CN105853418A - Composition containing levorotatory amlodipine and azilsartan - Google Patents

Composition containing levorotatory amlodipine and azilsartan Download PDF

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Publication number
CN105853418A
CN105853418A CN201610340421.8A CN201610340421A CN105853418A CN 105853418 A CN105853418 A CN 105853418A CN 201610340421 A CN201610340421 A CN 201610340421A CN 105853418 A CN105853418 A CN 105853418A
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azilsartan
levamlodipine
medicine composition
acceptable salt
pharmacy acceptable
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安日明
唐飞宇
廖文胜
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SHANGHAI STEPPHARM Co Ltd
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SHANGHAI STEPPHARM Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4245—Oxadiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to a pharmaceutical composition preparation of azilsartan and levorotatory amlodipine or medically-acceptable salt of azilsartan and levorotatory amlodipine and a preparing method of the pharmaceutical composition preparation. The pharmaceutical composition preparation is prepped from azilsartan and levorotatory amlodipine or medically-acceptable salt of azilsartan and levorotatory, and pharmaceutical auxiliaries. The pharmaceutical composition preparation is prepared with the technology combining wet granulation and dry granulation. The preparation is good in dissolution rate, stable and controllable in formulation and process and suitable for industrial production.

Description

Containing levamlodipine and the composition of Azilsartan
Technical field
The invention belongs to field of pharmaceutical preparations, specially relate to one and contain Azilsartan and levamlodipine or its medicine Learn composite preparation of acceptable salt and preparation method thereof.
Background technology
" Chinese residents nourishment and chronic disease status report (2015) " display of up-to-date issue, China in 2012 18 years old and with Upper prevalence of hypertension rate is 25.2%, and the male sex is higher than women, and city is higher than rural area, estimates that current China adult hypertension is suffered from Person is about 2.6 hundred million.Risk Factors of Hypertension (as smoking, excessive consumption of alcohol, high salt and high lipid food absorption, Underactivity, overweight and Fat and T-CHOL rises high) generally exist in crowd, and constantly raise or high, become hypertension, cardiac muscle The potential threat of the cardiovascular and cerebrovascular disease such as infarct and palsy.Hypertension drug combination is a weight of hypertensive patients Want principle.An external meta-analysis result show, double treatment with list pharmaceutical quantities compared with, two kind not same-actions are used in combination The antihypertensive drugs of mechanism will bring more preferable efficacy of antihypertensive treatment, and the hospital drug for hypertension of research report different stage is combined to be made It is up to 52.86%～80.6% by ratio.But, compared with drug combination, it is complementary that anti-hypertension compound medicine has Hypotensive Mechanism, Improve efficacy of antihypertensive treatment and/or alleviate bad reaction, improving the advantages such as patient compliance.
Azilsartan is a kind of Angiotensin II ARBs (ARB), by blocking Angiotensin II and blood vessel Pressurization functions of hormones reduces blood pressure.First Azilsartan is developed by Takede Chemical Industries Ltd, in January, 2012 Ah Qi Shatan sheet gets the Green Light listing in Japan, is used for treating hypertension, trade name Azilva.Specification is: 10mg, 20mg, 40mg.Azilsartan is compared with similar drugs Valsartan, Olmesartan and Candesartan, and antihypertensive effect is higher.Renal insufficiency Patient dosages need not adjust, for a new generation sartans.Therefore, this product has wide clinical value.
Levamlodipine besylate (L-amlodipine Besylate) chemical name is: (-) 3-ethyl-5-methyl- 2-(2-ammonia ethoxymethyl)-4-(2-chlorphenyl)-Isosorbide-5-Nitrae-dihydro-6-methyl-3,5-pyridine dicarboxylate benzene sulfonate, by Jilin It wind pharmacy is developed.It is applicable to hypertension (alone or drug combination), angina pectoris (especially spontaneous angina pectoris, the coronary heart disease heart Angina；Individually or merge use with other drug).As the levo-enantiomer of Amlodipine, it not only has Amlodipine Good and lasting hypotensive effect, simultaneously as eliminate inactive R(+)-AMLODIPINE and decrease sending out of its bad reaction Raw；And its calcium antagonistic activity is 2 times of Amlodipine, pharmacodynamic study finds, it can substantially reduce arterial pressure, strengthens coronary artery CBF, improves myocardial blood supply.Clinical research is reported, levamlodipine can disturb the reactivity of vascular smooth muscle, thus subtract Light adrenergic and the pressurization of non-adrenergic vaso-excitor material thing, with α 1, alpha-2 receptor effect slowly, it is lasting to produce Hypotensive effect, effectively controls blood pressure, reaches more than 24h, and every day only need to take 1 time, and compliance is good, decreases because of common calcium antagonist peak The side effect that value is high and produces.A large amount of clinical effectivenesses show, this medicine antihypertensive effect is definite, and continued smooth, long action time, to blood Have no adverse effects with routine urinalysis, liver and renal function, blood sugar, blood fat.Medication dose is only the half of Amlodipine, and security is good, Adverse reaction rate is low and mild degree, is one of first-selected medicine clinically.
A kind of containing Azilsartan and levamlodipine or the composite preparation of its pharmacy acceptable salt, use mesh Big hypotensor, i.e. calcium ion antagonist and the Angiotensin II ARBs of first two clinical application widest two (ARB) being combined into compound preparation, Hypotensive Mechanism is complementary, improves efficacy of antihypertensive treatment, improves patient compliance, reduce bad reaction.
Azilsartan is water insoluble, and for insoluble drug, insoluble drug is when making pharmaceutical preparation, and it is special to generally require Mode process, improve its external dissolution rate, and this specially treated mode easily affect the security of active component.
Use wet granulation after being mixed by Azilsartan with auxiliary material, it is ensured that the dissolution rate of Azilsartan；Use benzene sulphur Acid levamlodipine mix with auxiliary material after dry granulation, it is to avoid because of the damp and hot impurity increase caused of wet granulation.
The present invention through substantial amounts of prescription screening test and technical study investigate, determined by formulation and technology have higher Stability and preferably dissolution rate, each quality index all meets regulation, is suitable for industrialized production.
Present invention process is stablized controlled, and feasibility is high, is more suitable for the life of Azilsartan Levamlodipine beaylate tablets Produce and clinical practice.
Summary of the invention
The invention provides a kind of containing Azilsartan and levamlodipine or the combination of its pharmacy acceptable salt Thing preparation, the prescription of said composition preparation by Azilsartan, levamlodipine or its pharmacy acceptable salt, filler, Disintegrant, adhesive and lubricant composition.
Described Azilsartan accounts for the 4%～18% of per unit composite preparation gross weight.
Described levamlodipine or its pharmacy acceptable salt account for the 0.5% of per unit composite preparation gross weight ～2.2%.
The weight ratio of described Azilsartan and levamlodipine or its pharmacy acceptable salt should be 4～16:1.
Described filler is lactose, mannitol, one or more of starch and microcrystalline cellulose.Wherein lactose accounts for every list The 15%～40% of hyte compound total formulation weight amount；Wherein mannitol accounts for the 8%～18% of per unit composite preparation gross weight；Wherein Starch accounts for the 7%～12% of per unit composite preparation gross weight；Wherein microcrystalline cellulose accounts for per unit composite preparation gross weight 6%～35%.
Described disintegrant is one or more of low-substituted hydroxypropyl cellulose and calcium carboxymethylcellulose.The lowest replacement Hydroxypropylcellulose accounts for the 4%～14% of per unit composite preparation gross weight；Wherein calcium carboxymethylcellulose accounts for per unit composition The 4%～12% of total formulation weight amount.
Described adhesive is hydroxypropylcellulose.Wherein hydroxypropylcellulose accounts for the 1.5% of per unit composite preparation gross weight ～2.5%.
Described lubricant is magnesium stearate.Wherein magnesium stearate account for per unit composite preparation gross weight 0.8%～ 1.6%。
Of the present invention a kind of containing Azilsartan and levamlodipine or the medicine of its pharmacy acceptable salt The preparation method of combination preparation comprises the steps to be divided into five steps:
(1) Azilsartan and levamlodipine or its pharmacy acceptable salt are pulverized respectively；
(2) weigh the Azilsartan after pulverizing and carry out wet granulation, obtain Azilsartan wet granular；
(3) Azilsartan wet granular is dried, and crosses the 18 whole grains of mesh sieve, obtain Azilsartan particle；
(4) weigh the levamlodipine after pulverizing or its pharmacy acceptable salt carries out dry granulation, obtain left-handed ammonia chlorine Horizon or its pharmacy acceptable salt particle；
(5) by Azilsartan particle and levamlodipine or the mixing of its pharmacy acceptable salt particle, add lubricant, enter Row is total mixed, compressing tablet.
Azilsartan D after pulverizing in the preparation method of described medicine composition90Less than 10 μm.
Below by way of conceptual design and prescription screening, the present invention is described.
The composite preparation of Azilsartan and levamlodipine or its pharmacy acceptable salt is a kind of for treating The compound preparation of hypertension.Said preparation is when Formulation, and selecting lactose, mannitol, starch and microcrystalline cellulose is filler, Low-substituted hydroxypropyl cellulose and calcium carboxymethylcellulose are disintegrant, and magnesium stearate is lubricant, use solid pharmaceutical preparation granulation work Wet granulation the most conventional in skill and dry granulation process combine, compressing tablet and obtain.Investigate each auxiliary material during prescription screening to use Amount, and it is good and bad to evaluate prescription using element sheet proterties, sheet hardness, angle of repose, moisture, stripping curve etc. as Key Quality Indicator.
In the investigation of technique, owing to Azilsartan is practically insoluble in water, therefore it is the most molten to obtain to need to reduce its particle diameter Go out and bioavilability.Preparing sample by the bulk drug of screening different-grain diameter, the method investigating dissolution rate determines bulk drug Size controlling scope.Finally determining, needing Azilsartan micronization processes, Levamlodipine besylate pulverized 100 Mesh sieve processes.
Accompanying drawing explanation
The present invention is introduced, wherein below in conjunction with the drawings and specific embodiments:
Fig. 1 is embodiment 1-5 and comparative example 1-3 Azilsartan stripping curve figure；
Fig. 2 is embodiment 1-5 and comparative example 1-3 Levamlodipine Besylate stripping curve figure；
Fig. 3 is embodiment 1 and comparative example 5 Azilsartan stripping curve figure.
Detailed description of the invention
Below by specific embodiment, the present invention is described, below in an example, the various mistakes not described in detail Journey and method are conventional methods as known in the art.Should correct understanding, embodiments of the invention illustrate that this Invent and make rather than limitation of the present invention, so the simple of the present invention being transformed also under the method premise of the present invention Belong to the scope of the present invention.
Owing to the active constituents of medicine of levamlodipine or the therapeutic action of its pharmacy acceptable salt is identical, because of This, in the following example, levamlodipine can be understood as levamlodipine or its pharmacy acceptable salt.
Embodiments of the invention 1-6 and comparative example 1-5 further illustrate the beneficial effect of present composition preparation.
The preparation of the medicine composition of embodiment 1-5 and comparative example 1-3.
The prescription of embodiment 1-5 medicine composition, is shown in Table 1.
Composition/(g) Embodiment 1 Embodiment 2 Embodiment 3 Embodiment 4 Embodiment 5
Azilsartan 20 20 20 10 40
Levamlodipine 2.5 2.5 2.5 2.5 2.5
Lactose 81.5 18 75 81.5 81.5
Mannitol 40 10 70 40 40
Starch 25 9 43 25 25
Microcrystalline cellulose 35 36 150 45 15
Hydroxypropylcellulose 4 1.5 10 4 4
Low-substituted hydroxypropyl cellulose 10 11 63 10 10
Calcium carboxymethylcellulose 10 6 55 10 10
Magnesium stearate 2 1 7.5 2 2
Make/(sheet) altogether 1000 1000 1000 20 20
The prescription of comparative example 1-3 medicine composition, is shown in Table 2.
Composition/(g) Comparative example 1 Comparative example 2 Comparative example 3
Azilsartan 20 20 20
Levamlodipine 2.5 2.5 2.5
Lactose 11.5 131.5 27
Mannitol 9 65.5 10
Starch 5 196 8.5
Microcrystalline cellulose 23 263 9
Hydroxypropylcellulose 4 11.5 1
Low-substituted hydroxypropyl cellulose 10 80 5
Calcium carboxymethylcellulose 10 41 5
Magnesium stearate 2 9 2
Make/(sheet) altogether 1000 1000 1000
Concrete technology: by Azilsartan air-flow crushing, controlling air pressure is 0.3～0.8MPa so that it is particle diameter D90 is less than 10 μ M, is weighed micronized Azilsartan by recipe quantity, with the lactose of recipe quantity, microcrystalline cellulose, starch, hydroxypropylcellulose, low Replacing the calcium carboxymethylcellulose of hydroxypropylcellulose and 1/2 recipe quantity and mixed 30 mesh sieves in wet granulator, 600rpm stirs Mix 10 minutes, add appropriate purified water, stir 600rpm, shear 2000rpm, pelletize 2 minutes.Cross 24 mesh sieves wet whole, do for 60 DEG C Dry is 0.5%～4.0% to moisture, crosses the 20 whole grains of mesh sieve, obtains particle A.Levamlodipine besylate was pulverized 100 mesh Sieve, weighs the Levamlodipine besylate of recipe quantity, mannitol, starch, the calcium carboxymethylcellulose of 1/2 recipe quantity and 1/2 The magnesium stearate of recipe quantity, mixes in three-dimensional mixer.Add in dry granulating machine and pelletize, obtain particle B.By particle A and particle B adds in mixer, adds remaining magnesium stearate, mixes, compressing tablet.
Embodiment 1-5 and comparative example 1-3 investigate result, are shown in Table 3.
Investigate item Embodiment 1 Embodiment 2 Embodiment 3 Embodiment 4 Embodiment 5 Comparative example 1 Comparative example 2 Comparative example 3
Angle of repose 35.3° 34.9° 35.5° 34.8° 35.4° 37.9° 36.3° 35.4°
Element sheet outward appearance Smooth rounding, look Pool is homogeneous Smooth rounding, look Pool is homogeneous Smooth rounding, look Pool is homogeneous Smooth rounding, look Pool is homogeneous Smooth rounding, look Pool is homogeneous Smooth rounding, look Pool is homogeneous Smooth rounding, look Pool is homogeneous Smooth rounding, Color and luster is homogeneous
Hardness 76.29N 63.43N 123.94N 79.34N 78.98N 33.45N 53.16N 71.16N
Friability 0.1% 0.1% 0.2% 0.1% 0.1% 0.6% 2.1%, sheet defect 0.4%
Moisture (%) 2.17 2.39 2.19 2.22 2.19 2.56 4.59 3.08
0 day maximum single miscellaneous (%) 0.06 0.07 0.06 0.07 0.07 0.07 0.06 0.13
0 day (%) the most miscellaneous 0.28 0.29 0.28 0.29 0.28 0.28 0.29 0.43
Accelerate maximum list in June Miscellaneous (%) 0.12 0.13 0.12 0.11 0.12 0.14 0.13 0.49
Accelerate June the most miscellaneous (%) 0.43 0.41 0.43 0.40 0.41 0.46 0.48 0.97
Azilsartan dissolution Degree (%) 99 100 100 100 95 27 39 41
Levamlodipine Dissolution rate (%) 97 98 99 99 100 83 80 82
In table 3, angle of repose test uses the BT-1000 powder tester for overall characteristic of Dandong Bai Te Instrument Ltd. to enter Row detection.
From Fig. 1 and Fig. 2, can be seen that the dissolution rate of embodiment 1-5 Azilsartan and levamlodipine is the most right Ratio 1-3.
Comparative example 4: prescription, with reference to embodiment 1, uses wet granulation technology to prepare Levamlodipine besylate particle.
Embodiment 1 and comparative example 4 investigate result, are shown in Table 4.
Investigate item Embodiment 1 Comparative example 4
Angle of repose 35.3° 37.6°
Element sheet outward appearance Smooth rounding, color and luster is homogeneous Smooth rounding, color and luster is homogeneous
Hardness 76.29N 49.38N
Friability 0.1% 0.7%
Moisture (%) 2.17 3.08
0 day maximum single miscellaneous (%) 0.06 0.23
0 day (%) the most miscellaneous 0.28 0.56
Accelerate maximum list in June miscellaneous (%) 0.12 0.79
Accelerate June the most miscellaneous (%) 0.43 1.68
Azilsartan dissolution rate (%) 99 67
Levamlodipine dissolution rate (%) 100 81
Finding out from the data of table 4, the granulating process of embodiment 1 is substantially better than the technique in comparative example 4.
Comparative example 5: prescription is with reference to embodiment 1, by Azilsartan particle diameter D90Controlling as more than 10 μm, remaining technique is with implementing Example 1.
In Fig. 3, embodiment 1 compares with comparative example 5, Azilsartan particle diameter D90Its dissolution more sharp less than 10 μm.
Embodiment 6: the drop test of rat.
Experimental technique: take healthy SH SHR rat 120, male and female half and half, body weight 200-240g, female Mouse great and mighty or powerful is divided into 12 groups (concrete group technology is shown in Table 1) according to blood pressure height equilibrium, uses gastric infusion, for blood Pressure uses rat electronic sphygmomanometer, contraction pressure during the clear-headed peace and quiet of tail volumetric method indirect determination rat, respectively before medication, and medication One week, two weeks, three weeks, four weekends carry out tail systolic arterial pressure mensuration.Group technology is shown in Table 5.
Model group Same volume 0.9% physiological saline /
Single medicine 1 group Levamlodipine besylate 5mg.kg-1.d-1
Single medicine 2 groups Azilsartan 20mg.kg-1.d-1
Compound 1 group Levamlodipine besylate/Azilsartan 2.5mg.kg-1.d-1/10mg.kg-1.d-1
Experimental result: single medicine 1 group, single medicine 2 groups, compound 1 group compare with model group and have significant hypotensive effect；Multiple 1 group, side compares with single medicine 1 group, list medicine 2 groups and has significant hypotensive effect.
Single medicine and the compound medicine impact (n=10) on hypertension model blood pressure, be shown in Table 6.
Group Before medication (KPa) 1 weekend (KPa) 2 weekends (KPa) 3 weekends (KPa) 4 weekends (KPa)
Model group 27.16±1.19 27.09±1.23 26.91±1.32 27.03±1.04 27.11±1.39
Single medicine 1 group 27.38±1.45 27.01±1.15 25.98±1.22# 25.13±1.37# 24.37±1.26#
Single medicine 2 groups 27.53±1.49 27.22±1.23 26.21±1.32# 25.39±1.31# 24.51±1.39#
Compound 1 group 26.91±1.28 26.71±1.23 24.83±1.32#b1 23.56±1.04#a1b2 22.16±0.99#a2b2
In table 6, compare p ＜ 0.05, # with model group and compare p ＜ 0.01, a1 with model group and compare p ＜ with single medicine 1 group 0.05, a2 compares p ＜ 0.01, b1 with single medicine 1 group compares p ＜ 0.05, b2 with single medicine 2 groups and compares p ＜ with list medicine 2 groups 0.01。
Conclusion: levamlodipine has than levamlodipine and Azilsartan list medical instrument with the composite tablet of Azilsartan Preferably hypotensive effect, has significant difference on antihypertensive effect, and levamlodipine and Azilsartan are used in combination spontaneous The rat of property hypertension shows certain synergy, be better than two kinds of medicines alone time curative effect.
To the present invention it should be appreciated that embodiment described above, to the purpose of the present invention, technical scheme and useful effect Fruit carried out further details of explanation, these are only embodiments of the invention, be not intended to limit the present invention, every Within the spiritual principles of the present invention, done any modification, equivalent substitution and improvement etc., should be included in the protection of the present invention Within the scope of, protection scope of the present invention should be as the criterion with the protection domain that claim is defined.

Claims (9)

1. a medicine composition, it comprises Azilsartan, levamlodipine or its pharmacy acceptable salt and medicine Acceptable auxiliary material on.
Medicine composition the most according to claim 1, it is characterised in that per unit medicine composition contains A Qisha Smooth and Amlodipine or its pharmacy acceptable salt weight ratio is 4～16:1.
3. the medicine composition described in claim 1, it is characterised in that described levamlodipine pharmacy acceptable Salt is Levamlodipine besylate.
4. according to the medicine composition described in claim 1, it is characterised in that A Qisha in per unit medicine composition Smooth account for the 4%～18% of gross weight.
5. according to the medicine composition described in claim 1, it is characterised in that benzene sulfonic acid in per unit medicine composition Levamlodipine accounts for the 0.5%～2.2% of gross weight.
6. pharmaceutical composition as claimed in claim 1, it is characterised in that the described left-handed ammonia of benzene sulfonic acid in terms of levamlodipine Flordipine content is 2.5mg, and Azilsartan content is 10～40mg.
7. medicine composition any one of claim 1-6 is oral solid formulation, specially tablet, comprises the most further At least one in filler, disintegrant, adhesive or lubricant.
8. the preparation method of the medicine composition described in claim 1 comprises the steps:
(1) Azilsartan and levamlodipine or its pharmacy acceptable salt are pulverized respectively；
(2) weigh the Azilsartan after pulverizing and carry out wet granulation, obtain Azilsartan wet granular；
(3) Azilsartan wet granular is dried, and crosses the 18 whole grains of mesh sieve, obtain Azilsartan particle；
(4) weigh the levamlodipine after pulverizing or its pharmacy acceptable salt carries out dry granulation, obtain left-handed ammonia chlorine Horizon or its pharmacy acceptable salt particle；
(5) Azilsartan particle and levamlodipine or its pharmacy acceptable salt particle are mixed in mixer, add Enter lubricant, always mix, compressing tablet.
The preparation method of medicine composition the most according to claim 8, it is characterised in that in described step (1), pulverizes After Azilsartan D90Less than 10 μm.
CN201610340421.8A 2016-05-23 2016-05-23 Composition containing levorotatory amlodipine and azilsartan Pending CN105853418A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103566372A (en) * 2012-08-09 2014-02-12 江苏柯菲平医药有限公司 Pharmaceutical composition for lowering blood pressure
CN104644632A (en) * 2015-01-27 2015-05-27 美吉斯制药（厦门）有限公司 Orally taken tablet containing Azilsartan and benzenesulfonate amlodipine and preparation method thereof
CN105579031A (en) * 2013-10-08 2016-05-11 赞蒂瓦有限合伙公司 A stable pharmaceutical composition containing amlodipine and valsartan

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103566372A (en) * 2012-08-09 2014-02-12 江苏柯菲平医药有限公司 Pharmaceutical composition for lowering blood pressure
CN105579031A (en) * 2013-10-08 2016-05-11 赞蒂瓦有限合伙公司 A stable pharmaceutical composition containing amlodipine and valsartan
CN104644632A (en) * 2015-01-27 2015-05-27 美吉斯制药（厦门）有限公司 Orally taken tablet containing Azilsartan and benzenesulfonate amlodipine and preparation method thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
邹寿涛 等: "阿齐沙坦的临床应用进展", 《药学与临床研究》 *

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