CN100413542C - Pathogen inactivator composition for blood or blood component and its compounding process - Google Patents

Pathogen inactivator composition for blood or blood component and its compounding process Download PDF

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CN100413542C
CN100413542C CN 200610027224 CN200610027224A CN100413542C CN 100413542 C CN100413542 C CN 100413542C CN 200610027224 CN200610027224 CN 200610027224 CN 200610027224 A CN200610027224 A CN 200610027224A CN 100413542 C CN100413542 C CN 100413542C
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blood
photosensitizer
composition
inactivating agent
pathogen
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CN1857741A (en )
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琴 莫
谢如锋
钱开诚
黄宇闻
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上海市血液中心;南京逐陆医药科技有限公司
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本发明涉及临床输血用血液或血液成分病原体灭活剂及其配制方法技术领域。 The present invention relates to clinical blood for transfusion or blood components and pathogen-inactivating agent formulation FIELD. 本发明所述的血液病原体灭活剂的组合物,该组合物是由可进行血液或血液成分病原体灭活的光敏剂和可静脉输注的辅料所组成,其中可静脉输注的辅料质量是光敏剂质量的2-10倍。 Blood pathogen inactivating agent composition according to the present invention, the composition is carried by a pathogen photosensitizer and intravenous infusion of excipient inactivated blood or blood components, where the contents of an excipient is infused intravenously 2-10 times photosensitizer quality. 本发明组合物中的病原体灭活剂呈固态,不仅保证了病原体灭活光敏剂的稳定性,而且对病原体灭活剂及其相关辅料采用了高温除热原、无菌过滤的制备工艺,从而解决了目前血浆或血液成分进行光化学病原体灭活的病原体灭活剂的科学制备和添加问题。 The compositions of the invention are solid pathogen inactivation agents, not only to ensure the stability of the pathogen inactivation of the photosensitizer, and a pathogen inactivating agent employed and its related accessories pyrogen high temperature, sterile-filtered preparation in addition to to resolve the current plasma or blood component preparation for scientific and add questions photochemical pathogen inactivation of the pathogen inactivation agent.

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血液或血液成分病原体灭活剂组合物及其配制方法技术领域本发明涉及临床输血用血液或血液成分病原体灭活剂及其配制方法技术领域。 Blood or composition and its preparation method pathogen inactivating agent Technical Field The present invention relates to blood component transfusion of blood or clinical pathogen inactivating agent and its preparation Technical Field The blood component. 背录技术输血是现代医学的重要支持手段,临床输注的全血是一种由血浆和各种血细胞构成的广义的结缔组织,用物理方法可将全血分离成红细胞、血小板、粒细胞、血浆和冷沉淀等血液成分,将血液成分分别用于不同疾病治疗的输血方法称为成分输血。 Back recording technology is an important means of support of modern transfusion medicine, clinical whole blood transfusion generalized connective tissue is constructed by a variety of blood cells and plasma may be separated by physical methods whole blood into red blood cells, platelets, granulocytes, cryoprecipitate and plasma and other blood constituents, the blood component transfusion methods for treating various diseases are called component transfusion. 由于与全血输注相比较, 成分输血具有临床效果显著、不良反应发生率低、易于保存和节约血液资源等优点,因而舉广泛采用,成为临床输血的主要形式。 Since compared with the whole blood transfusion, blood component transfusion, a clinically significant effect, low incidence of adverse reactions, and easy to store blood conservation of resources, etc., which give widely used as the main form of clinical blood transfusion. 利用光化学方法灭活血液中包括病毒在内的病原体的研究是近年来输血医学领域中被广泛关注的研究方向,其原理为在全血或血液成分中添加病原体灭活剂一光敏剂,经光照射后, 光敏剂吸收光能,可发生电子转移或激发产生单态分子氧,在核酸特定区域形成共价加成化合物或破坏核酸的骨架结构以达到病原体灭活的效果,暈后滤除光敏剂,制备成安全的血液成分。 Photochemical inactivation methods including viruses in blood pathogens by transfusion in recent years, research has been widespread concern in the medical field, the principle of adding a photosensitizer agent pathogen inactivating whole blood or blood components, the light after irradiation, the photosensitizer absorbs light energy, or electron transfer can occur to produce singlet excited oxygen molecules, to form a covalent adduct compound or destroy the skeleton structure of nucleic acids to achieve the effect for inactivating a pathogen in a specific region of a nucleic acid, filtered off after the photosensitive halo agent to prepare a safe blood components. 中国专利号为98121328.6的"血浆病毒灭活的方法及其装置"发明专利详细阐述了亚甲蓝光化学方法在血浆病毒灭活中的应用。 The Chinese Patent No. 98121328.6 "plasma viral inactivation method and apparatus" patent application of the invention are set forth in detail in the methylene blue photochemical virus inactivation in plasma. 该病原体灭活方法已在全国较大范围内推广使用, 在使用过程中我们对光敏剂的载体、光敏剂用量的精确度、所加入光敏剂的质量控制等又进行了优化。 The pathogen inactivating methodology has been used in a wide range of the country, in the course of a degree of accuracy of the photosensitizer carrier, the amount of the photosensitizer, the photosensitizer quality control and the like to be added is optimized. 文献《中国输血杂志》2004年第n巻增刊pl85 "亚甲蓝固体剂型在血浆病毒灭活中的应用"黄宇闻等报道,现有技术主要是液体亚甲蓝操作,其主要缺点:亚甲兰在液体中欠稳定,遇光易发生化学反应:液体亚甲兰不适宜长期保存和运输;液体亚甲兰对血浆进行了再次稀释;限制了亚甲兰一多联袋系统的开发和生产。 Literature "Chinese Journal of Blood Transfusion" 2004 n Volume supplement pl85 "Application of methylene blue solid dosage form in plasma viral inactivation in the" Huang Yu Wen and other reports, the existing technology is mainly operating liquid methylene blue, its main drawback: methylene blue less stable, easily when exposed to light chemical reaction in the liquid: liquid methylene blue undesirable long-term preservation and transportation; methylene blue liquid plasma was diluted again; limits the development and production of methylene blue bags with more than one system. 目前国内外加入病原体灭活剂的主要方法是直接加入低浓度液体病原体灭活剂,液态病原体灭活光敏剂剂在低浓度时会很快降解而失去病原体灭活作用;也有使用固体型病原体灭活剂,存在单剂量不准确、不均匀,并且很难解决病原体灭活剂及所添加辅料的无菌、无热原和无不溶性微粒的难题。 Main methods abroad pathogen inactivation agent is added directly into the low concentration of the pathogen-inactivating agent is a liquid, the liquid photosensitizer agent pathogen inactivation at low concentrations will quickly degrade and lose pathogen inactivation; pathogen has a solid off surfactants, there is a single dose inaccurate, uneven and difficult to resolve sterile pathogen-inactivating agent is added excipients, pyrogen-free, and all problems of particulate matter. 发明内容本发明的目的在于提供一种既可以保持病原体灭活剂2年内稳定(光敏剂含量不低于标示量的90%)、又可以使病原体灭活剂的加入剂量准确,而且病原体灭活剂及其辅料无热原、无菌、无不溶性微粒,符合静脉滴注使用要求的血液或血液成分病原体灭活剂的配置方法,制得的该种病原体灭活剂对血液或血液成分进行充分病原体灭活的同时,不引入外源性的污染,不对接受输注者造成副反应。 Object of the present invention is to provide a pathogen-inactivating agent may be kept stable for 2 years (the photosensitizer content of not less than 90% of the labeled amount), but also allows the pathogen inactivating agent is added to the dose accuracy, and pathogen inactivation auxiliary agents and pyrogen-free, sterile, all insoluble particles, disposed in line with the requirements of intravenous infusion of blood or blood components pathogen inactivating agent, the kind of pathogen inactivating agent prepared for full blood or blood components pathogen inactivation while not introducing exogenous contamination, it does not cause side reactions by receiving an infusion. 本发明所述的血液或血液成分病原体灭活剂的配制方法包括以下步骤-第一步:取处方量的光敏剂(折除水分及杂质量)和光敏剂质量2-IO倍的可静脉输注用辅料溶于可用溶剂中,并使之溶解完全;第二步:加热至40-8(TC,然后向溶液中加入经活化的针用活性炭,保温挽拌20〜40分钟,趁热过滤,过滤液加入相同的溶剂至光敏剂的浓度为0.1mg/ml-lg/ml,反复精滤至中间体溶液无25um以上的微粒,过滤后的无微粒中间体经热原检测合格后备用;第三步:将中间体溶液按所需量滴加在洁净的载体上,在百级洁净条件下晾干。步骤二中,所述的中间体溶液中光敏剂的含量优选在0.5rag/m1-50mg/ml的浓度范围内, 最优选的浓度在2mg/ml-20mg/ml范围内。活性炭的使用量一般按光敏剂和辅料总重量的3%-10%加入。过滤时使用的孔滤膜的孔径最好小于0. 22um。步骤一和步骤二中所用的 Blood or blood components preparation method pathogen inactivating agent of the present invention comprises the following steps - first step: the formulation amounts of a photosensitizer (in addition to off water and impurities) and a photosensitizer mass 2-IO times may be intravenous infusion Note with available materials dissolved in a solvent and dissolved completely; Step: heating to 40-8 (TC, activated needle was then added to the solution with charcoal, stirred for 20~40 minutes incubation pull, filtered hot , the filtrate was added the same solvent to a concentration of photosensitizer 0.1mg / ml-lg / ml, fine filter repeatedly without intermediate solution to the above 25um particle, particle-free intermediate via pyrogen detected after passing standby after filtration; third step: the required amount of intermediate solution was dropped on a clean carrier, one hundred dried under clean conditions in two steps, the content of the photosensitizer in the intermediate solution is preferably in 0.5rag / m1. in the concentration range to 50 mg / ml, and most preferably a concentration of activated carbon is generally used in an amount of 3% -10% of the total weight of the excipients and the photosensitizer was added in the ng / ml 2mg / ml-20mg. when using the filter pore filter membrane pore size is preferably less than 0. 22um. steps one and two are used 溶剂可以是注射用水、乙醇、丙酮或乙醚,或是其中两种的混合液,优选为注射用水或乙醇,最优选为注射用水或注射用水与乙醇的混合溶液。步骤三中所用的载体可以是药用的高分子材料如涤纶薄膜等,优选为涤纶薄膜。其作用是将光敏剂溶液吸附在上面,然后进行晾干,这样形成固体后的血液病毒灭活剂组合物添加量比较准确,分散也很均匀。光敏剂是指可与血液中致病微生物核酸或包膜结合的光敏剂,如亚甲蓝、核黄素、补骨酯或其衍生物等,优选使用亚甲蓝、补骨酯及其衍生物,最优选使用亚甲蓝。可静脉输注用辅料选自葡萄糖、甘露醇、果糖、转化糖、麦芽糖、山梨醇、结晶麦芽糖、 赤藓糖、乳糖、半乳糖以及各种植物多糖、縮合葡萄糖、氧化聚明胶(聚明胶肽、琥珀明胶)、 羧甲基淀粉、羟乙基淀粉706、右旋糖酐10、 20、 40、 70、聚 The solvent may be water for injection, ethanol, acetone or diethyl ether, or a mixture of two, preferably water for injection or ethanol, most preferably water for injection or a mixed solution of ethanol and water for injection. In step three vector may be used pharmaceutically acceptable polymeric materials such as polyester film or the like, preferably a polyester film. its role is to the photosensitizer solution adsorbed thereon, and then drying, adding an amount of the composition of blood after the virus-inactivating agent to form a solid more accurate, dispersion very uniform. photosensitizer refers to pathogenic microorganisms in the blood or envelope photosensitizer nucleic acid binding, such as methylene blue, riboflavin, and the like make up bone ester or derivative thereof, preferably using methylene blue, fill bone and derivatives thereof, most preferably methylene blue. intravenous infusion materials selected from glucose, mannitol, fructose, invert sugar, maltose, sorbitol, crystalline maltose, erythritol, lactose, galactose and various plant polysaccharides, condensed glucose, gelatin, polyethylene oxide (polygeline, gelatin succinate), carboxymethyl starch, hydroxyethyl starch 706, dextran 10, 20, 40, 70, poly 吡酮、氣化钠、氣化钾、叛化钙、氯化镁、聚乙二醇1000、 2000、 L-亮氨酸、L-脯氨酸、L-异亮氨酸、L-苯丙氨酸、L-醋酸赖氨酸、L-苏氨酸、L"蛋氨酸、L-色氨酸、L-组氨酸(N-乙儎-L-色氨酸0.52)、 L-酪氨酸、 L-缬氨酸、L-丙氨酸、L-丝氨酸、甘氨酸、L-精氨酸、L-天门冬氨酸、L-盐酸半胱氨酸、L-谷氨酸等可静脉用原辅料或其混合物,最优选使用的辅料是注射级的葡萄糖、甘露醇、羟乙基淀粉或右旋糖苷中的单一成分或多种成分的组合物。本发明的有益效果:本发明组合物中的病原体灭活剂呈固态,不仅保证了病原体灭活光敏剂的稳定性,而且对病原体灭活剂及其相关辅料采用了高温除热原、无菌过滤的制备工艺,从而解决了目前血浆或血液成分进行光化学病原体灭活的病原体灭活剂的科学制备和添加问题。 Povidone, gas, sodium, potassium gasification, betray, calcium chloride, polyethylene glycol 1000, 2000, L- leucine, L- proline, L- isoleucine, L- phenylalanine , L- lysine acetate, L- threonine, L "methionine, L- tryptophan, L- histidine (N- acetyl Zai -L- tryptophan 0.52), L- tyrosine, L - valine, L- alanine, L- serine, glycine, L- arginine, L- aspartic acid, L- cysteine ​​hydrochloride, L- glutamic acid, etc. or raw materials can be intravenous mixtures thereof, most preferably used are materials injection grade glucose, or starch, dextran single component mannitol, hydroxyethyl or more components of the compositions of the present invention are beneficial effects: the composition of the present invention the pathogen inactivating agents are solid, not only to ensure the stability of the pathogen inactivation of the photosensitizer, and a pathogen inactivating agent employed and its related accessories pyrogen high temperature, in addition to preparation of sterile-filtered, thus solving the current plasma or blood components preparation and scientific issues added photochemical pathogen inactivation of the pathogen inactivating agent. 認輔对实施例1将处方量的亚甲蓝和葡萄糖加入到50ml注射用水中,充分溶解,加热至70t:,再向溶液中加入经活化的针用活性炭0.12g,保温搅拌三十分钟,趁热过滤,过滤用微孔滤胰的孔径小于0.22um,过滤后无微粒的中间体溶液再用精滤好的注射用水加至100ml定容后,备用。 70t :, secondary recognition was added again activated needle stirred for Example 1 formulation amounts of glucose and methylene blue was added to 50ml of water for injection, sufficiently dissolved, heated with charcoal 0.12g incubated thirty minutes filtered hot, was filtered through a Millipore filter pore size is less than 0.22um pancreas, filtered particulate-free intermediate solution was filtered and then fine good water for injection was added to the 100ml volume, backup. 然后在每片洁净的药用涤纶薄膜滴加上述病原体灭活剂中间体溶液10ul,在100级层流罩下晾干,经含量、无菌、热原、微粒等检验合格后,即制得固体的血液或血液成分病原体灭活剂组合物,与载体一起使用可应用于血液病原体灭活装置。 Then clean each piece of polyester film pharmaceutically added dropwise a solution of Intermediate 10 ul of pathogen inactivating agent, dried at 100 laminar flow hood, the content, sterility, pyrogens, particulate, etc. after passing inspection, i.e., to obtain the solid component of pathogen inactivation of blood or blood composition, using a blood pathogen inactivation may be applied to apparatus with a carrier. 具体的处方见表一:表一<table>table see original document page 5</column></row> <table>该实施例制备的涤纶薄膜吸附亚甲蓝组合物的含量经检测为20.8ug/片,无菌,热原检测合格,微粒检测符合2005年二部药典附录ixC规定,符合注射用要求。 A specific prescription table: Table 1 <table> table see original document page 5 </ column> </ row> <table> content was detected adsorbed methylene blue polyester film compositions prepared according to this embodiment is 20.8ug / tablets, sterile, pyrogen qualified, particle detection line with two Pharmacopoeia 2005 Appendix ixC predetermined, meet the requirements for injection. 该实施例制备的涤纶薄膜吸附亚甲蓝组合物的病原体灭活验证验证方法和效果见表二:表二<table>table see original document page 5</column></row> <table>-实施例2将处方量的亚甲蓝和葡萄糖加入到200ml容量瓶中,加入50。 Verification and authentication methods pathogen inactivation effect the adsorption of methylene blue polyester film compositions prepared in this Example are shown in Table II: Table II <table> table see original document page 5 </ column> </ row> <table> - Embodiment Example 2 the formulation amounts of glucose and methylene blue was added to the 200ml flask, was added 50. /。 /. 的药用乙醇100ml,充分溶解,加热至45C,充分溶解,加热至45'C,再向溶液中加入经活化的针用活性炭0.8g,保温搅拌三十分钟,趁热过滤,过滤用微孔滤膜的孔径小于0. 22um,过滤后无微粒的中间体溶液再用精滤好的50^乙醇加至200ml定容后,备用。 Medicinal ethanol 100ml, sufficiently dissolved, and heated to 45C, sufficiently dissolved, and heated to 45'C, was added again activated needles, stirred with charcoal 0.8g incubated thirty minutes, filtered hot, microporous filter filter pore size is less than 0. 22um, particle-free filtered solution of intermediate 50 ^ good fine filter and then ethanol was added to 200ml volume, backup. 然后在每片洁净的药用涤纶薄膜滴加上述病原体灭活剂中间体溶液20ul,在100级层流罩下晾干,经含量、无菌、热原、微粒等检验合格后,即制得固体的血液或血液成分病原体灭活剂组合物,与载体一起使用可应用于血液病原体灭活装置。 Then each piece of polyester film pharmaceutically acceptable clean pathogen-inactivating agent is added dropwise a solution of Intermediate 2OuI, dried at 100 laminar flow hood, the content, sterility, pyrogens, particulate, etc. after passing inspection, i.e., to obtain the solid component of pathogen inactivation of blood or blood composition, using a blood pathogen inactivation may be applied to apparatus with a carrier. 具体的处方见表三:表二<table>table see original document page 6</column></row> <table>该实施例制备的涤纶薄膜吸附亚甲蓝组合物的含量经检测为79.5ug/片,无菌、热原检测合格,微粒检测符合2005年二部药典附录ixC规定,符合注射用要求。 Specific prescription in Table III: Table II content was detected <table> table see original document page 6 </ column> </ row> <table> The polyester film prepared in Example adsorption of methylene blue composition 79.5ug / tablets, sterile, pyrogen qualified, particle detection line with two Pharmacopoeia 2005 Appendix ixC predetermined, meet the requirements for injection. 该实施例制备的涤纶薄膜吸附亚甲蓝组合物的病原体灭活验证验证方法和效果见表四:表四<table>table see original document page 6</column></row> <table>实施例3制备方法同实施例2,具体的处方见表五:表五<table>table see original document page 7</column></row> <table>该实施例制备的涤纶薄膜吸附亚甲蓝组合物的含量经检測为168.2ug/片,无菌、热原检测合格,微粒检测符合2005年二部药典附录ixC规定,符合注射用要求。 Verification and authentication methods pathogen inactivation effect the adsorption of methylene blue polyester film compositions prepared in this Example are shown in Table IV: Table IV <table> table see original document page 6 </ column> </ row> <table> Example polyester film composition of Methylene Blue adsorption table V <table> table see original document page 7 </ column> </ row> <table> this preparation Example: preparation Example 3 with the method 2, five specific prescription table the content was detected as 168.2ug / plate, sterile, pyrogen qualified, particle detection line with two Pharmacopoeia 2005 Appendix ixC predetermined, meet the requirements for injection. 该实施例制备的涤纶薄膜吸附亚甲蓝组合物的病原体灭活验证验证方法和效果见表六:表六<table>table see original document page 7</column></row> <table>实施例4制备方法:同实施例2,但活性炭加入量增加至1.88。 Verification and authentication methods pathogen inactivation effect the adsorption of methylene blue polyester film compositions prepared in this Example are shown in Table VI: Table VI <table> table see original document page 7 </ column> </ row> <table> Example preparation method 4: the same as Example 2, but increasing the amount of activated carbon was added to 1.88. 具体的处方见表七:表七<table>table see original document page 7</column></row> <table>该实施例制备的涤纶薄膜吸附核黄素组合物的含量经检測为768ug/片,无菌,热原检測合格,微粒检测符合2005年二部药典附录ixC规定,符合注射用要求。 Specific prescription shown in Table VII: Table VII <table> table see original document page 7 </ column> </ row> <table> The polyester film prepared in Example adsorption riboflavin content of the composition was detected 768ug / plate embodiment , sterile, pyrogen qualified, particle detection in line with Pharmacopoeia 2005 Appendix ixC two provisions, in line with the requirements for injection. 该实施例制备的涤纶薄膜吸附亚甲蓝组合物的病原体灭活验证验证方法和效果见表八:表八<table>table see original document page 8</column></row> <table>实施例5制备方法同实施例2。 Verification and authentication methods pathogen inactivation effect the adsorption of methylene blue polyester film compositions prepared in this Example are shown in Table VIII: Table VIII <table> table see original document page 8 </ column> </ row> <table> Example 5 was prepared with the method of Example 2. 具体的处方见表九:表九<table>table see original document page 8</column></row> <table>该实施例制备的涤纶薄膜吸附补骨酯衍生物组合物的含量经检测为45.4ug/片,无菌、 热原检测合格,微粒检測符合2005年二部药典附录ixC规定,符合注射用要求。 Specific prescription shown in Table IX: Table IX <table> table see original document page 8 </ column> </ row> <table> this embodiment the content of polyester film adsorbed Bugu ester derivative composition produced in Example 45.4 was detected ug / plate, sterile, pyrogen qualified, particle detection line with two Pharmacopoeia 2005 Appendix ixC predetermined, meet the requirements for injection. 该实施例制备的涤纶薄膜吸附亚甲蓝组合物的病原体灭活验证验证方法和效果见表十:表十<table>table see original document page 8</column></row> <table>以上5个实施例制备的样品经过6个月加速实验和18个月室温留样试验,其病原体灭活剂主成分含量均在标示量的90%-110%之间,无菌、热原检査均合格,微粒检査均符合注射用制剂的标准。 Verification and authentication methods pathogen inactivation effect the adsorption of methylene blue polyester film compositions prepared in this Example are shown in Table X: Table X <table> table see original document page 8 </ column> </ row> <table> or more 5 sample preparation Example embodiment of the acceleration test after 6 months and 18 months, the test sample left at room temperature, the content of the main component between pathogen inactivating agent were labeled amount of 90% -110%, sterile, pyrogen-average qualified, particle inspection are in line with the standard formulation for injection. 经检测分析、病毒验证和实际应用,其病原体灭活率达到99. 9%,在使用中溶解迅速,方便操作和使用。 Analysis detected the virus validation and practical application, which pathogen inactivation rate of 99.9%, was dissolved rapidly in use, convenient operation and use.

Claims (9)

  1. 1. 一种血液病原体灭活剂的组合物的配制方法,该方法包括以下步骤: a、取折除水分及杂质量的处方量的光敏剂和光敏剂质量2-10倍的可静脉输注用辅料溶于可用溶剂中,并使之溶解完全; b、加热至40-80℃,然后向溶液中加入经活化的针用活性炭,保温搅拌20~40分钟,趁热过滤,过滤液加入相同的溶剂至光敏剂的浓度为0.1mg/ml-1g/ml,反复精滤至中间体溶液无25μm以上的微粒,过滤后无25μm以上的微粒的中间体溶液经热原检测合格后备用; c、将中间体溶液按所需量滴加在洁净的载体上,在百级洁净条件下晾干。 1. A method of formulating a composition a blood pathogen inactivating agent, the method comprising the steps of: a, take off formulation amounts of water and impurities photosensitizer and a photosensitizer may be 2 to 10 times by mass in addition to intravenous infusion available materials dissolved with a solvent and dissolved completely; B, heated to 40-80 deg.] C, activated needle was then added to the solution with charcoal, stirred for 20 to 40 minutes heat, hot filtered, the filtrate was added the same solvents to a concentration of photosensitizer 0.1mg / ml-1g / ml, fine filter repeatedly without intermediate solution to the above 25μm particles, no particles above 25μm intermediate solution was filtered after passing pyrogen detecting standby; C , the required amount of intermediate solution was dropped on a clean carrier, one hundred dried under clean conditions.
  2. 2、 如权利要求1所述的血液病原体灭活剂的组合物的配制方法,其特征在于:歩骤h中所说的中间体溶液中光敏剂的含量为0. 5mg/ml-50mg/ml。 Formulating a composition as claimed in blood pathogen inactivating agent according to claim 1, wherein: step h ho of said intermediate solution in an amount of photosensitizer 0. 5mg / ml-50mg / ml .
  3. 3、 如权利要求2所述的血液病原体灭活剂的组合物的配制方法,其特征在于:步骤b中所说的中间体溶液中光敏剂的含量为2mg/ml-20mg/ml。 Formulating a composition as claimed blood pathogen inactivating agent according to claim 2, wherein: step (b) the content of said intermediate solution is photosensitizer 2mg / ml-20mg / ml.
  4. 4、 如权利要-求1所述的血液病原体灭活剂的组合物的配制方法,其特征在于:步骤b中所说的活性炭的使用量是光敏剂和辅料总重量的3%-10%。 4, as claims - a blood preparation method of seeking the pathogen inactivating agent composition 1, characterized in that: said step b activated carbon is used in an amount of 3% -10% of the total weight of the photosensitizer, and excipients .
  5. 5、 如权利要求1所述的血液病原体灭活剂的组合物的配制方法,其特征在于:步骤a和步骤b中所用的溶剂是注射用水、乙醉、丙酮或乙醚,或是其中两种的混合液。 5. The method according to claim 1 formulated blood pathogen inactivating agent composition, characterized in that: step a and step b the solvent used is water for injection, drunk acetate, acetone or diethyl ether, or two of the mixture.
  6. 6、 如权利要求5所述的血液病原体灭活剂的组合物的配制方法,其特征在于:步骤a和步骤b中所用的溶剂是注射用水或注射用水与乙醇的混合溶液。 6 formulating a composition, as claimed a blood pathogen inactivating agent according to claim 5, wherein: step a and step b the solvent used is a mixed solution of water for injection with ethanol or water for injection.
  7. 7、 如权利要求1所述的血液病原体灭活剂的组合物的配制方法,其特征在于:歩骤〔:中所用的载体是指药用的涤纶薄膜。 7. The method as claimed in claim 1 formulated blood pathogen inactivating agent composition, characterized in that: step [ho: support means used in the polyester film is pharmaceutically acceptable.
  8. 8、 如权利要求1所述的血液病原体灭活剂的组合物的配制方法,其特征在于:所说的光敏剂是指可与血液中致病微生物核酸或包膜结合的光敏剂。 8 formulating a composition, as claimed a blood pathogen inactivating agent according to claim 1, wherein: said photosensitizer refers to a nucleic acid pathogenic microorganisms in the blood bound to a photosensitizer or envelope.
  9. 9、 如权利要求1所述的血液病原体灭活剂的组合物的配制方法,其特征在于:所说的光敏剂是指亚甲蓝、核黄素、补骨酯或其衍生物。 9 formulating a composition, such as a blood pathogen inactivating agent according to claim 1, wherein: said means photosensitizer is methylene blue, riboflavin, an ester or a derivative thereof the bone complement. K)、 如权利要求1所述的血液病原体灭活剂的组合物的配制方法,其特征在于:所说的可静脉输注的辅料为注射级的葡萄糖、甘露醇、羟乙基淀粉或右旋糖苷中的单一成分或多种成分的组合物。 Formulating a composition K), a blood pathogen inactivating agent as claimed in claim 1, characterized in that: said adjuvants may be intravenous injection grade glucose, mannitol, hydroxyethyl starch or right rotary single component or composition glycoside more ingredients.
CN 200610027224 2006-06-01 2006-06-01 Pathogen inactivator composition for blood or blood component and its compounding process CN100413542C (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5908742A (en) 1992-03-02 1999-06-01 Cerus Corporation Synthetic media for blood components
CN1249952A (en) 1998-10-07 2000-04-12 上海市血液中心 Blood plasma virus deactivating method and apparatus
US20030219712A1 (en) 2002-02-01 2003-11-27 Laura Goodrich Addition of glycolysis inhibitor to a pathogen reduction and storage solution
CN2664661Y (en) 2003-10-30 2004-12-22 许亚勇 Disposable blood viral inactivation means

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5908742A (en) 1992-03-02 1999-06-01 Cerus Corporation Synthetic media for blood components
CN1249952A (en) 1998-10-07 2000-04-12 上海市血液中心 Blood plasma virus deactivating method and apparatus
US20030219712A1 (en) 2002-02-01 2003-11-27 Laura Goodrich Addition of glycolysis inhibitor to a pathogen reduction and storage solution
CN2664661Y (en) 2003-10-30 2004-12-22 许亚勇 Disposable blood viral inactivation means

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