Composite emulsion for intestinal obstruction as well as preparation method and application of composite emulsion

Abstract

The invention discloses a composite emulsion for intestinal obstruction, a preparation method thereof and application of the composite emulsion in intestinal obstruction treatment. The intestinal obstruction composite emulsion comprises the following components in percentage by weight: 10-30% of a traditional Chinese medicine extract, 60-85% of paraffin oil, 3-8% of an emulsifier and 0.5-2% of a stabilizer, and the intestinal obstruction composite emulsion is a W / O type emulsion. The invention has the beneficial effects that the lubricating effect of the traditional paraffin oil and the anti-inflammatory and detumescence effects of the traditional Chinese medicine extract are deeply fused through a nano-emulsification technology, and the core defects of single mechanism, systemic toxicity and poor targeting property of the existing therapy are overcome. According to the traditional Chinese medicine composition, the symptom remission rate can be greatly improved, inflammatory factors are obviously reduced, the curative effect is obviously improved, and safety is optimized and applicable people are expanded. The composite emulsion is expected to become a first-line choice for conservative treatment of intestinal obstruction, especially provides a new treatment hope for patients who cannot tolerate operations, and has remarkable clinical transformation value and social and economic benefits.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and more specifically, relates to a composite emulsion for intestinal obstruction and a preparation method of the composite emulsion for intestinal obstruction, and further relates to an application of the composite emulsion for intestinal obstruction. Background Art

[0002] Intestinal obstruction, caused by various factors, is a common surgical acute abdomen, characterized by rapid onset, complex pathology, numerous complications, and a high rate of postoperative recurrence. Based on etiology, it can be categorized as mechanical ileus (such as adhesions, tumors, or foreign body obstruction), dynamic ileus (such as paralytic and spastic), and vascular ileus (such as mesenteric vascular embolism). Mechanical ileus accounts for over 70% of cases.

[0003] According to the World Health Organization (WHO), the global incidence of intestinal obstruction is approximately 300-500 cases per 100,000 patients annually, of which mechanical obstruction accounts for 60%-80%, and adhesive obstruction accounts for 50%-70% of postoperative intestinal obstruction. In my country, over 600,000 patients are hospitalized for intestinal obstruction each year, with a recurrence rate of 15%-30% after surgery. This poses a serious threat to patients' lives and health and creates a heavy medical burden.

[0004] Current clinical treatments for intestinal obstruction mainly include: Traditional lubricated conservative therapy: fasting with water, gastrointestinal decompression, fluid support and enema with traditional lubricants (such as paraffin oil) is suitable for early incomplete intestinal obstruction.

[0005] Traditional Chinese medicine decoction therapy: Traditional Chinese medicine decoctions (such as Dachengqi Decoction) promote intestinal motility through laxative effects, but may increase the risk of intestinal dilatation in patients with mechanical obstruction; somatostatin reduces the secretion of digestive juices but has no direct effect on existing intestinal wall edema and inflammation.

[0006] Surgical treatment: It is suitable for patients with strangulated intestinal obstruction or those who fail conservative treatment, but surgical trauma may induce new adhesions, creating a treatment paradox.

[0007] Existing treatments all have significant limitations.

[0008] Paraffin oil is traditionally used as an intestinal lubricant, reducing the viscosity of intestinal contents through physical lubrication and promoting their excretion. However, its effect is limited to mechanical lubrication and lacks anti-inflammatory properties. It cannot address the core pathology of intestinal obstruction, including intestinal wall edema and inflammatory reactions. It cannot inhibit intestinal inflammatory exudation, and persistent intestinal wall edema can lead to worsening intestinal stenosis, creating a vicious cycle of "lubrication-edema-re-obstruction."

[0009] The use of traditional Chinese medicine decoctions such as Dachengqi Decoction (containing rhubarb, Glauber's salt, Magnolia officinalis, Citrus aurantium, etc.) will stimulate the intestinal wall nerve plexus and there is a risk of promoting intestinal peristalsis. For patients with clear mechanical obstruction (such as tumors, adhesion bands), it may also cause excessive expansion of the proximal intestinal tract of the obstruction, increase the risk of intestinal perforation, and aggravate the mechanical obstruction.

[0010] The synergistic effect of using a single therapy is missing. The pathological mechanism of intestinal obstruction involves multiple links, and it is difficult for a single therapy to achieve multi-target intervention. Traditional lubricants solve the problem of "unblocking", and anti-inflammatory drugs solve the problem of "inflammation", but the two cannot form a synergistic effect when used independently, and it is difficult to simultaneously solve problems such as intestinal wall edema, inflammatory exudation, and intestinal content retention.

[0011] Existing treatments for intestinal obstruction are unable to meet clinical needs due to their single mechanism of action, high risk of side effects, insufficient safety, and lack of precision. There is a need to develop a novel, targeted release drug with multi-mechanism synergy that can overcome the limitations of traditional therapies and provide an innovative solution for the conservative treatment of intestinal obstruction. Summary of the Invention

[0012] The present invention aims to address the deficiencies of the aforementioned existing main applications and treatments for intestinal obstruction. It provides a composite emulsion for intestinal obstruction that utilizes nanoemulsification technology to construct a "lubrication-anti-inflammatory-de-swelling" multi-mechanism compound, capable of achieving targeted release and multi-mechanism synergy. It also provides a method for preparing the composite emulsion for intestinal obstruction. Furthermore, it provides an application of the composite emulsion for intestinal obstruction.

[0013] In order to achieve the above object, the technical solution adopted by the present invention is as follows: A composite emulsion for intestinal obstruction comprises the following components: a traditional Chinese medicine extract, paraffin oil, an emulsifier, and a stabilizer, wherein the content of each component is as follows: 10-30% of the traditional Chinese medicine extract, 60-85% of the paraffin oil, 3-8% of the emulsifier, and 0.5-2% of the stabilizer. The traditional Chinese medicine extract, the paraffin oil, the emulsifier, and the stabilizer are homogenized to obtain the composite emulsion for intestinal obstruction. The traditional Chinese medicine extract is obtained by compounding Poria cocos, Rhizoma Alismatis, and Herba Patriniae in a weight ratio of Poria cocos: Rhizoma Alismatis: Herba Patriniae at 4:4:3, followed by supercritical CO2 extraction and water extraction and alcohol precipitation. The emulsifier is a nonionic emulsifier; the stabilizer is a cyclodextrin stabilizer. The composite emulsion for intestinal obstruction is a W / O emulsion.

[0014] Preferably, the Poria cocos, the Rhizoma Alismatis and the Herba Patriniae are subjected to supercritical CO2 extraction and an entrainer is added.

[0015] Preferably, the nonionic emulsifier is a mixture of polyoxyethylene hydrogenated castor oil and lecithin at a ratio of 1:0.5-2.

[0016] Furthermore, the nonionic emulsifier is a mixture of polyoxyethylene hydrogenated castor oil and lecithin in a ratio of 1:1.

[0017] Preferably, the cyclodextrin stabilizer is hydroxypropyl-β-cyclodextrin.

[0018] The present invention provides a method for preparing a composite emulsion for treating intestinal obstruction, comprising the following steps: Preparation of Chinese herbal medicine extracts: Poria cocos, Rhizoma Alismatis and Herba Patriniae are dried and then crushed to obtain crushed medicinal materials; The crushed medicinal materials are added with an entrainer according to a weight ratio to perform supercritical CO2 extraction to obtain a Chinese medicinal extract, and the extracts are combined and concentrated under reduced pressure to obtain a fat-soluble component; Separating the medicinal material residue, and subjecting the medicinal material residue to water extraction and alcohol precipitation treatment to obtain a water-soluble polysaccharide component; The fat-soluble component and the water-soluble polysaccharide component were mixed at a ratio of 6:4 and spray-dried to prepare a nanopowdered Chinese herbal medicine extract. Preparation of compound emulsion for intestinal obstruction: Heat paraffin oil to 50°C in a constant temperature water bath, and add an emulsifier and a stabilizer in sequence while maintaining the constant temperature. The emulsifier is a compound of polyoxyethylene hydrogenated castor oil and lecithin, and the ratio of polyoxyethylene hydrogenated castor oil to lecithin is 1:1. The stabilizer is hydroxypropyl-β-cyclodextrin. Stir and mix for 10 minutes at a stirring speed of 600 rpm to obtain a homogeneous oil phase matrix. The component content of the prepared nanopowdered Chinese medicine extract was slowly added to the oil phase, wherein the average particle size of the nanopowdered Chinese medicine extract was ≤200 nm. After continuing to stir for 15 minutes, high-pressure shear emulsification was performed using a high-pressure homogenizer. The pressure of the high-pressure homogenizer was set to 1000 bar, and the high-pressure shear emulsification cycle was repeated 3 times to finally form a W / O emulsion preparation with uniform particle size distribution.

[0019] Preferably, in the preparation method of the composite emulsion for intestinal obstruction, The specific steps of supercritical CO2 extraction are: Supercritical CO2 extraction process of Poria cocos: After cutting the Poria cocos into slices, dry them at 50℃ for 6 hours, grind them into 40-60 mesh, and sieve to remove the lignified part; The extraction and separation system pressure is set to 25-30 MPa, the temperature is set to 45-50°C, the time is 2-3 hours, 5% ethanol is added as an entrainer to perform supercritical CO2 extraction and secondary separation treatment to obtain an extract containing Poria triterpenoid acids; Supercritical CO2 extraction process of Alisma orientalis: After removing the fibrous roots, dry the rhizome at 60°C and grind it into 60-80 mesh; The extraction and separation system pressure is set to 20-25 MPa, the temperature is set to 50-55°C, the time is 2.5-3.5 hours, and 8% ethanol is added as an entrainer to perform supercritical CO2 extraction to obtain an extract containing 23-acetyl alismatol B from Alisma orientalis. Supercritical CO2 extraction process of Patrinia scabra: Patrinia scabra is naturally air-dried, cut and crushed into 40-60 mesh; The extraction and separation system pressure is set to 18-22 MPa, the temperature is set to 40-45°C, the extraction time is 1.5-2 hours, and 10% ethanol mixed with 2% water is added as an entrainer to perform supercritical CO2 extraction to obtain an extract containing Patrinia saponins; Set the CO2 storage tank temperature of the extraction and separation system to 3°C, the CO2 pump flow rate to 15-20L / h, set the extraction temperature of the extraction and separation system and start the circulating water bath. The filling density of the crushed medicinal materials into the extraction and separation system should be ≤0.4g / cm3; After the extracts were combined, the temperature was set at 40°C for reduced pressure concentration to obtain the fat-soluble fraction. The steps of the water extraction and alcohol precipitation treatment are: The medicinal residue obtained after supercritical CO2 extraction was added to purified water, with the ratio of the total dry weight of the medicinal residue obtained after supercritical CO2 extraction to purified water being 1:10, and placed in an extraction tank and decocted twice at 100°C for 1 hour each time, and the water extracts were filtered and combined; The combined aqueous extracts were transferred to a rotary evaporator and concentrated at 60°C under reduced pressure (the reduced pressure was set to -0.08 MPa) to concentrate the combined aqueous extracts to 1 / 4 of the original volume to form a concentrated aqueous extract; The concentrated water extract was slowly added dropwise to an equal volume of 70% ethanol under stirring. The stirring speed was set to 200 rpm, and the volume ratio of concentrated water extract to ethanol was 1:1. After stirring evenly, seal and store at 4°C for 18 hours to form a precipitate; The precipitate was collected by vacuum filtration, and the filter cake was washed once with anhydrous ethanol to remove impurities and then vacuum dried to obtain a water-soluble polysaccharide component.

[0020] Preferably, in the preparation method of the composite emulsion for intestinal obstruction, in the supercritical CO2 extraction process of Poria cocos, the Poria cocos is pre-moistened, sprayed with 70% ethanol, the ratio of Poria cocos to 70% ethanol is 1:0.3, and after spraying, it is allowed to stand for 30 minutes, the entrainer is added with 0.1% citric acid with a pH value of 4.0, and the secondary separation process is to perform secondary analytical extraction on the first-level product of Poria cocos extraction at 5 MPa; In the supercritical CO2 extraction process of Rhizoma Alismatis, the purity of CO2 in the CO2 storage tank is ≥99.9%; The extract of Patrinia saponin should be stored away from light.

[0021] Furthermore, in the preparation method of the composite emulsion for intestinal obstruction, the content of Poria triterpenic acid in the traditional Chinese medicine extract is ≥85%, and the average particle size of the nanopowder traditional Chinese medicine extract is ≤200 nm.

[0022] The compound emulsion for intestinal obstruction provided by the present invention is used in drug treatment of intestinal obstruction. The compound emulsion for intestinal obstruction is injected through rectal perfusion or nasogastric tube administration, with a daily dose of 0.3-0.8 mL / kg.

[0023] In view of the defects of traditional paraffin oil and traditional Chinese medicine decoctions in their lack of precise intervention in the core pathological area of ​​intestinal obstruction, the present invention achieves the synergistic effect of targeted delivery and sustained release in the inflammatory area through nanoemulsification technology. The present invention has the following beneficial effects: The composite emulsion for intestinal obstruction provided by the present invention combines the Poria cocos, Alisma orientalis, and Patrinia chinensis extracts with paraffin oil through nanoemulsification technology. The paraffin oil serves as a carrier to form a lubricating film in the intestine, and the Chinese medicine nanoparticles are sustained-released in the inflamed area to achieve targeted release. The Poria cocos triterpenoid acids in the emulsion are used to inhibit AQP4 water channel protein and reduce intestinal wall edema. Alisma orientalis 23-acetyl alisposide B regulates the NF-κB pathway and exerts an anti-inflammatory effect. Patrinia chinensis saponins inhibit TLR4 / MyD88 signal transduction, forming a multi-mechanism intervention with the lubricating effect of paraffin oil to achieve comprehensive synergistic effect.

[0024] This invention uses nanoemulsification technology to deeply integrate the lubricating properties of traditional paraffin oil with the anti-inflammatory and detumescent effects of traditional Chinese medicine extracts, addressing the core flaws of existing therapies: single mechanism, systemic toxicity, and poor targeting. This invention significantly improves symptom relief rates and significantly reduces inflammatory factors, significantly enhancing efficacy while also optimizing safety and expanding the applicable population. This composite emulsion is expected to become a first-line option for conservative treatment of intestinal obstruction, offering new therapeutic hope, particularly for patients unable to tolerate surgery, and possessing significant clinical translational value and socioeconomic benefits. DETAILED DESCRIPTION

[0025] To make the objectives, technical solutions, and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the described embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0026] The following embodiment provides a composite emulsion for intestinal obstruction, comprising the following components: a traditional Chinese medicine extract, paraffin oil, an emulsifier, and a stabilizer. The content of each component is: 10-30% of the traditional Chinese medicine extract, 60-85% of the paraffin oil, 3-8% of the emulsifier, and 0.5-2% of the stabilizer. The traditional Chinese medicine extract, the paraffin oil, the emulsifier, and the stabilizer are homogenized to obtain the composite emulsion for intestinal obstruction. The traditional Chinese medicine extract is obtained by compounding Poria cocos, Alisma orientalis, and Patrinia lappa in a weight ratio of Poria cocos: Alisma orientalis: Patrinia lappa = 4:4:3, followed by supercritical CO2 extraction and water extraction and alcohol precipitation. The emulsifier is a nonionic emulsifier; the stabilizer is a cyclodextrin stabilizer. The composite emulsion for intestinal obstruction is a W / O emulsion.

[0027] Preferably, the Poria cocos, the Rhizoma Alismatis and the Herba Patriniae are subjected to supercritical CO2 extraction and an entrainer is added.

[0028] Preferably, the nonionic emulsifier is a mixture of polyoxyethylene hydrogenated castor oil and lecithin at a ratio of 1:0.5-2.

[0029] Furthermore, the nonionic emulsifier is a mixture of polyoxyethylene hydrogenated castor oil and lecithin in a ratio of 1:1.

[0030] Preferably, the cyclodextrin stabilizer is hydroxypropyl-β-cyclodextrin.

[0031] The present invention provides a method for preparing a composite emulsion for treating intestinal obstruction, comprising the following steps: Preparation of Chinese herbal medicine extracts: Poria cocos, Rhizoma Alismatis and Herba Patriniae are dried and then crushed to obtain crushed medicinal materials; The crushed medicinal materials are added with an entrainer according to a weight ratio to perform supercritical CO2 extraction to obtain a Chinese medicinal extract, and the extracts are combined and concentrated under reduced pressure to obtain a fat-soluble component; Separating the medicinal material residue, and subjecting the medicinal material residue to water extraction and alcohol precipitation treatment to obtain a water-soluble polysaccharide component; The fat-soluble component and the water-soluble polysaccharide component were mixed at a ratio of 6:4 and spray-dried to prepare a nanopowdered Chinese herbal medicine extract. Preparation of compound emulsion for intestinal obstruction: Heat paraffin oil to 50°C in a constant temperature water bath, and add an emulsifier and a stabilizer in sequence while maintaining the constant temperature. The emulsifier is a compound of polyoxyethylene hydrogenated castor oil and lecithin, and the ratio of polyoxyethylene hydrogenated castor oil to lecithin is 1:1. The stabilizer is hydroxypropyl-β-cyclodextrin. Stir and mix for 10 minutes at a stirring speed of 600 rpm to obtain a homogeneous oil phase matrix. The component content of the prepared nanopowdered Chinese medicine extract was slowly added to the oil phase, wherein the average particle size of the nanopowdered Chinese medicine extract was ≤200 nm. After continuing to stir for 15 minutes, high-pressure shear emulsification was performed using a high-pressure homogenizer. The pressure of the high-pressure homogenizer was set to 1000 bar, and the high-pressure shear emulsification cycle was repeated 3 times to finally form a W / O emulsion preparation with uniform particle size distribution.

[0032] Preferably, in the preparation method of the composite emulsion for intestinal obstruction, The specific steps of supercritical CO2 extraction are: Supercritical CO2 extraction process of Poria cocos: After cutting the Poria cocos into slices, dry them at 50℃ for 6 hours, grind them into 40-60 mesh, and sieve to remove the lignified part; The extraction and separation system pressure is set to 25-30 MPa, the temperature is set to 45-50°C, the time is 2-3 hours, 5% ethanol is added as an entrainer to perform supercritical CO2 extraction and secondary separation treatment to obtain an extract containing Poria triterpenoid acids; Supercritical CO2 extraction process of Alisma orientalis: After removing the fibrous roots, dry the rhizome at 60°C and grind it into 60-80 mesh; The extraction and separation system pressure is set to 20-25 MPa, the temperature is set to 50-55°C, the time is 2.5-3.5 hours, and 8% ethanol is added as an entrainer to perform supercritical CO2 extraction to obtain an extract containing 23-acetyl alismatol B from Alisma orientalis. Supercritical CO2 extraction process of Patrinia scabra: Patrinia scabra is naturally air-dried, cut and crushed into 40-60 mesh; The extraction and separation system pressure is set to 18-22 MPa, the temperature is set to 40-45°C, the extraction time is 1.5-2 hours, and 10% ethanol mixed with 2% water is added as an entrainer to perform supercritical CO2 extraction to obtain an extract containing Patrinia saponins; Set the CO2 storage tank temperature of the extraction and separation system to 3°C, the CO2 pump flow rate to 15-20L / h, set the extraction temperature of the extraction and separation system and start the circulating water bath. The filling density of the crushed medicinal materials into the extraction and separation system should be ≤0.4g / cm3; After combining all the extracts, the temperature was set at 40°C for vacuum concentration to obtain the fat-soluble fraction. The steps of the water extraction and alcohol precipitation treatment are: The medicinal residue obtained after supercritical CO2 extraction was added to purified water, with the ratio of the total dry weight of the medicinal residue obtained after supercritical CO2 extraction to purified water being 1:10, and placed in an extraction tank and decocted twice at 100°C for 1 hour each time, and the water extracts were filtered and combined; The combined aqueous extracts were transferred to a rotary evaporator and concentrated at 60°C under reduced pressure (the reduced pressure was set to -0.08 MPa) to concentrate the combined aqueous extracts to 1 / 4 of the original volume to form a concentrated aqueous extract; The concentrated water extract was slowly added dropwise to an equal volume of 70% ethanol under stirring. The stirring speed was set to 200 rpm, and the volume ratio of concentrated water extract to ethanol was 1:1. After stirring evenly, seal and store at 4°C for 18 hours to form a precipitate; The precipitate was collected by vacuum filtration, and the filter cake was washed once with anhydrous ethanol to remove impurities and then vacuum dried to obtain a water-soluble polysaccharide component.

[0033] Preferably, in the preparation method of the composite emulsion for intestinal obstruction, in the supercritical CO2 extraction process of Poria cocos, the Poria cocos is pre-moistened, sprayed with 70% ethanol, the ratio of Poria cocos to 70% ethanol is 1:0.3, and after spraying, it is allowed to stand for 30 minutes, the entrainer is added with 0.1% citric acid with a pH value of 4.0, and the secondary separation process is to perform secondary analytical extraction on the first-level product of Poria cocos extraction at 5 MPa; In the supercritical CO2 extraction process of Rhizoma Alismatis, the purity of CO2 in the CO2 storage tank is ≥99.9%; The extract of Patrinia saponin should be stored away from light.

[0034] Furthermore, in the preparation method of the composite emulsion for intestinal obstruction, the content of Poria triterpenic acid in the traditional Chinese medicine extract is ≥85%, and the average particle size of the nanopowder traditional Chinese medicine extract is ≤200 nm.

[0035] The compound emulsion for intestinal obstruction provided by the present invention is used in drug treatment of intestinal obstruction. The compound emulsion for intestinal obstruction is injected through rectal perfusion or nasogastric tube administration, with a daily dose of 0.3-0.8 mL / kg.

[0036] First embodiment:

[0037] In this embodiment, the components and component contents for preparing the composite emulsion for intestinal obstruction include 20% of a Chinese herbal extract (a combined extract of 8 g of Poria cocos, 8 g of Rhizoma Alismatis, and 6 g of Herba Patriniae), 75% of paraffin oil, 3.5% of an emulsifier (polyoxyethylene hydrogenated castor oil and lecithin in a ratio of 1:1), and 1.5% of a stabilizer (hydroxypropyl-β-cyclodextrin).

[0038] In this example, a composite emulsion for intestinal obstruction was prepared.

[0039] In this embodiment, the supercritical CO2 extraction equipment comprises an extraction and separation system and an auxiliary system.

[0040] Extraction and Separation System: Extraction kettle: Pressure resistance ≥ 50 MPa, volume 1-100 L (5-20 L is common in laboratories), made of 316L stainless steel. Separation kettle: Two-stage separation (first stage pressure 8-12 MPa, second stage at atmospheric pressure), equipped with a temperature-controlled jacket. CO2 high-pressure pump: Plunger pump, flow rate range 5-50 L / h (liquid CO2). Refrigeration unit: Maintains the CO2 storage tank temperature between -5°C and 5°C (to maintain liquid state). Heating system: Precise temperature control within ±1°C, temperature range from room temperature to 100°C.

[0041] Auxiliary Systems: Entrainer Tank: Used to add polar solvents such as ethanol and water (to improve the extraction rate of polar components). Filter: 0.1μm titanium alloy filter element to prevent solid particles from entering the pipeline. Control System: PLC automatically adjusts pressure, temperature, and flow rate, and records data in real time.

[0042] To prepare Chinese herbal medicine extracts, Poria cocos, Alisma orientalis and Patrinia lappa were taken according to the amount and subjected to supercritical CO2 extraction.

[0043] Parameters and setup basis for supercritical CO2 extraction of Chinese herbal medicine extracts: medicinal materials Target ingredients Pressure (MPa) Temperature (℃) Time (h) entrainer Poria cocos Poria triterpenoid acid 25-30 45-50 2-3 5% ethanol Alisma orientalis Alisma 23-acetyl alismatol B 20-25 50-55 2.5-3.5 8% ethanol Patrinia scabra Patrinia saponins 18-22 40-45 1.5-2 10% ethanol + 2% water Set the CO2 storage tank temperature of the extraction and separation system to 3°C, the CO2 pump flow rate to 15-20L / h, set the extraction temperature of the extraction and separation system and start the circulating water bath. The filling density of the crushed medicinal materials into the extraction and separation system should be ≤0.4g / cm3; Supercritical CO2 extraction process of Poria cocos: Pre-moisten the Poria cocos and spray it with 70% ethanol. The ratio of Poria cocos to 70% ethanol is 1:0.3. After spraying, let it stand for 30 minutes. After cutting the Poria cocos into slices, dry them at 50℃ for 6 hours, grind them into 40-60 mesh, and sieve to remove the lignified part; The crushed medicinal materials are loaded into the extraction and separation system at a packing density of ≤0.4 g / cm3, the extraction and separation system pressure is set to 25-30 MPa, the temperature is set to 45-50°C, the extraction time is 2-3 hours, 5% ethanol is added as an entrainer to perform supercritical CO2 extraction and secondary separation treatment to obtain an extract containing Poria triterpenoid acids; The first separation vessel (10 MPa, 40°C) collects fat-soluble components. The second separation vessel (normal pressure, 35°C) collects polar components. The Poria cocos extract undergoes secondary separation, and the first product undergoes secondary analytical extraction at 5 MPa to improve the purity of the Poria cocos triterpenoid acids.

[0044] Since ethanol concentration > 5% will increase pigment impurities, 0.1% citric acid with a pH of 4.0 is added to the entrainer to inhibit oxidation.

[0045] Supercritical CO2 extraction for more than 3 hours will lead to the degradation of Poria triterpenoid acids. The extraction time must be limited to 2-3 hours, and the HPLC spectrum must be monitored in real time.

[0046] Supercritical CO2 extraction process of Alisma orientalis: After removing the fibrous roots, dry the rhizome at 60°C and grind it into 60-80 mesh; The purity of the CO2 used in the CO2 storage tank is ≥99.9% (to prevent hydrocarbon impurities from interfering with the structure of acetyl alismatol). The filling density of the crushed medicinal materials into the extraction and separation system is ≤0.4g / cm3. The pressure of the extraction and separation system is set to 20-25MPa, and the temperature is set to 50-55℃ (since Alisma orientalis is sensitive to temperature, 23-acetyl alismatol B will be induced to undergo epimerization when the processing temperature is greater than 55℃, so strict temperature control is required). The extraction time is 2.5-3.5h. 8% ethanol is added as an entrainer for supercritical CO2 extraction to obtain an extract containing 23-acetyl alismatol B from Alisma orientalis. Supercritical CO2 extraction of Alisma requires a gradient pressure increase in the extraction and separation system, which is set to 20 MPa in the first 30 minutes and then increased to 25 MPa in the later stage.

[0047] Supercritical CO2 extraction process of Patrinia scabra: Patrinia scabra is naturally air-dried, cut and crushed into 40-60 mesh; The crushed medicinal materials are loaded into the extraction and separation system at a packing density of ≤0.4 g / cm3. The pressure of the extraction and separation system is set to 18-22 MPa, the temperature is set to 40-45°C, and the extraction time is 1.5-2 hours. 10% ethanol mixed with 2% water is added as an entrainer to perform supercritical CO2 extraction treatment to obtain an extract containing patrinia saponins. The patrinia saponins extract is stored in the dark. After the extracts were combined, the temperature was set at 40°C for reduced pressure concentration to obtain the fat-soluble fraction. Separate the medicinal material residue and subject it to water extraction and alcohol precipitation treatment. The steps of water extraction and alcohol precipitation treatment are as follows: The medicinal residue obtained after supercritical CO2 extraction was added to purified water, with the ratio of the total dry weight of the medicinal residue obtained after supercritical CO2 extraction to purified water being 1:10, and placed in an extraction tank and decocted twice at 100°C for 1 hour each time, and the water extracts were filtered and combined; The combined aqueous extracts were transferred to a rotary evaporator and concentrated at 60°C under reduced pressure (the reduced pressure was set to -0.08 MPa) to concentrate the combined aqueous extracts to 1 / 4 of the original volume to form a concentrated aqueous extract; The concentrated water extract was slowly added dropwise to an equal volume of 70% ethanol under stirring. The stirring speed was set to 200 rpm, and the volume ratio of concentrated water extract to ethanol was 1:1. After stirring evenly, seal and store at 4°C for 18 hours to form a precipitate; The precipitate was collected by vacuum filtration, and the filter cake was washed once with anhydrous ethanol to remove impurities and then vacuum dried to obtain a water-soluble polysaccharide component.

[0048] The fat-soluble component and the water-soluble polysaccharide component were mixed at a ratio of 6:4 and spray-dried to prepare a nanopowdered Chinese herbal medicine extract. Preparation of intestinal obstruction compound emulsion, Based on the content of the Chinese herbal extract, paraffin oil, emulsifier (polyoxyethylene hydrogenated castor oil and lecithin in a ratio of 1:1), and stabilizer (hydroxypropyl-β-cyclodextrin) were added according to the content of the components. The paraffin oil was heated to 50°C, and the emulsifier and stabilizer were added according to the content of the components, and the mixture was homogenized to obtain an oil phase matrix. The component content is added to the prepared nanopowder of traditional Chinese medicine extract. The average particle size of the nanopowder of traditional Chinese medicine extract is ≤200 nm. After continuing to stir for 15 minutes, high-pressure shear emulsification is performed using a high-pressure homogenizer. The pressure of the high-pressure homogenizer is set to 1000 bar, and the number of high-pressure shear emulsification cycles is 3. Finally, a W / O type emulsion with uniform particle size distribution is formed to complete the preparation.

[0049] The preparation process of this embodiment utilizes supercritical CO2 directional extraction + entrainer polarity control to achieve efficient extraction of the active ingredients of the three component medicinal materials: the extraction rate of Poria triterpenoid acid can reach 2.8%, which is much higher than the 0.3% extraction rate of Poria triterpenoid acid by the traditional water decoction method; The purity of 23-acetyl alismatol B from Alisma orientalis was increased to 92%, 40% higher than that obtained by Soxhlet extraction. By taking advantage of thermal decomposition prevention, low-temperature (≤45℃) short-time (<2h) extraction treatment is adopted to retain the activity of Patrinia saponins, with the retention rate of Patrinia saponins being >95%, avoiding the loss of Patrinia saponin activity caused by thermal decomposition in traditional alcohol extraction.

[0050] In this embodiment, the prepared composite emulsion for intestinal obstruction is used in drug treatment of intestinal obstruction, and the composite emulsion for intestinal obstruction is injected through rectal perfusion or nasogastric tube administration, with a daily dose of 0.3-0.8 mL / kg.

[0051] In the efficacy verification experiment, an experimental group and a control group were set up. The animal model was established using SD rats with incomplete intestinal obstruction. The experimental group received rectal perfusion of 0.5 mL / kg of the compound emulsion prepared for intestinal obstruction, and the results were obtained within 24 hours; the control group received rectal perfusion of 0.5 mL / kg of simple paraffin oil, and the results were obtained within 24 hours.

[0052] Set up efficacy verification experiments, experimental animals and models: Experimental animal selection: SPF female SD rats, weighing about 200 g, a total of 12.

[0053] Experimental animal grouping: blank group, paraffin oil control group and compound emulsion experimental group were set up.

[0054] 1. Blank group (NS group): administered with normal saline; 2. Paraffin oil control group: given the same dose of paraffin oil as the experimental group; 3. Compound emulsion experimental group: The rats were given the compound emulsion for intestinal obstruction described in the examples.

[0055] Experimental animal grouping: 4 experimental animals were randomly assigned to each group.

[0056] Establishment of experimental animal model: A longitudinal incision approximately 2-3 cm is made along the rat's midline abdomen. The skin, muscularis, and peritoneum are dissected layer by layer, gently dissecting to avoid damaging internal organs. The small intestine is exposed, and a segment of small intestine 10 cm from the ileocecal valve is selected. Sterile silk suture (4-0) is wrapped around the target segment and gently tightened to narrow the intestinal lumen by approximately 50%. The suture is then tied to secure the suture. The obstructed area is slightly swollen or slightly narrowed, ensuring that the blood supply to the intestinal wall is not severely compromised and that complete occlusion or strangulation is avoided. After checking for obvious bleeding or leakage in the abdominal cavity, the surgical area is flushed with normal saline. The peritoneum, muscularis, and skin are sutured layer by layer. Postoperatively, iodine or antibacterial ointment is applied to the skin incision. Mild to moderate abdominal distension, decreased or delayed bowel movements, and other signs of intestinal obstruction will appear approximately 24 hours after surgery. Treatment is then initiated according to the experimental animal grouping.

[0057] Drug administration and experimental methods: Route of administration: Rectal instillation; Dosage: 0.5 mL / kg, once a day for 3 consecutive days; Experimental method: During the treatment period, the rats were allowed to drink water and fast. After 72 hours of treatment, the whole blood was taken and the rats were killed. The intestinal tube within 1 cm proximal to the small intestinal obstruction point was cut out, and the intestinal wall edema thickness and inflammatory factor expression levels of the cut intestinal tube were measured.

[0058] The experimental evaluation indicators and experimental control results are as follows: 1. Intestinal wall edema thickness (histological measurement) Grouping Intestinal wall thickness (μm) Edema reduction rate (%) Blank group 482.3 ± 23.5 — Paraffin oil control group 423.1 ± 21.7 12.3% Composite emulsion experimental group 276.3 ± 16.5 42.7% Compared with the blank group, the composite emulsion experimental group was the most significant in alleviating intestinal wall edema, with a decrease of 42.7%. Compared with the paraffin oil control group, the composite emulsion experimental group had a better result in alleviating intestinal wall edema, which was 12.3% better than that of the paraffin oil control group (P<0.001).

[0059] 2. Expression of inflammatory factors (serum ELISA test) Grouping IL-6 (pg / mL) TNF-α (pg / mL) Blank group 108.2 ± 9.3 94.7 ± 8.1 Paraffin oil control group 89.1 ± 6.7 85.4 ± 7.3 Composite emulsion experimental group 45.3 ± 4.6 47.7 ± 5.1 Compared with the blank group, the composite emulsion experimental group showed that the use of composite emulsion can significantly inhibit intestinal-related inflammatory response. Comparing the numerical values ​​of the composite emulsion experimental group using composite emulsion with those of the blank group without medication, the composite emulsion experimental group's IL-6 decreased by 62.9%, and the composite emulsion experimental group's TNF-α decreased by 47%. Compared with the paraffin oil control group, the composite emulsion experimental group's IL-6 decreased by 19.1%, and TNF-α decreased by only 9.3%. The composite emulsion experimental group had significantly better inflammation inhibition effect than the paraffin oil control group (P<0.001).

[0060] Analysis and conclusion Comprehensive evaluation of treatment effect: The composite emulsion of traditional Chinese medicine and paraffin oil for intestinal obstruction provided by the present invention has shown superior efficacy to traditional paraffin oil in an animal experimental model of incomplete intestinal obstruction, and has obvious advantages in the following aspects: Intestinal wall edema: significantly alleviated, indicating that it improves intestinal wall permeability and water metabolism; Inflammation inhibition: It significantly downregulated the levels of IL-6 and TNF-α, indicating a clear anti-inflammatory effect.

[0061] The incomplete intestinal obstruction prepared by the present invention embeds the active ingredients of traditional Chinese medicine in paraffin oil in nano form through a W / O emulsion system, so that the drug efficacy is targeted and released at the obstruction site, avoiding the risk of strong intestinal peristalsis that may be caused by traditional decoctions; at the same time, it integrates the three major mechanisms of physical lubrication + anti-inflammatory + anti-edema, and synergistically intervenes from multiple links, which can provide patients with non-strangulated intestinal obstruction with a safer and more effective new conservative treatment strategy, and has good clinical transformation prospects.

[0062] The above description of the embodiments is intended to facilitate understanding and use of the present invention by those skilled in the art. Those skilled in the art will readily be able to make various modifications to these embodiments and apply the general principles described herein to other embodiments without resorting to creative effort. Therefore, the present invention is not limited to the above-described embodiments. Any improvements or modifications made by those skilled in the art based on the principles of the present invention that do not depart from the scope of the present invention should be considered within the scope of protection of the present invention.

Claims

1. A composite emulsion for intestinal obstruction, characterized in that: The invention comprises the following components: Chinese herbal medicine extract, paraffin oil, emulsifier and stabilizer, wherein the content of each component is as follows: the Chinese herbal medicine extract is 10-30%, the paraffin oil is 60-85%, the emulsifier is 3-8%, and the stabilizer is 0.5-2%. The Chinese herbal extract, the paraffin oil, the emulsifier and the stabilizer are homogenized to obtain an intestinal obstruction composite emulsion. The Chinese medicine extract is obtained by compounding Poria cocos, Rhizoma Alismatis and Herba Patriniae in a weight ratio of Poria cocos: Rhizoma Alismatis: Herba Patriniae = 4:4:3, and then undergoing supercritical CO2 extraction and water extraction and alcohol precipitation treatment; The emulsifier is a nonionic emulsifier, the stabilizer is a cyclodextrin stabilizer, and the intestinal obstruction composite emulsion is a W / O emulsion.

2. The composite emulsion for intestinal obstruction according to claim 1, characterized in that: The Poria cocos, the Rhizoma Alismatis and the Herba Patriniae are subjected to supercritical CO2 extraction and an entrainer is added.

3. The composite emulsion for intestinal obstruction according to claim 1, characterized in that: The nonionic emulsifier is a compound of polyoxyethylene hydrogenated castor oil and lecithin at a ratio of 1:0.5-2.

4. The composite emulsion for intestinal obstruction according to claim 3, characterized in that: The nonionic emulsifier is a mixture of polyoxyethylene hydrogenated castor oil and lecithin in a ratio of 1:

1.

5. The composite emulsion for intestinal obstruction according to claim 1, characterized in that: The cyclodextrin stabilizer is hydroxypropyl-β-cyclodextrin.

6. The method for preparing the composite emulsion for intestinal obstruction according to claim 1, characterized in that: The following steps are involved: Preparation of Chinese herbal medicine extracts: Poria cocos, Rhizoma Alismatis and Herba Patriniae are dried and then crushed to obtain crushed medicinal materials; The crushed medicinal materials are added with an entrainer according to a weight ratio to perform supercritical CO2 extraction to obtain a Chinese medicinal extract, and the extracts are combined and concentrated under reduced pressure to obtain a fat-soluble component; Separating the medicinal material residue, and subjecting the medicinal material residue to water extraction and alcohol precipitation treatment to obtain a water-soluble polysaccharide component; The fat-soluble component and the water-soluble polysaccharide component were mixed at a ratio of 6:4 and spray-dried to prepare a nanopowdered Chinese herbal medicine extract. Preparation of compound emulsion for intestinal obstruction: Heat paraffin oil to 50°C in a constant temperature water bath, and add an emulsifier and a stabilizer in sequence while maintaining the constant temperature. The emulsifier is a compound of polyoxyethylene hydrogenated castor oil and lecithin, and the ratio of polyoxyethylene hydrogenated castor oil to lecithin is 1:

1. The stabilizer is hydroxypropyl-β-cyclodextrin. Stir and mix for 10 minutes at a stirring speed of 600 rpm to obtain a homogeneous oil phase matrix. The component content of the prepared nanopowdered Chinese medicine extract was slowly added to the oil phase, wherein the average particle size of the nanopowdered Chinese medicine extract was ≤200 nm. After continuing to stir for 15 minutes, high-pressure shear emulsification was performed using a high-pressure homogenizer. The pressure of the high-pressure homogenizer was set to 1000 bar, and the high-pressure shear emulsification cycle was repeated 3 times to finally form a W / O emulsion preparation with uniform particle size distribution.

7. The method for preparing the composite emulsion for intestinal obstruction according to claim 6, characterized in that: The specific steps of supercritical CO2 extraction are: Supercritical CO2 extraction process of Poria cocos: After cutting the Poria cocos into slices, dry them at 50℃ for 6 hours, grind them into 40-60 mesh, and sieve to remove the lignified part; The extraction and separation system pressure is set to 25-30 MPa, the temperature is set to 45-50°C, the time is 2-3 hours, 5% ethanol is added as an entrainer to perform supercritical CO2 extraction and secondary separation treatment to obtain an extract containing Poria triterpenoid acids; Supercritical CO2 extraction process of Alisma orientalis: After removing the fibrous roots, dry the rhizome at 60°C and grind it into 60-80 mesh; The extraction and separation system pressure is set to 20-25 MPa, the temperature is set to 50-55°C, the time is 2.5-3.5 hours, and 8% ethanol is added as an entrainer to perform supercritical CO2 extraction to obtain an extract containing 23-acetyl alismatol B from Alisma orientalis. Supercritical CO2 extraction process of Patrinia scabra: Patrinia scabra is naturally air-dried, cut and crushed into 40-60 mesh; The extraction and separation system pressure is set to 18-22 MPa, the temperature is set to 40-45°C, the extraction time is 1.5-2 hours, and 10% ethanol mixed with 2% water is added as an entrainer to perform supercritical CO2 extraction to obtain an extract containing Patrinia saponins; Set the CO2 storage tank temperature of the extraction and separation system to 3°C, the CO2 pump flow rate to 15-20L / h, set the extraction temperature of the extraction and separation system and start the circulating water bath. The filling density of the crushed medicinal materials into the extraction and separation system should be ≤0.4g / cm3; After the extracts were combined, the temperature was set at 40°C for reduced pressure concentration to obtain the fat-soluble fraction. The steps of the water extraction and alcohol precipitation treatment are: The medicinal residue obtained after supercritical CO2 extraction was added to purified water, with the ratio of the total dry weight of the medicinal residue obtained after supercritical CO2 extraction to purified water being 1:10, and placed in an extraction tank and decocted twice at 100°C for 1 hour each time, and the water extracts were filtered and combined; The combined aqueous extracts were transferred to a rotary evaporator and concentrated at 60°C under reduced pressure (the reduced pressure was set to -0.08 MPa) to concentrate the combined aqueous extracts to 1 / 4 of the original volume to form a concentrated aqueous extract; The concentrated water extract was slowly added dropwise to an equal volume of 70% ethanol under stirring. The stirring speed was set to 200 rpm, and the volume ratio of concentrated water extract to ethanol was 1:

1. After stirring evenly, seal and store at 4°C for 18 hours to form a precipitate; The precipitate was collected by vacuum filtration, and the filter cake was washed once with anhydrous ethanol to remove impurities and then vacuum dried to obtain a water-soluble polysaccharide component.

8. The method for preparing the composite emulsion for intestinal obstruction according to claim 6, characterized in that: In the supercritical CO2 extraction process of Poria cocos, Poria cocos is pre-wetted and sprayed with 70% ethanol. The ratio of Poria cocos to 70% ethanol is 1:0.

3. After spraying, the mixture is allowed to stand for 30 minutes. The entrainer is added with 0.1% citric acid with a pH value of 4.

0. The secondary separation process is to perform secondary analytical extraction on the first-level product of Poria cocos extraction at 5MPa. In the supercritical CO2 extraction process of Rhizoma Alismatis, the purity of CO2 in the CO2 storage tank is ≥99.9%; The extract of Patrinia saponin should be stored away from light.

9. The method for preparing the composite emulsion for intestinal obstruction according to any one of claims 6 or 7, characterized in that: The content of Poria triterpene acid in the traditional Chinese medicine extract is ≥85%, and the average particle size of the nano-powder traditional Chinese medicine extract is ≤200nm.

10. The use of the composite emulsion for intestinal obstruction in drug treatment of intestinal obstruction according to claim 1, characterized in that: The compound emulsion for intestinal obstruction is injected through rectal irrigation or nasogastric tube administration, with a daily dose of 0.3-0.8 mL / kg.