Traditional Chinese medicine compound for intervening AIDS immune reconstitution insufficiency, preparation method and application

Abstract

The invention relates to a traditional Chinese medicine compound for intervening AIDS immune function insufficiency reconstruction and a preparation method and application thereof. The traditional Chinese medicine compound mainly comprises the following raw materials: astragalus membranaceus, codonopsis pilosula, turmeric, lithospermum erythrorhizon, herba violae and liquorice. The active ingredients of the main medicines of the traditional Chinese medicine compound can regulate CD4 + T cells, so that the effects of immune regulation and the like are achieved, and the immune function reconstruction of AIDS patients is promoted.

Description

Technical Field

[0001] The present invention belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine compound for intervening in incomplete immune function reconstruction of AIDS, a preparation method and an application thereof. Background Art

[0002] I. Incomplete immune function reconstruction of AIDS is a difficult problem to be overcome at present AIDS is short for Acquired Immunodeficiency Syndrome (AIDS). It is a serious immunodeficiency infectious disease caused by the direct invasion and destruction of the human immune system, especially the cellular immune system, by the AIDS virus (i.e., human immunodeficiency virus, HIV), and its fatality rate is extremely high. In recent years, highly active antiretroviral therapy (HAART) can delay the onset of HIV / AIDS and has become an effective method recognized worldwide for the prevention and control of AIDS. However, this therapy has problems such as difficulty in radically curing the virus latent in cells, easy generation of drug resistance, and obvious side effects. Especially during the first 3 months of HAART treatment, the incidence of adverse reactions in HIV / AIDS patients is very high. Clinical symptoms such as nausea, abdominal pain, fatigue, and rash, and adverse reactions such as anemia, granulocytopenia, lymphocytopenia, and thrombocytopenia caused by peripheral blood myelosuppression are the most common, which often affect the compliance and efficacy of HAART antiviral treatment in HIV / AIDS patients. In addition, in developing countries with underdeveloped economies, the expensive HAART therapy limits its extensive and long-term (lifelong treatment) application. And incomplete immune function reconstruction of AIDS has attracted great attention in the academic community. How to restore the immune function of the body while maintaining the stability of the viral load is one of the hotspots and difficulties in the field of AIDS at present. Therefore, it is urgent to develop effective treatment measures for AIDS from the field of traditional medicine, and it is also very important to seek traditional Chinese medicine treatment methods for immune function reconstruction of immune deficiency caused by HIV / AIDS infection.

[0003] II. Research progress of traditional Chinese medicine in the treatment of incomplete immune function reconstruction of AIDS Since the discovery of the first AIDS case in China, traditional medicine has been tried for treatment. In recent years, the application of traditional Chinese medicine has also become an important breakthrough in immune reconstruction. Many scholars have carried out extensive basic and clinical studies to verify the safety and effectiveness of traditional Chinese medicine in restoring immune function. The advantages of traditional Chinese medicine in treating AIDS lie in achieving the effects of replenishing qi and strengthening the healthy qi, tonifying the kidney and consolidating the root, promoting blood circulation to remove stasis, and clearing heat and detoxifying through overall regulation and syndrome differentiation and treatment. Especially in combination with HARRT treatment, it can not only fight against viruses and mainly attack pathogenic factors, but also supplement healthy qi and mainly strengthen the healthy qi. Integrating traditional Chinese and Western medicine, promoting the healthy qi and eliminating pathogenic factors simultaneously, synergistically improving the clinical symptoms of patients, regulating immune function, and reducing toxicity and enhancing efficacy.

[0004] III. Etiology and pathogenesis of incomplete immune function reconstruction in AIDS Due to its characteristics such as fast transmission speed, wide spread, and similar disease manifestations, most scholars believe that AIDS belongs to the invasion of a kind of "epidemic toxin" pathogen. The invasion of the "epidemic toxin" pathogen into the human body damages the healthy qi of the human body. Moreover, AIDS patients often indulge in sexual pleasures and consume the essence of the kidney; or indulge in alcohol and accumulate toxins, worry and overwork, resulting in deficiency of various zang-fu organs and dysfunction, providing opportunities for the epidemic toxin, often making the condition more serious, leading to the formation of a series of pathological products (such as phlegm turbidity and blood stasis), and generating diseases such as "abdominal mass" and "accumulation", and even leading to the separation of yin and yang. Therefore, HIV / AIDS is the result of the invasion of pathogenic toxins on the basis of deficiency of essence and qi, the struggle between healthy qi and pathogenic factors, and the failure of healthy qi to overcome pathogenic factors. And "prolonged illness enters the collaterals, prolonged illness causes blood stasis", and blood stasis blocking the collaterals will inevitably occur in the long-term pathological process. Therefore, the basic pathological changes throughout the process are qi deficiency and blood stasis, and internal stagnation of pathogenic toxins. Clinical practice has also found that during the development of this disease, most patients always have symptoms such as limb pain and numbness, fatigue, lethargy, poor appetite, headache, chest pain, abdominal pain, limb pain or numbness, or emaciation, weight loss, skin itching, pale tongue, ecchymosis, and thready and unsmooth or stringy and unsmooth pulse of "qi deficiency, blood stasis, and toxin". Summary of the Invention

[0005] The purpose of the present invention is to provide a traditional Chinese medicine compound for intervening in incomplete immune function reconstruction in AIDS. The traditional Chinese medicine compound is made from the following raw materials in parts by weight: 50 - 70 parts of astragalus membranaceus, 35 - 60 parts of codonopsis pilosula, 15 - 40 parts of curcuma longa, 5 - 15 parts of lithospermum erythrorhizon, 60 - 90 parts of viola philippica, and 40 - 60 parts of licorice. Preferably, the traditional Chinese medicine compound is made from the following raw materials in parts by weight: 55 - 65 parts of astragalus membranaceus, 40 - 50 parts of codonopsis pilosula, 20 - 30 parts of curcuma longa, 8 - 12 parts of lithospermum erythrorhizon, 70 - 80 parts of viola philippica, and 45 - 55 parts of licorice. More preferably, the traditional Chinese medicine compound is made from the following raw materials in parts by weight: 60 parts of astragalus membranaceus, 45 parts of codonopsis pilosula, 25 parts of curcuma longa, 10 parts of lithospermum erythrorhizon, 75 parts of viola philippica, and 50 parts of licorice.

[0006] A traditional Chinese medicine compound preparation, the preparation comprising the above traditional Chinese medicine compound and pharmaceutically acceptable excipients.

[0007] The preparation method of the traditional Chinese medicine compound preparation comprises weighing six traditional Chinese medicine decoction pieces, namely astragalus root, codonopsis pilosula, turmeric, lithospermum erythrorhizon, viola philippica and liquorice, by weight parts as raw materials, and adding dextrin, magnesium stearate or other pharmaceutically acceptable excipients to prepare a compound granule through processes of boiling with water, filtering, concentrating, mixing, granulating, drying and sizing.

[0008] The present invention also provides the application of the traditional Chinese medicine compound in the preparation of a drug for intervening in incomplete immune function reconstruction of AIDS.

[0009] The traditional Chinese medicine compound of the present invention is composed of six traditional Chinese medicines, namely astragalus root, codonopsis pilosula, turmeric, lithospermum erythrorhizon, viola philippica and liquorice. In the formula, astragalus root and codonopsis pilosula are used as the monarch drugs, which are sweet and warm in nature, replenish qi and strengthen the healthy qi to dispel pathogenic factors. Codonopsis pilosula can tonify qi and nourish blood, and stays in one place without moving; astragalus root can tonify qi and support yang, and moves without staying. The two drugs are used in combination, having a powerful effect of tonifying qi and assisting the primordial qi. Moreover, one moves and the other stays, taking both yin and yang into consideration, reaching from the inside to the outside, and tonifying without purging. Liquorice is sweet in taste and neutral in nature, which can not only invigorate the spleen and moisten the lungs, clear heat and detoxify, but also strengthen the effects of the monarch and ministerial drugs, and is used as the adjuvant and guiding drug. In addition, multiple drugs in the formula are used in combination, with both tonifying and purging, regulating cold and heat together, promoting blood circulation to assist in dispersing toxins, detoxifying to expect collateral dredging, strengthening the healthy qi to suppress pathogenic toxins, and resisting toxins to promote healthy qi, jointly exerting the effects of tonifying qi and strengthening the healthy qi, promoting blood circulation and detoxifying. In the asymptomatic stage, it can assist the healthy qi; in the onset stage, it can be used by tonifying the healthy qi and attacking pathogenic factors simultaneously, and is also applicable to the "qi deficiency and stasis-toxin" syndrome of AIDS in this stage. The active ingredients of the main drugs in the compound can regulate CD4+ T cells, thus exerting immunomodulatory and other effects, and promoting the immune function reconstruction of AIDS patients.

[0010] Astragalus root: Slightly warm in nature and sweet in taste, it enters the lung and spleen meridians, replenishes the qi of the lung and spleen, and has the characteristic of ascending and spreading outward when tonifying qi. It has the effects of invigorating qi and consolidating the exterior, warming and nourishing the spleen and stomach, etc., and is mainly used to treat symptoms such as deficiency of both the lung and spleen, qi and blood weakness, spontaneous sweating, etc. "Ri Hua Zi" said: "It helps qi, strengthens muscles and bones, grows flesh and nourishes blood, breaks masses and scrofula, treats goiter... and also treats headache, heat toxin, red eyes, etc.". Astragalus root is the main drug for strengthening the healthy qi and dispelling pathogenic factors, and has been proven to have good immunomodulatory effects. Astragaloside IV, as one of the main active ingredients of astragalus root, can regulate CD4+ T cells, thus exerting immunomodulatory and other effects. Total flavonoids of astragalus can increase the weight of the immune organ spleen in hydrocortisone model mice, enhance the phagocytic function of mononuclear macrophages, increase the total number of T cells and adjust the disorder of T cell subsets. Generally speaking, astragalus can enhance the function of T cells and play an immunomodulatory role in AIDS patients.

[0011] Codonopsis pilosula: Sweet in taste and neutral in nature. It acts on the spleen and lung meridians. Its functions are to invigorate the spleen and replenish the lung, benefit qi and promote the production of body fluid. Zhang Shanlei said: "Codonopsis pilosula can strengthen the spleen and nourish the stomach, moisten the lung and promote the production of body fluid, and strengthen the transportation of the middle qi. It is not very different from ginseng. What is particularly valuable is that it can strengthen the transportation of the spleen without being dry, nourish the yin of the stomach without being damp, moisten the lung without being cold, nourish the blood without being overly greasy, encourage the clear yang, vibrate the middle qi, and have no disadvantages of being overly dry and rigid." The main active ingredient of Codonopsis pilosula - Codonopsis pilosula polysaccharide can have immunomodulatory effects; promote the compensatory hematopoietic function of the spleen; improve microcirculation. And the hematopoietic function is closely related to the immune function. If the immune function is low, it will seriously affect the hematopoietic function, thus leading to blood deficiency; if the hematopoietic function is insufficient and the red blood cell level drops, it will affect the body's immune function. By retrieving the research literature on the treatment of poor immune reconstruction in AIDS with traditional Chinese medicine, it is found that Astragalus membranaceus and Codonopsis pilosula are the top two traditional Chinese medicines in terms of the frequency of use, indicating the effectiveness of these two drugs in the immune reconstruction of AIDS.

[0012] Licorice: Sweet in taste and neutral in nature. It acts on the spleen, stomach, heart, and lung meridians. It has the functions of tonifying qi and strengthening the middle, relieving spasm and pain, moistening the lung and relieving cough, purging fire and detoxifying, and harmonizing various medicinal herbs. Miao Xiyong said of it: "It can treat the cold and heat pathogens of the five zang-organs and six fu-organs and strengthen the muscles and bones because it obtains the qi of the thoroughfare yang in the earth; with a sweet and flat taste and a gentle nature, it can relieve all kinds of toxins, calm the five zang-organs, and eliminate pathogenic heat. Once the cold and heat pathogens of the five zang-organs are relieved, the zang-organ qi will be harmonious and the genuine qi will be generated. As the qi becomes stronger day by day, the muscles and bones will be strengthened. It can promote the growth of muscles and increase strength because sweetness can benefit the spleen. The spleen governs the muscles and is also in charge of the four limbs. When the spleen is strong, the four limbs will generate strength, so it can promote the growth of muscles and increase strength." As early as the late 1980s, Japanese scholars first reported the anti-HIV effect of glycyrrhizic acid. In recent years, the important role of licorice in the treatment of HIV / AIDS has been continuously verified. Among them, glycyrrhizic acid can inhibit the replication potential of HIV by inducing the production of β-chemokines or indirectly inhibit the replication of HIV by reducing the activity of protein kinase C. At the same time, it also has the effect of inhibiting the adsorption of HIV to host cells. Research has also found that glycyrrhizic acid can also inhibit the reproduction and spread of HIV between cells by reducing the fluidity of the cell membrane to reduce cell-cell fusion. In addition, licorice also has broad-spectrum antiviral and antibacterial effects. Specific implementation methods

[0013] Example 1: Traditional Chinese medicine compound granule Prescription composition: 364 g of Astragalus membranaceus, 273 g of Codonopsis pilosula, 152 g of turmeric, 61 g of lithospermum, 455 g of viola yedoensis, and 304 g of licorice.

[0014] Preparation method: The above six herbs are decocted in water twice, each time for 2 hours. The decoctions are combined, filtered, and the filtrate is allowed to stand overnight. The supernatant is taken, filtered, concentrated into a clear paste with a relative density of 1.25 - 1.30 (60 °C), appropriate dextrin is added, granulated, dried, and sized to make granules.

[0015] After years of in-depth research, the applicant found in the previous research that the traditional Chinese medicine compound of the present invention can significantly up-regulate the expression of IFN-α mRNA in PBMCs of asymptomatic AIDS patients. On this basis, relevant clinical studies were carried out. The results showed that after 3 months of treatment, compared with the subjects treated with HAART alone, the subjects treated with this compound in combination with HAART had significantly increased peripheral blood RBC levels, decreased CR levels, decreased TCM symptom scores, improved fatigue, anorexia, and spontaneous sweating, and the CD4+ T lymphocyte count level was increased, and the quality of life score was improved. After testing, the differences were all statistically significant (p < 0.05). It can improve the clinical symptoms, blood toxicity side effects, and quality of life of patients after initial HAART treatment, reduce the adverse reactions of antiviral treatment, and the combined medication can significantly increase CD4+ T lymphocytes compared with single medication, thus improving the clinical efficacy. It shows the effectiveness and safety of this compound in the treatment of patients with incomplete immune reconstruction (qi deficiency, blood stasis, and toxin accumulation) of AIDS and has the value of popularization and application.

Claims

1. A traditional Chinese medicine compound for intervening in incomplete reconstruction of AIDS immune function, characterized in that, The traditional Chinese medicine compound is prepared from the following raw materials in parts by weight: 50 - 70 parts of Astragalus membranaceus, 35 - 60 parts of Codonopsis pilosula, 15 - 40 parts of Curcuma longa, 5 - 15 parts of Lithospermum erythrorhizon, 60 - 90 parts of Viola philippica, and 40 - 60 parts of Glycyrrhiza uralensis.

2. The traditional Chinese medicine compound according to claim 1, characterized in that, The traditional Chinese medicine compound is prepared from the following raw materials in parts by weight: 55 - 65 parts of Astragalus membranaceus, 40 - 50 parts of Codonopsis pilosula, 20 - 30 parts of Curcuma longa, 8 - 12 parts of Lithospermum erythrorhizon, 70 - 80 parts of Viola philippica, and 45 - 55 parts of Glycyrrhiza uralensis.

3. The traditional Chinese medicine compound according to claim 1, characterized in that, The traditional Chinese medicine compound is prepared from the following raw materials in parts by weight: 60 parts of Astragalus membranaceus, 45 parts of Codonopsis pilosula, 25 parts of Curcuma longa, 10 parts of Lithospermum erythrorhizon, 75 parts of Viola philippica, and 50 parts of Glycyrrhiza uralensis.

4. A traditional Chinese medicine compound preparation, characterized in that, The preparation comprises the traditional Chinese medicine compound according to claim 1 or 2 or 3 and pharmaceutically acceptable excipients.

5. A preparation method for preparing the traditional Chinese medicine compound preparation described in claim 4, characterized in that: Compound granules prepared by weighing six traditional Chinese medicine decoction pieces of Astragalus membranaceus, Codonopsis pilosula, Curcuma longa, Lithospermum erythrorhizon, Viola philippica, and Glycyrrhiza uralensis by weight and through the processes of boiling with water, filtering, concentrating, mixing, granulating, drying, and sizing.

6. Use of the traditional Chinese medicine compound according to claim 1 in the preparation of a drug for intervening in incomplete reconstruction of immune function in AIDS.