CN102406616B - Montmorillonite combined propranolol sustained-release dry suspension, preparation method thereof and preparation method of Na-montmorillonite used in propranolol sustained-release dry suspension - Google Patents
Montmorillonite combined propranolol sustained-release dry suspension, preparation method thereof and preparation method of Na-montmorillonite used in propranolol sustained-release dry suspension Download PDFInfo
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- CN102406616B CN102406616B CN201110389584.2A CN201110389584A CN102406616B CN 102406616 B CN102406616 B CN 102406616B CN 201110389584 A CN201110389584 A CN 201110389584A CN 102406616 B CN102406616 B CN 102406616B
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- propranolol
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- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000025102 vascular smooth muscle contraction Effects 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- CPYIZQLXMGRKSW-UHFFFAOYSA-N zinc;iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+3].[Fe+3].[Zn+2] CPYIZQLXMGRKSW-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to a montmorillonite combined propranolol sustained-release dry suspension, a preparation method thereof and a preparation method of Na-montmorillonite used in the propranolol sustained-release dry suspension. The propranolol sustained-release dry suspension comprises montmorillonite-propranolol compound, an outer coating sustained-release material, a flavoring agent and a suspending aid. The preparation method comprises the following steps: firstly, preparing the montmorillonite-propranolol compound; secondly, coating partial montmorillonite-propranolol compound; and finally, mixing the montmorillonite-propranolol compound, the montmorillonite-propranolol compound coating, the flavoring agent and the suspending aid. The propranolol sustained-release dry suspension provided by the invention has good compliance to a patient who has oral administration difficulty, utilizes particle exchange carrier namely montmorillonite, and can stay in a human body for longer time.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation and preparation method thereof, in particular, the present invention relates to a kind of Propranolol slow-release dry suspension, its preparation method and the preparation method for sodium montmorillonite wherein of combining Montmorillonitum.
Background technology
Propranolol hydrochloride chemical name is: 1-isopropylamino-3-(1-naphthoxy)-2-propanol hydrochloride
Its structural formula is:
Molecular formula: Cl
6h
21nO
2hCl
Molecular weight: 295.81
The pharmacological action of propranolol hydrochloride is mainly manifested in:
Propranolol is non-selective Competitive assays adrenergic alpha-agonists.There is the β 1, the beta 2 receptor that block on heart, the effect of antagonism sympathetic activation and catecholamine; Also there is the contractility and contraction speed that reduce heart, suppress vascular smooth muscle contraction simultaneously, reduce myocardial oxygen consumption, the effect that the oxygen relation between supply and demand of ischemic myocardium is restored balance in low-level, can be used for treating angina pectoris.
There is the adrenergic suppressing heartpacer current potential excited, be used for the treatment of arrhythmia.Also by maincenter, adrenergic neuron blockade, suppress the effect such as renin release and heart output reduction, be used for the treatment of hypertension.
Be applicable to hypertension (separately or share with other antihypertensive); Exertional angina pectoris; Control Supraventricular tachyarrhythmia, ventricular arrhythmia, particularly or Folium Digitalis Purpureae relevant with catecholamine causes arrhythmia.The room that can be used for Folium Digitalis Purpureae unsatisfactory curative effect is flutterred, the control of atrial fibrillation Ventricular Rate, also can be used for intractable premature beat, improves the symptom of patient; Lower hypertrophic cardiomyopathy efferent tract pressure reduction, alleviate the symptoms such as angina pectoris, cardiopalmus and faintness; Coordinate α receptor blocking agent to be used for pheochromocytoma patient and control tachycardia; For controlling the rapid heart rate of hyperthyroidism, also can be used for treating thyroid storm; As secondary prevention, reduce myocardial infarction mortality rate
The effect of competitive antagonism isoproterenol and norepinephrine, blocks beta 2 receptor, reduces plasma renin activity.Bronchospasm can be caused.Suppress insulin secretion, blood glucose is raised, covers Hypoglycemic symptoms, postpone hypoglycemic recovery.
Have obvious antiplatelet aggregative activity, this is mainly with the membrane stabilizing action of medicine and to suppress platelet membrane Ca+ to transport relevant.
After propranolol hydrochloride oral administration, gastrointestinal absorption is comparatively complete, widely at intrahepatic metabolism, and bioavailability about 30%.Within after medicine 1-1.5 hour, reach peak plasma concentrations, the elimination half-life is 2-3 hour, plasma protein binding rate 90-95%.There is notable difference, apparent volume of distribution 3.9 ± 6.0L/kg in individual blood drug level.Through renal excretion, be mainly metabolite, fraction (< 1%) is female medicine.Can not discharge through dialysis.
Montmorillonitum (montmorillonite) is processed by Purification of Bentonite and obtains.Bentonite has another name called bentonite (bentonite), take Montmorillonitum as the clay pit of main mineral constituent, its smectite content is 40%-90%, also containing mineral such as a small amount of kaolinite, allophane, chlorite, opal, Muscovitums, bentonitic performance is relevant with smectite content, more containing Montmorillonitum, its performance is more superior.American Pharmacopeia, British Pharmacopoeia and European Pharmacopoeia have recorded bentonite.Montmorillonitum has been applied for many years in pharmaceuticals industry as medicinal raw material and adjuvant, medicinal smectite odorless, has slight native taste, and near-white or micro-yellow have wax sample gloss, nonirritant.Measure bentonite to neural impact with mice autonomic activities instrument, two road physiographs measure respiratory depth and the frequency of rat, and Mus tail method measures rat blood pressure, uses ELG-8511 electrocardiograph, adopts two road translocations to determine Rat Ecg.Result: bentonite maximum tolerated dose is 8g/kg, be equivalent to 2666 times of people's consumption, toxicity is very little.Statistical result shows that bentonite does not affect nerve, breathing and cardiovascular system.Montmorillonitum has good absorbability, cation exchange capacity (CEC) and imbibition ability because of its special crystal structure.Montmorillonitum pharmacological research shows, it has good adsorption to escherichia coli, vibrio cholera, campylobacter jejuni, staphylococcus aureus and rotavirus and cholate; Fixation is have to bacterial poison; Montmorillonitum only adsorbs, fixed surface with the pathogenic charged pathogen of grain encoding proteins (CS31 A), the normal flora of effects on surface not with CS31 A is without fixing scavenging action.
Montmorillonitum, owing to having water absorption, suspension, dispersibility, caking property, thixotropy, can have the performance of emulsifying, thickening, suspending, absorption, is desirable pharmaceutic adjuvant, is widely used in various dosage form.
Such as: use gentian violet 1.2g, white vaseline 10g, liquid paraffin 6g, octadecanol 9g, sodium lauryl sulphate 1g, glycerol 5g, Montmorillonitum aqueous dispersions 80mL (ethyl hydroxybenzoate 0.5g), can obtain good stability, be easy to coating, easily eluting, nonirritant, avirulent methyl violet cream.
Montmorillonitum 70-85 part, surfactant 1-5 part, disinfectant 0.2-1 part, abrasive 12-25 part, can obtain the sterilization paste of hospital and family's use.
1% Montmorillonitum is as sucralfate suspending agent, and effect is better than CMC-Na, and redispersibility is good, and sedimentation is slow, and coagulated particles is fine and smooth; The suspending agent of Calamine Lotion made by 2% Montmorillonitum, its sedimentation volumn ratio, microgranule Brownian movement, heavy dispersion force, and caking situation, the indexs such as particle size are better than CMC-Na, the sodium alginate of same concentration.
Montmorillonitum 3.0g, CMC-Na 1.7g, tween 80 and glycerol in right amount each, obtained 600cm
2film.This Montmorillonitum film can with ulcer surface close contact, and medicine film dissolves for about 5 minutes.
Montmorillonitum can be used for the preparation of controlled release theophylline sheet, by tabletting after theophylline, microcrystalline Cellulose, Montmorillonitum, CaCO3, PVP mixing, then uses ethylcellulose coat, can obtain coated slow release theophylline sheet.
The thyroxine speed disintegrating tablet that Montmorillonitum and microcrystalline Cellulose and corn starch etc. are made as disintegrating agent and chewable tablet, be easy to patient especially and swallow, can disintegrate be just meticulous granule rapidly within the several seconds, is suitable for very much human body alimentary canal to thyroxinic absorption.
In the preparation capable of permeating skin process of preparation 17 beta estradiol, Montmorillonitum is added pressure sensitive adhesive, medicine can be made to discharge sooner.
When preparing microcapsule with solvent evaporation technique, add Montmorillonitum and can prevent gelling and cohesion.
Because propranolol hydrochloride slow releasing tablet has some limitations when difficult patient is swallowed in treatment, so the present invention develops slow-release suspension to overcome this difficulty, have certain scavenging action in conjunction with the harmful microorganism of Montmorillonitum to intestinal simultaneously and be good Ion exchangers support, the present invention develops the slow-release dry suspension of the complex of Montmorillonitum-propranolol hydrochloride.
Summary of the invention
The object of this invention is to provide a kind of Propranolol slow-release dry suspension of combining Montmorillonitum, to solve the problem of the difficulty of swallowing that existing propranolol hydrochloride exists, the Propranolol slow-release dry suspension of associating Montmorillonitum of the present invention obviously can also improve compliance and the convenience of administration, can stop the longer time in human body, bioavailability is high.
Another object of the present invention is to provide a kind of preparation method of combining the Propranolol slow-release dry suspension of Montmorillonitum.
Another object of the present invention is to provide a kind of preparation method of sodium montmorillonite.
In order to realize object of the present invention, technical scheme of the present invention is:
Combine a Propranolol slow-release dry suspension for Montmorillonitum, it is characterized in that, comprise Montmorillonitum-Propranolol complex, exterior coating slow-release material, correctives, suspending agent.
A part in wherein said Montmorillonitum-Propranolol complex forms Montmorillonitum-Propranolol complex coating thing by exterior coating slow-release material is coated, and described Propranolol slow-release dry suspension is the mixture that Montmorillonitum-Propranolol complex coating thing and Montmorillonitum-Propranolol complex, correctives, suspending agent are formed.
The mass ratio of described Montmorillonitum-Propranolol complex coating thing and Montmorillonitum-Propranolol complex is 4: 1 ~ 3: 1.
In the preferred embodiment of the present invention, described exterior coating slow-release material is the mixture of one or more in polyvinylpolypyrrolidone, hydroxypropyl emthylcellulose, ethyl cellulose, hydroxyethyl-cellulose, sodium alginate, Brazil wax, castor oil hydrogenated this law, and its consumption is 100% ~ 400% of propranolol hydrochloride quality.
In a more preferred embodiment of the present invention, described exterior coating slow-release material is polyvinylpolypyrrolidone.
In another more preferred embodiment of the present invention, described exterior coating slow-release material is hydroxypropyl emthylcellulose.
In the preferred embodiment of the present invention, described correctives is the mixture of one or more in sodium chloride, glucose, sucrose, aspartame, stevioside, vanillin, and its consumption is 10% ~ 40% of slow-release dry suspension gross mass.
In the preferred embodiment of the present invention, described suspending agent is the mixture of one or more in arabic gum, carbopol, polyvidone, glucosan, syrup, thixotrope, and its consumption is the 5wt% ~ 30wt% of slow-release dry suspension gross mass.
In a more preferred embodiment of the present invention, described suspending agent is polyvidone, glucosan or its mixture.
The preparation method of the Propranolol slow-release dry suspension of associating Montmorillonitum of the present invention, comprises the following steps:
(1) preparation of Montmorillonitum-Propranolol complex: Montmorillonitum is placed in water and obtains Montmorillonitum dispersion liquid, by in propranolol hydrochloride aqueous solution instillation Montmorillonitum dispersion liquid in 50 ~ 80 DEG C of water-baths, dropwise rear continuation stirring reaction 40 ~ 80 minutes, react rear filtration and washed with water, washings detect the content of propranolol hydrochloride, and the precipitate obtained is obtained Montmorillonitum-Propranolol complex after dry 20 ~ 30 hours at 50 ~ 70 DEG C;
(2) preparation of exterior coating slow-release material aqueous solution: exterior coating slow-release material is dissolved in water for injection and obtains exterior coating slow-release material aqueous solution
(3) the coating thing preparation of Montmorillonitum-Propranolol complex: the part Montmorillonitum-Propranolol complex of step (1) gained is placed in the suspension that water obtains Montmorillonitum-Propranolol complex, at 25 ~ 35 DEG C, exterior coating slow-release material aqueous solution step (2) prepared adds in the suspension of Montmorillonitum-Propranolol complex, react 30 ~ 300 minutes, then filter, the filtrate air dry oven drying of 50 ~ 70 DEG C obtains the coating thing of Montmorillonitum-Propranolol complex for 20 ~ 30 hours;
(4) preparation of Propranolol slow-release dry suspension: be obtain Propranolol slow-release dry suspension in 50 ~ 100 minutes by the coating thing of the Montmorillonitum-Propranolol complex of remaining Montmorillonitum-Propranolol complex and step (3) gained, correctives and suspending agent incorporation time.
In described step (1), the mass concentration of the general naphthalene Nore of hydrochloric acid is 3mg/mL ~ 9mg/mL, and the mass concentration of Montmorillonitum is 9mg/mL ~ 15mg/mL, and the mass ratio of Montmorillonitum and the general naphthalene Nore of hydrochloric acid is 5: 1 ~ 10: 1.
In described step (2), the mass concentration of exterior coating slow-release material aqueous solution is 1mg/mL ~ 6mg/mL.
In described step (3), the mass concentration of the suspension of Montmorillonitum-Propranolol complex is 8mg/mL ~ 12mg/mL, and the mass ratio of Propranolol-Montmorillonitum complex and outer coatings slow-release material is 20: 1 ~ 3: 1.
In described step (4), the addition of described correctives is 10% ~ 40% of slow-release dry suspension gross mass, and the addition of suspending agent is 5% ~ 30% of slow-release dry suspension gross mass.
In described step (4), the mass ratio of Montmorillonitum-Propranolol complex coating thing and Montmorillonitum-Propranolol complex is 4: 1 ~ 3: 1.
In the preferred embodiment of the present invention, in step (1), described Montmorillonitum is sodium montmorillonite.
The preparation method of sodium montmorillonite of the present invention, comprises the following steps:
(1) preparation of sodium montmorillonite: ca-montmorillonite is stirred in 0.05mol/L ~ 0.15mol/L sodium salt solution and reacts for 8 ~ 24 hours; Reactant is centrifugal, obtains sodium montmorillonite with detecting with silver nitrate in deionized water wash to washings without chloride ion;
(2) purification of sodium montmorillonite: sodium montmorillonite is put into distilled water, stir that to put into after 30 minutes be highly 10 ~ 30cm sedimentation pipe, sedimentation pipe is placed in the water-bath that bath temperature is 20 ~ 40 DEG C, sedimentation time is after 5 ~ 24 hours, collect float, sieve float crushed after being dried in the baking oven of 70-120 DEG C the sodium montmorillonite after obtaining purification.
Mixing time in described step (1) is 8-16 hour.
In the preferred embodiment of the present invention, the sodium salt in step (1) is sodium chloride.
In described step (2), the sedimentation time is 10-15 hour, and sedimentation pipe height is 14-18cm, and bath temperature is 26-32 DEG C.
Propranolol slow-release dry suspension makes specification is the most at last 40mg-80mg/ bag, every bag heavy 1g-3g in the present invention.
The present invention is in order to solve the difficulty of swallowing of propranolol hydrochloride, propranolol hydrochloride is developed to slow-release dry suspension, the principle of ion exchange is adopted for reaching slow release effect, utilize the inner the exchangeable cationic type between layer of the octahedral structure of Montmorillonitum inside, with the N ions binding of positively charged in propranolol hydrochloride, form Montmorillonitum-Propranolol complex, in order to better reach slow release effect by complex povidone solution coating, make the inner space pack portion polyvidone of complex, thus slow down the release of propranolol hydrochloride.The one or more combination thing in correctives sodium chloride, glucose, sucrose, aspartame, stevioside, vanillin is added in order to the complex soil taste covering Montmorillonitum-Propranolol.
Although the complex of Montmorillonitum-Propranolol has certain suspension effect in addition, in order to sedimentation volume ratio being controlled in suitable scope, suspending agent is added, as one or more in arabic gum, carbopol, polyvidone, glucosan, syrup, thixotrope in the complex of Montmorillonitum-Propranolol.In order to make release reach quality standards, non-coating Montmorillonitum-Propranolol complex is carried out mixing of proper proportion with the complex of coating.
The present invention uses Montmorillonitum as Ion exchangers support, and Montmorillonitum has certain effect at the harmful microorganism of absorption gastrointestinal cover, so this preparation not only has the main indications such as blood pressure lowering arrhythmia, also has certain protection gastrointestinal tract effect.
Accompanying drawing explanation
Fig. 1 measures release with dissolution method first method, and with hydrochloric acid solution (1 → 100) for dissolution medium, rotating speed is 100rpm per minute, measures the effect schematic diagram of absorbance with 290nm wavelength place.
Detailed description of the invention
The present invention can be understood more specifically by the following example, the present invention includes but be not limited to the content of following specific embodiment.
Example one
The preparation of sodium montmorillonite and purification:
Get 300g ca-montmorillonite to stir 12 hours in the sodium chloride solution of 3L 0.1mol/L, react 3 times, then centrifugal, obtain sodium montmorillonite crude product with detecting with silver nitrate in deionized water wash to washings without chloride ion; 150g sodium montmorillonite crude product is put into distilled water, stirs the sedimentation pipe putting into high 15cm after 30 minutes, sedimentation pipe is placed in the water-bath that bath temperature is 30 DEG C, sedimentation 10 hours, collect float; Float is dry in the baking oven of 90-100 DEG C, pulverize 200 mesh sieves after being dried to suitable moisture and obtain sodium montmorillonite purification product.
Example two
The preparation of sodium montmorillonite and purification:
Get 300g ca-montmorillonite to stir 8 hours in the sodium chloride solution of 3L 0.14mol/L, react 3 times, then centrifugal, obtain sodium montmorillonite crude product with detecting with silver nitrate in deionized water wash to washings without chloride ion; 150g sodium montmorillonite crude product is put into distilled water, stirs the sedimentation pipe putting into high 18cm after 30 minutes, sedimentation pipe is placed in the water-bath that bath temperature is 32 DEG C, sedimentation 14 hours, collect float; Float is dry in the baking oven of 90-100 DEG C, pulverize 200 mesh sieves after being dried to suitable moisture and obtain sodium montmorillonite purification product.
Example three
The preparation of sodium montmorillonite and purification:
Get 300g ca-montmorillonite to stir 15 hours in the sodium chloride solution of 3L 0.07mol/L, react 3 times, then centrifugal, obtain sodium montmorillonite crude product with detecting with silver nitrate in deionized water wash to washings without chloride ion; 150g sodium montmorillonite crude product is put into distilled water, stirs the sedimentation pipe putting into high 14cm after 30 minutes, sedimentation pipe is placed in the water-bath that bath temperature is 26 DEG C, sedimentation 10 hours, collect float; Float is dry in the baking oven of 90-100 DEG C, pulverize 200 mesh sieves after being dried to suitable moisture and obtain sodium montmorillonite purification product.
Detect above-mentioned three batches of obtained sodium montmorillonite, assay is as follows:
Can be drawn by example one, two, three and require that the sodium montmorillonite that interior purification parameter obtains all meets the requirements, wherein best with the cation exchange capacity (CEC) of example one.
Example four
The preparation of Montmorillonitum-Propranolol complex: the sodium montmorillonite that 1g is prepared by example one is placed in 100mL water for injection and obtains sodium montmorillonite dispersion liquid, another respectively by 200mg, 150mg, the propranolol hydrochloride of 100mg is dissolved in obtained propranolol hydrochloride solution in 25mL water for injection, then in 50 DEG C of water-baths, propranolol hydrochloride solution is instilled in sodium montmorillonite dispersion liquid with the speed of 1mL/min clock, dropwise rear continuation stirring reaction 45 minutes, after having reacted, filter and wash with water for injection, washings detect the content of propranolol hydrochloride, precipitate is obtained Montmorillonitum-Propranolol complex after dry 24 hours at 60 DEG C.
Testing result in example four in cleaning mixture is respectively 152mg, 121mg and 84mg.
Example five
The preparation of Montmorillonitum-Propranolol complex: the sodium montmorillonite that 1g is prepared by example one is placed in 75mL water for injection and obtains sodium montmorillonite dispersion liquid, another respectively by 200mg, 150mg, the propranolol hydrochloride of 100mg is dissolved in obtained propranolol hydrochloride solution in 25mL water for injection, then in 70 DEG C of water-baths, propranolol hydrochloride solution is instilled in sodium montmorillonite dispersion liquid with the speed of 1mL/min clock, dropwise rear continuation stirring reaction 60 minutes, react rear simple filtration and washed with water for injection, washings detect the content of propranolol hydrochloride, by precipitate at 60 DEG C dry 24 hours.After obtain Montmorillonitum-Propranolol complex.
Testing result in example five in cleaning mixture is respectively 136mg, 111mg and 69mg.Cationic abundant exchange is conducive to by when experiment four and known, the reaction temperature height high in propranolol hydrochloride concentration of experiment five.
Example six
The coating thing preparation of Montmorillonitum-Propranolol complex: take the Montmorillonitum-Propranolol complex 1g of preparation in example four as obtaining Montmorillonitum-Propranolol complex suspension in 100mL water for injection, separately join F1=50mg, F2=150mg, the PVP K30 of F3=300mg is dissolved in obtained povidone solution in 50mL water for injection, povidone solution is added in Montmorillonitum-Propranolol complex suspension under 30 DEG C of conditions, react 1 hour, then filter, then with the dry coating thing obtaining Montmorillonitum-Propranolol complex for 24 hours of air dry oven of 60 DEG C.
Example seven
The coating thing preparation of Montmorillonitum-Propranolol complex: take the Montmorillonitum-Propranolol complex 1g of preparation in example four as obtaining Montmorillonitum-Propranolol complex suspension in 100mL water for injection, separately join F4=50mg, F5=150mg, the PVP K30 of F6=300mg is dissolved in obtained povidone solution in 50mL water for injection, povidone solution is added in Montmorillonitum-Propranolol complex suspension under 40 DEG C of conditions, react 4 hours, then filter, then with the dry coating thing obtaining Montmorillonitum-Propranolol complex for 24 hours of air dry oven of 60 DEG C.
Measure release with dissolution method first method, with hydrochloric acid solution (1 → 100) for dissolution medium, rotating speed is 100rpm per minute, measures absorbance with 290nm wavelength place.Obtain a result and see Fig. 1.
Example eight
Montmorillonitum-Propranolol complex 200g that the coating thing 650g of the Montmorillonitum that treating excess syndrome example six F2 obtains-Propranolol complex and example four obtain, separately add aspartame 350g, polyvidone 200g, glucosan 90g, micropowder silica gel 10g, make every bag heavy 1.5g, the amount of propranolol hydrochloride is the Propranolol slow-release dry suspension of 40mg/ bag.
Example nine
Montmorillonitum-Propranolol complex 400g that the coating thing 1300g of the Montmorillonitum that treating excess syndrome example six F2 obtains-Propranolol complex and example four obtain, separately add aspartame 700g, polyvidone 400g, glucosan 180g, micropowder silica gel 20g, make every bag heavy 3.0g, the amount of propranolol hydrochloride is the Propranolol slow-release dry suspension of 80mg/ bag.
The sedimentation volume ratio of test case eight and example nine is respectively 0.97 and 0.96, release example eight is 1.5 hours (25%), 4 hours (50%), 8 hours (75%), 12 hours (86%), example nine is 1.5 hours (23%), 4 hours (54%), 8 hours (74%), 12 hours (88%), all meet the release requirement of slow releasing preparation, but release, trap and bioavailability need research further in vivo.
Claims (1)
1. combine the Propranolol slow-release dry suspension of Montmorillonitum for one kind, it is characterized in that, get coating thing 650g and the Montmorillonitum-Propranolol complex 200g of Montmorillonitum-Propranolol complex, separately add aspartame 350g, polyvidone 200g, glucosan 90g, micropowder silica gel 10g, make every bag heavy 1.5g, the amount of propranolol hydrochloride is the Propranolol slow-release dry suspension of 40mg/ bag;
The coating thing preparation method of Montmorillonitum-Propranolol complex is: take Montmorillonitum-Propranolol complex 1g and be placed in 100mL water for injection and obtain Montmorillonitum-Propranolol complex suspension, the PVP K30 of separately joining 150mg is dissolved in obtained povidone solution in 50mL water for injection, povidone solution is added in Montmorillonitum-Propranolol complex suspension under 30 DEG C of conditions, react 1 hour, then filter, then with the dry coating thing obtaining Montmorillonitum-Propranolol complex for 24 hours of air dry oven of 60 DEG C;
The preparation method of Montmorillonitum-Propranolol complex is: 1g sodium montmorillonite is placed in 100mL water for injection and obtains sodium montmorillonite dispersion liquid, another being dissolved in by the propranolol hydrochloride of 200mg in 25mL water for injection obtains propranolol hydrochloride solution, then in 50 DEG C of water-baths, propranolol hydrochloride solution is instilled in sodium montmorillonite dispersion liquid with the speed of 1mL/min, dropwise rear continuation stirring reaction 45 minutes, after having reacted, filter and wash with water for injection, washings detect the content of propranolol hydrochloride, precipitate is obtained Montmorillonitum-Propranolol complex after dry 24 hours at 60 DEG C, testing result in cleaning mixture is 152mg,
The preparation method of sodium montmorillonite is: get 300g ca-montmorillonite and stir 12 hours in the sodium chloride solution of 3L 0.1mol/L, react 3 times, then centrifugal, obtains sodium montmorillonite crude product with detecting with silver nitrate in deionized water wash to washings without chloride ion; 150g sodium montmorillonite crude product is put into distilled water, stirs the sedimentation pipe putting into high 15cm after 30 minutes, sedimentation pipe is placed in the water-bath that bath temperature is 30 DEG C, sedimentation 10 hours, collect float; Float is dry in the baking oven of 90-100 DEG C, pulverize 200 mesh sieves after being dried to suitable moisture and obtain sodium montmorillonite purification product.
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| Formulation and Evaluation of Oral Sustained Release Suspensions Using Ethyl Cellulose Microcapsules Containing Propranohol Hydrochloride Using Ion Exchange Resinates;N.SURESH et.al;《Asian Journal of Chemistry》;20071231;第19卷(第4期);第2757－2763页 * |
| Interaction of propranohol hydrochloride with montmorillonite;M.J.SANCHEZ MARTIN et.al;《J.Pharm.Pharmacol.》;19811231;第33卷;第408－410页 * |
| 高浓度氯化钠循环传质钠化钙基蒙脱石;黎艳等;《非金属矿》;20110930;第34卷(第5期);第4－7页 * |
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