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CN-121971399-A - Multi-layer slow-release dripping pill of herba Pogostemonis and its preparation method

CN121971399ACN 121971399 ACN121971399 ACN 121971399ACN-121971399-A

Abstract

The invention discloses a wrinkled giant hyssop vital energy multilayer slow release dripping pill and a preparation method thereof, belonging to the field of traditional Chinese medicine preparations, wherein the dripping pill comprises a three-layer structure of an inner core dripping pill, an intermediate slow release layer and an outer layer quick release layer, the inner core dripping pill consists of a fat-soluble extract, volatile oil microcapsules and polyethylene glycol 4000, the intermediate slow release layer consists of hydroxypropyl methylcellulose, sodium alginate and starch, the outer layer quick release layer consists of a water-soluble extract, poloxamer 188 and microcrystalline cellulose, fat-soluble components are extracted by adopting an ultrasonic auxiliary enzyme method, a nanofiltration membrane is used for separating and purifying volatile oil, and beta-cyclodextrin inclusion is used for preparing the volatile oil microcapsules.

Inventors

  • XIE YUPENG
  • WANG HUANHUAN
  • YAN FUQIN
  • YIN HONG
  • XU FENGHUA
  • SUN XIAODI
  • WANG KUN
  • WAN KUN
  • LIANG JIA
  • SU HUANHUAN

Assignees

  • 中国人民解放军总医院

Dates

Publication Date
20260505
Application Date
20251227

Claims (10)

  1. 1. The agastache rugosa healthy qi multilayer slow release dropping pill is characterized by comprising a three-layer structure of an inner core dropping pill, a middle slow release layer and an outer layer quick release layer: the kernel dripping pill comprises the following components in parts by weight: 8-15 parts of wrinkled giant hyssop vital energy prescription fat-soluble extract, 3-8 Parts of wrinkled giant hyssop vital energy prescription volatile oil microcapsule, Polyethylene glycol 4000 15-25 parts; The intermediate slow-release layer consists of the following components in parts by weight: 6-12 parts of hydroxypropyl methylcellulose, 2-6 Parts of sodium alginate, 3-8 Parts of starch; the outer quick-release layer consists of the following components in parts by weight: 10-20 parts of water-soluble extract of wrinkled giant hyssop vital energy prescription, 8-15 Parts of poloxamer 188, 4-10 Parts of microcrystalline cellulose; The agastache rugosa volatile oil microcapsule is prepared by clathrating volatile components separated by nanofiltration membrane with beta-cyclodextrin or its derivatives, the agastache rugosa water-soluble extract is prepared by water extraction and alcohol precipitation, and the agastache rugosa fat-soluble extract, agastache rugosa volatile oil microcapsule and agastache rugosa water-soluble extract are all derived from agastache rugosa.
  2. 2. The multi-layer slow release dripping pill for treating agastache of claim 1, wherein the core dripping pill comprises, by weight, 10-12 parts of an agastache of formula fat-soluble extract, 5-7 parts of an agastache of formula volatile oil microcapsule, and 4000 18-22 parts of polyethylene glycol.
  3. 3. The multi-layer slow release agastache rugosa pill according to claim 1 or 2, wherein the beta-cyclodextrin derivative is hydroxypropyl-beta-cyclodextrin or methyl-beta-cyclodextrin, and the weight ratio of the volatile oil in the volatile oil microcapsule to the beta-cyclodextrin or the derivative thereof is 1:3-1:8.
  4. 4. The multi-layer slow release dripping pill for treating agastache of claim 1, wherein the middle slow release layer comprises 8-10 parts by weight of hypromellose, 3-5 parts by weight of sodium alginate and 5-7 parts by weight of starch.
  5. 5. The multi-layer slow release agastache rugosa dripping pill according to claim 1 or 4, wherein the viscosity of the hypromellose is 4000-15000 mPa s, and the viscosity of the sodium alginate is 200-500 mPa s.
  6. 6. The multi-layer slow release dripping pill for treating the diarrhea of the wrinkled giant hyssop as claimed in claim 1, wherein the outer quick release layer comprises 12-18 parts of water-soluble extract of the wrinkled giant hyssop as well as 10-13 parts of poloxamer 188 and 6-8 parts of microcrystalline cellulose.
  7. 7. The multi-layer slow release dripping pill for treating the diarrhea according to claim 1, wherein the prescription for treating the diarrhea is prepared from, by weight, 10-15 parts of herba Pogostemonis, 8-12 parts of rhizoma atractylodis, 8-12 parts of pericarpium citri reticulatae, 5-10 parts of cortex magnoliae officinalis, 8-12 parts of radix angelicae, 10-15 parts of poria cocos, 8-12 parts of pericarpium arecae, 5-10 parts of pinellia ternate, 3-6 parts of rhizoma zingiberis and 3-6 parts of liquorice.
  8. 8. The method for preparing the multi-layer slow release dripping pill of wrinkled giant hyssop according to any one of claims 1-7, which is characterized in that the method comprises the following steps: (1) Preparation of fat-soluble extract: Pulverizing rhizoma Atractylodis, pericarpium Citri Tangerinae, cortex Magnolia officinalis and radix Angelicae Dahuricae into 40-80 mesh fine powder, adding cellulase or pectase, performing enzymolysis at pH 4.5-5.5 and temperature 45-55deg.C for 1-2 hr, performing ultrasonic assisted extraction with ultrasonic power of 300-600W and ultrasonic temperature 50-70deg.C for 30-60 min, extracting with 60-80% ethanol for 2-3 times, mixing extractive solutions, and concentrating under reduced pressure to obtain fat-soluble extract; (2) Preparing volatile oil microcapsules: extracting volatile oil from herba Agastaches and folium Perillae by steam distillation, separating and purifying the obtained volatile oil with nanofiltration membrane with molecular weight cut-off of 300-1000 Da to obtain purified volatile oil, mixing the purified volatile oil with beta-cyclodextrin or its derivatives at weight ratio of 1:4-1:6, preparing clathrate by saturated aqueous solution method or grinding method, and vacuum drying at 50-60deg.C to obtain volatile oil microcapsule; (3) Preparation of water-soluble extract: Taking the dregs of a decoction obtained in the step (1) and poria cocos, areca peel, pinellia ternate, dried ginger and liquorice in the Huoxiang Zhengqi prescription, adding 6-10 times of water, decocting and extracting for 2-3 times, 2-3 hours for 1 st time, 1.5-2.5 hours for 2 nd time, merging the extracting solutions, concentrating to the relative density of 1.20-1.30, adding 50-70% ethanol to enable the alcohol content to reach 50-60%, precipitating with ethanol for 12-24 hours, filtering, concentrating the filtrate under reduced pressure, and drying to obtain a water-soluble extract; (4) Preparing kernel dropping pills: Mixing the fat-soluble extract obtained in the step (1) and the volatile oil microcapsule obtained in the step (2) with polyethylene glycol 4000, heating to 65-75 ℃ to melt and mix uniformly, and dripping into core dripping pill under the conditions of dripping distance of 8-12 cm, dripping speed of 25-35 drops/min and condensate temperature of 8-12 ℃; (5) Preparation of an intermediate slow-release layer: Uniformly mixing hypromellose, sodium alginate and starch, adding a proper amount of water to prepare a coating solution, uniformly coating the coating solution on the surface of the inner core dripping pill obtained in the step (4) by adopting a fluidized bed coating technology or a pill making method, and drying to obtain dripping pills coated with an intermediate slow-release layer; (6) Preparing an outer quick release layer: Uniformly mixing the water-soluble extract obtained in the step (3), poloxamer 188 and microcrystalline cellulose, adding a proper amount of water to prepare a coating liquid, uniformly coating the coating liquid on the surface of the dripping pill obtained in the step (5) by adopting a fluidized bed coating technology or a pill making method, and drying to obtain the agastache rugosus healthy qi multilayer slow-release dripping pill.
  9. 9. The method according to claim 8, wherein the cellulase in the step (1) is added in an amount of 0.5 to 2.0% by weight of the medicinal material or the pectase is added in an amount of 0.5 to 2.0% by weight of the medicinal material.
  10. 10. The method according to claim 8 or 9, wherein the weight gain of the coating of the intermediate release layer in step (5) is 15-30% of the weight of the inner core drop pill, and the weight gain of the coating of the outer release layer in step (6) is 20-35% of the weight of the drop pill coated with the intermediate release layer.

Description

Multi-layer slow-release dripping pill of herba Pogostemonis and its preparation method Technical Field The invention belongs to the field of traditional Chinese medicine preparations, and in particular relates to a wrinkled giant hyssop vital energy multilayer slow-release dripping pill and a preparation method thereof. Background The Huoxiang Zhengqi prescription comes from Taiping Huimin He Ji Fang (Taiping Huimin Ji Fang), is composed of medicinal materials such as patchouli, rhizoma atractylodis, dried orange peel, magnolia officinalis, radix angelicae, poria cocos, pericarpium arecae, pinellia ternate, dried ginger, liquorice and the like, has the effects of relieving exterior syndrome and resolving dampness, regulating qi and regulating middle warmer, and is used for treating cold caused by exogenous wind-cold and internal injury and dampness stagnation, and symptoms such as headache and dizziness, chest and diaphragm stuffiness, epigastric and abdominal pain, vomiting and diarrhea. The prescription is a common prescription for clinically treating summer-heat damp cold and gastrointestinal cold, and is called as "damp-dispelling holy medicine" by the traditional Chinese medicine. In the prior art, the preparation formulation of the Huoxiang Zhengqi prescription mainly comprises Huoxiang Zhengqi water, huoxiang Zhengqi pills, huoxiang Zhengqi soft capsules and the like. For example, xie Yupeng et al in "preparation Process study of Huoxiang Zhengqi drop Heart pill" published in "Chinese pharmaceutical industry" 2011, volume 20, phase 3 disclose a preparation method of Huoxiang Zhengqi drop Heart pill, which adopts supercriticalExtracting fat-soluble components and volatile components from herba Agastaches by fluid extraction, making into dripping pill as core, and wrapping water-soluble components to form dripping pill with double-layer structure. The technical proposal well gathers the effective components in the prescription, but the following defects still exist: Firstly, the double-layer structure design adopted by the technology makes the release time difference of the inner-layer fat-soluble component and the outer-layer water-soluble component smaller, and the ideal sequential release effect cannot be realized. After the water-soluble components on the outer layer are rapidly disintegrated, the inner core dripping pill is rapidly exposed, and the fat-soluble components and the volatile components are rapidly released, so that the release curve of the active components in the body shows a burst release phenomenon, the fluctuation of the blood concentration is larger, the gastrointestinal tract irritation is increased, and the duration of the drug effect is reduced. Second, supercriticalAlthough the fluid extraction can extract fat-soluble and volatile components, the method needs high-pressure equipment, has harsh operation conditions, has extraction pressure of 15-25 MPa, extraction temperature of 30-50 ℃, has large equipment investment and high production cost, and has insufficient protection for the thermosensitive volatile oil components. Under high pressure, part of volatile components are easy to followThe loss caused by gas discharge has low extraction rate of active ingredients, and the yield of volatile oil is only 1.5-2.0%. Thirdly, the technology does not adopt stabilization measures to volatile components, the extracted volatile oil is directly mixed with fat-soluble extract to prepare dripping pill cores, volatile oil is easy to volatilize and lose in the storage process, the stability is poor, the volatile oil components are unevenly released in gastrointestinal tracts, and the bioavailability is limited. Therefore, there is a need to develop a novel slow release preparation of Huoxiang Zhengqi formula with higher extraction efficiency, lower cost and more optimized release mode, so as to overcome the above-mentioned defects in the prior art. Disclosure of Invention Aiming at the defects of the prior art, the invention provides the agastache rugosa healthy qi multilayer sustained-release dropping pill and the preparation method thereof, and the sequential release of fat-soluble components, volatile components and water-soluble components in the agastache rugosa healthy qi prescription is realized through the comprehensive application of three-layer multi-cavity sustained-release structural design, ultrasonic auxiliary enzyme extraction technology, membrane separation and purification technology and beta-cyclodextrin inclusion technology, thereby improving the bioavailability, reducing the production cost and enhancing the preparation stability. In order to achieve the aim, the first aspect of the invention provides a wrinkled giant hyssop vital energy multi-layer slow release dripping pill, which comprises a three-layer structure of an inner core dripping pill, a middle slow release layer and an outer quick release layer: The kernel dripping pill comprises (by weight parts) herba P