WO2020182181A1 - Use of nocardia rubra cell wall skeleton in treating white lesions on vulva - Google Patents

Abstract

Provided is the use of Nocardia rubra cell wall skeleton in treating white lesions on the vulva. Provided is a pharmaceutical composition, wherein same comprises a component derived from a Nocardia rubra cell wall, and can effectively treat white lesions on the vulva, including lichen sclerosus and squamous cell hyperplasia.

Description

Application of Nocardia rubra cell wall skeleton in treating white lesions of vulva

This application claims the priority of the patent application (application number CN201910191961.8) filed on March 14, 2019, which is incorporated herein by reference.

Technical field

The present disclosure relates to the medical field, the microbiological field, and the biopharmaceutical field. Specifically, this application relates to the use of Nocardia rubra cell wall skeleton in the preparation of drugs for treating white lesions of the vulva.

Background technique

Nocardia rubra (Nocardia rubra) is a kind of Nocardia. Nocardia rubra cell wall skeleton (hereinafter referred to as Nr-CWS or N-CWS) can be produced by fermentation, cell disruption, and protease degradation of Nocardia rubra cell wall.

Nocardia is polymorphous, with spherical, rod-shaped, or filamentous. Bacteria are not motility, some strains are weakly resistant to acid and obligate aerobic. On ordinary agar plates, colonies can be seen after 3 days of culture, and after 7 to 10 days, the colonies bulge and form aerial hyphae with a fluffy surface. The colonies of different strains are yellow, orange, or red. The molar content of G+C in DNA is 60 to 72%. Most Nocardia bacteria are saprophytes and exist in the soil.

In the prior art, the Nocardia rubra cell wall skeleton can be commercially available, such as a product produced by Liaoning Grace Biopharmaceutical Co., Ltd. (trade name "Nakejia"), or Fujian Shanhe Pharmaceutical Co., Ltd. , Fujian Guangshengtang Pharmaceutical Co., Ltd., Fujian Institute of Microbiology, etc. Nocardia rubra cell wall skeleton has been used to treat cervical erosion, cervical precancerous lesions (CN101073583A), anti-human papilloma virus (CN1935262A), skin damage (CN101209267A), skin lesions (eczema, neurodermatitis, non-specific dermatitis, Atopic dermatitis, psoriasis) (CN108938674A), acne (CN108295095A), fungal infection, herpes simplex, herpes zoster (CN1879661A).

White lesions of the vulva include white lesions of the vulva, leukoplakia or vulvar dystrophy. Because the vulvar mucosa of patients with lichen sclerosus and squamous cell hyperplasia is white, it is called vulvar white lesions (non-tumor-like lesions of the vulvar epithelium).

The proliferation of lichen sclerosus and squamous epithelial cells in different ages has changed its names due to different clinical and pathological understandings (leukoplakia of the vulva, leukoplakia vulvitis, dry vulva, proliferative or atrophic vulvitis, sclerosing atrophic Moss, etc.). Due to the confusion of the naming of the disease, the International Association for the Study of Vulvar Diseases (ISSVD) collectively referred to it as chronic vulvar dystrophy in 1975. In 1987, ISSVD and the International Society of Gynecological Pathologists (ISGYP) discussed and formulated a new classification of vulvar skin diseases (ISSVD, 1987), including:

(1) Non-neoplastic epithelial disorders of skin and mucosa (non-neoplastic epithelial disorders of skin and mucosa)

1) Lichen sclerosus;

2) Squamous cell hyperplasia;

(2) Intra-epithelial neoplasia

1) Squamous intra-epithelial neoplasia;

a. Mild dysplasia (mild dysplasia);

b. Moderate dysplasia (moderate dysplasia);

c. Severe dysplasia or carcinoma in situ (severe dysplasia or carcinoma in situ);

2) Non-squamous intra-epithelial neoplasia;

a. Paget's disease (Paget`sdisease);

b. Noninvasive tumors of melanocytes;

(3) Invasive tumors.

Treatments for white lesions of the vulva usually include:

1. Keep the vulva clean and dry, prohibit irritating drugs, avoid wearing airtight underwear, and avoid spicy and allergic foods. Sedative, sleeping and anti-allergic drugs can be added to those who have obvious symptoms of itching and cause insomnia.

2. Drug therapy: Commonly used drugs for lichen sclerosus are pyruvate ointment, compound vitamin A ointment and progesterone ointment, glucocorticoid ointment or immunotherapy. Squamous epithelial hyperplasia of the vulva can be treated with topical corticosteroids to control itching. Treatment is effective for most patients, but long-term medication must be adhered to.

3. Physiotherapy: It is suitable for those who are ineffective or severely ill. Microwave treatment, carbon dioxide laser, helium-neon laser, Pomer light, high-frequency electrosurgical knife, local electrocautery therapy, and liquid nitrogen local cryotherapy.

4. Surgical treatment: only suitable for patients with serious illness, repeated medication or physical therapy ineffective. When malignant transformation is suspected, surgical treatment is required.

In view of this, there is still a need in the art to provide a medicine for effectively treating white lesions of the vulva.

Summary of the invention

According to some embodiments of the present application, there is provided the use of the cell wall skeleton of Nocardia rubra in the preparation of drugs or medical devices for treating white lesions of the vulva or its recurrence.

In some embodiments, the white lesions of the vulva are selected from any one or a combination of the following: lichen sclerosus and squamous cell hyperplasia.

In some embodiments, the drug or medical device is administered by skin contact or mucosal contact.

In some embodiments, the drug or medical device includes a pharmaceutically acceptable carrier. Any suitable vector known to those skilled in the art can be used to implement the technical solutions of the present application.

In some embodiments, the drug is prepared into a dosage form selected from the group consisting of suppositories, ointments, creams, emulsions, suspensions, pastes, gels, lotions, tinctures, oils, tablets, aerosols , Spray, liniment, powder; wherein the ointment is selected from: ointment, plaster, and cream.

According to some embodiments, there is provided a method for treating or preventing the recurrence of white lesions of the vulva, comprising the steps of: providing a subject with a therapeutically effective amount of Nocardia rubra cell wall skeleton.

In some specific embodiments, drugs (or medical devices) are applied to the lesions according to the area and severity of the lesions. For example, but not limited to smearing with a drug containing Nocardia rubra cell wall skeleton, or covering the lesion with a patch impregnated with Nocardia rubra cell wall skeleton, or freeze-dried powder containing Nocardia rubra cell wall skeleton Apply directly to the lesion, or apply paste, suppository, lotion, etc. containing Nocardia rubra cell wall skeleton on the lesion.

In some embodiments, the medicament comprises:

-Nocardia rubra cell wall skeleton, and

-A pharmaceutically acceptable carrier.

In some embodiments, the pharmaceutically acceptable carrier is selected from but not limited to: fillers, stabilizers (e.g., trehalose, glycine), flavoring agents (e.g., xylitol), disintegrants (e.g., carboxymethyl) Base cellulose), binders (e.g. gelatin), lubricants (e.g. magnesium stearate).

In some embodiments, the stabilizer is selected from one or a combination of the following: glycine, lysine, arginine, hydroxyethyl starch, hydroxymethyl starch, trehalose, dextran.

In some embodiments, the flavoring agent is selected from one or a combination of the following: sucrose, monosaccharides, sodium saccharin, aspartame, sorbitol, xylitol, mannitol.

In some embodiments, the binder is selected from one or a combination of the following: sodium carboxymethyl cellulose, hypromellose, gelatin.

In some embodiments, the lubricant is selected from one or a combination of the following: talc, magnesium stearate, and micronized silica gel.

In some specific embodiments, the carrier suitable for this application can also be mentioned, such as but not limited to: dextran, lactose, microcrystalline cellulose, trehalose, glycine, xylitol, sodium carboxymethyl cellulose, erythritol Trisitol, gelatin, magnesium stearate, propellant, humectant, solvent, solubilizer, emulsifier, antioxidant, pH adjuster, preservative. Specifically, non-limiting examples also include: white petrolatum, carbomer, hypromellose, methyl cellulose, sodium hydroxymethyl cellulose, chitosan, sucralfate chitosan, polyvinylpyrrolidone, Polyvinyl alcohol, sodium hyaluronate, dimethyl ether, tetrafluoroethane, hydrofluoroalkane, glycerin, propylene glycol, deionized water, water for injection, distilled water, ethanol, cetyl alcohol, stearyl alcohol, p-aminobenzoic acid, ethyl Amide, isopropanol, Tween, polyoxyethyl hydrogenated castor oil, stearic acid, glyceryl monostearate, triglyceride monostearate, sucrose fatty acid ester, sucrose ester, sucrose acetate isobutyrate Esters, sorbitan tristearate, isopropyl myristate, cholesterol, squalene, squalane, n-butanol, ethylene glycol, ethanol, propylene glycol, polyglyceride, sulfite, cyste Acid, di-tert-butylhydroxytoluene, potassium sorbate, phosphate buffer solution, triethanolamine, sodium hydroxide, ethylenediamine, laurylamine, sodium bicarbonate, hydrochloric acid, parabens, thimerosal, chlorocresol, three Chlorobutanol, benzoic acid and its sodium salt.

In some embodiments, the pharmaceutically acceptable carrier is dextran.

In some embodiments, the medicament or medical device of the present application is administered 1-3 times a day, or once a day, or once every two days. Depending on the area and depth of the patient’s lesion, a different dose is used, usually 1 μg/unit dose/each time to 1000 μg/unit dose/each time. Specifically, such as 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120 , 130, 140, 150, 160, 170, 180, 190, 200 μg/unit dose/each time, and the range between any two of the foregoing values.

In some embodiments, the administration cycle lasts from 2 days to 6 months, for example, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks or longer, and the range between any two of the foregoing values.

In some embodiments, the Nocardia rubra cell wall skeleton is a commercially available Nocardia rubra cell wall skeleton.

In other embodiments, the Nocardia rubra cell wall skeleton is obtained in the following manner, which includes or consists of the following steps:

1) Provide Nocardia rubrum;

2) Crushing the Nocardia rubra to obtain a crushed product;

3.1) Optionally, perform a lipid removal operation on the pulverized product;

3.2) Optionally, perform the operation of removing nucleic acid on the crushed product;

3.3) Optionally, perform the operation of removing protein on the pulverized product;

3.4) Obtain the product derived from the cell wall of Nocardia rubra;

4) Optionally, freeze-dry the product derived from the cell wall of Nocardia rubra;

5) Optionally, subpackage;

among them,

Step 3.1), 3.2), 3.3) can be interchanged in order or in parallel,

Step 4) and step 5) can interchange the order;

The average particle size of the pulverization is 10 nm to 1000 nm, preferably 10 nm to 800 nm, more preferably 10 nm to 500 nm;

Preferably, the sub-packing refers to sub-packing into a container;

The container is selected from: bottles, tubes, bags, bags, plates, ampoules, injection devices, aluminum film packaging, dressings, capsules, and films.

For the crushing of Nocardia rubrum, the purpose is to remove the substances in the cells, so ultrasonic crushing, lysozyme and other technologies can be used. The skilled person understands that any known or future methods suitable for breaking Gram-positive bacteria are applicable to the technical solutions of the present disclosure.

Technicians have the ability to adjust the specific parameters and equipment of cultivation, crushing, separation, collection, impurity removal, and sub-packaging according to the subsequent application (for example, external application) of the active ingredients (cell wall and its constituent components), so as to avoid the introduction of the preparation steps that affect the follow-up Applied factors.

In some embodiments, an organic solvent is used to remove lipids from the fragmented product. In some embodiments, nucleases are used to remove DNA and RNA in the fragmented product. In some embodiments, a hydrolase is used to degrade the protein in the fragmented product. In some embodiments, a surfactant is used to remove the cell membrane in the disrupted product.

In some embodiments, the average particle size of pulverization is 10 nm to 1000 nm; mention may be made of 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190nm±10nm, and the range between any two of the above values. There are many testing methods for particle size (for example, Hu Songqing et al., Modern Particle Size Measurement Technology, Modern Engineering, 2002 22:1).

In some specific embodiments, the average particle size of the pulverization is 10 nm to 800 nm.

In other specific embodiments, the average particle size of the pulverization is 10 nm to 500 nm.

In a specific embodiment, the dispensing refers to dispensing into bottles/ampoules. Just before use, add solvent (such as sterile water) to the bottle/ampule.

In some specific embodiments, the subject is an animal other than humans, such as farm animals, pets, working animals, ornamental animals, and production animals.

In a specific embodiment, the subject is a human.

In some specific embodiments, the subject is suspected of having, confirmed to have, has had, or is susceptible to the target disease or its symptoms.

In the context of this application, the only therapeutically active ingredient in a drug or medical device is a product derived from Nocardia rubra, especially containing Nocardia rubra component (such as protein, nucleic acid, lipid, cell wall and Its components, carbohydrates, metabolites), specifically products containing Nocardia rubra cell wall (more preferably Nocardia rubra skeleton or its composition).

detailed description

Nocardia rubra cell wall

In the present disclosure, "Nocardia rubra cell wall" can be understood as both a complete cell wall and an incomplete cell wall (for example, broken or partially degraded). Under the teachings of the present disclosure, the skilled person will understand that the ingredients exhibiting the desired activity are derived from the cell wall of Nocardia rubra (for example, the cell wall itself or its composition). Therefore, various forms such as complete cell walls, broken cell walls, incomplete degradation products of cell walls, components of cell walls, and cell wall extracts are allowed to be used in clinical applications, which are all included in the scope of the present disclosure.

Cell wall skeleton

The constituent components that make up the main structure of the cell wall; however, it cannot be understood as merely representing the cross-linked network entities in the cell wall, and the skilled person understands that other cell wall components adsorbed, bound, and carried on the cross-linked network entities are not excluded.

Unit dose

The medicine or medical device of the present disclosure can be prepared in the form of a unit dose (or unit preparation).

"Optional" means that what is described later can happen, but does not have to happen; it depends on the situation. For example, "optionally, sub-package" means that the product is allowed to be sub-packaged, but it is not required to be sub-packaged; whether the product is sub-packaged or not does not affect the realization of the technical effect.

"One", "one", "single" and "the", if not explicitly stated, also include plural forms.

The present disclosure is further described below in conjunction with embodiments. However, these embodiments do not limit the scope of the present disclosure. When no specific conditions are indicated, operate in accordance with normal conditions and the conditions recommended by the raw material supplier. Reagents without specific sources are conventional reagents purchased on the market.

The skilled person particularly understands that although the following specific examples use a specific commercially available cell wall product, the realization of the technical effect is not limited to the specific commercially available product, and any species belonging to Nocardia rubra is applicable.

Example 1. Commercially available Nocardia rubra cell wall skeleton

Nocardia rubra cell wall skeleton (trade name: Na Kejia) was purchased from Liaoning Grace Biopharmaceutical Co., Ltd., and the approval number was National Medicine Zhunzi S20030009 (2ml/ampule; freeze-dried powder), which contained 60 μg of active ingredients and 15mg dextran 40.

Example 2. Preparation of Nocardia rubra cell wall skeleton

1. Cultivate and collect the bacteria according to a known method. The cells are pulverized (for example, but not limited to sonication). It is also allowed to use any appropriate well-known method in the art to disrupt the bacteria, such as CN101250490A or CN101323865A. Check the crushing condition under a microscope, and each visual field shall not exceed 5 visible bacteria. Check that several (10 to 30) visual fields meet this standard as qualified.

2. Nucleic acid removal: Centrifuge the broken supernatant, add DNase and RNase to the obtained precipitate, and remove nucleic acid according to the operation recommended by the enzyme supplier.

3. Remove protein: add common protease (such as trypsin) to the precipitate and remove protein according to the operation recommended by the enzyme supplier.

4. Removal of lipids: adding organic reagents (such as but not limited to one or a combination of acetone, ether, and ethanol) to the precipitate, and removing lipids according to conventional operations in the art.

5. Remove the cell membrane: Add TritonX-100 to the precipitate, collect the precipitate by centrifugation according to the conventional operation in the field, and rinse with PBS.

It should be understood that, between the steps of removing impurities, the technician can adjust the sequence to make the steps compatible. After removing the non-cell wall components, the precipitate was re-dissolved in water for injection and set aside. Optionally, it can be sterilized at 115°C for 20-30 minutes as the original solution of the cell wall skeleton (mainly containing the cell wall skeleton and its components).

Example 3. Preparation of pharmaceutical composition or medical device

1. Coat the product obtained in Example 2 (active ingredient 60μg to 120μg, such as 60μg, 70μg, 80μg, 90μg, 100μg, 110μg, 120μg) or the commercially available product of Example 1 on a dressing (such as sterile gauze), Prepared as an external medical device.

2. Alternatively, the product obtained in Example 2 (active ingredient 60 μg) was prepared into a freeze-dried powder, and it was directly applied to the lesion surface.

3. Alternatively, a lotion preparation method known in the art can also be used, for example:

The lotion mostly uses water and ethanol as the dispersion medium; it is made of active ingredients, electrolytes, isotonicity regulators, etc. in the dispersion medium. When the emulsion liquid lotion is stored, the oil phase and the water phase may separate, but they can be re-dispersed after shaking.

Test example. Treatment effect of white lesions of the vulva

Test case 1

1. First visit (2019-03-05):

Main complaint: skin whitening of the vulva with itching for 3 months;

History of present illness: 3 months ago, the patient had vulvar itching, unbearable itchiness, constant burning to relieve itching without obvious cause; after that, the skin of the vulva turned white, the local skin was rough, there was no history of trauma, and there was no systemic diseases such as hypertension and diabetes.

Past history: None;

Family history: None;

Inspection: T: 35.9°C P: 59 times/minute R: 18 times/minute BP: 118/63mmHg;

Gynecological examination: normal vulva development, 2×2cm ² white area on the right labia majora, local skin thickening, married birth, smooth vagina, smooth wall, a small amount of thin vaginal discharge, smooth cervix, no abnormalities, double The attachment is not abnormal;

Initial diagnosis: white lesions of the vulva.

2. Treatment plan:

Inform the patient of the condition and obtain informed consent.

Keep the perineum clean; avoid scratching and other physical stimulation; topical application of Nocardia rubrum cell wall skeleton (once every other day, 2ml/ampule (S20030009)). Check up every week and follow up if you are unwell.

3. The first follow-up visit (2019-03-12):

Follow-up visit: The patient followed the doctor's prescription after the last visit. He consciously reduced the lesion area and roughness of the right labia majora.

Inspection: There is a 2×1.5cm ² whitening area on the right labia majora, which is smaller than before treatment, and the local skin is slightly thickened. No vaginal discharge or bleeding is seen.

4. The second follow-up visit (2019-03-19):

Follow-up visit: The patient followed the doctor's prescription after the last visit. He consciously reduced the lesion area and roughness of the right labia majora.

Inspection: On the right side of the labia majora, there is a 0.8×1.2cm ² whitening area, which is smaller than the area before treatment, and the local skin is slightly thickened. There is no vaginal discharge or bleeding.

5. The third follow-up visit (2019-04-01):

Follow-up visit: The patient followed the doctor's prescription after the last visit and felt that the lesion on the right labia majora basically disappeared.

Inspection: The skin on the right labia majora basically returned to normal, no white lesions were seen, and it was better than before treatment, and no vaginal discharge or bleeding was seen.

Test case 2

1. First visit (2019-03-10):

Main complaint: genital itching for 1 month;

History of present illness: 1 month ago, the patient had no obvious cause of vulvar itching, no abnormal secretions and vaginal bleeding, no obvious abnormality in vaginal microecology, no history of trauma, no systemic diseases such as hypertension and diabetes.

Past history: None;

Family history: None;

Physical examination: Hypopigmentation spots of about 1.5×2.0cm ^{2 were} seen on both sides of the vulva, the labia majora was atrophy on both sides, there was no obvious ulceration or bleeding, and no purulent discharge.

Initial diagnosis: white lesions of the vulva.

2. Treatment plan:

Inform the patient of the condition and obtain informed consent.

Histopathological examination: local anesthesia with Primacaine STA, routine disinfection, take about 0.6×0.6×0.5cm ³ tissue from the left vulvar lesion and suture 2 stitches. The samples were fixed with 10% formalin, sent to pathology, and the stitches were removed one week after the doctor ordered them.

3. The first follow-up visit (2019-03-17):

Follow-up: The patient has no discomfort since the last biopsy. The pathological results (left vulva) were consistent with white lesions of the vulva.

Inspection: The biopsy site is healed well, and the sutures are stored in 2 stitches without falling off;

Disposal: Keep the perineum clean; avoid scratching and other physical irritation; topical application of Nocardia rubrum cell wall skeleton (once every other day, 2ml/ampoule (S20030009)). Check up every week and follow up if you are unwell.

4. The second follow-up visit (2019-03-24):

Follow-up visit: The patient followed the doctor's prescription after the last visit, and he consciously reduced the area of bilateral vulvar lesions and reduced the roughness.

Inspection: Hypopigmented spots of about 1.5×1.0cm ^{2 were} seen on both sides of the vulva, the labia majora was atrophy on both sides, there was no obvious ulceration and bleeding, and no purulent discharge.

5. The third follow-up visit (2019-03-31):

Follow-up visit: The patient followed the doctor's prescription after the last visit, and consciously reduced bilateral vulvar lesions.

Inspection: Hypopigmented spots of about 0.3×1.0cm ^{2 were} seen on both sides of the vulva, the labia majora was atrophy on both sides, there was no obvious ulceration and bleeding, and no purulent discharge.

6. The fourth follow-up visit (2019-04-14):

Follow-up visit: The patient followed the doctor's prescription after the last visit and felt that the bilateral vulva lesions were basically healed.

Inspection: the bilateral vulvar hypopigmentation spots basically recovered and disappeared, the labia majora was slightly atrophy, there was no obvious ulceration and bleeding, and no purulent discharge.

Test case 3

1. First visit (2019-04-10):

Main complaint: genital itching for 3 months;

History of present illness: The patient developed genital itching 3 months ago, scratching to relieve the itching constantly, no obvious improvement after self-administration, 2 months ago, the skin of the vulva was found to be white, the local skin is relatively rough, self-reported occasional purulent discharge, none Other skin lesions.

Past history: None;

Family history: None;

Physical examination: normal vulva development, 1.5×2cm ² white lesions on the right vulva, local atrophy, 0.4×0.6cm ² ulcers in the center of the lesions, no purulent secretions.

Initial diagnosis: white lesions of the vulva.

2. Treatment plan:

Inform the patient of the condition and obtain informed consent.

Keep the perineum clean; avoid scratching and other physical stimulation; topical application of Nocardia rubrum cell wall skeleton (once every other day, 2ml/ampule (S20030009)). Check up every week and follow up if you are unwell.

3. The first follow-up visit (2019-04-17):

Follow-up visit: The patient followed the doctor's prescription after the last visit. He consciously reduced the lesion area on the right vulva and healed the ulcer.

Inspection: The vulva development was normal, and a 0.8×2cm ² white lesion was seen on the right vulva, which was smaller than before treatment, local atrophy, and the central ulcer of the lesion healed without any purulent secretions.

4. The second follow-up visit (2019-04-24):

Follow-up visit: The patient followed the doctor's prescription after the last visit, and he consciously reduced the lesion area on the right vulva.

Inspection: The vulva development was normal, and there was a 0.8×1.2cm ² white lesion on the right vulva, which was smaller than before treatment, local atrophy, and no purulent discharge was seen.

5. The third follow-up visit (2019-05-08):

Follow-up visit: The patient followed the doctor's prescription after the last visit, and he consciously reduced the lesion area on the right vulva.

Inspection: The vulva development is normal, and there is a 0.8×0.5cm ² white lesion on the right vulva, which is smaller than before treatment, local atrophy, and no purulent discharge is seen.

Claims (9)

Use of Nocardia rubra cell wall skeleton in preparing medicine, wherein the medicine is used to treat white lesions of the vulva or prevent its recurrence. The use according to claim 1, wherein the white lesions of the vulva are lichen sclerosus of the vulva and/or squamous cell hyperplasia of the vulva. The use according to claim 1, wherein the medicine is prepared into a dosage form selected from the group consisting of ointments, creams, emulsions, suspensions, pastes, gels, lotions, tinctures, oils, liniments, Powders, tablets, suppositories, films, patches, dressings. The use according to claim 1, wherein the unit dose in the medicine contains 1 μg to 1000 μg Nocardia rubra cell wall skeleton; preferably 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200μg. The use according to claim 1, wherein the Nocardia rubra cell wall skeleton is a commercially available Nocardia rubra cell wall skeleton. The use according to claim 1, wherein the Nocardia rubra cell wall skeleton can be obtained by the following method, and the method comprises or consists of the following steps: 1) Provide Nocardia rubrum; 2) Crushing the Nocardia rubra to obtain a crushed product; 3.1) Optionally, perform a lipid removal operation on the pulverized product; 3.2) Optionally, perform the operation of removing nucleic acid on the crushed product; 3.3) Optionally, perform the operation of removing protein on the pulverized product; 3.4) Obtain the product derived from the cell wall of Nocardia rubra; 4) Optionally, subpackage; 5) Optionally, freeze-dry the product derived from the cell wall of Nocardia rubra; among them, Step 3.1), 3.2), 3.3) can be interchanged in order or in parallel, Step 4) and step 5) can interchange the order; The average particle size of the pulverization is 10 nm to 1000 nm, preferably 10 nm to 800 nm, more preferably 10 nm to 500 nm; Preferably, the sub-packing refers to sub-packing into a container; Preferably, the container is selected from: bottles, tubes, bags, bags, plates, ampoules, injection devices, aluminum film packaging, dressings, capsules, and films. A method for treating or preventing the recurrence of white lesions of the vulva, including the steps: Expose the subject to a therapeutically effective amount of Nocardia rubra cell wall skeleton; The white lesions of the vulva are lichen sclerosus of the vulva and/or squamous cell proliferation of the vulva; The Nocardia rubra cell wall skeleton is prepared in a form selected from: ointment, cream, emulsion, suspension, paste, gel, lotion, tincture, oil, liniment, powder, tablet , Suppositories, films, patches, dressings; The contact is applied twice a day, or once a day, or once two days, or once three days, or once a week; The contact lasts for 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 Weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks or longer. The method according to claim 7, wherein the Nocardia rubra cell wall skeleton is a commercially available Nocardia rubra cell wall skeleton. The method according to claim 7, wherein the Nocardia rubra cell wall skeleton is obtained in the following manner, and the method includes or consists of the following steps: 1) Provide Nocardia rubrum; 2) Crushing the Nocardia rubra to obtain a crushed product; 3.1) Optionally, perform a lipid removal operation on the pulverized product; 3.2) Optionally, perform the operation of removing nucleic acid on the crushed product; 3.3) Optionally, perform the operation of removing protein on the pulverized product; 3.4) Obtain the product derived from the cell wall of Nocardia rubra; 4) Optionally, subpackage; 5) Optionally, freeze-dry the product derived from the cell wall of Nocardia rubra; among them, Step 3.1), 3.2), 3.3) can be interchanged in order or in parallel, Step 4) and step 5) can interchange the order; The average particle size of the pulverization is 10 nm to 1000 nm, preferably 10 nm to 800 nm, more preferably 10 nm to 500 nm; Preferably, the sub-packing refers to sub-packing into a container; Preferably, the container is selected from: bottles, tubes, bags, bags, plates, ampoules, injection devices, aluminum film packaging, dressings, capsules, and films.