Gel plaster containing Chinese ladiestresses root and preparation method and application thereof

Abstract

The invention provides a gel plaster containing Chinese ladiestresses root as well as a preparation method and application of the gel plaster, and relates to the technical field of gel plaster pharmaceutical preparations. An auxiliary material composition in the gel plaster is prepared from the following components in parts by weight: 0.3 to 0.8 part of eucalyptus globulus leaf oil, 0.5 to 3 parts of azone, 0.5 to 2 parts of polyethylene glycol hexadecyl ether, 3 to 8 parts of polyethylene glycol, 0.03 to 0.1 part of tert-butyl p-hydroxyanisole, 5 to 15 parts of carbomer, 0.01 to 0.05 part of edetate disodium, 0.05 to 0.3 part of gellan gum, 15 to 40 parts of glycerol, 0.2 to 0.8 part of sodium carboxymethyl cellulose, 0.05 to 0.5 part of a cross-linking agent and 125 to 250 parts of water. The components are mixed step by step, and the gel plaster is prepared by adopting a gradient heating and pressurizing homogenization method and a gradient cooling and depressurizing homogenization method, has excellent initial adhesion, adhesive force, permeability and stability, and has better effects of promoting blood circulation, relieving pain and diminishing swelling.

Description

Technical Field

[0001] This invention belongs to the field of gel patch pharmaceutical preparation technology, specifically relating to a gel patch containing Panlongqi, its preparation method, and its application. Background Technology

[0002] Panlongqi is the dried rhizome of *Polygonutm taipaishanens* Kung, a plant in the Liao family. The rhizome is tuberous, twisted, and sometimes hook-shaped, with a bitter and astringent taste and cooling properties. It enters the spleen, stomach, and large intestine meridians and has hemostatic and wound-healing effects. As a variety of *Polygodium japonicum*, Panlongqi is recorded in the *Chinese Materia Medica*. Panlongqi contains polysaccharides and their glycosides, phenols and tannins, flavonoids, coumarins, and terpene lactones, and is generally used in compound prescriptions. It is one of the main raw materials for Panlongqi tablets and Panlongqi wine.

[0003] Gel patches consist of four parts: the active ingredient, the matrix, the backing layer, and the coating. The matrix is ​​composed of water-soluble polymers or hydrophilic substances, playing an important role in skin hydration, skin adherence, drug release, and stability. Gel patches have the following advantages: 1. Convenient administration, suitable for patients who have difficulty with oral or injection methods; 2. The drug is directly absorbed into the systemic circulation after transdermal absorption, avoiding the destructive effects of the gastrointestinal tract and the first-pass effect of the liver; 3. Long duration of action and stable blood drug concentration, avoiding excessively high or low peak drug concentrations; 4. Large drug loading capacity, reducing the frequency of administration compared to patches, and does not stain clothing; 5. Improved safety of drug therapy, allowing for immediate discontinuation of administration if side effects are observed.

[0004] Currently, there is little research on plasters containing Panlongqi (Panlongqi). While the transdermal absorption of publicly available gel plasters is improved by the addition of transdermal absorbents, enhancing transdermal absorption by increasing transdermal penetration enhancers is a readily conceived method. For example, Chinese invention patent CN113350320A discloses a Panlongqi compound poultice and its preparation method, which promotes blood circulation, removes blood stasis, reduces inflammation, and relieves pain. This Panlongqi compound poultice contains 29 traditional Chinese medicine ingredients, including Panlongqi, as well as humectants, adhesives, transdermal penetration enhancers, and thickeners. The transdermal penetration enhancer is azone, oleic acid, or a mixture of azone and oleic acid, which increases the bioavailability of the drug through transdermal absorption.

[0005] In addition, the gel matrix of a red gel plaster is disclosed in Chinese Invention Patent CN119185258A. The raw materials include: 20-30 parts of sodium polyacrylate, 5-10 parts of acrylic acid grafted starch, 0.5-1 part of triethanolamine, 15-20 parts of gelatin, 0.5-5 parts of disodium edetate, 0.5-2.5 parts of crosslinking agent, 1-5 parts of filler, 25-35 parts of humectant, 0.05-1 part of bacteriostatic agent, 0.005-1 part of antioxidant and 40-50 parts of water. This invention selects a mixture of lecithin and polyethylene glycol-12-hydroxystearate as the surfactant, which is beneficial to transdermal absorption.

[0006] However, for the excipient components of the current gel plasters, in order to simultaneously have high initial adhesiveness, adhesiveness and penetration ability, numerous components are often added. The effects brought are merely the simple addition of various components. Even due to the complex components, the compatibility is poor, resulting in unstable product quality and difficulty in meeting the stability requirements. There is a lack of excipient components with synergistic effects in the prior art to increase the penetration effect and stability of the active ingredients in the gel plaster, and at the same time significantly increase the initial tack and adhesiveness of the gel plaster. Summary of the Invention

[0007] Aiming at the problems existing in the prior art, the present invention provides a gel plaster containing Panlongqi, its preparation method and application. By using specific excipient components and the components cooperating with each other, the prepared gel plaster has excellent initial tack, adhesiveness, and also brings better penetration effect and stability effect. The gel plaster of the present invention has excellent effects of promoting blood circulation to remove pain and reducing swelling.

[0008] To achieve the above object, the technical scheme adopted by the present invention is as follows:

[0009] On the one hand, the present invention provides a gel plaster containing Panlongqi, which includes components: traditional Chinese medicine components and an excipient composition; The excipient composition, calculated by weight份, includes components: 0.3-0.8 parts of eucalyptus oil, 0.5-3 parts of laurocapram, 0.5-2 parts of polyethylene glycol cetyl ether, 3-8 parts of polyethylene glycol, 0.03-|0.1 part of tert-butyl-p-hydroxyanisole, 5-15 parts of carbomer, 0.01-0.05 part of disodium edetate, 0.05-0.3 part of gellan gum, 15-40 parts of glycerol, 0.2-0.8 part of sodium carboxymethylcellulose, 0.05-0.5 part of crosslinking agent, 0.5-1 part of preservative and 125-250 parts of water.

[0010] Preferably, the excipient composition, by weight, comprises the following components: 0.4-0.7 parts eucalyptus leaf oil, 1.5-2.5 parts lauryl acetone, 0.8-1.5 parts polyethylene glycol hexadecyl ether, 4-7 parts polyethylene glycol, 0.05-0.07 parts tert-butyl-p-hydroxyanisole, 8-12 parts carbomer, 0.02-0.04 parts disodium edetate, 0.15-0.25 parts gellan gum, 25-35 parts glycerin, 0.4-0.6 parts sodium carboxymethyl cellulose, 0.2-0.4 parts crosslinking agent, 0.6-0.9 parts preservative, and 150-220 parts water.

[0011] More preferably, the excipient composition, by weight, comprises the following components: 0.5 parts eucalyptus leaf oil, 2 parts lauryl azone, 1 part polyethylene glycol hexadecyl ether, 6 parts polyethylene glycol, 0.06 parts tert-butyl-p-hydroxyanisole, 10 parts carbomer, 0.03 parts disodium edetate, 0.2 parts gellan gum, 30 parts glycerin, 0.5 parts sodium carboxymethyl cellulose, 0.3 parts crosslinking agent, 0.8 parts preservative, and 200 parts water.

[0012] Preferably, the polyethylene glycol is polyethylene glycol 400.

[0013] Preferably, the carbomer is carbomer 980NF.

[0014] Preferably, the crosslinking agent is selected from one or more of aluminum hydroxyl, aluminum chloride, and aluminum hydroxide.

[0015] In this invention, the preservative is a conventional preservative component in the art, and is not limited to ethylparaben, benzyl alcohol, phenoxyethanol, sodium benzoate or potassium sorbate.

[0016] In this invention, the pH of the water is 7-10, and triethanolamine is used to adjust the pH; more preferably, the pH of the water is 8-9.

[0017] Preferably, the herbal ingredients are any herbal compound containing Panlongqi (Panax notoginseng), or Panlongqi alone. The type of herbal ingredients does not affect the initial tack, adhesion, penetration, or stability of the gel patch. The excipients and preparation method of the gel patch in this invention affect the solution of the technical problems.

[0018] In some specific embodiments of the present invention, the raw materials of the traditional Chinese medicine compound containing Panlongqi are: 100-150g Panlongqi, 20-30g Zhuangjindan, 100-150g Wujiapi, 100-150g Duzhong, 280-350g Danggui, 10-15g Zhuzishen, 10-15g Chuanshegan, 50-80g Guoshanlong, 10-150g Qinjiu, 50-80g Muxiang, 10-15g Zusima, 50-80g Luoshiteng, 10-15g Chuanwu, 20-30g of white-haired herb, 10-15g of iron rod hammer, 10-15g of aconite, 20-30g of jujube herb, 50-80g of pillar knotweed, 50-80g of safflower, 50-80g of myrrh, 50-80g of bamboo root herb, 100-150g of valerian, 20-30g of lycopodium, 100-150g of achyranthes, 150-200g of salvia miltiorrhiza, 50-80g of red sour herb, 50-80g of halite, 150-200g of Paris polyphylla, 50-80g of frankincense, and 30-50g of red yeast rice.

[0019] In one specific embodiment of the present invention, the raw materials of the traditional Chinese medicine compound containing Panlongqi are as follows: 125g Panlongqi, 25g Zhuangjindan, 125g Wujiapi, 125g Duzhong, 312.5g Danggui, 12.5g Zhuzishen, 12.5g Chuanshegan, 62.5g Guoshanlong, 125g Qinjiu, 62.5g Muxiang, 12.5g Zusima, 62.5g Luoshiteng, 12.5g Chuanwu. 25g white hairy herb, 12.5g iron rod hammer, 12.5g aconite, 25g jujube herb, 62.5g pillar knotweed, 62.5g safflower, 62.5g myrrh, 62.5g bamboo root herb, 125g valerian, 25g lycopodium, 125g achyranthes, 187.5g salvia miltiorrhiza, 62.5g red sour herb, 62.5g balima, 187.5g Paris polyphylla, 62.5g frankincense and 37.5g red yeast rice.

[0020] The traditional Chinese medicine compound containing Panlongqi (a traditional Chinese medicine ingredient) is prepared as follows: 30 kinds of traditional Chinese medicine raw materials are crushed into coarse powder, 16.5 times the mass of 60% (v / v) ethanol is added, the mixture is sealed and soaked for 7-10 days, filtered, and the pH value of the filtrate is adjusted to 6.0-6.5 with 20wt% sodium hydroxide solution, and then concentrated or dried.

[0021] Preferably, in the gel patch, the mass ratio of the traditional Chinese medicine ingredients (based on the amount of raw traditional Chinese medicine) to the excipient composition is 25-40:1; more preferably, in the gel patch, the mass ratio of the traditional Chinese medicine ingredients (based on the amount of raw traditional Chinese medicine) to the excipient composition is 30:1.

[0022] In the gel patch of the present invention, the addition of traditional Chinese medicine ingredients is not limited to solid powder form, or formulation into solution or paste form; the amount of traditional Chinese medicine ingredients added is calculated according to the amount of raw traditional Chinese medicine.

[0023] In the gel patch of this invention, the amount of traditional Chinese medicine ingredients added does not affect the effect of the excipient composition on promoting the penetration, stability, initial tack, and adhesion of the traditional Chinese medicine ingredients. Within the scope of the technical solution described in this invention, the aforementioned technical effects can be achieved.

[0024] In the gel patch of the present invention, the backing is non-woven fabric.

[0025] Furthermore, the present invention provides a method for preparing the above-mentioned gel patch, comprising the following steps: (1) Mix carbomer with 40%-60% of the weight of water in the formula to obtain a carbomer solution; Mixture A is prepared by mixing eucalyptus leaf oil, lauryl ketone, polyethylene glycol hexadecyl ether, polyethylene glycol, tert-butyl-p-hydroxyanisole, gellan gum, glycerin and carbomer solution. (2) Add the Chinese medicine ingredients, disodium edetate, sodium carboxymethyl cellulose (50%-70% by weight), crosslinking agent (70%-90% by weight), and water (the remaining weight by weight) to mixture A, and homogenize by gradient heating and pressure to obtain mixture B; (3) Add the remaining sodium carboxymethyl cellulose and crosslinking agent to mixture B, then mix with preservative at 40-50℃, homogenize by gradient cooling and pressure reduction, and let stand to obtain gel plaster.

[0026] Preferably, in step (1), the amount of water used is 50% of the total weight of water.

[0027] Preferably, in step (2), the Chinese medicine ingredients and water are mixed first, and then mixed with other ingredients.

[0028] Preferably, in step (2), the amount of sodium carboxymethyl cellulose used is 60% of the total weight of sodium carboxymethyl cellulose.

[0029] Preferably, in step (2), the amount of crosslinking agent used is 80% of the total weight of the crosslinking agent.

[0030] Preferably, in step (2), the amount of water used is 50% of the total weight of water.

[0031] Preferably, in step (2), the gradient heating and pressurization homogenization specifically involves: first heating to 30-40℃ and pressurizing to 3-5MPa, homogenizing for 2-4 minutes; then heating to 50-60℃ and pressurizing to 8-12MPa, homogenizing for 2-4 minutes.

[0032] More preferably, in step (2), the gradient heating and pressurization homogenization specifically involves: first heating to 35°C and pressurizing to 4MPa, homogenizing for 3 minutes; then heating to 55°C and pressurizing to 10MPa, homogenizing for 3 minutes.

[0033] Preferably, in step (3), the mixing temperature is 45°C.

[0034] Preferably, in step (3), the gradient cooling and depressurization homogenization is specifically: 40-50℃, pressure of 8-12MPa, homogenization for 2-4min; then cooling to 20-30℃, pressure of 2-4MPa, homogenization for 5-15min.

[0035] More preferably, in step (3), the gradient cooling and depressurization homogenization specifically involves: homogenizing at 45°C and 10MPa for 3 minutes; then cooling down to 25°C and 3MPa for 10 minutes.

[0036] Preferably, in step (3), the settling time is 3-6 hours; more preferably, in step (3), the settling time is 4 hours.

[0037] Preferably, step (3) further includes a coating step, in which the mixture after standing is coated onto a carrier; the carrier is not limited to non-woven fabric or elastic fabric.

[0038] Finally, this invention provides the application of the above-mentioned gel patch in the preparation of drugs for promoting blood circulation and relieving pain, dispelling wind and dampness, reducing swelling and / or removing blood stasis.

[0039] Preferably, the drug is a drug used to treat knee osteoarthritis and / or qi stagnation and blood stasis syndrome.

[0040] Compared with the prior art, the present invention has the following beneficial effects: 1. The gel patch of the present invention is prepared from a composition of specific ingredients and proportions of excipients. The ingredients work together to bring high penetration and stability. At the same time, the prepared gel patch has high initial tack and adhesion, and can be used repeatedly to adhere to the skin. It adheres firmly without feeling restrictive.

[0041] 2. The gel patch of the present invention is prepared by a specific method. Stepwise addition of samples allows for full cross-linking and mixing of each component, improving the uniformity of the material. At the same time, the preparation of the gel patch is carried out by gradient heating and pressurization homogenization and gradient cooling and pressurization homogenization, which improves the homogenization efficiency and bioavailability, and significantly enhances the stability and initial adhesion.

[0042] 3. The gel patch of the present invention, under the action of the excipient composition, not only improves the penetration effect of the active ingredients, but also significantly enhances the effect of inhibiting swelling in mice, exerts its efficacy quickly, and thus improves the effects of promoting blood circulation, relieving pain, and reducing swelling. Detailed Implementation

[0043] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and such changes should also fall within the scope of protection claimed by the present invention.

[0044] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0045] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all chemical reagents used in the embodiments of the present invention are obtained through conventional commercial means.

[0046] In a specific embodiment, the Eucalyptus globulus leaf oil was purchased from Maclean's and has the molecular formula C0.05. 10 H 18 O, CAS No.: 8000-48-4; the lauryl azone was purchased from Shanghai Yuanye Biotechnology Co., Ltd., catalog number S24042; the polyethylene glycol hexadecyl ether (CAS No.: 9004-95-9) was purchased from Shanghai Yuanye Biotechnology Co., Ltd., catalog number S99077; the disodium edetate was purchased from Adamas, catalog number 73260E; the polyethylene glycol 400 was purchased from Croda Chemicals (Shanghai); the tert-butyl-p-hydroxyanisole (BHA) was purchased from Sigma-Aldrich, catalog number B1253; the gellan gum was purchased from Shanghai Yuanye Biotechnology Co., Ltd., catalog number S24793; the sodium carboxymethyl cellulose was purchased from Adamas, catalog number 89132A; the chitosan was purchased from Adamas, catalog number 89296B. Products from different manufacturers do not significantly affect the efficacy.

[0047] In the following specific implementation method, the Chinese herbal medicine ingredients are a compound Chinese herbal medicine containing Panlongqi (Panlongqi), and the raw materials are: 125g Panlongqi, 25g Zhuangjindan (Zhuangjin Dan), 125g Wujiapi (Wujiapi), 125g Duzhong (Duzhong), 312.5g Danggui (Angelica sinensis), 12.5g Zhuzishen (Panax ginseng), 12.5g Chuanshegan (Belamcanda chinensis), 62.5g Guoshanlong (Smilax china), 125g Qinjiu (Gentiana macrophylla), 62.5g Muxiang (Saussurea costus), 12.5g Zusima (Zusima), 62.5g Luoshiteng (Trachelospermum jasminoides), 12.5g Chuan... Aconitum carmichaelii, 25g white hairy herb, 12.5g iron rod hammer, 12.5g aconite, 25g jujube herb, 62.5g pillar knotweed, 62.5g safflower, 62.5g myrrh, 62.5g bamboo root herb, 125g valerian, 25g lycopodium clavatum, 125g achyranthes bidentata, 187.5g salvia miltiorrhiza, 62.5g red sour herb, 62.5g halite, 187.5g Paris polyphylla, 62.5g frankincense and 37.5g red yeast rice. Thirty kinds of Chinese medicinal materials were pulverized into coarse powder, and 16.5 times their weight of 60% (v / v) ethanol were added. The mixture was sealed and soaked for 8 days. After filtration, the pH of the filtrate was adjusted to 6.3±0.2 with 20wt% sodium hydroxide solution. Tween 80 at a weight of 3.3 mL / g of raw herbs was added, and the mixture was stirred and allowed to stand. After filtration, the filtrate was concentrated under reduced pressure below 60℃ to a density of 1.25-1.29 (45℃) to obtain an extract. The extract was then mixed with an excipient composition to prepare a gel plaster.

[0048] In the following specific embodiments, the mass ratio of the Chinese herbal ingredients in the gel patch, calculated based on the amount of raw Chinese herbal medicine, to the excipient composition is 30:1.

[0049] In the following specific implementation, the water is water whose pH has been adjusted to 8 using triethanolamine.

[0050] Example 1 A gel patch containing Panlongqi, comprising: a traditional Chinese medicine compound containing Panlongqi and an excipient composition; the traditional Chinese medicine compound containing Panlongqi, based on the amount of raw Chinese medicinal material, has a mass ratio of 30:1 to the excipient composition. The excipient composition comprises, by weight, 0.5 parts eucalyptus leaf oil, 2 parts lauryl azone, 1 part polyethylene glycol hexadecyl ether, 6 parts polyethylene glycol 400, 0.06 parts tert-butyl-p-hydroxyanisole, 10 parts carbomer 980NF, 0.03 parts disodium edetate, 0.2 parts gellan gum, 30 parts glycerin, 0.5 parts sodium carboxymethyl cellulose, 0.3 parts crosslinking agent (aluminum hydroxyacetic acid), 0.8 parts preservative (ethylparaben), and 200 parts water; Prepare the gel patch according to the above-mentioned weight proportions: (1) Mix carbomer 980NF and 100 parts by weight of water to obtain a carbomer solution; Mixture A is prepared by mixing eucalyptus leaf oil, lauryl ketone, polyethylene glycol hexadecyl ether, polyethylene glycol 400, tert-butyl-p-hydroxyanisole, gellan gum, glycerin and carbomer solution. (2) The traditional Chinese medicine compound containing Panlongqi is mixed and dissolved with 100 parts by weight of water and added to mixture A. Disodium edetate, 0.3 parts by weight of sodium carboxymethyl cellulose and 0.24 parts by weight of aluminum hydroxyl are added to mixture A. First, the temperature is raised to 35°C and the pressure is 4 MPa, and homogenized for 3 min. Then, the temperature is raised to 55°C and the pressure is 10 MPa, and homogenized for 3 min to obtain mixture B. (3) Add 0.2 parts by weight of sodium carboxymethyl cellulose, 0.06 parts by weight of aluminum hydroxyl and ethylparaben to mixture B; homogenize at 45°C and 10 MPa for 3 min; then cool down to 25°C and 3 MPa for 10 min; let stand for 4 h, then coat it on non-woven fabric to obtain gel plaster.

[0051] Example 2 A gel patch containing Panlongqi, comprising: a traditional Chinese medicine compound containing Panlongqi and an excipient composition; the traditional Chinese medicine compound containing Panlongqi, based on the amount of raw Chinese medicinal material, has a mass ratio of 30:1 to the excipient composition. The excipient composition comprises, by weight, 0.4 parts eucalyptus leaf oil, 1.5 parts lauryl azone, 1.5 parts polyethylene glycol hexadecyl ether, 4 parts polyethylene glycol 400, 0.05 parts tert-butyl-p-hydroxyanisole, 12 parts carbomer 980NF, 0.04 parts disodium edetate, 0.25 parts gellan gum, 35 parts glycerin, 0.6 parts sodium carboxymethyl cellulose, 0.4 parts crosslinking agent (aluminum hydroxyacetic acid), 0.6 parts preservative (ethylparaben), and 220 parts water; Prepare the gel patch according to the above-mentioned weight proportions: (1) Mix carbomer 980NF and 88 parts by weight of water to obtain a carbomer solution; Mixture A is prepared by mixing eucalyptus leaf oil, lauryl ketone, polyethylene glycol hexadecyl ether, polyethylene glycol 400, tert-butyl-p-hydroxyanisole, gellan gum, glycerin and carbomer solution. (2) The traditional Chinese medicine compound containing Panlongqi was mixed and dissolved with 132 parts by weight of water and added to mixture A. Disodium edetate, 0.3 parts by weight of sodium carboxymethyl cellulose and 0.28 parts by weight of aluminum hydroxyl were added to mixture A. The mixture was first heated to 30°C and the pressure was 3 MPa, and homogenized for 4 min. Then the mixture was heated to 50°C and the pressure was 8 MPa, and homogenized for 4 min to obtain mixture B. (3) Add 0.3 parts by weight of sodium carboxymethyl cellulose, 0.12 parts by weight of aluminum hydroxyl and ethylparaben to mixture B; homogenize at 50°C and 12 MPa for 2 min; then cool down to 30°C and 4 MPa for 5 min; let stand for 3 h, then coat it on non-woven fabric to obtain gel plaster.

[0052] Example 3 A gel patch containing Panlongqi, comprising: a traditional Chinese medicine compound containing Panlongqi and an excipient composition; the traditional Chinese medicine compound containing Panlongqi, based on the amount of raw Chinese medicinal material, has a mass ratio of 30:1 to the excipient composition. The excipient composition comprises, by weight, 0.7 parts eucalyptus leaf oil, 2.5 parts lauryl acetone, 0.8 parts polyethylene glycol hexadecyl ether, 7 parts polyethylene glycol 400, 0.07 parts tert-butyl-p-hydroxyanisole, 8 parts carbomer 980NF, 0.02 parts disodium edetate, 0.15 parts gellan gum, 25 parts glycerin, 0.4 parts sodium carboxymethyl cellulose, 0.2 parts crosslinking agent (aluminum hydroxyacetic acid), 0.9 parts preservative (ethylparaben), and 150 parts water; Prepare the gel patch according to the above-mentioned weight proportions: (1) Mix carbomer 980NF and 90 parts by weight of water to obtain a carbomer solution; Mixture A is prepared by mixing eucalyptus leaf oil, lauryl ketone, polyethylene glycol hexadecyl ether, polyethylene glycol 400, tert-butyl-p-hydroxyanisole, gellan gum, glycerin, and carbomer solution in water. (2) The traditional Chinese medicine compound containing Panlongqi is mixed and dissolved with 60 parts by weight of water and added to mixture A. Disodium edetate, 0.28 parts by weight of sodium carboxymethyl cellulose and 0.18 parts by weight of aluminum hydroxyl are added to mixture A. First, the temperature is raised to 40°C and the pressure is 5 MPa, and homogenized for 2 min. Then, the temperature is raised to 60°C and the pressure is 12 MPa, and homogenized for 2 min to obtain mixture B. (3) Add 0.12 parts by weight of sodium carboxymethyl cellulose, 0.02 parts by weight of aluminum hydroxyl and ethylparaben to mixture B; homogenize at 40°C and 8 MPa for 4 min; then cool down to 20°C and homogenize at 2 MPa for 15 min; let stand for 6 h, then coat it on non-woven fabric to obtain gel plaster.

[0053] Example 4 A gel patch containing Panlongqi, comprising: a traditional Chinese medicine compound containing Panlongqi and an excipient composition; the traditional Chinese medicine compound containing Panlongqi, based on the amount of raw Chinese medicinal material, has a mass ratio of 30:1 to the excipient composition. The excipient composition comprises, by weight, 0.3 parts eucalyptus leaf oil, 0.5 parts lauryl acetone, 2 parts polyethylene glycol hexadecyl ether, 3 parts polyethylene glycol 400, 0.03 parts tert-butyl-p-hydroxyanisole, 15 parts carbomer 980NF, 0.05 parts disodium edetate, 0.3 parts gellan gum, 40 parts glycerin, 0.8 parts sodium carboxymethyl cellulose, 0.5 parts crosslinking agent (aluminum chloride), 0.5 parts preservative (ethylparaben), and 250 parts water; Prepare the gel patch according to the above-mentioned weight proportions: (1) Mix carbomer 980NF and 125 parts by weight of water to obtain a carbomer solution; Mixture A is prepared by mixing eucalyptus leaf oil, lauryl ketone, polyethylene glycol hexadecyl ether, polyethylene glycol 400, tert-butyl-p-hydroxyanisole, gellan gum, glycerin and carbomer solution. (2) The traditional Chinese medicine compound containing Panlongqi is mixed and dissolved with 125 parts by weight of water and added to mixture A. Disodium edetate, 0.48 parts by weight of sodium carboxymethyl cellulose and 0.4 parts by weight of aluminum chloride are added to mixture A. First, the temperature is raised to 35°C and the pressure is 4 MPa, and homogenized for 3 min. Then, the temperature is raised to 55°C and the pressure is 10 MPa, and homogenized for 3 min to obtain mixture B. (3) Add 0.32 parts by weight of sodium carboxymethyl cellulose, 0.1 parts by weight of aluminum chloride and ethylparaben to mixture B; homogenize at 45°C and 10 MPa for 3 min; then cool down to 25°C and 3 MPa for 10 min; let stand for 4 h, then coat it on non-woven fabric to obtain gel plaster.

[0054] Example 5 A gel patch containing Panlongqi, comprising: a traditional Chinese medicine compound containing Panlongqi and an excipient composition; the traditional Chinese medicine compound containing Panlongqi, based on the amount of raw Chinese medicinal material, has a mass ratio of 30:1 to the excipient composition. The excipient composition comprises, by weight, 0.8 parts eucalyptus leaf oil, 3 parts lauryl acetone, 0.5 parts polyethylene glycol hexadecyl ether, 8 parts polyethylene glycol 400, 0.1 parts tert-butyl-p-hydroxyanisole, 5 parts carbomer 980NF, 0.01 parts disodium edetate, 0.05 parts gellan gum, 15 parts glycerin, 0.2 parts sodium carboxymethyl cellulose, 0.05 parts crosslinking agent (aluminum chloride), 1 part preservative (ethylparaben), and 125 parts water; Prepare the gel patch according to the above-mentioned weight proportions: (1) Mix carbomer 980NF and 62.5 parts by weight of water to obtain a carbomer solution; Mixture A is prepared by mixing eucalyptus leaf oil, lauryl ketone, polyethylene glycol hexadecyl ether, polyethylene glycol 400, tert-butyl-p-hydroxyanisole, gellan gum, glycerin and carbomer solution. (2) The traditional Chinese medicine compound containing Panlongqi is mixed and dissolved with 62.5 parts by weight of water and added to mixture A. Disodium edetate, 0.12 parts by weight of sodium carboxymethyl cellulose and 0.04 parts by weight of aluminum chloride are added to mixture A. First, the temperature is raised to 35°C and the pressure is 4 MPa, and homogenized for 3 min. Then, the temperature is raised to 55°C and the pressure is 10 MPa, and homogenized for 3 min to obtain mixture B. (3) Add 0.08 parts by weight of sodium carboxymethyl cellulose, 0.01 parts by weight of aluminum chloride and ethylparaben to mixture B; homogenize at 45°C and 10 MPa for 3 min; then cool down to 25°C and 3 MPa for 10 min; let stand for 4 h, then coat it on non-woven fabric to obtain gel plaster.

[0055] Comparative Example 1 Unlike Example 1, the component eucalyptus leaf oil in the excipient composition was replaced with propylene glycol.

[0056] Everything else is the same as in Example 1.

[0057] Comparative Example 2 Unlike Example 1, the gellan gum component in the excipient composition was replaced with chitosan.

[0058] Everything else is the same as in Example 1.

[0059] Comparative Example 3 Unlike Example 1, the component of eucalyptus leaf oil in the excipient composition was omitted.

[0060] Everything else is the same as in Example 1.

[0061] Comparative Example 4 Unlike Example 1, the components lauryl ketone and polyethylene glycol hexadecyl ether in the excipient composition were omitted.

[0062] Everything else is the same as in Example 1.

[0063] Comparative Example 5 Unlike Example 1, the components eucalyptus leaf oil, lauryl ketone, and polyethylene glycol hexadecyl ether in the excipient composition were omitted.

[0064] Everything else is the same as in Example 1.

[0065] Comparative Example 6 Unlike Example 1, the weight ratio of each component in the excipient composition is different.

[0066] Specifically: The excipient composition, by weight, comprises: 0.1 parts eucalyptus leaf oil, 0.5 parts lauryl acetone, 2.9 parts polyethylene glycol hexadecyl ether, 6 parts polyethylene glycol 400, 0.06 parts tert-butyl-p-hydroxyanisole, 3.6 parts carbomer 980NF, 0.03 parts disodium edetate, 4 parts gellan gum, 26.1 parts glycerin, 7 parts sodium carboxymethyl cellulose, 0.3 parts aluminum hydroxyacetate, 0.8 parts ethylparaben, and 200 parts water.

[0067] Prepare the gel patch according to the above-mentioned weight proportions: (1) Mix carbomer 980NF and 100 parts by weight of water to obtain a carbomer solution; Mixture A is prepared by mixing eucalyptus leaf oil, lauryl ketone, polyethylene glycol hexadecyl ether, polyethylene glycol 400, tert-butyl-p-hydroxyanisole, gellan gum, glycerin and carbomer solution. (2) The traditional Chinese medicine compound containing Panlongqi is mixed and dissolved with 100 parts by weight of water and added to mixture A. Disodium edetate, 4.2 parts by weight of sodium carboxymethyl cellulose and 0.24 parts by weight of aluminum hydroxyl are added to mixture A. First, the temperature is raised to 35°C and the pressure is 4 MPa, and homogenized for 3 min. Then, the temperature is raised to 55°C and the pressure is 10 MPa, and homogenized for 3 min to obtain mixture B. (3) Add 2.8 parts by weight of sodium carboxymethyl cellulose, 0.06 parts by weight of aluminum hydroxyl and ethylparaben to mixture B; homogenize at 45°C and 10 MPa for 3 min; then cool down to 25°C and 3 MPa for 10 min; let stand for 4 h, then coat it on non-woven fabric to obtain gel plaster.

[0068] Comparative Example 7 Unlike Example 1, the preparation method of the gel patch is different; gradient heating and pressurization homogenization and gradient cooling and depressurization treatments were not used. A gel patch containing Panlongqi, comprising: a traditional Chinese medicine compound containing Panlongqi and an excipient composition; the traditional Chinese medicine compound containing Panlongqi, based on the amount of raw Chinese medicinal material, has a mass ratio of 30:1 to the excipient composition. The excipient composition comprises, by weight, 0.5 parts eucalyptus leaf oil, 2 parts lauryl azone, 1 part polyethylene glycol hexadecyl ether, 6 parts polyethylene glycol 400, 0.06 parts tert-butyl-p-hydroxyanisole, 10 parts carbomer 980NF, 0.03 parts disodium edetate, 0.2 parts gellan gum, 30 parts glycerin, 0.5 parts sodium carboxymethyl cellulose, 0.3 parts crosslinking agent (aluminum hydroxyacetic acid), 0.8 parts preservative (ethylparaben), and 200 parts water; Prepare the gel patch according to the above-mentioned weight proportions: (1) Mix carbomer 980NF and 100 parts by weight of water to obtain a carbomer solution; Mixture A is prepared by mixing eucalyptus leaf oil, lauryl ketone, polyethylene glycol hexadecyl ether, polyethylene glycol 400, tert-butyl-p-hydroxyanisole, gellan gum, glycerin and carbomer solution. (2) The traditional Chinese medicine compound containing Panlongqi is mixed and dissolved with 100 parts by weight of water and added to mixture A. Disodium edetate, 0.3 parts by weight of sodium carboxymethyl cellulose and 0.24 parts by weight of aluminum hydroxyl are added to mixture A and mixed and stirred evenly to obtain mixture B. (3) Add 0.2 parts by weight of sodium carboxymethyl cellulose, 0.06 parts by weight of aluminum hydroxyl and ethylparaben to mixture B, stir evenly, let stand for 4 hours, and apply to non-woven fabric to obtain gel plaster.

[0069] Experiment 1 Transdermal Permeability Test Using the modified Franz diffusion cell method, with the abdominal skin of pigs as a barrier, in vitro transdermal tests were conducted on the gel patches prepared in Examples 1-5 and Comparative Examples 1-6.

[0070] The specific experimental method was as follows: Cleaned pig skin was fixed at the release port of the Franz diffusion cell. A pH 7.4 phosphate buffer solution was added to the receiving chamber as the release medium, ensuring close contact between the endothelial layer and the solution. The gel patch was applied to the skin, and the water bath was adjusted to maintain a constant temperature of the outer layer at (32±0.5)℃. The stirring speed was 600 rpm. The release medium was collected at 0 h, 1 h, 2 h, 4 h, 8 h, and 12 h, and an equal volume of PBS was added simultaneously. The cumulative absorption percentage (i.e., the percentage of total ferulic acid, loganic acid, and gentiopicroside permeated relative to the total amount of ferulic acid, loganic acid, and gentiopicroside in the gel patch) was calculated.

[0071] In each embodiment and each comparative example, the gel patch contained 22.75g of raw medicinal material (the amount of raw medicinal material refers to the amount of raw material in a traditional Chinese medicine compound containing Panlongqi).

[0072] The cumulative percentage of total absorption of ferulic acid, loganic acid, and gentiopicroside in each embodiment and comparative gel patch is shown in Table 1.

[0073] Table 1

[0074] As can be seen from Table 1, the gel patch of the present invention exhibits excellent penetration effect in the transdermal penetration test. The cumulative absorption percentage within 1 hour is higher than that of all comparative examples, and the cumulative absorption percentage at 12 hours is as high as 88.6%-95.9%, which is significantly higher than that of the comparative examples (35.9%-65.8%). The penetration effect is nearly 1.5 times or more than that of the comparative examples. The technical effects of Comparative Examples 1 and 2 show that the components of the gel patch of the present invention cannot be arbitrarily replaced. Changing the components of the gel patch disrupts the synergistic effect of each component, leading to a decrease in the performance of promoting the penetration and absorption of the active ingredients. The technical effects of Comparative Examples 3 and 5 show that the three components in the gel patch—eucalyptus oil, lauryl ketone, and polyethylene glycol hexadecyl ether—work synergistically to enhance penetration. The combined use of these three components results in a higher cumulative absorption percentage than when used individually, leading to unexpected technical effects. The technical effects of Comparative Example 6 show that the dosage and ratio of each component in the gel patch have a significant impact on the technical effect. The specific component ratio of the present invention results in a significantly improved transdermal absorption effect.

[0075] Test 2 Stability Test The gel patches prepared in Examples 1-5 and Comparative Examples 1-7 were subjected to stability tests. Each gel patch sample contained 50 mg of traditional Chinese medicine compound (a traditional Chinese medicine compound containing Panlongqi ingredient).

[0076] The samples were subjected to related substance detection after being stored at 60℃ for 0 days and 30 days (detection method: high performance liquid chromatography, C8 column, wavelength: 205nm, methanol-acetonitrile-water (volume ratio 5:40:53)). The content of related substances in the samples stored at 60℃ for 30 days is shown in Table 2.

[0077] Table 2

[0078] As can be seen from Table 2, the gel patches prepared in Examples 1-5 of this invention exhibit significantly better stability than those in Comparative Examples 1-7, with lower content of related substances and less variation in their content. This demonstrates that the gel patches obtained from the components and preparation method of this invention possess high stability. In particular, the synergistic use of eucalyptus oil, lauryl ketone, and polyethylene glycol hexadecyl ether, along with the gel patch preparation method, greatly enhances the product's stability.

[0079] Experiment 3 The initial tack test was conducted according to Method 2 of General Chapter 0952 in Part IV of the 2020 edition of the Chinese Pharmacopoeia.

[0080] Adhesion test was performed according to Method 4 of General Chapter 0952 in Part IV of the 2020 edition of the Chinese Pharmacopoeia.

[0081] The detection results of the tack and adhesion of the hydrogel patches prepared in Examples 1-5, Comparative Example 2, Comparative Example 6 and Comparative Example 7 are shown in Table 3.

[0082] Table 3

[0083] As can be seen from Table 3, the hydrogel patches prepared in the examples of the present invention have excellent tack and are significantly superior to the tack of conventional commercially available products with steel balls No. 10-13. The hydrogel patches prepared in the examples of the present invention have significantly improved adhesion and have higher tack and adhesion effects compared to Comparative Example 2 with changed components, Comparative Example 6 with changed component ratios, and Comparative Example 7 with changed preparation methods.

[0084] Experiment 4 Mouse auricle swelling test The mice were purchased from Guangdong Vital River Laboratory Animal Technology Co., Ltd., and the experimental animal production license number was: SCXK (Guangdong) 2022-0063. The experimental animal quality certificate numbers were: No: 44829700041654 (male), No: 44829700041656 (female), No: 44829700041658 (male), No: 44829700041660 (female).

[0085] Quarantined ICR mice were randomly divided into 9 groups according to body weight, with 10 mice in each group, half male and half female. The normal control group and the model control group were given sodium carboxymethylcellulose, and the groups of Examples 1-3 were given the hydrogel patches of each group (dose: 1.60 g crude drug / kg), and the groups of Comparative Example 1 and Comparative Examples 3-5 were given the hydrogel patches of each group (dose: 1.60 g crude drug / kg). Each group of animals was administered by smearing, and the administration site was the right ear base of the mouse (pre-shaven and depilated), and the administration area was 0.5 cm 2 , twice a day, with an interval of about 4 h, for 3 consecutive days. Approximately 30 min after the last administration, xylene was smeared on the right auricle, and the mice were sacrificed 15 min later. Ear pieces with a diameter of 8 mm from the left and right auricles were taken for weighing, and the auricle swelling degree and inhibition rate were calculated.

[0086] Auricle swelling degree (%) = (right ear weight - left ear weight) / left ear weight × 100%; Inhibition rate (%) = (average swelling degree of the model control group - average swelling degree of the administration group) / average swelling degree of the model control group × 100%.

[0087] The auricle swelling degree and inhibition rate effects of each group of mice are shown in Table 4.

[0088] Table 4

[0089] In Table 4,# and ## This indicates that each group showed significant differences compared to the model control group. # This indicates that P < 0.05. ## This indicates that P < 0.01. △ and △△ This indicates that the comparative group showed a significant difference compared to the Example 1 group. △ This indicates that P < 0.05. △△ This indicates that P < 0.01.

[0090] The results in Table 4 show that, compared with the normal control group, the auricular swelling of the animals in the model control group was significantly increased. Compared with the model control group, the auricular swelling of the animals in the example groups was significantly lower, with a statistically significant difference. The auricular swelling inhibition rate of each example group was greater than 35%. The auricular swelling of the animals in the comparative proportion group was significantly lower than that of the model control group, but the auricular swelling was higher than that of the example group, indicating a weaker effect in inhibiting swelling compared to the example group.

[0091] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A gel patch containing Panlongqi, characterized in that, Including ingredients: a combination of traditional Chinese medicine ingredients and excipients; The excipient composition, by weight, comprises the following components: 0.3-0.8 parts eucalyptus leaf oil, 0.5-3 parts lauryl ketone, 0.5-2 parts polyethylene glycol hexadecyl ether, 3-8 parts polyethylene glycol, 0.03-0.1 parts tert-butyl-p-hydroxyanisole, 5-15 parts carbomer, 0.01-0.05 parts disodium edetate, 0.05-0.3 parts gellan gum, 15-40 parts glycerin, 0.2-0.8 parts sodium carboxymethyl cellulose, 0.05-0.5 parts crosslinking agent, 0.5-1 part preservative, and 125-250 parts water.

2. The gel patch according to claim 1, characterized in that, The excipient composition, by weight, comprises the following components: 0.4-0.7 parts eucalyptus leaf oil, 1.5-2.5 parts lauryl ketone, 0.8-1.5 parts polyethylene glycol hexadecyl ether, 4-7 parts polyethylene glycol, 0.05-0.07 parts tert-butyl-p-hydroxyanisole, 8-12 parts carbomer, 0.02-0.04 parts disodium edetate, 0.15-0.25 parts gellan gum, 25-35 parts glycerin, 0.4-0.6 parts sodium carboxymethyl cellulose, 0.2-0.4 parts crosslinking agent, 0.6-0.9 parts preservative, and 150-220 parts water.

3. The gel patch according to claim 2, characterized in that, The excipient composition, by weight, comprises the following components: 0.5 parts eucalyptus leaf oil, 2 parts lauryl ketone, 1 part polyethylene glycol hexadecyl ether, 6 parts polyethylene glycol, 0.06 parts tert-butyl-p-hydroxyanisole, 10 parts carbomer, 0.03 parts disodium edetate, 0.2 parts gellan gum, 30 parts glycerin, 0.5 parts sodium carboxymethyl cellulose, 0.3 parts crosslinking agent, 0.8 parts preservative, and 200 parts water.

4. The gel patch according to any one of claims 1-3, characterized in that, The crosslinking agent is selected from one or more of aluminum hydroxyl, aluminum chloride, and aluminum hydroxide; The polyethylene glycol is polyethylene glycol 400; The carbomer is carbomer 980NF; The pH of the water is 7-10, and triethanolamine is used to adjust the pH. The herbal ingredients are any herbal compound containing Panlongqi, or Panlongqi alone; the raw materials of the herbal compound containing Panlongqi are: 100-150g Panlongqi, 20-30g Zhuangjin Dan, 100-150g Wujiapi, 100-150g Duzhong, 280-350g Danggui, 10-15g Zhuzishen, 10-15g Chuanshegan, 50-80g Guoshanlong, 100-150g Qinjiu, 50-80g Muxiang, 10-15g Zusima, 50-80g Luoshiteng. 10-15g Aconitum carmichaelii, 20-30g Polygonum multiflorum, 10-15g Cibotium barometz, 10-15g Aconitum kusnezoffii, 20-30g Hovenia dulcis, 50-80g Polygonum cuspidatum, 50-80g Carthamus tinctorius, 50-80g Commiphora myrrha, 50-80g Polygonum aviculare, 100-150g Valerian, 20-30g Lycopodium clavatum, 100-150g Achyranthes bidentata, 150-200g Salvia miltiorrhiza, 50-80g Polygonum cuspidatum, 50-80g Hedyotis diffusa, 150-200g Paris polyphylla, 50-80g Boswellia carterii and 30-50g Yeast rice; In the gel patch, the ratio of the Chinese herbal medicine ingredients, calculated based on the amount of raw Chinese herbal medicine, to the excipient composition is 25-40:

1.

5. The method for preparing the gel patch according to any one of claims 1-4, characterized in that, Including the following steps: (1) Mix carbomer with 40%-60% of the weight of water in the formula to obtain a carbomer solution; Mixture A is prepared by mixing eucalyptus leaf oil, lauryl ketone, polyethylene glycol hexadecyl ether, polyethylene glycol, tert-butyl-p-hydroxyanisole, gellan gum, glycerin and carbomer solution. (2) Add the Chinese medicine ingredients, disodium edetate, sodium carboxymethyl cellulose (50%-70% by weight), crosslinking agent (70%-90% by weight), and water (the remaining weight by weight) to mixture A, and homogenize by gradient heating and pressure to obtain mixture B; (3) Add the remaining sodium carboxymethyl cellulose and crosslinking agent to mixture B, then mix with preservative at 40-50℃, homogenize by gradient cooling and pressure reduction, and let stand to obtain gel plaster.

6. The preparation method according to claim 5, characterized in that, In step (1), the amount of water used is 50% of the total weight of water; In step (2), the amount of sodium carboxymethyl cellulose used is 60% of the total weight of sodium carboxymethyl cellulose; In step (2), the amount of crosslinking agent used is 80% of the total weight of the crosslinking agent.

7. The preparation method according to claim 5, characterized in that, In step (2), the gradient heating and pressurization homogenization specifically involves: first heating to 30-40℃ and pressurizing to 3-5MPa, homogenizing for 2-4 minutes; then heating to 50-60℃ and pressurizing to 8-12MPa, homogenizing for 2-4 minutes.

8. The preparation method according to claim 7, characterized in that, In step (2), the gradient heating and pressurization homogenization specifically involves: first heating to 35°C and pressurizing to 4 MPa, then homogenizing for 3 minutes; then heating to 55°C and pressurizing to 10 MPa, and then homogenizing for 3 minutes.

9. The preparation method according to claim 5, characterized in that, In step (3), the gradient cooling and depressurization homogenization is specifically as follows: 40-50℃, pressure of 8-12MPa, homogenization for 2-4min; then cooling to 20-30℃, pressure of 2-4MPa, homogenization for 5-15min; In step (3), the settling time is 3-6 hours.

10. The use of the gel plaster according to any one of claims 1-4 in the preparation of drugs for promoting blood circulation and relieving pain, dispelling wind and dampness, reducing swelling and / or removing blood stasis.

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