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

Abstract

The invention discloses a traditional Chinese medicine composition for treating sicca syndrome as well as a preparation method and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 5-90 parts of dendrobium, 5-90 parts of radix ophiopogonis, 5-90 parts of radix scrophulariae, 5-90 parts of oldenlandia diffusa, 5-90 parts of radix polygonati officinalis, 5-90 parts of phyllanthus emblica, 5-90 parts of Chinese olive, 5-90 parts of changium smyrnioides, 5-90 parts of ginseng leaves and 5-90 parts of salvia miltiorrhiza. The invention provides a traditional Chinese medicine composition for treating sicca syndrome, which mainly has the effects of tonifying yin, promoting salivation, clearing away heat and toxic materials. The safety and effectiveness of the traditional Chinese medicine composition for treating sicca syndrome are verified by clinical research.

Description

Technical Field

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

[0002] Sjögren's syndrome mainly invades exocrine glands such as salivary glands and lacrimal glands, and can even cause progressive damage to the glands, leading to their functional impairment. It is a chronic, systemic, autoimmune, inflammatory disease. The disease is characterized by focal infiltration of plasma cells and lymphocytes. In severe cases, the alveoli may atrophy or even disappear, and are replaced by connective tissue and inflammatory cell infiltration. The main clinical manifestations are symptoms of insufficient glandular secretion such as dry mouth and tongue, dry eyes, etc., accompanied by multi-organ and multi-system involvement, fatigue, fever, joint and muscle pain, Raynaud's phenomenon, interstitial lung disease and other extra-glandular manifestations. A variety of autoantibodies and hyperimmunoglobulinemia can be seen in the serum, which can seriously affect the patient's quality of life. The onset of this disease is relatively hidden. At present, it is generally believed that its onset is related to factors such as genetics, infection, sex hormone levels, and immune imbalance. The specific pathogenesis has not yet been clarified.

[0003] At present, Western medicine guidelines recommend symptomatic or alternative treatment for this disease. For example, for patients with only dry symptoms, adequate and reasonable patient education should be carried out, and they should be advised to adjust their living habits and maintain hygiene. For those with dry mouth, xylitol or sugar-free chewing gum can be used to stimulate saliva secretion, and fluoride can be applied externally to prevent dental caries. For those with impaired salivary gland function, muscarinic agonists such as pilocarpine can be considered as appropriate, and artificial saliva can be added when necessary. For those with dry eyes, artificial tears can be used locally, and cyclosporine eye drops can be used for treatment in severe cases. For those with prominent systemic damage, the corresponding immunosuppressants, glucocorticoids or combined biological agents should be selected according to the condition. However, no matter which method is used, there is a dilemma that the disease cannot be cured. In comparison, Chinese herbal compound has the characteristics of being tailored to the individual and diversified in method, so it is of certain significance to observe the characteristics and clinical efficacy of Chinese herbal compound in the treatment of Sjögren's syndrome from multiple angles.

[0004] This disease belongs to the category of "dryness and arthralgia" in traditional Chinese medicine. Based on years of clinical experience, the inventor believes that the pathogenesis of this disease is yin and blood deficiency, dryness of body fluid and blood, and severe dryness turning into toxins. Therefore, a Chinese medicine composition for treating Sjögren's syndrome is proposed, which mainly focuses on nourishing yin, promoting body fluid, clearing away heat and detoxifying. Summary of the invention

[0005] The technical problem to be solved by the present invention is to provide a Chinese medicine composition for treating Sjögren's syndrome and a preparation method and application thereof in view of the problem that the current treatment effect of Sjögren's syndrome is poor.

[0006] The technical solution adopted by the present invention is:

[0007] First,

[0008] The invention provides a traditional Chinese medicine composition for treating Sjögren's syndrome. The raw material composition and proportion are as follows by weight: 5-90 parts of dendrobium, 5-90 parts of ophiopogon, 5-90 parts of scrophularia, 5-90 parts of oldenlandia diffusa, 5-90 parts of polygonatum, 5-90 parts of emblica, 5-90 parts of green fruit, 5-90 parts of codonopsis pilosula, 5-90 parts of ginseng leaves and 5-90 parts of salvia miltiorrhiza.

[0009] As a preferred embodiment, the composition and proportion of the raw materials are as follows: 10-30 parts of Dendrobium, 10-30 parts of Ophiopogon japonicus, 5-15 parts of Scrophularia ningpoensis, 10-30 parts of Oldenlandia diffusa, 10-30 parts of Polygonatum odoratum, 10-20 parts of Phyllanthus emblica, 5-15 parts of Green Fruit, 5-15 parts of Codonopsis pilosula, 5-15 parts of Ginseng Leaf, and 5-15 parts of Salvia miltiorrhiza.

[0010] As a more preferred embodiment, the composition and proportion of the raw materials are as follows: 20 parts of Dendrobium, 20 parts of Ophiopogon japonicus, 12 parts of Scrophularia ningpoensis, 20 parts of Oldenlandia diffusa, 15 parts of Polygonatum odoratum, 15 parts of Phyllanthus emblica, 10 parts of Green Fruit, 10 parts of Codonopsis pilosula, 10 parts of Ginseng Leaf, and 10 parts of Salvia miltiorrhiza.

[0011] Second,

[0012] The present invention also provides a medicine for treating Sjögren's syndrome, comprising the above-mentioned Chinese medicine composition and pharmaceutically acceptable excipients.

[0013] Furthermore, the drug is in oral dosage form.

[0014] Further, the dosage form of the drug is decoction, tablet, capsule, granule, powder, mixture, oral liquid, pill, drop pill or paste. It is understandable that suitable pharmaceutical excipients in the art can be selected for different dosage forms.

[0015] Further, the pharmaceutically acceptable excipients include: one or more of fillers, binders, lubricants, disintegrants, flavoring agents, solubilizers or solvents; fillers such as one or more of starch, sucrose, lactose, microcrystalline cellulose, etc.; binders such as one or more of cellulose derivatives, alginate, gelatin, polyvinyl pyrrolidone, etc.; lubricants such as one or more of talc, calcium stearate, magnesium stearate, micropowder silica gel, polyethylene glycol, etc.; disintegrants such as one or more of sodium carboxymethyl starch, hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, agar, calcium carbonate, sodium bicarbonate, etc.; flavoring agents such as one or more of sucrose or honey; solubilizers such as one or more of sodium lauryl sulfate, lecithin, polysorbate; solvents such as one or more of water and anhydrous ethanol.

[0016] Furthermore, the dosage form of the medicine is a decoction.

[0017] Thirdly,

[0018] The present invention also provides a method for preparing the above-mentioned medicine for treating Sjögren's syndrome. The dosage form of the medicine is a decoction, and the preparation method is to mix the raw material medicine pieces, soak them in water, decoct them, remove the residue and take out the juice to form a liquid dosage form.

[0019] In some embodiments, the preparation method comprises the following steps: first soaking the raw material medicine for 20-30 minutes, using a clay pot or casserole for decocting the medicine, decocting each dose of the medicine twice, adding cold water to soak the medicine surface by 3-5 cm during decocting, first boiling the water over high heat, then decocting over low heat for 30 min-60 min, combining the two medicinal liquids to prepare a decoction.

[0020] Fourthly,

[0021] The present invention also provides application of the above-mentioned traditional Chinese medicine composition in preparing medicine for treating Sjögren's syndrome.

[0022] In some embodiments, the TCM diagnosis of Sjögren's syndrome is Yin deficiency heat toxicity syndrome.

[0023] The drug mechanism of the present invention is as follows: Dendrobium officinale is sweet and slightly cold, nourishes yin and clears heat, benefits the stomach and produces fluid, and is the main drug; the assistant drug is Ophiopogon japonicus, which nourishes yin and moistens dryness, produces fluid and quenches thirst, Scrophularia ningpoensis, nourishes yin, clears heat and detoxifies, and Hedyotis diffusa, which, when used with the main drug, can clear heat and detoxify, nourish yin and produce fluid; Polygonatum odoratum and Phyllanthus emblica, nourish yin and clear heat, strengthen the stomach and produce fluid, Green fruit and Codonopsis pilosula, clear heat and detoxify, nourish yin and produce fluid, Ginseng leaf, invigorates qi and produces fluid and is suitable for the stomach, Salvia miltiorrhiza, which is slightly cold in nature and enters the blood, can activate blood circulation, remove blood stasis and dredge blood vessels, and are all adjuvant drugs; the combination of all the drugs can play the functions of clearing heat and detoxifying, nourishing yin and producing fluid.

[0024] The pharmacological effects of the raw materials are as follows:

[0025] Dendrobium: sweet in taste, slightly cold in nature, enters the stomach and kidney meridians, benefits the stomach and produces body fluid, nourishes yin and clears away heat. The chemical composition of Dendrobium is complex and diverse, mainly including alkaloids, phenanthrenes, sesquiterpenes, polysaccharides, flavonoids, etc. Its pharmacological effects include: enhancing the body's immunity, anti-tumor, promoting the secretion of digestive juices, inhibiting platelet aggregation, lowering blood lipids, lowering blood sugar, anti-oxidation, anti-inflammatory and anti-aging, and antipyretic and analgesic pharmacological effects. Studies have shown that Dendrobium has the effect of stimulating saliva secretion, relieving the symptoms of dry throat and dry mouth, and can improve the difficulty in swallowing when eating dry food. The bibenzyl compound isolated from the ethanol extract of Dendrobium can inhibit the production of NO, IL-1β and NF-α, and can be used to treat inflammatory diseases.

[0026] Scrophularia: It tastes sweet, bitter and salty, is slightly cold in nature, and enters the lung, stomach and kidney meridians. It can clear away heat and cool blood, nourish yin and reduce fire, and detoxify and disperse stagnation. The chemical components of Scrophularia mainly include terpenes, phenylpropanoids, organic acids, volatile oils, steroids, sugars, flavonoids, alkaloids and phenols, among which cycloterpenes and phenylpropanoids are the main active ingredients. It is reported that Scrophularia extracts or their active substances have pharmacological activities such as anti-inflammatory, antioxidant, antihypertensive, liver protection, anti-tumor, anti-fatigue, uric acid lowering, anti-depression, and myocardial cell protection, and can regulate the cardiovascular system, central nervous system and immune system.

[0027] Ophiopogon japonicus: sweet, slightly bitter, slightly cold in nature, enters the heart, lung, and stomach meridians, nourishes yin and produces body fluid, moistens the lungs and clears the heart. The active ingredients of Ophiopogon japonicus include ruscosaponin and Ophiopogon japonicus polysaccharide. Ruscosaponin inhibits acinar cell apoptosis and reverses the inflammation and acinar cell apoptosis induced by TNF-α. Ophiopogon japonicus polysaccharide can inhibit the infiltration of subalveolar lymphocytes, upregulate the expression of aquaporin 5 and vasoactive intestinal peptide mRNA; it can also increase serum superoxide dismutase, reduce malondialdehyde levels, increase spleen and thymus indexes, regulate their immune function, and inhibit peroxidation damage.

[0028] Oldenlandia diffusa: slightly bitter and sweet, cold in nature. It enters the stomach, large intestine, and small intestine meridians, clears away heat and detoxifies, and relieves dampness and relieving stranguria. Oldenlandia diffusa mainly contains a variety of chemical components such as cyclopentadiene ether terpenes, flavonoids, anthraquinones, polysaccharides, organic acids, and trace elements; it has pharmacological effects such as anti-tumor, anti-inflammatory, antioxidant activity, and immunomodulation.

[0029] Polygonatum odoratum: sweet in taste, slightly cold in nature, enters the lung and stomach meridians, nourishes yin and moistens dryness, promotes the production of body fluid and quenches thirst. Studies have found that Polygonatum odoratum extract can improve the spleen and thymus index of immunosuppressive model mice, play an immunomodulatory role; it can also achieve anti-inflammatory effects by regulating inflammatory cytokines, reduce leukocyte infiltration, reduce TNF-α and IL-6, and increase IL-10 levels; it can also improve the abundance of intestinal microorganisms in rats and regulate intestinal flora.

[0030] Phyllanthus emblica: sweet, sour, astringent, cool in nature, enters the lung and stomach meridians, clears away heat and cools blood, helps digestion and invigorates the stomach, promotes the production of body fluids and relieves cough. It is used for blood heat and blood stasis, indigestion, abdominal distension, cough, sore throat, and dry mouth. Phyllanthus emblica contains phenolic acids, amino acids, flavonoids, polysaccharides, sterols and other ingredients, and has potential medicinal value in anti-inflammatory, anti-fibrosis, antibacterial, anti-tumor, anti-oxidation, and immunity-enhancing effects. Among them, polyphenols such as gallic acid and methyl gallate are its main anti-inflammatory ingredients, and have a significant inhibitory effect on inflammation.

[0031] Green fruit: sweet and sour, neutral in nature, belongs to the lung and stomach meridians, clears away heat and detoxifies, relieves sore throat, and promotes the production of body fluids. It is used for sore throat, cough with sticky phlegm, irritability, thirst, and fish and crab poisoning. There are many types of chemical components in green fruit, including phenols, flavonoids, phenylpropanoids, coumarins, polysaccharides, triterpenes and volatile oils. Among them, the phenolic component in green fruit has the highest content and is its main active ingredient. Studies have confirmed that green fruit extracts or their active ingredients play an important role in antiviral, antibacterial and anti-inflammatory, blood lipid regulation, blood sugar reduction, anti-oxidation, anti-cancer, alcohol detoxification and liver protection.

[0032] Ming Codonopsis: sweet, slightly bitter, slightly cold in nature, enters the lung, spleen, and liver meridians, moistens the lungs and resolves phlegm, nourishes yin and harmonizes the stomach, soothes the liver, and detoxifies. It is used for lung heat cough, vomiting and nausea, poor appetite and dry mouth, red eyes and dizziness, carbuncle and ulcer. At present, more than 100 compounds have been identified from Ming Codonopsis, among which polysaccharides, fatty acids, coumarins and volatile oils are their important active ingredients. Ming Codonopsis polysaccharides have the effects of regulating immunity, resisting fatigue and anoxia tolerance, and also have the effects of lowering blood lipids, inhibiting platelet aggregation and anticoagulation, which can prevent thrombosis and prevent senile diseases such as atherosclerosis. Fatty acids, phospholipids, choline and amino acids are closely related to its effects of nourishing body fluid, soothing the liver and harmonizing the stomach, and have the effect of delaying aging. Coumarin has significant in vitro anti-tumor activity, and volatile oil has a good expectorant effect.

[0033] Ginseng leaf: bitter, sweet, cold in nature. Enters the lung and stomach meridians. Replenishes qi, benefits the lungs, dispels heat, and promotes the production of body fluids. Used for cough due to qi deficiency, irritability due to summer heat, thirst due to loss of body fluids, blurred vision, and fatigue in the limbs. Ginseng leaf is rich in saponins, as well as polysaccharides, flavonoids, amino acids, volatile oils and other chemical components. Its pharmacological effects include: enhancing immunity, anti-tumor, promoting secretion of digestive juices, inhibiting platelet aggregation, lowering blood lipids, lowering blood sugar, anti-oxidation, anti-aging, and antipyretic and analgesic effects.

[0034] Danshen: bitter, slightly cold. Enters the heart and liver meridians. Promotes blood circulation and removes blood stasis, relieves pain, clears the heart and eliminates vexation, cools blood and eliminates carbuncle. Used for chest pain, abdominal pain, accumulation of masses, heat pain, restlessness and insomnia, menstrual disorders, dysmenorrhea and amenorrhea, and sores and swelling. Danshen has anti-tumor, heart function protection, anti-fibrosis, and blood sugar lowering effects. The main components of Danshen are water-soluble salvianolic acids and fat-soluble tanshinones. The salvianolic acids mainly include salvianolic acid B / A, danshensu, rosmarinic acid, etc. Tanshinones mainly include tanshinone ⅡA, cryptotanshinone, and danshen diterpenoid quinones. Danshen diterpenoid quinones can inhibit the proliferation of Th17 and Treg cells to a certain extent, maintain intestinal immune balance, and improve human immunity.

[0035] The present invention has the following advantages and beneficial effects:

[0036] (1) The present invention proposes a Chinese medicine composition for treating Sjögren's syndrome, which mainly has the effects of nourishing yin and promoting the production of body fluid, clearing away heat and detoxifying. Clinical studies have verified its safety and effectiveness in treating Sjögren's syndrome.

[0037] (2) The formula of the present invention selects common Chinese herbal medicines and has a simple combination. The method of taking the medicine is convenient and diverse. The medicine can be boiled into a decoction for consumption, or made into pills and powders that are easy to store and carry.

[0038] (3) The formula of the present invention has outstanding therapeutic effects, few side effects, low clinical application costs, and is suitable for clinical promotion. DETAILED DESCRIPTION

[0039] Embodiments of the present invention are described in detail below. The embodiments described below are exemplary and intended to be used to explain the present invention, but should not be construed as limiting the present invention.

[0040] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0041] Where values ​​are described herein as a range, it should be understood that such disclosure includes disclosure of all possible sub-ranges within that range, as well as specific values ​​falling within that range, regardless of whether a specific value or a specific sub-range is explicitly stated.

[0042] In this document, "plurality" means at least two, unless otherwise clearly and specifically defined.

[0043] The term "pharmaceutically acceptable excipient" used in the present invention means any excipient conventionally used in the field of pharmaceutical preparations, as long as the excipient does not produce adverse reactions or influences on the expected quality and efficacy of the Chinese medicine composition of the present invention.

[0044] Example 1

[0045] A traditional Chinese medicine composition for treating Sjogren's syndrome, the raw material composition and proportion are as follows: 20g of dendrobium, 20g of ophiopogon, 12g of Scrophularia, 20g of Hedyotis diffusa, 15g of Polygonatum odoratum, 15g of Phyllanthus emblica, 10g of Cibotium barometz, 10g of Codonopsis pilosula, 10g of Ginseng leaf, and 10g of Salvia miltiorrhiza.

[0046] It is a dosage for one dose, prepared into a Chinese medicine decoction;

[0047] The preparation method of Chinese medicine decoction comprises the following steps: soaking the raw medicine for 30 minutes before decocting the medicine, using a clay pot or a casserole as the decocting utensil, using purified water for decocting the medicine, decocting each dose of the medicine twice, adding cold water to soak the medicine surface by 3-5 cm during decocting, first boiling the water with high heat, then decocting with low heat for 60 minutes, decocting about 200 ml each time, combining the two medicinal liquids to prepare the decoction.

[0048] Take 1 dose per day.

[0049] Example 2

[0050] A traditional Chinese medicine composition for treating Sjogren's syndrome, the raw material composition and proportion are as follows: 20g of dendrobium, 20g of ophiopogon, 15g of Scrophularia, 30g of Hedyotis diffusa, 15g of Polygonatum odoratum, 15g of Phyllanthus emblica, 10g of Cibotium barometz, 10g of Codonopsis pilosula, 10g of Ginseng leaf, and 5g of Salvia miltiorrhiza.

[0051] The rest is the same as in Example 1.

[0052] Example 3

[0053] A traditional Chinese medicine composition for treating Sjogren's syndrome, the raw material composition and proportion are as follows: 20g of dendrobium, 20g of ophiopogon, 12g of Scrophularia, 20g of Hedyotis diffusa, 15g of Polygonatum odoratum, 15g of Phyllanthus emblica, 10g of Cibotium barometz, 10g of Codonopsis pilosula, 15g of Ginseng leaf, and 10g of Salvia miltiorrhiza.

[0054] The rest is the same as in Example 1.

[0055] Example 4

[0056] A traditional Chinese medicine composition for treating Sjogren's syndrome, the raw material composition and proportion are as follows: 25g of dendrobium, 15g of ophiopogon, 10g of Scrophularia, 25g of Hedyotis diffusa, 10g of Polygonatum odoratum, 10g of Phyllanthus emblica, 15g of Cibotium barometz, 15g of Codonopsis pilosula, 15g of Ginseng leaf, and 10g of Salvia miltiorrhiza.

[0057] The rest is the same as in Example 1.

[0058] Example 5

[0059] A traditional Chinese medicine composition for treating Sjogren's syndrome, the raw material composition and proportion are as follows: 20g of dendrobium, 20g of ophiopogon, 12g of Scrophularia, 25g of Hedyotis diffusa, 15g of Polygonatum odoratum, 15g of Phyllanthus emblica, 10g of Cibotium barometz, 10g of Codonopsis pilosula, 15g of Ginseng leaf, and 10g of Salvia miltiorrhiza.

[0060] The rest is the same as in Example 1.

[0061] Example 6

[0062] A traditional Chinese medicine composition for treating Sjogren's syndrome, the raw material composition and proportion are as follows: 20g of dendrobium, 20g of ophiopogon, 12g of Scrophularia, 20g of Hedyotis diffusa, 15g of Polygonatum odoratum, 15g of Phyllanthus emblica, 10g of Cibotium barometz, 10g of Codonopsis pilosula, 15g of Ginseng leaf, and 10g of Salvia miltiorrhiza.

[0063] The rest is the same as in Example 1.

[0064] The therapeutic effect of the Chinese medicine composition of the present invention on Sjögren's syndrome is further illustrated below through clinical application examples of the Chinese medicine composition of the present invention.

[0065] Clinical trial information

[0066] 1. General Information

[0067] A total of 60 subjects who voluntarily participated in this trial and signed the informed consent were included. All cases were from the outpatient department of rheumatology of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from March 2022 to December 2023. They all met the international classification standards for primary Sjögren's syndrome jointly developed by the American College of Rheumatology and the European League Against Rheumatism in 2016, and met the diagnosis of Yin deficiency and heat toxicity syndrome in traditional Chinese medicine.

[0068] Among them, there were 30 cases in the observation group, including 29 females and 1 male; the age ranged from 29 to 77 years old, with an average age of (52.40±12.96) years old; the course of disease ranged from 5 to 217 months, with an average course of (86.20±62.17) months;

[0069] There were 30 cases in the control group, including 29 females and 1 male; the age ranged from 31 to 74 years old, with an average age of (54.43±12.54) years old; the course of disease ranged from 8 to 192 months, with an average course of (71.63±47.01) months;

[0070] There was no significant difference in general data between the two groups (P>0.05).

[0071] 2. Treatment Methods

[0072] Observation group: Chinese medicine decoction: The composition and proportion of the raw materials are as follows: 20g of Dendrobium, 20g of Ophiopogon japonicus, 12g of Scrophularia ningpoensis, 20g of Hedyotis diffusa, 15g of Polygonatum odoratum, 15g of Phyllanthus emblica, 10g of Qingguo, 10g of Codonopsis pilosula, 10g of Ginseng leaf, and 10g of Salvia miltiorrhiza. The raw materials are mixed and soaked in water, boiled, and the residue is removed to obtain the juice to form a liquid dosage form. Generally, before decocting the medicine, soak the raw materials for 20-30 minutes. The decocting utensils are preferably earthenware jars or casseroles. The water used for decoction is based on pure water quality. Each dose of medicine is generally boiled twice, and it is generally appropriate to soak the medicine surface 3-5cm. The amount of decoction each time is about 200ml. Take 1 dose per day, and take it warm twice in the morning and evening after meals. At the same time, the patient was treated with oral hydroxychloroquine sulfate tablets (0.1 g per tablet, produced by Shanghai Shangyao Zhongxi Pharmaceutical Co., Ltd., approval number: National Medicine Standard H19990263), 0.2 g each time, twice a day. The treatment lasted for 12 weeks.

[0073] Control group: Oral hydroxychloroquine sulfate tablets (0.1 g per tablet, produced by Shanghai Shangyao Zhongxi Pharmaceutical Co., Ltd., approval number: National Medicine Standard H19990263), 0.2 g each time, twice a day. Treatment lasted for 12 weeks.

[0074] 3. Observation indicators

[0075] 3.1 VAS score for dry mouth and dry eyes: Refer to the “TCM Diagnosis and Treatment Plan for 95 Diseases in 22 Specialties” published in 2017, and use the visual analogue scale (VAS) to evaluate the patient's dry mouth and dry eyes respectively.

[0076] 3.2 Disease activity evaluation indicators: Sjögren's syndrome disease activity index (ESSDAI), Sjögren's syndrome patient self-report index (ESSPRI). Refer to the evaluation and management guidelines for primary Sjögren's syndrome developed by the European League Against Rheumatism (EULAR) in 2016.

[0077] 3.3 Objective indicators: Schirmer test, static salivary flow rate.

[0078] 3.4 Immune indicators: immunoglobulin (Ig) G, IgA, IgM, complement (C) 3, complement C4.

[0079] 3.5 Inflammatory indicators: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF)

[0080] 4. Treatment

[0081] The observation course of patients was 12 weeks.

[0082] 5. The evaluation criteria for the efficacy of TCM syndromes were used in reference to the evaluation criteria for the diagnosis and treatment of dryness and bi (Sjogren's syndrome) in the "TCM Diagnosis and Treatment Schemes for 22 Specialties and 95 Diseases" promulgated by the State Administration of Traditional Chinese Medicine in 2017: markedly effective: the patient's score before and after treatment decreased by ≥70%; effective: the patient's score before and after treatment decreased by ≥50%; improved: the patient's score before and after treatment decreased by ≥20%; ineffective: the patient's score before and after treatment decreased by <20%. The calculation formula (nimodipine method) is: [(score before treatment - score after treatment) / score before treatment] × 100%. ②Total effective rate = (markedly effective + effective + improvement) / total number of cases × 100%. In addition, the subjects' dry mouth and dry eyes VAS scores, ESSDAI, ESSPRI, Schirmer test, static salivary flow rate, IgG, IgA, IgM, C3, C4, ESR, CRP, RF before and after treatment were recorded, and adverse events were monitored during the study.

[0083] 6. Statistical Analysis

[0084] SPSS 26.0 software was used for statistical analysis of the data. For count data, frequency and composition ratio (n, %) were used to express them, and chi-square test was used. For quantitative data, when comparing between two groups or before and after within a group, if the data all obeyed the normal distribution, mean ± standard deviation was used. Indicates that two independent sample t-tests or paired t-tests were used for statistical analysis; if one of the groups was not normally distributed, the median and upper and lower quartiles, i.e., M (P25, P75), were used to describe the data, and non-parametric tests were used. The test standard for statistical analysis in the study was α = 0.05, with P < 0.05 being considered statistically significant, P < 0.01 indicating that the difference was statistically significant, and P > 0.05 indicating that the difference was not statistically significant.

[0085] 7. Research Results

[0086] Both groups of patients completed 12 weeks of observation, and the results were analyzed as follows:

[0087] 7.1 The efficacy evaluation is shown in Table 1. Compared with the control group, the total effective rate, markedly effective rate, effective rate, improved rate and ineffective rate of the observation group were statistically significant. After treatment, the total effective rate of the observation group was 93.33%, and the total effective rate of the control group was 73.33%. The overall efficacy of the observation group was better than that of the control group.

[0088] Table 1 Comparison of efficacy evaluation results between the two groups of patients [cases (%)]

[0089]

[0090] 7.2 Comparison of VAS scores of dry mouth and dry eyes is shown in Table 2. Compared with before treatment, the VAS scores of dry mouth and dry eyes in the observation group and the control group after treatment were statistically significant (P<0.05); the differences between the observation group and the control group were statistically significant (P<0.05).

[0091] Table 2 Comparison of VAS scores of dry mouth and dry eyes between the two groups before and after treatment

[0092]

[0093] Note: Compared with the group before treatment, *P<0.05; compared with the control group during the same period, △P<0.05.

[0094] 7.3 Evaluation of disease activity ESSDAI and ESSPRI are shown in Table 3. Compared with before treatment, the differences in ESSDAI and ESSPRI in the observation group after treatment were statistically significant (P<0.05); the difference in ESSPRI in the control group was statistically significant (P<0.05); the difference in ESSPRI between the observation group and the control group was statistically significant (P<0.05).

[0095] Table 3 Comparison of disease activity evaluation between the two groups of patients before and after treatment

[0096]

[0097]

[0098] Note: Compared with the group before treatment, *P<0.05; compared with the control group during the same period, △P<0.05.

[0099] 7.4 Comparison of Schirmer test and static salivary flow rate is shown in Table 4. Compared with before treatment, the Schirmer test and static salivary flow rate in the observation group after treatment were statistically significant (P<0.05); compared with the control group, the differences were statistically significant (P<0.05).

[0100] Table 4 Comparison of Schirmer test and static salivary flow rate between the two groups before and after treatment

[0101]

[0102] Note: Compared with the group before treatment, *P<0.05; compared with the control group during the same period, △P<0.05.

[0103] 7.5 Comparison of immune indicators IgG, IgA, IgM, C3, and C4 is shown in Table 5. Compared with before treatment, the difference in IgG between the two groups after treatment was statistically significant (P<0.05), and the difference in IgA in the observation group was statistically significant (P<0.05); there was no statistically significant difference between the observation group and the control group.

[0104] Table 5 Comparison of immune indicators between the two groups of patients before and after treatment

[0105]

[0106] Note: Compared with the group before treatment, *P<0.05.

[0107] 7.6 Comparison of inflammatory indicators ESR, CRP, and RF is shown in Table 6. Compared with before treatment, there were significant differences in ESR and CRP in the observation group and ESR and RF in the control group after treatment (P<0.05); there were no significant differences between the observation group and the control group.

[0108] Table 6 Comparison of inflammatory indicators between the two groups of patients before and after treatment

[0109]

[0110] Note: Compared with the group before treatment, *P<0.05.

[0111] 7.7 Adverse Reactions During the study, 2 subjects in the observation group developed gastrointestinal reactions; 1 subject in the control group developed gastrointestinal reactions, 1 subject developed upper respiratory tract infection, and 1 subject developed insomnia. These reactions were considered to be related to intolerance to the smell of medicinal herbs, cold, and work pressure. All subjects improved after symptomatic treatment based on the original regimen, and no other serious adverse reactions occurred.

[0112] 8. Discussion The results show that the VAS scores of dry mouth and dry eyes, disease activity index (ESSDAI, ESSPRI), Schirmer test, static salivary flow rate, IgG, IgA, ESR, and CRP in the observation group were improved and corrected, and the clinical symptoms were significantly relieved, reflecting the good efficacy and safety of traditional Chinese medicine in treating this disease. The basis of its action may be related to the mechanism of traditional Chinese medicine regulating immunity, anti-inflammation, anti-oxidation, and protecting glands.

[0113] In summary, this study conducted a randomized controlled trial to explore the efficacy and safety of traditional Chinese medicine in the treatment of primary Sjögren's syndrome with Yin deficiency and heat toxicity. The results showed that the efficacy of traditional Chinese medicine combined with Western medicine in the treatment of patients with primary Sjögren's syndrome with Yin deficiency and heat toxicity was better than that of conventional Western medicine. It can effectively alleviate symptoms such as dry mouth and dry eyes, and can better reduce ESSPRI, improve Schirmer test and static salivary flow rate, and improve glandular secretion function. No serious adverse reactions occurred during the treatment, and it has good safety, showing the potential and value for further promotion to clinical practice.

[0114] Typical Cases

[0115] Case 1

[0116] Shen, female, 68 years old

[0117] First visit: 2023-02-14

[0118] Chief complaint: dry mouth and dry eyes for 4 years, aggravated for 1 month. Current medical history: The patient went to a local hospital for dry mouth, dry eyes, and heart discomfort 4 years ago. After relevant examinations, he was diagnosed with "Sjogren's syndrome" and was given 0.1g of hydroxychloroquine sulfate once a day. Hydroxychloroquine was discontinued due to eye discomfort in January 2020. On November 20, 2020, he was treated in the psychosomatic department of a western hospital for anxiety and depression, and was given 2mg of estazolam tablets once a night. On October 20, 2020, the eyes improved and he began to take hydroxychloroquine sulfate. The patient had red and purple spots on his fingers in the past month, and his dry mouth and dry eyes worsened, so he went to the rheumatology and immunology department of our hospital for treatment. The following symptoms: dry mouth, chapped lips, foreign body sensation in the throat, dry throat and sore throat, dry eyes, and frosted feeling; red and itchy cheeks, purple and red spots on the back of both hands, itching, and desquamation; sore muscles in both upper arms and shoulders, and pain in both elbows. Chest tightness, shortness of breath, cough, good appetite, restless sleep, difficulty falling asleep, constipation, defecation once every 3-4 days, scanty urination. Red tongue with little cracks in the coating, weak and rapid pulse.

[0119] TCM diagnosis: Dryness and Bi

[0120] Syndrome diagnosis: Yin deficiency heat toxicity syndrome

[0121] Treatment principle: clearing away heat and detoxifying, nourishing yin and promoting body fluid

[0122] prescription:

[0123] Dendrobium 20g Ophiopogon 20g Scrophularia 15g Hedyotis diffusa 30g

[0124] Polygonatum odoratum 15g Phyllanthus emblica 15g Qingguo 10g Codonopsis pilosula 10g

[0125] Ginseng leaf 10g Salvia miltiorrhiza 5g

[0126] 14 doses, 1 dose per day, decocted in 400ml of water, taken warm twice half an hour after breakfast and dinner 2023-02-28 Second visit: The patient's dry mouth and dry eyes are less severe than before, with a frosted feeling. Cough, chest tightness, and shortness of breath are better than before, and the redness and itching of the cheeks, the purple-red spots, itching, and desquamation on the back of both hands are less severe than before. The pain in the shoulder and wrist joints is less severe than before. The appetite is good, but the sleep is not good, and the difficulty in falling asleep is relieved than before. The stool is dry, one time every 1-2 days, and the urine is regular. The tongue is light red, with little coating, cracks in the middle, and the pulse is thin and rapid. The initial prescription of Hedyotis diffusa was reduced to 20g, Scrophularia ningpoensis was reduced to 12g, and Salvia miltiorrhiza was increased to 10g. 14 sets of continued service are taken in the same way as before.

[0127] 2023-03-14 Third visit: The patient's dry mouth and dry eyes have improved compared to before, with occasional chest tightness, good appetite, poor sleep, and normal bowel movements. The tongue is pale red, with little coating, and the pulse is thin and rapid. The patient continued to take the medicine at the second visit dose, and the symptoms did not worsen.

[0128] Case 2

[0129] Guo, male, 42 years old

[0130] First visit: 2023-06-21

[0131] Chief complaint: dry mouth and weakness in both lower limbs for more than 8 months.

[0132] Current medical history: The patient had dry mouth without obvious cause 8 months ago, which can be relieved by drinking water, and dry food needs to be taken with water. Subsequently, weakness of both lower limbs occurred, and even fell. On January 20, 2023, he went to the local hospital for treatment due to dry mouth and weakness of both lower limbs. After examination, he was diagnosed with "Sjogren's syndrome". Current symptoms: dry mouth, dry food needs to be taken with water, which can be relieved after drinking water, dry eyes. Weakness of both lower limbs. Cough, yellow sputum. Spontaneous sweating. Occasionally pain in both knee joints, with a burning sensation, good appetite, good sleep, yellow urine, and regular bowel movements. Dark tongue, yellow and greasy tongue coating, teeth marks on the edges, and a stringy and slippery pulse.

[0133] TCM diagnosis: Dryness and Bi

[0134] Syndrome diagnosis: Yin deficiency heat toxicity syndrome

[0135] Treatment principle: clearing away heat and detoxifying, nourishing yin and promoting body fluid

[0136] Prescription: Dendrobium 20g, Ophiopogon 20g, Scrophularia 12g, Hedyotis diffusa 25g

[0137] Polygonatum odoratum 15g Phyllanthus emblica 15g Qingguo 10g Codonopsis pilosula 10g

[0138] Ginseng leaf 15g Salvia miltiorrhiza 10g

[0139] 14 doses, 1 dose per day, decoct 400ml of water, take warm twice half an hour after breakfast and dinner 2023-07-04 Second visit: Dry mouth and dry eyes are better than before. Weakness in both lower limbs is relieved. Cough is relieved than before, but there is still yellow sputum, but the amount is small. Spontaneous sweating is relieved. Pain in both knee joints is relieved than before, with a burning sensation. Appetite is good, sleep is good, and bowel movements are regular. Dark tongue, thin yellow fur, slippery pulse. According to the initial prescription, ginseng leaves are reduced to 10g, and white flower snake tongue grass is reduced to 20g, and 14 doses are taken.

[0140] 2023-07-18 Third visit: Dry mouth and dry eyes are less severe than before. Weakness in both lower limbs is less severe. Appetite is good, sleep is good, bowel movements are normal. Dark tongue, thin yellow fur, deep pulse. Continue to take 14 doses of the second visit prescription to consolidate the therapeutic effect.

[0141] Case 3

[0142] Ms. Liu, 62 years old

[0143] 2023-02-08First visit

[0144] Chief complaint: dry mouth and dry eyes accompanied by fatigue and palpitations for 1 year.

[0145] Current medical history: The patient developed dry mouth, dry eyes, and recurrent oral ulcers 1 year ago. In February 2022, he had pain in multiple joints throughout his body, pain in the proximal interphalangeal joints of both hands, no swelling, and no morning stiffness. Pain in both knees, elbows, wrists, and heels, no swelling. He then went to the rheumatology and immunology department of a local hospital and was diagnosed with "Sjogren's syndrome". After taking Panlong Qi tablets, the joint pain was relieved. The patient sought further treatment and came to our outpatient clinic. Current symptoms: dry mouth, dry eyes, severe fatigue, occasional cough, palpitations, stomach pain and bloating after eating, good appetite, good sleep, constipation, one bowel movement every two days, and regular urination. Dark tongue, yellow and greasy fur, deep pulse.

[0146] TCM diagnosis: Dryness and Bi

[0147] Syndrome diagnosis: Yin deficiency heat toxicity syndrome

[0148] Treatment principle: clearing away heat and detoxifying, nourishing yin and promoting body fluid

[0149] prescription:

[0150] Dendrobium 20g Ophiopogon 20g Scrophularia 12g Hedyotis diffusa 20g

[0151] Polygonatum odoratum 15g Phyllanthus emblica 15g Qingguo 10g Codonopsis pilosula 10g

[0152] Ginseng leaf 15g Salvia miltiorrhiza 10g

[0153] 14 doses, 1 dose per day, decoct 400ml of water, take warm twice a day half an hour after breakfast and dinner 2023-02-22 Second visit: Dry mouth, dry eyes, fatigue are significantly relieved, palpitations are relieved, appetite is poor, sleep is good, stool is sticky, one dose every two days, urine is regular. Dark tongue, yellow fur, deep pulse. The initial prescription of ginseng leaf is reduced to 10g, and 14 doses are taken.

[0154] 2023-03-07 Third visit: Dry mouth, dry eyes, and fatigue are less severe than before. Appetite is good, sleep is good, bowel movements are normal. Dark tongue, thin yellow fur, deep pulse. Continue to take 14 doses of the second visit prescription to consolidate the therapeutic effect.

[0155] The above is only a preferred embodiment of the present invention, and does not limit the technical solution of the present invention in any form. Any simple modification, equivalent change and modification made to the above embodiment according to the technical essence of the present invention still falls within the scope of the technical solution of the present invention.

Claims

1. A Chinese medicine composition for treating Sjögren's syndrome, characterized in that: In terms of weight, the composition and proportion of the raw materials are as follows: 5-90 parts of Dendrobium, 5-90 parts of Ophiopogon japonicus, 5-90 parts of Scrophularia ningpoensis, 5-90 parts of Oldenlandia diffusa, 5-90 parts of Polygonatum odoratum, 5-90 parts of Phyllanthus emblica, 5-90 parts of Green Fruit, 5-90 parts of Codonopsis pilosula, 5-90 parts of Ginseng Leaf, and 5-90 parts of Salvia miltiorrhiza.

2. A Chinese medicine composition for treating Sjögren's syndrome according to claim 1, characterized in that: The composition and proportion of the raw materials are as follows by weight: 10-30 parts of Dendrobium, 10-30 parts of Ophiopogon japonicus, 5-15 parts of Scrophularia ningpoensis, 10-30 parts of Oldenlandia diffusa, 10-30 parts of Polygonatum odoratum, 10-20 parts of Phyllanthus emblica, 5-15 parts of Green Fruit, 5-15 parts of Codonopsis pilosula, 5-15 parts of Ginseng Leaf, and 5-15 parts of Salvia miltiorrhiza.

3. A Chinese medicine composition for treating Sjögren's syndrome according to claim 2, characterized in that: The composition and proportion of the raw materials are as follows by weight: 20 parts of Dendrobium, 20 parts of Ophiopogon japonicus, 12 parts of Scrophularia ningpoensis, 20 parts of Oldenlandia diffusa, 15 parts of Polygonatum odoratum, 15 parts of Phyllanthus emblica, 10 parts of Green Fruit, 10 parts of Codonopsis pilosula, 10 parts of Ginseng Leaf, and 10 parts of Salvia miltiorrhiza.

4. A drug for treating Sjögren's syndrome, characterized in that: The invention comprises the Chinese medicine composition according to any one of claims 1 to 3 and pharmaceutically acceptable excipients.

5. A drug for treating Sjögren's syndrome according to claim 4, characterized in that: The drug is in oral dosage form.

6. The drug for treating Sjögren's syndrome according to claim 4, characterized in that: The dosage form of the medicine is decoction, tablet, capsule, granule, powder, mixture, oral liquid, pill, drop pill or paste.

7. The method for preparing the drug for treating Sjögren's syndrome according to claim 6, characterized in that: The dosage form of the medicine is a decoction, and the preparation method thereof is to mix the raw material medicine pieces, soak them in water, decoct them, remove the residues and extract the juice to form a liquid dosage form.

8. The method for preparing the drug for treating Sjögren's syndrome according to claim 7, characterized in that: The preparation method comprises the following steps: firstly soaking the raw material medicine for 20-30 minutes, using a clay pot or a casserole for decocting the medicine, decocting each dose of the medicine twice, adding cold water to soak the medicine surface by 3-5 cm during decocting, firstly boiling the water with a high fire, then decocting with a low fire for 30 minutes to 60 minutes, combining the two medicinal liquids, and thus preparing a decoction.

9. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for treating Sjögren's syndrome.

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