CN112972426A - NMN-containing capsule and preparation method thereof - Google Patents
NMN-containing capsule and preparation method thereof Download PDFInfo
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- CN112972426A CN112972426A CN202110201449.4A CN202110201449A CN112972426A CN 112972426 A CN112972426 A CN 112972426A CN 202110201449 A CN202110201449 A CN 202110201449A CN 112972426 A CN112972426 A CN 112972426A
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- 239000002775 capsule Substances 0.000 title claims abstract description 149
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 43
- 239000002105 nanoparticle Substances 0.000 claims abstract description 40
- 239000003381 stabilizer Substances 0.000 claims abstract description 33
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 32
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 30
- 239000003605 opacifier Substances 0.000 claims abstract description 24
- 239000002904 solvent Substances 0.000 claims abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 30
- 235000006708 antioxidants Nutrition 0.000 claims description 28
- 108010068370 Glutens Proteins 0.000 claims description 24
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 22
- 239000000243 solution Substances 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 15
- 239000000126 substance Substances 0.000 claims description 14
- 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 claims description 12
- 230000005684 electric field Effects 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 12
- 235000010413 sodium alginate Nutrition 0.000 claims description 12
- 239000000661 sodium alginate Substances 0.000 claims description 12
- 229940005550 sodium alginate Drugs 0.000 claims description 12
- 230000009471 action Effects 0.000 claims description 11
- 239000001110 calcium chloride Substances 0.000 claims description 11
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 11
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 10
- 238000004140 cleaning Methods 0.000 claims description 10
- 239000011259 mixed solution Substances 0.000 claims description 10
- 239000012074 organic phase Substances 0.000 claims description 10
- 241001678082 Dendrobium huoshanense Species 0.000 claims description 8
- 150000004676 glycans Chemical class 0.000 claims description 8
- 229920001282 polysaccharide Polymers 0.000 claims description 8
- 239000005017 polysaccharide Substances 0.000 claims description 8
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 7
- 229920000053 polysorbate 80 Polymers 0.000 claims description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims description 6
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 239000012071 phase Substances 0.000 claims description 6
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 5
- 229930003427 Vitamin E Natural products 0.000 claims description 5
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 5
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 5
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 5
- 229920000136 polysorbate Polymers 0.000 claims description 5
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- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 5
- 229940068984 polyvinyl alcohol Drugs 0.000 claims description 5
- 238000010298 pulverizing process Methods 0.000 claims description 5
- 238000002791 soaking Methods 0.000 claims description 5
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 5
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 235000019165 vitamin E Nutrition 0.000 claims description 5
- 229940046009 vitamin E Drugs 0.000 claims description 5
- 239000011709 vitamin E Substances 0.000 claims description 5
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims description 4
- 239000008346 aqueous phase Substances 0.000 claims description 4
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 3
- 108010010803 Gelatin Proteins 0.000 claims description 3
- 229930003268 Vitamin C Natural products 0.000 claims description 3
- 235000010410 calcium alginate Nutrition 0.000 claims description 3
- 239000000648 calcium alginate Substances 0.000 claims description 3
- 229960002681 calcium alginate Drugs 0.000 claims description 3
- OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=O)[C@H]1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 claims description 3
- 229920000159 gelatin Polymers 0.000 claims description 3
- 239000008273 gelatin Substances 0.000 claims description 3
- 235000019322 gelatine Nutrition 0.000 claims description 3
- 235000011852 gelatine desserts Nutrition 0.000 claims description 3
- 239000003094 microcapsule Substances 0.000 claims description 3
- 239000004408 titanium dioxide Substances 0.000 claims description 3
- 238000001132 ultrasonic dispersion Methods 0.000 claims description 3
- 235000019154 vitamin C Nutrition 0.000 claims description 3
- 239000011718 vitamin C Substances 0.000 claims description 3
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- 229920001661 Chitosan Polymers 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 229920003145 methacrylic acid copolymer Polymers 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 229940100467 polyvinyl acetate phthalate Drugs 0.000 claims description 2
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 claims 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 claims 1
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 claims 1
- 229960003943 hypromellose Drugs 0.000 claims 1
- 239000002245 particle Substances 0.000 abstract description 2
- DAYLJWODMCOQEW-TURQNECASA-N NMN zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)([O-])=O)O2)O)=C1 DAYLJWODMCOQEW-TURQNECASA-N 0.000 description 100
- 230000000052 comparative effect Effects 0.000 description 16
- 239000000047 product Substances 0.000 description 11
- 235000019441 ethanol Nutrition 0.000 description 8
- 239000004615 ingredient Substances 0.000 description 7
- 230000003647 oxidation Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 239000001856 Ethyl cellulose Substances 0.000 description 4
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- -1 carboxymethyl ethyl Chemical group 0.000 description 4
- 235000019325 ethyl cellulose Nutrition 0.000 description 4
- 229920001249 ethyl cellulose Polymers 0.000 description 4
- 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 4
- 229950006238 nadide Drugs 0.000 description 4
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical group O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- OIRDTQYFTABQOQ-KQYNXXCUSA-N Adenosine Natural products C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 3
- FZAQROFXYZPAKI-UHFFFAOYSA-N anthracene-2-sulfonyl chloride Chemical compound C1=CC=CC2=CC3=CC(S(=O)(=O)Cl)=CC=C3C=C21 FZAQROFXYZPAKI-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 230000000112 colonic effect Effects 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- VNWKDIUSXQCPGN-UHFFFAOYSA-J dicalcium tetrachloride Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Ca+2].[Ca+2] VNWKDIUSXQCPGN-UHFFFAOYSA-J 0.000 description 2
- HHEAADYXPMHMCT-UHFFFAOYSA-N dpph Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1[N]N(C=1C=CC=CC=1)C1=CC=CC=C1 HHEAADYXPMHMCT-UHFFFAOYSA-N 0.000 description 2
- 210000004211 gastric acid Anatomy 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000031891 intestinal absorption Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000015532 Nicotinamide phosphoribosyltransferase Human genes 0.000 description 1
- 108010064862 Nicotinamide phosphoribosyltransferase Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 230000006154 adenylylation Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000007227 biological adhesion Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000007760 free radical scavenging Effects 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000006228 supernatant Substances 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
- 238000012546 transfer Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—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
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5169—Proteins, e.g. albumin, gelatin
-
- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
-
- 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
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Nanotechnology (AREA)
- Toxicology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Manufacturing Of Micro-Capsules (AREA)
Abstract
The invention discloses a capsule containing NMN and a preparation method thereof, wherein the capsule comprises NMN nanoparticles, a first capsule layer and a second capsule layer, wherein the first capsule layer and the second capsule layer sequentially coat the NMN particles from inside to outside; wherein the first capsule layer comprises the following components in parts by weight: 4-8 parts of opacifier, 1-3 parts of stabilizer, 1-3 parts of antioxidant, 8-15 parts of slow release agent and 8-15 parts of enteric solvent; the second layer of capsules comprise the following components in parts by weight: 6-12 parts of opacifier, 3-5 parts of stabilizer, 4-7 parts of antioxidant, 10-20 parts of slow release agent and 12-25 parts of enteric agent. According to the invention, two capsule layers are coated outside the NMN nanoparticles, so that the influence of moisture, air and light on NMN can be avoided, the stability of the product is improved, and the NMN product can be stored for a long time.
Description
Technical Field
The invention relates to the technical field of NMN, in particular to a capsule containing NMN and a preparation method thereof.
Background
β -nicotinamide mononucleotide, english name: Beta-Nicotinamide Mononucleotide; for short: NMN; the molecular formula is as follows: c11H15N2O8P; molecular weight: 334.22. beta-Nicotinamide Mononucleotide (NMN) is the substrate for the synthesis of coenzyme I, which becomes coenzyme I (NAD) after adenylation by nicotinamide nucleotide adenyltransferase. The level of NMN and the activity of nicotinamide nucleotide adenosine transferase (NAMPT) in organisms directly influence the concentration of NAD, and simultaneously NMN directly participates in adenosine transfer in vivo, and is an important synthetic substrate and function regulating substance in vivo. In the aspect of treatment and application, NMN can be used for resisting aging, treating chronic diseases and the like, and meanwhile, research shows that NMN also has a regulating effect on the secretion of insulin and has an influence on the expression level of mRNA. Therefore, NMN has wide application prospect in the aspect of medical treatment and also has wide market prospect in the aspect of chemical engineering as a reaction substrate.
However, the NMN is unstable in chemical property and very sensitive to light and oxygen, and due to the high sensitivity and unstable biological characteristics, the NMN is difficult to store for a long time, so that the application and popularization of the NMN in the field of human health care are greatly limited.
Disclosure of Invention
In order to solve the above-mentioned disadvantages of the prior art, the present invention aims to provide a NMN-containing capsule and a preparation method thereof, so as to solve the problems of the prior art that NMN is unstable in chemical property and difficult to store for a long time.
The technical scheme for solving the technical problems is as follows: providing a NMN-containing capsule comprising: the NMN nano-particle comprises a first capsule layer and a second capsule layer, wherein the first capsule layer and the second capsule layer sequentially coat the NMN nano-particle from inside to outside;
wherein the first capsule layer comprises the following components in parts by weight: 4-8 parts of opacifier, 1-3 parts of stabilizer, 1-3 parts of antioxidant, 8-15 parts of slow release agent and 8-15 parts of enteric solvent;
the second layer of capsules comprise the following components in parts by weight: 6-12 parts of opacifier, 3-5 parts of stabilizer, 4-7 parts of antioxidant, 10-20 parts of slow release agent and 12-25 parts of enteric agent.
The beneficial effects of the above technical scheme are: according to the invention, two capsule layers are coated outside the NMN nanoparticles, so that the influence of moisture, air and light on NMN can be avoided, the stability of the product is improved, and the NMN product can be stored for a long time. In addition, although the ingredients of the first capsule layer and the second capsule layer are the same, the contents of the ingredients are different, and the photostability and the antioxidant activity of the NMN can be effectively improved only by the fact that the positions of the ingredients are different and the combination contents are different.
On the basis of the technical scheme, the invention can be further improved as follows:
further, the NMN nanoparticles are prepared by the following method:
dissolving a stabilizer in water to form an aqueous phase;
dissolving hordein and NMN in 70-80% ethanol to form an organic phase;
adding the organic phase into the water phase, stirring, removing ethanol, concentrating, drying, and pulverizing.
The beneficial effects of the above technical scheme are: the hordein has the characteristics of biological adhesion, can increase the contact of NMN and intestinal absorption parts, and can better exert the effect on the intestinal absorption parts; the hordeins contain hydroxyl groups, and the hydroxyl groups can form hydrogen bonds with amide groups of the NMN, so that the free energy of the NMN can be reduced, and the light stability of the NMN is further improved on the basis that the light stability of the NMN is improved by the first capsule layer and the second capsule layer; moreover, the hordeins also have natural antioxidant performance, and the antioxidant performance of NMN can be further improved on the basis that the antioxidant performance of NMN is improved by the first capsule layer and the second capsule layer.
The NMN is prepared into the nanoparticles, the particle size is small, the NMN nanoparticles have high dispersibility and large surface area, the solubility and the dissolution speed of the medicine can be increased, and the contact with the intestinal canal wall can also be increased, so that the absorption opportunity is increased, and the utilization rate of the medicine is improved.
Further, the stabilizer used in the preparation process of the NMN nanoparticles is Tween-80, span-80 or polyvinyl alcohol.
Further, the weight ratio of hordein, NMN and stabilizer is 15-30: 100: 5-12, preferably 20: 100: 8.
further, the first capsule layer comprises the following components in parts by weight: 4 parts of opacifier, 2 parts of stabilizer, 1 part of antioxidant, 10 parts of slow release agent and 15 parts of enteric agent;
the second layer of capsules comprise the following components in parts by weight: 8 parts of opacifier, 4 parts of stabilizer, 5 parts of antioxidant, 15 parts of slow release agent and 20 parts of enteric agent.
Further, the opacifier in the first capsule layer and the second capsule layer is ferric oxide and/or titanium dioxide.
Further, the stabilizers in the first capsule layer and the second capsule layer are tween-80, span-80, polyvinyl alcohol, polysorbate or poloxamer.
Further, the antioxidants in the first layer of capsule layer and the second layer of capsule layer are at least one of vitamin C, vitamin E and dendrobium huoshanense polysaccharide.
Furthermore, the sustained release agent in the first layer capsule layer and the second layer capsule layer is at least one of gelatin, chitosan, sodium carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose and hydroxypropyl methylcellulose.
Further, the enteric-coated agent in the first capsule layer and the second capsule layer is at least one of acetic acid amber hydroxypropyl methylcellulose, phthalic acid hydroxypropyl methylcellulose, methacrylic acid copolymer, carboxymethyl ethyl cellulose and polyvinyl acetate phthalate.
The preparation method of the NMN-containing capsule comprises the following steps:
(1) ultrasonically dispersing NMN nanoparticles in water, then respectively adding the first capsule layer component and a sodium alginate solution with the mass fraction of 1-3% to continue ultrasonic dispersion to obtain a mixed solution, then dropwise adding the mixed solution into a calcium chloride solution under the action of a high-voltage electric field of 3.5-6.5kV, curing for 20-40min, and then cleaning; wherein the concentration of calcium chloride in the system is 50-150 mmol/L;
(2) uniformly mixing the components of the second layer of capsules, adding 1-3% of sodium alginate by mass, continuously and uniformly mixing to obtain a mixture, soaking the substance obtained in the step (1) in the mixture, dripping the substance into a calcium chloride solution under the action of a high-voltage electric field of 3.5-6.5kV, curing for 20-40min, and then cleaning to obtain the calcium alginate microcapsule; wherein the concentration of the calcium chloride in the system is 50-150 mmol/L.
The beneficial effects of the above technical scheme are: the capsule components are mixed with the sodium alginate solution, and then the mixture is added into the calcium chloride solution under the action of an electric field force to form a capsule with a specific function, and the NMN nanoparticles are wrapped in the capsule, so that the instability of NMN is avoided, and the storage time of an NMN product is further prolonged.
Further, the mass fraction of the sodium alginate solution in the steps (1) and (2) is 1.5%, and the concentration of calcium chloride in the system is 100 mmol/L.
Further, the voltage of the high-voltage electric field in the steps (1) and (2) is 4 kV.
The invention has the following beneficial effects:
two-layer capsule layer is wrapped up respectively outside NMN nanoparticle, and each layer of capsule layer comprises specific component for all have specific function in each layer of capsule layer, the kind and the content of component all influence each other in two-layer capsule layer, only under specific kind and content collocation, the better cooperative play effect of ability, and then improve NMN's light stability, oxidation resistance, can also effectually exert NMN's effect in the intestinal.
The NMN nanoparticles are prepared by a specific preparation method, so that the NMN nanoparticles have light stability and oxidation resistance, and are combined with the first capsule layer and the second capsule layer, so that the stability of an NMN product is further improved, the contact area with an intestinal wall is increased, and the utilization rate of a medicament is improved.
In addition, the antioxidant is added into the first layer of capsule layer and the second layer of capsule layer, so that the NMN capsule has an antioxidant function, but dendrobium huoshanense polysaccharide in the antioxidant has an antioxidant effect, and is a high molecular substance which can form a three-dimensional interpenetrating network structure with hordein in the NMN nanoparticles, so that the NMN can be protected, the problem that the NMN is exposed to light or is easy to oxidize is further solved, and the storage time of the NMN component is prolonged. In addition, the dendrobium huoshanense polysaccharide can be digested and absorbed by a human body in the gastrointestinal tract, and after the dendrobium huoshanense polysaccharide is digested and absorbed, the NMN can be released, so that the NMN can effectively exert the activity in the gastrointestinal tract.
Detailed Description
The principles and features of this invention are described below in conjunction with examples which are set forth to illustrate, but are not to be construed to limit the scope of the invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
Example 1:
a NMN-containing capsule comprising: the NMN nano-particle comprises a first capsule layer and a second capsule layer, wherein the first capsule layer and the second capsule layer sequentially coat the NMN nano-particle from inside to outside;
wherein the first capsule layer comprises the following components in parts by weight: 4 parts of opacifier, 1 part of stabilizer, 1 part of antioxidant, 8 parts of slow release agent and 8 parts of enteric solvent; the second layer of capsules comprise the following components in parts by weight: 6 parts of opacifier, 3 parts of stabilizer, 4 parts of antioxidant, 10 parts of slow release agent and 12 parts of enteric agent.
The opacifier in the first capsule layer and the second capsule layer is ferric oxide, the stabilizer is tween-80, the antioxidant is vitamin C, the slow release agent is gelatin, and the enteric-coated agent is acetic acid amber hydroxypropyl methylcellulose.
The NMN nano-particle is prepared by the following method:
dissolving tween-80 in water to form an aqueous phase;
dissolving hordein and NMN in 70% ethanol to form an organic phase;
adding the organic phase into the water phase, stirring, removing ethanol, concentrating, drying, and pulverizing to obtain extract; wherein the weight ratio of the hordein to the NMN to the stabilizer is 15: 100: 5.
the preparation method of the NMN-containing capsule comprises the following steps:
(1) ultrasonically dispersing NMN nanoparticles in water, then respectively adding the components of a first capsule layer and a sodium alginate solution with the mass fraction of 1%, continuously ultrasonically dispersing to obtain a mixed solution, then dropwise adding the mixed solution into a calcium chloride solution under the action of a high-voltage electric field of 3.5kV, curing for 40min, and then cleaning; wherein the concentration of calcium chloride in the system is 50 mmol/L;
(2) uniformly mixing the components of the second layer of capsules, adding 1% by mass of sodium alginate, continuously and uniformly mixing to obtain a mixture, soaking the substance obtained in the step (1) in the mixture, dripping the substance into a calcium chloride solution under the action of a high-voltage electric field of 3.5kV, curing for 40min, and then cleaning to obtain the calcium chloride-calcium composite capsule; wherein the concentration of the calcium chloride in the system is 50 mmol/L.
Example 2:
a NMN-containing capsule comprising: the NMN nano-particle comprises a first capsule layer and a second capsule layer, wherein the first capsule layer and the second capsule layer sequentially coat the NMN nano-particle from inside to outside;
wherein the first capsule layer comprises the following components in parts by weight: 8 parts of opacifier, 3 parts of stabilizer, 3 parts of antioxidant, 15 parts of slow release agent and 15 parts of enteric agent; the second layer of capsules comprise the following components in parts by weight: 12 parts of opacifier, 5 parts of stabilizer, 7 parts of antioxidant, 20 parts of slow release agent and 25 parts of enteric agent.
The opacifier in the first layer of capsule layer and the second layer of capsule layer is titanium dioxide, the stabilizer is polysorbate, the antioxidant is vitamin E and dendrobium huoshanense polysaccharide according to the mass ratio of 1: 3, the slow release agent and the enteric agent are all sodium carboxymethyl cellulose and carboxymethyl ethyl cellulose.
The NMN nano-particle is prepared by the following method:
dissolving polyvinyl alcohol in water to form a water phase;
dissolving hordein and NMN in 80% ethanol to form an organic phase;
adding the organic phase into the water phase, stirring, removing ethanol, concentrating, drying, and pulverizing to obtain extract; wherein the weight ratio of the hordein to the NMN to the stabilizer is 30: 100: 12.
the preparation method of the NMN-containing capsule comprises the following steps:
(1) ultrasonically dispersing NMN nanoparticles in water, then respectively adding the first capsule layer component and a sodium alginate solution with the mass fraction of 3% to continue ultrasonic dispersion to obtain a mixed solution, then dropwise adding the mixed solution into a calcium chloride solution under the action of a high-voltage electric field of 6.5kV, curing for 20min, and then cleaning; wherein the concentration of calcium chloride in the system is 150 mmol/L;
(2) uniformly mixing the components of the second layer of capsules, adding 3% by mass of sodium alginate, continuously and uniformly mixing to obtain a mixture, soaking the substance obtained in the step (1) in the mixture, dripping the substance into a calcium chloride solution under the action of a high-voltage electric field of 6.5kV, curing for 20min, and then cleaning to obtain the calcium chloride-calcium composite capsule; wherein the concentration of the calcium chloride in the system is 150 mmol/L.
Example 3:
a NMN-containing capsule comprising: the NMN nano-particle comprises a first capsule layer and a second capsule layer, wherein the first capsule layer and the second capsule layer sequentially coat the NMN nano-particle from inside to outside;
wherein the first capsule layer comprises the following components in parts by weight: 4 parts of opacifier, 2 parts of stabilizer, 1 part of antioxidant, 10 parts of slow release agent and 15 parts of enteric agent; the second layer of capsules comprise the following components in parts by weight: 8 parts of opacifier, 4 parts of stabilizer, 5 parts of antioxidant, 15 parts of slow release agent and 20 parts of enteric agent.
The opacifier in the first layer of capsule layer and the second layer of capsule layer is ferric oxide, the stabilizer is polysorbate, the antioxidant is vitamin E and dendrobium huoshanense polysaccharide according to the mass ratio of 1: 3, the slow release agent and the enteric agent are all sodium carboxymethyl cellulose and carboxymethyl ethyl cellulose.
The NMN nano-particle is prepared by the following method:
dissolving tween-80 in water to form an aqueous phase;
dissolving hordein and NMN in 75% ethanol to form an organic phase;
adding the organic phase into the water phase, stirring, removing ethanol, concentrating, drying, and pulverizing to obtain extract; wherein the weight ratio of the hordein to the NMN to the stabilizer is 20: 100: 8.
the preparation method of the NMN-containing capsule comprises the following steps:
(1) ultrasonically dispersing NMN nanoparticles in water, then respectively adding the components of a first capsule layer and a sodium alginate solution with the mass fraction of 1.5%, continuously ultrasonically dispersing to obtain a mixed solution, then dropwise adding the mixed solution into a calcium chloride solution under the action of a 4kV high-voltage electric field, curing for 30min, and then cleaning; wherein the concentration of calcium chloride in the system is 100 mmol/L;
(2) uniformly mixing the components of the second layer of capsules, adding 1.5 mass percent of sodium alginate, continuously and uniformly mixing to obtain a mixture, soaking the substance obtained in the step (1) in the mixture, dripping the substance into a calcium chloride solution under the action of a 4kV high-voltage electric field, curing for 30min, and then cleaning to obtain the calcium alginate microcapsule; wherein the concentration of the calcium chloride in the system is 100 mmol/L.
Comparative example 1:
comparative example 1 and example 3 differ by: the components and the dosage of the first capsule layer and the second capsule layer are exchanged, and the rest are the same.
Comparative example 2:
comparative example 2 differs from example 3 in that: the capsule layer has only one layer, has the same components and content as the second layer, and is only coated once in the preparation process, and the rest are the same.
Comparative example 3:
comparative example 3 differs from example 3 in that: the capsule layer has only one layer, the component types in the capsule layer are the same as the components of the second layer of the capsule layer in the example 3, but the content is the sum of the contents of the components of the first layer of the capsule layer and the second layer of the capsule layer in the example 3, the coating is only carried out once in the preparation process, and the rest are the same.
Comparative example 4:
comparative example 4 differs from example 3 in that: the types and the use amounts of the components in the first layer of capsule layer and the second layer of capsule layer are different, and the rest are the same, specifically:
the first capsule layer comprises the following components in parts by weight: 2 parts of opacifier, 2 parts of stabilizer, 1 part of antioxidant, 7 parts of slow release agent and 10 parts of enteric solvent; the second layer of capsules comprise the following components in parts by weight: 10 parts of opacifier, 4 parts of stabilizer, 5 parts of antioxidant, 18 parts of slow release agent and 25 parts of enteric agent.
The opacifier in the first layer of capsule layer and the second layer of capsule layer is ferric oxide, the stabilizer is polysorbate, the antioxidant is vitamin E and dendrobium huoshanense polysaccharide according to the mass ratio of 1: 3, the slow release agent and the enteric agent are all sodium carboxymethyl cellulose and carboxymethyl ethyl cellulose.
Comparative example 5:
comparative example 5 differs from example 3 in that: during the preparation of the NMN nanoparticles, hordeins are omitted, and the rest are the same.
Comparative example 6:
comparative example 6 differs from example 3 in that: in the preparation process of the NMN nanoparticles, hordeins are omitted, the capsule layer is only provided with one layer, the component types in the capsule layer are the same as those of the second capsule layer in example 3, but the content is the sum of the contents of the components of the first capsule layer and the second capsule layer in example 3, the preparation process is only carried out once, and the rest are the same.
Test example 1: light stability
After the capsules containing the NMN prepared in examples 1 to 3 and comparative examples 1 to 6 were respectively placed at normal temperature for 12 months, then the NMN nanoparticles in the capsules were taken out, dissolved with 55% by volume of isopropyl alcohol and made to a constant volume of 100mL, so that the concentration of the NMN in each group was 10ug/mL, then 10mL of each solution was taken, placed in a petri dish respectively, irradiated with 30W ultraviolet lamps at a short distance (20cm) for 18 hours, sampled for absorbance, and the average value of 3 times was used as the measurement result. The NMN nanoparticles which are not placed for 12 months at normal temperature and are not irradiated by ultraviolet in each group are used as a control group, and the percentage reduction of the light absorption value of NMN in each group is as follows:
as can be seen from the above table, in the comparative example, the photostability of the product was reduced when the capsule layer was changed to one layer, and in the case of one capsule layer, if the composition and the content were changed, the photostability of the product was reduced regardless of whether the composition was changed or both the composition and the content were changed, but the amount of reduction was small when the composition was not changed in kind and the content was the sum of the contents of the two layers in example 3. Meanwhile, the light stability can be reduced when the NMN nanoparticles lack hordeins, and the reduction amount is the largest when the capsule layer is changed and the hordeins are omitted, so that the light stability of the product can be synergistically improved by the gelatin capsule layer and the hordeins.
Test example 2: oxidation resistance
Respectively placing the capsules containing the NMN prepared in the examples 1-3 and the comparative examples 1-6 at normal temperature for 12 months, then taking out the NMN nanoparticles in the capsules, dissolving the NMN nanoparticles in the capsules by using 55% of isopropanol by volume fraction and fixing the volume to 100mL to ensure that the concentration of the NMN in each group is 10ug/mL, then taking out 2mL of each solution, adding 2mL of DPPH-absolute ethanol solution with the mass concentration of 0.04g/L, reacting for 20min after uniformly mixing, centrifuging for 10min at the rotating speed of 3500 Air/min, taking out supernate, and measuring the absorbance of the supernate at the wavelength of 517nm to be Ai; adding 2mL of absolute ethyl alcohol into another 2mL of sample to be detected in the test tube, uniformly mixing, reacting for 20min, centrifuging for 10min at the rotation speed of 3500r/min, taking supernatant, and measuring the absorbance Aj at the wavelength of 517 nm; the DPPH-absolute ethanol solution with the mass concentration of 2mL and the absolute ethanol solution with the mass concentration of 0.04g/L and 2mL are used as a contrast, the absorbance of the control solution at the wavelength of 517nm is recorded as A0, and the clearance rate of the sample to DPPH free radicals is calculated according to the following formula:
DPPH free radical scavenging ratio (%) (Ai-Aj)/A0X 100%
The results of the measurement were as follows:
as can be seen from the above, in the comparative example, when the capsule layer was changed to one layer, the antioxidant property of the product was lowered, and in the case of one capsule layer, if the ingredients and contents were changed, the contents were changed either without changing the ingredients or with changing both the ingredients and contents, but the amount of reduction was small when the kinds of ingredients were not changed and the contents were the sum of the contents of the two layers in example 3. Meanwhile, as the hordein has the oxidation resistance, the hordein can also form a three-dimensional interpenetrating network structure, the NMN is further protected on the basis of the capsule layer, and the problem that the NMN is exposed to light or is easy to oxidize can be further solved, so that the oxidation resistance can be reduced when the hordein is lacked in the NMN nanoparticle, and the reduction amount is the largest when the hordein is omitted while the capsule layer is changed, namely the oxidation resistance of the product can be synergistically improved by the capsule layer and the hordein.
Test example 3: release rate
The NMN-containing capsules prepared in example 3 were soaked for 2 hours in simulated gastric acid solution SGF pH 2, and then soaked for 6 hours in simulated colonic solution SGF pH 6.8, and NMN release rates at 2, 4, 6, 8, and 10 hours were measured, respectively, and the results were as follows:
| time/h | Rate of release/%) |
| 0 | 0 |
| 2 | 0.55 |
| 4 | 8.61 |
| 6 | 18.32 |
| 8 | 45.18 |
| 10 | 52.21 |
The NMN-containing capsules prepared in example 3 were soaked in a simulated colonic solution SGF at pH 6.8 for 6h, and NMN release rates at 2, 4, 6, and 8h were measured, respectively, as follows:
| time/h | Rate of release/%) |
| 0 | 0 |
| 2 | 45.51 |
| 4 | 75.17 |
| 6 | 88.32 |
| 8 | 95.22 |
The above table shows that the NMN-containing capsule provided by the invention can be slowly released under the immersion of simulated gastric acid solution and simulated colon solution, and especially can be effectively slowly released into the solution under the immersion of simulated colon solution, which indicates that the NMN-containing capsule provided by the invention can well play its role in intestinal tract, and further can reduce the dosage of the product and improve the drug effect.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (10)
1. A NMN-containing capsule comprising: the NMN nano-particle comprises a first capsule layer and a second capsule layer, wherein the first capsule layer and the second capsule layer sequentially coat the NMN nano-particle from inside to outside;
wherein the first capsule layer comprises the following components in parts by weight: 4-8 parts of opacifier, 1-3 parts of stabilizer, 1-3 parts of antioxidant, 8-15 parts of slow release agent and 8-15 parts of enteric solvent;
the second layer of capsules comprise the following components in parts by weight: 6-12 parts of opacifier, 3-5 parts of stabilizer, 4-7 parts of antioxidant, 10-20 parts of slow release agent and 12-25 parts of enteric agent.
2. The NMN-containing capsule according to claim 1, wherein the NMN nanoparticles are prepared by the following method:
dissolving a stabilizer in water to form an aqueous phase;
dissolving hordein and NMN in 70-80% ethanol to form an organic phase;
adding the organic phase into the water phase, stirring, removing ethanol, concentrating, drying, and pulverizing.
3. The NMN-containing capsule according to claim 2, wherein the stabilizer used in the NMN nanoparticle preparation process is tween-80, span-80 or polyvinyl alcohol.
4. NMN-containing capsules according to claim 2, characterized in that the weight ratio of hordein, NMN and stabilizer is 15-30: 100: 5-12.
5. The NMN-containing capsule according to claim 1, wherein the first capsule layer comprises the following components in parts by weight: 4 parts of opacifier, 2 parts of stabilizer, 1 part of antioxidant, 10 parts of slow release agent and 15 parts of enteric agent.
6. The NMN-containing capsule according to claim 1, wherein the second layer of capsules comprises the following components in parts by weight: 8 parts of opacifier, 4 parts of stabilizer, 5 parts of antioxidant, 15 parts of slow release agent and 20 parts of enteric agent.
7. NMN-containing capsules according to claim 1 or 5 or 6, characterized in that the opacifiers in the first and second capsule layers are both iron oxide and/or titanium dioxide; the stabilizer is tween-80, span-80, polyvinyl alcohol, polysorbate or poloxamer; the antioxidant is at least one of vitamin C, vitamin E and dendrobium huoshanense polysaccharide.
8. A NMN containing capsule according to claim 1, 5 or 6, wherein the slow release agent is at least one of gelatin, chitosan, sodium carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose and hypromellose.
9. NMN containing capsules according to claim 1 or 5 or 6, wherein the enteric agent is at least one of hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, methacrylic acid copolymers, carboxymethylethylcellulose and polyvinyl acetate phthalate.
10. A method of preparing NMN-containing capsules according to any of claims 1 to 9, comprising the steps of:
(1) ultrasonically dispersing NMN nanoparticles in water, then respectively adding the first capsule layer component and a sodium alginate solution with the mass fraction of 1-3% to continue ultrasonic dispersion to obtain a mixed solution, then dropwise adding the mixed solution into a calcium chloride solution under the action of a high-voltage electric field of 3.5-6.5kV, curing for 20-40min, and then cleaning; wherein the concentration of calcium chloride in the system is 50-150 mmol/L;
(2) uniformly mixing the components of the second layer of capsules, adding 1-3% of sodium alginate by mass, continuously and uniformly mixing to obtain a mixture, soaking the substance obtained in the step (1) in the mixture, dripping the substance into a calcium chloride solution under the action of a high-voltage electric field of 3.5-6.5kV, curing for 20-40min, and then cleaning to obtain the calcium alginate microcapsule; wherein the concentration of the calcium chloride in the system is 50-150 mmol/L.
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