CN112386583A - Method for manufacturing soft capsule shell based on modified gelatin - Google Patents
Method for manufacturing soft capsule shell based on modified gelatin Download PDFInfo
- Publication number
- CN112386583A CN112386583A CN202011477171.5A CN202011477171A CN112386583A CN 112386583 A CN112386583 A CN 112386583A CN 202011477171 A CN202011477171 A CN 202011477171A CN 112386583 A CN112386583 A CN 112386583A
- Authority
- CN
- China
- Prior art keywords
- gelatin
- modified gelatin
- soft capsule
- capsule shell
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
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Classifications
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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
- A61K9/4816—Wall or shell material
- A61K9/4825—Proteins, e.g. gelatin
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K9/4816—Wall or shell material
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开了一种基于改性明胶的软胶囊壳的制作方法，包括改性明胶、增塑剂、水、增稠剂，所述各组分的重量百分比为：改性明胶35％～60％；增塑剂10～25％；水20～35％；增稠剂2～10％；以及根据需要的软胶囊胶丸的颜色所添加的色素。本发明通过将传统胶囊囊材的主要成分明胶替换成改性明胶，克服了明胶的很多缺点，改性明胶具有生物相容性好、溶胀率高、性质稳定等特点，溶解速率优于明胶；由改性明胶制备的软胶囊，性质较为稳定，不易发生交联现象，而且用明胶替代材料制备的软胶囊没有氧化交联问题，无需添加抗氧化剂。The invention discloses a method for preparing a soft capsule shell based on modified gelatin, which comprises modified gelatin, plasticizer, water and thickener. The weight percentage of each component is: modified gelatin 35% to 60% %; plasticizer 10-25%; water 20-35%; thickening agent 2-10%; and pigments added according to the color of the soft capsule capsule. The present invention overcomes many shortcomings of gelatin by replacing the main component gelatin of the traditional capsule material with modified gelatin, and the modified gelatin has the characteristics of good biocompatibility, high swelling rate, stable properties and the like, and the dissolution rate is better than that of gelatin; Soft capsules prepared from modified gelatin have relatively stable properties and are not prone to cross-linking, and the soft capsules prepared with gelatin substitute materials have no problem of oxidative cross-linking and do not need to add antioxidants.
Description
Technical Field
The invention relates to the technical field of pharmaceutical industrial production, in particular to the technical field of a method for manufacturing a soft capsule shell based on modified gelatin.
Background
The soft capsule is prepared by mixing the medicinal material extract, liquid medicine or appropriate adjuvants, dripping or pressing, sealing in hydrophilic soft shell, and making into spherical, elliptical or other dosage forms. The soft capsule is suitable for unstable medicinal substances, such as chemical components sensitive to light, volatile, unstable and oxidizable to heat and humidity, and medicinal substances with unpleasant taste and unpleasant odor.
The soft capsule is a common dosage form of a nutritional supplement and a western medicine, the soft capsule becomes one of the reform directions of the traditional Chinese medicine dosage form, the capsule shell prescription comprises four substances of glue, a plasticizer, water and an additive, and the glue is a main component for forming the capsule shell, such as gelatin, a gelatin substitute material and the like; the plasticizer is glycerol or polyalcohol, and can be used alone or in combination; the additives include antiseptic, colorant, disintegrant, opacifier, antioxidant, etc. to maintain the quality stability of the medicine and soft capsule. The traditional method for preparing the soft capsule shell based on the modified gelatin mainly comprises the steps of gelatin, water, glycerol and selected pigment.
The disadvantages of the existing soft capsule shell sizing material due to the use of gelatin include: (1) and (3) crosslinking reaction: gelatin is susceptible to cross-linking reactions that cause instability of soft capsules, such as aldehydes, polyphenols, reducing sugars, multiply charged cations, electrolytes, cationic or anionic polymers, etc., thereby changing the mechanical or biological properties of the capsules.
(2) Safety problems are as follows: gelatin is a material derived from animals, the raw material is derived from animal skin and bone, and gelatin is animal protein colloid and contains small amount of animal fat. In recent years, with the occurrence of foot-and-mouth disease, mad cow disease, and avian influenza, the safety of gelatin is being questioned more and more, and it cannot be accepted by some special culturists and vegetarians.
(3) Disintegration, leakage problems: the problem of an unacceptable disintegration time during storage is often observed, which is often caused by aged crosslinking of the gelatin. The storage property is also poor, and the capsule shell becomes brittle due to water loss after long-term storage. The gelatin is easy to absorb water and dehydrate due to the hydrophilicity of the gelatin, so that the deformation, leakage and unqualified loading capacity of the capsule caused by the absorption of water in liquid medicine in the soft capsule are prevented, and the gelatin cannot be used for wrapping hydrophilic or easily-absorbed medicines.
Disclosure of Invention
The invention aims to solve the problems in the prior art, and provides a method for manufacturing a soft capsule shell based on modified gelatin, which overcomes many defects of gelatin, has stable property, is not easy to generate a cross-linking phenomenon, and is safe, reliable and good in storage performance.
In order to achieve the purpose, the application provides a method for manufacturing a soft capsule shell based on modified starch, which comprises the following components in percentage by weight:
35-60% of modified gelatin;
10-25% of a plasticizer;
20-35% of water;
2-10% of a thickening agent;
pigment added according to the required color of the soft capsule.
The invention replaces the main ingredient gelatin of the traditional capsule wall material with the modified gelatin, overcomes many defects of the gelatin, the modified gelatin has the characteristics of good biocompatibility, high swelling rate, stable property and the like, and the dissolution rate is superior to that of the gelatin; the soft capsule prepared by the modified gelatin has stable property and is not easy to generate crosslinking phenomenon, and the soft capsule prepared by the gelatin substitute material has no problem of oxidative crosslinking and does not need to be added with an antioxidant.
Detailed Description
In the following description, for purposes of explanation and not limitation, specific details are set forth, such as particular system structures, techniques, etc. in order to provide a thorough understanding of the embodiments of the invention. It will be apparent, however, to one skilled in the art that the present invention may be practiced in other embodiments that depart from these specific details. In other instances, detailed descriptions of well-known systems, devices, circuits, and methods are omitted so as not to obscure the description of the present invention with unnecessary detail.
In order to illustrate the technical scheme of the invention and achieve the purpose, the invention provides a method for manufacturing a soft capsule shell based on modified gelatin, which comprises the following components in percentage by weight:
35-60% of modified gelatin;
10-25% of a plasticizer;
20-35% of water;
2-10% of a thickening agent;
pigment added according to the required color of the soft capsule.
Preferably, the modified gelatin is EDTA-modified gelatin.
Preferably, the plasticizer is glycerol and xylitol, and the ratio of glycerol to xylitol is 0.6: 0.4.
Preferably, the thickening agent is seaweed gel and hydroxypropyl methylcellulose, and the ratio of the sodium alginate to the hydroxypropyl methylcellulose is 8.5-11.5: 0.005-0.015.
Preferably, the water used is purified water produced by a distillation apparatus, an ion exchange apparatus or a reverse osmosis apparatus.
Preferably, the pigment determines the color of the capsule, the type and the dosage of the pigment are determined according to the color of the capsule, for example, 1000 blue capsules require 0.132g of brilliant blue, full red capsules require 0.128g of carmine, the white part does not use the pigment but uses titanium dioxide mother liquor, and the full transparent capsules do not add the pigment and the titanium dioxide mother liquor.
The soft capsule shell prepared from the modified gelatin needs to consider the processing characteristics of the soft capsule shell besides the aspects of solubility, stability, bioavailability, safety, appearance and the like. Common modified gelatins comprise EDTA modified gelatins, succinic anhydride modified gelatins, phthalic anhydride modified gelatins and the like, the common modified gelatins are better than gelatins in comprehensive performance, and soft capsules prepared by taking the common modified gelatins as main raw materials of capsule shells are good in biocompatibility, high in swelling rate, stable in property and not easy to crosslink and age.
The analysis of each component is illustrated below:
a) properties of modified gelatin
Gelatin is widely used as an outer shell material of soft capsules because of its appearance gloss, neutral taste, easy processability, and thermal reversibility. The natural base material hydrogel is widely regarded by various countries due to the characteristics of no toxicity, degradability, good biocompatibility and the like, and part of the natural base material hydrogel has good swelling performance and environmental sensitivity and responsiveness and is researched to be applied to the aspect of biomedical materials, such as a drug carrier material. The gelatin is derived from animal collagen, and the side chain of the molecule of the gelatin has a plurality of active groups such as amino, carboxyl, hydroxyl and the like. Modification of these reactive groups by chemical or other means may enhance or enhance certain functional properties of the gelatin. Ethylene Diamine Tetraacetic Acid (EDTA) is a micromolecular modifier, EDT A and epsilon-NH 2 on gelatin are used for acylation modification, COO-is introduced into a gelatin protein molecular chain, the biocompatibility of the gelatin is kept, the functional characteristics of the gelatin can be improved, and the Ethylene Diamine Tetraacetic Acid (EDTA) is expected to be used as a novel material in the aspect of biological medicine. The soft capsule prepared by selecting proper modified gelatin can achieve the higher characteristic of the gelatin soft capsule.
b) Properties of xylitol
Xylitol, a monosaccharide, xylose pentaol, is an intermediate product in carbohydrate metabolism in humans and animals, and is found in many fruits and vegetable vegetables.
Xylitol is easy to dissolve in water and less hygroscopic, the water solution can be heated for a long time or stored stably without being influenced, the fructose and glucose which are the existing sucrose substitutes can generate a scorching reaction, but xylitol, sorbitol and mannitol have no such phenomenon, and the xylitol can generate slight yellow when being heated to more than 150 ℃. This is due to the impurity relationship that most microorganisms are unable to utilize xylitol, and therefore its product is generally not affected by microbial infestation.
Xylitol can supplement heat energy and improve sugar metabolism. The metabolism in vivo does not depend on the participation of insulin, and can directly permeate cell membrane to participate in sugar metabolism without increasing blood sugar concentration, and the sweetness and the heat produced are similar to those of glucose.
The plasticizer is added to increase the plasticity of the colloid material, ensure good spreadability of the product, keep the soft capsule from deforming for a long time and ensure that the capsule shell of the soft capsule product is soft and elastic. Commonly used plasticizers include glycerin and polyols. The glycerol has low viscosity and is easy to disperse uniformly. Glycerol can have good compatibility with many colloidal materials. Glycerol acts as a plasticizer and is sufficient to allow ethanol to diffuse therein even if the diffusion channels become clogged with some solid particles or the viscosity of the filled liquid increases. Polyols such as xylitol, sorbitol, hydrogenated corn steep liquor, and the like are commonly used. The polyhydric alcohol replaces the glycerol as a plasticizer, and the migration of the ethanol can be obviously inhibited. The reason is that glycerol and ethanol are completely miscible, whereas these polyols are slightly soluble in ethanol. The capsule shell using glycerin as plasticizer has strong oxygen penetration. The combination of glycerol and xylitol can minimize the gelatin soft capsule.
c) Properties of seaweed gel
The seaweed gel is also called algin, sodium alginate, seaweed gel and the like, is a natural polysaccharide, is extracted from natural seaweed, and has stability, solubility, viscosity and safety required by pharmaceutical preparation auxiliary materials. It has the ability to concentrate solutions, form gels and form films. The seaweed gel is soluble in water, and insoluble in organic solvent such as ethanol, diethyl ether, chloroform, etc. Dissolving in water to obtain viscous liquid, and adjusting pH of 1% water solution to 6-8. Viscosity is stable at pH 6-9, and decreases when heated above 80 ℃. The mild sol-gel process and good biocompatibility make the seaweed gel suitable for being used as a capsule for releasing or embedding medicines, proteins and cells. Alginate gel is hygroscopic, and the amount of water contained in the gel at equilibrium depends on the relative humidity. The dried seaweed gel is stable to storage at temperatures of 25 ℃ and below in a well-sealed container.
The seaweed gel is a safe food additive, can be used as a base material of a curative food, can slow down the absorption of fatty sugar and bile salt due to the fact that the seaweed gel is a natural cellulose, has the effects of reducing serum cholesterol, triglyceride in blood and blood sugar, and can prevent modern diseases such as hypertension, diabetes, obesity and the like. It can inhibit the accumulation of harmful metals such as strontium, cadmium, lead, etc. in the body in the intestinal tract, and has been increasingly paid attention to by people at home and abroad due to the important functions of sodium alginate.
It can be used for increasing blood volume, maintaining blood pressure, eliminating histamine toxoid caused by burn, and systemic dehydration such as wound hemorrhage, postoperative circulatory system stabilization, massive hemorrhagic shock, burn shock, high fever and acute dysentery, and has good therapeutic effect. It also has effects in discharging cholesterol, inhibiting absorption of Pb, Cd, and Sr by human body, protecting gastrointestinal tract, regulating intestine, reducing weight, and lowering blood sugar. The medicament is mainly used as a suspending agent, an emulsifying agent, a viscous agent, a microcapsule capsule material and the like. Alginate gel is used as a binder for tablets, and its effect on tablet properties depends on the amount put in the prescription, and in some cases, alginate gel promotes disintegration of tablets. The seaweed gel can be added in the granulating process, so that the preparation process is simpler.
d) Properties of hypromellose
Hydroxypropyl methylcellulose, also known as hypromellose, cellulose hydroxypropyl methyl ether, abbreviated as HPMC in english, is prepared by selecting highly pure cotton cellulose as a raw material and performing special etherification under alkaline conditions, and is white or quasi-white powder in appearance. It contains no active components such as animal organs and oil, is nonionic cellulose ether, is white powder, and has no odor and taste. It is safe and nontoxic, can be used as food additive, has no calorie, and has no irritation to skin and mucous membrane.
The hydroxypropyl methyl cellulose is soluble in water, and the aqueous solution has surface activity, high transparency and stable performance. HPMC has thermal gelation property, and the product water solution forms gel precipitation after heating and dissolves after cooling, and the gel temperature of the products with different specifications is different. Solubility varies with viscosity, the lower the viscosity, the greater the solubility. HPMC also has the characteristics of thickening ability, low salt tolerance, low ash content, pH stability, water retention, dimensional stability, excellent film forming property, wide enzyme resistance, dispersibility, cohesiveness and the like, and can prevent the capsule shell and the content components from mutually migrating.
e) Properties of EDTA
EDTA, also known as ethylenediaminetetraacetic acid, is a white odorless, tasteless, colorless crystalline powder having a melting point of 240 ℃ (decomposition). Insoluble in cold water, alcohol and common organic solvents, slightly soluble in hot water, soluble in a solution of sodium hydroxide, sodium carbonate and ammonia, soluble in 160 parts of 100 ℃ boiling water. The alkali metal salt is soluble in water and the solubility of the sodium salt in water is shown in the following table (g/L). EDTA, which is a good complexing agent in chemistry and has six coordinating atoms, is generally replaced by sodium salt of ethylenediamine tetraacetic acid, and the formed complex is called chelate, and EDTA is often used in coordination titration, and is generally used for measuring the content of metal ions and is used for eliminating the interference of most transition metal element ions (such as iron (III), nickel (II) and manganese (II)) in biological application. Interfering ions can be removed without affecting the function of the protein in protein engineering and experiments.
EDTA has a wide range of applications, and can be used as a bleaching fixing solution, a dyeing auxiliary agent, a fiber treatment auxiliary agent, a cosmetic additive, a blood anticoagulant, a detergent, a stabilizer, a synthetic rubber polymerization initiator and the like for the processing of color photosensitive materials, and EDTA is a representative substance of chelating agents. Can form stable water-soluble complex with alkali metal, rare earth element and transition metal. In addition to sodium salts, there are ammonium salts and various salts of iron, magnesium, calcium, copper, manganese, zinc, cobalt, aluminum, and the like.
The invention has the beneficial effects that:
1. the invention replaces the main ingredient gelatin of the traditional capsule wall material with the modified gelatin, thereby overcoming the defects of the gelatin, such as unsafe animal source, easy moisture absorption, easy cross-linking reaction, poor storage performance and the like. The modified gelatin has the characteristics of good biocompatibility, high swelling rate, stable property and the like, and the dissolution rate is superior to that of the gelatin. The soft capsule prepared by the modified gelatin has stable property and is not easy to generate crosslinking phenomenon, and the soft capsule prepared by the gelatin substitute material has no problem of oxidative crosslinking and does not need to be added with an antioxidant.
2. Xylitol is added in the capsule material formula, and is a good plasticizer, so that the capsule material has a good moisture-preserving effect, the soft capsule can keep certain moisture, the soft capsule can be effectively prevented from being dried and aged, the moisture-preserving performance of the soft capsule is improved, and the xylitol can supplement heat energy and improve sugar metabolism. The metabolism in vivo is independent of the participation of insulin, and can directly permeate cell membrane to participate in sugar metabolism without increasing blood sugar concentration. In the traditional formula, glycerol is usually used as a plasticizer alone, and if the dosage of the glycerol is large, the capsule shell is soft, easy to absorb moisture, easy to deform under pressure and long in drying time; the capsule shell is too small in dosage, the ratio of glycerol to gelatin is generally 0.3-0.5 in actual production, and xylitol as a plasticizer has the advantages of inhibiting migration of ethanol and reducing the penetrating power of oxygen to the capsule shell.
When the materials are mixed for use, the problems can be avoided, and the material migration can be well controlled. Glycerol belongs to low-alcohol and has low molecular weight, if the glycerol is used independently, the intermolecular gap is large, oxygen can freely pass through the glycerol, the oxidation probability of contents is increased, small molecular substances such as water molecules can also freely pass through the glycerol, and the substances are migrated, so that the loading problem is caused. Xylitol belongs to polyhydric alcohol, has large molecular weight, is mixed for use, not only reduces intermolecular clearance, but also prevents oxygen reaction and material migration. And the drying time is also shortened, the plasticity of the capsule is increased, and the product quality is ensured.
3. The capsule material formula is added with thickening agents of seaweed gel and hydroxypropyl methylcellulose to improve the viscosity of the glue solution, so that the flexibility and elasticity of the soft capsule can be properly improved, the soft capsule can be dissolved in a predetermined gastrointestinal region to release contents, and the soft capsule can be rapidly disintegrated, has good stability and low water content.
The features and advantages of the present invention will be described in detail by way of examples.
The invention provides a method for manufacturing a soft capsule shell based on modified gelatin, which comprises the following components in percentage by weight:
35-60% of modified gelatin;
10-25% of a plasticizer;
20-35% of water;
2-10% of a thickening agent;
pigment added according to the required color of the soft capsule.
The modified gelatin is EDTA modified gelatin; the plasticizer is glycerol and xylitol, and the ratio of the glycerol to the xylitol is 0.6: 0.4; the thickening agent is seaweed gum and hydroxypropyl methylcellulose, and the ratio of the sodium alginate to the hydroxypropyl methylcellulose is 8.5-11.5: 0.005-0.015; the water used is purified water prepared by distillation equipment, ion exchange equipment or reverse osmosis equipment; the pigment determines the color of the capsule, and the type and dosage of the pigment are determined according to the color of the capsule, for example, 1000 blue capsules need 0.132g of brilliant blue, full red capsules need 0.128g of carmine, the white part uses titanium dioxide mother liquor instead of the pigment, and the full transparent capsules do not add the pigment and the titanium dioxide mother liquor.
Example (b):
preparing a 3% (w/v) gelatin solution (namely 3g of gelatin needs to be added with 100ml of distilled water) and placing the gelatin solution in a beaker; then putting the mixture into a constant-temperature heating magnetic stirrer to swell the mixture, wherein the temperature is 40 ℃; taking out the gelatin after the gelatin is completely dissolved, and cooling to room temperature; 2.5mol/L sodium hydroxide was added to adjust the pH of the N-formylation study progress, with 1mol/L sodium hydroxide being used for fine adjustment to a pH of 9.5 (calibrated before use of the pH meter); 0.4g of EDTA is weighed and added in three times, and 1mol/L of sodium hydroxide is added in the period to keep the pH value of the solution stable; then placing the solution in a constant-temperature heating magnetic stirrer, keeping the temperature at 40 ℃, and acylating for 4 hours; filling the acylated solution into a dialysis bag, and dialyzing for three days; the dialyzed solution was freeze-dried and weighed after drying.
② preparing 3 percent (w/v) gelatin solution (namely 3g of gelatin needs to be added with 100ml of distilled water) and placing the gelatin solution in a beaker; then putting the mixture into a constant-temperature heating magnetic stirrer to swell the mixture, wherein the temperature is 40 ℃; taking out the gelatin after the gelatin is completely dissolved, and cooling to room temperature; 2.5mol/L sodium hydroxide was added to adjust the pH of the N-formylation study progress, with 1mol/L sodium hydroxide being used for fine adjustment to a pH of 9.5 (calibrated before use of the pH meter); 0.4g of EDTA is weighed and added in three times, and 1mol/L of sodium hydroxide is added in the period to keep the pH value of the solution stable; then placing the solution in a constant-temperature heating magnetic stirrer, keeping the temperature at 40 ℃, and acylating for 4.5 hours; filling the acylated solution into a dialysis bag, and dialyzing for three days; the dialyzed solution was freeze-dried and weighed after drying.
Firstly, 40kg of purified water, 22kg of glycerol and 18kg of xylitol are put into a sol pot, a feeding port is closed, stirring is carried out, the temperature of a mixed solution is raised to 60 ℃, and the temperature of interlayer water is ensured to be 60-80 ℃ in the whole sol process.
Then, 50kg of EDTA modified gelatin, 8kg of seaweed gel and 0.1kg of hydroxypropyl methylcellulose are added into the sol tank while stirring, the adding speed is controlled to prevent agglomeration, and the sol is carried out under the vacuum condition for 1 hour.
Dissolving 0.3kg of pigment in hot water, adding into the glue solution, preparing opacifier titanium dioxide into mother solution, adding into the glue solution, and stirring uniformly.
Sampling and detecting the viscosity and the moisture of the glue solution, closing the air outlet and locking the feed port when the viscosity is 18000pa.s and the moisture is 36.8%, introducing compressed air into the glue dissolving tank, and binding the filter bag glue solution with more than 120 meshes at the glue discharging port. Putting the glue solution into a glue storage barrel which is pre-insulated at 60 ℃, preserving heat, defoaming and standing the glue solution at 60 ℃ for 4 hours, and then pressing the glue solution into pills by using soft capsule equipment.
According to the invention, the main ingredient gelatin of the traditional capsule wall material is replaced by the modified gelatin, so that the defects of the gelatin, such as insufficient safety of animal sources, easiness in moisture absorption, easiness in cross-linking reaction, poor storage performance and the like, are overcome. The modified gelatin has the characteristics of good biocompatibility, high swelling rate, stable property and the like, and the dissolution rate is superior to that of the gelatin. The soft capsule prepared by the modified gelatin has stable property and is not easy to generate crosslinking phenomenon, and the soft capsule prepared by the gelatin substitute material has no problem of oxidative crosslinking and does not need to be added with an antioxidant.
Xylitol is added in the capsule material formula, and is a good plasticizer, so that the capsule material has a good moisture-preserving effect, the soft capsule can keep certain moisture, the soft capsule can be effectively prevented from being dried and aged, the moisture-preserving performance of the soft capsule is improved, and the xylitol can supplement heat energy and improve sugar metabolism. The metabolism in vivo is independent of the participation of insulin, and can directly permeate cell membrane to participate in sugar metabolism without increasing blood sugar concentration. In the traditional formula, glycerol is usually used as a plasticizer alone, and if the dosage of the glycerol is large, the capsule shell is soft, easy to absorb moisture, easy to deform under pressure and long in drying time; the capsule shell is too small in dosage, the ratio of glycerol to gelatin is generally 0.3-0.5 in actual production, and xylitol as a plasticizer has the advantages of inhibiting migration of ethanol and reducing the penetrating power of oxygen to the capsule shell.
When the materials are mixed for use, the problems can be avoided, and the material migration can be well controlled. Glycerol belongs to low-alcohol and has low molecular weight, if the glycerol is used independently, the intermolecular gap is large, oxygen can freely pass through the glycerol, the oxidation probability of contents is increased, small molecular substances such as water molecules can also freely pass through the glycerol, and the substances are migrated, so that the loading problem is caused. Xylitol belongs to polyhydric alcohol, has large molecular weight, is mixed for use, not only reduces intermolecular clearance, but also prevents oxygen reaction and material migration. And the drying time is also shortened, the plasticity of the capsule is increased, and the product quality is ensured.
The capsule material formula is added with thickening agents of seaweed gel and hydroxypropyl methylcellulose to improve the viscosity of the glue solution, so that the flexibility and elasticity of the soft capsule can be properly improved, the soft capsule can be dissolved in a predetermined gastrointestinal region to release contents, and the soft capsule can be rapidly disintegrated, has good stability and low water content.
The above embodiments are illustrative of the present invention, and are not intended to limit the present invention, and any simple modifications of the present invention are within the scope of the present invention.
Claims (6)
1. A method for preparing soft capsule shell based on modified gelatin comprises modified gelatin, plasticizer, water, and thickener.
The weight percentages of the components are as follows:
35-60% of modified gelatin;
10-25% of a plasticizer;
20-35% of water;
2-10% of a thickening agent;
pigment added according to the required color of the soft capsule.
2. The method for preparing a soft capsule shell based on modified gelatin according to claim 1, wherein the method comprises the following steps: the modified gelatin is EDTA modified gelatin.
3. The method for preparing a soft capsule shell based on modified gelatin according to claim 1, wherein the method comprises the following steps: the plasticizer is glycerol and xylitol, and the ratio of the glycerol to the xylitol is 0.6: 0.4.
4. The method for preparing a soft capsule shell based on modified gelatin according to claim 1, wherein the method comprises the following steps: the thickening agent is seaweed gel and hydroxypropyl methylcellulose, and the ratio of the sodium alginate to the hydroxypropyl methylcellulose is 8.5-11.5: 0.005-0.015.
5. The method for preparing a soft capsule shell based on modified gelatin according to claim 1, wherein the method comprises the following steps: the water used is purified water prepared by a distillation device, an ion exchange device or a reverse osmosis device.
6. The method for manufacturing a soft capsule shell based on modified gelatin according to any of claims 1 to 5, wherein: the pigment determines the color of the capsule, and the type and dosage of the pigment are determined according to the color of the capsule, for example, 1000 blue capsules need 0.132g of brilliant blue, full red capsules need 0.128g of carmine, the white part uses titanium dioxide mother liquor instead of the pigment, and the full transparent capsules do not add the pigment and the titanium dioxide mother liquor.
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| CN113712935A (en) * | 2021-09-13 | 2021-11-30 | 陕西中医药大学 | Modified vegetable gelatin soft capsule shell and preparation method thereof |
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