CN113598397A - Microencapsulated encapsulated particles and method for their preparation - Google Patents

Microencapsulated encapsulated particles and method for their preparation Download PDF

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Publication number
CN113598397A
CN113598397A CN202110898230.4A CN202110898230A CN113598397A CN 113598397 A CN113598397 A CN 113598397A CN 202110898230 A CN202110898230 A CN 202110898230A CN 113598397 A CN113598397 A CN 113598397A
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vitamin
microencapsulated
hydrophobic material
acid
embedding
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CN113598397B (en
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陈键濠
方素琼
陈文荣
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Sirio Pharma Co Ltd
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Sirio Pharma Co Ltd
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/03—Organic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/03—Organic compounds
    • A23L29/035—Organic compounds containing oxygen as heteroatom
    • A23L29/04—Fatty acids or derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/20—Agglomerating; Granulating; Tabletting
    • A23P10/28—Tabletting; Making food bars by compression of a dry powdered mixture
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
    • A23P10/35—Encapsulation of particles, e.g. foodstuff additives with oils, lipids, monoglycerides or diglycerides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/191—Carboxylic acids, e.g. valproic acid having two or more hydroxy groups, e.g. gluconic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/28—Compounds containing heavy metals
    • A61K31/30—Copper compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/28—Compounds containing heavy metals
    • A61K31/315—Zinc compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A61K31/51—Thiamines, e.g. vitamin B1
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7135—Compounds containing heavy metals
    • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A61K33/10—Carbonates; Bicarbonates
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • 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
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5015—Organic compounds, e.g. fats, sugars
    • 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
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5089—Processes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • B01J13/02—Making microcapsules or microballoons
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

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Abstract

The invention provides microencapsulated embedded particles and a preparation method thereof. Microencapsulated embedded particles are provided comprising a hydrophobic material as a capsule wall and an active ingredient, wherein the hydrophobic material comprises a first hydrophobic material and a second hydrophobic material, the first hydrophobic material is a mono-diglycerol fatty acid ester, and the second hydrophobic material is one or more of a higher saturated fatty acid or carnauba wax, wherein the weight ratio of the first hydrophobic material to the second hydrophobic material is 1:4-9:1, preferably 3:7-8: 2. The capsule wall material of the microencapsulated embedding particles has simple components and high embedding rate and retention rate of active ingredients.

Description

Microencapsulated encapsulated particles and method for their preparation
Technical Field
The invention belongs to the field of microencapsulation embedding, and particularly relates to a method for preparing microencapsulated embedding particles and the microencapsulated embedding particles.
Background
The microencapsulation embedding is a new process and technology for preparing micron-sized or nano-sized particle products by using natural or synthetic high molecular materials as microcapsule wall materials and wrapping solid and liquid medicinal products, foods and chemical raw materials which are called as capsule core materials. Has been applied in a plurality of fields such as medicine, food, fine chemical industry and the like. The microencapsulated embedding materials currently selected for use in the food processing industry are mainly water-soluble gums, starches, caseins, alginates and cellulose derivatives, such as gum arabic, alginates and carboxymethylcellulose, sodium caseinate and the like. The core material is selected from vitamins, enzymes, volatile essence and spice, sour agent, food preservative, wine, etc. Because alginate is cheap and good in biocompatibility, but is limited by conditions in the practical use process, in the presence of chelating agents such as phosphoric acid, lactic acid and citric acid, the chelating agents have stronger affinity to calcium than calcium alginate, so that the calcium alginate is unstable, and the problem of the stability of colloid shedding is encountered. In addition, the current microencapsulated embedding particles obtained by wall materials have the defects of low embedding rate and reduced stability with time. For example, Lee et al (Lee et al, research on vitamin C microencapsulation embedding process, applied chemical engineering, vol. 42, No. 3, pp 404-409) describe the use of sodium carboxymethylcellulose and gelatin as wall material for embedding vitamin C to obtain microencapsulated embedded particles with an embedding rate of 64%. Studies on the stability of vitamin A microcapsule preparations prepared from 4 different embedding materials such as Zhanglian (Zhanglian, etc., foods and medicines, 20 vol. 6, 456 st. su-b. 459) used acacia, gelatin, beta-cyclodextrin and modified starch as embedding agents to prepare the vitamin A microcapsule preparations. This study considered that gelatin, a polymeric material, is most suitable as an embedding agent for the preparation of vitamin a microcapsule formulations, but there were still cases where the stability decreased with time when gelatin was used as an embedding agent. In addition, gelatin is an animal derived material that is not accepted by vegetarians.
Therefore, there is still a need in the art for more microencapsulated embedding materials to obtain highly encapsulated embedding particles.
Disclosure of Invention
The present invention is based on the following findings of the present inventors in long-term work: the hydrophobic material of the present invention is selected as a capsule wall material to prepare microencapsulated embedding particles containing an active ingredient, and the microencapsulated embedding particles with a high active ingredient embedding rate can be obtained, the hydrophobic material comprises a first hydrophobic material and a second hydrophobic material, the first hydrophobic material is a mono-diglycerol fatty acid ester, the second hydrophobic material is one or more of higher saturated fatty acid or carnauba wax, wherein the weight ratio of the first hydrophobic material to the second hydrophobic material is 1:4-9:1, preferably 3:7-8: 2. The microencapsulated embedded particles have an embedding rate of more than 90% of active ingredients, and the hydrophobic material has simple components, does not contain animal-derived proteins such as gelatin and the like, and can be widely applied to the fields of food, medicines or cosmetics. In addition, when tablets are prepared using the microencapsulated embedding granules of the present invention as a raw material, tablets with long-term stability of the active ingredient can be obtained.
In one aspect, the present invention provides microencapsulated embedded particles comprising a hydrophobic material as a wall and an active ingredient as a core, wherein the hydrophobic material comprises a first hydrophobic material and a second hydrophobic material, the first hydrophobic material is a mono-diglycerol fatty acid ester, and the second hydrophobic material is one or more of a higher saturated fatty acid or carnauba wax, wherein the weight ratio of the first hydrophobic material to the second hydrophobic material is from 1:4 to 9:1, preferably from 3:7 to 8: 2. Preferably, the higher saturated fatty acid is one or more of dodecanoic acid, tetradecanoic acid, stearic acid, palmitic acid, eicosanoic acid, or docosanoic acid. In one embodiment, the raw material of the microencapsulated embedding particles comprises from 50% to 99% by weight, preferably from 60% to 99% by weight, of hydrophobic material and from 1% to 50% by weight, preferably from 1% to 40% by weight, of active ingredient. In one embodiment, the microencapsulated embedded particles are prepared by a spray cooling process.
In one embodiment, the active ingredient is an active ingredient susceptible to degradation by a factor selected from the group consisting of: pH, light, temperature, oxygen, humidity, or metal ions.
In one embodiment, the active ingredient is one or more of a vitamin, an enzyme, a probiotic, an amino acid, a carbohydrate, a polypeptide, or an oil.
In one embodiment, the vitamin is one or more of vitamin a, vitamin B, vitamin C, vitamin D, vitamin E, vitamin K, vitamin H, vitamin P, vitamin PP, vitamin M, vitamin T, vitamin U, folic acid, or biotin.
In one embodiment, the vitamin B is one or more of vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, or vitamin B12.
In one embodiment, the microencapsulated embedded particles are prepared by a spray cooling process. In one embodiment, the spray cooling method comprises heating 50 wt% to 99 wt%, preferably 60 wt% to 99 wt% of hydrophobic material to melt, adding 1 wt% to 50 wt%, preferably 1 wt% to 40 wt% of active ingredient, stirring to dissolve uniformly, and spray cooling to obtain microencapsulated embedded particles. In one embodiment, the hydrophobic material melts upon heating at a temperature of 70 ℃ to 80 ℃.
In another aspect, the present invention provides a process for preparing microencapsulated embedded particles, which comprises heating and melting a hydrophobic material, adding an active ingredient, stirring to dissolve uniformly, and spray cooling to obtain microencapsulated embedded particles. In one embodiment, the hydrophobic material melts upon heating at a temperature of 70 ℃ to 80 ℃.
In another aspect, the invention provides a composition comprising microencapsulated embedded particles of the invention.
In one embodiment, the composition comprises from 1 wt% to 20 wt% microencapsulated embedded particles.
In one embodiment, the microencapsulated embedded particles comprise vitamin B. Preferably, the vitamin B is one or both of vitamin B1 or vitamin B12.
In one embodiment, the composition comprises minerals required by the human body. In one embodiment, the tablet feedstock composition comprises from 10 wt% to 50 wt% of a human-desired mineral.
In one embodiment, the composition comprises a filler. In one embodiment, the tablet feedstock composition comprises 10 wt% to 50 wt% filler.
In one embodiment, the composition comprises a lubricant. In one embodiment, the tablet feedstock composition comprises 1 wt% to 3 wt% lubricant.
In one embodiment, the composition comprises other vitamins than vitamin B1 or vitamin B12, preferably one or more of vitamin B2, vitamin B3, vitamin B5, vitamin B6, folic acid, biotin, vitamin C, vitamin a, vitamin D, or vitamin K. In one embodiment, the other vitamins are present in an amount greater than 0 wt% and equal to or less than 20 wt%.
In one embodiment, the mineral is one or more of a calcium salt, a magnesium salt, a copper salt, or a zinc salt. In one embodiment, the mineral is one or more of calcium carbonate, calcium citrate, magnesium carbonate, magnesium oxide, copper gluconate, copper sulfate, or zinc oxide.
In one embodiment, the filler is one or more of sorbitol, starch, microcrystalline cellulose, dextrin, powdered sugar, lactose, or an inorganic calcium salt.
In one embodiment, the lubricant is one or more of magnesium stearate, talc, boric acid, hydrogenated vegetable oil, or PEG-based compounds.
In another aspect, the present invention provides a process for preparing a tablet from the composition of the present invention, comprising the step of tableting the composition of the present invention. In one embodiment, the microencapsulated embedded granules of the invention are mixed with minerals and fillers, or when other vitamins are present, the microencapsulated embedded granules, other vitamins, minerals and fillers are mixed, sieved, mixed with a lubricant, and finally subjected to a machine-tabletting step.
In another aspect, the invention provides a tablet prepared by the method of the invention.
In another aspect, the invention provides the use of a tablet in a food, health product or pharmaceutical product. In one embodiment, the present invention provides the use of a tablet in the preparation of a nutraceutical.
In another aspect, the present invention provides the use of a hydrophobic material as a wall of a microencapsulated embedded particle, wherein the hydrophobic material comprises a first hydrophobic material and a second hydrophobic material, the first hydrophobic material is a mono-diglycerol fatty acid ester and the second hydrophobic material is one or more of a higher saturated fatty acid or carnauba wax, wherein the weight ratio of the first hydrophobic material to the second hydrophobic material is from 1:4 to 9:1, preferably from 3:7 to 8: 2. Preferably, the raw material of the microencapsulated embedding particles comprises 60 wt% to 99 wt% of the hydrophobic material and 1 wt% to 40 wt% of the active ingredient. Preferably, the higher saturated fatty acid is one or more of dodecanoic acid, tetradecanoic acid, stearic acid, palmitic acid, eicosanoic acid, or docosanoic acid. Preferably, the microencapsulated embedded particles are prepared by spray cooling. Preferably, the spray cooling method comprises heating 50 wt% to 99 wt%, preferably 60 wt% to 99 wt% of hydrophobic material for melting, adding 1 wt% to 50 wt%, preferably 1 wt% to 40 wt% of active ingredient, stirring for dissolving to uniformity, and spray cooling to obtain microencapsulated embedded particles.
In this context, the tablet of the invention may be a tablet comprising microencapsulated particles of vitamin, for example a tablet comprising microencapsulated particles of vitamin B. Preferably, the vitamin B is one or both of vitamin B1 or vitamin B12.
The present invention provides the following advantages:
1) the capsule wall material of the microencapsulated embedded particles has simple components; when the mono-diglycerol fatty acid ester: the higher saturated fatty acid or carnauba wax has a high embedding rate of more than 90% in a certain proportion range (1:4-9:1, preferably 3:7-8: 2).
2) The wall material of the microencapsulated embedding granules of the invention does not contain gelatin of animal origin.
3) According to the invention, active ingredients such as vitamin B1 and/or vitamin B12 are processed by screening hydrophobic material combinations with specific proportions to prepare the high-embedding-rate vitamin microencapsulated embedding particles, and the high-embedding-rate vitamin microencapsulated embedding particles are applied to vitamin mineral tablet products to obtain the effect of high retention rate, so that the stability of the vitamin B1 and/or vitamin B12 tablets is improved, and the product quality is ensured.
Detailed Description
The present invention provides a process for preparing microencapsulated embedded particles. The method may comprise preparing the microencapsulated embedded particles by melting the wall material, then adding the active ingredient to dissolve, and by spray drying. The melting temperature of the wall material is not particularly limited as long as the hydrophobic material of the present invention can be melted. The melting temperature can be appropriately selected by those skilled in the art according to the melting point of the hydrophobic material. The melting temperature may be 70 ℃ to 90 ℃, such as 71 ℃, 72 ℃, 73 ℃, 74 ℃, 75 ℃, 76 ℃, 77 ℃, 78 ℃, 79 ℃, 80 ℃, 81 ℃, 82 ℃, 83 ℃, 84 ℃, 85 ℃, 86 ℃, 87 ℃, 88 ℃ or 89 ℃.
The wall material may comprise a first hydrophobic material and a second hydrophobic material. The first hydrophobic material may be a mono-diglycerol fatty acid ester. The second hydrophobic material may be one or more of a higher saturated fatty acid or carnauba wax. The weight ratio of the first hydrophobic material to the second hydrophobic material may be 1:4 to 9:1, preferably 3:7 to 8: 2. In one embodiment, the weight ratio of the first hydrophobic material to the second hydrophobic material is 1:3, 1:2, 2:3, 1:1, 2:1, 3:2, 7:3, 3:1, 4:1, 5:1, 6:1, 7:1, or 8: 1. In one embodiment, the hydrophobic material may be present in an amount of 50 wt% to 99 wt% of the microencapsulated embedding particle material. For example, the hydrophobic material can comprise 55 wt%, 60 wt%, 65 wt%, 70 wt%, 75 wt%, 80 wt%, 85 wt%, 90 wt%, 95 wt%, 96 wt%, 97 wt%, 98 wt%, or 99 wt% of the microencapsulated embedding particle material. The amount of active ingredient may be from 1 wt% to 50 wt%, e.g., 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt% or 45 wt% of the microencapsulated embedding particle material.
The mono-diglycerol fatty acid ester is a food additive, is prepared by reacting saturated or unsaturated fatty acid or oil with glycerol, and is processed by or without separation and purification to obtain mono-diglycerol fatty acid ester (oleic acid, linoleic acid, linolenic acid, palmitic acid, behenic acid, stearic acid and lauric acid), and can be specifically found in national standard GB 1886.65.
Higher saturated fatty acids refer to saturated fatty acids containing more than ten carbon atoms. Herein, the higher saturated fatty acid may refer to one or more of dodecanoic acid, tetradecanoic acid, palmitic acid (hexadecanoic acid), stearic acid (octadecanoic acid), eicosanoic acid, or docosanoic acid. In one embodiment, the higher saturated fatty acid is palmitic acid (hexadecanoic acid) and/or stearic acid (octadecanoic acid).
The active ingredient may be one susceptible to degradation by a factor selected from the group consisting of: pH, temperature, oxygen, humidity, light or metal ions. For example, the active ingredient may be one or more of a vitamin, an enzyme, a probiotic, an amino acid, a carbohydrate, a polypeptide or an oil. The vitamin may be one or more of vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, vitamin K, vitamin H, vitamin P, vitamin PP, vitamin M, vitamin T, vitamin U, folic acid or biotin. The vitamin B may be one or more of vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, or vitamin B12. The active ingredient can be appropriately selected by those skilled in the art in accordance with the above-mentioned specific influences. Preferably, the active ingredient is vitamin B, more preferably one or both of vitamin B1 or vitamin B12.
The microencapsulated embedded particles prepared by the process of the present invention may comprise an active ingredient and a structure of capsule walls encapsulating the active ingredient. The microencapsulated embedding particles can have a high embedding rate of active ingredients. In this context, the encapsulation rate of the active ingredient of the microencapsulated encapsulation particles can be 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%.
Since the microencapsulated particles of the present invention have a characteristic of high active ingredient encapsulation efficiency, a composition can be prepared by mixing the microencapsulated particles of the present invention with other ingredients. The composition may be in any suitable form, for example in the form of a solid, a suspension or a gel. Preferably, the composition is in the form of a solid. The tablet is well accepted by the public due to the advantages of convenient carrying and use, high mechanization degree of the preparation method, high yield and the like, and is also the most widely applied preparation formulation in the market. The composition may be prepared in tablet form. Other ingredients may be ingredients other than the active ingredient in the microencapsulated particles, such as nutritional ingredients, e.g. minerals such as calcium, copper, iron, manganese, magnesium salts and the like and vitamins. For example, when the active ingredient is vitamin B1 or vitamin B12, the other ingredients may contain other vitamins in addition to vitamin B1 or vitamin B12. The content of these other vitamins may be greater than 0 wt% and less than or equal to 20 wt%, such as 1 wt%, 5 wt%, 10 wt% or 15 wt%.
The minerals are minerals required by human body, such as chloride, carbonate, gluconate, oxide, citrate, sulfate, etc. of calcium, copper, iron, manganese, magnesium, zinc, and their combination. In one embodiment, the mineral may be one or more of calcium carbonate, calcium citrate, magnesium carbonate, magnesium oxide, copper gluconate, copper sulfate, or zinc oxide. The minerals may be present in the composition in an amount of 10 wt% to 50 wt%, such as 20 wt%, 30 wt%, or 40 wt%, and any value therebetween.
The composition may also include a filler. For example, the composition may also include 10 wt% to 50 wt% filler, such as 20 wt%, 30 wt%, or 40 wt%, and any values therebetween. The kind of the filler is not particularly limited. For example, the filler is one or more of sorbitol, starch, microcrystalline cellulose, dextrin, sugar powder, lactose, or an inorganic calcium salt.
The composition may also comprise a lubricant. For example, the composition may also include 1 wt% to 3 wt% lubricant, such as 1.5 wt%, 2 wt%, or 2.5 wt% lubricant. The kind of the lubricant is not particularly limited. For example, the lubricant is one or more of magnesium stearate, talc, boric acid, hydrogenated vegetable oil, or PEG-based compounds.
The compositions of the present invention may be prepared into tablets in conventional tableting procedures. For example, the encapsulated granules can be mixed with minerals and fillers, or when other vitamins are present, the encapsulated granules, other vitamins, minerals and fillers can be mixed, sieved, mixed with lubricant, and finally tableted on a machine to prepare tablets. In particular, the composition of the present invention can be made into vitamin mineral tablets, which can be supplemented with various vitamins and minerals at the same time.
In particular, the vitamin mineral tablets of the present invention are particularly useful for vitamin B1 (thiamine) and vitamin B12 (cobalamin) in the vitamin B group. Vitamin B1 (thiamine) is the least stable vitamin of the B vitamin family, and the stability of vitamin B1 (thiamine) is related to pH, temperature, medium and other reactions. Sensitive to metal ions (such as calcium, copper, iron, manganese, magnesium, etc.), temperature, oxygen, pH (neutral and alkaline), and strong light. The stability of vitamin B12 (cobalamin) is related to oxygen, light, heat, metal ions, reducing agents such as ascorbic acid, sulfite, etc. When sensitive metal ions are included in the tablet formulation, their stability is necessarily affected. The embedding material, such as the hydrophobic material described herein, is simply matched with vitamin B1 or B12, and the microencapsulated embedding particles can be prepared by a conventional process, but the defects of low embedding rate and low retention rate in the application of the microcapsule embedding particles to tablets exist. However, the encapsulation of vitamin B1 and/or vitamin B12 by the microencapsulated embedding particles of the present invention can protect vitamin B1 and/or vitamin B12 from degradation due to pH, temperature, metal ions, etc., thereby overcoming the problems of instability of vitamin B (including increased dosage of vitamin B, even toxicity; the initial content is likely to be out of the range required by regulatory labels; increased formulation cost, increased production cost, etc.) by increasing the dosage in the prior art. That is, the vitamin B mineral tablet with high retention rate can be prepared by selecting proper combination of hydrophobic materials and a specific proportion range, so that the stability (high embedding rate) of the vitamin B is improved, the reaction between the vitamin B and mineral components (containing sensitive metal ions) in the tablet can be effectively blocked, and the stability (high retention rate) of the vitamin B mineral tablet is improved.
The embedding rate herein can be determined by any suitable method known in the art. In this context, the encapsulation efficiency can be calculated as (total content of active ingredient in the microencapsulated embedding particles-content of non-encapsulated active ingredient in the microencapsulated embedding particles)/total content of active ingredient in the microencapsulated embedding particles X100%.
The retention in this context reflects the percentage of active substance retained after a certain time of storage of the tablet. For example, the retention rate can be calculated as (active ingredient content after tablet acceleration for 3 months)/(active ingredient content detected at 0 month of tablet) X100%. The acceleration conditions may be known to those skilled in the art. Herein, the acceleration condition may be a condition of a temperature of 40 ℃. + -. 2 ℃ and a relative humidity of 75%. + -. 5%.
In one embodiment, the active ingredient is vitamin B12. The embedding rate of vitamin B12 can be calculated by measuring the total content of vitamin B12 in the microencapsulated embedding granules and the content of non-encapsulated vitamin B12 in the microencapsulated embedding granules. The retention rate of vitamin B12 can be calculated by measuring the vitamin B12 content of the tablet after 3 months of acceleration/the detected vitamin B12 content of the tablet at 0 month X100%.
The vitamin B12 content can be determined using the method described in GB 5009.217. Briefly, the tablets to be tested are crushed, the samples are weighed into a centrifuge tube, water is added, mixed well, placed in an ultrasonic cleaner, centrifuged after ultrasonic extraction. And (5) sucking the supernatant and placing the supernatant in a centrifuge tube. Adding a certain amount of water into the residue according to the steps, repeatedly extracting for two times, and combining the extracting solutions in a centrifuge tube. Adding 5% tetrabutylammonium chloride solution and chloroform into the extractive solution, mixing with vortex mixer, and centrifuging. Transferring the water layer into an evaporating dish, and heating and evaporating to dryness in a water bath kettle. Dissolving the residue with ethanol, transferring to a centrifuge tube, ultrasonically dissolving, centrifuging, and sucking the supernatant into an evaporation dish. The extraction was repeated two more times and the extracts were combined in an evaporation dish. The ethanol was evaporated and the sample was quantitatively transferred to a test tube with 5% acetonitrile solution for solid phase extraction column. The solid phase extraction column is first activated with methanol and then equilibrated with water. The sample was applied to a solid phase extraction column. After loading, the interfering substances were eluted with a 5% acetonitrile solution as an elution solution, and finally vitamin B12 was eluted with a 25% acetonitrile solution. The eluate was measured by liquid chromatography. The liquid chromatography conditions were: column C18 reverse phase column; mobile phase: 0.025% trifluoroacetic acid (ph2.6) (solution a) and acetonitrile (solution B); the detection wavelength was 361 nm.
In one embodiment, the active ingredient is vitamin B1. The embedding rate of vitamin B1 can be calculated by measuring the total content of vitamin B1 in the microencapsulated embedding granules and the content of non-encapsulated vitamin B1 in the microencapsulated embedding granules. The retention rate of vitamin B1 can be calculated by measuring the vitamin B1 content of the tablet after 3 months of acceleration/the detected vitamin B1 content of the tablet at 0 month X100%.
Vitamin B1 content can be determined using the Method described in USP < oil-and-water-soluble-vitamins with minor tables (Method 1). Briefly, tablets were ground to a powder, which was placed in a centrifuge tube. 25mL of diluent (acetonitrile: glacial acetic acid: water ═ 5:1:94) was added and mixed using a vortex mixer for 30 seconds to completely suspend the powder. The centrifuge tubes were heated in a 65-75 ℃ water bath for 5 minutes and then mixed in a vortex mixer for 30 seconds. The tube was returned to the hot water bath for an additional 5 minutes and mixed in a vortex mixer for 30 seconds. The filtrate was used for sample testing after filtration through a 0.45um microfiltration membrane and cooling to room temperature. Chromatographic conditions are as follows: liquid chromatography, detector UV280nm, column 3.9-mm × 30-cm; packing L1; the flow rate is 1 mL/min; the injection volume was 10. mu.L.
The following examples are provided to facilitate an understanding of the invention. It is to be understood that these embodiments are illustrative only and not restrictive. The scope of the invention is only limited by the appended claims.
Examples
Method for preparing tablet
(1) Mixing hydrophobic materials with mono-diglycerol fatty acid ester and stearic acid, or mono-diglycerol fatty acid ester and palmitic acid, or mono-diglycerol fatty acid ester and carnauba wax according to a proportion, heating and melting at 70-80 ℃, adding vitamin B1 and/or vitamin B12 raw materials, stirring and dissolving uniformly, spray cooling, and collecting to obtain the vitamin B microencapsulated embedding particles.
(2) The vitamin mineral tablet comprises the following processing steps: mixing the vitamin B microencapsulated embedded granules, other vitamins, minerals and sorbitol, sieving, adding magnesium stearate, mixing, and tabletting. The contents of other vitamins, minerals, sorbitol and magnesium stearate are given in the table below.
Determination of embedding Rate
Method for measuring embedding rate of vitamin B1
1) The embedding rate of the vitamin B1 can be calculated by measuring the total content of the vitamin B1 and then measuring the content of the non-embedded vitamin B1.
2) Determination of total content of vitamin B1: appropriate modifications may be made to determine with reference to the USP vitamin B family method. In brief, a proper amount of sample is weighed in a volumetric flask, acetonitrile-glacial acetic acid-hydrosolvent is added, vortex dispersion is carried out, the microencapsulated embedded particles are heated and dissolved in water bath at the temperature of 65-75 ℃, then vortex extraction is repeated, cooling is carried out, and after filtration through a 0.45-micron microporous membrane, the total content of vitamin B1 in the embedded particles is measured by taking filtrate. Chromatographic conditions are as follows: liquid chromatography, detector UV280nm, column 3.9-mm × 30-cm; packing L1; the flow rate is 1 mL/min; the injection volume was 10. mu.L.
3) Determination of content of non-embedded vitamin B1: weighing a proper amount of sample in a volumetric flask, adding water, whirling, filtering by a 0.45um microporous filter membrane, and sampling and measuring filtrate. Chromatographic conditions are as follows: liquid chromatography, detector UV280nm, column 3.9-mm × 30-cm; packing L1; the flow rate is 1 mL/min; the injection volume was 10. mu.L.
Method for measuring embedding rate of vitamin B12
1) The embedding rate of the vitamin B12 can be calculated by measuring the total content of the vitamin B12 and then measuring the non-embedded content of the vitamin B12.
2) Determination of total content of vitamin B12: weighing a proper amount of sample in a volumetric flask, adding water, carrying out vortex dispersion, heating in a water bath at 65-75 ℃ to dissolve the embedded particles, carrying out vortex extraction, cooling, filtering through a 0.45-micron microporous filter membrane, and taking the filtrate for sample injection determination. The liquid chromatography conditions were: column C18 reverse phase column; mobile phase: 0.025% trifluoroacetic acid (ph2.6) (solution a) and acetonitrile (solution B); the detection wavelength is 361 nm; the flow rate is 1 mL/min; column temperature: and (4) room temperature. Mobile phase: adopting a gradient elution mode:
Figure BDA0003198841160000101
reference is made in particular to the method of GB 5009.217.
3) Determination of content of non-embedded vitamin B12: weighing the sample in a volumetric flask, adding water, whirling, shaking uniformly, immediately filtering through a 0.45um microporous filter membrane, and then taking the filtrate for sample injection and determination. The measurement was performed in the same manner as above.
The embedding rate is calculated as follows:
encapsulation (%: (total content of active ingredient in granule-content of non-encapsulated active ingredient in granule)/total content of active ingredient in granule X100%
Retention Rate determination
The Method for determining the retention of vitamin B1 follows the USP < oil-and-water-soluble-vitamins with minor tables (Method 1). Briefly, tablets were ground to a powder, which was placed in a centrifuge tube. 25mL of diluent (acetonitrile: glacial acetic acid: water ═ 5:1:94) was added and mixed using a vortex mixer for 30 seconds to completely suspend the powder. The centrifuge tubes were heated in a 65-75 ℃ water bath for 5 minutes and then mixed in a vortex mixer for 30 seconds. The tube was returned to the hot water bath for an additional 5 minutes and mixed in a vortex mixer for 30 seconds. The filtrate was used for sample testing after filtration through a 0.45um microfiltration membrane and cooling to room temperature. Chromatographic conditions are as follows: liquid chromatography, detector UV280nm, column 3.9-mm × 30-cm; packing L1; the flow rate is 1 mL/min; the injection volume was 10. mu.L.
The method for measuring the retention rate of the vitamin B12 follows GB/T5009.217 'determination of vitamin B12 in health food'. Briefly, the tablets to be tested are crushed, the samples are weighed into a centrifuge tube, water is added, mixed well, placed in an ultrasonic cleaner, centrifuged after ultrasonic extraction. And (5) sucking the supernatant and placing the supernatant in a centrifuge tube. Adding a certain amount of water into the residue according to the steps, repeatedly extracting for two times, and combining the extracting solutions in a centrifuge tube. Adding 5% tetrabutylammonium chloride solution and chloroform into the extractive solution, mixing with vortex mixer, and centrifuging. Transferring the water layer into an evaporating dish, and heating and evaporating to dryness in a water bath kettle. Dissolving the residue with ethanol, transferring to a centrifuge tube, ultrasonically dissolving, centrifuging, and sucking the supernatant into an evaporation dish. The extraction was repeated two more times and the extracts were combined in an evaporation dish. The ethanol was evaporated and the sample was quantitatively transferred to a test tube with 5% acetonitrile solution for solid phase extraction column. The solid phase extraction column is first activated with methanol and then equilibrated with water. The sample was applied to a solid phase extraction column. After loading, the interfering substances were eluted with a 5% acetonitrile solution as an elution solution, and finally vitamin B12 was eluted with a 25% acetonitrile solution. The sample determination method is as above.
The retention rate is calculated as follows:
the retention rate = (active ingredient content after tablet acceleration for 3 months)/(active ingredient content detected at 0 month of tablet) X100%.
The tablet acceleration condition is that the temperature is 40 ℃ plus or minus 2 ℃ and the relative humidity is 75 percent plus or minus 5 percent.
Examples 1 to 14: determination of embedding rate of vitamin B microencapsulated embedding particles
Mixing hydrophobic materials with mono-diglycerol fatty acid ester and stearic acid, or mono-diglycerol fatty acid ester and palmitic acid, or mono-diglycerol fatty acid ester and carnauba wax according to a proportion, heating and melting at 70-80 ℃, adding the raw material of vitamin B1, stirring and dissolving uniformly, spray cooling, collecting, and preparing the vitamin B microencapsulated embedding particles. The contents of the components are shown in tables 1 to 3 below. The resulting vitamin B microencapsulated embedding granules were measured for the embedding rate of vitamin B1.
TABLE 1
Figure BDA0003198841160000111
TABLE 2
Figure BDA0003198841160000112
Figure BDA0003198841160000121
TABLE 3
Figure BDA0003198841160000122
The vitamin B1 embedding rate of the prepared microencapsulated embedding particles is higher than that of the combination of the mono-diglycerol fatty acid ester and stearic acid or palmitic acid or carnauba wax in a specific ratio range (3: 7-8: 2). When the content range of the vitamin is adjusted (1% -40%), the vitamin B1 embedding rate is still high.
Examples 15 to 18: determination of embedding Rate
Heating and melting single monoglyceride and diglyceride fatty acid ester, single stearic acid, combination of monoglyceride and diglyceride fatty acid ester and beeswax, and combination of hydrogenated castor oil and stearic acid at 70-80 deg.C, adding vitamin B1 raw material, stirring and dissolving to uniformity, spray cooling, and collecting to obtain vitamin B microencapsulated embedding granule. The contents of the components are shown in table 4 below. The resulting vitamin B microencapsulated embedding granules were measured for the embedding rate of vitamin B1.
TABLE 4
Figure BDA0003198841160000123
Figure BDA0003198841160000131
Vitamin B1 is embedded by adopting single monoglyceride/diglycerol fatty acid ester or stearic acid, and the vitamin B microencapsulated embedding particles have a low vitamin B1 embedding rate. In addition, the vitamin B1 is embedded by adopting the combination of the mono-diglycerol fatty acid ester and the beeswax and the combination of the hydrogenated castor oil and the stearic acid, and the vitamin B1 embedding rate of the vitamin B microencapsulated embedded particles is also lower.
Examples 19 to 34: determination of the Retention Rate of tablets
Vitamin B1 microencapsulated granules obtained in the above examples were mixed with calcium citrate, sorbitol, and magnesium stearate to prepare vitamin mineral tablets, and the retention was measured. The process for preparing the vitamin mineral tablet comprises the following steps: mixing the vitamin B microencapsulated embedding granules, minerals and sorbitol, sieving, adding magnesium stearate, mixing, and tabletting. The contents of the components are shown in tables 5 to 7 below. The vitamin B1 tablets obtained were tested for vitamin B1 retention after 3 months under accelerated conditions (conditions of temperature 40 ℃ C. + -. 2 ℃ C., relative humidity 75%. + -. 5%).
TABLE 5
Examples 19 20 21 22 23 24
Vitamin B1 raw material (No treatment) 1％ 0 0 0 0 0
EXAMPLE 4 vitamin B1 microencapsulated Encapsulated particles 0 1％ 10％ 20％ 0 0
EXAMPLE 1 vitamin B1 microencapsulated Encapsulated particles 0 0 0 0 10％ 0
EXAMPLE 2 vitamin B1 microencapsulated Encapsulated particles 0 0 0 0 0 10％
Calcium citrate 50％ 50％ 50％ 50％ 50％ 50％
Sorbitol 48％ 48％ 39％ 29％ 39％ 39％
Magnesium stearate 1％ 1％ 1％ 1％ 1％ 1％
Accelerated retention rate of 3 months% 45.6 90.5 91.3 90.8 57.3 90.8
TABLE 6
Figure BDA0003198841160000132
Figure BDA0003198841160000141
TABLE 7
Examples 30 31 32 33 34
Example 9 vitamin B1 microencapsulated Encapsulated particles 10％ 0 0 0 0
EXAMPLE 10 vitamin B1 microencapsulated Encapsulated particles 0 10％ 0 0 0
EXAMPLE 12 vitamin B1 microencapsulated Encapsulated particles 0 0 10％ 0 0
Example 15 vitamin B1 microencapsulated Encapsulated particles 0 0 0 10％ 0
Example 17 vitamin B1 microencapsulated Encapsulated particles 0 0 0 0 10％
Calcium citrate 50％ 50％ 50％ 50％ 50％
Sorbitol 39％ 39％ 39％ 39％ 39％
Magnesium stearate 1％ 1％ 1％ 1％ 1％
Accelerated retention rate of 3 months% 90.9 93.2 91.7 49.5 68.8
When the mono-diglycerol fatty acid ester: the stearic acid, palmitic acid or carnauba wax are combined in a specific ratio range (3: 7-8:2), the obtained microencapsulated embedding particles have high vitamin B1 embedding rate, and the tablets containing the microencapsulated embedding particles have high vitamin B1 retention rate. When other combinations of hydrophobic materials are used, the resulting encapsulated granules have a low vitamin B1 entrapment rate and tablets containing the resulting encapsulated granules also have a low vitamin B1 retention rate.
Examples 35 to 42: retention Rate determination
Vitamin B1 microencapsulated granules obtained in the above example were mixed with minerals (copper gluconate, calcium carbonate or magnesium carbonate), sorbitol and magnesium stearate to prepare vitamin mineral tablets, and vitamin B1 retention was measured. The process for preparing the vitamin mineral tablet comprises the following steps: mixing the vitamin B microencapsulated embedding granules, minerals and sorbitol, sieving, adding magnesium stearate, mixing, and tabletting. The contents of the components are shown in table 8 below. The vitamin B1 retention was measured on the resulting tablets after 3 months at an accelerated speed (conditions of temperature 40 ℃ C. + -. 2 ℃ C., relative humidity 75%. + -. 5%).
TABLE 8
Figure BDA0003198841160000151
The vitamin B1 microcapsule embedding granule tablet has obviously improved vitamin B1 retention rate compared with the tablet prepared from conventional vitamin B1 raw material under the condition of containing different minerals, namely copper gluconate, calcium carbonate or magnesium carbonate.
Examples 43 to 49: determination of embedding rate and retention rate of vitamin B12 microencapsulated embedding particles
Mixing hydrophobic materials, namely the combination of mono-diglycerol fatty acid ester and stearic acid, the combination of mono-diglycerol fatty acid ester and palmitic acid, or the combination of mono-diglycerol fatty acid ester and carnauba wax according to a proportion, heating and melting at 70-80 ℃, adding the raw material of vitamin B12, stirring and dissolving to be uniform, spray-cooling, collecting, and preparing the vitamin B microencapsulated embedding particles. The contents of the components are shown in table 9 below.
The obtained vitamin B12 microencapsulated embedding granules are prepared into vitamin B12 mineral tablets with magnesium gluconate, calcium carbonate, sorbitol and magnesium stearate, and the retention rate of vitamin B12 is determined. The process for preparing the vitamin B12 mineral tablet comprises the following steps: mixing the vitamin B12 microcapsule embedding granule, mineral substance, and sorbitol, sieving, adding magnesium stearate, mixing, and tabletting. The contents of the components are shown in table 10 below. The resulting microencapsulated embedded granules and tablets were measured for vitamin B12 embedding rate and vitamin B12 retention rate after 3 months of acceleration (conditions of temperature 40 ℃ C. + -. 2 ℃ C., relative humidity 75%. + -. 5%).
TABLE 9
Examples 43 44 45
Vitamin B12 1％ 1％ 1％
Mono-and diglycerol fatty acid esters: stearic acid 99％(3:7) 99％(5:5) 99％(8:2)
The embedding rate% 92.4 91.5 90.8
Watch 10
Examples 46 47 48 49
Vitamin B12 raw material (No treatment) 1％ 0 1％ 0
EXAMPLE 43 vitamin B12 microencapsulated Encapsulated particles 0 10％ 0 10％
(iv) magnesium gluconate 50％ 50％ 0 0
Calcium carbonate 0 0 50％ 50％
Sorbitol 48％ 39％ 48％ 39％
Magnesium stearate 1％ 1％ 1％ 1％
Accelerated retention rate of 3 months% 51.3 93.2 69.5 82.1
The combination of the mono-diglycerol fatty acid ester and stearic acid is used for embedding the vitamin B12, the embedding rate of the vitamin B12 is up to 90%, and the retention rate of the vitamin B12 is obviously improved when the mineral-containing tablet prepared by using the vitamin B12 microencapsulated embedding particles contains different minerals, magnesium gluconate or calcium carbonate compared with the tablet prepared by using the conventional vitamin B12 raw material.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims (11)

1. A microencapsulated embedding particle comprising a hydrophobic material as a capsule wall and an active ingredient as a capsule core, wherein the hydrophobic material comprises a first hydrophobic material and a second hydrophobic material, the first hydrophobic material is a mono-diglycerol fatty acid ester, and the second hydrophobic material is one or more of a higher saturated fatty acid or carnauba wax, wherein the weight ratio of the first hydrophobic material to the second hydrophobic material is 1:4-9:1, preferably 3:7-8: 2;
preferably, the higher saturated fatty acid is one or more of dodecanoic acid, tetradecanoic acid, stearic acid, palmitic acid, eicosanoic acid, or docosanoic acid;
preferably, wherein the active ingredient is an active ingredient susceptible to degradation by a factor selected from the group consisting of: pH, light, temperature, oxygen, humidity, or metal ions;
preferably wherein the active ingredient is one or more of a vitamin, an enzyme, a probiotic, an amino acid, a carbohydrate, a polypeptide or an oil;
preferably wherein the vitamin is one or more of vitamin a, vitamin B, vitamin C, vitamin D, vitamin E, vitamin K, vitamin H, vitamin P, vitamin PP, vitamin M, vitamin T, vitamin U, folic acid or biotin;
preferably wherein vitamin B is one or more of vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6 or vitamin B12;
preferably, the raw material in which the microencapsulated embedding particles are made comprises 50 wt% to 99 wt%, preferably 60 wt% to 99 wt% of the hydrophobic material and 1 wt% to 50 wt%, preferably 1 wt% to 40 wt% of the active ingredient;
preferably, the microencapsulated embedded particles are prepared by a spray cooling method, and preferably, the spray cooling method comprises heating 60 wt% -99 wt% of hydrophobic material for melting, adding 1 wt% -40 wt% of active ingredient, stirring for dissolving uniformly, and spray cooling to obtain the microencapsulated embedded particles;
preferably wherein the hydrophobic material melts upon heating at a temperature of from 70 ℃ to 80 ℃.
2. A process for the preparation of microencapsulated embedding granules according to claim 1, which comprises heating to melt 50% to 99%, preferably 60% to 99%, by weight of a hydrophobic material, adding 1% to 50%, preferably 1% to 40%, by weight of an active ingredient, stirring to dissolve uniformly, and spray cooling to obtain microencapsulated embedding granules; preferably wherein the hydrophobic material melts upon heating at a temperature of from 70 ℃ to 80 ℃.
3. A composition comprising the microencapsulated embedded particles of claim 1, preferably from 1 wt% to 20 wt% microencapsulated embedded particles, preferably the microencapsulated embedded particles comprise vitamin B, preferably one or both of vitamin B1 or vitamin B12;
preferably wherein the composition comprises a human required mineral, preferably 10 wt% to 50 wt% of a human required mineral;
preferably wherein the composition comprises a filler, preferably 10 wt% to 50 wt% filler;
preferably wherein the composition comprises a lubricant, preferably 1 wt% to 3 wt% lubricant.
4. The composition of claim 3, further comprising other vitamins than vitamin B1 or vitamin B12, preferably one or more of vitamin B2, vitamin B3, vitamin B5, vitamin B6, folic acid, biotin, vitamin C, vitamin A, vitamin D or vitamin K, preferably in an amount of more than 0 wt% and equal to or less than 20 wt%.
5. The composition of any of claims 3-4, wherein the mineral is one or more of a calcium salt, a magnesium salt, a copper salt or a zinc salt, preferably the mineral is one or more of calcium carbonate, calcium citrate, magnesium carbonate, magnesium oxide, copper gluconate, copper sulfate or zinc oxide.
6. A composition according to any one of claims 3 to 5, wherein the filler is one or more of sorbitol, starch, microcrystalline cellulose, dextrin, powdered sugar, lactose or an inorganic calcium salt.
7. The composition of any of claims 3-6, wherein the lubricant is one or more of magnesium stearate, talc, boric acid, hydrogenated vegetable oil, or PEG-based compounds.
8. A process for preparing a tablet from the composition of any one of claims 3 to 7, comprising the step of tabletting the composition; preferably, the microencapsulated embedding granules according to claim 2 are mixed with minerals and fillers, or when other vitamins are present, the microencapsulated embedding granules, other vitamins, minerals and fillers are mixed, sieved, mixed with a lubricant, and finally subjected to a machine-tabletting step.
9. A tablet prepared by the process of claim 8.
10. Use of the tablet of claim 9 in food, health products or pharmaceuticals.
11. Use of a hydrophobic material as a wall of a microencapsulated embedded particle, wherein the hydrophobic material comprises a first hydrophobic material and a second hydrophobic material, the first hydrophobic material is a mono-diglycerol fatty acid ester, the second hydrophobic material is one or more of a higher saturated fatty acid or carnauba wax, wherein the weight ratio of the first hydrophobic material to the second hydrophobic material is 1:4-9:1, preferably 3:7-8: 2; preferably, the higher saturated fatty acid is one or more of dodecanoic acid, tetradecanoic acid, stearic acid, palmitic acid, eicosanoic acid, or docosanoic acid;
preferably, the raw material in which the microencapsulated embedding particles are made comprises 50 wt% to 99 wt%, preferably 60 wt% to 99 wt% of the hydrophobic material and 1 wt% to 50 wt%, preferably 1 wt% to 40 wt% of the active ingredient;
preferably, the microencapsulated embedded particles are prepared by a spray cooling method, and preferably, the spray cooling method comprises the steps of heating 60 wt% -99 wt% of hydrophobic materials for melting, adding 1 wt% -40 wt% of active ingredients, stirring for dissolving until the active ingredients are uniform, and performing spray cooling to obtain the microencapsulated embedded particles.
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