CN104188968A - Oral tablet for resisting high blood pressure and preparation method of oral tablet - Google Patents
Oral tablet for resisting high blood pressure and preparation method of oral tablet Download PDFInfo
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- CN104188968A CN104188968A CN201410491684.XA CN201410491684A CN104188968A CN 104188968 A CN104188968 A CN 104188968A CN 201410491684 A CN201410491684 A CN 201410491684A CN 104188968 A CN104188968 A CN 104188968A
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- telmisartan
- amlodipine besylate
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- 239000007935 oral tablet Substances 0.000 title claims abstract description 48
- 229940096978 oral tablet Drugs 0.000 title claims abstract description 48
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 206010020772 Hypertension Diseases 0.000 title abstract description 14
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 claims abstract description 219
- 239000003826 tablet Substances 0.000 claims abstract description 118
- ZPBWCRDSRKPIDG-UHFFFAOYSA-N amlodipine benzenesulfonate Chemical compound OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl ZPBWCRDSRKPIDG-UHFFFAOYSA-N 0.000 claims abstract description 111
- 239000005537 C09CA07 - Telmisartan Substances 0.000 claims abstract description 109
- 229960005187 telmisartan Drugs 0.000 claims abstract description 109
- 229960004005 amlodipine besylate Drugs 0.000 claims abstract description 108
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 78
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 72
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 68
- 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 claims abstract description 35
- 239000000600 sorbitol Substances 0.000 claims abstract description 35
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 34
- 229920000881 Modified starch Polymers 0.000 claims abstract description 34
- 229920002472 Starch Polymers 0.000 claims abstract description 34
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims abstract description 34
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 34
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 34
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 34
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 34
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 34
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 34
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 34
- 239000008107 starch Substances 0.000 claims abstract description 34
- 235000019698 starch Nutrition 0.000 claims abstract description 34
- 239000002994 raw material Substances 0.000 claims abstract description 26
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 18
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229920002261 Corn starch Polymers 0.000 claims abstract description 17
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims abstract description 17
- 239000008120 corn starch Substances 0.000 claims abstract description 17
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 17
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229960003194 meglumine Drugs 0.000 claims abstract description 17
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000000203 mixture Substances 0.000 claims description 60
- 239000008187 granular material Substances 0.000 claims description 54
- 239000011230 binding agent Substances 0.000 claims description 34
- 230000003276 anti-hypertensive effect Effects 0.000 claims description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 16
- 229960003943 hypromellose Drugs 0.000 claims description 16
- 238000010348 incorporation Methods 0.000 claims description 16
- 239000000741 silica gel Substances 0.000 claims description 16
- 229910002027 silica gel Inorganic materials 0.000 claims description 16
- 238000005469 granulation Methods 0.000 claims description 2
- 230000003179 granulation Effects 0.000 claims description 2
- 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 abstract 2
- 235000019441 ethanol Nutrition 0.000 abstract 2
- 239000011734 sodium Substances 0.000 abstract 2
- 229910052708 sodium Inorganic materials 0.000 abstract 2
- 239000000443 aerosol Substances 0.000 abstract 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 abstract 1
- WTFXARWRTYJXII-UHFFFAOYSA-N iron(2+);iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+2].[Fe+3].[Fe+3] WTFXARWRTYJXII-UHFFFAOYSA-N 0.000 abstract 1
- SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 abstract 1
- 238000004090 dissolution Methods 0.000 description 18
- 238000000034 method Methods 0.000 description 12
- 230000036772 blood pressure Effects 0.000 description 9
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- 239000002220 antihypertensive agent Substances 0.000 description 7
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- 208000024172 Cardiovascular disease Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
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- 238000004519 manufacturing process Methods 0.000 description 4
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 3
- 230000000857 drug effect Effects 0.000 description 3
- 230000001077 hypotensive effect Effects 0.000 description 3
- 229960001597 nifedipine Drugs 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 2
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 description 2
- 229940127282 angiotensin receptor antagonist Drugs 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
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- 230000001631 hypertensive effect Effects 0.000 description 2
- 208000021822 hypotensive Diseases 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000001694 spray drying Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229940043097 telmisartan and amlodipine Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 102000005862 Angiotensin II Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 102000015427 Angiotensins Human genes 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 239000002083 C09CA01 - Losartan Substances 0.000 description 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
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- 206010031127 Orthostatic hypotension Diseases 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
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- 239000000556 agonist Substances 0.000 description 1
- 229940077927 altace Drugs 0.000 description 1
- 229960000528 amlodipine Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
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- 229920001436 collagen Polymers 0.000 description 1
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- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
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- 238000003475 lamination Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 229960004773 losartan Drugs 0.000 description 1
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
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- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 229960003401 ramipril Drugs 0.000 description 1
- 239000003087 receptor blocking agent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 229960004699 valsartan Drugs 0.000 description 1
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses an oral tablet for resisting high blood pressure and a preparation method of the oral tablet. The oral tablet is a double-layer tablet and comprises a telmisartan layer and an amlodipine besylate layer, wherein the telmisartan layer is prepared from the following raw materials in parts by weight: 40 parts of telmisartan, 17-30 parts of sorbitol, 12-23 parts of meglumine, 50-68 parts of microcrystalline cellulose, 50-68 parts of pregelatinized starch, 5 parts of sodium hydroxide, 1 part of magnesium stearate, 4 parts of carboxymethyl starch sodium, 6 parts of polyvinylpyrrolidone, 10 parts of water and 10 parts of ethyl alcohol; the amlodipine besylate layer is prepared from the following raw materials in parts by weight: 5 parts of amlodipine besylate, 3-10 parts of aerosol, 6 parts of polyvinylpyrrolidone, 35-93 parts of sorbitol, 55-98 parts of corn starch, 37-102 parts of microcrystalline cellulose, 33-78 parts of pregelatinized starch, 1 part of magnesium stearate, 4-8 parts of carboxymethyl starch sodium, 90 parts of ethyl alcohol, 3 parts of hydroxypropyl methylcellulose, 0.315 part of black iron oxide and 0.002 part of yellow ferric oxide.
Description
Technical field
The present invention relates to drug world, especially relate to the research of preparing antihypertensive oral tablet with telmisartan and Amlodipine Besylate Tablet.
Background technology
Hypertension is one of common cardiovascular diseases of serious harm human health, is also the great public health problem in global range.Over nearly 50 years. the hypertensive prevalence of China is also being obvious ascendant trend always, according to the report survey data of Chinese residents nutrition in 2005 and health status, China's adult hypertension prevalence is 8.8%, estimate that national number of patients reaches 100,000,000 people, compared with 1991, prevalence has risen 31%.And report estimation according to the Chinese cardiovascular diseases of 2012, China's Prevalence of Hypertension is 11.8%, approximately has 1.5 hundred million hyperpietics.Hypertensive awareness is 33.2%, and treatment rate is 32.6%, and control rate is only 25%.There is 2/3 patient to need drug combination to control blood pressure.Most patients needs two or more medicines to make blood pressure reach target, and patient especially higher to initial blood pressure, that have target organ damage or relevant disease more needs drug combination.Except changing living habit, reducing body weight, Drug therapy is main Therapeutic Method at present.
Conventional depressor has following several types: diuretic, beta-blocker, calcium ion antagonist, converting enzyme inhibitor, angiotensin receptor antagonist, α receptor blocking agent and maincenter depressor.Wherein calcium ion antagonist comprises diltiazem, nifedipine, Amlodipine Besylate Tablet etc.Angiotensin receptor antagonist comprises losartan, valsartan, telmisartan etc.The independent treatment of antihypertensive drug of current clinical use can obtainable blood pressure lowering compliance rate less than 50%, needs drug combination for most of patients.Associating anti-hypertension treatment can obtain the Amplitude of Hypotensive similar or larger to single medicine doubling dosage with respectively less dosage, thereby greatly improves the blood pressure lowering compliance rate of anti-hypertension treatment.In the clinical trial of multiple antihypertensive drug, to light moderate hypertension patient, the blood pressure lowering compliance rate of associating antihypertensive drug all reaches more than 70%; Even to severe hyperpietic, also can obtain better curative effect, Amplitude of Hypotensive is larger, and controlling of blood pressure compliance rate is higher.Meanwhile, owing to using respectively less dosage and mechanism of drug action difference, clinical adverse incidence rate reduces, and safety and the toleration of receiving treatment for a long time significantly improve.Associating antihypertensive drug therapy should become blanket initial anti-hypertension treatment clinical strategy.
" Sha Tan " class is that angiotensin ii receptor antagonist class antihypertensive drug came out more than 10 years; because of its hypotensive effect obvious; better tolerance; especially clinical trial and follow card evidence show that it has unique curative effect and protective effect to cardiovascular disease; become one of the most general clinical antihypertensive drug; cause clinical common concern; and the adverse reaction rate such as dry cough, drug withdrawal knock-on and postural hypotension is low after prolonged application, be recommended as the line depressor with cardiovascular disease and albuminuretic hyperpietic by many treatment guides of WHO.In order to meet the demand of China market, improve people's health, significant to the further research of antihypertensive drug in conjunction with the situation of patients with hypertension.
Summary of the invention
An object of the present invention is to provide a kind of antihypertensive oral tablet, make Therapy of Patients with Hypertension successful, absorb soon, side effect is little, effectively regulates the balance of angiotensin and the feritin of human body, can effectively maintain patient's blood pressure balance and stablize; Another object is to provide a kind of method of preparing this antihypertensive oral tablet, to realizing the production that completes this oral tablet under conventional working condition.
To achieve these goals, the present invention has adopted following technical scheme.
This antihypertensive oral tablet is bilayer tablet, and it comprises telmisartan layer and Amlodipine Besylate Tablet layer; Wherein,
Described telmisartan layer is made up of the raw material of following components by weight percent: telmisartan 40, sorbitol 17-30, meglumine 12-23, microcrystalline Cellulose 50-68, pregelatinized Starch 50-68, sodium hydroxide 5, magnesium stearate 1, carboxymethyl starch receive 4, polyvinylpyrrolidone 6, water 10 and ethanol 10;
Described Amlodipine Besylate Tablet layer is made up of the raw material of following components by weight percent: Amlodipine Besylate Tablet 5, micropowder silica gel 3-10, polyvinylpyrrolidone 6, sorbitol 35-93, corn starch 55-98, microcrystalline Cellulose 37-102, pregelatinized Starch 33-78, magnesium stearate 1, carboxymethyl starch are received 4-8, ethanol 90, hypromellose 3, Black Rouge 0.315 and yellow ferric oxide 0.002.
Prepare the method for this antihypertensive oral tablet, adopt above-mentioned raw material components, comprise the steps:
(1) getting component is that meglumine 12-23 crosses 20 mesh sieves and mixs homogeneously with telmisartan 40, sorbitol 17-30, microcrystalline Cellulose 50-68, pregelatinized Starch 50-68, sodium hydroxide 5, magnesium stearate 1 and polyvinylpyrrolidone 6, incorporation time is 20-30min, obtains telmisartan layer mixture;
(2) getting component is that Amlodipine Besylate Tablet 5, micropowder silica gel 3-10, polyvinylpyrrolidone 6, sorbitol 35-93, corn starch 55-98, pregelatinized Starch 33-78, magnesium stearate 1 and carboxymethyl starch are received 4-8 mix homogeneously, incorporation time is 20-30min, obtains Amlodipine Besylate Tablet layer mixture;
(3) getting component is that hypromellose 3, ethanol 90, Black Rouge 0.315 and yellow ferric oxide 0.002 mix homogeneously obtain Amlodipine Besylate Tablet layer binding agent;
(4) getting component is that sodium hydroxide 5, water 10 and ethanol 10 obtain telmisartan layer binding agent;
(5) described telmisartan layer mixture mixed to the 20 mesh sieves telmisartan granule of granulating to obtain with telmisartan layer binding agent, described Amlodipine Besylate Tablet layer mixture and Amlodipine Besylate Tablet layer binding agent were mixed to the 20 mesh sieves Amlodipine Besylate Tablet granule of granulating to obtain;
(6) telmisartan granule is received and mixed homogeneously with carboxymethyl starch, described Amlodipine Besylate Tablet granule is mixed homogeneously with microcrystalline Cellulose, and be the composition tabletting of 239-339: 198-245 by weight proportion by mixed Amlodipine Besylate Tablet granule and telmisartan granule, obtain oral tablet.
Preferably, granulation bake out temperature, at 45-50 DEG C, and is controlled moisture in 3% in described step (5).
Preferably, in described step (6), by mixed Amlodipine Besylate Tablet granule and telmisartan granule be by weight proportion the composition tabletting of 279: 245.
Wherein, selected telmisartan is compound and the salt derivative thereof with following feature:
Chinese: telmisartan
English name: Telmisartan
Chemical name: 4 '-[(Isosorbide-5-Nitrae '-dimethyl-2 '-propyl group [2,6 '-bis--1H-benzimidazole]-1 '-yl)-methyl]-[1,1 '-dibiphenylyl]-2-carboxylic acid
Molecular formula: C33H30N4O2=514.63
Telmisartan is a kind of novel Altace Ramipril, is a species specificity angiotensin ii receptor antagonist, is used for the treatment of essential hypertension.Telmisartan AT I acceptor site without any position agonist effect, selectivity and AT I receptors bind, this combination is lasting.Other receptors, without affinity, are even comprised to AT2 and further feature AT receptor is still less also without affinity.Give 80 telmisartans at human body and almost can suppress the hypertension that Angiotensin II causes completely.Depression effect continues 24 hours, still can measure at 48 hours.
Wherein, selected Amlodipine Besylate Tablet is compound and the salt derivative thereof with following feature:
Chinese: Amlodipine Besylate Tablet
English name: Amlodipine
Chemical name: 3-ethyl-5-methyl-2-(2-ammonia ethoxymethyl)-4-(2-chlorphenyl)-Isosorbide-5-Nitrae-dihydro-6-methyl-3,5-pyridine dicarboxylate benzene sulfonate
Molecular formula: C20H25N2O5ClC6H6O3S=567.06
Amlodipine Besylate Tablet is nifedipine class calcium antagonists, the aorta contraction that suppresses calcium induction is 2 times of nifedipine, its feature is for slower with receptors bind and the speed of dissociating, therefore drug effect occurs late and the length of holding time, selectively acting to vascular smooth muscle is greater than nifedipine, and in myocardial ischemia person, this product can increase painstaking effort output and coronary flow, increase myocardial oxygen delivery and lower oxygen consumption, improving motor capacity.In addition, this product may activate ldl receptor, reduces fat in arterial wall accumulation and suppresses collagen and synthesize, thereby having arteriosclerosis effect.
Beneficial effect of the present invention:
The first, the oral tablet that the telmisartan layer of the present invention's preparation and Amlodipine Besylate Tablet lamination are made, when making telmisartan and Amlodipine Besylate Tablet more give full play to its drug effect separately, and obviously improve effect of their both stacks, this oral tablet is had the following advantages: (1) two kind of medicine has been brought into play antihypertensive synergism with different mechanisms from different perspectives, significantly reduce blood pressure, protect better target organ; (2) be conducive to take into account Other Risk Factors that patient exists with and deposit disease; (3) drug combination can reduce single pharmaceutical quantities, and the side effect relevant to dosage or untoward reaction are obviously reduced; (4) immobilised compound preparation is simplified treatment, and administration once a day can improve patient's compliance and quality of life.
The second, oral tablet of the present invention is bilayer tablet, and ground floor is Amlodipine Besylate Tablet, and the second layer is telmisartan.Existing mill run, by dry pharmaceutical aqueous solution spraying, obtains spray drying aqueous solution granule, then spray-dried granules is mixed with Sorbitol and obtains premix, then this premix and mix lubricant have been obtained to final admixture.In existing mill run technical process, use spray-drying process, need corresponding facility for granulating, this device structure complexity, expensive, the production cycle is long, has not only increased the difficulty of producing, and has also increased production cost simultaneously.In the time preparing telmisartan label, adopt fluid bed top spray granulating process, and Amlodipine Besylate Tablet pharmaceutical preparation adopts Amlodipine Besylate Tablet drug powder coating, so not only increased the difficulty of preparation process, very easily occur uniformity of dosage units problem simultaneously.Oral tablet of the present invention is double-layer tablet, and ground floor is Amlodipine Besylate Tablet layer, and adopting HPMC E50 and ethanol is binding agent, and the second layer is telmisartan layer, and adopting the mixture of sodium hydroxide, water and ethanol is binding agent.The fused property of adhesive therefor is good, has no side effect each other.Antihypertensive oral tablet of the present invention and preparation method thereof, has not only improved the efficiency of medicine disintegrate and stripping, and preparation method is easy simultaneously, and drug effect is high, has reduced production cost, has important Practical significance.
Specific implementation method
Below in conjunction with embodiment, the present invention is described in further detail, to make those skilled in the art can implement according to this with reference to description word.
Embodiment 1
This antihypertensive oral tablet is bilayer tablet, and it comprises telmisartan layer and Amlodipine Besylate Tablet layer; Wherein,
Telmisartan layer is made up of the raw material of following components by weight percent: telmisartan 40, sorbitol 17, meglumine 16.5, microcrystalline Cellulose 55, pregelatinized Starch 55, sodium hydroxide 5, magnesium stearate 1, carboxymethyl starch receive 4, polyvinylpyrrolidone 6, water 10 and ethanol 10.
Amlodipine Besylate Tablet layer is made up of the raw material of following components by weight percent: Amlodipine Besylate Tablet 5, micropowder silica gel 6, polyvinylpyrrolidone 6, sorbitol 68, corn starch 62, microcrystalline Cellulose 102, pregelatinized Starch 78, magnesium stearate 1, carboxymethyl starch receive 4, ethanol 90, hypromellose 3, Black Rouge 0.315 and yellow ferric oxide 0.002.
Adopt above-mentioned raw material components, prepare the method for this antihypertensive oral tablet, comprise the steps:
(1) getting component is that meglumine 16.5 mistake 20 mesh sieves are mixed homogeneously with telmisartan 40, sorbitol 17, microcrystalline Cellulose 55, pregelatinized Starch 55, sodium hydroxide 5, magnesium stearate 1 and polyvinylpyrrolidone 6, incorporation time is 20min, obtains telmisartan layer mixture;
(2) getting component is that Amlodipine Besylate Tablet 5, micropowder silica gel 6, polyvinylpyrrolidone 6, sorbitol 68, corn starch 62, pregelatinized Starch 78, magnesium stearate 1 and carboxymethyl starch are received 4 mix homogeneously, incorporation time is 20min, obtains Amlodipine Besylate Tablet layer mixture;
(3) getting component is that hypromellose 3, ethanol 90, Black Rouge 0.315 and yellow ferric oxide 0.002 mix homogeneously obtain Amlodipine Besylate Tablet layer binding agent;
(4) getting component is that sodium hydroxide 5, water 10 and ethanol 10 obtain telmisartan layer binding agent;
(5) described telmisartan layer mixture mixed to the 20 mesh sieves telmisartan granule of granulating to obtain with telmisartan layer binding agent, described Amlodipine Besylate Tablet layer mixture and Amlodipine Besylate Tablet layer binding agent were mixed to the 20 mesh sieves Amlodipine Besylate Tablet granule of granulating to obtain, and in granulating, bake out temperature, at 45-50 DEG C, and is controlled moisture in 3%;
(6) telmisartan granule is received and mixed homogeneously with carboxymethyl starch, described Amlodipine Besylate Tablet granule is mixed homogeneously with microcrystalline Cellulose, and the composition tabletting that is 337: 205 by weight proportion by mixed Amlodipine Besylate Tablet granule and telmisartan granule can also control hardness according to actual needs, obtain oral tablet.
Measure the disintegration of the oral tablet that is prepared into of the technical program in 37 DEG C of 900ml diluted hydrochloric acid aqueous solutions and dissolution when disintegrate completely.
Result: Amlodipine Besylate Tablet complete disintegration is 4-6 minute, dissolution when disintegrate is 93%-95% completely.Telmisartan complete disintegration is 46-52 minute, and dissolution when disintegrate is 81%-87% completely.
Embodiment 2
This antihypertensive oral tablet is bilayer tablet, and it comprises telmisartan layer and Amlodipine Besylate Tablet layer; Wherein,
Telmisartan layer is made up of the raw material of following components by weight percent: telmisartan 40, sorbitol 22, meglumine 12, microcrystalline Cellulose 60, pregelatinized Starch 60, sodium hydroxide 5, magnesium stearate 1, carboxymethyl starch receive 4, polyvinylpyrrolidone 6, water 10 and ethanol 10.
Amlodipine Besylate Tablet layer is made up of the raw material of following components by weight percent: Amlodipine Besylate Tablet 5, micropowder silica gel 10, polyvinylpyrrolidone 6, sorbitol 71, corn starch 55, microcrystalline Cellulose 98, pregelatinized Starch 78, magnesium stearate 1, carboxymethyl starch receive 4, ethanol 90, hypromellose 3, Black Rouge 0.315 and yellow ferric oxide 0.002.
Adopt above-mentioned raw material components, prepare the method for this antihypertensive oral tablet, comprise the steps:
(1) getting component is that meglumine 12 mistake 20 mesh sieves are mixed homogeneously with telmisartan 40, sorbitol 22, microcrystalline Cellulose 69, pregelatinized Starch 60, sodium hydroxide 5, magnesium stearate 1 and polyvinylpyrrolidone 6, incorporation time is 30min, obtains telmisartan layer mixture;
(2) getting component is that Amlodipine Besylate Tablet 5, micropowder silica gel 10, polyvinylpyrrolidone 6, sorbitol 71, corn starch 55, pregelatinized Starch 78, magnesium stearate 1 and carboxymethyl starch are received 4 mix homogeneously, incorporation time is 30min, obtains Amlodipine Besylate Tablet layer mixture;
(3) getting component is that hypromellose 3, ethanol 90, Black Rouge 0.315 and yellow ferric oxide 0.002 mix homogeneously obtain Amlodipine Besylate Tablet layer binding agent;
(4) getting component is that sodium hydroxide 5, water 10 and ethanol 10 obtain telmisartan layer binding agent;
(5) described telmisartan layer mixture mixed to the 20 mesh sieves telmisartan granule of granulating to obtain with telmisartan layer binding agent, described Amlodipine Besylate Tablet layer mixture and Amlodipine Besylate Tablet layer binding agent were mixed to the 20 mesh sieves Amlodipine Besylate Tablet granule of granulating to obtain, and in granulating, bake out temperature, at 45-50 DEG C, and is controlled moisture in 3%;
(6) telmisartan granule is received and mixed homogeneously with carboxymethyl starch, described Amlodipine Besylate Tablet granule is mixed homogeneously with microcrystalline Cellulose, and the composition tabletting that is 339: 215 by weight proportion by mixed Amlodipine Besylate Tablet granule and telmisartan granule can also control hardness according to actual needs, obtain oral tablet.
Measure the disintegration of the oral tablet that is prepared into of the technical program in 37 DEG C of 900ml diluted hydrochloric acid aqueous solutions and dissolution when disintegrate completely.
Result: Amlodipine Besylate Tablet complete disintegration is 5-8 minute, dissolution when disintegrate is 85%-91% completely.Telmisartan complete disintegration is 42-46 minute, and dissolution when disintegrate is 80%-85% completely.
Embodiment 3
This antihypertensive oral tablet is bilayer tablet, and it comprises telmisartan layer and Amlodipine Besylate Tablet layer; Wherein,
Telmisartan layer is made up of the raw material of following components by weight percent: telmisartan 40, sorbitol 22, meglumine 16.5, microcrystalline Cellulose 50, pregelatinized Starch 50, sodium hydroxide 5, magnesium stearate 1, carboxymethyl starch receive 4, polyvinylpyrrolidone 6, water 10 and ethanol 10.
Amlodipine Besylate Tablet layer is made up of the raw material of following components by weight percent: Amlodipine Besylate Tablet 5, micropowder silica gel 9, polyvinylpyrrolidone 6, sorbitol 93, corn starch 60, microcrystalline Cellulose 37, pregelatinized Starch 33, magnesium stearate 1, carboxymethyl starch receive 4, ethanol 90, hypromellose 3, Black Rouge 0.315 and yellow ferric oxide 0.002.
Adopt above-mentioned raw material components, prepare the method for this antihypertensive oral tablet, comprise the steps:
(1) getting component is that meglumine 16.5 mistake 20 mesh sieves are mixed homogeneously with telmisartan 40, sorbitol 22, microcrystalline Cellulose 50, pregelatinized Starch 50, sodium hydroxide 5, magnesium stearate 1 and polyvinylpyrrolidone 6, incorporation time is 25min, obtains telmisartan layer mixture;
(2) getting component is that Amlodipine Besylate Tablet 5, micropowder silica gel 9, polyvinylpyrrolidone 6, sorbitol 93, corn starch 60, pregelatinized Starch 33, magnesium stearate 1 and carboxymethyl starch are received 4 mix homogeneously, incorporation time is 20min, obtains Amlodipine Besylate Tablet layer mixture;
(3) getting component is that hypromellose 3, ethanol 90, Black Rouge 0.315 and yellow ferric oxide 0.002 mix homogeneously obtain Amlodipine Besylate Tablet layer binding agent;
(4) getting component is that sodium hydroxide 5, water 10 and ethanol 10 obtain telmisartan layer binding agent;
(5) described telmisartan layer mixture mixed to the 20 mesh sieves telmisartan granule of granulating to obtain with telmisartan layer binding agent, described Amlodipine Besylate Tablet layer mixture and Amlodipine Besylate Tablet layer binding agent were mixed to the 20 mesh sieves Amlodipine Besylate Tablet granule of granulating to obtain;
(6) telmisartan granule is received and mixed homogeneously with carboxymethyl starch, described Amlodipine Besylate Tablet granule is mixed homogeneously with microcrystalline Cellulose, and the composition tabletting that is 255: 199 by weight proportion by mixed Amlodipine Besylate Tablet granule and telmisartan granule can also control hardness according to actual needs, obtain oral tablet.
Measure the disintegration of the oral tablet that is prepared into of the technical program in 37 DEG C of 900ml diluted hydrochloric acid aqueous solutions and dissolution when disintegrate completely.
Result: Amlodipine Besylate Tablet complete disintegration is 10-13 minute, dissolution when disintegrate is 83%-86% completely.Telmisartan complete disintegration is 41-45 minute, and dissolution when disintegrate is 75%-81% completely.
Embodiment 4
This antihypertensive oral tablet is bilayer tablet, and it comprises telmisartan layer and Amlodipine Besylate Tablet layer; Wherein,
Telmisartan layer is made up of the raw material of following components by weight percent: telmisartan 40, sorbitol 20, meglumine 18, microcrystalline Cellulose 50, pregelatinized Starch 50, sodium hydroxide 5, magnesium stearate 1, carboxymethyl starch receive 4, polyvinylpyrrolidone 6, water 10 and ethanol 10.
Amlodipine Besylate Tablet layer is made up of the raw material of following components by weight percent: Amlodipine Besylate Tablet 5, micropowder silica gel 10, polyvinylpyrrolidone 6, sorbitol 35, corn starch 93, microcrystalline Cellulose 37, pregelatinized Starch 33, magnesium stearate 1, carboxymethyl starch receive 8, ethanol 90, hypromellose 3, Black Rouge 0.315 and yellow ferric oxide 0.002.
Adopt above-mentioned raw material components, prepare the method for this antihypertensive oral tablet, comprise the steps:
(1) getting component is that meglumine 18 mistake 20 mesh sieves are mixed homogeneously with telmisartan 40, sorbitol 20, microcrystalline Cellulose 50, pregelatinized Starch 50, sodium hydroxide 5, magnesium stearate 1 and polyvinylpyrrolidone 6, incorporation time is 30min, obtains telmisartan layer mixture;
(2) getting component is that Amlodipine Besylate Tablet 5, micropowder silica gel 10, polyvinylpyrrolidone 6, sorbitol 35, corn starch 93, pregelatinized Starch 33, magnesium stearate 1 and carboxymethyl starch are received 8 mix homogeneously, incorporation time is 30min, obtains Amlodipine Besylate Tablet layer mixture;
(3) getting component is that hypromellose 3, ethanol 90, Black Rouge 0.315 and yellow ferric oxide 0.002 mix homogeneously obtain Amlodipine Besylate Tablet layer binding agent;
(4) getting component is that sodium hydroxide 5, water 10 and ethanol 10 obtain telmisartan layer binding agent;
(5) described telmisartan layer mixture mixed to the 20 mesh sieves telmisartan granule of granulating to obtain with telmisartan layer binding agent, described Amlodipine Besylate Tablet layer mixture and Amlodipine Besylate Tablet layer binding agent were mixed to the 20 mesh sieves Amlodipine Besylate Tablet granule of granulating to obtain, and in granulating, bake out temperature, at 45-50 DEG C, and is controlled moisture in 3%;
(6) telmisartan granule is received and mixed homogeneously with carboxymethyl starch, described Amlodipine Besylate Tablet granule is mixed homogeneously with microcrystalline Cellulose, and be the composition tabletting of 239: 198 by weight proportion by mixed Amlodipine Besylate Tablet granule and telmisartan granule, obtain oral tablet.
Measure the disintegration of the oral tablet that is prepared into of the technical program in 37 DEG C of 900ml diluted hydrochloric acid aqueous solutions and dissolution when disintegrate completely.
Result: Amlodipine Besylate Tablet complete disintegration is 12-15 minute, dissolution when disintegrate is 75%-82% completely.Telmisartan complete disintegration is 48-53 minute, and dissolution when disintegrate is 83%-87% completely.
Embodiment 5
This antihypertensive oral tablet is bilayer tablet, and it comprises telmisartan layer and Amlodipine Besylate Tablet layer; Wherein,
Telmisartan layer is made up of the raw material of following components by weight percent: telmisartan 40, sorbitol 30, meglumine 16, microcrystalline Cellulose 68, pregelatinized Starch 68, sodium hydroxide 5, magnesium stearate 1, carboxymethyl starch receive 4, polyvinylpyrrolidone 6, water 10 and ethanol 10.
Amlodipine Besylate Tablet layer is made up of the raw material of following components by weight percent: Amlodipine Besylate Tablet 5, micropowder silica gel 10, polyvinylpyrrolidone 6, sorbitol 82, corn starch 93, microcrystalline Cellulose 37, pregelatinized Starch 33, magnesium stearate 1, carboxymethyl starch receive 4, ethanol 90, hypromellose 3, Black Rouge 0.315 and yellow ferric oxide 0.002.
Adopt above-mentioned raw material components, prepare the method for this antihypertensive oral tablet, comprise the steps:
(1) getting component is that meglumine 16 mistake 20 mesh sieves are mixed homogeneously with telmisartan 40, sorbitol 30, microcrystalline Cellulose 68, pregelatinized Starch 68, sodium hydroxide 5, magnesium stearate 1 and polyvinylpyrrolidone 6, incorporation time is 30min, obtains telmisartan layer mixture;
(2) getting component is that Amlodipine Besylate Tablet 5, micropowder silica gel 10, polyvinylpyrrolidone 6, sorbitol 82, corn starch 93, pregelatinized Starch 33, magnesium stearate 1 and carboxymethyl starch are received 4 mix homogeneously, incorporation time is 30min, obtains Amlodipine Besylate Tablet layer mixture;
(3) getting component is that hypromellose 3, ethanol 90, Black Rouge 0.315 and yellow ferric oxide 0.002 mix homogeneously obtain Amlodipine Besylate Tablet layer binding agent;
(4) getting component is that sodium hydroxide 5, water 10 and ethanol 10 obtain telmisartan layer binding agent;
(5) described telmisartan layer mixture mixed to the 20 mesh sieves telmisartan granule of granulating to obtain with telmisartan layer binding agent, described Amlodipine Besylate Tablet layer mixture and Amlodipine Besylate Tablet layer binding agent were mixed to the 20 mesh sieves Amlodipine Besylate Tablet granule of granulating to obtain, and in granulating, bake out temperature, at 45-50 DEG C, and is controlled moisture in 3%;
(6) telmisartan granule is received and mixed homogeneously with carboxymethyl starch, described Amlodipine Besylate Tablet granule is mixed homogeneously with microcrystalline Cellulose, and the composition tabletting that is 279: 245 by weight proportion by mixed Amlodipine Besylate Tablet granule and telmisartan granule can also control hardness according to actual needs, obtain oral tablet.
Measure the disintegration of the oral tablet that is prepared into of the technical program in 37 DEG C of 900ml diluted hydrochloric acid aqueous solutions and dissolution when disintegrate completely.
Result: Amlodipine Besylate Tablet complete disintegration is 5-8 minute, dissolution when disintegrate is 92%-96% completely.Telmisartan complete disintegration is 45-49 minute, and dissolution when disintegrate is 84%-90% completely.
Embodiment 6
This antihypertensive oral tablet is bilayer tablet, and it comprises telmisartan layer and Amlodipine Besylate Tablet layer; Wherein,
Telmisartan layer is made up of the raw material of following components by weight percent: telmisartan 40, sorbitol 26, meglumine 23, microcrystalline Cellulose 66, pregelatinized Starch 66, sodium hydroxide 5, magnesium stearate 1, carboxymethyl starch receive 4, polyvinylpyrrolidone 6, water 10 and ethanol 10.
Amlodipine Besylate Tablet layer is made up of the raw material of following components by weight percent: Amlodipine Besylate Tablet 5, micropowder silica gel 3, polyvinylpyrrolidone 6, sorbitol 81, corn starch 98, microcrystalline Cellulose 39, pregelatinized Starch 35, magnesium stearate 1, carboxymethyl starch receive 4, ethanol 90, hypromellose 3, Black Rouge 0.315 and yellow ferric oxide 0.002.
Adopt above-mentioned raw material components, prepare the method for this antihypertensive oral tablet, comprise the steps:
(1) getting component is that meglumine 23 mistake 20 mesh sieves are mixed homogeneously with telmisartan 40, sorbitol 26, microcrystalline Cellulose 66, pregelatinized Starch 66, sodium hydroxide 5, magnesium stearate 1 and polyvinylpyrrolidone 6, incorporation time is 20min, obtains telmisartan layer mixture;
(2) getting component is that Amlodipine Besylate Tablet 5, micropowder silica gel 3, polyvinylpyrrolidone 6, sorbitol 81, corn starch 98, pregelatinized Starch 35, magnesium stearate 1 and carboxymethyl starch are received 4 mix homogeneously, incorporation time is 30min, obtains Amlodipine Besylate Tablet layer mixture;
(3) getting component is that hypromellose 3, ethanol 90, Black Rouge 0.315 and yellow ferric oxide 0.002 mix homogeneously obtain Amlodipine Besylate Tablet layer binding agent;
(4) getting component is that sodium hydroxide 5, water 10 and ethanol 10 obtain telmisartan layer binding agent;
(5) described telmisartan layer mixture mixed to the 20 mesh sieves telmisartan granule of granulating to obtain with telmisartan layer binding agent, described Amlodipine Besylate Tablet layer mixture and Amlodipine Besylate Tablet layer binding agent were mixed to the 20 mesh sieves Amlodipine Besylate Tablet granule of granulating to obtain, and in granulating, bake out temperature, at 45-50 DEG C, and is controlled moisture in 3%;
(6) telmisartan granule is received and mixed homogeneously with carboxymethyl starch, described Amlodipine Besylate Tablet granule is mixed homogeneously with microcrystalline Cellulose, and the composition tabletting that is 280: 244 by weight proportion by mixed Amlodipine Besylate Tablet granule and telmisartan granule can also control hardness according to actual needs, obtain oral tablet.
Measure the disintegration of the oral tablet that is prepared into of the technical program in 37 DEG C of 900ml diluted hydrochloric acid aqueous solutions and dissolution when disintegrate completely.
Result: Amlodipine Besylate Tablet complete disintegration is 5-7 minute, dissolution when disintegrate is 92%-95% completely.Telmisartan complete disintegration is 41-46 minute, and dissolution when disintegrate is 82%-86% completely.
Although embodiment of the present invention are open as above, but it is not restricted to listed utilization in description and embodiment, it can be applied to various applicable the field of the invention completely, for those skilled in the art, can easily realize other amendment, therefore do not deviating under the general concept that claim and equivalency range limit, the present invention is not limited to specific details.
Claims (4)
1. an antihypertensive oral tablet, is characterized in that, described oral tablet is bilayer tablet, and it comprises telmisartan layer and Amlodipine Besylate Tablet layer; Wherein,
Described telmisartan layer is made up of the raw material of following components by weight percent: telmisartan 40, sorbitol 17-30, meglumine 12-23, microcrystalline Cellulose 50-68, pregelatinized Starch 50-68, sodium hydroxide 5, magnesium stearate 1, carboxymethyl starch receive 4, polyvinylpyrrolidone 6, water 10 and ethanol 10;
Described Amlodipine Besylate Tablet layer is made up of the raw material of following components by weight percent: Amlodipine Besylate Tablet 5, micropowder silica gel 3-10, polyvinylpyrrolidone 6, sorbitol 35-93, corn starch 55-98, microcrystalline Cellulose 37-102, pregelatinized Starch 33-78, magnesium stearate 1, carboxymethyl starch are received 4-8, ethanol 90, hypromellose 3, Black Rouge 0.315 and yellow ferric oxide 0.002.
2. a preparation method for antihypertensive oral tablet, is characterized in that, adopts raw material components as claimed in claim 1, comprises the steps:
(1) getting component is that meglumine 12-23 crosses 20 mesh sieves and mixs homogeneously with telmisartan 40, sorbitol 17-30, microcrystalline Cellulose 50-68, pregelatinized Starch 50-68, sodium hydroxide 5, magnesium stearate 1 and polyvinylpyrrolidone 6, incorporation time is 20-30min, obtains telmisartan layer mixture;
(2) getting component is that Amlodipine Besylate Tablet 5, micropowder silica gel 3-10, polyvinylpyrrolidone 6, sorbitol 35-93, corn starch 55-98, pregelatinized Starch 33-78, magnesium stearate 1 and carboxymethyl starch are received 4-8 mix homogeneously, incorporation time is 20-30min, obtains Amlodipine Besylate Tablet layer mixture;
(3) getting component is that hypromellose 3, ethanol 90, Black Rouge 0.315 and yellow ferric oxide 0.002 mix homogeneously obtain Amlodipine Besylate Tablet layer binding agent;
(4) getting component is that sodium hydroxide 5, water 10 and ethanol 10 obtain telmisartan layer binding agent;
(5) described telmisartan layer mixture mixed to the 20 mesh sieves telmisartan granule of granulating to obtain with telmisartan layer binding agent, described Amlodipine Besylate Tablet layer mixture and Amlodipine Besylate Tablet layer binding agent were mixed to the 20 mesh sieves Amlodipine Besylate Tablet granule of granulating to obtain;
(6) telmisartan granule is received and mixed homogeneously with carboxymethyl starch, described Amlodipine Besylate Tablet granule is mixed homogeneously with microcrystalline Cellulose, and be the composition tabletting of 239-339: 198-245 by weight proportion by mixed Amlodipine Besylate Tablet granule and telmisartan granule, obtain oral tablet.
3. the preparation method of antihypertensive oral tablet according to claim 2, is characterized in that, in described step (5), granulation bake out temperature, at 45-50 DEG C, and is controlled moisture in 3%.
4. the preparation method of antihypertensive oral tablet according to claim 2, is characterized in that, is the composition tabletting of 279: 245 in described step (6) by mixed Amlodipine Besylate Tablet granule and telmisartan granule by weight proportion.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106619552A (en) * | 2017-01-04 | 2017-05-10 | 北京汇诚瑞祥医药技术有限公司 | Telmisartan-amlodipine rapid-release tablet and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101052381A (en) * | 2004-11-05 | 2007-10-10 | 贝林格尔·英格海姆国际有限公司 | Bilayer tablet comprising telmisartan and amlodipine |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101052381A (en) * | 2004-11-05 | 2007-10-10 | 贝林格尔·英格海姆国际有限公司 | Bilayer tablet comprising telmisartan and amlodipine |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106619552A (en) * | 2017-01-04 | 2017-05-10 | 北京汇诚瑞祥医药技术有限公司 | Telmisartan-amlodipine rapid-release tablet and preparation method thereof |
| CN106619552B (en) * | 2017-01-04 | 2018-05-25 | 北京汇诚瑞祥医药技术有限公司 | A kind of telmisartan amlodipine fast-release tablet and preparation method thereof |
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