Traditional Chinese medicine composition for treating sicca syndrome and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating sicca syndrome, which is prepared by extracting the following traditional Chinese medicine decoction pieces: 10-20 parts of ginseng, 5-15 parts of codonopsis pilosula, 15-25 parts of Chinese yam, 10-20 parts of radix polygonati officinalis, 5-15 parts of cortex moutan, 10-20 parts of radix ophiopogonis, 5-15 parts of radix paeoniae alba, 5-15 parts of dendrobe, 10-20 parts of radix rehmanniae recen and the like, and discloses a preparation method and application of the traditional Chinese medicine composition. The traditional Chinese medicine achieves the purpose of treating the qi-yin deficiency type sicca syndrome through the functions of tonifying lung qi, tonifying lung yin, tonifying spleen, reinforcing earth, generating gold, promoting lung moistening, nourishing yin, tonifying stomach and promoting fluid, tonifying kidney yin, tonifying heart blood, promoting blood circulation, removing blood stasis, dredging collaterals, soothing the liver and regulating qi.

Description

Technical Field

[0001] The invention belongs to the technical field of medicine, and particularly relates to a traditional Chinese medicine composition for treating Sjögren's syndrome and a preparation method thereof. Background Art

[0002] Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by invasion of exocrine glands, with focal lymphocyte infiltration as the main pathological feature. Among them, chronic inflammatory cell infiltration and destruction of salivary glands and lacrimal glands are the most obvious, forming keratoconjunctivitis sicca and xerostomia. Clinically, in addition to symptoms of dry mouth and dry eyes, almost half of patients will develop extraglandular diseases, involving multiple systems of the body such as lungs, cardiovascular, kidneys, stomach, nervous system, thyroid, and skin. This disease can exist alone, called primary Sjögren's syndrome, or it can be secondary to symptoms such as dry mouth and eyes on the basis of a clear diagnosis of other connective tissue diseases. Common connective tissue diseases such as rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, etc. are called secondary Sjögren's syndrome. Epidemiological surveys show that SS is a global disease. The prevalence in my country is 0.33% to 0.77%. It is more common in middle-aged and elderly people, and is more common in women, with a male-to-female ratio of 1: (9-20), and the age of onset is mostly between 40 and 50 years old. Domestic studies have shown that Sjögren's syndrome has a certain familial tendency, with the prevalence in first-degree relatives being 4.4%, and the positive rates of anti-Ro / La antibodies in first-degree and second-degree relatives reaching 21% and 11%, respectively.

[0003] The etiology and pathogenesis of Sjögren's syndrome are still unclear. It is currently believed to be related to immune dysfunction caused by multiple factors such as genetics, viral infection, and abnormal sex hormones. Studies have found that B cell activation may be a key factor in the development of pSS, and regulatory B cells are a group of cells that negatively regulate B cell immune responses and inhibit autoimmune inflammation, which may play a role in excessive autoimmunity in pSS. In addition, T cell subsets and related cytokines also play a role in the development of Sjögren's syndrome. Lymphoid follicular helper T cells (Tfh) are a special type of CD4+ effector T cell subsets that can enter the blood circulation and participate in humoral immunity. Lymphoid follicular regulatory T cells (Tfr) can inhibit B cell and Tfh responses, thereby inhibiting autoimmune inflammation. The imbalance of T helper cell (Th) cytokine expression is the key to the occurrence and development of Sjögren's syndrome. Th is mainly divided into Th1 and Th2. Th1 participates in cellular immunity and secretes cytokines such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin (IL)-2; Th2 participates in humoral immunity and secretes cytokines such as IL-4, IL-6, IL-10, and IL-13. The pathogenesis of SS is mainly based on Th1 hyperactivity and Th2 reduction, resulting in Th1 / Th2 immune imbalance. Therefore, the treatment of Sjögren's syndrome can start with regulating the Th1 / Th2 immune balance.

[0004] At present, the treatment options of Western medicine mainly include glucocorticoids, immunosuppressants, symptomatic replacement and other treatments. For dry mouth, pilocarpine can be taken to increase salivary flow rate, but sweating, frequent urination and intestinal irritation may occur. For dry eyes, artificial tears can be used, but long-term use will damage vision. Although systemic treatment effectively improves the clinical symptoms of pSS patients and controls the progression of the disease, it also has many adverse reactions. Glucocorticoids are often used when pSS is combined with kidney, nervous system, blood system involvement or is in rapid development. Long-term use can cause severe osteoporosis. Non-steroidal anti-inflammatory drugs are often used for joint pain, and long-term use can cause digestive tract lesions. Immunosuppressants are often used to treat systemic symptoms. Hydroxychloroquine can cause visual field defects and cardiac toxicity, methotrexate can cause hepatotoxicity and gastrointestinal discomfort, and cyclophosphamide and cyclosporine often cause gastrointestinal irritation, nephrotoxicity and urinary damage. Biological agents are often used when traditional treatment methods are ineffective or combined with serious systemic lesions. Their safety and efficacy are not determined, and considering the high price, their application is limited. Western medicine still lacks satisfactory treatment measures for pSS, and safer and more effective treatment options are urgently needed.

[0005] There is no name for Sjögren's syndrome in ancient Chinese medical books. Its symptoms can be traced back to the Neijing (Inner Canon of Medicine), which puts forward the view that "dryness prevails and causes dryness" and "dryness moistens the body". According to its characteristics and features, most doctors classify it as "dryness syndrome" and "arthralgia syndrome". In the 1980s, Professor Lu Zhizheng, a master of Chinese medicine, first proposed to name Sjögren's syndrome as "dryness arthralgia" in Chinese medicine, which was adopted by the National Committee of Arthralgia Diseases in Chinese Medicine and promoted by the Rheumatology Branch of the Chinese Association of Traditional Chinese Medicine to guide clinical practice. As a result, Chinese medicine officially named Sjögren's syndrome as "dryness arthralgia". Professor Lu Zhizheng's syndrome differentiation and treatment is mainly caused by deficiency of both qi and yin, and blood stasis, heat toxicity and dryness toxicity are its symptoms. The mouth, eyes, nose, pharynx and other orifices may be affected, and the skin, muscles, joints, and internal organs may also be affected. Sun Hongyan et al. studied the distribution characteristics of TCM constitution syndrome types in pSS patients and concluded that the key to the pathogenesis of Sjögren's syndrome is the deficiency of lung and stomach fluid, which is caused by multi-factor body deficiency, damage to body fluid after illness, and the combination of dryness. Wang Longde used the method of soothing the liver and strengthening the spleen to treat Sjögren's syndrome from the spleen and stomach and achieved remarkable results. He believed that if the liver fails to soothe and release, the qi will not distribute its body fluid, and if the spleen and stomach are weak, the body fluid will lack its source. Studies have also shown that SS patients often have psychological disorders such as anxiety and depression, just as the "Suwen Linglan Secret Classic" said: "The liver is the general's office, and the plan comes from it." Peng Jiangyun proposed the "less fire to generate qi" theory and treated Sjögren's syndrome by supporting less fire. Starting from yin deficiency, Liu Ruilin and others explained the necessary stage of the development of dryness and arthralgia from dryness and heat to dryness and poison, focusing on the sweet, sour, pungent and moistening method based on "sweet and sour to transform yin" and "pungent to moisten it" to treat dryness and arthralgia.

[0006] At present, some Chinese medicines can also relieve the symptoms of Sjögren's syndrome, but there are certain shortcomings or room for improvement.

[0007] CN118217357A discloses a Chinese medicine compound for treating Sjogren's syndrome and its preparation method and application. The formula of the Chinese medicine compound is Astragalus, Salvia miltiorrhiza, Ophiopogon japonicus, Dendrobium candidum. The Chinese medicine for treating Sjogren's syndrome of the present invention has the functions of replenishing qi and promoting body fluid, nourishing yin and moistening dryness, and promoting blood circulation and removing blood stasis. The present invention has unique advantages in treating Sjogren's syndrome, can significantly improve dry mouth of Sjogren's syndrome, anti-fatigue, submandibular gland lymphocyte infiltration and T cell subset imbalance, and is an effective pure Chinese medicine preparation. The patent only has pharmacodynamic research, and has not been clinically verified. In addition, in the theory of traditional Chinese medicine, the compound can replenish qi and raise the clear, transform essence and micro, make the blood flow and body fluid flow, and can produce body fluid to control dryness and fire, so that the essence, blood and body fluid are sufficient, and the dryness symptoms can be moisturized; the third can remove blood stasis and dredge the meridians, and the qi mechanism is unobstructed, so that the body fluid can be applied; the four medicines are used together to play the effect of "replenishing qi, promoting body fluid, and removing blood stasis", so that the dryness syndrome heals itself; there is no discussion on the spleen and kidney.

[0008] CN116421685A discloses a Chinese medicine for treating Sjögren's syndrome of deficiency of both qi and yin and its preparation method, belonging to the technical field of Chinese medicine preparation for Sjögren's syndrome. A Chinese medicine for treating Sjögren's syndrome of deficiency of both qi and yin, comprising the following components: Radix Pseudostellariae, Rhizoma Dioscoreae, Radix Rehmanniae, Herba Dendrobii, Radix Ophiopogonis; the preparation method adopts the following steps: S1, screening and washing each component; S2, dissolving and mixing each component to prepare a medicament that can be taken; S3, packaging and storing the medicament; the present invention can be more convenient to take, can significantly relieve the symptoms of dry mouth and eyes, limb pain and fatigue of patients with Sjögren's syndrome, significantly improve immune inflammation indicators, low price, small side effects, wide applicable population, scientific and reasonable prescription, in line with TCM syndrome differentiation, and significant efficacy. There is no pharmacodynamics and clinical research. Summary of the invention

[0009] In view of the above-mentioned prior art, the purpose of the present invention is to provide a Chinese medicine composition for treating qi and yin deficiency type Sjögren syndrome and its preparation method and application. The Chinese medicine preparation adopts ginseng, codonopsis, yam, polygonatum, moutan bark, ophiopogon japonicus, white peony root as the main medicine, dendrobium, raw rehmannia root, wolfberry, cornus officinalis, black plum, adenophora as the ministerial medicine, spiny jujube seed, motherwort, angelica as the adjuvant medicine, citron, fructus aurantii, platycodon grandiflorum, and cypress seed as the guiding medicine, and the whole prescription has the effects of tonifying the middle and impregnating the body, tonifying lung qi, tonifying lung yin, tonifying spleen and promoting body fluid, tonifying kidney yin, promoting body fluid, tonifying heart blood, promoting blood circulation, removing blood stasis and unblocking collaterals, soothing the liver and regulating qi, and moistening the intestines and relieving constipation, playing the role of tonifying qi and nourishing yin, and is particularly suitable for treating qi and yin deficiency type Sjögren syndrome.

[0010] To achieve the above object, the present invention adopts the following technical solution:

[0011] The first aspect of the present invention provides a traditional Chinese medicine composition for treating Sjögren's syndrome, which is prepared by extracting the following traditional Chinese medicine pieces: 10-20 parts of ginseng, 5-15 parts of codonopsis pilosula, 15-25 parts of yam, 10-20 parts of polygonatum, 5-15 parts of moutan bark, 10-20 parts of ophiopogon japonicus, 5-15 parts of white peony root, 5-15 parts of dendrobium, 10-20 parts of raw rehmannia root, 20-30 parts of wolfberry, 15-25 parts of cornus officinalis, 10-20 parts of ebony, 5-15 parts of adenophora, 8-12 parts of spiny jujube seeds, 10-20 parts of motherwort, 10-20 parts of angelica, 5-15 parts of citrus aurantium, 5-15 parts of fructus aurantii, 10-20 parts of platycodon grandiflorum, and 8-12 parts of cypress seed.

[0012] Furthermore, the Chinese medicine composition for treating Sjögren's syndrome is prepared by extracting the following Chinese medicinal pieces: 15 parts of ginseng, 10 parts of Codonopsis pilosula, 20 parts of yam, 15 parts of Polygonatum odoratum, 10 parts of Moutan bark, 15 parts of Ophiopogon japonicus, 10 parts of White Peony Root, 10 parts of Dendrobium officinale, 15 parts of Rehmannia root, 25 parts of Lycium barbarum, 20 parts of Cornus officinalis, 15 parts of Prunus mume, 10 parts of Adenophora stellaria, 10 parts of Ziziphus jujuba seed, 15 parts of Leonurus japonicus, 15 parts of Angelica sinensis, 10 parts of Citrus aurantium, 10 parts of Platycodon grandiflorum, and 10 parts of Platycladus orientalis seed.

[0013] Furthermore, the Chinese medicine composition for treating Sjögren's syndrome is prepared by extracting the following Chinese medicinal pieces: 10 parts of ginseng, 15 parts of Codonopsis pilosula, 15 parts of yam, 20 parts of Polygonatum odoratum, 5 parts of Moutan bark, 20 parts of Ophiopogon japonicus, 5 parts of White Peony Root, 15 parts of Dendrobium officinale, 10 parts of Rehmannia root, 30 parts of Lycium barbarum, 15 parts of Cornus officinalis, 20 parts of Prunus mume, 5 parts of Adenophora strychnos, 12 parts of Ziziphus jujuba seeds, 10 parts of Leonurus japonicus, 20 parts of Angelica sinensis, 5 parts of Citrus citrus hand, 15 parts of Citrus aurantium, 10 parts of Platycodon grandiflorum, and 12 parts of Platycladus orientalis seeds.

[0014] Furthermore, the Chinese medicine composition for treating Sjögren's syndrome is prepared by extracting the following Chinese medicinal pieces: 20 parts of ginseng, 5 parts of Codonopsis pilosula, 25 parts of yam, 10 parts of Polygonatum odoratum, 15 parts of Moutan bark, 10 parts of Ophiopogon japonicus, 15 parts of White Peony Root, 5 parts of Dendrobium officinale, 20 parts of Rehmannia glutinosa, 20 parts of Lycium barbarum, 25 parts of Cornus officinalis, 10 parts of Prunus mume, 15 parts of Adenophora strychnos, 8 parts of Ziziphus jujuba seeds, 20 parts of Leonurus japonicus, 10 parts of Angelica sinensis, 15 parts of Citrus aurantium, 5 parts of Fructus aurantii, 20 parts of Platycodon grandiflorum, and 8 parts of Semen Platycladi.

[0015] Furthermore, the preparation method of the Chinese medicine composition for treating Sjögren's syndrome is as follows:

[0016] (1) mixing the above-mentioned Chinese medicinal pieces to obtain a mixture, adding water to the mixture for a decoction, filtering, and obtaining a residue and a primary filtrate;

[0017] (2) adding water to the medicinal residue for secondary decoction, and filtering to obtain a secondary filtrate;

[0018] (3) The first filtrate and the second filtrate are combined and concentrated to obtain a preparation.

[0019] Furthermore, in the Chinese medicine composition for treating Sjögren's syndrome, in step (1), the amount of water added is 10-15 times the mass of the mixture, and the decoction time is 60-120 minutes.

[0020] Furthermore, in the Chinese medicine composition for treating Sjögren's syndrome, in step (2), the amount of water added is 8-10 times the mass of the mixture, and the decoction time is 45-60 minutes.

[0021] Furthermore, the Chinese medicine composition for treating Sjögren's syndrome is characterized in that, in step (3), the crude drug concentration is concentrated to 1.0-1.2 g / mL.

[0022] Furthermore, in the Chinese medicine composition for treating Sjögren's syndrome, in step (3), the preparation is one of tablets, capsules, granules, mixtures or pills.

[0023] Furthermore, the Chinese medicine composition for treating Sjögren's syndrome is used in the preparation of a medicine for treating Qi and Yin deficiency type Sjögren's syndrome.

[0024] The above-mentioned Chinese herbal medicines all meet the pharmacopoeia standards.

[0025] Traditional Chinese medicine divides Sjögren's syndrome into seven categories: yin deficiency and internal dryness, qi and yin deficiency, yin deficiency and blood stasis, yin deficiency and dampness and heat, qi and yin deficiency and blood stasis, qi and yin deficiency and blood stasis and dampness and heat, and fluid deficiency and blood deficiency. Among them, qi and yin deficiency is the most common. The main symptoms of qi and yin deficiency type Sjögren's syndrome are dry eyes, dry mouth and throat, fatigue, and secondary symptoms are palpitations, poor appetite, shortness of breath and laziness, dry cough with little sputum, frequent urination at night, loose stools, red tongue with little dry or cracked coating, and weak or fine pulse. Qi deficiency and long-term illness are related to the decreased function of the lungs, spleen and other organs. Qi, blood and body fluids are converted into each other under the action of qi transformation. However, pSS patients have strong dryness, which consumes body fluids, and over time damages qi. The five internal organs cannot be moistened and nourished by body fluids, and their functions are reduced. If the qi and blood are insufficient, symptoms such as fatigue and exhaustion can be seen. Qi, blood and body fluids cannot replenish the head, so there will be dizziness. They cannot nourish the heart meridian, so there will be palpitations. Those with red tongue have slightly better dryness and heat, which also means that the deficiency of vital energy is less. Those with pale tongue may affect the spleen, lungs and other organs.

[0026] Qi and Yin deficiency refers to the coexistence of Qi deficiency and Yin deficiency. Qi deficiency is mainly manifested by low physiological function of the body, such as shortness of breath, lazy speech, fatigue, spontaneous sweating, etc., while Yin deficiency refers to insufficient Yin fluid in the body, which cannot nourish and control Yang, and is manifested by dry mouth, dry eyes, dry nose, fever in the five hearts, night sweats, etc. "Medical Law·Injury to Dryness" says: "Dryness prevails, and dryness occurs. The harm of dryness is not to turn the land red for thousands of miles. Some are dry on the outside and the skin peels; some are dry on the inside and the essence and blood dry up; some are dry on the body fluid and the health and defense qi declines, the flesh is scorched and the skin sticks to the bones. Therefore, ginseng, codonopsis, and yam are used to replenish lung qi, and polygonatum and moutan bark are used to replenish lung yin. Polygonatum nourishes yin and moistens dryness, produces body fluid and quenches thirst; moutan bark clears heat and reduces the loss of yin fluid. At the same time, because the spleen produces the lungs, that is, cultivating the earth to produce gold, such as spleen qi transportation and transformation, transforming qi to fill the lungs. Therefore, Ophiopogon japonicus and white peony root are used to nourish the spleen and produce body fluid. Ophiopogon japonicus is sweet and slightly bitter, slightly cold in nature, and belongs to the heart, lung, and stomach meridians. It can clear away heat and nourish yin, moisten the lungs and nourish yin, benefit the stomach and produce body fluid. It has a significant effect of nourishing the stomach and lungs, nourishing the yin of the heart, lungs, and stomach, and restoring the distribution of body fluid. White peony root is bitter and sour, slightly cold in nature, and belongs to the liver and spleen meridians. It has the functions of nourishing blood, softening the liver, supporting the spleen and producing body fluid. It can nourish the liver blood, nourish the eyes, and help the spleen and stomach produce body fluid to nourish the whole body. The coldness of Ophiopogon japonicus and the sourness and coldness of white peony root cooperate with each other, which can enhance the power of clearing heat while astringing yin fluid, making the effect of nourishing yin and moistening dryness better. Ginseng, Codonopsis, Chinese Yam, Polygonatum, Cortex Moutan, Ophiopogon japonicus, and White Peony Root are all monarch drugs; Qi and Yin deficiency also includes kidney qi deficiency. When the condition of patients with kidney qi deficiency worsens and kidney yin is damaged, it develops into kidney qi and yin deficiency. Therefore, Dendrobium, Rehmannia root, Lycium barbarum, and Cornus officinalis are used to nourish kidney yin. Dendrobium benefits the stomach and produces fluid, nourishes yin and clears heat; Rehmannia root clears heat and cools blood, nourishes yin and produces fluid; Lycium barbarum nourishes the liver and kidney, benefits essence and improves eyesight; Cornus officinalis nourishes the liver and kidney, astringes and consolidates, and is combined with Prunus mume to nourish yin and produce fluid, and Adenophora ginseng to nourish lung and stomach yin. Adenophora ginseng is sweet, moist, bitter and cold, belongs to the lung and stomach meridians, nourishes lung and stomach yin and clears lung and stomach heat; Prunus mume is sour and flat, has the effect of producing fluid and quenching thirst, and is matched with Rehmannia root to acidify yin, enhance the effect of nourishing yin and producing fluid, and assist the monarch drug to further replenish yin fluid. Dendrobium, Rehmannia root, Lycium barbarum, Cornus officinalis, Prunus mume, and Adenophora ginseng are all minister drugs. Sjögren's syndrome is a chronic inflammatory autoimmune disease, mainly due to the disorder of the body's immune function, which produces antibodies against its own antigen components. These antibodies activate immune cells after binding to complement, triggering an inflammatory response. Inflammatory factors accumulate locally in the heart, which may cause damage and necrosis of myocardial cells, which can manifest as myocardial ischemia. This disease is recurrent and lingering, which conforms to the disease development law of "long-term disease entering the meridians".Dryness harms Yin, and body fluid and blood have the same origin. If body fluid is deficient, blood will be deficient, and blood deficiency will lead to lack of nourishment to the blood vessels. If both Yin and blood are deficient, blood will stagnate, and blood stasis will be generated internally, and the collaterals will be blocked. If the collaterals are out of harmony and the Ying and Wei are not coordinated, then toxic evil will be generated internally. Therefore, Ziziphus jujuba seeds are used to nourish the heart blood, and Leonurus japonicus and Angelica sinensis are used as adjuvants to promote blood circulation, remove blood stasis and dredge the collaterals. The regulation of liver qi controls the balance of the human body. If the liver's regulation function is normal and liver qi is regulated, then qi and blood will be balanced, and the functions of the internal organs will be coordinated. The combination of internal dryness leads to The main pathogenesis of this disease is the deficiency of body fluid or abnormal distribution of body fluid. Dryness causes disease, with the liver and lung as the main lesions. Therefore, bergamot, fructus aurantii, and platycodon grandiflorum are used to soothe the liver and regulate qi. Bergamot soothes the liver and relieves depression, regulates qi and harmonizes the middle, fructus aurantii regulates qi and relieves chest tightness, relieves stagnation and eliminates accumulation, and platycodon grandiflorum has the function of harmonizing various drugs. Its ascending and floating nature can guide other drugs to ascend, so that the drug power can better act on the upper part of the heart and lungs, etc. It can carry drugs upward, open and promote lung qi, and regulate water channels. The lung is responsible for regulating water channels, and platycodon grandiflorum can open and promote lung qi to enable body fluid to be normally distributed throughout the body. For the problem of body fluid distribution disorder in patients with Sjögren's syndrome, platycodon grandiflorum, as a guiding drug, guides the drugs in the whole prescription to act on the lungs and related meridians, restores the lung's function of regulating water channels, promotes the generation, distribution and excretion of body fluid, improves the abnormal state of body fluid metabolism in the human body as a whole, and enables yin fluid to be normally moistened throughout the body. Sjögren's syndrome may cause intestinal dysfunction, slow down intestinal peristalsis, make food stay in the intestine for too long, and excessively absorb water, resulting in dry and hard stools that are difficult to excrete, thus causing constipation. Baiziren moistens the intestines and relieves constipation, nourishes the heart and calms the mind. Citron, Citrus aurantium, Platycodon grandiflorum, and Citrus aurantium are all the envoys. The whole formula contains ginseng, Codonopsis pilosula, Chinese yam, Polygonatum odoratum, Cortex Moutan, Ophiopogon japonicus, White Peony Root, Dendrobium officinale, Rehmannia root, Lycium barbarum, Cornus officinalis, Plum, Adenophora Root, Ziziphus jujuba seed, Motherwort, Angelica sinensis, Citron, Citrus aurantium, Platycodon grandiflorum, and Citrus aurantium. It has the effects of tonifying the middle and tonifying the movement, tonifying lung qi, tonifying lung yin, tonifying spleen and promoting fluid, tonifying kidney yin, promoting fluid, tonifying heart blood, promoting blood circulation, removing blood stasis and unblocking collaterals, soothing the liver and regulating qi, and moistening the intestines and tonifying constipation. It plays the role of tonifying qi and nourishing yin, and is especially suitable for treating qi and yin deficiency of dryness and arthralgia.

[0027] From the perspective of organ differentiation, Qi and Yin deficiency type Sjögren's syndrome mainly involves the lung, spleen, and kidney. The lung governs the skin and fur, opens to the nose, and controls breathing. If the lung qi is not released, the skin and nostrils will be dry; the spleen governs transportation and transformation, which is the foundation of acquired constitution. If the spleen fails to function properly, the body fluid will have no source, the lips will be chapped, and the tongue will be thin; the kidney governs water and stores essence and produces marrow. If the kidney essence is deficient, the yin will be deficient and the fire will be strong, and the dryness will be generated internally. This shows that the lung, spleen, and kidney play a key role in the metabolism and distribution of body fluid. In addition, the liver governs the release and regulates the qi. If the liver qi is stagnant, the qi will not flow smoothly, affecting the distribution of body fluid; the heart governs the blood vessels and stores the spirit. If the heart blood is insufficient, the spirit will lose its nourishment, resulting in the loss of yin fluid. The present invention starts with the lung and spleen, and by replenishing lung qi and lung yin, replenishing spleen and nourishing earth to produce gold, promotes the functions of moistening the lung and nourishing yin, benefiting the stomach and producing body fluid, while replenishing kidney yin, replenishing heart blood, promoting blood circulation, removing blood stasis and dredging collaterals, soothing the liver and regulating qi, the purpose of treating qi and yin deficiency type Sjögren's syndrome is achieved.

[0028] From the perspective of triple-burner syndrome differentiation, the upper burner includes the heart and lungs, the middle burner includes the spleen, stomach, liver, and gallbladder, and the lower burner contains the kidneys, bladder, and large and small intestines. Dryness and arthralgia are characterized by yin deficiency and fluid deficiency, and unresolved dryness and heat, often involving the lungs, spleen, stomach, kidneys and other internal organs. The triple burner is the "official for deciding drainage", which regulates the normal operation of the body's waterways and circulates the body's vital energy, which is of great significance to the normal distribution of body fluids. The patient's triple-burner internal organs have true yin deficiency, the triple-burner qi mechanism is unfavorable, the blood circulation is not smooth, and the internal organs lack nourishment. The present invention promotes the operation of the body's waterways by treating qi with upper dryness, increasing fluid with middle dryness, and treating blood with lower dryness.

[0029] The pharmaceutical composition of the present invention can significantly alleviate the dry mouth and dry eyes symptoms of patients with qi and yin deficiency type Sjögren's syndrome, improve the quality of life of patients, directly alleviate the pain of patients, and improve the comfort of their daily life. The Chinese medicine composition of the present invention has a reasonable ratio design, which is obtained through long-term clinical experience accumulation and improvement, and is further verified by clinical trials. It has the advantages of concise formula, obvious efficacy, and high safety, can significantly improve the quality of life of patients, and save social medical resources. DETAILED DESCRIPTION

[0030] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the content of the present invention, those skilled in the art can make various changes or modifications to the present invention, but these equivalent forms fall within the scope limited by the appended claims of the application equally.

[0031] Example 1: Take 150g of ginseng, 100g of Codonopsis pilosula, 200g of yam, 150g of Polygonatum odoratum, 100g of Moutan bark, 150g of Ophiopogon japonicus, 100g of White Peony Root, 100g of Dendrobium officinale, 150g of Rehmannia glutinosa, 250g of Lycium barbarum, 200g of Cornus officinalis, 150g of Plum, 100g of Adenophora scutellariae, 100g of Ziziphus jujuba seed, 150g of Leonurus japonicus, 150g of Angelica sinensis, 100g of Citrus aurantium, 100g of Platycodon grandiflorum, and 100g of Semen Platycladi. After the Chinese herbal medicine pieces are mixed, a mixture is obtained, water is added to the mixture for a decoction, the amount of water added is 12 times the mass of the mixture, the decoction time is 90 minutes, and the mixture is filtered to obtain a residue and a primary filtrate; the residue is added with water for a second decoction, the amount of water added is 9 times the mass of the mixture, the decoction time is 50 minutes, and the secondary filtrate is filtered to obtain a secondary filtrate; the primary filtrate and the secondary filtrate are combined, concentrated to a crude drug concentration of 1.1 g / mL, dextrin is added, granulated, and granules are obtained.

[0032] Example 2: Take 100g of ginseng, 150g of Codonopsis pilosula, 150g of yam, 200g of Polygonatum odoratum, 50g of Cortex Moutan, 200g of Ophiopogon japonicus, 50g of White Peony Root, 150g of Dendrobium officinale, 100g of Rehmannia glutinosa, 300g of Lycium barbarum, 150g of Cornus officinalis, 200g of Plum, 50g of Adenophora scutellariae, 120g of Semen Ziziphi Spinosae, 100g of Leonurus japonicus, 200g of Angelica sinensis, 50g of Citrus aurantium, 150g of Platycodon grandiflorum, and 120g of Semen Platycladi. After the pieces are mixed, a mixture is obtained, water is added to the mixture for a decoction, the amount of water added is 10 times the mass of the mixture, the decoction time is 120 minutes, and the mixture is filtered to obtain a residue and a primary filtrate; the residue is added with water for a second decoction, the amount of water added is 8 times the mass of the mixture, the decoction time is 60 minutes, and the secondary filtrate is filtered to obtain a secondary filtrate; the primary filtrate and the secondary filtrate are combined, concentrated to a crude drug concentration of 1.0 g / mL, starch is added, and tablets are obtained.

[0033] Example 3: Take 200g of ginseng, 50g of codonopsis, 250g of yam, 100g of polygonatum, 150g of moutan bark, 100g of ophiopogon, 150g of white peony root, 50g of dendrobium, 200g of raw rehmannia, 200g of wolfberry, 250g of cornus, 100g of ebony, 150g of adenophora, 80g of spiny jujube seed, 200g of motherwort, 100g of angelica, 150g of bergamot, 50g of fructus aurantii, 200g of platycodon, and 80g of cypress seed. After the tablets are mixed, a mixture is obtained, water is added to the mixture for a decoction, the amount of water added is 15 times the mass of the mixture, the decoction time is 60 minutes, and the mixture is filtered to obtain a residue and a primary filtrate; the residue is added with water for a second decoction, the amount of water added is 10 times the mass of the mixture, the decoction time is 45 minutes, and the secondary filtrate is filtered to obtain a secondary filtrate; the primary filtrate and the secondary filtrate are combined, concentrated to a crude drug concentration of 1.2 g / mL, and microcrystalline cellulose is added to prepare pills.

[0034] Example 4: Take 150g of ginseng, 100g of Codonopsis pilosula, 200g of yam, 150g of Polygonatum odoratum, 100g of Moutan bark, 150g of Ophiopogon japonicus, 100g of White Peony Root, 100g of Dendrobium officinale, 150g of Rehmannia glutinosa, 250g of Lycium barbarum, 200g of Cornus officinalis, 150g of Plum, 100g of Adenophora scutellariae, 100g of Ziziphus jujuba seed, 150g of Leonurus japonicus, 150g of Angelica sinensis, 100g of Citrus aurantium, 100g of Platycodon grandiflorum, and 100g of Semen Platycladi. After mixing the above-mentioned Chinese herbal medicine slices, a mixture is obtained, water is added to the mixture for a decoction, the amount of water added is 15 times the mass of the mixture, the decoction time is 60 minutes, and the mixture is filtered to obtain a residue and a primary filtrate; the residue is added with water for a second decoction, the amount of water added is 10 times the mass of the mixture, the decoction time is 45 minutes, and the secondary filtrate is filtered to obtain a secondary filtrate; the primary filtrate and the secondary filtrate are combined, concentrated to a crude drug concentration of 1.2 g / mL, and prepared into a mixture.

[0035] Example 5: Take 150g of ginseng, 100g of Codonopsis pilosula, 200g of yam, 150g of Polygonatum odoratum, 100g of Moutan bark, 150g of Ophiopogon japonicus, 100g of White Peony Root, 100g of Dendrobium officinale, 150g of Rehmannia glutinosa, 250g of Lycium barbarum, 200g of Cornus officinalis, 150g of Plum, 100g of Adenophora scutellariae, 100g of Ziziphus jujuba seed, 150g of Leonurus japonicus, 150g of Angelica sinensis, 100g of Citrus aurantium, 100g of Platycodon grandiflorum, and 100g of Semen Platycladi. After the Chinese herbal medicine pieces are mixed, a mixture is obtained, water is added to the mixture for a first decoction, the amount of water added is 10 times the mass of the mixture, the decoction time is 120 minutes, and the mixture is filtered to obtain a dregs and a primary filtrate; the dregs are added with water for a second decoction, the amount of water added is 8 times the mass of the mixture, the decoction time is 60 minutes, and the secondary filtrate is filtered to obtain a secondary filtrate; the primary filtrate and the secondary filtrate are combined, concentrated to a crude drug concentration of 1.0 g / mL, starch is added, and capsules are prepared.

[0036] Example 6: Pharmacodynamics Experiment

[0037] Experimental method: 50 large-eared white rabbits were randomly divided into 5 groups according to gender and weight, with a body weight of 1.8-1.2 kg, a blank control group (equal volume of normal saline), a positive Qi-Yin-Yangyin oral liquid group (Tonghua Jinhui Pharmaceutical Co., Ltd., approval number: National Medicine Standard B20020146, production batch number: 20240109, dosage of 10 g crude drug / kg), a high-dose group of the present invention (granules prepared in Example 1, dosage of 20 g crude drug / kg), a medium-dose group of the present invention (granules prepared in Example 1, dosage of 10 g crude drug / kg), and a low-dose group of the present invention (granules prepared in Example 1, dosage of 50 g crude drug / kg). The rabbits were given oral administration twice a day for 10 consecutive days. On the last day, 0.5 mg / kg of atropine sulfate was subcutaneously injected 30 minutes after administration. The saliva and tear volumes of the rabbits after atropine were measured 15 minutes, 30 minutes and 45 minutes later, respectively.

[0038] Method for measuring saliva and tear volume: Place the rabbit in a rabbit box and fix it. Use hemostats to place a dry cotton ball (100 mg ± 15 mg) of similar weight into the upper, lower, left and right sides of the rabbit's mouth and wipe it once. Wipe it once every 5 minutes in the same way, weigh it, subtract the dry weight of the cotton ball (200 mg), and combine the two weights as the saliva volume of the rabbit within 10 minutes. While measuring the saliva volume, hang 5 strips of 100х5mm filter paper on the lower eyelids of the left and right eyes of the rabbit. Measure the wet length of the filter paper strips after 10 minutes. Replace the filter paper strips every 10 minutes and measure 3 times in a row.

[0039] Results: The effects of the present invention on the saliva volume and tear volume of rabbits are shown in Tables 1 and 2.

[0040] Table 1 Effect of the present invention on the amount of saliva after injection of atropine in rabbits

[0041]

[0042] Compared with the blank control group, *P<0.05, **P<0.01

[0043] Table 2 Effect of the present invention on tear volume after atropine injection in rabbits

[0044]

[0045] Compared with the blank control group, *P<0.05, **P<0.01

[0046] Conclusion: It can be seen from Tables 1 and 2 that the saliva and tear secretions of rabbits in the high-dose group and the medium-dose group of the present invention are more than those in the blank control group and the positive drug group, and the effects of the high-dose group and the medium-dose group of the present invention are better than those of the positive drug group, indicating that the present invention can antagonize the tendency of atropine to inhibit the secretion of saliva and tears, promote the secretion of saliva and tears in rabbits, and prevent dry mouth and dry eyes.

[0047] Example 7: Clinical study

[0048] Case selection: From May to December 2023, our hospital admitted patients with Qi and Yin deficiency type Sjögren's syndrome, with an average age of 32-65 years old. They were randomly divided into a control group and an observation group, with 50 cases in each group. There were 24 males and 26 females in the control group, and 28 males and 22 females in the observation group. There was no statistically significant difference (P>0.05).

[0049] Western medicine diagnostic criteria: The diagnostic criteria for primary Sjögren's syndrome (pSS) established by the American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) in 2016: 1. Inclusion criteria: Patients with at least one symptom of dry eyes or dry mouth, that is, at least one of the following is positive: unbearable dry eyes every day for more than 3 months; repeated gritty feeling in the eyes; need to use artificial tears 3 or more times a day; dry mouth every day for more than 3 months; swallowing dry food requires frequent drinking of water. Or suspected SS patients with at least one system positive in the EULAR Sjögren's Syndrome (SS) Disease Activity Index (ESSDAI) questionnaire. 2. Exclusion criteria: Patients with the following diseases should be excluded because they may have overlapping clinical manifestations or interfere with diagnostic test results: history of head and neck radiotherapy; active hepatitis C virus infection; AIDS; sarcoidosis; amyloidosis; graft-versus-host disease; IgG4-related diseases. 3. Applicable to anyone who meets the above inclusion criteria and excludes the exclusion criteria, and the sum of the following five scores is ≥4, the diagnosis of pSS: (1) focal lymphocytic infiltration of the labial gland, and the focal index is ≥1 focus / 4mm2, 3 points; (2) serum anti-SSA antibody is positive, 3 points; (3) at least one eye corneal staining score (OSS) ≥5 or Van Bijsterveld score ≥4 points, 1 point; (4) at least one eye tear secretion test (Schirmer test) ≤5mm / 5min, 1 point; (5) unstimulated whole saliva flow rate ≤0.1ml / min (Navazesh and Kumar test), 1 point. Patients who routinely use cholinergic drugs should fully stop the drugs before performing the above (3), (4), and (5) tests to evaluate dry mouth and eyes. The sensitivity of this standard is 96% and the specificity is 95%. It is applicable in the validation analysis of the diagnostic criteria and the enrollment of clinical trials.

[0050] TCM diagnostic criteria: refer to the "Expert Consensus on TCM Symptoms of Sjögren's Syndrome" [Zhou Xinyao, Jiang Quan, Tang Xiaopo, et al. Expert Consensus on TCM Symptoms of Sjögren's Syndrome [J]. Journal of Beijing University of Chinese Medicine, 2023, 46(03): 310-314.], the main symptoms are dry eyes, dry mouth and throat, fatigue, secondary symptoms are palpitations, poor appetite, shortness of breath and laziness, dry cough with little sputum, frequent urination at night, loose stools, red tongue with little dry or cracked coating, weak or fine pulse. Patients with the main symptoms and two or more secondary symptoms, combined with tongue and pulse, can be diagnosed as patients with Qi and Yin deficiency type Sjögren's syndrome.

[0051] Treatment method: The control group used polyvinyl alcohol eye drops (Hubei Yuanda Tiantianming Pharmaceutical Co., Ltd., national medicine standard H20046681, batch number 20230122), twice a day, each time in an appropriate amount, for 2 months; hydroxychloroquine sulfate tablets (Jiangsu Zhiyuan Pharmaceutical Co., Ltd., national medicine standard H20243518, batch number 20230201), 200 mg per day, for 1 month; the treatment group took the invention The granules prepared in Example 1, daily dosage: 15g ginseng, 10g codonopsis, 20g yam, 15g polygonatum, 10g moutan bark, 15g ophiopogon, 10g white peony root, 10g dendrobium, 15g rehmannia root, 25g wolfberry, 20g cornus, 15g ebony, 10g adenophora, 10g spiny jujube seed, 15g motherwort, 15g angelica, 10g citrus hand, 10g fructus aurantii, 15g platycodon, 10g cyperus rotundus, 10g white osmanthus, 10g platycodon, 10g pine nuts, use for 2 months.

[0052] Efficacy criteria: Referring to the Practical TCM Rheumatology, dry eyes, dry mouth and throat, fatigue, and poor appetite were scored as 0, 3, 6, and 9 points, respectively, according to the criteria for none, mild, moderate, and severe. Referring to the TCM Disease Diagnosis and Efficacy Criteria, (1) markedly effective, clinical symptoms improved, and the TCM syndrome score decreased by ≥70%; (2) effective, clinical symptoms improved, and the TCM syndrome score decreased by 30%≤<70%; (3) ineffective, clinical symptoms did not improve or even worsened, and the TCM syndrome score decreased by <30%. Total effective rate = [(number of markedly effective cases + number of effective cases) / total number of cases] × 100%.

[0053] Results: The symptoms of the control group and the treatment group were scored before treatment and 1 month and 2 months after treatment. The results are shown in Table 3; the clinical efficacy after 2 months is shown in Table 4.

[0054] Table 3 Symptom scores of the control group and the treatment group before and after treatment

[0055]

[0056] Note: Compared with the same group before treatment, * P<0.05, ** P<0.01, compared with the control group, # P<0.05, ## P<0.01.

[0057] The results in Table 3 show that after 1 month and 2 months of treatment, the scores of the treatment group of the present invention in four aspects, such as dry eyes, dry mouth, fatigue, and poor appetite, were significantly reduced after treatment compared with the scores before treatment, indicating that the present invention can improve the symptoms of dry eyes, dry mouth, fatigue, and poor appetite, and compared with the control group, the scores of the treatment group were lower, indicating that the effect of the present invention is better than that of the control group.

[0058] Table 4 Clinical efficacy results

[0059] Group Significant effect efficient invalid Effectiveness (%) Treatment Group 12 34 4 92 Control group 6 31 13 74

[0060] The results in Table 4 show that the total clinical effective rate of the treatment group is 92%, and the total clinical effective rate of the control group is 74%. The total clinical effective rate of the treatment group is significantly higher than that of the control group, indicating that the present invention has a reasonable combination and has a good effect on Qi and Yin deficiency type Sjögren's syndrome.

[0061] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A Chinese medicine composition for treating Sjögren's syndrome, characterized in that: The invention is prepared by extracting the following Chinese medicinal pieces: 10-20 parts of ginseng, 5-15 parts of codonopsis pilosula, 15-25 parts of yam, 10-20 parts of polygonatum, 5-15 parts of moutan bark, 10-20 parts of ophiopogon japonicus, 5-15 parts of white peony root, 5-15 parts of dendrobium, 10-20 parts of raw rehmannia root, 20-30 parts of wolfberry, 15-25 parts of cornus officinalis, 10-20 parts of ebony, 5-15 parts of adenophora, 8-12 parts of spiny jujube seeds, 10-20 parts of motherwort, 10-20 parts of angelica, 5-15 parts of citrus aurantium, 5-15 parts of fructus aurantii, 10-20 parts of platycodon grandiflorum and 8-12 parts of cypress seed.

2. The Chinese medicine composition for treating Sjögren's syndrome according to claim 1, characterized in that: The preparation method is prepared by extracting the following Chinese medicinal pieces: 15 parts of ginseng, 10 parts of codonopsis pilosula, 20 parts of yam, 15 parts of polygonatum, 10 parts of moutan bark, 15 parts of ophiopogon japonicus, 10 parts of white peony root, 10 parts of dendrobium, 15 parts of raw rehmannia root, 25 parts of wolfberry, 20 parts of cornus officinalis, 15 parts of ebony, 10 parts of adenophora, 10 parts of spiny jujube seed, 15 parts of motherwort, 15 parts of angelica, 10 parts of citrus hand, 10 parts of fructus aurantii, 15 parts of platycodon grandiflorum, and 10 parts of cypress seed.

3. The Chinese medicine composition for treating Sjögren's syndrome according to claim 1, characterized in that: The preparation method is prepared by extracting the following Chinese medicinal pieces: 10 parts of ginseng, 15 parts of codonopsis pilosula, 15 parts of yam, 20 parts of polygonatum, 5 parts of moutan bark, 20 parts of ophiopogon japonicus, 5 parts of white peony root, 15 parts of dendrobium, 10 parts of raw rehmannia root, 30 parts of wolfberry, 15 parts of cornus officinalis, 20 parts of ebony, 5 parts of adenophora, 12 parts of spiny jujube seed, 10 parts of motherwort, 20 parts of angelica, 5 parts of citron, 15 parts of fructus aurantii, 10 parts of platycodon grandiflorum, and 12 parts of cypress seed.

4. The Chinese medicine composition for treating Sjögren's syndrome according to claim 1, characterized in that: The preparation method is prepared by extracting the following Chinese medicinal pieces: 20 parts of ginseng, 5 parts of codonopsis pilosula, 25 parts of yam, 10 parts of polygonatum, 15 parts of moutan bark, 10 parts of ophiopogon japonicus, 15 parts of white peony root, 5 parts of dendrobium, 20 parts of raw rehmannia root, 20 parts of wolfberry, 25 parts of cornus officinalis, 10 parts of ebony, 15 parts of adenophora, 8 parts of spiny jujube seed, 20 parts of motherwort, 10 parts of angelica, 15 parts of citron, 5 parts of fructus aurantii, 20 parts of platycodon grandiflorum, and 8 parts of cypress seed.

5. The Chinese medicine composition for treating Sjögren's syndrome according to claim 1, characterized in that: The preparation method is as follows: (1) mixing the above-mentioned Chinese medicinal pieces to obtain a mixture, adding water to the mixture for a decoction, filtering, and obtaining a residue and a primary filtrate; (2) adding water to the medicinal residue for secondary decoction, and filtering to obtain a secondary filtrate; (3) The first filtrate and the second filtrate are combined and concentrated to obtain a preparation.

6. The Chinese medicine composition for treating Sjögren's syndrome according to claim 5, characterized in that: In step (1), the amount of water added is 10-15 times the mass of the mixture, and the decoction time is 60-120 minutes.

7. The Chinese medicine composition for treating Sjögren's syndrome according to claim 5, characterized in that: In step (2), the amount of water added is 8-10 times the mass of the mixture, and the decoction time is 45-60 minutes.

8. The Chinese medicine composition for treating Sjögren's syndrome according to claim 5, characterized in that: In step (3), the crude drug is concentrated to a concentration of 1.0-1.2 g / mL.

9. The Chinese medicine composition for treating Sjögren's syndrome according to claim 5, characterized in that: In step (3), the preparation is one of tablets, capsules, granules, mixtures or pills.

10. Use of the Chinese medicine composition for treating Sjögren's syndrome as claimed in claim 1 in preparing a medicine for treating Sjögren's syndrome of qi and yin deficiency type.

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