Traditional Chinese medicine composition after conization for inhibiting HPV (human papillomavirus) and treating precancerous lesions of cervical cancer

Abstract

The invention relates to a traditional Chinese medicine composition for inhibiting HPV (human papilloma virus) and treating cervical precancerous lesions after conization, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition comprises the following traditional Chinese medicinal materials in parts by weight: 8-12 parts of inonotus obliquus, 6-10 parts of ganoderma applanatum, 0.5-1 part of saffron crocus, 2-3 parts of radix sophorae flavescentis, 5-8 parts of wild ganoderma lucidum, 4-8 parts of laetiporus sulphureus, 2-3 parts of ganoderma sinensis, 3-6 parts of golden cypress, 1-1.5 parts of fructus cnidii and 10-15 parts of phellinus igniarius. The traditional Chinese medicine composition has the advantages of remarkable clinical effect, natural traditional Chinese medicine components, no drug resistance, no side effect and small burden on the body of a patient, improves the local immunity of the vagina, enhances the capability of automatically removing pathogens of the body and effectively prevents the recurrence of diseases, and has remarkable progress compared with the prior art.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for inhibiting HPV and treating cervical intraepithelial neoplasia after conization. Background Art

[0002] HPV infection is a globally common disease transmitted through sexual contact or direct skin and mucosal contact, which can cause a series of lesions in the genital tract or other skin / mucosal sites. Among them, HPV infection is mainly closely related to the occurrence of cervical cancer, and may also cause various cancers such as anal cancer, penile cancer, vulvar cancer, vaginal cancer, oropharyngeal cancer, oral cancer, and laryngeal cancer. In China, HPV52 and HPV58 are relatively common types among ordinary women. A study of nearly 2.5 million cervical specimens published in 2021 showed that the infection rate of HPV52 was 4.7% and that of HPV51 was 2.1%. Multicenter large-sample studies across the country have shown that the detection rates of high-risk HPV in Chinese cervical squamous cell carcinoma and adenocarcinoma are as high as 97.6% and 74.5% respectively. According to the systematic review report of the ICOHPV Information Center, 69.1% of cervical cancers in China are related to HPV16 / 18, similar to the global results; while the proportion of cervical cancers related to HPV52 / 58 is 14.7%, higher than the global level of 7.4%.

[0003] Currently, there are many therapeutic drugs for HPV infection, and common dosage forms include gels, aqueous solutions, biological agents, etc. However, these existing drugs generally have the problem of a long treatment cycle. Patients need to take drugs for a long time, which not only increases the economic burden but also reduces the compliance of patients. At the same time, long-term use easily makes the pathogen develop drug resistance, resulting in a gradual decline in the efficacy of the drug. More seriously, the existing drugs are almost ineffective in the treatment of high-grade cervical intraepithelial neoplasia, which is extremely likely to delay the condition, making the lesion prone to progress into cervical cancer, seriously threatening the life and health of patients.

[0004] In view of this, the present invention is specifically proposed to solve the above problems. Summary of the Invention

[0005] The purpose of the present invention is to provide a traditional Chinese medicine composition for inhibiting HPV virus or treating cervical intraepithelial neoplasia, so as to solve the problems of long treatment cycle, easy generation of drug resistance, easy recurrence, and ineffective treatment of high-grade cervical intraepithelial neoplasia existing in the existing drugs for treating HPV infection. To achieve the above object, the present invention provides the following technical solutions: A traditional Chinese medicine composition for inhibiting HPV virus and treating cervical intraepithelial neoplasia, characterized by comprising the following Chinese medicinal materials in parts by weight: 8 - 12 parts of Inonotus obliquus, 6 - 10 parts of Ganoderma applanatum, 0.5 - 1 part of Crocus sativus, 2 - 3 parts of Sophora flavescens, 5 - 8 parts of Ganoderma lucidum, 4 - 8 parts of Laetiporus sulphureus, 2 - 3 parts of Ganoderma sinense, 3 - 6 parts of Phellodendron amurense, 1 - 1.5 parts of Fructus Cnidii, 10 - 15 parts of Sanghuangporus sanghuang.

[0006] Preferably, it includes the following traditional Chinese medicine materials by weight: 9 - 11 parts of Inonotus obliquus, 8 - 9 parts of Ganoderma applanatum, 0.5 - 1 part of Crocus sativus, 2 - 3 parts of Sophora flavescens, 6 - 7 parts of Ganoderma lucidum, 5 - 7 parts of Laetiporus sulphureus, 2 - 3 parts of Ganoderma sinense, 4 - 5 parts of Phellodendron amurense, 1 - 1.5 parts of Fructus Cnidii, 12 - 13 parts of Sanghuangporus sanghuang.

[0007] A preparation method of the above traditional Chinese medicine composition for inhibiting HPV virus and treating precancerous lesions of cervical cancer, comprising the following steps: Medicinal material selection: Select high-quality Inonotus obliquus, Ganoderma applanatum, Crocus sativus, Sophora flavescens, Ganoderma lucidum, Laetiporus sulphureus, Ganoderma sinense, Phellodendron amurense, Fructus Cnidii, Sanghuangporus sanghuang; Pretreatment: Wash the above traditional Chinese medicine materials respectively and soak them for 2 - 3 hours; Coarse powder preparation: Use a pulverizer to pulverize the soaked medicinal materials to 60 mesh to obtain coarse powder; Enzymolysis and fermentation: Add collapsing enzyme complex and lysing enzyme to the coarse powder, ferment at normal temperature and pressure for 65 - 75 hours, then raise the temperature to 80 - 90 °C and keep it for 1 - 2 hours for inactivation, and then carry out secondary enzymolysis extraction to obtain an extract; Vacuum negative pressure concentration: Put the extract into a vacuum concentration device and concentrate it to a relative density of 1.2 at 60 °C under vacuum negative pressure conditions, and collect the concentrated paste; Freeze-drying and ultrafine pulverization: Add powder to the concentrated paste, stir and mix, and then send it to a freeze-dryer for freeze-drying. The dried product is pulverized by an ultrafine pulverizer to obtain the final traditional Chinese medicine composition.

[0008] The following is an analysis of each traditional Chinese medicine component shown in the present invention: I. Monarch drug (core anti-cancer group) ‌Sanghuangporus sanghuang‌: Dominantly induces apoptosis of cancer cells and inhibits the formation of new tumor blood vessels, and its polysaccharide component can activate the activity of NK cells.

[0009] ‌Inonotus obliquus‌: Assists Sanghuangporus sanghuang to enhance the anti-tumor effect. The inotodiol contained directly inhibits the DNA replication of cancer cells and reduces the toxicity of radiotherapy and chemotherapy at the same time.

[0010] ‌Ganoderma applanatum‌: Blocks the tumor proliferation signaling pathway (such as the mTOR pathway) and forms a multi-target anti-cancer combination with Sanghuangporus sanghuang 26.

[0011] II. Ministerial drug (immune synergy group) Wild Ganoderma lucidum + Ganoderma sinense: Wild Ganoderma lucidum enriches β-glucan to activate T cells, and Ganoderma sinense triterpenoids scavenge free radicals. The two work together to enhance the immune surveillance function.

[0012] Sulphur polypore: Promote hematopoiesis through sulfur-containing compounds and improve the state of bone marrow suppression.

[0013] III. Adjuvant drugs (metabolism regulation and anti-inflammatory group) Phellodendron amurense: Berberine inhibits the NF-κB pathway and reduces the inflammatory response in the tumor microenvironment.

[0014] Sophora flavescens: Matrine regulates the Th1 / Th2 immune balance and synergistically exerts antiviral and anti-inflammatory effects.

[0015] IV. Guiding drugs (synergistic effect and guiding drug group) Crocus sativus: Crocin contained therein improves the blood supply of tumor tissues, enhances drug permeability, and at the same time inhibits platelet aggregation to prevent metastasis.

[0016] Cnidium monnieri: The volatile oil components play a role in drying dampness and relieving itching for the damp-heat symptoms (such as abnormal vaginal discharge) associated with gynecological tumors.

[0017] The beneficial effects of the present invention are as follows: Significant clinical effect: The traditional Chinese medicine composition of the present invention has been clinically verified, with a total effective rate reaching 100% and a cure rate of 90%. It has good therapeutic effects on high-risk HPV16, 18, 52, 58 infections and high-grade lesions of the cervix, vagina, vulva, and perianal area.

[0018] High safety: The pure traditional Chinese medicine components are natural, do not produce drug resistance, have no side effects, impose a small burden on the patient's body, and can also be used during lactation. During the treatment process, it does not affect normal vaginal delivery and protects the reproductive rights of female patients.

[0019] Improve immunity: This composition can fundamentally improve the local immunity of the vagina, enhance the body's ability to automatically clear pathogens, and effectively prevent the recurrence of diseases.

[0020] The above description is only an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and implement it according to the content of the specification, the following provides a detailed description of the preferred embodiments of the present invention. Detailed implementation manners

[0021] The technical solution of the present invention will be clearly and completely described below. Obviously, the described embodiments are some, but not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0022] In addition, the technical features involved in different embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other. Example

[0023] The traditional Chinese medicine composition for inhibiting HPV virus and treating precancerous lesions of cervical cancer shown in a preferred embodiment of the present application includes the following Chinese medicinal materials in parts by weight: Inonotus obliquus 8 parts, Ganoderma applanatum 6 parts, Crocus sativus 0.5 part, Sophora flavescens 2 parts, Ganoderma lucidum 5 parts, Laetiporus sulphureus 4 parts, Ganoderma sinense 2 parts, Phellodendron amurense 3 parts, Fructus Cnidii 1 part, Sanghuang 10 parts. Example

[0024] The traditional Chinese medicine composition for inhibiting HPV virus and treating precancerous lesions of cervical cancer shown in a preferred embodiment of the present application includes the following Chinese medicinal materials in parts by weight: Inonotus obliquus 10 parts, Ganoderma applanatum 8 parts, Crocus sativus 1 part, Sophora flavescens 2 parts, Ganoderma lucidum 6 parts, Laetiporus sulphureus 6 parts, Ganoderma sinense 2 parts, Phellodendron amurense 5 parts, Fructus Cnidii 1.5 parts, Sanghuang 12 parts. Example

[0025] The traditional Chinese medicine composition for inhibiting HPV virus and treating precancerous lesions of cervical cancer shown in a preferred embodiment of the present application includes the following Chinese medicinal materials in parts by weight: Inonotus obliquus 12 parts, Ganoderma applanatum 10 parts, Crocus sativus 2 parts, Sophora flavescens 3 parts, Ganoderma lucidum 8 parts, Laetiporus sulphureus 8 parts, Ganoderma sinense 3 parts, Phellodendron amurense 6 parts, Fructus Cnidii 1.5 parts, Sanghuang 15 parts. Example

[0026] A preparation method of a traditional Chinese medicine composition for inhibiting HPV virus and treating precancerous lesions of cervical cancer, adopting the traditional Chinese medicine composition formula shown in Example 1, includes the following steps: Medicinal material selection: Select high-quality Inonotus obliquus, Ganoderma applanatum, Crocus sativus, Sophora flavescens, Ganoderma lucidum, Laetiporus sulphureus, Ganoderma sinense, Phellodendron amurense, Fructus Cnidii, Sanghuang.

[0027] Preliminary treatment: Wash the above Chinese medicinal materials separately and soak them for 2 - 3 hours.

[0028] Coarse powder preparation: Use a pulverizer to pulverize the soaked medicinal materials to 60 meshes to obtain a coarse powder.

[0029] Enzymolysis and fermentation: Add an appropriate amount of collapse enzyme complex enzyme and lysing enzyme to the coarse powder, ferment at normal temperature and pressure for 72 hours, then raise the temperature to 80 - 90 °C, keep for 1 - 2 hours for inactivation, and then carry out secondary enzymolysis extraction.

[0030] Vacuum negative pressure concentration: Put the extract into a vacuum concentration device, concentrate it to a relative density of 1.2 at 60 °C under vacuum negative pressure conditions, and collect the concentrated paste.

[0031] Lyophilization and ultrafine grinding: An appropriate amount of powder was added to the concentrated paste. After fully stirring and mixing evenly, it was sent to a lyophilizer for freeze-drying. The dried product was ground to a suitable particle size using an ultrafine grinder to obtain the final traditional Chinese medicine enzymolysis extraction composition. Example

[0032] The powder before sterilization was prepared according to the method described in Example 4, sterilized, and then dispensed into vaginal applicators. Each applicator contained 1.405 g of crude drug. Dosage and administration: Once every two days, one applicator each time.

[0033] Clinical efficacy observation of the HPV virus inhibition of the present invention 1. Drug: The traditional Chinese medicine enzymolysis extraction composition prepared according to the method described in Example 4 of the present invention.

[0034] 2. Observation subjects: A total of 155 people infected with high-risk HPV and low-risk HPV, with the youngest age of 26 years and the oldest age of 56 years; the main high-risk virus subtypes were 16, 18, 51, 52, 68, 58, 31, and 33.

[0035] Among the above patients, 124 patients showed lesions such as low-grade squamous intraepithelial lesion (LSIL) or high-grade squamous intraepithelial lesion (HSIL) in the TCT (Thinprep cytologic test) test results. In this observation, HPV infection and TCT lesions were statistically analyzed separately.

[0036] 3. Observation and treatment methods: The traditional Chinese medicine enzymolysis extraction composition prepared according to the method described in Example 4 of the present invention, once every two days, one applicator each time.

[0037] Before use, clean the vulva and dilate the vagina with a special vaginal speculum. Take one applicator of this product, remove the cap of the vaginal applicator, and directly inject the vaginal applicator through the vaginal speculum at the cervical os, posterior fornix of the vagina, and vaginal wall. Use a large gynecological cotton swab to make the powder fully cover the above areas, take out the applicator, remove the vaginal speculum and throw it into the medical trash can. Reapply the vaginal powder of the present invention.

[0038] About 12 weeks after each patient uses the vaginal powder of the present invention, wait for one month and then review (TCT and HPV tests). If HPV turns negative, stop the treatment. 4. Efficacy judgment criteria: 1) HPV infection Marked effect: HPV turns negative; No effect: HPV does not turn negative.

[0039] 2) TCT lesion Effective: The TCT test results indicate: ① No intraepithelial lesion or malignancy was found. Ineffective: The TCT test results showed no change.

[0040] 5. Efficacy summary The medication duration for general patients is 12 weeks, with the shortest being 30 days and the longest 120 days. The efficacy summary is shown in Table 1.

[0041] Table 1 Clinical observation results of the vaginal powder of the present invention The above results show that the vaginal powder prepared from the traditional Chinese medicine composition of the present invention has a particularly significant therapeutic effect on patients with HPV infection. It not only has good efficacy but also rapid onset. At the same time, the traditional Chinese medicine composition of the present invention also shows a good therapeutic effect on cervical intraepithelial lesions, indicating that the traditional Chinese medicine composition of the present invention can treat cervical precancerous lesions.

[0042] 6. Typical cases 1) Ms. Li, 36 years old, positive for high-risk HPV types 33 and 39, for four consecutive years. After successive treatments with interferon, anti-HPV biological protein dressing, anti-HPV immunoglobulin gel, etc., the virus did not turn negative. In addition, in May 2022, Ms. Zhang was detected by TCT and found to have a high-grade squamous intraepithelial lesion, CIN II. After using the vaginal powder of the present invention and stopping the drug, upon reexamination, the positive HPV turned negative, CIN II completely disappeared, and the cell test result was mild inflammation. After one-year follow-up reexamination, no HPV infection was found. 2) Ms. Zuo, 29 years old, had a cervical conization surgery one year ago, with a size of 3×2.5×2.5 cm, an external orifice diameter of 3 cm, and a conization depth of 2.5 cm; the TCT test result was a high-grade squamous intraepithelial lesion, CINI-II, and positive for HPV type 16. After using the vaginal powder of the present invention for 60 days, upon reexamination, the HPV turned negative, and no intraepithelial lesion was detected by TCT. After one-year follow-up reexamination, no HPV infection was found. 3) Ms. Zhang, 56 years old, positive for HPV types 39, 56, 53, and 66, and the TCT test result was a low-grade squamous intraepithelial lesion (LSIL). She had previously been treated with interferon, stem cells, surgery, etc., but none of them were effective. After using the vaginal powder of the present invention for 60 days and stopping the drug for reexamination, 3 subtypes of HPV infection turned negative, and only 1 HPV subtype remained positive. No intraepithelial lesion was detected by TCT. After one-year follow-up reexamination, no new HPV subtype infection was found.

[0043] 4) Ms. Tian, 36 years old, positive for high-risk HPV type 51. After treatment with anti-HPV biological protein dressing, interferon, etc., it remained continuously positive. After using the vaginal powder of the present invention for 30 days and stopping the drug, upon reexamination, the HPV turned negative. After one-year follow-up reexamination, no HPV infection was found. 5) Ms. Dai, 36 years old, positive for high-risk HPV types 16, 18, 51, and 52. She had been treated with interferon and other means but to no avail, and had been continuously infected for over 2 years. After using the vaginal powder of the present invention for 30 days and having a follow-up examination after stopping the medication, HPV types 16 and 18 turned negative; after continuing to use the medication for another 30 days and having a follow-up examination, both HPV types 51 and 52 turned negative, and no HPV infection was found after one year of follow-up examination.

[0044] In summary, the traditional Chinese medicine composition shown in the present invention has good efficacy in inhibiting HPV virus and treating precancerous lesions of the cervix, has a short treatment cycle and a high efficiency, and has significant progress compared with the prior art.

[0045] The technical features of the above-described embodiments can be combined arbitrarily. For the sake of brevity of description, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered as the scope described in this specification.

[0046] The above-described embodiments merely represent several implementation manners of the present invention. The description is relatively specific and detailed, but it should not be construed as a limitation on the scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the invention patent should be subject to the appended claims.

Claims

1. A traditional Chinese medicine composition for inhibiting HPV virus and treating cervical intraepithelial neoplasia, characterized in that, Comprising the following parts by weight of Chinese medicinal materials: Inonotus obliquus 8 - 12 parts, Ganoderma applanatum 6 - 10 parts, Crocus sativus 0.5 - 1 part, Sophora flavescens 2 - 3 parts, Ganoderma lucidum 5 - 8 parts, Laetiporus sulphureus 4 - 8 parts, Ganoderma sinense 2 - 3 parts, Phellodendron amurense 3 - 6 parts, Fructus Cnidii 1 - 1.5 parts, Sanghuang 10 - 15 parts.

2. The traditional Chinese medicine composition for inhibiting HPV virus and treating precancerous lesions of cervical cancer according to claim 1, wherein Comprising the following parts by weight of Chinese medicinal materials: Inonotus obliquus 9 - 11 parts, Ganoderma applanatum 8 - 9 parts, Crocus sativus 0.5 - 1 part, Sophora flavescens 2 - 3 parts, Ganoderma lucidum 6 - 7 parts, Laetiporus sulphureus 5 - 7 parts, Ganoderma sinense 2 - 3 parts, Phellodendron amurense 4 - 5 parts, Fructus Cnidii 1 - 1.5 parts, Sanghuang 12 - 13 parts.

3. A method for preparing a traditional Chinese medicine composition for inhibiting HPV virus and treating precancerous lesions of cervical cancer as described in claim 1, characterized in that, Comprising the following steps: Medicinal material selection: Select high-quality Inonotus obliquus, Ganoderma applanatum, Crocus sativus, Sophora flavescens, Ganoderma lucidum, Laetiporus sulphureus, Ganoderma sinense, Phellodendron amurense, Fructus Cnidii, Sanghuang; Pretreatment: Wash the above Chinese medicinal materials separately and soak them for 2 - 3 hours; Coarse powder preparation: Use a pulverizer to pulverize the soaked medicinal materials to 60 mesh to obtain coarse powder; Enzymatic hydrolysis extraction and fermentation: Add collapsing enzyme complex enzyme and lysing enzyme to the coarse powder, ferment at normal temperature and pressure for 65 - 75 hours, then raise the temperature to 80 - 90 °C and maintain for 1 - 2 hours for inactivation, and then carry out secondary enzymatic hydrolysis extraction to obtain an extract; Vacuum negative pressure concentration: Put the extract into a vacuum concentration device and concentrate it to a relative density of 1.2 at 60 °C under vacuum negative pressure conditions, and collect the concentrated paste; Freeze-drying and ultrafine pulverization: Add powder to the concentrated paste, stir and mix, and then send it to a freeze-dryer for freeze-drying. The dried product is pulverized using an ultrafine pulverizer to obtain the final traditional Chinese medicine composition.