CN108159406B - Nattokinase pan-molding pill and preparation method thereof - Google Patents
Nattokinase pan-molding pill and preparation method thereof Download PDFInfo
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- CN108159406B CN108159406B CN201810136000.2A CN201810136000A CN108159406B CN 108159406 B CN108159406 B CN 108159406B CN 201810136000 A CN201810136000 A CN 201810136000A CN 108159406 B CN108159406 B CN 108159406B
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- 108010073682 nattokinase Proteins 0.000 title claims abstract description 137
- 229940086319 nattokinase Drugs 0.000 title claims abstract description 135
- 239000006187 pill Substances 0.000 title claims abstract description 58
- 238000000465 moulding Methods 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title claims abstract description 30
- 239000007779 soft material Substances 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims abstract description 31
- 235000012907 honey Nutrition 0.000 claims abstract description 29
- 239000000463 material Substances 0.000 claims abstract description 23
- 235000013871 bee wax Nutrition 0.000 claims abstract description 19
- 239000012166 beeswax Substances 0.000 claims abstract description 18
- 229920001353 Dextrin Polymers 0.000 claims abstract description 13
- 239000004375 Dextrin Substances 0.000 claims abstract description 13
- 235000019425 dextrin Nutrition 0.000 claims abstract description 13
- 235000013305 food Nutrition 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 9
- 239000011247 coating layer Substances 0.000 claims abstract description 6
- 239000012792 core layer Substances 0.000 claims abstract description 4
- 239000008188 pellet Substances 0.000 claims description 26
- 239000000843 powder Substances 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 238000002156 mixing Methods 0.000 claims description 12
- 238000007670 refining Methods 0.000 claims description 12
- 239000001993 wax Substances 0.000 claims description 11
- 150000001720 carbohydrates Chemical class 0.000 claims description 10
- 239000012174 chinese wax Substances 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 7
- 238000002844 melting Methods 0.000 claims description 7
- 230000008018 melting Effects 0.000 claims description 7
- 238000005303 weighing Methods 0.000 claims description 7
- 238000005485 electric heating Methods 0.000 claims description 6
- 239000004203 carnauba wax Substances 0.000 claims description 4
- 235000013869 carnauba wax Nutrition 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 235000013312 flour Nutrition 0.000 claims description 4
- 230000036541 health Effects 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 2
- 238000004806 packaging method and process Methods 0.000 claims description 2
- 229940100445 wheat starch Drugs 0.000 claims description 2
- 230000002779 inactivation Effects 0.000 abstract description 22
- 210000004051 gastric juice Anatomy 0.000 abstract description 13
- 229920003023 plastic Polymers 0.000 abstract description 7
- 239000004033 plastic Substances 0.000 abstract description 7
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 239000011248 coating agent Substances 0.000 abstract description 3
- 238000000576 coating method Methods 0.000 abstract description 3
- 235000013402 health food Nutrition 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 230000007774 longterm Effects 0.000 abstract 1
- 229940126680 traditional chinese medicines Drugs 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 41
- 102000004190 Enzymes Human genes 0.000 description 27
- 108090000790 Enzymes Proteins 0.000 description 27
- 229940088598 enzyme Drugs 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 210000002784 stomach Anatomy 0.000 description 13
- 230000000968 intestinal effect Effects 0.000 description 11
- 239000007787 solid Substances 0.000 description 10
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 9
- 230000002496 gastric effect Effects 0.000 description 8
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 8
- CNNRPFQICPFDPO-UHFFFAOYSA-N octacosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCO CNNRPFQICPFDPO-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- 238000001514 detection method Methods 0.000 description 6
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 239000012153 distilled water Substances 0.000 description 5
- 239000003094 microcapsule Substances 0.000 description 5
- 238000005070 sampling Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 229960002666 1-octacosanol Drugs 0.000 description 4
- 229920000426 Microplastic Polymers 0.000 description 4
- 235000021314 Palmitic acid Nutrition 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000013270 controlled release Methods 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 4
- 235000013557 nattō Nutrition 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 238000005096 rolling process Methods 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000002932 luster Substances 0.000 description 3
- 230000002537 thrombolytic effect Effects 0.000 description 3
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 2
- 244000063299 Bacillus subtilis Species 0.000 description 2
- 235000014469 Bacillus subtilis Nutrition 0.000 description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
- 239000004373 Pullulan Substances 0.000 description 2
- 229920001218 Pullulan Polymers 0.000 description 2
- 241000209140 Triticum Species 0.000 description 2
- 235000021307 Triticum Nutrition 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 235000021433 fructose syrup Nutrition 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 238000004898 kneading Methods 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 229940012957 plasmin Drugs 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 235000019423 pullulan Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 101710145796 Staphylokinase Proteins 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- 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 1
- 108050006955 Tissue-type plasminogen activator Proteins 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 239000004164 Wax ester Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127217 antithrombotic drug Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- SUPCQIBBMFXVTL-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate Chemical group CCOC(=O)C(C)=C SUPCQIBBMFXVTL-UHFFFAOYSA-N 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229940049370 fibrinolysis inhibitor Drugs 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000002874 hemostatic agent Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 235000015141 kefir Nutrition 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 108010070324 lumbrokinase Proteins 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000007180 physiological regulation Effects 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 235000019386 wax ester Nutrition 0.000 description 1
- 229940045860 white wax Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
-
- 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
- A23L29/06—Enzymes
-
- 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
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/288—Compounds of unknown constitution, e.g. material from plants or animals
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21062—Subtilisin (3.4.21.62)
-
- 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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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Food Science & Technology (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
- Botany (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention belongs to the technical field of food production, and particularly relates to a nattokinase pan-molding pill and a preparation method thereof. The invention comprises a soft material coating layer and an active pill core layer, wherein the soft material coating layer of the nattokinase plastic pill comprises beeswax, honey and dextrin; the nattokinase active pill core layer comprises dextrin: natto kinase =1:1, and the prepared pan-molding pill natto kinase has the content of 500 +/-20 FU/pill. The invention provides a method for preparing natto kinase coating pan-molding pills, which comprises the following steps: 1) preparing nattokinase; 2) pretreatment of honey; 3) preparing a soft material of the universal plastic pill; 4) preparing the coated plastic pill. The invention solves the key problem of inactivation in gastric juice of nattokinase, the used auxiliary materials are selected from the materials of homology of medicine and food of traditional Chinese medicines, and the method is scientific, reasonable in process and beneficial to environmental protection and is harmless to people after long-term use. The invention can be widely applied to the fields of food, health food, medicine production and the like.
Description
(I) technical field
The invention belongs to the technical field of food production, and particularly relates to a nattokinase pan-molding pill and a preparation method thereof.
(II) background of the invention
Thrombus diseases bring serious threats to human health, and nowadays, various novel antithrombotic drugs appear successively, such as streptokinase, urokinase, t-PA, lumbrokinase, staphylokinase and the like, and the thrombolytic agents have the defects of large side effect, high cost, low titer, easiness in causing bleeding, incapability of oral administration and only intravenous injection, high price, short source and the like.
Nattokinase was first discovered and named by Nakayasu et al in Japan, and was originally isolated from Natto, and a secondary metabolite produced by Bacillus subtilis was a serine protease having a thrombolytic activity 4 times that of plasmin and a single-chain polypeptide protease linked by 275 amino acids and having a relative molecular weight of 27728. Nattokinase can directly dissolve cross-linked thrombus, inactivate fibrinolysis inhibitor, increase synthesis of in vivo thrombolytic factor, catalyze the conversion of plasminogen into plasmin and the like, and has enhanced thrombolytic activity in vivo. It also has a number of advantages over other drugs, such as: the nattokinase has the advantages of high activity, high edible safety, no toxic or side effect, no corresponding immunogenicity, capability of being digested and absorbed by human bodies, capability of being injected into veins and directly taken orally, long half-life time of the medicine, low price, prevention effect and the like, and shows that the nattokinase has great application potential in the aspect of future thrombus treatment. However, the change of temperature and pH value in the external environment can promote the corresponding change of the structure of the nattokinase, thereby leading to the reduction or inactivation of the enzymatic activity of the nattokinase.
The beeswax is wax secreted by worker bee wax gland, and bee uses it to build nest, and has the special fragrance of honey and pollen. It can be divided into yellow wax and white wax according to color. Beeswax also has excellent malleability, consistency and plasticity. Beeswax is rich in flavonoid, wax ester, free fatty acid, fatty alcohol, hydrocarbon, vitamins and other chemical components, octacosanol is an important natural component in beeswax and the content of octacosanol can reach 10-25%, octacosanol is discovered to have certain prevention and treatment effects on reproductive disorders in 1937 and is widely concerned by researchers at home and abroad, and the octacosanol is discovered to have physiological regulation effects through research of scientists, for example: enhancing endurance and physical strength, improving reaction sensitivity, and promoting lipid metabolism. The polarity of the palmitic acid bee fat contained in the beeswax is small, the palmitic acid bee fat is insoluble in water, if the addition amount of the beeswax is large, the palmitic acid bee fat is directly prepared into a wax pill and then is released very slowly in the stomach and in the intestine, if the addition amount of the beeswax is small, the palmitic acid bee fat can be released and inactivated quickly in the stomach, and the purpose of releasing the target in the intestine cannot be achieved.
There have been many studies on the natto kinase dosage form. Chinese patent application CN02807004.6 of Nippon kefir corporation discloses a health food containing nattokinase and milk fermentation product, which is prepared by preparing nattokinase into a coating tablet; chinese patent CN201510599749.7 provides a preparation method of nattokinase microcapsules, which is characterized in that sodium alginate, hydroxypropyl methylcellulose and calcium chloride are used for embedding nattokinase to prepare the nattokinase microcapsules; chinese patent application CN201610852757.2 discloses a nattokinase microcapsule and a preparation method thereof, which is to mix protein, nattokinase and ethanol water evenly and carry out electrospray to obtain the nattokinase microcapsule; chinese patent CN200610104484.X provides natto kinase capsule and its preparation method; chinese patent application CN201210031516.3 discloses a nattokinase enteric capsule and a preparation method thereof, wherein the nattokinase is coated by methacrylic acid-ethyl acrylate-copolymer to obtain the nattokinase enteric capsule; chinese patent application CN201710672349.3 discloses a controlled release tablet health product containing nattokinase and a preparation method thereof, wherein a sustained release controlled release tablet is prepared by coating nattokinase, a boosting layer and a semipermeable membrane; chinese patent application CN201710231153.0 discloses a Longxiangyu nattokinase beverage and a preparation method thereof, which utilizes natto, bacillus subtilis natto, Longxiangyu powder and food additives to prepare the nattokinase beverage; patent CN20140198490.0 provides a nattokinase oral emulsion and a preparation method thereof, which utilizes phospholipid, beeswax, deoxycholic acid emulsifier and oil to prepare the nattokinase oral emulsion. In summary, the following problems exist in the production and application of the current nattokinase product: (1) ethanol is used as a solvent, so that potential safety hazards exist, and unpleasant odor cannot be improved. (2) The existing dosage forms such as tablets, capsules, granules and the like have complex process, low nattokinase active ingredients and low absorption rate and utilization rate, and the key is that the dosage forms are not suitable for food. (3) The embedding rate of the nattokinase microcapsules is low. (4) Nattokinase drinks, emulsifiers and the like have the problem that nattokinase is inactivated in gastric juice.
The invention solves the key problem of inactivation in the gastric juice of the nattokinase, realizes the controlled release of the nattokinase in the intestinal environment, has unpleasant odor when being orally taken, and adopts the materials which are homologous with the traditional medicine and food in China as auxiliary materials which are harmless to people after being taken for a long time.
Disclosure of the invention
The invention provides a nattokinase pan-molding pill and a preparation method thereof in order to make up for the defects of the prior art.
The invention is realized by the following technical scheme:
a nattokinase pan-molding pill and a preparation method thereof comprise the following steps:
(1) sugar pretreatment:
pouring the saccharide components into a beaker, slowly heating by using an electric heating sleeve, refining for about 2 hours when the temperature reaches 116-119 ℃, and stopping refining when bubbles with large reddish brown gloss appear;
(2) preparing a soft material:
putting the refined saccharide components and wax into a beaker, melting in water bath, adding auxiliary materials with equal weight, and quickly stirring and uniformly mixing to form a dough to obtain a soft material;
(3) preparing nattokinase:
according to the method, the method comprises the following steps of: the auxiliary material =1:1 (w/w), and the nattokinase diluted medicinal powder is obtained by mixing evenly, and the content is 20000 +/-80 FU/g;
(4) preparing the pan-molding pill:
weighing soft materials, and packaging nattokinase dilution powder into the soft materials, wherein the soft materials are as follows: and (3) kneading the nattokinase diluent powder = 16-20: 1 (w/w) into pellets to obtain the nattokinase pan-molded pellets, wherein each pellet contains 500 +/-20 FU of nattokinase.
Wherein the nattokinase pan-molding pill comprises a soft material coating layer and an active pill core layer.
Further, the saccharide component comprises: one or more of honey, fructose syrup, maltose syrup and pullulan.
Further, the auxiliary materials include: dextrin, starch, wheat flour or a combination of more than one of them.
Further, the wax includes: beeswax, Chinese wax, or carnauba wax.
Further, the soft material in the step (2) is a soft material coating layer and comprises the following components in parts by weight: 1.5-2.0 parts of wax, 3.0-3.5 parts of saccharide component and 5 parts of auxiliary material.
Further, the nattokinase diluted medicinal powder in the step (3) is an active pill core and comprises the following components in parts by weight: nattokinase: adjuvant =1:1 (w/w).
The preparation process is applied to the fields of food, health-care food and medicines; the method specifically comprises the following steps:
the natto kinase plastic pill is used for preparing food; the nattokinase pan-molding pill is used for preparing medicines; the natto kinase plastic pill is used for preparing health products.
The invention has the beneficial effects that: the invention effectively solves the problems of inactivation of gastric juice and unpleasant odor of the nattokinase and realizes the controlled release of the nattokinase in the intestinal environment. The method is scientific, reasonable in process and beneficial to environmental protection. The invention can be widely applied to the fields of food, health food, medicine production and the like, in particular to the field of food.
(IV) detailed description of the preferred embodiments
Example 1 Effect of different sugars in Nattokinase Pan-Molding pellets on Nattokinase Activity in stomach
(1) Sugar pretreatment
Pouring honey, fructose syrup, maltose syrup, pullulan and the like into a beaker, adding purified water, slowly heating by using an electrothermal sleeve at the temperature of 116-119 ℃, refining for about 2 hours until bubbles with large reddish brown gloss appear, and stopping refining;
(2) preparation of natto kinase
According to the method, the method comprises the following steps of: starch auxiliary material =1:1 (w/w), and mixing uniformly to obtain nattokinase diluted medicinal powder with the content of about 20000 FU/g;
(3) preparation of soft materials
Putting the refined sugar and Chinese wax (Chinese wax: honey =1.5:3.5 (w/w)) into a beaker, melting in water bath, adding starch auxiliary materials with equal weight, and quickly stirring and uniformly mixing to form a dough; obtaining the soft material.
(4) Preparation of pan-molded pellets
Weighing 0.45g of soft material, wrapping 0.025g of nattokinase dilution powder in the soft material, and rolling into pellets to obtain the nattokinase coated plastic pellets, wherein each pellet contains about 500FU of nattokinase.
(5) Detection of enzyme activity and gastric inactivation rate of nattokinase
Checking the pan-molded pill in a hydrochloric acid solution (9 → 1000) for 2 hours, sampling once every hour, washing the taken sample with distilled water, putting the sample into a centrifuge tube, adding intestinal juice, and measuring the activity loss rate of the enzyme in the stomach after treatment, wherein the activity of the enzyme of the nattokinase is measured according to the method disclosed in Chinese patent CN 201510685728.7.
TABLE 1 enzymatic in-stomach inactivation rates of nattokinase with different saccharides
As shown in the table above, the enzyme activity of the pan-molding pill after being added with honey and treated by the artificial gastric juice for 2h is 88 percent, and the enzyme activity of the nattokinase has the lowest inactivation quantity in the stomach.
Example 2 Effect of adding different excipients on the enzymatic in-stomach inactivation Rate of Nattokinase
(1) Pretreatment of honey
Pouring honey into a beaker, adding purified water, slowly heating by using an electric heating sleeve, refining for about 2 hours when the temperature reaches 116-119 ℃, and stopping refining the honey when bubbles with reddish brown luster are generated;
(2) preparation of natto kinase
Respectively and uniformly mixing dextrin, starch and wheat flour with nattokinase according to a ratio of 1:1 (w/w) to obtain nattokinase diluted medicinal powder with the content of about 20000 FU/g;
(3) preparation of soft materials
Putting the refined honey and Chinese wax (Chinese wax: honey =1.5:3.5 (w/w)) into a beaker, melting in water bath, adding the auxiliary materials (dextrin or starch or wheat flour) with equal weight, and rapidly stirring and uniformly mixing to form a dough; to obtain a soft material
(4) Preparation of pan-molded pellets
Weighing 0.45g of soft material, wrapping 0.025g of nattokinase dilution powder in the soft material, and rolling into pellets to obtain the nattokinase coated plastic pellets, wherein each pellet contains about 500FU of nattokinase.
(5) Detection of enzyme activity and gastric inactivation rate of nattokinase
Checking the pan-molded pill in a hydrochloric acid solution (9 → 1000) for 2 hours, sampling once every hour, washing the taken sample with distilled water, putting the sample into a centrifuge tube, adding intestinal juice, and measuring the activity loss rate of the enzyme in the stomach after treatment, wherein the activity of the enzyme of the nattokinase is measured according to the method disclosed in Chinese patent CN 201510685728.7.
TABLE 2 enzyme activity in stomach inactivation rate of nattokinase by adding different auxiliary materials
As shown in the table above, dextrin auxiliary materials are added into the pan-molding pill, the intra-gastric inactivation rate of the enzyme activity is 89% after the 2h enzyme activity is processed by the artificial gastric juice, and the intra-gastric inactivation amount of the nattokinase activity is the lowest.
Example 3 Effect of the addition of different waxes on the gastric inactivation of the enzyme Activity of Nattokinase
(1) Pretreatment of honey
Pouring honey into a beaker, adding purified water, slowly heating by using an electric heating sleeve, refining for about 2 hours when the temperature reaches 116-119 ℃, and stopping refining the honey when bubbles with reddish brown luster are generated;
(2) preparation of natto kinase
According to the method, the method comprises the following steps of: dextrin auxiliary material =1:1 (w/w), and is uniformly mixed to obtain nattokinase diluted medicinal powder with the content of about 20000 FU/g;
(3) preparation of soft materials
Putting beeswax or Chinese wax or carnauba wax and refined honey into a beaker according to the weight ratio of 1.5:3.5, melting in a water bath, adding dextrin auxiliary materials with equal weight, and quickly stirring and uniformly mixing to form a dough; obtaining the soft material.
(4) Preparation of pan-molded pellets
Weighing 0.45g of soft material, wrapping 0.025g of nattokinase dilution powder in the soft material, and rolling into pellets to obtain the nattokinase coated plastic pellets, wherein each pellet contains about 500FU of nattokinase.
(5) Detection of enzyme activity and gastric inactivation rate of nattokinase
Checking the pan-molded pill in a hydrochloric acid solution (9 → 1000) for 2 hours, sampling once every hour, washing the taken sample with distilled water, putting the sample into a centrifuge tube, adding intestinal juice, and measuring the activity loss rate of the enzyme in the stomach after treatment, wherein the activity of the enzyme of the nattokinase is measured according to the method disclosed in Chinese patent CN 201510685728.7.
TABLE 3 addition of different wax nattokinase enzyme activity in stomach inactivation rate
As shown in the table above, the enzyme activity of the pan-molding pill after being added with beeswax and being treated by artificial gastric juice for 2h is 91 percent, and the enzyme activity of the nattokinase has the lowest inactivation quantity in the stomach.
Example 4 Effect of different ratios of beeswax to Honey on the gastric inactivation of Nattokinase enzyme
(1) Pretreatment of honey
Pouring honey into a beaker, adding purified water, slowly heating by using an electric heating sleeve, refining for about 2 hours when the temperature reaches 116-119 ℃, and stopping refining the honey when bubbles with reddish brown luster are generated;
(2) preparation of natto kinase
According to the method, the method comprises the following steps of: dextrin auxiliary material =1:1 (w/w), and is uniformly mixed to obtain nattokinase diluted medicinal powder with the content of about 20000 FU/g;
(3) preparation of soft materials
Putting beeswax or Chinese wax or carnauba wax and refined honey into a beaker according to the weight ratio of table 4, melting in a water bath, adding dextrin auxiliary materials with equal weight, and quickly stirring and uniformly mixing to form a dough; obtaining the soft material.
(4) Preparation of pan-molded pellets
Weighing 0.45g of soft material, wrapping 0.025g of nattokinase dilution powder in the soft material, and rolling into pellets to obtain the nattokinase coated plastic pellets, wherein each pellet contains about 500FU of nattokinase.
(5) Disintegration time limit detection of coated and molded pill
The above-mentioned pellets were individually examined in a hydrochloric acid solution (9 → 1000) for 2 hours, followed by taking out the hanging baskets, washing with a small amount of water, adding baffles to each tube, and then examined in a phosphate buffer (pH6.8) as described above.
TABLE 4 disintegration of the Pan-plasto-pellets in artificial gastric juice and artificial intestinal juice
As seen from the above table, when the ratio of beeswax to honey is 1.8:3.2, there is no crack, disintegration or softening phenomenon in the artificial gastric juice, and the product can be disintegrated rapidly in the artificial intestinal juice, which meets the regulation of disintegration time limit inspection method in pharmacopoeia of the people's republic of China.
(6) Detection of enzyme activity and gastric inactivation amount of nattokinase in coated and molded pill
Checking the pan-molded pill in a hydrochloric acid solution (9 → 1000) for 2 hours, sampling once every hour, washing the taken sample with distilled water, putting the sample into a centrifuge tube, adding intestinal juice, and measuring the activity loss rate of the enzyme in the stomach after treatment, wherein the activity of the enzyme of the nattokinase is measured according to the method disclosed in Chinese patent CN 201510685728.7.
TABLE 5 enzymatic in-stomach inactivation rate of nattokinase in pan-molded pill
As shown in the table above, the enzyme activity of the natto kinase pan-molding pill after being treated by the artificial gastric juice for 2 hours reaches 93.6 percent, and the natto kinase can still keep high activity.
Example 5
The manufacturing method of the natto kinase solid pan-molding pill specifically comprises the following steps:
(1) pretreatment of honey
Pouring sugar such as honey into a beaker, slowly heating by using an electric heating sleeve at the temperature of 116-;
(2) preparation of natto kinase
According to the method, the method comprises the following steps of: dextrin auxiliary material =1:1 (w/w), and is uniformly mixed to obtain nattokinase diluted medicinal powder with the content of about 20000 FU/g;
(3) preparation of soft materials
Putting the refined honey and beeswax (beeswax: honey =1.5:3.5 (w/w)) into a beaker, melting in a water bath, adding dextrin auxiliary materials with equal weight, and quickly stirring and uniformly mixing to form a dough; obtaining the soft material.
(4) Preparation of solid plastic pill of natto kinase
Pouring the nattokinase mixed powder into the soft material, quickly stirring and uniformly mixing, weighing 0.475g, and kneading into pellets to obtain the nattokinase solid pan-molded pellets, wherein each pellet contains about 500FU of nattokinase.
(5) Disintegration time limit of solid and plastic pill
The solid pellets were examined in hydrochloric acid solution (9 → 1000) for 2 hours, the baskets were removed, washed with a small amount of water, and then the pellet was examined in phosphate buffer (pH6.8) as described above.
TABLE 6 disintegration of solid pan-molded pill in artificial gastric juice and artificial intestinal juice
As seen from the above table, the natto kinase solid pan-molded pill has no crack, disintegration or softening phenomenon in the artificial gastric juice, can be rapidly disintegrated in the artificial intestinal juice, and meets the regulation of disintegration time limit inspection method in pharmacopoeia of the people's republic of China.
(6) Detection of enzyme activity and stomach inactivation amount of nattokinase in solid pan-molded pill
Checking the pan-molded pill in a hydrochloric acid solution (9 → 1000) for 2 hours, sampling once every hour, putting the sampled sample into a centrifuge tube after being cleaned by distilled water, adding intestinal juice, manually processing, and measuring the activity loss rate of the enzyme in the stomach of the nattokinase, wherein the enzyme activity of the nattokinase is measured according to the method disclosed in Chinese patent CN 201510685728.7.
TABLE 7 gastric inactivation of enzyme activity of nattokinase in solid pan-molded pill
As shown in the table above, the enzyme activity of the solid natto kinase molding pill after being treated by the artificial gastric juice for 2 hours is 75.6 percent, and the gastric inactivation amount of the natto kinase activity enzyme is higher than that of the coated natto molding pill.
The present invention has been described above by way of example, but the present invention is not limited to the above-described specific embodiments, and any modification or variation made based on the present invention is within the scope of the present invention as claimed.
Claims (8)
1. A preparation method of nattokinase pan-molding pills is characterized by comprising the following steps: the method comprises the following steps:
(1) pretreatment of a saccharide component:
pouring the saccharide components into a beaker, slowly heating by using an electric heating sleeve, refining for 2 hours when the temperature reaches 116-119 ℃, and stopping refining when bubbles with large reddish brown gloss appear;
(2) preparing a soft material:
putting the refined saccharide components and wax into a beaker, melting in water bath, adding auxiliary materials with equal weight, and quickly stirring and uniformly mixing to form a dough to obtain a soft material;
(3) preparing nattokinase:
according to the method, the method comprises the following steps of: the auxiliary material =1:1 (w/w), and the nattokinase diluted medicinal powder is obtained by mixing evenly, and the content is 20000 +/-80 FU/g;
(4) preparing the pan-molding pill:
weighing soft materials, and packaging nattokinase diluted powder into the soft materials, wherein the honey cluster soft materials are as follows: the nattokinase diluent powder is = 16-20: 1 (w/w), and then the nattokinase diluent powder is kneaded into pellets to obtain nattokinase pan-molded pellets, wherein each pellet contains 500 +/-20 FU of nattokinase;
the saccharide component is honey;
the wax comprises: beeswax, Chinese wax, or carnauba wax.
2. The method for preparing natto kinase pan-molding pill according to claim 1, which is characterized in that: the nattokinase pan-molding pill comprises a soft material coating layer and an active pill core layer.
3. The method for preparing natto kinase pan-molding pill according to claim 1, which is characterized in that: the auxiliary materials comprise: dextrin, starch, wheat flour or a combination of more than one of them.
4. The method for preparing natto kinase pan-molding pill according to claim 1, which is characterized in that: the honey cluster soft material in the step (2) is a soft material coating layer and comprises the following components in parts by weight: 1.5-2.0 parts of wax, 3.0-3.5 parts of saccharide component and 5 parts of auxiliary material.
5. The method for preparing natto kinase pan-molding pill according to claim 1, which is characterized in that: the nattokinase diluted medicinal powder in the step (3) is an active pill core and comprises the following components in parts by weight: nattokinase: adjuvant =1:1 (w/w).
6. The use of the natto kinase pan-molding pill according to claim 1, which is characterized in that: the natto kinase pan-molding pill is used for preparing food.
7. The use of the natto kinase pan-molding pill according to claim 1, which is characterized in that: the nattokinase pan-molding pill is used for preparing medicines.
8. The use of the natto kinase pan-molding pill according to claim 1, which is characterized in that: the nattokinase pan-molding pill is used for preparing health products.
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