Traditional Chinese medicine composition for improving dry mouth symptom of sicca syndrome patient as well as traditional Chinese medicine preparation and application thereof

Abstract

The invention discloses a traditional Chinese medicine composition for improving a dry mouth symptom of a sicca syndrome patient as well as a traditional Chinese medicine preparation and application thereof. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 3 to 5 parts of radix scrophulariae, 3 to 5 parts of radix ophiopogonis, 3 to 5 parts of radix glehniae, 3 to 5 parts of radix polygonati officinalis, 3 to 5 parts of rhizoma phragmitis, 1 to 3 parts of flos mume, 1 to 3 parts of flos rosae rugosae, 1 to 2 parts of herba menthae and 1 to 2 parts of tangerine pith. The invention further discloses a preparation of the traditional Chinese medicine composition. The traditional Chinese medicine composition and the preparation thereof have the effects of nourishing yin, promoting the secretion of saliva or body fluid, moistening dryness, promoting qi circulation, dredging collaterals and regulating the middle warmer, most of the traditional Chinese medicine composition is a medicine-food homologous product, and the traditional Chinese medicine composition is high in safety, suitable for being taken for a long time and capable of being used for relieving the dry mouth symptom of a sicca syndrome patient.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and more specifically, to a traditional Chinese medicine composition for improving dry mouth symptoms in patients with Sjögren's syndrome, and a traditional Chinese medicine preparation and application thereof. Background Art

[0002] Sjögren's syndrome Sjögren syndrome (SS) is a chronic inflammatory autoimmune disease characterized by lymphocyte proliferation and progressive exocrine gland damage, including primary and secondary types. Common clinical manifestations include dryness, fatigue, musculoskeletal pain, and systemic symptoms. Epidemiological surveys show that the disease is a global disease, with a prevalence of 0.33% to 0.77% in my country, as high as 2% to 4.8% in the elderly, and a male-female ratio of about 1:22.9. The disease is more common in middle-aged and elderly women and is the most common rheumatic and immune disease in the middle-aged and elderly population. It is mainly manifested by dry mouth and eyes, and multiple organs and systems such as the lungs and kidneys may also be involved. Nearly 90% of patients feel that the symptoms of dry mouth and eyes are difficult to relieve for many years, accompanied by progressive glandular destruction; and SS is easily accompanied by complications and multi-system damage, which seriously affects the quality of life and endangers the health of patients. However, since the etiology and pathogenesis have not yet been elucidated, there is currently no cure. Treatment mainly takes measures such as improving symptoms, controlling and / or delaying the progression of tissue and organ damage caused by immune response. Moreover, studies have found that some biological drinks, immunosuppressive drinks and other drugs that are effective in animal experiments have not shown better results than placebo drinks in clinical randomized controlled trials.

[0003] About 80% of patients with Sjögren's syndrome have significant dry mouth symptoms, which is also one of the most painful manifestations of SS patients. Patients often experience reduced saliva secretion or viscous saliva, difficulty chewing and swallowing, dependence on soup for eating, and loss of taste. In severe cases, there may even be a breakdown in speech, which affects the patient's study and work and causes mental pain. At the same time, the prevalence of dental caries increases, often accompanied by oral microecological imbalance, which is one of the primary reasons for patients to seek medical treatment, seriously affecting the quality of life and reducing living standards. Studies have shown that severe dry mouth in SS patients may be closely related to changes in oral microecology. Patients have destruction of oral microecology, and its occurrence mechanism is closely related to changes in the nature and quantity of saliva and mucosal immune damage. At present, many studies have shown that oral microecological imbalance is not only the result of the disease, but also an important factor in promoting the development of the disease. At present, according to the latest international diagnosis and treatment guidelines, Western medicine still mainly uses symptomatic replacement therapy to improve dry mouth symptoms, using oral sprays, gels and mouthwashes, and some are combined with muscarinic stimulants, such as pilocarpine or bromhexine, N-acetylcysteine ​​and other secretion-promoting drinks, but such drugs have many restrictions on use and are prone to recurrence. Saliva substitutes, as a common local treatment method, cannot fundamentally improve the secretory function of the salivary glands, and dry mouth symptoms cannot be improved; biological treatment has good treatment prospects, but its safety and effectiveness still need to be verified by large-scale clinical trials. In recent years, more and more patients have begun to seek treatment with traditional Chinese medicine.

[0004] Chinese medicine tea substitute is a traditional Chinese medicine drink. The Chinese medicinal materials suitable for tea substitute are directly decocted in water or brewed with boiling water instead of tea and drunk frequently. It is easy to drink, has sufficient medicinal effect, is light and delicate, sweet and mild, and easy to carry. It greatly improves the patient's compliance and makes the actual feasibility of clinical application higher. It can be taken for a long time and its effect is sustained. The use of tea substitute in clinical practice is not limited to the preparation method of medicinal tea. Chinese medicine prescriptions can be directly decocted in water instead of tea and drunk frequently. It is actually a method of "taking medicine at any time". For chronic, difficult and serious diseases, it is often used to assist the main prescription in auxiliary treatment, and many good results are achieved.

[0005] Therefore, it is necessary to develop a Chinese medicine tea substitute that can satisfy the long-term drinking needs of patients and is used to relieve the dry mouth symptoms of Sjögren's syndrome. Summary of the invention

[0006] In view of the above technical problems, one object of the present invention is to provide a new Chinese medicine composition, which can effectively improve the dry mouth symptoms of patients with Sjögren's syndrome.

[0007] Another object of the present invention is to provide a Chinese medicine preparation comprising the above Chinese medicine composition for improving the dry mouth symptom of patients with Sjögren's syndrome.

[0008] Another object of the present invention is to provide the use of the above-mentioned Chinese medicine composition and Chinese medicine preparation thereof in improving the dry mouth symptoms of patients with Sjögren's syndrome.

[0009] In order to achieve the above object, the present invention adopts the following technical solutions:

[0010] In a first aspect, a traditional Chinese medicine composition for improving dry mouth symptoms in patients with Sjögren's syndrome, wherein the raw materials of the traditional Chinese medicine composition include, by weight: 3 parts of Scrophularia ningpoensis, 3 parts of Ophiopogon japonicus, 3 parts of Glehnia littoralis, 3 parts of Polygonatum odoratum, 3 parts of Phragmites australis, 1 part of White Plum Blossom, 1 part of Rose, 1 part of Mint, and 1 part of Orange Peel.

[0011] In the present invention, the whole prescription of the Chinese medicine composition is composed of nine herbs: Scrophularia, Ophiopogon, Glehnia littoralis, Polygonatum odoratum, Phragmites australis, Mentha, White Plum Blossom, Rose, and Citrus Reticulatae. Ophiopogon japonicus in the prescription has the effects of nourishing yin and moistening the lungs, benefiting the stomach and producing fluid, clearing the heart and relieving restlessness, has a sweet and moist taste, is bitter and cold in nature, enters the stomach meridian, is good at benefiting the stomach and producing fluid and clearing away heat, and is often used for dry tongue and thirst caused by heat in the stomach yin deficiency; for treating heat damage to the stomach yin, dry mouth and tongue, it is often used together with Polygonatum odoratum, Glehnia littoralis and other herbs, such as Yiwei Decoction (Treatise on Warm Diseases); Ophiopogon japonicus is a tonic Yin medicine has the functions of clearing the heart and moistening the lungs, nourishing yin and promoting body fluid. For example, it is recorded in Bencao Huiyan: "Ophiopogon japonicus is a medicine for clearing the heart and moistening the lungs...or fatigue, guest fever, dryness and lack of body fluids; or dryness of the spleen and stomach, constipation and difficulty in defecation; these are all symptoms of deficiency of the heart, lungs, kidneys and spleen, and fire depression". Modern pharmacological research has confirmed that it can effectively treat the symptoms of Sjögren's syndrome. Exploring its deep mechanism, it is found that Ophiopogon japonicus can maintain the balance of Th1 / Th2 cells, reduce lymphocyte infiltration, and protect the submandibular gland. It is especially effective in treating dry mouth. Polygonatum odoratum nourishes yin and moistens dryness, promotes fluid and quenches thirst. It is mainly used to treat insufficient stomach yin, dry throat, thirst, and loss of appetite. It is often used in combination with Ophiopogon japonicus, Adenophora scabra and other stomach-nourishing yin medicines. The Qing Dynasty's "Compendium of Materia Medica" clearly records: "Polygonatum odoratum, nourishes the spleen and moistens the lungs and can replenish yin. It has the image of gold and jade majesty. It dissipates heat and removes wind without hindering nourishment. It has the function of sweetness, mildness and moisturizing." The Song Dynasty's "Bencao Gangmu" calls it "eliminating depression, quenching thirst, and moistening the heart and lungs", which is a clear record of this product's function of moistening the lungs and quenching thirst; Polygonatum odoratum is rich in steroidal saponins, flavonoids, alkaloids, polysaccharides and other ingredients, and has the effects of anti-inflammatory and improving immunity. Ophiopogon japonicus and Polygonatum odoratum are both monarch drugs, which can nourish yin and promote fluid, nourish yin and moisten dryness, and have anti-inflammatory effects, so they are often used to relieve the symptoms of dry mouth in Sjögren's syndrome. The sweet and cold Radix Glehniae nourishes stomach yin, the bitter and cold Radix Scrophulariae and Radix Phragmites are sweet and cold in nature, can clear away heat and produce body fluid, nourish yin and moisten dryness, and are used together with the yin-nourishing and body-nourishing products such as the Radix Glehniae, Polygonatum odoratum, Radix Ophiopogonis to treat febrile diseases, body fluid damage, dry throat and thirst, and are all ministerial drugs; mint, white plum blossom, rose, tangerine peel are used as adjuvants to harmonize the middle and relieve depression, promote qi and dredge collaterals, and all the drugs are used together to play the effects of nourishing yin, promoting body fluid and moistening dryness, promoting qi and dredge collaterals and harmonizing the middle. The present invention focuses on the selection and compatibility of taste, so that patients can understand and accept it, which is beneficial for patients to drink it for a long time, and when the drugs are compatible, mild drugs are selected for prescription, without side effects.

[0012] Illustratively, the raw materials of the traditional Chinese medicine composition for improving dry mouth symptoms in patients with Sjögren's syndrome include, by weight: 3 parts of Scrophularia ningpoensis, 3 parts of Ophiopogon japonicus, 3 parts of Glehnia littoralis, 3 parts of Polygonatum odoratum, 3 parts of Phragmites australis, 1 part of white plum blossom, 1 part of rose, 1 part of mint, and 1 part of orange peel.

[0013] Illustratively, the raw materials of the traditional Chinese medicine composition for improving dry mouth symptoms in patients with Sjögren's syndrome include, by weight: 5 parts of Scrophularia ningpoensis, 5 parts of Ophiopogon japonicus, 5 parts of Glehnia littoralis, 5 parts of Polygonatum odoratum, 5 parts of Phragmites australis, 3 parts of white plum blossoms, 3 parts of roses, 2 parts of mint, and 2 parts of orange peel.

[0014] The basic formula of each raw material medicine of the above-mentioned Chinese medicine composition of the present invention can be adjusted according to clinical symptoms on the basis of the above-mentioned Chinese medicine composition in a specific embodiment to achieve the purpose of treating Sjögren's syndrome and improving certain special clinical symptoms, further enhance the adaptability of the composition of the present invention, and improve the therapeutic effect. These adjustments made based on the basic formula of the present invention are also within the protection scope of this application.

[0015] In a second aspect, the present invention provides a traditional Chinese medicine preparation for improving dry mouth symptoms in patients with Sjögren's syndrome, wherein the raw materials of the traditional Chinese medicine preparation include the above-mentioned traditional Chinese medicine composition.

[0016] Further, the Chinese medicine composition of the present invention can be prepared according to conventional preparation methods in the art, such as decoction, immersion, reflux, etc., and then made into various Chinese medicine dosage forms, including but not limited to decoction, tablets, granules, pills, powders, capsules or tea substitutes. Optionally, according to the actual preparation molding needs, pharmaceutically acceptable excipients can also be added during preparation. According to the principle of medicine reaching the disease, the drug dosage form of the present invention is preferably a Chinese medicine tea substitute.

[0017] In view of the symptoms of dry mouth, the inventor proposes to make a tea substitute for the preferred Chinese medicine that is both a medicine and a food. Most of the drugs used in the present invention are products that are both a medicine and a food, have high safety, are suitable for long-term use, and are fully adapted to the characteristics of a long course of dry arthritis. Chinese medicine tea substitutes are traditional Chinese medicine dosage forms. The Chinese medicinal materials suitable for tea substitutes are directly decocted with water or brewed with boiling water to replace tea for frequent drinking. It has the characteristics of convenient drinking, sufficient efficacy, light and delicate, sweet and mild, and easy to carry. It greatly improves the compliance of patients, makes the actual feasibility of clinical application higher, and can be taken for a long time to slow down its effect. The tea substitute of the present invention has the merit of nourishing yin and promoting body fluid, and has a significant effect on improving the symptoms of dry mouth in patients with Sjögren's syndrome.

[0018] Furthermore, the present invention provides a method for preparing a Chinese medicine tea substitute, comprising the following steps:

[0019] Take the raw materials (such as medicinal slices) according to the above formula ratio, crush them separately, mix them evenly, sterilize, disinfect and package them, and then you can get a tea substitute.

[0020] Furthermore, the subpackaging adopts a food-grade non-woven filter bag.

[0021] In a third aspect, the present invention also claims to protect the use of the above-mentioned Chinese medicine composition and Chinese medicine preparation thereof in the preparation of a drug for improving dry mouth symptoms in patients with Sjögren's syndrome.

[0022] The Chinese medicine composition or the pharmaceutical preparation thereof of the present invention is particularly suitable for patients with Sjögren's syndrome who have moderate to severe activities and a dry mouth VAS score of ≥4 points.

[0023] In addition, unless otherwise specified, the raw materials of the Chinese medicine composition of the present invention can be obtained commercially, and any range recorded in the present invention, including the end values ​​and any numerical value between the end values, and any sub-range of the Chinese medicine composition composed of the end values ​​or any numerical value between the end values, can achieve the purpose of improving the dry mouth symptoms of patients with Sjögren's syndrome.

[0024] The beneficial effects of the present invention are as follows:

[0025] The Chinese medicine composition of the present invention has the effects of nourishing yin, promoting body fluid, moistening dryness, promoting qi, unblocking channels and harmonizing the middle part, and most of them are medicine and food, have high safety and are suitable for long-term use. The present invention proposes to prepare the Chinese medicine composition into a traditional Chinese medicine dosage form - tea substitute, which has the characteristics of convenient drinking, sufficient efficacy, light and exquisite, sweet and mild, and convenient to carry, greatly improves the compliance of patients, makes the actual feasibility of clinical application higher, and can be taken for a long time to achieve its effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 A product diagram of a tea substitute beverage produced by the present invention is shown. DETAILED DESCRIPTION

[0027] In order to explain the present invention more clearly, the present invention is further described below in conjunction with preferred embodiments and drawings. It should be understood by those skilled in the art that the content described below is illustrative rather than restrictive, and should not be used to limit the scope of protection of the present invention.

[0028] Example 1 A Chinese medicine composition for improving dry mouth symptoms in patients with Sjögren's syndrome

[0029] Raw material formula: Scrophularia 5g, Ophiopogon japonicus 5g, Adenophora 5g, Polygonatum odoratum 5g, Phragmites australis 5g, White Plum Blossom 3g, Rose 3g, Mint 2g, Orange Peel 2g.

[0030] Example 2 A Chinese herbal tea substitute for improving dry mouth symptoms in patients with Sjögren's syndrome (tea substitute of the present invention)

[0031] Raw material formula: Scrophularia 3g, Ophiopogon 3g, Adenophora 3g, Polygonatum 3g, Phragmites australis 3g, White Plum Blossom 1g, Rose 1g, Mint 1g, Orange Peel 1g.

[0032] Preparation method: Take the raw materials according to the formula ratio; crush them separately, mix them evenly, sterilize them with ultraviolet light, disinfect them, and package them to obtain tea. For the product, see Figure 1 .

[0033] Example 3 Typical Cases

[0034] Typical case 1: Zhang, female, 41 years old, was diagnosed with "Sjögren's syndrome" (SS) in a local hospital in 2020 due to repeated dry mouth, dry eyes, and decreased white blood cells. She was tested for anti-SSA antibodies +++ and SSB antibodies +++ and then received regular Western medicine treatment. In May 2024, she was treated in the hospital outpatient department and a blood routine + CRP reexamination showed: white blood cells (WBC) 3.31×10 9 / L↓; erythrocyte sedimentation rate (ESR): 59mm / h↑; Rheumatology routine showed: immunoglobulin A (IgA): 4.26g / L↑, rheumatoid factor (RF): 38.74IU / ml↑, ink absorption test: left 5 right 3mm / 5min, salivary flow rate: 1.34ml / 15min, parotid ultrasound: 3 points; dry mouth VAS score: 6 points, started the original conventional Western medicine scheme combined with tea substitute (Chinese medicine tea substitute in Example 2) for 28 doses of treatment, re-examination after 1 week, WBC 3.52×10 9 / L, ESR 18mm / h, IgA 3.94g / L (all returned to normal values), the patient said, "For the first time, all three indicators were normal when I checked the blood, and I was willing to eat after my dry mouth improved." One month later, the blood routine + CRP showed: WBC 3.28×10 9 / L↓; erythrocyte sedimentation rate (ESR): 12mm / h (returned to normal); rheumatology routine showed: immunoglobulin A (IgA): 3.83g / L (returned to normal), rheumatoid factor (RF): 37.7IU / ml↑ (lower than before drinking tea), ink absorption test: left 5 right 6mm / 5min, salivary flow rate: 4.54ml / 15min (increased than before drinking tea), parotid ultrasound: 12 points; dry mouth VAS score: 4 points (lower than before drinking tea), the patient reported that "I used to have severe dry mouth in the morning, and I needed to drink a glass of water immediately after getting up. After taking the tea substitute of the present invention, I clearly feel that my mouth is moist in the morning."

[0035] Typical case 2: Guo, male, 40 years old, the patient had recurrent dry mouth and eyes as the first symptom. In November 2022, the above symptoms were aggravated compared with the previous ones, and there was obvious dry mouth and sticky mouth, no secretions in the eyes. He was diagnosed with SS. He started to take hydroxychloroquine sulfate tablets 200mg orally 2 / day regularly, and then adjusted the western medicine regimen according to the doctor's advice. In May 2024, he was treated in the hospital outpatient clinic, and the ESR was rechecked 22mm / h↑; Rheumatology routine showed: RF: 83.02IU / ml↑, ink absorption test: left 0 right 1mm / 5min, salivary flow rate: 0.12ml / 15min, parotid ultrasound: 22 points; dry mouth VAS score: 10 points, and started to treat 28 doses of the original conventional western medicine regimen combined with tea substitute (Chinese medicine tea substitute in Example 2). After 20 days, the ophthalmology department reexamined, the intraocular pressure was right 16, left 16 (compared to before drinking tea: intraocular pressure right 18, left 17 lower), and the staining of the right eye conjunctiva was slightly relieved. The patient said: "This tea substitute is really good. I feel dry immediately after drinking plain water, but this one is very comfortable and not dry at all." After drinking 28 doses of the tea substitute, the ESR was 2mm / h (returned to normal), RF: 74.03IU / ml↑ (decreased compared to before drinking the tea), ink absorption test: left 5 right 4mm / 5min, salivary flow rate: 4.67ml / 15min (increased compared to before), parotid ultrasound: 20 points, dry mouth VAS score: 6 points (decreased compared to before drinking the tea). The patient said: "This tea substitute is really effective, it's not bad."

[0036] Typical case 3: Liu, female, 68 years old, had dry mouth and dry skin without obvious cause in 2006. ESR, CRP, RF and other indicators were all elevated, SSA antibody was positive, and she was diagnosed with "Sjogren's syndrome". She was treated with hydroxychloroquine sulfate tablets and then adjusted the western medicine regimen according to the doctor's advice. In May 2024, she was treated in the outpatient department of the hospital, and the IgG was rechecked: 18.51g / L↑, and the ESR was rechecked. 20mm / h↑, RF20.81IU / ml↑, ink absorption test: left 0 right 0mm / 5min, salivary flow rate: 0.06ml / 15min, parotid ultrasound: 24 points; dry mouth VAS score: 10 points, started the original conventional Western medicine scheme combined with tea substitute (Chinese medicine tea substitute of Example 2) 28 doses of treatment, after drinking 28 doses of tea substitute, rechecked in our hospital IgG: 17.73g / L↑ (lower than before drinking tea), ESR17mm / h (return to normal value), RF: 28.08U / ml↑, ink absorption test: left 1 right 2mm / 5min, salivary flow rate: 0.99ml / 15min (increased than before), parotid ultrasound: 20 points, dry mouth VAS score: 7 points (lower than before drinking tea), the patient reported: "Compared with other tea substitutes I drank before, this tea substitute obviously feels effective, especially for the improvement of dry mouth symptoms."

[0037] Typical case 4: Zhao, female, was hospitalized in our hospital in May 2011 due to repeated facial numbness and joint pain. After completing relevant examinations, she was diagnosed with Sjögren's syndrome. After symptomatic treatment with 40 mg of prednisolone tablets, the above symptoms gradually eased. After discharge, the patient took Chinese medicine intermittently. The patient visited the outpatient department of the hospital in May 2024 and had stopped taking the medicine for more than 20 days. The results of the ink absorption test: left 0 and right 5 mm / 6 min, salivary flow rate: 2.26 ml / 15 min, parotid gland ultrasound: 6 points; VAS score for dry mouth: 10 points. He was treated with 28 doses of simple tea substitute (the Chinese herbal tea substitute of Example 2). After drinking 28 doses of tea substitute, his liver and kidney function, rheumatology routine, ESR, and blood routine were rechecked in our hospital and no obvious abnormalities were found. The ink absorption test: left 6 and right 6 mm / 5 min, salivary flow rate: 3.23 ml / 15 min (increased compared with before), parotid gland ultrasound: 4 points, and VAS score for dry mouth: 7 points (lowered compared with before drinking tea).

[0038] Typical case 5: Wu, female, 65 years old, was diagnosed with "Sjogren's syndrome" in 2002 and was treated with oral prednisone acetate tablets 8 tablets + hydroxychloroquine hydrochloride 4 tablets + Chinese herbal decoction. Within half a year, the dosage of prednisone acetate tablets was gradually reduced to 1.5 tablets. Later, she stopped taking it due to hand tremors. The symptoms did not improve significantly, and dry mouth symptoms appeared. She needed water to take dry food. For nearly 20 years, the patient insisted on Chinese herbal decoction treatment in our outpatient department, taking prednisone acetate tablets and hydroxychloroquine tablets intermittently, and the symptoms were well controlled. The patient visited our outpatient clinic in May 2024. At this time, she had stopped taking the medicine for more than one month. The WBC was rechecked: 2.56×10 9 / L↓, ESR 29mm / h↑, RF168.70IU / ml↑, alanine aminotransferase ALT 41.0U / L↑, aspartate aminotransferase AST:45.3U / L↑, ink absorption test: left 2 right 2mm / 5min, salivary flow rate: 0.04ml / 15min, parotid ultrasound: 25 points; dry mouth VAS score: 10 points, started simple tea substitute (Chinese herbal tea substitute of Example 2) for 28 doses of treatment, after drinking 28 doses of tea substitute, WBC was rechecked in our hospital: 3.60×10 9 / L (returned to normal value), ESR 28mm / h↑, RF 148.23IU / ml↑ (decreased compared with the value before drinking tea), alanine aminotransferase ALT 26U / L↑, aspartate aminotransferase AST: 35U / L↑ (returned to normal value), ink absorption test: left 4 right 3mm / 5min, salivary flow rate: 0.32ml / 15min (increased), parotid ultrasound: 27 points; dry mouth VAS score: 7 points (decreased compared with before drinking tea). The patient continued to copy the prescription and drink this tea in the follow-up clinic, and the follow-up effect was good.

[0039] Example 4 Clinical Trial

[0040] 1. Research subjects

[0041] 1.1 Case source

[0042] All cases were from patients diagnosed with SS in the outpatient clinic and ward of the Rheumatology and Immunology Department of Guang'anmen Hospital of China Academy of Chinese Medical Sciences from January to December 2024. A total of 60 patients were included in this study, including 30 cases in the observation group and 30 cases in the control group. This clinical trial was approved by the Ethics Committee of Guang'anmen Hospital of China Academy of Chinese Medical Sciences and registered in the China Clinical Registration Trial Center.

[0043] Since it is difficult to recruit enough patients in a short period of time, the actual research process adopts phased recruitment. Patients are numbered according to the order in which they enter the study, and then a member of the research team who does not participate in the preliminary recruitment and subsequent intervention study uses the random number generator of IBM SPSS27.0 statistical software to give each patient a random number. Then, the random numbers are arranged according to their size. The patients corresponding to the first half of the random numbers are assigned to the intervention group, and the patients corresponding to the second half of the random numbers are assigned to the control group.

[0044] 1.2 Diagnostic criteria

[0045] 1.2.1 Western medicine diagnostic criteria: These criteria were based on the American and European Consensus Group (AECG) international classification criteria revised in 2002 or the American College of Rheumatology (ACR) / European Alliance of Associations for Rheumatology (ACR / EULAR) classification criteria developed in 2016.

[0046] The SS international classification standard (American and European Consensus Group, AECG standard) revised by the United States and Europe in 2002:

[0047] Ⅰ. Oral symptoms: 1 or more of the following 3 items

[0048] (1) Daily dry mouth lasting for more than 3 months;

[0049] (2) Recurrent or persistent swelling of the parotid gland in adulthood;

[0050] (3) Swallowing dry food requires the help of water.

[0051] Ⅱ. Eye symptoms: 1 or more of the following 3 items

[0052] (1) Unbearable dry eyes lasting for more than 3 months;

[0053] (2) Repeated sand in the eyes or a grinding sensation;

[0054] (3) Artificial tears are needed daily.

[0055] III. Eye features: Any one or more of the following tests are positive

[0056] (1) Schirmer I test (+) (≤5 mm / 5 min);

[0057] (2) Corneal staining (+) (≥4 Van Bijsterveld score).

[0058] IV. Histological examination: Labial gland pathology shows ≥1 lymphocyte focus (a focus is defined as at least 50 lymphocytes gathered in the labial gland stroma within 4 mm2 of tissue)

[0059] Ⅴ. Salivary gland damage: any one or more of the following tests are positive

[0060] (1) Salivary flow rate (+) (≤1.5 ml / 15 min);

[0061] (2) Parotid gland angiography (+);

[0062] (3) Salivary gland radionuclide examination (+).

[0063] Ⅵ. Autoantibodies: anti-SSA antibody / anti-SSB antibody (+)

[0064] The specific criteria for determining the above items are as follows:

[0065] SS: In the absence of any underlying disease, the following two diagnoses are used: A. Meets 4 or more of the above items Ⅰ, Ⅱ, Ⅲ, Ⅳ, Ⅴ, and Ⅵ, but at least one of Ⅳ (histological examination) and Ⅵ (autoantibodies) must be positive; B. Any 3 of the 4 items Ⅲ, Ⅳ, Ⅴ, and Ⅵ are positive.

[0066] The SS classification criteria developed by the American College of Rheumatology (ACR) / European Alliance of Associations for Rheumatology (EULAR) in 2016 are as follows:

[0067] Inclusion criteria: patients with at least one symptom of dry eyes or dry mouth, that is, at least one of the following is positive: 1) unbearable dry eyes every day for more than 3 months; (2) repeated gritty feeling in the eyes; (3) need to use artificial tears 3 times or more every day; (4) dry mouth every day for more than 3 months; (5) swallowing dry food requires frequent drinking of water. Or suspected SS patients with at least one system positive in the EULAR SS Disease Activity Index (ESSDAI) questionnaire.

[0068] Exclusion criteria: Patients with the following diseases should be excluded because they may have overlapping clinical manifestations or interfere with diagnostic test results: (1) history of head and neck radiotherapy; (2) active hepatitis C virus infection; (3) AIDS; (4) sarcoidosis; (5) amyloidosis; (6) graft-versus-host disease; (7) IgG4-related disease.

[0069] Applicable to anyone who meets the above inclusion criteria and excludes the exclusion criteria, and the sum of the following five scores ≥ 4 is diagnosed as SS:

[0070] (1) Focal lymphocytic infiltration of the labial gland with a focal index ≥1 focus / 4 mm2, 3 points; (2) Positive serum anti-SSA antibodies, 3 points; (3) At least one eye with corneal staining score (OSS) ≥5 or Van Bijsterveld score ≥4, 1 point; (4) At least one eye with tear secretion test (Schirmer test) ≤5 mm / 5 min, 1 point; (5) Unstimulated whole saliva flow rate ≤0.1 ml / min (Navazesh and Kumar test), 1 point.

[0071] Patients who routinely use cholinergic drugs should fully stop taking the drugs before undergoing the above-mentioned examinations (3), (4), and (5) to assess dry mouth and eyes.

[0072] 1.2.2 TCM syndrome diagnostic criteria for dryness and arthralgia (Yin deficiency and fluid deficiency syndrome)

[0073] The TCM syndrome differentiation and classification standard for dryness and arthralgia (yin deficiency and fluid deficiency syndrome) refers to the diagnostic standard in the "Expert Consensus on TCM Syndrome Diagnosis and Treatment of Sjögren's Syndrome" compiled by the Rheumatology Branch of the Chinese Association of Traditional Chinese Medicine and the Guang'anmen Hospital of the Chinese Academy of Chinese Medical Sciences:

[0074] Main symptoms: ① dry mouth and tongue; ② dry eyes without tears

[0075] Secondary symptoms: ① dry throat; ② dry nose; ③ dry skin; ④ dry stool or bowel movement every few days

[0076] Tongue and pulse: red tongue, little or no coating, or cracked tongue, thin, deep or weak pulse

[0077] With two main symptoms, or one main symptom and two secondary symptoms, combined with tongue and pulse, the diagnosis can be made

[0078] 1.3 Inclusion criteria

[0079] Only those who meet all of the following conditions can be included:

[0080] ① Meet the 2002 / 2016 international classification (diagnosis) criteria of Sjögren's syndrome;

[0081] ② Patients who meet the TCM syndrome criteria for Yin deficiency and fluid deficiency;

[0082] ③Age 18 to 75 years old;

[0083] ④ Patients agree to receive treatment and examination for 1 month and sign the informed consent form;

[0084] ⑤Combined medication

[0085] 1) No concurrent medication; or

[0086] 2) Stop taking the medication for at least 12 weeks; or

[0087] 3) The dosage and type of medications are stable for at least 12 weeks (including nonsteroidal anti-inflammatory drugs, oral corticosteroids, pilocarpine, methotrexate, cyclophosphamide, cyclosporine, azathioprine, hydroxychloroquine sulfate, artificial tears, and Chinese patent medicines including Tripterygium wilfordii decoction and white peony total glucosides capsules, etc.).

[0088] During the study, all concomitant medications of the subjects (including start / end date and indication; name, usage, dosage, frequency) must be recorded in the patient's original information and the corresponding part of the medical record report form.

[0089] Except for the therapeutic drugs specified in this study, subjects are not allowed to use Chinese herbal decoctions or other tea substitutes that are known to have significant therapeutic effects on primary Sjögren's syndrome during the treatment period.

[0090] Simultaneous use of artificial saliva treatment was allowed, but it had to be discontinued 24 hours before each visit. Simultaneous use of nonsteroidal anti-inflammatory drugs, hydroxychloroquine, oral corticosteroids, pilocarpine, and topical cyclosporine was allowed. During the entire study, researchers were allowed to reduce the amount of oral corticosteroids according to the patient's condition, but were not allowed to increase the amount of corticosteroids or introduce new hormone treatments. The usage and dosage of other concurrently used drugs should remain unchanged after enrollment, or the dosage could be appropriately reduced according to the patient's condition.

[0091] 1.4 Exclusion criteria

[0092] Those who meet any of the following conditions shall be excluded:

[0093] ① Treatment with Chinese medicine decoction or granules within 3 months before enrollment;

[0094] ② Those with serious lesions of important organs such as heart, liver, kidney, brain, etc. not caused by this disease;

[0095] ③ Patients with concurrent nervous system damage, glomerular acidosis, interstitial pneumonia, liver damage, or severe damage (such as severe hypokalemia);

[0096] ④ Women who are pregnant, breastfeeding or planning to become pregnant, or women of childbearing age who are unwilling to take reliable contraceptive measures during the study;

[0097] ⑤ Those who are receiving any other experimental drugs or experimental medical devices;

[0098] ⑥ The researcher believes that the patient has concomitant diseases (such as neurological or psychiatric diseases) or any other conditions that may seriously endanger the patient's safety, may confuse the research results, or affect the patient's completion of the study.

[0099] 1.5 Case exclusion and dropout

[0100] ①Those who are found not to meet the inclusion criteria after inclusion;

[0101] ② The subjects have poor compliance (compliance with trial medication <80%), stop taking medication, change medication, add medication, or use Chinese and Western medicines prohibited by this protocol in combination, which affects the efficacy assessment.

[0102] 1.6 Shedding Standard

[0103] ① Those who do not follow the doctor's advice to take Chinese medicine instead of tea;

[0104] ② Those who failed to receive follow-up consultation at the prescribed time;

[0105] ③ Those who are unwilling to continue the trial during medication;

[0106] ③ Those who suffer from other digestive system diseases or other serious cardiovascular and cerebrovascular diseases, kidney diseases, hematological diseases, and lung diseases during the intervention period.

[0107] Note: When a subject drops out, the researcher should take the initiative to contact the subject by visiting the subject, making an appointment by phone, etc., to inquire and understand the reason for the dropout, and complete the record and evaluation work. If the patient withdraws from the trial due to adverse reactions to the treatment, the researcher should take corresponding measures to help the subject and do a good job of collecting statistics on the medical records.

[0108] 2. Research Methods

[0109] 2.1 Randomization method and grouping

[0110] According to the above criteria, the cases were selected and the patients were informed of the relevant matters, signed informed consent forms, and filled in basic information. An open randomized controlled method was used, and random grouping was performed using SPSS27.0 software. The groups were sorted according to the size of the numbers randomly generated by the software. The 60 patients who met the inclusion criteria were divided into 2 groups, with 30 cases in each group; the first group was set as the observation group, and the second group was set as the control group. The patients were randomly grouped according to the order of inclusion time. At the same time, it was ensured that the observed subjects understood the purpose of this experimental study.

[0111] 2.2 Pre-medication education

[0112] Before treatment, all patients were given health education to popularize the factors that may aggravate the symptoms of Sjögren's syndrome. Patients were advised to avoid factors that may aggravate the condition during the study, such as smoking, drinking, eating spicy food, and mood swings. They were also informed of the relevant precautions for the use of medications. Simultaneous use of artificial saliva was allowed, but it had to be discontinued 24 hours before each visit.

[0113] 2.3 Treatment methods

[0114] Control group:

[0115] Conventional medication regimen (the dosage and type of medication remain stable for at least 12 weeks) or stop medication for at least 12 weeks or no combined medication; drink boiled water when thirsty, and control daily water intake to about 500ml to 1000ml.

[0116] Observation Group:

[0117] The control group was given a tea substitute of the present invention, with the specific dosage of each bag being: 3g of Scrophularia ningpoensis, 3g of Radix Ophiopogonis, 3g of Radix Adenophorae, 3g of Polygonatum odoratum, 3g of Rhizoma Phragmites, 1g of White Plum Blossom, 1g of Rose, 1g of Mint, and 1g of Citrus zest (provided uniformly by the Chinese Medicine Pharmacy of Guang'anmen Hospital, China Academy of Chinese Medical Sciences). Preparation and taking method: one bag a day, put the medicinal tea in a teapot, brew it with hot water above 90°C, with the amount of water being about 150ml each time, and soak it for 15-20min to ensure that the medicine and food are of the same origin The effective ingredients of the substance are separated out. Drink it when you are thirsty. During the period, add water to soak the medicinal tea repeatedly for ≥ 4 times. You can drink it frequently. After taking it, you can add boiling water. It can be soaked several times until it has no taste. If you drink less water, take at least 500ml a day. The daily dose of 1000-1500mL is the best. Avoid drinking overnight. During the drinking process, the medicine can stay in the mouth for 10-15 seconds before swallowing, so that the liquid medicine can fully contact various parts of the mouth and throat. Take it daily, 1 drink / day, for a total of 4 weeks.

[0118] It is not advisable to take it with alkaline drugs such as sodium bicarbonate, aluminum hydroxide, magnesium oxide, bismuth carbonate, etc., and try to avoid taking it with other drugs at the same time. In addition, patients are given a diary to instruct them to fill in the diary after taking it every day.

[0119] 2.4 Observation indicators and evaluation methods

[0120] 2.4.1 General Record Items

[0121] Trial drug code, subject name, study start date, contact information, gender, and age.

[0122] 2.4.2 Diagnosis content

[0123] Physical signs, severity of illness, medical history, tongue appearance (tongue quality, tongue coating), symptom score.

[0124] Physical and chemical examination indicators: anti-SSA or anti-SSB (+) (double diffusion method); erythrocyte sedimentation rate, immunoglobulin, blood routine, C-reactive protein, complete biochemistry; antinuclear antibody (ANA) titer; ink absorption test, salivary flow rate; parotid gland ultrasound.

[0125] 2.4.3 Observation indicators

[0126] At 4 weeks of intervention and 8 weeks of follow-up, the changes in dry mouth VAS score and unstimulated salivary flow rate compared with the baseline;

[0127] 2.4.4 Safety indicators

[0128] ① Adverse events (AEs) and serious adverse events that occurred during treatment. AEs were evaluated according to the latest version of the International Medical Dictionary for Research on Drugs and Drugs (MedDRA). AEs were graded according to CTCAE 5.0.

[0129] ② General vital signs: body temperature, heart rate, respiration, blood pressure, etc.

[0130] 2.5 Statistical methods

[0131] SPSS27.0 software was used for processing. The measurement data that conformed to the normal distribution were described as mean ± standard deviation (±s), and the t-test was used for comparison; those that did not conform to the normal distribution were described as median (interquartile range) M (P25, P75)], and the non-parametric test was used for comparison; the independent sample t-test was used for inter-group data comparison; the paired sample t-test was used for comparison of the differences before and after the data if they conformed to the normal distribution, and the paired rank sum test was used if they did not conform to the normal distribution; P < 0.05 indicated that the difference tested was statistically significant, and P < 0.01 indicated that the difference tested was statistically significant.

[0132] 3. Research Results

[0133] 3.1 General data comparison

[0134] 3.1.1 Completion of the test

[0135] A total of 60 subjects were enrolled in this study, 30 in the observation group (1 male), and 30 in the control group (all female). 60 subjects (100%) completed the study, and 0 subjects dropped out (0%).

[0136] 3.1.2 Comparison of age and disease course between the two groups

[0137] The youngest patient in the observation group was 30 years old and the oldest was 72 years old. The shortest course of disease was 0.3 years and the longest was 18.9 years. In the control group, the youngest patient was 47 years old and the oldest was 75 years old. The shortest course of disease was 0.1 years and the longest was 20.8 years. There was no statistical difference in age, age of diagnosis and course of disease between the observation group and the control group (P>0.05), and the two groups were comparable (see Table 1).

[0138] Table 1 Comparison of general information of patients in the two groups

[0139]

[0140]

[0141] 3.2 Evaluation of efficacy indicators

[0142] 3.2.1 Comparison of dry mouth VAS scores

[0143] After 4 weeks of treatment, the VAS score of dry mouth in the observation group decreased significantly, from 7.67±1.97 to 5.6±1.16, and the P value was <0.001, indicating that the tea substitute of the present invention has a significant effect in relieving the subjective dry mouth of patients with Sjögren's syndrome; the control group increased from 7.53±1.80 to 8.03±1.59, indicating that the VAS score of dry mouth did not improve when drinking boiled water. Before the experiment, there was no statistical difference in the VAS score of dry mouth between the two groups of patients (P>0.05); after 4 weeks of treatment, the VAS score of dry mouth in the observation group was significantly lower than that in the control group (P<0.001), indicating that the treatment of the observation group was effective, and the tea substitute of the present invention may have better therapeutic effects than boiled water in the short term. (See Table 2)

[0144] Four weeks after the end of treatment, the two groups were crossed, the observation group used conventional medication and drank boiled water when thirsty, while the control group drank the tea substitute of the present invention on the basis of conventional medication. The VAS score of dry mouth in the observation group increased from 5.6±1.16 to 7.37±1.63, but it was lower than before treatment, and the P value was <0.001, indicating that when the observation group stopped using the tea substitute of the present invention and switched to drinking boiled water, the VAS score of dry mouth increased, while after the control group switched to the tea substitute of the present invention, the VAS score of dry mouth decreased from 8.03±1.59 to 5.77±0.94, further indicating that the tea substitute of the present invention has a certain effect on improving dry mouth symptoms, but it may be short-term, and the symptoms may rebound after discontinuation. (See Table 2)

[0145] Table 2 Comparison of VAS scores of dry mouth between the observation group and the control group before and after treatment and at follow-up (independent sample t test)

[0146]

[0147] 3.2.2 Comparison of unstimulated salivary flow rate

[0148] Before the experiment, there was no statistical difference in the non-stimulated salivary flow rate between the two groups of patients (P>0.05), and the data were comparable; after 4 weeks of treatment, the non-stimulated salivary flow rate score of the observation group increased significantly, from 1.21±0.77 to 1.87±0.71, and the P value was <0.001, indicating that the tea substitute of the present invention has a significant effect in promoting saliva secretion; the control group decreased from 1.25±0.81 to 1.19±0.79, indicating that the non-stimulated salivary flow rate score did not improve significantly when drinking boiled water. After 4 weeks of treatment, the non-stimulated salivary flow rate score of the observation group was significantly lower than that of the control group (P<0.001), indicating that the treatment of the observation group was effective. (See Table 3)

[0149] Four weeks after the end of the treatment, the two groups were crossed over. The observation group took conventional medication and drank boiled water when thirsty, while the control group drank the tea substitute of the present invention on the basis of conventional medication. The non-stimulated salivary flow rate score of the observation group decreased from 1.87±0.71 to 1.57±0.69, but it was still higher than before treatment, indicating that the effect of the tea substitute of the present invention may be weakened after the treatment is stopped, but there is still improvement compared to before treatment; and after the control group switched to the tea substitute of the present invention, the non-stimulated salivary flow rate score increased from 1.19±0.79 to 1.60±0.80, and the salivary flow rate increased slightly, showing an improvement in salivary flow rate after treatment. It may be that the change to the tea substitute of the present invention after the crossover played a positive role, but P>0.05, indicating that there was no significant difference in non-stimulated salivary flow rate between the two groups during the follow-up period. (See Table 3) Table 3 Comparison of non-stimulated salivary flow rate between the observation group and the control group before and after treatment and follow-up

[0150]

[0151] Conclusion: This study used a crossover design to compare the VAS scores of dry mouth and non-irritating salivary flow rate of the observation group (conventional medication + tea substitute of the present invention) and the control group (conventional medication + boiled water) before, after and during the follow-up period, to explore and verify the effect of the tea substitute of the present invention on the dry mouth symptoms of SS patients. The results showed that the tea substitute of the present invention significantly improved the symptoms of dry mouth in a short period of time. The VAS score of dry mouth in the observation group decreased significantly after treatment, and the difference was significant compared with the control group, indicating that the tea substitute of the present invention has a significant effect on relieving dry mouth. However, the VAS score of dry mouth in the follow-up period rebounded, indicating that the treatment effect weakened after drug withdrawal, which suggests that the improvement effect of the tea substitute of the present invention on dry mouth may be short-term and may need to be taken continuously to maintain the effect. The VAS score of dry mouth in the control group increased during the treatment period, indicating that boiled water has limited effect on improving dry mouth symptoms, and after cross-treatment, the VAS score decreased significantly when the tea substitute of the present invention was used instead, further supporting the effectiveness of traditional Chinese medicine.

[0152] Combined with the results of non-irritating salivary flow rate, the salivary flow rate of the observation group increased significantly after treatment, and the therapeutic effect recovered during the follow-up period, further verifying that the tea substitute of the present invention can not only relieve the symptoms of dry mouth, but also promote saliva secretion. The salivary flow rate of the control group decreased after treatment, proving that boiled water has no significant effect on promoting saliva secretion.

[0153] In general, the tea substitute of the present invention, as an effective treatment, can significantly improve dry mouth symptoms and promote saliva secretion in the short term, but continuous use may be the key to maintaining the efficacy, and a single short-term treatment may not be able to maintain long-term effects. The crossover design of the study enhances the credibility of the results and provides strong evidence support for clinical practice, indicating that the tea substitute of the present invention has potential for treating dry mouth symptoms. In addition, boiled water treatment has limited improvement on dry mouth and cannot be used as an effective treatment.

[0154] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not limitations on the implementation methods of the present invention. For ordinary technicians in the relevant field, other different forms of changes or modifications can be made based on the above description. It is impossible to list all the implementation methods here. All obvious changes or modifications derived from the technical solution of the present invention are still within the protection scope of the present invention.

Claims

1. A Chinese medicine composition for improving dry mouth symptoms in patients with Sjögren's syndrome, characterized in that: In terms of weight, the raw materials of the traditional Chinese medicine composition include: 3-5 parts of Scrophularia ningpoensis, 3-5 parts of Ophiopogon japonicus, 3-5 parts of Glehnia littoralis, 3-5 parts of Polygonatum odoratum, 3-5 parts of Phragmites australis, 1-3 parts of white plum blossom, 1-3 parts of rose, 1-2 parts of mint, and 1-2 parts of orange peel.

2. The Chinese medicine composition according to claim 1, characterized in that: In terms of weight, the raw materials of the traditional Chinese medicine composition include: 3 parts of Scrophularia ningpoensis, 3 parts of Ophiopogon japonicus, 3 parts of Glehnia littoralis, 3 parts of Polygonatum odoratum, 3 parts of Phragmites australis, 1 part of White Plum Blossom, 1 part of Rose, 1 part of Mint, and 1 part of Orange Peel.

3. The Chinese medicine composition according to claim 1, characterized in that In terms of weight, the raw materials of the traditional Chinese medicine composition include: 5 parts of Scrophularia ningpoensis, 5 parts of Ophiopogon japonicus, 5 parts of Glehnia littoralis, 5 parts of Polygonatum odoratum, 5 parts of Phragmites australis, 3 parts of White Plum Blossom, 3 parts of Rose, 2 parts of Mint, and 2 parts of Citrus tangerine peel.

4. A Chinese medicine preparation for improving dry mouth symptoms in patients with Sjögren's syndrome, characterized in that: The raw materials of the traditional Chinese medicine preparation include the traditional Chinese medicine composition according to any one of claims 1-3.

5. The Chinese medicine preparation according to claim 4, characterized in that: The raw materials of the traditional Chinese medicine preparation also include pharmaceutically acceptable excipients.

6. The Chinese medicine preparation according to claim 4, characterized in that: The dosage forms of the Chinese medicine preparation include decoction, tablet, granule, pill, powder, capsule or tea substitute.

7. The Chinese medicine preparation according to claim 6, characterized in that: The tea substitute is prepared by the following method: The raw materials are taken according to the formula ratio, crushed separately, mixed evenly, sterilized, disinfected and packaged to obtain the product.

8. The Chinese medicine preparation according to claim 7, characterized in that: The subpackaging adopts food grade non-woven filter bag.

9. Use of the Chinese medicine composition according to any one of claims 1 to 3 or the Chinese medicine preparation according to any one of claims 4 to 8 in the preparation of a medicament for improving dry mouth symptoms in patients with Sjögren's syndrome.

10. The use according to claim 9, characterized in that: The Sjögren's syndrome is moderate to severe activity with a dry mouth VAS score of ≥4 points.

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