An external-use traditional Chinese medicine composition for treating vulvar leukoplakia and a preparation method thereof

Abstract

The application provides a topical traditional Chinese medicine composition for treating vulvar leukoplakia and a preparation method thereof. The composition is composed of traditional Chinese medicinal materials such as angelica, cortex psoraleae and barks of dictamnus dasycarpus, and a penetration enhancer, an activating agent and a moisturizing agent. The penetration enhancer is composed of soybean lecithin, phosphatidylethanolamine and cholesterol, the activating agent is sodium cholate, sodium deoxycholate and sodium taurocholate, and the moisturizing agent is eucalyptus oil. The drugs are compatible to exert the effects of clearing heat and drying dampness, cooling blood and nourishing yin, activating blood and resolving stasis, warming yang and dispelling cold and supporting healthy qi and tonifying the body resistance. The traditional Chinese medicine composition is prepared through supercritical extraction, micronization treatment, solution preparation and intermittent ultrasonic homogenization. The traditional Chinese medicinal materials are used for treating the etiology, pathogenesis and symptoms of vulvar leukoplakia, the penetration enhancer reduces the skin barrier function, the activating agent enhances the drug activity and permeability, and the moisturizing agent maintains the skin moisture and assists in anti-inflammation. The clinical application effectively relieves the symptoms of patients with vulvar leukoplakia, improves the pathological state of local skin and improves the treatment effect, thereby providing a new effective option for the treatment of vulvar leukoplakia.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medicine preparation, in particular to a kind of external use traditional Chinese medicine composition for treating vulvar leukoplakia and preparation method thereof. BACKGROUND

[0002] Vulvar leukoplakia is a common chronic inflammatory non-tumor skin lesion of vulva, which was once called vulvar sclerosing atrophy, vulvar dystrophy, etc. It is now unified as female vulvar sclerosing lichen (vulvar lichen sclerosus, VLS), a group of chronic inflammatory diseases of vulvar skin and mucosa, which belongs to gynecological common diseases and is also one of the common causes of vulvar pruritus. It is characterized by progression, intractability and recurrence, and seriously affects the quality of life and prognosis of patients. At present, local drug treatment is mainly used, among which topical corticosteroid (TC) treatment is a more effective treatment method. However, many patients are not diagnosed in time, and the treatment is not standardized, which leads to repeated attacks and aggravation of the disease, and can affect the vulva, perineum and perianal region. Its etiology is unknown, which may be related to many factors, including autoimmune diseases, genetics, inflammation, endocrine, metabolism, local nerve blood vessels, infection and environmental factors, etc. At present, there is more evidence related to autoimmune diseases, about 28% of VLS patients, among which thyroid disease, alopecia areata and vitiligo are often combined, 1 / 3 of patients have increased autoantibodies, IgG increase, etc.; the second is genetic factor 1, 3, 6. According to literature reports, the incidence of VLS is 0.1%-3%, and due to no symptoms, not seeking medical treatment, misdiagnosis and data statistics, etc., the actual incidence may be higher-2. Its incidence shows a bimodal pattern, and prepubertal and postmenopausal women are two peaks, and postmenopausal women are more common, only about 1 / 3 occur before the age of 50 3.7. The lesion is characterized by atrophy, keratinization and porcelain / ivory white plaque of the epithelium.

[0003] At present, VLS treatment glucocorticoid treatment (TC) is a first-line treatment, if the initial treatment is invalid or poor effect, can use or combined with second-line treatment, physical therapy, etc. The first-line TC has many adverse reactions of drug use, principles and norms, strict control of indications, contraindications is the key to reduce adverse reactions. But children can have systemic effects. After drug use, capillary dilation, skin lines increase; skin mucosa atrophy thin, the incidence is about 1.1%~2%. Second-line treatment: immunosuppressive therapy, drug use may appear irritation, burning and secondary infection, and long-term safety is uncertain, there is a risk of using site cancer. Physical therapy includes fractional laser treatment, focused ultrasound treatment. These are traumatic treatment, the vulva is rich in nerves, because of obvious pain, patients are unwilling to accept, or multiple treatment is difficult to insist. Other treatments: for patients with excessive keratinization, severe skin thickening or hypertrophic scar who are invalid for first and second-line drugs, retinoids can help maintain epithelial and mucosal function, oral retinoids and assist multiple vitamins, or local use, but because of its adverse reactions and teratogenicity, it has not been widely used in clinical. Other treatment methods such as photodynamic therapy, light therapy, ultraviolet therapy, etc., but the above treatments still lack effective evidence, and need further study. In addition, local androgen therapy has many side effects, and is not good for improving symptoms, and is no longer used. SUMMARY

[0004] In view of this, the present application provides a kind of external use traditional Chinese medicine composition for treating vulvar leukoplakia and preparation method thereof, solve the above problems.

[0005] The technical scheme of the present application is as follows: an external use traditional Chinese medicine composition for treating vulvar leukoplakia, comprising the following raw materials by weight: 10-20 parts of angelica, 10-20 parts of cortex lycii, 20-30 parts of cortex dictamni, 20-30 parts of cumin, 10-20 parts of scrophularia, 20-30 parts of semen astragali, 10-20 parts of black smooth piece, 20-30 parts of elsholtzia, 20-30 parts of ilex pubescens, 10-20 parts of radix rehmanniae, 10-20 parts of dioscorea, 10-20 parts of patrinia, 10-20 parts of radix valerianae.

[0006] Further, an external use traditional Chinese medicine composition for treating vulvar leukoplakia, comprising the following raw materials by weight: 10 parts of angelica, 10 parts of cortex lycii, 20 parts of cortex dictamni, 30 parts of cumin, 10 parts of scrophularia, 20 parts of semen astragali, 10 parts of black smooth piece, 20 parts of elsholtzia, 30 parts of ilex pubescens, 10 parts of radix rehmanniae, 10 parts of dioscorea, 10 parts of patrinia, 10 parts of radix valerianae.

[0007] Further, it further comprises the following raw materials by weight: 3-5 parts of penetration enhancer, 0.1-0.3 parts of activator, 1-3 parts of humectant.

[0008] Further, the penetration enhancer is soybean lecithin, phosphatidylethanolamine and cholesterol in a mass ratio of (2-4):(1-3):(3-8).

[0009] Further, the activation agent is sodium cholate, sodium deoxycholate and sodium taurocholate in a mass ratio of (2-5):(1-3):(2-4).

[0010] Further, the humectant is selected from any one or a combination of menthol, eugenol or eucalyptus oil.

[0011] Further, a preparation method of an external use traditional Chinese medicine composition for treating vulvar leukoplakia comprises the following steps:

[0012] S1, the above-mentioned medicines are crushed, passed through a 60-100 mesh sieve, and put into a supercritical extraction device, and the supercritical CO2 extraction time is set to 1-3h to obtain a supercritical extract;

[0013] S2, the supercritical extract is micronized by airflow crushing or ball milling technology to make the particle size <5μm;

[0014] S3, the penetration enhancer is dissolved in anhydrous ethanol with a mass fraction of 65-75% to obtain a lipid solution;

[0015] S4, the extract of S2 is dissolved with a phosphate buffer to prepare a traditional Chinese medicine liquid with a concentration of 10-20mg / ml;

[0016] S5, the traditional Chinese medicine liquid is added to the lipid solution in a volume ratio of 10-20:1, and intermittent ultrasonic homogenization is used for 3-5 times, each time for 6-10min, and then the humectant is added and stirred to form a traditional Chinese medicine composition.

[0017] Further, the supercritical CO2 extraction temperature of S1 is 35-55℃, and the pressure is 15-30MPa.

[0018] Further, the mass / volume ratio g / mL of the penetration enhancer and anhydrous ethanol in S3 is 1:10-15.

[0019] Further, the ultrasonic frequency of S5 is 20-40kHz, the ultrasonic power is 100-300W, the ultrasonic temperature is 40-50℃, and the homogenization pressure is 60-100MPa.

[0020] Compared with the prior art, the present application has the following beneficial effects:

[0021] The treatment principle of the prescription is nourishing yin and blood, dispelling wind and relieving itching. Angelica is pungent and warm, and is distributed in heart, liver and spleen meridians. It is a blood tonic and can nourish and activate blood. Pericarpium Ziccy Lonicerae is sweet and slightly bitter, and can nourish yin and cool blood. Pericarpium Citri Reticulatae Viridis can dispel dampness and relieve itching. Cnidium is dry and can kill insects, and has significant antibacterial and anti-inflammatory effects. Scrophularia is cold, bitter, sweet and salty, and can activate blood and resolve stasis, nourish yin and moisten dryness. Fructus Kochiae can clear heat and relieve itching, and can regulate the immune function of the body and improve the microenvironment of the skin, thereby reducing the inflammatory response of the skin. Heishunpi can assist yang and dispel cold, has anti-ulcer effect, stimulates local skin, mucosa and sensory nerve endings, has certain local anesthetic effect and reduces scratching stimulation. Herba Moslae can dispel dampness, promote water and reduce swelling. It has anti-inflammatory properties, can inhibit the release of inflammatory factors and reduce the inflammatory response. It can also scavenge free radicals and protect cells from oxidative damage. Ilex hainanensis Merr. is cold and bitter, and can clear heat and resolve toxins, activate blood and unblock collaterals, and improve the local vulva. Radix Rehmanniae can clear heat and cool blood, nourish yin and generate body fluid and blood. Dioscorea can benefit qi and nourish yin, and can tonify the spleen, lung and kidney, and improve the immune function. Herba Patriniae can activate blood and resolve stasis, and can dispel dampness and relieve itching. Rhei Radix et Rhizoma can stop bleeding and activate blood and resolve stasis. By improving blood circulation and improving the local nutritional status, the itching can be relieved.

[0022] The various drugs are used together to treat the etiology, pathogenesis and symptoms of vulvar leukoplakia through the synergistic effects of clearing heat and drying dampness, cooling blood and nourishing yin, activating blood and resolving stasis, warming yang and dispelling cold, supporting healthy qi and tonifying the body and promoting drug absorption. The patient's uncomfortable symptoms can be effectively relieved, the pathological state of the local skin can be improved, tissue repair can be promoted, the treatment effect can be improved, and the purpose of treating both the symptoms and the root cause can be achieved.

[0023] The penetration enhancer, activator and humectant of the present application and the various drugs in the prescription cooperate with each other to promote drug absorption, enhance drug activity and improve the skin environment. They can make the effective components of traditional Chinese medicine better reach the lesion site, more fully exert the therapeutic effect, and improve the overall treatment effect, thereby providing a more effective treatment plan for patients with vulvar leukoplakia, relieving symptoms and improving the condition. DETAILED DESCRIPTION

[0024] In order to better understand the technical content of the present application, the following specific examples are provided to further illustrate the present application.

[0025] The experimental methods used in the examples of the present application are conventional methods unless otherwise specified.

[0026] The materials, reagents and the like used in the examples of the present application can be obtained from commercial channels unless otherwise specified.

[0027] The basic information of the main raw materials is introduced according to the Chinese Pharmacopoeia and the Chinese Herbal Medicine Dictionary as follows:

[0028] Angelica: sweet, pungent, warm, heart, liver, spleen, can blood, blood stasis, pain, moisten the role of the intestine. Modern pharmacological research, the main mechanism of blood tonic and angelica contains a variety of effective components closely related, including volatile oil, saponins and polysaccharides, etc., these components can promote the production of red blood cells, improve the blood oxygen carrying capacity, thus improving the overall health status of the body.

[0029] Cortex Lycii Radicis: is the root of the wolfberry, sweet, cold, lung, kidney. Can cool blood, clear heat. Modern pharmacological research: cortex Lycii Radicis has heat, cooling, detoxification and other multiple effects, widely used in the treatment of many diseases, such as fever, bleeding, skin disease, mainly cortex Lycii Radicis contains a variety of active ingredients such as flavonoids, phenolic acids and polysaccharides, etc., showing antioxidant, anti-inflammatory, immune regulation and anti-tumor and other multiple pharmacological effects.

[0030] Phellodendri Cortex: cold, bitter, spleen, stomach, has the effect of clearing heat and detoxifying, eliminating dampness and relieving itching, treating eczema, skin itching and other diseases have played a significant role. Modern pharmacological research: some active ingredients in Phellodendri Cortex can inhibit the growth and reproduction of pathogenic microorganisms, can inhibit bacteria and viruses, and effectively remove toxins in the body. In the aspect of swelling, the application of Phellodendri Cortex is also significant. Its swelling mechanism is mainly through improving local blood circulation and lymphatic return, reducing the degree of tissue edema. Phellodendri Cortex is widely used in the treatment of swelling caused by rheumatoid arthritis, soft tissue injury and other problems. Clinical studies have shown that the application of Phellodendri Cortex can significantly reduce local swelling, relieve pain, and promote functional recovery; its anti-inflammatory properties are closely related to its anti-inflammatory properties, which can inhibit the release of inflammatory mediators and reduce inflammation, thereby achieving the effect of swelling.

[0031] Cnidii Fructus: warm, bitter, kidney. Has the effect of warming kidney and strengthening yang, dispelling cold and dispelling wind, drying dampness and killing insects. It is often used to treat eczema, herpes zoster and other skin diseases, with significant antibacterial and anti-inflammatory effects. Studies have shown that Cnidii Fructus has multiple pharmacological effects such as antibacterial, anti-inflammatory and anti-tumor. In terms of antibacterial, Cnidii Fructus extract shows significant inhibitory activity against a variety of bacteria and fungi, especially against Staphylococcus aureus and Escherichia coli. In addition, active ingredients in Cnidii Fructus such as cnidimide and cnidic acid have been confirmed to have anti-tumor effects by regulating cell signaling pathways, which provides a theoretical basis for its application in tumor treatment

[0032] Scrophulariae Herba: cold, bitter, sweet, lung, stomach, kidney. Has the effect of clearing heat and resolving toxins, promoting blood circulation and removing blood stasis, nourishing yin and moistening dryness. It is used to treat warm disease, sore throat, swelling and soreness, and other diseases. Modern pharmacological research shows that it has multiple activities in anti-inflammatory, antioxidant, immune regulation and anti-tumor.

[0033] Fructus Kochiae: Cold in nature, bitter in taste, and belongs to the Bladder Meridian. It has the functions of clearing heat and promoting diuresis, and relieving itching. It is used to treat dysuria, stranguria, and pruritus. Its pharmacological effects make it effective in treating damp-heat diseases and skin diseases. Its mechanism is mainly through regulating the immune function of the body and improving the microenvironment of the skin, thereby reducing the inflammatory response of the skin.

[0034] Radix Aconiti: It is a kind of aconite, hot in nature, and bitter in taste. It belongs to the Heart, Kidney, and Spleen Meridians. Its main functions are restoring yang, tonifying fire and yang, and dispelling cold and pain. It is used for treating yang deficiency syndrome, with symptoms of cold sweating, cold limbs, and weak pulse. Aconite can assist heart yang to open the pulse and supplement kidney yang to benefit fire, thus saving the scattered yang and being the main drug for restoring yang. It is used for treating yang deficiency syndrome. It is good at tonifying fire and yang, and is suitable for those with weak yang qi in the kidney, spleen, and heart. It is used for treating arthralgia, especially for those with excessive cold and dampness, and joint pain. Modern pharmacological research shows that aconite can dilate peripheral blood vessels, have anti-inflammatory, sedative, and analgesic effects, promote platelet aggregation, inhibit cell stabilization, and have anti-ulcer and laxative effects. It can stimulate local skin, mucosa, and sensory nerve endings, and has a certain local anesthetic effect.

[0035] Herba Moslae: It is slightly warm in nature and bitter in taste, and belongs to the Lung and Stomach Meridians. It has the functions of sweating and relieving the exterior, harmonizing the center and eliminating dampness, and promoting diuresis and reducing swelling. It is used to treat edema, dysuria, fever and headache caused by summer heat or external wind-cold, and abdominal pain and diarrhea. Modern research shows that Herba Moslae extract has significant inhibitory effects on various bacteria and fungi. At the same time, some components in Herba Moslae have been found to have anti-inflammatory properties, which can inhibit the release of inflammatory factors and reduce inflammatory response. In addition, flavonoids in Herba Moslae are considered to be the main antioxidant components, which can scavenge free radicals and thus protect cells from oxidative damage.

[0036] Radix Ilicis Pubescentis: It is cold in nature, bitter and astringent in taste, and belongs to the Lung, Liver, and Large Intestine Meridians. It has the functions of clearing heat and resolving toxins, dispelling wind and cold, and promoting blood circulation and removing obstruction in the collaterals. It is used to treat sore throat, tonsillitis, burns, carbuncles, and thrombotic occlusive vasculitis. It shows good effects in the treatment of surgical diseases and skin diseases, especially in the treatment of inflammation and lumps. Modern pharmacological research shows that it has the effects of dilating blood vessels, promoting blood circulation and removing obstruction in the collaterals, and antibacterial.

[0037] Radix Rehmanniae: It is cold in nature, sweet and bitter in taste, and belongs to the Heart, Liver, and Kidney Meridians. It has the functions of clearing heat and cooling blood, nourishing yin and generating fluid, and nourishing blood and stopping bleeding. It is used for treating heat entering the blood and yin deficiency in heat disease. Research shows that Radix Rehmanniae has significant anti-inflammatory effects, which can inhibit the expression of inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and reduce the inflammatory response of tissues. Active ingredients in Radix Rehmanniae, such as radix rehmanniae glycosides, have obvious inhibitory effects on oxidative stress, and can effectively scavenge free radicals, thereby protecting cells from oxidative damage.

[0038] Yam: Neutral in nature, sweet in taste, and enters the lung, spleen, and kidney meridians. It nourishes qi and yin, tonifies the spleen, lungs, and kidneys, and improves immune function. It treats spleen deficiency, poor appetite and loose stools, kidney deficiency and seminal emission, frequent urination, and excessive vaginal discharge in women. Studies have shown that yam can regulate the immune system and enhance the body's self-defense capabilities through multiple mechanisms. Yam is rich in polysaccharides and amino acids, which can promote the activity of macrophages, enhance their phagocytic and bactericidal abilities, thereby improving the body's immune response. Furthermore, the natural components in yam can activate the proliferation and differentiation of T cells and B cells, enhancing cellular and humoral immunity, thus improving the body's resistance to pathogens. Simultaneously, yam has also been found to have antioxidant properties, which can reduce the damage of oxidative stress to immune cells, further promoting the health of the immune system.

[0039] Patrinia scabiosifolia: Slightly cold in nature, pungent and bitter in taste. It enters the stomach, large intestine, and liver meridians. It has the effects of clearing heat and detoxifying, promoting blood circulation and removing blood stasis, reducing swelling and relieving pain, eliminating carbuncles and draining pus, resolving phlegm and relieving cough. It can treat carbuncles caused by heat toxins and chest and abdominal pain due to blood stasis. Modern pharmacological studies have shown that it has multiple pharmacological effects, including anti-inflammatory, antioxidant, antitumor, and antibacterial activities. In terms of anti-inflammatory effects, extracts of Patrinia scabiosifolia can inhibit the release of inflammatory factors, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), thereby reducing the inflammatory response. This provides potential application value for the treatment of chronic inflammatory diseases. In addition, Patrinia scabiosifolia also shows inhibitory effects on certain cancer cells. Studies have found that its extracts can induce apoptosis in cancer cells and inhibit the proliferation of tumor cells; this effect may be related to the regulation of the cell cycle by its active ingredients.

[0040] Rhubarb (processed with alcohol): Warm in nature and bitter in taste. It enters the liver and stomach meridians. It has hemostatic and blood-activating effects. Rhubarb (processed with alcohol) has excellent hemostatic effects, especially significant for treating internal bleeding. Studies have shown that rhubarb (processed with alcohol) can effectively promote blood coagulation and shorten bleeding time, thus playing a key role in clinical hemostasis. This characteristic makes rhubarb (processed with alcohol) an important drug choice in the emergency treatment and management of patients with internal bleeding. Rhubarb (processed with alcohol) also has the effect of activating blood and removing blood stasis. By improving blood circulation, rhubarb (processed with alcohol) can effectively promote the dissipation of blood stasis, thereby relieving pain and discomfort caused by blood stasis. In treating some diseases caused by blood stasis, such as dysmenorrhea and traumatic injuries, it can significantly improve patients' symptoms and promote physical recovery.

[0041] Example 1

[0042] A topical traditional Chinese medicine composition for treating vulvar leukoplakia comprises the following ingredients by weight: 10g Angelica sinensis, 10g Lycium chinense root bark, 20g Dictamnus dasycarpus root bark, 20g Cnidium monnieri fruit, 10g Scrophularia ningpoensis root, 20g Kochia scoparia fruit, 10g Aconitum carmichaelii root slices, 20g Elsholtzia ciliata rhizome, 20g Ilex pubescens root, 10g Rehmannia glutinosa root, 10g Dioscorea opposita rhizome, 10g Patrinia scabiosaefolia herb, 10g Rheum palmatum root (processed with wine), 3g penetration enhancer, 0.1g activator, and 1g moisturizer;

[0043] The penetration enhancer is soybean lecithin, phosphatidylethanolamine and cholesterol in a mass ratio of 2:1:3; the activator is sodium cholate, sodium deoxycholate and sodium taurocholate in a mass ratio of 2:1:2; the humectant is selected from menthol.

[0044] Example 2

[0045] A topical traditional Chinese medicine composition for treating vulvar leukoplakia comprises the following ingredients by weight: 20g Angelica sinensis, 20g Lycium chinense root bark, 30g Dictamnus dasycarpus root bark, 30g Cnidium monnieri fruit, 20g Scrophularia ningpoensis root, 30g Kochia scoparia fruit, 20g Aconitum carmichaelii root slices, 30g Elsholtzia ciliata rhizome, 30g Ilex pubescens root, 20g Rehmannia glutinosa root, 20g Dioscorea opposita rhizome, 20g Patrinia scabiosaefolia herb, 20g Rheum palmatum root (processed with wine), 5g penetration enhancer, 0.3g activator, and 3g moisturizer;

[0046] The penetration enhancer is soybean lecithin, phosphatidylethanolamine and cholesterol in a mass ratio of 4:3:8; the activator is sodium cholate, sodium deoxycholate and sodium taurocholate in a mass ratio of 5:3:4; the humectant is selected from eugenol.

[0047] Example 3

[0048] A topical traditional Chinese medicine composition for treating vulvar leukoplakia comprises the following ingredients by weight: 10g Angelica sinensis, 10g Lycium chinense root bark, 20g Dictamnus dasycarpus root bark, 30g Cnidium monnieri fruit, 10g Scrophularia ningpoensis root, 20g Kochia scoparia fruit, 10g Aconitum carmichaelii root slices, 20g Elsholtzia ciliata rhizome, 30g Ilex pubescens root, 10g Rehmannia glutinosa root, 10g Dioscorea opposita rhizome, 10g Patrinia scabiosaefolia herb, 10g Rheum palmatum root (processed with wine), 4g penetration enhancer, 0.2g activator, and 2g moisturizer;

[0049] The penetration enhancer is soybean lecithin, phosphatidylethanolamine and cholesterol in a mass ratio of 3:2:5; the activator is sodium cholate, sodium deoxycholate and sodium taurocholate in a mass ratio of 4:2:3; the humectant is selected from eucalyptus oil.

[0050] The above Examples 1-3 were prepared using the following methods:

[0051] S1. The above-mentioned drugs are pulverized, passed through an 80-mesh sieve, and placed in a supercritical extraction device. The supercritical CO2 extraction time is set to 2 hours, the supercritical CO2 extraction temperature is 45℃, and the pressure is 25MPa to obtain the supercritical extract.

[0052] S2. The supercritical extract is micronized using air jet milling or ball milling technology to make the particle size <5μm;

[0053] S3. Dissolve the penetration enhancer in 70% anhydrous ethanol, with a mass-volume ratio of penetration enhancer to anhydrous ethanol of 1:13 g / mL, to obtain a lipid solution.

[0054] S4. Dissolve the extract from S2 in phosphate buffer to prepare a 15 mg / ml traditional Chinese medicine solution.

[0055] S5. Add the Chinese herbal liquid to the lipid solution at a volume ratio of 15:1, and homogenize using intermittent ultrasound 4 times, 8 minutes each time. The ultrasound frequency is 30kHz, the ultrasound power is 200W, the ultrasound temperature is 45℃, and the homogenization pressure is 80MPa. After the ultrasound is completed, add a humectant and stir to form the Chinese herbal composition.

[0056] Comparative Example 1

[0057] The difference between this comparative example and Example 3 is that the external Chinese medicine composition for treating vulvar leukoplakia includes the following raw materials in parts by weight: Angelica sinensis 3g, Lycium chinense root bark 25g, Dictamnus dasycarpus root bark 15g, Cnidium monnieri fruit 11g, Scrophularia ningpoensis root 21g, Kochia scoparia fruit 17g, Aconitum carmichaelii root slices 6g, Elsholtzia ciliata rhizome 38g, Ilex pubescens root 14g, Rehmannia glutinosa root 26g, Dioscorea opposita rhizome 30g, Patrinia scabiosaefolia herb 8g, Rheum palmatum root 25g, penetration enhancer 4g, activator 0.2g, and moisturizer 2g.

[0058] Comparative Example 2

[0059] The difference between this comparative example and Example 3 is that, in the preparation method of the topical Chinese medicine composition for treating vulvar leukoplakia, after the above-mentioned drugs are pulverized and extracted, a penetration enhancer, an activator and a moisturizer are directly added and stirred evenly to obtain the Chinese medicine composition.

[0060] Comparative Example 3

[0061] The difference between this comparative example and Example 3 is that the topical Chinese medicine composition for treating vulvar leukoplakia does not contain a penetration enhancer.

[0062] Comparative Example 4

[0063] The difference between this comparative example and Example 3 is that the topical Chinese medicine composition for treating vulvar leukoplakia does not contain an activator.

[0064] Test Example 1 - Permeability Test

[0065] 1. Experimental Preparation: Select pig skin, remove subcutaneous fat and hair, rinse thoroughly with physiological saline, then place the skin in physiological saline and store at 4℃ for later use; carefully cut the skin into 3cm×3cm pieces with a scalpel blade so that it can fit tightly against the separator of the Franz diffusion cell. Physiological saline was selected as the receiving medium.

[0066] 2. Assemble the Franz diffusion cell

[0067] Place the treated skin between the supply and receiving pools of the Franz diffusion cell, ensuring a good seal to prevent leakage; add the receiving medium preheated to 37°C to the receiving pool, taking care to avoid generating air bubbles; the volume of the receiving medium should submerge the subsurface of the skin.

[0068] Place a magnetic stir bar in the receiving cell, place the diffusion cell on the magnetic stirrer, and adjust the stirring speed to 100 rpm to ensure uniform mixing of the receiving medium and enable the drug to diffuse rapidly in the receiving medium.

[0069] 3. Apply medication

[0070] Accurately weigh 5g of the topical Chinese medicine composition for treating vulvar leukoplakia, and apply it evenly to the upper surface of the skin in the supply pool, covering the entire area of ​​the skin in contact with the supply pool, and maintaining a consistent application thickness.

[0071] 4. Sample Collection

[0072] At designated time points (1h, 4h, 6h, and 8h), 1mL of the receiving medium sample was aspirated from the receiving cell using a micropipette. Simultaneously, an equal volume of fresh receiving medium preheated to 37°C was rapidly added to maintain a constant liquid volume in the receiving cell and avoid affecting drug diffusion. The aspirated sample was then transferred to a suitable container. Based on the properties of the active ingredients in the traditional Chinese medicine composition, the concentration of the drug in the sample was determined using analytical instruments such as high-performance liquid chromatography (HPLC) and ultraviolet spectrophotometer.

[0073] 5. Data Processing

[0074] The cumulative drug penetration (Q) is calculated based on the drug concentrations measured at different time points.

[0075] The formula is: Q=C×V / A, where C is the concentration of the drug in the sample, V is the volume of each sample taken, and A is the effective diffusion area of ​​the skin or artificial membrane.

[0076] 6. Experimental Results

[0077]

[0078] Trial Example 2 - Clinical Trial

[0079] I. Subject Selection:

[0080] 1. Inclusion criteria: Patients aged 18-65 years with clinical and pathological diagnoses of vulvar leukoplakia, meeting the relevant diagnostic criteria. Patients must voluntarily participate in this trial and sign an informed consent form.

[0081] 2. Exclusion criteria:

[0082] Those allergic to any component of this traditional Chinese medicine composition.

[0083] Patients with serious diseases of vital organs such as the heart, liver, and kidneys.

[0084] Those who have used other medications or received related treatments for vulvar leukoplakia within the past 3 months.

[0085] Women who are pregnant or breastfeeding.

[0086] II. Experimental Design

[0087] 1. Trial type: randomized, double-blind, placebo-controlled trial.

[0088] 2. Trial grouping: Patients who meet the inclusion criteria are randomly divided into an experimental group (the topical Chinese medicine composition of this invention) and a control group (placebo), with 50 patients in each group.

[0089] 3. Treatment duration: 2 weeks.

[0090] III. Treatment Methods

[0091] Experimental group: This topical Chinese medicine composition was applied to the affected area of ​​the vulva twice a day, once in the morning and once in the evening.

[0092] Control group: A placebo with the same appearance and smell as the experimental group was used, and the application method was the same as that of the experimental group.

[0093] IV. Observation Indicators

[0094] 1. Therapeutic indicators:

[0095] Severity of vulvar pruritus: The Visual Analogue Scale (VAS) was used, with 0 points indicating no pruritus and 10 points indicating the most severe pruritus. The assessment was conducted before treatment, on day 5, day 10, and day 14 of treatment.

[0096] Vulvar skin lesion area: The improvement of the lesion is assessed by measuring the area of ​​the vulvar lesion. Measurements are taken before treatment and in the second week of treatment.

[0097] Pathological changes in vulvar skin tissue: Pathological examination of lesion tissue was conducted before treatment and in the second week of treatment to observe the morphology of epithelial cells, the degree of keratinization, and the infiltration of inflammatory cells.

[0098] 2. Safety indicators:

[0099] Record any adverse reactions that occur during treatment, such as skin redness, swelling, pain, and rash.

[0100] Before treatment and during the second week of treatment, blood routine tests, urine routine tests, liver function tests, and kidney function tests were performed to assess the effects of the drug on vital organs throughout the body.

[0101] V. Criteria for Evaluating Therapeutic Effect

[0102] Cure: The symptoms of vulvar itching have completely disappeared, and the area of ​​skin lesions has returned to normal.

[0103] Significant effect: Vulvar itching symptoms are significantly reduced, VAS score decreases by ≥70%, and skin lesion area shrinks by ≥70%.

[0104] Effective: Vulvar itching symptoms were alleviated, VAS score decreased by ≥30% and <70%, and the area of ​​skin lesions decreased by ≥30% and <70%.

[0105] Ineffective: No significant improvement in vulvar itching symptoms, VAS score decrease of <30%, and skin lesion area reduction of <30%.

[0106] Experimental results:

[0107] number of recovery cases number of marked improvement cases number of effective cases number of ineffective cases total effective rate (%) Example 1 14 20 14 2 96 Example 2 15 21 13 1 98 Example 3 16 22 12 0 100 Comparative Example 1 10 15 14 11 78 Comparative Example 2 9 12 13 16 68 Comparative Example 3 9 13 10 18 64 Comparative Example 4 8 12 11 19 62 control group 0 3 10 37 26

[0108] After using the topical Chinese medicine composition of this invention, the patient's vulvar itching symptoms completely disappeared, the total effective rate reached 100%, the area of ​​skin lesions returned to normal, and it effectively treated vulvar leukoplakia.

[0109] Typical cases

[0110] Case 1:

[0111] Patient Liang, female, 29 years old, office worker, unmarried, denies sexual activity. First visit on March 23, 2024. Chief complaint: Recurrent itching for 3 months. This patient had consulted multiple hospitals due to recurrent vulvar itching. Physical examination and auxiliary tests all suggested vaginitis, but since she had no history of sexual activity, she was treated with topical medications and sitz baths. The vulvar itching did not improve and even worsened. Physical examination: Sallow complexion, fatigue. Limited vaginal discharge with no obvious odor. Appetite and bowel movements were normal. Tongue was reddish with little coating; pulse was thready and wiry. Gynecological examination: Fresh scratch marks and redness were found on both labia majora, labia minora, clitoris, and perianal area; a fissure was present at the 6 o'clock position of the anal folds; both labia minora showed hypopigmentation, dullness, decreased elasticity, and significant swelling. Multiple examinations of vaginal discharge at other hospitals showed no significant abnormalities.

[0112] The applicant believes the TCM diagnosis is vulvar itching (Yin deficiency syndrome), and the Western medicine diagnosis is vulvar leukoplakia. Treatment should focus on nourishing Yin and blood, clearing heat and cooling blood to relieve itching. Prescription: This invention's herbal composition, used for sitz baths once daily for 5 consecutive days. The applicant is advised to maintain a regular sleep schedule and a light diet. Dietary adjustments should be made, avoiding spicy and irritating foods.

[0113] Second visit on March 30, 2024: The patient reported significant improvement in vulvar itching over two days. Gynecological examination: No obvious fresh scratch marks on the vulva. Continue treatment according to the original plan, using the herbal composition of this invention, for the vulva for one week.

[0114] Third visit on April 6, 2024: The patient complained of significant itching at night, but no significant itching during the day or at night.

[0115] On May 3, 2024, the fifth visit was conducted. There was no significant itching. Gynecological examination revealed no obvious scratches on the vulva. The labia majora and minora were nearly normal skin color, with slightly darker pigmentation near the labia minora and slightly reduced elasticity. The previous treatment plan was continued for another 10 days, and the patient was taught vulvar massage techniques.

[0116] Case 2:

[0117] Ms. Fu, female, 46 years old, office worker, married. First visit on November 28, 2023. Chief complaint: Vulvar itching for over 10 years. Denies history of diabetes. Multiple visits and treatments at different hospitals with no significant improvement. Gynecological examination: Vulva and clitoris (the inner third of both labia majora and labia minora) were pale; vagina was patent with a small amount of yellow discharge; cervix was smooth; uterus and adnexa were normal. Tongue was reddish with little coating; pulse was thready. Multiple examinations at other hospitals had not revealed any significant abnormalities in discharge.

[0118] The applicant believes the TCM diagnosis is vulvar itching (Yin deficiency syndrome), and the Western medicine diagnosis is vulvar leukoplakia. Treatment should focus on nourishing Yin and blood, clearing heat and cooling blood to relieve itching. Prescription: This invention's herbal composition, used for sitz baths once daily for 5 consecutive days. The applicant is advised to maintain a regular sleep schedule and a light diet. Dietary adjustments should be made, avoiding spicy and irritating foods.

[0119] The next day, the patient came to the hospital to report that the vulvar itching had significantly improved, and the itching had lessened considerably this morning.

[0120] Case 3:

[0121] Ms. Chen, 75 years old. Married. First diagnosis on November 23, 2023. Denies history of diabetes. Chief complaint: Vulvar itching for 2 months. Also experiences constipation and a feeling of heaviness and discomfort in the vulva when walking. Consulted gynecologists and dermatologists, but medication did not improve the condition. Tongue is reddish with a thin yellow coating; pulse is thready. Gynecological examination: Redness, swelling, and hardening of the bilateral groin, mons pubis, vulva, perineum, and perianal area; scattered lacerations, no obvious bleeding or oozing; pale and rough inner labia majora and labia minora bilaterally; prominent fissure-like changes around the clitoris; no bleeding or parasites; pale and edematous perineum; a pale and edematous lesion approximately 3*3cm in size on the left side of the anus; vagina patent with a small amount of yellowish-green purulent discharge; clear mucosal congestion. Cervical atrophy. No other abnormalities were found.

[0122] The applicant believes the TCM diagnosis is vulvar pruritus (Yin deficiency syndrome), and the Western medicine diagnosis is vulvar leukoplakia. Treatment should focus on nourishing Yin and blood, clearing heat and cooling blood to relieve itching. Prescription: This invention's herbal composition, used for sitz baths once daily for three consecutive days. The applicant is advised to maintain a regular sleep schedule and a light diet. Dietary adjustments should be made, avoiding spicy and irritating foods, and minimizing scratching.

[0123] The patient returned for a follow-up visit on December 5, 2023. The itching had significantly improved, except around 1-3 AM when it worsened considerably. At other times, the patient could tolerate scratching. This morning, the itching had significantly decreased. Physical examination revealed: the vulva and lower two-thirds of the mons pubis were firm, with a marked reduction in scattered vesicular changes. The upper one-third of both labia majora were slightly red. The patient was diagnosed as Dr. Wu Lousun. The clitoral area was pale, and a pale lesion approximately 3*3cm in size was observed on the left side of the anus. The patient was prescribed oral Rehmannia Decoction and a sitz bath with the above formula.

[0124] On December 16, 2023, I was informed via WeChat that there was no obvious itching.

[0125] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A topical traditional Chinese medicine composition for treating vulvar leukoplakia, characterized in that: Composed of the following ingredients by weight: Angelica sinensis 10-20 parts, Lycium chinense root bark 10-20 parts, Dictamnus dasycarpus root bark 20-30 parts, Cnidium monnieri fruit 20-30 parts, Scrophularia ningpoensis root 10-20 parts, Kochia scoparia fruit 20-30 parts, Aconitum carmichaelii root slices 10-20 parts, Elsholtzia ciliata rhizome 20-30 parts, Ilex pubescens root 20-30 parts, Rehmannia glutinosa root 10-20 parts, Dioscorea opposita rhizome 10-20 parts, Patrinia scabiosaefolia herb 10-20 parts, Rheum palmatum root (processed with wine) 10-20 parts, and a penetration enhancer 3 parts. -5 parts, activator 0.1-0.3 parts, humectant 1-3 parts; the penetration enhancer is soybean lecithin, phosphatidylethanolamine and cholesterol in a mass ratio of (2-4):(1-3):(3-8); the activator is sodium cholate, sodium deoxycholate and sodium taurocholate in a mass ratio of (2-5):(1-3):(2-4); the humectant is selected from any one or a combination of several of menthol, eugenol or eucalyptus oil.

2. The topical traditional Chinese medicine composition for treating vulvar leukoplakia as described in claim 1, characterized in that: It is composed of the following ingredients in parts by weight: Angelica sinensis 10 parts, Lycium chinense root bark 10 parts, Dictamnus dasycarpus root bark 20 parts, Cnidium monnieri fruit 30 parts, Scrophularia ningpoensis root 10 parts, Kochia scoparia fruit 20 parts, Aconitum carmichaelii root slices 10 parts, Elsholtzia ciliata fruit 20 parts, Ilex pubescens root 30 parts, Rehmannia glutinosa root 10 parts, Dioscorea opposita root 10 parts, Patrinia scabiosaefolia herb 10 parts, Rheum palmatum root (processed with wine) 10 parts, penetration enhancer 4 parts, activator 0.2 parts, and moisturizer 2 parts.

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