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1. 发明授权

US4503039A Coagulant plasma-protein solution 失效
标题翻译：凝血浆蛋白溶液
公开(公告)号：US4503039A
公开(公告)日：1985-03-05
申请号：US561390
申请日：1983-12-14
申请人： Ronald Kotitschke , Wolfgang Stephan
发明人： Ronald Kotitschke , Wolfgang Stephan
IPC分类号： A61K35/14 , A61K38/00 , A61K38/16 , A61K38/43 , C07K14/435 , C07K14/745 , C07K14/755 , C07K14/81 , C12N9/64 , A61K35/16
CPC分类号： C12N9/647 , C07K14/745 , C07K14/755 , C07K14/8128 , A61K38/00
摘要： A coagulant plasma-protein solution obtained by adsorbing stabilized human plasma at least once with 20-40 mg of colloidal silicic acid per gram of plasma protein and separating the adsorbent from the adsorbate, a method of manufacturing the solution, and a pharmaceutical preparation containing the solution and intended for the intravenous treatment of complex disorders of the hemostatic system. The solution is low in fibrinogen and factors XI and XII but otherwise close in composition to the starting material.
摘要翻译：通过用20-40mg胶体硅酸/克血浆蛋白吸附稳定的人血浆至少一次获得的凝血剂血浆蛋白溶液，并将吸附剂与吸附物分离，制备溶液的方法和含有解决方案，旨在静脉治疗止血系统的复杂疾病。该溶液的纤维蛋白原和XI和XII因子低，但是在组合物中起始材料接近。

2. 发明授权

US5099003A Method of preparing a sterile plasma-protein solution containing fibrinogen and Factor XIII 失效
标题翻译：制备含有纤连蛋白和因子XIII的纯等离子体蛋白质溶液的方法
公开(公告)号：US5099003A
公开(公告)日：1992-03-24
申请号：US256531
申请日：1988-10-12
申请人： Ronald Kotitschke , Axel W. Stemberger , Wolfgang Stephan
发明人： Ronald Kotitschke , Axel W. Stemberger , Wolfgang Stephan
IPC分类号： A61K35/14 , A61K38/00 , A61K38/16 , A61K38/43 , A61L2/00 , C07K14/435 , C07K14/745 , C07K14/75 , C12N9/10
CPC分类号： C12N9/1044 , A61L2/0088 , C07K14/75 , A61K38/00
摘要： A method of preparing a sterile and stable plasma-protein solution containing fibrinogen and Factor XIII from human blood plasma which has been stabilized with citrate, comprising treating the plasma with .beta.-propiolactone and irradiating it with ultraviolet light, removing the Factors II, VII, IX and X by adsorption onto anion exchangers that adsorb proteins, precipitating the companion proteins out by adding ethanol until the solution has a final concentration of about 9% by volume at -3.degree. C., centrifuging the precipitate off, dissolving the precipitate in a citrate buffer at a pH of about 6.35 and a temperature of about 37.degree. C., adjusting the protein level of the solution to about 13.3 g/l with sodium citrate solution, adding ethanol, a glycine citrate buffer, and a solution of sodium citrate to precipitate out the companion proteins, adding ethanol to the remaining solution until the solution has a final concentration of about 9% by volume at -3.degree. C., thereby precipitating fribrinogen and Factor XIII, dissolving the precipitate in a citrate buffer at a pH of about 6.35 and a temperature of about 37.degree. C., and filtering the solution.
摘要翻译：一种制备含有已经用柠檬酸盐稳定的人血浆中的纤维蛋白原和因子XIII的无菌且稳定的血浆蛋白溶液的方法，包括用β-丙内酯处理血浆并用紫外线照射，除去因子II， IX和X通过吸附到吸附蛋白质的阴离子交换剂上，通过加入乙醇沉淀出伴侣蛋白，直到溶液在-3℃下具有约9体积％的终浓度，离心沉淀，将沉淀物溶解在柠檬酸盐缓冲液，pH约6.35，温度约37℃，用柠檬酸钠溶液调节溶液的蛋白质水平至约13.3g / l，加入乙醇，柠檬酸甘氨酸缓冲液和柠檬酸钠溶液沉淀出伴侣蛋白质，向剩余的溶液中加入乙醇直到溶液在-3℃下具有约9体积％的终浓度，从而沉淀稀释蛋白原和因子XIII，将沉淀溶解在约6.35的pH和约37℃的柠檬酸盐缓冲液中，并过滤溶液。

3. 发明授权

US5075425A Process for the preparation of a pharmaceutical which contains IgG, IgA and IgM and can be administered intravenously 失效
标题翻译：制备IGG，IGA和IGM的药物的制备方法，并且可以被内窥镜
公开(公告)号：US5075425A
公开(公告)日：1991-12-24
申请号：US561033
申请日：1990-08-01
申请人： Ronald Kotitschke , Wolfgang Stephan , Wolfgang Moller , Detlef Piechaczek , Dieter Rudnick
发明人： Ronald Kotitschke , Wolfgang Stephan , Wolfgang Moller , Detlef Piechaczek , Dieter Rudnick
IPC分类号： A61K39/395 , A61K38/00 , C07K16/06
CPC分类号： C07K16/065 , A61K38/00
摘要： Process for the preparation of an immunoglobulin solution suitable for intravenous administration from a human blood protein fraction containing immunoglobulins IgG, IgA and IgM in partially concentrated from, with the process steps: addition of acetate buffer to the protein fraction, where appropriate removal of insoluble constituents by filtration, treatment with calcium phosphate and octanoic acid, centrifugation, removal of the supernatant and treatment thereof with an adsorbent, removal of the adsorbent and sterilization by filtration.
摘要翻译：用于制备适于从含有部分浓缩的免疫球蛋白IgG，IgA和IgM的人血液蛋白部分静脉内施用的免疫球蛋白溶液的方法，其中步骤：向蛋白质级分加入乙酸盐缓冲液，在适当的情况下除去不溶性成分通过过滤，用磷酸钙和辛酸处理，离心，除去上清液并用吸附剂处理，除去吸附剂并通过过滤灭菌。

4. 发明授权

US4370264A Method for the cold sterilization of preparations containing blood coagulation factor VIII 失效
标题翻译：血液凝固因子VIII制剂冷灭菌方法
公开(公告)号：US4370264A
公开(公告)日：1983-01-25
申请号：US300074
申请日：1981-09-08
申请人： Ronald Kotitschke , Wolfgang Stephan
发明人： Ronald Kotitschke , Wolfgang Stephan
IPC分类号： A61K35/14 , A61K38/43 , A61L2/00 , A61L2/10 , A61L2/20 , C07G7/00
CPC分类号： A61L2/0094 , A61L2/10 , A61L2/20 , Y10S530/83 , Y10S530/831
摘要： A process for the cold sterilization of a preparation containing blood coagulation factor VIII, comprising(A) contacting a protein solution containing factor VIII with a physiologically compatible, non-ionogenic tenside, and then subjecting the solution to(B) irradiation with ultraviolet light,(C) treatment with beta-propiolactione, and(D) to an adsorption treatment with colloidal silica, steps B-C-D being performed in the sequence B-C-D, B-D-C, D-C-B or D-B-C.
摘要翻译：一种含有凝血因子VIII的制剂的冷灭菌方法，包括（A）使含有因子VIII的蛋白质溶液与生理上相容的非离子型表面活性剂接触，然后使溶液进行（B）紫外线照射，（C）用β-丙酸溶液处理，和（D）用胶体二氧化硅进行吸附处理，步骤BCD在序列BCD，BDC，DCB或DBC中进行。

5. 发明授权

US4081431A Blood fractionation 失效
$Blood fractionation$
标题翻译：血液分离
公开(公告)号：US4081431A
公开(公告)日：1978-03-28
申请号：US639960
申请日：1975-12-11
申请人： Wolfgang Stephan , Ronald Kotitschke
发明人： Wolfgang Stephan , Ronald Kotitschke
IPC分类号： C07K14/745 , A61K35/14 , A61K38/00 , A61K38/16 , A61K38/48 , C07K14/00 , C07K14/755 , C07K14/76 , C07K16/00 , C12N9/74
CPC分类号： C12N9/6429 , C07K14/755 , C12Y304/21005 , A61K38/00 , Y10S530/83
摘要： A process for the fractionation of blood comprising passing said blood through a cation exchanger, separating the solids from the plasma, freezing the plasma, thawing the frozen plasma, and separating a first product comprising undissolved cryoprecipitate enriched in factor-VIII protein from plasma fluid. The cryoprecipitate can be concentrated by warm water dissolution and polyethylene glycol precipitation. The plasma fluid, optionally after treatment with .beta.-propiolactone and uv irridiation, is treated with tricalcium phosphate to adsorb factors II, VII, IX and X as a second product. These factors can be eluted with citrate solution. The residual plasma from the initial tricalcium phosphate adsorption is treated with colloidal silica to adsorb impurities and leave a third product which is a storage-stable serum protein solution.
摘要翻译：一种用于分离血液的方法，包括使所述血液通过阳离子交换剂，从血浆中分离固体，冷冻血浆，解冻冷冻的血浆，以及从血浆流体中分离富含因子VIII蛋白的未溶解的冷沉淀物的第一产物。冷沉淀物可以通过温水溶解和聚乙二醇沉淀来浓缩。等离子体流体，任选地在用β-丙内酯和紫外线照射处理之后，用磷酸三钙处理以吸附因子II，VII，IX和X作为第二产物。这些因素可以用柠檬酸溶液洗脱。来自初始磷酸三钙吸附的残留血浆用胶体二氧化硅处理以吸附杂质，并留下作为储存稳定的血清蛋白溶液的第三产物。

6. 发明授权

US4272523A Fractionating citrate-stabilized plasma 失效
标题翻译：分馏柠檬酸盐稳定的等离子体
公开(公告)号：US4272523A
公开(公告)日：1981-06-09
申请号：US75867
申请日：1979-09-17
申请人： Ronald Kotitschke , Wolfgang Stephan
发明人： Ronald Kotitschke , Wolfgang Stephan
IPC分类号： C07K14/745 , A61K35/14 , A61K38/00 , A61K38/16 , A61K38/48 , A61K38/55 , C07K1/00 , C07K14/75 , C07K14/81 , C12N9/74 , C07G7/00
CPC分类号： C12N9/6429 , C07K14/75 , C07K14/8128 , C12Y304/21005 , A61K38/00 , Y10S530/83
摘要： The present invention relates to a method for making fibrinogen, a prothrombin complex containing the coagulation factors II, VII, IX and X that can contain antithrombin III, antithrombin III and a solution of stable serum proteins from a blood plasma stabilized with citrate which is characterized in that from the plasma, by adsorption on colloidal silica of a specific surface of 50 to 400 m.sup.2 /g and a concentration of 50 to 400 mg per g plasma protein, fibrinogen is isolated; and in that thereupon (a) citrate and calcium ions are removed by ultrafiltration or dialysis and then from the protein solution, over anion exchangers or tricalcium phosphate that adsorb proteins, the coagulation factors II, VII, IX and X and antithrombin III are adsorbed, or (b) the coagulation factors II, VII, IX and X are adsorbed prior to the ultrafiltration or dialysis, antithrombin III then not being simultaneously adsorbed, and antithrombin III is adsorbed on the said adsorbents after the removal of the citrate and calcium ions by ultrafiltration or dialysis; and in that thereupon from the remaining plasma fluid further unstable proteins are removed by another adsorption on colloidal silica and a solution of stable serum proteins is obtained.
摘要翻译：本发明涉及一种制备纤维蛋白原的方法，一种含有凝血因子II，VII，IX和X的凝血酶原复合物，其可以含有抗凝血酶III，抗凝血酶III和用柠檬酸盐稳定的血浆中稳定的血清蛋白质的溶液，从等离子体中，通过吸附比表面积为50〜400m2 / g，浓度为50〜400mg / g血浆蛋白质的胶体二氧化硅，分离纤维蛋白原; 因此（a）通过超滤或透析除去柠檬酸盐和钙离子，然后从蛋白质溶液中吸附蛋白质的阴离子交换剂或磷酸三钙，吸附凝血因子II，VII，IX和X以及抗凝血酶III，或（b）凝血因子II，VII，IX和X在超滤或透析之前被吸附，抗凝血酶III然后不被同时吸附，并且在除去柠檬酸盐和钙离子之后，抗凝血酶III被吸附在所述吸附剂上超滤或透析; 并且因此从剩余的血浆液体中，通过胶体二氧化硅上的另一种吸附除去进一步不稳定的蛋白质，并获得稳定的血清蛋白质的溶液。

7. 发明授权

US4170590A Ion exchanger treatment of citrate-stabilized plasma 失效
标题翻译：离子交换剂处理柠檬酸盐稳定的等离子体
公开(公告)号：US4170590A
公开(公告)日：1979-10-09
申请号：US875489
申请日：1978-02-06
申请人： Wolfgang Stephan , Ronald Kotitschke
发明人： Wolfgang Stephan , Ronald Kotitschke
IPC分类号： A61K38/00 , C07K14/755 , C12N9/74 , A23J1/06
CPC分类号： C12N9/6429 , C07K14/755 , C12Y304/21005 , A61K38/00
摘要： A citrate-stabilized blood plasma is frozen and thawed, the undissolved cryoprecipitate is separated and is rich in factor VIII protein. The residual liquid is treated with cation and anion exchangers, either sequentially or in admixture, to separate calcium and citrate ions therefrom. The residual plasma is then subjected to adsorption to remove a fraction which is eluted and precipitated, enriched in factors II, VII, IX and X. The liquid left from adsorption is subjected to further adsorption with silicic acid, leaving a storage-stable serum. The silicic acid is eluted to dissolve adsorbed fibrinogen which then is re-precipitated.
摘要翻译：柠檬酸盐稳定的血浆被冷冻和解冻，未溶解的冷沉淀物被分离并富含因子VIII蛋白质。残余液体用阳离子和阴离子交换剂按顺序或混合物处理，以从其中分离出钙和柠檬酸根离子。然后对残留的等离子体进行吸附以除去洗脱和沉淀的级分，富集因子II，VII，IX和X.将吸附的液体进一步用硅酸吸附，留下储存稳定的血清。洗脱硅酸以溶解吸附的纤维蛋白原，然后再沉淀。

8. 发明授权

US4147765A Preparation of antiserum for quantitative determination of X and Y degradation products of fibrin and fibrinogen 失效
标题翻译：制备用于定量测定纤维蛋白和纤维蛋白原的X和Y降解产物的抗血清
公开(公告)号：US4147765A
公开(公告)日：1979-04-03
申请号：US706050
申请日：1976-07-16
申请人： Wolfgang Stephan , Ronald Kotitschke
发明人： Wolfgang Stephan , Ronald Kotitschke
IPC分类号： G01N33/53 , C07K16/06 , C07K16/18 , G01N33/86 , A23J1/06 , G01N31/02 , G01N33/16
CPC分类号： C07K16/18 , C07K16/065 , G01N33/86 , G01N2333/75 , Y10S436/815 , Y10S514/802 , Y10S530/813 , Y10S530/83
摘要： An antiserum for the quantitative determination of X and Y degradation products of fibrin and fibrinogen is produced by administering the purified degradation products to an experimental animal thereby to immunize said animal, drawing serum from said animal, contacting said serum with a plasma and separating the resultant precipitate, thereby to leave a supernatant liquid which constitutes said antiserum. The plasma may be a heparin, citrate, oxalate, ethylenediaminetetracetate or glutaraldehyde-treated plasma and as many as 12 or 15 precipitations may be made with the animal antiserum. The antiserum may be fractionated at any stage by adsorption on Sephadex modified dextran.
摘要翻译：通过向实验动物施用纯化的降解产物，从而免疫所述动物，从所述动物中抽出血清，使所述血清与血浆接触并分离所得的血浆，产生用于定量测定纤维蛋白和纤维蛋白原的X和Y降解产物的抗血清沉淀，从而留下构成所述抗血清的上清液。等离子体可以是肝素，柠檬酸盐，草酸盐，乙二胺四乙酸盐或戊二醛处理的血浆，并且可以用动物抗血清形成多达12或15个沉淀。抗血清可以在任何阶段通过Sephadex修饰的葡聚糖上的吸附进行分级。

9. 发明授权

US4900720A Replacement of human plasma using sterile solution of human plasma proteins excluding blood coagulation factors 失效
标题翻译：使用除血液凝固因子之外的人血浆蛋白质的无菌溶液替换人血浆
公开(公告)号：US4900720A
公开(公告)日：1990-02-13
申请号：US34468
申请日：1987-04-06
申请人： Ronald Kotitschke
发明人： Ronald Kotitschke
IPC分类号： A61K38/00 , A61K35/16 , A61K38/17 , A61K38/38 , A61K39/395 , A61K45/06 , A61P7/00
CPC分类号： A61K38/38 , A61K35/16 , A61K38/17 , A61K39/395 , A61K45/06 , Y10S530/861 , Y10S530/863
摘要： To maintain an almost unchanged plasma-protein profile in a patient subsequent to plasma exchange, the plasma-exchange medium contains the most essential human serum proteins, except for the coagulation factors, at a concentration of 75 g/l.
摘要翻译：为了在等离子体交换之后的患者中保持几乎不变的血浆蛋白质分布，等离子体交换培养基含有浓度为75g / l的凝血因子除外最重要的人血清蛋白。

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