A traditional Chinese medicine composition for treating Sjogren's syndrome and a preparation method thereof

Abstract

The application discloses a traditional Chinese medicine composition for treating Sjogren's syndrome, which is prepared from the following traditional Chinese medicine decoction pieces: 10-20 parts of ginseng, 5-15 parts of radix codonopsis, 15-25 parts of radix polygonati, 10-20 parts of polygonatum, 5-15 parts of cortex moutan, 10-20 parts of ophiopogon, 5-15 parts of radix paeoniae alba, 5-15 parts of dendrobium, 10-20 parts of radix rehmanniae, and the like, and discloses a preparation method and application thereof. The application can supplement lung qi and lung yin, supplement the spleen and the earth to generate gold, promote the functions of moistening the lung and nourishing yin, benefiting the stomach and generating saliva, supplement kidney yin and heart blood, activate blood and remove blood stasis, dredge the liver and regulate qi, and achieve the purpose of treating Sjogren's syndrome of qi and yin deficiency.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, and specifically relates to a traditional Chinese medicine composition for treating Sjögren's syndrome and its preparation method. Background Technology

[0002] Sjögren's syndrome (SS) is a chronic autoimmune disease primarily affecting exocrine glands, characterized by focal lymphocytic infiltration. The most prominent pathological features are chronic inflammatory cell infiltration and destruction of the salivary and lacrimal glands, leading to keratoconjunctivitis sicca and xerostomia. Clinically, in addition to dry mouth and dry eyes, almost half of patients develop extra-glandular diseases, affecting multiple systems throughout the body, including the lungs, cardiovascular system, kidneys, stomach, nervous system, thyroid, and skin. This disease can exist alone, known as primary Sjögren's syndrome, or it can develop secondary symptoms such as dry mouth and eyes on a confirmed diagnosis of other connective tissue diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and dermatomyositis; these are called secondary Sjögren's syndrome. Epidemiological surveys show that SS is a global disease, with a prevalence of 0.33%–0.77% in my country. It is more common in middle-aged and elderly people, and more prevalent in women, with a male-to-female ratio of 1:(9–20). 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 a prevalence rate of 4.4% among first-degree relatives, and positive rates of anti-Ro / La antibodies reaching 21% and 11% among first- and second-degree relatives, respectively.

[0003] The etiology and pathogenesis of Sjögren's syndrome (PSS) remain unclear, but it is currently believed to be related to immune dysfunction caused by multiple factors, including genetics, viral infection, and abnormal sex hormones. Studies have found that B cell activation may be a key factor in the development of pSS, while regulatory B cells, a group of cells that negatively regulate B cell immune responses and suppress autoimmune inflammation, 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 subset of CD4+ effector T cells that can enter the bloodstream and participate in humoral immunity. Lymphoid follicular regulatory T cells (Tfr) can suppress B cell and Tfh responses, thereby inhibiting autoimmune inflammation. Imbalance in the expression of T helper (Th) cytokines is key to the development and progression of Sjögren's syndrome. Th cells are mainly divided into Th1 and Th2. Th1 cells participate in cellular immunity, secreting cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin (IL)-2. Th2 cells participate in humoral immunity, secreting cytokines such as IL-4, IL-6, IL-10, and IL-13. The pathogenesis of Sjögren's syndrome is mainly characterized by Th1 hyperactivity and Th2 depletion, resulting in an imbalance of Th1 / Th2 immunity. Therefore, treatment of Sjögren's syndrome can begin with regulating the Th1 / Th2 immune balance.

[0004] Currently, Western medicine treatment options mainly include glucocorticoids, immunosuppressants, and symptomatic replacement therapy. For xerostomia, pilocarpine can be taken to increase saliva flow, but this may cause sweating, frequent urination, and irritable bowel syndrome. For xerophthalmia, artificial tears can be used, but long-term use can damage vision. While systemic therapy effectively improves clinical symptoms and controls disease progression in pSS patients, it also has many adverse reactions. Glucocorticoids are often used when pSS is complicated by kidney, nervous system, or hematologic system involvement, or when it is rapidly progressing; long-term use can cause severe osteoporosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used for joint pain; long-term use can cause gastrointestinal problems. Immunosuppressants are often used to treat systemic symptoms; hydroxychloroquine can cause visual field defects and cardiotoxicity, methotrexate can cause hepatotoxicity and gastrointestinal discomfort, and cyclophosphamide and cyclosporine often cause gastrointestinal irritation, nephrotoxicity, and urinary tract damage. Biologics are often used when traditional treatments are ineffective or when there are serious systemic diseases; their safety and efficacy are uncertain, and their use is limited due to their high cost. Western medicine still lacks satisfactory treatment measures for pSS, and there is an urgent need for safer and more effective treatment options.

[0005] The term "Sjögren's syndrome" does not appear in ancient Chinese medical texts. Its earliest known diagnosis, based on symptoms, can be traced back to the *Neijing* (Inner Canon of Medicine), which states that "dryness leads to dryness" and "dryness should be addressed by moistening." Clinically, based on its characteristics, most physicians classify it as "dryness syndrome" or "bi syndrome." In the 1980s, Professor Lu Zhizheng, a master of traditional Chinese medicine, first proposed naming Sjögren's syndrome "dryness-bi" in TCM. This was adopted by the National Committee of TCM Bi Syndrome Professionals and promoted by the Rheumatology Branch of the China Association of Traditional Chinese Medicine to guide clinical practice. Thus, TCM officially named Sjögren's syndrome "dryness-bi." Professor Lu Zhizheng's diagnostic and treatment approach focuses on Qi and Yin deficiency as the primary cause, with blood stasis, heat toxicity, and dryness toxicity as the secondary symptoms. The mouth, eyes, nose, and throat can be affected, as can the skin, muscles, joints, and internal organs. Sun Hongyan et al., through research on the distribution characteristics of TCM constitution patterns in pSS patients, summarized the key pathogenesis of Sjögren's syndrome as lung and stomach fluid deficiency, caused by multiple factors including overall deficiency, post-illness fluid damage, and subsequent invasion of dryness pathogens. Wang Longde achieved significant therapeutic effects in treating Sjögren's syndrome by using methods that soothe the liver and strengthen the spleen. He believed that when the liver fails to regulate qi, it cannot distribute fluids properly, and when the spleen and stomach are weak, fluids lack their source. Studies have also shown that many Sjögren's syndrome patients also suffer from anxiety, depression, and other psychological disorders, as stated in the *Suwen·Linglan Secret Canon*: "The liver is the general's organ, from which strategies arise." Peng Jiangyun proposed the theory of "generating qi with less fire," treating Sjögren's syndrome by supporting less fire. Liu Ruilin et al., starting from yin deficiency, elucidated the inevitable stage of dryness-related arthralgia developing from dryness-heat to dryness-toxin, focusing on the sweet-sour-pungent-moistening method based on "sweet and sour to transform yin" and "pungent to moisten," for treating dryness-related arthralgia.

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

[0007] CN118217357A discloses a traditional Chinese medicine compound for treating Sjögren's syndrome, its preparation method, and its application. The compound contains Astragalus membranaceus, Salvia miltiorrhiza, Ophiopogon japonicus, and Dendrobium officinale. This invention, a traditional Chinese medicine for treating Sjögren's syndrome, has the functions of replenishing qi and generating fluids, nourishing yin and moistening dryness, and promoting blood circulation and removing blood stasis. This invention has unique advantages in treating Sjögren's syndrome, significantly improving oral dryness, fatigue, submandibular gland lymphocyte infiltration, and T-cell subset imbalance, making it an effective pure traditional Chinese medicine preparation. However, this patent only includes pharmacodynamic studies and has not undergone clinical verification. Furthermore, in traditional Chinese medicine theory, this compound can: 1) replenish qi and promote the flow of essence and blood, thus facilitating the distribution of body fluids; 2) generate fluids to control dryness and heat, ensuring sufficient essence, blood, and body fluids to moisten dryness symptoms; 3) remove blood stasis and unblock the meridians, allowing qi to flow smoothly and body fluids to be distributed; and 4) the combined effects of replenishing qi, generating fluids, and removing blood stasis lead to the spontaneous healing of dryness symptoms. However, it does not address the spleen and kidneys in the treatment.

[0008] CN116421685A discloses a traditional Chinese medicine for treating Sjögren's syndrome of Qi and Yin deficiency and its preparation method, belonging to the technical field of traditional Chinese medicine preparation for Sjögren's syndrome. The traditional Chinese medicine for treating Sjögren's syndrome of Qi and Yin deficiency includes the following components: Codonopsis pilosula, Dioscorea opposita, Rehmannia glutinosa, Dendrobium nobile, and Ophiopogon japonicus. The preparation method involves the following steps: S1, screening and washing each component; S2, dissolving and mixing each component to prepare a edible preparation; S3, packaging and storing the preparation. This invention is easier to take, can significantly alleviate symptoms such as dry mouth and eyes, limb pain and weakness in patients with Sjögren's syndrome, significantly improves immune inflammatory indicators, is inexpensive, has few side effects, is suitable for a wide range of people, has a scientifically sound formula, conforms to traditional Chinese medicine diagnosis, and has significant efficacy. However, no pharmacodynamic or clinical studies have been conducted. Summary of the Invention

[0009] In view of the above-mentioned prior art, the purpose of this invention is to provide a traditional Chinese medicine composition for treating Sjögren's syndrome of Qi and Yin deficiency, its preparation method, and its application. This traditional Chinese medicine preparation uses ginseng, codonopsis, yam, polygonatum, peony bark, ophiopogon, and white peony root as the principal herbs; dendrobium, rehmannia root, wolfberry, cornus fruit, dried plum, and glehnia root as the assistant herbs; jujube seed, motherwort, and angelica as adjuvant herbs; and citron, bitter orange peel, platycodon root, and arborvitae seed as guiding herbs. The entire formula has the effects of tonifying the middle energizer while promoting circulation, tonifying lung Qi, tonifying lung Yin, tonifying spleen and promoting body fluid production, tonifying kidney Yin, promoting body fluid production, tonifying heart blood, promoting blood circulation and removing blood stasis, soothing the liver and regulating Qi, and moistening the intestines and promoting bowel movements. Together, they achieve the effect of tonifying Qi and nourishing Yin, making it particularly suitable for treating Sjögren's syndrome of Qi and Yin deficiency.

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

[0011] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating Sjögren's syndrome, which is prepared by extracting the following traditional Chinese medicine slices: 10-20 parts of ginseng, 5-15 parts of codonopsis, 15-25 parts of yam, 10-20 parts of polygonatum, 5-15 parts of peony bark, 10-20 parts of ophiopogon, 5-15 parts of white peony root, 5-15 parts of dendrobium, 10-20 parts of rehmannia root, 20-30 parts of wolfberry, 15-25 parts of cornus officinalis, 10-20 parts of dried plum, 5-15 parts of glehnia root, 8-12 parts of jujube seed, 10-20 parts of motherwort, 10-20 parts of angelica sinensis, 5-15 parts of citron, 5-15 parts of immature bitter orange, 10-20 parts of platycodon, and 8-12 parts of arborvitae seed.

[0012] Furthermore, the traditional Chinese medicine composition for treating Sjögren's syndrome is prepared by extracting the following traditional Chinese medicine slices: 15 parts ginseng, 10 parts codonopsis, 20 parts yam, 15 parts polygonatum, 10 parts peony bark, 15 parts ophiopogon, 10 parts white peony root, 10 parts dendrobium, 15 parts rehmannia root, 25 parts wolfberry, 20 parts cornus officinalis, 15 parts dried plum, 10 parts glehnia littoralis, 10 parts jujube seed, 15 parts motherwort, 15 parts angelica sinensis, 10 parts citron, 10 parts immature bitter orange peel, 15 parts platycodon grandiflorus, and 10 parts arborvitae seed.

[0013] Furthermore, the traditional Chinese medicine composition for treating Sjögren's syndrome is prepared by extracting the following traditional Chinese medicine slices: 10 parts ginseng, 15 parts codonopsis, 15 parts yam, 20 parts polygonatum, 5 parts peony bark, 20 parts ophiopogon, 5 parts white peony root, 15 parts dendrobium, 10 parts rehmannia root, 30 parts wolfberry, 15 parts cornus officinalis, 20 parts dried plum, 5 parts glehnia root, 12 parts jujube seed, 10 parts motherwort, 20 parts angelica sinensis, 5 parts citron, 15 parts immature bitter orange, 10 parts platycodon, and 12 parts arborvitae seed.

[0014] Furthermore, the traditional Chinese medicine composition for treating Sjögren's syndrome is prepared by extracting the following traditional Chinese medicine slices: 20 parts ginseng, 5 parts codonopsis, 25 parts yam, 10 parts polygonatum, 15 parts peony bark, 10 parts ophiopogon, 15 parts white peony root, 5 parts dendrobium, 20 parts rehmannia root, 20 parts wolfberry, 25 parts cornus officinalis, 10 parts dried plum, 15 parts glehnia littoralis, 8 parts jujube seed, 20 parts motherwort, 10 parts angelica sinensis, 15 parts citron, 5 parts immature bitter orange, 20 parts platycodon grandiflorus, and 8 parts arborvitae seed.

[0015] Furthermore, the traditional Chinese medicine composition for treating Sjögren's syndrome is prepared as follows:

[0016] (1) After mixing the above-mentioned Chinese herbal medicine pieces, a mixture is obtained. Water is added to the mixture for one decoction, and the mixture is filtered to obtain the dregs and the first filtrate.

[0017] (2) Add water to the dregs of the medicine and boil them a second time, then filter to obtain the second filtrate;

[0018] (3) Combine the primary and secondary filtrates, and concentrate them to obtain the formulation.

[0019] Furthermore, in the traditional 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 traditional 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 traditional Chinese medicine composition for treating Sjögren's syndrome is characterized in that, in step (3), the concentration of the raw medicinal material is concentrated to a concentration of 1.0-1.2 g / mL.

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

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

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

[0025] Traditional Chinese medicine classifies Sjögren's syndrome into seven categories: Yin deficiency with internal dryness, Qi and Yin deficiency, Yin deficiency with blood stasis, Yin deficiency with damp heat, Qi and Yin deficiency with blood stasis, Qi and Yin deficiency with blood stasis and damp heat, and fluid and blood deficiency. Among these, Qi and Yin deficiency is the most common. Patients with Qi and Yin deficiency type Sjögren's syndrome present with dry eyes, dry mouth and throat, and fatigue. Secondary symptoms include palpitations, poor appetite, shortness of breath, reluctance to speak, dry cough with little phlegm, frequent urination at night, and loose stools. Their tongue is red with little or no coating or cracks, and their pulse is thready and weak or thready and rapid. Qi deficiency and prolonged illness are related to the decline in the function of organs such as the lungs and spleen. Qi, blood, and body fluids are transformed into each other under the action of qi transformation. However, patients with pSS have excessive dryness, which consumes body fluids. Over time, this will damage qi. The five internal organs and six bowels cannot be nourished by body fluids, and their functions will decline. When qi and blood production is insufficient, symptoms such as weakness and fatigue can be seen. Qi, blood, and body fluids cannot fill the head and eyes, so dizziness will occur. They cannot nourish the heart vessels, so palpitations will occur. A red tongue indicates that dryness and heat are slightly more severe, which also means that the body's vital energy is less deficient. A pale tongue may affect organs such as the spleen and lungs.

[0026] Qi and Yin deficiency refers to the simultaneous presence of both Qi deficiency and Yin deficiency. Qi deficiency mainly manifests as low physiological functions, such as shortness of breath, fatigue, and spontaneous sweating. Yin deficiency, on the other hand, refers to insufficient Yin fluid in the body, which fails to nourish and restrain Yang, manifesting as dry mouth, dry eyes, dry nose, five-center heat (heat in the palms, soles, and chest), and night sweats. The *Medical Laws* states in the section on dryness: "Dryness prevails, causing parchedness. The harm of dryness is not merely the sudden reddening of the earth. Some suffer from external dryness causing peeling skin; some suffer from internal dryness causing depletion of essence and blood; some suffer from dryness of body fluids causing weakness of the *ying* and *wei* qi, resulting in scorched flesh and skin adhering to the bones." Therefore, ginseng, codonopsis, and yam are used to replenish lung Qi, while Solomon's seal and peony bark replenish lung Yin. Solomon's seal nourishes Yin, moistens dryness, and generates fluids to quench thirst; peony bark clears heat and reduces the loss of Yin fluid. Simultaneously, since the spleen generates the lungs (i.e., nourishing earth to generate metal), the spleen's function of transforming and transporting Qi nourishes the lungs. Therefore, Ophiopogon japonicus and Paeonia lactiflora are used to tonify the spleen and promote the production of body fluids. Ophiopogon japonicus is sweet and slightly bitter, and slightly cold in nature. It enters the heart, lung, and stomach meridians. It can clear heat and nourish yin, moisten the lungs and nourish yin, and benefit the stomach and promote the production of body fluids. Its effect of tonifying the stomach and benefiting the lungs is significant. It can nourish the yin of the heart, lungs, and stomach and restore the distribution of body fluids. Paeonia lactiflora is bitter and sour, and slightly cold in nature. It enters the liver and spleen meridians. It has the functions of nourishing blood and softening the liver, and supporting the spleen and promoting the production of body fluids. It can nourish liver blood, so that the eyes can be nourished, and it can also help the spleen and stomach to produce body fluids to nourish the whole body. The coldness of Ophiopogon japonicus and the sourness and coldness of Paeonia lactiflora complement each other, enhancing the heat-clearing power while also astringing yin fluids, making the effect of nourishing yin and moistening dryness even better. Ginseng, Codonopsis, Dioscorea, Polygonatum, Moutan Bark, Ophiopogon, and White Peony are the principal herbs. Qi and Yin deficiency also includes kidney qi deficiency. When the condition of those with kidney qi deficiency worsens and kidney yin is damaged, it develops into kidney qi and yin deficiency. Therefore, Dendrobium, Rehmannia, Lycium, and Cornus are used to replenish kidney yin. Dendrobium benefits the stomach, generates fluids, nourishes yin, and clears heat; Rehmannia clears heat, cools the blood, nourishes yin, and generates fluids; Lycium nourishes the liver and kidneys, benefits essence, and improves eyesight; Cornus tonifies the liver and kidneys, astringes and consolidates, and is combined with Prunus mume to nourish yin and generate fluids, and Adenophora to replenish lung and stomach yin. Adenophora is sweet, moist, bitter, and cold, and enters the lung and stomach meridians, replenishing lung and stomach yin and clearing lung and stomach heat; Prunus mume is sour and neutral, with the effect of generating fluids and quenching thirst. Combined with Rehmannia, it transforms into yin through sourness and sweetness, enhancing the effect of nourishing yin and generating fluids, assisting the principal herbs in further replenishing yin fluids. Dendrobium, Rehmannia, Lycium, Cornus, Prunus mume, and Adenophora are the assistant herbs. Sjögren's syndrome is a chronic inflammatory autoimmune disease, primarily caused by immune dysfunction, leading to the production of antibodies against autoantigens. These antibodies bind to complement, activating immune cells and triggering an inflammatory response. Inflammatory factors accumulate locally in the heart, potentially causing myocardial cell damage and necrosis, which can manifest as myocardial ischemia. This disease is characterized by its persistent and recurrent nature, consistent with the disease progression pattern of "prolonged illness affecting the collaterals."Dryness injures Yin, and since body fluids and blood share the same origin, deficiency of body fluids leads to blood deficiency, and blood deficiency results in malnourishment of the blood vessels. Deficiency of both Yin and blood leads to blood stasis, which in turn generates internal blood stasis and obstructs the blood vessels. Disharmony in the blood vessels and imbalance of Ying and Wei (nutritive and defensive Qi) lead to the internal generation of toxins. Therefore, Ziziphus jujuba seed is used to nourish heart blood, while Leonurus japonicus and Angelica sinensis are used to invigorate blood, remove blood stasis, and unblock the blood vessels, serving as adjuvant herbs. The liver's function of regulating and controlling the body's balance is crucial. When the liver's function of regulating and controlling Qi is normal, and liver Qi flows smoothly, Qi and blood are balanced, and the functions of the internal organs are coordinated. Internal dryness combined with other factors leads to… The main pathogenesis of this disease is insufficient body fluids or abnormal distribution of body fluids. Dryness is the pathogenic factor, primarily affecting the liver and lungs. Therefore, the formula uses bergamot, immature bitter orange, and platycodon to soothe the liver and regulate qi. Bergamot soothes the liver, relieves stagnation, regulates qi, and harmonizes the middle jiao; immature bitter orange regulates qi, widens the chest, and eliminates stagnation; platycodon harmonizes the other herbs, and its ascending nature guides other herbs upwards, allowing the medicinal effects to better reach the upper jiao, heart, and lungs. It can also carry the medicine upwards, open and disperse lung qi, and regulate water metabolism. The lungs govern the regulation of water metabolism, and platycodon, by opening and dispersing lung qi, allows body fluids to be normally distributed throughout the body. For patients with Sjögren's syndrome who have impaired body fluid distribution, platycodon, as a guiding herb, guides all the herbs in the formula to act on the lungs and related meridians, restoring the lungs' function of regulating water metabolism, promoting the generation, distribution, and excretion of body fluids, and improving the overall abnormal state of body fluid metabolism, allowing yin fluids to properly moisten the whole body. Sjögren's syndrome can cause intestinal dysfunction, slowing down intestinal peristalsis, causing food to stay in the intestines for too long, resulting in excessive water absorption, leading to hard, dry stools that are difficult to pass, thus causing constipation. Arborvitae seed moistens the intestines, promotes bowel movements, nourishes the heart, and calms the mind. The formula, containing ginseng, codonopsis, yam, polygonatum, peony bark, ophiopogon, white peony root, dendrobium, rehmannia root, wolfberry, cornus officinalis, dried plum, glehnia root, jujube seed, motherwort, angelica, bergamot, bitter orange peel, platycodon, and arborvitae seed, has the effects of tonifying the middle jiao and promoting circulation, tonifying lung qi, tonifying lung yin, tonifying spleen and generating fluids, tonifying kidney yin, generating fluids, tonifying heart blood, promoting blood circulation and removing blood stasis, soothing the liver and regulating qi, and moistening the intestines to promote bowel movements. It works synergistically to tonify qi and nourish yin, and is especially suitable for treating dryness-related arthralgia due to deficiency of both qi and yin.

[0027] From the perspective of visceral differentiation, Sjögren's syndrome of Qi and Yin deficiency mainly involves the lungs, spleen, and kidneys. The lungs govern the skin and hair, open to the nose, and control respiration. If lung Qi is not properly circulated, the skin will be dry and the nostrils will be dry. The spleen governs transportation and transformation, and is the foundation of acquired constitution. If the spleen fails to function properly, the production of body fluids will be insufficient, resulting in dry and cracked lips and a thin tongue. The kidneys govern water and store essence and marrow. If kidney essence is deficient, Yin deficiency and internal heat will occur, leading to internal dryness. This illustrates that the lungs, spleen, and kidneys play a crucial role in the metabolism and distribution of body fluids. In addition, the liver governs the free flow of Qi and regulates the Qi mechanism. If liver Qi is stagnant, the Qi mechanism will be obstructed, affecting the distribution of body fluids. The heart governs blood vessels and stores the spirit. If heart blood is insufficient, the spirit will not be nourished, leading to the depletion of Yin fluids. This invention addresses the lungs and spleen by tonifying lung qi and yin, strengthening the spleen to nourish the earth element and generate metal, promoting lung moistening and yin nourishment, benefiting the stomach and generating fluids, while simultaneously tonifying kidney yin, nourishing heart blood, promoting blood circulation and removing blood stasis, and soothing the liver and regulating qi, thereby achieving the goal of treating Sjögren's syndrome of qi and yin deficiency.

[0028] From the perspective of the Triple Burner theory, 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-related arthralgia is characterized by yin deficiency and fluid depletion, with unresolved dryness and heat, often affecting the lungs, spleen, stomach, and kidneys. The Triple Burner is the "official in charge of drainage," regulating the normal functioning of the body's waterways, facilitating the flow of vital energy, and playing a crucial role in the normal distribution of body fluids. In patients with true yin deficiency in the Triple Burner organs, impaired Qi circulation, and poor blood flow, the organs lack nourishment. This invention addresses this by treating upper dryness by regulating Qi, middle dryness by increasing fluids, and lower dryness by treating blood, thereby promoting the proper functioning of the body's waterways.

[0029] The pharmaceutical composition of this invention can significantly alleviate the symptoms of dry mouth and dry eyes in patients with Sjögren's syndrome of Qi and Yin deficiency, improve their quality of life, directly reduce their suffering, and enhance their daily comfort. The formulation of this traditional Chinese medicine composition is rationally designed, obtained through long-term clinical experience and improvement, and further verified through clinical trials. It has the advantages of concise formulation, significant efficacy, and high safety, and can significantly improve patients' quality of life while saving social medical resources. Detailed Implementation

[0030] The present invention will be further described below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the description of this invention, those skilled in the art can make various alterations or modifications to the invention, but these equivalent forms also fall within the scope defined by the appended claims.

[0031] Example 1: Take 150g of ginseng, 100g of codonopsis, 200g of yam, 150g of polygonatum, 100g of peony bark, 150g of ophiopogon, 100g of white peony root, 100g of dendrobium, 150g of rehmannia root, 250g of wolfberry, 200g of cornus officinalis, 150g of dried plum, 100g of glehnia root, 100g of jujube seed, 150g of motherwort, 150g of angelica sinensis, 100g of citrus medica, 100g of immature bitter orange peel, 150g of platycodon root, and 100g of arborvitae seed. Combine the above... After mixing the Chinese medicinal herbs, a mixture is obtained. Water is added to the mixture for a first decoction, with the amount of water being 12 times the mass of the mixture, and the decoction time being 90 minutes. The mixture is then filtered to obtain dregs and a first filtrate. The dregs are then added to water for a second decoction, with the amount of water being 9 times the mass of the mixture, and the decoction time being 50 minutes. The mixture is then filtered to obtain a second filtrate. The first and second filtrates are combined and concentrated to a crude drug concentration of 1.1 g / mL. Dextrin is added, and the mixture is granulated to obtain granules.

[0032] Example 2: Take 100g of ginseng, 150g of codonopsis, 150g of yam, 200g of polygonatum, 50g of peony bark, 200g of ophiopogon, 50g of white peony root, 150g of dendrobium, 100g of rehmannia root, 300g of wolfberry, 150g of cornus fruit, 200g of dried plum, 50g of glehnia root, 120g of jujube seed, 100g of motherwort, 200g of angelica, 50g of citrus medica, 150g of immature bitter orange peel, 100g of platycodon root, and 120g of arborvitae seed. Combine the above-mentioned Chinese herbs... After mixing the medicinal slices, a mixture is obtained. Water is added to the mixture for a first decoction, with the amount of water being 10 times the mass of the mixture, and the decoction time being 120 minutes. The mixture is then filtered to obtain dregs and a first filtrate. The dregs are then added to water for a second decoction, with the amount of water being 8 times the mass of the mixture, and the decoction time being 60 minutes. The mixture is then filtered to obtain a second filtrate. The first and second filtrates are combined and concentrated to a crude drug concentration of 1.0 g / mL. Starch is added, and the mixture is compressed into tablets to obtain tablets.

[0033] Example 3: Take 200g of ginseng, 50g of codonopsis, 250g of yam, 100g of polygonatum, 150g of peony bark, 100g of ophiopogon, 150g of white peony root, 50g of dendrobium, 200g of rehmannia root, 200g of wolfberry, 250g of cornus fruit, 100g of dried plum, 150g of glehnia root, 80g of jujube seed, 200g of motherwort, 100g of angelica root, 150g of citron, 50g of immature bitter orange peel, 200g of platycodon root, and 80g of arborvitae seed. Prepare a decoction of the above-mentioned Chinese herbs. After mixing the tablets, a mixture is obtained. Water is added to the mixture for a first decoction, with the amount of water being 15 times the mass of the mixture, and the decoction time being 60 minutes. The mixture is then filtered to obtain dregs and a first filtrate. The dregs are then added to water for a second decoction, with the amount of water being 10 times the mass of the mixture, and the decoction time being 45 minutes. The mixture is then filtered to obtain a second filtrate. The first and second filtrates are combined and concentrated to a crude drug concentration of 1.2 g / mL. Microcrystalline cellulose is then added to prepare pills.

[0034] Example 4: Take 150g of ginseng, 100g of codonopsis, 200g of yam, 150g of polygonatum, 100g of peony bark, 150g of ophiopogon, 100g of white peony root, 100g of dendrobium, 150g of rehmannia root, 250g of wolfberry, 200g of cornus officinalis, 150g of dried plum, 100g of glehnia root, 100g of jujube seed, 150g of motherwort, 150g of angelica sinensis, 100g of citrus medica, 100g of immature bitter orange peel, 150g of platycodon root, and 100g of arborvitae seed. After mixing the above-mentioned Chinese herbal medicine slices, a mixture is obtained. Water is added to the mixture for a first decoction, with the amount of water being 15 times the mass of the mixture, and the decoction time being 60 minutes. The mixture is then filtered to obtain dregs and a first filtrate. The dregs are then added to water for a second decoction, with the amount of water being 10 times the mass of the mixture, and the decoction time being 45 minutes. The mixture is then filtered to obtain a second filtrate. The first and second filtrates are combined and concentrated to a crude drug concentration of 1.2 g / mL to prepare a compound preparation.

[0035] Example 5: Take 150g of ginseng, 100g of codonopsis, 200g of yam, 150g of polygonatum, 100g of peony bark, 150g of ophiopogon, 100g of white peony root, 100g of dendrobium, 150g of rehmannia root, 250g of wolfberry, 200g of cornus officinalis, 150g of dried plum, 100g of glehnia root, 100g of jujube seed, 150g of motherwort, 150g of angelica sinensis, 100g of citrus medica, 100g of immature bitter orange peel, 150g of platycodon root, and 100g of arborvitae seed. After mixing the prepared Chinese medicinal herbs, a mixture is obtained. Water is added to the mixture for a first decoction, with the amount of water being 10 times the mass of the mixture, and the decoction time being 120 minutes. The mixture is then filtered to obtain dregs and a first filtrate. The dregs are then added to water for a second decoction, with the amount of water being 8 times the mass of the mixture, and the decoction time being 60 minutes. The mixture is then filtered to obtain a second filtrate. The first and second filtrates are combined and concentrated to a crude drug concentration of 1.0 g / mL. Starch is then added to prepare capsules.

[0036] Example 6: Pharmacodynamic Experiment

[0037] Experimental Methods: Fifty white rabbits were randomly divided into five groups according to sex and weight, with a weight of 1.8-1.2 kg. The groups included a blank control group (equal volume of physiological saline), a positive control group (Yiqi Yangyin Oral Liquid group (Tonghua Jinhui Pharmaceutical Co., Ltd., Approval No.: National Drug Approval No. B20020146, Production Batch No.: 20240109, dosage: 10g raw drug / kg), a high-dose group of the present invention (granules prepared in Example 1, dosage: 20g raw drug / kg), a medium-dose group of the present invention (granules prepared in Example 1, dosage: 10g raw drug / kg), and a low-dose group of the present invention (granules prepared in Example 1, dosage: 50g raw drug / kg). The rabbits were administered the medication by gavage twice daily for 10 consecutive days. On the last day, 30 minutes after administration, 0.5 mg / kg of atropine sulfate was injected subcutaneously. The saliva and tear volume of the rabbits after atropine administration were measured at 15, 30, and 45 minutes.

[0038] Methods for measuring saliva and tear volume: Rabbits were placed in a cage and secured. Using hemostatic forceps, approximately equal weights of dry cotton balls (100mg ± 15mg) were placed in the rabbit's mouth and used to wipe the upper, lower, left, and right sides. This process was repeated every 5 minutes. The cotton balls were weighed, and the dry weight (200mg) of the cotton balls was subtracted. The combined weights were the saliva volume measured over 10 minutes. Simultaneously, five strips of 100mm x 5mm filter paper were hung on the lower eyelids of both eyes. After 10 minutes of measurement, the filter paper strips were wet and replaced every 10 minutes. This process was repeated three times.

[0039] Results: The effects of this invention on the amount of saliva and tears in rabbits are shown in Tables 1 and 2.

[0040] Table 1. Effects of the present invention on saliva volume in rabbits after atropine injection.

[0041]

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

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

[0044]

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

[0046] Conclusion: As shown in Tables 1 and 2, the rabbits in the high-dose and medium-dose groups of this invention had more saliva and tear secretion than the blank control group and the positive drug group. Furthermore, the high-dose and medium-dose groups of this invention were more effective than the positive drug group. This indicates that this invention can antagonize atropine's inhibition of saliva and tear secretion, promote the secretion of saliva and tears in rabbits, and prevent dry mouth and dry eyes.

[0047] Example 7: Clinical Study

[0048] Case selection: Patients with Sjögren's syndrome of Qi and Yin deficiency admitted to our hospital from May 2023 to December 2023, with an average age of 32-65 years, 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 2016 American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) diagnostic criteria for primary Sjögren's syndrome (pSS) are as follows: 1. Inclusion Criteria: Patients must have at least one of the following symptoms: dry eyes or dry mouth, i.e., at least one of the following is positive: unbearable dry eyes lasting more than 3 months daily; recurrent gritty sensation in the eyes; need to use artificial tears 3 or more times daily; dry mouth lasting more than 3 months daily; frequent drinking to help swallow dry foods. Or, suspected SS patients with at least one positive systemic result on 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; HIV / AIDS; sarcoidosis; amyloidosis; graft-versus-host disease; IgG4-related diseases. 3. This standard applies to any individual who meets the above inclusion criteria and exclusion criteria, and whose total score of the following five items is ≥4, and who is diagnosed with pSS: (1) focal lymphocytic infiltration of the labial glands, with a focal index ≥1 foci / 4 mm2, 3 points; (2) positive serum anti-SSA antibody, 3 points; (3) at least one eye corneal staining score (OSS) ≥5 or Van Bijsterveld score ≥4, 1 point; (4) at least one eye tear secretion test (Schirmer test) ≤5 mm / 5 min, 1 point; (5) unstimulated total salivary flow rate ≤0.1 ml / min (Navazesh and Kumar assay), 1 point. Individuals routinely using cholinergic drugs should discontinue the drug completely before undergoing the above-mentioned assessments for dry mouth and eyes in items (3), (4), and (5). This standard has a sensitivity of 96% and a specificity of 95%, and is applicable in the validation analysis of diagnostic criteria and in the enrollment of clinical trials.

[0050] Traditional Chinese Medicine (TCM) diagnostic criteria: Referring to the "Expert Consensus on TCM Syndromes of Sjögren's Syndrome" [Zhou Xinyao, Jiang Quan, Tang Xiaopo, et al. Expert Consensus on TCM Syndromes of Sjögren's Syndrome [J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(03):310-314.], the main symptoms are dry eyes, dry mouth and throat, and fatigue; the secondary symptoms are palpitations, poor appetite, shortness of breath, reluctance to speak, dry cough with little phlegm, frequent urination at night, and loose stools; the tongue is red with little and dry coating or cracks; and the pulse is thready and weak or thready and rapid. If the patient has the main symptoms and two or more secondary symptoms, combined with the tongue and pulse, the patient can be diagnosed as a patient with Sjögren's syndrome of Qi and Yin deficiency type.

[0051] Treatment methods: The control group received polyvinyl alcohol eye drops (Hubei Yuanda Tianming Pharmaceutical Co., Ltd., National Drug Approval Number H20046681, Batch No. 20230122), twice daily, appropriate amount each time, for 2 months; and hydroxychloroquine sulfate tablets (Jiangsu Zhiyuan Pharmaceutical Co., Ltd., National Drug Approval Number H20243518, Batch No. 20230201), 200mg daily, for 1 month; the treatment group received the present invention. The granules prepared in Example 1 have the following daily dosage: ginseng 15g, codonopsis pilosula 10g, yam 20g, polygonatum odoratum 15g, peony bark 10g, ophiopogon japonicus 15g, white peony root 10g, dendrobium nobile 10g, rehmannia glutinosa 15g, wolfberry 25g, cornus officinalis 20g, dried plum 15g, glehnia littoralis 10g, jujube seed 10g, motherwort 15g, angelica sinensis 15g, citronella cirrhosa 10g, immature bitter orange 10g, platycodon grandiflorus 15g, and arborvitae seed 10g. This dosage is for 2 months.

[0052] Efficacy criteria: Referring to "Practical Traditional Chinese Medicine Rheumatology", dry eyes, dry mouth and throat, fatigue, and poor appetite were scored as 0, 3, 6, and 9 points respectively, representing none, mild, moderate, and severe symptoms. Referring to "Diagnosis and Efficacy Criteria for Traditional Chinese Medicine Diseases", (1) Significant effect: 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 cases with significant effect + Number of cases with effectiveness) / Total number of cases] × 100%.

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

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

[0055]

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

[0057] Table 3 shows that after 1 month and 2 months of treatment, the scores of the treatment group of the present invention were significantly lower after treatment compared with the scores before treatment in four aspects: dry eyes, dry mouth, fatigue, and poor appetite. This indicates that the present invention can improve symptoms such as dry eyes, dry mouth, fatigue, and poor appetite. Moreover, compared with the control group, the scores of the treatment group were lower, indicating that the present invention is more effective than the control group.

[0058] Table 4 Clinical efficacy results

[0059] Treatment group 12 34 4 92 control group 6 31 13 74

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

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

Claims

1. A traditional Chinese medicine composition for treating Sjögren's syndrome, characterized in that, It is prepared by extracting the following Chinese medicinal herbs: ginseng 10-20 parts, codonopsis 5-15 parts, yam 15-25 parts, polygonatum odoratum 10-20 parts, peony bark 5-15 parts, ophiopogon japonicus 10-20 parts, white peony root 5-15 parts, dendrobium 5-15 parts, rehmannia glutinosa 10-20 parts, wolfberry 20-30 parts, cornus officinalis 15-25 parts, dried plum 10-20 parts, glehnia littoralis 5-15 parts, jujube seed 8-12 parts, motherwort 10-20 parts, angelica sinensis 10-20 parts, citron 5-15 parts, immature bitter orange 5-15 parts, platycodon grandiflorus 10-20 parts, and arborvitae seed 8-12 parts.

2. The traditional Chinese medicine composition for treating Sjögren's syndrome as described in claim 1, characterized in that, It is prepared by extracting the following Chinese medicinal herbs: 15 parts ginseng, 10 parts codonopsis, 20 parts yam, 15 parts polygonatum, 10 parts peony bark, 15 parts ophiopogon, 10 parts white peony root, 10 parts dendrobium, 15 parts rehmannia root, 25 parts wolfberry, 20 parts cornus officinalis, 15 parts dried plum, 10 parts glehnia littoralis, 10 parts jujube seed, 15 parts motherwort, 15 parts angelica sinensis, 10 parts citrus medica, 10 parts immature bitter orange peel, 15 parts platycodon grandiflorus, and 10 parts arborvitae seed.

3. The traditional Chinese medicine composition for treating Sjögren's syndrome as described in claim 1, characterized in that, It is prepared by extracting the following Chinese medicinal herbs: 10 parts ginseng, 15 parts codonopsis, 15 parts yam, 20 parts polygonatum, 5 parts peony bark, 20 parts ophiopogon, 5 parts white peony root, 15 parts dendrobium, 10 parts rehmannia root, 30 parts wolfberry, 15 parts cornus officinalis, 20 parts dried plum, 5 parts glehnia littoralis, 12 parts jujube seed, 10 parts motherwort, 20 parts angelica sinensis, 5 parts citron, 15 parts immature bitter orange, 10 parts platycodon grandiflorus, and 12 parts arborvitae seed.

4. The traditional Chinese medicine composition for treating Sjögren's syndrome as described in claim 1, characterized in that, It is prepared by extracting the following Chinese medicinal herbs: ginseng 20 parts, codonopsis 5 parts, yam 25 parts, polygonatum odoratum 10 parts, peony bark 15 parts, ophiopogon japonicus 10 parts, white peony root 15 parts, dendrobium 5 parts, rehmannia glutinosa 20 parts, wolfberry 20 parts, cornus officinalis 25 parts, dried plum 10 parts, glehnia littoralis 15 parts, jujube seed 8 parts, motherwort 20 parts, angelica sinensis 10 parts, citron 15 parts, immature bitter orange 5 parts, platycodon grandiflorus 20 parts, and arborvitae seed 8 parts.

5. The traditional Chinese medicine composition for treating Sjögren's syndrome as described in claim 1, characterized in that, The preparation method is as follows: (1) After mixing the above-mentioned Chinese herbal medicine pieces, a mixture is obtained. Water is added to the mixture for one decoction, and the mixture is filtered to obtain the dregs and the first filtrate. (2) Add water to the dregs of the medicine and boil them a second time, then filter to obtain the second filtrate; (3) Combine the primary and secondary filtrates, and concentrate them to obtain the formulation.

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

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

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

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

10. The use of the traditional Chinese medicine composition for treating Sjögren's syndrome as described in claim 1 in the preparation of a treatment for Sjögren's syndrome of Qi and Yin deficiency type.

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