WO2019227746A1 - 一种壳聚糖口服液及其制备方法 - Google Patents

一种壳聚糖口服液及其制备方法 Download PDF

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WO2019227746A1
WO2019227746A1 PCT/CN2018/103513 CN2018103513W WO2019227746A1 WO 2019227746 A1 WO2019227746 A1 WO 2019227746A1 CN 2018103513 W CN2018103513 W CN 2018103513W WO 2019227746 A1 WO2019227746 A1 WO 2019227746A1
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chitosan
weight
oral solution
parts
tween
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PCT/CN2018/103513
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French (fr)
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苏政权
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广东药科大学
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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
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/722—Chitin, chitosan
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • 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
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • the invention relates to the field of medicine, in particular to an oral solution of chitosan and a preparation method thereof.
  • Chitosan is a natural high molecular alkaline polysaccharide second only to cellulose. It is composed of glucose ( ⁇ copolymer (1-4) and 2-amino-2-deoxy-D-glucose). And N-acetylglucosamine (2-acetamido-2-deoxy-d-glucose).
  • Chitosan has a variety of pharmacological activities, such as bacteriostatic effect, antitumor effect, lowering blood sugar, lowering cholesterol, antihypertensive, strengthening liver function, acid suppressing effect, health function for gastrointestinal system, anticoagulation Blood activity, antithrombotic effect, immune promotion effect.
  • chitosan is hardly soluble in water and has poor bioavailability in the body, making it difficult to fully exert its biologically active functions.
  • Chinese patent CN101298502 discloses a chitosan solid dispersion, specifically prepared by mixing chitosan with polyethylene glycol 4000-polyethylene glycol 6000 to increase the water solubility of chitosan.
  • chitosan microspheres and nanoparticle preparations There are reports of chitosan microspheres and nanoparticle preparations.
  • Chinese patent CN101978954A discloses a method for preparing chitosan microspheres and its use.
  • Oral liquid preparations have large dispersibility and fast absorption of the drug, and can quickly exert their effects compared with solid dosage forms. They are easy to divide into doses and are convenient to take, so they are widely used in clinical practice. At present, no oral solution of chitosan is found on the market.
  • the object of the present invention is to provide a chitosan oral solution in response to the problems in the prior art.
  • the oral solution has high chitosan solubility, good preparation stability, and can ensure the safety and effectiveness of clinical medication. Easy to take.
  • the inventors added a solubilizing agent during the research of chitosan oral solution to improve its dissolving effect.
  • the increase of solubilizing agent will increase the solubilizing effect to some extent, but the excess solubilizing agent will make the bioavailability increase to saturation.
  • the invention also optimizes the type and amount of solubilizer in the chitosan oral solution.
  • the chitosan oral solution of the present invention interacts with a solubilizer and chitosan to completely dissolve the chitosan in the solution.
  • the inventor finally determined the technical solution of the present invention through a large number of experimental studies.
  • the present invention is achieved by the following technical solutions.
  • the invention provides an oral solution of chitosan, which comprises the following raw materials and auxiliary materials in the following weight ratio:
  • Solubilizer 0.5 to 3.5 parts by weight
  • Preservative 0.1 to 0.5 parts by weight.
  • the chitosan oral solution comprises the following raw materials in a weight ratio:
  • Solubilizer 1.2 ⁇ 2.0 parts by weight
  • the preservative is 0.2 to 0.3 parts by weight.
  • the solubilizing agent is selected from one or more of propylene glycol, polyethylene glycol, and Tween; and the preservative is selected from ethyl paraben and propyl paraben.
  • the preservative is selected from ethyl paraben and propyl paraben.
  • potassium benzoate is selected from one or more of potassium benzoate.
  • the polyethylene glycol is one of polyethylene glycol 1000, polyethylene glycol 4000, polyethylene glycol 6000, or polyethylene glycol 8000.
  • the Tween is one of Tween 20, Tween 40 or Tween 60.
  • the solubilizer is propylene glycol and Tween 40 with a weight ratio of 1: 0.2; the above-mentioned solubilizer can significantly improve the solubility of chitosan, and the prepared chitosan is taken orally The liquid was clear and turbid.
  • the preservative is ethyl paraben and propyl paraben in a weight ratio of 1: 1.
  • the invention also provides a preparation method of the chitosan oral liquid.
  • the preparation method of the oral liquid includes the following steps: adding a solubilizing agent to 1/3 to 2/3 of purified water, stirring uniformly, and then adding chitosan, stirring at 35 to 40 ° C until completely dissolved; adding a preservative, and mixing and adding purification Fill with water to 1000ml, and sterilize at 115 ° C for 15-20 minutes.
  • the results of the accelerated test of the chitosan oral solution of the present invention show that its characteristics, microbial limit, pH value, and drug content have no significant changes compared with 0, and have good stability.
  • the long-term test and inspection results of the chitosan oral liquid of the present invention show that its characteristics, microbial limit, pH value, and drug content have no obvious changes compared with 0, and the stability is good.
  • the chitosan oral liquid of the present invention has better stability, indicating that the components and the ratio of the chitosan oral liquid of the present invention are reasonable.
  • the chitosan oral liquid of the present invention has the following advantages:
  • the present invention makes the oral solution stable by using specific auxiliary materials and the amount thereof, thereby ensuring the safety and effectiveness of clinical medication.
  • the chitosan oral liquid of the present invention has large drug dispersion, fast absorption, convenient taking, and quick effect of medicine.
  • the chitosan oral liquid of the present invention has a simple process and low cost, and is suitable for industrial production.
  • the preparation method comprises the following steps: adding a solubilizing agent to 1/3 to 2/3 of purified water, stirring uniformly, and then adding chitosan, stirring at 35 to 40 ° C until completely dissolved; adding a preservative, and adding purified water to 1000ml after mixing well , Filling, sterilization at 115 °C for 15-20 minutes, that is.
  • the preparation method comprises the following steps: adding a solubilizing agent to 1/3 to 2/3 of purified water, stirring uniformly, and then adding chitosan, stirring at 35 to 40 ° C until completely dissolved; adding a preservative, and adding purified water to 1000ml after mixing well , Filling, sterilization at 115 °C for 15-20 minutes, that is.
  • the preparation method comprises the following steps: adding a solubilizing agent to 1/3 to 2/3 of purified water, stirring uniformly, and then adding chitosan, stirring at 35 to 40 ° C until completely dissolved; adding a preservative, and adding purified water to 1000ml after mixing , Filling, sterilization at 115 °C for 15-20 minutes, that is.
  • the preparation method comprises the following steps: adding a solubilizing agent to 1/3 to 2/3 of purified water, stirring uniformly, and then adding chitosan, stirring at 35 to 40 ° C until completely dissolved; adding a preservative, and adding purified water to 1000ml after mixing , Filling, sterilization at 115 °C for 15-20 minutes, that is.
  • the preparation method comprises the following steps: adding a solubilizing agent to 1/3 to 2/3 of purified water, stirring uniformly, and then adding chitosan, stirring at 35 to 40 ° C until completely dissolved; adding a preservative, and adding purified water to 1000ml after mixing , Filling, sterilization at 115 °C for 15-20 minutes, that is.
  • the preparation method comprises the following steps: adding a solubilizing agent to 1/3 to 2/3 of purified water, stirring uniformly, and then adding chitosan, stirring at 35 to 40 ° C until completely dissolved; adding a preservative, and adding purified water to 1000ml after mixing well , Filling, sterilization at 115 °C for 15-20 minutes, that is.
  • Test example 1 accelerated test of the chitosan oral liquid of the present invention
  • the chitosan oral liquid obtained according to the prescription and preparation method of 1-6 obtained according to the prescription and preparation method of 1-6.
  • Accelerated test Take 20 parts of the chitosan oral solution of the present invention, and leave it for 6 months under the conditions of a temperature of 40 ° C ⁇ 2 ° C and a relative humidity of 75% ⁇ 5%. During the test period, the 0, 1, 3, 6 Samples were taken once a month to examine the properties, pH and content of the oral solution.
  • Comparative Example 1 Comparative Example 1
  • Comparative Example 2 the formulation and preparation method of Comparative Example 2 of the chitosan oral solution.

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Abstract

本发明提供了一种壳聚糖口服液及其制备方法。所述的壳聚糖口服液包含壳聚糖6～12重量份；增溶剂0.5～3.5重量份；防腐剂0.1～0.5重量份。

Description

一种壳聚糖口服液及其制备方法 技术领域
本发明涉及医药领域，特别是涉及一种壳聚糖的口服液及其制备方法。
背景技术
壳聚糖(chitosan，CTSH)是一种数量仅次于纤维素的天然的高分子碱性多糖，由葡萄糖(β共聚物(1-4)与2-氨基-2-脱氧-D-葡萄糖)和N-乙酰葡糖胺(2-acetamido-2-deoxy-d-glucose)组成。
壳聚糖具有多种药理活性，如抑菌作用、抗肿瘤作用、降低血糖、降低降脂固醇、抗高血压、强化肝脏功能、抑酸作用、对于胃肠道系统的保健功能、抗凝血活性、抗血栓作用、免疫促进作用。但壳聚糖难溶于水，在机体内生物利用度较差，难以充分发挥其生物活性功能。
中国专利CN101298502公开了一种壳聚糖固体分散体，具体是将壳聚糖与聚乙二醇4000-聚乙二醇6000混合制备得到，以增加壳聚糖的水溶性。尚有壳聚糖微球、纳米粒制剂的报道，如中国专利CN101978954A公开了一种壳聚糖微球的制备方法及其用途。
口服液体制剂具有药物的分散度大、吸收快，同固体剂型比较能迅速发挥药效；易于分剂量，服用方便，因此在临床上应用广泛。目前，市场上未发现壳聚糖的口服液。
发明内容
本发明的目的是针对现有技术中存在的问题，提供一种壳聚糖口服液，该口服液中壳聚糖溶解性高，制剂稳定性好，能够保证临床用药安全性和有效性，并且服用方便。
鉴于壳聚糖水溶性差，发明人在研究壳聚糖口服液的过程中，添加了增溶剂，以提升其溶解效果。增溶剂的增加会使增溶效果有一定的增加，但过量的增溶剂会使生物利用度的提高达到饱和。本发明还对壳聚糖口服液中增溶剂的种类和用量进行了优选。本发明的壳聚糖口服液将增溶剂与壳聚糖相互作用使得壳聚糖在溶液中完全溶解。
由于液体制剂中药物的分散度大，具有较大的相界面和界面能，因此，存在一定程度的不稳定性，并且水性液体制剂容易霉变。对于不同的药物而言，应根据其自身特点选择合适的辅料及其用量范围，以获得较好的稳定性，保证临床用药的安全性和有效性。
本发明人通过大量的试验研究，最终确定了本发明的技术方案。
本发明是通过以下的技术方案来实现的。
本发明提供了一种壳聚糖口服液，该口服液包含如下重量配比的原辅料：
壳聚糖6～12重量份；
增溶剂0.5～3.5重量份；
防腐剂0.1～0.5重量份。
优选地，所述的壳聚糖口服液包含如下重量配比的原辅料：
壳聚糖8～10重量份；
增溶剂1.2～2.0重量份；
防腐剂0.2～0.3重量份。
在本发明的壳聚糖口服液中，所述的增溶剂选自丙二醇、聚乙二醇、吐温中的一种或多种；防腐剂选自尼泊金乙酯、尼泊金丙酯、苯甲酸钾中的一种或多种。
所述的聚乙二醇为聚乙二醇1000、聚乙二醇4000、聚乙二醇6000或聚乙二醇8000中的一种。
所述的吐温为吐温20、吐温40或吐温60中的一种。
作为更加优选的实施方式，所述的增溶剂为重量比为1：0.2的丙二醇和吐温40；上述所述的增溶剂能够显著提高壳聚糖的溶解性，并且制得的壳聚糖口服液澄清，无浑浊。
进一步地，所述的防腐剂为重量比为1:1的尼泊金乙酯和尼泊金丙酯。
本发明还提供了所述壳聚糖口服液的制备方法。
口服液的制备方法包含以下步骤：将增溶剂加入1/3～2/3纯化水中，搅拌均匀，然后加入壳聚糖，35～40℃搅拌至完全溶解；加入防腐剂，混合均匀后加纯化水至1000ml，灌装，115℃灭菌15～20分钟，即得。
本发明的壳聚糖口服液加速试验考察结果表明，其性状、微生物限度、pH值和药物含量与0月相比均无明显变化，稳定性好。本发明的壳聚糖口服液长期试验考察结果表明，其性状、微生物限度、pH值和药物含量与0月相比均无明显变化，稳定性好。与对比例1、对比例2相比，本发明的壳聚糖口服液稳定性更好，表明本发明的壳聚糖口服液组分和配比合理。
本发明的壳聚糖口服液与现有技术相比，具有如下优点：
1、本发明通过使用特定的辅料及其用量，使得口服液的稳定性好，保证了临床用药的安全性和有效性。
2、本发明壳聚糖口服液药物分散度大、吸收快，服用方便，药效发挥迅速。
3、本发明的壳聚糖口服液工艺简单、成本低，适合工业化生产。
具体实施方式
下面通过具体实施例对本发明口服液的组成和实验效果进行详细说明。
实施例1
壳聚糖 6g
丙二醇 0.5g
苯甲酸钾 0.5g
纯化水 加至1000ml
制备方法包含以下步骤：将增溶剂加入1/3～2/3纯化水中，搅拌均匀，然后加入壳聚糖，35～40℃搅拌至完全溶解；加入防腐剂，混合均匀后加纯化水至1000ml，灌装，115℃灭菌15～20分钟，即得。
实施例2
壳聚糖 10g
丙二醇 1g
吐温40 0.2g
尼泊金乙酯 0.1g
尼泊金丙酯 0.1g
纯化水 加至1000ml
制备方法包含以下步骤：将增溶剂加入1/3～2/3纯化水中，搅拌均匀，然后加入壳聚糖，35～40℃搅拌至完全溶解；加入防腐剂，混合均匀后加纯化水至1000ml，灌装，115℃灭菌15～20分钟，即得。
实施例3
壳聚糖 8g
丙二醇 1.2g
吐温60 0.24g
尼泊金丙酯 0.3g
纯化水 加至1000ml
制备方法包含以下步骤：将增溶剂加入1/3～2/3纯化水中，搅拌均匀，然后加入壳聚糖，35～40℃搅拌至完全溶解；加入防腐剂，混合均匀后加纯化水至1000ml，灌装，115℃灭菌15～20分钟，即得。
实施例4
壳聚糖 12g
吐温20 2.0g
苯甲酸钾 0.1g
纯化水 加至1000ml
制备方法包含以下步骤：将增溶剂加入1/3～2/3纯化水中，搅拌均匀，然后加入壳聚糖，35～40℃搅拌至完全溶解；加入防腐剂，混合均匀后加纯化水至1000ml，灌装，115℃灭菌15～20分钟，即得。
实施例5
壳聚糖 10g
聚乙二醇1000 3.5g
尼泊金乙酯 0.3g
纯化水 加至1000ml
制备方法包含以下步骤：将增溶剂加入1/3～2/3纯化水中，搅拌均匀，然后加入壳聚糖，35～40℃搅拌至完全溶解；加入防腐剂，混合均匀后加纯化水至1000ml，灌装，115℃灭菌15～20分钟，即得。
实施例6
壳聚糖 8g
丙二醇 0.1g
尼泊金乙酯 0.15g
尼泊金丙酯 0.15g
纯化水 加至1000ml
制备方法包含以下步骤：将增溶剂加入1/3～2/3纯化水中，搅拌均匀，然后加入壳聚糖，35～40℃搅拌至完全溶解；加入防腐剂，混合均匀后加纯化水至1000ml，灌装，115℃灭菌15～20分钟，即得。
对比例1
壳聚糖 10g
丙二醇 0.8g
吐温40 0.4g
尼泊金乙酯 0.1g
尼泊金丙酯 0.1g
纯化水 加至1000ml
制备方法同实施例2。
对比例2
壳聚糖 10g
丙二醇 1g
吐温40 0.2g
尼泊金乙酯 0.05g
尼泊金丙酯 0.15g
纯化水 加至1000ml
制备方法同实施例2。
试验例1本发明壳聚糖口服液的加速试验
1、考察样品
参照1-6的处方和制备方法得到的壳聚糖口服液。
2、试验方法
加速试验：取本发明的壳聚糖口服液共20份，在温度40℃±2℃、相对湿度75％±5％的 条件下放置6个月，在试验期间第0、1、3、6个月各取样一次，考察口服液的性状、pH值和含量。
试验结果见表1。
3、试验结果
结果表明，本发明实施例1-6的壳聚糖口服液经加速考察6个月，其性状、微生物限度、pH值和药物含量与0月相比均无明显变化，说明本发明的壳聚糖口服液稳定性好。
表1本发明壳聚糖口服液加速试验结果
Figure PCTCN2018103513-appb-000001
Figure PCTCN2018103513-appb-000002
试验例2本发明壳聚糖口服液的长期试验
1、考察样品
参照实施例2、对比例1、对比例2的处方和制备方法得到的壳聚糖口服液。
2、试验方法
长期试验：取本发明的壳聚糖口服液共30份，在温度25℃±2℃、相对湿度60％±10％的条件下放置24个月，分别于0、3、6、12、24个月各取样一次，考察口服液的性状、pH值和含量。
试验结果见表2。
3、试验结果
结果表明，本发明实施例2的壳聚糖口服液经长期试验24个月，其性状、微生物限度、pH值和药物含量与0月相比均无明显变化，说明本发明的壳聚糖口服液稳定性好。对比例1的壳聚糖口服液长期试验时，出现浑浊现象，微生物限度检测也不符合规定；对比例2的壳聚糖口服液长期试验时，出现浑浊现象，微生物限度检测也不符合规定。上述结果表明本发明的壳聚糖口服液组方和配比合理。
表2本发明壳聚糖口服液长期试验结果
Figure PCTCN2018103513-appb-000003
Figure PCTCN2018103513-appb-000004

Claims (7)

  1. 一种壳聚糖口服液，其特征在于，所述口服液包含如下重量配比的原辅料：
    壳聚糖6～12重量份；
    增溶剂0.5～3.5重量份；
    防腐剂0.1～0.5重量份。
  2. 如权利要求1所述的壳聚糖口服液，其特征在于，所述口服液包含如下重量配比的原辅料：
    壳聚糖8～10重量份；
    增溶剂1.2～2.0重量份；
    防腐剂0.2～0.3重量份。
  3. 如权利要求1或2所述的壳聚糖口服液，其特征在于，所述的增溶剂选自丙二醇、聚乙二醇、吐温中的一种或多种；防腐剂选自尼泊金乙酯、尼泊金丙酯、苯甲酸钾中的一种或多种。
  4. 如权利要求3所述的壳聚糖口服液，其特征在于，所述的聚乙二醇为聚乙二醇1000、聚乙二醇4000、聚乙二醇6000或聚乙二醇8000中的一种。
  5. 如权利要求3所述的壳聚糖口服液，其特征在于，所述的吐温为吐温20、吐温40或吐温60中的一种。
  6. 如权利要求3所述的壳聚糖口服液，其特征在于，所述的增溶剂为重量比为1：0.2的丙二醇和吐温40；防腐剂为重量比为1:1的尼泊金乙酯和尼泊金丙酯。
  7. 如权利要求1～6任一所述的壳聚糖口服液的制备方法，其特征在于，包含以下步骤：将增溶剂加入1/3～2/3纯化水中，搅拌均匀，然后加入壳聚糖，35～40℃搅拌至完全溶解；加入防腐剂，混合均匀后加纯化水至1000ml，灌装，115℃灭菌15～20分钟，即得。
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1985845A (zh) * 2006-12-30 2007-06-27 哈尔滨华雨制药集团有限公司 降血脂口服液及其制备方法
CN101298502A (zh) * 2007-04-30 2008-11-05 福建省医学科学研究所 一种增加壳聚糖水溶性的方法
CN102441158A (zh) * 2010-10-15 2012-05-09 天津瑞普生物技术股份有限公司 一种含有天蚕素的宠物用滴眼液及其制备方法
CN104856978A (zh) * 2015-05-18 2015-08-26 福建中医药大学 一种壳聚糖喷雾膜剂及其制备方法
CN108498531A (zh) * 2018-06-01 2018-09-07 广东药科大学 一种壳聚糖口服液及其制备方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1985845A (zh) * 2006-12-30 2007-06-27 哈尔滨华雨制药集团有限公司 降血脂口服液及其制备方法
CN101298502A (zh) * 2007-04-30 2008-11-05 福建省医学科学研究所 一种增加壳聚糖水溶性的方法
CN102441158A (zh) * 2010-10-15 2012-05-09 天津瑞普生物技术股份有限公司 一种含有天蚕素的宠物用滴眼液及其制备方法
CN104856978A (zh) * 2015-05-18 2015-08-26 福建中医药大学 一种壳聚糖喷雾膜剂及其制备方法
CN108498531A (zh) * 2018-06-01 2018-09-07 广东药科大学 一种壳聚糖口服液及其制备方法

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