CN118976001B - Sodium alginate enteric hollow capsule and preparation method and application thereof - Google Patents
Sodium alginate enteric hollow capsule and preparation method and application thereof Download PDFInfo
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- 239000002775 capsule Substances 0.000 title claims abstract description 101
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 title claims abstract description 78
- 239000000661 sodium alginate Substances 0.000 title claims abstract description 78
- 235000010413 sodium alginate Nutrition 0.000 title claims abstract description 78
- 229940005550 sodium alginate Drugs 0.000 title claims abstract description 78
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 43
- 238000007598 dipping method Methods 0.000 claims abstract description 23
- 238000001035 drying Methods 0.000 claims abstract description 21
- 230000002308 calcification Effects 0.000 claims abstract description 18
- 239000004373 Pullulan Substances 0.000 claims abstract description 16
- 229920001218 Pullulan Polymers 0.000 claims abstract description 16
- 235000011187 glycerol Nutrition 0.000 claims abstract description 16
- 235000019423 pullulan Nutrition 0.000 claims abstract description 16
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 15
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims abstract description 15
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 15
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 15
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 15
- 239000001768 carboxy methyl cellulose Substances 0.000 claims abstract description 14
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims abstract description 13
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims abstract description 13
- 238000005520 cutting process Methods 0.000 claims abstract description 9
- 150000004676 glycans Chemical class 0.000 claims abstract description 7
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 7
- 239000005017 polysaccharide Substances 0.000 claims abstract description 7
- 239000003292 glue Substances 0.000 claims description 39
- 238000000465 moulding Methods 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 238000004321 preservation Methods 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 11
- 239000007963 capsule composition Substances 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 8
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 8
- 229920000053 polysorbate 80 Polymers 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 7
- 239000004227 calcium gluconate Substances 0.000 claims description 6
- 229960004494 calcium gluconate Drugs 0.000 claims description 6
- 235000013927 calcium gluconate Nutrition 0.000 claims description 6
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 claims description 6
- 238000009849 vacuum degassing Methods 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 239000006082 mold release agent Substances 0.000 claims description 5
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 3
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 claims description 3
- 239000001354 calcium citrate Substances 0.000 claims description 3
- 235000013337 tricalcium citrate Nutrition 0.000 claims description 3
- 240000008415 Lactuca sativa Species 0.000 claims description 2
- 235000019483 Peanut oil Nutrition 0.000 claims description 2
- ZOJBYZNEUISWFT-UHFFFAOYSA-N allyl isothiocyanate Chemical compound C=CCN=C=S ZOJBYZNEUISWFT-UHFFFAOYSA-N 0.000 claims description 2
- 230000001680 brushing effect Effects 0.000 claims description 2
- 239000001110 calcium chloride Substances 0.000 claims description 2
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 2
- 235000011148 calcium chloride Nutrition 0.000 claims description 2
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 claims description 2
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 claims description 2
- 239000002285 corn oil Substances 0.000 claims description 2
- 235000005687 corn oil Nutrition 0.000 claims description 2
- 238000007872 degassing Methods 0.000 claims description 2
- 229940057995 liquid paraffin Drugs 0.000 claims description 2
- 239000008164 mustard oil Substances 0.000 claims description 2
- 239000000312 peanut oil Substances 0.000 claims description 2
- 235000012045 salad Nutrition 0.000 claims description 2
- 239000003549 soybean oil Substances 0.000 claims description 2
- 235000012424 soybean oil Nutrition 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 3
- 210000002784 stomach Anatomy 0.000 abstract description 3
- 230000014759 maintenance of location Effects 0.000 abstract 1
- 210000000813 small intestine Anatomy 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 11
- 229940079593 drug Drugs 0.000 description 9
- 239000002002 slurry Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- 239000000499 gel Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000010586 diagram Methods 0.000 description 4
- 229910001220 stainless steel Inorganic materials 0.000 description 4
- 239000010935 stainless steel Substances 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 3
- 210000004211 gastric acid Anatomy 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 239000003349 gelling agent Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 210000003097 mucus Anatomy 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000004014 plasticizer Substances 0.000 description 2
- 229940080313 sodium starch Drugs 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241001474374 Blennius Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000199919 Phaeophyceae Species 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000007887 hard shell capsule Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
- A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
- A61J3/071—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use into the form of telescopically engaged two-piece capsules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- 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
- A61K47/38—Cellulose; Derivatives thereof
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the technical field of enteric hollow capsules, and particularly relates to a sodium alginate enteric hollow capsule and a preparation method and application thereof. Comprises the steps of taking sodium alginate, sodium carboxymethyl cellulose, microcrystalline cellulose, pullulan polysaccharide and glycerin as raw materials, and preparing the sodium alginate enteric hollow capsule through sol, gel retention, gel dipping, calcification, drying, demoulding and cutting. The enteric hollow capsule prepared by the invention is free from gel, has good toughness, is not brittle and stable, is insoluble in the stomach for two hours, is completely dissolved after entering the small intestine for half an hour, is completely disintegrated, has the characteristic of insoluble stomach and enteric, and has stable property.
Description
Technical Field
The invention belongs to the technical field of enteric hollow capsules, and particularly relates to a sodium alginate enteric hollow capsule and a preparation method and application thereof.
Background
With the development of pharmaceutical technology, the design and development of drug delivery systems has become increasingly important. Optimization of the drug delivery system not only can improve the bioavailability of the drug, but also can improve the therapeutic effect of the drug and reduce the risk of adverse reactions. The capsule is used as a common drug carrier and has wide application in the field of pharmaceutical preparations. However, conventional gelatin capsules have limitations such as sensitivity to temperature and humidity, potential for animal-derived problems, and the like. Therefore, finding new capsule materials is one of the key points of research.
Enteric capsules are a special type of capsule designed to remain intact in the gastric acid environment to protect the drug from gastric acid and to ensure release of the drug in the intestinal tract, which is important for some drugs. However, conventional enteric capsules typically employ complex chemical coating processes to perform the enteric function, which not only increases production costs, but may introduce additional chemicals. Therefore, it is important to develop a simple, economical and efficient method for preparing the enteric capsule.
Sodium alginate, which is a natural polysaccharide, has the characteristics of good biocompatibility, biodegradability, nontoxicity and the like, and is widely concerned in the field of medicines. Sodium alginate is capable of cross-linking with divalent cations (e.g., calcium ions) to form a gel, making it one of the ideal materials for making capsules. However, single sodium alginate capsules tend to have deficiencies in physical properties, particularly in terms of mechanical strength and drug release control.
In the prior art, the physical properties of the capsule are often improved by adding different auxiliary materials, such as increasing the mechanical strength, improving the drug release characteristics and the like, so that the practicability of the capsule can be obviously improved. For example, the invention patent with publication number CN 103877587A discloses a vegetable polysaccharide medicinal enteric hard shell capsule, the viscosity of the glue solution prepared from sodium alginate adopted by the capsule is not easy to control, and the stability, the compression resistance and the flexibility of the glue solution are poor. The invention patent with publication number of CN 104887643A discloses a sodium alginate/starch-based enteric hollow capsule and a one-step molding preparation method thereof, and the sodium alginate adopted in the raw materials of the hollow capsule consists of high-viscosity sodium alginate and low-viscosity sodium alginate, but the coagulant aid is added in the sodium alginate/starch-based enteric hollow capsule, so that the capsule is not beneficial to better disintegration in vivo and has residues.
Disclosure of Invention
The invention aims to provide a sodium alginate enteric hollow capsule, a preparation method and application thereof, and the sodium alginate enteric hollow capsule which has simple and safe raw material composition, easy manufacture and no gel is prepared by optimizing a formula and a process. Realizes the stability of the capsule in gastric acid environment and the controllable release in alkaline environment of intestinal canal, thereby providing a safer, more effective and easy-to-produce enteric carrier for oral medicine.
In order to achieve the above object, the present invention is realized by the following technical scheme:
the invention provides a sodium alginate enteric hollow capsule composition, which comprises, by weight, 3-5 parts of sodium alginate of 70-90cps, 4-6 parts of sodium alginate of 8-20cps, 1-2 parts of sodium carboxymethylcellulose, 0.5-1.5 parts of microcrystalline cellulose, 1.5-3 parts of pullulan polysaccharide, 3-4 parts of glycerol and the balance of water, wherein a gel is not added in the sodium alginate hollow capsule composition.
The inventor finds that the viscosity of sodium alginate has obvious influence on the viscosity of final glue solution, influences the thickness, flexibility and integrity of capsule molding, has certain correlation with the disintegration degree of the prepared hollow capsule in intestinal tracts, and the stability of mucus control and viscosity adjustment of single-viscosity sodium alginate can not be realized. The invention adopts two sodium alginate with two similar viscosities, which is beneficial to adjusting the stability and viscosity of mucus. Meanwhile, in order to improve the mechanical strength and the drug release characteristic of the capsule, the practicality of the capsule is obviously improved, sodium carboxymethylcellulose (CMC) is added as a thickening agent and a stabilizing agent to improve the formability and the stability of the capsule, pullulan can enhance the compression resistance of the capsule, glycerol is used as a plasticizer to help improve the flexibility and the durability of the capsule, and in addition, no gelling agent is added, so that the influence of the gelling agent on disintegration is avoided, and the disintegration performance of the product is stable and has no residue.
In some other embodiments of the invention, the sodium alginate enteric hollow capsule composition comprises, by weight, 3-5 parts of 70-85cps sodium alginate, 4-5 parts of 8-20cps sodium alginate, 1-1.5 parts of carboxymethylcellulose sodium, 0.5-1 part of microcrystalline cellulose, 1.5-3 parts of pullulan polysaccharide, 3-4 parts of glycerin and the balance of water;
Preferably, 5 parts of sodium alginate of 85cps, 5 parts of sodium alginate of 20cps, 1.5 parts of sodium carboxymethylcellulose, 1 part of microcrystalline cellulose, 3 parts of pullulan, 4 parts of glycerol and the balance of water.
In a second aspect, the invention provides a preparation method of a sodium alginate enteric hollow capsule, which is characterized by comprising the following steps:
(1) Mixing sodium alginate and water, sequentially adding sodium carboxymethylcellulose, microcrystalline cellulose, pullulan and glycerol, stirring to obtain colloidal liquid, preserving heat, vacuumizing and degassing to obtain a colloidal liquid;
(2) The glue dipping molding, namely, before glue dipping, brushing a release agent after preheating a die, wherein the capsule die is vertically immersed in glue solution during glue dipping;
(3) Calcification, namely, calcification is carried out after glue dipping molding;
(4) Drying, shelling, cutting, drying and molding, shelling, and cutting.
In some other embodiments of the invention, the temperature of the uniform mixing of sodium alginate and water is 70-80 ℃, the stirring time is 30-60min, the temperature of the heat preservation is 70-80 ℃, and the heat preservation time is 1-1.5h;
Preferably, the temperature of the uniform mixing of the sodium alginate and the water is 77 ℃, the stirring time is 50min, the temperature of the heat preservation is 77 ℃, and the heat preservation time is 1h.
In some other embodiments of the present invention, the viscosity of the dope at 60-65 ℃ after the vacuum degassing in step (1) is 5000-6000cps.
In some other embodiments of the invention, in step (2), the temperature of preheating the mold is 30-40 ℃, the time of vertical dipping in glue solution is 5-10s, and the temperature of dipping in glue is 55-60 ℃;
the release agent is one or more of Tween-80, liquid paraffin, salad oil, corn oil, peanut oil, soybean oil and mustard oil;
Preferably, the preheating temperature of the die is 35 ℃, the vertical dipping time of the die into glue solution is 8s, the dipping temperature of the die is 58 ℃, and the release agent is Tween-80.
In some other embodiments of the invention, in step (3), the calcified solution is one or more of calcium chloride, calcium gluconate, or calcium citrate, the concentration of the calcified solution is 3-5wt.%, and the calcification time is 20-30s;
Preferably, the calcified solution is calcium gluconate, the concentration of the calcified solution is 3.5wt.%, and the time of calcification is 20s.
In some other embodiments of the invention, in step (4), the temperature of drying is 30-35 ℃, the moisture of the capsule is 6-8wt.%;
Preferably, the drying temperature is 33 ℃, and the moisture of the capsule is 7wt.%.
In a third aspect, the present invention provides a hollow capsule, formulated in accordance with the sodium alginate enteric hollow capsule composition of the first aspect, preferably obtained in accordance with the preparation method of the second aspect.
In a fourth aspect, the invention provides an application of the sodium alginate enteric empty capsule composition in the first aspect in preparing empty capsules, wherein the empty capsules are enteric empty capsules or slow release empty capsules, and preferably, the empty capsules are medicine empty capsules.
Compared with the prior art, the invention has the following beneficial effects:
(1) The main capsule wall material of the sodium alginate enteric hollow capsule is derived from plant polysaccharide extracted from brown algae, does not contain animal components and organic solvents, has biodegradability, and can improve the stability of glue solution and control the viscosity of the glue solution by mixing sodium alginate with two different viscosities.
(2) The preparation process of the sodium alginate enteric hollow capsule does not need to use a gel, and the influence of the gel on disintegration does not exist, so that the disintegration performance of the product is stable, and no residue exists. The addition of sodium carboxymethyl cellulose, microcrystalline cellulose and pullulan can improve the formability, mechanical strength and flexibility of the capsule, and maintain the shape and integrity of the capsule under different environmental conditions.
(3) The sodium alginate and calcium ions are easy to crosslink, the calcification time is short, the concentration of calcified solution is low, and the formed capsule shell ensures that the capsule is not disintegrated in the stomach environment and is disintegrated only in the alkaline intestinal tract environment, so that the medicine is released, and no residue exists.
Drawings
FIG. 1 is a physical diagram of a finished capsule product prepared in example 1 of the present invention;
FIG. 2 is a physical diagram of a finished capsule product prepared in example 2 of the present invention;
FIG. 3 is a physical diagram of a finished capsule product prepared in example 3 of the present invention;
FIG. 4 is a physical diagram of a finished capsule product prepared in example 4 of the present invention.
Detailed Description
The reagents used in the examples of the present invention are all commercially available conventional reagents.
Wherein the sodium alginate is obtained from Qingdao open moon seaweed group Co., ltd, and has a viscosity of 70-90cps and 8-20cps (1 wt.% solution);
Microcrystalline cellulose is obtained from Shandong Liaocheng Anhua pharmaceutical Co., ltd, has a particle size of 100-150um, and has a polymerization degree of 260-350;
The pullulan has a kinematic viscosity of 50-100mm 2/s (10 wt.% solution) and a molecular weight of 2x10 5-3x105 Da, using Shandong Maitreya Biotechnology Co., ltd.
The following description is made in connection with specific embodiments:
Example 1
First 87 parts of water is heated to 75 ℃, then 3 parts of sodium alginate with a viscosity of 70-90cps and 4 parts of sodium alginate with a viscosity of 8-20cps are added and stirred until completely dissolved. 1 part of sodium carboxymethyl cellulose, 0.5 part of microcrystalline cellulose, 1.5 parts of pullulan and 3 parts of glycerin are sequentially added into the slurry, and the slurry is stirred for 40min at the temperature of 70 ℃ to form uniform colloidal liquid, and the heat preservation is continued for 1h. And (5) carrying out vacuum degassing on the glue solution after the heat preservation is finished, and measuring the viscosity of the glue solution at 60-65 ℃.
The stainless steel capsule mold preheated at 33 ℃ was brushed with tween-80 as a mold release agent, and then the mold was vertically immersed in the glue solution at 55 ℃ for 6s.
The capsule after glue dipping molding is immersed into 3wt.% calcium chloride solution for calcification for 20s, and then the capsule after calcification molding is placed into a blast drying oven at 30 ℃ for drying, shelling and cutting, and the moisture of the capsule after drying is 7.8wt.%.
Example 2
First 80.5 parts of water is heated to 77 ℃, then 5 parts of sodium alginate having a viscosity of 70-90cps and 5 parts of sodium alginate having a viscosity of 8-20cps are added and stirred until completely dissolved. 1.5 parts of sodium carboxymethyl cellulose, 1 part of microcrystalline cellulose, 3 parts of pullulan and 4 parts of glycerin are sequentially added into the slurry, and the slurry is stirred for 50 minutes at the temperature of 77 ℃ to form uniform colloidal liquid, and the heat preservation is continued for 1 hour. And (5) carrying out vacuum degassing on the glue solution after the heat preservation is finished, and measuring the viscosity of the glue solution at 60-65 ℃.
The stainless steel capsule mold preheated at 35 ℃ was brushed with tween-80 as a mold release agent, and then the mold was immersed vertically in the glue solution at 58 ℃ for 8s.
The capsule after glue dipping molding is immersed into 3.5wt.% calcium gluconate solution for calcification for 20s, and then the capsule after calcification molding is placed into a blast drying oven at 33 ℃ for drying, shelling and cutting are carried out, and the moisture of the capsule after drying is 7.3wt.%.
Example 3
First 78.5 parts of water is heated to 77 ℃, then 5 parts of sodium alginate having a viscosity of 70-90cps and 6 parts of sodium alginate having a viscosity of 8-20cps are added and stirred until completely dissolved. 2 parts of sodium carboxymethyl cellulose, 1.5 parts of microcrystalline cellulose, 3 parts of pullulan and 4 parts of glycerin are sequentially added into the slurry, and the slurry is stirred for 50 minutes at the temperature of 77 ℃ to form uniform colloidal liquid, and the heat preservation is continued for 1 hour. And (5) carrying out vacuum degassing on the glue solution after the heat preservation is finished, and measuring the viscosity of the glue solution at 60-65 ℃.
The stainless steel capsule mold preheated at 35 ℃ was brushed with tween-80 as a mold release agent, and then the mold was immersed vertically in the glue solution at 58 ℃ for 8s.
The capsule after glue dipping molding is immersed into 3.5wt.% calcium gluconate solution for calcification for 20s, and then the capsule after calcification molding is placed into a blast drying oven at 33 ℃ for drying, shelling and cutting are carried out, and the moisture of the capsule after drying is 7.3wt.%.
Example 4
First, 83 parts of water is heated to 80 ℃, followed by adding 4 parts of sodium alginate having a viscosity of 70-90cps and 5 parts of sodium alginate having a viscosity of 8-20cps, and stirring until complete dissolution. 1.5 parts of sodium carboxymethyl cellulose, 0.5 part of microcrystalline cellulose, 3 parts of pullulan and 3 parts of glycerin are sequentially added into the slurry, and the slurry is stirred for 45 minutes at the temperature of 80 ℃ to form uniform colloidal liquid, and the heat preservation is continued for 1 hour. And (5) carrying out vacuum degassing on the glue solution after the heat preservation is finished, and measuring the viscosity of the glue solution at 60-65 ℃.
The stainless steel capsule mold preheated at 37 ℃ was brushed with tween-80 as a mold release agent, and then the mold was immersed vertically in the glue solution at 60 ℃ for 7s.
The capsule after glue dipping molding is immersed into 3.5wt.% calcium citrate solution for calcification for 25s, then the capsule after calcification molding is placed into a blast drying oven at 35 ℃ for drying, shelling and cutting are carried out, and the moisture of the capsule after drying is 7.1wt.%.
Comparative example 1
In contrast to example 2, the composition of the sodium alginate enteric hollow capsules is shown in Table 1, and the other steps are exactly the same as in example 2.
Comparative example 2
In contrast to example 2, the composition of the sodium alginate enteric hollow capsules is shown in Table 1, and the other steps are exactly the same as in example 2.
Comparative example 3
In contrast to example 2, the composition of the sodium alginate enteric hollow capsules is shown in Table 1, and the other steps are exactly the same as in example 2.
Comparative example 4
In contrast to example 2, the composition of the sodium alginate enteric hollow capsules is shown in Table 1, and the other steps are exactly the same as in example 2.
Comparative example 5
In contrast to example 2, the composition of the sodium alginate enteric hollow capsules is shown in Table 1, and the other steps are exactly the same as in example 2.
Comparative example 6
In contrast to example 2, the composition of the sodium alginate enteric hollow capsules is shown in Table 1, and the other steps are exactly the same as in example 2.
TABLE 1 list of raw ingredients for sodium alginate enteric hollow capsules
The sodium alginate enteric hollow capsules prepared in examples 1 to 4 and comparative examples 1 to 6 of the present invention were subjected to friability, disintegration time, dissolution and release tests by referring to methods prescribed in four parts of the chinese pharmacopoeia 2020 edition, and quality detection items and results are shown in table 2.
TABLE 2 Performance index of sodium alginate enteric hollow capsules
The evaluation results of the formability, mechanical strength and flexibility of the sodium alginate enteric hollow capsules are shown in table 3:
TABLE 3 Performance index of sodium alginate enteric hollow capsules
As is clear from Table 3, the capsule of comparative example 1 has a low molding rate, mainly, sodium alginate with a viscosity of 70-90cps is not used, resulting in lower viscosity of the produced glue solution, easy bleeding during glue dipping and difficult molding, the capsule of comparative example 2 has a high transparency, but the capsule has a low thickness due to the fact that sodium alginate with a low viscosity is not used, the mechanical strength of the capsule is reduced, the flexibility is poor, partial disintegration occurs in gastric juice, the capsules prepared in comparative examples 3, 4 and 5 are well molded, the surface is smooth, but the auxiliary materials do cause the reduction of the bonding strength and the viscosity of the glue solution in the capsule, thus disintegration occurs in gastric juice, the glycerol is absent in comparative example 6, the viscosity of the glue solution is too high, foam occurs during glue dipping, and the capsule has bubbles, and meanwhile, as an important plasticizer, the glycerol is absent, resulting in reduced flexibility of the capsule and is easier to crush.
Claims (16)
1. The sodium alginate enteric hollow capsule composition is characterized by comprising, by weight, 3-5 parts of sodium alginate of 70-90cps, 4-6 parts of sodium alginate of 8-20cps, 1-2 parts of sodium carboxymethylcellulose, 0.5-1.5 parts of microcrystalline cellulose, 1.5-3 parts of pullulan polysaccharide, 3-4 parts of glycerol and the balance of water.
2. The sodium alginate enteric hollow capsule composition according to claim 1, which comprises the following components in parts by weight:
3-5 parts of sodium alginate with the concentration of 70-85cps, 4-5 parts of sodium alginate with the concentration of 8-20cps, 1-1.5 parts of sodium carboxymethylcellulose, 0.5-1 part of microcrystalline cellulose, 1.5-3 parts of pullulan, 3-4 parts of glycerol and the balance of water.
3. The sodium alginate enteric hollow capsule composition according to claim 2, which comprises the following components in parts by weight:
5 parts of 85cps sodium alginate, 5 parts of 20cps sodium alginate, 1.5 parts of carboxymethylcellulose sodium, 1 part of microcrystalline cellulose, 3 parts of pullulan, 4 parts of glycerol and the balance of water.
4. A method for preparing sodium alginate enteric hollow capsules by using the sodium alginate hollow capsule composition of any one of claims 1 to 3, comprising the following steps:
(1) Mixing sodium alginate and water, sequentially adding sodium carboxymethylcellulose, microcrystalline cellulose, pullulan and glycerol, stirring into colloidal liquid, preserving heat, vacuumizing and degassing to obtain a colloidal liquid;
(2) The glue dipping molding, namely, before glue dipping, brushing a release agent after preheating a die, wherein the capsule die is vertically immersed in glue solution during glue dipping;
(3) Calcification, namely, calcification is carried out after glue dipping molding;
(4) Drying, shelling, cutting, drying and molding, shelling, and cutting.
5. The preparation method according to claim 4, wherein in the step (1), the temperature at which sodium alginate is uniformly mixed with water is 70-80 ℃, the stirring time is 30-60min, the temperature at which heat is preserved is 70-80 ℃, and the heat preservation time is 1-1.5h.
6. The preparation method according to claim 5, wherein in the step (1), the temperature at which sodium alginate is uniformly mixed with water is 77 ℃, the stirring time is 50min, the temperature at which the sodium alginate is kept is 77 ℃, and the time at which the sodium alginate is kept for 1h.
7. The process according to claim 4, wherein the viscosity of the dope is 5000-6000cps at 60-65 ℃ after vacuum degassing in step (1).
8. The method according to claim 4, wherein in the step (2), the preheating temperature of the mold is 30-40 ℃, the vertical dipping time is 5-10s, and the dipping temperature is 55-60 ℃;
the release agent is one or more of Tween-80, liquid paraffin, salad oil, corn oil, peanut oil, soybean oil and mustard oil.
9. The method according to claim 8, wherein in the step (2), the mold is preheated to 35 ℃, the vertical dipping time is 8s, the dipping temperature is 58 ℃, and the mold release agent is Tween-80.
10. The method of claim 4, wherein in step (3), the calcified solution is one or more of calcium chloride, calcium gluconate or calcium citrate, the concentration of the calcified solution is 3-5wt.%, and the calcification time is 20-30s.
11. The method of claim 10, wherein in step (3), the calcified solution is calcium gluconate, the concentration of the calcified solution is 3.5wt.%, and the time of calcification is 20s.
12. The method of claim 4, wherein in step (4), the drying temperature is 30-35 ℃ and the water content of the capsule is 6-8 wt%.
13. The method of claim 12, wherein in step (4), the drying temperature is 33 ℃ and the moisture content of the capsule is 7 wt%.
14. A hollow capsule, characterized in that it is obtained according to the preparation method of any one of claims 4 to 13.
15. Use of a sodium alginate enteric empty capsule composition according to any one of claims 1 to 3 for the preparation of empty capsules, characterized in that said empty capsules are enteric empty capsules or slow release enteric empty capsules.
16. The use according to claim 15, wherein the empty capsule is a pharmaceutical empty capsule.
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| CN104887643A (en) * | 2015-05-08 | 2015-09-09 | 浙江万里学院 | Sodium alginate/starch-based enteric hollow capsule and one-shot molding preparation method thereof |
| CN116590364A (en) * | 2023-04-06 | 2023-08-15 | 中国海洋大学 | Low-viscosity sodium alginate for soft capsules and preparation method and application thereof |
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| CN116590364A (en) * | 2023-04-06 | 2023-08-15 | 中国海洋大学 | Low-viscosity sodium alginate for soft capsules and preparation method and application thereof |
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