CN115337321A - Antidepressant composition containing polydeoxyribonucleotide and medicine - Google Patents
Antidepressant composition containing polydeoxyribonucleotide and medicine Download PDFInfo
- Publication number
- CN115337321A CN115337321A CN202210789039.0A CN202210789039A CN115337321A CN 115337321 A CN115337321 A CN 115337321A CN 202210789039 A CN202210789039 A CN 202210789039A CN 115337321 A CN115337321 A CN 115337321A
- Authority
- CN
- China
- Prior art keywords
- parts
- pdrn
- antidepressant
- vitamin
- protamine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000935 antidepressant agent Substances 0.000 title claims abstract description 37
- 239000000203 mixture Substances 0.000 title claims abstract description 33
- 230000001430 anti-depressive effect Effects 0.000 title claims abstract description 32
- 229940005513 antidepressants Drugs 0.000 title claims abstract description 30
- 239000003814 drug Substances 0.000 title abstract description 26
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 33
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 28
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 claims abstract description 24
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims abstract description 24
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims abstract description 24
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 24
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims abstract description 24
- 102000007327 Protamines Human genes 0.000 claims abstract description 21
- 108010007568 Protamines Proteins 0.000 claims abstract description 21
- 229940048914 protamine Drugs 0.000 claims abstract description 21
- 102000019197 Superoxide Dismutase Human genes 0.000 claims abstract description 16
- 108010012715 Superoxide dismutase Proteins 0.000 claims abstract description 16
- 229920002472 Starch Polymers 0.000 claims abstract description 14
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000001768 carboxy methyl cellulose Substances 0.000 claims abstract description 14
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims abstract description 14
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims abstract description 14
- 239000008107 starch Substances 0.000 claims abstract description 14
- 235000019698 starch Nutrition 0.000 claims abstract description 14
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229930003268 Vitamin C Natural products 0.000 claims abstract description 13
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims abstract description 13
- 235000019154 vitamin C Nutrition 0.000 claims abstract description 13
- 239000011718 vitamin C Substances 0.000 claims abstract description 13
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 claims abstract description 12
- 108010024636 Glutathione Proteins 0.000 claims abstract description 12
- 241000251511 Holothuroidea Species 0.000 claims abstract description 12
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 claims abstract description 12
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 claims abstract description 12
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 claims abstract description 12
- 235000013734 beta-carotene Nutrition 0.000 claims abstract description 12
- 239000011648 beta-carotene Substances 0.000 claims abstract description 12
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 claims abstract description 12
- 229960002747 betacarotene Drugs 0.000 claims abstract description 12
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims abstract description 12
- 229960003180 glutathione Drugs 0.000 claims abstract description 12
- 235000003969 glutathione Nutrition 0.000 claims abstract description 12
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 claims abstract description 12
- 235000005875 quercetin Nutrition 0.000 claims abstract description 12
- 229960001285 quercetin Drugs 0.000 claims abstract description 12
- 229960003080 taurine Drugs 0.000 claims abstract description 12
- 108010035532 Collagen Proteins 0.000 claims abstract description 11
- 102000008186 Collagen Human genes 0.000 claims abstract description 11
- 229920001436 collagen Polymers 0.000 claims abstract description 11
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 claims abstract description 11
- 229940088594 vitamin Drugs 0.000 claims abstract description 7
- 229930003231 vitamin Natural products 0.000 claims abstract description 7
- 235000013343 vitamin Nutrition 0.000 claims abstract description 7
- 239000011782 vitamin Substances 0.000 claims abstract description 7
- 235000015165 citric acid Nutrition 0.000 claims abstract description 6
- 150000003722 vitamin derivatives Chemical class 0.000 claims abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 39
- 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 13
- 238000002360 preparation method Methods 0.000 claims description 12
- 239000008213 purified water Substances 0.000 claims description 7
- 229930003427 Vitamin E Natural products 0.000 claims description 6
- 235000003599 food sweetener Nutrition 0.000 claims description 6
- 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 6
- 239000003765 sweetening agent Substances 0.000 claims description 6
- 235000019165 vitamin E Nutrition 0.000 claims description 6
- 239000011709 vitamin E Substances 0.000 claims description 6
- 229940046009 vitamin E Drugs 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 5
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 239000004615 ingredient Substances 0.000 claims description 4
- 239000000049 pigment Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 2
- 239000001506 calcium phosphate Substances 0.000 claims description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 2
- 229960001714 calcium phosphate Drugs 0.000 claims description 2
- 235000011010 calcium phosphates Nutrition 0.000 claims description 2
- 229960000913 crospovidone Drugs 0.000 claims description 2
- 235000019425 dextrin Nutrition 0.000 claims description 2
- 235000002864 food coloring agent Nutrition 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 2
- 239000000853 adhesive Substances 0.000 claims 4
- 230000001070 adhesive effect Effects 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 230000000694 effects Effects 0.000 abstract description 24
- 238000011282 treatment Methods 0.000 abstract description 24
- 210000001320 hippocampus Anatomy 0.000 abstract description 16
- 230000000638 stimulation Effects 0.000 abstract description 11
- 230000014509 gene expression Effects 0.000 abstract description 8
- 210000003520 dendritic spine Anatomy 0.000 abstract description 7
- 208000019901 Anxiety disease Diseases 0.000 abstract description 5
- 230000002757 inflammatory effect Effects 0.000 abstract description 5
- 230000036542 oxidative stress Effects 0.000 abstract description 5
- 210000004720 cerebrum Anatomy 0.000 abstract description 4
- 230000009471 action Effects 0.000 abstract description 3
- 230000003956 synaptic plasticity Effects 0.000 abstract description 3
- 230000008901 benefit Effects 0.000 abstract description 2
- 102000040430 polynucleotide Human genes 0.000 abstract 1
- 108091033319 polynucleotide Proteins 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 46
- 241000699666 Mus <mouse, genus> Species 0.000 description 26
- 229940079593 drug Drugs 0.000 description 19
- 239000002158 endotoxin Substances 0.000 description 19
- 229920006008 lipopolysaccharide Polymers 0.000 description 19
- 238000002474 experimental method Methods 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 230000003542 behavioural effect Effects 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 230000006399 behavior Effects 0.000 description 9
- 210000004556 brain Anatomy 0.000 description 8
- 238000009472 formulation Methods 0.000 description 7
- 239000007928 intraperitoneal injection Substances 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000007267 depressive like behavior Effects 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 238000000465 moulding Methods 0.000 description 5
- 230000009182 swimming Effects 0.000 description 5
- 241000196324 Embryophyta Species 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 230000007529 anxiety like behavior Effects 0.000 description 3
- -1 beta-carotene carotenoids Chemical class 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000003651 drinking water Substances 0.000 description 3
- 235000020188 drinking water Nutrition 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 229940118019 malondialdehyde Drugs 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 102000003777 Interleukin-1 beta Human genes 0.000 description 2
- 108090000193 Interleukin-1 beta Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000008451 emotion Effects 0.000 description 2
- 235000019688 fish Nutrition 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 208000017194 Affective disease Diseases 0.000 description 1
- 208000007415 Anhedonia Diseases 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 241000252203 Clupea harengus Species 0.000 description 1
- 206010012374 Depressed mood Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 241000581650 Ivesia Species 0.000 description 1
- 102000010909 Monoamine Oxidase Human genes 0.000 description 1
- 108010062431 Monoamine oxidase Proteins 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 102000002488 Nucleoplasmin Human genes 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000277331 Salmonidae Species 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 206010072170 Skin wound Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 239000002390 adhesive tape Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000006400 anxiety behaviour Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003851 biochemical process Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000007323 disproportionation reaction Methods 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000037080 exercise endurance Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Natural products O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 description 1
- 235000011957 flavonols Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 150000002338 glycosides Chemical group 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 235000019514 herring Nutrition 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 239000000413 hydrolysate Substances 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000004630 mental health Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 108060005597 nucleoplasmin Proteins 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 208000020685 sleep-wake disease Diseases 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000008925 spontaneous activity Effects 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 125000002640 tocopherol group Chemical group 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
-
- 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
- A61K31/01—Hydrocarbons
- A61K31/015—Hydrocarbons carbocyclic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/01—Hydrolysed proteins; Derivatives thereof
- A61K38/012—Hydrolysed proteins; Derivatives thereof from animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
- A61K38/063—Glutathione
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1706—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from fish
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
-
- 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
- A61K38/44—Oxidoreductases (1)
- A61K38/446—Superoxide dismutase (1.15)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y115/00—Oxidoreductases acting on superoxide as acceptor (1.15)
- C12Y115/01—Oxidoreductases acting on superoxide as acceptor (1.15) with NAD or NADP as acceptor (1.15.1)
- C12Y115/01001—Superoxide dismutase (1.15.1.1)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Marine Sciences & Fisheries (AREA)
- Inorganic Chemistry (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses an antidepressant composition containing polydeoxyribonucleotide and a medicament, which comprise PDRN (polyribonucleotide), or PDRN and at least one auxiliary component; the auxiliary component is selected from one or more of sodium carboxymethylcellulose, protamine, dry starch, talcum powder, gamma-aminobutyric acid, sea cucumber peptide, collagen peptide, citric acid, vitamin C, glutathione, vitamin, beta-carotene, taurine, superoxide dismutase or quercetin. The inventor finds that PDRN can relieve the increase of inflammatory factors in the hippocampus cerebrum of a mouse caused by LPS stimulation, relieve the increase of oxidative stress products in the hippocampus cerebrum of the mouse caused by LPS stimulation, regulate and control synaptic plasticity by changing the number and the form of neuron dendritic spines in hippocampus, participate in antidepressant action, and effectively relieve anxiety-like expression. The prepared antidepressant composition has the advantages of definite curative effect, high safety, small side effect and strong comprehensive treatment capability.
Description
Technical Field
The invention belongs to the technical field of antidepressant drugs, and particularly relates to an antidepressant composition containing polydeoxyribonucleotide and a drug.
Background
The statements herein merely provide background information related to the present disclosure and may not necessarily constitute prior art.
The depression is an affective disorder mental disease which is mainly characterized by low mood, lack of interest, sleep disorder and the like, the incidence rate is increasingly improved nowadays when social competition is fierce and major sudden events occur frequently all over the world, the depression becomes one of the main causes of disability all over the world, and the prevention and treatment of the depression is listed as the national mental health work key point. At present, drugs for treating depression are mainly monoamine oxidase reuptake inhibitors, tricyclic drugs and the like, and the drugs generally have the defects of slow response, low effective rate, more adverse reactions and the like.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide an antidepressant composition containing polydeoxyribonucleotide and a medicament.
In order to realize the purpose, the invention is realized by the following technical scheme:
in a first aspect, the present invention provides an antidepressant composition comprising polydeoxyribonucleotides, comprising PDRN; or PDRN and at least one adjunct ingredient;
the auxiliary components are selected from one or more of protamine, sodium carboxymethylcellulose, dry starch, talcum powder, gamma-aminobutyric acid, sea cucumber peptide, collagen peptide, citric acid, vitamin C, glutathione, vitamin, beta-carotene, taurine, superoxide dismutase or quercetin.
In a second aspect, the invention provides an antidepressant drug containing polydeoxyribonucleotide, wherein the dosage form of the antidepressant drug is oral preparation or injection preparation, and the oral preparation is tablet, granule, capsule, pill or oral liquid.
In a third aspect, the invention provides the use of polydeoxyribonucleotides in the preparation of an antidepressant medicament.
The beneficial effects achieved by one or more of the embodiments of the invention described above are as follows:
the inventor finds that PDRN can relieve the increase of inflammatory factors in the hippocampus cerebrum of a mouse caused by LPS stimulation, relieve the increase of oxidative stress products in the hippocampus cerebrum of the mouse caused by LPS stimulation, regulate synaptic plasticity by changing the number and the form of neuron dendritic spines in hippocampus, participate in antidepressant action, and effectively relieve the anxiety-like expression of the mouse.
The prepared antidepressant composition has the advantages of definite curative effect, high safety, small side effect and strong comprehensive treatment capability.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, are included to provide a further understanding of the invention, and are included to illustrate an exemplary embodiment of the invention and not to limit the invention.
FIG. 1 is a graph showing the effect of intraperitoneal injection of PDRN on the improvement of chronic LPS-induced depression and anxiety-like behavior of mice in an embodiment of the present invention, where A is an experimental flowchart, B is the effect of different drug treatments on the body weight of the mice, C is the effect of different drug treatments on the behavior of the mice in a sweet water preference experiment, D is the effect of different drug treatments on the behavior of the mice in a forced swimming experiment, E is the effect of different drug treatments on the behavior of the mice in a tail suspension experiment, F is the effect of different drug treatments on the motor ability of the mice in an open field experiment, and G is the effect of different drug treatments on the anxiety behavior of the mice in the open field experiment.
FIG. 2 shows that PDRN can relieve high expression of inflammation-causing factors in the brains of mice of depression models in the embodiment of the invention, wherein A represents the influence of different drug treatments on IL-6 gene expression in the hippocampus of the mice, B represents the influence of different drug treatments on IL-1 beta gene expression in the hippocampus of the mice, and C represents the influence of different drug treatments on TNF-alpha gene expression in the hippocampus of the mice.
FIG. 3 shows that PDRN can relieve the occurrence of oxidative stress in the brain of a mouse in a depression model in an embodiment of the invention, wherein A is the influence of different drug treatments on MDA expression in the hippocampus of the mouse, and B is the influence of different drug treatments on SOD activity in the hippocampus of the mouse.
FIG. 4 shows that PDRN can alleviate the decrease of neuron dendritic spines in the brain of a mouse in a depression model in the embodiment of the invention, wherein A is the influence of different drug treatments on the morphology and the number of the neuron dendritic spines in the hippocampus of the mouse. Golgi staining representative plots, from left to right, are control, LPS treated and LPS + PDRN treated groups in that order, and B is a statistical plot of the effect of different drug treatments on the number of neuronal dendritic spines in the mouse hippocampus.
Fig. 5 shows that the PDRN-containing formulation of the present invention significantly slowed the behavior of mice in the form of depression, where a is the effect of different formulation drug treatments on the behavior of mice in forced swimming experiments and B is the effect of different formulation drug treatments on the behavior of mice in sugar water preference experiments.
Detailed Description
It is to be understood that the following detailed description is exemplary and is intended to provide further explanation of the invention as claimed. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
In a first aspect, the present invention provides an antidepressant composition comprising polydeoxyribonucleotides, comprising PDRN; or PDRN and at least one adjunct ingredient;
the auxiliary components are selected from one or more of protamine, sodium carboxymethylcellulose, dry starch, talcum powder, polyethylene glycol, lactose, microcrystalline cellulose, dextrin, calcium phosphate, hydroxypropyl cellulose, crospovidone, gamma-aminobutyric acid, sea cucumber peptide, collagen peptide, citric acid, vitamin C, glutathione, vitamin, beta-carotene, taurine, superoxide dismutase or quercetin.
Polydeoxyribonucleotides (PDRN), a naturally derived low-molecular-weight DNA derivative with a molecular weight of between 50 and 1500KDa and a base length of between 50 and 2000bp, are linear polymers of deoxyribonucleotides with phosphodiester bonds, have long been in clinical use, show definite effects in tissue repair, wound healing, anti-ischemia, anti-inflammatory, etc., and have been used in some countries for the treatment of skin wounds and burns. However, there is no report on the antidepressant effect of PDRN.
In some embodiments, the adjunct ingredient is selected from one or more of protamine, sodium carboxymethylcellulose, dry starch, talc, polyethylene glycol, gamma-aminobutyric acid, sea cucumber peptide, collagen peptide, citric acid, vitamin C, glutathione, vitamins, beta-carotene, taurine, superoxide dismutase, or quercetin.
In some embodiments, the antidepressant composition containing polydeoxyribonucleotide consists of the following components in parts by mass: 150-200 parts of PDRN, 150-200 parts of protamine, 400-450 parts of dry starch, 200-300 parts of sodium carboxymethylcellulose and 100-200 parts of talcum powder. Wherein the dry starch, the sodium carboxymethyl cellulose and the talcum powder are all pharmaceutic adjuvants.
Protamine is an alkaline protein that exists mainly as a nucleoplasmin bound to DNA in the nucleus of mature sperm cells of fish (e.g., salmon, trout, herring, etc.). The protamine has good antiseptic property and thermal stability, and has high nutrition and functionality, and has effects of lowering blood pressure, promoting respiration, promoting digestion, inhibiting tumor, resisting thrombi, enhancing liver function, inhibiting blood coagulation, etc. The protamine with positive charges and the PDRN molecules with negative charges form a compound through intermolecular electrostatic attraction, so that the cell penetrability of the PDRN can be enhanced, and the use effect is improved.
Preferably, the antidepressant composition containing polydeoxyribonucleotides consists of the following components in parts by mass: 160-190 parts of PDRN, 160-190 parts of protamine, 410-440 parts of dry starch, 230-270 parts of sodium carboxymethylcellulose and 140-170 parts of talcum powder.
Further preferably, the antidepressant composition containing polydeoxyribonucleotide comprises the following components in parts by mass: 180 parts of PDRN, 180 parts of protamine, 420 parts of dry starch, 260 parts of sodium carboxymethylcellulose and 150 parts of talcum powder.
In some embodiments, the antidepressant composition containing polydeoxyribonucleotide consists of the following components in parts by mass: 0.1-1 part of PDRN, 0.1-1 part of protamine, 3-10 parts of gamma-aminobutyric acid, 3-7 parts of sea cucumber peptide, 4-7 parts of collagen peptide, 1-3 parts of citric acid, 1-3 parts of vitamin C, 6-10 parts of glutathione, 1-3 parts of vitamin E, 2-4 parts of beta-carotene, 4-7 parts of taurine, 0.1-0.4 part of superoxide dismutase, 0.4-0.8 part of quercetin, a proper amount of edible pigment and sweetening agent and 50-80 parts of purified water.
Also comprises a proper amount of edible pigment and sweetener.
Gamma-aminobutyric acid is widely distributed in animals and plants. In animals, it is almost exclusively present in nervous tissues, an important inhibitory neurotransmitter, and has a regulatory effect on the normal physiological functions of the brain. When the human body is lack of the traditional Chinese medicine, emotions such as anxiety, uneasiness, fatigue, depression and the like can be generated.
The sea cucumber peptide has the effects of enhancing the exercise endurance of organisms, promoting glycogen storage and accelerating the urea nitrogen metabolism of the organisms, has an important regulating effect on the immune function and influences the expression of cell growth factors and inflammatory factors.
Vitamin C, also known as ascorbic acid, is an essential nutrient for higher primates and other minor organisms. Vitamin C is an antioxidant that protects the body from oxygen free radicals and is a coenzyme involved in various biochemical processes in the body.
Glutathione is short peptide composed of glutamic acid, hemisarcosine and glycine, and has effects of resisting oxidation, removing toxic substances and enhancing immunity.
Vitamin E is a fat-soluble vitamin whose hydrolysate is tocopherol, one of the most important antioxidants.
One of beta-carotene carotenoids is an antioxidant, is an indispensable nutrient for maintaining human health, and plays an important role in resisting cancer, preventing cardiovascular diseases and preventing various neurodegenerative diseases caused by aging.
Taurine is a sulfur-containing amino acid with a simple structure in an animal body, exists in a free state in the body, does not participate in the biosynthesis of proteins in the body, but is closely related to the metabolism of sarcosine and hemisarcosine. Has important effect on the development of the nervous system of the fetus and the infant. It can also be involved in regulating adverse mood by increasing electrical signal conduction of nerves.
Superoxide dismutase (SOD) for short is an important component of an antioxidant enzyme system in a biological system, is widely distributed in microorganisms, plants and animals, can catalyze superoxide anion free radical disproportionation to generate oxygen and hydrogen peroxide, plays a vital role in the balance of oxidation and antioxidation of the organism, and has better curative effects on inflammation, autoimmunity, cardiovascular and cerebrovascular diseases and the like caused by the action of free radicals.
Quercetin is a flavonol compound which is widely distributed in plant boundaries, has various biological activities, is widely present in stem bark, flowers, leaves, buds, seeds and fruits of many plants, is mostly present in a glycoside form, and can play roles of removing free radicals in vivo, resisting inflammation and the like.
The above composition has effects of resisting inflammation, resisting oxidation stress, relieving fatigue, nourishing nerve, regulating emotion, and resisting depression.
Preferably, the antidepressant composition containing polydeoxyribonucleotides consists of the following components in parts by mass: 0.2 part of PDRN, 0.2 part of protamine, 5 parts of gamma-aminobutyric acid, 5 parts of sea cucumber peptide, 5 parts of collagen peptide, 2 parts of citric acid, 2 parts of vitamin C, 8 parts of glutathione, 2 parts of vitamin E, 3 parts of beta-carotene, 5 parts of taurine, 0.2 part of superoxide dismutase, 0.5 part of quercetin and 60 parts of purified water.
Further preferably, the antidepressant composition also comprises food color and sweetener.
In a second aspect, the invention provides an antidepressant drug containing polydeoxyribonucleotide, and the dosage form of the antidepressant drug is oral preparation or injection preparation, and the oral preparation is tablets, granules, capsules, pills or oral liquid.
In some embodiments, the dosage form is an oral formulation.
In a third aspect, the invention provides the use of polydeoxyribonucleotides in the preparation of an antidepressant medicament.
The invention is further illustrated by the following figures and examples.
Example 1
The extraction method of PDRN comprises the following steps:
after 500g of fresh or frozen fish testis tissue was pulverized, 0.15M NaCl/0.03M sodium citrate mixed salt solution having pH of 8.0 was added at a ratio of 1.
Adding the above precipitate to a lysis solution containing 0.05M Tris-HCl (pH 7.6), 0.1M EDTA (pH 8.0), 0.15M NaCl and 1% SDS, at a ratio of precipitate to lysis solution of 1 (M/v), shaking in a shaker at 55 ℃ for 4h; the supernatant was collected by centrifugation.
Adding 3 times volume of saturated NaCl solution into the supernatant, and performing vortex oscillation for 30s; centrifuging at 14000rpm for 25min, and standing in a refrigerator at 4 deg.C for 40min;
sucking supernatant, adding precooled anhydrous ethanol with the same volume, fully reversing and uniformly mixing, and centrifuging at 14000rpm for 10min;
pouring out the liquid, adding 70% ethanol to wash DNA, and centrifuging at 14000rpm for 10min;
adding 500ul deionized water at 37 ℃ to dissolve DNA at the bottom of the tube, and detecting the concentration of the DNA; adding the restriction enzyme Sau3 AI into a solution at 37 ℃ for reaction for 1h;
adding precooled absolute ethyl alcohol with twice volume, fully oscillating, and centrifuging at 14000rpm for 10min;
and (3) pouring out the liquid, adding 70% ethanol, washing, centrifuging for 3 times, crushing the obtained DNA precipitate, and freeze-drying to obtain a white solid, namely PDRN.
The molding method for depression comprises the following steps: c57BL6 mice (weighing 22-25 g) were intraperitoneally injected with 0.5mg/kg Lipopolysaccharide (LPS) for 5 consecutive days. Behavioral assessment began on day 6.
The PDRN administration method comprises the following steps: the extracted PDRN was dissolved in physiological saline and then intraperitoneally injected into C57BL6 mice at a dose of 8mg/kg for 5 consecutive days.
Grouping: the test result is divided into four groups, namely a solvent control group, an LPS combined PDRN administration group and a PDRN administration group.
Monitoring the body weight: behavior detection day 8:00 and 18: the weight of the mice was measured 00, and the average was taken as the weight of the mice on the day. And (5) taking the average weight value of the control group mice on the day of behavior detection as a standard value, subtracting the actual weights of all the mice from the standard value, and calculating the weight change value delta.
And (3) behavioral detection:
open field experiment: in the case of confirming that the test environment is quiet, the mouse is gently placed in an open field box (40 cm. Times.40 cm). Mouse behavioural videos are recorded by using SMART v3.0 analysis software, behavioural test analysis (test time is 10 min) is carried out, and after the behavioural experiment of each mouse is finished, the bottom surface and the inner wall of the open-field box are wiped by 40% alcohol so as to eliminate the odor influence among different mice. The total movement distance reflects the movement capacity of the mouse, and the percentage of the residence time of the mouse in the central area (the area 1/4 of the midpoint of the bottom of the open field tank) to the total time is used as an index for measuring the anxiety-like behavior of the mouse.
Tail suspension experiment: used to reflect the despair degree of the mice. Under the condition of keeping the experimental environment quiet, a medical adhesive tape is wound at a position 1-2 cm away from the tail end of a mouse tail, the mouse is hung at a height of about 30cm away from the ground in an inverted mode, a camera is placed on the side edge of the mouse, a mouse behavioural video is recorded by using SMART v3.0 analysis software, behavioural test analysis (test time is 6 min) is carried out, and the standing time when the mouse abandons struggling is used as an index for measuring the behavior of the mouse depression sample.
Forced swimming experiment: forced swimming reflects its hopelessness mainly by how long a mouse struggles in water that cannot escape and gives up struggling. Firstly, a proper amount of water (the water level height is 15-20 cm) is added into a transparent acrylic cylindrical barrel (phi 12cm is multiplied by 30 cm). The video acquisition equipment is placed on the side edge so as to record the whole body movement condition of the mouse in the test process conveniently. Under the condition of ensuring that the test environment is quiet, slowly putting the mice into water, recording the behavioural video of the mice by using SMART v3.0 analysis software, carrying out behavioural test analysis (test time is 6 min), and replacing water every 3-5 mice to ensure the water temperature and cleanness. The immobility time of the mice abandoning struggling in water was taken as an index to measure the depression-like behavior of the mice.
Sweet water preference experiment: sugar water preference mainly reflects the perception of the mice on reward (1% sugar water), and whether the mice have anhedonia is reflected by the preference score of the mice on sugar water.
The sugar water test is divided into two stages: the first stage is a sugar water adaptation stage, namely, sugar water bottles are respectively placed on two sides of a feeding cage frame of the mouse for the mouse to freely eat and eat, and the adaptation time is 4 days and 2 hours every day. The second stage is a testing stage, wherein a pure water bottle is placed on one side of a feeding cage frame of the mouse, a sugar water bottle is placed on the other side of the feeding cage frame, the total mass of each water bottle and water is weighed before the feeding cage frame is placed, the mouse can drink freely, the positions of the pure water bottle and the sugar water bottle are changed after 1h, and the testing is continued for 1h. The total mass of the water bottle and the remaining water was weighed after 2h.
The sugar water preference score is used as an index for measuring the depression-like behavior of the mice: the sugar water preference score = sugar water consumption/(sugar water consumption + pure water consumption) × 100%.
Changes of the levels of inflammatory factors IL-1 beta, TNF-alpha and IL-6 in the brain homogenate are detected by a real-time fluorescence quantification method.
Enzyme-linked immunosorbent assay (ELISA) was used to detect changes in Malondialdehyde (MDA) and superoxide dismutase (SOD), which is an oxidative stress product, in brain homogenates.
Changes in the morphological structure and number of hippocampal dendritic spines were observed using a method of Golgi staining.
Evaluation experiment of formula function:
formula 1 containing PDRN: 180g of PDRN, 180g of protamine, 420g of dry starch, a proper amount of sodium carboxymethyl cellulose and talcum powder are prepared into granules, dried and pressed into 1000 tablets, and each tablet contains 180mg of PDRN.
PDRN-free formulation 1: except that the PDRN is not contained, the contents of other components are the same as that of the formula 1 containing the PDRN.
The PDRN-containing formula 1 and the PDRN-free formula 1 are respectively dissolved and uniformly mixed by 100ml of purified water to be used as daily drinking water for mice, and the drinking water is randomly drunk, starts to be suitable for drinking 2 days before LPS molding treatment is given, and continues until the molding is finished.
100ml of the PDRN formulation 2-containing beverage and the PDRN-free formulation 2-containing beverage were also used as daily drinking water for mice, and were drunk ad libitum, starting from 2 days before LPS molding treatment, and continuing until molding was completed.
Purified water was consumed during the control mice period.
Analysis of results
Intraperitoneal injection of PDRN can reverse weight loss due to LPS stimulation, as shown in fig. 1, panel B.
Intraperitoneal injection of PDRN can relieve the depression-like behavior of mice caused by LPS stimulation. LPS stimulation resulted in a significant increase in the immobility time and a significant decrease in the sugar water preference score in the forced swim and tail overhang tests in mice, while the simultaneous administration of PDRN-treated mice resulted in a significant recovery of the above-described behavioral manifestations, suggesting that LPS can lead to the development of depression-like symptoms in mice, and that PDRN can effectively alleviate the depression-like manifestations, as shown in fig. 1C-E.
Intraperitoneal injection of PDRN can relieve the occurrence of anxiety-like behaviors of mice caused by LPS stimulation. LPS stimulation can cause the time for the mice to enter the central region in the open field experiment to be obviously shortened, but the spontaneous activity of the mice is not influenced, and PDRN treatment can effectively increase the time for the mice to enter the central region, so that the LPS treatment can cause the anxiety-like symptoms of the mice to occur, and the PDRN can effectively relieve the anxiety-like symptoms, as shown in figures 1F-G.
The increase of inflammatory factors in hippocampus brains of mice caused by LPS stimulation can be relieved by intraperitoneal injection of PDRN, and is shown in figure 2.
Intraperitoneal injection of PDRN can alleviate the increase of oxidative stress products in hippocampus brain of mice caused by LPS stimulation, as shown in fig. 3.
Intraperitoneal injection of PDRN regulates synaptic plasticity to participate in antidepressant effects by altering the number and morphology of neuronal dendritic spines in the hippocampus, as shown in figure 4.
The oral administration of the formula containing the PDRN can effectively reduce the immobility time of the mice in forced swimming, increase the intake of sugar water and prompt that the two formulas containing the PDRN have better effect of relieving depression-like behaviors of the mice compared with a control group and a treatment group without the PDRN formula, as shown in figure 5.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. An antidepressant composition comprising polydeoxyribonucleotides, characterized in that: including PDRN; or PDRN and at least one adjunct ingredient;
the auxiliary components are selected from one or more of protamine, sodium carboxymethylcellulose, dry starch, talcum powder, polyethylene glycol, lactose, microcrystalline cellulose, dextrin, calcium phosphate, hydroxypropyl cellulose, crospovidone, gamma-aminobutyric acid, sea cucumber peptide, collagen peptide, citric acid, vitamin C, glutathione, vitamin, beta-carotene, taurine, superoxide dismutase or quercetin.
2. The antidepressant composition as claimed in claim 1, characterized in that: the auxiliary components are selected from one or more of protamine, sodium carboxymethylcellulose, dry starch, talcum powder, polyethylene glycol, gamma-aminobutyric acid, sea cucumber peptide, collagen peptide, citric acid, vitamin C, glutathione, vitamin, beta-carotene, taurine, superoxide dismutase or quercetin.
3. The antidepressant composition as claimed in claim 1, characterized in that: the adhesive comprises the following components in parts by mass: 150-200 parts of PDRN, 150-200 parts of protamine, 400-450 parts of dry starch, 200-300 parts of sodium carboxymethylcellulose and 100-200 parts of talcum powder.
4. The antidepressant composition as claimed in claim 3, characterized in that: the adhesive comprises the following components in parts by mass: 160-190 parts of PDRN, 160-190 parts of protamine, 410-440 parts of dry starch, 230-270 parts of sodium carboxymethylcellulose and 140-170 parts of talcum powder.
5. The antidepressant composition comprising polydeoxyribonucleotides according to claim 4, characterized in that: the adhesive comprises the following components in parts by mass: 180 parts of PDRN, 180 parts of protamine, 420 parts of dry starch, 260 parts of sodium carboxymethyl cellulose and 150 parts of talcum powder.
6. The antidepressant composition as claimed in claim 1, characterized in that: the composition consists of the following components: 0.1-1 part of PDRN, 0.1-1 part of protamine, 3-10 parts of gamma-aminobutyric acid, 3-7 parts of sea cucumber peptide, 4-7 parts of collagen peptide, 1-3 parts of citric acid, 1-3 parts of vitamin C, 6-10 parts of glutathione, 1-3 parts of vitamin E, 2-4 parts of beta-carotene, 4-7 parts of taurine, 0.1-0.4 part of superoxide dismutase, 0.4-0.8 part of quercetin, a proper amount of edible pigment and sweetening agent and 50-80 parts of purified water.
7. The antidepressant composition as claimed in claim 6, characterized in that: the adhesive comprises the following components in parts by mass: 0.2 part of PDRN, 0.2 part of protamine, 5 parts of gamma-aminobutyric acid, 5 parts of sea cucumber peptide, 5 parts of collagen peptide, 2 parts of citric acid, 2 parts of vitamin C, 8 parts of glutathione, 2 parts of vitamin E, 3 parts of beta-carotene, 5 parts of taurine, 0.2 part of superoxide dismutase, 0.5 part of quercetin and 60 parts of purified water.
8. The antidepressant composition comprising polydeoxyribonucleotides according to claim 7, characterized in that: the antidepressant composition also comprises food color and sweetener.
9. An antidepressant drug comprising polydeoxyribonucleotides, characterized in that: the antidepressant pharmaceutical composition containing polydeoxyribonucleotides according to any one of claims 1 to 8, wherein the antidepressant pharmaceutical composition is in the form of an oral preparation or an injection preparation, and the oral preparation is a tablet, a granule, a capsule, a pill or an oral liquid.
10. The application of polydeoxyribonucleotide in the preparation of antidepressant drugs.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210789039.0A CN115337321A (en) | 2022-07-06 | 2022-07-06 | Antidepressant composition containing polydeoxyribonucleotide and medicine |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210789039.0A CN115337321A (en) | 2022-07-06 | 2022-07-06 | Antidepressant composition containing polydeoxyribonucleotide and medicine |
Publications (1)
Publication Number | Publication Date |
---|---|
CN115337321A true CN115337321A (en) | 2022-11-15 |
Family
ID=83947792
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210789039.0A Pending CN115337321A (en) | 2022-07-06 | 2022-07-06 | Antidepressant composition containing polydeoxyribonucleotide and medicine |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115337321A (en) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113332162A (en) * | 2021-04-22 | 2021-09-03 | 润辉生物技术(威海)有限公司 | protamine-PDRN compound, composition and application in preparation of skin care product |
-
2022
- 2022-07-06 CN CN202210789039.0A patent/CN115337321A/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113332162A (en) * | 2021-04-22 | 2021-09-03 | 润辉生物技术(威海)有限公司 | protamine-PDRN compound, composition and application in preparation of skin care product |
Non-Patent Citations (2)
Title |
---|
HYUNGMO JEONG等: "Effect of Polydeoxyribonucleotide on Lipopolysaccharide and Sevoflurane-Induced Postoperative Cognitive Dysfunction in Human Neuronal SH-SY5Y Cells", INT NEUROUROL J, pages 93 - 101 * |
李巍等: "抗抑郁药潜在作用靶点-神经营养因子和神经发生", 中国医药导报, vol. 10, no. 6, pages 28 - 32 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20170136050A1 (en) | Anti-glycation methods and compositions | |
JP4470212B2 (en) | Skin improver | |
TWI516280B (en) | Use of chenopodium formosanum extract for manufacture of composition for enhancing secretion of collagen and preventing cutaneous aging | |
Su et al. | Effect of anchovy (Coilia mystus) protein hydrolysate and its Maillard reaction product on combating memory-impairment in mice | |
EP2859896B1 (en) | Pharmaceutical compositions for the treatment of muscular disorders | |
CN102973937B (en) | Composition with skin beauty effect and oral administration cosmetic containing composition | |
US7951844B2 (en) | Tranquilizer and functional food | |
CN111388511A (en) | Composition for improving memory and preventing senile dementia and preparation method and application thereof | |
JP6735224B2 (en) | Activator of glucose metabolism in astrocytes | |
JP4420358B1 (en) | Hyaluronic acid production promoter | |
CN106174494A (en) | A kind of compositions and the application in the product preparing nourishing the brain and improving intelligence thereof | |
CN117356667A (en) | Nicotinamide astaxanthin composition with functions of resisting oxidization, whitening and beautifying and application thereof | |
CN117017970A (en) | Pharmaceutical composition for relieving oxidative stress and application thereof | |
CN105495153B (en) | A kind of antioxidant health-care product containing phycocyanin and ginkgo biloba p.e | |
CN115337321A (en) | Antidepressant composition containing polydeoxyribonucleotide and medicine | |
JP2008266203A (en) | Method for improving activity of reactive oxygen species-scavenging enzyme group | |
KR101914441B1 (en) | Cosmetic compositions for improving skin moisturizing comprising fucosterol | |
KR101904501B1 (en) | Cosmetic compositions for improving skin wrinkles or skin elasticity comprising fucosterol | |
JP2014129252A (en) | Skin function improving agent | |
JP2010043036A (en) | Saccharometabolism promoter | |
CN107006864B (en) | Polypeptide resveratrol preparation, preparation method and application thereof, and health-care product or pharmaceutical composition containing polypeptide resveratrol preparation | |
JP2014129253A (en) | Skin function improving agent | |
See et al. | A comprehensive review and recent advances of vitamin C: Overview, functions, sources, applications, market survey and processes | |
CN108991358A (en) | A kind of auxiliary reducing blood lipid, it is hypoglycemic, alleviate gout health care food and production method | |
CN115397263B (en) | Composition containing N-acetylglucosamine and preparation method and application thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |