External traditional Chinese medicine preparation for treating diffuse toxic goiter and preparation method thereof

Abstract

The invention discloses an external traditional Chinese medicine preparation for treating diffuse toxic goiter (Graves disease). The external traditional Chinese medicine preparation is prepared from the following raw material medicines in parts by weight: 20-30 parts of radix pseudostellariae, 12-15 parts of radix glehniae, 12-15 parts of radix ophiopogonis, 20-30 parts of nacre mother of pearl, 15-20 parts of uncaria, 6-9 parts of radix bupleuri, 6-9 parts of codonopsis pilosula, 6-9 parts of honey-fried licorice root, 6-9 parts of scutellaria baicalensis, 6-9 parts of gentian, 12-15 parts of ligusticum wallichii, 6-9 parts of parched white peony root, 12-15 parts of parched white atractylodes rhizome, 12-15 parts of poria cocos and 6-9 parts of schisandra chinensis. The external traditional Chinese medicine preparation has a better treatment effect on diffuse toxic goiter, and the treatment medicine can be absorbed from the skin of the surface of thyroid gland and directly reaches the disease site. In addition, the invention further provides a preparation method of the external traditional Chinese medicine preparation.

Description

Technical Field

[0001] The invention relates to an external Chinese medicinal preparation for treating diffuse toxic goiter, and further relates to a preparation method of the external Chinese medicinal preparation. Background Art

[0002] Diffuse toxic goiter (Graves' disease), referred to as "hyperthyroidism", refers to a group of clinical syndromes caused by excessive production of thyroid hormone by the thyroid gland itself, with increased excitability and hypermetabolism of the nervous, circulatory, digestive and other systems as the main manifestations. The incidence of hyperthyroidism is increasing year by year and the age of patients is younger. Anti-thyroid Western medicine treatment is one of the current conventional treatments, but there are systemic adverse reactions such as granulocytopenia, toxic liver disease, rash, vasculitis, and even arthritis and lupus syndrome, involving the blood, lymph, endocrine, nervous, gastrointestinal tract, liver and gallbladder, skin and subcutaneous tissue, bone and muscle system. [2,3] Although 131I is simple, economical, and has a high cure rate, its disadvantages include increased incidence and aggravation of thyroid-related eye disease and lifelong hypothyroidism. Surgery is not a routine treatment due to the risk of postoperative complications.

[0003] Given that the thyroid gland is located superficially, hyperthyroidism causes the thyroid gland to swell and the blood and lymph flow through the thyroid gland to accelerate, which are beneficial for the thyroid gland to absorb the active drug components that penetrate the skin and reach its vicinity. [4] Modern medicine uses methimazole cream for external application, but it often causes local skin itching, burning, desquamation, papules, as well as abnormal liver function and leukopenia. In addition, there is dosage instability during patient use, which causes instability in thyroid function indicators. In view of the above situation, it is particularly important to actively explore more effective and safe drugs and routes of administration.

[0004] References

[0005] [1] Peng Like. Research progress on epidemiological characteristics of hyperthyroidism[J]. Chinese School Doctor, 2015, 29(11): 867-870.

[0006] [2]Wu X, Liu H, Zhu

[0007] [3] Wu Meng, Shao Xue, Yang Lanlan, et al. Methimazole cream for the treatment of hyperthyroidism complicated with liver failure: a report of two cases and a literature review [J]. Journal of Jilin University (Medical Edition), 2019, 45(01): 160-162.

[0008] [4] Chen Ling, Gao Yanyan, Zhang Junsheng. Preliminary study on the mechanism of transdermal administration of compound methimazole ointment in the treatment of hyperthyroidism[J]. Shandong Medicine, 2008(07):98~99. Summary of the invention

[0009] In view of the above-mentioned deficiencies in the prior art, according to an embodiment of the present invention, it is hoped to provide an external Chinese medicine preparation for treating diffuse toxic goiter, in which the production raw materials in the formula are all Chinese medicines, and no chemical reagents are added, so as to solve the adverse drug reactions existing in the use of methimazole cream mentioned in the background technology, so as to achieve better therapeutic effects for diffuse toxic goiter, so that the therapeutic drugs are absorbed from the surface skin of the thyroid gland and reach the diseased area directly, thereby increasing the drug concentration in the thyroid gland. At the same time, the pure Chinese medicine preparation greatly reduces related adverse reactions.

[0010] According to the embodiments, the present invention provides an external Chinese medicine preparation for treating diffuse toxic goiter, which is made of the following raw materials in parts by weight: 20-30 parts of Pseudostellariae Radix, 12-15 parts of Glehnia littoralis, 12-15 parts of Ophiopogon japonicus, 20-30 parts of Mother of Pearl, 15-20 parts of Uncaria rhynchophylla, 6-9 parts of Bupleurum chinense, 6-9 parts of Codonopsis pilosula, 6-9 parts of Radix Glycyrrhizae Preparata, 6-9 parts of Scutellariae Baicalensis, 6-9 parts of Gentiana scabra, 12-15 parts of Ligusticum chuanxiong, 6-9 parts of stir-fried White Peony Root, 12-15 parts of stir-fried Atractylodes macrocephala, 12-15 parts of Poria cocos, and 6-9 parts of Schisandrae Chinensis.

[0011] According to an embodiment, the preparation method of the above-mentioned external Chinese medicine preparation for treating diffuse toxic goiter provided by the present invention comprises the following steps:

[0012] (1) Weigh each raw material according to weight and wash it;

[0013] (2) drying the cleaned raw materials;

[0014] (3) The dried raw materials are decocted twice with water: for the first decoction, add 8 times the water, soak for half an hour, and cook for 2 hours after boiling; for the second decoction, add 6 times the water, and cook for 1 hour after boiling; the decoctions are combined, concentrated, and prepared into a Chinese medicine preparation for external use according to the dosage form requirements.

[0015] In the present invention, the pharmacology of each component is as follows:

[0016] Pseudostellariae Radix: replenishes qi and strengthens the spleen, produces body fluid and moistens the lungs. It is mainly used to treat spleen deficiency and fatigue, weakness after illness, insufficient qi and yin, spontaneous sweating and thirst, dry cough due to lung dryness, etc. Because its medicinal power is more moderate, it is more suitable for the elderly, children and people with weak constitutions, and is widely used in clinical practice.

[0017] Radix Adenophorae: sweet, slightly bitter, slightly cold in nature, and enters the lung and stomach meridians. It is beneficial to the stomach to produce body fluid, nourish yin and clear the lungs. It is mainly used for lung heat and dry cough, cough with blood in sputum, insufficient stomach yin, damage to body fluid due to fever, dry throat and thirst, etc. Radix Adenophorae can enhance the killing rate of NK cells and the transformation function of T lymphocytes, increase the levels of serum IgM and IgG, and enhance nonspecific immunity and specific immunity to treat diffuse toxic goiter.

[0018] Ophiopogon japonicus: sweet, slightly bitter and cold in nature, it enters the heart, lung and stomach meridians. It is often used to treat symptoms such as dry cough due to lung dryness, and cough due to yin deficiency.

[0019] Mother of pearl: sweet and salty in taste, cold in nature, enters the liver and heart meridians, soothes the liver and suppresses yang, clears the liver and improves eyesight, calms the nerves and soothes the mind, and can improve symptoms such as insomnia and depression in patients with diffuse toxic goiter.

[0020] Uncaria rhynchophylla: sweet and cool in nature, it enters the liver and pericardium meridians, clears away heat and soothes the liver, calms the wind and calms the nerves. It can be used together with mother of pearl to improve limb tremor symptoms in patients with diffuse toxic goiter.

[0021] Bupleurum: bitter, pungent, slightly cold, enters the liver and gallbladder meridians, and has the effect of soothing the liver and relieving depression.

[0022] Codonopsis pilosula: sweet and neutral in nature, it enters the spleen and lung meridians, has the effects of strengthening the spleen and lungs, nourishing blood and producing body fluids, and is used to treat spleen and lung qi deficiency, poor appetite and fatigue, cough and weak asthma, insufficient qi and blood, sallow complexion, palpitations and shortness of breath, thirst due to loss of body fluids, internal heat and thirst, etc.

[0023] Roasted licorice: It is mild in nature, sweet in taste, and enters the heart, lung, spleen, and stomach meridians. It has the effects of tonifying the spleen and replenishing qi, clearing away heat and detoxifying, removing phlegm and relieving cough, relieving acute pain, and harmonizing various medicines.

[0024] Scutellaria baicalensis: It is bitter and cold in nature, and is classified as belonging to the lung meridian, gallbladder meridian, small intestine meridian, large intestine meridian and spleen meridian. Its effects are clearing away heat and dampness, purging fire and detoxifying.

[0025] Gentiana: bitter in taste and cold in nature, it enters the liver and gallbladder meridians and is a commonly used Chinese medicine for clearing damp-heat in the liver and gallbladder and purging the stagnant fire in the lower jiao. Gentiana can inhibit NF-κB / MAPK signaling to alleviate inflammatory neuronal damage regulated by astrocytes, and improve LPS-induced depressive-like behavior by regulating the tryptophan degradation signaling pathway, thereby improving the emotional problems of patients with diffuse toxic goiter. Gentiana can also regulate urinary 17-OHCS excretion and serum total T4, improving symptoms related to hyperthyroidism.

[0026] Chuanxiong: warm in nature, pungent in taste, and enters the liver meridian, gallbladder meridian, and pericardium meridian. Chuanxiong has the effect of promoting blood circulation and qi, and can improve cardiac function by inhibiting inflammatory response, regulating cell apoptosis, and improving vasoconstriction function. It can also increase the NE content in the prefrontal lobe and striatum and the DA content in the hippocampus to play an anti-depressant role.

[0027] Stir-fried white peony root: bitter, sour, slightly cold, and enters the liver and spleen meridians. It has the effects of nourishing blood and softening the liver, relieving pain, and consolidating yin and sweating. It treats chest and abdominal pain, diarrhea and abdominal pain, spontaneous sweating, night sweats, yin deficiency fever, irregular menstruation, metrorrhagia, and leukorrhea. The main components of peony, monoterpenes, glycosides, and flavonoids, have liver protection, anti-inflammatory and analgesic effects. White peony total glycosides have immune regulation and liver protection effects. Hyperthyroidism often causes the patient's immune system to be disordered, and the use of modern medical antithyroid drugs can also cause damage to the patient's liver function. Therefore, white peony root is of great significance for the treatment of hyperthyroidism.

[0028] Stir-fried Atractylodes macrocephala: bitter, sweet, warm, and belongs to the spleen and stomach meridians. It has the effects of tonifying the spleen, benefiting the stomach, drying dampness, harmonizing the middle, and calming the fetus. It can treat weak spleen and stomach qi, loss of appetite, fatigue and shortness of breath, bloating, diarrhea, phlegm and fluid, edema, jaundice, dampness, dysuria, dizziness, spontaneous sweating, and restless fetus. Atractylodes macrocephala extract and its main chemical components such as Atractylodes lactone I have many pharmacological effects, such as anti-inflammatory, immune enhancement, and liver protection. Studies have found that Atractylodes lactone I can significantly reduce the levels of TNF-α, IL-1β and IL-6, alanine aminotransferase, aspartate aminotransferase, creatinine and urea nitrogen. Among them, TNF-α, IL-1β and IL-6 are important influencing factors of thyroid-related inflammation and are involved in the occurrence and development of thyroiditis and thyroid-related eye diseases. Atractylodes macrocephala can improve the body's immunity. Atractylodes polysaccharides have a positive effect on the number and function of white blood cells. Atractylodes polysaccharides and atractylodes ketone also have a certain liver protection effect, which is of great significance for the treatment of hyperthyroidism.

[0029] Poria: sweet, light, flat, belongs to the heart meridian, spleen meridian, lung meridian, and kidney meridian. It has the effects of penetrating dampness and promoting diuresis, benefiting the spleen and stomach, and calming the mind. It treats urinary dysfunction, edema, phlegm and cough, vomiting, diarrhea, spermatorrhea, stranguria, palpitations, and forgetfulness. Modern pharmacological studies have shown that Poria triterpenes can significantly reduce the liver damage process in mice and have a liver-protecting effect; Poria polysaccharides have a certain sedative effect, and its sedative effect tends to increase with the increase of dosage. When combined with Atractylodes macrocephala, the sedative and tranquilizing effect is stronger and can improve the symptoms of palpitations. White peony root is sour and sweet and enters the liver, softens the liver and nourishes yin. The combination of "Poria-Atractylodes macrocephala" can not only strengthen the spleen to prevent wood from riding, but also soften the liver. The liver is soft and does not insult the earth. It is a method of liver and spleen coordination and is often used in the treatment of hyperthyroidism.

[0030] Schisandra chinensis: sour, warm in nature, enters the lung meridian, heart meridian, and kidney meridian. It has the effects of astringency, invigorating qi and promoting the production of body fluid, tonifying the kidney and calming the mind. It is used for chronic cough, weak asthma, nocturnal emission, frequent urination, chronic diarrhea, spontaneous sweating, night sweats, thirst due to loss of body fluid, shortness of breath and weak pulse, internal heat and thirst, palpitations and insomnia. Schisandra chinensis contains a large amount of lignans, polysaccharides, etc. These active ingredients can repair acute liver damage and have a significant liver-protecting effect; the pharmacological effects of Schisandra chinensis extract and its active ingredients in the treatment of cardiovascular diseases such as anti-myocardial inflammation, anti-oxidative damage, inhibition of myocardial cell apoptosis, and relief of myocardial fibrosis are of great therapeutic significance for hyperthyroid heart disease.

[0031] When in use, the external Chinese medicine preparation of the present invention is applied externally to the thyroid gland part (6 cm long and 4 cm wide) in the anterior neck area.

[0032] The external Chinese medicine preparation of the present invention (hereinafter also referred to as Kangping Yuling prescription) is used as an external medicine for the treatment of diffuse toxic goiter in Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, and is composed of Radix Pseudostellariae, Radix Adenophorae, Radix Ophiopogonis, Mother of Pearl, Rhizoma Uncariae, Radix Bupleuri, Radix Codonopsis, Radix Glycyrrhizae Preparata, Radix Scutellariae, Radix Gentianae, Rhizoma Chuanxiong, Rhizoma Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Poria, Fructus Schisandrae Chinensis, etc. It has the effects of soothing the liver and clearing away heat, softening hard masses and activating blood circulation, and invigorating qi and nourishing yin.

[0033] The following examples and test examples will prove that the clinical use of the Chinese medicine preparation for external use of the present invention can effectively improve the clinical symptoms of patients, reduce FT3, FT4, TRAB, increase TSH, and shrink the enlarged thyroid gland. No side effects were observed, and local allergies were rare. DETAILED DESCRIPTION

[0034] The present invention will be further described below in conjunction with specific embodiments. These embodiments should be understood to be only used to illustrate the present invention and not to limit the scope of protection of the present invention. After reading the content of the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalent changes and modifications also fall within the scope defined by the claims of the present invention.

[0035] Example 1

[0036] Weigh 30g of Radix Pseudostellariae Radix, 15g of Radix Adenophorae, 15g of Radix Ophiopogonis, 30g of Mother of Pearl, 15g of Rhizoma Uncariae, 9g of Radix Bupleuri, 9g of Radix Codonopsis, 6g of Radix Glycyrrhizae Radix, 6g of Radix Scutellariae, 6g of Radix Gentianae, 12g of Rhizoma Chuanxiong, 9g of Radix Paeoniae Alba, 15g of Rhizoma Atractylodis Macrocephalae, 15g of Poria, and 9g of Fructus Schisandrae Chinensis. Wash; dry in the sun; decoct twice: for the first decoction, add 8 times of water, moisten for half an hour, boil for 2 hours after boiling; for the second decoction, add 6 times of water, boil for 1 hour after boiling, combine the decoctions and concentrate, and prepare the external Chinese medicine preparation according to the dosage form requirements.

[0037] Example 2

[0038] Weigh 25g of Radix Pseudostellariae Radix, 13g of Radix Adenophorae, 13g of Radix Ophiopogonis, 25g of Mother of Pearl, 17g of Rhizoma Uncariae, 7g of Radix Bupleuri, 7g of Radix Codonopsis, 7g of Radix Glycyrrhizae Radix, 7g of Radix Scutellariae, 7g of Radix Gentianae, 13g of Rhizoma Chuanxiong, 7g of Radix Paeoniae Alba, 13g of Rhizoma Atractylodis Macrocephalae, 13g of Poria, and 7g of Fructus Schisandrae Chinensis. Wash; dry in the sun; decoct twice: for the first decoction, add 8 times of water, moisten for half an hour, boil for 2 hours after boiling; for the second decoction, add 6 times of water, boil for 1 hour after boiling, combine the decoctions and concentrate, and prepare the external Chinese medicine preparation according to the dosage form requirements.

[0039] Example 3

[0040] Weigh 20g of Radix Pseudostellariae Radix, 12g of Radix Adenophorae, 12g of Radix Ophiopogonis, 20g of Mother of Pearl, 20g of Rhizoma Uncariae, 6g of Radix Bupleuri, 6g of Radix Codonopsis, 9g of Radix Glycyrrhizae Radix, 9g of Radix Scutellariae, 9g of Radix Gentianae, 15g of Rhizoma Chuanxiong, 6g of Radix Paeoniae Alba, 12g of Rhizoma Atractylodis Macrocephalae, 12g of Poria, and 6g of Fructus Schisandrae Chinensis. Wash; dry in the sun; decoct twice: for the first decoction, add 8 times of water, moisten for half an hour, boil for 2 hours after boiling; for the second decoction, add 6 times of water, boil for 1 hour after boiling, combine the decoctions and concentrate, and prepare the external Chinese medicine preparation according to the dosage form requirements.

[0041] Experimental case - Observation on the clinical efficacy of Kangping Yuling prescription in treating Graves' disease

[0042] 1. Materials and methods

[0043] 1.1 General Information

[0044] A total of 60 patients with Graves' disease with liver depression and fire, qi and yin deficiency, and phlegm and blood stasis who were admitted to the Department of Endocrinology of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from June 2022 to June 2023 were randomly divided into an observation group (Kangping Yuling Recipe) and a control group (methimazole cream), with 30 cases in each group. There were 9 males and 21 females in the observation group, aged 19 to 54 years old, with an average age of (33.54±3.24) years old; the course of disease was 4 to 24 months, with an average course of disease of (14.27±2.62) months. There were 12 males and 18 females in the control group, aged 26 to 56 years old, with an average age of (34.24±8.23) years old; the course of disease was 3 to 25 months, with an average course of disease of (13.75±4.29) months. There was no significant difference in general data between the two groups (P>0.05), and they were comparable. The study was approved by the Ethics Committee of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (2023-LHXS-033).

[0045] 1.2 Diagnostic criteria

[0046] 1.2.1 Western medicine diagnostic criteria

[0047] Refer to the "Guidelines for Primary Diagnosis and Treatment of Hyperthyroidism (Practical Edition 2019)"

[0048] (1) Diagnostic criteria for hyperthyroidism: ① Clinical symptoms and signs of hypermetabolic syndrome; ② Thyroid enlargement; ③ Increased serum thyroid hormone levels and decreased TSH concentrations.

[0049] (2) Graves' disease diagnostic criteria: ① Hyperthyroidism is diagnosed; ② Diffuse thyroid enlargement (confirmed by palpation and B-ultrasound), in a few cases, there may be no thyroid enlargement; ③ Decreased serum TSH concentration and increased TH concentration; ④ Proptosis and other infiltrative eye signs; ⑤ Pretibial myxedema; ⑥ TRAb or TSAb is positive. Among the above criteria, ① to ③ are essential conditions for diagnosis, and ④ to ⑥ are auxiliary conditions for diagnosis.

[0050] 1.2.2 Standards for TCM Syndrome Differentiation

[0051] It is formulated based on currently recognized industry standards and in reference to the "Guidelines for Clinical Research of New Chinese Medicines".

[0052] Main symptoms: swelling in the front of the neck, fever, sweating, fatigue;

[0053] Secondary symptoms: finger tremors, insomnia and frequent dreams, weight loss, increased appetite, and dry mouth;

[0054] Tongue: red tongue, or with ecchymosis, or dark purple veins under the tongue, thin yellow tongue coating;

[0055] Pulse: stringy, fine and rapid.

[0056] The diagnosis can be made if the above three main symptoms and any two secondary symptoms are present, as well as the above-mentioned tongue coating and pulse conditions.

[0057] 1.3 Inclusion and Exclusion Criteria

[0058] 1.3.1 Inclusion criteria

[0059] ① Meet the Western medical diagnostic criteria for diffuse toxic goiter;

[0060] ②Age 14-70, regardless of gender;

[0061] ③ The syndrome of TCM diagnosis is liver depression transforming into fire, deficiency of both qi and yin, and phlegm and blood stasis;

[0062] ④Sign the informed consent form;

[0063] ⑤ The patient can provide detailed contact information, has no short-term migration, and is willing to cooperate with follow-up.

[0064] 1.3.2 Exclusion criteria

[0065] ① Various types of acute and chronic thyroiditis;

[0066] ② Goiter or hypermetabolic syndrome caused by other diseases;

[0067] ③Thyroid crisis or tendency to thyroid crisis;

[0068] ④ Patients with serious diseases of important organs such as the heart, brain, and kidneys, or mental illness;

[0069] ⑤Women in special physiological conditions (pregnancy, lactation, and pregnancy preparation period).

[0070] 1.4 Treatment

[0071] 1.4.1 Observation Group

[0072] (1) Kangping Yuling prescription (drug composition: Pseudostellariae Radix 30g, Glehnia littoralis 15g, Radix Ophiopogonis 15g, Mother of Pearl 30g, Rhizoma Uncariae 15g, Radix Bupleuri 9g, Radix Paeoniae Alba 9g, Radix Codonopsis pilosulae 9g, Radix Glycyrrhizae Radix 6g, Radix Scutellariae 6g, Rhizoma Atractylodis Macrocephalae 15g, Fructus Schisandrae Chinensis 9g, Poriae 15g, Radix Gentianae 6g, Rhizoma Chuanxiong 12g, Rhizoma Cervi Paniculae 1g, etc., provided by the Pharmacy Department of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, preparation process as in Example 1). 4g / time, 2 times / day, evenly applied to the skin on the surface of the thyroid gland in front of the neck, the course of treatment is 3 months.

[0073] (2) Mental health counseling, dietary regulation guidance and guidance on a regular daily routine.

[0074] 1.4.2 Control group

[0075] (1) Jiaqiya (methimazole cream, Qilu Pharmaceutical Co., Ltd., national medicine standard H20030566), 0.1g / time, twice a day, evenly applied to the skin on the surface of the thyroid gland in front of the neck, the course of treatment is 3 months. (2) Maintain psychological health counseling, dietary adjustment guidance and daily life guidance.

[0076] 1.5 Index detection

[0077] 1.5.1 Baseline Indicators

[0078] General conditions such as gender, age, height, weight, blood pressure, heart rate, and clinical indicators such as liver function and granulocyte count (collected before clinical research).

[0079] 1.5.2 Effectiveness Evaluation Indicators

[0080] Laboratory indicators: FT3, FT4, TSH, TRAb (rechecked every 4 weeks during the treatment period and every 8 weeks during the follow-up period).

[0081] Imaging examination: thyroid volume (recheck every 4 weeks during treatment).

[0082] Thyroid volume measurement: Thyroid ultrasound usually uses the three-dimensional method to measure the thyroid volume. The thyroid volume is calculated according to the ellipse formula V (cm)3 = π / 6 length × width × height, and the total volume is the sum of the two lobes.

[0083] TCM syndrome: TCM symptom score (reviewed every 4 weeks during the treatment period).

[0084] 1.5.2.3 Safety indicators:

[0085] ALT, AST, granulocyte count (rechecked every 4 weeks during the treatment period and once after the follow-up period). General physical examination items, such as body temperature, respiration, heart rate, blood pressure, renal function, urine routine, stool routine, electrocardiogram (once at the 6th and 12th week of treatment and at the end of follow-up). Urine HCG test (once before female enrollment), detailed record of adverse events, and judgment of the correlation with the drug.

[0086] 1.6 Clinical efficacy assessment

[0087] It is formulated with reference to the relevant standards of the "Guidelines for Clinical Research of New Chinese Medicines (Trial)".

[0088] Clinical control: Clinical symptoms completely disappear, body weight returns to pre-onset weight, heart rhythm is regular, pulse rate is normal, thyroid hormone levels (FT3, FT4, TSH, TRAb) return to normal levels, and goiter symptoms are alleviated;

[0089] Markedly effective: Clinical symptoms basically disappeared, body weight returned to pre-onset weight, pulse rate was basically normal, goiter symptoms were alleviated, and thyroid hormone levels were basically normal (FT3, FT4, and TRAb were significantly reduced, and TSH levels were significantly increased);

[0090] Effective: Clinical symptoms were alleviated, weight was increased, goiter symptoms were alleviated, and thyroid hormone levels were improved (FT3, FT4, and TRAb were reduced, and TSH levels were increased);

[0091] Ineffective: All clinical symptoms, signs and thyroid function did not improve after treatment, and even worsened compared with before treatment. Total clinical effective rate = (number of clinical control cases + number of markedly effective cases + number of effective cases) / total number of cases × 100%.

[0092] 1.7 Statistical analysis

[0093] ① All statistical analyses will be calculated using SPSS 26.0 software, and all statistical tests will be two-sided. P values ​​less than or equal to 0.05 will be considered statistically significant; less than or equal to 0.01 will be considered statistically significant. The confidence interval uses a 95% confidence level.

[0094] ② The measurement data of each visit in different treatment groups will be statistically described using ±S. The paired t test will be used to compare the differences before and after treatment within the group. The changes before and after treatment in multiple groups will be compared using analysis of variance.

[0095] ③ The counting data of each visit in different treatment groups were statistically analyzed using frequency (constituent ratio). The changes before and after treatment in multiple groups were analyzed using chi-square test or non-parametric test.

[0096] 2. Test results

[0097] 2.1 Comparison of TCM syndrome scores between the two groups before and after treatment.

[0098] After treatment, the scores of the main symptoms (swelling in the front of the neck, aversion to heat and sweating, fatigue) and the secondary symptoms (finger tremor, insomnia and dreaminess, weight loss, polyphagia, dry mouth) in both groups were reduced compared with those before treatment (P<0.05). After treatment, the scores of the main symptoms and secondary symptoms in the observation group were better than those in the control group. See Table 1.

[0099] Table 1. Comparison of TCM syndrome scores between the two groups before and after treatment (points, )

[0100]

[0101] Note: Compared with the group before treatment, a P<0.05; compared with the control group, b P<0.05

[0102] 2.2 Clinical efficacy of TCM symptoms in the two groups before and after treatment.

[0103] The total effective rate of TCM syndrome in the observation group was 80%, and that in the control group was 40%. The total effective rate in the observation group was higher than that in the control group (P<0.05), as shown in Table 2.

[0104] Table 2. Clinical efficacy of TCM syndromes in the two groups before and after treatment [cases (%), n = 30]

[0105]

[0106] Note: Compared with the control group, b P<0.05

[0107] 2.3 Comparison of FT3, FT4, TSH, TRAb and thyroid volume between the two groups before and after treatment.

[0108] Compared with the group before treatment, FT3, FT4, and TRAb were significantly decreased, TSH was significantly increased, and thyroid volume decreased in both groups after treatment (P<0.05). After treatment, FT3 and FT4 in the control group were lower than those in the observation group, and TSH was higher than that in the observation group (P<0.05). However, the thyroid volume in the observation group was lower than that in the control group (P<0.05). There was no significant difference in TRAb between the two groups. See Table 3.

[0109] Table 3. Comparison of FT3, FT4, TSH, TRAb and thyroid volume between the two groups before and after treatment

[0110]

[0111] Note: Compared with the group before treatment, a P<0.05; compared with the control group after treatment, b P<0.05

[0112] 2.4 Safety evaluation results.

[0113] Regular follow-up during treatment showed that no serious adverse reactions occurred in either group. One case of mild skin redness and swelling occurred in the observation group, and two cases of skin itching occurred in the control group, all of which were relieved after symptomatic treatment. There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). After treatment, no obvious abnormalities were found in blood routine, urine routine, liver and kidney function, electrocardiogram and other related examinations in the two groups.

[0114] In summary, Kangping Yuling prescription can effectively improve patients' clinical symptoms, reduce FT3, FT4, TRAB, increase TSH, and shrink enlarged thyroid gland; no side effects were observed, and local allergies were rare.

Claims

1. A Chinese medicine preparation for external use for treating diffuse toxic goiter, characterized in that: The drug is prepared from the following raw materials in parts by weight: 20-30 parts of Pseudostellariae Radix, 12-15 parts of Adenophora Radix, 12-15 parts of Radix Ophiopogonis, 20-30 parts of Mother of Pearl, 15-20 parts of Uncaria Rhynchophylla, 6-9 parts of Bupleurum Root, 6-9 parts of Codonopsis Pilosula, 6-9 parts of Radix Glycyrrhizae Preparata, 6-9 parts of Scutellariae Baicalensis, 6-9 parts of Gentiana Scabra, 12-15 parts of Ligusticum chuanxiong, 6-9 parts of stir-fried white peony root, 12-15 parts of stir-fried Atractylodes Macrocephala, 12-15 parts of Poria and 6-9 parts of Schisandrae Chinensis.

2. The external Chinese medicine preparation for treating diffuse toxic goiter according to claim 1, characterized in that: The weight proportions of each raw material are respectively: 30 parts of Pseudostellaria heterophylla, 15 parts of Adenophora acuta, 15 parts of Ophiopogon japonicus, 30 parts of Mother of Pearl, 15 parts of Uncaria rhynchophylla, 9 parts of Bupleurum chinense, 9 parts of Codonopsis pilosula, 6 parts of Radix Glycyrrhizae Preparata, 6 parts of Scutellaria baicalensis, 6 parts of Gentiana scabra, 12 parts of Ligusticum chuanxiong, 9 parts of stir-fried White Peony Root, 15 parts of stir-fried Atractylodes macrocephala, 15 parts of Poria cocos, and 9 parts of Schisandra chinensis.

3. A method for preparing the external Chinese medicine preparation for treating diffuse toxic goiter according to claim 1 or 2, characterized in that: The steps include: (1) Weigh each raw material according to weight and wash it; (2) drying the cleaned raw materials; (3) The dried raw materials are decocted twice with water: for the first decoction, add 8 times the water, soak for half an hour, and cook for 2 hours after boiling; for the second decoction, add 6 times the water, and cook for 1 hour after boiling; the decoctions are combined, concentrated, and prepared into a Chinese medicine preparation for external use according to the dosage form requirements.

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