CN102579442B - Compound preparation containing benidipine hydrochloride and atorvastatin calcium and application for compound preparation - Google Patents
Compound preparation containing benidipine hydrochloride and atorvastatin calcium and application for compound preparation Download PDFInfo
- Publication number
- CN102579442B CN102579442B CN 201210068311 CN201210068311A CN102579442B CN 102579442 B CN102579442 B CN 102579442B CN 201210068311 CN201210068311 CN 201210068311 CN 201210068311 A CN201210068311 A CN 201210068311A CN 102579442 B CN102579442 B CN 102579442B
- Authority
- CN
- China
- Prior art keywords
- weight portions
- atorvastatin calcium
- compound preparation
- magnesium stearate
- mesh sieves
- 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
- 229960001770 atorvastatin calcium Drugs 0.000 title claims abstract description 115
- OJRHUICOVVSGSY-RXMQYKEDSA-N (2s)-2-chloro-3-methylbutan-1-ol Chemical compound CC(C)[C@H](Cl)CO OJRHUICOVVSGSY-RXMQYKEDSA-N 0.000 title claims abstract description 110
- QZVNQOLPLYWLHQ-ZEQKJWHPSA-N benidipine Chemical compound C1([C@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)O[C@H]2CN(CC=3C=CC=CC=3)CCC2)=CC=CC([N+]([O-])=O)=C1 QZVNQOLPLYWLHQ-ZEQKJWHPSA-N 0.000 title claims abstract description 41
- 229960004916 benidipine Drugs 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 35
- 150000001875 compounds Chemical class 0.000 title abstract description 29
- 239000000203 mixture Substances 0.000 claims abstract description 58
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 128
- KILKDKRQBYMKQX-MIPPOABVSA-N 5-o-[(3r)-1-benzylpiperidin-3-yl] 3-o-methyl (4r)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate;hydron;chloride Chemical compound Cl.C1([C@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)O[C@H]2CN(CC=3C=CC=CC=3)CCC2)=CC=CC([N+]([O-])=O)=C1 KILKDKRQBYMKQX-MIPPOABVSA-N 0.000 claims description 71
- 235000019359 magnesium stearate Nutrition 0.000 claims description 64
- 239000011230 binding agent Substances 0.000 claims description 47
- 239000008187 granular material Substances 0.000 claims description 36
- 206010013786 Dry skin Diseases 0.000 claims description 29
- 238000003113 dilution method Methods 0.000 claims description 29
- 238000001035 drying Methods 0.000 claims description 29
- 239000008213 purified water Substances 0.000 claims description 29
- 239000007779 soft material Substances 0.000 claims description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 24
- 239000011734 sodium Substances 0.000 claims description 24
- 229910052708 sodium Inorganic materials 0.000 claims description 24
- 229920000881 Modified starch Polymers 0.000 claims description 22
- -1 hydroxypropyl Chemical group 0.000 claims description 22
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 22
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 22
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 22
- 229960003943 hypromellose Drugs 0.000 claims description 22
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 21
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 21
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 21
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 21
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 19
- 239000008101 lactose Substances 0.000 claims description 19
- 239000000835 fiber Substances 0.000 claims description 11
- 239000002775 capsule Substances 0.000 claims description 8
- 239000003814 drug Substances 0.000 abstract description 36
- 206010020772 Hypertension Diseases 0.000 abstract description 32
- 229940079593 drug Drugs 0.000 abstract description 18
- 208000031226 Hyperlipidaemia Diseases 0.000 abstract description 16
- 230000000694 effects Effects 0.000 abstract description 14
- 239000008280 blood Substances 0.000 abstract description 11
- 210000004369 blood Anatomy 0.000 abstract description 11
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 abstract description 6
- 230000002526 effect on cardiovascular system Effects 0.000 abstract description 5
- 238000009472 formulation Methods 0.000 abstract description 5
- 208000026106 cerebrovascular disease Diseases 0.000 abstract description 4
- 230000000295 complement effect Effects 0.000 abstract description 3
- 201000001320 Atherosclerosis Diseases 0.000 abstract description 2
- 206010019280 Heart failures Diseases 0.000 abstract description 2
- 206010000891 acute myocardial infarction Diseases 0.000 abstract description 2
- 235000012000 cholesterol Nutrition 0.000 abstract description 2
- 208000029078 coronary artery disease Diseases 0.000 abstract description 2
- 206010067484 Adverse reaction Diseases 0.000 abstract 1
- 239000004480 active ingredient Substances 0.000 abstract 1
- 230000006838 adverse reaction Effects 0.000 abstract 1
- 238000013329 compounding Methods 0.000 abstract 1
- 230000007547 defect Effects 0.000 abstract 1
- 230000002892 effect on hypertension Effects 0.000 abstract 1
- 230000002503 metabolic effect Effects 0.000 abstract 1
- 230000002195 synergetic effect Effects 0.000 abstract 1
- 239000002671 adjuvant Substances 0.000 description 33
- 239000002994 raw material Substances 0.000 description 28
- 229920003081 Povidone K 30 Polymers 0.000 description 20
- 230000036772 blood pressure Effects 0.000 description 17
- 108010011485 Aspartame Proteins 0.000 description 15
- 239000000605 aspartame Substances 0.000 description 15
- 235000010357 aspartame Nutrition 0.000 description 15
- 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 15
- 229960003438 aspartame Drugs 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 229920002785 Croscarmellose sodium Polymers 0.000 description 13
- 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 13
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 13
- 208000032928 Dyslipidaemia Diseases 0.000 description 11
- 208000017170 Lipid metabolism disease Diseases 0.000 description 11
- 239000004698 Polyethylene Substances 0.000 description 11
- 229920000573 polyethylene Polymers 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 8
- 229920002472 Starch Polymers 0.000 description 8
- 229930006000 Sucrose Natural products 0.000 description 8
- 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 8
- 238000012856 packing Methods 0.000 description 8
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 8
- 239000008107 starch Substances 0.000 description 8
- 235000019698 starch Nutrition 0.000 description 8
- 239000005720 sucrose Substances 0.000 description 8
- 229960004793 sucrose Drugs 0.000 description 8
- 229920001353 Dextrin Polymers 0.000 description 7
- 239000004375 Dextrin Substances 0.000 description 7
- 239000011248 coating agent Substances 0.000 description 7
- 238000000576 coating method Methods 0.000 description 7
- 235000019425 dextrin Nutrition 0.000 description 7
- 239000000890 drug combination Substances 0.000 description 7
- 238000009413 insulation Methods 0.000 description 7
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 description 7
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 7
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 108010028554 LDL Cholesterol Proteins 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 6
- 208000024172 Cardiovascular disease Diseases 0.000 description 5
- 108010023302 HDL Cholesterol Proteins 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 4
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 230000001631 hypertensive effect Effects 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 4
- 229940085605 saccharin sodium Drugs 0.000 description 4
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 3
- 230000003276 anti-hypertensive effect Effects 0.000 description 3
- 230000007211 cardiovascular event Effects 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 3
- 230000003516 hyperlipidaemic effect Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- 208000007530 Essential hypertension Diseases 0.000 description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 description 2
- 229920002535 Polyethylene Glycol 1500 Polymers 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 229940127088 antihypertensive drug Drugs 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 230000035487 diastolic blood pressure Effects 0.000 description 2
- 239000007919 dispersible tablet Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 201000005577 familial hyperlipidemia Diseases 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000001077 hypotensive effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229940093430 polyethylene glycol 1500 Drugs 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 230000035488 systolic blood pressure Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 1
- XUKUURHRXDUEBC-SVBPBHIXSA-N (3s,5s)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@H](O)C[C@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-SVBPBHIXSA-N 0.000 description 1
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010003084 Areflexia Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010028594 Myocardial fibrosis Diseases 0.000 description 1
- 206010031127 Orthostatic hypotension Diseases 0.000 description 1
- 229940123934 Reductase inhibitor Drugs 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 230000036178 pleiotropy Effects 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000011125 single therapy Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a compound preparation containing benidipine hydrochloride and atorvastatin calcium and application for the compound preparation. The compound preparation comprises the following active ingredients: the benidipine hydrochloride and the atorvastatin calcium. By the compound preparation, the defect that hypertension and hyperlipidemia cannot be treated simultaneously by single medicines is overcome, and the compound preparation is prepared by compounding the benidipine hydrochloride and the atorvastatin calcium. The preparation can be prepared into oral formulations of different forms, and a treatment effect of the compound preparation is enhanced under the synergetic and complementary action of medicines, the using dose of the medicines is reduced in clinical application, and the adverse reaction of patients is relieved, so the compound preparation is accepted easily by the patients. The compound preparation has an obvious treatment effect on hypertension and hyperlipidemia, is suitable for the patients who suffer from serious cardiovascular cerebrovascular diseases accompanied with high cholesterol, blood fat metabolic disturbance, cardiac failure, atherosclerosis, coronary heart diseases, acute myocardial infarction and the like, and is low in cost, easy to prepare and convenient to popularize and apply.
Description
Technical field
The present invention relates to a kind of compound preparation and application thereof, be specifically related to a kind of compound preparation and application thereof that contains KW-3049 and Atorvastatin calcium, belong to the biological medicine technology field.
Background technology
Hypertension is popular disease the most widely in the world today, is called " noiseless killer " by people.Global disease burden survey result showed in 2000, and 50% cardiovascular disease is caused that by hypertension hypertension accounts for 4.5% in present global disease burden, no matter developed country or developing country, and hypertension is all very general.Data shows according to statistics, in recent years China more than 18 years old resident's hypertension prevalence be l8.8%, national number of patients has reached 200,000,000; Then rose to 60%～70% greater than 70 years old among the crowd.In China crowd's more than 40 years old the cause of death, heart disease and cerebrovascular are classified the-position and the 3rd respectively as, and first risk factor of total death is hypertension.Hypertension is the primary risk factor of cardiovascular and cerebrovascular disease and kidney disease, and annual also with nearly 3,000,000 people's speed increase, people's health in serious harm.Wherein half is with dyslipidemia, and along with the further expansion of obese people, this part patient's quantity also will further increase.Hypertension and dyslipidemia are the important risk factor of present two big controllable cardiovascular and cerebrovascular diseases of generally acknowledging.These two kinds of risk factors often merge existence, and influence each other.Framingham studies show that about 80% hyperpietic and deposits other risk factors of cardiovascular diseases, wherein the modal dyslipidemia that is; French hyperpietic below 55 years old investigates to 193784 examples, shows that also surpassing 50% patient merging exists dyslipidemia.Control blood pressure simultaneously and regulate dyslipidemia and make the bigger benefit of patient, the NHANES-m result of study showed in 2003: the control blood pressure, actively transfer fat to make LDL-C and HDL-C level incidence rate of male patient's cardiovascular event that will make up to standard descend 51%, female patient descends 43%.So, facing the patient of huge hypertensive patients dyslipidemia, blood pressure lowering transfers the fat treatment most important simultaneously, can better control blood pressure, reduces the cardiovascular event risk.
KW-3049 is a kind of novel, long-acting, second filial generation dihydropyridine calcium ion antagonist, is used for the treatment of essential hypertension clinically.Domestic literature is used for the treatment of hypertensive report about KW-3049, mostly is greatly once a day, and common dose is each 2～4mg, and maximal dose is each 8mg.Atorvastatin calcium is a kind of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-GoA) reductase inhibitor of novel synthetic tissue selectivity, synthetic by blocking-up liver cholesterol, and promote surface of hepatocytes low-density lipoprotein cholesterol (LDL-C) receptor expression, can effectively reduce LDL-C.The recommendation initial dose of Atorvastatin calcium is 10mg/ day, dosage range 10～60mg/ day, more merging hyperlipemia is arranged in Hypertensive Population, as the not development of control in early days with will promoting arteriosclerosis, on the basis of KW-3049 blood pressure lowering, the coupling Atorvastatin calcium can make blood pressure level further reduce after transferring the fat treatment, and can adjust blood lipid level and well change, the associating fat-reducing medicament can significantly reduce the cardiovascular event risk on the blood pressure lowering basis.But most of patients to hypertension and hyperlipidemia cognitive not enough, poor with prodrug complex, bad health idea, autocontrol force, to reach medical worker's Service Management not in place all be the main cause that influences hypertension and hyperlipemic patients drug compliance difference, for the compound preparation of effective treatment hypertension and hyperlipidemia is provided, improve patient's compliance, these two kinds of medicines are combined drug combination have good effect.
Summary of the invention
Needs and the raising drug compliance of the present invention in order to satisfy hypertension and hyperlipemic patients, a kind of compound preparation that contains KW-3049 and Atorvastatin calcium is provided, this compound preparation antihypertensive effect is remarkable, can treat hypertension and hyperlipidemia simultaneously, little to patient's toxic and side effects, be easy to be accepted by the patient.
The present invention also provides the application of this compound preparation.
When treating hypertension and hyperlipidemia clinically now, often have following problem: 1, list will be treated a kind of disease with a kind of drug main, the multiple complications such as hyperlipidemia but hypertension occurs together simultaneously must be used by multiple medicine simultaneously for guaranteeing curative effect, could guarantee therapeutic effect; 2, during drug combination, because nothing meets the pharmaceutical preparation standard of drug combination dosage, and use clinical inaccurately with dosage, influence curative effect of medication.The present invention has overcome above defective, be devoted to drug combination and treat the research of hypertension and hyperlipidemia simultaneously, to reach control blood pressure and blood fat and to slow down the important organ infringement simultaneously, reduce the purpose of the case fatality rate of hypertension and hyperlipemic patients, solve patient's misery of taking medicine.In research process, be active constituents of medicine with KW-3049 and Atorvastatin calcium, carry out the experiment of drug combination, find that the two combination can improve the therapeutic effect of hypertension and hyperlipidemia greatly, and the compound formulation that drug combination forms can improve patient's drug compliance, obviously alleviate patient's untoward reaction, be easy to be accepted by the patient.
Technical scheme of the present invention is as follows:
A kind of compound preparation that contains KW-3049 and Atorvastatin calcium is characterized in that: be effective ingredient with KW-3049 and Atorvastatin calcium.
In the above-mentioned compound formulation, active constituents of medicine content is: KW-3049 1～10 weight portion, and Atorvastatin calcium 1～320 weight portion, preferred: KW-3049 2～8 weight portions, Atorvastatin calcium 5～80 weight portions.
In the above-mentioned compound preparation, preferred: the mass ratio of KW-3049 and Atorvastatin calcium is 1:2～10, most preferably 1:5～10.
Compound formulation of the present invention, except active constituents of medicine, also contain acceptable accessories, according to the difference of clinical practice, the effective one-tenth of medicine and adjuvant can be made various medically acceptable oral formulations, the consumption of adjuvant can be measured to determine according to actual needs.For example, can be made into compound hydrochloric acid benidipine-atorvastatin calcium tablet (ordinary tablet, dispersible tablet, slow releasing tablet and other special tablets), compound hydrochloric acid benidipine-atorvastatin calcium capsule (conventional capsule, slow releasing capsule and other special capsules), compound hydrochloric acid benidipine-Atorvastatin calcium drop pill, compound hydrochloric acid benidipine-Atorvastatin calcium granule etc.
The used adjuvant of medicine of preparation different dosage form includes diluent, disintegrating agent, binding agent, dispersant, plasticizer, correctives, fluidizer, lubricant etc. substantially.Medicine of the present invention is when preparing different dosage forms, and used adjuvant can be selected microcrystalline Cellulose, pregelatinized Starch, super carboxymethylstach sodium, carboxymethylstach sodium, lactose, polyvinylpolypyrrolidone, cross-linked carboxymethyl cellulose sodium, dextrin, aspartame, 30 POVIDONE K 30 BP/USP 30, hypromellose, Polyethylene Glycol-1500, Polyethylene Glycol-4000, Polyethylene Glycol-6000, sucrose, soluble starch, saccharin sodium, micropowder silica gel and magnesium stearate etc.
Compound preparation of the present invention has the effect for the treatment of hypertension and hyperlipidemia simultaneously, can use it in the medicine of preparation treatment hypertension and hyperlipidemia.
The present invention carries out KW-3049 and Atorvastatin calcium composite, also can treat hyperlipidemia simultaneously in treatment hypertension, and this product can drug combination, and need not respectively hypertension and hyperlipidemia be treated taking convenience more respectively with single medicine.Empirical tests, medicine after composite can improve the curative effect of blood pressure lowering and blood fat reducing, collaborative, complementary action is arranged, and because the synergism of two kinds of medicines, the using dosage of each active drug is reduced, alleviated patient's untoward reaction, the compensation response that blood pressure and blood fat blood pressure lowering trigger when having prevented single therapy, increase patient's toleration, improved compliance.
Medicine of the present invention, oral, every day 1 time, the dosage of each KW-3049 is 1-4mg, the dosage of Atorvastatin calcium is 5-40mg.2 week back blood pressures and the rate and blood-lipid decreased of taking medicine do not reach effective standard person can increase to every day 2 times.3～5 h peaking concentration behind this drug oral, mean half-life in patient's body reaches 25 h, can keep at least 24 h hypotensive effects oral 1 time every day, heart rate, chamber conduction there is not obviously influence, areflexia tachycardia and postural hypotension, have the excellent drug toleration, general 4～8 weeks are a course for the treatment of.
The present invention has overcome the shortcoming that single drug can not treated hypertension and hyperlipidemia simultaneously, has obtained compound preparation of the present invention by KW-3049 and Atorvastatin calcium composite.Preparation of the present invention can be made into the peroral dosage form of different shape, because collaborative, the complementary action of medicine, this compound preparation therapeutic effect strengthens, and the medicine using dosage reduces in clinical practice, has alleviated patient's untoward reaction, is easy to be accepted by the patient.This compound preparation is remarkable to hypertension and hyperlipidemia therapeutic effect, is applicable to serious cardiovascular and cerebrovascular disease patients such as hypercholesterolemia, dysbolism of blood fat, heart failure, atherosclerosis, coronary heart disease, acute myocardial infarctions.And the present invention is cheap, and preparation is simple, and is easy to utilize.
The specific embodiment
The present invention will be further elaborated below by specific embodiment and clinical experiment, should be understood that following explanation only is in order to explain the present invention, its content not to be limited.
Tablet
Embodiment 1
KW-3049 1 weight portion, Atorvastatin calcium 1 weight portion, lactose 44 weight portions, microcrystalline Cellulose 20 weight portions, pregelatinized Starch 40 weight portions, carboxymethylstach sodium 15 weight portions, hypromellose 2.5 weight portions, magnesium stearate 1.5 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and hydroxypropyl first fiber is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, to be crossed 18 mesh sieves and granulated, 60 ℃ of dryings are abundant, and 18 mesh sieve granulate add the magnesium stearate mix homogeneously of recipe quantity, tabletting, coating, namely.Hydrochloric benidipine 1mg contains Atorvastatin calcium 1mg in every.
Embodiment 2
KW-3049 1 weight portion, Atorvastatin calcium 5 weight portions, lactose 40 weight portions, microcrystalline Cellulose 20 weight portions, pregelatinized Starch 45 weight portions, carboxymethylstach sodium 15 weight portions, cross-linked carboxymethyl cellulose sodium 20 weight portions, hypromellose 2.5 weight portions, magnesium stearate 1.5 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and 30 POVIDONE K 30 BP/USP 30 is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, to be crossed 20 mesh sieves and granulated, 65 ℃ of dryings are abundant, and 20 mesh sieve granulate add the magnesium stearate mix homogeneously of recipe quantity, tabletting, coating, namely.Hydrochloric benidipine 1 mg contains Atorvastatin calcium 5mg in every.
Embodiment 3
KW-3049 2 weight portions, Atorvastatin calcium 10 weight portions, microcrystalline Cellulose 30 weight portions, pregelatinized Starch 58 weight portions, carboxymethylstach sodium 20 weight portions, 30 POVIDONE K 30 BP/USP 30 3 weight portions, magnesium stearate 2 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and 30 POVIDONE K 30 BP/USP 30 is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, to be crossed 20 mesh sieves and granulated, 65 ℃ of dryings are abundant, and 20 mesh sieve granulate add the magnesium stearate mix homogeneously of recipe quantity, tabletting, coating, namely.Hydrochloric benidipine 2 mg contain Atorvastatin calcium 10 mg in every.
Embodiment 4
KW-3049 4 weight portions, Atorvastatin calcium 20 weight portions, lactose 30 weight portions, microcrystalline Cellulose 23 weight portions, pregelatinized Starch 26 weight portions, cross-linked carboxymethyl cellulose sodium 18 weight portions, hypromellose 3 weight portions, magnesium stearate 1 weight portion.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and hypromellose is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, to be crossed 18 mesh sieves and granulated, 70 ℃ of dryings are abundant, and 18 mesh sieve granulate add the magnesium stearate mix homogeneously of recipe quantity, tabletting, coating, namely.Hydrochloric benidipine 4mg contains Atorvastatin calcium 20mg in every.
Embodiment 5
KW-3049 4 weight portions, Atorvastatin calcium 40 weight portions, lactose 40 weight portions, microcrystalline Cellulose 50 weight portions, pregelatinized Starch 68.5 weight portions, carboxymethylstach sodium 40 weight portions, hypromellose 5 weight portions, magnesium stearate 2.5 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and hydroxypropyl first fiber is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, to be crossed 18 mesh sieves and granulated, 60 ℃ of dryings are abundant, and 18 mesh sieve granulate add the magnesium stearate mix homogeneously of recipe quantity, tabletting, coating, namely.Hydrochloric benidipine 4mg in every contains Atorvastatin calcium 40 mg.
Embodiment 6
KW-3049 8 weight portions, Atorvastatin calcium 80 weight portions, lactose 76 weight portions, pregelatinized Starch 82.5 weight portions, carboxymethylstach sodium 50 weight portions, 30 POVIDONE K 30 BP/USP 30 5 weight portions, magnesium stearate 2.5 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and 30 POVIDONE K 30 BP/USP 30 is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, to be crossed 18 mesh sieves and granulated, 60 ℃ of dryings are abundant, and 18 mesh sieve granulate add the magnesium stearate mix homogeneously of recipe quantity, tabletting, coating, namely.Hydrochloric benidipine 2mg in every contains Atorvastatin calcium 20 mg.
Embodiment 7
KW-3049 10 weight portions, Atorvastatin calcium 200 weight portions, lactose 50 weight portions, microcrystalline Cellulose 40 weight portions, pregelatinized Starch 41.5 weight portions, carboxymethylstach sodium 35 weight portions, cross-linked carboxymethyl cellulose sodium 20 weight portions, 30 POVIDONE K 30 BP/USP 30 3 weight portions, hypromellose 3 weight portions, magnesium stearate 2.5 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and 30 POVIDONE K 30 BP/USP 30, hydroxypropyl first fiber are mixed with suitable concentration with purified water and make binding agent, and be standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, to be crossed 18 mesh sieves and granulated, 60 ℃ of dryings are abundant, and 18 mesh sieve granulate add the magnesium stearate mix homogeneously of recipe quantity, tabletting, coating, namely.Hydrochloric benidipine 1mg contains Atorvastatin calcium 20mg in every.
Capsule
Embodiment 8
KW-3049 1 weight portion, Atorvastatin calcium 1 weight portion, lactose 30 weight portions, microcrystalline Cellulose 20 weight portions, pregelatinized Starch 30 weight portions, carboxymethylstach sodium 15 weight portions, hypromellose 2 weight portions, magnesium stearate 1 weight portion.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and hydroxypropyl first fiber is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, to be crossed 18 mesh sieves and granulated, 60 ℃ of dryings are abundant, and 18 mesh sieve granulate add the magnesium stearate mix homogeneously of recipe quantity, and are encapsulated, namely.Hydrochloric benidipine 1 mg contains Atorvastatin calcium 1mg in every.
Embodiment 9
KW-3049 2 weight portions, Atorvastatin calcium 5 weight portions, lactose 25 weight portions, microcrystalline Cellulose 20 weight portions, pregelatinized Starch 30 weight portions, carboxymethylstach sodium 15 weight portions, hypromellose 2 weight portions, magnesium stearate 1 weight portion.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and hydroxypropyl first fiber is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, to be crossed 18 mesh sieves and granulated, 60 ℃ of dryings are abundant, and 18 mesh sieve granulate add the magnesium stearate mix homogeneously of recipe quantity, and are encapsulated, namely.Hydrochloric benidipine 2 mg contain Atorvastatin calcium 5 mg in every.
Embodiment 10
KW-3049 2 weight portions, Atorvastatin calcium 10 weight portions, microcrystalline Cellulose 35 weight portions, pregelatinized Starch 29.5 weight portions, carboxymethylstach sodium 20 weight portions, 30 POVIDONE K 30 BP/USP 30 2 weight portions, magnesium stearate 1.5 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and 30 POVIDONE K 30 BP/USP 30 is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, to be crossed 18 mesh sieves and granulated, 60 ℃ of dryings are abundant, and 18 mesh sieve granulate add the magnesium stearate mix homogeneously of recipe quantity, and are encapsulated, namely.Hydrochloric benidipine 2 mg contain Atorvastatin calcium 10 mg in every.
Embodiment 11
KW-3049 4 weight portions, Atorvastatin calcium 40 weight portions, lactose 20 weight portions, microcrystalline Cellulose 25 weight portions, pregelatinized Starch 38.5 weight portions, cross-linked carboxymethyl cellulose sodium 18 weight portions, hypromellose 3 weight portions, magnesium stearate 1.5 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and hydroxypropyl first fiber is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, to be crossed 18 mesh sieves and granulated, 60 ℃ of dryings are abundant, and 18 mesh sieve granulate add the magnesium stearate mix homogeneously of recipe quantity, and are encapsulated, namely.Hydrochloric benidipine 4 mg contain Atorvastatin calcium 40mg in every.
Embodiment 12
KW-3049 4 weight portions, Atorvastatin calcium 80 weight portions, lactose 40 weight portions, microcrystalline Cellulose 40 weight portions, pregelatinized Starch 41 weight portions, carboxymethylstach sodium 20 weight portions, cross-linked carboxymethyl cellulose sodium 20 weight portions, hypromellose 4 weight portions, magnesium stearate 1 weight portion.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and hydroxypropyl first fiber is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, to be crossed 18 mesh sieves and granulated, 60 ℃ of dryings are abundant, and 18 mesh sieve granulate add the magnesium stearate mix homogeneously of recipe quantity, and are encapsulated, namely.Hydrochloric benidipine 2mg in every contains Atorvastatin calcium 40 mg.
Embodiment 13
KW-3049 8 weight portions, Atorvastatin calcium 80 weight portions, lactose 40 weight portions, microcrystalline Cellulose 50 weight portions, pregelatinized Starch 41 weight portions, carboxymethylstach sodium 20 weight portions, cross-linked carboxymethyl cellulose sodium 56 weight portions, hypromellose 4 weight portions, magnesium stearate 1 weight portion.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and hydroxypropyl first fiber is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, to be crossed 18 mesh sieves and granulated, 60 ℃ of dryings are abundant, and 18 mesh sieve granulate add the magnesium stearate mix homogeneously of recipe quantity, and are encapsulated, namely.Hydrochloric benidipine 1mg in every contains Atorvastatin calcium 10 mg.
Dispersible tablet
Embodiment 14
KW-3049 1 weight portion, Atorvastatin calcium 1 weight portion, microcrystalline Cellulose 20 weight portions, lactose 14.6 weight portions, pregelatinized Starch 25 weight portions, super carboxymethylstach sodium 16 weight portions, cross-linked carboxymethyl cellulose sodium 20 weight portions, hypromellose 1 weight portion, aspartame 1 weight portion, magnesium stearate 0.4 weight portion.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and hydroxypropyl first fiber is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, is crossed 18 mesh sieves and granulated, 75 ℃ of dryings 3 hours, 18 mesh sieve granulate add the magnesium stearate mix homogeneously, tabletting, namely.Hydrochloric benidipine 1 mg contains Atorvastatin calcium 1mg in every.
Embodiment 15
KW-3049 1 weight portion, Atorvastatin calcium 5 weight portions, microcrystalline Cellulose 10 weight portions, lactose 25 weight portions, pregelatinized Starch 30 weight portions, super carboxymethylstach sodium 36 weight portions, polyvinylpolypyrrolidone 61 weight portions, hypromellose 1 weight portion, aspartame 2 weight portions, saccharin sodium 3 weight portions, magnesium stearate 3 weight portions, micropowder silica gel 4 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and hydroxypropyl first fiber is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, is crossed 18 mesh sieves and granulated, 75 ℃ of dryings 3 hours, 18 mesh sieve granulate add the magnesium stearate mix homogeneously, tabletting, namely.Hydrochloric benidipine 1 mg contains Atorvastatin calcium 5 mg in every.
Embodiment 16
KW-3049 2 weight portions, Atorvastatin calcium 10 weight portions, microcrystalline Cellulose 25 weight portions, lactose 30 weight portions, pregelatinized Starch 36 weight portions, super carboxymethylstach sodium 64 weight portions, polyvinylpolypyrrolidone 10 weight portions, cross-linked carboxymethyl cellulose sodium 10 weight portions, 30 POVIDONE K 30 BP/USP 30 2 weight portions, aspartame 3 weight portions, saccharin sodium 3 weight portions, magnesium stearate 1 weight portion, micropowder silica gel 4 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and 30 POVIDONE K 30 BP/USP 30 is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, micropowder silica gel, with other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, cross 18 mesh sieves and granulate, 75 ℃ of dryings 3 hours, 18 mesh sieve granulate, add magnesium stearate, micropowder silica gel mix homogeneously, tabletting, namely.Hydrochloric benidipine 2 mg contain Atorvastatin calcium 10 mg in every.
Embodiment 17
KW-3049 4 weight portions, Atorvastatin calcium 20 weight portions, microcrystalline Cellulose 35 weight portions, pregelatinized Starch 28 weight portions, carboxymethylstach sodium 50 weight portions, super carboxymethylstach sodium 59 weight portions, polyvinylpolypyrrolidone 20 weight portions, cross-linked carboxymethyl cellulose sodium 20 weight portions, hypromellose 2 weight portions, 30 POVIDONE K 30 BP/USP 30 3 weight portions, aspartame 5 weight portions, magnesium stearate 2 weight portions, micropowder silica gel 2 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and hypromellose, 30 POVIDONE K 30 BP/USP 30 are mixed with suitable concentration with purified water and make binding agent, and be standby.Except magnesium stearate, micropowder silica gel, with other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, cross 18 mesh sieves and granulate, 75 ℃ of dryings 3 hours, 18 mesh sieve granulate, add magnesium stearate, micropowder silica gel mix homogeneously, tabletting, namely.Hydrochloric benidipine 4 mg contain Atorvastatin calcium 20 mg in every.
Embodiment 18
KW-3049 4 weight portions, Atorvastatin calcium 40 weight portions, microcrystalline Cellulose 40 weight portions, lactose 55 weight portions, pregelatinized Starch 40 weight portions, carboxymethylstach sodium 46 weight portions, polyvinylpolypyrrolidone 30 weight portions, cross-linked carboxymethyl cellulose sodium 30 weight portions, 30 POVIDONE K 30 BP/USP 30 4 weight portions, aspartame 7 weight portions, saccharin sodium 2 weight portions, magnesium stearate 2 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and 30 POVIDONE K 30 BP/USP 30 is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, is crossed 18 mesh sieves and granulated, 75 ℃ of dryings 3 hours, 18 mesh sieve granulate add the magnesium stearate mix homogeneously, tabletting, namely.Hydrochloric benidipine 4 mg contain Atorvastatin calcium 40 mg in every.
Embodiment 19
KW-3049 4 weight portions, Atorvastatin calcium 80 weight portions, microcrystalline Cellulose 50 weight portions, lactose 33 weight portions, pregelatinized Starch 44 weight portions, carboxymethylstach sodium 50 weight portions, super carboxymethylstach sodium 40 weight portions, polyvinylpolypyrrolidone 40 weight portions, cross-linked carboxymethyl cellulose sodium 40 weight portions, 30 POVIDONE K 30 BP/USP 30 5 weight portions, aspartame 10 weight portions, magnesium stearate 3 weight portions, micropowder silica gel 1 weight portion.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and 30 POVIDONE K 30 BP/USP 30 is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, micropowder silica gel, with other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, cross 18 mesh sieves and granulate, 75 ℃ of dryings 3 hours, 18 mesh sieve granulate, add magnesium stearate, micropowder silica gel mix homogeneously, tabletting, namely.Hydrochloric benidipine 2mg contains Atorvastatin calcium 40mg in every.
Embodiment 20
KW-3049 4 weight portions, Atorvastatin calcium 160 weight portions, microcrystalline Cellulose 40 weight portions, lactose 40 weight portions, pregelatinized Starch 68 weight portions, carboxymethylstach sodium 60 weight portions, super carboxymethylstach sodium 50 weight portions, polyvinylpolypyrrolidone 50 weight portions, cross-linked carboxymethyl cellulose sodium 50 weight portions, 30 POVIDONE K 30 BP/USP 30 6 weight portions, aspartame 15 weight portions, magnesium stearate 2 weight portions, micropowder silica gel 5 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and 30 POVIDONE K 30 BP/USP 30 is mixed with suitable concentration with purified water and makes binding agent, and is standby.Except magnesium stearate, micropowder silica gel, with other supplementary material with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, cross 18 mesh sieves and granulate, 75 ℃ of dryings 3 hours, 18 mesh sieve granulate, add magnesium stearate, micropowder silica gel mix homogeneously, tabletting, namely.Hydrochloric benidipine 1 mg contains Atorvastatin calcium 40 mg in every.
Drop pill
Embodiment 21
KW-3049 1 weight portion, Atorvastatin calcium 1 weight portion, Polyethylene Glycol-6,000 23 weight portions.
KW-3049, Atorvastatin calcium were pulverized 80 mesh sieves respectively, add Polyethylene Glycol-6000, and stirred evenly, 80 ± 2 ℃ of insulations are dripped and are made ball, namely.Hydrochloric benidipine 1 mg contains Atorvastatin calcium 1mg in every ball.
Embodiment 22
KW-3049 2 weight portions, Atorvastatin calcium 5 weight portions, Polyethylene Glycol-1,500 5 weight portions, Polyethylene Glycol-6,000 23 weight portions.
KW-3049, Atorvastatin calcium were pulverized 80 mesh sieves respectively, and adding Polyethylene Glycol-1500, Polyethylene Glycol-6000 stir evenly, and 80 ± 2 ℃ of insulations are dripped and made ball, namely.Hydrochloric benidipine 2mg contains Atorvastatin calcium 5mg in every ball.
Embodiment 23
KW-3049 2 weight portions, Atorvastatin calcium 10 weight portions, Polyethylene Glycol-4,000 5 weight portions, Polyethylene Glycol-6,000 23 weight portions.
KW-3049, Atorvastatin calcium were pulverized 80 mesh sieves respectively, add Polyethylene Glycol-4000, Polyethylene Glycol-6000, and stirred evenly, 80 ± 2 ℃ of insulations are dripped and are made ball, namely.Hydrochloric benidipine 2mg contains Atorvastatin calcium 10mg in every ball.
Embodiment 24
KW-3049 4 weight portions, Atorvastatin calcium 10 weight portions, Polyethylene Glycol-4,000 5 weight portions, Polyethylene Glycol-6,000 21 weight portions.
KW-3049, Atorvastatin calcium were pulverized 80 mesh sieves respectively, add Polyethylene Glycol-4000, Polyethylene Glycol-6000, and stirred evenly, 80 ± 2 ℃ of insulations are dripped and are made ball, namely.Hydrochloric benidipine 4 mg contain Atorvastatin calcium 10 mg in every ball.
Embodiment 25
KW-3049 4 weight portions, Atorvastatin calcium 20 weight portions, Polyethylene Glycol-6,000 21 weight portions.
KW-3049, Atorvastatin calcium were pulverized 80 mesh sieves respectively, add Polyethylene Glycol-6000, and stirred evenly, 80 ± 2 ℃ of insulations are dripped and are made ball, namely.Hydrochloric benidipine 4 mg contain Atorvastatin calcium 20 mg in every ball.
Embodiment 26
KW-3049 1 weight portion, Atorvastatin calcium 10 weight portions, Polyethylene Glycol-4,000 8 weight portions, Polyethylene Glycol-6,000 21 weight portions.
KW-3049, Atorvastatin calcium were pulverized 80 mesh sieves respectively, add Polyethylene Glycol-4000, Polyethylene Glycol-6000, and stirred evenly, 80 ± 2 ℃ of insulations are dripped and are made ball, namely.Hydrochloric benidipine 1 mg contains Atorvastatin calcium 10 mg in every ball.
Embodiment 27
KW-3049 1 weight portion, Atorvastatin calcium 20 weight portions, Polyethylene Glycol-6,000 24 weight portions.
KW-3049, Atorvastatin calcium were pulverized 80 mesh sieves respectively, add Polyethylene Glycol-6000, and stirred evenly, 80 ± 2 ℃ of insulations are dripped and are made ball, namely.Hydrochloric benidipine 1 mg contains Atorvastatin calcium 20mg in every ball.
Granule
Embodiment 28
KW-3049 1 weight portion, Atorvastatin calcium 5 weight portions, sucrose 984 weight portions, hypromellose 14 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and hypromellose is mixed with suitable concentration with purified water and makes binding agent, and is standby.KW-3049, Atorvastatin calcium and sucrose with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, are crossed 18 mesh sieves and granulated, 75 ℃ of dryings 3 hours, 18 mesh sieve granulate sieve, packing, namely.Hydrochloric benidipine 1 mg contains Atorvastatin calcium 5 mg in every bag.
Embodiment 29
KW-3049 2 weight portions, Atorvastatin calcium 10 weight portions, aspartame 20 weight portions, dextrin 968 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, standby.KW-3049, Atorvastatin calcium and dextrin with the equivalent dilution method mix homogeneously that progressively increases, with purified water soft material processed, are crossed 18 mesh sieves and granulated, 75 ℃ of dryings 3 hours, 18 mesh sieve granulate sieve, packing, namely.Hydrochloric benidipine 2mg in every bag contains Atorvastatin calcium 10 mg.
Embodiment 30
KW-3049 4 weight portions, Atorvastatin calcium 20 weight portions, aspartame 5 weight portions, hypromellose 20 weight portions, soluble starch 1971 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and hypromellose is mixed with suitable concentration with purified water and makes binding agent, and is standby.KW-3049, Atorvastatin calcium and soluble starch with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, are crossed 18 mesh sieves and granulated, 75 ℃ of dryings 3 hours, 18 mesh sieve granulate sieve, packing, namely.Hydrochloric benidipine 4mg contains Atorvastatin calcium 20mg in every bag.
Embodiment 31
KW-3049 4 weight portions, Atorvastatin calcium 40 weight portions, aspartame 5 weight portions, soluble starch 2431 weight portions, hypromellose 20 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and KW-3049, Atorvastatin calcium and sucrose with the equivalent dilution method mix homogeneously that progressively increases, with purified water preparation soft material, are crossed 18 mesh sieves and granulated, 75 ℃ of dryings 3 hours, 18 mesh sieve granulate sieve, packing, namely.Hydrochloric benidipine 4mg contains Atorvastatin calcium 40mg in every bag.
Embodiment 32
KW-3049 4 weight portions, Atorvastatin calcium 80 weight portions, aspartame 3 weight portions, dextrin 2113 weight portions, soluble starch 2800 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and KW-3049, Atorvastatin calcium and sucrose with the equivalent dilution method mix homogeneously that progressively increases, with purified water preparation soft material, are crossed 18 mesh sieves and granulated, 75 ℃ of dryings 3 hours, 18 mesh sieve granulate sieve, packing, namely.Hydrochloric benidipine 2mg in every bag contains Atorvastatin calcium 40 mg.
Embodiment 33
KW-3049 8 weight portions, Atorvastatin calcium 40 weight portions, aspartame 15 weight portions, dextrin 200 weight portions, soluble starch 737 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and KW-3049, Atorvastatin calcium and sucrose with the equivalent dilution method mix homogeneously that progressively increases, with purified water preparation soft material, are crossed 18 mesh sieves and granulated, 75 ℃ of dryings 3 hours, 18 mesh sieve granulate sieve, packing, namely.Hydrochloric benidipine 8mg contains Atorvastatin calcium 40mg in every bag.
Embodiment 34
KW-3049 8 weight portions, Atorvastatin calcium 80 weight portions, aspartame 20 weight portions, dextrin 300 weight portions, soluble starch 592 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and KW-3049, Atorvastatin calcium and sucrose with the equivalent dilution method mix homogeneously that progressively increases, with purified water preparation soft material, are crossed 18 mesh sieves and granulated, 75 ℃ of dryings 3 hours, 18 mesh sieve granulate sieve, packing, namely.Hydrochloric benidipine 1mg contains Atorvastatin calcium 10mg in every bag.
Embodiment 35
KW-3049 8 weight portions, Atorvastatin calcium 320 weight portions, aspartame 10 weight portions, dextrin 400 weight portions, soluble starch 1262 weight portions.
Raw material, adjuvant were pulverized 80 mesh sieves respectively, and KW-3049, Atorvastatin calcium and sucrose with the equivalent dilution method mix homogeneously that progressively increases, with purified water preparation soft material, are crossed 18 mesh sieves and granulated, 75 ℃ of dryings 3 hours, 18 mesh sieve granulate sieve, packing, namely.Hydrochloric benidipine 1mg contains Atorvastatin calcium 40mg in every bag.
Effective ingredient of the present invention has good therapeutical effect to hypertension, and the different choice of adjuvant mainly has influence on the dosage form of medicine, and is very little to the influence of its therapeutic effect, can ignore.Below by clinical experiment data declaration beneficial effect of the present invention, its test method and result are as follows:
1 data and method
1.1 clinical data
Dyslipidemia diagnostic criteria according to Evaluation of Diagnostic Criteria of Hypertension and the Chinese dyslipidemia guideline of prevention and treatment in 2007 of WHO/ISH1999, select outpatient service and inpatient to be 1 grade of essential hypertension or 2 grades of patients, and patient's 150 examples that merge hypercholesterolemia simultaneously, male 76 examples wherein, women 74 examples; 32～76 years old age, average (50.8 ± 7.3) year, the course of disease 1～22 year, average (12.3 ± 5.1) year.Systolic pressure (160.2 ± 9.8) mmHg when selected, diastolic pressure (96.7 ± 6.9) mmHg; Before the medication serum total cholesterol (TC) 〉=5.72 mmol/L and (or) triacylglycerol (TG) I 1.70 mmol/L.All patients sign Informed Consent Form before experiment.Through stopping using all antihypertensive drugs and to influential 1～2 week of medicine of blood pressure, blood pressure still meets inclusion criteria person is divided into 6 groups at random.All MethodsThe cases enrolled all do not have hydrochloric acid benidipine, Atorvastatin calcium contraindication and allergies, and get rid of severe cardiac, brain, kidney complication, liver, renal insufficiency person, statins taboo; Accepting the patient that statins treatment can not drug withdrawal in addition also gets rid of.The equal not statistically significants of difference such as patient's sex, age, the course of disease, classification between group (P〉0.05), have comparability.
Observation index
Diet keeps relative stability during the MethodsThe cases enrolled treatment, measures blood pressure weekly at least 4 times, and per 4 weeks are surveyed 1 blood fat, measure blood T-CHOL (TC), low-density lipoprotein cholesterol (LDL-C), blood triacylglycerol levels such as (TG).Liver function, indexs such as creatase, the not good untoward reaction person that maybe can not tolerate of blood pressure blood fat control withdraws from experiment.Observe untoward reaction during the treatment.
Therapeutic Method
Treatment group: embodiment 9 capsules, KW-3049 (Beni) 2mg/ Atorvastatin calcium (Atv) 5mg, oral, 1 time on the one, one time 1.
Matched group 1: KW-3049 (Beni) 2mg/ sheet, oral, 1 time on the one, one time 1; Atorvastatin calcium (Atv) 10mg/ sheet, oral, 1 time on the one, one time 0.5.
Matched group 2: KW-3049 (Beni) 2mg/ sheet, oral, 1 time on the one, one time 1.Treated for 8 weeks continuously.
Therapeutic evaluation
1.4.1, efficacy of antihypertensive treatment judges the curative effect of medication criterion with reference in April, 1999 whole nation cardiovascular meeting revision:
Produce effects: diastolic pressure (DBP) decline 〉=10mm Hg (1mm Hg=0.133kPa) also is down to normally, or systolic pressure (SBP) decline 〉=20mm Hg, but is not down to normal;
Effectively: DBP decline＜10mm Hg but be down to normal, or SBP 10～20mm Hg that descends;
Invalid: blood pressure drops does not reach above-mentioned standard person.
1.4.2, the hyperlipemia curative effect evaluates according to the dyslipidemia diagnostic criteria of Chinese dyslipidemia guideline of prevention and treatment in 2007:
Produce effects: lipids detection reaches following any one person.TC decline 〉=20%, TG decline 〉=40%, HDL-C rising 〉=0.26mmol/L (10mg/dL), TC-HDL-C/HDL-C descends 〉=20%;
Effectively: lipids detection reaches following any one person.TC descend 〉=10% but＜20%, TG descend 〉=20% but＜40%, HDL-C risings 〉=0.104mmol/L (4mg/dl) but＜0.26mmol/L (10mg/dL), TC-HDL-C/HDL-C decline 〉=10% but＜20%;
Invalid: lipids detection does not reach above standard person.
Effectively total=produce effects+effectively.
Date processing and statistical method
Measurement data with (
The t check is relatively adopted in ± s) expression between group; Enumeration data relatively adopts X with rate (%) expression between group
2Check.There is statistical significance P＜0.05 for difference.
Efficacy result
2.1 treatment hypertension effect
2.2 treatment hyperlipidemia effect
3, conclusion
KW-3049 has very high affinity to the vascular smooth muscle cell film, by blocking-up cell membrane potential dependent form calcium channel receptor binding site, has suppressed calcium ion and has flowed in the cell, has stoped vascular smooth muscle to shrink and distends the blood vessels.Because very slow with binding site affinity height and the speed of dissociating, thereby has hypotensive activity for a long time and slowly.
Atorvastatin calcium is the fat-reducing medicament of present clinical prescription flow control one, is generally acknowledged to have " pleiotropy ".Studies show that, except effective blood fat reducing, also have certain antihypertensive effect, can delay myocardial hypertrophy and fibrosis process simultaneously, therefore have concertedness with antihypertensive drugs in addition, use the Statins treatment for the patient of hypertensive patients dyslipidemia and can make that the patient is many-sided to be benefited.
Claims (1)
1. capsule preparations that contains KW-3049 and Atorvastatin calcium, it is characterized in that: composition is: KW-3049 2 weight portions, Atorvastatin calcium 5 weight portions, lactose 25 weight portions, microcrystalline Cellulose 20 weight portions, pregelatinized Starch 30 weight portions, carboxymethylstach sodium 15 weight portions, hypromellose 2 weight portions, magnesium stearate 1 weight portion;
Preparation method is: each composition was pulverized 80 mesh sieves respectively, and hydroxypropyl first fiber is mixed with suitable concentration with purified water and makes binding agent, and is standby; Except magnesium stearate, with other composition with the equivalent dilution method mix homogeneously that progressively increases, with the binding agent for preparing soft material processed, to cross 18 mesh sieves and granulate, 60 ℃ of dryings are abundant, 18 mesh sieve granulate, add the magnesium stearate mix homogeneously of recipe quantity, encapsulated, namely, hydrochloric benidipine 2 mg contain Atorvastatin calcium 5 mg in every.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210068311 CN102579442B (en) | 2012-03-15 | 2012-03-15 | Compound preparation containing benidipine hydrochloride and atorvastatin calcium and application for compound preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210068311 CN102579442B (en) | 2012-03-15 | 2012-03-15 | Compound preparation containing benidipine hydrochloride and atorvastatin calcium and application for compound preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102579442A CN102579442A (en) | 2012-07-18 |
| CN102579442B true CN102579442B (en) | 2013-08-28 |
Family
ID=46469051
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201210068311 Active CN102579442B (en) | 2012-03-15 | 2012-03-15 | Compound preparation containing benidipine hydrochloride and atorvastatin calcium and application for compound preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102579442B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104644666A (en) * | 2014-06-26 | 2015-05-27 | 黄心诚 | Medicine for treating coronary heart disease |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101618215A (en) * | 2009-08-16 | 2010-01-06 | 王丽燕 | Pharmaceutical composition containing calcium blocker, AII receptor blocker and statins |
-
2012
- 2012-03-15 CN CN 201210068311 patent/CN102579442B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101618215A (en) * | 2009-08-16 | 2010-01-06 | 王丽燕 | Pharmaceutical composition containing calcium blocker, AII receptor blocker and statins |
Non-Patent Citations (2)
| Title |
|---|
| 汪莉 等.贝尼地平与阿托伐他汀联合治疗对老年单纯收缩期高血压患者的抗炎症和改善血管内皮功能的作用.《中华高血压杂志》.2009,第17卷(第1期),第29-31页. |
| 贝尼地平与阿托伐他汀联合治疗对老年单纯收缩期高血压患者的抗炎症和改善血管内皮功能的作用;汪莉 等;《中华高血压杂志》;20090110;第17卷(第1期);第29-31页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102579442A (en) | 2012-07-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103006649B (en) | Compound preparation of valsartan amlodipine tablet (I) and preparation method thereof | |
| WO2011069326A1 (en) | Bilayer tablet comprising atenolol and amlodipine | |
| WO2014142607A1 (en) | Pharmaceutical combination drug | |
| CN100364532C (en) | Composition containing amlodipine and angiotensin II receptor inhibitor | |
| CN101632673B (en) | Medicinal composition containing losartan, pioglitazone and rosuvastatin and new application thereof | |
| CN107126423B (en) | Pitavastatin calcium tablet pharmaceutical composition and dry or wet preparation method thereof | |
| CN102579442B (en) | Compound preparation containing benidipine hydrochloride and atorvastatin calcium and application for compound preparation | |
| CN101653440B (en) | Treatment composition containing amlodipine series salt and pril medicament | |
| CN101632672B (en) | Compound medicinal composition for treating hypertension | |
| CN102485228B (en) | Pharmaceutical composition and purpose thereof | |
| CN101756993B (en) | Medical composition for losing weight or treating metabolic syndromes | |
| CN102755322B (en) | Compound preparation of lercanidipine and atorvastatin | |
| US20070275996A1 (en) | Use of Statins For The Treatment Of Metabolic Syndrome | |
| US20160045497A1 (en) | Complex preparation including valsartan and rosuvastatin calcium and manufacturing method therefor | |
| CN109394712A (en) | A kind of valsartan amlodipine composite tablet and preparation method thereof | |
| CN103721259A (en) | Angiotensin II receptor blocker/thiazide diuretics/5-methyltetrahydrofolate pharmaceutical composition | |
| CN102389431A (en) | Compound preparation containing benidipine hydrochloride and benazepril hydrochloride, as well as application thereof | |
| CN103800307A (en) | Medicinal composition for reducing blood pressure and preparation method thereof | |
| CN102349906B (en) | Atorvastatin calcium and nicotinic acid composition and preparation method thereof | |
| CN102475705B (en) | Medicine composition used for treating hypertension | |
| CN103272236B (en) | Medical composition and its use containing receptor,β blocker and vitamin B group | |
| CN102362865B (en) | Compound preparation containing benidipine hydrochloride and valsartan and application thereof | |
| CN102379875A (en) | Compound preparation containing benidipine hydrochloride and metoprolol tartrate and application thereof | |
| US20220079920A1 (en) | Pharmaceutical composition containing amlodipine, chlorthalidone, and amiloride and application thereof | |
| CN101590239A (en) | The medical composition and its use that contains diuretic, Ta Ting and folic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: SHANDONG HUAYANG PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: JINAN LONGHUA MEDICAL TECHNOLOGY CO., LTD. Effective date: 20130723 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| C53 | Correction of patent for invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Xu Dongsheng Inventor after: Liang Haiyong Inventor after: Chen Haixia Inventor after: Chu Maozhong Inventor after: Yang Yijuan Inventor after: Xu Yan Inventor after: Han Lili Inventor after: Ma Quanlong Inventor after: Wang Haohua Inventor after: Sun Shan Inventor before: Xu Dongsheng Inventor before: Ma Quanlong Inventor before: Wang Haohua Inventor before: Han Lili Inventor before: Sun Shan Inventor before: Liang Haiyong |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 250131 JINAN, SHANDONG PROVINCE TO: 255190 ZIBO, SHANDONG PROVINCE Free format text: CORRECT: INVENTOR; FROM: XU DONGSHENG MA QUANLONG WANG HAOHUA HAN LILI SUN SHAN LIANG HAIYONG TO: XU DONGSHENG CHEN HAIXIA CHU MAOZHONG YANG YIJUAN XU YAN HAN LILI MA QUANLONG WANG HAOHUA SUN SHAN LIANG HAIYONG |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20130723 Address after: 255190 Shandong city in Zibo province Shuangfeng science and Technology Industrial Park Applicant after: Shandong Huayang Pharmaceutical Co., Ltd. Address before: Wangsheren Street Licheng District 250131 in Shandong province Ji'nan City Daxinzhuang Village West Applicant before: Jinan Longhua Medical Technology Co., Ltd. |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20160317 Address after: 250131 No. 143-9 industrial North Road, Licheng District, Shandong, Ji'nan Patentee after: Shandong Xinbao Pharmaceutical Co.,Ltd. Address before: 255190 Shandong city in Zibo province Shuangfeng science and Technology Industrial Park Patentee before: Shandong Huayang Pharmaceutical Co., Ltd. |
|
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20120718 Assignee: JILIN SHUANGYAO PHARMACEUTICAL GROUP Co.,Ltd. Assignor: SHANDONG XINBAO PHARMACEUTICAL Co.,Ltd. Contract record no.: X2020370000010 Denomination of invention: A capsule preparation containing benidipine hydrochloride and atorvastatin calcium Granted publication date: 20130828 License type: Exclusive License Record date: 20200803 |
|
| EE01 | Entry into force of recordation of patent licensing contract | ||
| CB03 | Change of inventor or designer information |
Inventor after: Wang Haohua Inventor after: Liang Haiyong Inventor after: Xu Dongsheng Inventor after: Chen Haixia Inventor after: Chu Maozhong Inventor after: Yang Yijuan Inventor after: Xu Yan Inventor after: Han Lili Inventor after: Ma Quanlong Inventor after: Sun Shan Inventor before: Xu Dongsheng Inventor before: Liang Haiyong Inventor before: Chen Haixia Inventor before: Chu Maozhong Inventor before: Yang Yijuan Inventor before: Xu Yan Inventor before: Han Lili Inventor before: Ma Quanlong Inventor before: Wang Haohua Inventor before: Sun Shan |
|
| CB03 | Change of inventor or designer information | ||
| EC01 | Cancellation of recordation of patent licensing contract |
Assignee: JILIN SHUANGYAO PHARMACEUTICAL GROUP CO.,LTD. Assignor: SHANDONG XINBAO PHARMACEUTICAL Co.,Ltd. Contract record no.: X2020370000010 Date of cancellation: 20211028 |
|
| EC01 | Cancellation of recordation of patent licensing contract | ||
| EE01 | Entry into force of recordation of patent licensing contract | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20120718 Assignee: JILIN SHUANGYAO PHARMACEUTICAL GROUP CO.,LTD. Assignor: SHANDONG XINBAO PHARMACEUTICAL Co.,Ltd. Contract record no.: X2021980011634 Denomination of invention: The invention relates to a capsule preparation containing benidipine hydrochloride and atorvastatin calcium Granted publication date: 20130828 License type: Exclusive License Record date: 20211102 |