CN105535070B - The pharmaceutical composition and its preparation method and application for treating diabetes - Google Patents
The pharmaceutical composition and its preparation method and application for treating diabetes Download PDFInfo
- Publication number
- CN105535070B CN105535070B CN201610043265.9A CN201610043265A CN105535070B CN 105535070 B CN105535070 B CN 105535070B CN 201610043265 A CN201610043265 A CN 201610043265A CN 105535070 B CN105535070 B CN 105535070B
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- radix
- parts
- fructus corni
- gynurae divaricatae
- 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.)
- Active
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 67
- 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 54
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 239000003814 drug Substances 0.000 claims abstract description 47
- 239000000284 extract Substances 0.000 claims abstract description 25
- 229940079593 drug Drugs 0.000 claims abstract description 21
- 239000002994 raw material Substances 0.000 claims abstract description 17
- 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 3
- 208000001145 Metabolic Syndrome Diseases 0.000 claims abstract 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims abstract 2
- 239000000463 material Substances 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 238000000605 extraction Methods 0.000 claims description 15
- 239000000706 filtrate Substances 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 3
- 230000000694 effects Effects 0.000 abstract description 27
- 239000008186 active pharmaceutical agent Substances 0.000 abstract description 4
- 230000002195 synergetic effect Effects 0.000 abstract description 4
- 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 44
- 210000004369 blood Anatomy 0.000 description 36
- 239000008280 blood Substances 0.000 description 36
- 102000004877 Insulin Human genes 0.000 description 22
- 108090001061 Insulin Proteins 0.000 description 22
- 229940125396 insulin Drugs 0.000 description 22
- 239000008103 glucose Substances 0.000 description 17
- 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 15
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 14
- 206010022489 Insulin Resistance Diseases 0.000 description 12
- 241000700159 Rattus Species 0.000 description 8
- HIMXGTXNXJYFGB-UHFFFAOYSA-N alloxan Chemical compound O=C1NC(=O)C(=O)C(=O)N1 HIMXGTXNXJYFGB-UHFFFAOYSA-N 0.000 description 8
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 7
- 210000001789 adipocyte Anatomy 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
- 241000887125 Chaptalia nutans Species 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 230000002218 hypoglycaemic effect Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 210000003734 kidney Anatomy 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- YDGOIHYUXBNION-UHFFFAOYSA-N 3,7-dimethylocta-1,6-diene-3,4-diol Chemical compound CC(C)=CCC(O)C(C)(O)C=C YDGOIHYUXBNION-UHFFFAOYSA-N 0.000 description 4
- 235000003143 Panax notoginseng Nutrition 0.000 description 4
- 241000180649 Panax notoginseng Species 0.000 description 4
- 102100040918 Pro-glucagon Human genes 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 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 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 3
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 3
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 239000001116 FEMA 4028 Substances 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241001558017 Gynura Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 3
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 3
- 229960004853 betadex Drugs 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 241000411851 herbal medicine Species 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000003914 insulin secretion Effects 0.000 description 3
- 238000011552 rat model Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- YKXCWZVUWWQSAV-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O YKXCWZVUWWQSAV-BTVCFUMJSA-N 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 2
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 2
- 208000012287 Prolapse Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- HLXRWTJXGMHOFN-XJSNKYLASA-N Verbenalin Chemical compound O([C@@H]1OC=C([C@H]2C(=O)C[C@H](C)[C@H]21)C(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HLXRWTJXGMHOFN-XJSNKYLASA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 230000008727 cellular glucose uptake Effects 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229930003935 flavonoid Natural products 0.000 description 2
- 150000002215 flavonoids Chemical class 0.000 description 2
- 235000017173 flavonoids Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 2
- 229960001052 streptozocin Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 230000035922 thirst Effects 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- SPFMQWBKVUQXJV-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;hydrate Chemical compound O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O SPFMQWBKVUQXJV-BTVCFUMJSA-N 0.000 description 1
- WCGUUGGRBIKTOS-GPOJBZKASA-N (3beta)-3-hydroxyurs-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C WCGUUGGRBIKTOS-GPOJBZKASA-N 0.000 description 1
- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 241000208838 Asteraceae Species 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 235000007516 Chrysanthemum Nutrition 0.000 description 1
- 240000005250 Chrysanthemum indicum Species 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 241000142975 Cornaceae Species 0.000 description 1
- 241000209020 Cornus Species 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 101150026109 INSR gene Proteins 0.000 description 1
- 229940122199 Insulin secretagogue Drugs 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010027514 Metrorrhagia Diseases 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 244000131316 Panax pseudoginseng Species 0.000 description 1
- 235000003181 Panax pseudoginseng Nutrition 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 102000000070 Sodium-Glucose Transport Proteins Human genes 0.000 description 1
- 108010080361 Sodium-Glucose Transport Proteins Proteins 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 102000003673 Symporters Human genes 0.000 description 1
- 108090000088 Symporters Proteins 0.000 description 1
- HLXRWTJXGMHOFN-UHFFFAOYSA-N Verbenalin Natural products C12C(C)CC(=O)C2C(C(=O)OC)=COC1OC1OC(CO)C(O)C(O)C1O HLXRWTJXGMHOFN-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 244000273928 Zingiber officinale Species 0.000 description 1
- 235000006886 Zingiber officinale Nutrition 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940126678 chinese medicines Drugs 0.000 description 1
- 229940099352 cholate Drugs 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 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 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 235000008397 ginger Nutrition 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- 229960000346 gliclazide Drugs 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000002398 materia medica Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 230000012666 negative regulation of transcription by glucose Effects 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 235000018553 tannin Nutrition 0.000 description 1
- 229920001864 tannin Polymers 0.000 description 1
- 239000001648 tannin Substances 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 229940096998 ursolic acid Drugs 0.000 description 1
- PLSAJKYPRJGMHO-UHFFFAOYSA-N ursolic acid Natural products CC1CCC2(CCC3(C)C(C=CC4C5(C)CCC(O)C(C)(C)C5CCC34C)C2C1C)C(=O)O PLSAJKYPRJGMHO-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 235000020985 whole grains Nutrition 0.000 description 1
Classifications
-
- 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)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/40—Cornaceae (Dogwood family)
-
- 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)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- 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
- A61K9/20—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
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a kind of pharmaceutical compositions for treating diabetes.Described pharmaceutical composition is the medicament made of the raw material of following weight: 9 ~ 55 parts of Radix et Rhizoma Gynurae divaricatae, 7 ~ 53 parts of Fructus Corni.The pharmaceutical composition is only used as medicine by Radix et Rhizoma Gynurae divaricatae and two taste Chinese medicine compatibility of Fructus Corni, and adjusting its weight is 9 ~ 55 parts of Radix et Rhizoma Gynurae divaricatae, 7 ~ 53 parts of Fructus Corni, Radix et Rhizoma Gynurae divaricatae and Fructus Corni is set to play synergistic effect, it is significant to treat diabetes curative effect, and the pharmaceutical composition component is simple, quality is easy to control, it is curative for effect.The present invention also provides the preparation method of described pharmaceutical composition, which can effectively extract the active pharmaceutical ingredient in Radix et Rhizoma Gynurae divaricatae and Fructus Corni, and easy to operate.The present invention further provides application of the described pharmaceutical composition in the drug that preparation improves diabetes, hyperlipidemia or metabolic syndrome.
Description
Technical field
The invention belongs to pharmaceutical fields, are related to a kind of pharmaceutical composition, in particular to a kind of to treat diabetes or hyperlipidemia
Pharmaceutical composition and its preparation method and application.
Background technique
Diabetes (diabetes mellitus, DM) are impaired caused with hypoinsulinism or its biological effect
Metabolic disease characterized by hyperglycemia.According to the opposite of insulin secretion with can absolutely not be divided into type-1 diabetes mellitus and II completely
Patients with type Ⅰ DM；Wherein by islet beta cell function failure, diabetes caused by excreting insulin absolute magnitude is insufficient are type-1 diabetes mellitus；
It is sufficient with excreting insulin absolute magnitude, and because caused by insulin resistance diabetes type-2 diabetes mellitus.Cut-off 2014, in
State diabetic more than 100,000,000 people, accounts for the one third of whole world patient populations.More importantly with domestic population
Aging and the change of resident living mode are so that obvious ascendant trend is presented in diabetes prevalence.It is aobvious according to health ministry investigation
Show, China is 3000 about newly-increased daily, every year at least newly-increased 1,200,000 diabetics [Hu Shanlian, Liu Guoen, perhaps camphor tree
Honor waits the China diabetes epidemiology and study of disease financial burden status [J] China Health economy, 2008 (08):
5-8.].It can be seen that diabetes have become the significant problem for threatening broad masses of the people's general level of the health, exploitation treatment diabetes
Superior drug always be the effort target of Chinese and western medical personal.
Currently, the conventional medicament for the treatment of diabetes mainly includes sulfonylurea drugs, biguanides, α glucuroide
Inhibitor, insulin sensitizer, Insulin secretagogues, insulin preparation etc..These drugs can by the intake of glucose,
The modes such as the secretion of insulin, the enhanced sensitivity of insulin or direct supplement insulin level, which play, reduces blood glucose effect, however above-mentioned
There is gastrointestinal reaction, the influence of liver kidney, heart or maincenter adverse reaction to some extent in drug.It is new according to diabetes in recent years
Pathogenesis research and develop and used different types of drug, such as be directed to glucagon-like-peptide-1 (glucagon-like
Peptide 1, GLP-1) receptor play a role GLP-1 class drug, to GLP-1 hydrolase DPP IV
The DPP-IV inhibitor and the sodium-glucose association paid close attention to by industry that (Dipeptidyl Peptidase IV, DPP-IV) works
Same transport protein (Sodium-glucose co-transporters, SGLT) inhibitor etc., these drugs are considered as
The breakthrough for treating diabetes.However there is different degrees of adverse reaction (pharyngitis, headache, the infection of the upper respiratory tract, evil
The heart, vomiting, diarrhea, constipation, kidney function damage, symptomatic hypotension, fungal infection etc.), and the treatment in some patientss is made
With still person of modern times does not anticipate.So clinical still there is an urgent need to develop curative for effect, toxic side effect is small, and the newtype drug of affordable.
In recent years, domestic and international experts and scholars increasingly pay attention to Chinese medicine and natural drug, and are applied to diabetes clinical treatment.
Radix et Rhizoma Gynurae divaricatae is " Chinese draft " precious Chinese herbal medicine for including, be compositae plant Gynura divaricata (Gynura divaricata(L.) DC.) herb, alias rescues greatly, big fat cow, and divaricate gynura root and rhizome, white young dish medicine dissipate blood ginger etc..Mainly at
Divide includes alkaloids, flavonoids, triterpenes and some long-chain fat same clans compound；With hypoglycemic, blood pressure lowering, drop blood
The pharmacological actions such as rouge, resist oxygen lack, anti-mutagenesis.Existing document report Radix et Rhizoma Gynurae divaricatae, which has experimental type 2 diabetes mellitus, significantly to be controlled
Treatment effect, mechanism may with the ability of enhancing body Scavenger of ROS, mitigate oxygen radical to the damage of beta Cell of islet, promote
Into beta Cell of islet reparation the effects of related [Ma Zhengdong, Chen Lei, Song Hongtao wait Radix et Rhizoma Gynurae divaricatae water extract to 2 types sugar
Urinate the hypoglycemic effect and its mechanism [J] Chinese herbal medicine of sick rat, 2010 (04): 623-626.].Separately there is the white back of document report
Radix Notoginseng improves significantly to Insulin Resistance of Rats, and mechanism of action may be with the table of up-regulation InsR mRNA
[Han Haifeng, Zhang Xueying, Shen Hongli wait Radix et Rhizoma Gynurae divaricatae to insulin resistance rat hepatic insulin expression of receptor up to related
Influence [J] Pharmacology and Clinics of Chinese Materia Medica, 2014 (05): 102-105.].In addition, still thering are related patents to report Radix et Rhizoma Gynurae divaricatae
Purposes in diabetes discloses one kind including patent of invention CN100475232C with Radix et Rhizoma Gynurae divaricatae extract as original
The oral drugs and purposes of material treatment diabetes.Patent of invention CN101147749B discloses the preparation of white-backed pseudo-ginseng total flavonoid
Method and its application in hypoglycemic medicine.Patent of invention CN102389454B, CN103191039B, CN103988964A,
CN102389454B discloses a kind of compound preparation being made of multiple flavour of a drug containing Radix et Rhizoma Gynurae divaricatae and its application.But it is above-mentioned about
Mutual reinforcement between mutually makes between suffering for want of medical supplies when the patent of Radix et Rhizoma Gynurae divaricatae is applied alone, and excessive compound is unfavorable for drug development again.Therefore, above special
Radix et Rhizoma Gynurae divaricatae extract or compound disclosed in benefit cannot still play the combination between Radix et Rhizoma Gynurae divaricatae and important antidiabetic medicine completely
Object advantage and clinical value.
Fructus Corni be Cornaceae plant Fructus Corni (Cornus officinalisSieb. et Zucc.) maturation
Dry fruit, containing ingredients such as cornin, saponin(e, tannin, ursolic acid and vitamin As, Traditional Chinese Medicine thinks that Fructus Corni has benefit
Liver kidney, arresting seminal emission gas, solid collapse and hypoglycemic and other effects.Fructus Corni is since Han dynasty always as the key medicine for treating " diabetes ".
Document report shows that Fructus Corni can significantly reduce blood glucose in diabetic mice level, improves serum insulin level, and to glycerol three
Ester also has decreasing trend, and [Yang Yong, Rong Rong, Jiang Chunhong wait Zhu English opposed polarity extract drop blood in the mountain to ward off the research China of effect
Pharmacological Bulletin, 2009,25 (suppl): 181.].Mountain cornel cornel can also increase hepatic glycogen content simultaneously, significantly reduce saccharification blood
Albumin levels, to significantly reduce blood glucose in diabetic mice level, [Korea Spro's Jing is super, and Ji Hui, Xue Chengfeng wait Fructus Corni total
Hypoglycemic effect [J] the China natural drug of terpene, 2006,4 (02) .125-129.].In addition, the Chinese medicine compound prescription containing Fructus Corni
It is more in use patent in diabetes, including patent of invention CN 103479874A, CN 103705723A, CN
104336715A, CN103749819A, CN 101040982, CN101904994A etc. disclose it is a kind of containing Fructus Corni by multiple
The compound preparation of flavour of a drug composition and its application.It is combined the very rare of object research with two taste Chinese medicines, especially with white back three
Seven have not been reported with Fructus Corni independent compatible use, and obtaining the epidemic proportion of its composition by research is even more blank.
By upper sight, it is simple, curative for effect to find component, it is low in cost and to the significant Chinese medicine for the treatment of diabetes curative effect at
Fang Feichang is urgently and important.
Summary of the invention
It is an object of the invention to overcome the above-mentioned deficiency in the presence of the prior art, a kind of medicine for treating diabetes is provided
Compositions.The pharmaceutical composition is 9 ~ 55 parts of Radix et Rhizoma Gynurae divaricatae according to weight by Radix et Rhizoma Gynurae divaricatae and Fructus Corni, Fructus Corni 7
~ 53 parts are raw material, and component is simple, curative for effect, and Radix et Rhizoma Gynurae divaricatae and Fructus Corni from improvement insulin sensitivity and increase insulin
Secretion aspect plays synergistic effect, can effectively treat diabetes, significant in efficacy.
It is a further object of the present invention to provide the preparation methods of described pharmaceutical composition.The preparation method simple process, can
The active constituent of Radix et Rhizoma Gynurae divaricatae and Fructus Corni is effectively extracted, the pharmaceutical composition of preparation is curative for effect, and treatment diabetes effect is aobvious
It writes.
Another object of the present invention is to provide the application of described pharmaceutical composition.
In order to achieve the above-mentioned object of the invention, the present invention provides following technical schemes:
The pharmaceutical composition for the treatment of diabetes of the present invention, is the medicament made of the raw material of following weight:
9 ~ 55 parts of Radix et Rhizoma Gynurae divaricatae, 7 ~ 53 parts of Fructus Corni.
The pharmaceutical composition for the treatment of diabetes of the present invention, using Radix et Rhizoma Gynurae divaricatae and Fructus Corni as medicinal raw material.It is wherein white
It is sweet in flavor to carry on the back Radix Notoginseng, it is light, it is mild-natured；Return lung, the heart two pass through.Function is to dispel to quench one's thirst, clearing heat and cooling blood, promoting blood circulation and hemostasis analgesic；It can be used for sugar
Urinate disease, bronchitis, metrorrhagia and metrostaxis, traumatic injury etc..Fructus Corni is sour, puckery, tepor；It is cool in nature；Return liver and kidney channel；With tonify the liver and kidney,
The effect of arresting seminal emission prevent prolapse.Papillary can dispel quench one's thirst, tonify the liver and kidney, arresting seminal emission prevent prolapse.
Inventor has found through test of many times, only using two kinds of medicinal materials of Radix et Rhizoma Gynurae divaricatae and Fructus Corni as raw material, and adjusts white back three
Seven and Fructus Corni weight be 9 ~ 55 parts of Radix et Rhizoma Gynurae divaricatae, 7 ~ 53 parts of Fructus Corni, can effectively treat diabetes.The present invention
Described pharmaceutical composition is compared with the pharmaceutical composition of existing treatment diabetes, and component is simpler, and only there are two types of bulk pharmaceutical chemicals
Material is allowed to the available better control of quality, curative for effect, has no toxic and side effect to human body.Meanwhile it is aobvious to diabetes curative effect
It writes, and taking dose is small.
Diabetes of the present invention include type-1 diabetes mellitus, type-2 diabetes mellitus or insulin resistance related disease.
Preferably, described pharmaceutical composition is the medicament made of the raw material of following weight: Radix et Rhizoma Gynurae divaricatae 15 ~ 50
Part, 7 ~ 42 parts of Fructus Corni.
It is further preferred that described pharmaceutical composition is the medicament made of the raw material of following weight: white back three
7 15 ~ 30 parts, 7 ~ 25 parts of Fructus Corni.
It is further preferred that described pharmaceutical composition is the medicament made of the raw material of following weight: white back three
7 15 ~ 25 parts, 7 ~ 20 parts of Fructus Corni.
It is further preferred that described pharmaceutical composition is the medicament made of the raw material of following weight: white back
20 ~ 25 parts of Radix Notoginseng, 9 ~ 11 parts of Fructus Corni.
By to the preferred of Radix et Rhizoma Gynurae divaricatae in pharmaceutical composition and Fructus Corni weight, can be further improved above
Curative effect of the pharmaceutical composition to treatment diabetes.
Most preferably preferably, described pharmaceutical composition is the medicament made of the raw material of following weight: Radix et Rhizoma Gynurae divaricatae
22 parts, 10 parts of Fructus Corni.Preferably by this, the pharmaceutical composition can be made to reach best to the curative effect for the treatment of diabetes.
The preparation method of the pharmaceutical composition of above-mentioned treatment diabetes, comprising the following steps:
(1) Radix et Rhizoma Gynurae divaricatae medicinal material is taken, is added water to cook extraction 2 ~ 3 times, decocting extraction time every time is 1 ~ 3h, is filtered, and is merged
Filtrate is concentrated under reduced pressure, dry, obtains Radix et Rhizoma Gynurae divaricatae extract；
(2) Fructus Corni is taken, crushes as coarse powder, is extracted 2 ~ 3 times using the alcohol reflux of 40-80%, each return time
For 1 ~ 3h, filtering, merging filtrate is concentrated under reduced pressure, dry, obtains cornel extractive；
(3) above-mentioned Radix et Rhizoma Gynurae divaricatae extract and cornel extractive are mixed, acceptable pharmaceutical preparation is made.
Preparation method of the present invention can effectively extract the active pharmaceutical ingredient in Radix et Rhizoma Gynurae divaricatae and Fructus Corni, obtain
The pharmaceutical composition taking dose arrived is small, significant in efficacy, has no toxic and side effect to human body, and easy to operate.
Preferably, water boiling and extraction 2 ~ 3 times of 6 ~ 10 times of volumes are added in the step (1).By above preferred, Ke Yiyou
Effect extracts the active pharmaceutical ingredient in Radix et Rhizoma Gynurae divaricatae.
Preferably, it is added water to cook extraction 2 ~ 3 times in the step (2) with the water of 6 ~ 10 times of volumes.It, can by above preferred
Effectively to extract the active pharmaceutical ingredient in the Fructus Corni.
In the above preparation method, it is pharmaceutically acceptable to be added that acceptable pharmaceutical preparation is made described in step (3)
Carrier or excipient acceptable various pharmaceutical preparations, such as capsule, tablet, granule, powder, lozenge etc. is made.
The pharmaceutical composition for the treatment of diabetes of the present invention can be used for preparing the medicine for improving cognitive memory functions obstacle
Object.
Compared with prior art, the beneficial effects of the present invention are:
(1) it is of the present invention treatment diabetes pharmaceutical composition using two kinds of medicinal materials of Radix et Rhizoma Gynurae divaricatae and Fructus Corni as raw material,
And the weight for adjusting Radix et Rhizoma Gynurae divaricatae and Fructus Corni is 9 ~ 55 parts of Radix et Rhizoma Gynurae divaricatae, 7 ~ 53 parts of Fructus Corni.Medicine of the present invention
Compositions are compared with the pharmaceutical composition of existing treatment diabetes, and component is simpler, and only there are two types of raw medicinal materials, are allowed to
The available better control of quality, it is curative for effect, it is significant to diabetes curative effect, and taking dose is small.
(2) preparation method of pharmaceutical composition of the present invention can effectively extract the drug in Radix et Rhizoma Gynurae divaricatae and Fructus Corni
Active constituent, and it is easy to operate.
Specific embodiment
Below with reference to test example and specific embodiment, the present invention is described in further detail.But this should not be understood
It is all that this is belonged to based on the technology that the content of present invention is realized for the scope of the above subject matter of the present invention is limited to the following embodiments
The range of invention.
Embodiment 1
Raw medicinal material is weighed by following weight: 22 parts of Radix et Rhizoma Gynurae divaricatae, 10 parts of Fructus Corni.
Above-mentioned medicinal material is prepared as follows into the pharmaceutical composition for the treatment of diabetes:
(1) Radix et Rhizoma Gynurae divaricatae medicinal material is taken, extraction 3 times is added water to cook, for the first time plus the water boiling and extraction 2h of 8 times of volumes is filtered,
The water boiling and extraction 1h filtering of the water boiling and extraction 1h filtering of second plus 8 times volume, third time plus 6 times of volumes, merging filtrate,
It is concentrated under reduced pressure, it is dry, Radix et Rhizoma Gynurae divaricatae extract is obtained, receiving cream rate is 22.61%；
(2) Fructus Corni is taken, crushes as coarse powder, is extracted 3 times using 60% alcohol reflux, each return time is 2h,
Filtering, merging filtrate are concentrated under reduced pressure, dry, obtain cornel extractive；Receiving cream rate is 24.63%；
(3) Radix et Rhizoma Gynurae divaricatae extract and cornel extractive are uniformly mixed, obtain pharmaceutical composition A.
Embodiment 2
Raw medicinal material is weighed by following weight: 18 parts of Radix et Rhizoma Gynurae divaricatae, 18 parts of Fructus Corni.
Preparation method with embodiment 1, obtains pharmaceutical composition B.
Embodiment 3
Raw medicinal material is weighed by following weight: 30 parts of Radix et Rhizoma Gynurae divaricatae, 20 parts of Fructus Corni.
Preparation method with embodiment 1, obtains pharmaceutical composition C.
Embodiment 4
Raw medicinal material is weighed by following weight: 55 parts of Radix et Rhizoma Gynurae divaricatae, 35 parts of Fructus Corni.
Preparation method with embodiment 1, obtains pharmaceutical composition D.
Embodiment 5
Raw medicinal material is weighed by following weight: 40 parts of Radix et Rhizoma Gynurae divaricatae, 53 parts of Fructus Corni.
Preparation method with embodiment 1, obtains pharmaceutical composition E.
Comparative example 1
Raw medicinal material is weighed by following weight: 56 parts of Radix et Rhizoma Gynurae divaricatae, 6 parts of Fructus Corni.
Preparation method with embodiment 1, obtains pharmaceutical composition F.
Comparative example 2
Raw medicinal material is weighed by following weight: 8 parts of Radix et Rhizoma Gynurae divaricatae, 55 parts of Fructus Corni.
Preparation method with embodiment 1, obtains pharmaceutical composition G.
Test example 1
Investigate influence of the Radix et Rhizoma Gynurae divaricatae to insulin resistance 3T3-L1 fat cell glucose uptake
The method of reference literature report establishes insulin resistance 3T3-L1 fat cell model [Yang Guizhi, Gao little Ping, a surname
Chrysanthemum virtue waits the southwest molecule mechanism [J] of dexamethasone and insulin induction 3T3-L1 fat cell insulin resistance pedagogical
College journal (natural science edition), 2003 (03): 460-464.], i.e., 10%FBS, 100UmL (are contained using DMEM in high glucose-1It is green
Mycin, 100 μ gmL-1Streptomysin) 3T3-L1 PECTORAL LIMB SKELETON is incubated at 6 well culture plates, reach 90% to cell fusion degree
When, it uses instead containing 0.25 μm of ol L-1Dexamethasone, 0.5mmol L-1IBMX and 5 μ g mL-1The above-mentioned training of insulin
It supports base noble cells two days, then uses and only contain 0.25 μm of olL-1Dexamethasone and 5 μ gmL-1The culture medium of insulin is trained
It supports two days, 3T3-L1 PECTORAL LIMB SKELETON is divided into 3T3-L1 fat cell at this time, and seeds cells into 24 well culture plates, with just
Normal culture medium continues culture two days.Hereafter, by cell inoculation and it is divided into normal group (non-resistance group), model group (resistance group) and each
Pharmaceutical composition group, every group is set up 6 multiple holes, and guidance model group is resisted in the steps below: being used and is contained 1 μm of ol L-1Dexamethasone
And 10nmolL-1The DMEM in high glucose of insulin (contains 10%FBS, 100UmL-1Penicillin, 100 μ gmL-1Streptomysin) culture
It two days, then uses instead and contains 1 μm of olL without phenol red-1Dexamethasone and 10nmolL-1The DMEM in high glucose of insulin (contains 10%
FBS, 100 U·mL-1Penicillin, 100 μ gmL-1Streptomysin) culture two days, 5 μ l cell culture are taken out from every hole at this time
Base evaluates each pharmaceutical composition to 3T3-L1 fat cell with concentration of glucose in glucose determination reagent box detection culture medium
The influence of glucose uptake.
1 Radix et Rhizoma Gynurae divaricatae of table to concentration of glucose in insulin resistance 3T3-L1 adipocyte culture base influence (,n
=6)
Note: compared with model group,* P<0.05；** P<0.01
By table 1 the results show that Radix et Rhizoma Gynurae divaricatae of the present invention is to insulin resistance 3T3-L1 fat cell glucose uptake
There is facilitation, and is in concentration-dependent relation.The cell supernatant glucose for the Radix et Rhizoma Gynurae divaricatae extract that wherein prepared by embodiment 1
Concentration is 4.263 mmolL-1, optimal effect is in multiple concentration.
Test example 2
Investigate influence of the Fructus Corni to blood sugar reducing function and level of insulin secretion.
Reference literature method uses alloxan to establish mouse type i diabetes model, and [ Yang Yong, Rong Rong, Jiang Chunhong wait
The Liaoning research [J] Journal of Traditional Chinese Medicine of Fructus Corni opposed polarity extract blood sugar reducing function, 2011,38 (1): 170-172. ],
Use 1% Alloxan 50mgkg of tail vein injection-1;Continuous 3 days, the fasting 12h after final injection, next day docking
It takes blood to survey fasting blood-glucose, chooses blood sugar concentration and be higher than 11. 1mmolL-1Mouse be diabetic mice；And press blood glucose water
It is flat to be randomly divided into model group, positive group (gliclazide, 26.6mgkg-1), the high, medium and low dosage group (agent of cornusol extract
Amount is respectively 400 mgkg-1、200 mg·kg-1、100 mg·kg-1), every group 12；Separately take 12 with batch normal mouse
For Normal group.Each group successive administration 7 days, administered volume was 20 mLkg-1, normal group and model group are given isometric
Distilled water.It takes a blood sample before administration and after administration 7 days and measures fasting blood-glucose content, 1h is measured in serum after the last administration
Insulin level.
2 Fructus Corni of table alloxan is caused type-1 diabetes mellitus mouse blood sugar and insulin level influence (, n=12)
Note: compared with model group,* P<0.05；** P<0.01。
By table 2 the results show that cornusol extract of the present invention, which can reduce to dose-dependant alloxan, causes I type sugar
It is horizontal to urinate sick mouse blood sugar, and have extremely significant statistical difference (P< 0.01).It is exhausted to the insulin of type-1 diabetes mellitus mouse simultaneously
To lack have significantly improve effect (P< 0.05), show that Fructus Corni reduces the effect of type-1 diabetes mellitus mouse blood sugar and promotes pancreas islet
Plain secretion level is related.
Test example 3
Investigate influence of each pharmaceutical composition to diabetes B rat blood sugar, blood lipid and insulin resistance.
The method of reference literature report establishes diabetes B rat model, and [Ma Zhengdong, Chen Lei, Song Hongtao wait white
Carry on the back hypoglycemic effect and its mechanism [J] the Chinese herbal medicine of Radix Notoginseng water extract to diabetes B rat, 2010 (04): 623-
626.], i.e., low dosage streptozotocin is merged using high-sugar-fat-diet and establishes 2 patients with type Ⅰ DM rat models.Choose normal SD
Rat, feed high-sugar-fat-diet 1 month (high-sugar-fat-diet formula are as follows: lard 10.0%, sucrose 20.0%, cholesterol 2.5%,
Cholate 1.0%, conventional feed 66.5%)；Again with 30 mgkg-12% streptozotocin solution preparation 2 is injected intraperitoneally in dosage
Patients with type Ⅰ DM (T2DM) model, blood sampling detection blood glucose, chooses blood glucose >=16.7 mmolL after 72h-1It is dynamic that person is included in model
Object.Diabetes B rat will be successfully established and be randomly divided into model group, positive group (glibenclamide 25mgkg by blood glucose value-1·d-1), pharmaceutical composition A, B, C, D, E, F, G group and Radix et Rhizoma Gynurae divaricatae extract group, cornel extractive group, every group 10；Separately take 10
It is only Normal group with batch healthy animal；Pharmaceutical composition dosage group is 400 mgkg-1·d-1, daily stomach-filling one
Secondary, normal group and model group give corresponding solvent, and successive administration 30 days.Respectively at the preceding 1 day measuring blood sugar of blood extracting basis of administration
Value, 30 days measuring blood sugar of blood extracting (GLU), total cholesterol (TC), triglycerides (TG) and serum insulin (INS) water after administration
It is flat.
As shown in Table 3, pharmaceutical composition A ~ E of the present invention can significantly shorten blood glucose, the blood of diabetes B rat model
Rouge and the insulin level of resistance have extremely significant sex differernce compared with model group.Wherein, pharmaceutical composition prepared by embodiment 1
Blood glucose, blood lipid and the insulin level of resistance of A group, hence it is evident that be lower than drug alone group and other composition groups, be in composition
In optimal proportioning effect.
By pharmaceutical composition A of the present invention ~ E group latent time and Radix et Rhizoma Gynurae divaricatae extract group and cornel extractive
Group is compared, and difference is obvious, is shown Radix et Rhizoma Gynurae divaricatae extract and cornel extractive compatible use, and two kinds of medicinal materials can be effectively played
Synergistic function, significantly reduce the insulin level of blood glucose, blood lipid and resistance.
3 pharmaceutical composition of table to diabetes B rat blood sugar, blood lipid and insulin resistance influence (, n=10)
Note: compared with model group,* P<0.05；** P<0.01。
Pharmaceutical composition A of the present invention ~ E group latent time is compared with pharmaceutical composition F, G group, difference is bright
It is aobvious, show when the weight of Radix et Rhizoma Gynurae divaricatae and Fructus Corni not within the scope of the invention as claimed, reduce blood
Sugar, blood lipid and the insulin action of resistance weaken.
In summary experimental result, pharmaceutical composition of the present invention, by Radix et Rhizoma Gynurae divaricatae and Fructus Corni according to parts by weight
Proportion is 9 ~ 55 parts of Radix et Rhizoma Gynurae divaricatae, and 7 ~ 53 parts of compatibilities of Fructus Corni can effectively play the synergistic function of two kinds of raw medicinal materials, right
It is significant to treat diabetes curative effect, and dosage is small.Cancel any one of Radix et Rhizoma Gynurae divaricatae and Fructus Corni medicinal material to be used as medicine, all will
Its drug effect can largely be reduced.
Embodiment 6
Starch 60g, beta cyclodextrin 90g is added in the pharmaceutical composition A for taking 100g embodiment 1 to prepare, and mixes, granulation sieving,
It is packed into capsule after drying, capsule is made.
Embodiment 7
Raw medicinal material is weighed by following weight: 22 parts of Radix et Rhizoma Gynurae divaricatae, 10 parts of Fructus Corni.
Above-mentioned medicinal material is prepared as follows into the pharmaceutical composition for the treatment of diabetes.
(1) Radix et Rhizoma Gynurae divaricatae medicinal material is taken, extraction 2 times is added water to cook, for the first time plus the water boiling and extraction 3h of 10 times of volumes is filtered,
The water boiling and extraction 1h filtering of second plus 6 times volume, merging filtrate is concentrated under reduced pressure, dry, obtains Radix et Rhizoma Gynurae divaricatae extract；
(2) Fructus Corni is taken, coarse powder is ground into, adds water to cook extraction 2 times, for the first time plus the decoction of the water of 10 times of volumes mentions
3h is taken to filter, the water boiling and extraction 1h filtering of second plus 6 times volume, merging filtrate is concentrated under reduced pressure, and it is dry, obtain Fructus Corni
Extract；
(3) Radix et Rhizoma Gynurae divaricatae extract and cornel extractive are uniformly mixed, obtain pharmaceutical composition；
(4) the pharmaceutical composition 100g for taking step (3) to prepare, beta cyclodextrin 200g, sucrose 100g are mixed, and are pelletized, dry,
Whole grain mixing, obtains granule；
Or the pharmaceutical composition 100g for taking step (3) to prepare, starch 60g, beta cyclodextrin 90g are mixed, granulation sieving is done
Tabletting after dry, is made tablet.
Claims (11)
1. a kind of pharmaceutical composition for treating diabetes, which is characterized in that it is made of the raw material of following weight
Medicament: 9~55 parts of Radix et Rhizoma Gynurae divaricatae, 7~53 parts of Fructus Corni.
2. pharmaceutical composition according to claim 1, it is characterised in that: it is made of the raw material of following weight
Medicament: 15~50 parts of Radix et Rhizoma Gynurae divaricatae, 7~42 parts of Fructus Corni.
3. pharmaceutical composition according to claim 2, it is characterised in that: it is made of the raw material of following weight
Medicament: 15~30 parts of Radix et Rhizoma Gynurae divaricatae, 7~25 parts of Fructus Corni.
4. pharmaceutical composition according to claim 3, it is characterised in that: it is made of the raw material of following weight
Medicament: 15~25 parts of Radix et Rhizoma Gynurae divaricatae, 7~20 parts of Fructus Corni.
5. pharmaceutical composition according to claim 4, it is characterised in that: it is made of the raw material of following weight
Medicament: 20~25 parts of Radix et Rhizoma Gynurae divaricatae, 9~11 parts of Fructus Corni.
6. pharmaceutical composition according to claim 5, it is characterised in that: it is made of the raw material of following weight
Medicament: 22 parts of Radix et Rhizoma Gynurae divaricatae, 10 parts of Fructus Corni.
7. a kind of preparation method of any one of such as claim 1~6 described pharmaceutical composition, which is characterized in that including following step
It is rapid:
(1) Radix et Rhizoma Gynurae divaricatae medicinal material is taken, is added water to cook or alcohol extracting 2~3 times, each decoction/extraction time is 1~3h, is filtered, and is closed
And filtrate, it is concentrated under reduced pressure, it is dry, obtain Radix et Rhizoma Gynurae divaricatae extract；
(2) Fructus Corni is taken, crushes as coarse powder, is extracted 2~3 times using the alcohol reflux of 40-80%, each return time is
1~3h, filtering, merging filtrate are concentrated under reduced pressure, dry, obtain cornel extractive；
(3) above-mentioned Radix et Rhizoma Gynurae divaricatae extract and cornel extractive are mixed, acceptable pharmaceutical preparation is made.
8. preparation method according to claim 7, it is characterised in that: add the decocting of 6~10 times of volumes in the step (1)
It boils extraction 2~3 times.
9. a kind of application such as any one of claim 1~6 described pharmaceutical composition in the drug that preparation improves diabetes.
10. a kind of application such as any one of claim 1~6 described pharmaceutical composition in the drug that preparation improves hyperlipidemia.
11. a kind of answering in the drug that preparation improves metabolic syndrome such as any one of claim 1~6 described pharmaceutical composition
With.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610043265.9A CN105535070B (en) | 2016-01-23 | 2016-01-23 | The pharmaceutical composition and its preparation method and application for treating diabetes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610043265.9A CN105535070B (en) | 2016-01-23 | 2016-01-23 | The pharmaceutical composition and its preparation method and application for treating diabetes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105535070A CN105535070A (en) | 2016-05-04 |
| CN105535070B true CN105535070B (en) | 2019-10-08 |
Family
ID=55814995
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610043265.9A Active CN105535070B (en) | 2016-01-23 | 2016-01-23 | The pharmaceutical composition and its preparation method and application for treating diabetes |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105535070B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109182032A (en) * | 2018-10-10 | 2019-01-11 | 文山学院 | A kind of Radix Notoginseng rhizoma polygonati Fructus Corni dendrobium nobile health liquor for alleviating physical fatigue |
| CN116139160B (en) * | 2022-12-22 | 2025-01-03 | 广州中医药大学第一附属医院 | Application of verbena glycoside in treating diabetes and/or diabetic complications |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101176743B (en) * | 2006-11-07 | 2012-02-01 | 唐志书 | Chinese medicine for curing coronary disease angina pectoris |
| CN101843807A (en) * | 2009-11-18 | 2010-09-29 | 北京绿源求证科技发展有限责任公司 | Chinese medicament for treating diabetic cardiopathy |
-
2016
- 2016-01-23 CN CN201610043265.9A patent/CN105535070B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN105535070A (en) | 2016-05-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101313942B (en) | Chinese medicine composition for treating nephropathy | |
| CN103285231B (en) | Medicine composition for diabetes adjunctive therapy and preparation method thereof | |
| CN101116722A (en) | Pharmaceutical formulations with the raw material containing panax, ophiopogon root and schisandra fruit, processes for their preparation, the raw material and the quality control method for the prepa | |
| CN106606529A (en) | Composition with auxiliary blood sugar reduction efficacy, and preparation method and application thereof | |
| CN101091765A (en) | Medicinal comsns-and usage for preventing and treating diabets mellitus | |
| CN101002906A (en) | Compounding traditional Chinese medicine, and its use | |
| CN104027529A (en) | Traditional Chinese medicine composition for regulating blood lipids, blood pressure and blood glucose and preparation method thereof | |
| CN101953866A (en) | Preparation method of white-backed pseudo-ginseng total flavonoid as well as application | |
| CN1299742C (en) | Medicine for treating diabetes, and its prepn. method | |
| CN104352624A (en) | Application of Mongolian medicine Cymbaria n-butanol extract in preparation of medicine for preventing and curing diabetes | |
| CN105535070B (en) | The pharmaceutical composition and its preparation method and application for treating diabetes | |
| CN107375430A (en) | A kind of curcumin composition with preventing and treating diabetes and complication | |
| CN103385931B (en) | Blood-sugar-lowering medicine composition | |
| CN103432420B (en) | A kind of Chinese medicine composition for the treatment of diabetes and preparation method thereof and detection method | |
| CN102579530A (en) | Preparation method of aralia taibaiensis total saponin having diabetes mellitus resisting effect and medicament | |
| JP7340113B2 (en) | Chinese herbal composition and its production method and use | |
| CN104721467A (en) | Traditional Chinese medicine composition for treating diabetic nephropathy and application thereof | |
| CN108524811A (en) | Reduce uric acid, cholesterol, three high Chinese medicine compositions and its preparation method for the treatment of | |
| CN104042928B (en) | A kind of pharmaceutical composition for treating diabetes and its production and use | |
| CN104490904B (en) | It is a kind of to treat neurasthenic pharmaceutical composition and preparation method thereof | |
| CN1315499C (en) | Medicine for treating diabetes and its complications and process for preparing the same | |
| CN101293059B (en) | Compound Chinese medicine for treating diabetes | |
| CN100525786C (en) | Compound milettia reticulata capsule and method for preparing the same | |
| CN104547499A (en) | Traditional Chinese medicine composition for treating diabetic nephropathy and atherosclerosis | |
| CN103989940A (en) | Traditional Chinese medicine composition for treating diabetes mellitus |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |