WO2016058160A1 - 肠溶植物纤维素硬空心胶囊及其制备方法 - Google Patents
肠溶植物纤维素硬空心胶囊及其制备方法 Download PDFInfo
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- WO2016058160A1 WO2016058160A1 PCT/CN2014/088740 CN2014088740W WO2016058160A1 WO 2016058160 A1 WO2016058160 A1 WO 2016058160A1 CN 2014088740 W CN2014088740 W CN 2014088740W WO 2016058160 A1 WO2016058160 A1 WO 2016058160A1
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- capsule
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- pectin
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
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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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
Definitions
- the invention relates to an enteric plant cellulose hard hollow capsule and a preparation method thereof, and belongs to the technical field of pharmaceutical excipients.
- the hard hollow capsule shell is the main outer covering material for filling medicines and health foods, and is taken into the body together with the endocytic substances, thereby reducing the trouble of entrance and increasing the curative effect.
- Traditional gelatin capsules use gelatin which is hydrolyzed from the skin of animals as the main raw material. Although gelatin has good properties in the preparation of hollow capsules, the source is limited, and with the frequency of diseases such as mad cow disease, foot-and-mouth disease, and bird flu. Hair, the quality problems of gelatin capsules themselves cause doubts and concerns of consumers.
- the following problems are likely to occur: if the water content of the raw materials of the product is low (the solid matter is large), the fluidity of the raw materials is poor, and the homogeneity is poor, and the hollow capsule produced has the material and wall thickness of each point.
- the qualified rate of the finished product is low; if the water content of the raw material of the product is increased and the fluidity of the raw material is increased, the drying process of the product becomes longer, the power consumption increases, and the uncertainty of product formation increases due to the loss of water, Influencing the pass rate of finished products, the hollow capsules prepared by the existing production process have the disadvantages of different wall thickness, large difference in water content, low pass rate and high energy consumption, and the traditional gelatin hollow capsule is in the stomach acid. It disintegrates and releases within min, but the contents of the capsule are irritating to the stomach, or unstable to acid, and need to disintegrate in the intestine to exert its therapeutic effect. Accordingly, the present invention develops an enteric plant cellulose hard hollow capsule to address the deficiencies of prior art vegetable hollow capsules.
- An object of the present invention is to solve the deficiencies of the prior art and to provide an enteric plant cellulose hard hollow capsule.
- Another object of the present invention is to provide a method for preparing an enteric plant cellulose hard hollow capsule.
- An enteric plant cellulose hard hollow capsule comprising a hard hollow capsule body, wherein the hard hollow capsule body is processed by mixing the following weight percentage raw materials: plant cellulose derivative 20-28%, pectin 10-16%, surfactant 0.2-0.25%, coagulant 0.1-5%, colorant 0-0.05%, titanium dioxide 0-5%, plasticizer 0.1-0.5%, the balance is water, the surfactant is selected from sodium lauryl sulfate or Tween -80, the plasticizer is selected from the group consisting of glycerin or polyethylene glycol, and the coagulant is selected from any one or more of sodium alginate, agar, carrageenan, and refrigeration gel, and the colorant is synthesized. Any of a colorant, a natural colorant, and a plant colorant.
- Enteric plant cellulose hard hollow capsule of the invention The main raw materials are plant cellulose derivatives and pure natural plant acid multi-confectionery gum as the main raw material.
- Pectin is distributed as one of the main ingredients in the hard hollow capsule body, and the obtained hard hollow capsule does not need external coating. Can achieve stomach acid resistance To ensure that the hard hollow capsule does not disintegrate in the stomach, the hard hollow capsule does not crosslink with the contained drug, and the safety is good.
- the hard hollow capsule body is processed from the following weight percentages of raw materials: plant cellulose derivative 25%, pectin 12%, surfactant 0.24%, coagulant 2.5%, colorant 0 -0.05%, titanium dioxide 0-5%, plasticizer 0.25%, the balance is water, the surfactant is selected from sodium lauryl sulfate or Tween -80, the plasticizer is selected from the group consisting of glycerin or polyethylene glycol, and the coagulant is selected from the group consisting of a mixture of any two of sodium alginate, agar, carrageenan and refrigeration gel, the colorant being Natural colorant.
- the plant cellulose derivative is hypromellose, and the colorant is iron oxide red or iron oxide yellow.
- said enteric plant cellulose hard hollow capsule further comprises a single layer coating on the exterior of the hard hollow capsule body, the coating being made of pectin or hypromellose phthalate.
- the coating is made of pectin or hypromellose phthalate, preferably pectin, on the one hand, hard hollow
- the capsule body itself contains pectin, which is coated with pectin as a material, which is convenient for coating, has a better coating effect, and has a smooth coating surface.
- the method for preparing the hard hollow capsule of the present invention comprising uncoated and coated, uncoated enteric plant cellulose hard hollow capsules is carried out as follows:
- the preparation method of the coated enteric plant cellulose hard hollow capsule is carried out as follows:
- the primary capsule is coated with pectin or hypromellose phthalate material, then dried, cut and prepared according to the conventional capsule production process. The finished hollow capsule.
- the drying conditions in the step (3) of the above two methods are: oven temperature 55-65 ° C, relative humidity in the oven 45-55%, drying time is 3.5h.
- the primary capsule is coated once in the step (4), and the specific operation is as follows: the pectin is dissolved in the purified water, and the mass ratio of the pectin to the purified water is 1:12-15, after mixing, coat the primary capsule as a coating material within 3-5 hours, the coating amount is 10% of the capsule mass; or dissolve the hydroxypropyl methylcellulose phthalate In ethanol, the mass ratio of hypromellose phthalate to ethanol is 1:10-16, and after mixing, it is placed for 8-12 hours, and then the primary capsule is packaged as a coating material within 3-5 hours. Clothing, the amount of coating is 10% of the capsule quality .
- the main raw material of the present invention is a plant cellulose derivative, preferably hypromellose and pectin, a surfactant, a coagulant, a plasticizer and water.
- a coloring agent and titanium dioxide are added.
- enteric plant cellulose hard hollow capsules can be uncoated after drying, or the molded hollow capsules are automatically coated by automatic device once, then Drying, pulling out pills, entering downstream process cutting, semi-finished products inspection, nesting, printing, finished product inspection, internal packaging, outsourcing, physical and chemical inspection, storage.
- the main material hypromellose is a derivative of plant fiber, its main components are plant cell wall and polysaccharide, the molecular structure is very stable, and the film formation is excellent.
- Pectin is a pure natural acidic plant polysaccharide, safe. It has good sex and can resist stomach acid.
- the enteric plant cellulose hard hollow capsule has the following three characteristics:
- the plant cellulose hard hollow capsule of the invention belongs to the plant source, not only maintains the function of the gelatin capsule, but also satisfies the requirements of various products, has small pollution, good safety, low water content, and ensures the drying of the contents, and further Effectively exert the therapeutic effect of the contents, the molecular structure is stable, does not cross-link with the contents, and the dissolution is more sufficient.
- the enteric plant cellulose hard hollow capsule of the present invention has a water content of 5-7% between the special requirements, the water content can reach 3% It is suitable for filling all kinds of contents, ensuring that it has no cross-linking reaction. Because of its stable molecular structure, it is more suitable for filling oxygen-sensitive and immediate-release drugs, making the contents safer, more complete and more effective.
- the enteric plant cellulose hard hollow capsule of the invention has low water content, stable molecular structure, and is particularly suitable for filling of traditional Chinese medicine preparations, and the product does not require harsh gelatin hollow capsules for storage and transportation environment, and can meet various content requirements. Because plant cellulose has no side effects on the human body, it also provides new options for vegetarianism and different religious ceremonies.
- the invention adopts vegetable raw materials instead of animal raw materials to make capsules, so that oral drugs can exert better curative effect, which is the development trend and direction of the pharmaceutical capsule industry in the future, and is a major and revolutionary change of the pharmaceutical industry. It has great medical value and economic value.
- the high-temperature mixing and high-temperature drying processing technology overcomes the shortcomings of the difference in average water content caused by low water content of plant fibers, low qualification rate and high energy consumption.
- the medicinal ethanol and water are purified water obtained by secondary reverse osmosis purification, and other raw materials are commercially available conventional raw materials.
- An enteric plant cellulose hard hollow capsule comprising a hard hollow capsule body which is processed by mixing the following weight percentage raw materials: hypromellose 20%, pectin 16%, surfactant 0.2%, coagulant 0.1%, plasticizer 0.1%, balance is water, the surfactant is sodium lauryl sulfate, the plasticizer is glycerin, and the coagulant is sodium alginate .
- the preparation method of the above enteric plant cellulose hard hollow capsule is as follows:
- An enteric plant cellulose hard hollow capsule consisting of a hard hollow capsule body and a coating, wherein the hard hollow capsule body is processed by mixing the following weight percentage materials: hypromellose 28%, pectin 10% , surfactant 0.25%, coagulant 5%, colorant 0.05%, titanium dioxide 5%, plasticizer 0.5%, balance is water, the surfactant is selected from Tween-80, the plasticizer Selected from polyethylene glycol, the coagulant is an equal mixture of agar and carrageenan, the iron oxide yellow of the colorant, and the coating is a pectin material.
- the preparation method of the above enteric plant cellulose hard hollow capsule is as follows:
- the primary capsule is coated once with pectin material, then dried, cut and finished according to the conventional capsule production process.
- the coating is made of the enteric plant cellulose hard hollow capsule.
- the specific operation of the coating is as follows: The gum is dissolved in purified water, the mass ratio of pectin to purified water is 1:12, after mixing for 3-5h The primary capsule is coated as a coating material, and the coating amount is 10% of the capsule mass.
- Enteric plant cellulose hard hollow capsules including hard hollow capsules, which are processed from the following weight percentages of raw materials: plant cellulose derivatives 25%, pectin 12%, surfactant 0.24%, Coagulant 2.5%, colorant 0.02%, titanium dioxide 2.5%, plasticizer 0.25%, balance is water, the surfactant is selected from sodium lauryl sulfate, and the plasticizer is selected from polyethylene glycol An alcohol, the coagulant is selected from the group consisting of a refrigerant gel, and the colorant is iron oxide red.
- the preparation method of the above enteric plant cellulose hard hollow capsule is as follows:
- the hard hollow capsule body is processed from the following weight percentage raw materials: plant cellulose derivative 25%, pectin 12%, surface active Agent 0.24%, coagulant 2.5%, colorant 0.02%, titanium dioxide 2.5%, plasticizer 0.25%, balance is water, the surfactant is selected from sodium lauryl sulfate, the plasticizer is selected From the polyethylene glycol, the coagulant is selected from the group consisting of a refrigerant gel, the colorant is iron oxide yellow, and the coating material is pectin.
- the preparation method of the above enteric plant cellulose hard hollow capsule is as follows:
- the primary capsule is coated once with pectin material, then dried, cut and finished according to the conventional capsule production process.
- the coating is made of the enteric plant cellulose hard hollow capsule.
- the specific operation of the coating is as follows: The gum is dissolved in purified water, and the mass ratio of pectin to purified water is 1:15. After mixing, the primary capsule is coated as a coating material within 3-5 hours, and the coating amount is 10% of the capsule mass. .
- Enteric plant cellulose hard hollow capsule consisting of hard hollow capsule body and coating
- the hard hollow capsule body is processed from the following weight percentage raw materials: plant cellulose derivative 25%, pectin 12%, surface active Agent 0.24%, coagulant 2.5%, colorant 0.02%, titanium dioxide 2.5%, plasticizer 0.25%, balance is water
- the surfactant is selected from sodium lauryl sulfate
- the plasticizer is selected From the polyethylene glycol
- the coagulant is selected from the group consisting of a refrigerating gel
- the coloring agent is iron oxide yellow
- the coating material is hypromellose phthalate.
- the preparation method of the above enteric plant cellulose hard hollow capsule is as follows:
- the primary capsule is coated with pectin material once, then dried, cut and prepared according to the conventional capsule production process.
- the coating is processed as follows: The propylmethylcellulose phthalate is dissolved in ethanol, the mass ratio of hypromellose phthalate to ethanol is 1:10-16, and after mixing, it is placed for 8-12h, then at 3- The primary capsule was coated as a coating material within 5 hours, and the coating amount was 10% of the capsule mass. .
- the enteric plant cellulose hard hollow capsule has smooth capsule, uniform color, neat cut, no deformation, no odor, heavy metal content is less than 10 parts per million, and its tightness, friability, average weight , microbial limits and other indicators are in line with the Chinese Pharmacopoeia The relevant provisions in the second appendix of the 2010 edition.
- the enteric plant cellulose hard hollow capsule of the invention has been experimentally proved that the quality index completely conforms to the Chinese Pharmacopoeia enteric hollow capsule standard, is not dissolved in the gastric juice, and is dissolved in the intestinal juice, and the tested indicators are as follows:
- Example 1 Gastric fluid disintegration time limit Intestinal fluid disintegration time limit Example 1 3-4h 40-45min Example 2 4.5-5h 30-40min Example 3 3-4h 35-40min Example 4 5-6h 40-45min Example 5 3-4h 30-45min
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Abstract
本发明公开了一种肠溶植物性纤维素硬空心胶囊及其制备方法，所述胶囊体的原料组成如下(重量百分比)：植物纤维素衍生物 20-28%，果胶 10-16%，表面活性剂 0.2-0.25%，助凝剂 0.1-5%，二氧化钛 0-5%，增塑剂 0.1-0.5%，水余量。
Description
本发明涉及一种肠溶植物纤维素硬空心胶囊及其制备方法，属于药用辅料技术领域。
硬空心胶囊壳是填充药物、保健食品的主要外包材，与内吞物一并服入体内，减轻入口麻烦，增加疗效。传统明胶胶囊采用从动物的皮骨中水解熬制的明胶为主要原料，尽管明胶在制备空心胶囊时有很好的特性，但是来源受限，且随着疯牛病、口蹄疫、禽流感等疾病的频发，明胶胶囊自身存在的质量问题引起消费者的质疑和担忧。
目前，植物性空心胶囊的生产过程中容易发生以下问题：若产品原料的含水低（固形物多），则原料的流动性差，均质性差，生产出的空心胶囊因各位点的材质、壁厚不一而成品合格率低；若增加产品原料的含水量，原料的流动性提高，则产品的干燥成型过程变长，电耗增加，而且由于失水多，产品成型的不确定性增加，同样影响成品合格率，现有的生产工艺制备的空心胶囊具有壁厚不一，含水量差异大，合格率低，能耗高的缺点，且传统的明胶空心胶囊在胃酸中10
min内就崩解、释放，但胶囊内有的内容物对胃有刺激性，或遇酸不稳定，需要在肠内崩解才能发挥疗效。因此，本发明开发一种肠溶植物纤维素硬空心胶囊，以解决现有技术的植物性空心胶囊存在的不足。
本发明的目的在于解决现有技术的不足，提供一种 肠溶植物纤维素硬空心胶囊。
本发明的另一个目的是提供一种肠溶植物纤维素硬空心胶囊的制备方法。
本发明为解决其技术问题，采用的技术方案如下：
一种肠溶植物纤维素硬空心胶囊，包括硬空心胶囊体，其特征在于，所述硬空心胶囊体由下列重量百分比的原料混合加工而成：植物纤维素衍生物 20-28%，果胶
10-16%，表面活性剂 0.2-0.25%，助凝剂 0.1-5%，着色剂 0-0.05%，二氧化钛 0-5%，增塑剂
0.1-0.5%，余量为水，所述表面活性剂选自十二烷基硫酸钠或吐温
-80，所述增塑剂选自甘油或聚乙二醇，所述助凝剂选自海藻酸钠、琼脂、卡拉胶、制冷胶中的任意一种或几种，所述着色剂为合成着色剂、天然着色剂和植物着色剂中的任意一种。
本发明的肠溶植物纤维素硬空心胶囊
主要原料为植物纤维素衍生物以及纯天然的植物酸性多糖果胶为主要原料，果胶作为主料之一均分分布于硬空心胶囊体的内，制得的硬空心胶囊不需要外部包衣既能实现耐胃酸
，确保硬空心胶囊在胃里不崩解，该硬空心胶囊与盛放的药物不会发生交联反应，安全性好。
作为优选，所述硬空心胶囊体由下列重量百分比的原料加工而成：植物纤维素衍生物 25%，果胶
12%，表面活性剂 0.24%，助凝剂 2.5%，着色剂 0 -0.05%，二氧化钛 0-5%，增塑剂
0.25%，余量为水，所述表面活性剂选自十二烷基硫酸钠或吐温
-80，所述增塑剂选自甘油或聚乙二醇，所述助凝剂选自海藻酸钠、琼脂、卡拉胶、制冷胶中的任意两种的等比例混合物，所述着色剂为天然着色剂。
更优选， 所述植物纤维素衍生物为羟丙甲纤维素，所述着色剂为氧化铁红或氧化铁黄。
作为优选，所述
肠溶植物纤维素硬空心胶囊还包括位于硬空心胶囊体外部的单层包衣，所述包衣采用的材料为果胶或羟丙甲纤维素邻苯二甲酸酯。
为了更进一步的提高 硬空心胶囊耐胃酸
，确保硬空心胶囊在胃里不崩解，在硬空心胶囊体外再包裹一层包衣，包衣选用果胶或羟丙甲纤维素邻苯二甲酸酯，优选果胶，一方面硬空心胶囊体本身含有果胶，以果胶做材料来包衣，包衣方便，包衣效果更好，包衣表面光滑。
本发明的硬空心胶囊含不带包衣的和带包衣的，不带包衣的肠溶植物纤维素硬空心胶囊的制备方法按如下步骤进行：
（1）配料：将配方量的水添加入反应器中，加热至
80-95℃，加入配方量的植物纤维素衍生物和果胶，搅拌混合均匀，然后将混合溶液冷却至 50-55℃，保温 10-15min，然后再降温至
30-35℃，搅拌条件下加入配方量的表面活性剂、增塑剂、助凝剂、着色剂和二氧化钛，继续搅拌至均匀；
（2）烊胶：将步骤（1）制得的胶液于升温至 50-52℃，静置
2-2.5h，送入胶囊生产线；
（3）成型：将送入胶囊生产线的胶液进行蘸胶、成型后，送入烘箱内烘干得到初囊体，然后经过切割并按照常规胶囊制作流程制得肠溶植物纤维素硬空心胶囊成品。
带包衣的肠溶植物纤维素硬空心胶囊的制备方法按如下步骤进行：
（1）配料：将配方量的水添加入反应器中，加热至
80-95℃，加入配方量的植物纤维素衍生物和果胶，搅拌混合均匀，然后将混合溶液冷却至 50-55℃，保温 10-15min，然后再降温至
30-35℃，搅拌条件下加入配方量的表面活性剂、增塑剂、助凝剂、着色剂和二氧化钛，继续搅拌至均匀；
（2）烊胶：将步骤（1）制得的胶液于升温至 50-52℃，静置
2-2.5h，送入胶囊生产线；
（3）成型：将送入胶囊生产线的胶液进行蘸胶、成型后，送入烘箱内烘干得到初囊体；
（4）包衣：将初囊体采用果胶或羟丙甲纤维素邻苯二甲酸酯材料进行一次包衣，然后烘干、切割并按照常规胶囊制作流程制得肠溶植物纤维素硬空心胶囊成品。
作为优选，上述两种方法中步骤（3）中烘干条件为：烘箱温度 55-65℃，烘箱内相对湿度
45-55%，烘干时间为 3.5h 。
作为优选，上述含包衣的硬空心胶囊的制备方法中，步骤（4）中初囊体进行一次包衣，具体操作如下：将果胶溶于纯化水中，果胶与纯化水的质量比为1:12-15，混合后于3-5h内作为包衣材料对初囊体进行包衣，包衣量为胶囊质量的10%；或者将羟丙基甲纤维素邻苯二甲酸酯溶于乙醇中，羟丙甲纤维素邻苯二甲酸酯与乙醇的质量比为1:10-16，混合后放置8-12h，然后于3-5h内作为包衣材料对初囊体进行包衣，包衣量为胶囊质量的10%
。
本发明的主要原料为植物纤维素衍生物，优选羟丙甲纤维素以及果胶、表面活性剂、助凝剂、增塑剂和水，当需要制作有色胶囊时，添加着色剂和二氧化钛，通过植物纤维素衍生物如羟丙甲纤维素、果胶与表面活性剂、助凝剂和增塑剂的配比，制备过程采用与传统明胶胶囊低温溶化、低温烘干的相反工艺，而采用高温溶化混合、高温烘干工艺，进行肠溶植物纤维素硬空心胶囊的生产，硬空心胶囊囊体成型干燥后可以不包衣，或者成型干燥后的空心胶囊通过自动装置自动沾包衣一次，然后烘干，拔丸、进入下游流程切割、半成品检、套合、印字、成品检、内包、外包、理化检验、入库。其中，主料羟丙甲纤维素是植物纤维的衍生物，其主要成分有植物细胞壁和多聚糖组成，分子结构十分稳定，成膜性极好，果胶是纯天然的酸性植物多糖，安全性好，可以耐胃酸，制成的肠溶植物纤维素硬空心胶囊具有以下三大特点：
（ 1
）安全性：本发明的植物纤维素硬空心胶囊属植物源，既保持明胶胶囊的功能，又能满足各类产品要求，污染小、安全性好，含水量低，确保内容物的干燥，更有效的发挥内容物的疗效，分子结构稳定，不与内容物发生交联反应，溶出度更充分。
（ 2 ）稳定性：本发明的肠溶植物纤维素硬空心胶囊由于含水量在 5-7%
之间，特别要求时，含水量可达到 3%
，适合填充各类内容物，确保其无交联反应，由于分子结构稳定，更适合填充氧敏感性、速释性药物，使内容物更加安全，溶出更彻底，疗效更显著。
（ 3
）普适性：本发明的肠溶植物纤维素硬空心胶囊水分低，分子结构稳定，特别适应中药制剂的填充，产品对储运环境要求没有明胶空心胶囊苛刻，能满足各类内容物要求。由于是植物纤维素对人体无任何副作用，还给素食主义和不同宗教信仰者提供新的选择。
综上所述，本发明采用植物性原料取代动物性原料制作胶囊，让口服药物发挥更好的疗效，是今后药用胶囊产业的发展趋势和方向，是制药业的重大的、革命性的变革，具有极大的医学价值和经济价值；同时，采用高温混合、高温烘干的加工工艺，克服了植物纤维含水量低带来的平均含水量差异大，合格率低，能耗高的缺点。
下面通过具体实施例，对本发明的技术方案作进一步的具体说明。
本发明技术方案及具体实施方式中涉及到的乙醇为 95%
的药用乙醇，水采用二级反渗透净化得到的净化水，其它原料均系市购常规原料。
实施例 1 ：
一种肠溶植物纤维素硬空心胶囊，包括硬空心胶囊体，所述硬空心胶囊体由下列重量百分比的原料混合加工而成：羟丙甲纤维素20%，果胶16%，表面活性剂0.2%，助凝剂0.1%，增塑剂0.1%，余量为水，所述表面活性剂为十二烷基硫酸钠，所述增塑剂为甘油，所述助凝剂为海藻酸钠。
上述肠溶植物纤维素硬空心胶囊的制备方法如下：
（1）配料：将配方量的水添加入反应器中，加热至80-95℃，加入配方量的羟丙甲纤维素和果胶，搅拌混合均匀，然后将混合溶液冷却至50-55℃，保温10-15min，然后再降温至30-35℃，搅拌条件下加入配方量的表面活性剂、增塑剂、助凝剂，继续搅拌至均匀；
（2）烊胶：将步骤（1）制得的胶液于升温至50-52℃，静置2-2.5h，送入胶囊生产线；
（3）成型：将送入胶囊生产线的胶液进行蘸胶、成型后，送入烘箱内烘干得到初囊体，然后经过切割并按照常规胶囊制作流程制得肠溶植物纤维素硬空心胶囊成品。
实施例 2 ：
一种肠溶植物纤维素硬空心胶囊，由硬空心胶囊体和包衣构成，所述硬空心胶囊体由下列重量百分比的原料混合加工而成：羟丙甲纤维素28%，果胶10%，表面活性剂0.25%，助凝剂5%，着色剂0.05%，二氧化钛5%，增塑剂0.5%，余量为水，所述表面活性剂选自吐温-80，所述增塑剂选自聚乙二醇，所述助凝剂为琼脂和卡拉胶的等比例混合物，所述着色剂的氧化铁黄，所述包衣采用果胶材料。
上述肠溶植物纤维素硬空心胶囊的制备方法如下：
（1）配料：将配方量的水添加入反应器中，加热至80-95℃，加入配方量的羟丙甲纤维素和果胶，搅拌混合均匀，然后将混合溶液冷却至50-55℃，保温10-15min，然后再降温至30-35℃，搅拌条件下加入配方量的表面活性剂、增塑剂、助凝剂、着色剂和二氧化钛，继续搅拌至均匀；
（2）烊胶：将步骤（1）制得的胶液于升温至50-52℃，静置2-2.5h，送入胶囊生产线；
（3）成型：将送入胶囊生产线的胶液进行蘸胶、成型后，送入烘箱内烘干得到初囊体；
（4）包衣：将初囊体采用果胶材料进行一次包衣，然后烘干、切割并按照常规胶囊制作流程制得肠溶植物纤维素硬空心胶囊成品，包衣具体操作如下：将果胶溶于纯化水中，果胶与纯化水的质量比为1:12，混合后于3-5h
内作为包衣材料对初囊体进行包衣，包衣量为胶囊质量的10% 。
实施例 3 ：
肠溶植物纤维素硬空心胶囊，包括硬空心胶囊体，所述硬空心胶囊体由下列重量百分比的原料加工而成：植物纤维素衍生物25%，果胶12%，表面活性剂0.24%，助凝剂2.5%，着色剂0.02%，二氧化钛2.5%，增塑剂0.25%，余量为水，所述表面活性剂选自十二烷基硫酸钠，所述增塑剂选自聚乙二醇，所述助凝剂选自制冷胶，所述着色剂为氧化铁红。
上述肠溶植物纤维素硬空心胶囊的制备方法如下：
（1）配料：将配方量的水添加入反应器中，加热至80-95℃，加入配方量的植物纤维素衍生物和果胶，搅拌混合均匀，然后将混合溶液冷却至50-55℃，保温10-15min，然后再降温至30-35℃，搅拌条件下加入配方量的表面活性剂、增塑剂、助凝剂、着色剂和二氧化钛，继续搅拌至均匀；
（2）烊胶：将步骤（1）制得的胶液于升温至50-52℃，静置2-2.5h，送入胶囊生产线；
（3）成型：将送入胶囊生产线的胶液进行蘸胶、成型后，送入烘箱内烘干得到初囊体，然后经过切割并按照常规胶囊制作流程制得肠溶植物纤维素硬空心胶囊成品。
实施例4：
肠溶植物纤维素硬空心胶囊，由硬空心胶囊体和包衣构成，所述硬空心胶囊体由下列重量百分比的原料加工而成：植物纤维素衍生物25%，果胶12%，表面活性剂0.24%，助凝剂2.5%，着色剂0.02%，二氧化钛2.5%，增塑剂0.25%，余量为水，所述表面活性剂选自十二烷基硫酸钠，所述增塑剂选自聚乙二醇，所述助凝剂选自制冷胶，所述着色剂为氧化铁黄，所述包衣采用的材料为果胶。
上述肠溶植物纤维素硬空心胶囊的制备方法如下：
（1）配料：将配方量的水添加入反应器中，加热至80-95℃，加入配方量的羟丙甲纤维素和果胶，搅拌混合均匀，然后将混合溶液冷却至50-55℃，保温10-15min，然后再降温至30-35℃，搅拌条件下加入配方量的表面活性剂、增塑剂、助凝剂、着色剂和二氧化钛，继续搅拌至均匀；
（2）烊胶：将步骤（1）制得的胶液于升温至50-52℃，静置2-2.5h，送入胶囊生产线；
（3）成型：将送入胶囊生产线的胶液进行蘸胶、成型后，送入烘箱内烘干得到初囊体；
（4）包衣：将初囊体采用果胶材料进行一次包衣，然后烘干、切割并按照常规胶囊制作流程制得肠溶植物纤维素硬空心胶囊成品，包衣具体操作如下：将果胶溶于纯化水中，果胶与纯化水的质量比为1:15，混合后于3-5h内作为包衣材料对初囊体进行包衣，包衣量为胶囊质量的10%
。
实施例 5 ：
肠溶植物纤维素硬空心胶囊，由硬空心胶囊体和包衣构成，所述硬空心胶囊体由下列重量百分比的原料加工而成：植物纤维素衍生物25%，果胶12%，表面活性剂0.24%，助凝剂2.5%，着色剂0.02%，二氧化钛2.5%，增塑剂0.25%，余量为水，所述表面活性剂选自十二烷基硫酸钠，所述增塑剂选自聚乙二醇，所述助凝剂选自制冷胶，所述着色剂为氧化铁黄，所述包衣采用的材料为羟丙甲纤维素邻苯二甲酸酯。
上述肠溶植物纤维素硬空心胶囊的制备方法如下：
（1）配料：将配方量的水添加入反应器中，加热至80-95℃，加入配方量的羟丙甲纤维素和果胶，搅拌混合均匀，然后将混合溶液冷却至50-55℃，保温10-15min，然后再降温至30-35℃，搅拌条件下加入配方量的表面活性剂、增塑剂、助凝剂、着色剂和二氧化钛，继续搅拌至均匀；
（2）烊胶：将步骤（1）制得的胶液于升温至50-52℃，静置2-2.5h，送入胶囊生产线；
（3）成型：将送入胶囊生产线的胶液进行蘸胶、成型后，送入烘箱内烘干得到初囊体；
（4）包衣：将初囊体采用果胶材料进行一次包衣，然后烘干、切割并按照常规胶囊制作流程制得肠溶植物纤维素硬空心胶囊成品，包衣具体操作如下：将羟丙基甲纤维素邻苯二甲酸酯溶于乙醇中，羟丙甲纤维素邻苯二甲酸酯与乙醇的质量比为1:10-16，混合后放置8-12h，然后于3-5h内作为包衣材料对初囊体进行包衣，包衣量为胶囊质量的10%
。
实施例 1 至 5
制得的肠溶植物纤维素硬空心胶囊，囊体光滑，色泽均匀，切口整齐，无变形，无异臭，重金属含量均低于百万分之十，其松紧度、脆碎度、平均重量、微生物限度等指标均符合中国药典
2010 版第二部附录中的相关规定。
本发明的肠溶植物纤维素硬空心胶囊经过实验表明质量指标完全符合《中国药典》肠溶空心胶囊标准，在胃液中不溶解，在肠液中溶解，经检测指标如下：
| 胃液崩解时限 | 肠液崩解时限 | |
| 实施例1 | 3-4h | 40-45min |
| 实施例2 | 4.5-5h | 30-40min |
| 实施例3 | 3-4h | 35-40min |
| 实施例4 | 5-6h | 40-45min |
| 实施例5 | 3-4h | 30-45min |
以上所述的实施例只是本发明的一种较佳的方案，并非对本发明作任何形式上的限制，在不超出权利要求所记载的技术方案的前提下还有其它的变体及改型 。
Claims (1)
- 1. 一种肠溶植物纤维素硬空心胶囊，包括硬空心胶囊体，其特征在于，所述硬空心胶囊体由下列重量百分比的原料混合加工而成：植物纤维素衍生物20-28%，果胶10-16%，表面活性剂0.2-0.25%，助凝剂0.1-5%，着色剂0-0.05%，二氧化钛0-5%，增塑剂0.1-0.5%，余量为水，所述表面活性剂选自十二烷基硫酸钠或吐温-80，所述增塑剂选自甘油或聚乙二醇，所述助凝剂选自海藻酸钠、琼脂、卡拉胶、制冷胶中的任意一种或几种，所述着色剂为合成着色剂、天然着色剂和植物着色剂中的任意一种。2. 根据权利要求 1 所述的肠溶植物纤维素硬空心胶囊，其特征在于，所述硬空心胶囊体由下列重量百分比的原料加工而成：植物纤维素衍生物25%，果胶12%，表面活性剂0.24%，助凝剂2.5%，着色剂0 -0.05%，二氧化钛0-5%，增塑剂0.25%，余量为水，所述表面活性剂选自十二烷基硫酸钠或吐温-80，所述增塑剂选自甘油或聚乙二醇，所述助凝剂选自海藻酸钠、琼脂、卡拉胶、制冷胶中的任意两种的等比例混合物，所述着色剂为天然着色剂。3. 根据权利要求 2 所述的肠溶植物纤维素硬空心胶囊，其特征在于，所述植物纤维素衍生物为羟丙甲纤维素，所述着色剂为氧化铁红或氧化铁黄。4. 根据权利要求 3 所述的肠溶植物纤维素硬空心胶囊，其特征在于，还包括位于硬空心胶囊体外部的单层包衣，所述包衣采用的材料为果胶或羟丙甲纤维素邻苯二甲酸酯。5. 一种权利要求 1 至 3 任意一项所述肠溶植物纤维素硬空心胶囊的制备方法，其特征在于，所述制备方法按如下步骤进行：（1）配料：将配方量的水添加入反应器中，加热至80-95℃，加入配方量的植物纤维素衍生物和果胶，搅拌混合均匀，然后将混合溶液冷却至50-55℃，保温10-15min，然后再降温至30-35℃，搅拌条件下加入配方量的表面活性剂、增塑剂、助凝剂、着色剂和二氧化钛，继续搅拌至均匀；（2）烊胶：将步骤（1）制得的胶液于升温至50-52℃，静置2-2.5h，送入胶囊生产线；（3）成型：将送入胶囊生产线的胶液进行蘸胶、成型后，送入烘箱内烘干得到初囊体，然后经过切割并按照常规胶囊制作流程制得肠溶植物纤维素硬空心胶囊成品。6. 一种权利要求 4 所述肠溶植物纤维素硬空心胶囊的制备方法，其特征在于，所述制备方法按如下步骤进行：（1）配料：将配方量的水添加入反应器中，加热至80-95℃，加入配方量的植物纤维素衍生物和果胶，搅拌混合均匀，然后将混合溶液冷却至50-55℃，保温10-15min，然后再降温至30-35℃，搅拌条件下加入配方量的表面活性剂、增塑剂、助凝剂、着色剂和二氧化钛，继续搅拌至均匀；（2）烊胶：将步骤（1）制得的胶液于升温至50-52℃，静置2-2.5h，送入胶囊生产线；（3）成型：将送入胶囊生产线的胶液进行蘸胶、成型后，送入烘箱内烘干得到初囊体；（4）包衣：将初囊体采用果胶或羟丙甲纤维素邻苯二甲酸酯材料进行一次包衣，然后烘干、切割并按照常规胶囊制作流程制得肠溶植物纤维素硬空心胶囊成品。7. 根据权利要求 5 或 6 所述的肠溶植物纤维素硬空心胶囊的制备方法，其特征在于，步骤（3）中烘干条件为：烘箱温度55-65℃，烘箱内相对湿度45-55%，烘干时间为3.5h。8. 根据权利要求 6 所述的肠溶植物纤维素硬空心胶囊的制备方法，其特征在于，步骤（4）中初囊体进行一次包衣，具体操作如下：将果胶溶于纯化水中，果胶与纯化水的质量比为1:12-15，混合后于3-5h内作为包衣材料对初囊体进行包衣，包衣量为胶囊质量的10%；或者将羟丙基甲纤维素邻苯二甲酸酯溶于乙醇中，羟丙甲纤维素邻苯二甲酸酯与乙醇的质量比为1:10-16，混合后放置8-12h，然后于3-5h内作为包衣材料对初囊体进行包衣，包衣量为胶囊质量的10%。
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