CN114796152B - Vitamin A acetate particle and preparation method thereof - Google Patents
Vitamin A acetate particle and preparation method thereof Download PDFInfo
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- CN114796152B CN114796152B CN202210518281.4A CN202210518281A CN114796152B CN 114796152 B CN114796152 B CN 114796152B CN 202210518281 A CN202210518281 A CN 202210518281A CN 114796152 B CN114796152 B CN 114796152B
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- vitamin
- mass
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- acetate
- oil
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- 229960000342 retinol acetate Drugs 0.000 title claims abstract description 58
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 title claims abstract description 58
- 235000019173 retinyl acetate Nutrition 0.000 title claims abstract description 58
- 239000011770 retinyl acetate Substances 0.000 title claims abstract description 58
- 239000002245 particle Substances 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- 238000002156 mixing Methods 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 14
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical group OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims description 43
- 239000000843 powder Substances 0.000 claims description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 108010010803 Gelatin Proteins 0.000 claims description 11
- 239000008273 gelatin Substances 0.000 claims description 11
- 229920000159 gelatin Polymers 0.000 claims description 11
- 235000019322 gelatine Nutrition 0.000 claims description 11
- 235000011852 gelatine desserts Nutrition 0.000 claims description 11
- 229920002261 Corn starch Polymers 0.000 claims description 10
- 239000008120 corn starch Substances 0.000 claims description 10
- 229910052751 metal Inorganic materials 0.000 claims description 10
- 239000002184 metal Substances 0.000 claims description 10
- 235000012239 silicon dioxide Nutrition 0.000 claims description 10
- 239000000377 silicon dioxide Substances 0.000 claims description 10
- 239000003963 antioxidant agent Substances 0.000 claims description 9
- 230000003078 antioxidant effect Effects 0.000 claims description 9
- 235000006708 antioxidants Nutrition 0.000 claims description 9
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical group CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 8
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 8
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 8
- 229910001882 dioxygen Inorganic materials 0.000 claims description 8
- 239000000945 filler Substances 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- 235000000346 sugar Nutrition 0.000 claims description 8
- 229910052785 arsenic Inorganic materials 0.000 claims description 7
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 claims description 7
- 239000011248 coating agent Substances 0.000 claims description 7
- 238000000576 coating method Methods 0.000 claims description 7
- 238000000227 grinding Methods 0.000 claims description 7
- 239000003921 oil Substances 0.000 claims description 7
- 229930006000 Sucrose Natural products 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 238000004806 packaging method and process Methods 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 239000005720 sucrose Substances 0.000 claims description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000011148 porous material Substances 0.000 claims description 4
- 238000005070 sampling Methods 0.000 claims description 4
- 238000012216 screening Methods 0.000 claims description 4
- 238000007873 sieving Methods 0.000 claims description 4
- 239000001569 carbon dioxide Substances 0.000 claims description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 150000002739 metals Chemical class 0.000 claims 1
- 125000000185 sucrose group Chemical group 0.000 claims 1
- 239000007921 spray Substances 0.000 abstract description 12
- 238000005469 granulation Methods 0.000 abstract description 11
- 230000003179 granulation Effects 0.000 abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 6
- 239000000126 substance Substances 0.000 abstract description 4
- 230000014759 maintenance of location Effects 0.000 abstract description 2
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 229940045997 vitamin a Drugs 0.000 description 14
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 10
- 239000011859 microparticle Substances 0.000 description 8
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 235000019155 vitamin A Nutrition 0.000 description 7
- 239000011719 vitamin A Substances 0.000 description 7
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
- NCYCYZXNIZJOKI-IOUUIBBYSA-N 11-cis-retinal Chemical compound O=C/C=C(\C)/C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-IOUUIBBYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 102000004330 Rhodopsin Human genes 0.000 description 4
- 108090000820 Rhodopsin Proteins 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 229960003471 retinol Drugs 0.000 description 3
- 235000020944 retinol Nutrition 0.000 description 3
- 239000011607 retinol Substances 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102000010175 Opsin Human genes 0.000 description 2
- 108050001704 Opsin Proteins 0.000 description 2
- NCYCYZXNIZJOKI-OVSJKPMPSA-N Retinaldehyde Chemical compound O=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-OVSJKPMPSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 2
- AZJQQNWSSLCLJN-UHFFFAOYSA-N 2-ethoxyquinoline Chemical compound C1=CC=CC2=NC(OCC)=CC=C21 AZJQQNWSSLCLJN-UHFFFAOYSA-N 0.000 description 1
- WIGIZIANZCJQQY-UHFFFAOYSA-N 4-ethyl-3-methyl-N-[2-[4-[[[(4-methylcyclohexyl)amino]-oxomethyl]sulfamoyl]phenyl]ethyl]-5-oxo-2H-pyrrole-1-carboxamide Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCC(C)CC2)C=C1 WIGIZIANZCJQQY-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 206010017553 Furuncle Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 208000001140 Night Blindness Diseases 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010037888 Rash pustular Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 206010043515 Throat cancer Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 150000001746 carotenes Chemical class 0.000 description 1
- 235000005473 carotenes Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000009786 epithelial differentiation Effects 0.000 description 1
- 230000008472 epithelial growth Effects 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000021552 granulated sugar Nutrition 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 208000029561 pustule Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 235000020945 retinal Nutrition 0.000 description 1
- 239000011604 retinal Substances 0.000 description 1
- 108010021975 retinal isomerase Proteins 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 150000004492 retinoid derivatives Chemical class 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 230000037394 skin elasticity Effects 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 208000005494 xerophthalmia Diseases 0.000 description 1
Classifications
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/174—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
- A23L33/15—Vitamins
- A23L33/155—Vitamins A or D
-
- 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
- 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
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
-
- 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
- A61K9/5021—Organic macromolecular compounds
- A61K9/5052—Proteins, e.g. albumin
- A61K9/5057—Gelatin
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Immunology (AREA)
- Toxicology (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Dermatology (AREA)
- Animal Husbandry (AREA)
- Zoology (AREA)
- Diabetes (AREA)
- Nutrition Science (AREA)
- Obesity (AREA)
- Mycology (AREA)
- Emergency Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The application relates to vitamin A acetate particles and a preparation method thereof, which do not adopt a spray granulation method generally adopted in the prior art, avoid the addition of water and organic solvents and reduce the process steps. Compared with the spray granulation method, the direct physical mixing granulation method improves the bioavailability and the stability of the preparation, increases the retention rate of vitamin A acetate in the preparation, reduces related substances, and has obvious superiority compared with other vitamin A acetate particles.
Description
Technical Field
The application relates to the field of biological medicines and food and feed, in particular to vitamin A acetate particles and a preparation method thereof.
Background
Vitamin a (vitamine a), also known as retinol (its aldehyde derivative, retinaldehyde), is a fat-soluble alcohol, in a variety of molecular forms. Wherein VA1 is mainly present in the retina of the animal liver, blood and eyeball.
Vitamin a is a nutrient necessary for complex organisms and affects almost all tissue cells of the organism in different ways. Although it is the earliest vitamin discovered, its physiological function has not been completely uncovered until now. To the current knowledge, vitamin a (including carotenes) is the most important physiological function including: 1. vision is maintained: vitamin a can promote the formation of photopigments in visual cells. All-trans retinal can be catalyzed by retinal isomerase to 4-cis-retinal, and 4-cis-retinal can be combined with opsin to rhodopsin (rhodopsin). The 4-cis-retinal in rhodopsin turns into full-trans-retinal after encountering light, and the visual stimulus is caused by the change of conformation, so that vision is caused. And the rhodopsin after exposure to light is unstable and is rapidly decomposed into opsin and total reverse retinoid, and the whole circulation process is restarted. The vitamin A can regulate the capability of the eyes to adapt to the intensity of external light so as to reduce the occurrence of night blindness and vision deterioration, maintain normal visual response and be beneficial to the treatment of various eye diseases (such as xerophthalmia, conjunctivitis and the like). Vitamin a is the earliest discovered and most known function of vision. 2. Promoting growth and development: retinol also has an action equivalent to steroid hormone, which promotes glycoprotein synthesis. Promoting growth and development, strengthening bone, and maintaining hair, teeth and gum health. 3. Maintaining the integrity of the epithelial structure: retinol and retinoic acid regulate gene expression, attenuate epithelial cell differentiation into scaly forms, and increase the number of epithelial growth factor receptors. Thus, vitamin A can regulate the growth of epithelial tissue cells and maintain the normal morphology and function of epithelial tissue. The skin is kept moist, the skin mucous membrane is prevented from being dried and keratinized, and the skin mucous membrane is not easy to be damaged by bacteria, thereby being beneficial to the treatment of acne, pustule, furuncle, skin surface ulcer and other diseases; is helpful for removing senile plaques; can maintain the health of tissue or organ surface. The deficiency of vitamin a can reduce the function of epithelial cells, leading to reduced skin elasticity, dry roughness, and loss of gloss. 4. Enhancing immunity: vitamin A helps to maintain immune system normal, and can strengthen body resistance to infectious diseases, especially respiratory tract infection and parasitic infection; is useful for treating emphysema and hyperthyroidism. 5. Scavenging free radicals: vitamin A also has certain antioxidation effect, and can neutralize harmful free radicals. In addition, many studies have shown that skin, lung, throat, bladder and esophagus cancers are all related to vitamin a intake; however, these studies remain to be clinically proven even further.
The vitamin A commonly used in the prior art is vitamin A acetate, is yellow prismatic crystal, is insoluble in water, and is easily dissolved in ethanol, oil, chloroform and diethyl ether. The vitamin A is more stable than vitamin A and is often prepared into a preparation form of microparticle powder, and the preparation process is to add an antioxidant and gelatin to prepare microparticles through spraying, but the microparticles are easy to absorb moisture, heat and acid gas or decompose after being subjected to visible light or moisture absorption, so that the content is reduced.
The prior art vitamin A acetate microparticles are prepared by spray granulation. Such as: in CN104186976a vitamin a acetate was added to an emulsifying pot and sprayed to a fluidized bed to prepare microparticles. In CN114315675A, vitamin A acetate crystals are added into carrier emulsion, and then spray granulation is carried out to prepare the vitamin A acetate particles.
Because the vitamin A acetate has extremely poor water solubility, can not be fully absorbed and utilized by animals, and has the problems of poor stability and easy oxidation. In the prior art CN105104759A and CN106667920A, the performance of the vitamin A acetate particles is improved by adding an emulsifier Tween, maltodextrin, polyethylene glycol and the like.
Therefore, there is a need in the art for a preparation method or process that can improve the stability, bioavailability, etc. of vitamin a acetate particles without adding other ingredients.
Disclosure of Invention
The application provides a preparation method of vitamin A acetate particles, which is characterized by comprising the following steps of: adding 100-400 parts by mass of vitamin A acetate and 1-15 parts by mass of antioxidant into a container, heating under the protection of non-oxygen gas, stirring and dissolving to obtain vitamin A oil; and mixing 50-200 parts by mass of gelatin, 200-800 parts by mass of sugar filler, 120-600 parts by mass of corn starch and 5-20 parts by mass of silicon dioxide uniformly in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to carry out grinding coating so as to effectively coat the vitamin A oil and powder wall materials, and screening to obtain vitamin A acetate particles, wherein more than 99% of the vitamin A acetate particles pass through an analysis screen with the aperture of 0.84mm, the moisture is less than or equal to 5%, the Pb weight metal content is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0mg/kg.
The preparation method is characterized in that the non-oxygen gas is as follows: nitrogen, inert gas, carbon dioxide.
The preparation method is characterized in that the sugar filling agent is one or more of sucrose, white granulated sugar, glucose, lactose, galactose and fructose.
The preparation method is characterized in that the antioxidant is one or more of 2, 6-di-tert-butyl-4-methylphenol (BHT), ethoxyquinoline, vitamin C and citric acid.
The preparation method is characterized by further comprising the steps of detecting and packaging, sampling the vitamin A acetate particles, mixing the particles after the particles are detected to be qualified, and detecting, packaging and warehousing the particles after the particles are detected to be qualified.
The preparation method is characterized in that 200 parts by mass of vitamin A acetate and 6 parts by mass of antioxidant are added into a container, and the mixture is heated and stirred for dissolution under the protection of non-oxygen gas to obtain vitamin A oil; and mixing 100 parts by mass of gelatin, 400 parts by mass of sugar filler, 284 parts by mass of corn starch and 10 parts by mass of silicon dioxide uniformly in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to carry out grinding coating, so that the vitamin A oil and powder wall materials are effectively coated, and sieving to obtain vitamin A acetate particles, wherein more than 99% of the vitamin A acetate particles pass through an analysis sieve with the aperture of 0.84mm, the moisture is less than or equal to 5%, the weight metal content of Pb is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0mg/kg.
The preparation method is characterized in that 400 parts by mass of vitamin A acetate and 12 parts by mass of antioxidant are added into a container, and the mixture is heated and stirred for dissolution under the protection of non-oxygen gas to obtain vitamin A oil; and mixing 94 parts by mass of gelatin, 300 parts by mass of sugar filler, 184 parts by mass of corn starch and 10 parts by mass of silicon dioxide uniformly in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to carry out grinding coating, so that the vitamin A oil and powder wall materials are effectively coated, and sieving to obtain vitamin A acetate particles, wherein more than 99% of the vitamin A acetate particles pass through an analysis sieve with the aperture of 0.84mm, the moisture is less than or equal to 5%, the weight metal content of Pb is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0mg/kg.
The preparation method is characterized in that the container is an oil dissolving kettle.
The application also provides vitamin A acetate particles, which are characterized by being prepared by the preparation process.
The preparation process is physical mixing, avoids a spray granulation method generally adopted in the prior art, avoids the addition of water and organic solvents, and reduces the process steps. Compared with the spray granulation method, the direct physical mixing granulation method improves the bioavailability and the stability of the preparation, increases the retention rate of vitamin A acetate in the preparation, reduces related substances, and has obvious superiority compared with other vitamin A acetate particles.
Drawings
Fig. 1: process flow diagram
Detailed Description
Example 1: preparation of 20% vitamin a acetate microparticles:
adding 200kg of vitamin A acetate and 6kg of BHT into an oil dissolving kettle, heating under the protection of nitrogen, stirring and dissolving to obtain vitamin A oil; in addition, 100kg of gelatin, 400kg of sucrose, 284kg of corn starch and 10kg of silicon dioxide are uniformly mixed in a mixer according to a certain proportion to obtain powder, then the powder and the vitamin A oil are added into a ball mill according to a certain proportion to be ground and coated, so that the vitamin A oil and the wall material of the powder are effectively coated under the action of mechanical chemical force, and the vitamin A acetate particles are obtained through screening. Sampling the vitamin A acetate particles, carrying out mixed batch after the detection is qualified, and carrying out metal detection, packaging and warehousing after the detection is qualified.
Example 2: preparation of 40% vitamin a acetate microparticles:
adding 400kg of vitamin A acetate and 12kg of BHT into an oil dissolving kettle, heating under the protection of nitrogen, stirring and dissolving to obtain vitamin A oil; and mixing 94kg of gelatin, 300kg of sucrose, 184kg of corn starch and 10kg of silicon dioxide uniformly in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to perform grinding coating, so that the vitamin A oil and wall materials of the powder are effectively coated under the action of mechanical chemical force, obtaining vitamin A acetate particles through screening, sampling the vitamin A acetate particles, mixing the particles after the detection is qualified, and performing metal detection, packaging and warehousing after the detection is qualified.
For the vitamin A acetate particles prepared in examples 1-2, the appearance was pale yellow to tan powder. Through detection, 100% of vitamin A acetate particles can pass through an analysis sieve with the aperture of 0.84mm, the moisture is less than or equal to 5%, the Pb weight metal content is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0mg/kg.
Comparative example 1:
adding 200kg of vitamin A acetate and 6kg of BHT into an oil dissolving kettle, heating under the protection of nitrogen, stirring and dissolving to obtain vitamin A oil; mixing 100kg gelatin, 400kg sucrose and pure water (90% -150% of solid mass) in a mixer according to a certain proportion, and heating for dissolving; adding vitamin A oil, mixed liquid and 284kg of corn starch and 10kg of silicon dioxide into a spray fluidized bed for spray granulation; the granularity is as follows: more than 99% passes through an analysis screen with a pore size of 0.84 mm.
Comparative example 2:
adding 400kg of vitamin A acetate and 12kg of BHT into an oil dissolving kettle, heating under the protection of nitrogen, stirring and dissolving to obtain vitamin A oil; mixing 94kg gelatin, 300kg sucrose and pure water (90% -150% of solid mass) in a mixer according to a certain proportion, and heating for dissolving; adding vitamin A oil, mixed liquid and 184kg of corn starch and 10kg of silicon dioxide into a spray fluidized bed for spray granulation; the granularity is as follows: more than 99% passes through an analysis screen with a pore size of 0.84 mm.
Example 3: the appearance, bioavailability, stability, etc. of the vitamin a acetate microparticles of examples 1-2 and comparative examples 1-2 were examined to obtain the following results:
compared with the conventional spray preparation method, the preparation method of the vitamin A acetate particles has the advantages that the bioavailability and stability of the vitamin A acetate particles are greatly improved, and the stability of the vitamin A acetate particles with 20 percent of content is optimal. Although the stability of the vitamin a acetate particles is reduced at 40%, the stability and bioavailability are also greatly improved compared to spray granulation.
The above description is a general description of the application. Variations in form and value may be substituted for the purpose of illustration and not limitation, as the terms are used herein, depending on the circumstances or actual requirements. Various changes and modifications may be made by one skilled in the art, and such equivalents are intended to fall within the scope of the application as defined in the following claims.
Claims (7)
1. A preparation method of vitamin A acetate particles is characterized in that: adding 100-400 parts by mass of vitamin A acetate and 1-15 parts by mass of antioxidant into a container, heating under the protection of non-oxygen gas, stirring and dissolving to obtain vitamin A oil; mixing 50-200 parts by mass of gelatin, 200-800 parts by mass of sugar filler, 120-600 parts by mass of corn starch and 5-20 parts by mass of silicon dioxide uniformly in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to carry out grinding coating so as to effectively coat the vitamin A oil and powder wall materials, and screening to obtain vitamin A acetate particles, wherein more than 99% of the vitamin A acetate particles pass through an analysis screen with the aperture of 0.84mm, the moisture is less than or equal to 5%, the Pb weight metal content is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0mg/kg;
the non-oxygen gas is one or more of nitrogen, inert gas and carbon dioxide;
the sugar filler is sucrose;
the antioxidant is 2, 6-di-tert-butyl-4-methylphenol (BHT).
2. The method of claim 1, further comprising the steps of inspecting and packaging, sampling the vitamin a acetate particles, mixing the particles after the particles are inspected to be qualified, inspecting the metals after the particles are inspected to be qualified, packaging, and warehousing.
3. The preparation method according to claim 1, wherein 200 parts by mass of vitamin a acetate and 6 parts by mass of an antioxidant are added into a container, and the mixture is heated and stirred to be dissolved under the protection of non-oxygen gas to obtain vitamin a oil; and mixing 100 parts by mass of gelatin, 400 parts by mass of sugar filler, 284 parts by mass of corn starch and 10 parts by mass of silicon dioxide uniformly in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to carry out grinding coating, so that the vitamin A oil and powder wall materials are effectively coated, and sieving to obtain vitamin A acetate particles, wherein more than 99% of the vitamin A acetate particles pass through an analysis sieve with the aperture of 0.84mm, the moisture is less than or equal to 5%, the weight metal content of Pb is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0mg/kg.
4. The preparation method according to claim 1, wherein 400 parts by mass of vitamin a acetate and 12 parts by mass of an antioxidant are added into a container, and the mixture is heated and stirred to be dissolved under the protection of non-oxygen gas to obtain vitamin a oil; and mixing 94 parts by mass of gelatin, 300 parts by mass of sugar filler, 184 parts by mass of corn starch and 10 parts by mass of silicon dioxide uniformly in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to carry out grinding coating, so that the vitamin A oil and powder wall materials are effectively coated, and sieving to obtain vitamin A acetate particles, wherein more than 99% of the vitamin A acetate particles pass through an analysis sieve with the aperture of 0.84mm, the moisture is less than or equal to 5%, the weight metal content of Pb is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0mg/kg.
5. The method of any one of claims 1-4, wherein the vessel is an oil tank.
6. The method of any one of claims 1-4, wherein more than 99.5% of the vitamin a acetate particles pass through an analytical sieve having a pore size of 0.84 mm.
7. The method of claim 6, wherein 100% of the vitamin a acetate particles pass through an analytical sieve having a pore size of 0.84 mm.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104186976A (en) * | 2014-08-11 | 2014-12-10 | 嘉兴天和诚生物科技有限公司 | Vitamin A acetate beadlet and production method thereof |
| CN110250521A (en) * | 2019-05-15 | 2019-09-20 | 万华化学集团股份有限公司 | A kind of preparation method of retinyl acetate microcapsules |
| CN113785987A (en) * | 2021-09-14 | 2021-12-14 | 万华化学集团股份有限公司 | Preparation method of vitamin A microcapsule |
| CN114315675A (en) * | 2022-01-05 | 2022-04-12 | 万华化学集团股份有限公司 | Preparation of hot water insoluble vitamin A acetate particles |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012129765A1 (en) * | 2011-03-25 | 2012-10-04 | 浙江新和成股份有限公司 | Method for preparing stable-type vitamin a microcapsules continuously |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104186976A (en) * | 2014-08-11 | 2014-12-10 | 嘉兴天和诚生物科技有限公司 | Vitamin A acetate beadlet and production method thereof |
| CN110250521A (en) * | 2019-05-15 | 2019-09-20 | 万华化学集团股份有限公司 | A kind of preparation method of retinyl acetate microcapsules |
| CN113785987A (en) * | 2021-09-14 | 2021-12-14 | 万华化学集团股份有限公司 | Preparation method of vitamin A microcapsule |
| CN114315675A (en) * | 2022-01-05 | 2022-04-12 | 万华化学集团股份有限公司 | Preparation of hot water insoluble vitamin A acetate particles |
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