CN-121971384-A - Composite solution for treating reflux esophagitis and preparation method and application thereof

CN121971384ACN 121971384 ACN121971384 ACN 121971384ACN-121971384-A

Abstract

The invention discloses a compound solution for treating reflux esophagitis, a preparation method and application thereof, and relates to the technical field of medicinal preparations, wherein the compound solution is prepared by physically mixing drug-carrying microspheres and a gastric raft matrix solution; wherein the drug-carrying microsphere is solid particles which take sulfhydryl pectin as a carrier, are solidified through divalent metal ion crosslinking and are coated with American cockroach extract, and the gastric raft matrix solution comprises hydrophilic colloid, components generating gas when meeting acid and stabilizers. The sulfhydryl pectin magnesium microsphere provides excellent mucous membrane adhesiveness, prolongs the acting time of the medicine on esophageal lesions, and forms a physical barrier of the gastric raft matrix in gastric acid environment to inhibit reflux of gastric contents. The two cooperate to realize a dual treatment mechanism of local repair and source control. The preparation can remarkably prolong the residence time in vivo, effectively promote the healing of esophageal mucosa, and has better curative effect than the simple American cockroach extract preparation.

Inventors

YIN TIAN
ZHANG YU
Ji Muse
LIU YUXIN
WU TAO
ZHAO JIAN
SU YU

Assignees

沈阳药科大学

Dates

Publication Date: 20260505
Application Date: 20260206

Claims (10)

1. A composite solution for treating reflux esophagitis is characterized by being prepared by physically mixing drug-carrying microspheres and gastric raft matrix solution, wherein the drug-carrying microspheres are solid particles which are solidified by bivalent metal ion crosslinking and are coated with American cockroach extracts by taking sulfhydryl pectin as a carrier, and the gastric raft matrix solution comprises hydrocolloid, components generating gas when encountering acid and stabilizers.
2. The complex solution for treating reflux esophagitis according to claim 1, characterized in that the final concentration of the american cockroach extract in the complex solution is 0.1% (w/v) to 10.0% (w/v).
3. The complex solution for treating reflux esophagitis of claim 1, wherein the thiolated pectin is prepared from a low-ester pectin and thioglycolic acid by esterification.
4. The composite solution for treating reflux esophagitis of claim 1, wherein the divalent metal ions comprise magnesium ions, calcium ions, zinc ions, iron ions, copper ions, and manganese ions.
5. The composite solution for treating reflux esophagitis according to claim 1, wherein the hydrocolloid is capable of gelling in an acidic environment, and is selected from one or more of sodium alginate, pectin and xanthan gum, wherein the component generating gas when encountering acid is selected from one or more of sodium bicarbonate, sodium carbonate, calcium carbonate and magnesium carbonate, and the stabilizer is selected from one or more of glycerol monooleate, polysorbate 80, xanthan gum, hydroxypropyl methylcellulose, magnesium stearate and polyethylene glycol 4000.
6. The composite solution for treating reflux esophagitis according to claim 5, wherein the hydrocolloid is a combination of sodium alginate and pectin, the mass ratio of sodium alginate to pectin is 1:10-10:1, the component generating gas when encountering acid is sodium bicarbonate and/or calcium carbonate, and the stabilizer is a combination of glycerol monooleate and xanthan gum.
7. The compound solution for treating reflux esophagitis according to any one of claims 1 to 6, wherein the compound solution comprises, by volume percentage w/v of the final solution, 0.1% -10.0% of periplaneta americana extract, 0.1% -10.0% of thiolated pectin, 0.1% -10.0% of sodium alginate, 0.2% -15.0% of pectin, 1.0% -20.0% of sodium bicarbonate, 1.0% -20.0% of calcium carbonate, 0% -5.0% of xanthan gum, 1.0% -30.0% of glycerol monooleate, 1.0% -5.0% of magnesium chloride, and the balance being water.
8. A method of preparing a composite solution for the treatment of reflux esophagitis according to any one of claims 1 to 7, comprising the steps of: Preparing sulfhydrylation pectin; the prepared sulfhydryl pectin and the American cockroach extract are dissolved in water to obtain medicine-carrying glue solution, the medicine-carrying glue solution is dripped into divalent metal ion salt solution, and after crosslinking and solidification, the medicine-carrying microsphere is obtained through separation, washing and drying; sequentially dissolving or dispersing the hydrocolloid and the components generating gas when encountering acid in water, adding a stabilizer, and homogenizing to obtain a gastric raft matrix solution: and (3) adding the prepared drug-loaded microspheres into the prepared gastric raft matrix solution according to a proportion, and stirring at a low speed to uniformly disperse the drug-loaded microspheres to obtain the composite solution.
9. The method for preparing a composite solution for treating reflux esophagitis according to claim 8, wherein the concentration of the divalent metal ion salt solution is 1% -10% (w/v), and the solution is intermittently stirred at an extremely low rotation speed of 5 rpm-20 rpm for 8-15 minutes.
10. Use of a complex solution for the treatment of reflux esophagitis according to any one of claims 1 to 7 for the preparation of a medicament for the treatment of reflux esophagitis.

Description

Composite solution for treating reflux esophagitis and preparation method and application thereof Technical Field The invention relates to the technical field of medicinal preparations, in particular to a medicinal preparation for treating reflux esophagitis (GERD), and especially relates to a compound solution containing American cockroach extract and having dual functions of mucoadhesion and intragastric floating, a preparation method thereof and application thereof in pharmacy. Background Reflux esophagitis (Gastroesophageal Reflux Disease, GERD) is a chronic inflammatory disease caused by reflux of gastric, duodenal contents into the esophagus, characterized by changes in pathology to inflammation, erosion, or even ulceration of the esophageal mucosa. Global epidemiological surveys have shown that their incidence is on the rise and has become a common digestive system disease affecting public health. Although the existing first-line system therapeutic drugs (such as proton pump inhibitors) can effectively inhibit acid, the problems of long-term administration, potential side effects, incapacity of solving reflux physical stimulation and the like exist. The Periplaneta Americana Extract (PAE) is a natural drug known to have good anti-inflammatory and tissue repair activities, and the commercial preparation of the recovery solution is commonly used for mucous membrane repair in clinic. However, conventional liquid dosage forms have the obvious disadvantages of firstly poor adhesion on the surfaces of esophagus and stomach mucosa, rapid removal after oral administration, failure to form effective drug concentration at the focus and low local bioavailability, and secondly, lack of physical intervention for GERD core pathological links-gastric reflux, resulting in limited therapeutic effects. In the prior art, there are studies on bioadhesive materials (e.g., pectin, chitosan, etc.) for improving drug adhesion, and floating formulation techniques for gastric retention. However, the mere improvement of adhesion does not prevent the continued occurrence of reflux, whereas the mere gastric floating preparation lacks specific therapeutic effects on the damaged esophageal mucosa. Thus, there is a need in the art for innovative formulations that achieve both long-acting topical adhesive delivery and physical anti-reflux functions, with synergistic treatment of "long-acting topical delivery" with "immediate physical anti-reflux" to more effectively and more specifically treat reflux esophagitis. Disclosure of Invention The primary purpose of the invention is to overcome the defects of poor adhesiveness and no anti-reflux function of the existing PAE preparation and provide a novel composite solution preparation. The preparation aims to synchronously realize two main aims of 1) obviously prolonging the retention and acting time of PAE in the esophagus and the mucous membrane at the upper part of the stomach and 2) forming a physical barrier in the stomach and immediately inhibiting the upward reflux of the stomach content by innovative carrier and delivery system design, thereby achieving the dual synergistic curative effects of 'local repair' and 'etiology control'. In order to achieve the above purpose, the present invention provides the following technical solutions: in a first aspect, the present invention provides a composite solution for treating reflux esophagitis, which is formed by physically mixing drug-loaded microspheres with a gastric raft matrix solution. The medicine carrying microsphere is solid particles which take sulfhydryl pectin as a carrier, are solidified through divalent metal ion crosslinking and are coated with American cockroach extract. The gastric raft matrix solution comprises a hydrocolloid, components generating gas when encountering acid and a stabilizer. In the compound solution, the final concentration of the American cockroach extract is 0.1% (w/v) to 10.0% (w/v), preferably 0.5% (w/v) to 2.0% (w/v), and the final concentration of the sulfhydryl pectin is 0.1% (w/v) to 10.0% (w/v), preferably 1.0% (w/v) to 5.0% (w/v). The periplaneta americana extract is obtained through an alcohol extraction and water precipitation process. Further, the sulfhydrylation pectin is prepared from low-ester pectin and thioglycollic acid through esterification reaction, and the preparation method comprises the following steps: dissolving low-ester pectin (esterification degree < 50%) in hot water, adding thioglycollic acid and catalytic amount of hydrochloric acid, reacting at 70-85 ℃, precipitating reaction product with organic solvent, washing, and drying. Further, the divalent metal ion includes magnesium ion, calcium ion, zinc ion, iron ion, copper ion, and manganese ion, preferably magnesium ion. Further, the hydrocolloid in the gastric raft matrix solution is capable of gelling in an acidic environment, and is selected from one or more of sodium alginate, pectin and xanthan gum, preferably a comb