Application of body resistance strengthening Ermiao detoxification granules in preparation of anti-human papilloma virus medicine

Abstract

The invention discloses application of body resistance strengthening Ermiao detoxification granules in preparation of anti-human papilloma virus drugs, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine is characterized by being prepared from the following components in parts by weight: 30 parts of astragalus membranaceus, 15 parts of codonopsis pilosula, 12 parts of bighead atractylodes rhizome, 15 parts of poria cocos, 9 parts of rhizoma atractylodis, 6 parts of golden cypress, 10 parts of paris polyphylla, 10 parts of rhizoma smilacis glabrae, 10 parts of sculellaria barbata, 10 parts of Chinese lobelia, 15 parts of patrinia, 30 parts of coix seeds, 15 parts of oldenlandia diffusa and 6 parts of liquorice. The number of infected HPV subtypes before treatment, the total score of traditional Chinese medicine syndromes, the TCT result and the pathological result have no significant statistical difference (P is greater than 0.05); after treatment, traditional Chinese medicine syndrome points and clinical index curative effects have a significant statistical difference (Plt; and 0.05), so that the healthy-energy-strengthening ermiao toxin-clearing granules have a remarkable curative effect on high-risk HPV infected patients.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and particularly to the application of Fuzheng Ermiao Qingdu Granules in the preparation of drugs against human papillomavirus. Background Art

[0002] Human papillomavirus (HPV) is a DNA virus that can invade the cervical mucosa, causing cervical intraepithelial lesions and the occurrence of cervical cancer. In particular, persistent infection with high-risk HPV (HR-HPV) is closely related to cervical lesions and is a key pathogenic factor for cervical lesions. HPV infection generally has no specific symptoms, and occasionally there are clinical manifestations such as increased vaginal discharge, with or without odor, and contact bleeding after sexual intercourse or gynecological examination. According to epidemiological and survey data, cervical cancer, as the second most common malignant tumor endangering women's health after breast cancer, has an increasing incidence year by year. It usually takes only 10 - 15 years for cervical HR-HPV infection to gradually develop into cervical intraepithelial neoplasia (CIN) and then deteriorate into cervical cancer. However, for women with weakened immune function, once infected with HPV and untreated, they will develop into cervical cancer in about 5 - 10 years.

[0003] HPV virus was first discovered by Stauss under an electron microscope in 1949. HPV belongs to the genus Papovaviridae and is a closed circular double-stranded DNA virus. It has multiple genetic subtypes, and HPV infection with different genetic subtypes can lead to different clinical lesions. Based on biological characteristics and carcinogenic potential, it is divided into high-risk and low-risk types. High-risk types such as HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68 are associated with cancer and precancerous lesions, while low-risk types such as HPV6, 11, 42, 43, 44 are mainly associated with mild squamous intraepithelial lesions, urogenital warts, and recurrent respiratory polyps. Nearly 90% of cervical squamous intraepithelial lesions (SIL) and 99% of cervical cancer tissues are found to be associated with HPV types 16 and 18. HPV has a high degree of host specificity and mainly invades the stratified squamous epithelium of the skin and mucous membranes in specific parts of the human body. Sexual contact is its main route of transmission. During a woman's lifetime, she may be repeatedly infected with HPV, or she may be infected with multiple different types of HPV at the same time, but most of them are transient infections that can be cleared after the body's immunity is enhanced. Generally, they can disappear on their own in 8-10 months without the need for drug intervention. It is currently recognized that persistent high-risk HPV infection is the primary risk factor for cervical cancer. Therefore, the necessity of early intervention in high-risk HPV infection that is difficult to clear by itself is the key to preventing the disease from further deteriorating. Summary of the invention

[0004] The purpose of the present invention is to provide an application of Fuzheng Ermiao Qingdu Granules in the preparation of anti-human papillomavirus drugs to solve the problems existing in the above-mentioned prior art.

[0005] To achieve the above object, the present invention provides the following solutions:

[0006] One of the technical solutions of the present invention is a traditional Chinese medicine composition for resisting human papillomavirus, which is prepared from the following components in parts by weight: 30 parts of astragalus, 15 parts of codonopsis, 12 parts of atractylodes, 15 parts of tuckahoe, 9 parts of atractylodes, 6 parts of phellodendron, 10 parts of parsley, 10 parts of smilax glabra, 10 parts of bark scutellaria, 10 parts of lobelia, 15 parts of patrinia herb, 30 parts of coix seed, 15 parts of oldenlandia diffusa and 6 parts of liquorice.

[0007] The third technical solution of the present invention is the use of the traditional Chinese medicine composition in the preparation of anti-human papillomavirus drugs.

[0008] A fourth technical solution of the present invention is an anti-human papillomavirus drug, comprising the above-mentioned Chinese medicine composition.

[0009] Based on the above technical solution, the present invention has the following technical effects:

[0010] In this invention, by observing the clinical efficacy of Fuzheng Ermiao Qingdu Granule in treating patients with high-risk HPV infection, the baseline data of the two groups of patients (age, sexual history, number of sexual partners, number of pregnancies), the number of HPV subtypes infected before treatment, the total score of traditional Chinese medicine syndromes, the TCT results, and the pathological results were compared, and there were no significant statistical differences (P>0.05); after treatment, there were significant statistical differences in the scores of traditional Chinese medicine syndromes and the efficacy of clinical indicators (P<0.05). It was concluded that Fuzheng Ermiao Qingdu Granule has significant efficacy in treating patients with high-risk HPV infection. Specific Embodiments

[0011] The various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, characteristics, and implementation schemes of the present invention.

[0012] It should be understood that the terms used in the present invention are only for describing specific embodiments and are not used to limit the present invention. Additionally, for the numerical ranges in the present invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each intermediate value within any stated value or stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0013] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present invention pertains. Although the present invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein can also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the documents. In case of conflict with any incorporated document, the content of this specification shall prevail.

[0014] Without departing from the scope or spirit of the present invention, various improvements and changes can be made to the specific embodiments of the present invention specification, which are obvious to those skilled in the art. Other embodiments obtained from the specification of the present invention are obvious to those skilled in the art. The specification and examples of this application are only exemplary.

[0015] Regarding the use of "comprising", "including", "having", "containing", etc. in this article, they are all open-ended terms, meaning including but not limited to.

[0016] The technical solutions described in the present invention, unless otherwise specified, are all conventional solutions in the art, and the reagents or raw materials used, unless otherwise specified, are all purchased from commercial channels or have been publicly disclosed.

[0017] The embodiment of the present invention provides an anti-human papillomavirus Chinese medicine composition, which is prepared from the following components in parts by weight: 30 parts of astragalus, 15 parts of codonopsis, 12 parts of atractylodes, 15 parts of tuckahoe, 9 parts of atractylodes, 6 parts of phellodendron, 10 parts of parsley, 10 parts of smilax glabra, 10 parts of bark scutellaria, 10 parts of lobelia, 15 parts of patrinia herb, 30 parts of coix seed, 15 parts of oldenlandia diffusa and 6 parts of liquorice.

[0018] The embodiment of the present invention also provides the use of the traditional Chinese medicine composition in preparing anti-human papillomavirus drugs.

[0019] The embodiment of the present invention also provides an anti-human papillomavirus drug, comprising the traditional Chinese medicine composition.

[0020] In some specific embodiments, the dosage form of the drug is granules.

[0021] This disease belongs to the category of "leucorrhea" in medicine. This disease is based on spleen deficiency and toxic dampness as the symptom. Evil dampness is the inevitable pathological product of leucorrhea, and the spleen and stomach are the hub of the transportation and transformation of the middle jiao. Evil dampness includes internal dampness and external dampness. Internal dampness is caused by spleen deficiency, inability to transport and transform, and dysfunction of transportation, which allows evil dampness to be generated. Water and dampness stagnate inside and flow down to the uterus. The dampness is heavy, turbid and sticky, and stays in the body, lingering and difficult to cure; external dampness is infected by evil dampness during menstruation or after childbirth when the uterus is wide open, and accumulates in the uterus. The combination of the two evil dampness causes endless leucorrhea, and spleen deficiency is the root cause of the formation of evil dampness. At the same time, the spleen likes dryness and hates dampness. Spleen deficiency produces dampness, and evil dampness blocks the spleen, thereby affecting the transportation and transformation function of the spleen and aggravating the degree of spleen deficiency, which is mutually causal. HPV, as an external evil toxin, combines with evil dampness to cause this disease.

[0022] The present invention is based on the etiology and pathogenesis of "Qi deficiency and heat toxicity", and is modified by Sijunzi Decoction + Ermiao Pills. In the prescription, Astragalus and Codonopsis pilosula replenish the middle qi, Atractylodes lancea strengthens the spleen and dries dampness, Phellodendron clears heat and dries dampness, and are the main medicines; Atractylodes macrocephala strengthens the spleen and replenishes qi, Poria and Coix seed strengthen the spleen and penetrate dampness, and are the ministers; Paris, Scutellaria barbata, Lobelia, Hedyotis diffusa clears heat and detoxifies, Patrinia clears heat and removes blood stasis, and Smilax glabra detoxifies and removes dampness, and are the adjuvants; Licorice harmonizes all the medicines, and is the guiding medicine; the whole prescription plays the effect of replenishing qi and strengthening the body, clearing heat and detoxifying. This study observed clinical cases, clarified the clinical efficacy of Fuzheng Ermiao Qingdu Granules in the treatment of HPV infection, and provided a basis for clinical application.

[0023] Fu Zheng Er Miao Qing Du Granules have significant therapeutic effect in treating patients with high-risk HPV infection and deserve further clinical promotion.

[0024] Example 1

[0025] 1 Materials and methods

[0026] 1.1 Sources

[0027] 40 patients with high-risk HPV infection who visited Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine and Traditional Chinese Medicine Research Institute from October 1, 2023 to October 1, 2024 were selected as the research objects.

[0028] 1.1.1 Inclusion criteria

[0029] ① Age: 20 - 65 years old, with a history of sexual life; ② Meeting the above-mentioned traditional Chinese and Western medicine diagnostic criteria; ③ No other physical and drug treatment history within 2 months before treatment; ④ Following the principle of voluntariness and signing the informed consent form.

[0030] 1.1.2 Exclusion criteria

[0031] ① Patients who do not meet the above inclusion criteria; ② Patients with allergic constitution or allergic to the drugs in this study; ③ Cervical intraepithelial neoplasia or cervical cancer found by pathological examination; ④ Those who use antiviral drugs, Baofukang Suppository and interferon 3 months before and after treatment; ⑤ Those with combined cervical polyps, or a history of cervical trauma in the past, or those who have received physical treatment due to cervical lesions; ⑥ Those with combined severe organ dysfunction or autoimmune system diseases; ⑦ Those with combined infections of other organs (such as pneumonia, encephalitis, hepatitis, nephritis, etc.); ⑧ Those who are not willing to receive treatment or do not sign the informed consent form.

[0032] 1.2 Methods

[0033] 1.2.1 Clinical grouping

[0034] In this embodiment, the single-center randomized controlled principle is adopted. The 40 patients who meet the inclusion criteria are numbered in the order of the visit time, and then they are assigned to the treatment group and the control group according to the random number table method, with 20 patients in each group.

[0035] 1.2.2 Treatment methods

[0036] Control group: ① Drugs: Baofukang Suppository, Recombinant Human Interferon α2b Suppository; ② Sources: Baofukang Suppository (Hainan Bikai Pharmaceutical Co., Ltd., specification: 1.74g * 14 capsules / box, national drug approval number: Z46020058); Recombinant Human Interferon α2b Suppository (Changchun Institute of Biological Products Co., Ltd., specification: 50IU / 3 capsules / box, national drug approval number: S19991019); ③ Alternately used vaginally every other day, one capsule each time, once a day, avoiding menstruation; ④ Course of treatment: 3 months.

[0037] Treatment group: ① Drugs: Fuzheng Ermiao Qingdu Granules combined with Baofukang Suppositories and recombinant human interferon α2b suppositories; ② Source: Ningxia Hui Autonomous Region Institute of Traditional Chinese Medicine and the Preparation Room of the Institute of Traditional Chinese Medicine, processed into granules according to conventional methods in this field; ③ Dosage: take 200 ml, 2 doses per day (avoid menstruation); ④ Course of treatment: 3 months; ⑤ Drug composition (each dose contains): 30g of Astragalus, 15g of Codonopsis, 12g of Atractylodes, 15g of Poria, 9g of Atractylodes, 6g of Phellodendron, 10g of Paris polyphylla, 10g of Smilax glabra, 10g of Scutellaria barbata, 10g of Lobelia, 15g of Patrinia scabra, 30g of Coix seeds, 15g of Hedyotis diffusa and 6g of Licorice.

[0038] 1.2.3 Observation indicators

[0039] (1) General indicators (patient's age, BMI, sexual history, pregnancy or parity, and other relevant personal information);

[0040] (2) Efficacy indicators: HPV negative conversion rate after treatment; TCT examination results and changes in cervical biopsy before and after treatment; TCM symptom score: the change in TCM symptom score before and after treatment was scored according to the relevant contents of the "TCM Symptom Scoring Method". The main symptoms were scored as 0, 2, 4, and 6 points respectively according to the severity of the disease, and the concomitant symptoms were scored as 0, 1, 2, and 3 points.

[0041] 1.2.4 Efficacy determination

[0042] ① Determined based on clinical indicators:

[0043] Cure: clinical symptoms disappeared or almost disappeared, HPV (-), TCT (-), tissue biopsy (-);

[0044] Markedly effective: Most of the clinical symptoms disappeared, HPV (-), TCT (+), tissue biopsy (-);

[0045] Effective: clinical symptoms improved, HPV (-), TCT (+), tissue biopsy (+);

[0046] Ineffective: clinical symptoms remained unchanged or aggravated, HPV (+), TCT (+), tissue biopsy (+).

[0047] ② Criteria for judging the efficacy of TCM syndromes:

[0048] Recovery: clinical symptoms disappear or almost disappear, and the syndrome score decreases by ≥95%;

[0049] Markedly effective: clinical symptoms improved significantly, 70%≤, symptom score decreased <95%;

[0050] Effective: clinical symptoms improved, 30%≤, symptom score decreased <70%;

[0051] Invalid: The clinical symptoms showed no improvement or deterioration, and the syndrome score decreased by less than 30.

[0052] The efficacy judgment criteria were formulated with reference to the "Guiding Principles for Clinical Research of New Chinese Medicines" (Trial) (2002) and the Nimodipine method calculation formula:

[0053] Efficacy index (%) = (total score before treatment - total score after treatment) / total score before treatment × 100.

[0054] 2 Statistical methods and results

[0055] 2.1 Basic information

[0056] SPSS 27.0 statistical software was used to analyze the relevant data. Analysis of variance was used for measurement data, and independent sample t-tests were used for between-group comparisons, expressed as mean ± standard deviation For count data, the X 2 test was used. When the frequency was less than 5, the fisher exact precision method was used, expressed as rate (frequency / total number of cases) [% (n / N)]. P < 0.05 indicated that the difference was statistically significant. There were no significant statistical differences in the baseline data (age, sexual history, number of sexual partners, number of pregnancies) between the two groups of patients (P > 0.05) (see Table 1 for details).

[0057] Table 1 General information

[0058]

[0059]

[0060] Note: The number of pregnancies includes the number of births and the number of miscarriages.

[0061] 2.2 Comparison of the number of HPV subtypes infected, total TCM syndrome scores, TCT results, and pathological results in the two groups of patients before treatment.

[0062] 2.2.1 Comparison of the number of HPV subtypes infected in the two groups of patients before treatment

[0063] The rank sum test for two independent samples was used, P = 0.605 > 0.05, and there was no significant difference between the groups, with comparability. Among them, 6 patients in the treatment group were infected with HPV16 and 1 patient was infected with HPV18. In the control group, 4 patients were infected with HPV16 and 2 patients were infected with HPV18. After chi-square test, P = 0.416 > 0.05, with comparability (see Table 2 for details).

[0064] Table 2 Comparison of the number of high-risk HPV subtypes infected in the two groups of patients

[0065]

[0066] 2.2.2 Comparison of the total scores of traditional Chinese medicine syndromes in the two groups of patients before treatment

[0067] The independent samples t-test was used. The average score of traditional Chinese medicine syndromes in the treatment group before treatment was 15.40±2.23, and the average score of traditional Chinese medicine syndromes in the control group before treatment was 15.25±2.12. P = 0.829>0.05, indicating no significant difference between the groups and comparability (see Table 3 for details).

[0068] Table 3 Comparison of the total scores of traditional Chinese medicine syndromes in the two groups of patients before treatment

[0069]

[0070] 2.2.3 Comparison of TCT results in the two groups of patients before treatment

[0071] The rank sum test for two independent samples was used. P = 0.704>0.05, indicating no significant difference between the groups and comparability (see Table 4 for details).

[0072] Table 4 Comparison of TCT results in the two groups of patients before treatment

[0073]

[0074] Note: NILM represents no epithelial lesion or malignant lesion; ASC-US represents atypical squamous epithelial cells with unclear significance; LSIL represents low-grade intraepithelial neoplasia.

[0075] 2.2.4 Comparison of TCT results in the two groups of patients before treatment

[0076] The rank sum test for two independent samples was used. P = 0.605>0.05, indicating no significant difference between the groups and comparability (see Table 5 for details).

[0077] Table 5 Comparison of pathological biopsy results in the two groups of patients before treatment

[0078]

[0079] 2.3 Efficacy evaluation

[0080] 2.3.1 Comparison of the efficacy of traditional Chinese medicine syndromes in the two groups of patients after treatment

[0081] After treatment, the total effective rates of the experimental group and the control group were 90% (18 cases) and 50% (10 cases) respectively. After chi-square test, P = 0.039<0.05, showing statistical significance (P<0.05), as shown in Table 6.

[0082] Table 6 Comparison of the efficacy of traditional Chinese medicine syndromes in the two groups of patients after treatment

[0083]

[0084] 2.3.2 Comparison of Therapeutic Effects of Clinical Indicators

[0085] Treatment outcome of 40 patients after treatment: The high-risk cervical HPV test turned negative in 13 patients (10 in the treatment group and 3 in the control group), the viral load of high-risk cervical HPV in 1 patient (0 in the treatment group and 1 in the control group) decreased significantly but did not turn negative, and the high-risk cervical HPV test remained positive in 27 patients (10 in the treatment group and 17 in the experimental group).

[0086] After treatment, the total effective rates of the experimental group and the control group were 15 cases / 75% in the treatment group and 6 cases / 30% in the control group respectively. After chi-square test, P = 0.049 < 0.05, which was statistically significant (P < 0.05), as shown in Table 7.

[0087] Table 7 Therapeutic Effects of Clinical Indicators of Two Groups of Patients after Treatment

[0088]

[0089] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, rather than limitations on the implementation manners of the present invention. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to enumerate all the implementation manners here. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the claims of the present invention.

Claims

1. A Chinese medicine composition for resisting human papillomavirus, characterized in that: It is made of the following components in parts by weight: 30 parts of Astragalus, 15 parts of Codonopsis, 12 parts of Atractylodes, 15 parts of Poria, 9 parts of Atractylodes, 6 parts of Phellodendron, 10 parts of Paris polyphylla, 10 parts of Smilax glabra, 10 parts of Scutellaria barbata, 10 parts of Lobelia, 15 parts of Patrinia herb, 30 parts of Coix seeds, 15 parts of Oldenlandia diffusa and 6 parts of Licorice.

2. Use of the Chinese medicine composition as claimed in claim 1 in the preparation of anti-human papillomavirus drugs.

3. An anti-human papillomavirus drug, characterized in that: Including the Chinese medicine composition according to claim 1.

4. The drug according to claim 3, characterized in that The dosage form of the medicine is granules.

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