CN-121971529-A - Preparation method of coptis chinensis six-ingredient decoction and suppository thereof

CN121971529ACN 121971529 ACN121971529 ACN 121971529ACN-121971529-A

Abstract

The invention relates to the technical field of Mongolian medicine preparations, in particular to a preparation method of coptis chinensis six-ingredient decoction and suppositories thereof, which comprises the following steps of. Based on the traditional Mongolian medicine coptis-6 decoction, 3 heat-clearing anti-inflammatory Mongolian medicines are added into the coptis-six decoction, and the total content of active ingredients is more than or equal to 12 percent through compound enzymolysis, supercritical CO 2 extraction and gradient membrane separation and purification, and then the stability is enhanced through compound embedding. The suppository is formed by constructing a drug carrying system through a pH-ROS double-response carrier and magnetic targeting and combining self-healing hydrogel, a temperature-sensitive composite matrix and microfluidic spray forming, and the intelligent package ensures the storage stability. The preparation provided by the invention has the advantages of strong targeting, high mucous membrane adhesion, long residence time, convenient and comfortable administration, remarkably improved stability and bioavailability, and suitability for ulcerative colitis treatment, and promotes modernization conversion of Mongolian medicines, and can be accurately enriched in intestinal inflammation areas.

Inventors

LI CHANGSHENG
BAO HASHEN
YA RU
BAO WUENQI
TA NA
GA LATAI
BAI LONG
WU QIZHU

Assignees

内蒙古医科大学

Dates

Publication Date: 20260505
Application Date: 20260208

Claims (10)

1. The coptis root six-ingredient soup is characterized by comprising 1 part of rhizoma picrorhizae, 1 part of fringed pink, 1 part of weeping reed flower, 1 part of madder root, 1 part of gentiana macrophylla flower, 1 part of pseudo-ginseng, 0.8 part of cape jasmine, 0.8 part of costal flower and 0.8 part of fructus terminaliae, wherein the effective components of the coptis root six-ingredient soup comprise rhizoma picrorhizae alkaloid, jasminoidin and a costal flower extract, and the total content is more than or equal to 12 percent, and the coptis root six-ingredient soup is prepared by the following steps of: (1) Crushing the medicinal materials, sieving the medicinal materials by a 80-mesh sieve, carrying out compound enzymolysis on the medicinal materials, wherein pectase=2:1, enzyme addition amount is 0.5-1%, pH is 4.5-5.5, and enzymolysis is carried out for 1-1.5 hours at 45-50 ℃; (2) Extracting by supercritical CO 2 at 35-40 ℃ under 20-30 MPa with 60% ethanol as entrainer for 2-3 h; (3) Ceramic film of 0.1-0.2 μm with a thickness of 1000-3000 Da and (3) carrying out gradient separation and purification by a nanofiltration membrane.
2. The six-ingredient coptis soup according to claim 1, wherein the enzymolysis liquid-solid ratio in the step (1) is 1:15-1:20, and the entrainer in the step (2) accounts for 10-15% of the mass of the medicinal materials.
3. The six-ingredient coptis soup according to claim 1 is characterized in that beta-cyclodextrin and tea polyphenol nano particles are compositely embedded, the mass ratio is 1:0.3:0.1, the embedding rate is more than or equal to 90%, and the degradation rate of effective components stored for 2 years is less than or equal to 8%.
4. The six ingredient decoction of claim 1 wherein the decoction is formulated as suppositories, enemas, or capsules, preferably as rectal dosage forms.
5. A method for preparing the coptis chinensis six ingredient soup suppository according to any one of claims 1 to 4, which comprises the following steps: (1) The targeted drug-carrying system is constructed by loading the embedded coptis chinensis six-ingredient soup extract on a pH-ROS dual-response polymer carrier, adding Fe 3 O 4 magnetic nano particles with the mass ratio of 2-3%, and dispersing the Fe 3 O 4 magnetic nano particles in Schiff base bonding self-healing hydrogel; (2) The temperature-sensitive composite matrix is prepared by mixing poloxamer 407/188 with nano hydroxyapatite according to the mass ratio of 5:3:2, melting and changing the phase temperature to 36-38 ℃; (3) The auxiliary materials are precisely proportioned, namely, the auxiliary materials for adhesion of mucous membrane are injected through a microfluidic chip, and chitosan quaternary ammonium salt is adopted, wherein sodium alginate=1:0.8; (4) Spray molding, namely mixing the liquid-carrying hydrogel with the composite matrix according to the mass ratio of 1:3, and carrying out low-pressure rectal spray molding to obtain 2 g/grain torpedo-shaped suppository; (5) Intelligent package, namely polylactic acid breathable waterproof film single-grain package, and a built-in miniature humidity sensor.
6. The method of claim 5, wherein the pH-ROS responsive polymer in the step (1) is poly (beta-amino ester) -polyethylene glycol-curcumin graft copolymer, and the Fe 3 O 4 magnetic nanoparticles have a particle size of 50-100 nm.
7. The preparation method of the coptis chinensis six-ingredient soup suppository according to claim 5, wherein the mass ratio of chitosan to sodium alginate of the self-healing hydrogel in the step (1) is 1:1.2, and the dosage of the glyoxal is 5-8% of the mass of the chitosan.
8. The method for preparing a coptis chinensis six-ingredient soup suppository according to claim 5, wherein the channel width of the microfluidic chip in the step (3) is 50-100 μm, the weight difference of the suppositories in the step (4) is +/-7.5%, and the melting time limit is less than or equal to 25 minutes.
9. The method for preparing the coptis chinensis six-ingredient decoction suppository according to claim 5, wherein the mucosa adhesion of the suppository is more than or equal to 15kPa, the rectal residence time is more than or equal to 8 hours, and the medicine enrichment rate of inflammatory parts is more than or equal to 70%.
10. The method for preparing a coptis chinensis six-ingredient soup suppository according to claim 5, wherein the thickness of the polylactic acid film in the step (5) is 50-80 μm, the response range of a humidity sensor is 30-80% RH, and the suppository is stable in performance after being stored for 2 years under the conditions of 4 ℃ and 60% RH.

Description

Preparation method of coptis chinensis six-ingredient decoction and suppository thereof Technical Field The invention relates to the technical field of Mongolian medicine preparations, in particular to a coptis chinensis six-ingredient decoction and a preparation method of suppositories thereof. Background The Mongolian medicine "Huanglian-6 Wei Tang" is a Mongolian medicine classical prescription recorded in several books of "Lantaibu" and "four-part manna", and is composed of picrorhiza rhizome, fringed pink herb, weeping reed flower, madder root, gentiana macrophylla flower and notoginseng, and possesses the function of qingqi Greek, curing the diseases of heat injury, such as warm disease and intestinal inflammation, etc.. The subject group is based on clinical experience of the Guoqiao Shi Surong zab, 3 Mongolian medicines of gardenia, costal flower and fructus terminaliae Billericae are added on the basis of the original prescription, so that the modified coptis chinensis-6 decoction is formed, and the modified coptis chinensis-6 decoction is used for treating ulcerative colitis and has obvious curative effect. However, the traditional application mode is rectal clysis, which has complex operation and poor patient compliance, and the suppository developed later has a plurality of core defects in the existing preparation method although the use is simplified: 1. The extraction efficiency is low, the single 60% ethanol reflux extraction is adopted, the extraction of the effective components is insufficient, the thermosensitive components are easy to degrade, and the purity is less than 8%; 2. the molding process is crude, the matrix adopts lanolin and mixed fatty glyceride to carry out polysorbate 80, the mixture is easy to adhere and fragile, and the batch-to-batch difference is large; 3. The preparation formulation has poor performance, uneven distribution and short retention time (only 2-4 hours) after rectal administration, is easy to leak, and has the bioavailability of less than 30 percent; 4. The stability is insufficient, the active ingredients are easy to oxidize, the degradation rate of the active ingredients stored for 6 months reaches more than 25%, 5. The targeting is absent, the active ingredients cannot precisely act on an intestinal inflammation area, and the curative effect is limited. Therefore, based on the classical Mongolian medicine theory, the prescription and the extraction process of the coptis chinensis six-ingredient decoction are optimized, and the suppository preparation method with strong targeting, stable molding and high bioavailability is developed, so that the method has important significance in promoting the modernization of the Mongolian medicine and improving the treatment effect of ulcerative colitis. Disclosure of Invention Aiming at the problems in the prior art, the invention provides a preparation method of coptis chinensis six-ingredient soup and suppositories thereof, which optimizes prescription composition and extraction process, solves the problems of low extraction efficiency, forming defects, poor targeting, insufficient stability and the like of the traditional preparation by targeting medicine carrying, intelligent forming and stable strengthening technology, and prepares the Mongolian medicine preparation with definite curative effect, convenient use and strong stability. The technical scheme adopted for solving the technical problems is that the coptis chinensis six-ingredient soup comprises the following raw materials by weight ratio of 1 part of rhizoma picrorhizae, 1 part of fringed pink, 1 part of weeping reed flower, 1 part of madder, 1 part of gentiana macrophylla flower, 1 part of pseudo-ginseng, 0.8 part of gardenia, 0.8 part of costal flower and 0.8 part of fructus terminaliae Billericae; the effective components of the coptis chinensis six-ingredient decoction comprise picrorhiza alkaloid, jasminoidin and costa extract, and the total content is more than or equal to 12 percent, and the coptis chinensis six-ingredient decoction is prepared by the following method: (1) Crushing the medicinal materials, sieving the medicinal materials with a 80-mesh sieve, and carrying out compound enzymolysis (cellulase: pectase=2:1, enzyme addition amount is 0.5-1%, pH is 4.5-5.5, and enzymolysis is carried out at 45-50 ℃ for 1-1.5 h); (2) Supercritical CO 2 extraction (35-40 ℃, 20-30 MPa,60% ethanol as entrainer, 2-3 h extraction); (3) And (3) gradient separation and purification of a ceramic membrane (0.1-0.2 μm) and a nanofiltration membrane (1000-3000 Da). Specifically, in the step (1), the enzymolysis liquid-solid ratio is 1:15-1:20, and the entrainer dosage in the step (2) is 10-15% of the medicinal material mass. Specifically, the beta-cyclodextrin and tea polyphenol nano particles are compositely embedded (the mass ratio is 1:0.3:0.1), the embedding rate is more than or equal to 90%, and the degradation rate of the effective components is less than o