CN104055750B - And preparation of hollow capsules having a targeting function - Google Patents

And preparation of hollow capsules having a targeting function Download PDF

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CN104055750B
CN104055750B CN 201410313574 CN201410313574A CN104055750B CN 104055750 B CN104055750 B CN 104055750B CN 201410313574 CN201410313574 CN 201410313574 CN 201410313574 A CN201410313574 A CN 201410313574A CN 104055750 B CN104055750 B CN 104055750B
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pectin
chitosan
solution
water
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CN104055750A (en )
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杨公明
吴丽
王荣辉
朱小花
王皓
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王荣辉
杨公明
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Abstract

本发明公开了一种具有靶向功能的空心胶囊,其组分有壳聚糖,果胶,卡拉胶,抗性淀粉,增塑剂,疏水剂,增塑剂选用山梨醇、甘油、丙二醇、甘露醇与聚乙二醇;疏水剂选用聚乙烯醇与二氧化硅;首先制备果胶‑壳聚糖聚合物;再进行原料混合溶解;最后用常规蘸模法制成具有靶向功能的空心胶囊。 The present invention discloses a hollow capsule having a targeting function, which component has a chitosan, pectin, carrageenan, resistant starch, a plasticizer, a water repellent, a plasticizer selected sorbitol, glycerol, propylene glycol, mannitol and polyethylene glycol; selection of polyvinyl alcohol and water repellent silica; first preparing a pectin - chitosan polymers; then the mixed material is dissolved; Finally conventional dip-die method to have a targeted function of empty capsules . 本发明可以根据需要按不同的组分和方法制备具有十二指肠靶向、回肠靶向和结肠靶向胶囊,壳聚糖中质子化的氨基和果胶中电离的羧基通过静电引力结合成次价键,形成聚电解质配合物,制备的十二指肠、回肠和结肠靶向胶囊定位准确,药物释放效果好,具有以剂量小、疗效高、毒副作用低的优点。 According to the present invention may be required by the different components and methods of preparing a targeting duodenum, ileum and colon targeted capsule, chitosan pectin protonated amino and carboxyl groups ionized by electrostatic attraction to bind secondary bonds, polyelectrolyte complexes, prepared duodenum, ileum and colon targeted capsule positioning accuracy, good drug delivery effect, having a small dose, high efficacy, low toxicity advantages.

Description

具有靶向功能的空心胶囊及制备方法 And preparation of hollow capsules having a targeting function

技术领域 FIELD

[0001]本发明涉及一种空心胶囊及制备方法,具体是一种具有靶向功能的空心胶囊及制备方法,属于医药食品领域。 [0001] The present invention relates to a method of preparing a hollow capsule and, in particular to a method of preparing a hollow capsule and having a targeting function, food field of medicine.

背景技术 Background technique

[0002]胶囊剂作为保健食品药品剂型中最常见的剂型,凭借其良好的掩味作用、较好的生物利用度,且美观易于吞服等诸多优点,已经成为口服固体制剂的主要包装材料,随着经济水平和人们消费能力的提高,以及医疗卫生事业和消费者对自身健康的日益重视,药品消耗量将逐年增大,医药行业以年均近20%的增长速度为硬胶囊行业提供了广阔发展空间。 [0002] capsules as a health food and drug dosage form of the most common forms, with its good taste-masking, good bioavailability, ease of swallowing and beautiful and many other advantages, the packaging material has become a major oral solid preparations, with the improvement of people's spending power and economic level, as well as health care and consumer's increasing emphasis on their own health, drug consumption will increase year by year, the pharmaceutical industry average annual growth rate of nearly 20% for the industry to provide a hard capsule broad space for development.

[0003]近年来随着国内外医药工业的迅速发展,以药物制剂新剂型及新品种的研究与开发尤为重要,这对于提高药物的疗效,降低药物毒副作用,增加药物生物有效性,方便病人用药起到了重要的作用。 [0003] In recent years, with the rapid development of domestic pharmaceutical industry to research and development of new dosage forms and pharmaceutical preparations of new varieties is particularly important, which is to improve the efficacy of drugs, reduce drug side effects, the increase of drug bioavailability, patient convenience medication played an important role. 以最小剂量、最高疗效、最低毒副作用、最方便的途径靶向给药,特别是结肠靶向给药的研究与开发具有重大临床价值。 With a minimum dose, the highest efficacy, low toxicity, most, most convenient way to targeted drug delivery, especially colon targeted drug research and development is of great clinical value. 目前的肠溶空心胶囊主要由抗胃酸的肠溶包衣材料和明胶组成。 Currently mainly of hollow capsules enteric gastric acid-resistant enteric coatings and gelatin. 抗胃酸的肠溶包衣材料多为邻苯二甲酸醋酸纤维素、丙烯酸树月旨、羟丙甲纤维素邻苯二甲酸酯、虫胶等,而且在包衣时必须使用有机溶剂来溶解制成包衣,有些采用多次包衣才能实现肠溶效果,不仅工艺繁杂,成本较高,而且使用大量有机溶剂,污染环境;明胶以动物皮等为原料,但因原料有限,往往利用皮革下脚料制备。 Gastric acid-resistant enteric coatings are mostly cellulose acetate phthalate, acrylic resin month purpose, hydroxypropyl methylcellulose phthalate, shellac, and must use an organic solvent during coating to dissolve coating made some use of multiple enteric coating to achieve the effect, not only complex process, higher cost, and a large amount of organic solvents, environmental pollution; gelatin is animal skin as raw materials, but the raw material is limited, often using leather waste preparation. 其食用安全和卫生难以保证,媒体近年屡屡曝光。 It is difficult to guarantee food safety and hygiene, the media in recent years repeatedly exposed. 新型胶囊研究成为近年热点,有针对原料开发出一次蘸胶成型的肠溶性空心胶囊:如中国专利CN101317830A公开了《一种肠溶空心胶囊及其制备方法》,以明胶、纤维素类或多糖类中的一种或几种的混合物制成的肠溶空心胶囊,但是需要对原料进行改性才能达到肠溶的效果;CN101708171A公开了《一种肠溶植物空心胶囊》,采用果胶作为主要原料制备肠溶空心胶囊,虽然省去了包衣工序,简化了工艺;但是这两个发明制备的胶囊只能达到在人体小肠溶解的效果。 Research in recent years become a new hot spot of the capsule, has developed a material for forming the plastic dip enteric hollow capsules: Chinese Patent CN101317830A discloses "a method of preparing a hollow capsule and enteric", gelatin, cellulosic or polysaccharide a mixture of one or more classes of hollow capsules made enteric, but needs to be modified in order to achieve the effect of feed enteric; CN101708171A discloses "an enteric hollow capsules plant" as the main use of pectin preparation of enteric-coated hollow capsule material, although the coating step is omitted, simplifying the process; however, the two capsules made to the invention can achieve the effect of dissolving in the small intestine.

发明内容 SUMMARY

[0004]本发明的目的是针对传统空心胶囊所存在过分依赖明胶等缺陷,在重视所制备胶囊本身对人体保健作用的同时,也充分考虑到所选原料本身的保健功能,而提供一种具有靶向功能的空心胶囊及制备方法。 [0004] The object of the present invention is directed to a conventional hollow capsules such as gelatin over-reliance on the existence of defects in the preparation of the capsule itself while the emphasis on human health effects, but also fully take into account the health function of the selected material itself, and to provide a the method of preparation of hollow capsules and targeting functions.

[0005]本发明选用果胶、壳聚糖、卡拉胶、抗性淀粉为主要原料,进行复合。 [0005] The present invention selects pectin, chitosan, carrageenan, resistant starch as the main raw material, composite. 果胶作为一种可溶性膳食纤维,具有不可替代的功能特性,除了具有良好的胶凝性、蛋白质稳定性、乳化特性外,还对高血压、便秘等慢性病具有一定的疗效;壳聚糖作为天然的多糖类物质,具有无毒、无免疫抗原性、不溶血等特点,在人体内可逐渐被降解吸收,并且具有独特的生理活性,如生物相容性、生物活性,抑菌性,可以显著地抑制微生物的生长。 Soluble dietary fiber as a pectin, an irreplaceable functional properties, in addition to having good gelling properties, protein stability, emulsifying properties, but also has a certain effect on hypertension, chronic constipation; native chitosan the polysaccharides, non-toxic, non-immunogenicity, without hemolysis, etc., in the human body can be gradually degraded and absorbed, and has a unique physiological activity, such as a biocompatible, bioactive, antibacterial activity, can be significantly inhibited the growth of microorganisms. 壳聚糖是一种含有-NH2的弱碱性聚电解质,果胶是一种带有-COOH的弱酸性聚电解质,当二者混合时,壳聚糖中质子化的氨基和果胶中电离的羧基通过静电引力结合成次价键,形成聚电解质配合物,该聚合物不溶于胃酸,可作为靶向给药物的新材料;抗性淀粉具有调节肠道功能、降血压、减月巴、通便、降糖等多种功能。 Chitosan is a copolymer containing weakly basic polyelectrolyte -NH2, -COOH Pectin is a weak acid with a polyelectrolyte, when a mixture of the two, the protonated amino group of chitosan and pectin ionization carboxy binding by electrostatic attraction to the secondary bonds, polyelectrolyte complexes, the polymer is insoluble in acid, can be used as new materials for drug targeting; resistant starch having intestinal function regulation, blood pressure, reduction month bar, laxative, hypoglycemic and other features. 这些原料来源丰富,性能优良,安全可靠,且具有多种功能性。 The rich source of raw materials, excellent performance, safety and reliability, and has a variety of functionality.

[0006]本发明具有靶向功能的空心胶囊由以下重量份的组分所组成: [0006] The present invention has a hollow capsule targeting function consists of the following parts by weight of component:

[0007] 壳聚糖1~5份,果胶12〜25,卡拉胶5〜10,抗性淀粉I〜10,增塑剂I〜5,疏水剂I〜3,水50〜100,其增塑剂选用山梨醇、甘油、丙二醇、甘露醇与聚乙二醇中的一种或两种以上混合物;其疏水剂选用聚乙烯醇与二氧化硅中的一种或两种混合物; [0007] 1 to 5 parts of chitosan, pectin 12~25, carrageenan 5 to 10, resistant starch I~10, plasticizers I~5, water repellent I~3, 50~100 water, which increases choose one plasticizer sorbitol, glycerol, propylene glycol, mannitol and polyethylene glycol or a mixture of two or more; the selection of polyvinyl alcohol and water repellent silica or a mixture of two;

[0008]具有靶向功能的空心胶囊其制备方法如下: [0008] The targeting function having a hollow capsule was prepared as follows:

[0009] a.制备果胶-壳聚糖聚合物 [0009] a preparation of pectin - chitosan polymers

[0010] a.1将壳聚糖溶于0.3%乙酸(V/V)溶液中,制成质量百分数为0.5〜1%的壳聚糖乙酸溶液, [0010] a.1 0.3% chitosan was dissolved in acetic acid (V / V), prepared mass percentage of 0.5~1% acetic acid solution of chitosan,

[0011] a.2将3倍壳聚糖重量的果胶溶于蒸馏水中,制成质量百分数为2~5%的果胶溶液, [0011] a.2 3 times the weight of chitosan pectin dissolved in distilled water to prepare a mass percentage of 2 to 5% pectin solution,

[0012] a.3将壳聚糖溶液缓慢加入到果胶溶液中,在15000〜20000r/min速度下用打浆机匀浆2〜3min,使聚合成乳化状, [0012] a.3 chitosan solution was slowly added to a solution of pectin, under 15000~20000r / min speed beater homogenizer 2~3min, emulsified into the polymerization,

[0013] a.4将聚合的果胶-壳聚糖溶液在室温下放置24〜48h,使果胶和壳聚糖反应完全,[00M] 3.5将聚合完全的果胶-壳聚糖溶液在30001'/111;[11的速度下离心10~151]1;[11,滤去上清液,得果胶-壳聚糖聚合物备用; [0013] a.4 polymerization pectin - chitosan solution is kept at room temperature 24~48h, pectin and chitosan completion of the reaction, [00M] 3.5 The complete polymerization pectin - chitosan solution 30001 '/ 111; [at a speed of 151 rpm for 10 ~ 11] 1; [11, was separated by filtration to give pectin - chitosan polymers standby;

[0015] b.原料混合溶解 [0015] b. Dissolving the mixed raw material

[0016] b.1将抗性淀粉加入水中,加热至60〜70°C,保持10〜20min,搅拌均 [0016] b.1 the resistant starch was added to water and heated to 60~70 ° C, holding 10~20min, stirring was

[0017]匀,制备成质量百分数为20〜30%的溶液, [0017] homogenized to prepare a 20 to 30% by mass percentage of a solution,

[0018] b.2将果胶-壳聚糖聚合物、卡拉胶与重量份中余量的果胶加入到抗性淀粉溶液中,并按组分比例补充水分,在80〜100°C温度下加热并搅拌均匀,使溶液细腻无颗粒感,然后按重量份加入增塑剂、疏水剂,混合均匀得胶体溶液; [0018] b.2 pectin - chitosan polymers, carrageenan and pectin remaining in parts by weight was added to the resistant starch solution, add water and press the component ratio, at a temperature of 80~100 ° C and stir under heating, the solution was no fine grainy, and then press parts by weight of plasticizer is added, a hydrophobic agent, uniformly mixed to obtain a colloidal solution;

[0019] c.蘸胶成型 [0019] c. Dipped plastic molding

[0020]将混合均匀的胶体溶液进行消泡,用常规蘸模法制成具有靶向功能的空心胶囊。 [0020] The mixed colloidal solution was defoamed, using a conventional dip molding SYSTEM hollow capsules with a targeted function.

[0021]本发明根据需要按不同的组分和方法制备具有靶向功能的十二指肠靶向、回肠靶向和结肠靶向胶囊,壳聚糖中质子化的氨基和果胶中电离的羧基通过静电引力结合成次价键,形成聚电解质配合物,制备的十二指肠靶向胶囊可实现在十二指肠内持续给药,具有以剂量小、疗效高、毒副作用低的优点,回肠和结肠靶向胶囊进入定位准确,药物释放效果好;原料来源丰富,天然安全,工艺简单,相对于现有市场上的包衣片成本低,安全性好,可作为明胶的替代物,为解决胶囊危机问题提供有力的发展方向;靶向功能空心胶囊在作为药物的载体的同时,又是一种辅助保健品,具有很好的保健功能。 [0021] According to the present invention is required by the different components and methods of preparing a targeting function of the targeting duodenum, ileum and colon targeted capsule, protonated amino group of chitosan and pectin ionization binding to a carboxyl group by electrostatic attraction of secondary bonds, polyelectrolyte complexes, duodenum targeted sustained capsule preparation may be administered in the duodenum, small a dose, high efficacy, low toxicity advantages , ileum and colon targeted capsule into the positioning accuracy, good drug release effect; rich source of raw materials, natural and safe, simple process, low-coated tablet with respect to the existing market cost, safety, and can be used as an alternative to gelatin, to solve the problem of providing a capsule crisis vigorous development direction; targeting function hollow capsules at the same time as the drug carrier, but also a complementary health care products, it has a good health care.

具体实施方式 detailed description

[0022]以下通过实例对本发明做进一步详细说明,这些实例仅用来说明本发明,并不限制本发明的范围。 [0022] The following further detailed description of the present invention by way of example, these examples are merely to illustrate the invention and do not limit the scope of the present invention.

[0023]实施例一:具有十二指肠靶向功能的空心胶囊由以下重量份的组分所组成: [0023] Example a: duodenum targeting function having a hollow capsule by the weight of component parts consisting of:

[0024] 壳聚糖1~2份,果胶20〜25,卡拉胶5〜10,抗性淀粉I〜5,甘油I〜5,聚乙烯醇I〜3,水50〜100 ; [0024] 1 to 2 parts of chitosan, 20 ~ 25 pectin, carrageenan 5 to 10, resistant starch I~5, glycerol I~5, polyvinyl alcohol I~3, water 50~100;

[0025]具有十二指肠靶向功能的空心胶囊的制备方法,包括如下步骤: [0025] The method of preparation of hollow capsules having duodenum targeting function, comprising the steps of:

[0026] a.制备果胶-壳聚糖聚合物 [0026] a preparation of pectin - chitosan polymers

[0027] a.1将壳聚糖溶于0.3%乙酸(V/V)溶液中,制成质量百分数为0.5%的壳聚糖乙酸溶液, [0027] a.1 0.3% chitosan was dissolved in acetic acid (V / V), prepared mass percentage of 0.5% acetic acid solution of chitosan,

[0028] a.2将3倍壳聚糖重量的果胶溶于蒸馏水中,制成质量百分数为5%的果胶溶液, [0028] a.2 3 times the weight of chitosan pectin dissolved in distilled water to prepare a 5% by mass percentage of pectin solution,

[0029] a.3将壳聚糖溶液缓慢加入到果胶溶液中,在20000r/min速度下用打浆机匀浆2min,使聚合成乳化状, [0029] a.3 chitosan solution was slowly added to the pectin solution, homogenized with a beater 2min at 20000r / min speed, into the polymerization emulsified,

[0030] a.4将聚合的果胶-壳聚糖溶液在室温下放置48h,使果胶和壳聚糖反应完全, [0030] a.4 polymerization pectin - chitosan solution is kept at room temperature for 48h, the reaction was complete pectin and chitosan,

[°031 ] a.5将聚合完全的果胶-壳聚糖溶液在3000r/min的速度下离心1min,滤去上清液,得果胶-壳聚糖聚合物备用; [° 031] a.5 completely polymerized pectin - chitosan solution was centrifuged 1min at a speed of 3000r / min, and the supernatant was filtered off to give pectin - chitosan polymers standby;

[0032] b.原料混合溶解 [0032] b. Dissolving the mixed raw material

[0033]按配方将卡拉胶,余量的果胶、溶解后的抗性淀粉溶液和制备的果胶- [0033] The formulated carrageenan, pectin balance, resistant starch solution prepared after dissolving and pectin -

[0034]壳聚糖混合,并加水溶解 [0034] Chitosan were mixed and dissolved in water

[0035] b.1将抗性淀粉加入水中,加热至70°C,保持lOmin,搅拌均匀,制 [0035] b.1 resistant starch added to the water and heated to 70 ° C, holding lOmin, stirred uniformly, Ltd.

[0036]备成质量百分数为30%的溶液; [0036] Preparation of 30% as a percentage by mass of the solution;

[0037] b.2将果胶-壳聚糖聚合物、卡拉胶和配方中余量的果胶加入到抗性淀粉溶液中,并按配方比例补充水分,在80°C温度下加热并搅拌均匀,使溶液细腻无颗粒感,然后加入甘油,聚乙烯醇,混合均匀得胶体溶液; [0037] b.2 pectin - chitosan polymers, carrageenan and pectin balance of the formulation is added to the resistant starch solution, add water to the prescribed ratio, heated and stirred at a temperature of 80 ° C for uniform, fine grain-free solution was then added to glycerin, polyvinyl alcohol, colloidal solution to obtain a uniform mixture;

[0038] c.蘸胶成型 [0038] c. Dipped plastic molding

[0039]将混合均匀的胶体溶液进行消泡,用常规蘸模法制成具有靶向功能的空心胶囊。 [0039] The mixed colloidal solution was defoamed, using a conventional dip molding SYSTEM hollow capsules with a targeted function.

[0040]用上述方法制备的胶囊具有十二指肠靶向功能,胶囊在胃内不溶解,到达十二指肠药物释放,剂量小,效果好。 [0040] Capsules prepared by the above method has a targeting function duodenum, the capsule does not dissolve in the stomach, the drug release reaches the duodenum, small dose, the effect is good.

[0041]实施例二:具有回肠靶向功能的空心胶囊由以下重量份的组分所组成: [0041] Example II: with ileal targeting function of the following parts by weight of hollow capsules composed of components:

[0042] 壳聚糖2〜3份,果胶15〜25,卡拉胶5〜10,抗性淀粉I〜5,山梨醇I〜2,甘油I〜3,二氧化石圭I〜3,水50〜100; [0042] 2 ~ chitosan parts of 15~25 pectin, carrageenan 5 to 10, resistant starch I~5, sorbitol I~2, glycerol I~3, silica stone Kyu I~3, water 50~100;

[0043]具有回肠靶向功能的空心胶囊的制备方法,包括如下步骤: Preparation [0043] The method of ileal targeting function having a hollow capsule, comprising the steps of:

[0044] a.制备果胶-壳聚糖聚合物 [0044] a preparation of pectin - chitosan polymers

[0045] a.1将壳聚糖溶于0.3%乙酸(V/V)溶液中,制成质量百分数为1%的壳聚糖乙酸溶液, [0045] a.1 0.3% chitosan was dissolved in acetic acid (V / V), prepared mass percentage of 1% acetic acid solution of chitosan,

[0046] a.2将3倍壳聚糖重量的果胶溶于蒸馏水中,制成质量百分数为2%的果胶溶液, [0046] a.2 3 times the weight of chitosan pectin dissolved in distilled water to prepare a mass percentage of 2% pectin solution,

[0047] a.3将壳聚糖溶液缓慢加入到果胶溶液中,在15000r/min速度下用打浆机匀浆3min,使聚合成乳化状, [0047] a.3 chitosan solution was slowly added to the pectin solution at 15000r / min speed beater homogenizer 3min, emulsified into the polymerization,

[0048] a.4将聚合的果胶-壳聚糖溶液在室温下放置24h,使果胶和壳聚糖反应完全, [0048] a.4 polymerization pectin - chitosan solution is kept at room temperature for 24h, the reaction was complete pectin and chitosan,

[0049] &.5将聚合完全的果胶-壳聚糖溶液在300(^/11^11的速度下离心151^11,滤去上清液,得果胶-壳聚糖聚合物备用; [0049] .5 & complete the polymerization pectin - chitosan solution was centrifuged at a speed of 11 151 300 ^ (^ / 11 ^ 11, was separated by filtration to give pectin - chitosan polymers standby;

[0050] b.原料混合溶解 [0050] b. Dissolving the mixed raw material

[0051 ] b.1将抗性淀粉加入水中,加热至60°C,保持20min,搅拌均匀,制 [0051] b.1 the resistant starch was added to water and heated to 60 ° C, kept 20min, stirred uniformly, Ltd.

[0052]备成质量百分数为20%的溶液, [0052] The mass percentage to prepare a 20% solution,

[0053] b.2将果胶-壳聚糖聚合物、卡拉胶与组分量中余量的果胶加入到抗性淀粉溶液中,并按组分比例补充水分,在100°C温度下加热并搅拌均匀,使溶液细腻无颗粒感,然后加入山梨醇、甘油和二氧化硅,混合均匀得胶体溶液; [0053] b.2 pectin - chitosan polymers, carrageenan and pectin component amount in the balance of resistant starch added to the solution, add water and press the component ratio, heated at a temperature of 100 ° C for and stir the fine grain-free solution, followed by addition of sorbitol, glycerol and silica, colloidal solution to obtain a uniform mixture;

[0054] c.蘸胶成型 [0054] c. Dipped plastic molding

[0055]将混合均匀的胶体溶液进行消泡,用常规蘸模法制成具有靶向功能的空心胶囊。 [0055] The mixed colloidal solution was defoamed, using a conventional dip molding SYSTEM hollow capsules with a targeted function.

[0056]用上述方法制备的胶囊具有回肠靶向功能,在胃内不溶解,到达回肠后药物释放,符合回肠靶向给药的要求。 [0056] Capsules prepared by the above method ileal targeting function, does not dissolve in the stomach, the drug release reaches the ileum, ileum meet the requirements of targeted drug delivery.

[0057]实施例三:具有结肠靶向功能的空心胶囊由以下重量份的组分所组成: [0057] Example Three: colon targeting functions having the following parts by weight of hollow capsules composed of components:

[0058] 壳聚糖3〜5份,果胶12〜25,卡拉胶5〜10,抗性淀粉5〜10,丙二醇I〜5,聚乙烯醇I〜1.5,二氧化硅I〜I.5,7X50-100; [0058] 3 ~ 5 parts of chitosan, pectin 12~25, carrageenan 5 to 10, 5 to 10 resistant starch, propylene glycol I~5, polyvinyl alcohol I~1.5, silica I~I.5 , 7X50-100;

[0059]具有结肠靶向功能的空心胶囊的制备方法,包括如下步骤: [0059] The method of preparation of hollow capsules having colon targeting function, comprising the steps of:

[0060] a.制备果胶-壳聚糖聚合物 [0060] a preparation of pectin - chitosan polymers

[0061] a.1将壳聚糖溶于0.3%乙酸(V/V)溶液中,制成质量百分数为1%的壳聚糖乙酸溶液, [0061] a.1 0.3% chitosan was dissolved in acetic acid (V / V), prepared mass percentage of 1% acetic acid solution of chitosan,

[0062] a.2将3倍壳聚糖重量的果胶溶于蒸馏水中,制成质量百分数为3%的果胶溶液, [0062] a.2 3 times the weight of chitosan pectin dissolved in distilled water to prepare a mass percentage of 3% pectin solution,

[0063] a.3将壳聚糖溶液缓慢加入到果胶溶液中,在18000r/min速度下用打浆机匀浆3min,使聚合成乳化状, [0063] a.3 chitosan solution was slowly added to the pectin solution at 18000r / min speed beater homogenizer 3min, emulsified into the polymerization,

[0064] a.4将聚合的果胶-壳聚糖溶液在室温下放置36h,使果胶和壳聚糖反应完全, [0064] a.4 polymerization pectin - chitosan solution is kept at room temperature for 36h, the reaction was complete pectin and chitosan,

[0065] &.5将聚合完全的果胶_壳聚糖溶液在300(^/1^11的速度下离心121^11,滤去上清液,得果胶-壳聚糖聚合物备用; [0065] & complete the polymerization .5 _ chitosan pectin solution was centrifuged at a speed of 11 121 300 ^ (^ / 1 ^ 11, was separated by filtration to give pectin - chitosan polymers standby;

[0066] b.原料混合溶解 [0066] b. Dissolving the mixed raw material

[0067] b.1将抗性淀粉加入水中,加热至65°C,保持20min,搅拌均匀,制 [0067] b.1 the resistant starch was added to water and heated to 65 ° C, kept 20min, stirred uniformly, Ltd.

[0068]备成质量百分数为25%的溶液; [0068] Preparation as mass percentage of 25% solution;

[0069] b.将果胶-壳聚糖聚合物、卡拉胶与组分量中余量的果胶加入到抗性淀粉溶液中,并按组分比例补充水分,在90°C温度下加热并搅拌均匀,使溶液细腻无颗粒感,然后加入丙二醇,聚乙烯醇,二氧化硅,混合均匀得胶体溶液; [0069] b pectin - chitosan polymers, carrageenan and pectin component amount in the balance of resistant starch added to the solution, add water and press the ratio of components was heated at 90 ° C for temperature and stir the solution was no fine grainy, and propylene glycol, polyvinyl alcohol, silica, colloidal solution to obtain a uniform mixture;

[0070] c.蘸胶成型 [0070] c. Dipped plastic molding

[0071]将混合均匀的胶体溶液进行消泡,用常规蘸模法制成具有靶向功能的空心胶囊。 [0071] The mixed colloidal solution was defoamed, using a conventional dip molding SYSTEM hollow capsules with a targeted function.

[0072]用上述方法制备的胶囊具有结肠靶向功能,在胃和小肠内不溶解,到达结肠后一小时内药物完全释放,符合结肠革G向给药的要求。 [0072] The capsules prepared by the above method colon function, does not dissolve in the stomach and small intestine, one hour after the complete release of the drug reaches the colon, colonic compliance leather G to administration.

[0073]经对本发明具有靶向功能的空心胶囊进一步试验检测结果如下: [0073] with a targeted function by the present invention is a hollow capsule further testing result is as follows:

[0074]空心胶囊外观表面光滑平整,有光泽,无瘪头、薄头、皱纹、梅花头等现象;壁厚 [0074] The hollow capsules Appearance smooth surface, glossy, no flat head, thin head, wrinkles, plum top phenomenon; thickness

0.09-,0.12mm;含水率5.8-9.6%(相对湿度:50%);当含水量大于5%时脆碎率为O。 0.09-, 0.12mm; moisture content 5.8-9.6% (relative humidity: 50%); when the water content was greater than 5% Friability O.

[0075]药物释放度测定:溶液配制,pH值为1.5的酸性溶液的配制:将去离子水溶液用HCl调节pH值到1.5,最终HCI浓度约为0.0llmol/L;模拟胃液的配制:在去离子水溶液中加入质量体积比为1%的胃蛋白酶,然后用0.1M的HCl调节pH至1.5;模拟小肠液的配制:在pH为6.8的0.02M的磷酸缓冲液中,加入质量体积比为1%的胰蛋白酶;模拟结肠液的配制:将SD大鼠麻痹后把结肠从腹部取出,在充氮环境中收集结肠内容物,并用PH为7.8的磷酸缓冲液稀释到30%(w/v)。 [0075] Drug release assay: solution preparation, the pH value of the acidic solution prepared 1.5: deionized water solution to adjust the pH to 1.5 with HCl, final concentration of about HCI 0.0llmol / L; formulated simulated gastric fluid: in de ion aqueous solution was added to a volume ratio of 1% by mass of pepsin and pH was adjusted to 1.5 with a 0.1M HCI; simulated intestinal fluid is formulated: in 0.02M phosphate buffer pH 6.8 was added 1 volume ratio of mass % trypsin; simulated colonic fluid formulation: SD rats were paralyzed after the colon was removed from the abdomen, colon contents were collected in a nitrogen environment, 7.8 phosphate buffer and diluted to 30% (w / v) was used PH .

[0076]根据国家药典委员会编制的《中华人民共和国药典》药物释放度检查法,将空心胶囊分别按顺序置于模拟胃液2h、模拟小肠液3h和模拟结肠液中Ih,测定其释放效果。 [0076] According to "Pharmacopoeia of People's Republic of China" drug release test method Pharmacopoeia Commission prepared, the hollow capsules are sequentially placed in simulated gastric fluid 2h, 3h simulated intestinal fluid and simulated colonic fluid Ih is, measured release effect.

[0077]选取Vc作为模拟药物来测定胶囊的体外溶出药物含量,判断胶囊是否具有良好的靶向给药能力。 [0077] Select Vc measured in vitro as a model drug elution capsule drug content, determines whether the capsule has a good ability of targeted drug delivery. 取6粒胶囊制剂,将装载200mgVc,分别按照上述方法先后置于模拟胃液、小肠液和结肠液中,每隔30min测量一次溶液中Vc的含量。 Taking 6 capsules formulations loaded 200mgVc, respectively, according to the method described above has to simulated gastric, small intestine and colon fluid, was measured once every 30min Vc content solution. 结果表明:十二指肠靶向胶囊中装载的Vc在胃液中没有药物释放,进入十二指肠内药物完全,并在Ih内释放完全;回肠革巴向胶囊在胃液中没有释放,进入小肠后前Ih没有释放,第2h缓慢释放,释放率9.54%,3h内释放完全,释放率达到98.27%;结肠靶向胶囊在胃液中没有释放,在小肠液中释放6.8%,在结肠液中释放度飞速上升,第6h达到测定量最大值96.09,符合结肠靶向给药的要求。 The results showed that: Targeting capsule loaded in duodenum Vc no drug release in gastric fluid, the drug completely into the duodenum, and in Ih is completely released; ileal Gerba not release the capsule in gastric fluid, into the small intestine not released before and after Ih, 2h of slow release, the release rate of 9.54%, completely release of 3h, the release rate of 98.27%; colon targeted capsule are not released in gastric fluid, the release of 6.8% in the small intestine, in the colon to release liquid the rapid rise of the first 6h reaches a maximum measured amount of 96.09, to meet the requirements of the colon targeted drug delivery. 测定结果最大释放率没有达到100%的原因是释放出的Vc被氧化或其它原因反应掉一部分。 The maximum release rate measurement result does not reach 100% because of the release of Vc is oxidized or otherwise reacted part.

Claims (4)

  1. 1.具有靶向功能的空心胶囊的制备方法,其特征在于具有靶向功能的空心胶囊是由以下重量份的组分所制成: 壳聚糖I〜5份,果胶12〜25,卡拉胶5〜10,抗性淀粉卜10,增塑剂卜5,疏水剂I〜3,水50〜100,其增塑剂选用山梨醇、甘油、丙二醇、甘露醇与聚乙二醇中的一种或两种以上混合物;其疏水剂选用聚乙烯醇与二氧化硅中的一种或两种混合物;并按以下技术流程完成:a.制备果胶-壳聚糖聚合物a.1将壳聚糖溶于0.3%V/V乙酸溶液中,制成质量百分数为0.5~1%的壳聚糖乙酸溶液,a.2将3倍壳聚糖重量的果胶溶于蒸馏水中,制成质量百分数为2~5%的果胶溶液,a.3将壳聚糖溶液缓慢加入到果胶溶液中,在15000〜20000r/min速度下用打浆机匀浆2〜3min,使聚合成乳化状, a.4将聚合的果胶-壳聚糖溶液在室温下放置24〜48h,使果胶和壳聚糖反应完全, &.5将聚合完全的果胶-壳聚糖 1. A method of preparing a hollow capsule having a targeting function, wherein the hollow capsules having a targeting function is made of the following parts by weight of component: parts I~5 chitosan, pectin 12~25, karaoke 5 to 10 gum, resistant starch 10 Bu, Bu 5 plasticizer, water repellent I~3, water 50~100, which is a plasticizer selected sorbitol, glycerol, propylene glycol, mannitol and polyethylene glycol or a mixture of two or more species; hydrophobic agent which polyvinyl alcohol or a mixture of two selected with one of silica; process is completed according to the following technique: a preparing pectin - chitosan polymers will a.1 shell. glycans were dissolved in 0.3% V / V acetic acid solution to prepare a mass percentage of 0.5 to 1% acetic acid solution of chitosan, chitosan A.2 3 times the weight of the pectin dissolved in distilled water to prepare a mass percentage of 2 to 5% pectin solution, A.3 chitosan solution was slowly added to the pectin solution at 15000~20000r / min speed beater homogenizer 2~3min, emulsified into the polymerization, a.4 polymerization pectin - chitosan solution is kept at room temperature 24~48h, pectin and chitosan reaction was complete, the polymerization .5 & complete pectin - chitosan 液在300(^/1^11的速度下离心10~151^11,滤去上清液,得果胶-壳聚糖聚合物备用; b.原料混合溶解b.1将抗性淀粉加入水中,加热至60〜70°C,保持10〜20min,搅拌均匀, 制备成质量百分数为20~30%的溶液, b.2将果胶-壳聚糖聚合物、卡拉胶与重量份中余量的果胶加入到抗性淀粉溶液中,并按组分比例补充水分,在80〜100°C温度下加热并搅拌均匀,使溶液细腻无颗粒感,然后按重量份加入增塑剂、疏水剂,混合均匀得胶体溶液; c.蘸胶成型将混合均匀的胶体溶液进行消泡,用常规蘸模法制成具有靶向功能的空心胶囊。 It was centrifuged at a speed of 300 (^ / 1 ^ 10 to 11 ^ 11 151, was separated by filtration to give pectin - chitosan polymers standby;. B b.1 dissolving the mixed raw material was added to water resistant starch and heated to 60~70 ° C, holding 10~20min, uniform stirring to prepare a mass percentage of 20 to 30% solution, B.2 pectin - chitosan polymers, carrageenan and the remaining parts by weight resistant starch is added to the pectin solution, add water and press the component ratio, uniformly heated and stirred at a temperature of 80~100 ° C, the solution was no fine grainy, and then press parts by weight of plasticizer is added, a hydrophobic agent , uniformly mixed to obtain a colloidal solution; C dipped in the plastic molding mixed colloidal solution was defoamed, using a conventional dip molding SYSTEM hollow capsules with a targeted function.
  2. 2.根据权利要求1所述的具有靶向功能的空心胶囊的制备方法,其特征在于所述的空心胶囊具有十二指肠靶向功能,是由以下重量份的组分所制成:壳聚糖I〜2份,果胶20〜25,卡拉胶5〜10,抗性淀粉I〜5,甘油I〜5,聚乙烯醇I〜3,水50〜100。 The method of preparation of hollow capsules having a targeting function according to claim 1, wherein the hollow capsules have a targeting function duodenum, is made of the following parts by weight of component: shell glycans I~2 parts, 20 ~ 25 pectin, carrageenan 5 to 10, resistant starch I~5, glycerol I~5, polyvinyl alcohol I~3, water 50~100.
  3. 3.根据权利要求1所述的具有靶向功能的空心胶囊的制备方法,其特征在于所述的空心胶囊具有回肠靶向功能,是由以下重量份的组分所制成:壳聚糖2〜3份,果胶15〜25,卡拉胶5〜10,抗性淀粉I〜5,山梨醇I〜2,甘油I〜3,二氧化硅I〜3,水50〜100。 The method of preparation of hollow capsules having a targeting function according to claim 1, wherein the hollow capsules have ileal targeting function, is made of the following parts by weight of component: Chitosan 2 ~ 3 parts of 15~25 pectin, carrageenan 5 to 10, resistant starch I~5, sorbitol I~2, glycerol I~3, silica I~3, water 50~100.
  4. 4.根据权利要求1所述的具有靶向功能的空心胶囊的制备方法,其特征在于所述的空心胶囊具有结肠靶向功能,是由以下重量份的组分所制成:壳聚糖3~5份,果胶12〜25,卡拉胶5〜10,抗性淀粉5〜10,丙二醇I〜5,聚乙烯醇I〜1.5,二氧化硅I〜1.5,水50〜100。 The preparation of hollow capsules having a targeting function according to claim 1, wherein the hollow capsules have a colon targeting function, is made of the following parts by weight of component: chitosan 3 to 5 parts, 12~25 pectin, carrageenan 5 to 10, 5 to 10 resistant starch, propylene glycol I~5, polyvinyl alcohol I~1.5, silica I~1.5, water 50~100.
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CN1606978A (en) * 2003-10-15 2005-04-20 浙江省新昌县药联胶丸有限公司 Hollow capsule of natural plant gum and its preparing process
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