Application of Guiqi Huoxue preparation in the preparation of drugs for treating chronic pelvic inflammatory disease

Abstract

The application belongs to the technical field of traditional Chinese medicines, and particularly relates to application of a Guqi Huoxue preparation in preparation of a medicine for treating chronic pelvic inflammation. The Guqi Huoxue preparation is made of 13 raw medicinal materials, including Huangqi, Danggui, Baishao, Hechouwu, Gouqizi, Suanzaoren, Lurong, Gushugu, Weilingxian, Tougucao, artificial musk, Gegen and Chuanxiong. Pharmacodynamic experiments prove that the Guqi Huoxue preparation can obviously reduce the uterus coefficient of rats, reduce the content of TNF-α, IL-1β and IL-6 in serum, increase the content of IgA, IgG, IgM and IL-10 in serum, reduce inflammatory reaction, improve immunity and improve chronic pelvic inflammation, and can be used for treating chronic pelvic inflammation. The Guqi Huoxue preparation has high safety and small toxic and side effects, and enriches the clinical drug selection of patients.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to the application of Astragalus and Angelica sinensis blood-activating preparations in the preparation of drugs for treating chronic pelvic inflammatory disease. Background Technology

[0002] Pelvic inflammatory disease (PID) refers to inflammation of the female pelvic reproductive organs, the connective tissue surrounding the uterus, and the pelvic peritoneum. Chronic PID often results from incomplete treatment of the acute phase, and is characterized by a long duration and stubborn symptoms. The main manifestations include recurrent lower abdominal distension and pain, lumbosacral pain, and may be accompanied by excessive vaginal discharge and pelvic masses. In severe cases, it can lead to infertility and is highly correlated with the development of ovarian tumors. Western medicine treatment primarily uses antibiotics for acute PID; however, antibiotics have significant side effects and are not suitable for long-term use. Furthermore, chronic PID is often caused by multiple pathogens, and broad-spectrum antibiotic combinations, such as non-targeted therapy, are often less effective. More importantly, long-term use of large doses of antibiotics often leads to secondary infections, and patients are more prone to developing drug resistance.

[0003] Traditional Chinese medicine (TCM) has its own unique theories and experiences in understanding chronic pelvic inflammatory disease (PID), which falls under the categories of "abdominal pain in women," "emaciation," and "leukorrhea." The etiology of this disease is complex, resulting from the interaction of multiple factors such as cold, heat, dampness, blood stasis, and deficiency. TCM believes that the main pathological mechanism of chronic PID is the incomplete recovery of the body's vital energy (Qi) and the lingering effects of pathogenic factors. These pathogenic factors, such as wind, cold, dampness, heat, and insect toxins, invade the body, leading to stagnation of Qi and blood, obstruction of blood flow, accumulation in the uterus and uterine vessels, repeated cycles of invasion and retreat, depletion of Qi and blood, and a lingering, difficult-to-cure condition. Common causes include Qi stagnation and blood stasis, damp-heat stagnation, cold-dampness stagnation, Qi deficiency and blood stasis, and kidney deficiency and blood stasis. Treatment focuses on promoting blood circulation and removing blood stasis, depending on the etiology and symptoms. Treatment may involve clearing heat and dampness, dispelling cold and dampness, promoting Qi circulation and removing blood stasis, tonifying Qi and removing blood stasis, or warming the kidneys and removing blood stasis. Emphasis is placed on combined internal and external treatment, considering the body's vital energy, and harmonizing the mind and body.

[0004] Traditional Chinese medicine (TCM) has accumulated rich experience in treating chronic pelvic inflammatory disease (PID). Prepared Chinese medicines (TCM patent medicines), as one of the main forms of TCM treatment for chronic PID, are an indispensable part of TCM's therapeutic characteristics, and many guidelines / consensus statements mention them when recommending treatments. Because TCM has advantages such as multiple components, multiple targets, multiple pathways of action, and fewer toxic side effects, exploring TCM treatments for chronic PID is of paramount importance. This invention discloses the application of an Astragalus and Angelica sinensis blood-activating preparation in the preparation of drugs for treating chronic PID. Its therapeutic principle is to eliminate inflammation, repair lesions, and simultaneously improve the body's immunity. The treatment focuses on regulating function, supplemented by continuous repair and consolidation of lesions, as well as further relief and elimination of symptoms, ultimately leading to a complete cure of chronic PID. Summary of the Invention

[0005] In order to enrich the selection of drugs for the clinical treatment of chronic pelvic inflammatory disease, the purpose of this invention is to provide a new use for the Guiqi Huoxue preparation in the treatment of chronic pelvic inflammatory disease.

[0006] The inventors unexpectedly discovered in clinical practice that the Astragalus and Angelica blood-activating preparation has a good preventive and therapeutic effect on chronic pelvic inflammatory disease.

[0007] Application of Astragalus and Angelica sinensis blood-activating preparations in the preparation of drugs for treating chronic pelvic inflammatory disease.

[0008] Preferably, the pelvic inflammatory disease is acute pelvic inflammatory disease or chronic pelvic inflammatory disease.

[0009] Preferably, the pelvic inflammatory disease is chronic pelvic inflammatory disease.

[0010] The blood-activating preparation of Astragalus and Angelica sinensis described in this invention is made from 13 raw medicinal materials: Astragalus membranaceus, Angelica sinensis, Paeonia lactiflora, processed Polygonum multiflorum, Lycium barbarum, Loranthus parasiticus, deer antler, Drynaria fortunei, Clematis chinensis, Clematis armandii, artificial musk, Pueraria lobata, and Ligusticum chuanxiong.

[0011] The aforementioned Astragalus and Angelica sinensis blood-activating preparation is made from the following raw medicinal materials in parts by weight:

[0012] Astragalus membranaceus 600 parts by weight, Angelica sinensis 240 parts by weight, Paeonia lactiflora 240 parts by weight

[0013] Prepared Polygonum multiflorum 240 parts by weight, Lycium barbarum 320 parts by weight, and Mistletoe 160 parts by weight

[0014] 5 parts by weight of deer antler, 240 parts by weight of drynaria fortunei, and 320 parts by weight of clematis chinensis.

[0015] 240 parts by weight of Clematis chinensis, 1 part by weight of artificial musk, and 240 parts by weight of Pueraria lobata.

[0016] 240 parts by weight of Ligusticum chuanxiong

[0017] The Guiqi Huoxue preparation of the present invention is Guiqi Huoxue capsule.

[0018] Guiqi Huoxue Capsules (Approval Number: Z20090686) are a marketed traditional Chinese medicine product of Lunan Houpu Pharmaceutical Co., Ltd. They are made from raw medicinal materials including Astragalus membranaceus, Angelica sinensis, Paeonia lactiflora, processed Polygonum multiflorum, Lycium barbarum, Loranthus parasiticus, deer antler, Drynaria fortunei, Clematis chinensis, Clematis armandii, artificial musk, Pueraria lobata, and Ligusticum chuanxiong. They have the effects of clearing heat and detoxifying, promoting blood circulation and reducing swelling, and relieving pain. In the formula, Angelica sinensis and Astragalus membranaceus are the principal herbs, replenishing qi and blood, and also clearing the meridians. Paeonia lactiflora, processed Polygonum multiflorum, Lycium barbarum, Loranthus parasiticus, deer antler, and Drynaria fortunei are the assistant herbs, assisting the principal herbs in tonifying the liver and kidneys, strengthening tendons and bones, and promoting blood circulation and relieving pain. Clematis chinensis, Clematis armandii, musk, Pueraria lobata, and Ligusticum chuanxiong are the adjuvant herbs, dispelling wind and penetrating the bones, promoting blood circulation and relieving pain, assisting the principal and assistant herbs in clearing the meridians and relieving pain. Chuanxiong (Ligusticum striatum) also serves as an adjuvant, guiding the other herbs upwards to the neck to dispel wind, cold, and dampness from the blood. Together, these herbs work to invigorate qi and nourish blood, tonify the liver and kidneys, relax muscles and tendons, and relieve pain.

[0019] Compared with the prior art, the present invention has achieved significant technical effects:

[0020] Modern medicine has shown that Guiqi Huoxue Capsules can reduce the levels of TNF-α, IL-1β, and IL-6 in the serum of rats with chronic pelvic inflammatory disease, while increasing the level of IL-10, indicating that Guiqi Huoxue preparations have an inhibitory effect on inflammatory responses, thus providing protection for rats with chronic pelvic inflammatory disease. Simultaneously, Guiqi Huoxue Capsules can increase the levels of IgA, IgG, and IgM in the serum, thus enhancing the body's immunity.

[0021] The Guiqi Huoxue Capsules of this invention follow traditional Chinese medicine theory and combine it with modern medical research theories. They provide a new option for the clinical treatment of chronic pelvic inflammatory disease, and have broad application prospects in the preparation of drugs for treating chronic pelvic inflammatory disease. Detailed Implementation

[0022] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following examples.

[0023] Experiment Example 1: Study on the effect of Guiqi Huoxue Capsules on a rat model of chronic pelvic inflammatory disease.

[0024] 1. Materials and Methods

[0025] 1.1 Laboratory Animals and Their Care

[0026] 60 healthy female SPF - grade SD rats, 6 - 8 weeks old, body weight: 200 ± 20 g. Provided by Lunan Pharmaceutical Group Co., Ltd., Laboratory Animal License Number: SYXK(Lu)20230023. Room temperature 22 - 24 °C, relative humidity 40% - 60%, 12 - hour light / 12 - hour dark cycle. The animals can move, eat and drink freely in the breeding cages. The experiment started after 7 days of adaptive feeding in the laboratory.

[0027] 1.2 Reagents and Instruments

[0028] AG285 electronic analytical balance (Mettler - Toledo, Switzerland); low - temperature high - speed centrifuge (Eppendorf, Germany); ELISA kits for rat TNF - α, IL - 1β, IL - 6 and IL - 10 (Wuhan Eclite Biotechnology Co., Ltd.); ELISA kits for rat IgA, IgG, IgM (Wuhan Aidy Anti - Biotechnology Co., Ltd.); positive drug Fuke Qianjin Capsule (Zhuzhou Qianjin Pharmaceutical Co., Ltd., National Medicine Approval Number: Z20020024); test drug Guiqi Huoxue Capsule (Lunan Houpu Pharmaceutical Co., Ltd., National Medicine Approval Number: Z20090686).

[0029] 1.3 Animal Grouping and Model Preparation

[0030] Using a random number table, the 60 rats were randomly divided into 6 groups, namely normal control group, model control group, positive control group, low - dose group of Guiqi Huoxue Capsule (abbreviated as "test low - dose group"), medium - dose group of Guiqi Huoxue Capsule (abbreviated as "test medium - dose group"), high - dose group of Guiqi Huoxue Capsule (abbreviated as "test high - dose group"), with 10 SD rats in each group.

[0031] Except for the blank control group, rats in the other groups were anesthetized by intraperitoneal injection of 10% chloral hydrate (0.5 mL / 100 g), then fixed in the supine position on the operating table. The hair in the middle of the lower abdomen was shaved off. After routine disinfection, a skin incision was made 2 cm above the pubic symphysis in the middle of the lower abdomen under sterile conditions. In each group, the left uterus was damaged organically by pulling the needle back and forth twice with a needle, and 0.06 mL of 25% phenol glue was slowly injected into the right uterus. To prevent the liquid from flowing out, the needle hole was clamped after withdrawing the needle. The abdomen was sutured and disinfected. After the operation, the animals were fed normally according to the previous feeding conditions.

[0032] 1.4 Administration Method

[0033] After successful model establishment, rats in each group were fed a standard diet for 7 days, followed by gavage. Dosage was calculated based on the clinical dosage of Guiqi Huoxue Capsules. The low-dose, medium-dose, and high-dose groups were administered Guiqi Huoxue Capsules at doses of 0.215 g / kg / d, 0.43 g / kg / d, and 0.86 g / kg / d, respectively. The positive control group was administered Fuke Qianjin Capsules at a dose of 0.216 g / kg / d. The normal control and model control groups were administered an equal volume of physiological saline. All rats were given the medication once daily for 21 consecutive days. Blood was collected via the abdominal aorta after anesthesia. 2. Detection Indicators and Methods

[0034] 2.1 General Characteristic Observation

[0035] Observe and record the changes in general behavior of rats, such as mental state and vaginal secretions, before and after modeling and during treatment.

[0036] 2.2 Rat uterine coefficient

[0037] After blood was collected, the rats were euthanized, and the uterine tissue was weighed and its uterine coefficient was calculated.

[0038]

[0039] 2.3 Determination of serum TNF-α, IL-1β, IL-6, and IL-10 levels in rats

[0040] After the blood clotted naturally at room temperature for 10–20 minutes, it was centrifuged for approximately 20 minutes (3000 rpm), and the supernatant was collected. The levels of TNF-α, IL-1β, IL-6, and IL-10 in rat serum were determined using an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's instructions.

[0041] 2.4 Determination of serum IgA, IgG, and IgM levels in rats

[0042] After allowing rat blood to stand in the blood collection tube for 30 minutes, centrifuge the tube and use the double antibody sandwich method to detect the levels of IgA, IgG, and IgM in rat serum, following the instructions.

[0043] 2.5 Statistical Analysis: SPSS 22.0 software was used for statistical analysis. Experimental data are expressed as mean ± standard deviation. The results were expressed in the form of “”. One-way ANOVA was used for comparisons among multiple groups, with P < 0.05 considered statistically significant.

[0044] 3 Experimental Results

[0045] 3.1 Effects of Guiqi Huoxue Capsules on the General Condition of Rats with Chronic Pelvic Inflammatory Disease

[0046] The rats in the model group were lethargic, sluggish, and had dull eyes. They also had a lot of yellow, thick, and foul-smelling vaginal discharge. Their hair was dry, damp, or tangled. They also had reduced food and water intake. In contrast, the rats in the blank control group were active, responsive, and had a moderate amount of white, thin, and odorless vaginal discharge. They also had normal food and water intake.

[0047] 3.2 Effect of Guiqi Huoxue Capsules on Uterine Coefficient in Rats with Chronic Pelvic Inflammatory Disease

[0048] Compared with the normal group, the uterine coefficient of the model control group was significantly increased, and the difference was statistically significant (P<0.05). In this study, after administration of Guiqi Huoxue Capsules, compared with the model group, there was no statistically significant difference in the low-dose group (P>0.05), while the uterine coefficient of the other administration groups was significantly decreased, and the differences were statistically significant (P<0.05). See Table 1.

[0049] Table 1 Comparison of uterine coefficients among different groups of rats

[0050]

[0051]

[0052] Note: Compared with the normal control group, P < 0.05 is indicated by "". * "" indicates that compared with the model control group, P < 0.05 is indicated by "". # "express.

[0053] 3.3 Effects of Guiqi Huoxue Capsules on Serum Levels of TNF-α, IL-1β, IL-6, and IL-10 in Rats with Chronic Pelvic Inflammatory Disease

[0054] Compared with the normal control group, the serum levels of TNF-α, IL-1β, and IL-6 in the model control group rats were significantly increased (P < 0.05). In this study, after administration of Guiqi Huoxue Capsules, compared with the model control group, the serum levels of TNF-α, IL-1β, and IL-6 in the positive control group and the medium and high dose groups were significantly decreased (P < 0.05). See Table 2.

[0055] Compared with the normal control group, the serum IL-10 level in the model control group was significantly decreased (P < 0.001). In this study, after administration of Guiqi Huoxue Capsules, compared with the model control group, the serum IL-10 level in the positive control group and the low, medium, and high dose groups was significantly increased (P < 0.05). See Table 2.

[0056] Table 2. Effects of Guiqi Huoxue Capsules on the serum levels of TNF-α, IL-1β, IL-6, and IL-10 in model rats.

[0057]

[0058] Note: Compared with the normal control group, P < 0.05 is indicated by "". * "" indicates that compared with the model control group, P < 0.05 is indicated by "". # "express.

[0059] 3.4 Effects of Guiqi Huoxue Capsules on Serum IgA, IgG, and IgM Levels in Rats with Chronic Pelvic Inflammatory Disease

[0060] Compared with the normal control group, the serum levels of IgA, IgG, and IgM in the model control group were significantly decreased (P < 0.05). In this study, after administration of Guiqi Huoxue Capsules, compared with the model control group, the serum levels of IgA, IgG, and IgM in the positive control group and the low, medium, and high dose groups were significantly increased (P < 0.05). See Table 3.

[0061] Table 3. Effects of Guiqi Huoxue Capsules on serum IgA, IgG, and IgM levels in model rats.

[0062]

[0063]

[0064] Note: Compared with the normal control group, P < 0.05 is indicated by "". * "" indicates that compared with the model control group, P < 0.05 is indicated by "". # "express.

[0065] This invention, Guiqi Huoxue Capsules, follows traditional Chinese medicine principles in its formulation and, combined with modern medical research, has demonstrated that it can improve the uterine coefficient in rats with chronic pelvic inflammatory disease; increase serum IL-10 levels and decrease TNF-α, IL-1β, and IL-6 levels; and increase serum IgA, IgG, and IgM levels. These findings indicate that Guiqi Huoxue preparations can enhance the regulation of inflammatory responses in model rats and improve the body's immunity, thereby having a preventative or therapeutic effect on chronic pelvic inflammatory disease.

Claims

1. Application of Astragalus and Angelica sinensis blood-activating preparations in the preparation of drugs for treating pelvic inflammatory disease.

2. The application according to claim 1, characterized in that, The pelvic inflammatory disease mentioned refers to either acute or chronic pelvic inflammatory disease.

3. The application according to claim 2, characterized in that, The pelvic inflammatory disease mentioned is chronic pelvic inflammatory disease.

4. The application according to claim 1, characterized in that, The aforementioned Guiqi Huoxue preparation is made from 13 raw medicinal materials: Astragalus membranaceus, Angelica sinensis, Paeonia lactiflora, processed Polygonum multiflorum, Lycium barbarum, Loranthus parasiticus, deer antler, Drynaria fortunei, Clematis chinensis, Clematis armandii, artificial musk, Pueraria lobata, and Ligusticum chuanxiong.

5. The application according to claim 1, characterized in that, The aforementioned Astragalus and Angelica sinensis blood-activating preparation is made from the following raw medicinal materials in parts by weight:

6. The application according to claim 1, characterized in that, The aforementioned Guiqi Huoxue preparation is Guiqi Huoxue capsule.

Images