CN101007014B - A compound puerarin preparation - Google Patents
A compound puerarin preparation Download PDFInfo
- Publication number
- CN101007014B CN101007014B CN200610049229XA CN200610049229A CN101007014B CN 101007014 B CN101007014 B CN 101007014B CN 200610049229X A CN200610049229X A CN 200610049229XA CN 200610049229 A CN200610049229 A CN 200610049229A CN 101007014 B CN101007014 B CN 101007014B
- Authority
- CN
- China
- Prior art keywords
- puerarin
- preparation
- injection
- compound
- moschus
- 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.)
- Expired - Fee Related
Links
- RXUWDKBZZLIASQ-UHFFFAOYSA-N Puerarin Natural products OCC1OC(Oc2c(O)cc(O)c3C(=O)C(=COc23)c4ccc(O)cc4)C(O)C(O)C1O RXUWDKBZZLIASQ-UHFFFAOYSA-N 0.000 title claims abstract description 74
- HKEAFJYKMMKDOR-VPRICQMDSA-N puerarin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=CC(C2=O)=C1OC=C2C1=CC=C(O)C=C1 HKEAFJYKMMKDOR-VPRICQMDSA-N 0.000 title claims abstract description 74
- 238000002360 preparation method Methods 0.000 title claims abstract description 49
- 150000001875 compounds Chemical class 0.000 title claims abstract description 47
- 239000003814 drug Substances 0.000 claims description 21
- 239000007924 injection Substances 0.000 claims description 20
- 238000002347 injection Methods 0.000 claims description 20
- 238000002156 mixing Methods 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 238000005516 engineering process Methods 0.000 claims description 8
- 238000005303 weighing Methods 0.000 claims description 8
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 6
- 239000008215 water for injection Substances 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 4
- 230000008030 elimination Effects 0.000 claims description 3
- 238000003379 elimination reaction Methods 0.000 claims description 3
- 239000004576 sand Substances 0.000 claims description 3
- 238000003556 assay Methods 0.000 claims description 2
- 238000007689 inspection Methods 0.000 claims description 2
- 239000012528 membrane Substances 0.000 claims description 2
- 241000972155 Moschus Species 0.000 claims 2
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 abstract description 26
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 14
- 208000026106 cerebrovascular disease Diseases 0.000 abstract description 14
- 230000002526 effect on cardiovascular system Effects 0.000 abstract description 13
- 239000000463 material Substances 0.000 abstract description 3
- 239000000470 constituent Substances 0.000 abstract description 2
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 abstract 1
- 229940116229 borneol Drugs 0.000 abstract 1
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 abstract 1
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 abstract 1
- 244000153234 Hibiscus abelmoschus Species 0.000 description 24
- 239000006187 pill Substances 0.000 description 18
- 230000000694 effects Effects 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 229920002472 Starch Polymers 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 239000008107 starch Substances 0.000 description 10
- 235000019698 starch Nutrition 0.000 description 10
- 239000008187 granular material Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 8
- 230000008499 blood brain barrier function Effects 0.000 description 7
- 210000001218 blood-brain barrier Anatomy 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 208000007536 Thrombosis Diseases 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 206010006148 Brain stem ischaemia Diseases 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- 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 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000000763 evoking effect Effects 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 231100000331 toxic Toxicity 0.000 description 5
- 230000002588 toxic effect Effects 0.000 description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 210000000133 brain stem Anatomy 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 4
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 4
- 239000000700 radioactive tracer Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 206010042772 syncope Diseases 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- 241000700199 Cavia porcellus Species 0.000 description 3
- 238000012449 Kunming mouse Methods 0.000 description 3
- 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 3
- 208000002193 Pain Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 230000001476 alcoholic effect Effects 0.000 description 3
- 210000000709 aorta Anatomy 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 229960004756 ethanol Drugs 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 230000036407 pain Effects 0.000 description 3
- 235000021251 pulses Nutrition 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 210000002385 vertebral artery Anatomy 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 108010011485 Aspartame Proteins 0.000 description 2
- 206010008132 Cerebral thrombosis Diseases 0.000 description 2
- 206010008190 Cerebrovascular accident Diseases 0.000 description 2
- 206010010071 Coma Diseases 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010062717 Increased upper airway secretion Diseases 0.000 description 2
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 2
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920003081 Povidone K 30 Polymers 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 208000010513 Stupor Diseases 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000002421 anti-septic effect Effects 0.000 description 2
- 239000000605 aspartame Substances 0.000 description 2
- 235000010357 aspartame Nutrition 0.000 description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 2
- 229960003438 aspartame Drugs 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000002826 coolant Substances 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- 229960000935 dehydrated alcohol Drugs 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 230000002439 hemostatic effect Effects 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229960002275 pentobarbital sodium Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 208000026435 phlegm Diseases 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- -1 polyoxyethylene stearate Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 229920002545 silicone oil Polymers 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 239000007779 soft material Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 241000282994 Cervidae 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
- 206010010904 Convulsion Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 241000123611 Dipterocarpaceae Species 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 244000046146 Pueraria lobata Species 0.000 description 1
- 235000010575 Pueraria lobata Nutrition 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
- 206010061373 Sudden Hearing Loss Diseases 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- 206010048010 Withdrawal syndrome Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000003461 brachial plexus Anatomy 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 210000003109 clavicle Anatomy 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000008384 feverfew Nutrition 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 235000021374 legumes Nutrition 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 231100001252 long-term toxicity Toxicity 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000001898 sternoclavicular joint Anatomy 0.000 description 1
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 1
- 229940013618 stevioside Drugs 0.000 description 1
- 235000019202 steviosides Nutrition 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a compound preparation for treating cardiovascular and cerebrovascular diseases, which comprises the constituents of (by weight percent) puerarin 1 part, borneol 0.1-2 parts, and pharmaceutically acceptable carrying agents or auxiliary materials.
Description
Technical field
The present invention relates to a kind of compound preparation for the treatment of cardiovascular and cerebrovascular disease, relate in particular to a kind of compound puerarin preparation.
Background technology
Cardiovascular and cerebrovascular disease is commonly encountered diseases, frequently-occurring disease, is the first human killer.Because cardiovascular and cerebrovascular disease has characteristics such as chronic, sudden, but causing death when serious, the medicine that is used for treating cardiovascular and cerebrovascular disease usually is the chemical classes medicine, but this type of medicine usually can produce side reaction (as gastrointestinal reaction), a series of untoward reaction such as toxic reaction (as toxicity such as infringement circulation, breathing and nervous functions) withdrawal reaction; So people more and more rely on for counsel in Chinese patent medicine and treat cardiovascular and cerebrovascular disease.But Chinese patent medicine uses traditional oral formulations, has problems such as dissolve scattered time limit is long, dissolution is low, absorption is relatively poor, bioavailability is lower.Therefore develop a kind of can be used for rescuing do not influence medicine used in everyday again, be one of solution.Dosage forms such as drop pill, oral cavity disintegration tablet, injection have characteristics such as speed of action is fast, bioavailability is high, clinical effectiveness is good, meet the clinical requirement of preventing and treating cardiovascular and cerebrovascular disease.As Chinese patent application (200310122493.8) puerarin drop pill and preparation method thereof, this patent application is raw material with the puerarin, proportionally add a certain amount of Polyethylene Glycol and mix homogeneously, mixed material is heated to fusion, fully stir and make evenly, insert special-purpose drop pill machine,, splash in the condensing agent and form with suitable speed.Though this patent application provides a kind of to extensive patients and medical personnel cardiovascular disease had quick release, quick produce effects, toxic and side effects is little, the puerarin drop pill that effective ingredient is clear and definite, but having ignored human body, this patent application has blood brain barrier, medicine is difficult to enter the problem of cerebral tissue, so this patent application still is not satisfactory to the treatment of cerebrovascular disease, can not meet the clinical requirement of all control cardiovascular and cerebrovascular diseases.
Summary of the invention
The object of the present invention is to provide a kind of not only to the curative effect of cardiovascular disease is better, rapid-action, bioavailability is high but also to the curative effect of cerebrovascular disease is better, rapid-action, bioavailability is high compound puerarin preparation.
Above-mentioned technical purpose of the present invention solves by the following technical programs: a kind of compound puerarin preparation, it is characterized in that comprising the ingredient of following weight parts: 1 part of puerarin, 0.1～2 part of Borneolum Syntheticum mixes with pharmaceutically acceptable pharmaceutical carrier or adjuvant, makes compound preparation.
Its feature of technique scheme of the present invention also is: can also contain 0.05～1 part in Moschus in the described ingredient, mix with pharmaceutically acceptable pharmaceutical carrier or adjuvant, make compound preparation.
Its feature of technique scheme of the present invention also is: described dosage form comprises all dosage forms that pharmaceutically allow.
Its feature of technique scheme of the present invention also is: preferred dosage form is injection, tablet, pill, drop pill, capsule, granule and oral liquid.
In the compound puerarin preparation component of the present invention, the Radix Puerariae prime system is by extracting, separate the 8-β-D-glucopyanosyl-4 ' that obtains in the dry root of legume pueraria lobata, and the 7-dihydroxy isoflavone is pressed dry product and calculated, and contains C
21H
20O
9Should be greater than 80%.Puerarin is a vasodilator, coronary artery there is dilating effect, can reduces myocardial oxygen consumption, and have the effect of blood circulation promoting and blood stasis dispelling, microcirculation improvement, be mainly used in coronary heart disease, acute angina pectoris, myocardial infarction, retina arteriovenous obstruction, diseases such as sudden deafness.
In the compound puerarin preparation component of the present invention, Borneolum Syntheticum is the processed goods of Dipterocarpaceae aiphyllium XIANGSHU resin, or is the Blumeae preparatum Tabellae made of raw material and is the BORNEOLUM SYNTHETICUM that raw material is made with the Oleum Terebinthinae with the feverfew Herba Blumeae Balsamiferae, contains C
10H
18O should be greater than 55%.Borneolum Syntheticum is a drugs of causing resuscitation by administering aromatic drugs, has the effect of the refreshment of having one's ideas straightened out, clearing away heat to alleviate pain.Be used for diseases such as calentura coma, convulsions, apoplexy syncope due to accumulation of phlegm, stagnation of QI sudden syncope, attacked by pestiferous factors stupor.
In the compound puerarin preparation component of the present invention, Moschus is the dry secretions in the ripe male body note capsule of animal in deer family woods Moschus moschiferous, horse Moschus moschiferous or former Moschus moschiferous, because the natural Moschus source is difficult, and the existing main artificial Moschus that adopts.The effect that it has the refreshment of having one's ideas straightened out, promoting blood circulation to restore menstrual flow, reducing swelling and alleviating pain is mainly used in diseases such as calentura coma, apoplexy syncope due to accumulation of phlegm, stagnation of QI sudden syncope, attacked by pestiferous factors stupor, trusted subordinate's sudden pain.
Add Borneolum Syntheticum, Moschus in puerarin preparation, cardiovascular and cerebrovascular vessel patient is after medication, and its symptom can be controlled effectively in a short period of time; Borneolum Syntheticum is a Chinese medicine commonly used simply, finds to have the effect of " fragrance is walked to scurry, priming up " after deliberation.Generally, medicine is generally lower in cerebral tissue concentration, and this is because due to the blood brain barrier.If general medicine can not pass through blood brain barrier, just be difficult to reach effective blood drug level, bioavailability is very low.Borneolum Syntheticum not only self can pass through blood brain barrier, can also increase blood brain barrier permeability, impel other drug to enter cerebral tissue by blood brain barrier.Add Borneolum Syntheticum in puerarin preparation, can impel puerarin to arrive diseased region by blood brain barrier, strengthened the curative effect of medicine, improved the speed of medicine arrival diseased region, this meets the treatment requirement of cardiovascular and cerebrovascular disease.And Borneolum Syntheticum often uses with the Moschus compatibility, and this is because the pharmacological action of Moschus is stronger than Borneolum Syntheticum, and Moschus has analgesia, plays quick treatment and alleviates the pathological changes symptom of bringing out the cardiovascular and cerebrovascular disease outbreak, reduces the chance that cardiovascular and cerebrovascular disease shows effect.
Compound puerarin preparation of the present invention, the not only clear and definite ingredient that said preparation contained gives the proportion compatibility of three kinds of medicines, has solved controllability, safety, the effectiveness of pharmaceutical preparation preferably.
As preferably, described compound puerarin preparation, it is characterized in that comprising the ingredient of following weight parts: 1 part of puerarin, 0.3～1 part of Borneolum Syntheticum mixes with pharmaceutically acceptable pharmaceutical carrier or adjuvant, makes compound preparation.
In above-mentioned compound puerarin preparation, it is characterized in that can also containing in the described ingredient 0.05～1 part in Moschus, mix with pharmaceutically acceptable pharmaceutical carrier or adjuvant, make compound preparation.
Described compound puerarin preparation also comprises pharmaceutically acceptable excipient substance.
Described pharmaceutically acceptable excipient substance can be one or more in drop pill substrate, isotonic agent, buffer agent, proppant, disintegrating agent, cosolvent, antiseptic, correctives, fluidizer, the filler.
Described drop pill substrate can be one or more in Macrogol 4000, polyethylene glycol 6000, poloxamer, polyoxyethylene stearate (40) ester, gelatin, stearic acid, glyceryl monostearate, the hydrogenating glycerol ester.
Described isotonic agent can be little one or more of sodium chloride, glucose, xylitol, sorbitol, mannitol, fructose.
Described buffer agent can be one or more in sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium carbonate, sodium bicarbonate, sodium hydroxide, lactic acid, hydrochloric acid, the acetic acid.
Described proppant can be one or more in sorbitol, mannitol, the dextran.
Described disintegrating agent can be one or more of carboxymethyl starch sodium, starch, microcrystalline Cellulose, sodium carboxymethyl cellulose.
Described cosolvent can be a kind of of HYDROXYPROPYL BETA-CYCLODEXTRIN, ethanol, propylene glycol, Polyethylene Glycol, glycerol, benzyl benzoate, dimethyl acetylamide or two kinds.
Described antiseptic can be one or more of sorbic acid, benzoic acid, propanoic acid.
Described correctives can be one or more of Mel, simple syrup, glycyrrhizin, stevioside, sucrose.
Described fluidizer can be micropowder silica gel, sodium stearate, talcous one or more.
Described filler can be one or more in starch, dextrin, lactose, the calcium hydrogen phosphate.
The present invention is as follows through the toxicological test result:
(1) acute toxicity test: the kunming mice four times a day is irritated stomach compound puerarin preparation of the present invention (Cmax 0.40g/ml, maximum volume 50ml/ (kg d), dosage is 65g/ (kgd)) be equivalent to clinical day kilogram dosage (325 times of 0.2g/ (kgd), observed for 1 week and do not have 1 kunming mice death, toxic reaction does not appear, compound puerarin preparation acute toxic reaction of the present invention is minimum, the clinical practice dosage safety.
(2) long term toxicity test: rat continuous irrigation stomach compound puerarin preparation 5g/ of the present invention (kgd), 18g/ (kgd), 30g/ (kgd) are equivalent to clinical day kilogram dosage (25 times, 90 times, 150 times of 0.2g/ (kgd) respectively.After 12 weeks of administration, biochemical indicators such as organ coefficient, hemogram and liver, renal function are detected no abnormality seen; Also no abnormal to the tissue slice pathological examination.Prove that compound puerarin preparation of the present invention does not have the continuity toxic reaction, clinical used dosage is safe.
Therefore, it is clear and definite that the present invention has active constituent content, and pharmaceutical preparation safety, effective, controlled characteristics are that a kind of compatibility is better, the higher compound preparation that can be used for preventing and treating cardiovascular and cerebrovascular disease of bioavailability.
The specific embodiment
Below by specific embodiment, technical scheme of the present invention is described in further detail.But the present invention is not limited only to these embodiment
Embodiment 1: compound puerarin drop pill (A) preparation method
Prescription: puerarin 300.00g
Borneolum Syntheticum 100.00g
Moschus 50.00g
Macrogol 4000 400.00g
Make 10000
Preparation method: get the Macrogol 4000 of recipe quantity, fusion; Get dehydrated alcohol 350mL, add puerarin, Borneolum Syntheticum, the Moschus stirring makes molten; With medicinal liquid and fused Macrogol 4000 mixing, continue to stir, fling to ethanol, place the drop pill machine of preheating, 90 ℃ of insulations are dripped as coolant with methyl-silicone oil and to be made ball, promptly.
Embodiment 2: compound puerarin drop pill (B) preparation method
Prescription: puerarin 250.00g
Borneolum Syntheticum 125.00g
Polyethylene glycol 6000 430.00g
Make 10000
Preparation method: get the polyethylene glycol 6000 of recipe quantity, fusion; Get dehydrated alcohol 300mL, add puerarin, Borneolum Syntheticum, stirring makes molten; With medicinal liquid and fused polyethylene glycol 6000 mixing, continue to stir, fling to ethanol, place the drop pill machine of preheating, 88 ℃ of insulations are dripped as coolant with methyl-silicone oil and to be made ball, promptly.
Embodiment 3: the preparation of compound puerarin injection
One, prescription
Puerarin 200g
Moschus 30g
HYDROXYPROPYL BETA-CYCLODEXTRIN 15g
Make 1000
Two, preparation technology
Take by weighing Moschus 30g, add HYDROXYPROPYL BETA-CYCLODEXTRIN 15g hydrotropy, add puerarin 200g mixing, add water for injection to 8000ml, warm dissolving adds activated carbon decolorizing, remove thermal source,, add water for injection to 10000ml with sand rod elimination active carbon, regulating pH value is 6.0～7.0, detects its content, when qualified, through 0.22 μ m microporous filter membrane fine straining, canned in 10ml peace bottle, sterilized 30 minutes, cool off laggard portable lighter inspection,, obtain the liquid drugs injection finished product again through after the assay was approved.
Embodiment 4: the preparation of compound puerarin injectable powder
One, prescription
Puerarin 150g
Borneolum Syntheticum 100g
Moschus 50g
HYDROXYPROPYL BETA-CYCLODEXTRIN 50g
Mannitol 50g
Make 1000 bottles
Two, preparation technology
Take by weighing Borneolum Syntheticum 100g, Moschus 30g, add HYDROXYPROPYL BETA-CYCLODEXTRIN 50g hydrotropy, add puerarin 150g mixing, add water for injection to 1600ml, add mannitol 50g, warm dissolving stirs, and adds activated carbon decolorizing, remove thermal source, with sand rod elimination active carbon, add water for injection to 2000ml, regulating pH value is 6.0～7.5.With 0.22 μ m filtering with microporous membrane, cannedly in the glass tube vial of cleaning, put the freeze dryer lyophilization, the vacuum lid that falls obtains 1000 bottles of freeze-dried powder finished products.
Embodiment 5: the preparation of compound puerarin sheet
One: prescription
Puerarin 200g
Moschus 100g
Borneolum Syntheticum 50g
Lactose 80g
Sodium carboxymethyl cellulose 20g
Starch is an amount of
Magnesium stearate is an amount of
Make 1000
Two, preparation technology
Take by weighing puerarin 200g, Moschus 100g, Borneolum Syntheticum 50g, lactose 80g, sodium carboxymethyl cellulose 20g, mixing is made soft material with 10% starch slurry, the granulation of sieving, 60 ℃ of dryings, granulate, the adding magnesium stearate is an amount of, with granule mixing, tabletting, gets product 1000.
Embodiment 6: the preparation of compound puerarin oral liquid
One, prescription:
Puerarin 200g
Moschus 100g
Borneolum Syntheticum 50g
Sucrose 50g
Mel 100mL
Benzoic acid 20g
Make 1000 bottles
Two, preparation technology
Take by weighing puerarin 200g, Moschus 100g, Borneolum Syntheticum 50g, sucrose 50g, Mel 100mL, benzoic acid 20g adds water to 10000mL, stirs, and regulating pH value is 7.0～7.5, leaves standstill, and filters, and fill is in the 10mL vial, and sterilization gets product 1000 bottles.
Embodiment 7: the capsular preparation of compound puerarin
One, prescription:
Puerarin 150g
Borneolum Syntheticum 80g
Starch 70g
Micropowder silica gel is an amount of
Magnesium stearate is an amount of
30% alcoholic solution of 4% 30 POVIDONE K 30 BP/USP 30 is an amount of
Make 1000
Two, preparation technology:
Take by weighing puerarin 150g, Borneolum Syntheticum 80g pulverized 100 mesh sieves, starch, micropowder silica gel, magnesium stearate Guo's 60 mesh sieves.Principal agent and starch are placed the mixer mixing, 30% alcoholic solution that adds 4% 30 POVIDONE K 30 BP/USP 30, stir molding, granulate, be dried to moisture at 60 ℃ and be lower than 5%, dried granule 40 order granulate, add micropowder silica gel and magnesium stearate and mix mixing, measure granule content, encapsulated, get product 1000.
Embodiment 8: the particulate preparation of compound puerarin
One, prescription:
Puerarin 180g
Moschus 80g
Borneolum Syntheticum 150g
Sucrose 1200g
Starch is an amount of
Aspartame is an amount of
Make 1000 bags
Two, preparation technology:
Take by weighing puerarin 180g, Moschus 80g, it is standby that Borneolum Syntheticum 150g pulverized 60 mesh sieves.Take by weighing sucrose 1200g and cross 60 mesh sieves, starch is crossed 80 mesh sieves and principal agent mix homogeneously in mixer, with containing 50% alcoholic solution system soft material of aspartame, granulation, 70 ℃ of air blast catch up with dry to moisture less than 1%.Dried granule is crossed 10 mesh sieves and 80 mesh sieves, mixing respectively.Measure drug content in the granule, packing, 1000 bags get product.
Embodiment 9: compound puerarin drop pill that the present invention is made and single puerarin drop pill are as follows in bioavailability animal test results relatively:
Used material is a kunming mice when wherein testing, and tracer is
14C, label are puerarin; Adopt the form of irritating stomach to carry out administration; Dosage is respectively 50mg/kg; Per 2 hours sacrificed by decapitation one or eight mices after the administration are abscissa with time, are vertical coordinate with the tracer in the mouse blood; Phase area under a curve when wherein AUC1 is compound puerarin drop pill concentration of tracer, phase area under a curve when AUC2 is single puerarin drop pill concentration of tracer; AUC1: AUC2=1.2, the bioavailability that compound puerarin drop pill of the present invention is described is really than the bioavailability height of single puerarin drop pill.
Embodiment 10: treatment cerebral thrombosis aspect: set up model and prepare the rat experiment thrombus model for reducing the blood flow rate method.What animal was used is Cavia porcellus, is provided by Zhejiang (Chinese Academy of Sciences zoopery center).
The method for building up of model: 200 of Cavia porcelluss randomly drawing body weight and be 250-300g, 3% pentobarbital sodium (20mg/kg) intraperitoneal injection of anesthesia, open abdomen, separate ventral aorta and the total tremulous pulse of right bone, with a coarse plastic tube of front end (the about 0.8mm of diameter), be inserted into ventral aorta from the total tremulous pulse rotation of right bone.The total tremulous pulse of the right bone of tube drawing and ligation at the auxilliary homemade arc bulldog clamp of ventral aorta, is sewed up, is protected from infection modelling with penicillin injection then.Detect the thrombosis situation always, find that the formation length of thrombosis occurrence rate and thrombosis all reaches requirement.
Being divided into 2 groups through the operation Cavia porcellus, 100 every group, the I group is injected compound puerarin injection of the present invention, and wherein dosage is 10mg/kg, once a day, and continuous 15 days intravenous administrations; The II group is the puerarin injection of group employing single in contrast, and wherein dosage is 10mg/kg, once a day, and continuous 15 days intravenous administrations; Its result is as shown in table 1:
From the statistical significance of table 1 compound puerarin injection of the present invention as can be seen the treatment thrombosis aspect significantly better than matched group (p＜0.01)
Two kinds of Drug therapy results of table 1 relatively
| Group | The thromboembolism number | Thrombosis does not dissolve number | Add up to |
| I organizes II combination meter | 85 29 114 | 1 5 71 86 | 100 100 200 |
Annotate: compound puerarin injection group of the present invention is compared P＜0.01 with matched group.Illustrate that compound puerarin injection group of the present invention compared significant difference with matched group.
Inject the thromboclastic speed of compound puerarin injection of the present invention in addition also than comparatively fast, after behind the injection compound puerarin injection of the present invention 15 minutes, just take effect, drug effect reaches 11 hours, illustrates that thus compound puerarin preparation of the present invention is having better curative effect aspect the treatment cerebral thrombosis.
Embodiment 11, treatment brain stem ischemia aspect: setting up model is the non-cranium art brain stem ischemia model of opening.What animal was used is the SD rat, is provided by Zhejiang (Chinese Academy of Sciences zoopery center).
The method for building up of model: 200 of SD rat randomly drawing 220g～280g, with 3% pentobarbital sodium (20mg/kg) intraperitoneal injection of anesthesia, be fixed on the toy operating-table, be hung on sutures on the last front tooth of rat, stretching cervical region is also fixing, between two sternoclavicular joint, cut the otch of 25mm, separate being attached to SC muscle and hemostasis by ligation along median line; Remove the clavicle of both sides again, continue separating muscle successively, blood vessel is sought and separation vertebral artery 3～4mm along inferior division to brachial plexus, writes down brainstem auditory evoked potential with potentiometer; Close vertebral artery with miniature hemostatic clamp folder then, use potentiometer simultaneously, the variation of record auditory evoked potential proves when the brainstem auditory evoked phone of ischemia appears in brain stem really, the otch top layer is sewed up, but will be exposed miniature hemostatic clamp (being convenient to allow vertebral artery lead to again) modelling.
Being divided into two groups through operation SD rat, 100 every group, the I group is used compound puerarin injection of the present invention, and wherein dosage is 10mg/kg, once a day, and continuous 30 days intravenous administrations; The II group is the puerarin injection of group employing single in contrast, and wherein dosage is 10mg/kg, once a day, and continuous 30 days intravenous administrations; By table 2 observe brainstem auditory evoked potential as can be seen the I group effective percentage of brain stem ischemia is organized apparently higher than II
Table 2: the change of treatment back auditory evoked potential
| Group | The produce effects number | Obvious effective rate | Significant figure | Invalid number | Effective percentage |
| I group (n=100) II group (n=100) | 34 16 | 34.0％ 16.0％ | 54 32 | 12 52 | 88.0％ 48.0％ |
Annotate: therapeutic outcome shows: compound puerarin preparation group of the present invention effect than matched group aspect treatment brain stem ischemia is obviously good.Inject the thromboclastic speed of compound puerarin injection of the present invention in addition also than comparatively fast, after behind the injection compound puerarin injection of the present invention 10 minutes, just take effect, drug effect reaches 11 hours, illustrates that thus compound puerarin preparation of the present invention is having better curative effect aspect the treatment brain stem ischemia.
Specific embodiment described in the present invention only is that the present invention's spirit is illustrated.The technical staff of the technical field of the invention can make various modifications or replenishes or adopt similar mode to substitute described specific embodiment, but can't depart from spirit of the present invention or surmount the defined scope of appended claims.
Although the present invention has been made detailed explanation and has quoted some instantiations as proof, to those skilled in the art, only otherwise leave that the spirit and scope of the present invention can be done various variations or correction is obvious.
Claims (1)
1. a compound puerarin preparation is characterized in that described preparation is an injection, and its prescription is as follows:
Puerarin 200g
Moschus 30g
HYDROXYPROPYL BETA-CYCLODEXTRIN 15g
Make 1000,
Its preparation technology is as follows:
Take by weighing Moschus 30g, add HYDROXYPROPYL BETA-CYCLODEXTRIN 15g hydrotropy, add puerarin 200g mixing, add water for injection to 8000ml, warm dissolving adds activated carbon decolorizing, remove thermal source,, add water for injection to 10000ml with sand rod elimination active carbon, regulating pH value is 6.0～7.0, detects its content, when qualified, through 0.22 μ m microporous filter membrane fine straining, canned in 10ml peace bottle, sterilized 30 minutes, cool off laggard portable lighter inspection,, obtain the liquid drugs injection finished product again through after the assay was approved.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200610049229XA CN101007014B (en) | 2006-01-24 | 2006-01-24 | A compound puerarin preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200610049229XA CN101007014B (en) | 2006-01-24 | 2006-01-24 | A compound puerarin preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101007014A CN101007014A (en) | 2007-08-01 |
| CN101007014B true CN101007014B (en) | 2010-10-13 |
Family
ID=38695824
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200610049229XA Expired - Fee Related CN101007014B (en) | 2006-01-24 | 2006-01-24 | A compound puerarin preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101007014B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104042602A (en) * | 2014-05-28 | 2014-09-17 | 西北农林科技大学 | Application of sodium glutamate in puerarin injection |
| CN104042603B (en) * | 2014-05-28 | 2019-11-05 | 西北农林科技大学 | Application of the γ-aminobutyric acid on the drug for the intravascular hemolysis that preparation prevention and treatment puerarin injection induces |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1389211A (en) * | 2002-07-18 | 2003-01-08 | 北京四环科宝制药有限公司 | Puerarin injection and its prepn. process |
| CN1394603A (en) * | 2002-08-09 | 2003-02-05 | 陕西镇坪制药厂 | Application of hydroxyethyl puerarin in preparation of new medicine for curing cerebrovascular diseases |
-
2006
- 2006-01-24 CN CN200610049229XA patent/CN101007014B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1389211A (en) * | 2002-07-18 | 2003-01-08 | 北京四环科宝制药有限公司 | Puerarin injection and its prepn. process |
| CN1394603A (en) * | 2002-08-09 | 2003-02-05 | 陕西镇坪制药厂 | Application of hydroxyethyl puerarin in preparation of new medicine for curing cerebrovascular diseases |
Non-Patent Citations (5)
| Title |
|---|
| CN 1389211 A,实施例5. |
| 刘洋，等.冰片的药理实验研究概况.天津中医药20 8.2003,20(8),85-87. |
| 刘洋等.冰片的药理实验研究概况.天津中医药20 8.2003,20(8),85-87. * |
| 卢薇，等.中药对血脑屏障作用的实验研究进展.中西医结合心脑血管杂志3 1.2005,3(1),60-61. |
| 卢薇等.中药对血脑屏障作用的实验研究进展.中西医结合心脑血管杂志3 1.2005,3(1),60-61. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101007014A (en) | 2007-08-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101891505B1 (en) | Use of anhydroicaritin in preparing medicine for preventing or treating decrease in blood cells | |
| AU2017317950A1 (en) | Sublingual pharmaceutical composition of edaravone and (+)-2-borneol | |
| WO2019206159A1 (en) | Use of chlorogenic acid and composition thereof in preparation of medicament for treating sarcoma | |
| CN105998019A (en) | Medicine composition for treating brain glioma and application thereof | |
| CN106074463A (en) | Cannabidiol application in preparation treatment gouty arthritis medicine | |
| CN104922143B (en) | The composition and its preparation method and application of EGCG and chitosan oligosaccharide | |
| CN102342931B (en) | Injectable parenteral medicinal preparation of temozolomide and preparation method thereof | |
| CN101007014B (en) | A compound puerarin preparation | |
| CN101219128A (en) | Dexibuprofen pharmaceutical composition with improved dissolving out capability and method for preparing the same | |
| CN113546089B (en) | Application of 1-ethyl-3, 7-dimethyl xanthine in preparation of medicine for treating pneumonia | |
| CN101757443A (en) | Traditional Chinese medicine preparation for treating hemophilia | |
| CN101156849A (en) | A kind of phenytoin sustained-release gel for promoting periodontal regeneration and its preparation method and application | |
| CN101057965A (en) | Compound traditional Chinese medicine preparation for treating cardiovascular and cerebrovascular disease | |
| CN106943390B (en) | Application of the Strychnos nux-vomica aglycon in preparation prevention or treatment antiarrhythmic medicament | |
| CN101081227B (en) | Composition of diammonium glycyrrhizinate | |
| CN109364071A (en) | A kind of drug and purposes promoting salivary secretion treatment xerostomia syndrome | |
| CN102451170B (en) | Granisetron hydrochloride freeze-drying tablet and preparation method thereof | |
| CN1994345B (en) | Compound Chinese medicinal formulation for treating cardiovascular and cerebrovascular disease | |
| CN107951885B (en) | A kind of combination of oral medication for treating capillary leak syndrome | |
| CN113577090B (en) | Application of arctiin in preparation of prostatic hyperplasia medicine | |
| CN107998117B (en) | A kind of combination of oral medication for treating capillary leak syndrome | |
| CN100396295C (en) | Medicine for treating virus hepatitis | |
| CN113368098A (en) | Application of icaritin in preparation of medicine for preventing and treating hemophilia | |
| CN1762341A (en) | Salvianolic acid compound for treating cardiovascular and cerebrovascular disease and liver disease, and application thereof | |
| CN105288107A (en) | Compound hippophae rhamnoides composition for clearing heat from throat and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20101013 Termination date: 20120124 |