CN116585338A - Weight-losing and lipid-lowering pharmaceutical composition and application thereof - Google Patents
Weight-losing and lipid-lowering pharmaceutical composition and application thereof Download PDFInfo
- Publication number
- CN116585338A CN116585338A CN202310497205.4A CN202310497205A CN116585338A CN 116585338 A CN116585338 A CN 116585338A CN 202310497205 A CN202310497205 A CN 202310497205A CN 116585338 A CN116585338 A CN 116585338A
- Authority
- CN
- China
- Prior art keywords
- timosaponin
- composition
- weight
- berberine hydrochloride
- lipid
- 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
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 8
- 229930193981 timosaponin Natural products 0.000 claims abstract description 85
- VKJGBAJNNALVAV-UHFFFAOYSA-M Berberine chloride (TN) Chemical compound [Cl-].C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 VKJGBAJNNALVAV-UHFFFAOYSA-M 0.000 claims abstract description 81
- 239000000203 mixture Substances 0.000 claims abstract description 72
- 239000003814 drug Substances 0.000 claims abstract description 23
- 150000002632 lipids Chemical class 0.000 claims abstract description 20
- 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 9
- 239000000047 product Substances 0.000 claims description 86
- 230000000694 effects Effects 0.000 claims description 22
- 210000002966 serum Anatomy 0.000 claims description 17
- 230000001603 reducing effect Effects 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 11
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 10
- 230000036541 health Effects 0.000 claims description 6
- 239000000413 hydrolysate Substances 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 235000013305 food Nutrition 0.000 claims description 5
- 230000004580 weight loss Effects 0.000 claims description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 208000004930 Fatty Liver Diseases 0.000 claims description 4
- 206010019708 Hepatic steatosis Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000002255 enzymatic effect Effects 0.000 claims description 4
- 208000010706 fatty liver disease Diseases 0.000 claims description 4
- 231100000240 steatosis hepatitis Toxicity 0.000 claims description 4
- 239000003826 tablet Substances 0.000 claims description 4
- -1 transdermal patches Substances 0.000 claims description 4
- 108010009736 Protein Hydrolysates Proteins 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 208000029078 coronary artery disease Diseases 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 239000000829 suppository Substances 0.000 claims description 3
- 239000006188 syrup Substances 0.000 claims description 3
- 235000020357 syrup Nutrition 0.000 claims description 3
- 150000003626 triacylglycerols Chemical class 0.000 claims description 3
- 108010010234 HDL Lipoproteins Proteins 0.000 claims description 2
- 102000015779 HDL Lipoproteins Human genes 0.000 claims description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 claims description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 239000000443 aerosol Substances 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000008176 lyophilized powder Substances 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- ZGVRGXGXZKITGK-MCKZXVOHSA-N timosaponin AII Natural products C[C@@H]1CC[C@@]2(OC1)O[C@@H]3C[C@H]4[C@@H]5CC[C@@H]6C[C@@H](O[C@@H]7O[C@H](CO)[C@H](O)[C@H](O)[C@H]7O[C@@H]8O[C@H](CO)[C@@H](O)[C@H](O)[C@H]8O)[C@H](O)C[C@]6(C)[C@H]5CC[C@]4(C)[C@@H]3[C@@H]2C ZGVRGXGXZKITGK-MCKZXVOHSA-N 0.000 claims 1
- 230000002195 synergetic effect Effects 0.000 abstract description 9
- 230000009467 reduction Effects 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 31
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 241000699670 Mus sp. Species 0.000 description 22
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 18
- MMTWXUQMLQGAPC-YXOKLLKRSA-N Timosaponin A-III Chemical compound O([C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1C[C@H]2CC[C@H]3[C@@H]4C[C@H]5[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@@H]([C@]1(OC[C@@H](C)CC1)O5)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O MMTWXUQMLQGAPC-YXOKLLKRSA-N 0.000 description 15
- XWHLRGYHAKFVSN-NIYSFEGRSA-N Timosaponin AIII Natural products O([C@@H]1[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H](COC(C)=O)O[C@H]1O[C@@H]1C[C@H]2CC[C@H]3[C@@H]4C[C@H]5[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@@H]([C@]1(OC[C@@H](C)CC1)O5)C)[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O XWHLRGYHAKFVSN-NIYSFEGRSA-N 0.000 description 15
- MMTWXUQMLQGAPC-XWIAVXRASA-N timosaponin A-III Natural products C[C@@H]1CC[C@@]2(OC1)O[C@@H]3C[C@H]4[C@H]5CC[C@@H]6C[C@H](CC[C@]6(C)[C@H]5CC[C@]4(C)[C@@H]3[C@@H]2C)O[C@@H]7O[C@H](CO)[C@H](O)[C@H](O)[C@H]7O[C@@H]8O[C@H](CO)[C@@H](O)[C@H](O)[C@H]8O MMTWXUQMLQGAPC-XWIAVXRASA-N 0.000 description 15
- 108010028554 LDL Cholesterol Proteins 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 108010023302 HDL Cholesterol Proteins 0.000 description 10
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 9
- 235000021314 Palmitic acid Nutrition 0.000 description 9
- 210000000577 adipose tissue Anatomy 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 9
- 239000000469 ethanolic extract Substances 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 208000008589 Obesity Diseases 0.000 description 7
- 235000020824 obesity Nutrition 0.000 description 7
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 235000021588 free fatty acids Nutrition 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000011740 C57BL/6 mouse Methods 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 description 5
- 229940093265 berberine Drugs 0.000 description 5
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 238000001514 detection method Methods 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000605447 Anemarrhena Species 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 208000032928 Dyslipidaemia Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 208000017170 Lipid metabolism disease Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 229930191283 anemarrhena Natural products 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 102000006995 beta-Glucosidase Human genes 0.000 description 3
- 108010047754 beta-Glucosidase Proteins 0.000 description 3
- 230000024245 cell differentiation Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 210000000229 preadipocyte Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- SORUXVRKWOHYEO-UHFFFAOYSA-N timosaponin B-II Natural products O1C(CO)C(O)C(O)C(O)C1OCC(C)CCC(C(C1C2(C)CCC3C4(C)CC5)C)(O)OC1CC2C3CCC4CC5OC1OC(CO)C(O)C(O)C1OC1OC(CO)C(O)C(O)C1O SORUXVRKWOHYEO-UHFFFAOYSA-N 0.000 description 3
- UDUSTUNNFSNCPR-QFNYSWOCSA-N timosaponin BII Natural products C[C@H](CC[C@@]1(O)O[C@H]2C[C@H]3[C@@H]4CC[C@@H]5C[C@H](CC[C@]5(C)[C@H]4CC[C@]3(C)[C@H]2[C@@H]1C)O[C@@H]6O[C@H](CO)[C@H](O)[C@H](O)[C@H]6O[C@@H]7O[C@H](CO)[C@@H](O)[C@H](O)[C@H]7O)[C@@H]8O[C@H](CO)[C@@H](O)[C@H](O)[C@H]8O UDUSTUNNFSNCPR-QFNYSWOCSA-N 0.000 description 3
- SORUXVRKWOHYEO-UJDJZYEZSA-N timosaponin bii Chemical compound O([C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1C[C@H]2CC[C@H]3[C@@H]4C[C@@H]5O[C@]([C@H]([C@@H]5[C@@]4(C)CC[C@@H]3[C@@]2(C)CC1)C)(O)CC[C@H](C)CO[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SORUXVRKWOHYEO-UJDJZYEZSA-N 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 239000012224 working solution Substances 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 210000001789 adipocyte Anatomy 0.000 description 2
- 210000003486 adipose tissue brown Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000013116 obese mouse model Methods 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- XDVZNDLANFJOQR-UHFFFAOYSA-N Coptisine Natural products O=Cc1c2OCOc2ccc1C=C3/NCCc4cc5OCOc5cc34 XDVZNDLANFJOQR-UHFFFAOYSA-N 0.000 description 1
- MXTLAHSTUOXGQF-UHFFFAOYSA-O Jatrorrhizine Chemical compound COC1=CC=C2C=C3C(C=C(C(=C4)O)OC)=C4CC[N+]3=CC2=C1OC MXTLAHSTUOXGQF-UHFFFAOYSA-O 0.000 description 1
- 241000283953 Lagomorpha Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100102907 Mus musculus Wdtc1 gene Proteins 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- PTPHDVKWAYIFRX-UHFFFAOYSA-N Palmatine Natural products C1C2=C(OC)C(OC)=CC=C2C=C2N1CCC1=C2C=C(OC)C(OC)=C1 PTPHDVKWAYIFRX-UHFFFAOYSA-N 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 241000283089 Perissodactyla Species 0.000 description 1
- 241000972672 Phellodendron Species 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241001493546 Suina Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- CDXSJGDDABYYJV-UHFFFAOYSA-N acetic acid;ethanol Chemical compound CCO.CC(O)=O CDXSJGDDABYYJV-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 210000000593 adipose tissue white Anatomy 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000019577 caloric intake Nutrition 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- XYHOBCMEDLZUMP-UHFFFAOYSA-N coptisine Chemical compound C1=C2C=C(C3=C(C=C4OCOC4=C3)CC3)[N+]3=CC2=C2OCOC2=C1 XYHOBCMEDLZUMP-UHFFFAOYSA-N 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- FPJQGFLUORYYPE-UHFFFAOYSA-N epiberberine Chemical compound C1=C2C=C(C3=C(C=C(C(=C3)OC)OC)CC3)[N+]3=CC2=C2OCOC2=C1 FPJQGFLUORYYPE-UHFFFAOYSA-N 0.000 description 1
- 210000000918 epididymis Anatomy 0.000 description 1
- 201000010063 epididymitis Diseases 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229940089161 ginsenoside Drugs 0.000 description 1
- 229930182494 ginsenoside Natural products 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000000055 hyoplipidemic effect Effects 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000006993 memory improvement Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229960004329 metformin hydrochloride Drugs 0.000 description 1
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin hydrochloride Natural products CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 230000008722 morphological abnormality Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- QUCQEUCGKKTEBI-UHFFFAOYSA-N palmatine Chemical compound COC1=CC=C2C=C(C3=C(C=C(C(=C3)OC)OC)CC3)[N+]3=CC2=C1OC QUCQEUCGKKTEBI-UHFFFAOYSA-N 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000001991 scapula Anatomy 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical compound [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- PKVRCIRHQMSYJX-AIFWHQITSA-N trabectedin Chemical compound C([C@@]1(C(OC2)=O)NCCC3=C1C=C(C(=C3)O)OC)S[C@@H]1C3=C(OC(C)=O)C(C)=C4OCOC4=C3[C@H]2N2[C@@H](O)[C@H](CC=3C4=C(O)C(OC)=C(C)C=3)N(C)[C@H]4[C@@H]21 PKVRCIRHQMSYJX-AIFWHQITSA-N 0.000 description 1
- 229960000977 trabectedin Drugs 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- 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
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
- A61K36/8964—Anemarrhena
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Botany (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Child & Adolescent Psychology (AREA)
- Alternative & Traditional Medicine (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The application relates to the field of biological medicine, in particular to a weight-losing and lipid-lowering pharmaceutical composition and application thereof. The application provides a composition, which comprises timosaponin enzymolysis products and berberine hydrochloride. The composition of timosaponin enzymolysis products and berberine hydrochloride can effectively treat hyperlipidemia, and has synergistic effect, and has wide application prospect in the field of weight and lipid reduction.
Description
Technical Field
The application relates to the field of biological medicine, in particular to a weight-losing and lipid-lowering pharmaceutical composition and application thereof.
Background
Obesity (Obesity) is an excessive accumulation of fat caused by a long-term imbalance in energy intake and energy expenditure, and obese patients often show disorders of energy metabolism, especially dyslipidemia. Obesity has become a global public health problem, is a risk factor for various diseases such as diabetes, fatty liver, cardiovascular diseases and the like, and seriously threatens human health, so that the control of the blood lipid level of an obese patient has important significance for preventing and treating serious diseases caused by obesity.
Berberine is a quaternary ammonium alkaloid, also called berberine, which is yellow needle-like crystal and bitter in taste, and is mainly used in clinical application. The berberine hydrochloride has obvious hypolipidemic effect, can reduce the content of venous blood triglyceride and total cholesterol of patients with hyperlipidemia, slightly raise the content of high-density lipoprotein cholesterol, and has the total effective rate of 90% (lucky glow, zong Yong science. Berberine treats 59 cases of hyperlipidemia [ J ]. People's military medical science, 1995 (2): 35-36.). The patent (CN 110123843B) discloses a composition for losing weight and reducing blood fat and application thereof, wherein the composition is a combination of berberine hydrochloride and a constellation short-belly ecteinascidin fat-soluble extract, and has remarkable functions of reducing weight and regulating blood fat.
The timosaponin enzymolysis product uses timosaponin AIII as main ingredient. Timosaponin AIII belongs to timosaponin components, and is the main active ingredient in rhizoma anemarrhenae. Timosaponin AIII has various biological activities such as platelet aggregation resistance, learning ability and memory improvement, antitumor, and blood sugar lowering effects. Timosaponin AIII also has the effect of reducing blood lipid, and the patent of the application (issued publication number: CN 1265797C) discloses application of timosaponin AIII in preparation of medicaments for reducing blood glucose and treating type II diabetes, and the timosaponin AIII can reduce blood lipid of KKAy diabetic mice when the dosage is 400mg/kg, but the blood lipid does not refer to specific indexes and is regarded as complications of type II diabetes. Modern pharmacological researches show that timosaponin has good blood lipid reducing effect, however timosaponin reduces blood lipid of high-fat dietary rats, the dosage is 100-400 mg/kg, the dosage of timosaponin BII which is the main component in timosaponin for improving hyperlipidemia is about 100mg/kg, the dosage is large, and the lipid reducing effect is difficult to reach satisfactory level.
In conclusion, the single administration effect of the weight-losing and lipid-lowering medicines needs to be further improved, the dosage of timosaponin AIII in the existing medicines is larger, and a medicine composition with more obvious effect needs to be screened.
Disclosure of Invention
In view of the above-mentioned shortcomings of the prior art, in order to solve the technical problems of poor single administration effect of the weight-losing and lipid-lowering medicines in the prior art and further to be improved, the present application aims to provide a weight-losing and lipid-lowering pharmaceutical composition and application thereof.
The inventors of the present application found by analysis: the traditional Chinese medicine has synergistic effect, and the pharmacokinetics study of the rhizoma anemarrhenae-phellodendron medicine pair shows that the combined use of the medicine pair can increase the in vivo content of timosaponin AIII which is a metabolite of rhizoma anemarrhenae and berberine which is a main alkaloid of phellodendron, and liver exposure, so the inventor combines the timosaponin AIII and berberine according to a certain proportion, and discovers that the effects of reducing fat can be enhanced, and the effects of reducing weight and reducing fat can be achieved.
To achieve the above and other related objects, one aspect of the present application provides a composition comprising timosaponin enzymatic hydrolysate and berberine hydrochloride.
In another aspect, the application provides application of the composition in preparation of a weight-reducing and lipid-lowering product.
In another aspect, the application provides application of the composition in preparing medicines, foods or health care products for preventing and treating hyperlipidemia, fatty liver, coronary heart disease, cardiovascular diseases and diabetes.
In another aspect, the application provides a method of treating obesity and lipid lowering comprising administering to a subject an effective amount of the foregoing composition.
Compared with the prior art, the application has the beneficial effects that:
1. the application provides a new application of a timosaponin enzymolysis product and berberine hydrochloride composition, in particular to an application of the timosaponin enzymolysis product and berberine hydrochloride composition in preparation of weight-losing and lipid-lowering drugs.
2. According to the application, after the timosaponin enzymolysis product and berberine hydrochloride composition are adopted to intervene in a C57BL/6 mouse, the weight and dyslipidemia of the obese mouse can be obviously improved, and the fat morphological abnormality is improved, namely, the timosaponin enzymolysis product and berberine hydrochloride composition can effectively treat hyperlipidemia, and meanwhile, the effects of the timosaponin enzymolysis product and berberine hydrochloride composition have a synergistic effect, so that the timosaponin enzymolysis product and berberine hydrochloride composition has a relatively wide application prospect in the field of weight reduction and lipid reduction.
Drawings
FIG. 1 is a schematic diagram showing the influence of different weight ratios of timosaponin enzymolysis products and berberine hydrochloride on the content of cell triglyceride.
Fig. 2 shows timosaponin enzymolysis product and berberine hydrochloride with a weight ratio of 1.6: schematic of the effect of combination on cellular triglyceride content at 1.
FIG. 3 is a schematic diagram showing the effect of timosaponin enzymolysis product and berberine hydrochloride composition on mouse body weight.
FIG. 4 is a schematic diagram showing the effect of timosaponin enzymolysis product and berberine hydrochloride composition on serum blood lipid level of mice.
FIG. 5 is a schematic diagram showing the results of H & E staining of mouse adipose tissue with timosaponin enzymolysis product and berberine hydrochloride composition.
Detailed Description
In order to make the objects, technical solutions and advantageous effects of the present application clearer, the present application will be further described with reference to examples. It is to be understood that the examples are provided for the purpose of illustrating the application and are not intended to limit the scope of the application. The test methods used in the following examples are conventional, and other advantages and effects of the present application will be readily apparent to those skilled in the art from the disclosure herein.
The "range" disclosed herein is defined in terms of lower and upper limits, with the given range being defined by the selection of a lower and an upper limit, the selected lower and upper limits defining the boundaries of the particular range. Ranges that are defined in this way can be inclusive or exclusive of the endpoints, and any combination can be made, i.e., any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60 to 120 and 80 to 110 are listed for a particular parameter, it is understood that ranges of 60 to 110 and 80 to 120 are also contemplated. Furthermore, if the minimum range values 1 and 2 are listed, and if the maximum range values 3,4 and 5 are listed, the following ranges are all contemplated: 1 to 3, 1 to 4, 1 to 5, 2 to 3, 2 to 4 and 2 to 5. In the present application, unless otherwise indicated, the numerical ranges "a-b" represent a shorthand representation of any combination of real numbers between a and b, where a and b are both real numbers. For example, the numerical range "0-5" means that all real numbers between "0-5" have been listed throughout, and "0-5" is only a shorthand representation of a combination of these values. When a certain parameter is expressed as an integer of 2 or more, it is disclosed that the parameter is, for example, an integer of 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12 or the like.
Where numerical ranges are provided in the examples, it is understood that unless otherwise stated herein, both endpoints of each numerical range and any number between the two endpoints are significant both in the numerical range. 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 application belongs. In addition to the specific methods, devices, materials used in the embodiments, any methods, devices, and materials of the prior art similar or equivalent to those described in the embodiments of the present application may be used to practice the present application according to the knowledge of one skilled in the art and the description of the present application.
Unless otherwise indicated, the experimental methods, detection methods, and preparation methods disclosed in the present application employ conventional techniques in biomedical engineering, biophysics, pharmacy, pharmaceutical analytics, pharmaceutical chemistry, analytical chemistry, molecular biology, biochemistry, and related fields, which are conventional in the art. These techniques are well described in the prior art.
The inventor of the present application has found a pharmaceutical composition for weight loss and lipid lowering and its application through a great deal of research and study, and completed the present application on the basis.
In one aspect, the application provides a composition comprising timosaponin enzymolysis product and berberine hydrochloride. The timosaponin enzymolysis product is obtained by extracting timosaponin decoction pieces with alcohol and hydrolyzing with beta-glucosidase.
According to the application, after the timosaponin enzymolysis product and berberine hydrochloride composition are adopted to intervene in a C57BL/6 mouse, the weight and dyslipidemia of the obese mouse can be obviously improved, and the fat morphology abnormality is improved, namely, the timosaponin enzymolysis product and berberine hydrochloride composition can effectively treat hyperlipidemia, and meanwhile, the timosaponin enzymolysis product and berberine hydrochloride composition has a synergistic effect, and has a relatively wide application prospect in the field of weight loss and lipid reduction.
In the composition provided by the application, the molecular formula of berberine hydrochloride is C 20 H 18 ClNO 4 The structure is as follows:
in the composition provided by the application, berberine hydrochloride can be replaced by a structural analogue of berberine hydrochloride. In some embodiments, the structural analogs of berberine hydrochloride refer to structural analogs having the same function as berberine hydrochloride, including, but not limited to, one or more of jateorhizine, palmatine, epiberberine, and coptisine.
In the composition provided by the application, the timosaponin enzymolysis product comprises timosaponin AIII.
In the composition provided by the application, the molecular formula of timosaponin AIII is C 39 H 64 O 13 The structure is as follows:
the composition provided by the application comprises, by weight, 1-3 parts of berberine hydrochloride and 1.6-4.8 parts of timosaponin enzymolysis products, wherein the parts by weight of timosaponin enzymolysis products are calculated by dry weight. In some embodiments of the application, the weight ratio of timosaponin enzymolysis products to berberine hydrochloride in the composition is 0.53-4.8: 1, a step of; preferably, 0.53 to 1: 1.1 to 1.6: 1. 1.6 to 2:1 or 2 to 4.8:1, etc. In a preferred embodiment of the application, the weight ratio of timosaponin enzymolysis product to berberine hydrochloride is 1.6:1, and the weight-reducing and lipid-lowering effects are optimal.
The composition provided by the application further comprises a pharmaceutically acceptable carrier, an additive, an auxiliary agent or an excipient. The compositions provided herein may include one or more pharmaceutically acceptable carriers, which generally refer to carriers for administration of therapeutic agents that do not themselves induce the production of antibodies harmful to the individual receiving the composition, and which do not have undue toxicity after administration. Such carriers are well known to those skilled in the art, and related content is disclosed, for example, in Remington's Pharmaceutical Sciences (Mack Pub.Co., N.J.1991) for pharmaceutically acceptable carriers. In particular, the carrier may be a combination including, but not limited to, one or more of saline, buffer, glucose, water, glycerol, ethanol, adjuvants, and the like.
The compositions provided herein may be adapted for any form of administration, be it oral or parenteral, for example, be it pulmonary, nasal, rectal and/or intravenous, more particularly intradermal, subcutaneous, intramuscular, intra-articular, intraperitoneal, pulmonary, buccal, sublingual, nasal, transdermal, vaginal, oral or parenteral.
In another aspect, the application provides the use of the composition in the preparation of a weight-reducing and lipid-lowering product. The weight-losing and lipid-lowering product has one or more of the following effects:
1) Weight loss;
2) Reducing serum total cholesterol;
3) Lowering serum triglycerides;
4) Lowering serum low density lipoprotein;
5) Raise serum high density lipoprotein.
In another aspect, the application provides application of the composition in preparing medicines, foods or health care products for preventing and treating hyperlipidemia, fatty liver, coronary heart disease, cardiovascular diseases and diabetes. The dosage forms of the medicine, the food or the health care product comprise tablets, capsules, aerosols, pills, powders, solutions, syrups, transdermal patches, emulsions, freeze-dried powder injection or suppositories. The skilled artisan can select a suitable formulation depending on the mode of administration, for example, a formulation suitable for oral administration may be a formulation including, but not limited to, a pill, tablet, chew, capsule, granule, drop, or syrup, etc., and for further example, a formulation suitable for parenteral administration may be a formulation including, but not limited to, a solution, suspension, reconstitutable dry preparation, spray, etc., and for further example, a suppository may be generally suitable for rectal administration.
In another aspect, the application provides a method of treating obesity and lipid lowering comprising administering to a subject an effective amount of the foregoing composition.
In the method of treatment provided by the present application, the subject is a mammal, for example, a rodent, artiodactyla, perissodactyla, lagomorpha, primate, or the like. The primate is, for example, a monkey, ape or homo.
The application is further illustrated by the following examples, which are not intended to limit the scope of the application.
The percentages are by weight unless otherwise indicated.
Example 1
Preparation method of timosaponin enzymolysis product
1. Experimental reagent and material
Rhizoma anemarrhenae decoction pieces, no.210113, shanghai Kangqiao Chinese medicinal decoction pieces, inc.; timosaponin AIII control, lot number: R12S8F43634, purity >98%, shanghai Yuan Ye Biotechnology Co., ltd; timosaponin BII, lot number R14D9F77658, purity >98%, shanghai Yuan Ye Biotechnology Co., ltd; beta-glucosidase, shanghai Feng Biochemical Co., ltd; methanol (chromatographic purity), acetonitrile (chromatographic purity), absolute ethanol (analytical purity), national pharmaceutical chemicals, inc.
2. Experimental method
(1) Preparation of anemarrhena rhizome ethanol extract
Weighing rhizoma anemarrhenae decoction pieces 60g, adding 6 times of 50% ethanol, and extracting under reflux for 2 hr for 2 times. Filtering, mixing the extractive solutions, rotary evaporating under reduced pressure, recovering ethanol, evaporating in water bath, transferring to vacuum drying oven, drying at 60deg.C under reduced pressure overnight to obtain mother ethanol extract, and weighing.
(2) Preparation of rhizoma anemarrhenae ethanol extract enzyme hydrolysate
Weighing 4g of each of the anemarrhena ethanol extract and the beta-glucosidase, placing into a conical flask with a plug, adding 200ml of acetic acid-sodium acetate buffer solution with pH of 5.0, placing into a constant temperature oscillator, and shaking for 3h at 55 ℃. Extracting the extract with water saturated n-butanol with equal volume for 3 times, washing with ammonia solution for 3 times, mixing n-butanol extractive solutions, rotary evaporating under reduced pressure, recovering n-butanol, vacuum drying at 60deg.C, and drying under reduced pressure to obtain enzymolysis product of ginsenoside. And measuring the contents of timosaponin BII and timosaponin AIII after enzymolysis of the extract by HPLC.
Example 2
Explore the optimal weight proportion of timosaponin enzymolysis product and berberine hydrochloride composition
1. Experimental reagent and material
Timosaponin enzymolysis product, prepared in example 1; berberine hydrochloride with purity >98%, shanghai Yuan Ye Biotechnology Co., ltd; 3T3-L1 cells (from the cell bank of the national academy of sciences); the following materials were purchased from the sameidie technology: DMEM, fetal bovine serum, 0.25% trypsin, isobutylmethylxanthine, dexamethasone, insulin; oleic acid (from merck life sciences), palmitic acid (from merck life sciences).
2. Experimental method
(1) Preparation of experimental medicine
After the timosaponin enzymolysis product and berberine hydrochloride are dissolved by DMSO, 3g/L of storage solution is prepared and stored (-20 ℃) for standby.
(2) Culture conditions
3T3-L1 preadipocytes were resuscitated with DMEM medium containing 10% Fetal Bovine Serum (FBS), and inoculated into culture flasks at 37deg.C with 5% CO 2 And (5) standing and culturing in an incubator. Inverted every 1-2 days with naked eyesThe 3T3-L1 preadipocytes and the culture medium are observed under a microscope, and if characteristic changes, such as color changes, are carried out on the culture medium, fresh culture medium is replaced and then the culture medium is put into an incubator again for culture.
(3) Cell passage
3-4 days after cell inoculation, after 3T3-L1 preadipocyte monolayer grows densely and the fusion degree reaches 80-90%, 0.25% trypsin is used for digestion, after the cells are observed under an inverted microscope until cytoplasmatic retraction and cell gaps are increased, pancreatin is immediately poured out, 2mL of DMEM medium containing 10% FBS is added, digestion is stopped, suspended cells are gently blown and collected, and the cells are centrifuged, resuspended, counted and uniformly inoculated in a 12-well plate.
(4) Cell differentiation
After selection of the DMEM medium containing 10% FBS, which is well grown after passage and has a fusion density of 60-70%, the differentiation medium, i.e., the DMEM medium containing 0.5mM isobutyl methylxanthine (IBMX), 1mM dexamethasone (Dex) and 10. Mu.g/mL insulin, is replaced, after 48 hours of culture, the differentiation medium, i.e., the DMEM medium containing only 10. Mu.g/mL insulin, is replaced, and finally replaced with the DMEM medium containing 10% FBS for 8-12 days, and is used for the experiment after the cells differentiate to maturity.
(5) Determination of Triglyceride (TG) content in cells
Blank (Blank) was cultured in serum-free DMEM after complete differentiation of cells. Model group (PA) was cultured in serum free DMEM containing free fatty acids (free fatty acid conditions are a mixture of palmitic acid and BSA, with a final concentration of palmitic acid of 0.1 mM). After the cells are pre-protected by respectively adding the mixture of timosaponin enzymolysis products and berberine hydrochloride with different concentrations for 30min, free fatty acid (the condition of the free fatty acid is the mixture of palmitic acid and BSA, wherein the final concentration of the palmitic acid is 0.1 mM), wherein the mixture 1 (weight ratio is 1.6:3) =timosaponin enzymolysis products 1.19 mg/L+berberine hydrochloride 2.22mg/L, the mixture 2 (weight ratio is 1.6:2) =timosaponin enzymolysis products 1.19 mg/L+berberine hydrochloride 1.48mg/L, the mixture 3 (weight ratio is 1.6:1) =timosaponin enzymolysis products 1.19 mg/L+berberine hydrochloride 0.74mg/L, the mixture 4 (weight ratio is 3.2:1) =timosaponin enzymolysis products 2.37 mg/L+berberine hydrochloride 0.74mg/L, and the mixture 5 (weight ratio is 4.8:1) =timosaponin enzymolysis products 3.56 mg+berberine hydrochloride 0.74 mg/L). All cells were cultured for a further 12h, lysed to collect cells, and cell TG content was determined as required by the commercial kit instructions and divided by cell protein amount.
(6) Determination of synergistic effect of timosaponin enzymolysis product and berberine hydrochloride
According to the above cell differentiation method, 3T3-L3 cells are differentiated into mature adipocytes, and divided into Blank group (Blank), model group (PA), and timosaponin enzymolysis product (E-TA III, final concentration 2.37 mg/L), berberine hydrochloride (BBR, final concentration 1.48 mg/L), mixture 1 of timosaponin enzymolysis product and berberine hydrochloride (Mix 1, timosaponin enzymolysis product 1.19 mg/L+berberine hydrochloride 0.74 mg/L), mixture 2 of timosaponin enzymolysis product and berberine hydrochloride (Mix 2, timosaponin enzymolysis product 2.37 mg/L+berberine hydrochloride 1.48 mg/L) are added respectively. The cells were pre-protected with the drug for 30min, free fatty acid (the condition of free fatty acid is a mixture of palmitic acid and BSA, wherein the final concentration of palmitic acid is 0.1 mM) was added, the culture was continued for 12h, the cells were collected by lysis, and the cell TG content was determined as required by the commercial kit instructions and divided by the cell protein amount.
The results are shown in FIGS. 1 to 2.
Example 3
Weight-losing and lipid-lowering efficacy evaluation method of timosaponin enzymolysis product and berberine hydrochloride composition
1. Experimental reagent and material
(1) Experimental animals: male C57BL/6 mice, 60, 5 week old, were purchased from Shanghai Ji Hui laboratory animal feeding Co. Animal feeding is carried out at an animal experiment center of Shanghai traditional Chinese medicine university, and the experimental animals use a production license number; SYXK (Shanghai) 2020-0009. The raising temperature is 25+/-1 ℃, the humidity is 60+/-2%, the free diet is adopted, the cage raising is carried out, the artificial light and dark circulation is carried out for 12 hours, and all animal experiment operations accord with the animal center regulation system of Shanghai Chinese medicine university.
(2) Reagent: timosaponin enzymolysis product (E-TA III); berberine hydrochloride (BBR, purity >98%, division of bioengineering (Shanghai)); metformin hydrochloride (division of bioengineering (Shanghai)). qPCR premix kit (Highway Biotech (Shanghai Co., ltd.); the following reagents were purchased from institute of bioengineering with south Beijing: TC kit, TG kit, HDL-C kit, LDL-C kit; ethanol (national drug group); isopropyl alcohol (national drug group); TRIzol reagent (TaKaRa). Common feed and high fat feed (60% caloric) for mice were purchased from Jiangsu province collaborative medical bioengineering, inc.
2. Experimental method
C57BL/6 mice were randomly divided into 6 groups (10 per group), the blank group was fed with normal feed, and the rest were fed with high-fat feed: high-fat group, timosaponin enzymolysis product group, berberine hydrochloride group, timosaponin enzymolysis product+berberine hydrochloride medicine combination 1 group, timosaponin enzymolysis product+berberine hydrochloride medicine combination 2 group. After the animal is raised for 7 weeks, gastric administration is started after the animal is subjected to obesity model, the timosaponin enzymolysis product group is used for carrying out gastric administration, the timosaponin enzymolysis product E-AIII (15.8 mg/kg), the berberine hydrochloride group is used for carrying out gastric administration, the berberine hydrochloride (10 mg/kg), the timosaponin enzymolysis product and berberine hydrochloride pharmaceutical composition 1 group are used for carrying out simultaneous gastric administration, the timosaponin enzymolysis product (7.9 mg/kg) and berberine hydrochloride (5 mg/kg), the timosaponin enzymolysis product and berberine hydrochloride pharmaceutical composition 2 group are used for carrying out simultaneous gastric administration, the timosaponin enzymolysis product (15.8 mg/kg) and berberine hydrochloride (10 mg/kg), and the mice eat and drink water freely, and the pharmaceutical intervention is carried out for 10 weeks.
By gavage, it is meant, unless otherwise specified, that the compound is suspended in CMC-Na in solid form and is gavaged as a solution.
All mice were fed last, fasted for 12h without water withdrawal, and after anesthesia, the mice were bled and serum was isolated for detection of Total Cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) levels in serum. Mice were sacrificed by cervical vertebra removal after blood collection, three adipose tissues of scapula brown fat (BAT), inguinal beige fat (iWAT) and epididymis white fat (eWAT) were taken out, stained sections were examined after 4% paraformaldehyde immersion, and the remaining tissues were stored in a refrigerator at-80℃for use.
3. Index detection
(1) Weight measurement
The weight of each group of mice was weighed before high fat feeding, each group of mice was weighed before the last administration, and the percentage of weight gain of each group of mice was calculated.
(2) Serum blood lipid level detection
Determination of Triglycerides (TG): taking 2 mu L of serum and distilled water as blank, taking a standard substance as a standard hole, adding 200 mu L of working solution, incubating for 10min at 37 ℃, and detecting TG absorbance at a wavelength of 510 nm. Serum TG content (mmol/L) = (sample OD value-blank OD value)/(standard cone OD value-blank OD value) ×standard concentration (2.26 mmol/L) was calculated according to the formula.
Total Cholesterol (TC) was measured as above with a standard concentration of (5.17 mmol/L).
Measurement of Low Density lipoprotein cholesterol (LDL-C): taking 2.5 mu L of serum and distilled water as blank, taking a standard substance as a standard hole, adding 180 mu L of first working solution, incubating for 5min at 37 ℃, detecting LDL-C absorbance A1 at 546nm wavelength, adding 60 mu L of second working solution, incubating for 5min at 37 ℃, and detecting LDL-C absorbance A2 at 546nm wavelength. Serum LDL-C content (mmol/L) = [ (sample A2-sample A1) - (blank A2-blank A1) ]/[ (standard A2-standard A1) - (blank A2-blank A1) ]xstandard concentration (2.20 mmol/L) as calculated by the formula.
The procedure for high density lipoprotein cholesterol (HDL-C) determination was as above with a standard concentration of 1.05mmol/L.
(3) Adipose tissue sections and observations
Fresh adipose tissues were sent for paraffin section treatment and hematoxylin-eosin (HE) staining was performed. The dyeing method comprises the following steps: firstly, paraffin sections are put into dimethylbenzene for dewaxing; taking out the slices, rehydrating the slices by 100%, 95%, 85%, 75% and 50% ethanol in sequence, and cleaning the slices with distilled water for 3 times; placing the slice into hematoxylin dye solution, passing for 10min, taking out the slice, immersing the slice into distilled water for reverse blue, and washing with distilled water after about 5 min; then putting into 0.5% concentration acetic acid ethanol for differentiation, and washing with distilled water once; then placing the slice into eosin dye solution for 30sec, taking out, and soaking in 95% ethanol for 10sec for color separation treatment; finally, the slices are dehydrated, transparent, then are sealed by a sealing tablet, and observed and left under an optical microscope.
The results are shown in FIGS. 3 to 5.
Example 4
Experimental results
1. Ethanol extract of rhizoma anemarrhenae and its enzyme hydrolysate containing TB II and TA III
Respectively precisely weighing 150.00mg of rhizoma anemarrhenae ethanol extract and 10.00mg of enzyme hydrolysate, placing in a 25ml volumetric flask, dissolving with ultrasound, fixing volume with 50% ethanol, filtering with 0.45 μm filter membrane, and determining TB II and TA III content. Conversion of TA iii = (m1×m2)/(m2×m1) ×100) was calculated, where: m1 represents the actual measured amount of TA III in the enzyme hydrolysate; m2 represents the actual measured amount of TB II in the ethanol extract; m1 represents TA III relative molecular weight; m2 represents the relative molecular weight of TB II.
The results show that in the prepared rhizoma anemarrhenae ethanol extract, the TB II content is (31.3+/-1.4)%, the TB II extraction rate is (95.3+/-4.9)%, and the TA III content is (3.2+/-0.3)%; in the enzyme hydrolysate, TA III content was (62.5.+ -. 0.3)% (RSD was 0.5%, n=3), TB II was not detected, and TA III conversion was (82.6.+ -. 1.7)% (RSD was 1.6%, n=3), indicating complete conversion. The main component of the enzymolysis product of the anemarrhena alcohol extract is timosaponin AIII.
2. Optimal combination ratio of timosaponin enzymolysis product and berberine hydrochloride composition for reducing cell triglyceride
Under the action of palmitic acid, the content of cell triglyceride in the differentiated 3T3-L1 cells is increased, and the composition of the timosaponin enzymolysis product and berberine hydrochloride can reduce the content of the cell triglyceride in different weight ratios. When the weight ratio of timosaponin enzymolysis product to berberine hydrochloride is 1.6:1, the effect is optimal, and 68.31% (figure 1) is reduced.
3. Timosaponin enzymolysis product and berberine hydrochloride composition for reducing cell triglyceride have synergistic effect
Whether the composition is superior to the single medicine, the 3T3-L1 cell triglyceride level of differentiation is increased by adopting palmitic acid, as shown in figure 2, the cell triglyceride content can be reduced by using timosaponin enzymolysis product or berberine hydrochloride, and the content is respectively reduced by 38.17% (p < 0.05) and 56.82% (p < 0.001); the timosaponin enzymolysis product and berberine hydrochloride are combined 1, the dosages of the components are respectively half of the dosages of the independent administration, the triglyceride content is reduced by 64.92 percent (p < 0.001), and the effect is obviously better than that of the independent administration; the timosaponin enzymolysis product and berberine hydrochloride are combined to form 2, the dosages of the components are respectively single administration dosages, the triglyceride content is reduced by 73.97 percent (p < 0.001), and the effect is better than that of single administration and that of combination 1. The timosaponin enzymolysis product and berberine hydrochloride composition have synergistic effect in reducing cell triglyceride.
4. Influence of timosaponin enzymolysis product and berberine hydrochloride composition on weight of mice
The C57BL/6 mice were weighed before molding and 10 weeks after gavage administration, respectively. Compared with the blank group, the weight of the mice in the high-fat model group is obviously increased after the administration of high-fat feed; in contrast, the dosing groups all significantly reduced the body weight of the mice given high fat compared to the high fat model group (fig. 3). Wherein the capability of the timosaponin enzymolysis product and berberine hydrochloride combination 1 for reducing the weight of mice is respectively 1.28 times of timosaponin AIII and 1.70 times of berberine hydrochloride; the effect of reducing the weight of the timosaponin enzymolysis product and berberine hydrochloride combined 2 is optimal and is 1.29 times of that of the timosaponin enzymolysis product and berberine hydrochloride combined 1.
5. Influence of timosaponin enzymolysis product and berberine hydrochloride composition on serum blood lipid level of mice
The high fat control group had elevated serum TG, TC and LDL-C levels and reduced HDL-C levels as compared to the placebo group, with TG, TC, LDL-C, HDL-C levels increased by 92.73%,198.77%,429.52% and 34.53% respectively as compared to the placebo group. The timosaponin enzymolysis product, berberine hydrochloride, timosaponin enzymolysis product and berberine hydrochloride composition can obviously reduce TG of high-fat mice, raise HDL-C content, and obviously reduce TC and LDL-C content. The combination 1 of timosaponin enzymolysis product and berberine hydrochloride can reduce TG, TC, LDL-C level or raise HDL-C level, which is obviously superior to timosaponin enzymolysis product or berberine hydrochloride alone, and the combination 2 of timosaponin enzymolysis product and berberine hydrochloride has better effect than timosaponin enzymolysis product and berberine hydrochloride combination 1. The result shows that timosaponin enzymolysis product and berberine hydrochloride have synergistic effect in improving lipid abnormality of high-fat mice.
6. Influence of timosaponin enzymolysis product and berberine hydrochloride composition on fat morphology of mice
Three adipose tissues of mice were extracted and separated, and then, the mice were embedded in sections and subjected to HE staining. The different adipose tissue morphologies of the mice are shown in the figure (figure 5), and compared with the blank group, fat drops in the fat of the three adipose tissues of the high-fat group mice are obviously enlarged; each dosing group significantly reduced adipocyte lipid droplet size compared to the high lipid model group. After the timosaponin enzymolysis product and berberine hydrochloride are combined 1 and 2, the diameters of adipose tissue cells are obviously reduced, the number of cells per unit area is increased, and the effect is better than that of the timosaponin enzymolysis product or berberine hydrochloride which are singly used. The timosaponin enzymolysis product and berberine hydrochloride group are suggested to have synergistic effect in improving the adipose tissue morphology.
The above embodiments are merely illustrative of the principles of the present application and its effectiveness, and are not intended to limit the application. Modifications and variations may be made to the above-described embodiments by those skilled in the art without departing from the spirit and scope of the application. Accordingly, it is intended that all equivalent modifications and variations of the application be covered by the claims, which are within the ordinary skill of the art, be within the spirit and scope of the present disclosure.
Claims (10)
1. A composition, which is characterized by comprising timosaponin enzymolysis products and berberine hydrochloride.
2. The composition of claim 1, wherein the timosaponin enzymatic hydrolysate comprises timosaponin aii.
3. The composition of claim 1, wherein the composition comprises, in parts by weight, 1 to 3 parts berberine hydrochloride and 1.6 to 4.8 parts timosaponin enzymatic hydrolysate, the parts by weight of timosaponin enzymatic hydrolysate being on a dry weight basis.
4. The composition of claim 1, further comprising a pharmaceutically acceptable carrier, additive, adjuvant, or excipient.
5. Use of a composition according to any one of claims 1 to 4 for the preparation of a weight-reducing and lipid-lowering product.
6. The use according to claim 5, wherein the fat-reducing and lipid-lowering product has one or more of the following effects:
1) Weight loss;
2) Reducing serum total cholesterol;
3) Lowering serum triglycerides;
4) Lowering serum low density lipoprotein;
5) Raise serum high density lipoprotein.
7. Use of a composition according to any one of claims 1 to 4 for the preparation of a medicament, food or health product for the prophylaxis and treatment of hyperlipidemia, fatty liver, coronary heart disease, cardiovascular disease, diabetes.
8. The use as claimed in claim 7, wherein the pharmaceutical, food or health product comprises a dosage form selected from the group consisting of tablets, capsules, aerosols, pills, powders, solutions, syrups, transdermal patches, emulsions, lyophilized powders for injection and suppositories.
9. A method of treatment for weight loss and lipid lowering comprising administering to a subject an effective amount of a composition according to any one of claims 1 to 4.
10. The method of treatment of claim 7, wherein the subject is a mammal.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310497205.4A CN116585338A (en) | 2023-05-05 | 2023-05-05 | Weight-losing and lipid-lowering pharmaceutical composition and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310497205.4A CN116585338A (en) | 2023-05-05 | 2023-05-05 | Weight-losing and lipid-lowering pharmaceutical composition and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116585338A true CN116585338A (en) | 2023-08-15 |
Family
ID=87607155
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310497205.4A Pending CN116585338A (en) | 2023-05-05 | 2023-05-05 | Weight-losing and lipid-lowering pharmaceutical composition and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116585338A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112168833A (en) * | 2020-10-12 | 2021-01-05 | 上海中医药大学 | Timosaponin enzymolysis product and medical application of timosaponin AIII as main component thereof |
-
2023
- 2023-05-05 CN CN202310497205.4A patent/CN116585338A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112168833A (en) * | 2020-10-12 | 2021-01-05 | 上海中医药大学 | Timosaponin enzymolysis product and medical application of timosaponin AIII as main component thereof |
Non-Patent Citations (1)
| Title |
|---|
| XIAOTING TIAN ET AL.: "Enhanced Anti-diabetic Effect of Berberine Combined With Timosaponin B2 in Goto-Kakizaki Rats, Associated With Increased Variety and Exposure of Effective Substances Through Intestinal Absorption", 《FRONTIERS IN PHARMACOLOGY》, vol. 10, 31 January 2019 (2019-01-31), pages 1 - 15 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107441078B (en) | A kind of pharmaceutical composition and its preparation method and application for treating diabetes | |
| CN115304653B (en) | Four iridoid glycoside compounds extracted from dogwood, and preparation method and application thereof | |
| CN102133221B (en) | Compound traditional Chinese medicine extract preventing glucose metabolism disturbance and preparation method thereof | |
| CN105722519A (en) | Composition containing a borage officinalis extract for alleviating, preventing, or treating metabolic diseases | |
| KR101501233B1 (en) | Pharmaceutical composition or health food containing black tea ethanol solution extracts which is effective for reducing body weight and body fats or preventing or treating lipid related metabolic disease | |
| CN111840425A (en) | Traditional Chinese medicine composition for treating diabetic nephropathy and application thereof | |
| CN114989234B (en) | Preparation method and application of iridoid glycoside compound C in dogwood | |
| CN111184774A (en) | Corydalis saxicola bunting and application of corydalis saxicola bunting preparation in preparation of drug for treating non-alcoholic fatty liver disease | |
| CN116585338A (en) | Weight-losing and lipid-lowering pharmaceutical composition and application thereof | |
| CN103860565B (en) | Medicinal composition for treating diabetes hepatic fibrosis | |
| CN105999195B (en) | Preparation method of ginseng branch poria cocos preparation | |
| CN105920051B (en) | Flammulina velutipes extract and preparation method and application thereof | |
| WO2018008973A1 (en) | Composition comprising forsythiae fructus extract as effective ingredient for preventing, ameliorating or treating peripheral neuropathy | |
| CN1272290C (en) | Capejasmine cycloolefines ether terpene extract and its preparation method and use | |
| KR20190003092A (en) | Composition for preventing, improving or treating stress and depression comprising medicinal herb complex extract as effective component | |
| CN109260205B (en) | Application of tetrandrine in preparation of medicine for resisting diabetes and hypertension | |
| CN110772563B (en) | Preparation method of rheum bracteatum extract and application of rheum bracteatum extract in preparation of anti-type 2 diabetes products | |
| CN111773323A (en) | Application of dendrobium water extract in treating type 2 diabetes | |
| CN111544440A (en) | Application of diosmin and composition in preparation of anti-obesity product | |
| CN111249271A (en) | Medicament for treating diabetes and preparation method and application thereof | |
| CN116712445A (en) | Timosaponin enzymolysis product and application of timosaponin AIII in preparation of medicines for treating hyperlipidemia | |
| CN1466951A (en) | Gardenoside general extracts preparation and making method and uses | |
| CN105232676B (en) | A kind of Chinese medicine for treating diabetes and preparation method thereof | |
| CN115317534B (en) | Application of myrtle extract in reducing blood sugar and treating diabetic nephropathy | |
| CN113308495B (en) | Gastrodia elata fermentation product polar component for assisting in improving memory 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 |