A traditional Chinese medicine composition for treating dry eye associated with Sjögren's syndrome and its application

Abstract

This invention discloses a traditional Chinese medicine composition for treating Sjögren's syndrome-related dry eye and its application. The composition is rationally formulated and obtained through extensive experimental screening and long-term clinical experience. It possesses the functions of nourishing kidney essence, replenishing qi and yin, and moistening dryness and improving vision. It can enhance lacrimal gland secretion function in Sjögren's syndrome model mice, improve corneal staining scores, improve lacrimal gland lymphocyte infiltration, reduce TCM syndrome scores in patients with Sjögren's syndrome-related dry eye, and ultimately improve the clinical symptoms of related dry eye. It is particularly effective and has a more significant effect on Sjögren's syndrome-related dry eye caused by kidney essence deficiency. The traditional Chinese medicine composition of this invention can be administered alone or in combination. This pharmaceutical composition is a safe and effective pure traditional Chinese medicine preparation with no toxic side effects. The quality of the constituent herbs is easy to control, the cost is low, and it has good application prospects.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition for treating dry eye associated with Sjögren's syndrome and its application. Background Technology

[0002] Sjögren's syndrome is an autoimmune disease in which exocrine glands are infiltrated and destroyed by lymphocytes. The lacrimal glands and salivary glands are most easily affected. When Sjögren's syndrome affects the lacrimal glands and causes related clinical manifestations of lacrimal gland dysfunction, such as dry eyes, foreign body sensation, stinging, tearing or burning sensation, it is called Sjögren's syndrome-associated dry eye (SSDE).

[0003] Epidemiological studies show that the prevalence of Sjögren's syndrome in the general population is approximately 0.2% to 0.6%, with related dry eye occurring in as many as 72% to 85% of this group. Sjögren's syndrome (SSDE) is characterized by its prolonged course, high recurrence rate, and clinical difficulty in treatment. Patients often experience anxiety disorders and even depressive tendencies due to persistent dryness and irritation of the ocular surface, ultimately leading to a significant decline in mental health and social function. Currently, Western medicine primarily employs symptomatic and supportive treatment strategies, such as artificial tears. While these can temporarily alleviate subjective symptoms, they are insufficient to halt the progression of glandular parenchymal damage, and long-term use may induce iatrogenic complications such as secondary infections. Surgical treatment lacks universal applicability and carries significant risks and high costs. Therefore, there is an urgent need to find new clinical treatment methods.

[0004] The pathogenesis of Sjögren's syndrome (SSDE) is not yet fully understood. It is generally believed that the disease is closely related to factors such as genetics, immune system dysfunction, and viral infection. Clinical practice and some studies have shown that traditional Chinese medicine (TCM) treatment has significant advantages, particularly in improving ocular surface function, relieving dry eyes, reducing disease recurrence, and improving patients' quality of life, often leading to a greater sense of satisfaction for patients. Currently, the TCM pathogenesis of Sjögren's syndrome largely focuses on "yin deficiency and dryness-heat," so clinical interventions commonly employ heat-clearing and yin-nourishing principles. For example, invention patent CN119548593A discloses a TCM composition for treating Sjögren's syndrome, containing 10 parts Artemisia annua, 10 parts Paeonia lactiflora, 10 parts Scutellaria baicalensis, 10 parts Citrus reticulata peel, 10 parts Dendrobium nobile, and 10 parts Salvia miltiorrhiza. This composition inhibits Tfh proliferation and reduces IL-21 secretion by acting on STAT3 phosphorylation, thereby alleviating humoral immune disorders and treating Sjögren's syndrome. The main approach is to clear damp-heat, remove blood stasis, and promote fluid production to improve exocrine gland function, regulate immunity, and relieve dryness. However, in actual clinical practice, there are few traditional Chinese medicines used to treat SSDE alone, so there is an urgent need to find new and effective treatment methods. Summary of the Invention

[0005] To address the shortcomings of the existing technologies, the technical problem this invention aims to solve is: how to provide a traditional Chinese medicine composition for treating Sjögren's syndrome-related dry eye, which significantly improves the clinical symptoms, enhances quality of life, and slows disease progression in patients with Sjögren's syndrome-related dry eye. Its application in the treatment of Sjögren's syndrome-related dry eye has also been explored, showing particularly good efficacy in patients with kidney deficiency, thus providing a new approach to the treatment of Sjögren's syndrome-related dry eye.

[0006] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: a traditional Chinese medicine composition for treating dry eye related to Sjögren's syndrome, comprising the following components by weight: 5-30 parts of salted raspberry, 5-30 parts of salted dodder seed, 10-45 parts of astragalus, 15-45 parts of dried dendrobium, 5-20 parts of Sichuan achyranthes root, 5-15 parts of honey-processed polygala root, 5-15 parts of honeysuckle flower, 5-20 parts of wolfberry fruit, 5-20 parts of salted plantain seed, 5-15 parts of schisandra fruit, and 15-45 parts of scrophularia root; wherein the dry eye related to Sjögren's syndrome is of the kidney essence deficiency type. This invention combines clinical practice and research on the treatment of Sjögren's syndrome-related dry eye with traditional Chinese medicine. It uses the improvement of lacrimal gland secretion function in patients with Sjögren's syndrome-related dry eye and Sjögren's syndrome activity score as efficacy indicators. Through dialectical analysis of the pathogenesis of Sjögren's syndrome-related dry eye and a review of the efficacy of traditional Chinese medicine, it was found that salt-processed raspberry, salt-processed dodder seed, astragalus, dried dendrobium, Sichuan achyranthes root, honey-processed polygala root, honeysuckle, wolfberry, salt-processed plantain seed, schisandra fruit, and scrophularia root have a synergistic effect of nourishing kidney essence, and have a good therapeutic effect on Sjögren's syndrome-related dry eye due to kidney essence deficiency, thus forming this invention.

[0007] The medicinal properties of each component are as follows:

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

[0009] Salt-processed dodder seed: It enters the liver, kidney, and spleen meridians. It has the effects of tonifying the liver and kidneys, consolidating essence and reducing urination, calming the fetus, and improving eyesight.

[0010] Astragalus: Enters the Lung and Spleen meridians. It has the effects of tonifying Qi and strengthening the exterior, promoting diuresis and eliminating toxins, draining pus, and promoting wound healing and 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 irritability, and benefiting the stomach and promoting the production of body fluids.

[0012] Achyranthes bidentata: It enters the liver and kidney meridians. It has the effects of removing blood stasis and promoting menstruation, tonifying the liver and kidneys, strengthening tendons and bones, and promoting diuresis and relieving strangury.

[0013] Honey-processed Polygala tenuifolia: Enters the heart, kidney, and lung meridians. It has the effects of calming the mind and improving intelligence, harmonizing the heart and kidneys, and clearing phlegm and opening the orifices.

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

[0015] Goji berries: They enter the liver and kidney meridians. They nourish the liver and kidneys, and benefit the essence and eyesight.

[0016] Salt-processed plantain seeds: Enter the liver, kidney, and lung meridians. They have the effects of clearing heat, promoting diuresis, relieving urinary tract infections, eliminating dampness, stopping diarrhea, and improving eyesight.

[0017] Schisandra chinensis: It enters the lung, heart, and kidney meridians. It has the effects of astringing and consolidating, replenishing qi and promoting body fluids, and tonifying the kidneys and calming the mind.

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

[0019] In this invention, salt-processed Cuscuta chinensis and salt-processed Raspberry are the principal herbs, working synergistically to tonify the kidneys and replenish essence. The salting process enhances their kidney-tonifying effect, addressing the root cause of kidney essence deficiency. They replenish kidney essence while simultaneously consolidating the lower abdomen to prevent loss of vital essence. Raspberry also nourishes the liver and improves eyesight. Goji berries are the assistant herbs, gently tonifying the liver and kidneys, nourishing kidney yin and liver blood, moistening the eyes and relieving dryness. Astragalus membranaceus is also an assistant herb, used for its qi-tonifying, yang-raising, and defensive qi-strengthening effects. It greatly tonifies the spleen and lung qi; when qi is abundant, it promotes fluid circulation, guiding fluids upwards to the eyes, resolving the pathogenesis of "qi failing to distribute fluids," and simultaneously improving systemic qi deficiency symptoms. Dried Dendrobium nobile, sweet, cold, and moistening, is also an assistant herb. Due to its yin-nourishing, heat-clearing, stomach-nourishing, fluid-generating, and vision-improving effects, it nourishes the yin of the kidneys and stomach, generating fluids and moistening dryness. Combined with Astragalus membranaceus, it forms a "dual tonification of qi and yin" pattern, addressing the secondary contradiction of qi and yin deficiency. Scrophularia ningpoensis acts as an assistant herb, nourishing yin and reducing fire, clearing deficiency heat without harming yin. It targets eye injuries caused by yin deficiency and excessive fire, preventing further depletion of body fluids by the deficiency fire. Honey-processed Polygala tenuifolia and Lonicera japonica work together as adjuvant herbs; the former calms the mind, improves intelligence, eliminates phlegm, and opens the orifices, while the latter clears heat, detoxifies, reduces swelling, and dissipates nodules. Their synergistic effect alleviates discomfort such as palpitations and shortness of breath, and clears internal heat toxins. Achyranthes bidentata primarily functions to invigorate blood circulation, remove blood stasis, and guide fire downwards, helping to regulate blood circulation in the eyes and reduce eye fatigue; it serves as an adjuvant herb. Schisandra chinensis, with its sour and astringent properties, consolidates kidney essence; it also serves as an adjuvant herb, working synergistically with Cuscuta chinensis and Rubus idaeus to prevent the leakage of essence and enhance the yin-nourishing effect. Plantago asiatica promotes urination, clears turbidity, separates clear from turbidity, and brightens the eyes, ensuring that tonification is not stagnant; after salt processing, it specifically enters the kidney meridian, guiding deficiency heat out through urination; it serves as the guiding herb. The combined use of these herbs addresses both the core pathogenesis of kidney essence deficiency and the secondary contradiction of qi and yin deficiency. Through rational formulation, the entire formula nourishes kidney essence, replenishes qi and yin, moistens dryness and improves vision, thereby significantly improving the symptoms of dry eye associated with Sjögren's syndrome.

[0020] Preferably, the traditional Chinese medicine composition comprises the following components in parts by weight: 15 parts salted raspberry, 15 parts salted dodder seed, 30 parts astragalus, 30 parts dried dendrobium, 15 parts Sichuan achyranthes root, 10 parts honey-processed polygala root, 10 parts honeysuckle flower, 15 parts wolfberry, 10 parts salted plantain seed, 10 parts schisandra fruit, and 30 parts scrophularia root.

[0021] Another object of the present invention is to provide the application 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 also includes a drug-acceptable carrier 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 uses the above-mentioned traditional Chinese medicine composition or an extract of the traditional Chinese medicine composition as the 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, the compound pharmaceutical preparation comprising 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 includes a pharmaceutically acceptable carrier and excipients.

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

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

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

[0030] 1. The formulation of the herbal composition of this invention is rationally designed and obtained through extensive experimental screening and long-term clinical experience accumulation. It possesses the functions of nourishing kidney essence, replenishing qi and nourishing yin, moistening dryness and improving vision. It can enhance the lacrimal gland secretion function in Sjögren's syndrome model mice, improve corneal staining scores, improve lacrimal gland lymphocyte infiltration, and reduce the TCM syndrome scores of patients with Sjögren's syndrome-related dry eye. It is particularly effective and has a more significant effect on Sjögren's syndrome-related dry eye caused by kidney essence deficiency. The pharmaceutical composition of this invention is a safe and effective pure herbal preparation with no toxic side effects. The quality of the constituent herbs is easy to control, and the cost is low, showing good application prospects. This invention provides new ideas and theoretical basis for the research on the treatment of Sjögren's syndrome-related dry eye, and is of great significance.

[0031] 2. Animal experiments show that when used alone, the traditional Chinese medicine composition of the present invention can enhance the lacrimal gland secretion function of mice with Sjögren's syndrome-related dry eye model, reduce the corneal staining score of mice, and reduce lymphocyte infiltration in the lacrimal glands of mice, indicating that the traditional Chinese medicine composition of the present invention can be used for the treatment of Sjögren's syndrome-related dry eye. It has been found in clinical application that when the traditional Chinese medicine composition of the present invention is combined with hydroxychloroquine sulfate, the synergistic effect of the two can improve the lacrimal gland secretion function of patients with Sjögren's syndrome, reduce the traditional Chinese medicine syndrome score of patients with Sjögren's syndrome, and improve the quality of life of patients, and the effect is significantly better than that of single medication. The traditional Chinese medicine composition of the present invention can be administered alone or in combination, and both achieve significant therapeutic effects. Description of Drawings

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

[0033] Figure 2 Shows comparative photographs of corneal staining of mice in different treatment groups before and after 12 weeks of treatment.

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

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

[0036] Figure 5 Shows a comparison diagram of lymphocyte infiltration area in lacrimal glands of mice in different treatment groups after 12 weeks of treatment. Detailed Description of Embodiments

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

[0038] I. A traditional Chinese medicine composition for treating Sjögren's syndrome-related dry eye

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

[0040] 1) Weigh each raw material in the following parts by weight: 15 parts of salt-processed Rubi Fructus, 15 parts of salt-processed Cuscutae Semen, 30 parts of Astragali Radix, 30 parts of dried Dendrobii Caulis, 15 parts of Cyathulae Radix, 10 parts of honey-processed Polygalae Radix, 10 parts of Lonicerae Japonicae Flos, 15 parts of Lycii Fructus, 10 parts of salt-processed Plantaginis Semen, 10 parts of Schisandrae Chinensis Fructus, and 30 parts of Scrophulariae Radix.

[0041] 2) Soak all the raw materials in water for 30 minutes, bring to a boil over high heat and then simmer over low heat for 30 minutes. Filter out the decoction, repeat twice, mix the decoctions, and concentrate into a liquid containing 0.5g / mL of raw herbs. Store in a refrigerator at 4℃ for later use.

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

[0043] 1) Weigh each ingredient according to the following weight proportions: 20 parts salted raspberry, 20 parts salted dodder seed, 20 parts astragalus, 20 parts dried dendrobium, 10 parts Sichuan achyranthes root, 10 parts honey-processed polygala root, 10 parts honeysuckle, 20 parts wolfberry, 10 parts salted plantain seed, 5 parts schisandra fruit, and 15 parts scrophularia root.

[0044] 2) Soak all the raw materials in water for 30 minutes, bring to a boil over high heat and then simmer over low heat for 30 minutes. Filter out the decoction, repeat twice, mix the decoctions, and concentrate into a liquid containing 0.5g / mL of raw herbs. Store in a refrigerator at 4℃ for later use.

[0045] II. Application of Traditional Chinese Medicine Combinations

[0046] 1. To verify whether the herbal composition of this invention has a therapeutic effect on dry eye associated with Sjögren's syndrome, 7-week-old female NOD / Ltj mice and female ICR mice were selected. The female NOD mice served as the model mice. NOD mice are commonly used as a spontaneous mouse model of Sjögren's syndrome; at 9 weeks of age, the peripheral glands are gradually infiltrated and destroyed by lymphocytes. Eighteen NOD mice were randomly divided into three groups after one week of acclimatization: a model group, a low-dose group, and a high-dose group. Six ICR mice were used as a control group after one week of acclimatization. The high-dose group was administered the herbal solution prepared in Example 1 by gavage at 28.8 g / kg daily, the low-dose group was administered the herbal solution prepared in Example 1 by gavage at 14.4 g / kg daily, and the model group and control group were administered the same dose of physiological saline daily. After 4 weeks, the administration was changed to once every other day for 8 weeks.

[0047] 1) Tear secretion in mice was measured once at 8 weeks and 20 weeks of age (before and after intervention) without topical anesthesia of the eyes. The specific method was as follows: A phenol-red cotton thread (Tianjin Jingming New Technology Development Co., Ltd.) was held with micro-forceps and placed at the outer canthus of both eyes of the mouse for 30 seconds. The length of the moistened and reddened portion of the phenol-red cotton thread was measured as an estimate of tear volume (in millimeters). Measurements were repeated three times for each eye, and the average value was taken from the readings taken by two people. Results are as follows: Figure 1 As shown.

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

[0049] 2) Corneal staining scores were measured in mice at 8 weeks and 20 weeks of age (before and after intervention). The specific method was as follows: 1 μL of 1% sodium fluorescein solution (International Medical Systems, LTD) was instilled into the conjunctival sac of unanescorted NOD mice using a micro-instillation device. After 3 minutes, the cornea was examined and photographed under a slit-lamp microscope using cobalt blue light. The cornea was divided into four quadrants: superior nasal, inferior nasal, superior temporal, and inferior temporal. The scoring criteria for each quadrant were: no staining, 0 points; slight punctate staining (less than 30 points), 1 point; punctate staining (more than 30 points), 2 points; severe diffuse staining without obvious patches, 3 points; obvious patchy staining, 4 points. The scores for each quadrant were summed to obtain the final score (total score: 16 points). The results are as follows: Figure 2 and Figure 3 As shown.

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

[0051] 3) Mice were sacrificed at 20 weeks of age (i.e., 12 weeks after intervention), and one lacrimal gland was harvested. The tissue was immediately fixed in 4% paraformaldehyde and embedded in paraffin. All sections were cut into 2 μm thick slices and stained with hematoxylin and eosin for 3 minutes. The sections were observed under a microscope, and images were acquired. 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. Results are as follows: Figure 4 and Figure 5 As shown.

[0052] As shown in the figure, compared with the control group (Control) mice, the proportion of lymphocyte infiltration area in the lacrimal gland of the model group mice was significantly increased (p < 0.0001); compared with the model group (Model), the lymphocyte infiltration area in both the low-dose group (Low) and the high-dose group (High) mice was significantly reduced (p < 0.05), indicating that this combination of traditional Chinese medicine can significantly reduce lymphocyte infiltration in the lacrimal gland of experimental mice.

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

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

[0055] 1) Case inclusion criteria

[0056] Traditional Chinese Medicine Diagnostic Criteria

[0057] Referring to the diagnosis of dryness and leukorrhea in the "Traditional Chinese Medicine Diagnosis and Treatment Plan for 22 Specialties and 95 Diseases" issued by the State Administration of Traditional Chinese Medicine in 2010, the following criteria are established: (1) Primary symptoms ① Dry and dull eyes; ② Dry mouth; ③ Fatigue and weakness; (2) Secondary symptoms ① Dry skin and nasal cavity; ② Soreness and weakness of the waist and knees; ③ Palpitation and shortness of breath; ④ Dark circles under the eyes; ⑤ Poor appetite; ⑥ Frequent urination at night; ⑦ Loose stools or constipation; (3) Tongue and pulse: Pale or red tongue, white or little coating, thin and weak or thin and rapid pulse. Diagnostic criteria: Primary symptoms ① and ② are essential; 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 the tongue and pulse, if the above criteria are met, it can be diagnosed as kidney essence deficiency syndrome.

[0058] Western medicine diagnostic criteria

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

[0060] Inclusion criteria: Individuals with at least one of the following symptoms: dry eyes or dry mouth, i.e., at least one of the following is positive:

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

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

[0063] (3) Artificial tears need to be used 3 or more times a day;

[0064] (4) Feeling dry mouth every day for more than 3 months;

[0065] (5) Frequent water intake is required to help swallow dry food. Or, a suspected SS patient with at least one systemic positive result on the EULAR SS Disease Activity Index (ESSDAI) questionnaire.

[0066] Exclusion criteria: 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 anticholinergic drugs within the past 3 months.

[0067] This applies to anyone who meets the above inclusion criteria and excludes other individuals, and whose total score of the following five items is ≥4, and who is diagnosed with Sjögren's syndrome:

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

[0069] (2) Positive serum anti-SSA antibody, score 3;

[0070] (3) At least one eye with a corneal staining score (OSS) ≥5 or a Van Bijsterveld score ≥4 is considered as 1 point;

[0071] (4) A score of 1 point is given if the single tear secretion test (Schirmer test) is ≤5mm / 5min.

[0072] (5) Unstimulated total saliva flow rate ≤0.1ml / min (Navazesh and Kumar assay) is 1 point.

[0073] Patients who routinely use cholinergic drugs should discontinue the medication completely before undergoing the above-mentioned assessments for dry mouth and eyes in items (3), (4), and (5).

[0074] Dry eye diagnostic criteria: formulated with reference to the "Chinese Expert Consensus on Dry Eye: Examination and Diagnosis (2020)".

[0075] (1) Patients complain of one of the following subjective symptoms: dryness, foreign body sensation, burning sensation, redness, or fluctuating vision; scores ≥7 on the Chinese Dry Eye Questionnaire or ≥13 on the OSDI scale (see Appendix 1, 2); and 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 eye can be diagnosed.

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

[0077] Case inclusion criteria

[0078] ① Meet the above-mentioned Western medicine diagnostic criteria and traditional Chinese medicine (TCM) syndrome diagnostic criteria for Sjögren's syndrome and dry eye;

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

[0080] ③ Have not received drug treatment within 1 month.

[0081] Case exclusion criteria

[0082] ① Those allergic to the study drugs;

[0083] ② Patients already diagnosed with other connective tissue diseases;

[0084] ③ Have a previous history of eye surgery, or are complicated with other ocular surface diseases;

[0085] ④ Women in pregnancy, lactation or preparing for pregnancy;

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

[0087] Any subject meeting any of the above items shall be excluded.

[0088] Criteria for elimination, dropout and termination of the trial

[0089] ① Elimination: Subjects who should not have been enrolled but have been enrolled shall be eliminated, including: wrongly included, misdiagnosed, never used any study drug, and those without any test records.

[0090] The reason for elimination shall be specified, and the data of eliminated cases shall be kept for future reference. Such cases are not included in the efficacy statistical analysis, but those who have received at least one treatment and have at least one safety record can participate in the adverse reaction analysis.

[0091] ② Dropout: Enrolled cases that have not completed the clinical protocol shall be regarded as dropout under the following circumstances: voluntary withdrawal by the patient, loss to follow-up, poor compliance, and withdrawal ordered by the physician due to concomitant diseases.

[0092] The reason for dropout shall be specified. If there is baseline efficacy data, the result of the last main efficacy indicator can be transferred as the final result for statistical analysis, and the data of dropout cases shall 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 protocol.

[0094] 2) This study included 66 patients, all from the Rheumatology Department of Chongqing Traditional Chinese Medicine Hospital. Based on their existing treatment regimens, they were divided into a combined traditional Chinese and Western medicine group and a Western medicine group (33 patients in each group). During the clinical observation period, 2 patients in the combined traditional Chinese and Western medicine group dropped out due to loss of contact; 3 patients in the Western medicine group dropped out due to changes in their treatment regimens. The actual number of patients included was 31 in the combined traditional Chinese and Western medicine group and 30 in the Western medicine group, totaling 61 patients (see Table 1). The combined traditional Chinese and Western medicine group consisted of 31 patients (0 males and 31 females); the Western medicine group consisted of 30 patients (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 ocular surface disease word count scale (OSDI), bilateral Schimer I test (SIT), tear film breakup time (BUT) and tear hemoth height (TMH) of the two groups were tested. Statistical analysis showed that there were no statistically significant differences in the above indicators between the two groups, 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 scale scores before treatment

[0098]

[0099] Table 3 Comparison of SIT trials before treatment

[0100]

[0101] Table 4 Comparison of BUT tests before treatment

[0102]

[0103] Table 5 Comparison of TMH tests before treatment

[0104]

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

[0106]

[0107] Patients in the Western medicine group took hydroxychloroquine sulfate tablets (Fenle) (0.1g / tablet, manufacturer: Shanghai Shangyao Zhongxi Pharmaceutical Co., Ltd., National Drug Approval Number: H19990263), 2 tablets twice daily, after meals. Patients in the combined traditional Chinese and Western medicine group received the same treatment as the Western medicine group, combined with the preparation of the drug described in Example 1 of this invention, one dose daily (the drug solution prepared in Example 1), divided into three doses after meals, 30 minutes apart from the Western medicine. The treatment course for both the combined traditional Chinese and Western medicine group and the Western medicine group was 8 weeks. The total effective rate, ocular surface disease word count scale score (OSDI), bilateral Schimer I test (SIT), tear film breakup time (BUT), and tear river height (TMH) were then compared between the two groups. Specific data are shown in Tables 7-12.

[0108] Traditional Chinese Medicine Symptom-Based Efficacy Evaluation Criteria (referring to the "Standards for Diagnosis and Efficacy Evaluation of Diseases and Syndromes in Traditional Chinese Medicine" promulgated by the State Administration of Traditional Chinese Medicine):

[0109] Significant effect: TCM symptoms and signs disappear or basically disappear, and the TCM symptom score reduction rate is ≥70%;

[0110] Effective: Both TCM symptoms and signs improved, with a reduction rate of 30% ≤ TCM symptom score < 70%;

[0111] Ineffective: There is no significant improvement in TCM symptoms and signs, or even a worsening of symptoms; the reduction rate of TCM symptom scores is <30%.

[0112] The reduction rate of TCM symptom scores = [(pre-treatment score - post-treatment score) / pre-treatment score] × 100%

[0113] Overall effectiveness rate = [Number of effective cases / Total number of cases] × 100%

[0114] Table 7 Overall effective rate after treatment in cases.

[0115]

[0116] Table 8 OSDI scores of cases after treatment

[0117]

[0118] Table 9. SIT Trial After Treatment in Cases

[0119]

[0120]

[0121] Table 10 BUT test results after treatment in cases.

[0122]

[0123] Table 11 TMH Measurements After Treatment in Cases

[0124]

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

[0126]

[0127] The results showed that, as shown in Table 6, the total effective rate of the combined traditional Chinese medicine and Western medicine group was 90.32%, while that of the Western medicine group was 63.33%. Intra-group comparisons of OSDI scores after treatment indicated that both drugs had significant therapeutic effects on patients with Sjögren's syndrome (p<0.001), while inter-group comparisons showed that the OSDI score reduction in the combined traditional Chinese medicine and Western medicine group was significantly greater than that in the Western medicine group (Table 7), and the difference between the two groups was statistically significant (p<0.001). Regarding the SIT test, both groups effectively improved tear secretion (p<0.001), but inter-group comparisons showed that the combined traditional Chinese medicine and Western medicine group was more effective than the Western medicine group in enhancing tear secretion (p<0.05). Regarding the BUT test, both groups effectively prolonged the tear film breakup time (p<0.05).

[0128] While both groups showed an improvement of 0.001, intergroup comparisons showed that the combined traditional Chinese medicine and Western medicine group was superior to the Western medicine group in prolonging tear film breakup time (p = 0.012). Regarding the TMH test, both groups effectively increased the tear helix height (p < 0.001), but intergroup comparisons showed that the combined traditional Chinese medicine and Western medicine group was superior to the Western medicine group in increasing tear helix height (p < 0.001). In terms of TCM symptom scores, both groups reduced patients' TCM symptom scores, but intergroup comparisons showed that the combined traditional Chinese medicine and Western medicine group had significantly lower TCM syndrome scores than the Western medicine group (p < 0.001).

[0129] In summary, in terms of overall efficacy, the combination of traditional Chinese and Western medicine is more effective, improving lacrimal gland secretion, tear film breakup time, and tear meniscus height in patients with Sjögren's syndrome, and alleviating their symptoms.

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

Claims

1. A traditional Chinese medicine composition for treating dry eye associated with Sjögren's syndrome, characterized in that, It is made from the following ingredients in parts by weight: 15-20 parts salted raspberry, 15-20 parts salted dodder seed, 20-30 parts astragalus, 20-30 parts dried dendrobium, 10-15 parts Sichuan achyranthes root, 10 parts honey-processed polygala root, 10 parts honeysuckle, 15-20 parts wolfberry, 10 parts salted plantain seed, 5-10 parts schisandra fruit, and 15-30 parts scrophularia root; the dry eye associated with Sjögren's syndrome is of the kidney essence deficiency type.

2. The traditional Chinese medicine composition for treating dry eye associated with Sjögren's syndrome according to claim 1, characterized in that, It is made from the following ingredients in parts by weight: 15 parts salted raspberry, 15 parts salted dodder seed, 30 parts astragalus, 30 parts dried dendrobium, 15 parts Sichuan achyranthes root, 10 parts honey-processed polygala root, 10 parts honeysuckle, 15 parts wolfberry, 10 parts salted plantain seed, 10 parts schisandra fruit, and 30 parts scrophularia root.

3. The use of the traditional Chinese medicine composition as described in claim 1 or 2 in the preparation of a drug for treating dry eye associated with Sjögren's syndrome.

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

5. The application according to claim 3, characterized in that, The dosage forms of the drug include decoctions, granules, tablets, capsules, or oral liquids.

6. A pharmaceutical preparation for treating dry eye associated with Sjögren's syndrome, characterized in that, The pharmaceutical preparation is prepared using the traditional Chinese medicine composition or extract of the traditional Chinese medicine composition as the active ingredient as described in claim 1 or 2.

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