WO2017107628A1

WO2017107628A1 - Chitosan oligosaccharide capsule and method for preparation thereof

Info

Publication number: WO2017107628A1
Application number: PCT/CN2016/102114
Authority: WO
Inventors: 苏政权; 郭姣; 黄兰兰
Original assignee: 广东药科大学
Priority date: 2015-12-24
Filing date: 2016-10-14
Publication date: 2017-06-29
Also published as: CN105380924B; CN105380924A

Abstract

The present disclosure belongs to the technical field of pharmaceutical preparations and specifically relates to a chitosan oligosaccharide capsule and method for preparation thereof. The chitosan oligosaccharide capsule comprises content and a capsule shell; said content consists primarily of chitosan oligosaccharide, microcrystalline cellulose, adhesive, calcium stearate, ethanol, and micropowder silicone; said capsule shell consists primarily of hydroxypropyl starch, xanthan gum, thickener, plasticizer, and water. The chitosan oligosaccharide capsule is odorless, has a neat appearance, and is smooth; its content uniformity and solubility satisfy the relevant provisions of the Pharmacopoeia of China, and the capsule has relatively good sealing tightness and resistance to oxidation; it effectively addresses the problem of chitosan oligosaccharide being prone to oxidation and moisture absorption, facilitating the long-term storage of chitosan oligosaccharide.

Description

Shell oligosaccharide capsule and preparation method thereof

Technical field

The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a chitosan oligosaccharide capsule and a preparation method thereof.

Background technique

Chitosan naoligosaccharide (COS) is a homopolymer or heteropolymer of glucosamine and N-acetylglucosamine linked by β-1,4 glycosidic bonds. COS is the only abundant organic polysaccharide in natural sugar. In addition to its chitosan-like properties, it also has the advantages of low viscosity, good water solubility, small molecular weight, easy absorption and degradability, and its biological activity and function. The properties are superior to chitosan. A large number of studies have shown that COS has the functions of regulating blood sugar, blood sugar, anti-oxidation, anti-infection, enhancing immunity and anti-tumor. It is an ideal bioactive substance with broad medical application prospects.

Chinese patent CN103316031B discloses a slimming and lipid-lowering application of chitosan oligosaccharide, which has a remarkable application effect in controlling body weight, reducing body fat ratio and lowering serum total cholesterol and low density lipoprotein cholesterol content, indicating shell Oligosaccharides have significant weight loss and lipid-lowering effects, and also have the function of relieving fatty liver and reducing blood lipids in serum.

Chen Jian published a paper titled "Study on chitosan oligosaccharide, glucosamine slimming activity and capsaicin-containing chitosan microsphere enteric-coated tablets", which showed that chitosan oligosaccharides have better weight loss effects, but also It has the advantages of no toxic side effects, fast absorption and good compatibility. It is an ideal weight loss drug.

However, since chitosan oligosaccharides have the characteristics of low molecular weight, easy moisture absorption, and easy oxidation, their application in the field of health care products or medicines is greatly limited. At present, the application of chitosan oligosaccharides is mainly focused on crops. Chinese patent CN102613197B discloses the use of chitosan oligosaccharide for preventing premature aging, which can effectively prevent premature aging of crops and ensure stable yield and income of agriculture. Chinese patent CN101818181B discloses a method for enzymatically preparing agricultural chitosan oligosaccharide and a crop nutrient preparation containing chitooligosaccharide, which can not only provide nutrition for crops, stimulate crop growth, but also inhibit the reproduction of harmful bacteria and improve the crop itself. Disease resistance.

Therefore, researching and developing a chitosan oligosaccharide dosage form with good stability and high oxidation resistance is an effective way to promote the application of chitosan oligosaccharide in the field of health care products or medicines.

Summary of the invention

In order to solve the defects of low molecular weight, easy moisture absorption and easy oxidation in the prior art, the object of the present invention is to provide a chitosan oligosaccharide capsule and a preparation method thereof to solve the above defects.

The present invention provides a chitosan oligosaccharide capsule comprising a content and a capsule comprising the following components and their weight percentages: chitosan oligosaccharide 80-100%, microcrystalline cellulose 0-6%, bonding Agent 0-5%, calcium stearate 0-3%, ethanol 0-4% and micronized silica gel 0-2%;

The capsule comprises the following components and parts by weight: 4-10 parts of hydroxypropyl starch, 2-6 parts of xanthan gum, 4-8 parts of thickener, 3-6 parts of plasticizer and 10 parts of water. 20 copies.

Further, the content includes the following components and their weight percentages: chitosan oligosaccharide 80-92%, microcrystalline cellulose 2-6%, binder 2-5%, calcium stearate 1-3%, ethanol 2-4% and micronized silica gel 1-2%.

Further, the contents include the following components and their weight percentages: chitosan oligosaccharide 85.5%, microcrystalline cellulose 4%, binder 4%, calcium stearate 2%, ethanol 3%, and micronized silica gel 1.5% .

Further, the binder is a povidone solution having a concentration of 5%, and the ethanol is anhydrous ethanol.

Further, the capsule comprises the following components and parts by weight: 8 parts of hydroxypropyl starch, 4 parts of xanthan gum, 5 parts of thickener, 4 parts of plasticizer and 16 parts of water.

Further, the thickener is composed of guar gum and propylene glycol alginate in a weight ratio of 1-2:3-4, preferably, the thickener is composed of guar gum and propylene glycol alginate by weight. It is composed of 1.2:3.5.

Further, the plasticizer is composed of glycerin and triethyl citrate in a weight ratio of 2-4:1-3, preferably, the plasticizer is 3.5:2 by weight of glycerin and triethyl citrate. composition.

The content of the capsule provided by the invention adopts a povidone solution having a concentration of 5% as a binder, which can improve the uniformity of the particles without occurrence of the phenomenon that the particles cannot be granulated, the particles are loose or agglomerated. The use of anhydrous ethanol as a wetting agent can prevent the appearance of mushy or lumps of chitosan oligosaccharides. The composition of the capsule contents provided by the invention is reasonable, and the prepared contents are dry, moderately tight, and the moisture content is qualified, which complies with the relevant provisions of the Chinese Pharmacopoeia on the contents of the capsules.

The hydroxypropyl starch in the capsule provided by the invention has the formula C ₃ H ₈ O ₂ ·x, the CAS number is 9049-76-7, and has the advantages of high stability, good expandability and good film forming property, yellow The original rubber has the advantages of high viscosity, good thermal stability and acid-base stability, and is an ideal bio-adhesive. The combination of hydroxypropyl starch and xanthan gum can improve the gelation and gel temperature of hydroxypropyl starch, which is beneficial to the film formation of hydroxypropyl starch.

The guar gum in the capsule provided by the present invention is a nonionic galactomannan which has good water solubility and exhibits a high viscosity at a low mass fraction. The propylene glycol alginate is a deep-processed alginic acid extracted from natural seaweed, which does not gel in an acidic solution, and is an environmentally-friendly thickener. The combination of guar gum and propylene glycol alginate in a certain proportion can greatly enhance the thickening effect of propylene glycol alginate. Glycerin has the characteristics of low viscosity, easy dispersion and good compatibility, while triethyl citrate has the advantages of strong solubility and good mold resistance. Glycerin and triethyl citrate are used in combination in a certain ratio to have a remarkable plasticizing effect.

The capsules provided by the invention have reasonable distribution, and the prepared capsules have no odor, the appearance is neat, no sticking, deformation, leakage or capsule rupture, and the sealing property is good, the oxidation resistance is high, and the improvement is greatly improved. The stability of the capsule is beneficial to the preservation of the capsule.

In addition, the present invention also provides a method for preparing a chitosan oligosaccharide capsule, comprising the following steps:

S1 grinds chitosan oligosaccharide, microcrystalline cellulose, calcium stearate and micro-powder silica gel into a fine powder, and mixes with a binder and ethanol to pass through a sieve of 18-25 mesh to obtain a fine powder;

S2, the fine powder obtained in the step S1 is subjected to wet granulation, the wet granulation temperature is 22-28 ° C, the humidity is 35-45%, and the granulation is dried to less than 10% moisture to obtain a content;

S3 grinds the hydroxypropyl starch into a fine powder, adds xanthan gum, thickener, plasticizer and water to mix evenly, and dries at a temperature of 55-60 ° C for 4-5 h, then at a temperature of 50 ° C Carrying out silicone, drying, demoulding, cutting, nesting, and obtaining a capsule;

S4, the content obtained in step S2 is filled into the capsule obtained in step S3, and the capsule is sealed.

Compared with the prior art, the chitosan oligosaccharide capsule provided by the present invention has the following advantages:

(1) The chitosan oligosaccharide capsule provided by the invention has no odor, has a neat appearance, is smooth, and has high solubility, and is beneficial to the effect of medicine, and is an ideal chitosan oligosaccharide capsule;

(2) The chitosan oligosaccharide capsule provided by the invention has good sealing property and high oxidation resistance, and can effectively solve the problem that the chitosan oligosaccharide is easy to oxidize and absorb moisture, and is beneficial to the long-term preservation of chitooligosaccharide.

detailed description:

The invention is further illustrated by the following description of the specific embodiments, but this is not a limitation of the invention, and various modifications and improvements can be made by those skilled in the art based on the basic idea of the invention, without departing from the basic scope of the invention. Ideas are within the scope of the invention.

Example 1. A chitosan oligosaccharide capsule

The content is 100% chitosan oligosaccharide;

The capsule comprises the following components and parts by weight: hydroxypropyl starch 8 parts, xanthan gum 4 parts, thickener 5 parts, plasticizer 4 parts and water 16 parts; the thickener is made of melon The guar gum and the propylene glycol alginate were composed at a weight ratio of 1.2:3.5, and the plasticizer was composed of glycerin and triethyl citrate in a weight ratio of 3.5:2.

Preparation:

S1 grinds the chitosan oligosaccharide into a fine powder and passes through a 20 mesh sieve to obtain a fine powder;

S2, the fine powder obtained in the step S1 is subjected to wet granulation, the wet granulation temperature is 25 ° C, the humidity is 40%, and the granulation is dried to less than 10% moisture to obtain a content;

S3 grinds the hydroxypropyl starch into a fine powder, adds xanthan gum, a thickener, a plasticizer and water to mix uniformly, and dries at a temperature of 60 ° C for 4 h, and then writes the tannin at a temperature of 50 ° C. Drying, demoulding, cutting, nesting, obtaining a capsule;

Example 2: A chitosan oligosaccharide capsule

The contents include the following components and their weight percentages: chitosan oligosaccharide 92%, microcrystalline cellulose 2%, 5% povidone solution 2%, calcium stearate 1%, absolute ethanol 2%, and fine powder Silicone 1%;

The capsule comprises the following components and parts by weight: 4 parts of hydroxypropyl starch, 2 parts of xanthan gum, 4 parts of thickener, 3 parts of plasticizer and 10 parts of water; the thickener is made of melon The guar gum and the propylene glycol alginate were composed at a weight ratio of 1:4, and the plasticizer was composed of glycerin and triethyl citrate in a weight ratio of 2:3.

Preparation:

S1 grinds chitosan oligosaccharide, microcrystalline cellulose, calcium stearate and micro-powder silica gel into fine powder, and mixes with 5% povidone solution and absolute ethanol, and passes through a 20 mesh sieve to obtain a fine powder;

Example 3, a chitosan oligosaccharide capsule

The contents include the following components and their weight percentages: chitosan oligosaccharide 85.5%, microcrystalline cellulose 4%, 5% povidone solution 4%, calcium stearate 2%, anhydrous ethanol 3%, and fine powder Silicone 1.5%;

The preparation method was similar to that of Example 2.

Example 4, a chitosan oligosaccharide capsule

The contents include the following components and their weight percentages: chitosan oligosaccharide 80%, microcrystalline cellulose 6%, 5% povidone solution 5%, calcium stearate 3%, absolute ethanol 4%, and fine powder Silicone 2%;

The capsule comprises the following components and parts by weight: 10 parts of hydroxypropyl starch, 6 parts of xanthan gum, 8 parts of thickener, 6 parts of plasticizer and 20 parts of water; the thickener is made of melon The guar gum and the propylene glycol alginate were composed at a weight ratio of 2:3, and the plasticizer was composed of glycerin and triethyl citrate in a weight ratio of 4:1.

The preparation method was similar to that of Example 2.

Comparative Example 1, a chitosan oligosaccharide capsule

The components of the contents and their weight percentages are as in Example 3.

The components of the capsule and parts by weight thereof are: the thickener is composed of guar gum and propylene glycol alginate at a weight ratio of 3:2, and the remaining components are as in Example 3.

The preparation method was similar to that of Example 2.

Comparative Example 2, a chitosan oligosaccharide capsule

The components of the capsule and the parts by weight thereof are: the plasticizer is composed of glycerin and triethyl citrate in a weight ratio of 1:4, and the remaining components are as in Example 3.

The preparation method was similar to that of Example 2.

Test Example 1. Quality Test of Shell Oligosaccharide Capsules

1. Test materials: Shell oligosaccharide capsules prepared in Example 1, Example 2, Example 3, Example 4, Comparative Example 1 and Comparative Example 2.

2, detection method:

The contents and moisture of the chitosan oligosaccharide capsules prepared in Example 1, Example 2, Example 3, Example 4, Comparative Example 1 and Comparative Example 2 were examined with reference to the detection method of "Chinese Pharmacopoeia 2010 Edition 2". The content was measured, and the appearance, odor, volume difference and solubility of the chitosan oligosaccharide capsules were examined. The solubility of the chitosan oligosaccharide capsules at 45 min was measured by the pulp method.

3. Test results:

The test results are shown in Table 1.

Table 1 Results of quality test of chitosan oligosaccharide capsules

It can be seen from Table 1 that the contents of the shell oligosaccharide capsules prepared in Examples 1-4 of the present invention are dry, moderately tight, and the moisture content is less than 9.0%, and the capsule has no peculiar smell, and the appearance is neat, without sticking, deformation, and seepage. Leakage or capsule rupture, its loading difference and solubility are in line with the relevant provisions of the Chinese Pharmacopoeia, while the capsules prepared in Comparative Example 1 and Comparative Example 2 have irregularities in appearance, such as sticking, deformation, leakage or rupture of the shell. The dissolution rate is less than 90% at 45 min, which does not comply with the relevant regulations of the Chinese Pharmacopoeia, indicating that the capsule formulation provided by the invention is reasonable, can greatly improve the product quality, and promote the promotion and application of the chitosan oligosaccharide capsule.

Test Example 2, Accelerated test of chitosan oligosaccharide capsules

2. Test method:

The accelerated test of chitosan oligosaccharide capsules prepared in Example 1, Example 2, Example 3, Example 4, Comparative Example 1 and Comparative Example 2 was carried out with reference to the test method of "Chinese Pharmacopoeia 2010 Edition Part II Appendix XIX C". .

3. Test results:

The test results are shown in Table 2.

Table 2 Accelerated test results of chitosan oligosaccharide capsules

It can be seen from Table 2 that the chitosan oligosaccharide capsules prepared in Examples 1-4 of the present invention are placed under the conditions of temperature of 40 ° C ± 2 ° C and relative humidity of 75% ± 5% for 6 months, and the indexes thereof are all in accordance with The quality requirements of the Chinese Pharmacopoeia for the capsules, while the stability of the chitosan oligosaccharide capsules prepared in Comparative Example 1 and Comparative Example 2 were inferior to those of the chitosan oligosaccharide capsules prepared in Examples 1-4, indicating the shell oligomer provided by the present invention. The formula of the sugar capsule is reasonable, and the stability of the chitosan oligosaccharide capsule is greatly improved.

Test Example 3: Long-term test of chitosan oligosaccharide capsules

1. Test materials: Shell oligosaccharide capsules prepared in Example 1, Example 2, Example 3 and Example 4.

2. Test method:

The chitosan oligosaccharide capsules prepared in Example 1, Example 2, Example 3 and Example 4 were subjected to long-term tests with reference to the test method of "Chinese Pharmacopoeia 2010 Edition Part II Appendix XIX C".

3. Test results:

The test results are shown in Table 3.

Table 3 Long-term test results of chitosan oligosaccharide capsules

It can be seen from Table 3 that the chitosan oligosaccharide capsules prepared in Examples 1-4 of the present invention are placed under the conditions of a temperature of 25 ° C ± 2 ° C and a relative humidity of 60% ± 10% for 12 months, and the indexes thereof are in accordance with The Chinese Pharmacopoeia's quality requirements for capsules indicate that the capsules provided by the present invention have high stability and good moisture-proof effect, which is beneficial to the preservation of the capsules.

Claims

A chitosan oligosaccharide capsule comprising a content and a capsule comprising the following components and their weight percentages: chitosan oligosaccharide 80-100%, microcrystalline cellulose 0-6%, adhesive Agent 0-5%, calcium stearate 0-3%, ethanol 0-4% and micronized silica gel 0-2%;

The capsule comprises the following components and parts by weight: 4-10 parts of hydroxypropyl starch, 2-6 parts of xanthan gum, 4-8 parts of thickener, 3-6 parts of plasticizer and 10 parts of water. 20 copies.
The chitosan oligosaccharide capsule according to claim 1, wherein the content comprises the following components and their weight percentages: chitosan oligosaccharide 80-92%, microcrystalline cellulose 2-6%, binder 2 -5%, 1-3% calcium stearate, 2-4% ethanol and 1-2% silica gel.
The chitosan oligosaccharide capsule according to claim 2, wherein the content comprises the following components and their weight percentages: chitosan oligosaccharide 85.5%, microcrystalline cellulose 4%, binder 4%, stearin Calcium acid 2%, ethanol 3% and fine powder silica gel 1.5%.
The chitosan oligosaccharide capsule according to any one of claims 1 to 3, wherein the binder is a povidone solution having a concentration of 5%, and the ethanol is anhydrous ethanol.
The chitosan oligosaccharide capsule according to claim 1, wherein the capsule comprises the following components and parts by weight: hydroxypropyl starch 8 parts, xanthan gum 4 parts, thickener 5 parts, 4 parts of plasticizer and 16 parts of water.
The chitosan oligosaccharide capsule according to claim 1 or 5, wherein the thickener is composed of guar gum and propylene glycol alginate in a weight ratio of 1-2:3-4.
The chitosan oligosaccharide capsule according to claim 6, wherein the thickener is composed of guar gum and propylene glycol alginate at a weight ratio of 1.2:3.5.
The chitosan oligosaccharide capsule according to claim 1 or 5, wherein the plasticizer is composed of glycerin and triethyl citrate in a weight ratio of 2-4:1-3.
The chitosan oligosaccharide capsule according to claim 6, wherein the plasticizer is composed of glycerin and triethyl citrate in a weight ratio of 3.5:2.
A method for preparing a chitosan oligosaccharide capsule according to any one of claims 1-9, comprising the steps of:

S1 grinds chitosan oligosaccharide, microcrystalline cellulose, calcium stearate and micro-powder silica gel into a fine powder, and mixes with a binder and ethanol to pass through a sieve of 18-25 mesh to obtain a fine powder;

S2, the fine powder obtained in the step S1 is subjected to wet granulation, the wet granulation temperature is 22-28 ° C, the humidity is 35-45%, and the granulation is dried to less than 10% moisture to obtain a content;

S3 grinds the hydroxypropyl starch into a fine powder, adds xanthan gum, thickener, plasticizer and water to mix evenly, and dries at a temperature of 55-60 ° C for 4-5 h, then at a temperature of 50 ° C Carrying out silicone, drying, demoulding, cutting, nesting, and obtaining a capsule;

S4, the content obtained in step S2 is filled into the capsule obtained in step S3, and the capsule is sealed.