A Chinese medicine composition for treating Yin deficiency and phlegm-heat syndrome of Graves' disease and its application

Abstract

The present invention provides a Chinese medicine composition for treating Yin deficiency and phlegm heat syndrome of Graves' disease and its application. According to weight, the Chinese medicine composition comprises: 9-30 parts of Prunella Vulgaris, 9-40 parts of Scrophularia, 15-30 parts of raw oyster, 9-30 parts of Fritillaria Thunbergii, 9-30 parts of White Peony Root, and 9-30 parts of Rhizoma Dioscoreae. The Chinese medicine composition is screened for Chinese medicine prescription according to the theory of traditional Chinese medicine and accurate theory of TCM syndrome differentiation and treatment, and the formula is rigorous, the number of medicinal flavors is small, and for Graves' disease patients with Yin deficiency and phlegm heat syndrome in TCM syndrome differentiation, it can effectively reduce goiter, reduce FT3 and FT4 levels of Graves' disease patients, regulate TSH levels, reduce TRAb and TPOAb levels, and has the advantages of definite efficacy, convenient use, high safety, few adverse reactions, wide application range, etc. in treating Yin deficiency and phlegm heat syndrome of Graves' disease, and is better than conventional anti-thyroid western medicine treatment alone when used in combination with conventional anti-thyroid western medicine, and plays a synergistic effect.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and specifically comprises a traditional Chinese medicine composition for treating Yin deficiency and phlegm-heat syndrome of Graves' disease and application thereof. Background Art

[0002] Hyperthyroidism is a common disease of the endocrine system. It is caused by multiple factors inside or outside the thyroid gland, resulting in an increase in thyroid hormones, leading to a high metabolic syndrome. Among them, the most common type of hyperthyroidism is Graves' disease, accounting for about 85%. The disease is characterized by a long course of illness, easy recurrence, and is easily accompanied by clinical symptoms and signs such as hand tremors, irritability, exophthalmos, and neck pain, which have a great impact on the patient's life, work, and image.

[0003] There are three methods for treating hyperthyroidism in Western medicine: drug therapy, surgical resection and isotope therapy. Although they have played a good role in controlling hyperthyroidism, they all have certain limitations and shortcomings. At present, taking antithyroid drugs is the main treatment method of Western medicine. Commonly used antithyroid drugs include thioureas, iodine and iodide, radioactive iodine and beta-receptor blockers. Generally, the medication should be taken for one and a half to two years. Thioureas include thiouracils (methylthiouracil and propylthiouracil) and imidazoles (methimazole and carbimazole). Their pharmacological effects include: ① Inhibiting the synthesis of thyroid hormones by inhibiting thyroid peroxidase (itself as a substrate of peroxidase is oxidized), thereby inhibiting the iodination and coupling of tyrosine, but it is ineffective for synthesized thyroid hormones, so it often takes 2 to 3 weeks to improve symptoms and 1 to 2 months to restore the basal metabolic rate; ② Inhibiting the conversion of T4 in peripheral tissues into T3 with strong biological activity; ③ Reducing thyroid stimulating immunoglobulins in the blood circulation. Western anti-thyroid drug therapy has the disadvantages of long course of treatment, serious side effects, and high recurrence rate. It can cause drug-induced rash, suppress white blood cells, and even damage the liver. Surgical therapy is suitable for patients with thyroid enlargement of grade II or above. Inadvertent damage to the recurrent laryngeal nerve during surgery can cause hoarseness, and damage to the parathyroid gland can cause hypocalcemic convulsions. Radioisotope therapy is suitable for non-childbearing patients over 18 years old, and some patients are concerned about the side effects of isotopes. Surgical resection and isotope treatment may cause lifelong hypothyroidism, aggravated exophthalmos, and other complications. Therefore, how to improve the clinical cure rate, reduce the recurrence rate, and reduce the potential damage to the liver and blood system caused by Western medicine treatment has become the main direction of clinical research in traditional Chinese medicine.

[0004] Graves' disease is the most common type of hyperthyroidism. In traditional Chinese medicine, it belongs to the category of "goiter" and "goiter qi". Symptoms include neck discomfort and / or eye swelling, heat intolerance and sweating, irritability, palpitations and shortness of breath, dry throat and thirst, restlessness and insomnia, excessive eating and weight loss, frequent bowel movements, yellow urine, red tongue, yellow and greasy fur, and thin and smooth pulse. The pathogenesis is based on yin deficiency, and the excessive fire is the symptom. Qi stagnation, phlegm coagulation, and blood stasis are its pathological products. At present, the traditional Chinese medicine community believes that the syndrome of hyperthyroidism is mainly liver depression and qi stagnation syndrome, yin deficiency and yang hyperactivity syndrome, qi and yin deficiency syndrome, and phlegm and blood stasis syndrome. However, after many years of clinical summary, the applicant found that most patients with Graves' disease have phlegm heat, and the disease has the characteristics of long treatment cycle and easy recurrence. Combined with the traditional Chinese medicine theory that "strange diseases are all caused by phlegm". Starting from the treatment of yin deficiency and phlegm heat, the applicant has developed a Chinese medicine composition for the treatment of Graves' disease yin deficiency and phlegm heat syndrome, with significant therapeutic effect. Summary of the invention

[0005] In view of the above problems existing in the prior art, the first object of the present invention is to provide a Chinese medicine composition for treating Yin deficiency and phlegm heat syndrome of Graves' disease. The Chinese medicine composition is suitable for Graves' disease patients with Yin deficiency and phlegm heat syndrome diagnosed by traditional Chinese medicine, can effectively reduce goiter, reduce FT3 and FT4 levels of Graves' disease patients, regulate TSH levels, reduce TRAb and TPOAb levels, and can reduce the dosage and side effects of Western medicine in combination with classical Western medicine treatment.

[0006] The second object of the present invention is to provide a Chinese medicine preparation for treating Yin deficiency and phlegm heat syndrome of Graves' disease.

[0007] The third object of the present invention is to provide a use of the above-mentioned Chinese medicine composition or the above-mentioned Chinese medicine preparation in the preparation of a medicine for treating Graves' disease with Yin deficiency and phlegm-heat syndrome.

[0008] To achieve the above first object, the technical solution adopted by the present invention includes:

[0009] The present invention discloses a traditional Chinese medicine composition for treating Yin deficiency and phlegm-heat syndrome of Graves' disease. The traditional Chinese medicine composition comprises, by weight:

[0010] 9-30 parts of Prunella Vulgaris, 9-40 parts of Scrophularia, 15-30 parts of Raw Oyster, 9-30 parts of Fritillaria Thunbergii, 9-30 parts of White Peony Root, and 9-30 parts of Rhizoma Dioscoreae.

[0011] The Chinese medicine composition provided by the present invention is an empirical prescription obtained by the applicant summarizing many years of clinical experience. The Chinese medicine prescription is screened according to the theory of traditional Chinese medicine and the precise theory of syndrome differentiation and treatment. The prescription is rigorous and the number of medicinal ingredients is small. It is aimed at Graves' disease patients with Yin deficiency and phlegm-heat syndrome in traditional Chinese medicine differentiation. The Chinese medicine composition can effectively reduce goiter and reduce the TRAb level of Graves' disease patients. In the treatment of Graves' disease Yin deficiency and phlegm-heat syndrome, the Chinese medicine composition has the advantages of definite efficacy, convenient use, high safety, few adverse reactions, wide application range, etc. The combination with conventional anti-thyroid Western medicine is better than the conventional anti-thyroid Western medicine treatment alone, and plays a synergistic role.

[0012] The pharmacological effects and efficacies of the components of the Chinese medicine composition provided by the present invention are as follows:

[0013] Prunella vulgaris: The dried fruit spike of Prunella vulgaris L., a plant of the Labiatae family, is pungent, bitter and cold. It enters the liver and gallbladder meridians, specifically purging the fire of the liver meridian, and has the effects of improving eyesight, dispersing stagnation and reducing swelling. "Shennong's Herbal Classic" states: "It is used to treat cold and heat, arthralgia, carbuncle, rat bite, head sore, tumor breaking, dispersing gall qi, and swelling and dampness of the feet."

[0014] Scrophularia: It tastes sweet, bitter and salty, and is slightly cold in nature. It has the effects of clearing heat and cooling blood, nourishing yin and reducing fire, and detoxifying and dispersing nodules.

[0015] Raw oysters: salty and astringent, slightly cold in nature, enter the liver, gallbladder, and kidney meridians. Functions: nourishing yin and suppressing yang, softening and dispersing lumps. "Compendium of Materia Medica" says: "It can dissolve phlegm and soften lumps, clear away heat and remove dampness, stop pain in the heart and spleen, relieve dysentery with red and white turbidity, eliminate hernia, lumps, goiter, and tuberculosis."

[0016] Fritillaria thunbergii: bitter in taste and cold in nature, it enters the lung and heart meridians. It has the functions of clearing away heat, resolving phlegm and relieving cough, detoxifying, dispersing nodules and eliminating carbuncle. "Supplement to Compendium of Materia Medica" says: "It can detoxify, relieve phlegm, open up the lung qi, and is suitable for those with lung diseases with wind-fire and phlegm."

[0017] White peony root: The root of Paeonia lactiflora Pall., a plant of the Ranunculaceae family. It is slightly cold in nature, bitter and sour in taste, and enters the liver and spleen meridians. It has the effects of calming the liver and relieving pain, nourishing blood and regulating menstruation, and astringing yin and stopping sweating. It is a blood tonic drug under the category of tonic drugs.

[0018] Rhizoma Dioscoreae: It is the rhizome of Dioscorea zingiberensis and Dioscorea zingiberensis of the Dioscoreaceae family. It is mild and bitter in nature, and belongs to the liver meridian and lung meridian. It is mainly used to dispel wind and dampness, promote blood circulation and dredge meridians, relieve cough, and treat rheumatism, limb numbness, chest pain, heart pain, chronic bronchitis, contusions, malaria, carbuncles, etc.

[0019] The Chinese medicine composition provided by the present invention is explained as follows:

[0020] The herb Prunella Vulgaris in the prescription is bitter, pungent and cold, and mainly enters the liver and gallbladder meridians. It is bitter and cold, so it is good at clearing liver fire, and its pungent and moving taste can disperse nodules and reduce swelling, so it is the main drug. Scrophularia ningpoensis is sweet, bitter, salty and cold, which can not only purge fire and detoxify, but also nourish yin and reduce fire, and is good at dispersing throat nodules. In addition, oyster nourishes yin and suppresses yang, and its salty and cold properties soften nodules. Both of them are assistant drugs, while taking into account yin and fluid, they play the role of purging fire, calming the liver, softening nodules and dispersing nodules. Fritillaria thunbergii is specialized in clearing heat and resolving phlegm, detoxifying, dispersing nodules and eliminating carbuncle; white peony root is sour and astringent, good at nourishing yin and blood, and is a wonderful medicine for softening the liver. When combined with herb Prunella Vulgaris, it can not only assist the main drug to calm liver fire, but also assist in controlling its excessive pungent and dispersing properties that damage yin and blood, and comply with the liver's nature of using yin and yang; Rhizoma Dioscoreae is sweet, bitter and warm, good at resolving phlegm and unblocking meridians, and helps eliminate phlegm, turbidity and blood stasis in front of the neck. The medicines are matched together, taking into account both the underlying deficiency and the superficial excess, and using pungent dispersing and sour astringent effects together to achieve the effects of nourishing yin, clearing heat, resolving phlegm and dispersing nodules.

[0021] Furthermore, the Chinese medicine composition comprises, by weight:

[0022] 9-15 parts of Prunella Vulgaris, 9-30 parts of Scrophularia, 15-20 parts of Raw Oyster, 9-15 parts of Fritillaria Thunbergii, 9-15 parts of White Peony Root, and 9-15 parts of Rhizoma Dioscoreae.

[0023] Furthermore, the Chinese medicine composition comprises, by weight:

[0024] 15 parts of Herba Prunellae, 20 parts of Scrophulariae, 20 parts of Concha Ostreae, 9 parts of Fritillariae Thunbergii, 12 parts of White Peony Roots, 15 parts of Rhizoma Dioscoreae.

[0025] Furthermore, the Chinese medicine composition comprises, by weight:

[0026] 9 parts of Herba Prunellae, 15 parts of Scrophulariae, 15 parts of Concha Ostreae, 9 parts of Fritillariae Thunbergii, 9 parts of White Peony Roots, 9 parts of Rhizoma Dioscoreae.

[0027] To achieve the above second purpose, the technical solution adopted by the present invention includes:

[0028] The invention discloses a traditional Chinese medicine preparation for treating Yin deficiency and phlegm-heat syndrome of Graves' disease, wherein the traditional Chinese medicine preparation comprises the traditional Chinese medicine composition as an active ingredient.

[0029] Furthermore, the traditional Chinese medicine preparation also includes pharmaceutically acceptable excipients.

[0030] Furthermore, the dosage form of the Chinese medicine preparation includes but is not limited to tablets, capsules, powders, granules, pills, granules, decoctions, pills, oral liquids or soups.

[0031] Furthermore, the granules are prepared according to the following steps:

[0032] Weigh various Chinese medicinal materials according to the weight ratio of the raw materials, clean and break them, combine the medicines, add 8-10 times of water for decoction, filter, collect the filtrate, add 8-10 times of water to the residue for secondary decoction, filter, combine the filtrates, concentrate to a clear paste, spray dry, sieve, mix, and dry granulate to obtain the paste.

[0033] To achieve the third objective above, the technical solution adopted by the present invention includes:

[0034] The present invention discloses an application of the above-mentioned traditional Chinese medicine composition or the above-mentioned traditional Chinese medicine preparation in preparing a medicine for treating Yin deficiency and phlegm-heat syndrome of Graves' disease.

[0035] Furthermore, the drug is used for one or more of the following effects:

[0036] (1) Reduce FT3 and FT4 levels;

[0037] (2) reduce TPOAb levels;

[0038] (3) reduce TRAb levels;

[0039] (4) Regulate TSH levels;

[0040] (5) Improve thyroid enlargement.

[0041] Beneficial effects of the present invention:

[0042] The Chinese medicine composition provided by the present invention is an empirical prescription obtained by the applicant summarizing many years of clinical experience. The Chinese medicine prescription is screened according to the theory of traditional Chinese medicine and the precise theory of syndrome differentiation and treatment. The formula is rigorous and the number of medicinal ingredients is small. For Graves' disease patients with Yin deficiency and phlegm-heat syndrome in traditional Chinese medicine differentiation, the Chinese medicine composition can effectively reduce thyroid enlargement, reduce FT3 and FT4 levels of Graves' disease patients, regulate TSH levels, and reduce TRAb and TPOAb levels. In the treatment of Graves' disease Yin deficiency and phlegm-heat syndrome, the Chinese medicine composition has the advantages of definite efficacy, convenient use, high safety, few adverse reactions, wide application range, etc. The combination with conventional anti-thyroid Western medicine is better than conventional anti-thyroid Western medicine treatment alone, and plays a synergistic role.

[0043] The Chinese medicine composition for treating Yin deficiency and phlegm-heat syndrome of Graves' disease provided by the present invention can be conveniently prepared into various dosage forms with pharmaceutical carriers and is convenient to take clinically. DETAILED DESCRIPTION

[0044] In order to explain the present invention more clearly, the present invention is further described below in conjunction with preferred embodiments. It should be clear that the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0045] Example 1

[0046] The Chinese medicine composition comprises:

[0047] Prunella Vulgaris 15g, Scrophularia 20g, Raw Oyster 20g, Fritillaria thunbergii 9g, White Peony 12g, Rhizoma Cynoglossi 15g.

[0048] Jiangyin Tianjiang Pharmaceutical Co., Ltd. was commissioned to prepare granules. The specific preparation process is as follows:

[0049] 1) Extraction process:

[0050] According to the above raw material formula, various Chinese medicinal materials are weighed, cleaned and broken, and all the medicines are combined. 10 times of water are added for one decoction, heated to boiling, and kept slightly boiling for 1.5 hours, filtered (200 mesh), and the filtrate is collected. 8 times of water is added to the residue for a second decoction, heated to boiling, and kept slightly boiling for 1.5 hours, filtered (200 mesh), the two filtrates are combined, concentrated to a clear paste, spray dried, powdered, sieved, and mixed to obtain the extracted intermediate.

[0051] 2) Granulation and packaging:

[0052] The extracted intermediate is granulated into 12-40 mesh granules by dry method and packaged to obtain compound goiter granules.

[0053] Example 2

[0054] The Chinese medicine composition comprises:

[0055] Prunella Vulgaris 9g, Scrophularia 15g, Raw Oyster 15g, Fritillaria thunbergii 9g, White Peony 9g, Rhizoma Cynoglossi 9g.

[0056] Jiangyin Tianjiang Pharmaceutical Co., Ltd. was commissioned to prepare granules. The specific preparation process is as follows:

[0057] 1) Extraction process:

[0058] According to the above raw material formula, various Chinese medicinal materials are weighed, cleaned and broken, and all the medicines are combined. 10 times of water are added for one decoction, heated to boiling, and kept slightly boiling for 1.5 hours, filtered (200 mesh), and the filtrate is collected. 8 times of water is added to the residue for a second decoction, heated to boiling, and kept slightly boiling for 1.5 hours, filtered (200 mesh), the two filtrates are combined, concentrated to a clear paste, spray dried, powdered, sieved, and mixed to obtain the extracted intermediate.

[0059] 2) Granulation and packaging:

[0060] The extracted intermediate is granulated into 12-40 mesh granules by dry method and packaged to obtain compound goiter granules.

[0061] Clinical trials

[0062] 1 Research subjects

[0063] 1.1 Case sources and sample analysis

[0064] This trial adopted a randomized, double-blind, placebo-controlled clinical trial design. The selected subjects were patients with Graves' disease with Yin deficiency and phlegm-heat syndrome, and they were divided into the treatment group and the control group in a 1:1 ratio. On the basis of conventional Western medicine treatment, the two groups were given the compound Xiaoying granules prepared in Example 1 in the treatment group, and the control group was given a placebo of compound Xiaoying granules, and the course of treatment was 12 weeks. There were 30 subjects in the treatment group and 30 subjects in the control group, all of whom were recruited from July 2021 to October 2022 at Guang'anmen Hospital of China Academy of Chinese Medical Sciences, and there were no dropouts in both groups. The baseline data of the three aspects of gender distribution, age and TCM syndrome score before treatment of the enrolled patients were statistically analyzed.

[0065] In terms of gender distribution: there were 30 patients in the treatment group, including 11 males and 19 females; there were 30 patients in the control group, including 10 males and 20 females. The chi-square test showed that there was no statistically significant difference in gender between the two groups (P>0.05), and they were comparable. The specific situation is shown in Table 1.

[0066] Table 1 Comparison of gender distribution

[0067]

[0068] Note: X 2 Test analysis showed no significant difference between the two groups (P>0.05).

[0069] Age: The average age of the treatment group was 40.47±8.81 years old, and the average age of the control group was 43.77±9.86 years old. According to T test analysis, there was no statistically significant difference in age between the two groups (P>0.05), and they were comparable. The specific situation is shown in Table 2.

[0070] Table 2 Comparison of age

[0071]

[0072] Note: T-test analysis showed no statistically significant difference between the two groups (P>0.05).

[0073] In terms of TCM syndrome scores before treatment: the scores of the treatment group before treatment were 15.97±2.22, and the scores of the control group before treatment were 16.73±2.77. According to T-test analysis, there was no statistically significant difference in TCM syndrome scores between the two groups before treatment (P>0.05), and they were comparable. The specific situation is shown in Table 3.

[0074] Table 3 Comparison of TCM syndrome scores before treatment

[0075]

[0076] Note: T-test analysis showed no statistically significant difference between the two groups (P>0.05).

[0077] 1.2 Diagnostic criteria

[0078] 1.2.1 Western medicine diagnostic criteria

[0079] Refer to the textbook "Internal Medicine" (9th edition) and the "Chinese Thyroid Disease Diagnosis and Treatment Guidelines - Hyperthyroidism" Graves' disease diagnostic criteria: Diagnosis is based on ① hypermetabolic symptoms and signs: hypermetabolic symptoms and signs: such as irritability, irritability and insomnia, palpitations, fatigue, heat intolerance, sweating, weight loss, hyperphagia, eye swelling and tearing, finger tremor, increased bowel movement or diarrhea, and scanty menstruation in women; ② diffuse thyroid enlargement (confirmed by palpation and B-ultrasound), and a few cases may have no thyroid enlargement; ③ serum FT3 and FT4 increased, TSH decreased; ④ proptosis and other infiltrative eye signs; ⑤ pretibial myxedema; ⑥ positive thyroid stimulating hormone receptor antibodies (TRAb) and anti-thyroid peroxidase antibodies (TPOAb). ①②③ are essential for diagnosis, and ④⑤⑥ are auxiliary conditions for diagnosis.

[0080] 1.2.2 TCM diagnostic criteria

[0081] Referring to the syndrome section of the National Standard of TCM Clinical Diagnosis and Treatment Terminology and the relevant content of the second edition of Chinese Internal Medicine, the diagnostic criteria for Graves' disease with Yin deficiency and phlegm-heat syndrome are as follows:

[0082] Main symptoms: ① Swelling in front of neck ② Hotness in palms and soles ③ Dry throat and thirst ④ Increased appetite and weight loss ⑤ Anxiety and insomnia

[0083] Secondary symptoms: ① palpitations and restlessness ② irritability ③ heat and sweating ④ finger tremors ⑤ abdominal distension ⑥ frequent bowel movements

[0084] Tongue and pulse: red tongue, yellow and greasy tongue coating, thin, smooth and rapid pulse.

[0085] The diagnosis can be confirmed by combining 3 main symptoms and 2 secondary symptoms with tongue and pulse.

[0086] 1.3 Inclusion criteria

[0087] (1) Meet the Western medical diagnosis of Graves' disease;

[0088] (2) TCM diagnosis is Yin deficiency and phlegm heat syndrome;

[0089] (3) Aged 18 to 65, regardless of gender;

[0090] (4) During the lead-in period, FT3 and FT4 were higher than the normal range, and TSH was lower than the normal range;

[0091] (5) The patient voluntarily signed the informed consent form.

[0092] 1.4 Exclusion criteria

[0093] (1) Hyperthyroidism caused by other reasons or not consistent with TCM syndrome differentiation of yin deficiency and phlegm heat;

[0094] (2) Those who have had hyperthyroid crisis or concurrent infection within the past month;

[0095] (3) Uncooperative persons (referring to those who are unable to cooperate with diet control or take medication as prescribed, or who are unable to follow the doctor's orders to monitor thyroid function regularly) and mentally ill patients;

[0096] (4) Pregnant or lactating women, or those planning to become pregnant;

[0097] (5) Patients with primary diseases such as obvious cardiovascular disease (New York Heart Association grade 2 or 3), abnormal liver function (ALT and AST are more than 1 times higher than the upper limit of normal), abnormal renal function (creatinine greater than 200 μmol / L), cerebrovascular disease (acute stage) and hematopoietic system disease (needing treatment);

[0098] (6) Those with allergic constitution or a history of allergy to multiple drugs (more than two or known ingredients in the drug);

[0099] (7) Patients with thyroid cancer and other malignant tumors;

[0100] (8) Patients with active thyroid eye disease;

[0101] (9) Participated in other drug clinical trials in the past 4 weeks;

[0102] (10) Those who are considered unsuitable to participate in clinical trials by researchers.

[0103] 1.5 Elimination and termination criteria

[0104] (1) Exclusion criteria: Those who were found not to meet the inclusion criteria after inclusion; those who took other treatments that would affect this study.

[0105] (2) Termination criteria: Patients who experience endpoint events or poor compliance during treatment and are not suitable for continued treatment or cannot adhere to treatment are considered dropouts. The reasons for dropout should be recorded in detail, and the results of the last major efficacy test should be transferred as the final results for statistical analysis. If serious complications occur during treatment or the condition worsens, the treatment should be discontinued, and the reasons and evaluation indicators at the time of termination should be recorded.

[0106] 1.6 Criteria for termination of the trial

[0107] Termination of a trial means that the clinical trial has not been completed as planned and all trials are stopped midway. The main purpose is to protect the rights and interests of the subjects and ensure the quality of the trial.

[0108] (1) Serious safety issues occurred during the trial, including death of subjects;

[0109] (2) During the trial, it was discovered that the clinical trial protocol contained major errors, making it difficult to evaluate the drug effect.

[0110] 2 Treatment options

[0111] 2.1 Medication regimen

[0112] On the basis of conventional anti-thyroid treatment of Western medicine, the treatment group was given Compound Xiaoying Granules, and the control group was given Compound Xiaoying Granules placebo. The course of treatment was 12 weeks, and follow-up was once every 4 weeks. There were 30 subjects in the treatment group and 30 subjects in the control group.

[0113] (1) Source of test drugs

[0114] Methimazole (10 mg / tablet, manufacturer: Merck KGaA, Germany, approval number: National Medicine Standard: J20171078)

[0115] Compound Xiaoying Granules (the formulation of Example 1, commissioned by Jiangyin Tianjiang Pharmaceutical Co., Ltd. to prepare)

[0116] Compound Xiaoying Granule Placebo (Composition: maltodextrin, lemon yellow pigment, sunset yellow pigment, caramel pigment, lactose, bittering agent, citric acid, 10% Compound Xiaoying Granule)

[0117] (2) Usage of test drugs: Oral administration

[0118] Treatment group: methimazole (5-20 mg / time, once / day) + compound Xiaoying granules (1 bag / time, twice / day)

[0119] Control group: methimazole (5-20 mg / time, once / day) + compound Xiaoying granules placebo (1 bag / time, twice / day)

[0120] Conventional anti-thyroid treatment in Western medicine: gradually adjust the dosage according to the condition, once every 4 weeks.

[0121] Symptomatic treatment: If the heart rate is >100 beats per minute, give propranolol 10-20 mg orally 3 times a day. As the condition improves, gradually reduce the dosage until the drug is stopped.

[0122] 2.2 Observation indicators

[0123] 2.2.1 Effectiveness evaluation indicators:

[0124] (1) Thyroid function (FT3, FT4, TSH): tested once at baseline, 4 weeks, 8 weeks, and 12 weeks after drug administration.

[0125] (2) Thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb): once at baseline and once every 12 weeks.

[0126] (3) Thyroid stimulating hormone receptor antibody (TRAb): once at baseline and once every 12 weeks.

[0127] (4) TCM syndrome score: baseline, 4 weeks, 8 weeks, and 12 weeks of medication, each with one observation and record.

[0128] (5) Goiter score and exophthalmos score: baseline, 4 weeks, 8 weeks, and 12 weeks after administration, each recorded once.

[0129] 2.2.2 Safety evaluation indicators:

[0130] (1) Routine blood test: once at baseline, 4 weeks, 8 weeks, and 12 weeks after drug administration.

[0131] (2) Liver function (ALT, AST): tested once at baseline, 4 weeks, 8 weeks, and 12 weeks after drug administration.

[0132] (3) Adverse events: keep detailed records at all times

[0133] 2.4 Efficacy evaluation criteria

[0134] 2.4.1 TCM Syndrome Score

[0135] The TCM syndrome scoring table is formulated with reference to: TCM Clinical Diagnosis and Treatment Terminology (Part 2: Syndromes) Standard Number: GB / T16751.2-2021.

[0136] Palpitations: No obvious palpitations after work, 0 points; obvious palpitations after work, 1 point; palpitations when moving, 2 points; palpitations even at rest, 3 points.

[0137] Shortness of breath: No obvious shortness of breath after work (0 point); shortness of breath after work (1 point); shortness of breath when moving (2 points); shortness of breath even at rest (3 points).

[0138] Irritability: Stable mood, not easily irritable 0 points; unstable mood, irritable 1 point; irritable and easily irritable, mostly able to control 2 points; irritable and easily irritable, uncontrollable 3 points.

[0139] Hyperphagia: similar to before the onset of the disease, 0 points; slightly increased by 1 point; increased by 2 points; significantly increased by 3 points.

[0140] Restlessness and insomnia: 0 points for no obvious attacks; 1 point for 1-2 times / week; 2 points for 3-5 times / week; 3 points for 5-7 times / week.

[0141] Aversion to heat and excessive sweating: no change 0 points; feeling hot and sweating easily at the slightest movement 1 point; feeling hot and sweating even when still and sweating when moving 2 points; feeling hot and sweating at still and sweating more than 3 points.

[0142] Dry throat and thirst: no obvious attack, 0 point; occasional attack, 1 point; frequent attack, 2 points; continuous attack, 3 points.

[0143] Frequency of bowel movements: 1 time / day 0 points; 2-3 times / day 1 point; 4-5 times / day 2 points; 6 times or more / day 3 points.

[0144] 2.4.2 Criteria for determining efficacy of TCM syndromes

[0145] The efficacy of TCM syndromes was determined based on the integral method.

[0146] Therapeutic index (n) = [(pre-treatment score - post-treatment score) ÷ pre-treatment score] × 100%

[0147] Markedly effective: Clinical symptoms and signs of TCM were significantly improved, and the syndrome score was reduced by ≥70%.

[0148] Effective: TCM clinical symptoms and signs improved, and syndrome scores decreased by ≥30%.

[0149] Ineffective: There is no significant improvement in TCM clinical symptoms and signs, or they may even get worse, and the syndrome score is reduced by less than 30%.

[0150] 2.5 Observation of adverse events

[0151] 2.5.1 Occurrence and recording of adverse events

[0152] Adverse events occurring at any time during the clinical trial, whether or not related to the study intervention, should be recorded in the CRF.

[0153] 2.5.2 Grading of severity of adverse events

[0154] (1) Mild: Patients can tolerate it easily, or it causes slight discomfort but does not affect daily life.

[0155] (2) Medium: May cause discomfort to patients, thus affecting their normal daily life.

[0156] (3) Severe: The patient loses the ability to lead a normal life or is hampered from living a normal daily life.

[0157] 2.6 Statistical analysis

[0158] SPSS 26.0 software was used for statistical analysis. All hypothesis tests were two-sided, and P values ​​< 0.05 were considered statistically significant. The mean ± standard deviation was used for statistical description of measurement data. When comparing between groups, a normality test was first performed. If the data obeyed the normal distribution, a T test was performed. If the data did not obey the normal distribution, the Wilcoxon rank sum test between the two groups was used. The chi-square test was used for comparison of count data between groups. 2 test.

[0159] 3 Clinical efficacy

[0160] 3.1 Comparison of TCM syndrome scores

[0161] There was no significant difference in the TCM syndrome scores between the treatment group and the control group before treatment (P>0.05), and the two groups were comparable. After T test and variance analysis, the TCM symptom scores of the treatment group and the control group decreased within the group at the three time points of 4 weeks, 8 weeks, and 12 weeks after treatment (P<0.05). At the three time points of 4 weeks, 8 weeks, and 12 weeks after treatment, the differences between the treatment group and the control group were statistically significant (P<0.05), among which the TCM syndrome scores of the treatment group improved more significantly. The specific situation is shown in Table 4.

[0162] Table 4 Comparison of TCM syndrome scores between the two groups

[0163]

[0164] Note: Compared with the group before treatment, *P<0.05, the difference is statistically significant; compared with the control group after treatment, # P<0.05, the difference was statistically significant.

[0165] 3.2 Comparison of TCM syndrome efficacy

[0166] After 3 months of treatment, 15 cases in the treatment group showed marked effect, 14 cases were effective, and 1 case was ineffective, with a total effective rate of 96.7%. In the control group, 7 cases showed marked effect, 13 cases were effective, and 10 cases were ineffective, with a total effective rate of about 66.7%. Comparison of the efficacy of TCM syndromes in the two groups after 3 months of treatment showed that the improvement of the efficacy in the treatment group was significantly better than that in the control group. The difference between the two groups was statistically significant (P<0.05) after rank sum test analysis. The specific situation is shown in Table 5.

[0167] Table 5 Comparison of TCM syndrome efficacy between the two groups after 3 months of treatment

[0168]

[0169] Note: The rank-sum test showed that the difference between the two groups was statistically significant (P<0.05).

[0170] 3.3 Comparison of the number of people with exophthalmos

[0171] There were mild to moderate cases of exophthalmos in both groups before and after treatment, but no severe cases of exophthalmos. The chi-square test showed that there was no statistical difference in the number of patients with different degrees of exophthalmos between the two groups at 4, 8, and 12 weeks after treatment (P>0.05). The specific situation is shown in Table 6.

[0172] Table 6 Comparison of the number of exophthalmos in the two groups

[0173]

[0174] 3.4 Comparison of thyroid enlargement

[0175] The chi-square test showed that there was no significant difference in the number of thyroid enlargement cases between the treatment group and the control group before treatment (P>0.05), and the two groups were comparable. After 4 weeks and 8 weeks of treatment, the chi-square test showed that there was still no significant difference in the number of thyroid enlargement cases (P>0.05). After 12 weeks of treatment, the chi-square test showed that there was a statistically significant difference in the number of thyroid enlargement cases between the treatment group and the control group (P<0.05). The specific situation is shown in Table 7.

[0176] Table 7 Number of cases of thyroid enlargement in the two groups

[0177]

[0178] 3.5 Changes in FT3 levels

[0179] There was no significant difference in the levels of the treatment group and the control group before treatment (P>0.05), and the two groups were comparable. After treatment, the FT3 levels of the treatment group decreased at 4, 8, and 12 weeks of treatment, and the difference was statistically significant (P<0.05). The FT3 level of the control group also decreased after treatment, but the difference was not statistically significant (P>0.05). At the 12-week time point, the comparison of the FT3 levels of the two groups after treatment showed that the reduction of the FT3 level in the treatment group was better than that in the control group, and the difference between the groups was significant and statistically significant (P<0.05). The specific situation is shown in Table 8.

[0180] Table 8 Changes in FT3 levels in the two groups

[0181]

[0182] Note: Compared with the group before treatment, *P<0.05, the difference is statistically significant; compared with the control group after treatment, #P<0.05, the difference was statistically significant.

[0183] 3.6 Changes in FT4 levels

[0184] There was no significant difference in FT4 levels between the treatment group and the control group before treatment (P>0.05), and the two groups were comparable. At the time point of 12 weeks after treatment, the FT4 level in the treatment group decreased significantly, and the difference within the treatment group was statistically significant (P<0.05), and the difference between the treatment group and the control group was also statistically significant (P<0.05). The specific situation is shown in Table 9.

[0185] Table 9 Changes of FT4 levels in the two groups

[0186]

[0187] Note: Compared with the group before treatment, *P<0.05, the difference is statistically significant; compared with the control group after treatment, # P<0.05, the difference was statistically significant.

[0188] 3.7 Changes in TSH Levels

[0189] There was no significant difference in TSH levels between the treatment group and the control group before treatment (P>0.05), and the two groups were comparable. At the three time points of 4 weeks, 8 weeks and 12 weeks, the TSH levels in the treatment group increased, and the difference was statistically significant (P<0.05); while the control group increased at 8 weeks and 12 weeks compared with before treatment, but there was no statistical difference (P>0.05). At the two time points of 4 weeks and 12 weeks after treatment, the differences between the treatment group and the control group were statistically significant (P<0.05), and the TSH level of the treatment group improved more significantly. The specific situation is shown in Table 10.

[0190] Table 10 Changes of TSH levels in the two groups

[0191]

[0192] Note: Compared with the group before treatment, *P<0.05, the difference is statistically significant; compared with the control group after treatment, # P<0.05, the difference was statistically significant.

[0193] 3.8 Changes in TPOAb Levels

[0194] There was no significant difference in TPOAb levels between the treatment group and the control group before treatment (P>0.05), and the two groups were comparable. After treatment, the TPOAb level in the treatment group was significantly lower than that before treatment, and the difference was statistically significant (P<0.05). At 12 weeks after treatment, there was no statistically significant difference between the treatment group and the control group (P>0.05). The specific situation is shown in Table 11.

[0195] Table 11 Changes in TPOAb levels in the two groups

[0196]

[0197] Note: Compared with the group before treatment, *P<0.05, the difference is statistically significant; compared with the control group after treatment, # P<0.05, the difference was statistically significant.

[0198] 3.9 Changes in TGAb Levels

[0199] There was no significant difference in TGAb levels between the treatment group and the control group before treatment (P>0.05), and the two groups were comparable. After treatment, TGAb levels in both the treatment group and the control group decreased compared with those before treatment, but the difference was not statistically significant (P>0.05). At 12 weeks after treatment, there was no statistically significant difference between the treatment group and the control group (P>0.05). The specific situation is shown in Table 12.

[0200] Table 12 Changes of TGAb levels in the two groups

[0201]

[0202] Note: Compared with the group before treatment, *P<0.05, the difference is statistically significant; compared with the control group after treatment, # P<0.05, the difference was statistically significant.

[0203] 3.10 Changes in TRAb levels

[0204] There was no significant difference in TRAb levels between the treatment group and the control group before treatment (P>0.05), and the two groups were comparable. After treatment, the TRAb levels of the treatment group and the control group were reduced and the difference was statistically significant (P<0.05). At 12 weeks after treatment, there was no statistically significant difference between the treatment group and the control group (P>0.05). The specific situation is shown in Table 13.

[0205] Table 13 Changes in TRAb levels in the two groups

[0206]

[0207] Note: Compared with the group before treatment, *P<0.05, the difference is statistically significant; compared with the control group after treatment, # P<0.05, the difference was statistically significant.

[0208] 4 Safety evaluation

[0209] 4.1 Comparison of abnormal liver function rates

[0210] Both the treatment group and the control group had abnormal liver function. The chi-square test showed that there was no significant difference in the abnormal rate between the treatment group and the control group (P>0.05). The specific situation is shown in Table 14.

[0211] Table 14 Comparison of abnormal liver function rates between the two groups after treatment

[0212]

[0213] Note: X 2 Test analysis showed no significant difference between the two groups (P>0.05).

[0214] 4.2 Comparison of leukopenia rates

[0215] Both the treatment group and the control group had leukocytopenia. The chi-square test showed that there was no significant difference in the abnormal rate between the treatment group and the control group (P>0.05). The specific situation is shown in Table 15.

[0216] Table 15 Comparison of leukopenia rate between the two groups after treatment

[0217]

[0218] Note: X 2 Test analysis showed no significant difference between the two groups (P>0.05).

[0219] 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 treating Yin deficiency and phlegm-heat syndrome of Graves' disease, characterized in that: In parts by weight, the Chinese medicine composition comprises: The invention is prepared from 9-15 parts of Prunella Vulgaris, 9-30 parts of Scrophularia ningpoensis, 15-20 parts of raw oysters, 9-15 parts of Fritillaria thunbergii, 9-15 parts of white peony root and 9-15 parts of Rhizoma Dioscoreae.

2. The Chinese medicine composition according to claim 1, characterized in that: In parts by weight, the Chinese medicine composition comprises: The composition is made from 15 parts of Herba Prunellae, 20 parts of Scrophulariae, 20 parts of Raw Oysters, 9 parts of Fritillariae Thunbergii, 12 parts of White Peony Roots and 15 parts of Rhizoma Dioscoreae.

3. The Chinese medicine composition according to claim 1, characterized in that In parts by weight, the Chinese medicine composition comprises: It is made from 9 parts of Herba Prunellae, 15 parts of Scrophulariae, 15 parts of Raw Oysters, 9 parts of Fritillariae Thunbergii, 9 parts of White Peony Roots and 9 parts of Rhizoma Dioscoreae.

4. A Chinese medicine preparation for treating Graves' disease with Yin deficiency and phlegm-heat syndrome, characterized in that: The Chinese medicine preparation uses the Chinese medicine composition according to any one of claims 1 to 3 as an active ingredient.

5. The Chinese medicine preparation according to claim 4, characterized in that: The traditional Chinese medicine preparation also contains pharmaceutically acceptable auxiliary materials.

6. The Chinese medicine preparation according to claim 4, characterized in that: The dosage form of the Chinese medicine preparation is tablet, capsule, powder, pill, granule, oral liquid or decoction.

7. The Chinese medicine preparation according to claim 6, characterized in that: The pills are drop pills.

8. The Chinese medicine preparation according to claim 6, characterized in that: The granules are prepared according to the following steps: Weigh various Chinese medicinal materials according to the weight ratio of the raw materials, clean and break them, combine the medicines, add 8-10 times of water for decoction, filter, collect the filtrate, add 8-10 times of water to the residue for secondary decoction, filter, combine the filtrates, concentrate to a clear paste, spray dry, sieve, mix, and dry granulate to obtain the paste.

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 preparing a medicine for treating Yin deficiency and phlegm-heat syndrome of Graves' disease.

10. The use according to claim 9, characterized in that: The drug is used for one or more of the following effects: (1) Reduce FT3 and FT4 levels; (2) Reduce TPOAb levels; (3) Reduce TRAb levels; (4) Regulate TSH levels; (5) Improve thyroid enlargement.

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