CN105287435A - Nicardipine hydrochloride sustained release pellets and preparation method thereof - Google Patents
Nicardipine hydrochloride sustained release pellets and preparation method thereof Download PDFInfo
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- CN105287435A CN105287435A CN201510881466.1A CN201510881466A CN105287435A CN 105287435 A CN105287435 A CN 105287435A CN 201510881466 A CN201510881466 A CN 201510881466A CN 105287435 A CN105287435 A CN 105287435A
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- sustained release
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- nicardipine hydrochloride
- release pellets
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- 239000008188 pellet Substances 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 229960002289 nicardipine hydrochloride Drugs 0.000 title claims abstract description 21
- AIKVCUNQWYTVTO-UHFFFAOYSA-N nicardipine hydrochloride Chemical compound Cl.COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 AIKVCUNQWYTVTO-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 238000013268 sustained release Methods 0.000 title claims abstract description 20
- 239000012730 sustained-release form Substances 0.000 title claims abstract description 20
- 238000000576 coating method Methods 0.000 claims abstract description 34
- 239000003814 drug Substances 0.000 claims abstract description 29
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000011248 coating agent Substances 0.000 claims abstract description 20
- 239000000945 filler Substances 0.000 claims abstract description 10
- 239000000314 lubricant Substances 0.000 claims abstract description 10
- 239000000463 material Substances 0.000 claims abstract description 7
- 238000002156 mixing Methods 0.000 claims abstract description 7
- 239000004033 plastic Substances 0.000 claims abstract description 7
- 229920003023 plastic Polymers 0.000 claims abstract description 7
- 238000011049 filling Methods 0.000 claims abstract description 4
- 235000010603 pastilles Nutrition 0.000 claims description 24
- 239000011230 binding agent Substances 0.000 claims description 18
- 229940079593 drug Drugs 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
- 239000000843 powder Substances 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 12
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 9
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 9
- 239000002775 capsule Substances 0.000 claims description 9
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
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- 238000007599 discharging Methods 0.000 claims description 6
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- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 6
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- 239000002994 raw material Substances 0.000 claims description 5
- 239000006187 pill Substances 0.000 claims description 4
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- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
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- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
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- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
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- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides nicardipine hydrochloride sustained release pellets. The nicardipine hydrochloride sustained release pellets comprise medicine-containing pellets and coating layers, wherein the medicine-containing pellets are coated with the coating layers; the medicine-containing pellets comprise nicardipine hydrochloride, hollow cores, filling agents, lubricating agents and bonding agents; and the coating layers comprise Eudragit NE30D and talcum powder. A preparation method of the nicardipine hydrochloride sustained release pellets comprises the following procedures: 1. material preparation; 2. mixing; 3. preparation of the bonding agents; 4. preparation of the pellets; 5. preparation of coating agents; 6. coating; 7. filling; and 8. aluminium-plastic packaging and preparation of finished products. The nicardipine hydrochloride sustained release pellets are applicable to primary hypertension, are stable in medicine release, have good effects, have minor irritation to gastrointestinal tracts, have good bioavailability, are convenient to package, transport and store and are suitable for industrial production. The products are well absorbed after being orally administrated. Although the products can be taken on an empty stomach or after the meal, the total absorbed dose of the products can be increased by food.
Description
Technical field
the invention belongs to chemical medicine slow releasing preparation field, be specifically related to a kind of nicardipine hydrochloride sustained release pellets and preparation method thereof.
Background technology
based on current medical development level and detection methods, the definite cause of disease causing blood pressure to raise can be found, be referred to as secondary hypertension; Otherwise, the definite cause of disease causing blood pressure to raise can not be found, be then called essential hypertension.In Hypertensive Population, majority is essential hypertension, but essential hypertension of clarifying a diagnosis, secondary hypertension except needing first.Think at present, secondary hypertension accounts for 5% ~ 10% of Hypertensive Population, but along with the continuous progress of medical development level and detection methods, the ratio of secondary hypertension will constantly increase, the continuous decline of ratio regular meeting of essential hypertension.
most of essential hypertension sees person in middle and old age, onset is hidden, make slow progress, the course of disease reaches more than ten years to many decades, seldom there is symptom at initial stage, about half patient is because of health check-up or because of after Measure blood pressure when other diseases is sought medical advice, just chance on blood pressure to increase, many patients are once after knowing and suffering from hypertension, various neurosis sample symptom can be produced on the contrary, such as dizzy, feeling of fullness in the head, insomnia, forgetful, tinnitus, weak, dreaminess, emotional etc., 1/3 ~ 1/2 hyperpietic is because of headache, feeling of fullness in the head or cardiopalmus and seek medical advice, also many patients are had until there is hypertensive severe complication and target organ is functional or organic lesion.
at present, market is treated in the Licardipine Hydrochloride medicine of essential hypertension, there is drug release stablizing effect low, large to gastrointestinal irritation, bioavailability is low, packaging, transport, storage inconvenience, and the deficiency such as preparation method is complicated.
Summary of the invention
the object of this invention is to provide a kind of infection be applicable to caused by responsive pathogen, drug release stablizing effect is good, little to gastrointestinal irritation, bioavailability is good, packaging, transport, storage a kind of nicardipine hydrochloride sustained release pellets and preparation method thereof easily.
object of the present invention is achieved through the following technical solutions: a kind of nicardipine hydrochloride sustained release pellets, comprise pastille micropill, coatings, it is characterized in that: pastille micropill wraps up by described coatings, described pastille micropill comprises: 10mg Licardipine Hydrochloride, 70mg celphere, 110-150mg filler, 18-68mg lubricant, 2-10mg binding agent, and described coatings comprises: 29-145mg is strange NE30D, 4-44mg Pulvis Talci especially.
the best in quality proportioning of described pastille micropill Raw is: 10mg Licardipine Hydrochloride, 70mg celphere, 140mg filler, 35mg lubricant, 5mg binding agent.
the best in quality proportioning of described coatings Raw is: 59mg is strange NE30D, 13mg Pulvis Talci especially.
described filler is microcrystalline Cellulose.
described lubricant is Pulvis Talci.
described binding agent is hypromellose.
sodium lauryl sulphate or Polyethylene Glycol trace is also comprised in described coatings.
the preparation method of described a kind of nicardipine hydrochloride sustained release pellets, comprises following operation:
step 1: get the raw materials ready: by above-mentioned quality proportioning, use pulverizer to pulverize Licardipine Hydrochloride, crosses 100 mesh sieves;
step 2: mixing: take Licardipine Hydrochloride according to above-mentioned quality proportioning, microcrystalline Cellulose put into three-dimensional mixer mixing 30 minutes, make fine drug powder, take out for subsequent use;
step 3: the preparation of binding agent: take appropriate hypromellose by above-mentioned quality proportioning, adds appropriate hot water and is mixed with the binding agent that concentration is 2%, for subsequent use;
step 4: pill: the charging spout mixed fine drug powder being put into centrifugal pellet processing machine, binding agent puts into feed tank, and celphere is put in pot, opens machine, adjustment parameter, start hydrojet, start for powder, after fine drug powder has all spread when ball core has during damp, Pulvis Talci is added in charging spout, continue for powder, after Pulvis Talci has all spread, discharging; Then use vulcanization bed drying machine to dry, first use cool breeze dry, after epidermis parches, open Hot-blast Heating, inlet temperature is at 50-55 degree Celsius, and use 14,24 mesh sieve after drying, the pastille micropill getting 14-24 order size is for subsequent use;
step 5: the preparation of coating materials: take especially strange NE30D, Pulvis Talci, sodium lauryl sulphate, purified water by above-mentioned quality proportioning, first sodium lauryl sulphate is joined in purified water and stir evenly dissolving, add after especially strange NE30D stirs evenly again, limit is stirred and is just added Pulvis Talci, stirs for subsequent use after 10 minutes;
step 6: coating: by the pastille micropill of 14-24 order size, put into fluidized-bed coating machine, coating materials is put into feed tank, stir constantly, open machine, adjustment parameter, starts coating, to be coated dose be finished after, start to heat up and keep temperature of charge more than 40 degree, dry 30 minutes, cooling, discharging, closing machine;
step 7: fill: the pastille micropill after above-mentioned coating is used capsule filling machine, loads pastille micropill in 0# capsule;
step 8: plastic-aluminum: above-mentioned capsule is used aluminium-plastic bubble plate packing machine, is packaged into aluminium-plastic panel, packed products.
beneficial effect of the present invention: of the present invention take Licardipine Hydrochloride as the slow-release micro-pill of effective ingredient, is mainly used in the treatment of essential hypertension.The more novel slow releasing preparation adopted and pellet preparations, slow release-refer to by delaying medicine from the rate of releasing drug this dosage form, reduces the absorption rate that medicine enters body, thus plays more stable therapeutic effect; Micropill has medicine and increases at gastrointestinal tract surface distributed area, can reduce zest, improves bioavailability, does not affect by gastric emptying factor simultaneously, and drug absorption in vivo is even, and individual variation is little; Two kinds of advanced technology apply the technical advantage more enhancing this medicine simultaneously.Its preparation method is simple, is applicable to commercial production.
the present invention is through two groups of clinical verifications, and wherein one group is that treatment group uses the present invention, and every day uses once, within 7 days, be a course for the treatment of, another group contrast uses existing Licardipine Hydrochloride controlled release tablet, every group selection outpatient 142 example, wherein man 42 example, female 100 example, measures 70 years old large age, minimal ages 33 years old, every day uses once, within 5 days, be a course for the treatment of, clinical manifestation is dizziness, feeling of fullness in the head, insomnia, forgetful, tinnitus, weak, dreaminess, and table one is for taking the contrasting data after the course for the treatment of:
table 1 is taken front and back and is compared (unit: people) two groups of courses for the treatment of
there were significant differences for treatment group and matched group, thus can find out that the present invention's application clinically has significant curative effect.
process characteristic of the present invention: 1, select raw material science, production technology is advanced, and its product is conveniently deposited and used; 2, product Chinese medicine composition is easily absorbed by the body; 3, raw material sources are extensive, add process line short, the easy processing and manufacturing of product.
Detailed description of the invention
embodiment 1
a kind of nicardipine hydrochloride sustained release pellets, comprise pastille micropill, coatings, it is characterized in that: pastille micropill wraps up by described coatings, described pastille micropill comprises: 10mg Licardipine Hydrochloride, 70mg celphere, 110-150mg filler, 18-68mg lubricant, 2-10mg binding agent, and described coatings comprises: 29-145mg is strange NE30D, 4-44mg Pulvis Talci especially.
the best in quality proportioning of described pastille micropill Raw is: 10mg Licardipine Hydrochloride, 70mg celphere, 140mg filler, 35mg lubricant, 5mg binding agent.
the best in quality proportioning of described coatings Raw is: 59mg is strange NE30D, 13mg Pulvis Talci especially.
described filler is microcrystalline Cellulose.
described lubricant is Pulvis Talci.
described binding agent is hypromellose.
sodium lauryl sulphate or Polyethylene Glycol trace is also comprised in described coatings.
embodiment 2
a preparation method for nicardipine hydrochloride sustained release pellets, comprises following operation:
step 1: get the raw materials ready: by above-mentioned quality proportioning, use pulverizer to pulverize Licardipine Hydrochloride, crosses 100 mesh sieves;
step 2: mixing: take Licardipine Hydrochloride according to above-mentioned quality proportioning, microcrystalline Cellulose put into three-dimensional mixer mixing 30 minutes, make fine drug powder, take out for subsequent use;
step 3: the preparation of binding agent: take appropriate hypromellose by above-mentioned quality proportioning, adds appropriate hot water and is mixed with the binding agent that concentration is 2%, for subsequent use;
step 4: pill: the charging spout mixed fine drug powder being put into centrifugal pellet processing machine, binding agent puts into feed tank, and celphere is put in pot, opens machine, adjustment parameter, start hydrojet, start for powder, after fine drug powder has all spread when ball core has during damp, Pulvis Talci is added in charging spout, continue for powder, after Pulvis Talci has all spread, discharging; Then use vulcanization bed drying machine to dry, first use cool breeze dry, after epidermis parches, open Hot-blast Heating, inlet temperature is at 50-55 degree Celsius, and use 14,24 mesh sieve after drying, the pastille micropill getting 14-24 order size is for subsequent use;
step 5: the preparation of coating materials: take especially strange NE30D, Pulvis Talci, sodium lauryl sulphate, purified water by above-mentioned quality proportioning, first sodium lauryl sulphate is joined in purified water and stir evenly dissolving, add after especially strange NE30D stirs evenly again, limit is stirred and is just added Pulvis Talci, stirs for subsequent use after 10 minutes;
step 6: coating: by the pastille micropill of 14-24 order size, put into fluidized-bed coating machine, coating materials is put into feed tank, stir constantly, open machine, adjustment parameter, starts coating, to be coated dose be finished after, start to heat up and keep temperature of charge more than 40 degree, dry 30 minutes, cooling, discharging, closing machine;
step 7: fill: the pastille micropill after above-mentioned coating is used capsule filling machine, loads pastille micropill in 0# capsule;
step 8: plastic-aluminum: above-mentioned capsule is used aluminium-plastic bubble plate packing machine, is packaged into aluminium-plastic panel, packed products.
embodiment 3
indication: essential hypertension.
drug interaction:
1. this product and the same use of beta-blocker, well-tolerated.
2. this product and cimetidine share, and this product blood drug level increases.
3. when this agent and other depressor drug combinations, likely produce summation action, should add during use to note.
4., when this agent and digoxin drug combination, measure digoxin plasma concentration.
5. when this product and ciclosporin share, ciclosporin blood drug level increases.
6. the furosemide, Propranolol, dipyridamole, warfarin, quinidine etc. of in vitro, treating concentration are added on the protein binding rate not changing this product in human plasma.
embodiment 4
pharmacological toxicology:
this product is calcium ion antagonist, plays vasorelaxation action, thus make blood pressure drops by suppressing calcium ion to flow in vascular smooth muscle cell.This product has the cardioselective of height, the calcium antagonism of vascular smooth muscle is better than to 30000 times of Myocardial Effects.In Canis familiaris L. and rat experiment, show natriuretic diuretic effect simultaneously; Expansion vertebral artery, coronary artery, femoral artery, renal artery effect is also shown anesthesia Canis familiaris L.; This product can increase the blood flow of the main organs such as brain, heart kidney, and hypotensive effect is definite, lasting, and long-term prescription can not produce drug resistance, and can suppress the progress of myocardial hypertrophy because hypertension causes and the generation of prevention apoplexy.
embodiment 5
pharmacokinetics:
measuring blood drug level after 12 health adult's experimenter's singles take this product 40mg is bimodal state, be 0.79 ± 0.45h during first peak, reaching peak concentration is 14.2 ± 8.2ng/ml, be 5.08 ± 0.79h during the second peak, reaching peak concentration is 16.3 ± 5.8ng/ml (blood drug level is that bimodal curve conforms to the pharmaceutics feature that this preparation is made up of rapid release and slow release two kinds of compositions); Every day oral twice, each 40mg, surveys blood drug level after serveing on 7 days, and peak concentration is 36.9 ± 6.1ng/ml, within 7 days, reach steady state.The half-life of continuous oral administration is about 7.6 hours.This product is mainly through the extensive metabolism of liver, and only the metabolite of 21% is discharged by urine, does not detect nicardipine original shape thing in urine.
Claims (8)
1. a nicardipine hydrochloride sustained release pellets, comprise pastille micropill, coatings, it is characterized in that: pastille micropill wraps up by described coatings, described pastille micropill comprises: 10mg Licardipine Hydrochloride, 70mg celphere, 110-150mg filler, 18-68mg lubricant, 2-10mg binding agent, and described coatings comprises: 29-145mg is strange NE30D, 4-44mg Pulvis Talci especially.
2. a kind of nicardipine hydrochloride sustained release pellets according to claim 1, is characterized in that: the best in quality proportioning of described pastille micropill Raw is: 10mg Licardipine Hydrochloride, 70mg celphere, 140mg filler, 35mg lubricant, 5mg binding agent.
3. a kind of nicardipine hydrochloride sustained release pellets according to claim 1, is characterized in that: the best in quality proportioning of described coatings Raw is: 59mg is strange NE30D, 13mg Pulvis Talci especially.
4. a kind of nicardipine hydrochloride sustained release pellets according to claim 1, is characterized in that: described filler is microcrystalline Cellulose.
5. a kind of nicardipine hydrochloride sustained release pellets according to claim 1, is characterized in that: described lubricant is Pulvis Talci.
6. a kind of nicardipine hydrochloride sustained release pellets according to claim 1, is characterized in that: described binding agent is hypromellose.
7. a kind of nicardipine hydrochloride sustained release pellets according to claim 1, is characterized in that: also comprise sodium lauryl sulphate or Polyethylene Glycol trace in described coatings.
8. the preparation method of a kind of nicardipine hydrochloride sustained release pellets according to claim 1-7 any one, is characterized in that: comprise following operation:
Step 1: get the raw materials ready: by above-mentioned quality proportioning, use pulverizer to pulverize Licardipine Hydrochloride, crosses 100 mesh sieves;
Step 2: mixing: take Licardipine Hydrochloride according to above-mentioned quality proportioning, microcrystalline Cellulose put into three-dimensional mixer mixing 30 minutes, make fine drug powder, take out for subsequent use;
Step 3: the preparation of binding agent: take appropriate hypromellose by above-mentioned quality proportioning, adds appropriate hot water and is mixed with the binding agent that concentration is 2%, for subsequent use;
Step 4: pill: the charging spout mixed fine drug powder being put into centrifugal pellet processing machine, binding agent puts into feed tank, and celphere is put in pot, opens machine, adjustment parameter, start hydrojet, start for powder, after fine drug powder has all spread when ball core has during damp, Pulvis Talci is added in charging spout, continue for powder, after Pulvis Talci has all spread, discharging; Then use vulcanization bed drying machine to dry, first use cool breeze dry, after epidermis parches, open Hot-blast Heating, inlet temperature is at 50-55 degree Celsius, and use 14,24 mesh sieve after drying, the pastille micropill getting 14-24 order size is for subsequent use;
Step 5: the preparation of coating materials: take especially strange NE30D, Pulvis Talci, sodium lauryl sulphate, purified water by above-mentioned quality proportioning, first sodium lauryl sulphate is joined in purified water and stir evenly dissolving, add after especially strange NE30D stirs evenly again, limit is stirred and is just added Pulvis Talci, stirs for subsequent use after 10 minutes;
Step 6: coating: by the pastille micropill of 14-24 order size, put into fluidized-bed coating machine, coating materials is put into feed tank, stir constantly, open machine, adjustment parameter, starts coating, to be coated dose be finished after, start to heat up and keep temperature of charge more than 40 degree, dry 30 minutes, cooling, discharging, closing machine;
Step 7: fill: the pastille micropill after above-mentioned coating is used capsule filling machine, loads pastille micropill in 0# capsule;
Step 8: plastic-aluminum: above-mentioned capsule is used aluminium-plastic bubble plate packing machine, is packaged into aluminium-plastic panel, packed products.
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| CN201510881466.1A CN105287435A (en) | 2015-12-07 | 2015-12-07 | Nicardipine hydrochloride sustained release pellets and preparation method thereof |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101011395A (en) * | 2007-02-02 | 2007-08-08 | 东南大学 | Sustained release preparation of licardipine hydrochloride and its preparing process |
| CN101433538A (en) * | 2007-11-12 | 2009-05-20 | 北京瑞康医药技术有限公司 | Therapeutic compositions containing amlodipine and niacin medicament |
| CN101836963A (en) * | 2009-03-16 | 2010-09-22 | 鲁南制药集团股份有限公司 | Medicinal application preparation for curing hypertension |
| CN102038662A (en) * | 2009-10-12 | 2011-05-04 | 杭州赛利药物研究所有限公司 | Nifedipine controlled release micro-pill preparation and preparation method thereof |
| CN102247366A (en) * | 2010-05-18 | 2011-11-23 | 广州白云山制药股份有限公司广州白云山制药总厂 | Medicinal composition comprising quick-release pellets containing Enalapril or Enalapril-acid addition salt and slow-release pellets containing Felodipine |
-
2015
- 2015-12-07 CN CN201510881466.1A patent/CN105287435A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101011395A (en) * | 2007-02-02 | 2007-08-08 | 东南大学 | Sustained release preparation of licardipine hydrochloride and its preparing process |
| CN101433538A (en) * | 2007-11-12 | 2009-05-20 | 北京瑞康医药技术有限公司 | Therapeutic compositions containing amlodipine and niacin medicament |
| CN101836963A (en) * | 2009-03-16 | 2010-09-22 | 鲁南制药集团股份有限公司 | Medicinal application preparation for curing hypertension |
| CN102038662A (en) * | 2009-10-12 | 2011-05-04 | 杭州赛利药物研究所有限公司 | Nifedipine controlled release micro-pill preparation and preparation method thereof |
| CN102247366A (en) * | 2010-05-18 | 2011-11-23 | 广州白云山制药股份有限公司广州白云山制药总厂 | Medicinal composition comprising quick-release pellets containing Enalapril or Enalapril-acid addition salt and slow-release pellets containing Felodipine |
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