A compound preparation of traditional Chinese medicine for relieving post-herpetic neuralgia and trigeminal neuralgia and a preparation method thereof

Abstract

The application discloses a traditional Chinese medicine compound preparation for external use for relieving post-herpetic neuralgia and trigeminal neuralgia, which comprises effective components and auxiliary materials; the effective components specifically comprise rhizoma corydalis, rhabdophis nigrscens, chuanxiong rhizome, radix paeoniae alba, radix stellae, zanthoxylum bungeanum, menthol, and borneol; and the auxiliary materials comprise carbomer 940, glycerol, choline chloride, triethanolamine, and disodium edetate. The traditional Chinese medicine preparation can effectively relieve post-herpetic neuralgia and trigeminal neuralgia and has an antipruritic effect.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, and mainly relates to a topical traditional Chinese medicine compound preparation and its preparation method, specifically a topical traditional Chinese medicine compound preparation for relieving postherpetic neuralgia and trigeminal neuralgia and its preparation method. Background Technology

[0002] Neuropathic pain is highly prevalent in clinical practice. Postherpetic neuralgia and trigeminal neuralgia have long courses, severe pain, and are prone to recurrence, which seriously affect the quality of life of patients. Their pathological mechanisms are mostly related to nerve inflammation, nerve damage repair disorders, and abnormal pain signal transmission, making clinical treatment extremely difficult.

[0003] The mainstream clinical treatment for postherpetic neuralgia is mainly oral Western medicine, including calcium channel modulators, tricyclic antidepressants and opioid analgesics. However, these drugs have significant side effects, poor patient tolerance, and are difficult to use long-term.

[0004] Trigeminal neuralgia is more difficult to treat due to the special anatomical location of the nerve. Oral medications face similar side effects and efficacy bottlenecks as postherpetic neuralgia. Nerve blocks are invasive procedures that are prone to infection and nerve damage, and their effects are short-lived. Surgical treatment has high risks and a long recovery period, and is not suitable for elderly or frail patients.

[0005] Traditional Chinese medicine (TCM) has advantages in pain treatment due to its syndrome differentiation and multi-target effects. Topical preparations have attracted much attention due to their fewer side effects and direct action on the lesion. However, existing products still have key defects: the formula lacks scientific compatibility optimization, fails to give full play to the synergistic effect between various effective components, and is difficult to specifically solve the problems of nerve inflammation and damage repair; the preparation process is outdated, and traditional methods such as water decoction and ethanol reflux lead to insufficient release of effective components of plant medicines, the inability of large molecular proteins of animal medicines to be converted into active peptides, and easy loss of volatile components.

[0006] Based on the above problems, a formula was developed that scientifically combines multiple components to achieve synergistic effects, specifically improving nerve inflammation and repair. Innovative processes were used to enhance the release rate of effective ingredients from plant-based medicines, convert active peptides from animal-based medicines and retain volatile components. This topical Chinese medicine compound preparation has few side effects, acts directly on the lesion, and has a clear therapeutic effect, thus effectively treating postherpetic neuralgia and trigeminal neuralgia. Summary of the Invention

[0007] To address the aforementioned problems, this invention develops a topical traditional Chinese medicine compound preparation for relieving postherpetic neuralgia and trigeminal neuralgia, along with its preparation method. In a first aspect, the present invention provides a traditional Chinese medicine compound preparation for external use to relieve postherpetic neuralgia and trigeminal neuralgia, comprising, by weight 100%, the following: Active ingredients: Corydalis rhizome 1.5-2.0%, Zaocys dhumnades 1.0-1.5%, Ligusticum chuanxiong rhizome 0.8-1.2%, Paeonia lactiflora rhizome 0.8-1.2%, Prunella vulgaris rhizome 0.8-1.2%; Zanthoxylum bungeanum rhizome 0.4-0.6%, Menthol rhizome 0.4-0.6%, Borneol rhizome 0.2-0.4%; Excipients: Carbomer 940 0.8-1.0%, pharmaceutical grade glycerin 15-20%, choline chloride (equimolar amount with menthol), triethanolamine (to adjust pH to 6.1-6.3), disodium edetate 0.05-0.1%; Purified water: Add to 100%.

[0008] Preferably, the Corydalis Rhizome, Ligusticum Rhizome, White Peony Root, and Summer Pepper are prepared by enzymatic hydrolysis with compound plant enzymes and extraction with ethanol.

[0009] Preferably, the black-striped snake is treated with a compound protease hydrolysis.

[0010] Preferably, the Sichuan pepper is subjected to supercritical CO2 extraction coupled with alcohol extraction, specifically: the Sichuan pepper is first extracted with supercritical fluid to obtain volatile oil, and the residue is then extracted with ethanol to obtain Sichuan pepper alcohol extract.

[0011] Preferably, after the menthol and equimolar choline chloride form a homogeneous transparent liquid under stirring in a water bath at 65°C, the mixture is cooled to 35-40°C to obtain a homogeneous transparent choline chloride-menthol deep eutectic solvent penetration enhancer.

[0012] Secondly, this invention provides a topical traditional Chinese medicine compound preparation for relieving postherpetic neuralgia and trigeminal neuralgia, and its preparation process. The specific preparation steps for preparing 1000g of the preparation are as follows: Step 1: Raw material pretreatment: Weigh 15-20g of Corydalis Rhizome, 8-12g of Ligusticum Rhizome, 8-12g of White Peony Root, and 8-12g of Summer Pepper. Mix the above herbs evenly and grind them to 50 mesh to obtain plant powder; Weigh 10-15g of Zaocys dhumnades and grind them separately to 80 mesh to obtain Zaocys dhumnades powder; Weigh 4-6g of Sichuan pepper and grind it separately to 50 mesh to obtain Sichuan pepper powder. Step 2: Compound extraction of plant powder: Put the plant powder into the extraction tank, add 10 times the weight of the plant powder in pH 4.8 sodium acetate buffer, add compound plant enzyme at 50℃ and stirring at 300-350r / min, and carry out enzymatic hydrolysis for 3h; then raise the temperature of the liquid to 92℃ and keep it at that temperature for 15min; add 6 times the weight of 70% ethanol solution, adjust the temperature to 65℃, and perform dynamic cyclic extraction twice, 2h each time. The extract is filtered through a plate and frame filter press with 200 mesh filter cloth, and the two filtrates are combined to obtain the plant extract. Step 3: Enzymatic hydrolysis of Zaocys dhumnades: Place the fine powder of Zaocys dhumnades in a reaction vessel, add 15 times the amount of purified water at 50℃, adjust the pH value to 7.5±0.2 with sodium hydroxide solution, add the compound protease, and hydrolyze by stirring at 200-250 r / min in a 50℃ water bath for 4 hours. Heat the solution to 95℃ and maintain for 10 minutes to inactivate the enzyme. After inactivation, centrifuge at 10000 r / min for 15 minutes and collect the supernatant to obtain the Zaocys dhumnades enzyme hydrolysate for later use. Step 4: Extraction of Sichuan pepper components: Put Sichuan pepper powder into a supercritical CO2 extraction device, set the extraction pressure to 20-25 MPa, temperature to 45-50℃, CO2 flow rate to 20-25 L / h, and extraction time to 2-2.5 h, and collect the volatile oil of Sichuan pepper in the separation vessel; add 6-8 times the amount of 70% ethanol to the extracted residue, extract at 40-45℃ for 1 h, filter, and concentrate under reduced pressure until no ethanol remains to obtain the Sichuan pepper alcohol extract; Step 5: Extract Concentration and Permeation Enhancer Preparation: The plant extract was transferred to a vacuum concentration tank at 60℃ and a vacuum degree of -0.09MPa, and concentrated to a relative density of 1.20 to obtain a plant extract. The enzymatic hydrolysate of *Zaocys dhumnades* and the alcohol extract of *Zanthoxylum bungeanum* were mixed evenly and concentrated to 1 / 5 of the original volume at 65℃ and a vacuum degree of -0.08MPa to obtain a concentrated extract of *Zaocys dhumnades* and *Zanthoxylum bungeanum*. 4-6g of menthol (menthol dried under vacuum to a moisture content ≤0.1%) and an equimolar amount of choline chloride (choline chloride dried under vacuum to a moisture content ≤0.3%) were placed in a reaction flask (pre-baked at 120℃ for 2 hours to remove water). Under nitrogen protection at 5mL / min, the mixture was magnetically stirred in a water bath at 65℃ for 45 minutes to form a homogeneous and transparent liquid. The mixture was then cooled to 40℃ to obtain a choline chloride-menthol deep eutectic solvent permeation enhancer. Step 6: Gel matrix preparation: Add 500g of purified water to a mixing tank, and slowly add 8-10g of Carbomer 940 powder while stirring at 300r / min. After the addition is complete, increase the stirring speed to 800r / min and continue stirring for 4 hours until the Carbomer is completely swollen into a colorless and transparent gel matrix. Let it stand for 12 hours to allow the gel matrix to fully swell. Dissolve 2-4g of borneol in 5mL of 95% ethanol, add the Sichuan pepper volatile oil obtained in step 4, then add 150-200g of glycerol and 80-100g of purified water. Place the mixture in a high-speed shear emulsifier at 1100... The mixture was sheared and emulsified at 0 rpm for 5-8 minutes to form an emulsion. This emulsion was then mixed thoroughly with the aforementioned plant extract, concentrated extracts of Zaocys dhumnades and Zanthoxylum bungeanum, and a choline chloride-menthol deep eutectic solvent and penetration enhancer. The mixture was then added to a carbomer matrix at 500 rpm, and the pH was adjusted to 6.2 ± 0.1 with 10% triethanolamine solution. 0.5-1 g of disodium edetate was added, and purified water was added to bring the total weight to 1000 g. The mixture was then transferred to a homogenizer and homogenized at -0.06 MPa for 15 minutes to remove bubbles, resulting in a uniform, brownish-yellow gel formulation.

[0013] Thirdly, the preparations prepared in this invention have the effects of relieving postherpetic neuralgia and trigeminal neuralgia and relieving itching.

[0014] Preferably, the compound plant enzyme in the second step of the present invention is cellulase and β-glucosidase.

[0015] Preferably, the concentration of cellulase in the second step of the present invention is 2000-2500 U / g (based on substrate).

[0016] Preferably, the concentration of β-glucosidase in the second step of the present invention is 600-800 U / g (based on substrate).

[0017] Preferably, the concentration of sodium hydroxide in the third step of the present invention is 0.1 mol / L.

[0018] Preferably, the complex protease in the third step of the present invention is a medium-alkaline protease and a flavor protease.

[0019] Preferably, the concentration of alkaline protease in the third step of the present invention is 10,000-12,000 U / g (based on the raw material of black snake).

[0020] Preferably, the concentration of the flavor protease in the third step of the present invention is 800-1000 U / g (based on the raw material of black snake).

[0021] Preferably, in the fourth step of the present invention, 8 times the amount of ethanol is added during the alcohol extraction.

[0022] The present invention has the following beneficial effects: 1. The traditional Chinese medicine compound preparation of this invention achieves targeted treatment for two types of refractory neuropathic pain, namely postherpetic neuralgia and trigeminal neuralgia, as well as atopic dermatitis-related pruritus, through precise formulation and optimized process. 2. Technological innovation ensures efficacy. Through processes such as compound plant enzymatic hydrolysis-alcohol extraction, compound proteolytic hydrolysis, and supercritical CO2 extraction, the release rate of effective components of plant medicines is improved, and the active peptides of animal medicines are converted and volatile components are retained, providing a solid efficacy foundation for the dual effects of analgesia and antipruriticity. 3. High transdermal efficiency and long-lasting effect: The drug delivery system combines choline chloride-menthol deep eutectic solvent penetration enhancer with carbomer gel matrix to promote the penetration of active ingredients through the skin barrier and reach subcutaneous nerve target tissue and skin inflammation sites, exerting analgesic and antipruritic effects simultaneously, with stable and long-lasting effects. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0024] Figure 1 This is a product diagram of the present invention.

[0025] Figure 2 This is a comparison chart of the thermal pain threshold of rats in Examples 1-3 and Comparative Examples 1-12.

[0026] Figure 3 This is a comparison chart of the number of scratches made by mice in Examples 1-3 and Comparative Examples 1-12 within 10 minutes. Detailed Implementation

[0027] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention. It should be noted that, unless otherwise specified, the following embodiments and features described therein can be combined with each other.

[0028] Corydalis rhizome, Ligusticum chuanxiong rhizome, and Paeonia lactiflora were purchased from Bozhou Fushuotang Biotechnology Co., Ltd.; Xia Tianwu (a type of herb) and Menthol were purchased from Bozhou Xiuwentang Pharmaceutical Co., Ltd.; Zaocys dhumnades were purchased from Haozhou Xianyang Yushan Pharmaceutical Co., Ltd.; and Choline chloride was purchased from Wuhan Baixing Biotechnology Co., Ltd.

[0029] Example 1

[0030] This embodiment provides a method for preparing a topical traditional Chinese medicine compound preparation, the specific steps of which are as follows: Step 1: Raw material pretreatment Accurately weigh 15g of Corydalis Rhizome, 8g of Ligusticum Rhizome, 8g of White Peony Root, and 8g of Summer Pepper. Mix the herbs evenly, pulverize them, and pass them through a 50-mesh sieve to obtain plant powder. Separately, take 10g of Zaocys dhumnades, pulverize them separately, and pass them through an 80-mesh sieve for later use, which is Zaocys dhumnades powder. Weigh 4g of Sichuan pepper, pulverize it separately, and pass it through a 50-mesh sieve to obtain Sichuan pepper powder. Step 2: Compound Extraction of Plant Powders The prepared plant powder was placed in an extraction vessel, and 10 times the volume of pH 4.8 sodium acetate buffer was added. A compound plant enzyme (composed of cellulase and β-glucosidase, with cellulase concentration of 2000 U / g (substrate) and β-glucosidase concentration of 600 U / g (substrate)) was added under stirring at 50℃ and 300 rpm. The enzymatic hydrolysis reaction continued for 3 hours. After hydrolysis, the solution was heated to 92℃ and held for 15 minutes to inactivate the enzyme. Then, 6 times the volume of 70% ethanol solution was added, and the temperature was adjusted to 65℃. Extraction was performed twice using a dynamic circulation method, with each extraction lasting 2 hours. After extraction, the extract was filtered through a plate and frame filter press equipped with a 200-mesh filter cloth. The two filtrates were combined to obtain the plant extract.

[0031] Step 3: Enzymatic hydrolysis of black-striped snake Place the powdered *Zaocys dhumnades* in a reaction vessel, add 15 times the volume of purified water at 50℃, and adjust the pH of the system to 7.5±0.2 with 0.1mol / L sodium hydroxide solution. Add a complex protease (containing alkaline protease and flavor protease, with the alkaline protease concentration being 10000 U / g based on the *Zaocys dhumnades* raw material and the flavor protease concentration being 800 U / g based on the *Zaocys dhumnades* raw material). Hydrolyze the mixture in a 50℃ water bath at 200 rpm for 4 hours. Then, heat the solution to 95℃ and maintain the temperature for 10 minutes to inactivate the enzyme. After enzyme inactivation, transfer the solution to a centrifuge, set the speed to 10000 rpm, and centrifuge for 15 minutes. Collect the supernatant, which is the *Zaocys dhumnades* enzymatic hydrolysate, for later use. Step 4: Sichuan pepper CO2 extraction-alcohol extraction process Sichuan pepper powder was added to a supercritical CO2 extraction device. The extraction pressure was set to 20 MPa, the extraction temperature to 45℃, and the CO2 flow rate to 20 L / h. After extraction for 2 hours, the volatile oil of Sichuan pepper in the separation vessel was collected. The extracted residue was then added to 8 times the amount of 70% ethanol and extracted at 40-45℃ for 1 hour. After filtration, the extract was concentrated under reduced pressure until no ethanol was found, thus obtaining the Sichuan pepper alcohol extract. Step 5: Concentration of extract and preparation of penetration enhancer The plant extract was transferred to a vacuum concentration tank and concentrated to a relative density of 1.20 at 60℃ and a vacuum of -0.09MPa to obtain a plant extract. The enzymatic hydrolysate of *Zaocys dhumnades* and the alcoholic extract of *Zanthoxylum bungeanum* were mixed evenly and concentrated to 1 / 5 of the original volume at 65℃ and a vacuum of -0.08MPa to obtain a *Zaocys dhumnades*-*Zanthoxylum bungeanum* concentrate. 4g of menthol, vacuum-dried to a moisture content ≤0.1%, and an equimolar amount of choline chloride, vacuum-dried to a moisture content ≤0.3%, were placed together in a reaction flask pre-baked at 120℃ for 2 hours to remove water. Nitrogen gas was introduced at a flow rate of 5mL / min throughout the process, and the mixture was magnetically stirred at 300r / min for 45 minutes in a 65℃ water bath to form a homogeneous and transparent liquid. The mixture was then cooled to 40℃ to obtain a choline chloride-menthol deep eutectic solvent penetration enhancer. Step 6: Gel matrix preparation and formulation molding Add 500g of purified water to a preparation tank. While stirring at 300 rpm, slowly sprinkle in 8g of Carbomer 940 powder. After the addition is complete, increase the stirring speed to 800 rpm and continue stirring for 4 hours until the Carbomer is completely swollen, forming a colorless and transparent gel matrix. Let it stand for 12 hours to ensure the matrix is ​​fully swollen. Dissolve 2g of borneol in 5mL of 95% ethanol, add the Sichuan pepper volatile oil obtained in step four, then add 150g of glycerol and 80g of purified water. Place the mixture in a high-speed shear emulsifier and shear emulsify at 11000 rpm for 5 minutes to form an emulsion. Mix this emulsion with the aforementioned plant extract, concentrated extracts of Zaocys dhumnades and Sichuan pepper, and choline chloride-menthol deep eutectic solvent penetration enhancer. Add the mixture to the Carbomer matrix at 500 rpm and adjust the pH of the system to 6.1 with 10% triethanolamine solution. Then add 0.5g of disodium edetate, add purified water to make up to 1000g of total weight, transfer the material to a homogenizer, and homogenize for 15 minutes under -0.06MPa conditions to finally obtain a gel preparation with uniform texture and brownish-yellow color.

[0032] Example 2

[0033] This embodiment provides a method for preparing a topical traditional Chinese medicine compound preparation, the specific steps of which are as follows: Step 1: Raw material pretreatment Accurately weigh 17g of Corydalis Rhizome, 10g of Ligusticum Rhizome, 10g of White Peony Root, and 10g of Summer Pepper. Mix the herbs evenly, pulverize them, and pass them through a 50-mesh sieve to obtain plant powder. Separately, take 13g of Zaocys dhumnades, pulverize them separately, and pass them through an 80-mesh sieve for later use, which is Zaocys dhumnades powder. Weigh 5g of Sichuan pepper, pulverize it separately, and pass it through a 50-mesh sieve to obtain Sichuan pepper powder. Step 2: Compound Extraction of Plant Powders The prepared plant powder was placed in an extraction vessel, and 10 times the volume of pH 4.8 sodium acetate buffer was added. A compound plant enzyme (composed of cellulase and β-glucosidase, with cellulase concentration of 2200 U / g (substrate) and β-glucosidase concentration of 700 U / g (substrate)) was added under stirring at 50℃ and 330 rpm. The enzymatic hydrolysis reaction continued for 3 hours. After hydrolysis, the solution was heated to 92℃ and held for 15 minutes to inactivate the enzyme. Then, 6 times the volume of 70% ethanol solution was added, and the temperature was adjusted to 65℃. Extraction was performed twice using a dynamic circulation method, with each extraction lasting 2 hours. After extraction, the extract was filtered through a plate and frame filter press equipped with a 200-mesh filter cloth. The two filtrates were combined to obtain the plant extract.

[0034] Step 3: Enzymatic hydrolysis of black-striped snake Place the powdered *Zaocys dhumnades* in a reaction vessel, add 15 times the volume of purified water at 50℃, and adjust the pH of the system to 7.5±0.2 with 0.1mol / L sodium hydroxide solution. Add a complex protease (containing alkaline protease and flavor protease, with an alkaline protease concentration of 11000 U / g based on the *Zaocys dhumnades* raw material and a flavor protease concentration of 900 U / g based on the *Zaocys dhumnades* raw material). Hydrolyze the mixture in a 50℃ water bath at 230 rpm for 4 hours. Then, heat the solution to 95℃ and maintain the temperature for 10 minutes to inactivate the enzyme. After enzyme inactivation, transfer the solution to a centrifuge at 10000 rpm for 15 minutes. Collect the supernatant, which is the *Zaocys dhumnades* enzymatic hydrolysate, for later use. Step 4: Sichuan pepper CO2 extraction-alcohol extraction process The Sichuan pepper powder was put into a supercritical CO2 extraction device, and the extraction pressure was set to 23 MPa, the extraction temperature to 47℃, and the CO2 flow rate to 23 L / h. After extraction for 2.3 h, the volatile oil of Sichuan pepper in the separation vessel was collected. The extracted residue was then added to 8 times the amount of 70% ethanol and extracted at 40-45℃ for 1 h. After filtration, the extract was concentrated under reduced pressure until no ethanol was found, and the Sichuan pepper alcohol extract was obtained. Step 5: Concentration of extract and preparation of penetration enhancer The plant extract was transferred to a vacuum concentration tank and concentrated to a relative density of 1.20 at 60℃ and a vacuum of -0.09MPa to obtain a plant extract. The enzymatic hydrolysate of *Zaocys dhumnades* and the alcoholic extract of *Zanthoxylum bungeanum* were mixed evenly and concentrated to 1 / 5 of the original volume at 65℃ and a vacuum of -0.08MPa to obtain a *Zaocys dhumnades*-*Zanthoxylum bungeanum* concentrate. 5g of menthol, vacuum-dried to a moisture content ≤0.1%, and an equimolar amount of choline chloride, vacuum-dried to a moisture content ≤0.3%, were weighed and placed together in a reaction flask pre-baked at 120℃ for 2 hours to remove water. Nitrogen gas was introduced at a flow rate of 5mL / min throughout the process, and the mixture was magnetically stirred at 300r / min for 45 minutes in a 65℃ water bath to form a homogeneous and transparent liquid. The mixture was then cooled to 40℃ to obtain a choline chloride-menthol deep eutectic solvent penetration enhancer. Step 6: Gel matrix preparation and formulation molding Add 500g of purified water to a preparation tank, and slowly sprinkle in 9g of carbomer 940 powder while stirring at 300 rpm. After the addition is complete, increase the stirring speed to 800 rpm and continue stirring for 4 hours until the carbomer is completely swollen, forming a colorless and transparent gel matrix. Let it stand for 12 hours to ensure the matrix is ​​fully swollen. Dissolve 3g of borneol in 5mL of 95% ethanol, add the pepper volatile oil obtained in step four, then add 170g of glycerol and 90g of purified water. Place the mixture in a high-speed shear emulsifier and shear emulsify at 11000 rpm for 7 minutes to form an emulsion. Mix the emulsion with the aforementioned plant extract, concentrated extracts of black sedge and pepper, and choline chloride-menthol deep eutectic solvent penetration enhancer. Add the mixture to the carbomer matrix at 500 rpm and adjust the pH of the system to 6.2 with 10% triethanolamine solution. Then, 0.7g of disodium edetate was added, and purified water was added to bring the total weight to 1000g. The material was then transferred to a homogenizer and homogenized for 15 minutes at -0.06MPa to remove bubbles, ultimately yielding a uniform, brownish-yellow gel formulation. A picture of the product is shown below. Figure 1 As shown.

[0035] Example 3

[0036] This embodiment provides a method for preparing a topical traditional Chinese medicine compound preparation, the specific steps of which are as follows: Step 1: Raw material pretreatment Accurately weigh 20g of Corydalis Rhizome, 12g of Ligusticum Rhizome, 12g of White Peony Root, and 12g of Summer Pepper. Mix the herbs evenly, pulverize them, and pass them through a 50-mesh sieve to obtain plant powder. Separately, take 15g of Zaocys dhumnades, pulverize it separately, and pass it through an 80-mesh sieve for later use; this is Zaocys dhumnades powder. Weigh 6g of Sichuan pepper, pulverize it separately, and pass it through a 50-mesh sieve to obtain Sichuan pepper powder. Step 2: Compound Extraction of Plant Powders The prepared plant powder was placed in an extraction vessel, and 10 times the volume of pH 4.8 sodium acetate buffer was added. A compound plant enzyme (composed of cellulase and β-glucosidase, with cellulase concentration of 2500 U / g (substrate) and β-glucosidase concentration of 800 U / g (substrate)) was added under stirring at 50℃ and 350 rpm. The enzymatic hydrolysis reaction continued for 3 hours. After hydrolysis, the solution was heated to 92℃ and held for 15 minutes to inactivate the enzyme. Then, 6 times the volume of 70% ethanol solution was added, and the temperature was adjusted to 65℃. Extraction was performed twice using a dynamic circulation method, with each extraction lasting 2 hours. After extraction, the extract was filtered through a plate and frame filter press equipped with a 200-mesh filter cloth. The two filtrates were combined to obtain the plant extract.

[0037] Step 3: Enzymatic hydrolysis of black-striped snake Place the powdered *Zaocys dhumnades* in a reaction vessel, add 15 times the volume of purified water at 50℃, and adjust the pH of the system to 7.5±0.2 with 0.1mol / L sodium hydroxide solution. Add a complex protease (containing alkaline protease and flavor protease, with an alkaline protease concentration of 12000 U / g based on the *Zaocys dhumnades* raw material and a flavor protease concentration of 1000 U / g based on the *Zaocys dhumnades* raw material). Hydrolyze the mixture in a 50℃ water bath at 250 rpm for 4 hours. Then, heat the solution to 95℃ and maintain the temperature for 10 minutes to inactivate the enzyme. After enzyme inactivation, transfer the solution to a centrifuge at 10000 rpm for 15 minutes. Collect the supernatant, which is the *Zaocys dhumnades* enzymatic hydrolysate, for later use. Step 4: Sichuan pepper CO2 extraction-alcohol extraction process The pepper powder was put into a supercritical CO2 extraction device, and the extraction pressure was set to 25 MPa, the extraction temperature to 50℃, and the CO2 flow rate to 25 L / h. After extraction for 2.5 h, the volatile oil of pepper in the separation vessel was collected. The extracted residue was then added to 8 times the amount of 70% ethanol and extracted at 40-45℃ for 1 h. After filtration, the extract was concentrated under reduced pressure until no ethanol was found, and the pepper alcohol extract was obtained. Step 5: Concentration of extract and preparation of penetration enhancer The plant extract was transferred to a vacuum concentration tank and concentrated to a relative density of 1.20 at 60℃ and a vacuum of -0.09MPa to obtain a plant extract. The enzymatic hydrolysate of *Zaocys dhumnades* and the alcoholic extract of *Zanthoxylum bungeanum* were mixed evenly and concentrated to 1 / 5 of the original volume at 65℃ and a vacuum of -0.08MPa to obtain a *Zaocys dhumnades*-*Zanthoxylum bungeanum* concentrate. 6g of menthol, vacuum-dried to a moisture content ≤0.1%, and an equimolar amount of choline chloride, vacuum-dried to a moisture content ≤0.3%, were weighed and placed together in a reaction flask pre-baked at 120℃ for 2 hours to remove water. Nitrogen gas was introduced at a flow rate of 5mL / min throughout the process, and the mixture was magnetically stirred at 300r / min for 45 minutes in a 65℃ water bath to form a homogeneous and transparent liquid. The mixture was then cooled to 40℃ to obtain a choline chloride-menthol deep eutectic solvent penetration enhancer. Step 6: Gel matrix preparation and formulation molding Add 500g of purified water to a preparation tank. While stirring at 300 rpm, slowly sprinkle in 10g of carbomer 940 powder. After the addition is complete, increase the stirring speed to 800 rpm and continue stirring for 4 hours until the carbomer is completely swollen, forming a colorless and transparent gel matrix. Let it stand for 12 hours to ensure the matrix is ​​fully swollen. Dissolve 4g of borneol in 5mL of 95% ethanol, add the Sichuan pepper volatile oil obtained in step four, then add 200g of glycerol and 100g of purified water. Place the mixture in a high-speed shear emulsifier and shear emulsify at 11000 rpm for 8 minutes to form an emulsion. Mix this emulsion with the aforementioned plant extract, concentrated extracts of black snake and Sichuan pepper, and choline chloride-menthol deep eutectic solvent penetration enhancer. Add the mixture to the carbomer matrix at 500 rpm and adjust the pH of the system to 6.3 with 10% triethanolamine solution. Then add 1g of disodium edetate, add purified water to make up to 1000g of total weight, transfer the material to a homogenizer, and defoam and homogenize for 15min under -0.06MPa conditions to finally obtain a gel formulation with uniform texture and brownish-yellow color.

[0038] Comparative Example 1: Corydalis was not added in the first step of raw material pretreatment, and all other steps were the same as in Example 2.

[0039] Comparative Example 2: No black snake was added in the first step of raw material pretreatment, and all other steps were the same as in Example 2.

[0040] Comparative Example 3: No chuanxiong was added in the first step of raw material pretreatment, and all other steps were the same as in Example 2.

[0041] Comparative Example 4: No white peony root was added in the first step of raw material pretreatment, and all other steps were the same as in Example 2.

[0042] Comparative Example 5: Summer is not added in the first step of raw material pretreatment, and all other steps are the same as in Example 2.

[0043] Comparative Example 6: In the sixth step of gel matrix preparation and formulation molding, no choline chloride-menthol deep eutectic solvent or penetration enhancer was added, and all other steps were the same as in Example 2.

[0044] Comparative Example 7: The enzymatic hydrolysis process was omitted in the second step of plant powder compound extraction, and all other steps were the same as in Example 2.

[0045] Comparative Example 8: In the second step of plant powder compound extraction, only cellulase was used for enzymatic hydrolysis, and all other steps were the same as in Example 2.

[0046] Comparative Example 9: In the second step of plant powder compound extraction, only β-glucosidase was used for enzymatic hydrolysis, and all other steps were the same as in Example 2.

[0047] Comparative Example 10: The third step of the enzymatic hydrolysis process of black shad was replaced with an alcohol extraction process, that is, 8 times the amount of 40% ethanol was added at 50°C and extracted for 1.5 hours. All other steps were the same as in Example 2.

[0048] Comparative Example 11: The fourth step of the Sichuan pepper CO2 extraction process was replaced with the traditional steam distillation method to extract the volatile oil of Sichuan pepper. Specifically, the same amount of Sichuan pepper powder was taken and continuously distilled and extracted for 2.5 hours at a slight boiling state using a steam distillation device. The volatile oil of Sichuan pepper was collected. All other steps were the same as in Example 2.

[0049] Comparative Example 12: Corydalis rhizome, Ligusticum chuanxiong rhizome, Paeonia lactiflora rhizome, Smilax china rhizome, Zaocys dhumnades and Zanthoxylum bungeanum rhizome were mixed evenly and pulverized to 500 mesh. Eight times the amount of 75% ethanol was added and statically refluxed at 65°C for 3 times (1.5h each time). The filtrates were filtered and combined and concentrated until no ethanol was found. The treatment of other active ingredients and excipients was the same as in Example 2.

[0050] Study 1: An Investigation into the Effect of Traditional Chinese Medicine Compound Preparations on Postherpetic Neuralgia SPF-grade male SD rats, weighing between 200-220g, were used as the animals and were provided by Jiangsu Airingfei Biotechnology Co., Ltd. All rats were initially placed in a constant temperature and humidity environment of 22-25℃, 50%-60% relative humidity, and alternating 12h light / 12h dark conditions for 7 days for acclimatization. During this period, the rats were provided with free access to food and water.

[0051] VZV suspension preparation and titer determination: African green monkey kidney cells (BS-C-1) were cultured in EMEM medium containing 10% fetal bovine serum at 37℃ and 5% CO2 until the cell density reached 90%. The culture medium was discarded, and human herpesvirus type 3 (VZV, ATCC VR-1433, purchased from Wuhan Gray Algae Biotechnology Co., Ltd.) was inoculated. Adsorption was carried out at 37℃ for 1.5 h, with gentle shaking of the culture flask during this period. After adsorption, the virus solution was discarded, and EMEM medium containing 2% fetal bovine serum (maintenance medium) was added for continued culture. Cell morphology was observed daily. When more than 80% of the cells showed typical cytopathic effects (CPE), the cells and supernatant were collected. The collected solution was repeatedly frozen and thawed three times to fully release the virus. The cells were centrifuged at 4℃ and 8000 r / min for 10 min, and the supernatant was aliquoted to obtain the VZV virus stock solution, which was stored at -80℃ for later use.

[0052] The Reed-Muench method was used to determine the median tissue culture infectious dose (TCID50) of the viral stock solution: The viral stock solution was serially diluted 10-fold with maintenance medium and inoculated sequentially into 100 μL of pre-converted BS-C-1 cells in 96-well plates, with a control well containing normal cells. The plates were incubated at 37°C in a 5% CO2 incubator for 7 days, and the cell proliferation activity (CPE) of each well was recorded daily under an inverted microscope. Based on the results on day 7, the TCID50 of the viral stock solution was calculated using the Reed-Muench method. For subsequent modeling, the viral stock solution was diluted to the required concentration with maintenance medium based on the measured TCID50 value, and prepared fresh for each use.

[0053] The specific preparation method of the matrix control group (strictly parallel to the excipient composition and process of Example 2): Add 500g of purified water to a mixing tank, and slowly sprinkle in 9g of carbomer 940 powder while stirring at 300r / min. After the addition is complete, increase the speed to 800r / min and continue stirring for 4 hours until completely swollen to form a colorless and transparent gel matrix. Let it stand for 12 hours to allow the matrix to fully swell. Add 170g of pharmaceutical-grade glycerol and 90g of purified water, and mix thoroughly. Add choline chloride (vacuum dried to a moisture content ≤0.3% and equimolar with 5g of menthol), mix thoroughly, and adjust the pH of the system to 6.2 with 10% triethanolamine solution. Add 0.7g of disodium edetate, and add purified water to a total weight of 1000g. Transfer to a homogenizer and homogenize at -0.06MPa for 15 minutes to obtain a blank gel matrix without any effective Chinese medicine components, which is recorded as the gel preparation. (The preparation methods for the matrix control groups in the following two experiments are the same.) Before modeling, all rats underwent thermal pain threshold testing, and rats with abnormal thermal pain thresholds (too high or too low) were excluded. After the test, 9 rats were selected as the blank group, and the remaining rats were subcutaneously inoculated with 50 μL of VZV suspension (containing 15 TCID50 viral load) between the webs of the 1st and 2nd fingers of the left forelimb. The blank group rats were injected with an equal volume of physiological saline at the same site.

[0054] Rats were randomly divided into the following groups using a random number table: model group, Examples 1-3 groups, Comparative Examples 1-12 groups, positive control group, and matrix control group, with 9 rats in each group. Rats in each group were housed separately, and hair was removed from the back area of ​​the rats (3 cm × 3 cm). Drug intervention began 2 hours after infection modeling.

[0055] Traditional Chinese Medicine Intervention Group: Rats in Examples 1-3 and Comparative Examples 1-12 had their corresponding traditional Chinese medicine compound preparations applied to the skin on their backs at a dose of 11 mg / cm², covering an area of ​​9 cm². 2The drug was administered three times daily. In the control and model groups, rats received the same volume of saline solution applied to the same area, without any drug intervention. In the positive control group, rats received acyclovir cream applied to the skin of their backs at a dose of 10 mg / cm², covering an area of ​​9 cm². 2 Four times daily. The matrix control group received the same amount of gel preparation as the traditional Chinese medicine intervention group, three times daily.

[0056] All interventions lasted for 10 days, and indicator testing was carried out uniformly after the intervention ended.

[0057] Detection of thermal pain threshold in rats: The thermal pain threshold in rats was determined using a hot and cold plate analgesia device. The temperature of the hot plate was set to 55℃ ± 0.5℃. The time from contact with the hot plate to the appearance of the paw withdrawal reflex was recorded as the thermal pain threshold. To avoid tissue damage, a cutoff time of 30 seconds was set. Each rat was tested three times, with each test 10 minutes apart. The average value was taken as the final result. Specific results are shown in Table 1 and [Table data missing]. Figure 2 .

[0058] Table 1

[0059] Table 1 shows the comparison results of thermal pain threshold (TWL) in rats of Examples 1-3 and Comparative Examples 1-12. The data show that the control group rats were not pathologically damaged, their pain reflex function was normal, and their thermal pain threshold remained at a normal physiological level. In the model group, after VZV virus inoculation, nerve tissue damage led to pain sensitization, and the thermal pain threshold decreased significantly, clearly exhibiting the typical pathological characteristics of postherpetic neuralgia. Compared with the model group, the matrix control group showed no significant changes. Both Examples 1-3 and Comparative Examples 1-12 groups improved the thermal pain threshold to varying degrees, but the improvement effects differed significantly: the increase in thermal pain threshold in Comparative Examples 1-12 groups was limited, and the improvement in pain tolerance was insufficient; while the thermal pain threshold in Examples 1-3 groups showed the best upward trend, and pain tolerance was significantly enhanced, with the thermal pain threshold in Example 2 approaching the normal level of the control group. This result fully demonstrates that the traditional Chinese medicine compound preparations prepared in Examples 1-3, relying on the complete formula composition, the synergistic effect between the components, and the optimized process to ensure the high efficiency of the effective components, have a therapeutic effect far exceeding that of the comparison ratios. They can more accurately improve the pain tolerance of rats with postherpetic neuralgia and have the best effect on postherpetic neuralgia.

[0060] Furthermore, the choline chloride-menthol system described in this invention substantially forms a deep eutectic solvent (DES) at a specific molar ratio. Compared to conventional single-component physical mixing penetration enhancers, this system constructs a stable amphiphilic network through intermolecular hydrogen bonds between the hydrophilic groups of choline chloride and the lipid-soluble structure of menthol. During transdermal transmission, this amphiphilic network can not only embed into and disrupt the lipid bilayer structure of the stratum corneum, but also simultaneously construct hydrophilic ion transport channels within the stratum corneum, thereby achieving dual-channel synergistic penetration enhancement for polar / nonpolar complex components such as corydalis alkaloids and Zaocys dhumnades active peptides, significantly improving the enrichment of pharmacologically active ingredients at the target site.

[0061] Study 2: Efficacy of Traditional Chinese Medicine Compound Preparations in Improving Trigeminal Neuralgia The experimental animals were C57BL / 6 mice, with an equal number of males and females, weighing between 18-22g, provided by Jiangsu Airingfei Biotechnology Co., Ltd. All mice were initially placed in a constant temperature and humidity environment (22-25℃, 50%-60% relative humidity, 12h light / 12h dark) for 7 days for acclimatization. During this period, the mice were provided with free access to food and water.

[0062] Before modeling, all mice were deeply anesthetized by intraperitoneal injection of sodium pentobarbital at a dose of 50 mg / kg. After the anesthesia took full effect, the mouse head was fixed and its mouth was kept open. A longitudinal incision of about 1 cm was made on the buccal margin of the gingiva next to the first molar on the left buccal mucosa of the mouse. The subcutaneous tissue was carefully dissected to fully expose the infraorbital nerve. The nerve was loosely ligated with 4-0 medical absorbable sutures (two ligatures, about 1 mm apart). The ligation criteria were: under a surgical microscope, the ligation should cause a slight reduction in the diameter of the nerve (about 1 / 3 reduction), and congestion of the epineurium veins, but without complete occlusion of blood flow. The incision was then sutured to complete the modeling process. In the control group (9 mice), only the nerve was exposed, and no nerve ligation was performed.

[0063] Mice that successfully developed the model were randomly divided into the following groups using a random number table: model group, Examples 1-3, Comparative Examples 1-12, and matrix control group, with 9 mice in each group. Mice in each group were housed separately, and hair was removed from the left infraorbital nerve projection area (1.0cm × 1.0cm) of the cheek. After acclimatization for 1 day, drug intervention was initiated.

[0064] Traditional Chinese Medicine Intervention Group: For Examples 1-3 and Comparative Examples 1-12, the corresponding traditional Chinese medicine compound preparation was applied to the hair removal area on the left cheek at a dosage of 11 mg / cm², covering an area of ​​1 cm². 2 Administer three times daily.

[0065] Sham-operated group and model group: Mice in the sham-operated group and model group were not given drug intervention.

[0066] Matrix control group: The same amount of gel preparation as the traditional Chinese medicine intervention group was applied.

[0067] All interventions lasted for 14 days, after which indicators were measured.

[0068] The detection method is as follows: Mice were placed in a transparent observation box with a mesh floor. After the mice adapted to the environment and their condition stabilized, an electronic von Frey pain threshold meter was used for testing. During the test, the stimulation pressure was gradually increased from low to high intensity, applied vertically to the whisker pad area on the surgical side (left side) of the mouse. The minimum pressure value that could induce a rapid withdrawal of the paw, avoidance, or head shaking pain response in the mouse was recorded. This value is the mechanical pain threshold. To ensure the reliability of the test results, the judgment criterion was set as follows: in 5 consecutive stimulations, at least 3 clear pain responses should be induced at the same pressure value. The specific experimental results are shown in Table 2.

[0069] Table 2

[0070]

[0071] Table 2 compares the mechanical pain thresholds of mice in Examples 1-3 and Comparative Examples 1-12. The results show that the nerves in the sham-operated group were undamaged, and the pain transmission function was normal. In the model group, after infraorbital nerve ligation, nerve structure damage led to extreme pain sensitization, and the mechanical pain threshold was significantly lower than that in the sham-operated group, indicating that the trigeminal neuralgia model was successfully established. Compared with the model group, the matrix control group showed no significant changes; Examples 1-3 and Comparative Examples 1-12 all showed varying degrees of improvement; the improvement effect in Examples 1-3 was significantly higher than that in Comparative Examples 1-12, indicating that the herbal preparation of this invention has an effect on improving trigeminal neuralgia.

[0072] Study 3: Research on the antipruritic efficacy of traditional Chinese medicine compound preparations

[0073] The experimental animals were female Balb / c mice, weighing between 18-22g, provided by Jiangsu Airingfei Biotechnology Co., Ltd. All mice were placed in a constant temperature and humidity environment of 22-25℃, 40%-50% relative humidity, with alternating 12h light / 12h dark conditions for 7 days for acclimatization. During this period, the mice were provided with free access to food and water.

[0074] Before modeling, all mice underwent dorsal shaving and were randomly grouped using a random number table into four groups: a control group, a model group, Examples 1-3, Comparative Examples 1-12, and a matrix control group, with nine mice in each group. After shaving, except for the control group, all other groups of mice had 200 μL of 1% DNCB-acetone-olive oil solution (acetone to olive oil volume ratio 3:1) applied to their backs for four consecutive days. Starting on day 6, 200 μL of 0.5% DNCB-acetone-olive oil solution was applied, followed by applications every other day until day 18. The model was considered successfully established when obvious scaling, erythema, and other typical atopic dermatitis-like manifestations were observed on the back skin of the mice.

[0075] Drug intervention began on day 5 of the experiment, including: Traditional Chinese medicine intervention group: For example groups 1-3 and comparative groups 1-12, the corresponding traditional Chinese medicine compound preparations were applied to the affected skin at a dose of 11 mg / cm², covering an area of ​​2 cm², and administered 3 times daily.

[0076] Control group and model group: Mice in the control group and model group were not given drug intervention.

[0077] Matrix control group: The same amount of gel preparation as the traditional Chinese medicine intervention group was applied.

[0078] All interventions lasted for 14 days, after which testing was conducted.

[0079] Scratching frequency statistics: Mice in each group were placed in independent transparent observation cages and allowed to acclimatize to the environment for 15 minutes to eliminate stress response. The number of scratching behaviors on the ear and back lesions was then continuously observed and recorded within 10 minutes. The experimental results are shown in Table 3 and... Figure 3 As shown.

[0080] Table 3

[0081]

[0082] Table 3 shows that mice in the blank group scratched very little under normal, undisturbed conditions. After the atopic dermatitis model was induced by DNCB, the model group showed typical inflammatory reactions and obvious itching symptoms, with a significant increase in the number of scratches within 10 minutes. Compared with the model group, the matrix control group showed no significant changes. Groups 1-3 of Examples and Groups 1-12 of Comparative Examples all reduced the number of scratches to varying degrees, but the effects were significantly different. Among them, Groups 1-12 of Comparative Examples could only reduce the number of scratches to a limited extent due to the lack of raw materials, insufficient auxiliary components, or process defects, and the antipruritic effect was not good. However, Groups 1-3 of Examples, with their complete raw material composition, optimized preparation process, and synergistic anti-inflammatory and antipruritic effects among the components, significantly reduced the number of scratches on the lesion area by mice, and showed a gradual improvement trend. This fully demonstrates that the traditional Chinese medicine compound preparations prepared in Examples 1-3 have a clear antipruritic effect and can effectively relieve the itching symptoms caused by atopic dermatitis.

[0083] The above-described embodiments are merely illustrative of specific implementations of the present invention, and while the descriptions are detailed, they should not be construed as limiting the scope of protection of the present invention. It should be noted that for those skilled in the art, any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention should be considered equivalent substitutions and are included within the scope of protection of the present invention.

Claims

1. A topical traditional Chinese medicine compound preparation for relieving postherpetic neuralgia and trigeminal neuralgia, characterized in that: The traditional Chinese medicine compound preparation comprises, by mass percentage: Active ingredients: Corydalis rhizome 1.5-2.0%, Zaocys dhumnades 1.0-1.5%, Ligusticum chuanxiong rhizome 0.8-1.2%, Paeonia lactiflora rhizome 0.8-1.2%, Prunella vulgaris rhizome 0.8-1.2%, Zanthoxylum bungeanum rhizome 0.4-0.6%, Menthol 0.4-0.6%, Borneol 0.2-0.4%; Excipients: Carbomer 940 0.8-1.0%, pharmaceutical grade glycerin 15-20%, choline chloride in an equimolar amount with menthol, triethanolamine as a pH adjuster to adjust the pH to 6.1-6.3, disodium edetate 0.05-0.1%; Purified water: Add to 100%.

2. The traditional Chinese medicine compound preparation for external use to relieve postherpetic neuralgia and trigeminal neuralgia according to claim 1, characterized in that: The Corydalis Rhizome, Ligusticum Rhizome, White Peony Root, and Summer Pepper were prepared using a compound plant enzymatic hydrolysis-ethanol synergistic extraction process. Specifically, the ingredients were first pretreated with a compound plant enzyme consisting of cellulase and β-glucosidase, and then extracted with 70% ethanol. The concentration of cellulase was 2000-2500 U / g based on substrate, and the concentration of β-glucosidase was 600-800 U / g based on substrate.

3. The traditional Chinese medicine compound preparation for external use to relieve postherpetic neuralgia and trigeminal neuralgia according to claim 1, characterized in that: The *Zaocys dhumnades* was subjected to hydrolysis treatment with a complex protease; the complex protease consisted of a medium-alkaline protease and a flavor protease, wherein the concentration of the medium-alkaline protease was 10,000-12,000 U / g based on the *Zaocys dhumnades* raw material, and the concentration of the flavor protease was 800-1,000 U / g based on the *Zaocys dhumnades* raw material.

4. The traditional Chinese medicine compound preparation for external use to relieve postherpetic neuralgia and trigeminal neuralgia according to claim 1, characterized in that: The Sichuan pepper is subjected to supercritical CO2 extraction coupled with alcohol extraction, specifically: the Sichuan pepper is first extracted with supercritical fluid to obtain volatile oil, and the residue is then extracted with ethanol to obtain Sichuan pepper alcohol extract.

5. The traditional Chinese medicine compound preparation for external use to relieve postherpetic neuralgia and trigeminal neuralgia according to claim 1, characterized in that: The specific preparation method of menthol and equimolar choline chloride is as follows: Weigh 4-6g of menthol dried under vacuum to a moisture content ≤0.1%, and place it together with equimolar choline chloride dried under vacuum to a moisture content ≤0.3% in a reaction flask that has been preheated at 120℃ for 2 hours to remove water. Nitrogen gas is introduced at a flow rate of 5mL / min for protection throughout the process. The mixture is then magnetically stirred at 300r / min for 45 minutes in a 65℃ water bath to form a homogeneous and transparent liquid. The mixture is then cooled to 40℃ to obtain the choline chloride-menthol deep eutectic solvent penetration enhancer.

6. A method for preparing a topical traditional Chinese medicine compound preparation for relieving postherpetic neuralgia and trigeminal neuralgia as described in any one of claims 1-5, characterized in that: The specific preparation method of the preparation, based on the amount of 1000g of formulation, includes: Step 1: Weigh out 15-20g of Corydalis Rhizome, 8-12g of Ligusticum Rhizome, 8-12g of White Peony Root, and 8-12g of Summer Pepper. Mix the above herbs evenly and grind them to 50 mesh to obtain plant powder. Weigh out 10-15g of Zaocys dhumnades and grind them to 80 mesh to obtain Zaocys dhumnades powder. Weigh out 4-6g of Sichuan pepper and grind it to 50 mesh to obtain Sichuan pepper powder. Step 2: Place the plant powder into the extraction tank, add pH 4.8 sodium acetate buffer, and add compound plant enzymes under stirring conditions of 50℃ and 300-350r / min. The enzymatic reaction is carried out for 3 hours. Then, the liquid is heated to 92℃ and kept at this temperature for 15 minutes to inactivate the enzymes. Add 6 times the amount of 70% ethanol solution, adjust the temperature to 65℃, and perform dynamic cyclic extraction twice, 2 hours each time. The extract is then filtered through a plate and frame filter press with a 200-mesh filter cloth. The two filtrates are combined to obtain the plant extract. Step 3: Place the fine powder of *Zaocys dhumnades* in a reaction vessel, add purified water at 50℃, adjust the pH value to 7.5±0.2 using sodium hydroxide solution, add the complex protease, and hydrolyze by stirring at 200-250 r / min in a 50℃ water bath for 4 hours. Heat the solution to 95℃ and maintain for 10 minutes to inactivate the enzyme. After inactivation, centrifuge at 10000 r / min for 15 minutes and collect the supernatant to obtain the *Zaocys dhumnades* enzyme hydrolysate for later use. Step 4: Add the Sichuan pepper powder to the supercritical CO2 extraction device, set the extraction pressure to 20-25 MPa, the temperature to 45-50℃, the CO2 flow rate to 20-25 L / h, and the extraction time to 2-2.5 h; collect the volatile oil of Sichuan pepper in the separation vessel, add 6-8 times the weight of the extracted residue to 70% ethanol, extract at 40-45℃ for 1 h, filter, and concentrate under reduced pressure until no ethanol remains to obtain the Sichuan pepper alcohol extract; Step 5: Transfer the plant extract to a vacuum concentration tank at 60℃ and a vacuum degree of -0.09MPa, and concentrate it to a relative density of 1.20 to obtain a plant extract. Mix the enzymatic hydrolysate of *Zaocys dhumnades* and the alcohol extract of *Zanthoxylum bungeanum* evenly, and concentrate it to 1 / 5 of the original volume at 65℃ and a vacuum degree of -0.08MPa to obtain a concentrated extract of *Zaocys dhumnades* and *Zanthoxylum bungeanum*. Weigh 4-6g of menthol dried to a moisture content of ≤0.1% under vacuum, and place it together with an equimolar amount of choline chloride dried to a moisture content of ≤0.3% in a reaction flask that has been pre-baked at 120℃ for 2 hours to remove water. Probe nitrogen gas at a flow rate of 5mL / min throughout the process, and stir magnetically at 300r / min for 45 minutes in a 65℃ water bath to form a homogeneous and transparent liquid. Cool the liquid to 40℃ to obtain a choline chloride-menthol deep eutectic solvent penetration enhancer. Step 6: Add 500g of purified water to a mixing tank, and slowly add 8-10g of Carbomer 940 powder while stirring at 300r / min. After the addition is complete, increase the stirring speed to 800r / min and continue stirring for 4 hours until the carbomer is completely swollen into a colorless and transparent gel matrix. Let it stand for 12 hours to allow the gel matrix to fully swell. Dissolve 2-4g of borneol in 5mL of 95% ethanol, add the Sichuan pepper volatile oil obtained in step 4, then add 150-200g of glycerol and 80-100g of purified water. Place the mixture in a high-speed shear emulsifier at 11000r / min. Shear emulsification at 100 rpm for 5-8 min to form an emulsion. Mix the emulsion with the aforementioned plant extract, concentrated extracts of Zaocys dhumnades and Zanthoxylum bungeanum, and choline chloride-menthol deep eutectic solvent and penetration enhancer. Add the mixture to the carbomer matrix at 500 rpm and adjust the pH to 6.2 ± 0.1 with 10% triethanolamine solution. Add 0.5-1 g of disodium edetate and add purified water to a total weight of 1000 g. Transfer the mixture to a homogenizer and homogenize at -0.06 MPa for 15 min to obtain a uniform texture and brownish-yellow color gel formulation.

7. The method for preparing a topical traditional Chinese medicine compound preparation for relieving postherpetic neuralgia and trigeminal neuralgia according to claim 6, characterized in that: In the second step, the amount of pH 4.8 sodium acetate buffer added during the enzymatic hydrolysis of the plant powder is 10 times the weight of the plant powder.

8. The method for preparing a topical traditional Chinese medicine compound preparation for relieving postherpetic neuralgia and trigeminal neuralgia according to claim 6, characterized in that: In the third step, the amount of purified water added during the enzymatic hydrolysis of *Zaocys dhumnades* is 15 times the amount of fine *Zaocys dhumnades* powder.

9. The method for preparing a topical traditional Chinese medicine compound preparation for relieving postherpetic neuralgia and trigeminal neuralgia according to claim 6, characterized in that: In the third step, the concentration of sodium hydroxide is 0.1 mol / L.

10. The method for preparing a topical traditional Chinese medicine compound preparation for relieving postherpetic neuralgia and trigeminal neuralgia according to claim 6, characterized in that: In the fourth step, ethanol is added at a rate of 8 times the weight of the medicinal residue during alcohol extraction.

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