WO2018133107A1 - 一种地榆皂苷ii注射剂及其制备方法和用途 - Google Patents

一种地榆皂苷ii注射剂及其制备方法和用途 Download PDF

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WO2018133107A1
WO2018133107A1 PCT/CN2017/072227 CN2017072227W WO2018133107A1 WO 2018133107 A1 WO2018133107 A1 WO 2018133107A1 CN 2017072227 W CN2017072227 W CN 2017072227W WO 2018133107 A1 WO2018133107 A1 WO 2018133107A1
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injection
saponin
preparation
group
injection according
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PCT/CN2017/072227
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French (fr)
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杨世林
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四川英路维特医药科技有限公司
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • 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
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics

Definitions

  • the invention relates to a saponin II injection, a preparation method thereof and use thereof, and belongs to the field of medicine.
  • the saponin II is a compound which has obvious activity from the mantle of the genus Rosaceae.
  • the chemical name is 3-O- ⁇ -L-arabinosyl-19 ⁇ -hydroxy-Uso-12--28-carboxylic acid. (ziyu-glycoside II), its structural formula is:
  • saponin II has a good effect on raising blood cells.
  • saponin II is usually used in combination with other drugs, and no reports of use alone have been reported.
  • the present invention provides a saponin II injection which is a preparation comprising the following raw materials:
  • Earthworm saponin II Earthworm saponin II, solubilizer, pH adjuster.
  • the weight ratio of the saponin II to the solubilizer is 1:0.005-120.
  • solubilizing agent is Tween 80, polyoxyethylene castor oil EL or poloxamer 188; and the pH adjusting agent is sodium hydroxide.
  • the concentration of the saponin II in the injection was 0.2 mg/mL.
  • the injection is an injection, a powder injection, a water injection or a large infusion.
  • the present invention also provides a method of preparing the aforementioned injection, comprising the steps of:
  • the ratio of saponin II it is dispersed in water for injection, and the corresponding ratio of solubilizer and pH adjuster is added, the pH is adjusted to 10, stirred and dissolved, and then water for injection is added, filtered, and sterilized, thereby obtaining the injection of the present invention.
  • concentration of the solubilizer is 0.1% (w/v).
  • filtration was filtered using a 0.22 um microporous membrane.
  • the present invention also provides the use of the above-mentioned injection for the preparation of a drug for raising blood cells.
  • the drug is a drug that increases peripheral blood leukocytes, neutrophils, red blood cells, platelets, and/or hemoglobin.
  • the present invention also provides a method of raising blood cells which is treated using the aforementioned injection.
  • mantle saponin II has problems such as low solubility and low oral absorption rate, which results in low oral bioavailability of the component, which limits the effect of the component on blood cell growth.
  • the inventors have solved the problem of low solubility of saponin II by using the saponin II injection prepared by the invention through the research on the dosage form and the formulation thereof, thereby improving the bioavailability of the saponin II and improving the effect of raising blood cells. It is of great significance for the development of new dosage forms of saponin II and better clinical application.
  • Figure 1 is a comparison of bone marrow hematopoietic stem cell counts in mice of each experimental group.
  • the saponin II was 0.5 g
  • the Tween 80 was 0.001 g
  • the pH adjuster was 0.1 g.
  • the preparation method is as follows:
  • the saponin II was dispersed in 100 mL of water for injection, 0.1% (w/v) of Tween 80 and sodium hydroxide were added, the pH was adjusted to 10, stirred and dissolved, and 2400 mL of water for injection was added to make the saponin II in the solution.
  • the concentration of the sample was 0.2 mg/mL, and it was filtered and sterilized with a 0.22 um microporous membrane to obtain an injection of the present invention.
  • the preparation method is as follows:
  • the saponin II was dispersed in 100 mL of water for injection, 0.1% (w/v) of polyoxyethylene castor oil EL, sodium hydroxide was added, the pH was adjusted to 10, stirred and dissolved, and 2400 mL of water for injection was added to make the solution sputum.
  • the concentration of saponin II was 0.2 mg/mL, and it was filtered and sterilized with a 0.22 um microporous membrane to obtain an injection of the present invention.
  • the preparation method is as follows:
  • the saponin II was dispersed in 2000 mL of water for injection, 0.1% (w/v) of poloxamer 188, sodium hydroxide was added, the pH was adjusted to 10, stirred and dissolved, and 48,000 mL of water for injection was added to make the saponin in the solution.
  • the concentration of II was 0.2 mg/mL, and it was filtered and sterilized with a 0.22 um microporous membrane to obtain an injection of the present invention.
  • the preparation method is as follows: 0.2 g of saponin II is dispersed in 100 mL of water for injection, and different auxiliary materials (Tween 80, polyoxyethylene castor oil EL, poloxamer 188, propylene glycol, vitamin C) and sodium hydroxide are separately added. Adjust pH to 10, stir and dissolve, add 900 mL of water for injection to make the concentration of saponin II in the solution 0.2 mg/mL, filter and sterilize with 0.22 um microporous membrane to obtain the injection of the present invention. 1.
  • auxiliary materials Teween 80, polyoxyethylene castor oil EL, poloxamer 188, propylene glycol, vitamin C
  • sodium hydroxide sodium hydroxide
  • the pyrogen is determined according to the Chinese Pharmacopoeia (2010 edition) pyrogen inspection method.
  • the clarification degree can be checked by the light inspection method under the foreign matter inspection law.
  • the content of saponin II was determined by HPLC. Chromatographic conditions: Agilent extend-C 18 column (250 ⁇ 4.6 mm, 5 ⁇ m), ELSD detector, flow rate: 1.0 mL ⁇ min -1 ; column temperature: 35 ° C; Sample size: 10 ⁇ L; drift tube temperature: 100 ° C; gas flow rate: 3.0 L ⁇ min -1 .
  • Mobile phase A acetonitrile
  • mobile phase B water, gradient elution (0 to 20 min, A: 60% ⁇ 85%, B: 40% ⁇ 15%; 20 to 21 min, A: 85% ⁇ 60%, B: 15% ⁇ 40%; 21 to 23 minutes, A: 60%, B: 40%).
  • the saponin II injection prepared by using Tween 80, polyoxyethylene castor oil EL and poloxamer 188 of the invention has passed the examination of the heat source, and the clarity is checked.
  • the content of the saponin II is high. It is indicated that the saponin II injection prepared by using the excipient Tween 80, polyoxyethylene castor oil EL and poloxamer 188 of the invention meets the requirements of the preparation and retains the saponin II component to the greatest extent.
  • the other two kinds of adjuvant propylene glycol, vitamin C prepared saponin II injection, the heat source was qualified, the clarity was unqualified, and the content of saponin II was low.
  • the preparation method is as follows: 0.2 g of saponin II is dispersed in 100 mL of water for injection, and different amounts of solubilizing agent (Tween 80) and sodium hydroxide are added respectively, the pH is adjusted to 10, stirred and dissolved, and 900 mL of water for injection is added to make the solution.
  • the concentration of the saponin II was 0.2 mg/mL, and it was filtered and sterilized with a 0.22 um microporous membrane to obtain the injection of the present invention. The results are shown in Table 2.
  • the present invention is the saponin II injection group A (prepared according to Example 1), group B (prepared according to Example 2), group C (prepared according to Example 3), saponin II 10% DMSO-physiology Saline group, cyclophosphamide.
  • mice All animals were fed ad libitum for 1 week and were randomly divided into: blank group; model group; saponin II injection group A, B, C, 2.5 mg ⁇ kg-1 suspension, prepared before use; Saponin II group: The saponin II powder was dissolved in 10% DMSO-physiological saline to prepare a 2.5 mg ⁇ kg-1 suspension, which was prepared immediately before use.
  • the other groups of mice were intraperitoneally injected with cyclophosphamide physiological saline solution at a dose of 50 mg ⁇ kg -1 for 3 consecutive days.
  • the blank group of mice was injected with an equal volume of normal saline in the tail vein.
  • Each experimental group was given the corresponding drug by dose and administration from the first day of the experiment.
  • the blank group and the model group were injected with the same volume of normal saline in the tail vein for 7 consecutive days.
  • Peripheral blood test Peripheral blood leukocytes (WBC), neutrophils (NEUT) red blood cells (RBC), platelets (PLT), and hemoglobin (HGB) were counted in each experimental group by an automatic blood cell counter.
  • WBC Peripheral blood leukocytes
  • NUT neutrophils
  • RBC red blood cells
  • PHT platelets
  • HGB hemoglobin
  • Bone marrow hematopoietic stem cell count (based on bone marrow cell CD34+ antigen expression) with bovine serum albumin concentration 0.2% PBS buffer was used to punch out the right femur bone marrow cells, 106 cells were removed, the supernatant was discarded, 30 ⁇ L of normal mouse serum was added to block the non-specific binding site, and 10 ⁇ L of FITC-labeled rat was added.
  • Mouse CD34+ antibody, 10 ⁇ L of the corresponding control antibody was added to the control tube, and reacted at 4 ° C for 30 min in the dark.
  • the saponin II injection prepared by the invention solves the problem of low solubility of the saponin II, improves the bioavailability of the saponin II, and further improves the therapeutic effect of the blood cell, and the saponin II is more Good clinical application is of great significance.

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Abstract

一种地榆皂苷II注射剂及其制备方法和用途。其原料包括：地榆皂苷II、增溶剂、pH调节剂。所述注射剂在制备升高血细胞的药物中的用途。所述注射剂解决了地榆皂苷II溶解度低的问题，提高了地榆皂苷II生物利用度。

Description

一种地榆皂苷II注射剂及其制备方法和用途 技术领域
本发明涉及一种地榆皂苷II注射剂及其制备方法和用途，属药物领域。
背景技术
地榆皂苷II是从蔷薇科地榆属地榆中提取制备有明显活性作用的化合物，化学名：3-O-α-L-阿拉伯糖基-19α-羟基乌索-12烯-28-羧酸(ziyu-glycoside II)，其结构式为：
Figure PCTCN2017072227-appb-000001
现代研究表明，地榆皂苷II具有良好地升高血细胞的作用。目前，地榆皂苷II通常与其他药物联合使用，未见单独使用的报道。
发明内容
为解决上述问题，本发明提供了一种地榆皂苷II注射剂，它是包含下述原料制备而成的制剂：
地榆皂苷II、增溶剂、pH调节剂。
进一步地，它是包含下述重量配比的原料制备而成的制剂：
地榆皂苷II0.5-10份、增溶剂0.001-60份、pH调节剂0.1-10份。
进一步地，所述地榆皂苷II与增溶剂的重量配比为1:0.005～120。
进一步地，所述的增溶剂为吐温80、聚氧乙烯蓖麻油EL或泊洛沙姆188；所述的pH调节剂为氢氧化钠。
进一步地，所述注射剂中地榆皂苷II的浓度为0.2mg/mL。
进一步地，所述的注射剂是注射液、粉针剂、水针剂或大输液。
本发明还提供了一种制备前述的注射剂的方法，包括下述步骤：
按配比地榆皂苷II分散于注射用水中，加入相应配比的增溶剂、pH调节剂，调节pH至10，搅拌溶解，再加入注射用水，过滤、灭菌，即得本发明注射剂。
进一步地，所述的增溶剂的浓度为0.1％(w/v)。
进一步地，过滤需用0.22um微孔滤膜过滤。
本发明还提供了所述的注射剂在制备升高血细胞的药物中的用途。
进一步地，所述的药物是升高外周血白细胞、中性粒细胞、红细胞、血小板和/或血红蛋白的药物。
本发明还提供了一种升高血细胞的方法，它是使用前述的注射剂进行治疗。
发明人前期研究发现，地榆皂苷II存在溶解度低、口服胃肠吸收率小等问题，造成该成分口服生物利用度低，限制了该成分升高血细胞效果的发挥。
发明人经过对剂型及其配方的研究，通过本发明制备的地榆皂苷II注射剂解决了地榆皂苷II溶解度低的问题，提高了地榆皂苷II生物利用度，进而提高其升高血细胞的疗效，对地榆皂苷II的新剂型开发及更好的临床应用具有十分重要的意义。
显然，根据本发明的上述内容，按照本领域的普通技术知识和惯用手段，在不脱离本发明上述基本技术思想前提下，还可以做出其它多种形式的修改、替换或变更。
以下通过实施例形式的具体实施方式，对本发明的上述内容再作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。凡基于本发明上述内容所实现的技术均属于本发明的范围。
附图说明
图1为各实验组小鼠骨髓造血干细胞计数比较。
具体实施方式
实施例1本发明注射剂的制备
按下述配比称取原料：
地榆皂苷II 0.5g、吐温80 0.001g、pH调节剂0.1g。
制备方法如下：
取地榆皂苷II分散于100mL注射用水中，加入0.1％(w/v)的吐温80、氢氧化钠，调节pH至10，搅拌溶解，再加入注射用水2400mL使溶液中地榆皂苷II的浓度为0.2mg/mL，用0.22um微孔滤膜过滤、灭菌，即得本发明注射剂。
实施例2本发明注射剂的制备
按下述配比称取原料：地榆皂苷II 0.5g、聚氧乙烯蓖麻油EL 0.001g、pH调节剂0.1g
制备方法如下：
取地榆皂苷II分散于100mL注射用水中，加入0.1％(w/v)的聚氧乙烯蓖麻油EL、氢氧化钠，调节pH至10，搅拌溶解，再加入注射用水2400mL使溶液中地榆皂苷II的浓度为0.2mg/mL，用0.22um微孔滤膜过滤、灭菌，即得本发明注射剂。
实施例3本发明注射剂的制备
按下述配比称取原料：
地榆皂苷II 10g、泊洛沙姆188 60g、pH调节剂10g。
制备方法如下：
取地榆皂苷II分散于2000mL注射用水中，加入0.1％(w/v)的泊洛沙姆188、氢氧化钠，调节pH至10，搅拌溶解，再加入注射用水48000mL使溶液中地榆皂苷II的浓度为0.2mg/mL，用0.22um微孔滤膜过滤、灭菌，即得本发明注射剂。
以下通过具体实验证明本发明的有益效果。
实验例1采用不同辅料制备的地榆皂苷II注射剂的质量评价
本研究根据地榆皂苷II的性质，选用吐温80、聚氧乙烯蓖麻油EL、泊洛沙姆188、丙二醇、维生素C为辅料，制成地榆皂苷II注射剂。
制备方法如下：取地榆皂苷II 0.2g分散于100mL注射用水中，分别加入不同的辅料(吐温80、聚氧乙烯蓖麻油EL、泊洛沙姆188、丙二醇、维生素C)、氢氧化钠，调节pH至10，搅拌溶解，再加入注射用水900mL使溶液中地榆皂苷II的浓度为0.2mg/mL，用0.22um微孔滤膜过滤、灭菌，即得本发明注射剂，结果见表1。
热原按《中国药典》(2010年版)热原检查法测定。
澄明度按《中国药典》(2010年版)可见异物检查法项下的灯检法检查。
地榆皂苷II含量，采用HPLC法测定，色谱条件：Agilent extend-C18色谱柱(250×4.6mm，5μm)，ELSD检测器，流速：1.0mL·min-1；柱温：35℃；进样量：10μL；漂移管温度：100℃；气体流速：3.0L·min-1。流动相A：乙腈，流动相B：水，梯度洗脱(0～20min，A:60％→85％，B：40％→15％；20～21min，A:85％→60％，B：15％→ 40％；21～23min，A:60％，B：40％)。
表1 采用不同辅料制备的地榆皂苷II注射剂的质量评价
Figure PCTCN2017072227-appb-000002
实验结果：采用本发明辅料吐温80、聚氧乙烯蓖麻油EL、泊洛沙姆188制备的地榆皂苷II注射剂，热源检查合格，澄明度检查合格，地榆皂苷II含量测定显示含量较高，表明采用本发明辅料吐温80、聚氧乙烯蓖麻油EL、泊洛沙姆188制备的地榆皂苷II注射剂符合制剂要求，且最大程度保留地榆皂苷II成分。其它二种辅料丙二醇、维生素C制备的地榆皂苷II注射剂，热源检查合格，澄明度检查不合格，地榆皂苷II含量测定显示含量较低。
实验例2采用不同量辅料制备的地榆皂苷II注射剂的质量评价
制备方法如下：取地榆皂苷II 0.2g分散于100mL注射用水中，分别加入不同量的增溶剂(吐温80)、氢氧化钠，调节pH至10，搅拌溶解，再加入注射用水900mL使溶液中地榆皂苷II的浓度为0.2mg/mL，用0.22um微孔滤膜过滤、灭菌，即得本发明注射剂，结果见表2。
表2 采用不同量增溶剂制备的地榆皂苷II注射剂的质量评价
Figure PCTCN2017072227-appb-000003
实验结果：仅在本发明地榆皂苷II0.2g和增溶剂用量为1.0mg-60g比例下制备的地榆皂苷II注射剂热源合格，澄明度符合要求，含量高，制剂最佳，可制备符合要求的地榆皂苷II注射剂。
实验例3本发明地榆皂苷II注射剂药效学研究
1实验材料
1.1受试药物本发明地榆皂苷II注射剂A组(按照实施例1制备)、B组(按照实施例2制备)、C组(按照实施例3制备)、地榆皂苷II 10％DMSO-生理盐水组、环磷酰胺。
1.2实验动物KM-小鼠：18.5～22.5g。
1.3实验仪器：全自动血球分析仪；BS-600L电子天平：规格：600g/0.1g，
上海友声衡器有限公司。
1.4统计方法
用SPSS 17.0软件进行统计分析。数据以均数±标准差()表示，组间采用单因素方差分析，方差齐者组间进行LSD检验，方差不齐者进行Tamhane’s T2检验。
2实验方法
2.1实验动物分组及模型制备
所有动物适应性喂养1周后按体重随机分为：空白组；模型组；地榆皂苷II注射剂A、B、C组，制成2.5mg·kg-1混悬液，临用前配制；地榆皂苷II组：地榆皂苷II粉末，用10％DMSO-生理盐水溶解，配制成2.5mg·kg-1混悬液，临用前配制。实验第1天，除空白组外，其余各组小鼠按50mg·kg-1剂量腹腔注射环磷酰胺生理盐水溶液，连续3天，空白组小鼠尾静脉注射等体积生理盐水。
2.2给药
各实验组自实验第1天开始按剂量、给药方式给予相应药物，空白组和模型组小鼠尾静脉注射等体积生理盐水，连续7天。
2.3标本采集
实验第8天，各实验组小鼠眼眶取血，用装有EDTA抗凝剂的0.5mlEP管收集待测。
2.4检测指标及方法
外周血象检测：采用全自动血球计数仪对各实验组小鼠外周血白细胞(WBC)、中性粒细胞(NEUT)红细胞(RBC)、血小板(PLT)、血红蛋白(HGB)进行计数。
骨髓造血干细胞计数(以骨髓细胞CD34+抗原表达量计)用含牛血清白蛋白浓度为 0.2％的PBS缓冲液冲出小鼠右侧股骨骨髓细胞，取出106个细胞离心，弃上清，加入30μL正常小鼠血清以封闭非特异结合位点，再加入10μL FITC标记的大鼠抗小鼠CD34+抗体，对照管加入10μL相应对照抗体，4℃避光反应30min。加入2mL红细胞裂解液，作用5min，洗细胞2次，加入终浓度为3μg/mL的PI染液，采用流式细胞仪检测骨髓细胞CD34+抗原表达。
3实验结果
3.1外周血主要血细胞计数比较，见表3、表4。
表3 各实验组小鼠外周血血细胞数量
Figure PCTCN2017072227-appb-000004
注：与模型组比较，*P<0.05，**P<0.01；注：与地榆皂苷II组比较，△P<0.05，△△P<0.01。
结果显示，与模型组比较，地榆皂苷II注射剂A组、地榆皂苷II注射剂B组、地榆皂苷II注射剂C组小鼠造血干细胞数量均有显著升高(P<0.05)，地榆皂苷II组无显著性差异；与地榆皂苷II组比较，地榆皂苷II注射剂A组、地榆皂苷II注射剂B组、地榆皂苷II注射剂C组小鼠外周血WBC、RBC、PLT数量均有显著升高(P<0.05)。
表4 各实验组小鼠外周血血细胞数量
Figure PCTCN2017072227-appb-000005
注：与模型组比较，*P<0.05，**P<0.01；注：与地榆皂苷II组比较，△P<0.05，△△P<0.01。
结果显示，与模型组比较，地榆皂苷II注射剂A组、地榆皂苷II注射剂B组、地榆皂苷II注射剂C组小鼠外周血NEUT和HGB数量均有显著升高(P<0.05)，地榆皂苷II组无显著性差异；与地榆皂苷II组比较，地榆皂苷II注射剂A组、地榆皂苷II注射剂B组、地榆皂苷II注射剂C组组小鼠外周血NEUT和HGB数量均有显著升高(P<0.05)。
以上实验结果表明，本发明地榆皂苷II注射剂可以有效升高血细胞，药效明显优于直接用地榆皂苷元原药给药。
综上所述，本发明制备的地榆皂苷II注射剂解决了地榆皂苷II溶解度低的问题，提高了地榆皂苷II生物利用度，进而提高其升高血细胞的疗效，对地榆皂苷II更好的临床应用具有十分重要的意义。

Claims (11)

  1. 一种地榆皂苷II注射剂，其特征在于：它是包含下述原料制备而成的制剂：
    地榆皂苷II、增溶剂、pH调节剂。
  2. 根据权利要求1所述的注射剂，其特征在于：它是包含下述重量配比的原料制备而成的制剂：
    地榆皂苷II 0.5-10份、增溶剂0.001-60份、pH调节剂0.1-10份。
  3. 根据权利要求1或2所述的注射剂，其特征在于：所述地榆皂苷II与增溶剂的重量配比为1:0.005～120。
  4. 根据权利要求1-3任意一项所述的注射剂，其特征在于：所述的增溶剂为吐温80、聚氧乙烯蓖麻油EL或泊洛沙姆188；所述的pH调节剂为氢氧化钠。
  5. 根据权利要求1-4任意一项所述的注射剂，其特征在于：所述注射剂中地榆皂苷II的浓度为0.2mg/mL。
  6. 根据权利要求1-5任意一项所述的注射剂，其特征在于：所述的注射剂是注射液、粉针剂、水针剂或大输液。
  7. 一种制备权利要求1-6任意一项所述的注射剂的方法，其特征在于：包括下述步骤：
    按配比称取地榆皂苷II分散于注射用水中，加入相应配比的增溶剂、pH调节剂，调节pH至10，搅拌溶解，再加入注射用水，过滤、灭菌，即得本发明注射剂。
  8. 根据权利要求7所述的方法，其特征在于：所述的增溶剂的浓度为0.1％(w/v)。
  9. 权利要求1-6任意一项所述的注射剂在制备升高血细胞的药物中的用途。
  10. 根据权利要求9所述的用途，其特征在于：所述的药物是升高外周血白细胞、中性粒细胞、红细胞、血小板和/或血红蛋白的药物。
  11. 一种升高血细胞的方法，其特征在于：它是使用权利要求1-6任意一项所述的注射剂进行治疗。
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CN1504478A (zh) * 2002-12-02 2004-06-16 成都地奥制药集团有限公司 地榆总皂苷提取物及其制备方法和用途
CN106551899A (zh) * 2015-09-18 2017-04-05 四川英路维特医药科技有限公司 一种地榆皂苷ii注射剂及其制备方法和用途

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CN1504478A (zh) * 2002-12-02 2004-06-16 成都地奥制药集团有限公司 地榆总皂苷提取物及其制备方法和用途
CN106551899A (zh) * 2015-09-18 2017-04-05 四川英路维特医药科技有限公司 一种地榆皂苷ii注射剂及其制备方法和用途

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