CN1235833A - 新颖的救治用的药物组合物及其制备方法 - Google Patents
新颖的救治用的药物组合物及其制备方法 Download PDFInfo
- Publication number
- CN1235833A CN1235833A CN98108902A CN98108902A CN1235833A CN 1235833 A CN1235833 A CN 1235833A CN 98108902 A CN98108902 A CN 98108902A CN 98108902 A CN98108902 A CN 98108902A CN 1235833 A CN1235833 A CN 1235833A
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- Prior art keywords
- sodium
- molecular weight
- chloride
- gram
- pharmaceutical composition
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- Granted
Links
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/765—Polymers containing oxygen
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及一种药物组合物及其制备方法,包括1.5—6.9%(w/v)选自氯化钠、碳酸氢钠、氯化钾、硫酸镁、氯化钙、葡萄糖酸钙等的一种或多种物质和3—18%(w/v]选自羟乙基淀粉、右旋糖酐、羧甲基淀粉、聚乙烯吡咯烷酮、明胶衍生物等的一种或多种物质,以及余量的常规用注射液,条件是氯化钠不能少于1.5%(w/v)。本发明的药物组合物用于救治伤病员和抗休克,具有使用安全方便、疗效快、效果好、维持时间长及用途广泛等优点。
Description
本发明涉及一种新颖的救治伤病员的药物组合物及其制备方法。
目前，输血输液是治疗伤病员，特别是创伤性休克的重要措施，通常补液的原则是“缺什么、补什么，缺多少、补多少”。例如以失血为主时，给予补血，有时需要抽取正常人的血液输给病人；以失血浆为主时，输血浆或血浆增量剂；以失去细胞间液为主时，则补生理盐水。其实这种按正常人配制(即生理性溶液)或从正常人体内抽取血液给予已发生明显病理生理变化的病人的救治方法，是将生物体视作机械体对待，因此这些措施往往存在如下的缺陷：
(1)输血：通常输血量接近或超过失血量，用量大则造成血液来源困难、费用昂贵、制备及保存须有一定的条件。另外输血前需花一定的时间做血型鉴定和交叉试验，对少见血型者只能使用代用品。输血会产生抗血小板抗体及抗白细胞抗体，还有可能导致各种血源性传染病，如艾滋病、乙肝、丙肝等。
(2)输白蛋白：白蛋白的用量大，价格昂贵，来源困难，制备复杂，对保存有一定的要求。应用后白蛋白容易通过毛细血管渗漏，且不能自由地回吸收到血管中，因而往往形成间质水肿，有可能造成肺水肿、肾功能衰竭和心功能不全，反而增加了死亡率。输入白蛋白后会引起α1、α2、β、γ球蛋白及纤维蛋白原的明显下降，造成免疫力降低，并影响凝血功能。
(3)输氟碳代血浆：输入量较大，输入时须吸人高分压氧，否则不能满足机体的需要。所述的氟碳代血浆需低温保存，运输不便。输入前手续繁多，例如，病人在使用前30分钟需注射地塞米松10毫克、药液需解冻，静注后须观察5-10分钟等。输入氟碳代血浆还可能引起类过敏反应、低血压、血小板降低、肝脾肿大、免疫功能降低及血凝纤维溶解系统异常等不良反应。
(4)输平衡液：输入量须在失血量的三倍以上才能维持血压，所输入液体的60-80％会渗漏到血管外，往往形成组织水肿如脑水肿、肺水肿及肾功能不全，造成后续治疗上的困难。
(5)输生理盐水：输入量也需在失血量的三倍以上，疗效较之平衡液更差，副作用更明显。
为了解决输血输液所存在的问题，本技术领域的人员也曾经研究用高渗氯化钠进行抗休克。如Velasco提议用7.5％(w/v)氯化钠，但此高渗浓度的氯化钠对机体有一定的毒性。
大多数研究者提出用高渗的氯化钠进行静脉推注来抗休克。但该推注法往往会导致明显的并发症，如低血压、过高渗导致的血细胞破裂、心功能不全、肾功能减退及神经系统障碍等。
由此可见，需要有新颖的抗休克药物来逆转休克的病理生理状况，以便在急救应用后可为后续处理争取时间及创造条件以提高救治伤病员的效果，增加存活率。
本发明的一个目的是提供来源方便、用量少、见效快、疗效好、副作用少、用途广、无需特别储存条件也不受血型限制的药物组合物。
本发明的再一个目的是提供所述药物组合物的制备方法。
本发明是通过下列方案来实施的：一种药物组合物，包括1.5-6.9％(w/v)选自氯化钠、碳酸氢钠、氯化钾、硫酸镁、氯化钙、葡萄糖酸钙、乳酸钙、乳酸钠、乙酸钠及三羟甲基氨基甲烷中的一种或多种物质和3-18％(w/v)选自羟乙基淀粉、右旋糖酐、羧甲基淀粉、聚乙烯吡咯烷酮、明胶衍生物、缩合葡萄糖、葡萄糖、果糖、乳糖、甘油、木糖醇、海藻酸钠、N-2-羟基丙基丙烯酰胺、环氧乙烷-聚丙二醇、果胶、甘露醇及Pentastarch中的一种或多种物质，以及余量的常规用注射液，条件是组合物中氯化钠不少于1.5％(w/v)，且钠离子的浓度不超过相当于6.9％(w/v)的氯化钠中的钠离子浓度。
本发明优选的组合物是每百毫升液体中含有4.2±0.2克氯化钠和7.6±0.6克羟乙基淀粉。
其中：
所述的羟乙基淀粉中至少有10％的羟乙基淀粉的分子量为25,000-45,000。
所述的右旋糖酐的分子量为40,000-230,000；羧甲基淀粉的分子量为30,000-80,000；聚乙烯吡咯烷酮的分子量为5,000-700,000；缩合葡萄糖的分子量为8,000-12,000；海藻酸钠的分子量为20,000-26,000；果胶的分子量为20,000-40,000；Pentastarch是杜邦公司的产品，分子量为264,000。
所述的明胶衍生物的分子量为20,000-35,000，它选自脲交链明胶、改良液体明胶、氧化聚明胶和降解明胶多肽。
所述的液体选自常规注射用的注射用水、生理盐水、平衡液、葡萄糖溶液、乳酸钠溶液、乙酸钠溶液、三羟甲基氨基甲烷溶液和糖盐水。
本发明的组合物是通过这样的方法来制备的：使总量为3-18克选自羟乙基淀粉、右旋糖酐、羧甲基淀粉、聚乙烯吡咯烷酮、明胶衍生物、缩合葡萄糖、葡萄糖、果糖、乳糖、甘油、木糖醇、海藻酸钠、N-2-羟基丙基丙烯酰胺、环氧乙烷-聚丙二醇、果胶、甘露醇及Pentastarch中的一种或多种物质溶于总量为100毫升选自常规注射用的注射用水、生理盐水、平衡液、葡萄糖溶液、乳酸钠溶液、乙酸钠溶液、三羟甲基氨基甲烷溶液和糖盐水溶液中的一种或多种混合的液体，再加入1.5克氯化钠和0-5.4克选自氯化钠、碳酸氢钠、氯化钾、硫酸镁、氯化钙、葡萄糖酸钙、乳酸钙、乳酸钠、乙酸钠和三羟甲基氨基甲烷中的一种或多种物质，按上述配比经混合溶解后得到本发明组合物。
本发明优选的技术方案是这样的：(ⅰ)制备羟乙基淀粉：按1∶0.8-0.875∶0.04-0.042(w/v/v)的比例使玉米淀粉或高粱淀粉与95％乙醇及35-38％盐酸混合，将温度升高到65-80℃进行淀粉水解，再以与淀粉按0.6-0.7∶1(v/w)的比例加入16％氢氧化钠溶液，然后以与淀粉按0.35-0.5∶1(w/w)的比例加入环氧乙烷，再加热到65-75℃使淀粉羟乙基化；(ⅱ)配制组合物：加入适量的水，使羟乙基淀粉在100毫升溶液中含量为7.6±0.6克，加入适量活性碳进行吸附脱色过滤；调节pH至5.5-7，加入氯化钠使其总量达4.2±0.2克，再加入适量活性碳吸附脱色，经0.8微米的微孔滤膜，得到本发明优选的组合物。
下面结合具体实施例对本发明作进一步详细的阐述。
制备实施例
羟乙基淀粉的制备：
100克玉米淀粉或高粱淀粉与87毫升95％乙醇及4.2毫升35％盐酸混合，将温度升高到70℃，使淀粉在该温度下水解，再加入60毫升16％氢氧化钠溶液，然后加入45克环氧乙烷，再加热到70℃，使淀粉羟乙基化。按此配比及制备方法，可得到分子量为25,000-45,000的羟乙基淀粉。
实施例1
按下列配比配制：羟乙基淀粉 7.6克氯化钠 4.2克注射用水 加到100毫升
将7.6克羟乙基淀粉溶于100毫升注射用水，加入0.5克活性碳，在90℃下搅拌加热15分钟，通过石棉板框过滤后加入4.2克氯化钠(医用纯)搅拌溶解，加入0.5克活性碳，在90℃下搅拌加热10分钟，经石棉板框过滤，再通过0.8微米的微孔滤膜。将所得的滤液灌装入250毫升或500毫升的大输液玻璃瓶或塑料瓶(袋)中，封盖后经1.05kg/cm2、121-123℃灭菌15-30分钟，即得到本发明的药物组合物。
实施例2
按下列配比配制：右旋糖酐 9克羟乙基淀粉 3克氯化钠 1.5克碳酸氢钠 3.4克生理盐水 加到100毫升
将上述右旋糖酐(上海葡萄糖厂生产)、羟乙基淀粉(制备实施例制备)溶于生理盐水，按照实施例1所述的方法用活性碳吸附脱色，然后依次加入上述氯化钠、碳酸氢钠，搅拌后溶解，接着按照实施例1所述的方法脱色过滤、灭菌和灌装，得到本发明药物。
实施例3
按下列配比配制：聚乙烯吡咯烷酮(Bayer生产) 12克氯化钠 2克乙酸钠 4克葡萄糖溶液 加到100毫升
除了用聚乙烯吡咯烷酮代替右旋糖酐和羟乙基淀粉、以乙酸钠代替碳酸氢钠、以葡萄糖溶液代替生理盐水外，其它按实施例2所述的方法，得到本发明的组合物。
实施例4
按下列配比配制：海藻酸钠(广西南宁制药厂生产) 18克氯化钠 1.5克注射用水 加到100毫升
按照实施例1所述的方法对上述配方进行配制，得到本发明的药物组合物。
实施例5
按下列配比配制：果胶(解放军185医院生产) 3克Pentastarch(杜邦公司生产) 4克氯化钠 4克甘露醇 7克乳酸钠溶液(2％) 加到100毫升
根据实施例1所述的方法，将果胶、Pentastarch和甘露醇先溶于乳酸钠溶液，然后加入氯化钠至溶。
实施例6
按下列配比配制：缩合葡萄糖(重庆西南制药五厂生产) 7克N-2-羟基丙基丙烯酰胺 2克氯化钠 4.4克注射用水 加到100毫升
按照实施例1的方法，根据上述配方制备本发明药物组合物。
实施例7
按下列配比配制：果糖(上海试剂二厂生产) 5克木糖醇(辽阳有机化工厂生产) 4克氯化钠 4.8克注射用水 加到100毫升
按照实施例1的方法，根据上述配方制备本发明药物组合物。
实施例8
按下列配比配制：甘油 2克乳糖(上海试剂二厂生产) 5克氯化钠 6克注射用水 加到100毫升
按照实施例1的方法，根据上述配方制备本发明药物组合物。
试验一：动物试验
取成年健康杂种狗，雌雄均可，局麻下分离出股动、静脉，分别插入导管，动脉导管与CF-Ⅱ型心血管功能检诊仪[沪药器监(准)字97第221103号]连接以监测其动脉压。使狗放血到平均动脉压(MAP)为40-50mmHg，放血时间控制在15分钟左右。使该血压维持一小时后，按8毫升/kg输入实施例1的产品。
在输液后的4小时里监测血压和尿量。在下表中，血压为恢复到基础血压水平的百分数，尿量单位为毫升/kg体重/小时。
| 输入期末 | 输入后1小时 | 输入后2小时 | 输入后3小时 | 输入后4小时 | ||||||
| 血压 | 尿量 | 血压 | 尿量 | 血压 | 尿量 | 血压 | 尿量 | 血压 | 尿量 | |
| 本发明组合物 | 71.57±4.21 | 0.6±0.35 | 77.69±2.94 | 3.13±0.77 | 79.54±3.07 | 1.56±0.59 | 80.7±3.47 | 1.33±0.5 | 81.04±4.25 | 1.12±0.27 |
| 等量全血 | 62.37±6.8 | 0 | 70.67±6.7 | 0.33±0.21 | 7.5±4.21 | 0.27±0.16 | 74.32±5.15 | 0.73±0.41 | 79.82±9.81 | 0.61±0.25 |
| 国外研究 | 44.44±11.28 | 0.11±0.25 | 58.98±15.06 | 1.79±1.6 | 47.63±14.19 | 0.4±0.52 | 38.54±16.83 | 0.23±0.43 | 18.85±28.56 | 0.17±0.38 |
试验二：人体临床试验
本发明实施例1组合物曾给安徽省合肥市第105医院的48例病人使用过，总有效率达100％。绝大多数病人在注入期间血压升高，尿量增加，肢体温暖。对于常规用药已经不能逆转的数例病例，输入本发明实施例1组合物后5-10分钟即生效，病人的循环功能基本恢复，临床上无明显并发症的发生。
试验三：急性毒性试验：
以人体给药量的2.5倍给予狗，不产生任何毒副作用；给予推荐剂量的5倍，给药狗发生流涎及呕吐；推荐剂量的3.75倍给药，狗发生呕吐，但不流涎。以上所有的给药狗的存活天数在45天以上。以推荐剂量的7.5倍给药，给药狗出现死亡，靶器官是肺，出现灶性出血。
本发明药物组合物可以静脉滴入给药，其给药量为8毫升本发明组合物/kg病人体重。它可直接用于救治发生休克、复合伤、大出血等状态的病人，使病人的病理生理状况产生逆转，同时也为后继治疗争取了时间。
本发明的药物组合物与现有技术相比有着如下突出的特点和进步：
1．大大减少液体的用量：一般而言，大部分病人的用量在500毫升或500毫升之内，即使发生致死性大出血的病人，也仅以1/4-1/6的失血量输入即可。这可以明显减少组织水肿、心功能负荷过重的发生率。
2．疗效快：从输入开始的5-10分钟内即可明显改善血液动力学。
3．效果好：上述试验一显示，本发明组合物的效果优于等量的新鲜全血。而且本发明的药物虽无携氧作用，但可通过改善微循环与一般情况从而减少氧的消耗并增加氧的运输。因此可至少节约50％的用血，从而缓解血源紧张的矛盾，减少因输血导致的诸多并发症，同时也可明显降低病人的经济及身体负担。
4．维持时间长：从试验一结果可知，输入本发明组合物后，即使不再给予任何其它液体及药物，所改善的血液动力学及一般情况可维持3-4小时以上。
5．无需特殊储藏条件，室温即可；使用简单，可作静脉滴注或骨内滴注；运输方便，无需特殊设备及特殊的交通工具。
6．无须作血型及交叉试验，对任何血型均适用。为抢救伤病员赢得了宝贵的时间。
7．用途广：可广泛地用于各种类型的休克、脑外伤、烧伤、复合伤、右心室梗塞引起的心源性休克、血透引起的低血压、胆汁性胰腺炎、手术病人、麻醉药品引起的心血管毒性及肝包虫病的治疗。
8．改变了给药方法，本发明的组合物可采用静脉滴注，不必采用静脉推注，方便了使用，也减少了并发症的发生。
综上所述，本发明的救治病人的药物组合物由于具备了与以往疗法相比所独具的有益效果和理论上的创新，因此具有积极的意义。
Claims (7)
1．一种药物组合物，包括1.5-6.9％(w/v)选自氯化钠、碳酸氢钠、氯化钾、硫酸镁、氯化钙、葡萄糖酸钙、乳酸钙、乳酸钠、乙酸钠及三羟甲基氨基甲烷中的一种或多种物质和3-18％(w/v)选自羟乙基淀粉、右旋糖酐、羧甲基淀粉、聚乙烯吡咯烷酮、明胶衍生物、缩合葡萄糖、葡萄糖、果糖、乳糖、甘油、木糖醇、海藻酸钠、N-2-羟基丙基丙烯酰胺、环氧乙烷-聚丙二醇、果胶、甘露醇及Pentastarch中的一种或多种物质，以及余量的常规用注射液，条件是组合物中氯化钠不能少于1.5％(w/v)，且钠离子的浓度不超过相当于6.9％(w/v)的氯化钠中的钠离子浓度。
2．根据权利要求1所述的药物组合物，其特征在于每百毫升液体中含有4.2±0.2克氯化钠和7.6±0.6克羟乙基淀粉。
3．根据权利要求1或2所述的药物组合物，其特征在于所述的常规注射用液体选自注射用水、生理盐水、平衡液、葡萄糖溶液、乳酸钠溶液、乙酸钠溶液、三羟甲基氨基甲烷溶液及糖盐水。
4．根据权利要求1或2所述的药物组合物，其特征在于其中所述的羟乙基淀粉中至少有10％的羟乙基淀粉的分子量为25,000-45,000。
5．根据权利要求1所述的药物组合物，其特征在于其中所述的明胶衍生物的分子量为20,000-35,000，它选自脲交链明胶、改良液体明胶、氧化聚明胶及降解明胶多肽。
6．根据权利要求1所述的药物组合物，其特征在于其中所述的右旋糖酐的分子量为40,000-230,000；羧甲基淀粉的分子量为30,000-80,000；聚乙烯吡咯烷酮的分子量为5,000-700,000；缩合葡萄糖的分子量为8,000-12,000；海藻酸钠的分子量为20,000-26,000；果胶的分子量为20,000-40,000；Pentastarch是杜邦公司的产品，分子量为264,000。
7．一种如权利要求1所述的药物组合物的制备方法，包括使3-18克选自羟乙基淀粉、右旋糖酐、羧甲基淀粉、聚乙烯吡咯烷酮、明胶衍生物、缩合葡萄糖、葡萄糖、果糖、乳糖、甘油、木糖醇、海藻酸钠、N-2-羟基丙基丙烯酰胺、环氧乙烷-聚丙二醇、果胶、甘露醇及Pentastarch中的一种或多种物质溶于总量为100毫升选自常规注射用的注射用水、生理盐水、平衡液、葡萄糖溶液、乳酸钠溶液、乙酸钠溶液、三羟甲基氨基甲烷溶液和糖盐水中的一种或多种液体，再加入1.5克氯化钠和0-5.4克选自氯化钠、碳酸氢钠、氯化钾、硫酸镁、氯化钙、葡萄糖酸钙、乳酸钙、乳酸钠、乙酸钠和三羟甲基氨基甲烷中的一种或多种物质，按此比例配制，经混合溶解后得到本发明组合物。
Priority Applications (22)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN98108902A CN1068778C (zh) | 1998-05-15 | 1998-05-15 | 救治用的药物组合物及其制备方法 |
| CA002332038A CA2332038C (en) | 1998-05-15 | 1999-04-16 | Novel pharmaceutical composition for use in emergency treatment and preparation method thereof |
| APAP/P/2000/002010A AP1185A (en) | 1998-05-15 | 1999-04-16 | Novel pharmaceutical composition for the use in emergency treatment and preparation method thereof. |
| TR2000/03315T TR200003315T2 (tr) | 1998-05-15 | 1999-04-16 | Acil durumda kullanılmaya uygun yeni farmasötik terkip ve bunun hazırlanma yöntemi |
| DE69941996T DE69941996D1 (de) | 1998-05-15 | 1999-04-16 | Pharmazeutische zusammenstellung zur verwendung in notbehandlungen und dessen herstellungsverfahren |
| IL13965899A IL139658A (en) | 1998-05-15 | 1999-04-16 | Pharmaceutical preparations for treatment and prevention and a method for their preparation |
| OA1200000312A OA11553A (en) | 1998-05-15 | 1999-04-16 | Novel pharmaceutical composition for use in emergency treatment and preparation method thereof. |
| AT99916742T ATE456954T1 (de) | 1998-05-15 | 1999-04-16 | Pharmazeutische zusammenstellung zur verwendung in notbehandlungen und dessen herstellungsverfahren |
| JP2000549266A JP2002515441A (ja) | 1998-05-15 | 1999-04-16 | 傷病者の処置および救済のための新規な医薬組成物およびその調製法 |
| AU35147/99A AU754537B2 (en) | 1998-05-15 | 1999-04-16 | Novel pharmaceutical composition for use in emergency treatment and preparation method thereof |
| MXPA00011216A MXPA00011216A (es) | 1998-05-15 | 1999-04-16 | Composiciones farmaceuticasnovedosas para tratamiento y salvamiento y el metodo para la preparacion de las mismas. |
| ROA200001120A RO122394B1 (ro) | 1998-05-15 | 1999-04-16 | Compoziţii farmaceutice pentru tratamentul de urgenţă şi procedeu de preparare a acestora |
| PCT/CN1999/000055 WO1999059602A1 (fr) | 1998-05-15 | 1999-04-16 | Nouvelle composition pharmaceutique pour traitement d'urgence et son procede de preparation |
| EP99916742A EP1078636B1 (en) | 1998-05-15 | 1999-04-16 | Pharmaceutical composition for use in emergency treatment and preparation method thereof |
| KR1020007012724A KR20010043585A (ko) | 1998-05-15 | 1999-04-16 | 부상자를 치료하기 위한 신규한 의약조성물 및 그의제조방법 |
| BR9911020-2A BR9911020A (pt) | 1998-05-15 | 1999-04-16 | Novas composições farmacêuticas para tratamento e salvamento, e método para a sua preparação |
| UA2000116454A UA72735C2 (en) | 1998-05-15 | 1999-04-16 | Pharmaceutical composition for treatment of patients in intensive care units and method for its preparation |
| EA200001191A EA003369B1 (ru) | 1998-05-15 | 1999-04-16 | Новые фармацевтические композиции для лечения и жизнеобеспечения (поддержания жизненных функций) и способ их приготовления |
| PL344246A PL196087B1 (pl) | 1998-05-15 | 1999-04-16 | Nowe kompozycje farmaceutyczne do leczenia i ratowania rannych oraz sposób otrzymywania tych kompozycji |
| US09/713,498 US6986905B1 (en) | 1998-05-15 | 2000-11-15 | Pharmaceutical compositions for treating and saving and the method for the preparation thereof |
| HK01105848.2A HK1035146A1 (en) | 1998-05-15 | 2001-08-20 | Pharmaceutical composition for use in emergency treatment and preparation method thereof |
| US11/198,696 US7309502B2 (en) | 1998-05-15 | 2005-08-05 | Pharmaceutical compositions for treating and saving and the method for the preparation thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN98108902A CN1068778C (zh) | 1998-05-15 | 1998-05-15 | 救治用的药物组合物及其制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1235833A true CN1235833A (zh) | 1999-11-24 |
| CN1068778C CN1068778C (zh) | 2001-07-25 |
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| CN98108902A Expired - Lifetime CN1068778C (zh) | 1998-05-15 | 1998-05-15 | 救治用的药物组合物及其制备方法 |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US6986905B1 (zh) |
| EP (1) | EP1078636B1 (zh) |
| JP (1) | JP2002515441A (zh) |
| KR (1) | KR20010043585A (zh) |
| CN (1) | CN1068778C (zh) |
| AP (1) | AP1185A (zh) |
| AT (1) | ATE456954T1 (zh) |
| AU (1) | AU754537B2 (zh) |
| BR (1) | BR9911020A (zh) |
| CA (1) | CA2332038C (zh) |
| DE (1) | DE69941996D1 (zh) |
| EA (1) | EA003369B1 (zh) |
| HK (1) | HK1035146A1 (zh) |
| IL (1) | IL139658A (zh) |
| MX (1) | MXPA00011216A (zh) |
| OA (1) | OA11553A (zh) |
| PL (1) | PL196087B1 (zh) |
| RO (1) | RO122394B1 (zh) |
| TR (1) | TR200003315T2 (zh) |
| UA (1) | UA72735C2 (zh) |
| WO (1) | WO1999059602A1 (zh) |
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| CN100394924C (zh) * | 2005-09-23 | 2008-06-18 | 赵超英 | 一种高渗液药物组合物在制备麻醉前使用的药物中的应用 |
| WO2008080336A1 (fr) | 2006-12-28 | 2008-07-10 | Chaoying Zhao | Utilisation d'une composition liquide fortement osmotique dans la préparation d'un médicament permettant d'améliorer la cicatrisation |
| CN100544734C (zh) * | 2007-10-16 | 2009-09-30 | 中国大冢制药有限公司 | 复方果糖电解质注射液及其制备方法 |
| CN101167740B (zh) * | 2007-10-16 | 2010-05-19 | 中国大冢制药有限公司 | 复方醋酸钠电解质注射液及其制备方法 |
| CN102000109A (zh) * | 2010-09-30 | 2011-04-06 | 泰山医学院 | 基于氢为治疗物质的药物制剂及其制备方法 |
| CN103845358A (zh) * | 2012-12-04 | 2014-06-11 | 江苏恒瑞医药股份有限公司 | 包含羟乙基淀粉和含有碳酸氢根离子的电解质溶液的药物组合物 |
| CN104644669A (zh) * | 2013-11-19 | 2015-05-27 | 北大方正集团有限公司 | 一种急救用的代血浆药物组合物及其制备方法 |
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| BR9904471A (pt) * | 1999-08-02 | 2001-03-13 | Mateus Sommer Neto | Composção coloidal para correção estética |
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-
1998
- 1998-05-15 CN CN98108902A patent/CN1068778C/zh not_active Expired - Lifetime
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1999
- 1999-04-16 JP JP2000549266A patent/JP2002515441A/ja not_active Ceased
- 1999-04-16 WO PCT/CN1999/000055 patent/WO1999059602A1/zh active Application Filing
- 1999-04-16 PL PL344246A patent/PL196087B1/pl not_active IP Right Cessation
- 1999-04-16 EP EP99916742A patent/EP1078636B1/en not_active Expired - Lifetime
- 1999-04-16 AT AT99916742T patent/ATE456954T1/de not_active IP Right Cessation
- 1999-04-16 RO ROA200001120A patent/RO122394B1/ro unknown
- 1999-04-16 AP APAP/P/2000/002010A patent/AP1185A/en active
- 1999-04-16 TR TR2000/03315T patent/TR200003315T2/xx unknown
- 1999-04-16 BR BR9911020-2A patent/BR9911020A/pt not_active IP Right Cessation
- 1999-04-16 IL IL13965899A patent/IL139658A/en not_active IP Right Cessation
- 1999-04-16 UA UA2000116454A patent/UA72735C2/uk unknown
- 1999-04-16 KR KR1020007012724A patent/KR20010043585A/ko not_active Application Discontinuation
- 1999-04-16 OA OA1200000312A patent/OA11553A/en unknown
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- 1999-04-16 EA EA200001191A patent/EA003369B1/ru not_active IP Right Cessation
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Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100333728C (zh) * | 2005-05-11 | 2007-08-29 | 中国人民解放军第二军医大学 | 一种复方电解质果糖注射液 |
| CN100394924C (zh) * | 2005-09-23 | 2008-06-18 | 赵超英 | 一种高渗液药物组合物在制备麻醉前使用的药物中的应用 |
| WO2008080336A1 (fr) | 2006-12-28 | 2008-07-10 | Chaoying Zhao | Utilisation d'une composition liquide fortement osmotique dans la préparation d'un médicament permettant d'améliorer la cicatrisation |
| CN101209344B (zh) * | 2006-12-28 | 2012-07-04 | 赵超英 | 高渗液组合物在制备促进伤口愈合的药物中的应用 |
| CN100544734C (zh) * | 2007-10-16 | 2009-09-30 | 中国大冢制药有限公司 | 复方果糖电解质注射液及其制备方法 |
| CN101167740B (zh) * | 2007-10-16 | 2010-05-19 | 中国大冢制药有限公司 | 复方醋酸钠电解质注射液及其制备方法 |
| CN102000109A (zh) * | 2010-09-30 | 2011-04-06 | 泰山医学院 | 基于氢为治疗物质的药物制剂及其制备方法 |
| CN102000109B (zh) * | 2010-09-30 | 2013-06-05 | 泰山医学院 | 基于氢为治疗物质的药物制剂及其制备方法 |
| CN103845358A (zh) * | 2012-12-04 | 2014-06-11 | 江苏恒瑞医药股份有限公司 | 包含羟乙基淀粉和含有碳酸氢根离子的电解质溶液的药物组合物 |
| CN103845358B (zh) * | 2012-12-04 | 2015-11-25 | 江苏恒瑞医药股份有限公司 | 包含羟乙基淀粉和含有碳酸氢根离子的电解质溶液的药物组合物 |
| CN104644669A (zh) * | 2013-11-19 | 2015-05-27 | 北大方正集团有限公司 | 一种急救用的代血浆药物组合物及其制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| PL344246A1 (en) | 2001-10-22 |
| OA11553A (en) | 2004-05-26 |
| CN1068778C (zh) | 2001-07-25 |
| RO122394B1 (ro) | 2009-05-29 |
| US7309502B2 (en) | 2007-12-18 |
| EA003369B1 (ru) | 2003-04-24 |
| BR9911020A (pt) | 2002-03-05 |
| PL196087B1 (pl) | 2007-12-31 |
| IL139658A (en) | 2005-12-18 |
| AU754537B2 (en) | 2002-11-21 |
| EP1078636B1 (en) | 2010-02-03 |
| US6986905B1 (en) | 2006-01-17 |
| ATE456954T1 (de) | 2010-02-15 |
| EA200001191A1 (ru) | 2001-08-27 |
| MXPA00011216A (es) | 2003-04-22 |
| KR20010043585A (ko) | 2001-05-25 |
| TR200003315T2 (tr) | 2001-06-21 |
| CA2332038A1 (en) | 1999-11-25 |
| EP1078636A4 (en) | 2003-07-02 |
| AU3514799A (en) | 1999-12-06 |
| EP1078636A1 (en) | 2001-02-28 |
| UA72735C2 (en) | 2005-04-15 |
| WO1999059602A1 (fr) | 1999-11-25 |
| HK1035146A1 (en) | 2001-11-16 |
| IL139658A0 (en) | 2002-02-10 |
| US20050288235A1 (en) | 2005-12-29 |
| JP2002515441A (ja) | 2002-05-28 |
| AP1185A (en) | 2003-07-04 |
| AP2000002010A0 (en) | 2000-12-31 |
| DE69941996D1 (de) | 2010-03-25 |
| CA2332038C (en) | 2009-01-27 |
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