A traditional Chinese medicine composition for treating herpes, and a preparation method and application thereof

Abstract

This invention discloses a traditional Chinese medicine composition for the prevention and / or treatment of herpes and / or its complications. By weight, the composition comprises: 8-14 parts of Sophora flavescens, 5-11 parts of Bistorta officinalis, 9-15 parts of Rheum palmatum, 0.5-6 parts of Coptis chinensis, 1-7 parts of Forsythia suspensa, 1-7 parts of Taraxacum mongolicum, 1-7 parts of Viola yedoensis, 1-7 parts of Paeonia lactiflora, 1-7 parts of Paeonia suffruticosa, 1-7 parts of Gardenia jasminoides, 3-9 parts of Rehmannia glutinosa, 1-7 parts of Chrysanthemum indicum, 1-7 parts of Lonicera japonica, 1-7 parts of Atractylodes lancea, 0.5-6 parts of Phellodendron chinense, 0.5-1.5 parts of Cicadae periostracum, 2-8 parts of Smilax glabra, 1-7 parts of Anemarrhena asphodeloides, 1-7 parts of Ophiopogon japonicus, 0.5-6 parts of Alisma plantago-aquatica, and 1-7 parts of Gypsum fibrosum. The complications are pain and / or inflammation. This traditional Chinese medicine composition is safe, effective, and has a simple and efficient preparation method with controllable quality. It also exhibits significant analgesic and anti-inflammatory effects and can treat shingles and its sequelae.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to a traditional Chinese medicine composition for treating herpes, its preparation method, and its application. Background Technology

[0002] Herpes, such as herpes zoster, is an acute infectious skin disease caused by the varicella-zoster virus (VZV). After infection, clusters of blisters appear along a nerve distribution, often occurring suddenly, usually unilaterally, and frequently accompanied by neuralgia. Viral infection can cause chickenpox outbreaks in susceptible populations. Clinically, the common manifestations are chickenpox and herpes zoster; chickenpox is more common in children, while herpes zoster is more common in adults, especially the elderly. Factors that trigger herpes zoster include local trauma, acute and chronic infectious diseases, and poisoning. Postherpetic neuralgia is a viral pathological pain that occurs after the blisters have disappeared following infection with the varicella-zoster virus, often with recurrence.

[0003] Currently, commonly used antiviral drugs for treating shingles include acyclovir, valacyclovir, and famciclovir, all of which possess unique antiviral effects. After entering cells infected with the varicella-zoster virus, acyclovir is phosphorylated to activated acyclovir triphosphate, interfering with viral DNA polymerase and significantly inhibiting viral replication. Acyclovir is widely used as a classic drug for treating varicella-zoster virus, but it also has many drawbacks, such as significant side effects, poor oral absorption, short half-life, and the need for multiple doses, leading to poor patient compliance and affecting clinical efficacy.

[0004] Traditional Chinese medicine (TCM) believes that shingles is mostly caused by emotional distress and dietary imbalances, leading to impaired spleen function, internal accumulation of dampness and turbidity, which transforms into heat, and the combination of dampness and heat with the invasion of pathogenic factors. Elderly individuals are often weak, and damp-heat obstructs the skin, disrupts the meridians, and causes qi and blood stagnation, often resulting in persistent pain. TCM treatment typically focuses on eliminating dampness and toxins, clearing the meridians, and relieving pain. However, most commercially available TCM preparations for treating shingles have limited applicability, and their mechanisms of action and pharmacological effects are not well understood.

[0005] Therefore, finding a traditional Chinese medicine that is widely applicable, has good compliance, good efficacy, and few toxic side effects for the prevention and / or treatment of herpes has become an urgent need. Summary of the Invention

[0006] Based on this, the present invention provides a traditional Chinese medicine composition for the prevention and / or treatment of herpes and / or its complications, comprising, by weight: 8-14 parts of Sophora flavescens, 5-11 parts of Bistorta officinalis, 9-15 parts of Rheum palmatum, 0.5-6 parts of Coptis chinensis, 1-7 parts of Forsythia suspensa, 1-7 parts of Taraxacum mongolicum, 1-7 parts of Viola yedoensis, 1-7 parts of Paeonia lactiflora, 1-7 parts of Paeonia suffruticosa, 1-7 parts of Gardenia jasminoides, 3-9 parts of Rehmannia glutinosa, 1-7 parts of Chrysanthemum indicum, 1-7 parts of Lonicera japonica, 1-7 parts of Atractylodes lancea, 0.5-6 parts of Phellodendron chinense, 0.5-1.5 parts of Cicadae periostracum, 2-8 parts of Smilax glabra, 1-7 parts of Anemarrhena asphodeloides, 1-7 parts of Ophiopogon japonicus, 0.5-6 parts of Alisma plantago-aquatica, and 1-7 parts of Gypsum fibrosum, wherein the complications are pain and / or inflammation.

[0007] In this invention, when proportions, equivalents, temperatures, concentrations, times, mesh counts, parts by weight, weight ratios, or other values ​​or parameters are expressed as ranges, preferred ranges, or a series of upper and lower preferred values, this should be understood as specifically disclosing all ranges formed by any pairing of any upper or preferred value with any lower or preferred value, regardless of whether the range is disclosed individually. For example, when the range "1-7" is disclosed, the described range should be interpreted as including ranges "1-7", "1-6", "1-5", "1-4", "1-3", "1-2", "2-7", "2-6", "2-5", "2-4", "2-3", "3-7", "3-6", "3-5", "3-4", "4-7", "4-6", "4-5", "5-7", "5-6", and "6-7", etc.; when the range "8-14" is disclosed, The described ranges should be interpreted as including the ranges “8–14”, “8–13”, “8–12”, “8–11”, “8–10”, “8–9”, “9–14”, “9–13”, “9–12”, “9–11”, “9–10”, “10–14”, “10–13”, “10–12”, “10–11”, “11–14”, “11–13”, “11–12”, “12–14”, “12–13”, and “13–14”, etc. When numerical ranges are described herein, unless otherwise stated, the range is intended to include its endpoints and all integers and fractions within that range, and all values ​​within that range are sufficient to achieve the effects of this invention.

[0008] Further, by weight, the traditional Chinese medicine composition includes: 9-13 parts of Sophora flavescens, 6-10 parts of Bistorta officinalis, 10-14 parts of Rheum palmatum, 1-5 parts of Coptis chinensis, 2-6 parts of Forsythia suspensa, 2-6 parts of Taraxacum mongolicum, 2-6 parts of Viola yedoensis, 2-6 parts of Paeonia lactiflora, 2-6 parts of Paeonia suffruticosa, 2-6 parts of Gardenia jasminoides, 4-8 parts of Rehmannia glutinosa, 2-6 parts of Chrysanthemum indicum, 2-6 parts of Lonicera japonica, 2-6 parts of Atractylodes lancea, 1-5 parts of Phellodendron chinense, 0.5-2 parts of Cicadae periostracum, 3-7 parts of Smilax glabra, 2-6 parts of Anemarrhena asphodeloides, 2-6 parts of Ophiopogon japonicus, 1-5 parts of Alisma plantago-aquatica, and 2-6 parts of Gypsum fibrosum.

[0009] Furthermore, by weight, the traditional Chinese medicine composition includes: approximately 11 parts of Sophora flavescens, approximately 8 parts of Bistorta officinalis, approximately 12 parts of Rheum palmatum, approximately 3 parts of Coptis chinensis, approximately 4 parts of Forsythia suspensa, approximately 4 parts of Taraxacum mongolicum, approximately 4 parts of Viola yedoensis, approximately 4 parts of Paeonia lactiflora, approximately 4 parts of Paeonia suffruticosa, approximately 4 parts of Gardenia jasminoides, approximately 6 parts of Rehmannia glutinosa, approximately 4 parts of Chrysanthemum indicum, approximately 4 parts of Lonicera japonica, approximately 4 parts of Atractylodes lancea, approximately 3 parts of Phellodendron chinense, approximately 1 part of Cicadae periostracum, approximately 5 parts of Smilax glabra, approximately 4 parts of Anemarrhena asphodeloides, approximately 4 parts of Ophiopogon japonicus, approximately 3 parts of Alisma plantago-aquatica, and approximately 4 parts of Gypsum fibrosum.

[0010] In this invention, "about" refers to a value within a range of ±5% of a specific value. For example, "about 3" includes ±5% of 3, or from 2.85 to 3.15; "about 4" includes ±5% of 4, or from 3.8 to 4.2; "about 1" includes ±5% of 1, or from 0.95 to 1.05; "about 5" includes ±5% of 5, or from 4.75 to 5.25; "about 6" includes ±5% of 6, or from 5.7 to 6.3; "about 12" includes ±5% of 12, or from 11.4 to 12.6; "about 11" includes ±5% of 11, or from 10.45 to 11.55; and "about 8" includes ±5% of 8, or from 7.6 to 8.4.

[0011] Further, by weight, the traditional Chinese medicine composition comprises: 10.45–11.55 parts of Sophora flavescens, 7.6–8.4 parts of Bistorta officinalis, 11.4–12.6 parts of Rheum palmatum, 2.85–3.15 parts of Coptis chinensis, 3.8–4.2 parts of Forsythia suspensa, 3.8–4.2 parts of Taraxacum mongolicum, 3.8–4.2 parts of Viola yedoensis, 3.8–4.2 parts of Paeonia lactiflora, 3.8–4.2 parts of Paeonia suffruticosa, and 3.8–4.2 parts of Gardenia jasminoides. 4.2 parts, Rehmannia glutinosa 5.7–6.3 parts, Chrysanthemum indicum 3.8–4.2 parts, Lonicera japonica 3.8–4.2 parts, Atractylodes lancea 3.8–4.2 parts, Phellodendron chinense 2.85–3.15 parts, Cicadae periostracum 0.95–1.05 parts, Smilax glabra 4.75–5.25 parts, Anemarrhena asphodeloides 3.8–4.2 parts, Ophiopogon japonicus 3.8–4.2 parts, Alisma plantago-aquatica 2.85–3.15 parts, and Gypsum fibrosum 3.8–4.2 parts.

[0012] Furthermore, the gardenia is stir-fried gardenia. Furthermore, the rehmannia is raw rehmannia. Furthermore, the atractylodes is stir-fried atractylodes with wheat bran. Furthermore, the gypsum is raw gypsum.

[0013] Furthermore, the pain is postherpetic neuralgia.

[0014] Furthermore, the traditional Chinese medicine composition is further used in combination with one or more drugs and / or extracts used for the prevention and / or treatment of herpes. Further, the drug is selected from one or more of the following: antiviral drugs, anti-inflammatory drugs, analgesics, and neurotrophic drugs. Further, the antiviral drug is selected from one or more of the following: acyclovir, valacyclovir, penciclovir, famciclovir, ganciclovir, valganciclovir, brivudine, and sodium phosphonate. Further, the anti-inflammatory drug is prednisone. Further, the analgesic is selected from one or more of the following: tramadol, morphine, oxycodone, pregabalin, and gabapentin. Further, the neurotrophic drug is selected from one or more of the following: methylcobalamin, vitamin B1, and vitamin B12.

[0015] The one or more drugs and / or extracts for the prevention and / or treatment of herpes and / or its complications claimed in this invention are not limited to the drugs listed above, but may also include other types of drugs for the prevention and / or treatment of herpes and / or its complications, as well as effective ingredients of traditional Chinese medicine, etc.

[0016] According to another aspect of the present invention, a formulation comprising the above-described traditional Chinese medicine composition is provided.

[0017] Further, the formulation includes one or more pharmaceutically acceptable excipients. Further, the excipients are selected from one or more of the following: binders, preservatives, and flavoring agents. Further, the binder is selected from one or more of the following: water, 5% starch paste, 10% starch paste, rice wine, vinegar, sugar solution, and an aqueous solution containing less than 5% refined honey. Further, the binder is water. Further, the dosage form of the formulation is an oral preparation, such as pills.

[0018] The excipients and formulations described above in this invention are merely illustrative examples and are not limited to those examples. Any excipient that can be mixed with the traditional Chinese medicine composition of this invention is within the scope of protection claimed by this invention.

[0019] According to another aspect of the present invention, a method for preparing the above-mentioned traditional Chinese medicine composition is provided, the method comprising: weighing appropriate amounts of Sophora flavescens, Bistorta officinalis, Rheum palmatum, Coptis chinensis, Forsythia suspensa, Taraxacum mongolicum, Viola yedoensis, Paeonia lactiflora, Paeonia suffruticosa, Gardenia jasminoides, Rehmannia glutinosa, Chrysanthemum indicum, Lonicera japonica, Atractylodes lancea, Phellodendron chinense, Cicadae periostracum, Smilax glabra, Anemarrhena asphodeloides, Ophiopogon japonicus, Alisma plantago-aquatica, and Gypsum fibrosum; mixing for the first time; drying for the first time; pulverizing for the first time; mixing for the second time; sterilizing; drying for the second time; pulverizing for the second time to obtain the traditional Chinese medicine composition.

[0020] Of these, the 21 medicinal materials mentioned above were sourced from the market and have all been identified as appropriate medicinal materials. Among them, Sophora flavescens and Bistorta officinalis are the principal herbs, rhubarb, Coptis chinensis slices and Forsythia suspensa are the assistant herbs, and the remaining sixteen herbs are the adjuvant herbs.

[0021] According to another aspect of the present invention, a method for preparing the above-mentioned preparation is provided, the method comprising: mixing the above-mentioned traditional Chinese medicine composition with an appropriate amount of excipients for a third time, forming into pills, drying for a third time, adding a polishing agent such as white beeswax, and optionally dispensing to obtain the preparation.

[0022] Further, the excipient is selected from one or more of the following: binder, preservative, and flavoring agent. Further, the binder is selected from one or more of the following: water, 5% starch paste, 10% starch paste, rice wine, vinegar, sugar solution, or an aqueous solution containing less than 5% refined honey. Further, the binder is water. Further, the ratio of the herbal composition to the binder is 1:0.7 to 0.8, for example, about 1:0.75. Further, the refining time for making the pills is 15 to 25 minutes, for example, about 20 minutes. Further, the forming time for making the pills is 5 to 15 minutes, for example, about 10 minutes. Further, the polishing agent is selected from one or more of the following: paraffin wax, white beeswax, and PEG6000. Further, the amount of polishing agent added is 0.1% to 1% of the weight of the pills.

[0023] Furthermore, the method includes any one or more of the following items [1] to

[11] :

[0024] [1] The first mixing and / or the second mixing and / or the third mixing is carried out by sieving or stirring, for example, stirring; [2] The time for the first mixing and / or the second mixing and / or the third mixing is 20-40 min, for example, about 30 min; [3] The sterilization method is dry heat sterilization, moist heat sterilization, cobalt-60 irradiation sterilization and / or ethanol sterilization, for example, moist heat sterilization; [4] The sterilization time is 10-40 min, for example, about 30 min; [5] The temperature of the moist heat sterilization method is 110-135℃, for example, about 127℃; [6] The thickness of the material for the moist heat sterilization method is 1-3 cm, for example, about 2 cm; [7] The first drying is performed at 40-60°C for 8-12 hours, for example, at 50-55°C for about 10 hours; [8] The second drying is performed at 70-90°C for 0.5-1.5 hours, for example, at 75-85°C for about 1 hour; [9] The first pulverization is performed by coarsely crushing with a 60-80 mesh sieve and then pulverizing with a 100-150 mesh sieve, for example, by coarsely crushing with a 60 mesh sieve and then pulverizing with a 100 mesh sieve;

[10] The second pulverization is performed by pulverizing with a 100-150 mesh sieve, for example, by pulverizing with a 100 mesh sieve;

[11] The third drying is performed at 70-90°C for 3-5 hours, for example, at about 80°C for about 4 hours.

[0025] According to another aspect of the present invention, there is provided the use of the above-described traditional Chinese medicine composition or the above-described preparation in the preparation of food, medicine and / or health products for the prevention and / or treatment of herpes and / or its complications, the complications being pain and / or inflammation.

[0026] The terms “food,” “health product,” “food product,” “health product,” “health composition,” or “food composition” in this invention mean a product or composition intended to be ingested by an animal (including a human) and to provide that animal with nutrition or health benefits.

[0027] According to another aspect of the present invention, the above-described traditional Chinese medicine composition or preparation is provided for the prevention or treatment of herpes and / or its complications in a subject.

[0028] According to another aspect of the present invention, a method for preventing or treating herpes and / or its complications in a subject is provided, comprising administering to the subject an effective amount of the above-described traditional Chinese medicine composition or the above-described preparation.

[0029] In this invention, the terms "subject," "individual," or "patient" are used interchangeably and refer to a vertebrate, preferably a mammal. The mammal may be a human, a non-human primate, a mouse, a rat, a dog, a cat, a horse, or a cow, but is not limited to these examples. Mammals other than humans can advantageously be used as subjects representing models of herpes and / or its complications. Preferably, the subject is a human. Such subjects typically suffer from or are susceptible to a condition that can be prevented or treated by administration of the above-described traditional Chinese medicine composition or preparation of this invention.

[0030] The "effective amount" of the above-described traditional Chinese medicine composition or preparation used in this invention can achieve the desired therapeutic and / or preventive effects. The effective amount for this purpose will depend on factors such as the route of delivery, the activity of the specific active substance or preparation used, the type of herpes and / or its complications, the stage and severity of the disease being treated, the individual's weight and overall health status, and the prescribing physician's judgment. Dosage can be administered once a week, twice a week, once a day, or even several times a day. Dosage units can be administered over a short period (e.g., weeks to months) or a longer period (months to years). "Effective amount" specifically refers to the amount of the above-described traditional Chinese medicine composition or preparation that imparts a therapeutic effect (e.g., control, relief, improvement, mitigation, or slowing of progression) or prevents (e.g., delaying onset or reducing the risk of development) of a disease, condition, or symptom or its symptoms to the treated subject.

[0031] Furthermore, the herpes is virus-induced herpes. Furthermore, the pain is acute or chronic, such as postherpetic neuralgia. Furthermore, the pain is peripheral or central. Furthermore, the inflammation is specific or nonspecific. Furthermore, the inflammation is acute or chronic. Furthermore, the virus is selected from one or more of the following: herpes simplex virus type 1, herpes simplex virus type 2, varicella-zoster virus, human cytomegalovirus, Epstein-Barr virus, human herpesvirus type 6, human herpesvirus type 7, and human herpesvirus type 8.

[0032] The beneficial effects of this invention are:

[0033] The traditional Chinese medicine composition of this application is safe, effective, and has a simple and efficient preparation method with controllable quality. It also exhibits significant analgesic and anti-inflammatory effects and can treat shingles and its sequelae. Attached Figure Description

[0034] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying 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 exceeding the scope of protection claimed by the present invention.

[0035] Figure 1 This is a flowchart illustrating the preparation process of the formulation of this application. Detailed Implementation

[0036] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0037] The singular forms “a,” “an,” and “the” used in the specification and appended claims include plural indicators unless the context clearly specifies otherwise.

[0038] Unless otherwise stated, all technical and scientific terms and abbreviations used herein have the meanings commonly understood by one of ordinary skill in the field of this invention or the field of application of such terms. While any methods, conditions, substances, or materials similar to or equivalent to those disclosed herein may be used in the practice of this invention, preferred methods, conditions, substances, or materials are described herein.

[0039] In this invention, the term "comprising" and "including" are synonymous. The terms "comprising," "including," "having," "containing," or any other variations thereof as used herein are intended to cover a non-exclusive inclusion. For example, a composition, step, method, article, or apparatus that includes the listed elements is not necessarily limited to those elements, but may include other elements not expressly listed or elements inherent to such a composition, step, method, article, or apparatus.

[0040] Example

[0041] Example 1: Screening of Preparation Process Route

[0042] 1.1 Processing Technology for the Preparation of Traditional Chinese Medicine Compositions

[0043] 1.1.1 First Investigation of Drying Process

[0044] Because the medicinal materials used in this application contain a large amount of fiber and sugar, direct pulverization results in high viscosity, which is not conducive to pulverization and sieving. Therefore, a mixed pulverization method is adopted to ensure that the medicinal materials can be smoothly pulverized and sieved. The medicinal materials were first dried. Considering that the medicinal materials used in this application may contain volatile and heat-sensitive components, a low-temperature drying temperature of 50–55℃ was selected. Drying was carried out for 0 h, 5 h, 10 h, and 15 h respectively, followed by pulverization, and the pulverization effect was observed. The results are shown in Table 1.

[0045] Table 1. Statistical table of drying time investigation results

[0046]

[0047] The results showed that without drying, the medicinal slices were difficult to pulverize and sieve, and the particle size data did not meet the requirements for powder preparation. After drying for 5 to 15 hours, pulverization and sieve preparation were relatively smooth, and the particle size data basically met the requirements for powder preparation. However, the particle size data after drying for 5 hours was of high risk. In view of the above, considering the impact of energy consumption, it was determined that the medicinal slices of this application should be dried at a low temperature of 50 to 55℃ for 10 hours before pulverization.

[0048] 1.1.2 Examination of the mesh size of the crushing sieve

[0049] The mesh size of the sieve affects the powder yield of the medicinal slices, which in turn affects the product yield. Therefore, the effects of sieve mesh sizes of 100, 120, and 150 on the powder yield and appearance uniformity were investigated. Given the large size of the medicinal slice prescription in this application, and the high sugar content of some ingredients, repeated pulverization would increase viscosity, which is unfavorable for industrial production. Furthermore, since there are no expensive, rare, highly toxic, or extremely toxic medicinal materials, considering ease of operation and energy conservation, the ingredients were mixed before pulverization. Because direct pulverization into fine powder is difficult, it was first coarsely pulverized at 60 mesh before further pulverization. Each portion of the medicinal slices was weighed according to the prescription ratio, 100g per portion, divided into three parallel portions. After coarse pulverization at 60 mesh, the following sieve mesh sizes were used for pulverization and sieving: ① Pulverized, 100 mesh sieve; ② Pulverized, 120 mesh sieve; ③ Pulverized, 150 mesh sieve. The ease of sieving was observed, and the initial powder yield was calculated. The results are shown in Table 2.

[0050] Table 2 Statistical Table of Grinding Screen Mesh Count Investigation Results

[0051]

[0052] Note: Powder yield (%) = Weight of powder after pulverization and sieving / Weight of medicinal slices before pulverization and sieving × 100%.

[0053] The results showed that the sieving process was easier with 100-mesh and 120-mesh sieves than with 150-mesh sieves; the powder yield was higher with 100-mesh sieves than with 120-mesh sieves than with 150-mesh sieves; and the uniformity and particle size of the powder sieved at all sieve mesh sizes met the requirements. Since the medicinal materials used in this application do not contain expensive, rare, highly toxic, or extremely toxic herbs, considering ease of operation and energy conservation, the pulverization method for the medicinal materials used in this application was determined to be pulverization after mixing the medicinal materials. Based on the ease of operation and powder yield, the medicinal materials used in this application were dried at a low temperature of 55℃ for 10 hours before pulverization, using a 100-mesh sieve.

[0054] 1.1.3 Combined Investigation

[0055] Since the active ingredients of the medicinal materials in this application include both phenolic acids and alkaloids, uneven mixing may affect the results of the sterilization process evaluation. Therefore, the uniformity of the mixture of the samples was evaluated before sterilization.

[0056] 1.1.3.1 Investigation of Hybrid Approach

[0057] The most commonly used methods for mixing Chinese herbal medicine powders are sieving and stirring. Therefore, this study investigated the effects of sieving and stirring on the uniformity of mixing the medicinal herb powders in this application. The preparation methods for each test sample are as follows:

[0058] Sieve analysis method: Weigh the Chinese herbal medicine slices according to the prescription ratio, crush them, pass the powder through a 100-mesh sieve, and take samples according to the ten-point method;

[0059] Stirring method: Weigh the Chinese herbal medicine pieces according to the prescription ratio, crush them, mix for 30 minutes, and take samples according to the ten-point method.

[0060] The uniformity of mixing was examined using appearance uniformity and characteristic spectrum as evaluation indicators.

[0061] Feature map:

[0062] Determined by high performance liquid chromatography (General Chapter 0512, Chinese Pharmacopoeia 2015).

[0063] Chromatographic conditions and system suitability tests were performed using octadecylsilane-bonded silica gel as the stationary phase (Thermo Fisher Scientific Hypersil GOLD, 4.6 mm × 250 mm, 5 μm or equivalent column); acetonitrile was used as mobile phase A, and 0.1% phosphoric acid solution (containing 0.15% triethylamine) was used as mobile phase B, with gradient elution performed according to the specifications in Table 3; the column temperature was 20 °C; the flow rate was 0.8 mL / min; and the detection wavelength was 290 nm. The theoretical plate number, calculated based on the berberine hydrochloride peak, should be no less than 50,000.

[0064] Table 3 Gradient elution conditions for feature maps

[0065]

[0066]

[0067] Preparation of reference solution: Take appropriate amounts of chlorogenic acid reference standard, forsythoside A reference standard, astilbene reference standard, palmatine hydrochloride reference standard, berberine hydrochloride reference standard, scutellarin reference standard, paeonol reference standard, rhein reference standard, and atractylodes reference standard, accurately weigh them, and add methanol to prepare a mixed solution containing 0.1 mg of each per ml.

[0068] Preparation of the test solution: Take 6g of the medicinal material powder of this application, accurately weigh it, place it in a stoppered conical flask, accurately add 50ml of methanol, stopper tightly, weigh it, heat under reflux for 60 minutes, remove it, cool it, weigh it again, make up the weight loss with methanol, shake well, filter it, and take the filtrate to obtain the test solution.

[0069] Assay: Accurately pipette 10 μl each of the reference solution and the test solution into the liquid chromatograph, measure and record the chromatogram after 105 minutes.

[0070] The chromatogram of the test sample should contain 11 characteristic peaks, of which 9 peaks should have the same retention time as the corresponding reference peak. The peak corresponding to the berberine hydrochloride reference peak is designated as the S peak. Calculate the relative retention times of characteristic peaks 2, 6, and 9 with the S peak. The relative retention times of each characteristic peak should be within ±10% of the specified values. The specified values ​​are: 0.50 (peak 2), 1.00 (peak 6), and 1.42 (peak 9).

[0071] The results showed that both mixing methods produced uniform color without patterns or spots, and the characteristic spectra all met the requirements, indicating that both methods could make the medicinal herb powder of this application uniformly mixed. Therefore, considering the ease of operation, the mixing method of the medicinal herb powder of this application was determined to be the stirring method.

[0072] 1.1.3.2 Investigation of Mixing Time Considering that there may be slight deviations in the timing function of the equipment during the production process, the effect of mixing time on mixing uniformity was investigated. Three portions of Chinese herbal medicine slices were weighed according to the prescription ratio, crushed, passed through a 100-mesh sieve, and placed in a trough mixer. They were mixed for 20 minutes, 30 minutes, and 40 minutes respectively. Samples were taken according to the ten-point method, and the appearance uniformity and characteristic spectrum were used as evaluation indicators for measurement.

[0073] The results showed that when the mixing times were 20 minutes, 30 minutes, and 40 minutes, the color was uniform, without any patterns or spots, and the characteristic spectra all met the requirements. This indicates that mixing for 20–40 minutes can ensure uniform mixing of the medicinal material powder in this application. To ensure uniform mixing of large quantities of medicinal powder in production, a mixing time of 30 minutes was determined.

[0074] 1.1.4 Sterilization Examination

[0075] 1.1.4.1 Investigation of sterilization methods

[0076] Traditional Chinese medicine powders can be sterilized using dry heat sterilization, moist heat sterilization, cobalt-60 irradiation sterilization, and ethanol sterilization. Because the medicinal materials used in this application are raw powders containing a significant amount of fiber and other flammable substances, dry heat sterilization is difficult to control the powder's properties and could easily lead to safety accidents. Therefore, dry heat sterilization will not be used for the medicinal materials in this application. Furthermore, the medicinal materials in this application's prescription, including Coptis chinensis, Forsythia suspensa, Taraxacum mongolicum, Cicadae periostracum, Anemarrhena asphodeloides, Ophiopogon japonicus, and Alisma plantago-aquatica, are not listed in the "List of Chinese Herbal Medicines for the Treatment of Herbal Powders" published by the Ministry of Health. 60 The list of Chinese medicinal materials permitted for irradiation is not included in the "Standards for Sterilization Doses of Chinese Herbal Medicines by Co-Irradiation" document. Therefore, the medicinal materials used in this application will not be sterilized by Co-60 irradiation. Only the moist heat sterilization method and the ethanol sterilization method are compared.

[0077] Take 100g of the uniformly mixed powdered medicinal materials of this application, and divide it into 6 parallel portions. Three portions are placed in a moist heat sterilizer, with a layer thickness of 2cm; sterilize at 121℃ for 20 minutes, then dry at 85℃. The other three portions are each sprayed with 25ml of 75% ethanol, stirred evenly, sealed, and left to stand for 48 hours. Then, evaporate the ethanol at 40℃ in a hot air circulating drying oven until no alcohol odor remains, and dry at 85℃. Microbial limits are used as the evaluation index.

[0078] Microbial limit testing results showed that ethanol sterilization was ineffective in killing microorganisms in the powder, and the microbial limits did not meet the requirements; moist heat sterilization was effective in killing microorganisms in the powder, and the microbial limits met the requirements. For safety reasons, moist heat sterilization was chosen as the sterilization method for the medicinal herb powder in this application.

[0079] 1.1.4.2 Investigation of sterilization temperature

[0080] The commonly used temperature for moist heat sterilization is 121℃. Therefore, 121℃ is used as the median value to investigate the effects of sterilization temperatures of 110℃, 121℃, and 127℃, with a material thickness of 2cm and a sterilization time of 20 minutes, on the properties, characteristic spectrum, and microbial limits.

[0081] Take 100g of the evenly mixed powder, divide it into 9 portions, and place them in a moist heat sterilizer. Three portions are spread to a thickness of 2cm and sterilized at 110℃ for 20 minutes; another three portions are spread to a thickness of 2cm and sterilized at 121℃ for 20 minutes; and the last three portions are spread to a thickness of 2cm and sterilized at 127℃ for 20 minutes. Analyze the properties, characteristic chromatograms, and microbial limits of each portion.

[0082] The results showed that sterilization at 110℃, 121℃, and 127℃ for 20 minutes resulted in virtually no loss of the total amounts of aloe-emodin, rhein, emodin, chrysophanol, and emodin methyl ether. The total amounts of matrine and oxymatrine first decreased and then increased with increasing temperature, with the content transfer rate at 127℃ (93.33%–97.95%) > 110℃ (85.64%–88.72%) > 121℃ (70.77%–80.00%), having little impact on the characteristic chromatograms, and all characteristic peaks could be detected. All methods effectively killed microorganisms in the powder, and the microbial limits met the requirements. When the sterilization temperature is 127℃, the loss of each component content is minimal, and oxymatrine is completely converted into matrine, which is beneficial to process stability. Since the medicinal materials in this application are whole powders and have not undergone extraction, there is a significant risk of microbial contamination, especially spores. Furthermore, the sterilization equipment temperature is a range value. Considering that the thickness of the spreading material and the performance of the equipment may differ from those in the laboratory during the later production sterilization process, the more reliable 127℃ was selected as the sterilization temperature. At a sterilization temperature of 127℃, microorganisms, especially spores, are killed more thoroughly, and the impact on the content is within a controllable range. Therefore, the wet heat sterilization temperature for the medicinal material powder in this application is determined to be 127±5℃.

[0083] 1.1.4.3 Examination of sterilization time

[0084] Considering the impact of sterilization time on characteristic spectra and microbial limits, this experiment was conducted at 127℃ with a material thickness of 2cm. Since the commonly used sterilization time for moist heat sterilization is 20 minutes, to ensure the stability of the sterilization effect, the effects of sterilization times of 10 minutes, 20 minutes, and 30 minutes on the powder properties, characteristic spectra, and microbial limits of the medicinal materials in this application were investigated.

[0085] Take 100g of the uniformly mixed medicinal powder of this application, in a total of 9 portions. Place 3 portions in a moist heat sterilizer with a layer thickness of 2cm, sterilize at 127℃ for 10 minutes; place another 3 portions in a moist heat sterilizer with a layer thickness of 2cm, sterilize at 127℃ for 20 minutes; and place another 3 portions in a moist heat sterilizer with a layer thickness of 2cm, sterilize at 127℃ for 30 minutes.

[0086] The results showed that the rhubarb content in the powder remained essentially unchanged at sterilization times of 10, 20, and 30 minutes. The sophora flavescens content increased with increasing time, with similar losses at 20 and 30 minutes. The content transfer rate was lower at 10 minutes (85.08%–87.29%) than at 20 minutes (86.74%–87.84%), and lower at 30 minutes (87.85%–88.40%), likely due to the interconversion of matrine and oxymatrine. The sterilization had little impact on the characteristic chromatograms, and all characteristic peaks were detectable. All sterilization methods effectively killed microorganisms in the powder, and the microbial limits met the requirements. Considering the large volume of material in large-scale production, a sterilization time of 30 minutes was determined to ensure sterilization effectiveness.

[0087] In summary, the sterilization process was determined to be: moist heat sterilization, with a sterilization temperature of 127±5℃ and a sterilization time of 30 minutes.

[0088] 1.1.5 Second Drying Process

[0089] Because the multi-functional Chinese medicine sterilizer has a drying function, it is used to dry the sterilized powder in order to reduce the number of process steps. In order to avoid condensation on the surface of the powder due to rapid cooling and secondary contamination, the drying temperature is set to 75℃~85℃, for example, 85℃, based on experience. The drying time is 1 hour, and the moisture content is controlled to be no higher than 9%.

[0090] 1.2 Formulation Process

[0091] Since this product is a pill, the types and amounts of binders, refining time, molding time, drying method, drying temperature, drying time, and types and amounts of polishing agent were examined based on the characteristics of the formulation. The process flow diagram for the preparation of this formulation is shown below. Figure 1 .

[0092] 1.2.1 Investigation of the mixing process

[0093] The premixed sample is the same as the total mixed sample and uses the same mixing equipment based on the same principle. Therefore, the process parameters are kept consistent with those of the premixed sample, which is to mix for 30 minutes by stirring.

[0094] 1.2.2 Research on pelleting technology

[0095] 1.2.2.1 Examination of Adhesive Types

[0096] Commonly used binders for pills include water, starch paste, rice wine, vinegar, diluted medicinal juice, sugar solution, and aqueous solution containing less than 5% refined honey. Based on the characteristics of this product and considering cost, water and different proportions of starch paste are proposed as binders for further investigation.

[0097] Take three portions of the evenly mixed medicinal powder and add water (1:0.75 ratio), 5% starch slurry, and 10% starch slurry as binders respectively to prepare soft materials. After kneading the materials into a ball, refine the mixture for 30 minutes. Then, roll the soft materials into strips, place them in a 5mm mold pelletizing machine, cut them into pellets, and roll them into rounds in a pelletizing pan. Dry them at 60℃. The pellet yield and dissolution time were used as evaluation indicators. The results are shown in Table 4.

[0098] Table 4. Statistical Results of the Investigation on Adhesive Types

[0099]

[0100] The results showed that using water as a binder resulted in a shorter time for the surface of the medicinal materials to be evenly moistened compared to using 5% starch paste or 10% starch paste as binders. The resulting soft material was also softer in texture, easier to process, and produced pills with uniform color, a smooth surface, and rapid dissolution. Therefore, water was determined to be the binder for this product.

[0101] 1.2.2.2 Investigation of the amount of adhesive added

[0102] The amount of binder added has a significant impact on the physicochemical properties of pills, such as yield, dissolution time, etc. Therefore, the amount of binder added was investigated.

[0103] Take three portions of the evenly mixed medicinal powder and add water at ratios of 1:0.65, 1:0.75, and 1:0.85 respectively. Stir for 5 minutes to ensure the powder is evenly moistened and formed into a ball. Then, refine the mixture for 30 minutes. Next, roll the soft material into strips, place them in a 5mm mold pelleting machine, cut them into pellets, and roll them into round shapes in a pelletizing pan. Dry at 60℃. The evaluation indicators are appearance, pellet yield, and dissolution time. The results are shown in Table 5.

[0104] Table 5. Statistical table of the results of the investigation on the amount of adhesive added.

[0105]

[0106] The results showed that material-to-liquid ratios of 1:0.65, 1:0.75, and 1:0.85 all resulted in powder with good viscosity, allowing it to be cut into pellets in a pelletizing machine. A material-to-liquid ratio of 1:0.65, used as a binder, resulted in poor powder viscosity, making refining relatively difficult, and the powder was prone to breakage during rolling, making pelletizing relatively difficult. A material-to-liquid ratio of 1:0.85, used as a binder, resulted in soft material sticking together during rolling, making pelletizing relatively difficult. A material-to-liquid ratio of 1:0.75, used as a binder, resulted in moderate powder viscosity, making both refining and pelletizing relatively easy. Therefore, the material-to-liquid ratio for the binder in this product was determined to be 1:0.75.

[0107] 1.2.2.3 Examination of Refining Time

[0108] The refining time affects the viscosity of the soft material, which has a significant impact on the yield of pills and the physicochemical properties such as the dissolution time of the pills. Therefore, the refining time was investigated. Since the commonly used refining time in production is 20 minutes, considering the differences between different varieties, refining times of 10 minutes, 20 minutes, and 30 minutes were selected for investigation.

[0109] Take 3 parts of the well-mixed medicinal powder, add water to make soft material with a material-to-liquid ratio of 1:0.75, and refine the medicine for 10 minutes, 20 minutes and 30 minutes respectively. Then roll the soft material into strips, put them into a 5mm mold pelletizing machine, cut them into pellets, put the pellets into a pelletizing pot to roll them into round shape, and dry them at 60℃.

[0110] The results are shown in Table 6, with the evaluation indicators being appearance, pill yield, and dissolution time.

[0111] Table 6. Statistical Results of the Investigation on Drug Refining Time

[0112]

[0113] The results showed that refining times of 10 minutes, 20 minutes, and 30 minutes all enabled the soft material to be cut into pills, but the pills were prone to breakage when rolled at a refining time of 30 minutes. The pill yield and properties of the pills refined at a refining time of 20 minutes were better than those refined at 10 minutes and 30 minutes. The refining time of 10 minutes, 20 minutes, and 30 minutes had little effect on the dissolution time. In conclusion, a refining time of 20 minutes was determined to be optimal.

[0114] 1.2.2.4 Examination of Molding Time

[0115] The molding time affects the density of the pills and has a significant impact on the yield and dissolution time of the pills, as well as other physicochemical properties. Therefore, the molding time was investigated. Since the commonly used molding time in production is 10 minutes, considering the differences between different varieties, molding times of 5 minutes, 10 minutes, and 15 minutes were selected for investigation.

[0116] Take 3 parts of the well-mixed medicinal powder, add water at a ratio of 1:0.75 to form a soft material, and refine for 20 minutes. Then, roll the soft material into strips, place them in a 5mm mold pelletizing machine, and cut them into pellets. Place the pellets in a pelletizing pan (temperature 50℃) and roll them into rounds for 5 minutes, 10 minutes, and 15 minutes respectively, and then dry them at 60℃. The evaluation indicators are appearance, pellet yield, and dissolution time. (Results are in [Error! Reference source not found]).

[0117] Table 7 Statistical Table of Pelletizing Time Investigation Results

[0118]

[0119] The results showed that when the forming time was between 5 and 15 minutes, the weight difference of the pills was small, and all met the requirements of the pills section of the 2020 edition of the Chinese Pharmacopoeia; there were no significant differences in pill yield and dissolution time. Therefore, the pill-forming time for this product was determined to be 10 minutes.

[0120] 1.3 Investigation of the Third Drying Process

[0121] The drying method, temperature, and time affect the density of the pills, and have a significant impact on the physicochemical properties such as the yield, appearance, and dissolution time of the pills. Therefore, the drying method, temperature, and time were investigated.

[0122] Take 3 parts of the well-mixed medicinal powder, add water at a ratio of 1:0.75 to make soft material, refine the medicine for 20 minutes, then roll the soft material into strips, put them into a 5mm mold pelleting machine, cut them into pellets, put the pellets into a pelleting pan (temperature 50℃) and roll them into rounds for 10 minutes, then dry them. The thickness of the spread material is 1cm. (1) The temperature is set to 50℃. After drying for 1 hour, the temperature is increased to 70℃ and then dried for another 3 hours. (2) The temperature is set to 50℃. After drying for 1 hour, the temperature is increased to 80℃ and then dried for another 3 hours. (3) The temperature is set to 50℃. After drying for 1 hour, the temperature is increased to 90℃ and then dried for another 3 hours. (4) The temperature is set to 60℃ and dried for 4 hours. (5) The temperature is set to 70℃ and dried for 4 hours. (6) The temperature is set to 80℃ and dried for 4 hours. (7) The temperature is set to 90℃ and dried for 4 hours. (8) The temperature is set to 80℃ and dried for 3 hours. (9) The temperature is set to 80℃ and dried for 5 hours. Since the temperature will change drastically during the drying process, it may affect the effective ingredients. Therefore, the properties, moisture content, characteristic spectrum, and dissolution time are used as evaluation indicators. The results are shown in Table 9.

[0123] Table 8. Statistical results of the investigation on drying temperature (process parameters)

[0124]

[0125] Table 9. Statistical table of the results of the investigation on drying temperature (test data)

[0126] Experiment No. Moisture (%) Properties Feature Map Dissolution time (min) 1 4.5 Brown pellets with a smooth appearance Compliant 16 2 4.0 Brown pellets with a smooth appearance Compliant 20 3 3.4 Brown pellets with a smooth appearance Compliant 23 4 8.1 Brown pellets with a smooth appearance Compliant 27 5 6.0 Brown pellets with a smooth appearance Compliant 19 6 4.8 Brown pellets with a smooth appearance Compliant 18 7 5.4 Brown pellets with a smooth appearance Compliant 24 8 4.5 Brown pellets with a smooth appearance Compliant 18 9 3.4 Brown pellets with a smooth appearance Compliant 19

[0127] The results showed that: I. Drying method investigation: Experiments 1-3 and 5-7 showed that the drying method had little effect on the moisture content, characteristic spectrum, properties and dissolution time of the pills. However, the content of rhubarb and sophora flavescens was higher in the direct heating method than in the segmented heating method. Therefore, the direct heating method was selected from the perspective of simple operation and content.

[0128] II. Drying Temperature Investigation: The results of experiments 4 to 7 show that the moisture content of the pills first decreases and then increases with the increase of drying temperature. Among them, the moisture content of pill No. 7 is slightly higher than that of pills No. 5 and 6, possibly because the pills are heated too quickly at 90℃, forming a "hard shell" that prevents further evaporation of moisture. There are no significant differences in the characteristic spectrum, properties and dissolution time results. Since all drying methods can meet the moisture limit requirements of the pills, 80℃ is selected as the drying temperature after comprehensive consideration.

[0129] III. Drying Time Investigation: The results of experiments 6, 8 and 9 show that with the increase of drying time, the moisture and rhubarb content of the pills decreased to a certain extent. There were no significant differences in the characteristic spectrum, properties and dissolution time of Sophora flavescens. Taking all factors into consideration, a drying time of 4 hours was selected.

[0130] 1.4 Polishing Process Research

[0131] 1.4.1 Examination of Polishing Agent Types

[0132] Different polishing agents affect the appearance, dissolution time, and other physicochemical properties of pellets, so the types of polishing agents were investigated.

[0133] Three portions of Qingxue Baidu Pills were taken and polished with 0.25% of the pill's weight of paraffin, white beeswax, and PEG6000, respectively. The pill's appearance and dissolution time were used as evaluation indicators. (See Error! Reference source not found.)

[0134] Table 10 Statistical Table of the Investigation Results of Polishing Agent Types

[0135]

[0136] The results showed that paraffin wax, white beeswax, and PEG6000 could all make the molded pills glossy and darken the color, with little difference in dissolution time. From an economic point of view, white beeswax was selected as the polishing agent for Qingxue Baidu Pills.

[0137] 1.4.2 Investigation of the amount of polishing agent added

[0138] The amount of polishing agent added affects the appearance, dissolution time, and other physicochemical properties of the pills, so the types of polishing agents were investigated.

[0139] Three portions of Qingxue Baidu Pills were taken and polished twice with 0.1%, 0.5%, and 1.0% of the pill's weight of white beeswax, respectively. The pill's appearance and dissolution time were used as evaluation indicators. (See Error! Reference source not found.)

[0140] Table 11 Statistical table of the results of the investigation on the amount of polishing agent added.

[0141]

[0142] The results showed that both 0.5% and 1.0% white beeswax could give the molded pellets a glossy appearance and deepen their color, with little difference in dissolution time. From an economic perspective, the polishing agent used in this application was determined to be 0.5% white beeswax.

[0143] Example 2: Preparation Process Example

[0144] 2.1 Preparation process

[0145] Weigh out the following 21 medicinal slices (Sophora flavescens 110g, Polygonum bistorta 80g, Rheum palmatum 120g, Coptis chinensis 30g, Forsythia suspensa 40g, Taraxacum mongolicum 40g, Viola yedoensis 40g, Paeonia lactiflora 40g, Paeonia suffruticosa 40g, Gardenia jasminoides 40g, Rehmannia glutinosa 60g, Chrysanthemum indicum 40g, Lonicera japonica 40g, Atractylodes lancea 40g, Phellodendron chinense 30g, Cicadae periostracum 10g, Smilax glabra 50g, Anemarrhena asphodeloides 40g, Ophiopogon japonicus 40g). Mix (30g of Alisma plantago-aquatica and 40g of gypsum), dry at 50-55℃ for 10 hours, coarsely crush with a 60-mesh sieve, then pulverize with a 100-mesh sieve, mix for 30 minutes, sterilize with moist heat at 127±5℃ for 30 minutes, dry at 75-85℃ for 1 hour, pulverize with a 100-mesh sieve, mix for 30 minutes, make into pills, dry at 80℃ for 4 hours, add white beeswax for polishing, package, and make 1000g of pills to obtain pill one.

[0146] 2.2 Preparation Process Two

[0147] Weigh out the following 21 medicinal slices: 80g of Sophora flavescens, 110g of Polygonum bistorta, 90g of Rheum palmatum, 60g of Coptis chinensis, 10g of Forsythia suspensa, 70g of Taraxacum mongolicum, 20g of Viola yedoensis, 20g of Paeonia lactiflora, 60g of Paeonia suffruticosa, 70g of Gardenia jasminoides (fried), 30g of Rehmannia glutinosa, 10g of Chrysanthemum indicum, 60g of Lonicera japonica, 40g of Atractylodes lancea (fried with wheat bran), 5g of Phellodendron chinense, 15g of Cicadae periostracum, 20g of Smilax glabra, 70g of Anemarrhena asphodeloides, and 10g of Ophiopogon japonicus. Mix 60g of Alisma plantago-aquatica and 70g of gypsum, dry at 55-60℃ for 10 hours, coarsely crush with a 60-mesh sieve, then pulverize with a 100-mesh sieve, mix for 20 minutes, sterilize with moist heat at 127±5℃ for 30 minutes, dry at 75-85℃ for 1 hour, pulverize with a 100-mesh sieve, mix for 30 minutes, make into pills, dry at 90℃ for 3 hours, add white beeswax for polishing, package, and make 1000g of pills to obtain pill two.

[0148] 2.3 Preparation Process Three

[0149] Weigh out the following 21 medicinal slices: 80g of Sophora flavescens, 50g of Polygonum bistorta, 150g of Rheum palmatum, 5g of Coptis chinensis, 70g of Forsythia suspensa, 10g of Taraxacum mongolicum, 70g of Viola yedoensis, 40g of Paeonia lactiflora, 30g of Paeonia suffruticosa, 20g of Gardenia jasminoides (fried), 30g of Rehmannia glutinosa (raw), 70g of Chrysanthemum indicum (wild chrysanthemum), 10g of Lonicera japonica, 70g of Atractylodes lancea (fried with wheat bran), 5g of Phellodendron chinense, 15g of Cicadae periostracum, 20g of Smilax glabra, 10g of Anemarrhena asphodeloides, and 70g of Ophiopogon japonicus. Mix 5g of Alisma plantago-aquatica and 70g of gypsum, dry at 50-55℃ for 10 hours, coarsely crush with a 60-mesh sieve, then pulverize with a 100-mesh sieve, mix for 40 minutes, sterilize with moist heat at 127±5℃ for 20 minutes, dry at 75-85℃ for 1 hour, pulverize with a 100-mesh sieve, mix for a total of 30 minutes, make into pills, dry at 70℃ for 5 hours, add white beeswax for polishing, package, and make 1000g of pills to obtain pill three.

[0150] 2.4 Preparation Process Four

[0151] Weigh out the following 21 medicinal slices: 90g of Sophora flavescens, 60g of Polygonum bistorta, 100g of Rheum palmatum, 5g of Coptis chinensis, 70g of Forsythia suspensa, 70g of Taraxacum mongolicum, 10g of Viola yedoensis, 40g of Paeonia lactiflora, 10g of Paeonia suffruticosa, 10g of Gardenia jasminoides (fried), 90g of Rehmannia glutinosa, 10g of Chrysanthemum indicum, 70g of Lonicera japonica, 70g of Atractylodes lancea (fried with wheat bran), 60g of Phellodendron chinense, 15g of Cicadae periostracum, 50g of Smilax glabra, 10g of Anemarrhena asphodeloides, and 50g of Ophiopogon japonicus. Mix 30g of Alisma plantago-aquatica and 60g of gypsum, dry at 50-55℃ for 10 hours, coarsely crush with a 60-mesh sieve, then pulverize with a 100-mesh sieve, mix for 30 minutes, sterilize with moist heat at 127±5℃ for 30 minutes, dry at 75-85℃ for 1 hour, pulverize with a 100-mesh sieve, mix for 30 minutes, make into pills, dry at 75℃ for 5 hours, add white beeswax for polishing, package, and make 1000g of pills to obtain pill four.

[0152] Example 3: Pharmacological Efficacy Example

[0153] 3.1 Reagents and Materials

[0154] The following products were prepared according to "2.1 Preparation Process One" (named Qingxue Baidu Wan): Pill One (provided by Hunan Yineng Biomedical Co., Ltd.); Aspirin and Vitamin C Effervescent Tablets (provided by Bayer Bitterfeld GmbH); Isoflurane (provided by Bayer Bitterfeld); Xylene, Evans Blue, and Acetic Acid (glacial acetic acid) (provided by Sinopharm Chemical Reagent Co., Ltd.); Herpes Simplex Virus I and II Genotyping Nucleic Acid Detection Kit (provided by Shanghai ZJ Biotechnology Co., Ltd.); Trizol Reagent (provided by Ambion by Life Technologies); Acyclovir Tablets (provided by Shenzhen Haiwang Pharmaceutical Co., Ltd.); Varicella-Zoster Virus (VZV) Real-Time Fluorescent Quantitative PCR Kit (provided by Shanghai ZJ Biotechnology Co., Ltd.); IL-1β ELISA Kit, TNFα ELISA Kit, NKA ELISA Kit, and SP ELISA Kit (provided by Cloud-Clone Corp.).

[0155] 3.2 Instruments and Equipment

[0156] Electronic balance, model: YP1002MAX100g, manufacturer: Shanghai Yueping Scientific Instruments Co., Ltd.; Electronic analytical balance, model: AR1140MAX110g, manufacturer: Ohaus, USA; IVC mouse cage, model: ZJ-4, manufacturer: Suzhou Fengshi Co., Ltd.; Multifunctional microplate reader, model: Enspire, manufacturer: PerkinElmer, Germany; Real-Time PCR instrument, model: QuantStudio 5, manufacturer: Appliedbiosystems; Mini centrifuge with eight tubes, model: LX-300, manufacturer: Kylin-Bell Lab; Mini vortex mixer, model: OL-901, manufacturer: Haimen Qilin Bell Instrument Co., Ltd.; Centrifuge, model: Centrifuge 5430, manufacturer: Eppendorf, Germany; Low-temperature high-speed centrifuge, model: Eppendorf-5810R, manufacturer: Eppendorf, Germany; A2 type biosafety cabinet, model: Thermo MSC1.8, manufactured by Thermo Scientific, USA; Cold / Hot Pain Monitor, model: ZS-CTE, manufactured by Beijing Zhongshi Dichuang Technology Development Co., Ltd.

[0157] 3.3 Virus strains and cells

[0158] Virus strains: Varicella-zoster virus (VZV) and Herpes simplex virus type 1 (HSV-1), purchased from ATCC in the United States, passaged in the laboratory, and stored in a -80°C refrigerator. Cell lines: African green monkey kidney cells (BS-C-1) were purchased from Beijing Beina Chuanglian Biotechnology Research Institute, and human laryngeal epidermoid carcinoma cells (hep-2) were purchased from ATCC in the United States, passaged in the laboratory, and stored in liquid nitrogen.

[0159] 3.4 Statistics and analysis

[0160] The significant figures of the data in this experiment were rounded according to the rule of rounding up if the digit is 5 or more and rounding down if the digit is less than 5. Measurement data were expressed as mean ± standard deviation and the statistical software used was SPSS. For pairwise comparison, the Independent-Samples T test was used; for comparison among multiple groups, homogeneity of variance and normality were compared first. When the variance was homogeneous and the data conformed to normality, the LSD-t or Dunnett-t test was used. When the data did not conform to normality, the Nonparametric T test was used. When the data conformed to normality but the variance was inhomogeneous, the Dunnett’s T3 or Tamhane’s T2 test was used. The statistical results were based on a test limit of α = 0.05, where P ≤ 0.05 indicated statistical significance, and P ≤ 0.01 indicated very significant differences in the tests.

[0161] 3.5 Effects of Qingxue Baidu Pills on ear swelling in mice induced by xylene

[0162] 3.5.1 Experimental animals

[0163] ICR mice were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. Animal license: SCXK(Beijing)2021-0011. SPF grade, 18 - 20 g, 30 mice, with 15 males and 15 females. Animal certificate number: 110011211110098031 / 110011211110097953, Ethics number: D2021027.

[0164] 3.5.2 Experimental methods

[0165] 3.5.2.1 Grouping and drug administration

[0166] Thirty ICR mice, with 15 males and 15 females, weighing 19 ± 1 g, were randomly divided into 3 groups according to body weight grades, namely the model control group, the aspirin control group, and the Qingxue Baidu Pills dosage group, with 10 mice in each group. The mice were administered orally at a dose of 0.2 ml / 10 g once a day for 3 consecutive days. The model control group was given distilled water under the same conditions. One hour after the last administration, 30 μl of xylene was evenly applied to both the front and back of the left ear of each mouse, and physiological saline was applied to the right ear as a blank control. One hour later, the mice were sacrificed by cervical dislocation. The two ears were aligned and cut along the auricle baseline, and round ear pieces (diameter 8 mm) were punched out with a puncher and weighed with an electronic balance. The difference in weight between the two ears was used as the degree of inflammatory swelling, and statistical analysis was performed using the T-test. The swelling inhibition rate of the treated group was calculated according to the following formula. Ear swelling rate (%) = (weight of the right ear - weight of the left ear) / weight of the left ear × 100%. Swelling inhibition rate (%) = (swelling rate of the model control group - swelling rate of the treated group) / swelling rate of the model group × 100%.

[0167] 3.5.3 Experimental Results

[0168] Table 12 Effects of Qingxue Baidu Pills on Xylene-induced Ear Swelling in Mice

[0169]

[0170] Note: Compared with the model group ** p < 0.01

[0171] Table 12 results showed that compared with the model control group, the Qingxue Baidu Pills dosage group could significantly relieve xylene-induced ear swelling in mice, with a significant difference compared with the model group (p < 0.01). The swelling inhibition rate was 57.69%, indicating that Qingxue Baidu Pills could significantly relieve xylene-induced ear swelling in mice.

[0172] 3.6 Effects of Qingxue Baidu Pills on the Permeability of Mesenteric Capillaries in Mice

[0173] 3.6.1 Experimental Animals

[0174] ICR mice were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. Animal license: SCXK (Beijing) 2021-0011. SPF grade, 18 - 20 g, 70 mice, with 35 males and 35 females. Animal certificate number: 110011211110098031 / 110011211110097953, Ethics number: D2021027.

[0175] 3.6.2 Experimental Methods

[0176] 3.6.2.1 Grouping and Administration

[0177] Forty ICR mice, weighing 19±1 g, with an equal number of males and females, were randomly divided into 4 groups according to body weight grades, namely the normal control group, the model control group, the aspirin control group, and the Qingxue Baidu Pills dosage group, with 10 mice in each group. Each dosing group was given intragastric administration at a dose of 0.2 ml / 10 g, once a day for 3 consecutive days. The normal control group and the model control group were given distilled water under the same conditions. 1 h after the last intragastric administration, each mouse was intraperitoneally injected with 0.15 ml / only of 1% glacial acetic acid solution, and 0.2 ml / only of 0.5% Evans blue solution was injected into the tail vein. After 20 min, the mice were sacrificed by decapitation, the abdominal cavity was rinsed with normal saline at 4 ml / each and the peritoneal fluid was collected, centrifuged at 1000 r / min for 5 min, the supernatant was taken, and the absorbance was measured at 590 nm with a multifunctional microplate reader. Statistical analysis was performed using the T test to compare whether there were statistical differences between the model control group and the dosing groups.

[0178] 3.6.2.3 Experimental results

[0179] Table 13 Effects of Qingxue Baidu Pills on the permeability of peritoneal capillaries in mice

[0180]

[0181] Note: Compared with the normal control group ## p<0.01; compared with the model group ** p<0.01

[0182] As shown in the results of Table 13, after modeling, the permeability of peritoneal capillaries in the mice of the model control group was significantly increased, showing a significant difference compared with the normal control group (p<0.01); after 3 days of dosing with Qingxue Baidu Pills, the permeability of the abdominal skin could be significantly reduced, showing a significant difference compared with the model control group (p<0.01). Qingxue Baidu Pills could significantly improve the increase in the permeability of peritoneal capillaries in mice caused by glacial acetic acid, and its inhibition rate was 31.27%.

[0183] 3.7 Therapeutic effect of Qingxue Baidu Pills on the rabbit skin infection model induced by herpes simplex virus type 1 (HSV-1)

[0184] 3.7.1 Experimental animals

[0185] Big-ear white rabbits were purchased from Beijing Jinmuyang Experimental Animal Breeding Co., Ltd. Animal license: SCXK (Beijing) 2021-0002. Ordinary grade, 2 - 2.5 kg, 24 rabbits, with an equal number of males and females. Animal certificate number: 110333211100084261 / 110333211100095135, Ethics number: D2021031.

[0186] 3.7.2 Experimental methods

[0187] 3.7.2.1 Grouping and Dosing

[0188] Twenty-four domestic rabbits were randomly divided into four groups according to weight: a normal control group, a model control group, an acyclovir control group, and a Qingxue Baidu Pill dosage group, with six rabbits in each group (half male and half female). Hair was removed from the back area of ​​each group (5×5cm). 2 Afterwards, the skin on the back of the rabbits was scratched with sandpaper. 100 μl of HSV-1 virus solution diluted 100 times was applied to the damaged areas on the backs of the model group and each treatment group. The normal control group received an equal volume of physiological saline. Infection continued for 2 days. Four hours after infection on day 1, each treatment group received oral administration once daily for 7 consecutive days. The normal control group and the model control group received distilled water under the same conditions. The lesions on the backs of the rabbits in each group were observed starting on the day of infection and continued for 7 days. Scores were recorded according to the evaluation criteria in Table 14 below. All Arabic and Roman numeral scores during the infection process were added together to obtain a cumulative score. The rabbits were sacrificed on day 7 after infection, and the infected skin was collected for viral DNA detection and pathological histological examination. All results were statistically analyzed using t-tests for inter-group comparisons.

[0189] Table 14 Evaluation Criteria

[0190]

[0191] 3.7.3 Experimental Results

[0192] 3.7.3.1 Effects on the severity of lesions and the number of papules and vesicles: As shown in Table 15, after HSV-1 infection of rabbit skin, a large number of large vesicles were initiated, with local ulceration. Seven days after infection, large scabs appeared on the back, which was significantly different from the normal group (p<0.01). After administration of Qingxue Baidu Pill, the ulceration of a large number of vesicles was significantly relieved, with only small scabs, which was significantly different from the model group (p<0.01).

[0193] Table 15 Effects of Qingxue Baidu Pill on the Degree of Skin Lesions Induced by HSV-1 Infection in Rabbits

[0194]

[0195] Note: Compared with the normal control group ## p<0.01; compared with the model group ** p<0.01

[0196] 3.7.3.2 Effect on viral DNA in diseased skin: As shown in Table 16, no virus was expressed in the skin of rabbits in the normal group. After scratching the skin and infecting it with HSV-1, obvious viral DNA expression was observed in the skin of the rabbits. After administration of Qingxue Baidu Pill, viral nucleic acid expression in the skin of rabbits was significantly reduced, and the difference was statistically significant compared with the model (p < 0.01).

[0197] Table 16 Effects of Qingxue Baidu Pills on Viral Load in Diseased Skin of Rabbits Infected with HSV-1

[0198]

[0199] Note: Compared with the model group ** p < 0.01; compared with acyclovir △△ p < 0.01

[0200] 3.7.3.3 Histopathological Examination of the Skin: In the normal group, the epithelium of the dorsal skin tissue of rabbits showed no hyperkeratosis, no hyperplasia in the epithelial layer, no increase in the granular layer, no inflammatory exudation under the epithelium, no swelling of the tissue, no abnormality in the hair follicles, normal sebaceous glands, and normal tissue structure. In the model group, the dorsal skin of rabbits showed crusting in varying degrees, with thick and diffuse crusts. There was bleeding under the skin in some rabbits, mucus exudation, and the surface was yellowish-brown. There was a significant difference in the lesion grade compared with the normal group (p < 0.01). After administration of Qingxue Baidu Pills, the skin lesions such as skin damage, hyperkeratosis, epithelial crusting, subcutaneous inflammatory exudation, and congestion and edema in rabbits were alleviated in varying degrees, and there was a significant difference in the lesion grade compared with the model group (p < 0.05). The results are shown in Table 17.

[0201] Table 17 Effects of Qingxue Baidu Pills on Skin Lesions of Rabbits Infected with HSV-1

[0202]

[0203] Note: p value of the model control group compared with the normal control group; each administration group compared with the model control group

[0204] Qingxue Baidu Pills can significantly relieve a large number of herpes and deep ulcerations caused by HSV-1 infection of the skin. There are only small patches of crusting on the skin surface. Microscopic observation can significantly reduce skin hyperkeratosis, subcutaneous inflammatory exudation, congestion and edema, etc., and can significantly reduce the expression of viral nucleic acid in the skin.

[0205] 3.8 Therapeutic Effect of Qingxue Baidu Pills on the Skin Infection Model of Guinea Pigs Induced by Varicella-Zoster Virus (VZV)

[0206] 3.8.1 Experimental Animals

[0207] Guinea pigs were purchased from Beijing Jinmuyang Experimental Animal Breeding Co., Ltd. Animal License SCXK(Beijing) 2021-0002. Ordinary grade, 250 - 350 g, 32 animals, with 16 males and 16 females. Animal Certificate Number: 110333221100015083, Ethics Number: D2021031.

[0208] 3.8.2 Experimental Methods

[0209] 3.8.2.1 Grouping and Dosing

[0210] Thirty-two guinea pigs were randomly divided into four groups according to weight: a normal control group, a model control group, an acyclovir control group, and a Qingxue Baidu Pill dosage group, with eight guinea pigs in each group (half male and half female). Hair loss was performed on the back area of ​​the guinea pigs (4×4cm). 2 After the infection, the skin on the back of the guinea pigs was scratched. 100 μl of varicella-zoster virus (VZV) diluted 100 times was applied to the damaged areas on the backs of the model group and each treatment group. The normal control group received an equal volume of physiological saline. Infection was continued for 2 days. Four hours after infection on day 1, each treatment group received oral administration once daily for 7 consecutive days. The normal control and model control groups received distilled water under the same conditions. The lesions on the backs of the guinea pigs in each group were observed from the day of infection for 7 consecutive days, and scores were recorded according to the evaluation criteria in Table 18 below. All Arabic and Roman scores during the infection process were added together to obtain a cumulative score. The guinea pigs were euthanized on day 7, and the infected skin was collected for viral DNA testing and pathological histological examination. All results were statistically analyzed using t-tests for inter-group comparisons.

[0211] Table 18 Evaluation Criteria

[0212]

[0213] 3.8.3 Experimental Results

[0214] 3.8.3.1 Effects on lesion severity and number of papules and vesicles: As shown in Table 19, simple scratching of guinea pig skin did not produce vesicles, only slight redness and swelling and almost no trauma. After scratching and VZV infection of guinea pig skin, ulceration appeared at the infected site, producing a large number of tightly connected vesicles. After the vesicles dried, complete and dark-colored scabs were formed, which was significantly different from the normal control group (p<0.01). After administration of Qingxue Baidu Pill, the production of vesicles was significantly reduced, the ulceration was alleviated, and only a small amount of scabs remained on the skin, which was significantly different from the model group (p<0.05, p<0.01).

[0215] Table 19. Effects of Qingxue Baidu Pills on the Severity of Skin Lesions Induced by VZV Infection in Guinea Pigs

[0216]

[0217]

[0218] Note: Compared with the normal control group ## p<0.01; compared with the model group * p<0.05, ** p<0.01.

[0219] 3.8.3.2 Effect on viral DNA in diseased skin: As shown in Table 20, no virus was expressed in the skin of guinea pigs in the normal group. After VZV was applied to the scratched skin, there was obvious viral DNA expression in the skin of guinea pigs. After administration of Qingxue Baidu Pill, viral nucleic acid expression in the skin of guinea pigs was significantly reduced, and there was a significant difference compared with the model control group (p<0.01).

[0220] Table 20. Effects of Qingxue Baidu Pills on viral load in skin lesions of VZV-infected guinea pigs.

[0221] Group Dosage (g / kg) Animal number Viral load (copies) normal control group - 8 Negative Model control group - 8 <![CDATA[10.97±0.92×10 7 <!-- 20 -->]]> Acyclovir control group 0.287 8 <![CDATA[7.76±0.33×10 7** ]]> Qingxue Baidu Pills 0.86 8 <![CDATA[4.69±0.77×10 7**△△ ]]>

[0222] Note: Comparison with model group ** p<0.01; compared with acyclovir △△ p<0.01.

[0223] 3.8.3.3 Pathological and histological examination of the skin: In the normal control group, the epithelial layer of the dorsal skin of guinea pigs showed no excessive keratinization, no hyperplasia of the epithelial layer, no increase in the granular layer, no inflammatory exudation under the epithelium, no swelling of the tissue, no abnormalities in hair follicles, and normal sebaceous glands and tissue structure. In the model control group, the dorsal skin of guinea pigs showed more severe segmental damage. The main lesions were: segmental skin shedding, with the stratum corneum, granular layer, sebaceous glands, and hair follicles disappearing at the shedding sites; subcutaneous swelling; a large number of proliferating cells of different types, varying in size and shape; severe congestion; and disappearance of hair follicles and sebaceous glands. Hyphae appeared to be present within the proliferating cells, with numerous sporophytes in the hair follicles and disappearance of sebaceous glands. The lesion grade was significantly different from that of the normal control group (p < 0.01). After administration of Qingxue Baidu Pill, the segmental damage to the skin on the back of guinea pigs was reduced and even disappeared. Compared with the model control group, the lesions of hair follicles and sebaceous glands recovered to varying degrees, and the lesion grade was significantly different from that of the model control group (p<0.01).

[0224] Table 21 Effects of Qingxue Baidu Pills on VZV-infected guinea pig lesions

[0225]

[0226]

[0227] Note: Comparison of p-value between the model control group and the normal control group; comparison of each drug administration group with the model control group.

[0228] 3.9 Effects of Qingxue Baidu Pill on a rat model of post-varicella-zoster virus (VZV)-induced neuralgia

[0229] 3.9.1 Laboratory Animals

[0230] SD rats were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. Animal license: SCXK(Beijing)2021-0011. SPF level, 170-200 g, 32 rats, with 16 males and 16 females. Animal certificate number: 110011221103233387 / 110011221103233224, ethics number: D2021027.

[0231] 3.9.2 Experimental method

[0232] 3.9.2.1 Grouping and administration

[0233] Thirty-two male SD rats were randomly divided into 4 groups according to body weight, namely normal control group, model control group, acyclovir control group, and Qingxue Baidu Pills dose group, with 8 rats in each group. Except for the normal control group, the diluted VZV virus suspension was inoculated subcutaneously between the webs of the first and second fingers of the left forelimb of the rats, and the rats were subjected to thermal pain behavior detection before inoculation, and on the 1st, 3rd, 5th, 7th, and 10th days after inoculation. On the day of inoculation, the rats were given oral medications. The normal group and the model group were given distilled water under the same conditions. After the behavioral examination on the 10th day of virus inoculation, the rats were anesthetized, the chest cavity was opened, the heart was exposed, a perfusion needle was inserted into the left ventricle from the apex of the heart, the tip of the needle was fixed with a hemostat, and the right auricle was cut open to form a perfusion fluid drainage duct. 0.9% sodium chloride solution at 37°C was rapidly perfused from the left ventricle until the fluid flowing out of the right auricle was colorless, and at the same time, the rat liver was pale and the intestinal tract was swollen, then the perfusion was stopped. The left sciatic nerve was quickly exposed, then the bone was cut open, the spinal dorsal root ganglion was retrogradely found and removed, and immediately placed in liquid nitrogen for standby. Then the corresponding spinal cord segments on the operative side that emitted nerves were retrogradely found and removed, and immediately placed in liquid nitrogen for standby. ELISA was used to detect substance P, neurokinin A, and inflammatory neurotransmitters TNF-α and IL-1β in the DRG and spinal cord of rats. All results were statistically processed by t-test for inter-group comparison.

[0234] 3.9.3 Experimental results

[0235] 3.9.3.1 Effects on the thermal pain threshold of rats: As shown in Tables 22 and 23, after subcutaneous injection of VZV virus suspension between the webs of the first and second fingers of the left forelimb of rats, the thermal pain threshold of rats began to decrease significantly on the third day, showing a significant difference compared with the normal group (p < 0.01). After administration of Qingxue Baidu Pills, the thermal pain threshold of rats could be significantly increased, showing a significant difference compared with the model group (p < 0.05).

[0236] Table 22 Effects of Qingxue Baidu Pills on the thermal pain threshold of rats at different time points (T0, T1, and T3)

[0237]

[0238] Note: Compared with the normal control group ##p<0.01; compared with the model group * p<0.05.

[0239] Table 23 Effects of Qingxue Baidu Pills on Rats at Different Time Points (T5, T7, and T8) 10 The effect of thermal pain threshold

[0240]

[0241] Note: Compared with the normal control group ## p<0.01; compared with the model group ** p<0.01.

[0242] 3.9.3.2 Effects on substance P, neurokinin A, and inflammatory neurotransmitters TNF-α and IL-1β in the dorsal root ganglion (DRG) and spinal cord of rats.

[0243] As shown in Tables 24 and 25, after subcutaneous injection of VZV virus suspension between the webs of the first and second fingers of the left forelimb of rats, the levels of neurokinin A, substance P, TNF-α, and IL-1β in the DRG and spinal cord of the model group rats were significantly increased compared with those of the normal control group (P<0.01). After drug intervention in rats, Qingxue Baidu Wan significantly reduced the levels of neurokinin A, substance P, TNF-α, and IL-1β in the DRG and spinal cord of rats, with significant differences compared with those of the model group (P<0.01).

[0244] Table 24 Effects of Qingxue Baidu Pill on DRG and related factors (SP and NKA) in rat spinal cord

[0245]

[0246]

[0247] Note: Compared with the normal control group ## p<0.01; compared with the model group * p<0.05, ** p<0.01.

[0248] Table 25 Effects of Qingxue Baidu Pill on related factors (TNF-α and IL-1β) in rat DRG and spinal cord

[0249] Group Dosage (g / kg) Animal number TNF-α IL-1β normal control group 8 122.27±3.90 135.34±7.35 Model control group 6 <![CDATA[422.69±44.52 ## ]]> <![CDATA[394.83±43.13 ## ]]> Acyclovir group 0.373 7 <![CDATA[217.77±60.81 ** ]]> <![CDATA[192.29±44.87 ** ]]> Qingxue Baidu Pills 1.12 7 <![CDATA[182.19±26.80 ** ]]> <![CDATA[166.48±20.03 ** ]]>

[0250] Note: Compared with the normal control group ## p<0.01; compared with the model group ** p<0.01.

[0251] VZV virus significantly reduced the thermal pain threshold in rats while increasing the levels of neurokinin A, substance P, TNF-α, and IL-1β in the dorsal root ganglia and spinal cord. Qingxue Baidu Wan (a traditional Chinese medicine formula) significantly increased the thermal pain threshold in infected rats and significantly reduced the levels of neurokinin A, substance P, TNF-α, and IL-1β.

[0252] 3.10 Conclusion and Evaluation

[0253] This invention utilizes a rabbit skin infection model induced by herpes simplex virus type 1 (HSV-1) and a guinea pig skin infection model induced by varicella-zoster virus (VZV). Through examinations including lesion severity grading (inflammation, edema, vesicles, erosion, crusting, etc.), area of ​​skin redness and swelling, papule and vesicle count, local intradermal viral DNA detection, and skin histopathology, the therapeutic effect of Qingxue Baidu Wan on herpes zoster is systematically studied. Furthermore, combined with mouse xylene ear swelling test and mouse abdominal skin capillary permeability test, the anti-inflammatory effect of Qingxue Baidu Wan is investigated, exploring its efficacy and simple mechanism in treating herpes zoster. In addition, addressing postherpetic neuralgia, the most common but serious adverse complication of herpes zoster, this invention uses a rat model of postherpetic neuralgia induced by VZV infection. By detecting indicators such as heat pain threshold, substance P, neurokinin A, and inflammatory factors, the efficacy of Qingxue Baidu Wan in treating herpes zoster is comprehensively evaluated.

[0254] The results showed that Qingxue Baidu Wan significantly alleviated xylene-induced ear swelling and reduced abdominal skin permeability in mice, indicating that Qingxue Baidu Wan has a significant anti-inflammatory effect. Qingxue Baidu Wan improved the extensive herpes ulceration caused by HSV-1 infection in rabbits, reducing crusting. Microscopic observation showed that it alleviated various lesions on the rabbit's back skin, including skin damage, hyperkeratosis, epithelial crusting, subcutaneous inflammatory exudation, congestion, and edema, and reduced viral nucleic acid expression in the skin tissue. In VZV-infected guinea pigs, it significantly reduced herpes production, alleviated ulceration, and left only a small amount of crust remaining on the skin, and reduced viral nucleic acid expression in the skin tissue, demonstrating that Qingxue Baidu Wan has a direct therapeutic effect on herpes zoster. Simultaneously, Qingxue Baidu Wan significantly increased the thermal pain threshold in a VZV-infected rat model of postherpetic neuralgia and reduced the levels of neurokinin A, substance P, TNF-α, and IL-1β in the dorsal root ganglia and spinal cord, indicating that Qingxue Baidu Wan can alleviate postherpetic neuralgia caused by herpes zoster. In conclusion, Qingxue Baidu Pills have significant anti-inflammatory effects and can treat shingles and its sequelae.

[0255] The embodiments of the present invention have been described in detail above. Specific examples have been used to illustrate the principles and implementation methods of the present invention. The descriptions of the embodiments above are only for the purpose of helping to understand the method and core ideas of the present invention. Furthermore, any changes or modifications made by those skilled in the art based on the ideas of the present invention, and on the specific implementation methods and application scope of the present invention, are all within the scope of protection of the present invention. Therefore, the content of this specification should not be construed as a limitation of the present invention.

Claims

1. A traditional Chinese medicine composition for the prevention and / or treatment of herpes and / or its complications, characterized in that, By weight, the traditional Chinese medicine composition comprises 10.45-11.55 parts of Sophora flavescens, 7.6-8.4 parts of Polygonum bistorta, 11.4-12.6 parts of Rheum palmatum, 2.85-3.15 parts of Coptis chinensis, 3.8-4.2 parts of Forsythia suspensa, 3.8-4.2 parts of Taraxacum mongolicum, 3.8-4.2 parts of Viola yedoensis, 3.8-4.2 parts of Paeonia lactiflora, 3.8-4.2 parts of Paeonia suffruticosa, 3.8-4.2 parts of Gardenia jasminoides, and 5.7-6 parts of Rehmannia glutinosa. The formula consists of 3 parts of wild chrysanthemum, 3.8-4.2 parts of honeysuckle, 3.8-4.2 parts of atractylodes, 2.85-3.15 parts of phellodendron bark, 0.95-1.05 parts of cicada slough, 4.75-5.25 parts of smilax, 3.8-4.2 parts of anemarrhena, 3.8-4.2 parts of ophiopogon, 2.85-3.15 parts of alisma, and 3.8-4.2 parts of gypsum, wherein the accompanying symptoms are pain and / or inflammation.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The gardenia mentioned is stir-fried gardenia.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The Rehmannia glutinosa mentioned is raw Rehmannia glutinosa.

4. The traditional Chinese medicine composition according to claim 1, characterized in that, The Atractylodes lancea mentioned is stir-fried with wheat bran.

5. The traditional Chinese medicine composition according to claim 1, characterized in that, The gypsum mentioned is raw gypsum.

6. The traditional Chinese medicine composition according to claim 1, characterized in that, The pain described is postherpetic neuralgia.

7. A formulation comprising the traditional Chinese medicine composition according to any one of claims 1 to 6.

8. The formulation according to claim 7, characterized in that, The formulation includes one or more pharmaceutically acceptable excipients.

9. The formulation according to claim 8, characterized in that, The excipients are selected from one or more of the following: adhesives, preservatives, and flavoring agents.

10. The formulation according to claim 9, characterized in that, The adhesive is selected from one or more of the following: water, 5% starch paste, 10% starch paste, rice wine, vinegar, sugar solution, and an aqueous solution containing less than 5% refined honey.

11. The formulation according to claim 10, characterized in that, The adhesive is water.

12. The formulation according to claim 7, characterized in that, The dosage form of the preparation is an oral preparation.

13. The formulation according to claim 12, characterized in that, The dosage form of the preparation is pills.

14. A method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 6, characterized in that, The method includes: weighing appropriate amounts of Sophora flavescens, Bistorta officinalis, rhubarb, Coptis chinensis, Forsythia suspensa, Taraxacum mongolicum, Viola yedoensis, Paeonia lactiflora, Paeonia suffruticosa, Gardenia jasminoides, Rehmannia glutinosa, Chrysanthemum indicum, Lonicera japonica, Atractylodes lancea, Phellodendron chinense, Cicadae periostracum, Smilax glabra, Anemarrhena asphodeloides, Ophiopogon japonicus, Alisma plantago-aquatica, and Gypsum fibrosum; mixing for the first time; drying for the first time; pulverizing for the first time; mixing for the second time; sterilizing; drying for the second time; and pulverizing for the second time to obtain the Chinese herbal composition.

15. A method for preparing the formulation according to any one of claims 7 to 13, characterized in that, The method includes: mixing the traditional Chinese medicine composition according to any one of claims 1 to 6 with an appropriate amount of excipients for a third time, making pills, drying for a third time, adding a polishing agent, and obtaining the preparation.

16. The method according to claim 15, characterized in that, The method further includes: dispensing the product after adding the polishing agent to obtain the formulation.

17. The method according to claim 15, characterized in that, The excipients are selected from one or more of the following: adhesives, preservatives, and flavoring agents.

18. The method according to claim 17, characterized in that, The adhesive is selected from one or more of the following: water, 5% starch paste, 10% starch paste, rice wine, vinegar, sugar solution, and an aqueous solution containing less than 5% refined honey.

19. The method according to claim 18, characterized in that, The adhesive is water.

20. The method according to claim 17, characterized in that, The ratio of the traditional Chinese medicine composition to the adhesive is 1:0.7~0.

8.

21. The method according to claim 20, characterized in that, The ratio of the traditional Chinese medicine composition to the adhesive is 1:0.

75.

22. The method according to claim 15, characterized in that, The refining time for making the pills is 15-25 minutes.

23. The method according to claim 22, characterized in that, The pill-making process takes 20 minutes.

24. The method according to claim 15, characterized in that, The pelleting time is 5-15 minutes.

25. The method according to claim 24, characterized in that, The pelleting time is 10 minutes.

26. The method according to claim 15, characterized in that, The polishing agent is selected from one or more of the following: paraffin wax, white beeswax, and PEG6000.

27. The method according to claim 15, characterized in that, The amount of polishing agent added is 0.1% to 1% of the weight of the pill.

28. The method according to claim 14 or 15, characterized in that, The method includes any one or more of the following items [1] to [11]: [1] The first mixing and / or the second mixing and / or the third mixing shall be carried out by sieving or stirring. [2] The time for the first mixing and / or the second mixing and / or the third mixing is 20-40 min; [3] The sterilization method is dry heat sterilization, moist heat sterilization and / or cobalt-60 irradiation sterilization; [4] The sterilization time is 10-40 min; [5] The temperature of the moist heat sterilization method is 110-135℃; [6] The thickness of the material used in the moist heat sterilization method is 1-3 cm; [7] The first drying process is carried out at 40-60℃ for 8-12 hours; [8] The second drying process is carried out at 70-90℃ for 0.5-1.5 hours; [9] The first crushing is coarse crushing with a 60-80 mesh sieve followed by crushing with a 100-150 mesh sieve; [10] The second crushing is performed by crushing with a 100-150 mesh sieve; [11] The third drying is performed at 70-90℃ for 3-5 hours.

29. The method according to claim 28, characterized in that, The first mixing and / or the second mixing and / or the third mixing are performed by stirring.

30. The method according to claim 28, characterized in that, The time for the first mixing and / or the second mixing and / or the third mixing is 30 minutes.

31. The method according to claim 28, characterized in that, The sterilization method is moist heat sterilization.

32. The method according to claim 28, characterized in that, The sterilization time is 30 minutes.

33. The method according to claim 28, characterized in that, The temperature for the moist heat sterilization method is 127°C.

34. The method according to claim 28, characterized in that, The thickness of the material used in the moist heat sterilization method is 2 cm.

35. The method according to claim 28, characterized in that, The first drying process involves drying at 50-55°C for 10 hours.

36. The method according to claim 28, characterized in that, The second drying process involves drying at 75-85℃ for 0.95-1.05 hours.

37. The method according to claim 28, characterized in that, The first crushing process involves coarse crushing with a 60-mesh sieve followed by pulverizing with a 100-mesh sieve.

38. The method according to claim 28, characterized in that, The second crushing is performed using a 100-mesh sieve.

39. The method according to claim 28, characterized in that, The third drying process involves drying at 80°C for 3.8 to 4.2 hours.

40. The use of the traditional Chinese medicine composition according to any one of claims 1 to 6 or the preparation according to any one of claims 7 to 13 in the preparation of a medicament for the prevention and / or treatment of herpes and / or its complications, characterized in that, The complications are pain and / or inflammation.

41. The use according to claim 40, characterized in that, The herpes described is a virus-induced herpes.

42. The use according to claim 40, characterized in that, The pain can be acute or chronic.

43. The use according to claim 40, characterized in that, The pain described is postherpetic neuralgia.

44. The use according to claim 40, characterized in that, The pain is either peripheral or central.

45. The use according to claim 40, characterized in that, The inflammation can be specific or nonspecific.

46. ​​The use according to claim 40, characterized in that, The inflammation can be acute or chronic.

47. The use according to claim 41, characterized in that, The virus is selected from one or more of the following: herpes simplex virus type 1, herpes simplex virus type 2, varicella-zoster virus, human cytomegalovirus, EB virus, human herpesvirus type 6, human herpesvirus type 7 and human herpesvirus type 8.

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