阅读说明：本技术 一种阿司匹林组合物及其制备方法和应用 (Aspirin composition and preparation method and application thereof ) 是由 王天怡 姜海涛 于 2020-08-04 设计创作，主要内容包括：本发明适用于医药技术领域,提供了一种阿司匹林组合物及其制备方法和应用,该阿司匹林组合物包括：阿司匹林；肠溶包衣层,包括用于肠液中溶解且在胃中不溶解的肠溶材料；第一隔离衣层,设置在阿司匹林与肠溶包衣层之间；胃溶包衣层,包括用于在胃中溶解且不能在水和肠液中溶解的胃溶材料；以及第二隔离衣层,用于隔离胃溶包衣层与肠溶包衣层；所述第二隔离衣层包括粘合剂。本发明提供的阿司匹林组合物,通过在阿司匹林外侧依次包覆第一隔离衣层、肠溶包衣层、第二隔离衣层和胃溶包衣层,可以使得药物在口腔及胃液的条件下均不会溶出,且能够在肠道条件下快速溶出,从而制备适用于儿童的可以口服剂型且解决阿司匹林对胃刺激性的问题。(The invention is suitable for the technical field of medicine, and provides an aspirin composition and a preparation method and application thereof, wherein the aspirin composition comprises the following components: aspirin; an enteric coating layer comprising an enteric material for dissolution in intestinal fluid and not in the stomach; a first isolation coating layer disposed between the aspirin and the enteric coating layer; a gastro-soluble coating layer comprising a gastro-soluble material for dissolution in the stomach and insoluble in water and intestinal fluids; and a second isolating coating layer for isolating the gastric coating layer from the enteric coating layer; the second release coat layer includes an adhesive. According to the aspirin composition provided by the invention, the first isolation coating layer, the enteric coating layer, the second isolation coating layer and the gastric dissolution coating layer are sequentially coated on the outer side of aspirin, so that a medicament can be not dissolved out under the conditions of oral cavity and gastric juice and can be quickly dissolved out under the intestinal tract condition, and thus, an oral preparation suitable for children is prepared, and the problem of irritation of aspirin to stomach is solved.)

1. An aspirin composition comprising aspirin, further comprising:

an enteric coating layer comprising an enteric material for dissolution in intestinal fluid and not in the stomach;

a first isolation coating layer disposed between the aspirin and the enteric coating layer; the first release coating layer comprises a binder;

a gastro-soluble coating layer comprising a gastro-soluble material for dissolution in the stomach and insoluble in water and intestinal fluids; and

a second isolating coating layer for isolating the gastric coating layer from the enteric coating layer; the second release coat layer includes an adhesive.

2. An aspirin composition according to claim 1, wherein the enteric material is at least one of acrylic resin based enteric material, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, polyvinyl alcohol phthalate.

3. An aspirin composition in accordance with claim 1, wherein the binding agent is at least one of hydroxypropylmethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, xanthan gum, gum arabic.

4. An aspirin composition in accordance with claim 1, wherein said gastric soluble material is an acrylic gastric soluble material.

5. A process for preparing an aspirin composition as claimed in any one of claims 1-4, comprising the steps of:

taking aspirin as a raw material medicine;

preparing a first isolation coating solution from an adhesive;

coating the raw material medicine by using first isolation coating liquid to form a first isolation coating layer to obtain a material A;

preparing enteric coating solution from enteric materials;

coating the material A with an enteric coating solution to form an enteric coating layer to obtain a material B;

preparing a second isolation coating solution by using an adhesive;

coating the material B with a second isolation coating solution to form a second isolation coating layer to obtain a material C;

preparing gastric-soluble coating liquid from gastric-soluble materials;

and (3) coating the material C with a gastric-soluble coating solution to form a gastric-soluble coating layer to obtain the aspirin composition.

6. A process for preparing an aspirin composition in accordance with claim 5, wherein:

the first isolation coating liquid comprises the following components in percentage by mass: 2-25% of adhesive, 1-20% of anti-sticking agent and the balance of solvent, wherein the sum of the mass percentages of the components is 100%;

the enteric coating solution comprises the following components in percentage by mass: 10-55% of enteric material, 1-10% of plasticizer, 1-10% of anti-sticking agent, 0-0.8% of surfactant and the balance of solvent, wherein the sum of the mass percentages of the components is 100%;

the second isolation coating liquid comprises the following components in percentage by mass: 5-20% of adhesive, and the balance of solvent, wherein the sum of the mass percentages of the components is 100%;

the gastric coating solution comprises the following components in percentage by mass: 5-10% of gastric soluble material, 0.5-8% of plasticizer, 2-5% of anti-sticking agent, 0-0.5% of surfactant and the balance of solvent, wherein the sum of the mass percentages of the components is 100%.

7. A process for preparing an aspirin composition in accordance with claim 6, wherein:

the solvent is at least one of water, ethanol, acetone and isopropanol;

the anti-sticking agent is silicon dioxide and/or talcum powder;

the plasticizer is citric acid ester and/or phthalic acid ester;

the surfactant is sodium dodecyl sulfate and/or tween.

8. A process for preparing an aspirin composition in accordance with claim 5, wherein:

the weight of the first isolation coating layer is 5-15% of the weight of the raw material medicine;

the weight of the enteric coating layer is 12 to 30 percent of the weight of the material A;

the weight of the second isolation coating layer is 5-15% of the weight of the material B;

the weight of the gastric-soluble coating layer is 7-25% of the weight of the material C.

9. An aspirin composition produced by the production method according to any one of claims 5 to 8.

10. Use of the aspirin composition according to any one of claims 1 to 4 and claim 9 in the preparation of a medicament for the prophylaxis of thrombosis in children.

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to an aspirin composition as well as a preparation method and application thereof.

Background

Congenital heart diseases are the most common congenital malformations, account for about 28% of various congenital malformations and account for 0.4% -1% of life infants, which means that 15-20 ten thousand congenital heart disease patients are newly increased every year in China. Children with 1/3 children were killed with serious complications within 1 year after birth without immediate treatment. Most children need surgical treatment to correct deformity. At present, most children patients can recover to normal conditions like normal people if timely surgical treatment is carried out. But no matter the intervention treatment or the surgical treatment, the infant has potential thrombus after the operation. Therefore, aspirin is needed to prevent thrombus formation after operation. After operation, the children need to take small dose of aspirin from half a year to life, and cannot stop taking the aspirin automatically. Kawasaki disease is an acute febrile eruptive pediatric disease with systemic vasculitis as the main pathological feature. Kawasaki disease has become the most important cause of acquired heart disease in children at present. Kawasaki disease is mostly seen in children under 5 years old, the most serious complication is coronary artery thrombotic occlusion, and aspirin is the first choice medicine for the anti-platelet treatment of children suffering from the Kawasaki disease.

The above two diseases are both administrated by common tablets or enteric-coated tablets. The tablet is difficult for children to swallow, and the compliance of children patients is extremely poor. The tablets are also broken or ground for administration, the administration dose is inaccurate, and the broken or ground administration destroys the enteric coating, so that the sperelin stimulates the stomach, and the stomach of a child patient is greatly damaged after long-term administration. Dispersible tablets also have the problems of indistinguishable doses and gastric irritation.

The children require good compliance of children patients, the oral administration is convenient, and the dosage can be accurately adjusted according to different ages. Suitable for children, such as oral liquid, granule, and suspension. Oral liquid is the best choice, but aspirin cannot be made into oral liquid because it is unstable in water and easily degrades in water.

In addition, aspirin has strong stimulation to the stomach, which can cause erosion, bleeding, ulcer and the like of the gastric mucosa. Most patients take aspirin with a medium dose for a plurality of days, and the fecal occult blood test is positive; the incidence rate of ulcer diseases is high when the medicine is taken for a long time. Aspirin can permeate the sebaceous protein membrane layer on gastric mucosa to destroy the protective effect of the lipoprotein membrane, so that gastric acid can be reversibly diffused into tissues to damage cells, and capillaries are damaged to cause bleeding. As a preventive agent for thrombus, it is required to be taken for a long period of time. Therefore, it is required that aspirin is not dissolved in the oral cavity and in an aqueous solution (children's medicine is usually taken with a water suspension), is not dissolved in a gastric juice (gastric irritation is avoided), and is rapidly dissolved in an intestinal tract (rapid onset of action) when the aspirin is orally administered.

However, the intestinal conditions, the aqueous solution conditions and the oral conditions are very similar, and the pH value is 6.5-7.5. If the drug is not dissolved in water or in the oral cavity, it is difficult to achieve dissolution of the drug in intestinal conditions, and thus the conventional enteric preparation cannot achieve the purpose.

Therefore, how to develop a novel aspirin preparation which is convenient for children to administer and can avoid the gastric irritation to children patients is an urgent technical problem to be solved.

Disclosure of Invention

An object of an embodiment of the present invention is to provide an aspirin composition, which aims to solve the problems set forth in the background art.

The embodiment of the invention is realized in such a way that the aspirin composition comprises the following components:

aspirin;

an enteric coating layer comprising an enteric material for dissolution in intestinal fluid and not in the stomach;

a first isolation coating layer disposed between the aspirin and the enteric coating layer; the first release coating layer comprises a binder;

a gastro-soluble coating layer comprising a gastro-soluble material for dissolution in the stomach and insoluble in water and intestinal fluids; and

a second isolating coating layer for isolating the gastric coating layer from the enteric coating layer; the second release coat layer includes an adhesive.

In a preferred embodiment of the present invention, the enteric material is at least one of an acrylic resin enteric material, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, and polyvinyl alcohol phthalate.

In another preferred embodiment of the present invention, the binder is at least one of hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, xanthan gum and acacia gum.

In another preferred embodiment of the present invention, the gastric soluble material is an acrylic gastric soluble material.

Another object of an embodiment of the present invention is to provide a method for preparing the aspirin composition, which includes the following steps:

taking aspirin as a raw material medicine;

preparing a first isolation coating solution from an adhesive;

coating the raw material medicine by using first isolation coating liquid to form a first isolation coating layer to obtain a material A;

preparing enteric coating solution from enteric materials;

coating the material A with an enteric coating solution to form an enteric coating layer to obtain a material B;

preparing a second isolation coating solution by using an adhesive;

coating the material B with a second isolation coating solution to form a second isolation coating layer to obtain a material C;

preparing gastric-soluble coating liquid from gastric-soluble materials;

and (3) coating the material C with a gastric-soluble coating solution to form a gastric-soluble coating layer to obtain the aspirin composition.

As another preferred scheme of the embodiment of the invention:

the first isolation coating liquid comprises the following components in percentage by mass: 2-25% of adhesive, 1-20% of anti-sticking agent and the balance of solvent, wherein the sum of the mass percentages of the components is 100%;

the enteric coating solution comprises the following components in percentage by mass: 10-55% of enteric material, 1-10% of plasticizer, 1-10% of anti-sticking agent, 0-0.8% of surfactant and the balance of solvent, wherein the sum of the mass percentages of the components is 100%;

the second isolation coating liquid comprises the following components in percentage by mass: 5-20% of adhesive, and the balance of solvent, wherein the sum of the mass percentages of the components is 100%;

the gastric coating solution comprises the following components in percentage by mass: 5-10% of gastric soluble material, 0.5-8% of plasticizer, 2-5% of anti-sticking agent, 0-0.5% of surfactant and the balance of solvent, wherein the sum of the mass percentages of the components is 100%.

As another preferred scheme of the embodiment of the invention:

the solvent is at least one of water, ethanol, acetone and isopropanol;

the anti-sticking agent is silicon dioxide and/or talcum powder;

the plasticizer is citric acid ester and/or phthalic acid ester;

the surfactant is sodium dodecyl sulfate and/or tween.

As another preferred scheme of the embodiment of the invention:

the weight of the first isolation coating layer is 5-15% of the weight of the raw material medicine;

the weight of the enteric coating layer is 12 to 30 percent of the weight of the material A;

the weight of the second isolation coating layer is 5-15% of the weight of the material B;

the weight of the gastric-soluble coating layer is 7-25% of the weight of the material C.

Another object of the embodiments of the present invention is to provide an aspirin composition prepared by the above preparation method.

Another object of the embodiments of the present invention is to provide an application of the aspirin composition in preparing a medicine for preventing children thrombus.

According to the aspirin composition provided by the embodiment of the invention, the first isolation coating layer, the enteric coating layer, the second isolation coating layer and the gastric dissolution coating layer are sequentially coated outside aspirin, so that a medicament can not be dissolved out under the conditions of oral cavity and gastric juice and can be quickly dissolved out under the condition of intestinal tract, and the problem of irritation of aspirin to stomach can be solved.

In addition, the aspirin composition prepared by the embodiment of the invention can be prepared into granules or dry suspensions, is more suitable for children to take compared with common tablets, solves the problem that children take medicine and swallow difficultly, and can accurately divide the dose according to the age of children so as to solve the problem that children take medicine and accurately divide the dose.

Drawings

FIG. 1 is a graph showing the dissolution profiles of aspirin compositions prepared in example 1 of the present invention in various media.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.