WO2022179050A1 - 一种防治酒精性肝损伤的组合物及其制备方法与应用 - Google Patents
一种防治酒精性肝损伤的组合物及其制备方法与应用 Download PDFInfo
- Publication number
- WO2022179050A1 WO2022179050A1 PCT/CN2021/110092 CN2021110092W WO2022179050A1 WO 2022179050 A1 WO2022179050 A1 WO 2022179050A1 CN 2021110092 W CN2021110092 W CN 2021110092W WO 2022179050 A1 WO2022179050 A1 WO 2022179050A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- composition
- parts
- preventing
- liver injury
- sodium alginate
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 87
- 206010067125 Liver injury Diseases 0.000 title claims abstract description 82
- 231100000753 hepatic injury Toxicity 0.000 title claims abstract description 74
- 230000001476 alcoholic effect Effects 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 150000008442 polyphenolic compounds Chemical class 0.000 claims abstract description 62
- 235000013824 polyphenols Nutrition 0.000 claims abstract description 61
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 claims abstract description 56
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 53
- 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 abstract description 40
- 239000000661 sodium alginate Substances 0.000 claims abstract description 40
- 235000010413 sodium alginate Nutrition 0.000 claims abstract description 40
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 40
- 229940063673 spermidine Drugs 0.000 claims abstract description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 65
- 241001474374 Blennius Species 0.000 claims description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 23
- 238000003756 stirring Methods 0.000 claims description 21
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 16
- 239000002131 composite material Substances 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 239000000843 powder Substances 0.000 claims description 14
- 239000002775 capsule Substances 0.000 claims description 13
- 208000022309 Alcoholic Liver disease Diseases 0.000 claims description 12
- 229920002261 Corn starch Polymers 0.000 claims description 12
- 239000008120 corn starch Substances 0.000 claims description 12
- 229940099112 cornstarch Drugs 0.000 claims description 12
- 239000000463 material Substances 0.000 claims description 11
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 11
- 235000019359 magnesium stearate Nutrition 0.000 claims description 8
- 239000000454 talc Substances 0.000 claims description 8
- 229910052623 talc Inorganic materials 0.000 claims description 8
- 239000008187 granular material Substances 0.000 claims description 7
- 239000005457 ice water Substances 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- 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 4
- 239000003814 drug Substances 0.000 claims description 4
- 238000004108 freeze drying Methods 0.000 claims description 4
- 229920003063 hydroxymethyl cellulose Polymers 0.000 claims description 4
- 229940031574 hydroxymethyl cellulose Drugs 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 235000012222 talc Nutrition 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 241000195493 Cryptophyta Species 0.000 abstract description 4
- 210000004185 liver Anatomy 0.000 description 39
- 241000699670 Mus sp. Species 0.000 description 38
- 230000000694 effects Effects 0.000 description 34
- 230000003078 antioxidant effect Effects 0.000 description 26
- 239000003963 antioxidant agent Substances 0.000 description 19
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 18
- 235000006708 antioxidants Nutrition 0.000 description 18
- 108020002663 Aldehyde Dehydrogenase Proteins 0.000 description 15
- 102000005369 Aldehyde Dehydrogenase Human genes 0.000 description 15
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 14
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 14
- 230000000052 comparative effect Effects 0.000 description 14
- 239000012153 distilled water Substances 0.000 description 13
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 11
- 108010082126 Alanine transaminase Proteins 0.000 description 11
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 235000010443 alginic acid Nutrition 0.000 description 9
- 229920000615 alginic acid Polymers 0.000 description 9
- 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 9
- 238000000034 method Methods 0.000 description 9
- 150000003254 radicals Chemical class 0.000 description 9
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 8
- 230000002292 Radical scavenging effect Effects 0.000 description 8
- 210000005228 liver tissue Anatomy 0.000 description 8
- 229940118019 malondialdehyde Drugs 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 102000019197 Superoxide Dismutase Human genes 0.000 description 7
- 108010012715 Superoxide dismutase Proteins 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 230000007760 free radical scavenging Effects 0.000 description 7
- 231100000234 hepatic damage Toxicity 0.000 description 7
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 7
- 230000008818 liver damage Effects 0.000 description 7
- 230000002000 scavenging effect Effects 0.000 description 7
- 102000016938 Catalase Human genes 0.000 description 6
- 108010053835 Catalase Proteins 0.000 description 6
- 238000002835 absorbance Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 229930003268 Vitamin C Natural products 0.000 description 5
- 229960001126 alginic acid Drugs 0.000 description 5
- 239000000783 alginic acid Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 238000003304 gavage Methods 0.000 description 5
- 210000003494 hepatocyte Anatomy 0.000 description 5
- -1 hydroxyl radicals Chemical class 0.000 description 5
- 231100000915 pathological change Toxicity 0.000 description 5
- 230000036285 pathological change Effects 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 235000019154 vitamin C Nutrition 0.000 description 5
- 239000011718 vitamin C Substances 0.000 description 5
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 229940072056 alginate Drugs 0.000 description 4
- 150000004781 alginic acids Chemical class 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000002195 synergetic effect Effects 0.000 description 4
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical group O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000003064 anti-oxidating effect Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000000084 colloidal system Substances 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000035622 drinking Effects 0.000 description 3
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 3
- 230000002440 hepatic effect Effects 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- 230000003859 lipid peroxidation Effects 0.000 description 3
- 210000005229 liver cell Anatomy 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 230000036542 oxidative stress Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000003449 preventive effect Effects 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000003642 reactive oxygen metabolite Substances 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000012488 sample solution Substances 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 241000512259 Ascophyllum nodosum Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000007071 enzymatic hydrolysis Effects 0.000 description 2
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000002376 fluorescence recovery after photobleaching Methods 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 235000013372 meat Nutrition 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000002503 metabolic effect 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
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 1
- 244000003416 Asparagus officinalis Species 0.000 description 1
- 235000005340 Asparagus officinalis Nutrition 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 102000006587 Glutathione peroxidase Human genes 0.000 description 1
- 108700016172 Glutathione peroxidases Proteins 0.000 description 1
- 241000206581 Gracilaria Species 0.000 description 1
- 206010019728 Hepatitis alcoholic Diseases 0.000 description 1
- 206010019837 Hepatocellular injury Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 231100000111 LD50 Toxicity 0.000 description 1
- 241000218588 Lactobacillus rhamnosus Species 0.000 description 1
- SEBFKMXJBCUCAI-UHFFFAOYSA-N NSC 227190 Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000237502 Ostreidae Species 0.000 description 1
- 240000005373 Panax quinquefolius Species 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- JPYHHZQJCSQRJY-UHFFFAOYSA-N Phloroglucinol Natural products CCC=CCC=CCC=CCC=CCCCCC(=O)C1=C(O)C=C(O)C=C1O JPYHHZQJCSQRJY-UHFFFAOYSA-N 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 241000195474 Sargassum Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical group [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 102000009618 Transforming Growth Factors Human genes 0.000 description 1
- 108010009583 Transforming Growth Factors Proteins 0.000 description 1
- 241001261506 Undaria pinnatifida Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 231100000439 acute liver injury Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 208000002353 alcoholic hepatitis Diseases 0.000 description 1
- 108010081577 aldehyde dehydrogenase (NAD(P)+) Proteins 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000002929 anti-fatigue Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000002032 cellular defenses Effects 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 208000027744 congestion Diseases 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- HEILIGJNYTWOHU-UHFFFAOYSA-N ethanol 2-hydroxybenzoic acid Chemical compound CCO.OC(=O)C1=CC=CC=C1O HEILIGJNYTWOHU-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 210000004024 hepatic stellate cell Anatomy 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 231100000849 liver cell damage Toxicity 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 230000006996 mental state Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 235000020636 oyster Nutrition 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 150000002989 phenols Chemical group 0.000 description 1
- 229960001553 phloroglucinol Drugs 0.000 description 1
- 125000002444 phloroglucinyl group Chemical group [H]OC1=C([H])C(O[H])=C(*)C(O[H])=C1[H] 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000011506 response to oxidative stress Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- SEBFKMXJBCUCAI-HKTJVKLFSA-N silibinin Chemical compound C1=C(O)C(OC)=CC([C@@H]2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-HKTJVKLFSA-N 0.000 description 1
- 229960004245 silymarin Drugs 0.000 description 1
- 235000017700 silymarin Nutrition 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 102000014898 transaminase activity proteins Human genes 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000009723 vascular congestion Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Images
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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/132—Amines having two or more amino groups, e.g. spermidine, putrescine
-
- 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
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/734—Alginic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/618—Molluscs, e.g. fresh-water molluscs, oysters, clams, squids, octopus, cuttlefish, snails or slugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/02—Algae
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/02—Algae
- A61K36/03—Phaeophycota or phaeophyta (brown algae), e.g. Fucus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/02—Algae
- A61K36/04—Rhodophycota or rhodophyta (red algae), e.g. Porphyra
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/485—Inorganic compounds
-
- 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
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- 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
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
Definitions
- the invention relates to the technical field of biomedicine, in particular to a composition for preventing and treating alcohol-induced liver injury and a preparation method and application thereof.
- alcohol After alcohol enters the human body, it is first converted into acetaldehyde under the action of alcohol dehydrogenase, and then further oxidized into acetic acid and water by acetaldehyde dehydrogenase, and finally enters the tricarboxylic acid cycle system.
- the body ingests a large amount of alcohol, the alcohol itself will not cause harm to the body, but the acetaldehyde and free radicals formed in the metabolic process, such as superoxide anion groups and highly active hydroxyl radicals, can cause adverse effects on the body. .
- Acetaldehyde can combine with a variety of proteins in cells, resulting in the accumulation of a large amount of proteins and lipids in liver cells, which eventually leads to necrosis of cells, inflammation, and alcoholic hepatitis. Acetaldehyde can also inhibit DNA repair and methylation. , through transforming growth factor-induced activation of hepatic stellate cells, promote inflammation and destroy tissue regeneration and repair function, thereby promoting the pathological changes of liver fibrosis. The pathogenesis of alcoholic liver injury is complex. Modern pathological studies have found that the "second hit" theory is oxidative stress and inflammatory response, and oxidative stress is a key factor in the occurrence and development of alcoholic liver injury. Therefore, it has a certain market value to prepare a product that can quickly remove a large number of free radicals produced by the body after drinking, thereby reducing the side effects of alcohol on the human body.
- Chinese patent CN 202010728038.6 discloses a composition of American ginseng and Fructus Aurantii for preventing and treating alcohol-induced liver injury. Alcohol-induced liver injury is protective.
- Chinese patent CN 201210046322.0 discloses a Lactobacillus rhamnosus capable of relieving chronic alcoholic liver injury, which has the effects of anti-oxidation and relieving chronic alcoholic liver injury.
- Chinese patent CN 201811162358.9 discloses polypeptides for the prevention and treatment of alcoholic liver injury, mainly by polypeptides with antioxidant and liver protection activities to prevent and treat alcoholic liver injury.
- Chinese patent CN 201811339367.0 discloses desmethylenetetrahydroberberine hydrochloride for the prevention and treatment of alcoholic liver injury, mainly through anti-inflammatory and antioxidant activities to treat alcoholic liver disease. Most of these products prevent and treat alcohol-induced liver damage through antioxidant pathways, but antioxidants are unstable, cannot fully ensure the antioxidant activity of active ingredients in the body, cannot quickly remove excess free radicals in the body, and are slow to take effect.
- the object of the present invention is to provide a composition for preventing and treating alcoholic liver injury and its preparation method and application, so as to solve the instability of antioxidant active substances and single action pathway in the existing products for preventing and treating alcoholic liver injury in the prior art.
- the composition has the advantages of simple formula, good stability, strong anti-oxidation, and good liver protection effect.
- the present invention provides the following scheme:
- the invention provides a composition for preventing and treating alcohol-induced liver injury, which comprises the following components in parts by weight: 10-30 parts of seaweed polyphenol, 2-6 parts of sodium alginate, 30-55 parts of abalone peptide and spermidine 0.5 to 3 servings.
- the composition includes the following components: 20 parts of seaweed polyphenols, 4 parts of sodium alginate, 40 parts of abalone peptides and 1.5 parts of spermidine.
- the present invention also provides a preparation method of the above-mentioned composition for preventing and treating alcoholic liver injury, comprising the following steps:
- the mass concentration of the sodium alginate solution is 1%-3.5%; the mass concentration of the abalone peptide solution is 18%-26%.
- the pH of the sodium alginate solution is adjusted to 6.5.
- the present invention also provides an application of the above-mentioned composition in preparing a medicine for treating/preventing alcoholic liver injury.
- the present invention also provides a pharmaceutical preparation for preventing and treating alcoholic liver injury, comprising the above-mentioned composition and pharmaceutically acceptable excipients.
- the pharmaceutical preparation is a capsule
- the auxiliary materials include lactose, cornstarch and talc;
- the mass fraction of each component in the capsule is:
- composition is 10-30 wt %, lactose 10-20 wt %, corn starch 50-60 wt % and talc 5-15 wt %.
- the pharmaceutical preparation is a tablet
- the auxiliary materials include corn starch, talc and magnesium stearate
- the mass fraction of each component in the tablet is:
- composition is 10-20wt%, corn starch 65-75wt%, talc 11-17wt% and magnesium stearate 0.5-2wt%.
- the pharmaceutical preparation is a granule
- the auxiliary materials include corn starch, sodium hydroxymethyl cellulose and magnesium stearate;
- the mass fraction of each component in the granules is:
- the composition comprises 5-15 wt %, corn starch 74-84 wt %, sodium hydroxymethyl cellulose 5-15 wt % and magnesium stearate 0.5-2 wt %.
- the present invention combines seaweed polyphenols with antioxidant and antibacterial functions and abalone peptides rich in various nutrients and multiple biological effects, and forms a complex through multiple actions such as hydrogen bonds, static electricity, and ⁇ - ⁇ stacking.
- the animal model test proves that the composition plays a multi-path, multi-target and synergistic effect in the prevention and treatment of alcoholic liver injury.
- the present invention utilizes the hydrogel properties of alginate to form alginate colloid in the stomach with a low pH environment, and encapsulates the algae polyphenol and abalone peptide complexes to avoid the loss of its activity in the complex environment of the body;
- the alginic acid in the intestine is converted into an ionic salt state, and the algal polyphenols and abalone peptides are released slowly and controlled to exert a lasting active effect.
- the raw materials of the present invention all come from natural food materials, which are green and safe; the preparation process is simple, and it is easy to industrialize production; and it is safe, non-toxic, convenient to take, has no bad smell, and has good compliance.
- Figure 1 shows the scavenging ability of the composition for preventing and treating alcohol-induced liver injury prepared by the present invention to DPPH free radicals.
- Figure 2 shows the scavenging ability of the composition for preventing and treating alcoholic liver injury prepared by the present invention to OH free radicals.
- Figure 3 shows the antioxidant stability of the composition for preventing and treating alcoholic liver injury prepared by the present invention.
- Figure 4 is the effect of the composition for preventing and treating alcoholic liver injury prepared by the present invention on the liver index of mice.
- Fig. 5 is the effect of the composition for preventing and treating alcohol-induced liver injury prepared by the present invention on the pathological section of mouse liver.
- the present embodiment aims to provide a composition for preventing and treating alcoholic liver injury, which, in parts by weight, comprises the following components: 10-30 parts of seaweed polyphenols, 2-6 parts of sodium alginate, 30-55 copies of abalone peptides and 0.5-3 copies of spermidine.
- seaweed polyphenol is a polyphenolic compound extracted from seaweed, the main component is phloroglucinol and its derivatives, and its hydroxyl group is an important group with antioxidant activity. Due to the ability of seaweed polyphenols to scavenge free radicals and reactive oxygen species directly or indirectly, they are considered as natural antioxidants to prevent or reduce chronic diseases. However, polyphenols have poor stability and low bioavailability in vivo.
- Sodium alginate is a kind of biopolymer material extracted from the ocean. It has the advantages of biocompatibility, hydrophilicity and non-toxicity. It can form hydrogels through ionization under mild conditions. Alginic acid hydrogels are prepared by chemical cross-linking, enzymatic cross-linking, etc., and are widely used in controlled release systems for pharmaceutical active peptides and proteins.
- Abalone peptide is made by enzymatic hydrolysis of abalone meat. It has a complete range of amino acids and a reasonable ratio. It is known as the "soft gold" of the ocean. Abalone is rich in nutrients such as EPA, DHA, trace elements, taurine and superoxide dismutase, and has the functions of anti-oxidation, enhancing immunity and anti-fatigue.
- Spermidine a naturally occurring polyamine, is a safe and efficient inducer of autophagy, exists in almost all cells, and has anti-aging, anti-cancer, cardiovascular and neuroprotective effects.spermidine is conducive to assisting drug delivery, improving the water solubility, stability and membrane permeability of drug molecules, thereby further improving drug absorption in vivo.
- seaweed polyphenol particles are prepared by blending alginate and spermidine with seaweed polyphenol with antioxidative and antibacterial functions.
- the spermidine molecule contains three amino groups, and the two ends and the middle amino groups can be connected with sodium alginate and seaweed polyphenol respectively, forming an "umbrella" protective structure for the seaweed polyphenol and improving the stability of the product.
- Seaweed polyphenol particles and abalone peptides rich in multiple nutrients and multiple functions form complex compositions through multiple non-covalent bonds such as hydrogen bonds, electrostatics, and ⁇ - ⁇ stacking. It has a synergistic effect on the prevention and treatment of alcoholic liver injury.
- sodium alginate forms alginic acid colloid under the action of gastric acid, which encapsulates algae polyphenols and abalone peptides to avoid the loss of activity in the complex environment in the body; alginic acid is converted into ionic salt state in the intestinal tract, which lasts for a long time. Releases seaweed polyphenols and abalone peptides for long-lasting activity and improved bioavailability.
- the composition for preventing and treating alcoholic liver damage in parts by weight, includes the following components: 20 parts of seaweed polyphenols, 4 parts of sodium alginate, 40 parts of abalone peptides and 1.5 parts of spermidine .
- the seaweed polyphenols are derived from edible macroalgae, including kelp, kelp, sargassum, asparagus, hijiki, wakame or gracilaria.
- the extraction method of the seaweed polyphenol can be carried out according to the conventional extraction method of seaweed polyphenol in the art.
- the total phenol weight content in the seaweed polyphenol used in the embodiment of the present invention is not less than 30%.
- the abalone peptide is a composite peptide prepared from abalone meat through biological enzymolysis.
- the enzymatic hydrolysis method of the abalone peptide can be carried out according to the conventional method in the art.
- the molecular weight distribution range of the abalone peptides used in the embodiment of the present invention is: the content of polypeptides with molecular weight >3.0kDa is 2.15%, the content of polypeptides with molecular weights of 1.0-3.0kDa is 16.59%, and the content of polypeptides with molecular weights ⁇ 1.0kDa is 81.26%.
- seaweed polyphenols can also be purchased from Shandong Jiejing Group Co., Ltd.
- abalone peptides can also be purchased from Shandong Hailongyuan Biotechnology Co., Ltd.
- the present embodiment also provides a preparation method of the above-mentioned composition for preventing and treating alcoholic liver injury, comprising the following steps:
- the concentrations of the sodium alginate solution and the abalone peptide solution have an important influence on the stability and synergistic effect of the composition.
- the mass concentration of the sodium alginate solution is 1%-3.5%, and more preferably 1.5%;
- the formation of uniform seaweed polyphenol particles has poor efficacy; if the mass concentration of the sodium alginate solution is too small ( ⁇ 1%), the effect with spermidine is weak, and the protective effect on the seaweed polyphenol cannot be achieved.
- the mass concentration of the abalone peptide solution is 18%-26%, more preferably 22%; if the mass concentration of the abalone peptide solution is too large (>26%), it is susceptible to microbial infection and loses activity ; If the mass concentration of abalone peptide solution is too small ( ⁇ 18%), the synergistic effect with seaweed polyphenols is weakened, and the effect of preventing and treating alcoholic liver damage cannot be achieved.
- the pH range of the solution needs to be strictly controlled.
- the method for adjusting the pH of the present invention is a conventional method. Since the sodium alginate solution is weakly alkaline, the present invention adopts a 0.1 mol/L HCl solution for adjusting the pH. If the pH of the solution is too low ( ⁇ 6.0), the acidity will be too strong, and sodium alginate will form alginic acid colloids; if the pH of the solution is too high (>7.5), spermidine will be difficult to interact with sodium alginate and algae through electrostatic interaction. Phenols form complex "umbrella" structures. Therefore, in this embodiment, the pH of the sodium alginate solution is preferably 6.0-7.5, more preferably 6.5.
- the room temperature involved in the present invention is also referred to as normal temperature or general temperature, and is generally defined as 25°C, which can be reasonably adjusted by those skilled in the art, which is also within the protection scope of the present invention.
- composition for preventing and treating alcoholic liver injury provided by the present invention is described in detail below with reference to the examples, but they should not be construed as limiting the protection scope of the present invention.
- a composition for preventing and treating alcohol-induced liver damage comprising the following components in parts by weight: 20 parts of seaweed polyphenols, 4 parts of sodium alginate, 40 parts of abalone peptides and 1.5 parts of spermidine.
- the preparation method of the composition comprises the following steps:
- a composition for preventing and treating alcoholic liver damage comprising the following components in parts by weight: 15 parts of seaweed polyphenols, 3 parts of sodium alginate, 35 parts of abalone peptides and 1 part of spermidine.
- the preparation method of the composition comprises the following steps:
- a composition for preventing and treating alcohol-induced liver damage comprising the following components in parts by weight: 10 parts of seaweed polyphenols, 2 parts of sodium alginate, 30 parts of abalone peptides and 0.5 parts of spermidine.
- the preparation method of the composition comprises the following steps:
- a composition for preventing and treating alcoholic liver damage comprising the following components in parts by weight: 30 parts of seaweed polyphenols, 6 parts of sodium alginate, 55 parts of abalone peptides, and 3 parts of spermidine.
- the preparation method of the composition comprises the following steps:
- Example 1 The only difference from Example 1 is that the seaweed polyphenols are replaced by vitamin C.
- Example 1 The only difference from Example 1 is that spermidine is used instead of spermidine.
- Example 1 The only difference from Example 1 is that the direct raw materials are blended, as follows:
- a composition for preventing and treating alcohol-induced liver damage comprising the following components in parts by weight: 20 parts of seaweed polyphenols, 4 parts of sodium alginate, 40 parts of abalone peptides and 1.5 parts of spermidine.
- the preparation method of the composition comprises the following steps:
- composition is obtained by taking the raw materials of sodium alginate, spermidine, seaweed polyphenol and abalone peptide according to the stated weight parts, adding distilled water, suspending uniformly, and freeze-drying.
- Example 1 The only difference from Example 1 is that oyster peptide is used instead of abalone peptide.
- AX is the absorbance of the sample, Absorbance of blank control.
- Vitamin C (Vc) a strong antioxidant, served as a positive control.
- the DPPH free radical scavenging effect of the composition for preventing and treating alcohol-induced liver injury is shown in Figure 1.
- the IC 50 of Examples 1 to 4 are all close to the vitamin C group, showing a strong DPPH free radical scavenging effect, especially Example 1.
- the DPPH free radical scavenging ability is the strongest.
- Group 1 of Comparative Example also showed a DPPH free radical scavenging effect similar to that of Groups 1 to 4, the scavenging ability of DPPH free radicals of Groups 2 to 4 of Comparative Example was far inferior to that of Groups 1 to 4.
- Vitamin C (Vc), a strong antioxidant, served as a positive control.
- the hydroxyl radical scavenging effect of the composition for preventing and treating alcohol-induced liver injury is shown in Figure 2.
- the IC 50 of Examples 1 to 4 is almost close to the vitamin C group, showing a strong hydroxyl radical scavenging effect, especially Example 1.
- the hydroxyl radical scavenging ability is the strongest.
- the comparative example 1 group also showed a hydroxyl radical scavenging effect similar to that of the examples 1 to 4, the hydroxyl radical scavenging ability of the comparative examples 2 to 4 was far inferior to that of the examples 1 to 4.
- the groups of Examples 1-4 all showed strong free radical scavenging effects, indicating that the composition for preventing and treating alcoholic liver injury prepared by the present invention has strong antioxidant activity, especially the anti-oxidative activity of Example 1 group. The most oxidative activity. If the formulation or preparation method of the composition of the present invention is changed, the expected antioxidant effect cannot be achieved.
- the total antioxidant capacity of the composition during storage was measured using the iron ion reduction/antioxidative capacity assay (FRAP method).
- Samples are stored in brown bottles at room temperature. Samples were taken at regular intervals and tested for total antioxidant capacity.
- Test method Take 0.02mL FeSO 4 solution, add 0.18mL FRAP solution (prepared and used now), mix well, take a water bath at 37°C for 10min, and measure the absorbance at 593nm using a UV-Vis spectrophotometer. Taking the concentration of FeSO 4 solution as the abscissa and the absorbance value as the ordinate, the FeSO 4 equivalent standard curve was established. Taking the VC solution as the positive control, the FeSO 4 equivalent was calculated according to the standard curve. The relative percent VC was calculated for each sample based on FeSO 4 equivalents.
- mice Kunming male mice, 6-8 weeks old, body weight 18-22 grams, SPF grade, animal feeding conditions: (25 ⁇ 1)° C., relative humidity: (55 ⁇ 5)%.
- mice were randomly divided into 11 groups, 12 mice in each group, divided into blank control group, model group, silymarin positive control group, Example 1-4 groups and Comparative Example 1-4 groups.
- mice in each group were given the corresponding volume of the test substance by gavage at a dose of 10 g/kg ⁇ BW (body weight) every day, and the blank control group and the model group were given distilled water by gavage for 6 consecutive days. Start fasting without water for 24h. Continue to give the test substance after 24 hours, and give each group of mice 56 degrees Hongxing Erguotou Liquor by gavage at a dose of 13 mL/kg BW after 60 minutes, and the blank control group with distilled water, and collect samples after 60 minutes:
- liver index was calculated by the formula:
- Liver index (%) liver weight (g) / body weight (g) ⁇ 100%
- liver tissue homogenate (4) Quickly dissect the liver, store it at -80°C, prepare it into 10% liver tissue homogenate, and perform strict operations according to the requirements of the corresponding kit to measure alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the liver tissue homogenate ( ALDH) content.
- ADH alcohol dehydrogenase
- ALDH aldehyde dehydrogenase
- the liver index has a certain significance for the assessment of the health status of the liver, and the changes of the liver index in mice taking the composition for preventing and treating alcohol-induced liver injury are shown in FIG. 4 .
- the liver index increases, it is likely that the liver is enlarged, with hyperplasia, congestion, edema and other lesions.
- the liver index of the model group was significantly increased, and compared with the blank control group, there was a significant difference (p ⁇ 0.01), indicating that the modeling was successful.
- the liver indexes of the mice in the examples 1 to 4 were significantly reduced, with a statistical difference (p ⁇ 0.01), and the effect of the example 1 group was better, almost close to the level of the blank control group, indicating the present invention
- the prepared composition for preventing and treating alcohol-induced liver injury can effectively improve liver index, reduce liver hyperplasia, edema and other pathological changes, and has a significant preventive and therapeutic effect on alcohol-induced liver injury.
- the liver indexes of the mice in the control groups 1 to 4 were reduced, there was no statistical difference, and they were all higher than the positive control group. This shows that the changes in the formulation or preparation method of the composition of the present invention cannot effectively improve the liver index.
- the pathological changes of mouse liver tissue can be visually observed by HE staining of liver tissue sections.
- Figure 5 HE staining, magnification ⁇ 200
- the structure of the hepatic lobules was clear, the hepatocytes were arranged radially and neatly, the hepatic sinusoids were normal, and the nucleus structure was clear.
- alcohol gavage led to severe liver damage in mice.
- the liver cells were disordered, the hepatic sinuses were narrowed and scattered, and pathological changes such as vascular congestion were seen.
- the hepatocytes of the groups of Examples 1 to 4 were obviously normalized to different degrees, among which the hepatocytes of the Example 1 group were particularly obvious. It is indicated that the composition for preventing and treating alcohol-induced liver damage prepared by the present invention can effectively alleviate the liver cell damage caused by alcohol.
- the early stage of alcoholic liver injury is mainly manifested by the increase in the permeability of hepatocyte membrane, and the activity content of ALT and AST released into the blood will be significantly increased.
- the effect of the composition for prevention and treatment of alcoholic liver injury on the active content of ALT and AST in mice is shown in Table 1.
- the content of ALT and AST in the serum of mice was significantly higher than that of the blank control group, with a significant difference (p ⁇ 0.01).
- the levels of ALT and AST in the serum of the mice in the examples 1 to 4 were significantly reduced, with a statistical difference (p ⁇ 0.01), and the effect of the example 1 group was better, indicating that the prevention and treatment of alcoholic
- the composition for liver injury can effectively reduce the content of ALT and AST in serum and relieve liver injury.
- ADH and ALDH are the main metabolic enzymes after ethanol enters the body.
- ADH catalyzes the conversion of ethanol into acetaldehyde
- ALDH catalyzes the conversion of acetaldehyde into acetic acid
- Table 2 shows the effects of the composition for preventing and treating alcoholic liver injury on the activities of ADH and ALDH in the liver of mice. Compared with the blank control group, the activities of ADH and ALDH in the liver of the mice in the model group decreased significantly, with a statistical difference (p ⁇ 0.01), indicating that acute large-scale alcohol intake inhibits the activities of ADH and ALDH in the liver, which can easily cause alcoholic liver damage. .
- the activities of ADH and ALDH in the liver of the mice in Examples 1 to 4 were significantly increased (p ⁇ 0.01), indicating that the intervention of the composition for preventing and treating alcoholic liver injury prepared by the present invention can improve the activities of ADH and ALDH in the liver of the mice. , accelerates the metabolic decomposition of ethanol, catalyzes the further oxidation of acetaldehyde to acetic acid, slows down the direct poisoning of ethanol and its metabolites to the mouse liver, and protects the mouse from acute liver injury induced by alcohol.
- the comparative examples 1 to 4 except for the comparative example 3, there is no statistical difference in the changes of the activities of ADH and ALDH in the mouse liver. It has no obvious effect on the activity of ALDH, and has no preventive effect on alcoholic liver injury.
- ROS reactive oxygen species
- the contents of SOD, GSH-Px and CAT in the liver tissue of the mice in the groups of Examples 1 to 4 were significantly increased (p ⁇ 0.01), among which the group of Example 1 was particularly strong, indicating that the method for preventing and treating alcoholic liver disease prepared by the present invention
- the damaged composition can significantly reduce alcohol-induced peroxide levels in the liver of mice and enhance the body's antioxidant capacity.
- MDA is the product of free radicals acting on lipid peroxidation, and the amount of MDA can reflect the degree of lipid peroxidation in the body.
- the MDA content in the liver tissue of the mice in Examples 1-4 was significantly lower than that in the model control group (p ⁇ 0.01), wherein the MDA content of Example 1 group is the lowest, indicating that the composition for preventing and treating alcohol-induced liver injury prepared by the present invention can reduce the degree of lipid peroxidation in the body and alleviate alcohol-induced liver injury.
- mice 20 healthy mice, weighing 18-22g, half male and half male, were randomly divided into the experimental group and the blank control group.
- Test substance The composition of Example 1 was used as the test substance.
- mice In the pre-experiment, the median lethal dose could not be measured, so the above-mentioned experimental dosage was used for the test. Based on the body weight of the mice, at a dose of 10 g/kg, the mice were gavaged once every 24 hours. The mice in the experimental group were continuously gavaged with distilled water for 2 weeks. During the period, the activity status, diet, feces, respiration, body weight and death of the mice were observed.
- mice There was no death in the experimental group mice within 2 weeks of gavage with the test substance. Compared with the control group, there was no significant difference in body weight change, and there was no abnormality in eating and drinking. The mice were in good mental state and active. After the animals were sacrificed, there was no abnormality in the main organs observed with the naked eye.
- the results show that the oral application of the composition for preventing and treating alcohol-induced liver injury of the present invention has no obvious damage to animals, no toxic reaction to the body, and is safe and non-toxic.
- Example 5 A tablet for preventing and treating alcoholic liver injury
- the tablet for preventing and treating alcohol-induced liver injury in terms of mass fraction, includes the following components:
- Example 6 A tablet for preventing and treating alcoholic liver injury
- the tablet for preventing and treating alcohol-induced liver injury in terms of mass fraction, includes the following components:
- Example 7 A tablet for preventing and treating alcoholic liver injury
- the tablet for preventing and treating alcohol-induced liver injury in terms of mass fraction, includes the following components:
- Example 8 A capsule for preventing and treating alcoholic liver injury
- the capsule for preventing and treating alcohol-induced liver injury in terms of mass fraction, includes the following components:
- Embodiment 9 A kind of capsule for preventing and treating alcoholic liver injury
- the capsule for preventing and treating alcohol-induced liver injury in terms of mass fraction, includes the following components:
- Embodiment 10 A kind of capsule for preventing and treating alcoholic liver injury
- the capsule for preventing and treating alcohol-induced liver injury in terms of mass fraction, includes the following components:
- Example 11 A kind of granule for preventing and treating alcohol-induced liver injury
- the capsule for preventing and treating alcohol-induced liver injury in terms of mass fraction, includes the following components:
- Example 12 A kind of granule for preventing and treating alcohol-induced liver injury
- the capsule for preventing and treating alcohol-induced liver injury in terms of mass fraction, includes the following components:
- Example 13 A kind of granule for preventing and treating alcohol-induced liver injury
- the capsule for preventing and treating alcohol-induced liver injury in terms of mass fraction, includes the following components:
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medical Informatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Botany (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Marine Sciences & Fisheries (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本发明公开了一种防治酒精性肝损伤的组合物及其制备方法与应用,属于生物医药技术领域,该组合物,以重量份计,包括以下组分:海藻多酚10~30份、海藻酸钠2~6份、鲍鱼肽30~55份和亚精胺0.5~3份。
Description
本发明涉及生物医药技术领域,特别是涉及一种防治酒精性肝损伤的组合物及其制备方法与应用。
酒是人类生活中的主要饮料之一。适量饮酒具有促进血液循环、疏通经络、益气养胃、祛痛、止湿等功效。然而,随着经济的发展和社交活动的增加,爱好饮酒的人群比例不断上升,酒精引起的疾病和问题日益严重。长期过度饮酒则会引起慢性酒精中毒,导致酒精性肝病,使人体产生心肌乏力、黏膜损伤、血管变脆、肾功能衰竭等病理变化,还会引起机体生理功能紊乱,危害人体健康。
酒精进入人体后,首先在乙醇脱氢酶的作用下转化为乙醛,随之通过乙醛脱氢酶进一步氧化成乙酸和水,最终进入三羧酸循环系统。当机体摄入大量的酒精时,酒精本身不会对身体造成危害,但在代谢过程中形成的乙醛和自由基比如超氧阴离子基团、高活性氢氧自由基却能对身体造成不良影响。乙醛能够与细胞中的多种蛋白质结合,使得肝细胞内堆积大量的蛋白质和脂质,最终导致细胞病变坏死,出现炎症反应,引发酒精性肝炎;乙醛还能抑制DNA修复和甲基化,通过转化生长因子诱导肝星状细胞活化,促进炎症并破坏组织再生和修复功能,进而促进肝纤维化的病理变化。酒精性肝损伤的发病机制复杂,现代病理学研究发现“二次打击”学说即氧化应激和炎症性反应,其中氧化应激是酒精性肝损伤发生与发展的关键因素。因此,制备一种能快速清除饮酒后机体产生的大量自由基的产品,进而降低酒精对人体的副作用,具有一定的市场价值。
现有技术中公开了多种防治酒精性肝损伤的物质,如中国专利CN 202010728038.6公开了一种防治酒精性肝损伤的西洋参和枳椇子组合物,通过改善脂质代谢和提高抗氧化性对酒精性肝损伤具有保护作用。中国专利CN 201210046322.0公开了一种能够缓解慢性酒精性肝损伤的鼠李糖乳杆菌,具有抗氧化、缓解慢性酒精性肝损伤的作用。中国专利CN 201811162358.9公开了防治酒精性肝损伤的多肽,主要由具有抗氧化和护肝活性的多肽来起到防治酒精性肝损伤的功效。中国专利CN 201811339367.0公开了防治酒精性肝损伤的盐酸去亚甲基四氢小檗碱,主要通过抗炎和抗氧化活性治疗酒精性肝病。这些产品多数通过抗氧化途径来防治酒精性肝损伤,但抗氧化剂具有不稳定性, 不能完全确保有效成分在体内的抗氧化活性,不能快速清除体内过量的自由基,见效慢。
发明内容
本发明的目的是提供一种防治酒精性肝损伤的组合物及其制备方法与应用,以解决上述现有技术存在的现有防治酒精性肝损伤产品中抗氧化活性物质不稳定及作用途径单一的问题,该组合物配方简单,稳定性好,抗氧化性强,保肝护肝效果好。
为实现上述目的,本发明提供了如下方案:
本发明提供一种防治酒精性肝损伤的组合物,以重量份计,包括以下组分:海藻多酚10~30份、海藻酸钠2~6份、鲍鱼肽30~55份和亚精胺0.5~3份。
进一步地,以重量份计,所述组合物包括以下组分:海藻多酚20份、海藻酸钠4份、鲍鱼肽40份和亚精胺1.5份。
本发明还提供一种上述的防治酒精性肝损伤的组合物的制备方法,包括以下步骤:
S1.取海藻酸钠加入水中配制成海藻酸钠溶液,调节溶液pH 6.0-7.5,加入亚精胺,室温搅拌5-8小时,冰水浴处理,待溶液体系降温至5-10℃,加入海藻多酚,继续搅拌1-3小时,冷冻干燥,液氮碎化,得到海藻多酚复合粉粒;
S2.用水溶解鲍鱼肽,制成鲍鱼肽溶液,在搅拌状态下加入所述海藻多酚复合粉粒,混悬均匀,冷冻干燥,即得所述防治酒精性肝损伤的组合物。
进一步地,所述海藻酸钠溶液的质量浓度为1%-3.5%;所述鲍鱼肽溶液的质量浓度为18%-26%。
进一步地,所述海藻酸钠溶液pH调节至6.5。
本发明还提供一种上述的组合物在制备治疗/预防酒精性肝损伤的药物中的应用。
本发明还提供一种防治酒精性肝损伤的药物制剂,包括上述的组合物,及药学上可接受的辅料。
进一步地,所述药物制剂为胶囊剂,所述辅料包括乳糖、玉米淀粉和滑石粉;
所述胶囊剂中各组分的质量分数为:
所述组合物10-30wt%、乳糖10-20wt%、玉米淀粉50-60wt%和滑石粉5-15wt%。
进一步地,所述药物制剂为片剂,所述辅料包括玉米淀粉、滑石粉和硬脂酸镁;
所述片剂中各组分的质量分数为:
所述组合物10-20wt%、玉米淀粉65-75wt%、滑石粉11-17wt%和硬脂酸镁0.5-2wt%。
进一步地,所述药物制剂为颗粒剂,所述辅料包括玉米淀粉、羟甲基纤维素钠和硬脂酸镁;
所述颗粒剂中各组分的质量分数为:
所述组合物5-15wt%、玉米淀粉74-84wt%、羟甲基纤维素钠5-15wt%和硬脂酸镁0.5-2wt%。
本发明公开了以下技术效果:
(1)本发明将具有抗氧化、抗菌功能的海藻多酚和富含多种营养、多重生物功效的鲍鱼肽组合,通过氢键、静电、π-π堆叠等多重作用,二者形成复合物;经动物模型试验证明,该组合物在酒精性肝损伤的防治中发挥多途径、多靶点、协同增效作用。
(2)本发明利用海藻酸盐的水凝胶特性,在胃中低pH环境下形成海藻酸胶质,包裹海藻多酚和鲍鱼肽复合物,避免其在体内复杂环境中活性的丧失;在肠道中海藻酸转换为离子盐状态,缓控释放海藻多酚和鲍鱼肽,发挥持久活性效应。
(3)本发明中添加的亚精胺,利用其“三胺”特性,分别与海藻酸盐和海藻多酚相连接,对海藻多酚形成“伞”式保护结构,使得海藻多酚的稳定性、物理性状及口感均得到改善,有利于其发挥在酒精性肝损伤中的保肝护肝作用。
(4)本发明原料均来自天然食材,绿色安全;制备工艺简单,易于工业化生产;而且安全无毒,服用方便,无不良气味,依从性好。
为了更清楚地说明本发明实施例或现有技术中的技术方案,下面将对实施例中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图仅仅是本发明的一些实施例,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他的附图。
图1是本发明制备的防治酒精性肝损伤的组合物对DPPH自由基清除能力。
图2是本发明制备的防治酒精性肝损伤的组合物对OH自由基清除能力。
图3是本发明制备的防治酒精性肝损伤的组合物的抗氧化稳定性。
图4是本发明制备的防治酒精性肝损伤的组合物对小鼠肝脏指数的影响。
图5是本发明制备的防治酒精性肝损伤的组合物对小鼠肝脏病理切片的影响。
现详细说明本发明的多种示例性实施方式,该详细说明不应认为是对本发明的限 制,而应理解为是对本发明的某些方面、特性和实施方案的更详细的描述。
应理解本发明中所述的术语仅仅是为描述特别的实施方式,并非用于限制本发明。另外,对于本发明中的数值范围,应理解为还具体公开了该范围的上限和下限之间的每个中间值。在任何陈述值或陈述范围内的中间值以及任何其他陈述值或在所述范围内的中间值之间的每个较小的范围也包括在本发明内。这些较小范围的上限和下限可独立地包括或排除在范围内。
除非另有说明,否则本文使用的所有技术和科学术语具有本发明所述领域的常规技术人员通常理解的相同含义。虽然本发明仅描述了优选的方法和材料,但是在本发明的实施或测试中也可以使用与本文所述相似或等同的任何方法和材料。本说明书中提到的所有文献通过引用并入,用以公开和描述与所述文献相关的方法和/或材料。在与任何并入的文献冲突时,以本说明书的内容为准。
在不背离本发明的范围或精神的情况下,可对本发明说明书的具体实施方式做多种改进和变化,这对本领域技术人员而言是显而易见的。由本发明的说明书得到的其他实施方式对技术人员而言是显而易见得的。本申请说明书和实施例仅是示例性的。
关于本文中所使用的“包含”、“包括”、“具有”、“含有”等等,均为开放性的用语,即意指包含但不限于。
作为本发明的一方面,本实施方式旨在提供一种防治酒精性肝损伤的组合物,以重量份计,包括以下组分:海藻多酚10~30份、海藻酸钠2~6份、鲍鱼肽30~55份和亚精胺0.5~3份。
其中,海藻多酚是从海藻中提取出来的多酚类化合物,主要成分是间苯三酚及其衍生物,其羟基是具有抗氧化活性的重要基团。由于海藻多酚具有直接或间接清除自由基和活性氧的能力,被认为是预防或减少慢性疾病的天然抗氧化剂。但多酚类物质稳定性差,体内生物利用度低。
海藻酸钠是一类从海洋中提取的生物高分子材料,具有生物相容性、亲水性、无毒等优点,可在温和条件下通过电离作用形成水凝胶,通常采用物理交联、化学交联、酶交联等方式制备海藻酸水凝胶,广泛应用于药物活性肽和蛋白质的控制释放系统。
鲍鱼肽是鲍鱼肉经过酶解制成,其氨基酸种类齐全、配比合理,被誉为海洋“软黄金”。鲍鱼中EPA、DHA、微量元素、牛磺酸及超氧化物歧化酶等营养成分丰富,具有抗氧化、增强免疫力、抗疲劳等作用。
亚精胺是一种天然存在的多胺,是一种安全、高效的细胞自噬诱导剂,几乎存在于所有细胞中,具有抗衰老、抗癌、保护心血管和神经等作用。亚精胺有利于辅助药物输送,提高药物分子的水溶解度、稳定性和膜渗透能力从而进一步提高药物在生物体内的吸收。
本发明是将海藻酸盐和亚精胺与具有抗氧化、抗菌功能的海藻多酚通过共混,制成海藻多酚颗粒。亚精胺分子含有三个氨基,两端和中间的氨基可以分别与海藻酸钠、海藻多酚相连接,对海藻多酚形成“伞”式保护结构,提高产品的稳定性。海藻多酚颗粒和富含多种营养与多重功效的鲍鱼肽通过氢键、静电、π-π堆叠等多重非共价键作用,形成复配组合物,通过多种途径、多个靶点,对酒精性肝损伤的防治产生对协同增效作用。当组合物进入胃中,海藻酸钠在胃酸的作用下形成海藻酸胶体,包裹海藻多酚和鲍鱼肽,避免在体内复杂环境下活性的丧失;在肠道中海藻酸转换为离子盐状态,持续释放海藻多酚和鲍鱼肽,发挥持久活性,提高其生物利用度。
作为一优先的实施方式,所述防治酒精性肝损伤的组合物,以重量份计,包括以下组分:海藻多酚20份、海藻酸钠4份、鲍鱼肽40份和亚精胺1.5份。
进一步优选,所述海藻多酚来源于可食用大型海藻,包括海带、昆布、马尾藻、龙须菜、羊栖菜、裙带菜或江蓠。所述海藻多酚的提取方法可按本领域海藻多酚的常规提取方法进行。进一步优选,本发明实施例所采用的海藻多酚中总酚重量含量不少于30%。
进一步优选,所述鲍鱼肽是采用鲍鱼肉经生物酶解制备得到的复合肽。所述鲍鱼肽的酶解方法可按本领域的常规方法酶解进行。进一步优选,本发明实施例所采用的鲍鱼肽的分子量分布范围为:分子量>3.0kDa多肽含量为2.15%,分子量1.0~3.0kDa多肽含量为16.59%,分子量<1.0kDa多肽含量为81.26%。
作为另一实施方式,所述海藻多酚也可购自山东洁晶集团股份有限公司,所述鲍鱼肽也可购自山东海龙元生物科技有限公司。
作为本发明的另一方面,本实施方式还提供一种上述的防治酒精性肝损伤的组合物的制备方法,包括以下步骤:
S1.取海藻酸钠加入水中配制成海藻酸钠溶液,调节溶液pH 6.0-7.5,加入亚精胺,室温搅拌5-8小时,冰水浴处理,待溶液体系降温至5-10℃,加入海藻多酚,继续搅拌1-3小时,冷冻干燥,液氮碎化,得到海藻多酚复合粉粒;
S2.用水溶解鲍鱼肽,制成鲍鱼肽溶液,在搅拌状态下加入所述海藻多酚复合粉粒,混悬均匀,冷冻干燥,即得所述防治酒精性肝损伤的组合物。
在所述防治酒精性肝损伤的组合物的制备过程中,海藻酸钠溶液和鲍鱼肽溶液的浓度对组合物的稳定性和协同增效作用有重要影响。
作为一优先的实施方式,所述海藻酸钠溶液的质量浓度为1%-3.5%,更优选为1.5%;若海藻酸钠溶液的质量浓度过大(>3.5%),容易粘团,难以形成均匀的海藻多酚颗粒,功效差;若海藻酸钠溶液的质量浓度过小(<1%),与亚精胺作用弱,达不到对海藻多酚的保护效果。
作为一优先的实施方式,所述鲍鱼肽溶液的质量浓度为18%-26%,更优选为22%;若鲍鱼肽溶液的质量浓度过大(>26%),易受微生物感染,丧失活性;若鲍鱼肽溶液的质量浓度过小(<18%),与海藻多酚的协同作用减弱,达不到防治酒精性肝损伤的效果。
作为一优先的实施方式,在步骤S1中,需要严格控制溶液的pH范围。本发明调节pH的方法为常规方法,由于海藻酸钠溶液呈弱碱性,因此,本发明调节pH采用的为0.1mol/L的HCl溶液。若溶液的pH过小(<6.0),则酸性过强,海藻酸钠生成海藻酸胶体析出;若溶液的pH过大(>7.5),亚精胺难以通过静电作用与海藻酸钠和海藻多酚形成复合“伞”式结构。因此,本实施方式中,所述海藻酸钠溶液pH优选为6.0-7.5,更优选为6.5。
作为说明,本发明中所涉及的室温,也成为常温或者一般温度,一般定义为25℃,本领域技术人员可对其进行合理调整,其也在本发明的保护范围内。
为了进一步说明本发明,下面结合实施例对本发明提供的防治酒精性肝损伤的组合物进行详细地描述,但不能将它们理解为对本发明保护范围的限定。
实施例1
一种防治酒精性肝损伤的组合物,以重量份计,包括以下组分:海藻多酚20份、海藻酸钠4份、鲍鱼肽40份和亚精胺1.5份。
所述组合物的制备方法,包括以下步骤:
S1.按所述重量份数,取海藻酸钠加入蒸馏水中配制成1.5wt%海藻酸钠溶液,调节溶液pH 6.5,加入亚精胺,室温搅拌6.5小时,冰水浴处理,待溶液体系降温至8℃,加入海藻多酚,继续搅拌2小时,冷冻干燥,液氮碎化,得到海藻多酚复合粉粒;
S2.按所述重量份数,用蒸馏水溶解鲍鱼肽,制成22wt%鲍鱼肽溶液,在搅拌状态下,加入S1所述海藻多酚复合粉粒,混悬均匀,冷冻干燥,即可得到所述组合物。
实施例2
一种防治酒精性肝损伤的组合物,以重量份计,包括以下组分:海藻多酚15份、海藻酸钠3份、鲍鱼肽35份和亚精胺1份。
所述组合物的制备方法,包括以下步骤:
S1.按所述重量份数,取海藻酸钠加入蒸馏水中配制成2.0wt%海藻酸钠溶液,调节溶液pH 7.0,加入亚精胺,室温搅拌7小时,冰水浴处理,待溶液体系降温至6℃,加入海藻多酚,继续搅拌1.5小时,冷冻干燥,液氮碎化,得到海藻多酚复合粉粒;
S2.按所述重量份数,用蒸馏水溶解鲍鱼肽,制成24wt%鲍鱼肽溶液,在搅拌状态下,加入S1所述海藻多酚复合粉粒,混悬均匀,冷冻干燥,即可得到所述组合物。
实施例3
一种防治酒精性肝损伤的组合物,以重量份计,包括以下组分:海藻多酚10份、海藻酸钠2份、鲍鱼肽30份和亚精胺0.5份。
所述组合物的制备方法,包括以下步骤:
S1.按所述重量份数,取海藻酸钠加入蒸馏水中配制成1wt%海藻酸钠溶液,调节溶液pH 6.0,加入亚精胺,室温搅拌5小时,冰水浴处理,待溶液体系降温至5℃,加入海藻多酚,继续搅拌1小时,冷冻干燥,液氮碎化,得到海藻多酚复合粉粒;
S2.按所述重量份数,用蒸馏水溶解鲍鱼肽,制成18wt%鲍鱼肽溶液,在搅拌状态下,加入S1所述海藻多酚复合粉粒,混悬均匀,冷冻干燥,即可得到所述组合物。
实施例4
一种防治酒精性肝损伤的组合物,以重量份计,包括以下组分:海藻多酚30份、海藻酸钠6份、鲍鱼肽55份、亚精胺3份。
所述组合物的制备方法,包括以下步骤:
S1.按所述重量份数,取海藻酸钠加入蒸馏水中配制成3.5wt%海藻酸钠溶液,调节溶液pH 7.5,加入亚精胺,室温搅拌8小时,冰水浴处理,待溶液体系降温至10℃,加入海藻多酚,继续搅拌3小时,冷冻干燥,液氮碎化,得到海藻多酚复合粉粒;
S2.按所述重量份数,用蒸馏水溶解鲍鱼肽,制成26wt%鲍鱼肽溶液,在搅拌状态下,加入S1所述海藻多酚复合粉粒,混悬均匀,冷冻干燥,即可得到所述组合物。
对比例1
与实施例1的不同之处仅在于,用维生素C代替海藻多酚。
对比例2
与实施例1的不同之处仅在于,用精胺代替亚精胺。
对比例3
与实施例1的不同之处仅在于,直接原料共混,具体如下:
一种防治酒精性肝损伤的组合物,以重量份计,包括以下组分:海藻多酚20份、海藻酸钠4份、鲍鱼肽40份和亚精胺1.5份。
所述组合物的制备方法,包括以下步骤:
按所述重量份数,取海藻酸钠、亚精胺、海藻多酚和鲍鱼肽原料,加入蒸馏水,混悬均匀,冷冻干燥,即可得到所述组合物。
对比例4
与实施例1的不同之处仅在于,用牡蛎肽代替鲍鱼肽。
应用例1 防治酒精性肝损伤的组合物的抗氧化实验
1、实验方法
(1)1,1-二苯基-2-三硝基苯肼(DPPH)自由基清除能力的测定
将2.0mL不同质量浓度的样品溶液(实施例1~4组和对比例1~4组制备得到的组合物)与2mLDPPH无水乙醇溶液混合,室温下避光放置60min后,在517nm处测定溶液的吸光度。以蒸馏水代替样品溶液作空白对照,按下式(1)计算DPPH自由基的清除率,用IC
50表示清除效果。
(2)羟自由基清除能力的测定
在同一比色管中分别加入浓度为1mL H
2O
2溶液(8.8mmol/L)、1mL FeSO
4溶液(9mmol/L)和12mL不同质量浓度的样品溶液(实施例1~4组和对比例1~4组制备得到的组合物),再加入1mL水杨酸的乙醇溶液(9mmol/L),摇匀,置37℃水浴30min,在波长510nm处测定吸光度;以蒸馏水替代样品溶液作空白对照。羟自由基清除率按公式(1)计算,用IC
50表示清除效果。
2、实验结果
(1)DPPH自由基清除效果
IC
50值越小,清除自由基能力越强。维生素C(Vc)是一种强抗氧化剂,作为阳性对照。防治酒精性肝损伤的组合物的DPPH自由基清除效果如图1所示,实施例1~4组的IC
50都接近维生素C组,表现出强的DPPH自由基清除效果,尤以实施例1的DPPH自由基清除能力最强。虽然对比例1组也表现出与实施例1~4组接近的DPPH自由基清除效果,但对比例2-4组的DPPH自由基清除能力远远不如实施例1~4组。
(2)羟自由基清除效果
维生素C(Vc)是一种强抗氧化剂,作为阳性对照。防治酒精性肝损伤的组合物的羟自由基清除效果如图2所示,实施例1~4组的IC
50差不多接近维生素C组,表现出强的羟自由基清除效果,尤以实施例1的羟自由基清除能力最强。虽然对比例1组也表现出与实施例1~4组接近的羟自由基清除效果,但对比例2-4组的羟自由基清除能力远远不如实施例1~4组。
综合以上两个实验结果,实施例1-4组都表现出强的自由基清除效果,说明本发明制备的防治酒精性肝损伤的组合物具有强的抗氧化活性,尤以实施例1组抗氧化活性最强。本发明组合物的配方或者制备方法改变,都达不到预期的抗氧化效果。
应用例2 防治酒精性肝损伤组合物的抗氧化稳定性实验
采用铁离子还原/抗氧化能力法(FRAP法)检测组合物存储期间的总抗氧化能力。
样品储存:样品存储于棕色瓶中,室温条件下放置。样品每隔一定时间取样,进行总抗氧化能力测试。
测试方法:取0.02mL FeSO
4溶液,加入0.18mL FRAP液(现配现用),混匀,37℃水浴10min,采用紫外-可见分光光度计在593nm测吸光值。以FeSO
4溶液浓度为横坐标,吸光值为纵坐标,建立FeSO
4当量标准曲线。以V
C溶液为阳性对照,根据标准曲线计算出FeSO
4当量。根据FeSO
4当量计算出各样品的V
C相对百分比。
防治酒精性肝损伤的组合物的抗氧化稳定性结果如图3所示,由于多酚性质的不稳定性,多酚易被氧化,长期储存中极易变质,对比例3组合物的总抗氧化能力在储存过程中几乎呈直线下降,而实施例1的组合物在相同的环境中,在5天内随着储存时间的延长,其总抗氧化能力几乎保持稳定状态。由此可见,本发明组合物的配方和制备方法,可有效提高组合物的抗氧化稳定性。
应用例3 防治酒精性肝损伤组合物的护肝功效测定
1、实验方法
实验动物:昆明雄性小鼠,6-8周龄,体重18-22克,SPF级,动物饲养条件:(25±1)℃,相对湿度:(55±5)%。
实验分组:取132只小鼠随机分为11组,每组12只,分为空白对照组、模型组、水飞蓟素阳性对照组,实施例1~4组和对比例1~4组。
各组小鼠每日按照剂量10g/kg·BW(体重)灌胃小鼠相对应体积的受试物,空白对照组和模型组灌胃蒸馏水,连续6天,第6天给受试物后开始禁食不禁水24h。24h后继续给受试物,并在60min后按13mL/kg·BW的剂量分别给各组小鼠灌胃56度红星二锅头白酒,空白对照组灌胃蒸馏水,60min后进行样本采集:
(1)摘眼球取血,静置至分层,冷冻离心,转速1000rpm,4℃离心15min取血清,采用速度法以全自动生化分析仪测定小鼠血清中的谷丙转氨酶(ALT)和谷草转氨酶(AST)含量。
(2)小鼠解剖后,取出肝脏,用预冷的生理盐水洗去表面的血水,用滤纸吸干后快速称重,用公式计算肝脏指数:
肝脏指数(%)=肝脏重量(g)/体重(g)×100%
(3)快速解剖肝脏,取肝左叶组织固定于4%多聚甲醛中,梯度乙醇逐步脱水,二甲苯透明,石蜡包埋,切片,苏木精-伊红(HE)染色,用普通光学显微镜观察。
(4)快速解剖肝脏,-80℃保存,制备成10%肝组织匀浆,按照相应试剂盒要求,严格操作,测定肝组织匀浆中乙醇脱氢酶(ADH)和乙醛脱氢酶(ALDH)的含量。
(5)快速解剖肝脏,-80℃保存,制备成10%肝组织匀浆,按照相应试剂盒要求,严格操作,测定抗氧化系统中过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)的含量。
2、实验结果
(1)肝脏指数
肝脏指数对肝脏的健康状况的评定有一定的意义,小鼠服用防治酒精性肝损伤的组合物的肝脏指数变化如图4所示。当肝脏指数增加时,很可能是肝脏发生了肿大,出现增生、充血、水肿等病变。小鼠造模后,模型组肝脏指数显著升高,与空白对照组比较,具有显著差异(p<0.01),表明造模成功。与模型组对比,实施例1~4组的小鼠肝脏指数均显著降低,具有统计学差异(p<0.01),其中实施例1组的效果更优, 几乎接近空白对照组水平,说明本发明制备的防治酒精性肝损伤的组合物能有效地改善肝脏指数,减少肝脏出现增生、水肿等病变,对酒精性肝损伤具有显著的防治作用。与模型组对比,虽然对比例1~4组的小鼠肝脏指数都有降低,但无统计学差异,且都高于阳性对照组。由此说明,本发明组合物的配方或者制备方法改变,都不能有效地改善肝脏指数。
(2)HE染色结果
通过对肝脏组织切片的HE染色,能够直观地观察出小鼠肝脏组织病理的变化。如图5所示(HE染色,放大倍数×200),在空白对照组中,肝小叶的结构清楚,肝细胞呈放射状排列且排列整齐,肝窦正常,细胞核结构清晰。相比之下,酒精灌胃后导致小鼠出现严重的肝损伤,酒精模型组小鼠肝细胞排列无序,肝窦变窄、分散,可见血管充血等病理改变。实施例1~4组肝细胞均有明显地不同程度地正常化,其中实施例1组肝细胞尤为明显,肝细胞排列逐渐趋于整齐,肝小叶的结构有所恢复。说明本发明制备的防治酒精性肝损伤的组合物可以有效缓解酒精引起的肝细胞损伤。
(3)ALT和AST分析结果
酒精性肝损伤的早期阶段主要表现为肝细胞膜通透性增加,而释放入血的ALT和AST活性含量则会显著提高。防治酒精性肝损伤的组合物对小鼠ALT和AST活性含量的影响如表1所示,模型组中,小鼠血清中ALT和AST含量显著高于空白对照组,具有显著性差异(p<0.01)。与模型组对比,实施例1~4组小鼠血清中ALT和AST含量显著降低,具有统计学差异(p<0.01),其中实施例1组的效果更优,说明本发明制备的防治酒精性肝损伤的组合物能有效地降低血清中ALT和AST含量,缓解肝损伤。与模型组对比,对比例1~4组小鼠血清中ALT和AST含量的变化无统计学差异,由此说明,本发明组合物的配方或者制备方法改变,对小鼠血清中ALT和AST含量无明显影响,对酒精性肝损伤无防治效果。
表1 各组小鼠血清中ALT和AST浓度(U/L)
注:与空白对照组比较,
##p<0.01;与模型组比较,**p<0.01。
(4)ALDH和ADH结果分析
ADH和ALDH是乙醇进入机体后主要的代谢酶,首先ADH催化乙醇转化为乙醛,进而ALDH催化乙醛转化为乙酸,最后进入三羧酸循环,生成二氧化碳和水。由于生成的乙醛对肝细胞具有直接毒害作用,乙醇的过量摄入在一定程度上会抑制肝脏ADH和ALDH活力。当机体内的细胞防御体系不能及时清除乙醛时,其残留的乙醛会导致肝细胞的损伤或炎症反应的发生、细胞外基质的产生和纤维化的形成。防治酒精性肝损伤的组合物对小鼠肝脏ADH及ALDH活性影响结果见表2。与空白对照组相比,模型组小鼠肝脏ADH和ALDH活力下降显著,具有统计学差异(p<0.01),表明急性大量酒精摄入了抑制肝脏ADH和ALDH活力,极易造成酒精性肝损伤。与模型组对比,实施例1~4组小鼠肝脏ADH和ALDH活力显著提高(p<0.01),说明本发明制备的防治酒精性肝损伤的组合物干预均能够提高小鼠肝脏ADH和ALDH活力,加速乙醇代谢分解,催化乙醛进一步氧化成乙酸,减缓乙醇及其代谢产物直接毒害小鼠肝脏,从而保护酒精诱导所致小鼠急性肝损伤。与模型组对比,在对比例1~4中,除了对比例3外,小鼠肝脏ADH和ALDH活力的变化无统计学差异,由此说明,本发明组合物的配方改变,对小鼠肝脏ADH和ALDH活力无明显影响,对酒精性肝损伤无防治效果。
表2 各组小鼠肝脏中ADH和ALDH含量(U/mg-protein)
注:与空白对照组比较,
##p<0.01;与模型组比较,**p<0.01。
(4)CAT、SOD、GSH-Px和MDA结果分析
酒精会在人体代谢中产生大量的活性氧物质(ROS),影响机体的抗氧化系统,导致酒精性肝损伤。以多种抗氧化酶作为评价小鼠肝脏氧化应激水平的参数,结果如表3所示。与空白对照组相比,模型组小鼠肝脏组织中SOD、GSH-Px和CAT含量显著降低,具有统计学差异(p<0.01),表明造模后小鼠肝脏氧化应激能力降低,容易造成酒精性肝损伤。与模型组对比,实施例1~4组小鼠肝脏组织中SOD、GSH-Px和CAT含量显著提高(p<0.01),其中实施例1组尤以为甚,说明本发明制备的防治酒精性肝损伤的组合物能显著降低酒精引起小鼠肝脏中过氧化物水平,增强机体抗氧化能力。MDA是自由基作用于脂质过氧化的产物,通过测定MDA的量可以反映体内脂质过氧化的程度,实施例1~4组小鼠肝脏组织中MDA含量显著低于模型对照组(p<0.01),其中实施例1组MDA含量最低,说明本发明制备的防治酒精性肝损伤的组合物能降低体内脂质过氧化的程度,减轻酒精性肝损伤。
表3 各组小鼠肝脏中SOD、GSH-Px、CAT和MDA含量
注:与空白对照组比较,
##p<0.01;与模型组比较,*p<0.05,**p<0.01。
应用例4 急性毒性实验
动物:取健康小鼠,体重18-22g,雌雄各半,共20只,随机分为实验组和空白对照两组。
受试物:以实施例1的组合物作为受试物。
实验方法:在预实验中,未能测出半数致死量,故选用上述实验给药量进行试验。以小鼠的体重为准,按10g/kg的剂量,每24h灌胃一次,连续灌胃实验组小鼠2周,空白对照组灌胃蒸馏水,在饲喂期间均自由饮水和觅食,实验期间观察小鼠的活动状态、饮食、粪便、呼吸、体重及死亡情况。
实验结果:实验组小鼠灌胃受试物2周内无一例死亡,与对照组相比,体重变化无显著差异,进食和饮水均无异常,且小鼠精神状态良好,活泼好动。将动物处死后,肉眼观察各主要脏器无异常现象。结果表明,本发明的防治酒精性肝损伤组合物口服应用,对动物无明显损害,未发现对机体产生的毒性反应,安全无毒。
实施例5 一种防治酒精性肝损伤的片剂
该防治酒精性肝损伤的片剂,以质量分数计,包括以下组分:
实施例6 一种防治酒精性肝损伤的片剂
该防治酒精性肝损伤的片剂,以质量分数计,包括以下组分:
实施例7 一种防治酒精性肝损伤的片剂
该防治酒精性肝损伤的片剂,以质量分数计,包括以下组分:
实施例8 一种防治酒精性肝损伤的胶囊剂
该防治酒精性肝损伤的胶囊剂,以质量分数计,包括以下组分:
实施例9 一种防治酒精性肝损伤的胶囊剂
该防治酒精性肝损伤的胶囊剂,以质量分数计,包括以下组分:
实施例10 一种防治酒精性肝损伤的胶囊剂
该防治酒精性肝损伤的胶囊剂,以质量分数计,包括以下组分:
实施例11 一种防治酒精性肝损伤的颗粒剂
该防治酒精性肝损伤的胶囊剂,以质量分数计,包括以下组分:
实施例12 一种防治酒精性肝损伤的颗粒剂
该防治酒精性肝损伤的胶囊剂,以质量分数计,包括以下组分:
实施例13 一种防治酒精性肝损伤的颗粒剂
该防治酒精性肝损伤的胶囊剂,以质量分数计,包括以下组分:
以上所述的实施例仅是对本发明的优选方式进行描述,并非对本发明的范围进行限定,在不脱离本发明设计精神的前提下,本领域普通技术人员对本发明的技术方案做出的各种变形和改进,均应落入本发明权利要求书确定的保护范围内。
Claims (10)
- 一种防治酒精性肝损伤的组合物,其特征在于,以重量份计,包括以下组分:海藻多酚10~30份、海藻酸钠2~6份、鲍鱼肽30~55份和亚精胺0.5~3份。
- 根据权利要求1所述的组合物,其特征在于,以重量份计,包括以下组分:海藻多酚20份、海藻酸钠4份、鲍鱼肽40份和亚精胺1.5份。
- 一种权利要求1或2任一项所述的防治酒精性肝损伤的组合物的制备方法,其特征在于,包括以下步骤:S1.取海藻酸钠加入水中配制成海藻酸钠溶液,调节溶液pH 6.0-7.5,加入亚精胺,室温搅拌5-8小时,冰水浴处理,待溶液体系降温至5-10℃,加入海藻多酚,继续搅拌1-3小时,冷冻干燥,液氮碎化,得到海藻多酚复合粉粒;S2.用水溶解鲍鱼肽,制成鲍鱼肽溶液,在搅拌状态下加入所述海藻多酚复合粉粒,混悬均匀,冷冻干燥,即得所述防治酒精性肝损伤的组合物。
- 根据权利要求3所述的制备方法,其特征在于,所述海藻酸钠溶液的质量浓度为1%-3.5%;所述鲍鱼肽溶液的质量浓度为18%-26%。
- 根据权利要求3所述的制备方法,其特征在于,所述海藻酸钠溶液pH调节至6.5。
- 一种权利要求1-2任一项所述的组合物在制备治疗/预防酒精性肝损伤的药物中的应用。
- 一种防治酒精性肝损伤的药物制剂,其特征在于,包括权利要求1或2所述的组合物,及药学上可接受的辅料。
- 根据权利要求7所述的药物制剂,其特征在于,所述药物制剂为胶囊剂,所述辅料包括乳糖、玉米淀粉和滑石粉;所述胶囊剂中各组分的质量分数为:所述组合物10-30wt%、乳糖10-20wt%、玉米淀粉50-60wt%和滑石粉5-15wt%。
- 根据权利要求7所述的药物制剂,其特征在于,所述药物制剂为片剂,所述辅料包括玉米淀粉、滑石粉和硬脂酸镁;所述片剂中各组分的质量分数为:所述组合物10-20wt%、玉米淀粉65-75wt%、滑石粉11-17wt%和硬脂酸镁0.5-2wt%。
- 根据权利要求7所述的药物制剂,其特征在于,所述药物制剂为颗粒剂,所述辅料包括玉米淀粉、羟甲基纤维素钠和硬脂酸镁;所述颗粒剂中各组分的质量分数为:所述组合物5-15wt%、玉米淀粉74-84wt%、羟甲基纤维素钠5-15wt%和硬脂酸镁0.5-2wt%。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110202812.4 | 2021-02-23 | ||
CN202110202812.4A CN112870331B (zh) | 2021-02-23 | 2021-02-23 | 一种防治酒精性肝损伤的组合物及其制备方法与应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2022179050A1 true WO2022179050A1 (zh) | 2022-09-01 |
Family
ID=76054855
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2021/110092 WO2022179050A1 (zh) | 2021-02-23 | 2021-08-02 | 一种防治酒精性肝损伤的组合物及其制备方法与应用 |
Country Status (3)
Country | Link |
---|---|
CN (1) | CN112870331B (zh) |
LU (1) | LU500771B1 (zh) |
WO (1) | WO2022179050A1 (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112870331B (zh) * | 2021-02-23 | 2021-10-15 | 广东海洋大学 | 一种防治酒精性肝损伤的组合物及其制备方法与应用 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103446174A (zh) * | 2013-09-12 | 2013-12-18 | 中国海洋大学 | 低聚甘露糖醛酸在制备预防和治疗酒精性肝损伤的药物、保健品或饮食补充剂中的应用 |
CN105380261A (zh) * | 2015-10-13 | 2016-03-09 | 南京贝杉国际贸易有限公司 | 一种含有寡肽的保肝护肝配方食品及其制备方法 |
CN105495578A (zh) * | 2015-10-16 | 2016-04-20 | 青岛海能海洋生物技术有限公司 | 一种鲍参复合液及其制备方法和应用 |
CN105996027A (zh) * | 2016-05-07 | 2016-10-12 | 集美大学 | 一种护肝明目的功能食品 |
CN110710678A (zh) * | 2019-11-20 | 2020-01-21 | 颐海产业控股有限公司 | 一种滋补肝肾、养血安神海洋多肽阿胶膏及其制备方法 |
CN110742878A (zh) * | 2019-11-15 | 2020-02-04 | 浙江工业大学 | 一种亚腈胺在制备治疗脂肪肝药物中的应用 |
CN112870331A (zh) * | 2021-02-23 | 2021-06-01 | 广东海洋大学 | 一种防治酒精性肝损伤的组合物及其制备方法与应用 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040161435A1 (en) * | 2003-02-14 | 2004-08-19 | Gupta Shyam K. | Skin Firming Anti-Aging Cosmetic Mask Compositions |
CN101926489B (zh) * | 2010-07-01 | 2012-10-03 | 石狮市华宝明祥食品有限公司 | 海藻饮料及其加工工艺 |
CN105249434A (zh) * | 2015-11-10 | 2016-01-20 | 集美大学 | 一种以鲍鱼内脏酶液制备天然褐藻寡糖保水剂的方法 |
CN107960629B (zh) * | 2017-07-20 | 2021-01-15 | 浙江省海洋开发研究院 | 一种海鲜虾味汤冻及其制作方法 |
CN108125937A (zh) * | 2017-12-28 | 2018-06-08 | 中国医学科学院基础医学研究所 | 亚精胺在预防和治疗脂肪肝和2型糖尿病中的用途 |
CN108926745B (zh) * | 2018-08-01 | 2019-09-27 | 北京大学 | 一种纳米多孔微支架的制备方法及其复合体系 |
-
2021
- 2021-02-23 CN CN202110202812.4A patent/CN112870331B/zh active Active
- 2021-08-02 LU LU500771A patent/LU500771B1/en active IP Right Grant
- 2021-08-02 WO PCT/CN2021/110092 patent/WO2022179050A1/zh active Application Filing
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103446174A (zh) * | 2013-09-12 | 2013-12-18 | 中国海洋大学 | 低聚甘露糖醛酸在制备预防和治疗酒精性肝损伤的药物、保健品或饮食补充剂中的应用 |
CN105380261A (zh) * | 2015-10-13 | 2016-03-09 | 南京贝杉国际贸易有限公司 | 一种含有寡肽的保肝护肝配方食品及其制备方法 |
CN105495578A (zh) * | 2015-10-16 | 2016-04-20 | 青岛海能海洋生物技术有限公司 | 一种鲍参复合液及其制备方法和应用 |
CN105996027A (zh) * | 2016-05-07 | 2016-10-12 | 集美大学 | 一种护肝明目的功能食品 |
CN110742878A (zh) * | 2019-11-15 | 2020-02-04 | 浙江工业大学 | 一种亚腈胺在制备治疗脂肪肝药物中的应用 |
CN110710678A (zh) * | 2019-11-20 | 2020-01-21 | 颐海产业控股有限公司 | 一种滋补肝肾、养血安神海洋多肽阿胶膏及其制备方法 |
CN112870331A (zh) * | 2021-02-23 | 2021-06-01 | 广东海洋大学 | 一种防治酒精性肝损伤的组合物及其制备方法与应用 |
Also Published As
Publication number | Publication date |
---|---|
LU500771B1 (en) | 2022-04-22 |
CN112870331B (zh) | 2021-10-15 |
CN112870331A (zh) | 2021-06-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Wang et al. | The biological activity mechanism of chlorogenic acid and its applications in food industry: A review | |
Mei et al. | Diosmetin alleviated cerebral ischemia/reperfusion injury in vivo and in vitro by inhibiting oxidative stress via the SIRT1/Nrf2 signaling pathway | |
WO2022179260A1 (zh) | 一种组合物在防治酒精性脑损伤中的应用 | |
TW201536341A (zh) | 紅藜萃取物用於製備促進膠原蛋白生成及抗皮膚老化之組合物之用途 | |
EP2978436A1 (en) | Compositions comprising complexes of proanthocyanidins with vegetable proteins | |
WO2022179050A1 (zh) | 一种防治酒精性肝损伤的组合物及其制备方法与应用 | |
Wang et al. | Preparing, optimising, and evaluating chitosan nanocapsules to improve the stability of anthocyanins from Aronia melanocarpa | |
Wang et al. | Silk sericin stabilized proanthocyanidins for synergetic alleviation of ulcerative colitis | |
CN103005255A (zh) | 一种壳寡糖-胶原肽复配物保健食品及其制备方法 | |
Liang et al. | Engineering probiotics-derived membrane vesicles for encapsulating fucoxanthin: evaluation of stability, bioavailability, and biosafety | |
CN112843025A (zh) | 一种白藜芦醇营养补充剂的制备方法 | |
Veronica et al. | Microencapsulation of lemongrass leaves effect on Reactive Oxygen Species (ROS) fibroblasts | |
CN116898098A (zh) | 一种牛肝肽解酒配方及原料制备方法 | |
JP2003048839A (ja) | 免疫反応性NO合成を誘導するiNOS酵素を刺激する組成剤およびその製造方法 | |
RU2762824C1 (ru) | Комбинация для снижения окислительного стресса в организме и поддержания функций печени | |
KR101073624B1 (ko) | 갈대순 분말 또는 이의 추출물을 포함하는 비만 예방 및 개선용, 또는 항산화용 조성물 | |
CN114887029B (zh) | 一种药物组合物、制备方法及其应用 | |
Chen et al. | Construction and functional evaluation of oral long-acting insulin hydrogel microparticles based on physical and chemical double crosslinking | |
CN113181173B (zh) | 药用组合物及其在制备用于预防和/或治疗肝癌的产品中的应用 | |
CN114468295B (zh) | 一种基于藻蓝蛋白尺寸可控的叶黄素纳米粒子 | |
Wang et al. | A novel sunflower-like nanocarrier based on dual milk-derived proteins for improved bio-accessibility, stability and antioxidant activity of anthocyanin | |
KR100783205B1 (ko) | 운지버섯 추출물과 운지버섯 조다당 분획물을 함유하는간기능 개선 효과를 갖는 조성물 | |
RU2330679C1 (ru) | Композиция для профилактики и лечения астмы и заболеваний верхних дыхательных путей и способ ее получения | |
Changqing et al. | Anti-Tumor, Immunomodulatory, Hepatoprotective and Antioxidant Activity of Oysters Polysaccharides | |
Jafari et al. | Glucosamine Hydrochloride and Glucosamine‐Gallic Acid Nanoparticles for the Treatment of Osteoarthritis: Synthesis, Antioxidant, and Anti‐Inflammatory |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21927479 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 21927479 Country of ref document: EP Kind code of ref document: A1 |