Traditional Chinese medicine composition for treating dry eyes related to sicca syndrome and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for treating sicca syndrome related dry eyes and application thereof.The traditional Chinese medicine composition is reasonable in proportion design and obtained through a large number of experimental screening and long-term clinical experience accumulation, has the effects of nourishing kidney essence, reinforcing qi, nourishing yin, moistening dryness and improving eyesight, and has the advantages of being free of toxic and side effects and free of toxic and side effects. The lacrimal gland secretion function of sicca syndrome model mice can be enhanced, the mouse cornea staining score can be improved, mouse lacrimal gland lymphocyte infiltration can be improved, the traditional Chinese medicine syndrome score of sicca syndrome related dry eye patients can be reduced, and finally the clinical symptoms of related dry eye can be improved. Especially, the traditional Chinese medicine composition has the advantages of good curative effect and more obvious effect on kidney essence deficiency type sicca syndrome related dry eyes. The traditional Chinese medicine composition disclosed by the invention can be independently administered or jointly administered. The pharmaceutical composition is a safe and effective pure traditional Chinese medicine preparation, has no toxic or side effect, is easy to control the quality of the composition medicines, is low in cost and has a good application prospect.

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 dry eye associated with Sjögren's syndrome and application thereof. Background Art

[0002] Sjögren's syndrome is an autoimmune disease in which the exocrine glands are destroyed by lymphocyte infiltration. The lacrimal glands and salivary glands are most susceptible to involvement. When Sjögren's syndrome involves the lacrimal glands and related clinical manifestations of lacrimal gland dysfunction appear, such as dryness, foreign body sensation, or stinging, tearing or burning sensation in the eyes, it is called Sjögren's syndrome-associated dry eye (SSDE).

[0003] Epidemiological research data show that the prevalence of Sjögren's syndrome in the general population is approximately 0.2% to 0.6%, and the proportion of patients with concurrent dry eye in this population can be as high as 72%-85%. SSDE is characterized by a prolonged course, easy relapse, and clinical difficulty in cure. Patients often develop anxiety disorders or even depression due to persistent ocular surface dryness and irritation symptoms, which ultimately leads to a significant decrease in mental health and social function. However, at present, Western medicine clinical treatment mainly adopts symptomatic supportive treatment strategies, such as artificial tears. Although it can temporarily relieve subjective symptoms, it is difficult to block the process of glandular parenchyma damage, and long-term use may induce iatrogenic complications such as secondary infection. Surgical treatment is not universal, and has high risks and high costs. Therefore, there is an urgent need to find new clinical treatment methods.

[0004] At present, the pathogenesis of SSDE is still not very clear. It is generally believed that the onset of this disease is often closely related to factors such as the body's genetics, immune system dysfunction, and viral infection. Clinical practice and some studies have shown that traditional Chinese medicine treatment has significant advantages, especially in improving ocular surface function, relieving dry eyes, reducing disease recurrence, and improving patients' quality of life, which often gives patients a stronger sense of gain. At present, the traditional Chinese medicine pathogenesis of Sjögren's syndrome focuses more on "yin deficiency and dryness", so clinical intervention generally adopts the principle of clearing heat and nourishing yin. For example, the invention patent CN119548593A discloses a traditional Chinese medicine composition for the treatment of Sjögren's syndrome, which contains 10 parts of Artemisia annua, 10 parts of white peony root, 10 parts of Scutellaria baicalensis, 10 parts of dried tangerine peel, 10 parts of Dendrobium candidum, and 10 parts of Salvia miltiorrhiza. It acts on STAT3 phosphorylation to inhibit Tfh proliferation, reduce IL-21 secretion, and alleviate humoral immune disorders to treat Sjögren's syndrome. It mainly clears damp heat, removes blood stasis and promotes fluid production, so as to achieve the purpose of improving exocrine gland function, regulating immunity, and relieving dryness. However, in actual clinical practice, there are few traditional Chinese medicines that can be used to treat SSDE alone. Therefore, there is an urgent need to find new and effective treatments. Summary of the Invention

[0005] In response to the shortcomings of the aforementioned prior art, the present invention aims to provide a traditional Chinese medicine composition for treating Sjögren's syndrome-related dry eye, which significantly improves the clinical symptoms, enhances lifestyle, and slows the progression of the disease. The present invention also explores its application in the treatment of Sjögren's syndrome-related dry eye, demonstrating particularly promising results for patients with kidney-essence deficiency, providing a novel approach to the treatment of Sjögren's syndrome-related dry eye.

[0006] In order to solve the above technical problems, the present invention adopts the following technical solution: a traditional Chinese medicine composition for treating dry eye associated with Sjögren's syndrome, comprising the following components in parts by weight: 5-30 parts of salt raspberry, 5-30 parts of salt dodder seed, 10-45 parts of astragalus, 15-45 parts of dried dendrobium, 5-20 parts of Sichuan cyperus, 5-15 parts of honey polygala, 5-15 parts of honeysuckle, 5-20 parts of wolfberry, 5-20 parts of salt plantain seed, 5-15 parts of schisandra and 15-45 parts of Scrophularia; the dry eye associated with Sjögren's syndrome is of the kidney essence deficiency type. The present invention combines the clinical practice and working basis of traditional Chinese medicine in treating dry eye associated with Sjögren's syndrome, takes the improvement of the lacrimal gland secretion function of patients with Sjögren's syndrome and mice with Sjögren's syndrome dry eye model, and uses the Sjögren's syndrome activity score as the efficacy index. Through dialectical analysis of the pathogenesis of dry eye associated with Sjögren's syndrome and sorting out the efficacy of Chinese herbal medicines, it is found that salt raspberry, salt dodder seed, astragalus, dry dendrobium, Sichuan cypress, honey polygala, honeysuckle, wolfberry, salt plantain seed, schisandra chinensis, and Scrophularia ningpoensis have a synergistic effect of nourishing kidney essence, and have a good therapeutic effect on kidney essence deficiency type Sjögren's syndrome related dry eye, thus forming the present invention.

[0007] Among them, the medicinal properties of each component are as follows:

[0008] Salt raspberry: enters the liver, kidney and bladder meridians. It has the effects of nourishing the kidney, consolidating essence and reducing urine, nourishing the liver and improving eyesight.

[0009] Salt Cuscuta: Enters the liver, kidney, and spleen meridians. It has the effects of nourishing the liver and kidneys, consolidating essence and reducing urine, calming the fetus, and improving eyesight.

[0010] Astragalus: It enters the lung and spleen meridians. It has the effects of replenishing qi and strengthening the exterior, promoting diuresis and expelling toxins, draining pus, and healing sores and promoting tissue regeneration.

[0011] Dried Dendrobium: It enters the Heart, Lung and Stomach meridians. It has the effects of nourishing Yin and moistening the lungs, clearing the heart and relieving restlessness, and benefiting the stomach and promoting fluid production.

[0012] Sichuan Cyathula: Enters the liver and kidney meridians. It has the effects of removing blood stasis, tonifying the liver and kidneys, strengthening the tendons and bones, and promoting diuresis and relieving stranguria.

[0013] Honey Polygala: It enters the heart, kidney and lung meridians. It has the effects of calming the mind, improving intelligence, connecting the heart and kidney, and removing phlegm and opening the orifices.

[0014] Honeysuckle: It enters the lung, heart, and stomach meridians. It has the effects of clearing away heat, detoxifying, and dispersing wind-heat.

[0015] Wolfberry: Enters the liver and kidney meridians. It has the effect of nourishing the liver and kidneys, improving intelligence and vision.

[0016] Salt Plantago Seed: It enters the liver, kidney and lung meridians. It has the effects of clearing away heat, promoting diuresis, promoting blood circulation, dissipating dampness and stopping diarrhea, and improving eyesight.

[0017] Schisandra chinensis: It enters the lung, heart, and kidney meridians. It has the effects of astringing, strengthening qi, promoting fluid production, and nourishing the kidneys and calming the mind.

[0018] Scrophularia: It enters the lung, stomach, and kidney meridians. It has the effects of clearing heat and cooling blood, nourishing yin and reducing fire.

[0019] The salt dodder seed and salt raspberry fruit in the composition of the present invention are both monarch drugs. The two drugs complement each other and are used to nourish the kidney and benefit the essence. After being processed with salt, the power of entering the kidney is enhanced. It targets the root of kidney essence deficiency, replenishes kidney essence while consolidating the lower part of the body to prevent the loss of essence and fine particles, and raspberry fruit has the effect of nourishing the liver and improving eyesight. Lycium barbarum is a ministerial drug, which can nourish the liver and kidney, nourish kidney yin, nourish liver blood, moisten the eyes and relieve dryness. Astragalus is a ministerial drug, which takes its power of tonifying qi and raising yang, benefiting the defense and strengthening the exterior, greatly tonifying the qi of the spleen and lungs, and promoting the circulation of body fluids when qi is strong, promoting the upward flow of body fluids to the eyes, solving the pathogenesis of "qi not distributing body fluids", and improving the symptoms of systemic qi deficiency at the same time. Dried dendrobium is sweet, cold and moist as a ministerial drug. Because it has the effects of nourishing yin and clearing heat, nourishing the stomach and promoting the production of body fluids, and improving eyesight, it can nourish the yin of the kidney and stomach, promote the production of body fluids and moisten dryness. It forms a "qi and yin double tonification" pattern with astragalus, targeting the secondary contradiction of qi and yin deficiency. Scrophularia ningpoensis acts as an adjuvant, nourishing yin and reducing internal heat, clearing away heat without damaging yin. It targets eye burns caused by yin deficiency and excessive internal heat, preventing further depletion of body fluids by the internal heat. Polygala tenuifolia and honeysuckle act together as adjuvants: the former calms the mind, improves intelligence, and relieves phlegm and invigorates the orifices, while the latter clears heat and detoxifies, reducing swelling and dispersing stagnation. Their synergistic effect can alleviate discomfort such as palpitations and shortness of breath, while also clearing internal heat and toxins. Cyathula officinalis primarily functions to promote blood circulation and dissipate stasis, guiding internal heat downward, helping to regulate blood circulation in the eyes and alleviate eye fatigue, thus serving as an adjuvant. Schisandra chinensis, with its acidic properties that astringe body fluids and consolidate kidney essence, also acts as an adjuvant. It synergizes with Cuscuta chinensis and Rubus idaeus to prevent the loss of essence and enhance the efficacy of yin-nourishing herbs. Plantago seed promotes diuresis, relieves stranguria, clears turbidity, and brightens the eyes, providing nourishment without stagnation. After being processed with salt, it specifically enters the kidney meridian, channeling internal heat through urination, thus serving as an adjuvant. The combined use of these herbs not only addresses the core pathogenesis of kidney-essence deficiency, but also addresses the secondary paradox of qi and yin deficiency. Through rational compatibility, the entire formula nourishes kidney-essence, replenishes qi and yin, moistens dryness, and improves eyesight, thereby significantly improving the symptoms of dry eye associated with Sjögren's syndrome.

[0020] Preferably, the Chinese medicine composition includes the following components in parts by weight: 15 parts of salt raspberry, 15 parts of salt dodder seed, 30 parts of astragalus, 30 parts of dried dendrobium, 15 parts of Sichuan cyperus, 10 parts of honey polygala, 10 parts of honeysuckle, 15 parts of wolfberry, 10 parts of salt plantain seed, 10 parts of schisandra, and 30 parts of Scrophularia.

[0021] Another object of the present invention is to provide the use of the above-mentioned traditional Chinese medicine composition in the preparation of a drug for treating dry eye associated with Sjögren's syndrome.

[0022] Preferably, the drug further comprises pharmaceutically acceptable carriers and excipients.

[0023] Preferably, the dosage form of the drug includes decoction, granules, tablets, capsules or oral liquid.

[0024] Another object of the present invention is to provide a pharmaceutical preparation for treating dry eye associated with Sjögren's syndrome, wherein the pharmaceutical preparation contains the above-mentioned traditional Chinese medicine composition or the extract of the traditional Chinese medicine composition as an active ingredient.

[0025] Another object of the present invention is to provide a compound pharmaceutical preparation for treating dry eye associated with Sjögren's syndrome, wherein the compound pharmaceutical preparation comprises the above-mentioned traditional Chinese medicine composition or an extract of the traditional Chinese medicine composition and hydroxychloroquine sulfate.

[0026] Preferably, the pharmaceutical preparation further comprises pharmaceutically acceptable carriers and excipients.

[0027] Preferably, the dosage form of the pharmaceutical preparation includes decoction, granules, tablets, capsules or oral liquid.

[0028] Preferably, the Sjögren's syndrome-related dry eye is of the kidney essence deficiency type.

[0029] Compared with the prior art, the present invention has the following beneficial effects:

[0030] 1. The proportion design of the Chinese medicine composition of the present invention is reasonable, and it is obtained through a large number of experimental screenings and long-term clinical experience accumulation, so that it has the functions of nourishing kidney essence, replenishing qi and nourishing yin, moistening dryness and improving eyesight. It can enhance the lacrimal gland secretion function of Sjögren's syndrome model mice, improve the corneal staining score of mice, improve the lymphocyte infiltration of the lacrimal glands of mice, and reduce the TCM syndrome score of patients with Sjögren's syndrome-related dry eyes. It has the advantages of good efficacy and more significant effect on dry eyes related to Sjögren's syndrome with insufficient kidney essence. The pharmaceutical composition of the present invention is a safe and effective pure Chinese medicine preparation with no toxic side effects, the quality of the medicinal ingredients is easy to control, the cost is low, and it has good application prospects. The present invention provides a new idea and theoretical basis for the research on the treatment of dry eyes related to Sjögren's syndrome, which is of great significance.

[0031] 2. Animal experiments have shown that the Chinese medicine composition of the present invention can enhance the lacrimal gland secretion function of mice with dry eye model associated with Sjögren's syndrome, reduce the corneal staining score of mice, and reduce the lymphocyte infiltration of the lacrimal glands of mice, indicating that the Chinese medicine composition of the present invention can be used to treat dry eye associated with Sjögren's syndrome. In clinical applications, it was found that the Chinese medicine composition of the present invention combined with hydroxychloroquine sulfate can synergistically improve the lacrimal gland secretion function of patients with Sjögren's syndrome, reduce the TCM syndrome score of patients with Sjögren's syndrome, and improve the quality of life of patients. Its effect is significantly better than that of using the medicine alone. The Chinese medicine composition of the present invention can be administered alone or in combination, and the therapeutic effect is significant. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 The tear secretion of mice in different treatment groups before and after 12 weeks of treatment.

[0033] Figure 2 Comparative photos of corneal staining of mice in different treatment groups before and after 12 weeks of treatment.

[0034] Figure 3 Corneal staining scores of mice in different treatment groups before and after 12 weeks of treatment.

[0035] Figure 4 HE staining of lacrimal gland pathological sections of mice in different treatment groups before and after 12 weeks of treatment.

[0036] Figure 5 The figure shows the comparison of the lacrimal gland lymphocyte infiltration area of ​​mice in different treatment groups after 12 days of treatment. DETAILED DESCRIPTION

[0037] The present invention will be further described in detail below with reference to the examples. The mice used in the following examples were purchased from Jiangsu Jicui Yaokang Biotechnology Co., Ltd., weighing 20±2 grams, SPF grade, and the animal license number is SCXK (Su) 2024-0008. The experimental animals were raised in the SPF animal laboratory of Chongqing Traditional Chinese Medicine Hospital at a room temperature of (25±2)°C, with free access to food and water. All the Chinese medicinal raw materials used were purchased from Chongqing Traditional Chinese Medicine Hospital.

[0038] 1. A Chinese medicine composition for treating dry eyes associated with Sjögren's syndrome

[0039] Example 1: This example includes the following steps:

[0040] 1) Weigh the following raw materials in parts by weight: 15 parts of salt raspberry, 15 parts of salt dodder seed, 30 parts of astragalus, 30 parts of dried dendrobium, 15 parts of Sichuan cyperus, 10 parts of honey polygala, 10 parts of honeysuckle, 15 parts of wolfberry, 10 parts of salt plantain seed, 10 parts of schisandra chinensis and 30 parts of Scrophularia ningpoensis.

[0041] 2) Soak all ingredients in water for 30 min, boil over high heat, then simmer over low heat for 30 min, filter out the medicinal juice, repeat this process twice, mix the medicinal juices, and concentrate them into a medicinal solution containing 0.5 g / mL of crude drug. Place the solution in a 4°C refrigerator until ready for use.

[0042] Example 2: This example includes the following steps:

[0043] 1) Weigh the following raw materials in parts by weight: 20 parts of salt raspberry, 20 parts of salt dodder seed, 20 parts of astragalus, 20 parts of dried dendrobium, 10 parts of Sichuan cyperus, 10 parts of honey polygala, 10 parts of honeysuckle, 20 parts of wolfberry, 10 parts of salt plantain seed, 5 parts of schisandra and 15 parts of scrophularia.

[0044] 2) Soak all ingredients in water for 30 min, boil over high heat, then simmer over low heat for 30 min, filter out the medicinal juice, repeat this process twice, mix the medicinal juices, and concentrate them into a medicinal solution containing 0.5 g / mL of crude drug. Place the solution in a 4°C refrigerator until ready for use.

[0045] 2. Application of Chinese medicine compositions

[0046] 1. In order to verify whether the Chinese medicine composition of the present invention has a therapeutic effect on dry eye associated with Sjögren's syndrome, 7-week-old NOD / Ltj female mice and ICR female mice were selected. Female NOD mice were used as model mice. NOD mice are a type of spontaneous mouse model commonly used for Sjögren's syndrome. When the mice are 9 weeks old, the peripheral glands are gradually infiltrated and destroyed by lymphocytes. After 1 week of adaptive feeding, 18 NOD mice were randomly divided into 3 groups, namely, model group (Model), low-dose group (Low), and high-dose group (High). 6 ICR mice were adaptively fed for 1 week as control group (Control). The high-dose group was gavaged with 28.8 g / kg of the medicinal solution prepared in Example 1 every day, the low-dose group was gavaged with 14.4 g / kg of the medicinal solution prepared in Example 1 every day, and the model group and the control group were gavaged with the same dose of normal saline every day. After 4 weeks, it was changed to gavage every other day for 8 weeks.

[0047] 1) The tear secretion of mice without surface anesthesia was measured once at 8 weeks and 20 weeks of age (i.e., before and after intervention). The specific method is as follows: clamp a phenol red cotton thread (Tianjin Jingming New Technology Development Co., Ltd.) with microtweezers and place it on the outer canthus of the mouse's eyes for 30 seconds. The length of the wet and red part of the phenol red cotton thread was measured as the estimated tear volume (in millimeters). Each eye was measured three times, and the readings were taken by two people and the average value was calculated. The results are as follows Figure 1 shown.

[0048] from Figure 1As can be seen in the results, before treatment (8 weeks of age), there was no significant difference in tear secretion between the model group (Model) mice and the control, low-dose (Low) and high-dose (High) groups (p>0.05). After 12 weeks of treatment (20 weeks of age), tear secretion in both the low-dose and high-dose groups increased significantly compared to the model group, with the high-dose group showing a more pronounced increase (p=0.0026), approaching that of the control group, indicating that the Chinese medicine combination significantly enhanced tear secretion in experimental mice.

[0049] 2) The corneal staining scores of mice were measured once at 8 weeks of age and 20 weeks of age (i.e., before and after intervention). The specific method is as follows: Use a micropipette to drip 1uL of 1% sodium fluorescein solution (internationalmedicationsystems, LTD) into the conjunctival sac below the NOD mouse without surface anesthesia. After 3 minutes, use cobalt blue light to examine and record under a slit lamp microscope. The cornea is divided into four quadrants: above the nose, below the nose, above the temporal, and below the temporal. Each quadrant is scored according to the following criteria: no staining, 0 points; slight punctate staining with less than 30 points, 1 point; punctate staining with more than 30 points, 2 points; severe diffuse staining but no obvious flakes, 3 points; obvious flake staining, 4 points. The scores of each area are added together to obtain the final score (total score: 16 points). The results are as follows: Figure 2 and Figure 3 shown.

[0050] from Figure 2 It can be seen that before treatment, there was no significant difference in the corneal staining scores of the mice in the model group, low-dose group and high-dose group (p>0.05); after 12 weeks of treatment, the corneal staining scores of the mice in the high-dose group (High) were significantly reduced compared with the model group (p=0.0094), a decrease of about 15%, and slightly higher than the control group ( Figure 3 ), indicating that the Chinese medicine combination can significantly reduce the corneal staining score of mice.

[0051] 3) At 20 weeks of age (i.e., 12 weeks after intervention), the mice were killed, and one lacrimal gland was removed and immediately fixed with 4% paraformaldehyde and embedded in paraffin. All sections were cut into 2 μm thick sections and stained with hematoxylin and eosin for 3 minutes. The sections were observed and images were collected under a microscope, and the area of ​​lymphocyte infiltration lesions in each field of view was calculated using ImageJ software. Finally, the ratio of the lymphocyte infiltration area to the total area of ​​the lacrimal gland was calculated. The results are shown in Figure 2. Figure 4 and Figure 5 shown.

[0052] As can be seen from the figure, compared with the pathological HE staining of the lacrimal glands of the control group (Control) mice, the proportion of lymphocyte infiltration area in the lacrimal glands of the model group mice was significantly increased (p < 0.0001); compared with the model group (Model), the lymphocyte infiltration area of ​​the low-dose group (Low) and the high-dose group (High) mice were significantly reduced (p values ​​were less than 0.05), indicating that the Chinese medicine combination can significantly reduce the lymphocyte infiltration of the lacrimal glands of experimental mice.

[0053] In summary, the Chinese medicine composition of the present invention can enhance the lacrimal gland secretion function of Sjögren's syndrome model mice, reduce the corneal staining score of mice, and improve lacrimal gland lymphocyte infiltration.

[0054] 2. The Chinese medicine composition of the present invention is used in combination with hydroxychloroquine sulfate

[0055] 1) Case inclusion criteria

[0056] Traditional Chinese Medicine diagnostic criteria

[0057] With reference to the diagnosis of dryness and white astringency syndrome in the "TCM Diagnosis and Treatment Plan for 95 Diseases in 22 Specialties" issued by the State Administration of Traditional Chinese Medicine in 2010, the following criteria were established: (1) Main symptoms ① Dry, dull, and astringent eyes; ② Dry mouth; ③ Fatigue and weakness; (2) Secondary symptoms ① Dry skin and nasal cavity; ② Weakness in waist and knees; ③ Palpitations and shortness of breath; ④ Dark eyes; ⑤ Poor appetite; ⑥ Frequent urination at night; ⑦ Loose stool or constipation (3) Tongue and pulse: Pale or red tongue, white or scanty fur, weak or thready pulse. Diagnostic criteria: Main symptoms ① and ② are required; Secondary symptoms ③, ⑤, and ⑦ must have one or more of them, and ②, ④, and ⑥ must have one or more of them. Combined with tongue and pulse, if the above criteria are met, it can be diagnosed as kidney essence deficiency syndrome.

[0058] Western medicine diagnostic standards

[0059] Diagnostic criteria for Sjögren's syndrome: refer to the Sjögren's syndrome classification criteria developed by the American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) in 2016.

[0060] Inclusion criteria: Patients with at least one of the symptoms of dry eyes or dry mouth, that is, at least one of the following is positive:

[0061] (1) Unbearable dry eyes every day for more than 3 months;

[0062] (2) recurring gritty sensation in the eyes;

[0063] (3) need to use artificial tears 3 or more times a day;

[0064] (4) Daily dry mouth for more than 3 months;

[0065] (5) Swallowing dry food requires frequent drinking of water. Or suspected SS patients with at least one positive system in the EULAR SS Disease Activity Index (ESSDAI) questionnaire.

[0066] Exclusion criteria included history of head and neck radiotherapy, active hepatitis C virus infection, acquired immunodeficiency syndrome, sarcoidosis, amyloidosis, graft-versus-host disease, immunoglobulin G4 (IgG4)-related diseases, and use of anti-acetylcholine drugs within the past 3 months.

[0067] Applicable to anyone who meets the above inclusion criteria and excludes the exclusion criteria, and whose total score of the following five items is ≥4 is diagnosed as Sjögren's syndrome:

[0068] (1) Focal lymphocytic infiltration of the labial gland with a focal index ≥ 1 foci / 4 mm 2 , which is 3 points;

[0069] (2) serum anti-SSA antibody positive, 3 points;

[0070] (3) at least one eye had an OSS score ≥5 or a Van Bijsterveld score ≥4, which was 1 point;

[0071] (4) at least one tear secretion test (Schirmer test) ≤ 5 mm / 5 min, 1 point;

[0072] (5) Unstimulated whole saliva flow rate ≤ 0.1 ml / min (Navazesh and Kumar method), scored 1 point.

[0073] 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.

[0074] Diagnostic criteria for dry eye: formulated with reference to the "Chinese Dry Eye Expert Consensus: Examination and Diagnosis (2020)":

[0075] (1) Patients complain of one of the subjective symptoms such as dry eyes, foreign body sensation, burning sensation, red eyes, and visual fluctuations; the Chinese Dry Eye Questionnaire Scale is ≥7 points or the OSDI Scale is ≥13 points (see Appendix 1, 2). At the same time, the patient's tear film break-up time (FBUT) is ≤5s or the Schirmer I test (without anesthesia) is ≤5mm / 5min. Dry eyes can be diagnosed.

[0076] (2) The patient has dry eye-related symptoms, with a score of ≥7 on the Chinese Dry Eye Questionnaire or ≥13 on the OSDI scale; meanwhile, if the patient has 5s < BUT ≤ 10s and 5mm / 5min < Schirmer I test (without anesthesia) ≤ 10mm / 5min, then the fluorescein sodium staining method should be used to examine the cornea and conjunctiva, and a positive staining (≥5 points) can diagnose dry eye.

[0077] Case inclusion criteria

[0078] ① Meeting the above-mentioned Western medicine diagnostic criteria for Sjogren's syndrome and dry eye, as well as the traditional Chinese medicine syndrome diagnostic criteria;

[0079] ② Meeting the diagnostic criteria for the syndrome of deficiency of kidney essence in traditional Chinese medicine;

[0080] ③ Those who have not received drug treatment within 1 month.

[0081] Case exclusion criteria

[0082] ① Those who are allergic to the study drugs;

[0083] ② Those who have been diagnosed with other connective tissue diseases;

[0084] ③ Those with a history of previous eye surgery or combined with other ocular surface diseases;

[0085] ④ Pregnant, lactating, or women in the preconception period;

[0086] ⑤ Those with combined severe cardiovascular and cerebrovascular diseases, liver and kidney damage, hematopoietic system abnormalities, etc., as well as those with mental disorders.

[0087] Those who meet any one of the above shall be excluded.

[0088] Criteria for exclusion, dropout, and termination of the experiment

[0089] ① Exclusion: Subjects who should not have been included but have been included should be excluded, including: misenrolled, misdiagnosed, those who have not taken any medicine, and those without any detection records.

[0090] The reasons for excluding the cases should be explained, and their data should be retained for future reference. Those who do not undergo efficacy statistical analysis but have received at least one treatment and have at least one safety record can participate in the adverse reaction analysis.

[0091] ② Dropout: Cases that have been included but have not completed the clinical protocol should be regarded as dropouts in the following situations: patients withdrawing on their own, being lost to follow-up, having poor compliance, or being withdrawn by the doctor due to complications.

[0092] The reasons for the dropout cases should be explained. If there are baseline efficacy data, the results of their last main efficacy index can be transferred as the final result for statistical analysis, and their data should be retained for future reference.

[0093] ③ Complete termination of the trial: when safety issues are discovered, the efficacy is too poor, or there are major errors in the plan.

[0094] 2) A total of 66 patients were enrolled in this study, all from the outpatient department of rheumatology at Chongqing Traditional Chinese Medicine Hospital. They were divided into a combined Chinese and Western medicine group and a Western medicine group (33 patients in each group) based on their existing treatment regimen. During clinical observation, two patients in the combined Chinese and Western medicine group dropped out due to loss of contact; three patients in the Western medicine group dropped out due to changes in treatment regimen. A total of 31 patients were actually enrolled in the combined Chinese and Western medicine group and 30 patients in the Western medicine group, for a total of 61 patients (see Table 1). There were 31 patients in the combined Chinese and Western medicine group, including 0 males and 31 females; there were 30 patients in the Western medicine group, including 0 males and 30 females. The gender distribution of the two groups was comparable (P = 0.305). Before treatment, the average age of patients in the combined Chinese and Western medicine group and the Western medicine group was determined. At the same time, the two groups of patients were tested for the ocular surface disease scale score (OSDI), binocular Schimer I test (SIT), tear film breakup time (BUT) and tear meniscus height (TMH). Statistical analysis showed that there was no statistically significant difference in the above indicators between the two groups of patients, and they were comparable (P=>0.05). See Tables 1 to 6 for details.

[0095] Table 1 Age distribution of cases

[0096]

[0097] Table 2 Comparison of OSDI scores before treatment

[0098]

[0099] Table 3 Comparison of SIT test before treatment

[0100]

[0101] Table 4 Comparison of BUT test before treatment

[0102]

[0103] Table 5 Comparison of TMH test before treatment

[0104]

[0105] Table 6 Comparison of TCM symptom scores before treatment

[0106]

[0107] The patients in the Western medicine group were made to take hydroxychloroquine sulfate tablets (Fenle) (0.1g / tablet, manufacturer: Shanghai Shangyao Zhongxi Pharmaceutical Co., Ltd., national medicine standard: H19990263), 2 times a day, 2 tablets each time, taken after meals. The patients in the combined Chinese and Western medicine group were made to take the medicament prepared by Example 1 of the present invention on the basis of the Western medicine group, 1 dose (medicinal liquid prepared by Example 1) every day, divided into 3 doses after meals, 30 minutes apart from the Western medicine. The combined Chinese and Western medicine group and the Western medicine group were observed for a course of treatment of 8 weeks. Then the total effective rate, ocular surface disease word count scale score (OSDI), binocular Schimer I test (SIT), tear film breakup time (BUT) and tear meniscus height (TMH) of the combined Chinese and Western medicine group and the Western medicine group were compared. The specific data are shown in Tables 7 to 12.

[0108] TCM symptom efficacy evaluation standards (refer to the "TCM Disease Diagnosis and Efficacy Standards" issued by the State Administration of Traditional Chinese Medicine):

[0109] Markedly effective: TCM symptoms and signs disappear or almost disappear, and the TCM symptom score reduction rate is ≥70%;

[0110] Effective: TCM symptoms and signs have improved, with a TCM symptom score reduction rate of 30% or less and less than 70%;

[0111] Ineffective: There is no significant improvement in TCM symptoms and signs, or they may even worsen, and the TCM symptom score reduction rate is less than 30%.

[0112] TCM symptom score reduction rate = [(score before treatment - score after treatment) / score before treatment] × 100%

[0113] Total effective rate = [number of effective cases / total number of cases] × 100%

[0114] Table 7 Total effective rate of cases after treatment

[0115]

[0116] Table 8 OSDI scores of patients after treatment

[0117]

[0118] Table 9 SIT test after treatment of patients

[0119]

[0120]

[0121] Table 10 BUT test of cases after treatment

[0122]

[0123] Table 11 TMH determination of cases after treatment

[0124]

[0125] Table 12 Comparison of TCM symptom scores after treatment

[0126]

[0127] The results showed that: as can be seen from Table 6, the total effective rate of the combined Chinese and Western medicine group was 90.32%, and the total effective rate of the Western medicine group was 63.33%. The intra-group comparison of OSDI scores after treatment showed that both groups of drugs had a significant therapeutic effect on patients with Sjögren's syndrome (p<0.001), while the inter-group comparison showed that the OSDI score of the combined Chinese and Western medicine group decreased significantly more than that of the Western medicine group (Table 7), and the difference between the two groups was statistically significant (p<0.001). From the perspective of the SIT test, both groups can effectively improve the patients' tear secretion (p<0.001), but the inter-group comparison showed that the combined Chinese and Western medicine group was better than the Western medicine group in enhancing tear secretion (p<0.05). From the perspective of the BUT test, both groups can effectively prolong the patients' tear film breakup time (p<

[0128] 0.001), but inter-group comparison showed that the combined Chinese and Western medicine group was superior to the Western medicine group in prolonging tear film breakup time (p = 0.012). In terms of TMH test, both groups were able to effectively increase the patients' tear meniscus height (p < 0.001), but inter-group comparison showed that the combined Chinese and Western medicine group was superior to the Western medicine group in increasing the tear meniscus height (p < 0.001). In terms of Traditional Chinese Medicine symptom scores, both groups were able to reduce the patients' Traditional Chinese Medicine symptom scores, but inter-group comparison showed that the Traditional Chinese Medicine syndrome scores of the combined Chinese and Western medicine group were significantly lower than those of the Western medicine group (p < 0.001).

[0129] In summary, in terms of overall efficacy, the combination of Chinese and Western medicine group has better efficacy, which can improve the lacrimal gland secretion, tear film breakup time, tear meniscus height, and symptoms of patients with Sjögren's syndrome.

[0130] The above description is only a preferred embodiment of the present invention and does not limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating dry eye associated with Sjögren's syndrome, characterized in that: The invention comprises the following components in parts by weight: 5-30 parts of salt raspberry, 5-30 parts of salt dodder seed, 10-45 parts of astragalus, 15-45 parts of dried dendrobium, 5-20 parts of cyathula, 5-15 parts of honey polygala, 5-15 parts of honeysuckle, 5-20 parts of wolfberry, 5-20 parts of salt plantain seed, 5-15 parts of schisandra and 15-45 parts of scrophularia; the dry eye associated with Sjögren's syndrome is of the kidney essence deficiency type.

2. The Chinese medicine composition for treating dry eye associated with Sjögren's syndrome according to claim 1, characterized in that: The invention comprises the following components in parts by weight: 15 parts of salt raspberry, 15 parts of salt dodder seed, 30 parts of astragalus, 30 parts of dried dendrobium, 15 parts of cyathula, 10 parts of honey polygala, 10 parts of honeysuckle, 15 parts of wolfberry, 10 parts of salt plantain seed, 10 parts of schisandra chinensis and 30 parts of scrophularia.

3. Use of the Chinese medicine composition according to claim 1 or 2 in the preparation of a drug for treating dry eyes associated with Sjögren's syndrome.

4. The application according to claim 3, characterized in that The medicine also includes pharmaceutically acceptable carriers and excipients.

5. The application according to claim 3, characterized in that: The dosage form of the medicine includes decoction, granules, tablets, capsules or oral liquid.

6. A pharmaceutical preparation for treating dry eye associated with Sjögren's syndrome, characterized in that: The pharmaceutical preparation uses the Chinese medicine composition or the extract of the Chinese medicine composition according to claim 1 or 2 as an effective ingredient.

7. A composite pharmaceutical preparation for treating dry eye associated with Sjögren's syndrome, characterized in that: The compound pharmaceutical preparation comprises the traditional Chinese medicine composition or the extract of the traditional Chinese medicine composition according to claim 1 or 2 and hydroxychloroquine sulfate.

8. The pharmaceutical preparation according to claim 6 or 7, characterized in that The pharmaceutical preparation also includes pharmaceutically acceptable carriers and excipients.

9. The pharmaceutical preparation according to claim 6 or 7, characterized in that The dosage form of the pharmaceutical preparation includes decoction, granules, tablets, capsules or oral liquid.

10. The pharmaceutical preparation according to claim 6 or 7, characterized in that The dry eye associated with Sjögren's syndrome is of the kidney essence deficiency type.

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