Traditional Chinese medicine composition and application thereof

Abstract

The invention discloses a traditional Chinese medicine composition and application thereof. Relates to the technical field. The invention provides application of the traditional Chinese medicine composition, an astragalus membranaceus and cassia twig five-material decoction extracted concentrated solution, an astragalus membranaceus and cassia twig five-material decoction nanoemulsion, an astragalus membranaceus and cassia twig five-material decoction gel plaster and the like. Aiming at the active ingredients of the optimized traditional Chinese medicine composition, the invention develops a nano-emulsion gel plaster preparation for relieving diseases such as muscle pain and rheumatic arthritis. The O / W nano-emulsion technology is used for achieving efficient loading of hydrophilic and hydrophobic functional substances in the radix astragali and cassia twig five-material decoction and the skin penetrating capacity of the hydrophilic and hydrophobic functional substances in the radix astragali and cassia twig five-material decoction. The nanoemulsion is uniformly dispersed in a three-dimensional network structure formed by absorption and swelling of polyacrylic acid, so that the medicine can be slowly and stably released, and the phenomenon of unstable crystallization caused by thermodynamic movement of supersaturated medicine molecules can be hindered. In addition, the gel plaster has a good moisturizing effect and is good in skin attaching feeling and excellent in swelling performance and thixotropic performance.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and more particularly to a traditional Chinese medicine composition and application thereof. Background Art

[0002] Huangqi Guizhi Wuwu Tang is recorded in classic Chinese medicine books such as "Golden Chamber" and "Treatise on Febrile Diseases". It is a classic prescription based on Huangqi and Guizhi, with added herbs such as peony, ginger, and jujube. Huangqi is the main drug in the prescription, which replenishes qi and consolidates the exterior; Guizhi warms and dredges the meridians, and is used with Huangqi to replenish qi, warm yang, and harmonize blood and dredge the meridians. Guizhi is invigorated by Huangqi and invigorates Weiyang, while Huangqi is invigorated by Guizhi and consolidates the exterior without retaining evil. Peony nourishes blood and harmonizes Ying and dredges blood stasis. It is used together with Guizhi to regulate Ying and Wei, harmonize the exterior and interior, and dredge blood vessels, which means that treating wind should first treat blood. The two drugs are ministerial drugs.

[0003] External treatment with Chinese medicine refers to the process whereby the drug is directly absorbed through the skin, orifices, acupoints, and other external skin or mucous membranes, flows through the blood vessels, and reaches the site of the disease. External treatment with Chinese medicine has the advantages of definite efficacy, simple operation, and few side effects. It is suitable for the treatment and health care of locally effective diseases. According to the treatment method and medication form, it can be divided into application, fumigation, washing, etc. As a representative of warming agents, Huangqi Guizhi Wuwu Decoction is often used for grinding application or fumigation to treat traumatic injuries, rheumatic pain, rheumatic arthritis, skin diseases, etc.

[0004] Furthermore, the traditional external treatment method based on Huangqi Guizhi Wuwu Decoction has not been widely promoted due to limiting factors such as the complex operation process, limited contact time and part of the preparation, poor effect in reaching the deep skin site of action, and the risk of burns caused by fumigation and washing.

[0005] Gel patches are semi-solid preparations composed of cross-linked polymers that can absorb and retain a large amount of water or drug solutions. This structural feature allows the gel patch to maintain a certain shape while having good softness and adaptability, and is suitable for long-term adhesion to the skin surface of different parts. Nanoemulsion refers to a metastable system with an internal phase droplet diameter of less than 1000nm, also known as microemulsion, ultrafine emulsion and submicron emulsion. Nanoemulsion is an oil-in-water (O / W) or water-in-oil (W / O) dispersion system obtained by surfactant stabilization. Since the droplet size of nanoemulsion is very small, the gravity acting on the droplet is significantly reduced, and its Brownian motion is sufficient to resist gravity, so no stratification or precipitation occurs during storage. Therefore, nanoemulsion is a kinetically stable system with long-term physical stability. More importantly, the size effect of nanoemulsion gives it a higher surface tension and a large surface area, which can be evenly distributed on the skin surface, and the active substances can easily penetrate into the skin. The permeability and bioavailability of hydrophobic and hydrophilic active substances dissolved in the system will be significantly increased.

[0006] Nanoemulsion gel patch refers to a type of combined preparation in which O / W nanoemulsion is evenly dispersed in the aqueous skeleton matrix of the gel patch to form a stable reservoir. This preparation has the dual advantages of nanoemulsion and gel. Nanoemulsion can improve drug solubility and drug stability, while gel can improve nanoemulsion adhesion, increase drug retention time on the skin surface, and continuously and stably deliver drugs.

[0007] Therefore, whether the formulation can be optimized to provide a nanoemulsion gel patch is an urgent problem to be solved by those skilled in the art. Summary of the invention

[0008] In view of this, the present invention provides a Chinese medicine composition and its application. In order to improve the efficacy, pungent and warm meridian-dredging drugs are added to Huangqi Guizhi Wuwu Decoction (main drug), including ginger, which is pungent and warm meridian-dredging, which can warm the meridians and dispel cold, and help Guizhi warm and dredge the blood vessels; angelica and jujube, which are pungent and moist meridian-dredging, can nourish blood and promote blood circulation. In addition, safflower is added to the prescription to promote blood circulation and remove blood stasis, and clematis is added to promote menstruation and relieve pain, so as to increase the efficacy. Licorice harmonizes the medicinal properties and can also relieve pain. Therefore, the whole prescription can not only replenish qi and blood, nourish blood and promote blood circulation, but also warm and dredge the meridians.

[0009] In order to achieve the above object, the present invention adopts the following technical solution:

[0010] A Chinese medicine composition, comprising, by weight: 10-30 parts of astragalus, 10-20 parts of cassia twig, 10-20 parts of peony, 5-15 parts of ginger, 5-15 parts of angelica, 2-10 parts of safflower, 5-10 parts of clematis, 5-10 parts of jujube, 5-10 parts of liquorice,

[0011] The invention also provides a method for preparing the Huangqi Guizhi Wuwu Decoction extract concentrate, which comprises mixing the above-mentioned Chinese medicine composition, soaking in water, decocting and concentrating.

[0012] Preferably: soaking in water, boiling and concentrating: soaking in water for 60 minutes, then adding 8 to 10 times the amount of water of the Chinese medicine composition, soaking and boiling at 90°C for 90 minutes, extracting twice, filtering, combining the two decoctions, concentrating to 90 mL at 100°C and cooling for use.

[0013] The present invention also provides a Huangqi Guizhi Wuwu Decoction nanoemulsion, which comprises, by weight, 10 to 30 parts of a surfactant, 8.5 to 30 parts of a co-surfactant, 10 to 20 parts of an oil phase, 35 to 45 parts of the Huangqi Guizhi Wuwu Decoction extract concentrate, and 10 to 20 parts of water.

[0014] Preferably: the surfactant is one or more of lauryl alcohol polyoxyethylene ether, stearic acid polyoxyethylene ether, Tween 80, Tween 20 and EL40;

[0015] The co-surfactant is one or more of 1,2-propylene glycol, polyethylene glycol 400, anhydrous ethanol and n-butanol;

[0016] The oil phase is one or more of IPM, MCT, oleic acid, soybean oil, and ethyl oleate.

[0017] The present invention also provides a method for preparing the Huangqi Guizhi Wuwu Decoction nanoemulsion, which comprises adding the Huangqi Guizhi Wuwu Decoction extract into water, and ultrasonicating to obtain a drug-containing aqueous phase;

[0018] The surfactant and the co-surfactant were added to the oil phase; then, the drug-containing aqueous phase was poured into the oil phase during stirring at 300 r / min, and then sheared at 12000 r / min to prepare a crude emulsion;

[0019] The crude emulsion was homogenized three times under a pressure of 100 MPa to obtain the Huangqi Guizhi Wuwu Decoction nanoemulsion.

[0020] The present invention also provides a Huangqi Guizhi Wuwu Decoction gel patch, which comprises, by weight, 5 to 10 parts of the Huangqi Guizhi Wuwu Decoction nanoemulsion prepared according to claim 6, 5 to 10 parts of sodium polyacrylate NP700, 2 to 5 parts of kaolin, 2 to 5 parts of CMC-Na, 3 to 7 parts of gelatin, 1 to 3 parts of polyvinyl alcohol, 0.1 to 0.5 parts of aluminum glycolate, 0.1 to 0.3 parts of tartaric acid, 0.1 to 0.3 parts of sodium tartrate, 0.2 to 0.5 parts of EDTA-2Na, 20 to 30 parts of glycerol, and 25 to 35 parts of purified water.

[0021] The present invention also provides a method for preparing the Huangqi Guizhi Wuwu Decoction gel plaster.

[0022] Weigh sodium polyacrylate NP-700, kaolin, aluminum glycolate, CMC-Na, and EDTA-2Na, add glycerol and stir well to prepare a matrix dispersed phase for later use;

[0023] Weigh gelatin, polyvinyl alcohol, tartaric acid, sodium tartrate and Huangqi Guizhi Wuwu Decoction nanoemulsion, add purified water to dilute and fully stir to obtain a drug-containing aqueous phase, and set aside;

[0024] The drug-containing aqueous phase is quickly added to the matrix dispersed phase, and the mixture is fully stirred at a stirring speed that is first slow and then fast. The paste is coated on a composite non-woven fabric, covered with a release protective film, cut and placed according to specifications, and solidified to obtain the Huangqi Guizhi Wuwu Decoction nanoemulsion gel patch.

[0025] The present invention also provides the use of the above-mentioned Chinese medicine composition, the above-mentioned Huangqi Guizhi Wuwu Decoction extract concentrate, the above-mentioned Huangqi Guizhi Wuwu Decoction nanoemulsion, and the above-mentioned Huangqi Guizhi Wuwu Decoction gel patch in pharmaceutical manufacturing or preparation of medical supplies.

[0026] Preferably, the medicine or medical product is a medicine or medical product for treating muscle pain or rheumatoid arthritis.

[0027] It can be known from the above technical scheme that, compared with the prior art, the present invention discloses a Chinese medicine composition and its application, and the technical effect achieved is to develop a nanoemulsion gel patch preparation for relieving muscle pain, rheumatoid arthritis and other diseases for the active ingredients of the optimized Chinese medicine composition. The O / W nanoemulsion technology is used to achieve efficient loading and skin penetration of hydrophilic and hydrophobic functional substances in Huangqi Guizhi Wuwu Decoction. The nanoemulsion is evenly dispersed in the three-dimensional network structure formed by the absorption and swelling of polyacrylic acid, which can enable the drug to be released slowly and stably and hinder the crystallization instability caused by the thermodynamic motion of supersaturated drug molecules. In addition, the gel patch has a good moisturizing effect, a good skin feel, and excellent swelling and thixotropic properties. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying creative work.

[0029] Figure 1 The attached drawing is a photograph of the appearance of the Huangqi Guizhi Wuwu Decoction nanoemulsion provided by the present invention.

[0030] Figure 2 The attached drawing is a sample photo of the Huangqi Guizhi Wuwu Decoction nanoemulsion gel patch provided by the present invention.

[0031] Figure 3 The attached figure is a photograph of the stirring state during the preparation process of the Huangqi Guizhi Wuwu Decoction nanoemulsion gel patch provided by the present invention.

[0032] Figure 4 The attached drawing is a diagram of the dynamic hydration particle size and dispersion index of the Huangqi Guizhi Wuwu Decoction nanoemulsion detected by DLS provided by the present invention.

[0033] Figure 5 The attached drawing is a photograph showing the adhesion test state of the Astragalus Cinnamon Twig Five Ingredients Decoction nanoemulsion gel patch provided by the present invention using a rolling ball method.

[0034] Figure 6 The accompanying drawing is a transdermal absorption curve diagram of key quality markers in the Huangqi Guizhi Wuwu Decoction nanoemulsion gel patch provided by the present invention.

[0035] Figure 7 The accompanying drawing is a transdermal absorption curve diagram of key quality markers in the Huangqi Guizhi Wuwu Decoction Gel Patch provided in Control Example 1 provided by the present invention.

[0036] Figure 8 The accompanying drawing is a graph showing the levels of inflammatory factors in the inflammatory tissue 12 hours after the lesion of rats swollen by application of Chondrus provided by the present invention. DETAILED DESCRIPTION

[0037] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in 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 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.

[0038] The embodiment of the present invention discloses a Chinese medicine composition and its application

[0039] The raw materials not mentioned in the embodiment are commercially available, and the processes not mentioned are conventional processes. In addition, according to the results of the previous research and the manufacturer's quality control standards related to the applicant, the main chemical components of Huangqi Guizhi Wuwu Decoction are mainly divided into flavonoids, triterpenes, monoterpenes, organic acids, alkaloids and glycosides. Among them, astragaloside, formononetin, kaempferol, quercetin, cinnamic acid, cinnamaldehyde, 6-gingerol, paeoniflorin, leucanthoside, and gallic acid can be used as key quality markers of Huangqi Guizhi Wuwu Decoction. Therefore, fat-soluble components (astragaloside, cinnamic acid, 6-gingerol) and hydrophilic active ingredients (peoniflorin and formononetin) can be used as key quality markers in Huangqi Guizhi Wuwu Decoction to reflect the overall effect of the compound.

[0040] Example 1

[0041] A traditional Chinese medicine composition comprises, by weight, 25g of astragalus, 15g of cassia twig, 10g of peony root, 10g of ginger, 8g of angelica root, 3g of safflower, 7g of clematis root, 10g of jujube and 5g of liquorice.

[0042] A preparation method of Huangqi Guizhi Wuwu Decoction extract concentrate: the above-mentioned drugs are mixed, placed in a 2000mL round-bottom flask, soaked in water for 60 minutes, then 8 times the amount of water of the mixed drugs is added, soaked and boiled at 90°C for 90 minutes, extracted twice, filtered, combined the two water decoctions, concentrated to 90mL at 100°C, and cooled for use.

[0043] Example 2

[0044] A traditional Chinese medicine composition comprises, by weight, 10g of astragalus, 10g of cassia twig, 10g of peony root, 5g of ginger, 5g of angelica, 2g of safflower, 5g of clematis, 5g of jujube and 5g of liquorice.

[0045] A preparation method of Huangqi Guizhi Wuwu Decoction extract concentrate: the above-mentioned drugs are mixed, placed in a 2000mL round-bottom flask, soaked in water for 60 minutes, then 8 times the amount of water of the mixed drugs is added, soaked and boiled at 90°C for 90 minutes, extracted twice, filtered, combined the two water decoctions, concentrated to 90mL at 100°C, and cooled for use.

[0046] Example 3

[0047] A traditional Chinese medicine composition comprises, by weight, 30g of astragalus, 20g of cassia twig, 20g of peony root, 15g of ginger, 15g of angelica root, 10g of safflower, 10g of clematis root, 10g of jujube and 10g of liquorice.

[0048] A preparation method of Huangqi Guizhi Wuwu Decoction extract concentrate: the above-mentioned drugs are mixed, placed in a 2000mL round-bottom flask, soaked in water for 60 minutes, then 8 times the amount of water of the mixed drugs is added, soaked and boiled at 90°C for 90 minutes, extracted twice, filtered, combined the two water decoctions, concentrated to 90mL at 100°C, and cooled for use.

[0049] Example 4

[0050] A Huangqi Guizhi Wuwu Decoction nanoemulsion is prepared from the following raw materials in mass: 10.5 mL of lauryl alcohol polyoxyethylene ether (surfactant), 8.5 mL of anhydrous ethanol (cosurfactant), 15.5 mL of IPM (oil phase), 35 mL of Huangqi Guizhi Wuwu Decoction extract concentrate prepared in Example 1, and 15.5 mL of purified water.

[0051] Preparation method:

[0052] Purified water was placed in a 250mL beaker, and the extract of Huangqi Guizhi Wuwu Decoction was added. The suspension system was prepared by probe ultrasound (power 100w, ultrasound for 3 seconds, pause for 3 seconds, and this cycle was repeated for 20 minutes); IPM was placed in another beaker, and precisely weighed lauryl alcohol polyoxyethylene ether and anhydrous ethanol were added. Subsequently, during high-speed stirring (300r / min), the drug-containing aqueous phase was poured into the oil phase, followed by high-speed shearing (16000r / min) to prepare a crude emulsion, which was transferred to a high-pressure homogenizer (AH100D high-pressure homogenizer, ATS, Canada) and homogenized 3 times at a pressure of 100MPa to obtain Huangqi Guizhi Wuwu Decoction nanoemulsion ( Figure 1 ).

[0053] Example 5

[0054] The same as Example 4, except that 40 mL of Huangqi Guizhi Wuwu Decoction extract concentrate and 12.5 mL of purified water are used; MCT (oil phase) is used instead of IPM, 1,2-propylene glycol (co-surfactant) is used instead of anhydrous ethanol, and stearic acid polyoxyethylene ether (surfactant) is used instead of lauryl alcohol polyoxyethylene ether.

[0055] Example 6

[0056] The same as Example 4, except that 45 mL of Huangqi Guizhi Wuwu Decoction extract concentrate and 10 mL of purified water are used; oleic acid is used instead of IPM, polyethylene glycol 400 is used instead of anhydrous ethanol, and EL40 is used instead of lauryl alcohol polyoxyethylene ether.

[0057] Example 7

[0058] The same as Example 4, except that soybean oil is used instead of IPM, polyethylene glycol 400 is used instead of anhydrous ethanol, and Tween 80 is used instead of polyoxyethylene lauryl alcohol ether.

[0059] Example 8

[0060] A Huangqi Guizhi Wuwu Decoction nanoemulsion gel patch is prepared from the following raw materials by weight: 10 g of the Huangqi Guizhi Wuwu Decoction nanoemulsion prepared in Example 4, 10 g of sodium polyacrylate (NP700), 3 g of kaolin, 3 g of CMC-Na, 4 g of gelatin, 3 g of polyvinyl alcohol, 0.2 g of aluminum glycolate, 0.15 g of tartaric acid, 0.15 g of sodium tartrate, 0.2 g of EDTA-2Na, 20 g of glycerol, and 30 g of purified water.

[0061] Weigh the weight of sodium polyacrylate NP-700, kaolin, aluminum glycolate, CMC-Na, and EDTA-2Na, add glycerol and stir well to prepare a matrix dispersed phase for later use;

[0062] Weigh the gelatin, polyvinyl alcohol, tartaric acid, sodium tartrate and Huangqi Guizhi Wuwu Decoction nanoemulsion, add purified water to dilute and fully stir to obtain a drug-containing aqueous phase, and set aside;

[0063] The drug-containing aqueous phase containing the Huangqi Guizhi Wuwu Decoction nanoemulsion is quickly added to the matrix dispersed phase, and stirred thoroughly at a slow and then fast stirring speed. The paste is stirred at a speed of 10-20 g / 140 cm 2 The coating thickness is coated on the composite non-woven fabric, covered with a release protective film, cut according to the specifications and placed for 14 days to solidify to obtain the Huangqi Guizhi Wuwu Decoction Nanoemulsion Gel Patch ( Figure 2 ), the stirring state of the preparation process is shown in Figure 3 .

[0064] Example 9

[0065] A Huangqi Guizhi Wuwu Decoction nanoemulsion gel patch is prepared from the following raw materials by weight: 5 g of Huangqi Guizhi Wuwu Decoction nanoemulsion prepared in Example 4, 5 g of sodium polyacrylate (NP700), 2 g of kaolin, 2 g of CMC-Na, 3 g of gelatin, 1 g of polyvinyl alcohol, 0.1 g of aluminum glycolate, 0.1 g of tartaric acid, 0.1 g of sodium tartrate, 0.2 g of EDTA-2Na, 20 g of glycerol, and 25 g of purified water.

[0066] The preparation method is the same as Example 8.

[0067] Example 10

[0068] A Huangqi Guizhi Wuwu Decoction nanoemulsion gel patch is prepared from the following raw materials by weight: 10 g of the Huangqi Guizhi Wuwu Decoction nanoemulsion prepared in Example 4, 10 g of sodium polyacrylate (NP700), 5 g of kaolin, 5 g of CMC-Na, 7 g of gelatin, 3 g of polyvinyl alcohol, 0.5 g of aluminum glycolate, 0.3 g of tartaric acid, 0.3 g of sodium tartrate, 0.5 g of EDTA-2Na, 30 g of glycerol, and 35 g of purified water.

[0069] The preparation method is the same as Example 8.

[0070] Comparative experiment

[0071] Comparative Example 1: Same as Example 8, except that 4.7 g of Huangqi Guizhi Wuwu Decoction concentrate was added to replace 10 g of Huangqi Guizhi Wuwu Decoction nanoemulsion, and the drug component contents of the two were the same. At the same time, the missing 5.3 g was replaced by purified water.

[0072] In order to illustrate the various properties of the Astragalus Cinnamon Twig Five Ingredients Decoction nanoemulsion and the Astragalus Cinnamon Twig Five Ingredients Decoction nanoemulsion gel patch provided by the present invention, the Astragalus Cinnamon Twig Five Ingredients Decoction nanoemulsion provided by Example 4 and the Astragalus Cinnamon Twig Five Ingredients Decoction nanoemulsion gel patch provided by Example 8 were tested.

[0073] 1. Structural characterization and performance testing of the Huangqi Guizhi Wuwu Decoction nanoemulsion provided in Example 4.

[0074] (1) The type of emulsion was identified by dyeing method. The specific method was as follows: 5 mL of Huangqi Guizhi Wuwu Decoction nanoemulsion was placed in a 10 mL test tube, 0.5 mL of methylene blue (water-soluble dye) and Sudan red (oil-soluble dye) were added to the test tube, and the diffusion rate of different dyes in the nanoemulsion was observed. The results showed that the diffusion rate of methylene blue was significantly faster than that of Sudan red, indicating that Huangqi Guizhi Wuwu Decoction nanoemulsion was an O / W type nanoemulsion.

[0075] (2) The particle size and polymer dispersion index (PDI) of the Huangqi Guizhi Wuwu Decoction nanoemulsion were measured using a Malvern laser force meter. The specific method was to dilute 100 μL of the prepared Huangqi Guizhi Wuwu Decoction nanoemulsion with 900 μL of purified water, and after equilibration at room temperature, the particle size and PDI of the Huangqi Guizhi Wuwu Decoction nanoemulsion were measured, and the results were repeated 3 times. Figure 4 It can be seen that the average particle size of the prepared Huangqi Guizhi Wuwu Decoction nanoemulsion is 290.5±32.3nm, and the PDI is 0.243±0.05, indicating that the particle size meets the requirements and is evenly dispersed.

[0076] (3) The turbidity of the Huangqi Guizhi Wuwu Decoction nanoemulsion was detected using a WGZ-B turbidity meter. The specific method was to dilute the Huangqi Guizhi Wuwu Decoction nanoemulsion 100 times with purified water and measure it three times after equilibration at room temperature. The results showed that the average turbidity of the Huangqi Guizhi Wuwu Decoction nanoemulsion was 183.43±25.6cm -1 , proving that the emulsion is mainly distributed in the form of droplets of smaller size, reflecting the good stability of the nanoemulsion.

[0077] (4) The centrifugal stability constant of the Huangqi Guizhi Wuwu Decoction nanoemulsion was detected by low-speed centrifugation and ultraviolet spectrophotometry. The specific method was as follows: the Huangqi Guizhi Wuwu Decoction nanoemulsion was placed in a 15 mL centrifuge tube and centrifuged at 3500 r / min for 30 min. The absorbance value (A) of the Huangqi Guizhi Wuwu Decoction nanoemulsion at 680 nm before and after centrifugation was measured. 680 ) is used to calculate the centrifugal stability constant, and the calculation formula is as follows:

[0078] K=A 1-680 / A 0-680

[0079] Among them: A 1-680 is the measured value after nanoemulsion centrifugation, A 0-680 It is the measured value before nanoemulsion centrifugation.

[0080] The results showed that the nanoemulsion of Huangqi Guizhi Wuwu Decoction was milky yellow after centrifugation, without stratification, flocculation, demulsification and other phenomena, and the K index was 93.34% (A 1-680 =0.42±0.03, A 0-680 =0.45±0.01). The Huangqi Guizhi Wuwu Decoction nanoemulsion was not affected by centrifugation.

[0081] (5) The centrifugal stability and storage stability of the emulsion were investigated using particle size and PDI as indicators. The centrifugal stability was measured in the same manner as before. The storage stability was measured at room temperature and 4°C. The average particle size and PDI of the Huangqi Guizhi Wuwu Tang nanoemulsion were measured at different times. The results showed that during the storage time, the Huangqi Guizhi Wuwu Tang nanoemulsion did not show any stratification, aggregation, or demulsification, and had good stability.

[0082] Storage stability of Huangqi Guizhi Wuwu Decoction nanoemulsion (n=3)

[0083]

[0084] 2. Performance evaluation and in vitro transdermal behavior detection of the Huangqi Guizhi Wuwu Decoction nanoemulsion gel patch provided in Example 8

[0085] (1) The rolling ball method was used to detect the initial adhesion of the Astragalus Cinnamon Twig and Five Ingredients Decoction Nanoemulsion Gel Patch. The specific method was to take a sample of the Astragalus Cinnamon Twig and Five Ingredients Decoction Nanoemulsion Gel Patch, place it at room temperature in an environment with a relative humidity of 70% for 2 hours, and equilibrate to a stable state. With the sticky side of the gel patch facing up, fix it with double-sided tape between the two scale lines on the inclined plate of the initial adhesion tester (CNY-1 model, produced by Sanquan Zhongshi) to ensure that the test sample fits flat on the steel plate. Adjust the inclined plate at a 30° inclination angle, and place steel balls of different models specified in the pharmacopoeia on the starting line from small to large, allowing them to fall freely from the top of the inclined surface. Record the maximum ball number that can be pasted at the last time, and repeat the experiment three times. The results show that the maximum ball number that can be pasted by the Astragalus Cinnamon Twig and Five Ingredients Decoction Nanoemulsion Gel Patch is ball number 23. The results were consistent after three repetitions, see Figure 5 , indicating that the prepared Huangqi Guizhi Wuwu Decoction nanoemulsion gel patch has good initial adhesion effect and meets the application characteristics.

[0086] (2) Quantitative analysis of the key quality markers in Huangqi Guizhi Wuwu Decoction Nanoemulsion Gel Patch by HPLC. The specific method was based on references and pharmacopoeia standards. The results were analyzed using an UltiMate 3000 HPLC. Chromatographic conditions: Hypersil ODS C 18 Chromatographic column (4.6mm×250mm, 5μm), mobile phase: methanol-water (20:80), detection wavelength: 205nm (0-10min, detection of astragaloside IV), 250nm (10-35min, detection of paeoniflorin and formononetin), 280nm (35-50min, detection of cinnamic acid and 6-gingerol), flow rate: 1.0mL / min, column temperature: 40℃.

[0087] Preparation of reference solution: Accurately weigh appropriate amount of astragaloside IV, paeoniflorin, formononetin, cinnamic acid, and 6-gingerol reference substances (all purchased from China Food and Drug Inspection Institutes), place them in a volumetric flask, and dilute with methanol to obtain a mixed reference solution. According to the specificity, linear relationship, precision, stability, repeatability, and sample recovery experiments, an HPLC detection method for detecting quality markers was established.

[0088] Preparation of test solution: Take the Astragalus Cinnamon Twig Wuwu Decoction Nanoemulsion Gel Patch as the test sample, remove the non-woven fabric and release film, and take 10 g of the patch. After precise weighing, add 30 mL of 70% ethanol, seal, and extract with vigorous shaking for 40 minutes, make up for the lost weight, shake well, and filter through a 0.45 μm filter membrane.

[0089] (2) The modified Franz diffusion cell method was used to detect the permeation of Huangqi Guizhi Wuwu Decoction nanoemulsion gel patch on pig skin. The specific in vitro transdermal experiment was performed using a fully automatic DHC-6TD dry heating transdermal diffusion instrument (produced by Logan, USA). The device was fixed, and the back skin of the purchased Bama Xiang pig was taken and thawed naturally. A fixed area was cut and the gel patch was applied to the skin. The diffusion medium was a PBS buffer solution with a pH of 7.4. The temperature was set to 32±0.5℃, and the rotor stirring speed was 300rpm. 4.5mL of the receiving solution was taken at 1, 2, 3, 4, 6, 8, 10, and 12 hours, and an equal volume of fresh diffusion medium was added. The sample solution was filtered through a 0.45μm filter membrane to obtain the test solution.

[0090] The cumulative permeation amount and steady-state permeation rate of key components were calculated according to the following formula.

[0091]

[0092] Among them, Q n is the cumulative permeation of the component to be measured in the receiving liquid during the nth sampling, s (cm 2 ) is the effective diffusion area, V (mL) is the total volume of the receiving liquid in the receiving chamber, C n is the mass concentration of the component to be tested in the receiving solution at the time of sampling for the nth time (mg / L), C i (mg / L) is the mass concentration of the component to be measured in the receiving solution at the i-th sampling.

[0093] The cumulative permeation amount Q (μg / cm -2 ) as the ordinate and the sampling time t as the abscissa to draw the cumulative penetration-time curve. The results are shown in Figure 6 and Figure 7 , take the straight line part of the curve for linear regression, and its slope is the steady-state transdermal rate J ss .

[0094] Figure 6The results showed that the cumulative permeation of five key ingredients, astragaloside IV, peony lactone glycosides, formononetin, cinnamic acid, and 6-gingerol, were and the steady-state transdermal rates were. The cumulative permeation of fat-soluble ingredients (astragaloside IV, cinnamic acid, and 6-gingerol) was higher, which was related to the encapsulation mechanism and high drug loading of the nanoemulsion. At the same time, the hydrophilic active ingredients (peony lactone glycosides and formononetin) also had a higher steady-state transdermal rate due to their high content in the compound.

[0095] Figure 7 It can be seen that the effect of fat-soluble components is significantly improved without affecting the permeation of hydrophilic components, which proves the key role of nanoemulsion in this compound nanoemulsion.

[0096] 3. To investigate the expression of inflammatory factors in the inflammatory tissue of the rat model of Chondrus crispus-induced inflammation after application of the Huangqi Guizhi Wuwu Decoction nanoemulsion gel patch.

[0097] (1) Carrageenan rat inflammation model establishment method and dosing regimen: Carrageenan was used to induce rat dorsum skin inflammation model to simulate the pathological characteristics of clinical inflammatory edema, with small differences and high sensitivity and repeatability. That is, 40 SD male rats were selected and randomly divided into 4 groups: model control group, dexamethasone positive control group (2×10 -5 g / mL), Huangqi Guizhi Wuwu Decoction gel patch provided in Control Example 1, and Huangqi Guizhi Wuwu Decoction nanoemulsion gel patch provided in Example 8, 10 in each group. After grouping, the model control group was given pure water, and the other groups were given different drugs. The gel patch was cut into 2×2cm 2 0.2 mL of 1% carrageenan solution was injected into the subcutaneous tissue of the rat's back, and the drug was started 2 hours after the inflammation was induced. The subcutaneous inflammatory tissue of the rat was taken after 12 hours, and the ELISA method was used to detect the IL-6 and PGE2 content in the serum according to the instructions of the kit.

[0098] Compared with the model control group, dexamethasone, Huangqi Guizhi Wuwu Decoction gel patch and Huangqi Guizhi Wuwu Decoction nanoemulsion gel patch can effectively reduce the levels of IL-6 and PGE2 in the inflammatory site. Among them, Huangqi Guizhi Wuwu Decoction nanoemulsion gel patch showed the lowest content level equivalent to dexamethasone, proving that nanoemulsion plays an important role in promoting the penetration of key active ingredients.

[0099] The various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referenced to each other.

[0100] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A Chinese medicine composition, characterized in that: The composition comprises, by weight, 10-30 parts of astragalus, 10-20 parts of cassia twig, 10-20 parts of peony, 5-15 parts of ginger, 5-15 parts of angelica, 2-10 parts of safflower, 5-10 parts of clematis, 5-10 parts of jujube, and 5-10 parts of liquorice.

2. A method for preparing an extract concentrate of Huangqi Guizhi Wuwu Decoction, characterized in that: The method comprises mixing the Chinese medicine composition according to claim 1, soaking in water, decocting and concentrating.

3. The preparation method according to claim 2, characterized in that: The water soaking, decoction and concentration are as follows: soaking in water for 60 minutes, then adding 8 to 10 times the amount of water of the Chinese medicine composition, soaking and decocting at 90° C. for 90 minutes, extracting twice, filtering, combining the two decoctions, concentrating to 90 mL at 100° C. and cooling for use.

4. A Huangqi Guizhi Wuwu Decoction nanoemulsion, characterized in that: The composition comprises, by weight, 10 to 30 parts of a surfactant, 8.5 to 30 parts of a co-surfactant, 10 to 20 parts of an oil phase, 35 to 45 parts of the Huangqi Guizhi Wuwu Decoction extract concentrate according to claim 2 or 3, and 10 to 20 parts of water.

5. The Astragalus and Cinnamon Twig Five Ingredients Decoction nanoemulsion according to claim 4, characterized in that: The surfactant is one or more of lauryl alcohol polyoxyethylene ether, stearic acid polyoxyethylene ether, Tween 80, Tween 20 and EL40; The co-surfactant is one or more of 1,2-propylene glycol, polyethylene glycol 400, anhydrous ethanol and n-butanol; The oil phase is one or more of IPM, MCT, oleic acid, soybean oil, and ethyl oleate.

6. The method for preparing the Huangqi Guizhi Wuwu Decoction nanoemulsion according to claim 5, characterized in that: Add the extract of Huangqi Guizhi Wuwu Decoction into the water and perform ultrasonic treatment to obtain the drug-containing aqueous phase; The surfactant and the co-surfactant were added to the oil phase; then, the drug-containing aqueous phase was poured into the oil phase during stirring at 300 r / min, and then sheared at 12000 r / min to prepare a crude emulsion; The crude emulsion was homogenized three times under a pressure of 100 MPa to obtain the Huangqi Guizhi Wuwu Decoction nanoemulsion.

7. A Huangqi Guizhi Wuwu Decoction gel patch, characterized in that: The invention comprises, by weight, 5 to 10 parts of the Huangqi Guizhi Wuwu Decoction nanoemulsion prepared according to claim 6, 5 to 10 parts of sodium polyacrylate NP700, 2 to 5 parts of kaolin, 2 to 5 parts of CMC-Na, 3 to 7 parts of gelatin, 1 to 3 parts of polyvinyl alcohol, 0.1 to 0.5 parts of aluminum glycolate, 0.1 to 0.3 parts of tartaric acid, 0.1 to 0.3 parts of sodium tartrate, 0.2 to 0.5 parts of EDTA-2Na, 20 to 30 parts of glycerol, and 25 to 35 parts of purified water.

8. The method for preparing the Huangqi Guizhi Wuwu Decoction gel patch according to claim 7, characterized in that: Weigh sodium polyacrylate NP-700, kaolin, aluminum glycolate, CMC-Na, and EDTA-2Na, add glycerol and stir well to prepare a matrix dispersed phase for later use; Weigh gelatin, polyvinyl alcohol, tartaric acid, sodium tartrate and Huangqi Guizhi Wuwu Decoction nanoemulsion, add purified water to dilute and fully stir to obtain a drug-containing aqueous phase, and set aside; The drug-containing aqueous phase is quickly added to the matrix dispersed phase, and the mixture is fully stirred at a stirring speed that is first slow and then fast. The paste is coated on a composite non-woven fabric, covered with a release protective film, cut and placed according to specifications, and solidified to obtain the Huangqi Guizhi Wuwu Decoction nanoemulsion gel patch.

9. Use of the Chinese medicine composition of claim 1, the Huangqi Guizhi Wuwu Decoction extract concentrate of claim 2, the Huangqi Guizhi Wuwu Decoction nanoemulsion of claim 4, and the Huangqi Guizhi Wuwu Decoction gel patch of claim 7 in pharmaceutical manufacturing or preparation of medical supplies.

10. The use according to claim 9, characterized in that The medicine or medical product is a medicine or medical product for treating muscle pain or rheumatoid arthritis.

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