CN1714786A - Medicinal composition of silibin - Google Patents
Medicinal composition of silibin Download PDFInfo
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- CN1714786A CN1714786A CN 200410019830 CN200410019830A CN1714786A CN 1714786 A CN1714786 A CN 1714786A CN 200410019830 CN200410019830 CN 200410019830 CN 200410019830 A CN200410019830 A CN 200410019830A CN 1714786 A CN1714786 A CN 1714786A
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- Prior art keywords
- silibinin
- phospholipid
- preparation
- lecithin
- pharmaceutical composition
- Prior art date
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- 239000000203 mixture Substances 0.000 title abstract description 14
- SEBFKMXJBCUCAI-DBMPWETRSA-N silybin Chemical group C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-DBMPWETRSA-N 0.000 title abstract 3
- 238000002360 preparation method Methods 0.000 claims abstract description 36
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- SEBFKMXJBCUCAI-UHFFFAOYSA-N NSC 227190 Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-UHFFFAOYSA-N 0.000 claims description 69
- SEBFKMXJBCUCAI-HKTJVKLFSA-N silibinin Chemical compound C1=C(O)C(OC)=CC([C@@H]2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-HKTJVKLFSA-N 0.000 claims description 69
- 235000014899 silybin Nutrition 0.000 claims description 66
- 229950000628 silibinin Drugs 0.000 claims description 65
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- 238000010992 reflux Methods 0.000 claims description 15
- 239000000243 solution Substances 0.000 claims description 15
- 239000002671 adjuvant Substances 0.000 claims description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- 239000002775 capsule Substances 0.000 claims description 10
- 238000002347 injection Methods 0.000 claims description 10
- 239000007924 injection Substances 0.000 claims description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 9
- 150000003904 phospholipids Chemical class 0.000 claims description 9
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 8
- 239000000787 lecithin Substances 0.000 claims description 8
- 229940067606 lecithin Drugs 0.000 claims description 8
- 235000010445 lecithin Nutrition 0.000 claims description 8
- 239000008347 soybean phospholipid Substances 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 239000007962 solid dispersion Substances 0.000 claims description 3
- 238000005352 clarification Methods 0.000 claims description 2
- 238000001291 vacuum drying Methods 0.000 claims 2
- 238000010438 heat treatment Methods 0.000 claims 1
- 230000006837 decompression Effects 0.000 abstract description 2
- 229940083466 soybean lecithin Drugs 0.000 description 25
- 239000000047 product Substances 0.000 description 13
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 11
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 11
- 239000008101 lactose Substances 0.000 description 11
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 6
- 229960000935 dehydrated alcohol Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- CYGIJEJDYJOUAN-UHFFFAOYSA-N Isosilychristin Natural products C1=C(O)C(OC)=CC(C2C3C=C(C4C(C3=O)(O)OCC42)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 CYGIJEJDYJOUAN-UHFFFAOYSA-N 0.000 description 3
- 229940114079 arachidonic acid Drugs 0.000 description 3
- 235000021342 arachidonic acid Nutrition 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229960004245 silymarin Drugs 0.000 description 3
- 235000017700 silymarin Nutrition 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108010010234 HDL Lipoproteins Proteins 0.000 description 2
- XAEMHHAVNYDWEO-CVEVMTCXSA-N [1-[(4e,9e,12e)-hexadeca-4,9,12-trienoyl]oxy-3-[(6e,10e,12e)-hexadeca-6,10,12-trienoyl]oxypropan-2-yl] 2-(trimethylazaniumyl)ethyl phosphate;(2r,3r)-3,5,7-trihydroxy-2-[3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2,3- Chemical compound C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1.CCC\C=C\C\C=C\CCC\C=C\CCC(=O)OCC(OP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCC\C=C\CC\C=C\C=C\CCC XAEMHHAVNYDWEO-CVEVMTCXSA-N 0.000 description 2
- 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 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 229960004756 ethanol Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000002443 hepatoprotective effect Effects 0.000 description 2
- 150000002617 leukotrienes Chemical class 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 210000001589 microsome Anatomy 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- CYGIJEJDYJOUAN-JSGXPVSSSA-N silydianin Chemical compound C1=C(O)C(OC)=CC([C@H]2[C@H]3C=C([C@@H]4[C@@](C3=O)(O)OC[C@@H]42)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 CYGIJEJDYJOUAN-JSGXPVSSSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000002137 ultrasound extraction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- HIYAVKIYRIFSCZ-CVXKHCKVSA-N Calcimycin Chemical compound CC([C@H]1OC2([C@@H](C[C@H]1C)C)O[C@H]([C@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-CVXKHCKVSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 235000008495 Chrysanthemum leucanthemum Nutrition 0.000 description 1
- 244000192528 Chrysanthemum parthenium Species 0.000 description 1
- 235000000604 Chrysanthemum parthenium Nutrition 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- 108010023302 HDL Cholesterol Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- FDQAOULAVFHKBX-UHFFFAOYSA-N Isosilybin A Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC(=CC=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 FDQAOULAVFHKBX-UHFFFAOYSA-N 0.000 description 1
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- 102000003820 Lipoxygenases Human genes 0.000 description 1
- 108090000128 Lipoxygenases Proteins 0.000 description 1
- 101000905241 Mus musculus Heart- and neural crest derivatives-expressed protein 1 Proteins 0.000 description 1
- VLGROHBNWZUINI-UHFFFAOYSA-N Silybin Natural products COc1cc(ccc1O)C2OC3C=C(C=CC3OC2CO)C4Oc5cc(O)cc(O)c5C(=O)C4O VLGROHBNWZUINI-UHFFFAOYSA-N 0.000 description 1
- RIAZZJBPJQWPIS-UHFFFAOYSA-N Silychristin Natural products COc1cc(ccc1O)C2OC3C(C=C(C=C3O)C4Oc5cc(O)cc(O)c5C(=O)C4O)C2CO RIAZZJBPJQWPIS-UHFFFAOYSA-N 0.000 description 1
- MZBGBHVFCYCYLX-UHFFFAOYSA-N Silydianin Natural products COc1cc(ccc1O)C2C3COC4(O)C3C=C(C5Oc6cc(O)cc(O)c6C(=O)C5O)C2C4=O MZBGBHVFCYCYLX-UHFFFAOYSA-N 0.000 description 1
- 241000282894 Sus scrofa domesticus Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000003035 anti-peroxidant effect Effects 0.000 description 1
- 210000001841 basilar artery Anatomy 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- 208000006218 bradycardia Diseases 0.000 description 1
- HIYAVKIYRIFSCZ-UHFFFAOYSA-N calcium ionophore A23187 Natural products N=1C2=C(C(O)=O)C(NC)=CC=C2OC=1CC(C(CC1)C)OC1(C(CC1C)C)OC1C(C)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-UHFFFAOYSA-N 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 230000002057 chronotropic effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- -1 experiment shows Chemical compound 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 235000008384 feverfew Nutrition 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 210000003677 hemocyte Anatomy 0.000 description 1
- 229940000351 hemocyte Drugs 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229950004304 silidianin Drugs 0.000 description 1
- 229940043175 silybin Drugs 0.000 description 1
- BMLIIPOXVWESJG-LMBCONBSSA-N silychristin Chemical compound C1=C(O)C(OC)=CC([C@H]2[C@@H](C3=C(C(=CC(=C3)[C@@H]3[C@H](C(=O)C4=C(O)C=C(O)C=C4O3)O)O)O2)CO)=C1 BMLIIPOXVWESJG-LMBCONBSSA-N 0.000 description 1
- BMLIIPOXVWESJG-UHFFFAOYSA-N silychristin A Natural products C1=C(O)C(OC)=CC(C2C(C3=C(C(=CC(=C3)C3C(C(=O)C4=C(O)C=C(O)C=C4O3)O)O)O2)CO)=C1 BMLIIPOXVWESJG-UHFFFAOYSA-N 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention discloses a kind of medicinal composition containing silibin and its preparation process. Specifically, silibin and phosphatide are dissolved in organic solvent, the solution is heated and refluxed until becoming clear, and the solution is decompression concentrated to certain volume to obtain phosphatide dispersed matter, and the phosphatide dispersed matter is dried to obtain the medicinal composition.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to Pharmaceutical composition of a kind of silibinin and preparation method thereof.
Background technology
Herba Silybi mariani is that feverfew originates in southern Europe and north African, the hepatic disease that is used for the treatment of among the people.Nineteen sixty-eight Wagner etc. therefrom extracts a kind of flavonoid platform thing 1 called after silymarin (Sily marin), the main component that has now proved silymarin is silibinin (Silybin, Sil), the isomers silidianin (Silydianin) and the Silychristin (Silychristinin) that also have a small amount of silibinin, experiment shows, silibinin has multiple pharmacological effect, is summarized as follows.
Hepatoprotective effect
Silibinin can resist multiple poisonous substance and the medicine detrimental effect to liver.Can alleviate the toxic action of carbon tetrachloride as Sil to liver.As for hepatoprotective effect mechanism, there is research to think that Sil can go in the close and distant water bilayer of microsome in fusion, influence coinciding of acyl chain, thereby influence the structure of film, strengthen the resistance of biomembrane to chemical compound lot.
Influence to hemocyte
Silibinin is 10
-8-10
-6Can strengthen the resistance of erythrocyte during mol/L concentration to osmotic pressure, and can be to erythrocyte and the thrombocytolysis due to the anti peroxidation of lipid.
Lipoid peroxidization resistant
Silibinin can suppress liver cell mitochondria and MC lipid peroxidation.It is a very strong free radical scavenger, and its antioxidation intensity is 10 times of alpha-tocopherol.
Effect for reducing fat
Blasovic etc. fed rat 8 days with the hypercholesterolemia diet, added Sil25mg/kg/ days in back 5 days, found that the total fat of microsome, T-CHOL, triglyceride all descend.To feed the rat of hyperlipemia in Sil600mg/kg/ days, serum total cholesterol, low-density lipoprotein cholesterol and C-VLDL all reduce after 10-20 days, and can increase HDL-C HDL-C, HDL
2-Cb is to HDL
3-C does not then have influence.
Influence to cardiovascular system
Silibinin has negativity muscular strength and negative chronotropic action to heart.Vogel etc. give Canis familiaris L. or rat intravenous injection with 30mg/kg, and discovery can cause bradycardia and hypotension.
Influence to arachidonic acid metabolic
Lipoxygenase is one of enzyme of arachidonic acid metabolic bypass, and the metabolite of this bypass may participate in inflammatory reaction, and silibinin can suppress this enzyme.The Medulla sus domestica basilar artery that will exsomatize such as Lin Aiyou are cultivated with indometacin, arachidonic acid, calcimycin, can produce the leukotriene of biologically active.After adding Sil, leukotriene discharges significantly and reduces.
By the modern pharmacology research means we as can be seen, silibinin not only has traditional liver-protective effect, and cardiovascular and other aspects are also had good effect.
Because silibinin is insoluble in water and common organic solvents, oral absorption is poor, and bioavailability is low, thereby has influenced its clinical efficacy.Positive active development is developed its complex both at home and abroad, or improves its oral administration biaavailability, or develops its injection, to increase curative effect, enlarges range of application.
There is the silibinin complex of report to have at present, silibinin-meglumine salt (silybin-N-methyl-glucamine), silibinin-phthalic monoester sodium salt (Silybin-phthalic acid monoester sodium salt), silibinin-bis-bias succinate sodium salt (silybin-dihemisuccimate sodium salt), silibinin-cyclodextrin (silybin-β-cyclodextrins), silibinin-phosphatidylcholine double salt (silybin-phosphatidylcholine) etc.
Wherein, silibinin-phosphatidylcholine double salt claims IdB1016 again, is the fat-soluble preparation by Italian Imverni della beffa company Development and Production.Compare with other silibinin complex, IdB1016 has very high lipotropy, absorbs characteristics such as fast.But pure product lecithin preparation is difficulty very, costs an arm and a leg, and unstable, therefore not only make its preparation cost increase greatly, and character is also very unstable.Be starved of clinically that a kind of preparation cost is cheap, the metastable SLC complex of character.
Summary of the invention
The objective of the invention is to overcome the deficiencies in the prior art, a kind of silibinin preparation of high-quality cheapness is provided.
Another object of the present invention is to provide this preparation method that contains the silibinin preparation.
The present invention is implemented by following scheme:
A. get an amount of silibinin and phospholipid;
B. above-mentioned silibinin and phospholipid are dissolved in the organic solvent, reflux makes the solution clarification;
C. above-mentioned solution decompression is concentrated into certain volume, continues drying, obtains silibinin-phosphatide complexes;
D. dry above-mentioned solid dispersion adds adjuvant, makes preparation.
Wherein, the phosphide that said method relates to comprises lecithin, soybean phospholipid and injection soybean phospholipid and oral soybean phospholipid etc., sets out the preferred oral soybean phospholipid for the therapeutic effect that reduces production costs with medicine itself; Phospholipid among the step a is commercially available oral soybean lecithin, the ratio of silibinin and oral soybean lecithin is 1: 1～4, and optimal proportion is 1: 1.85, and silibinin adopts the extraction method preparation, comprise heat reflow method and ultrasonic extraction etc., but be not limited to these methods; Organic solvent among the step b can be chloroform, methanol, ethanol, ethyl acetate and acetone, and preferred solvent is an ethanol; The reflux time is 0.5～1.5 hour, and Best Times is 1 hour; The volume of concentrating under reduced pressure is 5%～15% among the step c, preferred 10%; Drying mode comprises low-temperature reduced-pressure drying, fluid bed drying etc., and wherein, the concentrating under reduced pressure temperature is 60～80 ℃, and optimum temperature is 70 ℃; Continuing baking temperature is 30-50 ℃, preferred 40 ℃; Silibinin solid in the steps d disperses thing can make acceptable dosage form on any one pharmaceutics.
The present invention compared with prior art has advantages such as production cost is low, process stabilizing.Prior art is made complex with silibinin and lecithin, but pure product lecithin costs an arm and a leg, and the character instability.In experiment, after the inventor finds to adopt homemade oral soybean lecithin and silibinin molten altogether, the solid dispersion of making, its fat-soluble increase when having satisfied technology, has reduced production cost, and more patients are benefited.
The specific embodiment
The present invention is further illustrated below in conjunction with specific embodiment, and following this embodiment only is used to the present invention is described and to the present invention without limits.
Embodiment 1
The preparation of silibinin:
It is a certain amount of to get the Herba Silybi mariani seed, pulverizes and uses ethyl acetate extraction 20 hours in the rearmounted apparatus,Soxhlet's, and extracting solution is concentrated in rotary evaporator, reclaims solvent, gets pale brown color extractum. with the surperficial oils and fats of petroleum ether, get paste silibinin crude product.Through defat, recrystallization, drying, get silibinin 350g again.
The preparation of product:
A. get silibinin 350g, oral soybean lecithin 650g, lactose 1000g, Pulvis Talci 500g;
B. above-mentioned silibinin and oral soybean lecithin are added in the 15000ml dehydrated alcohol, reflux made solution clarify in 1 hour;
C. be evaporated to 1500ml in 70 ℃, 40 ℃ are continued dryly down, obtain SLC and disperse thing;
D. the SLC that obtains among the step c is disperseed thing, mix, make 10000 of capsules with dry good adjuvant in advance.
Embodiment 2
The preparation of silibinin: with embodiment 1.
The preparation of product:
A. get silibinin 350g, oral soybean lecithin 350g, lactose 1000g, Pulvis Talci 500g;
B. above-mentioned silibinin and oral soybean lecithin are added in the 15000ml dehydrated alcohol, reflux made solution clarify in 1 hour;
C. be evaporated to 1500ml in 70 ℃, 40 ℃ are continued dryly down, obtain SLC and disperse thing;
D. the SLC that obtains among the step c is disperseed thing, mix, make 10000 of capsules with dry good adjuvant in advance.
Embodiment 3
The preparation of silibinin: with embodiment 1.
The preparation of product:
A. get silibinin 350g, oral soybean lecithin 1400g, lactose 1000g, Pulvis Talci 500g;
B. above-mentioned silibinin and oral soybean lecithin are added in the 15000ml dehydrated alcohol, reflux made solution clarify in 1 hour;
C. be evaporated to 1500ml in 70 ℃, 40 ℃ are continued dryly down, obtain SLC and disperse thing;
D. the SLC that obtains among the step c is disperseed thing, mix, make 10000 of capsules with dry good adjuvant in advance.
Embodiment 4
The preparation of silibinin:
Get the Herba Silybi mariani seed, add the ethyl acetate ultrasonic extraction after the pulverizing three times, merging filtrate concentrates filtrate with rotary evaporator, reclaim solvent, gets pale brown color extractum, and exquisiteness gets silibinin 350g.
The preparation of product:
A. get silibinin 350g, oral soybean lecithin 1400g, lactose 1000g, Pulvis Talci 500g;
B. above-mentioned silibinin and oral soybean lecithin are added in the 15000ml dehydrated alcohol, reflux made solution clarify in 1 hour;
C. be evaporated to 1500ml in 70 ℃, 40 ℃ are continued dryly down, obtain SLC and disperse thing;
D. the SLC that obtains among the step c is disperseed thing, mix, make 10000 of capsules with dry good adjuvant in advance.
Embodiment 5
The preparation of silibinin: with embodiment 4.
The preparation of product:
A. get silibinin 350g, oral soybean lecithin 1050g, lactose 1000g, Pulvis Talci 500g;
B. above-mentioned silibinin and oral soybean lecithin are added in the 15000ml dehydrated alcohol, reflux made solution clarify in 0.5 hour;
C. be evaporated to 1500ml in 70 ℃, 40 ℃ are continued dryly down, obtain SLC and disperse thing;
D. the SLC that obtains among the step c is disperseed thing, mix, make 10000 of capsules with dry good adjuvant in advance.
Embodiment 6
The preparation of silibinin: with embodiment 4.
The preparation of product:
A. get silibinin 350g, oral soybean lecithin 650g, lactose 1000g. Pulvis Talci 500g;
B. above-mentioned silibinin and oral soybean lecithin are added in the 15000ml acetone, reflux made solution clarify in 1.5 hours;
C. be evaporated to 750ml in 60 ℃, 40 ℃ are continued dryly down, obtain SLC and disperse thing;
D. the SLC that obtains among the step c is disperseed thing, mix, make 10000 of capsules with dry good adjuvant in advance.
Embodiment 7
The preparation of silibinin: with embodiment 4.
The preparation of product:
A. get silibinin 350g, soybean lecithin for injection 650g, lactose 1000g, Pulvis Talci 500g;
B. above-mentioned silibinin and soybean lecithin for injection are added in the 15000ml ethyl acetate, reflux made solution clarify in 1 hour;
C. be evaporated to 2250ml in 80 ℃, 30 ℃ are continued dryly down, obtain SLC and disperse thing;
D. the SLC that obtains among the step c is disperseed thing, mix, make 10000 of capsules with dry good adjuvant in advance.
Embodiment 8
The preparation of silibinin: with embodiment 4.
The preparation of product:
A. get silibinin 350g, soybean lecithin for injection 650g, lactose 1000g, Pulvis Talci 500g;
B. above-mentioned silibinin and soybean lecithin for injection are added in the 15000ml methanol, reflux made solution clarify in 1 hour;
C. be evaporated to 1500ml in 75 ℃, 50 ℃ are continued dryly down, obtain SLC and disperse thing;
D. the SLC that obtains among the step c is disperseed thing, mix, make 10000 of capsules with dry good adjuvant in advance.
Embodiment 9
The preparation of silibinin: with embodiment 4.
The preparation of product:
A. get silibinin 350g, soybean lecithin for injection 1050g, lactose 1000g, Pulvis Talci 500g;
B. above-mentioned silibinin and soybean lecithin for injection are added in the 15000ml methanol, reflux made solution clarify in 1 hour;
C. be evaporated to 1500ml in 75 ℃, 50 ℃ are continued dryly down, obtain SLC and disperse thing;
D. the SLC that obtains among the step c is disperseed thing, mix, make 10000 of capsules with dry good adjuvant in advance.
Embodiment 10
The preparation of silibinin: with embodiment 4.
The preparation of product:
A. get silibinin 350g, oral soybean lecithin 700g, lactose 1000g, Pulvis Talci 500g;
B. above-mentioned silibinin and oral soybean lecithin are added in the 15000ml methanol, reflux made solution clarify in 1 hour;
C. be evaporated to 1500ml in 75 ℃, 50 ℃ are continued dryly down, obtain SLC and disperse thing;
D. the SLC that obtains among the step c is disperseed thing, mix, make 10000 in tablet with dry good adjuvant in advance.
Embodiment 11
The preparation of silibinin: with embodiment 4.
The preparation of product:
A. get silibinin 350g, oral soybean lecithin 1400g, lactose 1000g, Pulvis Talci 500g;
B. above-mentioned silibinin and oral soybean lecithin are added in the 15000ml methanol, reflux made solution clarify in 1 hour;
C. be evaporated to 1500ml in 75 ℃, 50 ℃ are continued dryly down, obtain SLC and disperse thing;
D. the SLC that obtains among the step c is disperseed thing, mix, make 10000 in tablet with dry good adjuvant in advance.
Claims (11)
1. a Pharmaceutical composition that contains silibinin comprises silibinin and phospholipid, and its weight ratio is 1: 1～4.
2. the Pharmaceutical composition of claim 1, wherein said part by weight is 1: 1.85.
3. claim 1 or 2 Pharmaceutical composition, phospholipid wherein is selected from lecithin, fabaceous lecithin, injection soybean phospholipid, oral soybean phospholipid.
4. preparation method that contains the Pharmaceutical composition of silibinin, form by the following step:
A. get an amount of silibinin and phospholipid;
B. above-mentioned silibinin and phospholipid are dissolved in the organic solvent, reflux makes the solution clarification;
C. above-mentioned dissolving is evaporated to certain volume, and drying obtains SLC and disperses thing;
D. dry above-mentioned solid dispersion adds adjuvant, makes preparation.
5. the method for claim 4, phospholipid wherein is selected from lecithin, fabaceous lecithin, injection soybean phospholipid, oral soybean phospholipid.
6. claim 4 or 5 method, wherein the weight ratio of silibinin described in the step a and phospholipid is 1: 1～4.
7. the method for claim 4, wherein the organic solvent described in the step b is selected from chloroform, methanol, ethanol, ethyl acetate and acetone, and the reflux time is 0.5～1.5 hour.
8. claim 4 or 7 method, wherein the organic solvent described in the step b is an ethanol, be 1 hour heat time heating time.
9. the method for claim 4, wherein the spissated volume described in the step c is 5%～15%; The concentrating under reduced pressure temperature is 60～80 ℃, and the low-temperature vacuum drying temperature is 30-50 ℃.
10. claim 3 or 7 described methods, wherein the spissated volume described in the step c is 10%; The concentrating under reduced pressure temperature is 70 ℃; The low-temperature vacuum drying temperature is 40 ℃.
11. the described method of claim 4, wherein the preparation in the steps d is tablet or capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410019830 CN1714786A (en) | 2004-06-30 | 2004-06-30 | Medicinal composition of silibin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410019830 CN1714786A (en) | 2004-06-30 | 2004-06-30 | Medicinal composition of silibin |
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| Publication Number | Publication Date |
|---|---|
| CN1714786A true CN1714786A (en) | 2006-01-04 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 200410019830 Pending CN1714786A (en) | 2004-06-30 | 2004-06-30 | Medicinal composition of silibin |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100356969C (en) * | 2006-08-17 | 2007-12-26 | 陈乃车 | Traditional Chinese medicine and western medicine cooperative compositions comprising Silybum marianum |
| US11318112B2 (en) | 2015-03-23 | 2022-05-03 | Tasly Pharmaceutical Group Co., Ltd. | Pharmaceutical composition containing silybin and ve |
-
2004
- 2004-06-30 CN CN 200410019830 patent/CN1714786A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100356969C (en) * | 2006-08-17 | 2007-12-26 | 陈乃车 | Traditional Chinese medicine and western medicine cooperative compositions comprising Silybum marianum |
| US11318112B2 (en) | 2015-03-23 | 2022-05-03 | Tasly Pharmaceutical Group Co., Ltd. | Pharmaceutical composition containing silybin and ve |
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Address after: 300402 Tianjin Beichen Xinyi white road Liaohe Road No. 1 Applicant after: Tasly Pharmaceutical Group Co., Ltd. Address before: 300402 Tianjin Beichen Xinyi white road Liaohe Road No. 1 Applicant before: Tianjin Tianshili Pharmaceutical Co., Ltd. |
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Application publication date: 20060104 |