CN113413366A

CN113413366A - Dry-suspension oral in-situ gel for treating chronic gastritis and preparation method thereof

Info

Publication number: CN113413366A
Application number: CN202110737015.6A
Authority: CN
Inventors: 刘艳华; 毕嘉威; 刘金霞; 牛阳; 杨嘉玉; 朱溶月
Original assignee: Ningxia Medical University
Current assignee: Ningxia Medical University
Priority date: 2021-06-30
Filing date: 2021-06-30
Publication date: 2021-09-21

Abstract

The invention discloses a dry-mixed suspension type oral in-situ gel for treating chronic gastritis and a preparation method thereof, belongs to the technical field of traditional Chinese medicine preparations, and particularly discloses the following raw materials in parts by weight: 1-10 parts of traditional Chinese medicine components, 0.2-10 parts of ion sensitive gel materials and 0.01-1 part of suspending agents. Simultaneously discloses the following preparation method: (1) weighing the raw materials for later use; (2) preparing Chinese medicinal material micropowder; (3) and mixing the Chinese medicinal micro powder, the ion sensitive gel material and the suspending agent uniformly, and granulating to obtain the dry suspension type oral in-situ gel for treating chronic gastritis. The dry-suspension oral in-situ gel prepared by micronizing the traditional Chinese medicinal materials has good dispersibility and suspension performance, wide distribution area in gastrointestinal tracts and quick absorption, and simultaneously has long retention and slow release performance, thereby effectively improving the bioavailability.

Description

Dry-suspension oral in-situ gel for treating chronic gastritis and preparation method thereof

Technical Field

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to a dry-suspension oral in-situ gel for treating chronic gastritis and a preparation method thereof.

Background

Chronic gastritis is a common disease of the digestive tract system, often combined with peptic ulcer, and is one of gastric cancer precancerous diseases. In recent years, the prevalence of chronic gastritis has been increasing year by year due to the improvement of living standard and the increase of working pressure. The clinical symptoms of the patients are anorexia, acid regurgitation, abdominal distension and pain and the like, and relevant clinical researches prove that the reversal of the progression of chronic gastritis is also the key for preventing the generation of gastric cancer.

At present, western medicine treatment still lacks of treatment medicines with definite curative effect and ideal treatment methods, and traditional Chinese medicine treatment has unique advantages. However, in the prior art, most of the traditional Chinese medicine preparations for treating chronic gastritis are powder, but the powder for treating chronic gastritis is mainly absorbed by gastrointestinal tracts, the retention time of the powder in the stomach after oral administration is short, the local bioavailability of the stomach is low, and the drug effect is difficult to exert.

Therefore, the problem to be solved by the technical personnel in the field is urgent to provide a traditional Chinese medicine preparation for treating chronic gastritis, which has high bioavailability and is beneficial to exerting the drug effect.

Disclosure of Invention

In view of the above, the invention provides a dry suspension type oral in-situ gel for treating chronic gastritis, which has wide distribution area in gastrointestinal tract, fast absorption, and long retention and slow release properties.

In order to achieve the purpose, the invention adopts the following technical scheme:

a dry-suspension oral in-situ gel for treating chronic gastritis comprises the following raw materials in parts by weight: 1-10 parts of traditional Chinese medicine components, 0.2-10 parts of ion sensitive gel materials and 0.01-1 part of suspending agents.

Preferably, the traditional Chinese medicine components comprise the following raw materials in parts by weight: 5-15 parts of codonopsis pilosula, 10-20 parts of dried orange peel, 10-20 parts of fructus aurantii, 20-30 parts of radix paeoniae alba, 10-20 parts of perilla stem, 10-20 parts of pearl, 10-20 parts of angelica sinensis, 20-30 parts of Chinese yam, 10-20 parts of dark plum, 10-20 parts of liquorice and 5-15 parts of pseudo-ginseng powder.

Preferably, the ion-sensitive gel material is one or a combination of several of deacetylated gellan gum, sodium alginate and xanthan gum.

Preferably, the suspending agent is one or a combination of more of sodium carboxymethylcellulose, hypromellose and polyvinylpyrrolidone.

Has the advantages that: the traditional Chinese medicine prescription for treating chronic gastritis consists of codonopsis pilosula, dried orange peel, bitter orange, white paeony root, perilla stem, pearl, Chinese angelica, Chinese yam, dark plum, liquorice and pseudo-ginseng powder, and the combination of the medicines can improve the blood circulation of ulcer surfaces, enhance the nutrition of the ulcer surfaces, repair damaged gastric mucosa and promote the ulcer surfaces to heal, thereby being effectively used for treating the chronic gastritis. The solid particles have unique solution-gel transition properties, so that the solid particles have the advantages of strong affinity with the application part, particularly mucous membrane tissues, long retention time and the like, and the action time of the medicine is prolonged, so that the medicine can better exert the medicine effect. The dry suspension particles are uniformly dispersed, have good stability, are wide in distribution area in the gastrointestinal tract and fast to absorb, and have long retention and slow release performance. The traditional Chinese medicine prescription is prepared into dry-suspension oral in-situ gel, so that the defects of the prior art are effectively avoided, and the bioavailability is effectively improved in the aspect of treating chronic gastritis.

A preparation method of dry-suspension type oral in-situ gel for treating chronic gastritis is characterized in that solid particles are prepared into the dry-suspension type oral in-situ gel, and the preparation method comprises the following steps:

(1) respectively weighing the traditional Chinese medicine components, the ion-sensitive gel material and the suspending agent for later use;

(2) cleaning the traditional Chinese medicine components, volatilizing water, spraying 50-200 parts of alcohol, standing at room temperature for 12-24 hours, and then drying; then, coarsely pulverizing the obtained traditional Chinese medicine components to the particle size of 100-200 mu m, and then carrying out ultrafine pulverization to the particle size of 10-50 mu m to obtain traditional Chinese medicine micropowder;

(3) and (2) sieving the traditional Chinese medicine micro powder, the ion sensitive gel material and the suspending agent by a sieve of 80-100 meshes, uniformly mixing, adding 20-100 parts of 75-95% ethanol serving as a wetting agent, performing wet granulation by a sieve of 10-20 meshes, drying, granulating by a sieve of 12-24 meshes, and subpackaging to obtain the dry-mixed suspension type oral in-situ gel for treating chronic gastritis.

Preferably, the drying temperature in the step (2) is 50-90 ℃, and the drying is carried out until the water content is 3-8%.

Preferably, in the step (3), the drying temperature is 30-60 ℃, and the drying time is 6-18 h.

According to the technical scheme, compared with the prior art, the invention discloses a dry suspension type oral in-situ gel for treating chronic gastritis and a preparation method thereof. Furthermore, the dry-mixed suspension type oral in-situ gel prepared by the invention can improve the fluidity of the micronized Chinese medicine, has uniformly dispersed particles, increases the stability and moisture resistance of the Chinese medicine, is beneficial to storage and simultaneously ensures that the product is convenient to package. In addition, the dry-suspension oral in-situ gel has unique solution-gel transition property, so that the dry-suspension oral in-situ gel has the advantages of strong affinity with the application part, particularly mucous membrane tissues, long retention time and the like, prolongs the retention time of the medicament in the stomach, improves the local bioavailability of the stomach by gastrointestinal absorption after oral administration, and effectively exerts the drug effect.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.

FIG. 1 is a graph of rheological data for dry suspension oral in situ gels at different CMC-Na dosages at room temperature;

FIG. 2 shows three forms of dry-mixed suspension oral in-situ gel in the using process, wherein A is in a granular form, B is in a suspension form, and C is in a gel state.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

An oral dry-suspension oral in-situ gel for treating chronic gastritis comprises the following raw materials in parts by weight: 6 parts of traditional Chinese medicine components, 0.5 part of deacetylated gellan gum and 0.1 part of sodium carboxymethylcellulose;

the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 15 parts of codonopsis pilosula, 10 parts of dried orange peel, 10 parts of fructus aurantii, 20 parts of radix paeoniae alba, 10 parts of perilla stem, 10 parts of pearl, 10 parts of angelica, 20 parts of Chinese yam, 10 parts of dark plum, 10 parts of liquorice and 5 parts of pseudo-ginseng powder.

A preparation method of an oral dry-suspension type oral in-situ gel for treating chronic gastritis comprises the following steps:

(2) cleaning the traditional Chinese medicine components, volatilizing water, spraying alcohol, standing, and drying, wherein the drying temperature is controlled at 50 ℃; then coarsely pulverizing the obtained Chinese medicinal materials, and micronizing to obtain Chinese medicinal micropowder;

(3) and (2) sieving the Chinese medicinal micro powder, the ion sensitive gel material and the suspending agent by a 100-mesh sieve, uniformly mixing, performing wet granulation by a 16-mesh sieve by using 75% ethanol as a wetting agent, drying in a 60-DEG C oven, finishing granules by a 12-mesh sieve, and subpackaging to obtain the dry-suspension oral in-situ gel for treating the chronic gastritis.

Example 2

An oral dry-suspension oral in-situ gel for treating chronic gastritis comprises the following raw materials in parts by weight: 6 parts of traditional Chinese medicine components, 0.4 part of deacetylated gellan gum and 0.9 part of hydroxypropyl cellulose;

the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 5 parts of codonopsis pilosula, 10 parts of dried orange peel, 20 parts of fructus aurantii, 20 parts of radix paeoniae alba, 10 parts of perilla stem, 10 parts of pearl, 10 parts of angelica, 20 parts of Chinese yam, 10 parts of dark plum, 10 parts of liquorice and 15 parts of pseudo-ginseng powder.

Example 3

An oral dry-suspension oral in-situ gel for treating chronic gastritis comprises the following raw materials in parts by weight: 6 parts of traditional Chinese medicine components, 0.5 part of sodium alginate and 0.1 part of sodium carboxymethyl cellulose;

the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 15 parts of codonopsis pilosula, 15 parts of dried orange peel, 20 parts of fructus aurantii, 25 parts of white paeony root, 15 parts of perilla stem, 10 parts of pearl, 15 parts of angelica, 20 parts of Chinese yam, 15 parts of dark plum, 20 parts of liquorice and 5 parts of pseudo-ginseng powder.

Technical effects

(I) screening test of the drug formulation of the present invention

1. Screening dosage of gel matrix of dry-mixed suspension type oral in-situ gel

Respectively weighing 1%, 5%, 10%, 15%, 20% of Deacetylated Gellan Gum (DGG), 1% of sodium carboxymethylcellulose (CMC-Na) and 6 parts by weight of traditional Chinese medicine components, wherein the traditional Chinese medicine components consist of codonopsis pilosula, dried orange peel, bitter orange, white paeony root, perilla stem, pearl, angelica, Chinese yam, dark plum, liquorice and pseudo-ginseng powder. All raw materials were sieved through a 100 mesh sieve and mixed well. Using 75% ethanol as wetting agent, granulating with 16 mesh sieve, oven drying at 60 deg.C, and grading with 12 mesh sieve. Taking a proper amount of dry-suspension oral in-situ gel, adding artificial gastric juice (simulating the amount of human gastric juice and pH value configuration) to determine the amount of the artificial gastric juice required for gelling, and simultaneously determining the sedimentation volume ratio of the gelling agent, wherein the result is shown in table 1, when the gel matrix is screened, the gelling critical ion concentration of the gelling agent is preferably considered, and the five groups of experimental sedimentation volume ratios all accord with the specification of pharmacopoeia, so that 1-10% of deacetylated gellan gum is selected.

TABLE 1 examination of the quality of Dry suspension oral in situ gels with different amounts of deacetylated Gellan gum

2. Screening the dosage of the dry-mixed suspension type oral in-situ gel suspending agent

Respectively weighing 0.1%, 0.5%, 1%, 3%, 5%, 7% of CMC-Na, 5% of deacetylated gellan gum and 6 parts of traditional Chinese medicine components by weight, wherein the traditional Chinese medicine components consist of codonopsis pilosula, dried orange peel, bitter orange, white paeony root, perilla stem, pearl, angelica, Chinese yam, dark plum, liquorice and pseudo-ginseng powder. All raw materials were sieved through a 100 mesh sieve and mixed well. Using 75% ethanol as wetting agent, granulating with 16 mesh sieve, oven drying at 60 deg.C, and grading with 12 mesh sieve. Taking a proper amount of dry-suspension oral in-situ gel, adding artificial gastric juice, measuring the amount of the artificial gastric juice required by gelling, and measuring the sedimentation volume ratio of the gel. The results are shown in Table 2. The viscosity of the dry suspension type oral in-situ gel in different suspending agent CMC-Na dosage in the table III under the condition of room temperature is measured by using a rotary viscosity agent under different shearing speeds, and a rheological data curve is made, and the result is shown in figure 1. The results show that: the sedimentation volume ratio of the group I and the group II does not accord with the specification of Chinese pharmacopoeia, the suspension in each formula has pseudoplastic fluid property, the addition of excessive suspending agent can cause the system to be excessively viscous and not easy to pour, and the particles are not easy to disperse after sedimentation. Therefore, 1% to 5% of sodium carboxymethylcellulose is preferable.

TABLE 2 examination of quality of Dry suspension oral in situ gels with different CMC-Na amounts

Example 5

Pharmacological test method

1. Preparation of model of chronic gastritis

150g/L hot saline at 55 ℃, 10 mL/(kg. d), and gavage for 3 times/d; the salicylic acid solution is used for intragastric administration in an amount of 10 mL/(kg. d) for 1 time/d; the 20mmoL/L sodium deoxycholate solution is freely drunk and matched with hunger and satiety disorder, namely 2 days of satiety and 1 day of fasting, and is continuously molded for 12 weeks to form a chronic gastritis model; one rat in each group is randomly selected at the 4 th week, 8 th week and 12 th week of molding respectively, the stomach is sacrificed and taken, and the pathological characteristics of the obvious chronic gastritis are proved to appear through the pathological histological examination, which indicates the success of molding.

Normal rats were orally gavaged with 10mL/kg of 0.9% NaCl solution 2 times/day, and provided with a sufficient diet and clean tap water.

2. Animal grouping and administration method

All animals (90 clean male SD rats, 8 weeks old, 200 + -20 kg body weight, randomly divided into a normal group, a model control group, an effective part suspension group, and an effective part solid particle group in examples 1 to 3) were treated as follows on day 2 after successful molding: the rats in the normal group and the model control group continue to be subjected to oral gavage for 2 times/day and 10mL/kg of 0.9% sodium chloride solution; the suspension group rats are subjected to oral gavage with 0.01g/mL of effective part suspension 10mL/kg for 2 times/d; examples 1-3 treatment groups were given 10mL/kg dry suspension oral in situ gel, oral gavage, 2 times/day. All rats were continuously administered the relevant factors for 4 weeks with adequate diet and water.

3. Observation method and index

At the end of 16 weeks of experiment, rats are fasted for 24h and forbidden to be watered for 8h, 10% chloral hydrate solution is used for abdominal anesthesia, blood is taken from heart, serum is separated, and prostaglandin E in the serum of the rat to be tested₂(PEG2) and Nitric Oxide Synthase (NOS). The determination method adopts ELISA and nitrate reductase method, and strictly operates according to the kit instruction. Taking out the whole stomach 1.5cm away from cardia and pylorus, cutting open along the side of greater curvature of stomach, washing with ice physiological saline, sucking with filter paper, spreading, and fixing in 10% neutral formalin solution for pathological tissue section.

(II) pharmacological test results

PGE in each treatment group compared to model control group₂The level is obviously increased (P is less than 0.01), the NOS level is obviously reduced (P is less than 0.01), and the treatment effect on the chronic gastritis is proved by each treatment group; compared with the suspension group, the dry suspension type oral in-situ gel in the groups 1 to 3 shows stronger effect of treating chronic gastritis.

TABLE 3 serum PEG of various groups of rats₂And comparison of NOS content

Note: comparison with model group P < 0.01

The embodiments in the present description are described in a progressive manner, each embodiment focuses on differences from other embodiments, and the same and similar parts among the embodiments are referred to each other. The device disclosed by the embodiment corresponds to the method disclosed by the embodiment, so that the description is simple, and the relevant points can be referred to the method part for description.

The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. The dry-suspension oral in-situ gel for treating chronic gastritis is characterized by comprising the following raw materials in parts by weight: 1-10 parts of traditional Chinese medicine components, 0.2-10 parts of ion sensitive gel materials and 0.01-1 part of suspending agents.

2. The dry-suspension oral in-situ gel for treating chronic gastritis is characterized in that the traditional Chinese medicine components comprise the following raw materials in parts by weight: 5-15 parts of codonopsis pilosula, 10-20 parts of dried orange peel, 10-20 parts of fructus aurantii, 20-30 parts of radix paeoniae alba, 10-20 parts of perilla stem, 10-20 parts of pearl, 10-20 parts of angelica sinensis, 20-30 parts of Chinese yam, 10-20 parts of dark plum, 10-20 parts of liquorice and 5-15 parts of pseudo-ginseng powder.

3. The dry suspension type oral in-situ gel for treating chronic gastritis is characterized in that the ion sensitive gel material is one or a combination of several of deacetylated gellan gum, sodium alginate and xanthan gum.

4. The dry suspension type oral in-situ gel for treating chronic gastritis is characterized in that the suspending agent is one or a combination of several of sodium carboxymethylcellulose, hypromellose and polyvinylpyrrolidone.

5. A method for preparing a dry suspension oral in situ gel for treating chronic gastritis according to any one of claims 1 to 4, comprising the steps of:

6. The method for preparing dry suspension type oral in-situ gel for treating chronic gastritis according to claim 5, wherein the drying temperature in the step (2) is 50-90 ℃, and the drying is carried out until the water content is 3-8%.

7. The preparation method of the dry suspension type oral in-situ gel for treating chronic gastritis according to claim 5, wherein the drying temperature in the step (3) is 30-60 ℃, and the drying time is 6-18 h.