CN101411713A - Compound Nimodipine tablet, and enteric tablet thereof, as well as preparation method thereof - Google Patents
Compound Nimodipine tablet, and enteric tablet thereof, as well as preparation method thereof Download PDFInfo
- Publication number
- CN101411713A CN101411713A CNA200810229079XA CN200810229079A CN101411713A CN 101411713 A CN101411713 A CN 101411713A CN A200810229079X A CNA200810229079X A CN A200810229079XA CN 200810229079 A CN200810229079 A CN 200810229079A CN 101411713 A CN101411713 A CN 101411713A
- Authority
- CN
- China
- Prior art keywords
- nimodipine
- enteric
- aspirin
- compound
- tablet
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the technical field of medicine, and discloses nimodipine compound, an enteric coatel tablet thereof and a preparation method of the tablet. The weight ratio of the nimodipine and aspirin is between 1:0.01 and 1:30, preferably between 1:0.05 and 1:20. The formulation of the enteric coatel tablet of the nimodipine compound comprises loading agent, disintegrant, antitackiness agent, glidant and bonding agent according to a weight ratio 20-80 to 20-80 to 0-20 to 0-20 to 0-20 to 0-20 to 0-20; and the enteric coating comprises the following enteric materials plasticizing agent, the antitackiness agent and a dispersing medium according to a weight ratio of 200-500 to 5-30 to 18-37 to 433-777. Through the compound preparation made by the nimodipine and the aspirin, thrombosis can be obviously synergistically inhibited, drug effect can be improved, medicine dosage can be reduced, and incidence rate of untoward effect can be reduced.
Description
Technical field
The invention belongs to medical technical field, be specifically related to nimodipine compound recipe, its enteric coatel tablets and preparation method thereof.
Background technology
(Nimodipine NMD) is second filial generation dihydropyridine type calcium antagonists to nimodipine, chemistry (±) isopropyl by name-2-methoxyethyl-1,4-dihydro-2,6-dimethyl-4 (3-nitrobenzophenone)-3,5-pyridine dicarboxylate.This product is faint yellow crystallization or crystalline powder, odorless, tasteless.
The nimodipine pharmacological property is the level of regulating intracellular Ca2+ effectively, makes it to keep normal physiological function.Particularly outstanding to cerebrovascular effect; can combine with the special receptor of nervus centralis; this specificity makes this product can effectively prevent and treat the cerebral tissue ischemic lesions that causes because of the caused cerebral vasospasm of subarachnoid hemorrhage; the interior stream that suppresses the outer calcium ion of vascular smooth muscle cell all has dilating effect to stripped or intravital cerebral arteries, cerebral arteries normal or ischemia.Selectivity expansion of cerebral vascular under optimal dose influences peripheral blood vessel hardly, but increase dosage hypertension is also had curative effect preferably.
Since finding that aspirin has antiplatelet aggregative activity the seventies, aspirin has been widely used in preventing and treating various arterial thrombotic diseases, as transient ischemic attack, myocardial infarction etc., but untoward reaction such as that life-time service can occur is hemorrhage, ulcer.In order to improve the anti thrombotic action of aspirin, reduce its incidence rate of adverse reaction, other anti-arterial thrombus medicines of aspirin use in conjunction have become the focus of people's research.
Nimodipine is since the exploitation listing eighties, and research in the past mainly concentrates on cerebrovascular and spiritual neuropharmacology aspect.Nimodipine attracts much attention the influence of platelet function in recent years.Test shows can obviously work in coordination with inhibition thrombosis after nimodipine and aspirin share by a certain percentage, improve drug effect, reduce dosage, reduce adverse reaction rate, have more significant cerebral protection, can obviously improve cerebral tissue ultrastructure (Zhang Yijun, war is with rosy clouds etc. aspirin and nimodipine combination are to the protection [J] of cerebral ischemia reperfusion injury Medulla Leporis seu Oryctolagi tissue. Chinese clinical rehabilitation, 2006,10 (34); Hu Xiangjie, Lv Aigang etc. aspirin and nimodipine combination are to the thrombotic influence of rat carotid artery [J]. Chinese Journal of New Drugs and Clinical Remedies, 1999,18 (1): 26-28.)。Clinically aspirin tablet and nimodipine tablet are united diseases such as using the treatment migraine at present and obtain good efficacy (the former China that builds, former day is red etc. and nimodipine and enteric coated aspirin share prevents and treats migraine 80 routine observation of curative effect [J]. the practical sacred disease magazine in Henan, 2000,3 (4)).But use in conjunction aspirin tablet and nimodipine tablet exist and take inconvenience, do not have the optimal proportion administration according to pharmacological testing, the shortcoming that dosage is bigger than the optimal dose of bibliographical information.Therefore develop the compound recipe of nimodipine and aspirin, significant to cardiovascular disease such as control cerebrovasculars.
In order further to reduce the untoward reaction of aspirin, the invention discloses prescription of compound enteric-coated of nimodipine-aspirin and preparation method thereof.
Summary of the invention
One of purpose of the present invention provides a kind of nimodipine compound recipe.
Two of purpose of the present invention is to provide the prescription and the preparation technology of compound enteric-coated of a kind of nimodipine, thereby reduces toxic and side effects, improves curative effect.
The present invention is achieved through the following technical solutions:
The nimodipine compound recipe that the present invention relates to is made up of nimodipine and aspirin and pharmaceutic adjuvant.Wherein nimodipine and aspirin weight ratio are 1:0.01～30, and nimodipine and aspirin weight ratio can also be 1:0.05～20.List the part prescription below and form, but be not limited to listed prescription:
Prescription one: the weight ratio of nimodipine and aspirin is: 1:0.05
Prescription two: the weight ratio of nimodipine and aspirin is: 1:0.15
Prescription three: the weight ratio of nimodipine and aspirin is: 1:0.20
Prescription four: the weight ratio of nimodipine and aspirin is: 1:0.5
Prescription five: the weight ratio of nimodipine and aspirin is: 1:1.5
Prescription six: the weight ratio of nimodipine and aspirin is: 1:2
Prescription seven: the weight ratio of nimodipine and aspirin is: 1:5
Prescription eight: the weight ratio of nimodipine and aspirin is: 1:15
Prescription nine: the weight ratio of nimodipine and aspirin is: 1:20
In these prescriptions, we again to the weight ratio of nimodipine and aspirin be the prescription of 1:0.20 carried out the drug efficacy study method and the result as follows:
Method: select 15 healthy adult new zealand rabbits for use, be divided into into 5 groups at random, be i.e. sham operated rats, cerebral ischemia re-pouring model group, aspirin group, nimodipine group, aspirin and nimodipine combination group, 3 every group.Except that sham operated rats, each group is all made rabbit global brain ischemia re-perfusion model according to Pulsinelli four artery ligation legal systems.Each organizes rabbit all in modeling beginning in preceding 4 days gastric infusion, continuous use 4 days.Sham operated rats and cerebral ischemia re-pouring model group give normal saline 3mg/ml; The aspirin group gives aspirin 2.35mg/ (kg.d); The nimodipine group gives nimodipine 5.64mg/ (kg.d); Aspirin and nimodipine combination group give aspirin 0.56mg/ (kg.d), nimodipine 2.82mg/ (kg.d).Postoperative was used the content that enzyme linked immunological absorption competition method is measured TXA2., prostacyclin, PGE2 in the cerebral tissue in 1 day; And the application transmission electron microscopy is observed the ultrastructural change of cerebral tissue.
The result: 1. 15 rabbit all enter interpretation of result, do not have and take off mistake.The ischemia-reperfusion postoperative is respectively organized TXA2. in the rabbit cerebral tissue, prostacyclin, PGE2 content relatively: compare thromboxane B2 content, thromboxane B2/6-ketone-prostaglandin 1a ratio significantly raise (P＜0.05) in the cerebral ischemia re-pouring model group cerebral tissue with sham operated rats.Compare with model group, thromboxane B2 content, thromboxane B2/6-ketone-prostaglandin 1a ratio significantly reduce (P＜0.05) in aspirin group, nimodipine group, aspirin and the nimodipine combination group cerebral tissue.Compare with aspirin group, nimodipine group, thromboxane B2 content, thromboxane B2/6-ketone-prostaglandin 1a ratio significantly reduce (P＜0.05) experimental result and see Table 1 in aspirin and the nimodipine combination group cerebral tissue.2. the ischemia-reperfusion postoperative is respectively organized the ultrastructure comparison of rabbit cerebral tissue: in the sham operated rats neuron kytoplasm a large amount of mitochondrions are arranged, and rounded or oval; Cerebral ischemia re-pouring model group mitochondrion is the cavity sample and becomes; In aspirin group and the nimodipine group minority mitochondrion little cavity is arranged; The visible a large amount of mitochondrions of aspirin and nimodipine combination group.
Table 1
Conclusion: compare with aspirin, the independent use of nimodipine; two medicines share has significant more cerebral protection; can obviously improve the ultrastructure of cerebral tissue, its action pathway may never ipsilateral reduces cerebral tissue thromboxane B2 content, to keep thromboxane B2/6-ketone-prostaglandin 1a balance relevant with two medicines.
The nimodipine compound recipe can be mixed and made into tablet, capsule, oral liquid, dispersible tablet, chewable tablet, granule, injection, dosage forms such as sustained-release preparation with the carrier of pharmaceutically accepting.
Compound enteric-coated of nimodipine of the present invention comprises label and enteric coating, and wherein label is by nimodipine, aspirin, and pharmaceutic adjuvant is formed.
Label of the present invention comprises nimodipine compound recipe, filler, disintegrating agent, antiplastering aid, fluidizer, binding agent, stabilizing agent.The nimodipine compound recipe, filler, disintegrating agent, antiplastering aid, fluidizer, binding agent, the weight ratio of stabilizing agent is 20～80:20～80:0～20:0～20:0～20:0～20:0～20.Wherein said filler is selected from microcrystalline Cellulose, lactose, one or more mixture in the starch; Disintegrating agent is selected from polyvinylpolypyrrolidone, sodium carboxymethyl cellulose, one or more mixture of carboxymethyl starch sodium or above-mentioned adjuvant; Antiplastering aid and fluidizer are selected from micropowder silica gel, Pulvis Talci, one or more mixture in the magnesium stearate.
Enteric coatel tablets enteric coating layer disclosed by the invention is by enteric material, plasticizer, and antiplastering aid is formed, and adds suitable disperse medium during preparation.Enteric coating layer enteric material wherein, plasticizer, antiplastering aid, the weight ratio of disperse medium is 200～500:5～30:18～37:433～777.Described enteric material is selected from crylic acid resin such as Eudragit series enteric polymer, cellulose acetate phthalate ester, one or more mixture of hypromellose phthalate ester or above-mentioned material; Plasticizer is selected from phthalic acid ester, PEG6000, triethyl citrate, dibutyl sebacate, the mixture of one or more in the propylene glycol; Antiplastering aid is a Pulvis Talci; Disperse medium is a water, ethanol, acetone, one or more mixture in the isopropyl alcohol.
The preparation method of enteric coatel tablets of the present invention comprises:
1. label preparation method
1) take by weighing supplementary material (all crossing 60～120 mesh sieves) mixing by recipe quantity, add binding agent and make soft material in right amount, 14～40 mesh sieves are granulated, and in 30～60 ℃ of dry 1h, add Pulvis Talci, cross 14～40 mesh sieve granulate, and tabletting promptly.
2) take by weighing supplementary material (all crossing 60～120 mesh sieves) mixing by recipe quantity, direct powder compression promptly.
2. the preparation of coated tablet: get the recipe quantity coating material, be dissolved or dispersed in the disperse medium, even matter 45min in the homogenizer.Add label in the coating pan, regulate 80 ℃ of inlet temperature, 30～35 ℃ of sheet bed tempertaures, atomizing pressure 1.5bar, coating pan rotating speed 15～23rmp, sample introduction flow velocity 4～6g/min treats that the coating solution charging finishes, promptly.
According to compound enteric-coated of the nimodipine of above-mentioned prescription and preparation technology's gained, in being 1.5 hydrochloric acid solution, pH checks 2 hours, there are not softening, disintegrate, crack phenomenon.And then be to check in 6.8 phosphate buffer solutions at pH, disintegrate fully in 1 hour, stripping is more than 90% in 45 minutes.
Use separately with the nimodipine preparation; Genprin uses separately; the nimodipine preparation is united use with Genprin and is compared; the nimodipine compound recipe has the following advantages: have collaborative antiplatelet aggregation; suppress the effect of artery thrombosis, have significant more cerebral protection, can obviously improve the ultrastructure of cerebral tissue; reduce dosage, taking convenience.
The specific embodiment
One, the following preparation that can be made into embodiment 1 to embodiment 9 explanation nimodipine compound recipe, but be not limited to listed embodiment.
Embodiment 1
Tablet (1000)
Nimodipine 20g
Aspirin 20g
Starch 130g
Starch slurry (15%) is an amount of
Carboxymethyl starch sodium 10g
Pulvis Talci 10g
Tartaric acid (or citric acid) is an amount of
Technology: with nimodipine, aspirin, starch and part of sodium carboxymethyl starch mixing with starch slurry system soft material, are crossed 18 mesh sieve system wet granulars, and drying adds Pulvis Talci and residue carboxymethyl starch sodium mixing, tabletting.
Embodiment 2
Effervescent tablet (1000)
Nimodipine 20g
Aspirin 20g
Tartaric acid 850g
Sodium bicarbonate 1100g
PEG6000 150g
PVPS630 40g
Aspartame 50g
Fructus Citri tangerinae essence 50g
Micropowder silica gel 20g
Water colo(u)r 1.5g
Starch slurry (15%) is an amount of
Technology: with nimodipine, aspirin and tartaric acid mixing with starch slurry system soft material, are crossed 18 mesh sieve system wet granulars, drying.With sodium bicarbonate system granule, add remaining adjuvant, mixing, tabletting in addition.
Embodiment 3
Buccal tablet (1000)
Nimodipine 20g
Aspirin 20g
Sorbitol 50g
Lactose 50g
Starch1500 30g
PVPK30 5g
Aspartame 5g
Fructus Citri Limoniae essence 5g
Herba Menthae essence 5g
Pulvis Talci 20g
Starch slurry (15%) is an amount of
Technology: press embodiment 11 similarity method film-makings, get final product.
Embodiment 4
Powder
Nimodipine 20g
Aspirin 20g
Xylitol 200g
Embodiment 5
Granule
Nimodipine 20g
Aspirin 20g
Dextrin 150g
Embodiment 6
Capsule (1000 pieces)
Nimodipine 20g
Aspirin 20g
Microcrystalline Cellulose 100g
Micropowder silica gel 5g
Embodiment 7
Dispersible tablet
Nimodipine 20g
Aspirin 20g
HPMCE3 200g
Micropowder silica gel 20g
Cross-linking sodium carboxymethyl cellulose 20
Microcrystalline Cellulose 15g
Tartaric acid 3g
Embodiment 8
Slow releasing tablet
Nimodipine 20g
Aspirin 20g
HPMCK15 100g
Lactose 50g
Micropowder silica gel 5g
Embodiment 9
Enteric coatel tablets (1000)
The label prescription:
Nimodipine 20g
Aspirin 20g
Lactose 50g
Carboxymethyl starch sodium 5g
Micropowder silica gel 2g
Coating solution:
Eudragit E udragit L 300g
PEG6000 20g
Pulvis Talci 30g
Water 600g
Embodiment 10
Oral liquid
Nimodipine 20g
Aspirin 20g
Aspartame 5g
Fructus Citri Limoniae essence 10g
Herba Menthae essence 10g
Distilled water 5000ml
In addition, can also make dosage forms such as chewable tablet, effervescent granule, injection.
Two, following prescription and preparation method with compound enteric-coated of 11 to embodiment 17 pairs of nimodipine of embodiment is illustrated, but is not limited to listed embodiment.
Embodiment 11
Label prescription (1000):
Nimodipine 20g
Aspirin 20g
Microcrystalline Cellulose 60g
Lactose 30g
Carboxymethyl starch sodium 14g
Pulvis Talci 5g
Starch slurry (15%) is an amount of
Tartaric acid (or citric acid) is an amount of
Coating solution (1000):
Eudragit E udragit L 200g
PEG6000 10g
Pulvis Talci 18g
Water 775g
Preparation method:
1. label preparation method: take by weighing supplementary material (all crossing 100 mesh sieves) mixing by recipe quantity, add binding agent and make soft material in right amount, 20 mesh sieves are granulated, and in 30 ℃ of dry 1h, add Pulvis Talci, cross 20 mesh sieve granulate, and tabletting promptly.
2. the preparation of coated tablet: get Eudragit E udragit L and add the about 200g of water, stir evenly.Add PEG6000 and Pulvis Talci in surplus water, even matter is 45 minutes in the homogenizer.The Pulvis Talci suspension is slowly poured in the Eudragit E udragit L aqueous dispersion, slowly stirred 30 minutes.The coating solution for preparing is filtered through 80 eye mesh screens.Add label 500g in the coating pan, regulate 80 ℃ of phoenix temperature, 30～35 ℃ of sheet bed tempertaures, atomizing pressure 1.5bar, coating pan rotating speed 15-23rmp, sample introduction flow velocity 4-6g/min treats that the coating solution charging finishes, promptly.
Embodiment 12
Label prescription (1000):
Nimodipine 20g
Aspirin 20g
Microcrystalline Cellulose 50g
Pregelatinized Starch 20g
Cross-linking sodium carboxymethyl cellulose 14g
Pulvis Talci 5g
Coating solution (1000):
Cellulose acetate phthalate ester 500g
PEG6000 10g
Triethyl citrate 5g
Pulvis Talci 30g
Water 500g
Preparation method:
1. label preparation method: take by weighing supplementary material (all crossing 100 mesh sieves) mixing by recipe quantity, direct powder compression promptly.
2. the preparation of coated tablet: get the cellulose acetate phthalate ester and add the about 200g of water, stir evenly.Add triethyl citrate and Pulvis Talci in surplus water, even matter is 45 minutes in the homogenizer.The Pulvis Talci suspension is slowly poured in the cellulose acetate Phthalate Aqueous Dispersion, slowly stirred 30 minutes.The coating solution for preparing is filtered through 80 eye mesh screens.Add label 500g in the coating pan, regulate 80 ℃ of phoenix temperature, 30～35 ℃ of sheet bed tempertaures, atomizing pressure 1.5bar, coating pan rotating speed 15-23rmp, sample introduction flow velocity 4-6g/min treats that the coating solution charging finishes, promptly.
Embodiment 13
Label prescription (1000):
Nimodipine 20g
Aspirin 20g
Lactose 30g
Cross-linked pvp 15g
Micropowder silica gel 4.2g
Coating solution (1000):
Eudragit E udragit L 200g
Diethyl phthalate 40ml
Pulvis Talci 18g
Tween 80 40ml
Oleum Ricini 15ml
95% ethanol 300g
Water 300g
Preparation method:
1. label preparation method: take by weighing supplementary material (all crossing 100 sieves) mixing by recipe quantity, direct powder compression promptly.
2. the preparation of coated tablet: get Eudragit E udragit L and add the about 300g of water, stir evenly.In 95% ethanol, add tween 80, Oleum Ricini, and Pulvis Talci, even matter is 45 minutes in the homogenizer.The Pulvis Talci suspension is slowly poured in the Eudragit E udragit L aqueous dispersion, slowly stirred 30 minutes.The coating solution for preparing is filtered through 80 eye mesh screens.Add label 500g in the coating pan, regulate 80 ℃ of phoenix temperature, 30～35 ℃ of sheet bed tempertaures, atomizing pressure 1.5bar, coating pan rotating speed 15-23rmp, sample introduction flow velocity 4-6g/min treats that the coating solution charging finishes, promptly.
Embodiment 14
Label prescription (1000):
Nimodipine 20g
Aspirin 20g
Pregelatinized Starch 60g
Lactose 30g
Cross-linked pvp 15g
Starch slurry (15%) is an amount of
Tartaric acid (or citric acid) is an amount of
Micropowder silica gel 5g
Coating solution (1000):
Hypromellose phthalate ester 400g
Phthalic acid ester 20g
Pulvis Talci 18g
Water 500g
Preparation method:
1. label preparation method: take by weighing supplementary material (all crossing 100 mesh sieves) mixing by recipe quantity, add binding agent and make soft material in right amount, cross 20 mesh sieves and granulate, in 30 ℃ of dry 1h, add Pulvis Talci, cross 20 mesh sieve granulate, tabletting promptly.
2. the preparation of coated tablet: get the hypromellose phthalate ester and add the about 200g of water, stir evenly.Add phthalic acid ester and Pulvis Talci in surplus water, even matter is 45 minutes in the homogenizer.The Pulvis Talci suspension is slowly poured in the hypromellose Phthalate Aqueous Dispersion, slowly stirred 30 minutes.The coating solution for preparing is filtered through 80 eye mesh screens.Add label 500g in the coating pan, regulate 80 ℃ of inlet temperature, 30～35 ℃ of sheet bed tempertaures, atomizing pressure 1.5bar, coating pan rotating speed 15～23rmp, sample introduction flow velocity 4～6g/min treats that the coating solution charging finishes, promptly.
Embodiment 15
Label prescription (1000):
Nimodipine 20g
HPMCE5 20
Aspirin 20g
Microcrystalline Cellulose 60g
Lactose 60g
Carboxymethyl starch sodium 14g
Micropowder silica gel 20g
Coating solution (1000):
Enteric Opadry 400g
80% ethanol 1000g
Preparation method:
1. label preparation method: take by weighing nimodipine by recipe quantity, HPMCE5, micropowder silica gel, preparation solid dispersion.The solid dispersion crushed after being dried is crossed 100 mesh sieves.Press recipe quantity and other adjuvant (all crossing 100 mesh sieves) mixing, direct powder compression promptly.
2. the preparation of coated tablet: get part enteric Opadry and join in 80% ethanol, stir evenly.Add whole enteric Opadries gradually, even matter is 45 minutes in the homogenizer.The coating solution for preparing is filtered through 80 eye mesh screens.Add label 500g in the coating pan, regulate 80 ℃ of inlet temperature, 30～35 ℃ of sheet bed tempertaures, atomizing pressure 1.5bar, coating pan rotating speed 15～23rmp, sample introduction flow velocity 4～6g/min treats that the coating solution charging finishes, promptly.
Embodiment 16
Label prescription (1000):
Label prescription (1000):
Nimodipine 20g
Aspirin 20g
Microcrystalline Cellulose 100g
HPMCE5 20g
Micropowder silica gel 1g
Pulvis Talci 2g
Sodium carboxymethyl cellulose 8.5g
Coating solution (1000):
Eudragit E udragit L 350g
PEG6000 20g
Pulvis Talci 31g
Water 1000g
Preparation method:
1. label preparation method: take by weighing nimodipine by recipe quantity, HPMCE5, micropowder silica gel, preparation solid dispersion.The solid dispersion crushed after being dried is crossed 100 mesh sieves.Press recipe quantity and other adjuvant (all crossing 100 mesh sieves) mixing, direct powder compression promptly.
2. the preparation of coated tablet: get the cellulose acetate phthalate ester and add the about 200g of water, stir evenly.Add triethyl citrate and Pulvis Talci in surplus water, even matter is 45 minutes in the homogenizer.The Pulvis Talci suspension is slowly poured in the cellulose acetate Phthalate Aqueous Dispersion, slowly stirred 30 minutes.The coating solution for preparing is filtered through 80 eye mesh screens.Add label 500g in the coating pan, regulate 80 ℃ of inlet temperature, 30～35 ℃ of sheet bed tempertaures, atomizing pressure 1.5bar, coating pan rotating speed 15～23rmp, sample introduction flow velocity 4～6g/min treats that the coating solution charging finishes, promptly.
Embodiment 17
Label prescription (1000):
Nimodipine 20g
Aspirin 20g
Microcrystalline Cellulose 100g
HPMCE5 20g
Micropowder silica gel 1g
Pulvis Talci 2g
Sodium carboxymethyl cellulose 8.5g
Coating solution (1000):
Eudragit E udragit L 350g
PEG6000 20g
Pulvis Talci 31g
Water 1000g
Preparation method:
1. label preparation method: take by weighing nimodipine by recipe quantity, HPMCE5, micropowder silica gel, preparation solid dispersion.The solid dispersion crushed after being dried is crossed 100 sieves.Press recipe quantity and other adjuvant (all crossing 100 mesh sieves) mixing, direct powder compression promptly.
2. the preparation of coated tablet: get Eudragit E udragit L and add the about 200g of water, stir evenly.Add PEG6000 and Pulvis Talci in surplus water, even matter is 45 minutes in the homogenizer.The Pulvis Talci suspension is slowly poured in the Eudragit E udragit L aqueous dispersion, slowly stirred 30 minutes.The coating solution for preparing is filtered through 80 eye mesh screens.Add label 500g in the coating pan, regulate 80 ℃ of inlet temperature, 30～35 ℃ of sheet bed tempertaures, atomizing pressure 1.5bar, coating pan rotating speed 15-23rmp, sample introduction flow velocity 4-6g/min treats that the coating solution charging finishes, promptly.
Claims (10)
1, a kind of nimodipine compound recipe is characterized in that: be made up of active component nimodipine and aspirin and pharmaceutic adjuvant, the weight ratio of nimodipine and aspirin is 1:0.01～30.
2, nimodipine compound recipe according to claim 1 is characterized in that: the weight ratio of nimodipine and aspirin is 1:0.05～20.
3, nimodipine compound recipe according to claim 1 is characterized in that: can also comprise other calcium channel blockers in this compound recipe, beta-blocker, angiotensin ii receptor antagonist, angiotensin-convertion enzyme inhibitor, directly vasodilation.
4, nimodipine compound recipe according to claim 1 is characterized in that: described pharmaceutic adjuvant is: starch, pregelatinized Starch, dextrin, Icing Sugar, lactose, glucose, mannitol, microcrystalline Cellulose, calcium sulfate, calcium hydrogen phosphate, light magnesium oxide, calcium carbonate, starch, Aluminium Hydroxide, hypromellose, polyvidone, starch slurry, syrup, rubber cement, methylcellulose, carboxymethyl cellulose, sodium alginate, ethyl cellulose, Polyethylene Glycol, aluminium-magnesium silicate, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, carboxymethyl starch, hydroxypropyl starch, low-substituted hydroxypropyl cellulose, stearic acid, calcium stearate, Pulvis Talci, hydrogenated vegetable oil, sodium lauryl sulphate.
5, nimodipine compound recipe according to claim 1, it is characterized in that: this compound recipe can be made tablet, capsule, oral liquid, dispersible tablet, chewable tablet, granule, injection, sustained-release preparation.
6, nimodipine is compound enteric-coated, comprises label and enteric coating layer, it is characterized in that: the composition and the percentage ratio of label are as follows: the nimodipine compound recipe, filler, disintegrating agent, antiplastering aid, fluidizer, binding agent, the weight ratio of stabilizing agent is 20～80:20～80:0～20:0～20:0～20:0～20:0～20, enteric coating layer comprises enteric material, plasticizer, antiplastering aid, disperse medium, its weight ratio is 200～500:5～30:18～37:433～777.
7, nimodipine according to claim 6 is compound enteric-coated, it is characterized in that: Buddhist nun not nimodipine and aspirin can be a crude drug, can also be the solid dispersion that contains nimodipine and/or aspirin, clathrate or other intermediate product.
8, nimodipine according to claim 6 is compound enteric-coated, it is characterized in that: described filler is selected from microcrystalline Cellulose, lactose, one or more mixture of starch or above-mentioned adjuvant; Disintegrating agent is selected from polyvinylpolypyrrolidone, sodium carboxymethyl cellulose, one or more mixture of carboxymethyl starch sodium or above-mentioned adjuvant; Antiplastering aid and fluidizer are selected from micropowder silica gel, Pulvis Talci, one or more mixture in the magnesium stearate; Described enteric material is selected from crylic acid resin such as Eudrag it series enteric polymer, cellulose acetate phthalate ester, one or more mixture of hypromellose phthalate ester or above-mentioned material; Plasticizer is selected from phthalic acid ester, PEG6000, triethyl citrate, dibutyl sebacate, the mixture of one or more in the propylene glycol; Antiplastering aid is a Pulvis Talci; Disperse medium is a water, ethanol, acetone, one or more mixture in the isopropyl alcohol.
9, nimodipine according to claim 6 is compound enteric-coated, it is characterized in that: wherein said enteric coating layer can also comprise pigment and defoamer.
10, nimodipine according to claim 9 is compound enteric-coated, it is characterized in that: described pigment comprises the titanium dioxide white pigment, aluminum color lake, iron oxide pigment; Defoamer is a methyl-silicone oil.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200810229079XA CN101411713A (en) | 2008-11-26 | 2008-11-26 | Compound Nimodipine tablet, and enteric tablet thereof, as well as preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200810229079XA CN101411713A (en) | 2008-11-26 | 2008-11-26 | Compound Nimodipine tablet, and enteric tablet thereof, as well as preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101411713A true CN101411713A (en) | 2009-04-22 |
Family
ID=40592592
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA200810229079XA Pending CN101411713A (en) | 2008-11-26 | 2008-11-26 | Compound Nimodipine tablet, and enteric tablet thereof, as well as preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101411713A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102512400A (en) * | 2011-12-31 | 2012-06-27 | 深圳万乐药业有限公司 | Preparation method of efonidipine hydrochloride tablet |
-
2008
- 2008-11-26 CN CNA200810229079XA patent/CN101411713A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102512400A (en) * | 2011-12-31 | 2012-06-27 | 深圳万乐药业有限公司 | Preparation method of efonidipine hydrochloride tablet |
| CN102512400B (en) * | 2011-12-31 | 2014-04-16 | 深圳万乐药业有限公司 | Preparation method of efonidipine hydrochloride tablet |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2436523T3 (en) | Therapeutic dosage forms | |
| JP2004501099A (en) | Aldosterone antagonist composition for release during aldosterone vertex phase | |
| CN101166543A (en) | Composition containing antidementia agent | |
| CN101646461A (en) | Oral disintegrating tablet | |
| CN101703513B (en) | Compound sustained-release preparation of aspirin and clopidogrel or pharmaceutically acceptable salt thereof | |
| KR101230731B1 (en) | Pharmaceutical formulation | |
| JP2007500699A (en) | Tranexamic acid preparation with reduced side effects | |
| CN102813664A (en) | Oral enteric preparation containing Grel drugs and aspirin | |
| CN100488515C (en) | Ground erythromycin enteric micropill and its preparation method | |
| CN102300558A (en) | galenic formulations of organic compounds | |
| CN107320462B (en) | A kind of sustained release preparation and preparation method thereof of levamlodipine or its salt | |
| CN101406472A (en) | Pharmaceutical composition of atenolol/amlodipine/folacin compound and uses thereof | |
| CN102247366B (en) | Medicinal compositionslow-releaseformulation containing Enalapril and Felodipine | |
| CN104138376A (en) | A sustained release agent improving anoxia endurance | |
| CN101697970A (en) | Medicine composite for treating and relieving high blood pressure | |
| CN101411713A (en) | Compound Nimodipine tablet, and enteric tablet thereof, as well as preparation method thereof | |
| CN101185624A (en) | Novel composing prescription sustained-release preparation for treating high blood pressure and preparation method thereof | |
| CN100577152C (en) | Losartan potassium and hydrochlorothiazide tablets and preparation method thereof | |
| CN101554377B (en) | Pharmaceutical composition containing prasugrel and carbazochrome sodium sulfonate | |
| CN101317842A (en) | Treating uses of imidazole-5-carboxylic acid derivant | |
| KR20090107954A (en) | Pharmaceutical formulation | |
| CN1961859B (en) | Novel formulation of Tizanidine and derivative thereof and preparation method thereof | |
| CN103721259A (en) | Angiotensin II receptor blocker/thiazide diuretics/5-methyltetrahydrofolate pharmaceutical composition | |
| CN108703956A (en) | A kind of solid composite medicament containing Bosentan | |
| CN101987200B (en) | Compound medicine containing antihypertensive peptide and aldosterone receptor antagonist for curing hypertension |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20090422 |