丝分裂活性物质以及支气管痉挛物质。

5. 发明授权

US4904641A Method of inactivating reproducible filterable pathogens in blood plasma products 失效
标题翻译：灭活血浆中可再生可过滤病原体的方法
公开(公告)号：US4904641A
公开(公告)日：1990-02-27
申请号：US293085
申请日：1989-01-03
申请人： Johann Eibl , Otto Schwarz , Fritz Elsinger , Gunter Wober , Anton Philapitsch , Yendra Linnau , Friedrich Dorner , Karl Trambauer , Wolfgang Frechinger
发明人： Johann Eibl , Otto Schwarz , Fritz Elsinger , Gunter Wober , Anton Philapitsch , Yendra Linnau , Friedrich Dorner , Karl Trambauer , Wolfgang Frechinger
IPC分类号： A61K35/14 , A61L2/00
CPC分类号： A61L2/0023
摘要： There is disclosed a method of inactivating reproducible filterable pathogens in blood plasma products by applying elevated temperatures. The blood plasma products are heat treated in a solid state in a closed inactivation container in the presence of specific amounts of water and organic compounds, provided that the water substantially remains physically bound to the blood plasma products, while the organic compound is present in a gaseous form in the atmosphere. The water content of the blood plasma products is 0.08 to 0.40. The concentration of the organic compounds in the gaseous phase is 0.01 to 10 g per liter of container volume.
摘要翻译：公开了通过施加升高的温度来灭活血浆产品中可再现的可过滤病原体的方法。在特定量的水和有机化合物的存在下，在封闭的灭活容器中将血浆产物以固态热处理，条件是水基本上保持与血浆产物的物理结合，而有机化合物存在于气体形式在大气中。血浆产品的含水量为0.08〜0.40。气相中有机化合物的浓度为每升容器体积0.01至10g。

6. 发明授权

US5410022A Method of producing a factor VIII preparation 失效
标题翻译：生产因子VIII制剂的方法
公开(公告)号：US5410022A
公开(公告)日：1995-04-25
申请号：US49585
申请日：1993-04-20
申请人： Johann Eibl , Friedrich Elsinger , Herbert Gritsch , Yendra Linnau , Otto Schwarz , Peter Turecek , Gunther Wober
发明人： Johann Eibl , Friedrich Elsinger , Herbert Gritsch , Yendra Linnau , Otto Schwarz , Peter Turecek , Gunther Wober
IPC分类号： A61K38/43 , A61K38/00 , A61K38/37 , A61L2/04 , A61L2/16 , A61L2/18 , A61P7/04 , C07K1/14 , C07K1/16 , C07K14/435 , C07K14/745 , C07K14/755 , C12N9/74 , C07K3/20 , C07K15/06
CPC分类号： C07K14/755 , A61K38/00 , Y10S530/83 , Y10S530/831
摘要： The invention relates to a method of producing virus-safe highly purified factor VIII. The method includes a combination of the following measures:a) chromatographic purification of a factor VIII-containing fraction,b) tenside treatment of factor VIII in an aqueous solution at a tenside/protein ratio of from 1:1 to 1000:1, andc) heat treatment of the factor VIII preparation in the solid state.
摘要翻译：本发明涉及一种生产病毒安全高度纯化因子VIII的方法。该方法包括以下措施的组合：a）含有因子VIII的级分的色谱纯化，b）在表面活性剂/蛋白质比例为1:1至1000:1的水溶液中进行因子VIII的表面活性剂处理，以及 c）在固体状态下热处理VIII因子制剂。

7. 发明授权

US4814435A Method of producing a factor VIII (AHF) containing fraction 失效
$Method of producing a factor VIII (AHF) containing fraction$
标题翻译：制备含有因子VIII（AHF）的级分的方法
公开(公告)号：US4814435A
公开(公告)日：1989-03-21
申请号：US108458
申请日：1987-10-15
申请人： Otto Schwarz , Yendra Linnau
发明人： Otto Schwarz , Yendra Linnau
IPC分类号： A61K35/14 , A61K38/00 , A61K38/43 , A61P7/04 , C07K1/30 , C07K14/435 , C07K14/745 , C07K14/755 , A61K35/16 , C07K15/14
CPC分类号： C07K14/755 , A61K38/00 , Y10S530/83
摘要： There is disclosed a method of producing a Factor VIII (AHF) containing fraction having a specific activity of at least 2.5 units of Factor VIII/mg protein as well as a portion of immunoglobulin G (IgG) of 10 mg/1000 units of Factor VIII at the most. Its risk of transmission of viral or bacterial infections is to be avoided or largely reduced. The method consists in that undesired proteins are at first precipitated from a Factor VIII (AHF) containing plasma fraction in the presence of SPS. The purified Factor VIII containing solution is treated with suitable salts or salt mixtures in order to obtain a Factor VIII containing precipitate. This precipitate is dissolved, lyophilized and finally heat-treated.
摘要翻译：公开了一种生产含有至少2.5单位因子VIII / mg蛋白的比活性的因子VIII（AHF）的部分以及10mg / 1000单位因子VIII的免疫球蛋白G（IgG）的一部分的方法至多，最多。其传播病毒或细菌感染的风险是要避免或大大降低。该方法包括在SPS存在下首先从含有血浆级分的因子VIII（AHF）沉淀不需要的蛋白质。用合适的盐或盐混合物处理纯化的含Ⅷ因子的溶液，以获得含Ⅷ因子的沉淀物。将该沉淀溶解，冻干，最后进行热处理。

8. 发明授权

US4404131A Method of producing a factor-VIII(AHF)-high-concentrate 失效
标题翻译：生产因子VIII（AHF） - 高浓缩物的方法
公开(公告)号：US4404131A
公开(公告)日：1983-09-13
申请号：US287912
申请日：1981-07-29
申请人： Otto Schwarz , Yendra Linnau
发明人： Otto Schwarz , Yendra Linnau
IPC分类号： C07K14/745 , A61K35/14 , A61K38/00 , A61K38/16 , A61K38/43 , C07K14/435 , C07K14/755 , C07G7/00
CPC分类号： C07K14/755 , A61K38/00 , Y10S530/83 , Y10S530/831
摘要： In a method of producing a factor-VIII(AHF)-high-concentrate having a specific activity of at least 2.5 units AHF and a fibrinogen content of less than 0.25 mg/mg protein from human or animal plasma, the plasma is subjected to a multi-step fractionation. The fraction purified by these fractionation measures and enriched in factor VIII (AHF) is subjected to a cryoalcohol precipitation and the resulting precipitate is processed into a stable form.
摘要翻译：在生产具有至少2.5单位AHF的比活性和来自人或动物血浆的纤维蛋白原含量小于0.25mg / mg蛋白质的因子VIII（AHF） - 高浓缩物的方法中，将等离子体进行多步分馏。通过这些分级测量纯化并富集因子VIII（AHF）的级分进行冷冻醇沉淀，并将所得沉淀物加工成稳定的形式。

9. 发明授权

US4522751A Method for producing a preparation containing factor VIII (AHF) 失效
标题翻译：制备含有因子VIII（AHF）的制剂的方法
公开(公告)号：US4522751A
公开(公告)日：1985-06-11
申请号：US611638
申请日：1984-05-18
申请人： Yendra Linnau , Otto Schwarz
发明人： Yendra Linnau , Otto Schwarz
IPC分类号： A61K35/14 , A61K35/16 , A61K38/00 , A61K38/43 , A61P7/04 , C07K14/755 , C07G7/00
CPC分类号： C07K14/755 , A61K38/00 , Y10S530/83
摘要： There is described a method for producing a preparation having a high content of Factor VIII (AHF), i.e. with a specific activity of at least 1.5 units of Factor VIII/mg protein, immunoglobulin G (IgG) of from 15 to 30 mg/1000 units of Factor VIII and fibrinogen of from 20 to 40 mg/100 units of Factor VIII. The method consists in that a Factor VIII containing plasma fraction is dissolved in a buffer, the solution is purified from undesired proteins by precipitation and is concentrated, the precipitation of undesired proteins being carried out in the presence of sulfated polysaccharide at a pH of from 6 to 7. After separation of the undesired proteins, a Factor VIII concentrate is precipitated, dissolved and processed into stable form. If desired, an antithrombin III-heparin complex or an antithrombin III-heparinoid complex is added to the solution.
摘要翻译：描述了一种制备具有高含量因子VIII（AHF）的制剂的方法，即具有至少1.5单位因子VIII / mg蛋白质的比活性，15至30mg / 1000的免疫球蛋白G（IgG）因子VIII和纤维蛋白原单位为20至40mg / 100单位因子VIII。该方法包括将含有因子VIII的血浆级分溶解在缓冲液中，通过沉淀将溶液从不想要的蛋白质中纯化并浓缩，不需要的蛋白质的沉淀在硫酸化多糖的存在下进行，pH为6 在分离不需要的蛋白质之后，将因子VIII浓缩物沉淀，溶解并加工成稳定的形式。如果需要，向溶液中加入抗凝血酶III-肝素复合物或抗凝血酶III-类肝素复合物。

10. 发明授权

US4276283A Method of preparing an intravenously administrable immune globulin preparation containing antibodies and preparations produced according to this method 失效
标题翻译：制备含有根据该方法制备的抗体和制剂的静脉内施用的免疫球蛋白制剂的方法
公开(公告)号：US4276283A
公开(公告)日：1981-06-30
申请号：US74257
申请日：1979-09-10
申请人： Martha Eibl , Otto Schwarz , Yendra Linnau
发明人： Martha Eibl , Otto Schwarz , Yendra Linnau
IPC分类号： A61K39/395 , C07K16/06 , A61K39/00
CPC分类号： C07K16/065 , Y10S530/83
摘要： A method of preparing an intravenously administrable immune globulin preparation containing antibodies, in which human blood plasma is fractionated and an immune-globulin-containing fraction is freed from undesired protein impurities by a single or repeated precipitation with polyethylene glycol, is characterized in that the immune-globulin-containing fraction is subjected in a first purification step prior to the polyethylene glycol precipitation to a treatment with an aqueous solution of a salt of an inorganic acid, and in that at least one of the following purification steps is carried out with polyethylene glycol in the presence of a soluble carbohydrate or a non-protein-precipitating polyol, whereupon the immune globulin freed from protein impurities is precipitated from the remaining solution by water-soluble polymers and is finished in a known manner to the pharmaceutical preparation.
摘要翻译：制备含有抗体的静脉内施用的免疫球蛋白制剂的方法，其中人血浆被分级，并且含有免疫球蛋白的级分通过用聚乙二醇单次或重复沉淀而不含有不需要的蛋白质杂质，其特征在于免疫含有球蛋白的级分在聚乙二醇沉淀之前的第一纯化步骤中经过无机酸盐的水溶液处理，并且至少一个以下纯化步骤用聚乙二醇在可溶性碳水化合物或非蛋白沉淀多元醇的存在下，免去蛋白质杂质的免疫球蛋白从剩余的溶液中被水溶性聚合物沉淀，并以已知的方式完成药物制剂。

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