CN105616382A - Colloidal bismuth pectin capsule preparation and preparation method - Google Patents

Abstract

The invention provides a colloidal bismuth pectin capsule preparation and a preparation process therefor. A capsule shell of the capsule is a hollow capsule shell containing hydroxypropyl starch. The capsule has good dispersion uniformity and uniform drug concentration in a gastric acid environment, and the preparation process is simple.

Description

A kind of Couoidal bismuth pectin capsules preparation and preparation method

Technical field

The present invention relates to the capsule preparations of a kind of Colloidal Bismuth Pectin and its preparation method, it is specially the capsule of a kind of Colloidal Bismuth Pectin adopting hydroxypropylated starch Capsules shell to prepare, belongs to medical art.

Background technology

Tradition gelatine capsule is hydrolyzed obtained animal proteinum colloid gelatin as capsule shell material using the skin of animal, bone, therefore there is multiple security risk. Limited owing to originating, illegal businessman utilizes the processing scrap stock of industrial hides, or the non-leather reclaimed treated made the animal derived Capsules that edible or pharmagel thus supports and may be had that heavy metals exceeding standard, water content are too high, cholesterol levels height and cause the security risks such as animal source transmissible disease.

Therefore, select a kind of safe and effective, quality controllable and possess good pharmacoeconomics be worth capsule preparations, there is irreplaceable use value.

Hydroxypropylated starch capsule then possesses the remarkable advantages such as natural safety, long quality-guarantee period, adaptation be wide. Starch capsule derives from natural cassava, and starch is after denaturing treatment, it is possible to effectively improve the character of starch paste, strengthens the wetting ability of starch paste, the transparency of starch paste and stability is increased to some extent, not easily precipitates, good film-forming property, have excellent toughness. Not only there is many advantages such as raw material sources are natural, security good, wide adaptability, shelf-stable, also avoid the animal source disease of conventional capsules.

Prior art prepares Capsules shell as CN104083768A discloses one, is made up of the composition of following weight proportion: component A: starch and derivative 15-30 part thereof; B component: vegetable jelly 2-13 part; Component C: tinting material 0-5 part. Wherein, starch described in component A and derivative thereof are the combination of starch and hydroxypropylated starch.

Colloidal Bismuth Pectin is a kind of novel colloidal state bismuth preparation, is the salt that biomacromolecule pectic acid (D-polygalacturonic acid) is formed with bismuth metal ion and potassium ion. Colloidal Bismuth Pectin mechanism of action is that it has stronger colloid property; Colloidal Bismuth Pectin is the small molecules acid group that instead of in existing bismuth preparation with biomacromolecule pectic acid; thus change the colloid feature of colloidal bismuth; make it form high viscosity colloidal sol in acidic medium, gastric mucosa is formed one layer of firmly protective membrane.

The barrier action experiment in vitro strengthening gastric mucosa is also it has proven convenient that the collosol property colloidal bismuth more any than other that formed in acidic medium of Colloidal Bismuth Pectin is all good. It can be deposited on the cell walls of helicobacter pylori, makes the cavity having in thalline in various degree, causes cell wall rupture, and the activity of anti-bacteria enzyme, interference bacterial metabolism effect, makes it that the normal defense function of human body is become more responsive.

Colloidal Bismuth Pectin also directly stimulates the generation of prostaglandin(PG) and Urogastron, makes ulcer surface and rotten to the corn face quickly-healing and stops blooding.

But, owing to the viscosity of Colloidal Bismuth Pectin is relatively big, can be agglomerating in water, need vigorous stirring just can scatter, it is diluted with a large amount of weighting agent by prior art usually, but effect is poor, meet water and be still easier to agglomerating.

The present inventor is by experiment, it unexpectedly has been found that Couoidal bismuth pectin capsules prepared by the Capsules shell adopting hydroxypropylated starch to prepare, and can solve the problems of the technologies described above well. Capsule shell and colloid can fully mix even in stomach, form the disintegration point of equal, avoid local drug concentration excessive, cause damage, it is to increase bioavailability.

Summary of the invention

It is an object of the invention to provide that a kind of dispersing uniformity is good in gastric acid environment, drug level even, and the simple Couoidal bismuth pectin capsules agent of preparation technology and preparation technology thereof.

It is an object of the invention to provide a kind of Couoidal bismuth pectin capsules, it is characterised in that capsule shell is for containing hydroxypropylated starch Capsules shell.

As one of specific embodiment of the invention scheme, in the capsule shell of Capsules except hydroxypropylated starch, also can add jelling agent, help the conventional additives such as jelling agent, softening agent, wetting Agent for Printing Inks.

Jelling agent, includes but not limited to gum arabic, xanthan gum, carrageenin, chitosan, trehalose konjak gum, carrageenin;

Help jelling agent, include but not limited to sodium salt or the sylvite of Citric Acid, tartrate, phosphoric acid, acetic acid and ethylenediamine tetraacetic acid (EDTA);

Softening agent, includes but not limited to glycerine, sorbyl alcohol, N.F,USP MANNITOL, triethyl citrate, stearic acid, sucrose, fructose;

Wetting Agent for Printing Inks, includes but not limited to Sodium.alpha.-hydroxypropionate, propylene glycol, poly(oxyethylene glycol) 400, sorbyl alcohol, polyvidone.

As one of specific embodiment of the invention scheme, thing in the capsule of Capsules, except Colloidal Bismuth Pectin, the supplementary additive being suitable for active medicine can be added, include but not limited to weighting agent, lubricant, tackiness agent, disintegrating agent, glidant etc.

Weighting agent, includes but not limited to starch, Microcrystalline Cellulose, lactose, N.F,USP MANNITOL, dextrin, pregelatinized Starch, N.F,USP MANNITOL, sorbyl alcohol etc.

Lubricant, includes but not limited to Magnesium Stearate, talcum powder, Glyceryl Behenate, polyoxyethylene glycol, sodium lauryl sulphate etc.

Tackiness agent, includes but not limited to starch slurry, polyvidone, hypromellose, hydroxypropylcellulose, gum arabic, xanthan gum, Xylo-Mucine etc.

Disintegrating agent, includes but not limited to carboxymethylstach sodium, polyvinylpolypyrrolidone, croscarmellose sodium, low-substituted hydroxypropyl cellulose etc.

Glidant, includes but not limited to silicon-dioxide, talcum powder etc.

Another object of the present invention, it provides a kind of prepare the preparation method containing hydroxypropylated starch Capsules shell, it is characterised in that comprising:

(1) glue is changed: by purified water in entering glue tank, be heated to 80��100 DEG C, then add hydroxypropylated starch, insulated and stirred 90��180min; Then add jelling agent, help jelling agent, softening agent and wetting Agent for Printing Inks, stir 10��15min, add gac and stir decolouring 15min, be filtered in insulated tank temporary;

(2) sol solution obtained is processed into hydroxypropylated starch Capsules shell by full-automatic hollow capsule maker.

Another object of the present invention, it provides a kind of method preparing Couoidal bismuth pectin capsules, it is characterised in that comprise following preparation method:

(1) stock and adjunct taking recipe quantity mixes, and granulates according to feedstock property selectivity, wet granulation or dry granulation;

(2) by the mixed powder or particles filled in capsule shell of preparation.

Accompanying drawing explanation

Hereinafter, come by reference to the accompanying drawings embodiment of the present invention are described in detail, wherein:

Fig. 1 Couoidal bismuth pectin capsules plasma concentration curve figure.

Embodiment

Following examples are the further explanations to the present invention, but never limit the scope of the present invention. Elaborate the present invention further referring to embodiment, but it will be understood and appreciated by those or skill in the art that the present invention is not limited to the preparation method of these embodiments and use. And, the present invention can be carried out equivalent replacement, combination, improvement according to description of the invention or modify by those skilled in the art, but these all will comprise within the scope of the invention.

Embodiment 1Containing the preparation of the capsule shell of hydroxypropylated starch

Prescription:

Supplementary material	Consumption
		Hydroxypropylated starch	80g
Carrageenin	7g
		Chitosan	5g
Sodium Citrate	3.5g
		Triethyl citrate	2.7g
Propylene glycol	2g

Preparation method:

(1) glue is changed: by purified water in entering glue tank, be heated to 80��100 DEG C, then add hydroxypropylated starch, insulated and stirred 90��180min; Then add remaining component, stir 10��15min, add gac and stir decolouring 15min, be filtered in insulated tank temporary;

(2) sol solution obtained is processed into hydroxypropylated starch Capsules shell by full-automatic hollow capsule maker.

Comparative example 1aDo not contain the preparation of the capsule shell of hydroxypropylated starch

Prescription:

Supplementary material	Consumption
		Gelatin	39g
Polyvinyl alcohol	30.75g
		Starch succsinic acid	26g
Hydroxyethylamyle	26.25g

Preparation method:

(1) by the supplementary material of recipe quantity, by changing, gluing equipment boiling becomes gelatin solution; Changing glue temperature controls at 56��75 DEG C, is finally 63 DEG C;

(2) it is processed into Capsules shell by full-automatic hollow capsule maker.

Comparative example 1bContaining the preparation of hydroxypropylated starch He other vehicle capsule shell

Prescription:

Supplementary material	Consumption
		Hydroxypropylated starch	100g
Starch	200g
		Gum arabic	8g
Carrageenin	20g
		Guar gum	8g
Xanthan gum	20g
		Light blue	3g

Preparation method:

(1) get hydroxypropylated starch 100g, starch 200g mix even after, add 90 DEG C of purified water 4L, stir become thick liquid, insulation 2h. Then liquid enters centrifugal spraying spray-dryer and carries out spraying dry, and control inlet temperature is 180 DEG C, and air outlet temperature is 90 DEG C, obtains mixed powder A.

(2) get gum arabic 8g, carrageenin 20g, guar gum 8g, xanthan gum 20g mix even after, add purified water 600ml, stirring becomes thick liquid, add decolorization and impurity removal by active carbon again, filtering, filtrate adds ethanol 280ml and precipitates, filtration under diminished pressure, vacuum-drying under 50 DEG C of conditions, obtains mixed powder B.

(3) 120g mixed powder A, 20g mixed powder B is got and 3g light blue mixes in proportion.

(4) in the powder mixed, add purified water, stir and evenly obtain glue liquid; It is processed into Capsules shell by full-automatic hollow capsule maker.

Comparative example 1cContaining the preparation of the capsule shell of gelatin

Prescription:

Preparation method:

(1) glue is changed: by purified water in entering glue tank, be heated to 80��100 DEG C, then add gelatin, insulated and stirred 90��180min; Then add jelling agent, help jelling agent, softening agent and wetting Agent for Printing Inks, stir 10��15min, add gac and stir decolouring 15min, be filtered in insulated tank temporary;

(2) sol solution obtained is processed into hydroxypropylated starch Capsules shell by full-automatic hollow capsule maker.

Embodiment 2aPrepare thing in the capsule of Couoidal bismuth pectin capsules

Specification 50mg batch 1000

Prescription

Component	Weight
		Colloidal Bismuth Pectin	50g
Microcrystalline Cellulose	50g
		PVP K30	2g
Purified water	18g
		Magnesium Stearate	1g

Preparation process:

(1) tackiness agent preparation: the PVP K30 of recipe quantity is dissolved in as tackiness agent in purified water, for subsequent use;

(2) batch mixing: the Colloidal Bismuth Pectin and the Microcrystalline Cellulose that take recipe quantity cross 60 order sieves, are mixed to evenly;

(3) granulate: tackiness agent is added softwood processed in above-mentioned mixed powder, cross 24 order sieves and granulate;

(4) dry: above-mentioned wet granular is placed in 60 DEG C of forced air dryings 1 hour;

(5) whole grain: with 24 order sieves, dried particle is carried out whole grain, obtain thing in required capsule capsule.

Embodiment 2bPrepare thing in the capsule of Couoidal bismuth pectin capsules

Specification 50mg

Batch 1000

Prescription

Preparation process:

(1) Colloidal Bismuth Pectin and diatomite being added in ball mill and pulverize, must contain medicine adsorptive, control is less than 30 microns containing the median size of medicine adsorptive;

(2) step (1) gained is mixed with polyvinylpolypyrrolidone, sodium stearyl fumarate containing medicine adsorptive, obtain thing in required capsule capsule.

Embodiment 2cPrepare thing in the capsule of Couoidal bismuth pectin capsules

Specification 50mg

Batch 1000

Prescription:

Component	Weight
		Colloidal Bismuth Pectin	50g
Acrylic resin IV	35g
		Light calcium carbonate	10g
Ethanol	900g

Preparation process:

(1) being dissolved in ethanol by acrylic resin IV, add light calcium carbonate and stir evenly, clarifixator processes, for subsequent use;

(2) Colloidal Bismuth Pectin is added in fluidized-bed, adopt spray coating method at the bottom of fluidized-bed to spray into the suspension dressing of step (1), inlet temperature 35 DEG C, atomizing pressure 0.3-0.4MPa, liquid feeding pump rotating speed 10-15rpm. Dressing is complete, puts burin-in process 12h in 50 DEG C of baking ovens, obtains Colloidal Bismuth Pectin coated micropill;

(3) by micro-ball obtained for step (2) respectively with 40 orders, 80 order sieve screenings, 40 order-80 micro-balls of order are got, i.e. thing in required capsule capsule.

Embodiment 3 prepares Couoidal bismuth pectin capsules

Thing in the capsule of preparation in the capsule shell of preparation in embodiment 1 and comparative example 1a-1c and embodiment 2a-2c is combined, is prepared as follows sample.

Preparation method:

By thing in the capsule capsule of embodiment 2a-2c, it is respectively charged into embodiment 1, in the Capsules shell of comparative example 1a-1c.

Test example 1 study on the stability

Sample 2a1-2c1c is amounted to 12 samples detect, is then placed in 40 DEG C �� 2 DEG C, place 6 months under relative humidity 75% �� 5% condition, respectively at 1,2,3, detection in June, the content of detection Colloidal Bismuth Pectin and disintegration, the results are shown in following table 1��2:

Table 1: content detection result (%)

Time	2a1	2b1	2c1	2a1a	2b1a	2c1a	2a1b	2b1b	2c1b	2a1c	2b1c	2c1c
													0 month	99.	99.6	99.9	99.7	99.8	99.8	99.7	99.6	99.7	99.9	99.8	99.9
1 month	99.7	99.6	99.9	99.0	99.1	99.4	99.7	99.6	99.5	99.1	98.9	99.2
													2 months	99.6	99.5	99.7	98.4	98.5	98.7	99.4	99.4	99.3	98.5	98.4	98.3
3 months	99.5	99.3	99.4	97.0	97.1	97.7	99.2	99.1	99.1	97.9	97.4	97.9
													6 months	99.3	99.1	99.2	95.1	96.4	96.5	99.1	98.9	99.0	97.1	96.4	97.5

Table 2: disintegration detected result

Conclusion: above-mentioned test-results shows, sample puts 40 DEG C �� 2 DEG C, place 6 months under relative humidity 75% �� 5% condition, the content of 2a1,2b1,2c1,2a1b, 2b1b, 2c1b six samples and disintegration considerable change does not occur, and obvious change all occur in other six samples, content reduction and disintegration are elongated. Because the capsule shell of 2a1,2b1,2c1,2a1b, 2b1b, 2c1b sample does not all contain in other six sample capsules shells this composition containing hydroxypropylated starch, therefore, this test demonstrates and adopts that to prepare the quality of Couoidal bismuth pectin capsules agent containing the capsule shell of hydroxypropylated starch more excellent, and character is stablized unexpectedly.

Test example 2 dissolution in vitro detects

Sample 2a1-2c1c being amounted to 12 samples and carries out dissolution in vitro detection, result is as follows:

Table 3: dissolution rate detected result

Brief summary: from above-mentioned testing data, the Couoidal bismuth pectin capsules of the different prescriptions that the Capsules containing hydroxypropylated starch adopting embodiment 1 and comparative example 1b to prepare is made, its dissolution in vitro is greater than the Couoidal bismuth pectin capsules that comparative example 1a and comparative example 1c does not make containing the Capsules of hydroxypropylated starch, has absolutely proved that the Couoidal bismuth pectin capsules that the present invention adopts hydroxypropylated starch capsule shell to prepare is improving the superiority in dissolution in vitro.

Test example 3 bioavailability

Sample 2a1-2c1c is amounted to 12 samples and carries out bioequivalence test in body, Plasma Concentration is detected, the results are shown in accompanying drawing 1.

Conclusion: from accompanying drawing 1, the Couoidal bismuth pectin capsules of the different prescriptions that the Capsules containing hydroxypropylated starch adopting embodiment 1 and comparative example 1b to prepare is made, in its body, Plasma Concentration is greater than the Couoidal bismuth pectin capsules that comparative example 1a and comparative example 1c does not make containing the Capsules of hydroxypropylated starch, has absolutely proved that Couoidal bismuth pectin capsules that the present invention adopts hydroxypropylated starch capsule shell to prepare is improving in body the superiority in bioavailability.

Claims (5)

1. a Couoidal bismuth pectin capsules preparation, it is characterised in that capsule shell is the Capsules shell containing hydroxypropylated starch.

2. Couoidal bismuth pectin capsules preparation according to claim 1, it is characterised in that in described Capsules shell except hydroxypropylated starch, also can add jelling agent, help the conventional additives such as jelling agent, softening agent, wetting Agent for Printing Inks.

3. Couoidal bismuth pectin capsules preparation according to the arbitrary item of claim 1-3, it is characterized in that thing in capsule, except Colloidal Bismuth Pectin, the supplementary additive being suitable for active medicine can be added, include but not limited to weighting agent, lubricant, tackiness agent, disintegrating agent, glidant etc.

4. prepare the method for Couoidal bismuth pectin capsules for one kind, it is characterised in that comprising:

(1) stock and adjunct taking recipe quantity mixes, and granulates according to feedstock property selectivity, wet granulation or dry granulation;

(2) by the mixed powder or particles filled in capsule shell of preparation.

5. method according to claim 4, it is characterised in that, the preparation method of described capsule shell is as follows:

(1) glue is changed: by purified water in entering glue tank, be heated to 80��100 DEG C, then add hydroxypropylated starch, insulated and stirred 90��180min; Then add jelling agent, help jelling agent, softening agent and wetting Agent for Printing Inks, stir 10��15min, add gac and stir decolouring 15min, be filtered in insulated tank temporary;

(2) sol solution obtained is processed into hydroxypropylated starch Capsules by full-automatic hollow capsule maker.