CN101647776B - Doxofylline venous injection with small volume as well as preparation method and quality control method thereof - Google Patents

Doxofylline venous injection with small volume as well as preparation method and quality control method thereof Download PDF

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CN101647776B
CN101647776B CN 200910306505 CN200910306505A CN101647776B CN 101647776 B CN101647776 B CN 101647776B CN 200910306505 CN200910306505 CN 200910306505 CN 200910306505 A CN200910306505 A CN 200910306505A CN 101647776 B CN101647776 B CN 101647776B
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doxofylline
small volume
isotonic
injection
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CN101647776A (en
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吴光彦
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吴光彦
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Abstract

The invention discloses Doxofylline venous injection with a small volume and a preparation method thereof. The preparation unit of the isotonic small volume of doxofylline venous injection is 1-20ml, the weight percentage concentration of doxofylline is01-4 percent, and the isotonic value of the venous injection is 257-340mosmol/kg. The invention enlarges the optional range of clinical application of doxofylline and provides the isotonic doxofylline venous injection with favorable security.

Description

多索茶碱小容量静脉注射液及其制备方法和质量控制方法 Doxofylline small volume intravenous injection and its preparation method and quality control method

[0001] 技术领域本发明涉及一种多索茶碱小容量静脉注射液,特别涉及一种等渗的多索茶碱小容量注射液及其制备方法。 [0001] Technical Field The present invention relates to a small volume doxofylline intravenous injection, particularly to a isotonic Doxofylline small volume injection and its preparation method.

[0002] 背景技术多索茶碱为一种黄嘌呤类的抗哮喘药。 [0002] BACKGROUND Doxofylline one xanthine as an antiasthmatic agent class. 在80年代由意大利ABC公司上市,国外上市的剂型有小容量注射液、片和糖浆,其中小容量注射液的使用方法为稀释后静脉滴注,没有静脉推注给药的方式。 Listed in the 1980s by the Italian company ABC, the formulations are listed foreign small volume injection, tablets and syrups, wherein the use of small-volume injection is intravenous infusion after dilution, no iv bolus administration.

[0003] 在中国,2000年由黑龙江华星制药集团股份有限公司开发上市了多索茶碱注射液(大容量和小容量)、片剂,后来又陆续开发了缓释胶囊、颗粒和口服溶液等多种剂型,上述剂型的上市,极大的丰富了多索茶碱的临床给药形式。 [0003] In China, Co., Ltd. developed in 2000 by the Heilongjiang Huaxing Pharmaceutical Group listed doxofylline injection (large capacity and small capacity), tablets, and later we have developed a sustained-release capsules, granules and oral solutions, etc. a variety of formulations, dosage forms listed above, greatly enriching the form of clinical administration Dosso theophylline. 但是,对于哮喘病的治疗,最有临床意义的还是注射给药。 However, for the treatment of asthma, the most clinically significant or injection. 哮喘的急性发作非常普遍,而临床可供选择的用于急救的哮喘药物最有效的即为茶碱类,其中氨茶碱和茶碱的治疗指数和安全指数接近, 多索茶碱注射液的安全范围要大的多。 Acute attack of asthma is very common, and clinical alternative for asthma medication is the most effective first aid theophylline, aminophylline and theophylline treatment in which the index and the index close to safety, Dosso theophylline injection safe range is much greater. 虽然注射给药有很大的优点,现有的多索茶碱注射液仍然存在着渗透压偏低的问题,按照该药品的使用说明书,当在IOOml的5%的葡萄糖注射液或0.9%的氯化钠注射液中加入3支IOml的多索茶碱注射液时,渗透压将最低会降到207m0smol/kg,因人体体液和血液渗透压的范围为280—310m0smol/kg,所以目前多索茶碱注射液在临床使用时溶液的渗透压和人体血液的渗透压相差很远,,在临床上会带来很大的安全隐患。 Although administration by injection has a great advantage, conventional injection doxofylline there remains a problem of low osmotic pressure, in accordance with the instructions for use of the drug, when the glucose injection or a 5% IOOml 0.9% injection of sodium chloride was added 3 IOml Doxofylline injections, osmotic pressure will be reduced to the minimum 207m0smol / kg, due to the osmotic pressure of blood and body fluids range of 280-310m0smol / kg, so the current Dosso theophylline injection solution in the clinical use of human blood osmotic pressure and the osmotic pressure of a far cry ,, clinically will bring a great security risk.

[0004] 人体细胞内外渗透压的取得平衡,是依靠细胞内外之间水分的移动。 [0004] osmotic pressure inside and outside of human cells balance, is to rely on the water between the inside and outside of cells to move. 当细胞外液比细胞内液的渗透压高时,水分由细胞内流向细胞外,反之则由细胞外流向细胞内。 When extracellular osmotic pressure higher than the intracellular fluid, extracellular water flows from the cell, whereas the outer cells by intracellular flow. 若细胞外液的渗透压小于细胞内液的渗透压时,细胞内水分随之外流,使细胞发生皱缩和变形,这种溶液属高渗液;若细胞外液的渗透压大于细胞内液的渗透压时,部分水分被吸入红细胞内,使之肿胀,这种溶液属低渗液。 If the osmotic pressure is less than the osmotic pressure of the extracellular fluid within a cell, intracellular water will drain the shrinkage and deformation of cells, this solution is a high exudate; osmolarity of the extracellular fluid is greater than if the intracellular fluid when the osmotic pressure, part of the water is sucked into the erythrocytes, so that swelling, this solution is a low exudate. 无论渗透压降低而造成溶血,还是渗透压的增高将造成患者红细胞萎缩,都是严重危及患者的健康。 Whether osmotic pressure caused by hemolysis, or osmotic pressure will result in increased patient red blood cells shrink, they are seriously endanger the patient's health.

[0005] 虽然,通过氯化钠、葡萄糖等物质调节注射液的渗透压为本领域技术人员所公知,比如市售的IOOml的大容量的多索茶碱氯化钠或葡萄糖注射液,临床上渗透压问题得到了些改善,但是由于非等渗大量多索茶碱溶液(20-30毫升,渗透压为20m0smol/ kg)的加入后,该溶液会变为低渗溶液且注入的体积较大(130毫升)。 [0005] Although, by adjusting the injection sodium chloride, glucose and other substances known to those skilled in the osmotic pressure of well known, commercially available, such as large-capacity IOOml Doxofylline sodium chloride or dextrose injection, clinical some improvement in osmotic pressure problem, but because a large number of non-doxofylline isotonic solution (20-30 ml, osmolality 20m0smol / kg) was added, the solution was injected and the hypotonic solution becomes larger volume (130 ml). 临床上如果大量注入低渗溶液,会使人感到头胀、胸闷、严重的可发生麻木、寒战、高热、甚至尿中出现血红蛋白。 If clinically significant infusion of hypotonic solution, will make people feel stretching, chest tightness, severe numbness can occur, chills, fever, and even hemoglobin appears in urine. 所以解决小容量多索茶碱注射液给药时的渗透压过低的问题,临床上是非常迫切和必须的,也能大大增加临床上的安全性。 So osmotic pressure is too low to solve the problem of theophylline injection administered small capacity Dosso, clinically very urgent and necessary, can greatly increase the safety of the clinic.

[0006] 发明内容本发明目的是提供了一种等渗的多索茶碱小容量注射液。 [0006] SUMMARY OF THE INVENTION An object of the present invention is to provide Doxofylline small volume injection of an isotonic solution.

[0007] 本发明另外一个目的是提供了上述小容量注射液的制备方法。 [0007] The present invention further object is to provide a method for preparing the small volume injection.

[0008] 本发明还提供了一种多索茶碱小容量注射液的质量控制方法。 [0008] The present invention further provides a method of quality control Doxofylline small volume injection.

[0009] 本发明的多索茶碱小容量静脉注射液,其中静脉注射液的制剂单位为l_20ml, 多索茶碱的重量百分浓度为1_4%,静脉注射液为等渗溶液,静脉注射液的等渗值在257 〜340m0smol/kg。 [0009] doxofylline small volume intravenous solution of the invention, wherein the formulation is a unit of intravenous fluids l_20ml, the weight percent concentration of Doxofylline 1_4%, isotonic intravenous solution injection, intravenous injection isotonic value 257 ~340m0smol / kg.

[0010] 本发明的等渗的多索茶碱小容量静脉注射液,其中静脉注射液的等渗值为265 〜331mOsmol/kg。 [0010] isotonic doxofylline small volume isotonic intravenous solution of the present invention, wherein the value of intravenous fluids 265 ~331mOsmol / kg.

[0011] 本发明的等渗的多索茶碱小容量静脉注射液,其中等渗溶液的等渗调节剂选自氯化钠、葡萄糖、木糖醇、甘露醇、右旋糖酐单独一种或混合使用。 [0011] doxofylline small volume isotonic intravenous solution of the present invention, wherein the solution isotonic tonicity agent is selected from sodium chloride, glucose, xylitol, mannitol, dextran alone or as a mixture .

[0012] 本发明的多索茶碱小容量静脉注射液,其中等渗调节剂选自氯化钠、葡萄糖, 制剂单位为IOml和20ml,多索茶碱的重量百分浓度为和1.5%。 Doxofylline small volume intravenous injection [0012] the present invention, wherein the isotonicity adjusting agent is selected from sodium chloride, glucose, and the formulation unit is IOml 20ml, doxofylline weight percent concentration of 1.5%.

[0013] 本发明的多索茶碱的小容量静脉注射液,还需加入pH调节剂,pH调节剂的选自盐酸、氢氧化钠,其中盐酸的浓度为lmol/L、氢氧化钠的浓度为O.lmol/L。 [0013] The present invention Doxofylline intravenous injection of small capacity, the need to add a pH adjusting agent, pH adjusting agent is selected from hydrochloric acid, sodium hydroxide, wherein the concentration of hydrochloric acid, sodium hydroxide concentration of lmol / L of O.lmol / L.

[0014] 本发明的等渗的多索茶碱小容量静脉注射液的制备方法为:用注射用水制备含有多索茶碱及渗透压调节剂的浓配步骤,用pH调节剂的调节pH值步骤,脱碳过滤步骤,中间体控制步骤,分装步骤,和灭菌步骤。 [0014] The production method of the present invention, an isotonic Doxofylline small volume of intravenous fluids: Preparation of water for injection containing concentrated endothal step with theophylline and tonicity adjusting agent, the pH is adjusted with a pH adjusting agent step, decarburization filtration step, the intermediate control step, dispensing step, and the sterilization step.

[0015] 本发明的等渗的多索茶碱小容量静脉注射液的制备方法,其中中间体控制步骤中,多索茶碱含量应为标示量的95-105%、pH值应为4.5-6.5,灭菌步骤中,灭菌条件为115"C、蒸汽灭菌30min。 [0015] The production method of the present invention, an isotonic Doxofylline small volume intravenous fluids, wherein the intermediate control step, doxofylline content should be 4.5 for the labeled amount of 95-105%, pH value 6.5, sterilization step, the sterilization conditions of 115 "C, steam sterilization 30min.

[0016] 本发明的多索茶碱小容量静脉注射液的质量控制方法,包括有关物质测定、含量测定、pH值测定、细菌内毒素测定、鉴别,还包括渗透压测定:取所述的多索茶碱小容量静脉注射液,照2005年版中国药典的渗透压摩尔浓度测定法测定,应为268.2〜 327.8mOsmol/kg。 [0016] Quality control method doxofylline small volume intravenous fluids according to the present invention, including determination of related substances, determination of, measuring the pH value, bacterial endotoxin determination, identification, osmometry further comprising: taking said plurality doxophylline small volume intravenous fluids, according to China Pharmacopoeia 2005 Edition osmolality assay measurement, should 268.2~ 327.8mOsmol / kg.

[0017] 下面对本发明进一步说明: [0017] The present invention is further described below:

[0018] 本发明的小容量注射液的规格为中国药典所定义的规格,包括lml、2ml、 5ml、10ml、20ml,当然不能理解为发明人局限于上述规格,只要在l_20ml之内的规格均属本发明保护范围之内。 [0018] Specifications of the small volume injection of the present invention is defined by the Chinese Pharmacopoeia specifications, including lml, 2ml, 5ml, 10ml, 20ml, of course, not limited to the above specification is understood as inventors, as long as the size of the average l_20ml genus within the scope of the present invention.

[0019] 本发明的多索茶碱的重量百分浓度理解为每IOOml含有的多索茶碱的克数。 [0019] Doxofylline weight percent concentration of the present invention is understood to be grams per IOOml Doxofylline contained.

[0020] 本发明的有益效果是丰富多索茶碱的临床用药可选择范围,提供了一种安全性好的等渗的多索茶碱注射液。 [0020] Advantageous effects of the present invention is to enrich the clinical use doxofylline selectable range, a good safety doxofylline isotonic injection. 在临床中,将小容量注射液加入输液中进行滴注使用或者进行静脉推注给药,为公知常识,虽然人体渗透压会有变化,但是由于人体的自身调节能力,对人体健康影响较小。 In the clinic, was added a small volume injection or infusion using an intravenous infusion for bolus administration, for the common knowledge, although the body will change the osmotic pressure, but because of the body's ability to regulate itself, has little effect on human health . 然而对于大量多索茶碱注射液加入到5%葡萄糖100毫升或0.9%的氯化钠100毫升后得到的混合溶液(120-130ml)输入体内后,渗透压引起的改变,对于患者的影响确是非常大,经常出现不同程度的医疗事故,限制了多索茶碱静脉途径给药的应用,这是本领域技术人员没有想到的,本发明针对上述情况,提供了相应的更适合推注的等渗小容量注射液。 However, for the (120-130ml) the mixed solution into the body Doxofylline large injection was added to 100 ml of 5% dextrose or 0.9% sodium chloride obtained after 100 ml, varying the osmotic pressure caused by impact to the patient's correct It is very large, with varying degrees of medical malpractice often limits the use of the intravenous route of administration doxofylline, as one skilled in the art did not occur, the present invention addresses the above situation, is more suitable to provide the corresponding bolus small volume injection isotonic.

[0021 ] 下面通过具体实施方式进一步对本发明进行说明。 [0021] The present invention will be further illustrated by the specific embodiments.

[0022] 具体实施方式实施例1每支IOml :含O.lg多索茶碱,用氯化钠调节等渗 Example 1 Each IOml [0022] DETAILED DESCRIPTION: containing O.lg Doxofylline, adjusting isotonic with sodium chloride

[0023] 标示处方: [0023] Prescription marked:

[0024] 多索茶碱IOOg [0024] Doxofylline IOOg

[0025] 氯化钠 8 Ig [0025] Sodium Chloride 8 Ig

[0026]加水至 10000ml [0026] Water to 10000ml

[0027] -------------------------- [0027] --------------------------

[0028]制得 1000 支 [0028] prepared 1000

[0029] 取注射用水6000ml,加热升温,在搅拌下加入多索茶碱115g(多索茶碱被活性炭吸附量为15%,故比处方量多加15克,下文为叙述方便,不再注释)及氯化钠81g, 待液温升至80°C左右,药粉全部溶解后加入活性炭5g,继续搅拌10分钟,待温度降至40过滤除炭,得浓配液。 [0029] 6000ml water for injection, heating temperature, under stirring Jiaruduosuo theophylline 115g (doxophylline adsorbed by activated charcoal in an amount of 15%, so that pay more than the prescribed amount of 15 grams, hereinafter descriptive convenience, no comment) and sodium chloride 81g, until the liquid temperature rose to about 80 ° C, activated charcoal was added after the powder is completely dissolved 5g, stirring continued for 10 minutes, the temperature dropped to 40 carbon removed by filtration to afford concentrate dosing. 取浓配液加注射用水补至10000ml,搅拌均勻,微孔滤膜过滤至澄明度合格后,取样检查含量、PH值。 Take dosing concentrate made up to 10000ml water for injection, stirred uniformly, to the filter membrane after passing clarity, the content of the sampling inspection, PH value. 含量应为标示量的95-105%,PH值应为5.0-6.5。 The content of the labeled amount of 95-105%, PH value should be 5.0-6.5. 在洁净区分装于IOml安瓿中,容封后置高压灭菌器内,于115°C蒸汽灭菌30min,经成品检验,印字,包装,即得。 Installed in a clean distinction IOml ampoule, opposite to win the title receiving the autoclave, steam sterilization at 115 ° C 30min, by product testing, printing, packaging, i.e., too. 成品渗透压为298mOsmol/kg,多索茶碱标示含量为99.7%。 Finished osmotic pressure of 298mOsmol / kg, doxofylline designated content was 99.7%.

[0030] 实施例2每支IOml :含O.lg多索茶碱,用葡萄糖调节等渗 [0030] Example 2 Each IOml: containing O.lg Doxofylline, isotonic glucose regulation

[0031] 标示处方: [0031] Prescription marked:

[0032] 多索茶碱IOOg [0032] Doxofylline IOOg

[0033]葡萄糖 450g [0033] 450g of glucose

[0034]加水至 10000ml [0034] Water to 10000ml

[0035] ------------------------ [0035] ------------------------

[0036]制得 1000 支 [0036] prepared 1000

[0037] 取注射用水6000ml,加热升温,在搅拌下加入多索茶碱115g及葡萄糖450g, 待液温升至80°C左右,药粉全部溶解后加入活性炭5g,继续搅拌10分钟,待温度降至40过滤除炭,得浓配液。 [0037] 6000ml water for injection, heating temperature, under stirring 450 g of glucose and 115g of theophylline Jiaruduosuo, until the liquid temperature rose to about 80 ° C, was added 5g of activated carbon powder after complete dissolution, stirring was continued for 10 minutes, until the temperature drop 40 to the filter to remove carbon, concentrated to give dosing. 取浓配液加注射用水补至10000ml,搅拌均勻,微孔滤膜过滤至澄明度合格后,取样检查含量、pH值。 Take dosing concentrate made up to 10000ml water for injection, stirred uniformly, to the filter membrane after passing clarity, sampling check content, pH. 含量应为标示量的95-105%,PH值应为4.5-5.5。 The content of the labeled amount of 95-105%, PH value should be 4.5-5.5. 在洁净区分装于IOml安瓿中,容封后置高压灭菌器内,于115°C蒸汽灭菌30min,经成品检验,印字,包装,即得。 Installed in a clean distinction IOml ampoule, opposite to win the title receiving the autoclave, steam sterilization at 115 ° C 30min, by product testing, printing, packaging, i.e., too. 成品渗透压为295mOsmol/k,多索茶碱标示含量为99.4%。 Finished osmolality 295mOsmol / k, doxofylline designated content of 99.4%.

[0038] 实施例3-11制备方法同实施例1或2,所不同是多索茶碱的用量、等渗调剂用量 [0038] Examples 3-11 prepared in Example 1 or 2, except that the amount of Doxofylline, the amount of toner isotonic

和种类 And species

[0039] [0039]

Figure CN101647776BD00051
Figure CN101647776BD00061

[0041 ] 下面通过试验例进一步说明本发明的有益效果。 [0041] The following advantageous effects of the present invention is further described by Test Examples.

[0042] 试验例1渗透压比较试验 [0042] Test Example 1 Comparative Test osmotic

[0043] 本发明的等渗值是通过上海医大仪器厂的全自动冰点渗透压计FM-8P测定的。 [0043] The present invention is an isotonic value by Shanghai Medical Instrument Factory automatic freezing point osmometer FM-8P assay.

[0044] 实验方法: [0044] Experimental method:

[0045] 取实施例1、8下制得的等渗的多索茶碱注射液(以下简称供试品)、以及市售的本厂的未调等渗的多索茶碱注射液(以下简称对照品)按照上市产品的说明书要求,分别取3支加入0.9%的氯化钠溶液IOOml和5%葡萄糖溶液IOOml中,测定渗透压,结果见表(表中渗透压的单位为mOsmol/kg): [0045] The resulting isotonic doxofylline injection (hereinafter referred to as test), and doxofylline unregulated injection isotonic commercially available under factory 1,8 embodiments taken (hereinafter referred to control) in accordance with the specification requirements of the market, were taken 3 0.9% sodium chloride solution and 5% glucose solution IOOml IOOml in osmotic pressure was measured, the results shown in table (table osmotic units mOsmol / kg ):

[0046] (1)、0.9%氯化钠注射液分别加入3支(10毫升/支)等渗和非等渗的多索茶碱 [0046] (1), 0.9% sodium chloride solution were added 3 (10 mL / branched) isotonic and non isotonic Doxofylline

注射液 Injection

[0047] [0047]

Figure CN101647776BD00062

[0048] (2)、5%葡萄糖注射液分别加入3支(10毫升/支)等渗和非等渗的多索茶碱注射液 [0048] (2), 5% glucose solution were added 3 (10 mL / branched) Doxofylline injection isotonic and non isotonic

[0049] [0049]

Figure CN101647776BD00063

[0050] (3)、0.9%氯化钠注射液分别加入20ml实施例8样品和非等渗的多索茶碱注射 [0050] (3), 0.9% sodium chloride solution were added 20ml Doxofylline Example 8 Sample injection isotonic and non embodiment

液; liquid;

[0051] [0051]

Figure CN101647776BD00064

[0052] (4)、5%葡萄糖注射液分别加入20ml实施例8样品和非等渗的多索茶碱注射液; [0052] (4), a 5% glucose injection 20ml Example 8 were added and the sample injection Doxofylline non-isotonic embodiment;

[0053] [0053]

Figure CN101647776BD00071

[0054] 结论:将本发明的等渗的多索茶碱注射液加入到IOOml的0.9%氯化钠注射液或5%葡萄糖注射液中后几乎没有引起渗透压变化,而非等渗的多索茶碱注射液按相同方式使用的渗透压却降低非常明显。 [0054] Conclusion: The Doxofylline injection isotonic present invention is added to 0.9% sodium chloride injection or 5% glucose IOOml after injection hardly causes change of osmotic pressure, not more isotonic doxophylline osmotic pressure injection was used in the same manner obvious decrease.

Claims (7)

1、 一种多索茶碱小容量静脉注射液,其特征在于,所述静脉注射液的制剂单位为l-20ml,所述多索茶碱的重量百分浓度为1_4%,所述静脉注射液为等渗溶液,所述静脉注射液的等渗值在265〜331mOsmol/kg。 A small volume doxofylline intravenous injection, wherein said formulation unit for intravenous fluids l-20ml, the weight percent concentration of Doxofylline 1_4%, the intravenous solution isotonic solution, an isotonic intravenous solution of said value 265~331mOsmol / kg.
2、如权利要求1所述的多索茶碱小容量静脉注射液,其特征在于,所述等渗溶液的等渗调节剂选自氯化钠、葡萄糖、木糖醇、甘露醇、右旋糖酐单独一种或混合使用。 Doxofylline small volume intravenous fluids as claimed in claim 1, wherein said isotonic solution is an isotonic modifier selected from sodium chloride, glucose, xylitol, mannitol, dextran alone One or a mixture thereof.
3、如权利要求2所述的多索茶碱小容量静脉注射液,其特征在于,所述等渗调节剂选自氯化钠、葡萄糖,所述制剂单位为10ml,所述多索茶碱的重量百分浓度为1%。 3, as claimed in claim 2 doxofylline small volume intravenous fluids, wherein the isotonicity adjusting agent is selected from sodium chloride, glucose, a formulation unit is 10ml, the Doxofylline the weight percentage concentration of 1%.
4、如权利要求2所述的多索茶碱小容量静脉注射液,其特征在于,所述等渗调节剂选自氯化钠、葡萄糖,所述制剂单位为20ml,所述多索茶碱的重量百分浓度为1.5%。 4, as claimed in claim 2 doxofylline small volume intravenous fluids, wherein the isotonicity adjusting agent is selected from sodium chloride, glucose, a formulation unit is 20ml, the Doxofylline the weight percent concentration of 1.5%.
5、如权利要求1所述的多索茶碱的小容量静脉注射液,其特征在于,还需加入pH调节剂,所述pH调节剂的选自盐酸、氢氧化钠,其中盐酸的浓度为lmol/L、氢氧化钠的浓度为0.lmol/L。 5, as claimed in claim 1 doxofylline small volume intravenous fluids claims, characterized in that the addition of a pH adjusting agent needs to, sodium hydroxide, wherein the concentration of hydrochloric acid of pH adjusting agent is selected from hydrochloric acid lmol / L, the concentration of sodium hydroxide was 0.lmol / L.
6、如权利要求1所述的多索茶碱小容量静脉注射液的制备方法为:用注射用水制备含有多索茶碱及渗透压调节剂的浓配步骤,用pH调节剂调节pH值步骤,脱碳过滤步骤,中间体控制步骤,分装步骤,和灭菌步骤。 Preparation doxofylline small volume intravenous fluids as claimed in claim 1 is: concentrated with step Doxofylline tonicity adjusting agents and prepared as water for injection containing, the step of adjusting pH value with a pH adjusting agent decarburization filtration step, the intermediate control step, dispensing step, and the sterilization step.
7、如权利要求6所述的多索茶碱小容量静脉注射液的制备方法,所述中间体控制步骤中,多索茶碱含量应为标示量的95—105%、pH值应为4.5—6.5,所述灭菌步骤中,灭菌条件为115°C、蒸汽灭菌30min。 Preparation doxofylline small volume intravenous fluids as claimed in claim 6, said intermediate control step, doxofylline content should be 95-105% of the labeled amount, pH value should be 4.5 -6.5, the sterilization step, the sterilization conditions of 115 ° C, steam sterilization 30min.
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