CN1919195A - Vinpocetine drop pills and its preparation method - Google Patents

Abstract

The invention relates to a drop pill preparation with Vinpocetine as the main ingredient and process for preparing it, compared with the existing dosage forms, the drop pill preparation has the advantages of quick-effectiveness, high biological availability, good taste, and fitting for mass production.

Description

Vinpocetine drop pills and preparation method thereof

Technical field

The present invention relates to the novel formulation and the preparation technology thereof of vinpocetine, be specifically related to Vinpocetine drop pills preparation and preparation method thereof.

Background technology

Vinpocetine (vinpocetine is the derivant of the indole alkaloid vincamine (vincamine) of extraction in the little graceful Herba Catharanthi Rosei of Apocynaceae (Vinca minorL.) VIN), and structural formula is as follows:

Vinpocetine belongs to indoles alkaloid, can see through blood brain barrier easily enters in the brain, at first succeed in developing by Hungary Gedeon Richter company, this medicine is not only effective to the high blood viscosity that prevents and treat cerebral arteriosclerosis, cerebral ischemia and hemorrhagic apoplexy sequela and hypertension, coronary heart disease, and the Pathophysiology of research cerebrovascular disease is also had important value.Be used for the treatment of the spirituality that causes owing to cerebrum blood circulatory disturbance or nerve symptom such as memory disorder, aphasia, action obstacle, giddy, headache etc. clinically, hypertensive encephalopathy, cerebri cerebral vasospasm, arteriae cerebri intimitis, carrying out property cerebrovascular sclerosis.Aspect ophthalmology, be used for the macula degeneration that causes because of retina and choroidal vessels sclerosis and vasospasm.Aspect otology, be used for the treatment of presbyacusis, dizzy etc.Because vinpocetine determined curative effect, the mechanism of action are clear and definite, side effect is little, does not have in the body and accumulates, clinical development and having a extensive future.

Because vinpocetine is water-soluble hardly, and it is many to use the vinpocetine tablet at present clinically, but preparation type tradition relatively, and this conventional formulation is long because of disintegration time, absorb slow, the performance of problems affect curative effect such as bioavailability is low; How to overcome these shortcomings, make the medicine quick acting become the problem of people's active research, drop pill is a kind of spheric pill that utilizes the solid dispersion technology system of dripping to form, it utilizes water-solubility carrier to improve the dissolubility and the dissolution rate of medicine, improve the infiltration rate and the absorbtivity of medicine, thereby improve bioavailability of medicament and improve the curative effect of medicine, but composition between medicine active ingredient and the adjuvant and preparation method then are the factors that influences drop pill, and the present invention forms just on this basis.

Summary of the invention

The objective of the invention is to overcome the deficiencies in the prior art, a kind of rapid-action, oral Vinpocetine drop pills preparation that bioavailability is high and preparation method thereof is provided.

The Vinpocetine drop pills of making by using ultramicro communication technique and dropping pill formulation Technology not only have disintegrate molten loose fast, dissolution and dissolution rate improve, steady quality, the pill volume is little, and both can swallow also can buccal, easy to carry and use, onset is rapid, and compliance is good, is particularly suitable for the characteristics that child, old people, bed patient and dysphagia patients are taken, but also have working condition and production equipment is simple, compare the less advantage of supplementary product consumption with capsule with tablet.

For achieving the above object, the inventor determines to adopt following substrate to prepare Vinpocetine drop pills but is not limited to following substrate: poloxamer, PEG400, cetomacrogol 1000, polyethylene glycol 1500, Macrogol 4000, polyethylene glycol 6000, cetomacrogol 1000 0, sodium stearate, glycerin gelatine, stearic acid, glyceryl monostearate, worm are cured, xylitol, starch or its mixed system.

Because vinpocetine is soluble in the ethanol, thus in a technical scheme, can adopt vinpocetine to be dissolved in a spot of ethanol after, carry out drop pill then and prepare; In another technical scheme, can adopt the vinpocetine using ultramicro communication technique crossed 150 mesh sieves after, carry out the preparation of drop pill.

When adopting single adjuvant to carry out the preparation of drop pill, be preferably Macrogol 4000, polyethylene glycol 6000, adopt two kinds of adjuvants to carry out drop pill when preparing, be preferably Macrogol 4000 and polyethylene glycol 6000, polyethylene glycol 1500 and polyethylene glycol 6000, xylitol and starch, the ratio of two kinds of adjuvants can be various ways; When adopting the adjuvant of two or more form of mixtures, its ratio can adopt various ways.

During the preparation Vinpocetine drop pills, the weight ratio of vinpocetine and adjuvant is 1: 2-20 is preferably 1: 4-15 most preferably is 1: 4-10.

After drop pill is finished, can adopt plain ball directly to use; Or adopted film-coated technique that plain ball is carried out coating, can effectively cover the bitterness of medicine and prevent the drop pill moisture absorption, the dissolve accretions phenomenon, guarantee drop pill in preservation not dried ball, split ball, also guarantee the stability of drop pill in the middle of storing.Described coating material comprises for example conventional coating material or Opadry coating material.

In addition, part exemplary compositions and preparation process parameter thereof are selected listed as following table in the drop pill of the present invention:

Project	Scope	Preferable range
			Poloxamer accounts for weight ratio polyethylene glycol 1500 in the matrix and accounts for weight ratio Macrogol 4000 in the matrix and account for weight ratio Macrogol 6000 in the matrix and account for weight ratio main ingredient in the matrix-matrix ratio material temperature dripping temperature cooling medium condensate temperature water dropper to condensate liquid and increase weight apart from coating solution concentration dressing	0%-50% 0%-100% 0%-100% 0%-100% 1: 2-20 70-100 ℃ 75-100 ℃ atoleine, dimethicone, soybean oil 0-20 ℃ 0-60cm 8-20% 1-8%	0%-20% 0%-30% 0%-100% 0%-100% 1: 4-15 85-95 ℃ 80-95 ℃-atoleine 5-12 ℃, silicone oil 6-18 ℃ of soybean oil 5-15 ℃ of 25-45cm 12-15% 2-6%

The preparation method of drop pill of the present invention comprises the steps:

(1) by the weight proportion of each component,, makes its fusion, stir, add the vinpocetine alcoholic solution of recipe quantity or the atomizing vinpocetine of ultra micro of mistake 150 mesh sieves, stir heating in selected putting of the adjuvant batch can;

(2) with the preheating of drop pill machine, fluid storage compartment temperature constant temperature is fluid temperature, and selecting cooling medium is liquid paraffin or silicone oil or soybean oil, and being chilled to temperature in advance is 0-20 ℃.

(3) pour medicinal liquid into fluid storage compartment, start valve, medicinal liquid is splashed into to condensed fluid,, absorb surface condensation liquid, promptly get plain ball in collecting a mouthful collection drop pill.

(4) plain ball is adopted conventional coating material or Opadry coating material carry out coating, get coated drop pill.

Vinpocetine drop pills smooth surface of the present invention, hardness is suitable and roundness good, and particle diameter can be 2-5mm, is suitable for easily, without any the administration of uncomfortable ground.

Vinpocetine is water insoluble, and the absorption rate of medicine depends on dissolution rate, and dissolution rate improves with the increase of dispersion.Vinpocetine drop pills is the preparation that adopts the preparation of solid dispersion principle, will be in water the medicine dissolution of indissoluble in the water-soluble base Polyethylene Glycol or other substrate of thermosol, solidify by system of dripping and quenching, make medicine be molecule, colloid or microcrystalline state and be scattered in the substrate.Because the total surface area of medicine increases, substrate is hydroaropic substance, and medicine disengages with crystallite or unformed microgranule, and therefore, medicine dissolution and absorption are accelerated, and bioavailability improves.

Following table is the comparing data of Vinpocetine drop pills and marketed tablet.

Project	Drop pill	Tablet
			The molten diffusing time (minute) 10 minutes dissolutions	5.0 more than 60%	20-35 5-25％

Measuring the dissolution method is: change the oar method, dissolution medium is a 900ml water, 37 ℃ of temperature, and rotating speed is 100 rev/mins, calculates with vinpocetine.

Following examples are intended to further specify, and the scope of the invention are not limited.

Embodiment 1

Drop pill (coated pill is not plain ball 1)

Prescription is formed	Consumption
		The vinpocetine polyethylene glycol 6000	5g 20g

Preparation process: in putting of 20g polyethylene glycol 6000 batch can, changing the batch can temperature is 90 ℃, makes its fusion, stirs, and adds the vinpocetine that 150 mesh sieves are crossed in the efflorescence of 5g recipe quantity ultra micro, stirs; With the preheating of drop pill machine, it is 95 ℃ that the fluid storage compartment temperature is promptly dripped system temperature constant temperature, and cooling medium adopts liquid paraffin, and being chilled to temperature in advance is 8-12 ℃, regulate water dropper to condensed fluid apart from 25cm.Pour medicinal liquid into fluid storage compartment, start valve, medicinal liquid is splashed into to condensed fluid,, absorb surface condensation liquid, promptly in collecting a mouthful collection drop pill.

Embodiment 2

Drop pill (coated pill is not plain ball 2)

Prescription is formed	Consumption
		Vinpocetine Macrogol 4000 polyethylene glycol 6000	5g 8g 22g

Preparation process: in 22g polyethylene glycol 6000,8g Macrogol 4000 batch can, changing the batch can temperature is 85 ℃, makes its fusion, stirs, and adds the 5g vinpocetine that is dissolved in the small amount of ethanol, stirs; With the preheating of drop pill machine, it is 90 ℃ that the fluid storage compartment temperature is promptly dripped system temperature constant temperature, and cooling medium adopts dimethicone, and being chilled to temperature in advance is 8-12 ℃, regulate water dropper to condensed fluid apart from 30cm.After the ethanol flavor disappears, pour medicinal liquid into fluid storage compartment, start valve, medicinal liquid is splashed into to condensed fluid, collect drop pill, absorb surface condensation liquid, promptly in collecting mouth.

Embodiment 3

Drop pill (plain ball 3)

Prescription is formed	Consumption
		Vinpocetine poloxamer Macrogol 4000 polyethylene glycol 6000	10g 2g 20g 15g

Preparation process: in 2g poloxamer, 20g Macrogol 4000,15 putting of gram polyethylene glycol 6000 batch cans, changing the batch can temperature is 95 ℃, makes its fusion, stirs, and adds the vinpocetine that 150 mesh sieves are crossed in the efflorescence of 10g recipe quantity ultra micro, stirs; With the preheating of drop pill machine, it is 95 ℃ that the fluid storage compartment temperature is promptly dripped system temperature constant temperature, and cooling medium adopts dimethicone, and being chilled to temperature in advance is 8-10 ℃, regulate water dropper to condensed fluid apart from 25cm.Pour medicinal liquid into fluid storage compartment, start valve, medicinal liquid is splashed into to condensed fluid,, absorb surface condensation liquid, promptly in collecting a mouthful collection drop pill.

Embodiment 4

Drop pill (plain ball 4)

Prescription is formed	Consumption
		Vinpocetine polyethylene glycol 1500 polyethylene glycol 6000	2.5g 5g 20g

Preparation process: in 5g PEG400, putting of 20g polyethylene glycol 6000 batch can, changing the batch can temperature is 95 ℃, makes its fusion, stirs, and adds the 2.5g vinpocetine that is dissolved in the small amount of ethanol, stirs; With the preheating of drop pill machine, it is 95 ℃ that the fluid storage compartment temperature is promptly dripped system temperature constant temperature, and cooling medium adopts liquid paraffin, and being chilled to temperature in advance is 10-12 ℃, regulate water dropper to condensed fluid apart from 35cm.Pour medicinal liquid into fluid storage compartment, start valve, medicinal liquid is splashed into to condensed fluid,, absorb surface condensation liquid, promptly in collecting a mouthful collection drop pill.

Embodiment 5

Drop pill (plain ball 5)

Prescription is formed	Consumption
		The vinpocetine Macrogol 4000	5g 30g

Preparation process: in putting of 30g Macrogol 4000 batch can, changing the batch can temperature is 80 ℃, makes its fusion, stirs, and adds the vinpocetine that 150 mesh sieves are crossed in the efflorescence of 10g recipe quantity ultra micro, stirs; With the preheating of drop pill machine, it is 85 ℃ that the fluid storage compartment temperature is promptly dripped system temperature constant temperature, and cooling medium adopts liquid paraffin, and being chilled to temperature in advance is 8-12 ℃, regulate water dropper to condensed fluid apart from 30cm.Pour medicinal liquid into fluid storage compartment, start valve, medicinal liquid is splashed into to condensed fluid,, absorb surface condensation liquid, promptly in collecting a mouthful collection drop pill.

Embodiment 6

Drop pill (plain ball 6)

Prescription is formed	Consumption
		Vinpocetine starch xylitol	5g 10g 50g

Preparation process: in 10g starch, putting of 50g xylitol batch can, changing the batch can temperature is 85 ℃, makes its fusion, stirs, and adds the vinpocetine that the 5g recipe quantity is dissolved in small amount of ethanol, stirs; With the preheating of drop pill machine, it is 85 ℃ that the fluid storage compartment temperature is promptly dripped system temperature constant temperature, and cooling medium adopts dimethicone, and being chilled to temperature in advance is 8-12 ℃, regulate water dropper to condensed fluid apart from 30cm.Pour medicinal liquid into fluid storage compartment, start valve, medicinal liquid is splashed into to condensed fluid,, absorb surface condensation liquid, promptly in collecting a mouthful collection drop pill.

Embodiment 7

Drop pill (plain ball 7)

Prescription is formed	Consumption
		Vinpocetine poloxamer polyethylene glycol 6000	5g 5g 35g

Preparation process: in 5g poloxamer, putting of 35g polyethylene glycol 6000 batch can, changing the batch can temperature is 90 ℃, makes its fusion, stirs, and adds the vinpocetine that 150 mesh sieves are crossed in the efflorescence of 5g recipe quantity ultra micro, stirs; With the preheating of drop pill machine, it is 90 ℃ that the fluid storage compartment temperature is promptly dripped system temperature constant temperature, and cooling medium adopts soybean oil, and being chilled to temperature in advance is 10-12 ℃, regulate water dropper to condensed fluid apart from 25cm.Pour medicinal liquid into fluid storage compartment, start valve, medicinal liquid is splashed into to condensed fluid,, absorb surface condensation liquid, promptly in collecting a mouthful collection drop pill.

Embodiment 8

Coated drop pill

Preparation process:

1). get any one of the plain ball of embodiment 1-7 gained, carry out following operation.

2). drop pill adopts Opardry II coating materials, presses the conventional preparation of Opardry II coating materials coating solution, carries out coating.Full water is solvent, coating solution solid content 15%.Inlet temperature is 85 ℃, and the sheet bed tempertaure is 35-38 ℃, and atomizing pressure is 1.5bar, and the coating pan rotating speed is 15-23 rev/min, charging flow velocity 3-4g/min.Product clothing film-strength is good, and adhesive force is better, uniform coloring.

Claims (8)

1. Vinpocetine drop pills, comprise with the vinpocetine being active ingredient,, xylitol cured with poloxamer, PEG400, cetomacrogol 1000, polyethylene glycol 1500, Macrogol 4000, polyethylene glycol 6000, cetomacrogol 1000 0, sodium stearate, glycerin gelatine, stearic acid, glyceryl monostearate, worm, starch or its mixed system are pharmaceutic adjuvant, and the weight ratio of vinpocetine and adjuvant is 1: 2-20.

2. drop pill according to claim 1, pharmaceutic adjuvant are selected from and are polyethylene glycol 6000, Macrogol 4000 or their mixture.

3. drop pill according to claim 1, pharmaceutic adjuvant are Macrogol 4000.

4. drop pill according to claim 1, the weight ratio of wherein said active ingredient vinpocetine and adjuvant is 1: 4-15.

5. drop pill according to claim 1, the weight ratio of wherein said active ingredient vinpocetine and adjuvant is 1: 4-10.

6. drop pill according to claim 1, wherein the vinpocetine of Jia Ruing is the vinpocetine of ultra micro powdered form.

7. drop pill according to claim 1, wherein the vinpocetine of Jia Ruing is the vinpocetine solution that is dissolved in small amount of ethanol.

8. the preparation method of each described drop pill among the claim 1-7 is followed successively by the following step:

(1) by the weight proportion of each component,, makes its fusion, stir, add the vinpocetine alcoholic solution of recipe quantity or the atomizing vinpocetine of ultra micro of mistake 150 mesh sieves, stir heating in selected putting of the adjuvant batch can;

(2) with the preheating of drop pill machine, fluid storage compartment temperature constant temperature is fluid temperature, and selecting cooling medium is liquid paraffin or silicone oil or soybean oil, and being chilled to temperature in advance is 0-20 ℃.

(3) pour medicinal liquid into fluid storage compartment, start valve, medicinal liquid is splashed into to condensed fluid,, absorb surface condensation liquid, promptly get plain ball in collecting a mouthful collection drop pill.

(4) plain ball is adopted conventional coating material or Opadry coating material carry out coating, get coated drop pill.