CN110787155A - Itopride hydrochloride pharmaceutical composition and preparation method thereof - Google Patents

Itopride hydrochloride pharmaceutical composition and preparation method thereof Download PDF

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CN110787155A
CN110787155A CN201911238715.XA CN201911238715A CN110787155A CN 110787155 A CN110787155 A CN 110787155A CN 201911238715 A CN201911238715 A CN 201911238715A CN 110787155 A CN110787155 A CN 110787155A
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itopride hydrochloride
pharmaceutical composition
prepared
parts
preparation
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CN110787155B (en
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朱德其
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Chengdu Hengrui Pharmaceutical Co Ltd
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Chengdu Hengrui Pharmaceutical Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/80—Polymers containing hetero atoms not provided for in groups A61K31/755 - A61K31/795
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/485—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents

Abstract

The invention belongs to the technical field of preparation of pharmaceutical preparations, and particularly relates to an itopride hydrochloride pharmaceutical composition and a preparation method thereof. The itopride hydrochloride pharmaceutical composition is prepared from the following components in parts by weight: 50-150 parts of itopride hydrochloride, 20-80 parts of croscarmellose sodium, 20-80 parts of simethicone, 5-20 parts of fumed silica, 10-40 parts of starch, 20-80 parts of lactose, 4-10 parts of hydroxypropyl cellulose and 1-5 parts of magnesium stearate. The itopride hydrochloride pharmaceutical composition prepared by the invention is a composition prepared from itopride hydrochloride and simethicone, has different pharmacological effects, plays respective roles, generates a coordination and synergism effect, eliminates flatulence of gastrointestinal tract while enhancing gastrointestinal peristalsis, obviously shortens the gastric emptying time of diabetic gastroparesis rats, and protects gastrointestinal mucosa.

Description

Itopride hydrochloride pharmaceutical composition and preparation method thereof
Technical Field
The invention belongs to the technical field of preparation of pharmaceutical preparations, and particularly relates to an itopride hydrochloride pharmaceutical composition and a preparation method thereof.
Background
Itopride hydrochloride has dopamine D2 receptor antagonistic activity and acetylcholinesterase inhibition activity, and plays a role in gastrointestinal motility under the synergistic action of the dopamine D2 receptor antagonistic activity and the acetylcholinesterase inhibition activity; in addition, the product has certain anti-vomiting effect due to the effect of antagonizing the activity of dopamine D2 receptor, and is clinically used for treating dyspepsia symptoms caused by gastrointestinal motility slowing (such as functional dyspepsia, chronic gastritis and the like), including upper abdominal fullness, upper abdominal pain, inappetence, nausea, vomiting and the like. Itopride hydrochloride is converted in the liver mainly through a flavin monooxygenase pathway to form metabolites Ml, M2 and M3, and only one of the 3 metabolites has weak dopamine D2 receptor blocking effect and has no pharmacological relevance. Itopride hydrochloride and its metabolites are mainly excreted by the kidney (75%), with a clearance half-life of about 6 hours. The actuation force of itopride hydrochloride is linearly related to the dose over the therapeutic dose range. Itopride hydrochloride tablets originally developed into abeyangshan factory ltd (abbott japan co., ltd., katsuyama plant) were marketed in a size of 50mg, and currently marketed in China are tablets, capsules and granules.
The dimethicone is also called methyl silicone oil, polydimethylsiloxane liquid, colorless transparent viscous liquid, and has no odor and toxicity, and molecular formula is CH3[Si(CH3)2]nSi(CH3)3And the average molecular weight is 5000-100000. The dimeticone is a dimethyl siloxane bulk polymer, is obtained by hydrolyzing and polycondensing dichlorodimethylsilane and a small amount of monochlorotrimethylsilane, has different viscosities due to different degrees of polymerization, can be divided into ten types of 20, 50, 100, 200, 350, 500, 750, 1000, 12500 and 30000 according to different kinematic viscosities, has small surface tension and strong defoaming force, can break residual bubbles in gastrointestinal tracts and discharge gas, thereby eliminating flatulence and protecting gastrointestinal mucosa. The simethicone tablets and the simethicone powder are available in the market at home.
The publication number is CN105267171A, the invention name is an itopride hydrochloride sustained-release tablet composition, and each 1000 tablet cores of the itopride hydrochloride sustained-release tablet contain 75g of itopride hydrochloride, 45g of hydroxypropyl methylcellulose, 15g of sodium alginate, 40g of microcrystalline cellulose, 8g of superfine silica gel powder, povidone K307 g and 3g of magnesium stearate. The publication number is CN102600091A, the invention name is itopride hydrochloride dispersible tablet composition, and the dispersible tablet composition with unit dose contains 50mg of itopride hydrochloride, 50-80 mg of microcrystalline cellulose, 12mg of crospovidone, 16mg of hydroxypropyl cellulose, 80-110 mg of lactose, 0.25mg of sodium dodecyl sulfate, 5mg of silicon dioxide, 1.25mg of magnesium stearate, 60mg of methylcellulose and 15mg of polyacrylic resin IV.
At present, the existing research is the preparation of itopride hydrochloride, and no development and application of the composition of itopride hydrochloride and simethicone exist.
Disclosure of Invention
The invention adopts modern pharmaceutical preparation technology to prepare the itopride hydrochloride and the dimeticone into a composition, wherein the itopride hydrochloride in the composition enhances gastrointestinal motility, the dimeticone silicon dioxide mixture eliminates gastrointestinal bubbles, and the etopride hydrochloride enhances the gastrointestinal motility to increase the defoaming capability of the dimeticone silicon dioxide mixture; the dimeticone silicon dioxide mixture eliminates bubbles in the gastrointestinal tract and reduces the gastrointestinal peristalsis resistance; the two have respective characteristics to generate synergistic action, accelerate elimination of flatulence of gastrointestinal tract while enhancing gastrointestinal peristalsis, obviously shorten gastric emptying time of diabetic gastroparesis rats and protect gastrointestinal tract mucosa.
The invention provides an itopride hydrochloride pharmaceutical composition, which is prepared from the following components in parts by weight:
further, the itopride hydrochloride pharmaceutical composition is prepared from the following components in parts by weight:
further, the itopride hydrochloride pharmaceutical composition is prepared from the following components in parts by weight:
Figure BDA0002305591010000031
further, the ritonavir hydrochloride pharmaceutical composition has a settlement volume of 20-30 mL of croscarmellose sodium. Croscarmellose sodium is a crosslinked carboxymethyl ether of cellulose (about 70% of carboxyl groups are in the sodium salt form), is insoluble in water due to the presence of crosslinking bonds, can absorb water with the weight several times of the weight of the croscarmellose sodium to swell without dissolving, and has good disintegrating effect.
Simethicone emulsion or tablet, the main indication is 1, is used for improving abdominal symptoms caused by gas in gastrointestinal tract; 2. removing the foam mucus in stomach during the gastric endoscopy; 3. when the abdomen is examined by X-ray, intestinal gas is removed. Further, the itopride hydrochloride pharmaceutical composition has the viscosity of the dimeticone of 500mm2/s～1000mm2/s。
Further, the itopride hydrochloride pharmaceutical composition is hydrophobic in fumed silica, has a carbon content of not less than 0.3%, an average particle size of 10-20 nm and a specific surface area of 20-400 m2(ii) in terms of/g. The fumed silica is mainly used for enhancing the defoaming activity of the dimeticone and improving the defoaming force.
Further, the itopride hydrochloride pharmaceutical composition is characterized in that the type of the hydroxypropyl cellulose is EF or ELF. Hydroxypropyl cellulose is used as a wet granulation adhesive, wherein the type is EF or ELF with the best performance, and the compressibility and dissolution performance can be improved during tabletting.
The invention also provides a preparation method of the itopride hydrochloride pharmaceutical composition, which comprises the following steps:
a: preparation of mixture of itopride hydrochloride and croscarmellose sodium
Mixing itopride hydrochloride and croscarmellose sodium according to a mass ratio of 1-5: 1, ball-milling, and collecting for later use;
b: preparation of mixture of dimeticone and fumed silica
Fully stirring and uniformly mixing dimeticone and fumed silica at a mass ratio of 2-5: 1 at 80-150 ℃, cooling to normal temperature, and sieving with a 200-mesh sieve for later use;
c: preparing an adhesive:
adding hydroxypropyl cellulose into boiling water, fully dispersing, continuously stirring, and cooling for later use, wherein the mass ratio of the hydroxypropyl cellulose to the water is 1: 5-20;
d: preparation of granules of the composition
Mixing the mixture of itopride hydrochloride and croscarmellose sodium prepared in the step A, starch, lactose and the adhesive prepared in the step C until the mixture is dry and wet uniformly, extruding and granulating through a 20-30-mesh sieve, drying at 40-70 ℃ until the moisture content of the granules is 1-6%, granulating through a 30-mesh sieve, adding a lubricant magnesium stearate and the mixture of the dimethicone and the fumed silica prepared in the step B, and mixing uniformly to obtain composition granules for subpackaging into capsules or pressing into tablets;
E. subpackaging into capsule and pressing into tablet
① Capsule, which is prepared by filling the obtained medicinal granules into capsules according to the labeled amount of 50mg and 100mg of itopride hydrochloride;
② tabletting, wherein the obtained medicinal granule is tabletted according to the labeled amount of itopride hydrochloride 50mg and 100mg, and the hardness of the tablet is controlled
The degree is 30N-80N, and the disintegration time is 1 min-5 min.
Further, in the preparation method of the itopride hydrochloride pharmaceutical composition, in the step a, the ball milling is performed for 30 minutes at each time by using a planetary mill at a rotation speed of 200 revolutions per minute, and the grinding is performed for 4 times in a total cycle.
Compared with the prior art, the invention has the following beneficial effects:
1. the itopride hydrochloride pharmaceutical composition prepared by the invention is a composition prepared from itopride hydrochloride and dimethicone, the two exert respective effects and generate a coordination synergistic effect, gastrointestinal peristalsis is enhanced, gastrointestinal flatulence is eliminated, gastric emptying time of diabetic gastroparesis rats is obviously shortened, and gastrointestinal mucosa is protected.
2. The invention can effectively eliminate bubbles in the gastrointestinal tract, thereby exhausting gas and eliminating flatulence.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments, but it should not be construed that the scope of the present invention is limited to the following examples. Various substitutions and alterations can be made by those skilled in the art and by conventional means without departing from the spirit of the method of the invention described above.
Example 1
The formulation of the itopride hydrochloride pharmaceutical composition is shown in the following table 1:
TABLE 1
Name (R) Mass (mg) In percentage by weight%
Itopride hydrochloride 50 38.5
Croscarmellose sodium 20 15.4
Dimethicone 20 15.4
Fumed silica 5 3.8
Starch 10 7.6
Lactose 20 15.4
Hydroxypropyl cellulose (EF or ELF) 4 3.1
Magnesium stearate 1 0.8
The preparation method of the itopride hydrochloride pharmaceutical composition comprises the following steps:
a: preparation of mixture of itopride hydrochloride and croscarmellose sodium
Circularly grinding itopride hydrochloride and croscarmellose sodium for 4 times at the rotating speed of 200 revolutions per minute for 30 minutes each time by using a planetary grinding machine (Model-PMRetsch Haan) according to the mass ratio of 2.5:1, and collecting for later use;
b: preparation of mixture of dimeticone and fumed silica
Fully stirring and uniformly mixing the dimeticone and the fumed silica at the mass ratio of 4:1 at the temperature of 80-150 ℃, cooling to normal temperature, and sieving with a 200-mesh sieve for later use;
c: preparing an adhesive:
adding hydroxypropyl cellulose into boiling water, fully dispersing, continuously stirring, and cooling for later use, wherein the mass ratio of the hydroxypropyl cellulose to the water is 1: 12;
d: preparation of granules of the composition
Mixing the mixture of itopride hydrochloride and croscarmellose sodium prepared in the step A, starch, lactose and the adhesive prepared in the step C until the mixture is dry and wet uniformly, extruding and granulating through a 20-30-mesh sieve, drying at 40-70 ℃ until the moisture content of the granules is 1-6%, granulating through a 30-mesh sieve, adding a lubricant magnesium stearate and the mixture of the dimethicone and the fumed silica prepared in the step B, and mixing uniformly to obtain composition granules for subpackaging into capsules or pressing into tablets;
E. subpackaging into capsule and pressing into tablet
① Capsule, prepared by filling the obtained medicinal granule into capsule at a dosage of 130mg per granule, wherein the dosage of the medicinal granule contains itopride hydrochloride 50 mg;
② tabletting, namely tabletting the obtained medicinal granules into tablets according to the marked amount of 50mg of itopride hydrochloride, wherein each tablet contains 130mg, the hardness of the tablets is controlled to be 30-80N, and the disintegration time is 1-5 min.
Example 2
The formulation of the itopride hydrochloride pharmaceutical composition is shown in the following table 2:
TABLE 2
Name (R) Mass (mg) In percentage by weight%
Itopride hydrochloride 100 38.5
Croscarmellose sodium 40 15.4
Dimethicone 40 15.4
Fumed silica 10 3.8
Starch 20 7.6
Lactose 40 15.4
Hydroxypropyl cellulose (EF or ELF) 8 3.1
Magnesium stearate 2 0.8
The preparation method of the itopride hydrochloride pharmaceutical composition comprises the following steps:
a: preparation of mixture of itopride hydrochloride and croscarmellose sodium
Circularly grinding itopride hydrochloride and croscarmellose sodium for 4 times at the rotating speed of 200 revolutions per minute for 30 minutes each time by using a planetary grinding machine (Model-PMRetsch Haan) according to the mass ratio of 2.5:1, and collecting for later use;
b: preparation of mixture of dimeticone and fumed silica
Fully stirring and uniformly mixing the dimeticone and the fumed silica at the mass ratio of 4:1 at the temperature of 80-150 ℃, cooling to normal temperature, and sieving with a 200-mesh sieve for later use;
c: preparing an adhesive:
adding hydroxypropyl cellulose into boiling water, fully dispersing, continuously stirring, and cooling for later use, wherein the mass ratio of the hydroxypropyl cellulose to the water is 1: 11;
d: preparation of granules of the composition
Mixing the mixture of itopride hydrochloride and croscarmellose sodium prepared in the step A, starch, lactose and the adhesive prepared in the step C until the mixture is dry and wet uniformly, extruding and granulating through a 20-30-mesh sieve, drying at 40-70 ℃ until the moisture content of the granules is 1-6%, granulating through a 30-mesh sieve, adding a lubricant magnesium stearate and the mixture of the dimethicone and the fumed silica prepared in the step B, and mixing uniformly to obtain composition granules for subpackaging into capsules or pressing into tablets;
E. subpackaging into capsule and pressing into tablet
① Capsule, which is prepared by filling the obtained medicinal granules into capsules according to the labeled amount of 100mg of itopride hydrochloride, wherein each capsule is 260 mg;
② tabletting, namely tabletting the obtained medicinal granules into tablets according to the marked amount of 100mg of itopride hydrochloride, wherein each tablet contains 260mg, the hardness of the tablets is controlled to be 30-80N, and the disintegration time is 1-5 min.
Example 3
The formulation of the itopride hydrochloride pharmaceutical composition is shown in the following table 3:
TABLE 3
Name (R) Mass (mg) In percentage by weight%
Itopride hydrochloride 150 33.1
Crosslinked carboxylic acidSodium methyl cellulose 75 16.6
Dimethicone 80 17.6
Fumed silica 20 4.4
Starch 40 8.8
Lactose 75 16.6
Hydroxypropyl cellulose (EF or ELF) 10 2.2
Magnesium stearate 3 0.7
The preparation method of the itopride hydrochloride pharmaceutical composition comprises the following steps:
a: preparation of mixture of itopride hydrochloride and croscarmellose sodium
Grinding itopride hydrochloride and croscarmellose sodium according to the mass ratio of 2:1 for 4 times by a planetary grinder (Model-PMRetsch Haan) at the rotating speed of 200 revolutions per minute for 30 minutes each time in a circulating manner, and collecting for later use;
b: preparation of mixture of dimeticone and fumed silica
Fully stirring and mixing simethicone and fumed silica at the mass ratio of 4.4:1 at 80-150 ℃, cooling to normal temperature, and sieving with a 200-mesh sieve for later use;
c: preparing an adhesive:
adding hydroxypropyl cellulose into boiling water, fully dispersing, continuously stirring, and cooling for later use, wherein the mass ratio of the hydroxypropyl cellulose to the water is 1: 10;
d: preparation of granules of the composition
Mixing the mixture of itopride hydrochloride and croscarmellose sodium prepared in the step A, starch, lactose and the adhesive prepared in the step C until the mixture is dry and wet uniformly, extruding and granulating through a 20-30-mesh sieve, drying at 40-70 ℃ until the moisture content of the granules is 1-6%, granulating through a 30-mesh sieve, adding a lubricant magnesium stearate and the mixture of the dimethicone and the fumed silica prepared in the step B, and mixing uniformly to obtain composition granules for subpackaging into capsules or pressing into tablets;
E. subpackaging into capsule and pressing into tablet
① Capsule, prepared by filling the obtained medicinal granule into capsule according to the labeled amount of itopride hydrochloride of 50mg, each granule is 151 mg;
② tabletting, wherein the obtained medicinal granule is tabletted according to the marked amount of itopride hydrochloride of 150mg, each tablet is 453mg, the tablet hardness is controlled to be 30N-80N, and the disintegration time is 1 min-5 min.
Comparative example 1: blank particles of active ingredient-free composition
The formulation of itopride hydrochloride pharmaceutical compositions (free of the ingredients itopride hydrochloride, simethicone and silicon dioxide) is shown in table 4 below:
TABLE 4
Name (R) Mass (mg) In percentage by weight%
Croscarmellose sodium 40 36.4
Starch 20 18.2
Lactose 40 36.4
Hydroxypropyl cellulose (EF or ELF) 8 7.2
Magnesium stearate 2 1.8
The preparation method comprises the following steps:
A. adhesive formulation
Adding hydroxypropyl cellulose into boiling water, fully dispersing, continuously stirring, and cooling for later use, wherein the mass ratio of the hydroxypropyl cellulose to the water is 1: 11;
B. uniformly mixing the croscarmellose sodium, the starch and the lactose, adding the prepared adhesive, fully stirring until the mixture is dry and wet, extruding and granulating by using a 20-mesh sieve, drying at 70 ℃ until the moisture content is 1-6%, granulating by using a 30-mesh sieve, adding the magnesium stearate, and uniformly mixing to obtain the finished product.
Comparative example 2: itopride hydrochloride composition (without dimethicone silicon dioxide mixture)
The formulation of itopride hydrochloride pharmaceutical compositions (without simethicone, silicon dioxide) is shown in table 5 below:
TABLE 5
Name (R) Mass (mg) In percentage by weight%
Itopride hydrochloride 100 47.6
Croscarmellose sodium 40 19.0
Starch 20 9.5
Lactose 40 19.0
Hydroxypropyl cellulose (EF or ELF) 8 3.9
Magnesium stearate 2 1.0
The preparation method of the itopride hydrochloride pharmaceutical composition (without simethicone and silicon dioxide) comprises the following steps:
a: preparation of mixture of itopride hydrochloride and croscarmellose sodium
Circularly grinding itopride hydrochloride and croscarmellose sodium for 4 times at the rotating speed of 200 revolutions per minute for 30 minutes each time by using a planetary grinding machine (Model-PMRetsch Haan) according to the mass ratio of 2.5:1, and collecting for later use;
b: preparing an adhesive:
adding hydroxypropyl cellulose into boiling water, fully dispersing, continuously stirring, and cooling for later use, wherein the mass ratio of the hydroxypropyl cellulose to the water is 1: 11;
c: preparation of granules of the composition
And C, mixing the mixture of itopride hydrochloride and croscarmellose sodium prepared in the step A, starch, lactose and the adhesive prepared in the step B until the mixture is dry and wet uniformly, extruding and granulating the mixture through a 20-30-mesh sieve, drying the granules at 40-70 ℃ until the moisture content of the granules is 1-6%, grading the granules through a 30-mesh sieve, adding a lubricant magnesium stearate, and mixing the granules uniformly to obtain the itopride hydrochloride/croscarmellose sodium composite material.
Comparative example 3: dimethicone composition (without itopride hydrochloride)
The formulation of the simethicone pharmaceutical composition (without itopride hydrochloride) is shown in table 6 below:
TABLE 6
Name (R) Mass (mg) In percentage by weight%
Croscarmellose sodium 40 25
Dimethicone 40 25
Fumed silica 10 6.3
Starch 20 12.5
Lactose 40 25
Hydroxypropyl cellulose (EF or ELF) 8 5
Magnesium stearate 2 1.2
The preparation method of the simethicone pharmaceutical composition comprises the following steps:
a: preparation of mixture of dimeticone and fumed silica
Fully stirring and uniformly mixing the dimeticone and the fumed silica at the mass ratio of 4:1 at the temperature of 80-150 ℃, cooling to normal temperature, and sieving with a 200-mesh sieve for later use;
b: preparation of granules of the composition
And (3) uniformly mixing the blank particles prepared in the comparative example 1 with the mixture of the dimeticone and the fumed silica according to the proportion of 11:5 to obtain the composite material.
Performance test method:
① male Wistar rat of experimental animal, the body mass is 220-260 g, total 60, 50 used for diabetes modeling.
② the experimental groups were divided into blank control group (group A), diabetes group (group B), itopride hydrochloride group (group C), simethicone composition (group D) and composition of the present invention (group E)
③ model of diabetic rat, injecting 5% alloxan solution into abdominal cavity of rat at a dosage of 120mg/kg, 1 time per day, continuously injecting for 2 days, measuring blood sugar after 72 hours, and determining blood sugar over 13.6mmol/L for 3 days as success of model making, wherein 49 models are made in total of 50 models.
④ test method, diabetic rats successfully molded were randomly divided into 4 groups of 12 animals each, each group was assigned to B, C, D, E animals, 10 animals not molded were assigned to group A, and feeding was performed as follows:
TABLE 7
Figure BDA0002305591010000091
Note: the daily administration amount is equivalent to 12.5mg of itopride hydrochloride.
The compositions of the invention were tested between groups at gastric emptying:
continuously feeding for 1 week, and fasting for 24 hr13C breath test, the gastric emptying time was recorded as shown in table 8 below.
TABLE 8
Group of Number of rats/n 13C gastric solids half-emptying time/min
A-blank pairPhoto group 10 133.25±11.31
B-diabetes group 12 241.17±9.72
C-itopride hydrochloride group 12 176.12±10.51
D-dimeticone group 12 183.77±11.58
E-compositions of the invention 12 137.44±10.11
As a result: as can be seen from Table 8, the composition group of the present invention showed almost no difference in gastric emptying time as compared with the blank control group A (normal mice, rats not subjected to diabetes molding); compared with the diabetes group in the aspect of emptying time, the composition group can obviously shorten the gastric emptying time by 40-60 percent; compared with itopride hydrochloride group and dimethyl silicon oil group, the gastric emptying time can be obviously shortened. Therefore, the composition prepared from itopride hydrochloride and simethicone can generate a coordination and synergism effect, eliminate flatulence of gastrointestinal tracts while enhancing gastrointestinal peristalsis, obviously shorten the gastric emptying time of diabetic gastroparesis rats compared with the single use of the composition, and protect gastrointestinal mucosa.

Claims (9)

1. The itopride hydrochloride pharmaceutical composition is characterized by being prepared from the following components in parts by weight:
Figure FDA0002305590000000011
2. the itopride hydrochloride pharmaceutical composition according to claim 1, which is prepared from the following components in parts by weight:
Figure FDA0002305590000000012
3. the itopride hydrochloride pharmaceutical composition according to claim 1 or 2, which is prepared from the following components in parts by weight:
Figure FDA0002305590000000013
4. itopride hydrochloride pharmaceutical composition according to any one of claims 1 to 3, wherein the settled volume of croscarmellose sodium is 20 to 30 mL.
5. Itopride hydrochloride pharmaceutical composition according to any one of claims 1 to 3, wherein the dimethicone has a viscosity of 500mm2/s～1000mm2/s。
6. The itopride hydrochloride pharmaceutical composition according to any one of claims 1 to 3, wherein the fumed silica is hydrophobic, has a carbon content of 0.3 wt% or more, an average particle size of 10 to 20nm, and a specific surface area of 20 to 400m2/g。
7. The itopride hydrochloride pharmaceutical composition according to any one of claims 1 to 3, wherein the hydroxypropyl cellulose is of type EF or ELF.
8. The process for the preparation of itopride hydrochloride pharmaceutical composition according to any one of claims 1 to 7, characterized in that it comprises the following steps:
a: preparation of mixture of itopride hydrochloride and croscarmellose sodium
Mixing itopride hydrochloride and croscarmellose sodium according to a mass ratio of 1-5: 1, ball-milling, and collecting for later use;
b: preparation of mixture of dimeticone and fumed silica
Fully stirring and uniformly mixing dimeticone and fumed silica at a mass ratio of 2-5: 1 at 80-150 ℃, cooling to normal temperature, and sieving with a 200-mesh sieve for later use;
c: preparing an adhesive:
adding hydroxypropyl cellulose into boiling water, fully dispersing, continuously stirring, and cooling for later use, wherein the mass ratio of the hydroxypropyl cellulose to the water is 1: 5-20;
d: preparation of granules of the composition
Mixing the mixture of itopride hydrochloride and croscarmellose sodium prepared in the step A, starch, lactose and the adhesive prepared in the step C until the mixture is dry and wet uniformly, extruding and granulating through a 20-30-mesh sieve, drying at 40-70 ℃ until the moisture content of the granules is 1-6%, granulating through a 30-mesh sieve, adding a lubricant magnesium stearate and the mixture of the dimethicone and the fumed silica prepared in the step B, and mixing uniformly to obtain composition granules which are used for subpackaging into capsules or pressing into tablets;
E. subpackaging into capsule and pressing into tablet
① Capsule, which is prepared by filling the obtained medicinal granules into capsules according to the labeled amount of 50mg and 100mg of itopride hydrochloride;
② tabletting, namely, tabletting the obtained medicinal granules according to the marked amount of 50mg and 100mg of itopride hydrochloride, controlling the hardness of the tablets to be 30N-80N, and disintegrating for 1 min-5 min.
9. The method for preparing itopride hydrochloride pharmaceutical composition according to claim 8, wherein the ball milling in step A is performed by a planetary mill at a rotation speed of 200 rpm for 30 minutes per milling, and 4 times of milling are performed in a cycle.
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