A traditional Chinese medicine composition for treating toxic diffuse goiter and application thereof

Abstract

This invention relates to a traditional Chinese medicine composition for treating toxic diffuse goiter, the composition being made from the following raw materials in parts by weight: Gardenia jasminoides 7-11 parts, vinegar-processed turtle shell 7-11 parts, processed Pinellia ternata 7-11 parts, Bupleurum chinense 7-11 parts, and Panax notoginseng 4-8 parts. This invention also provides applications of the traditional Chinese medicine composition. This invention invigorates blood circulation, disperses stagnation, clears heat, and eliminates goiter. This formula uses Bupleurum chinense as the chief ingredient, combined with Gardenia jasminoides to clear stagnation and guide fire, and processed Pinellia ternata to dispel dampness and resolve phlegm; turtle shell, a yin-strengthening herb, tonifies kidney yin and clears heart fire. Furthermore, there is the theory that prolonged illness often leads to blood stasis, obstructing the meridians, with qi, phlegm, fire, and blood stasis intertwined; Panax notoginseng is added to invigorate blood circulation, unblock the meridians, disperse stagnation, and eliminate masses to interrupt the process. The combination of these herbs clears and drains heart and liver fire, directly addressing the pathogenesis. This invention, combined with a small dose of antithyroid drugs, leads to faster improvement in thyrotoxicosis symptoms. It also improves the patient's depression and anxiety, prevents liver damage and leukopenia, and significantly reduces side effects.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a traditional Chinese medicine composition for treating toxic diffuse goiter and its application. Background Technology

[0002] Toxic diffuse goiter, also known as Graves' disease (GD), is an autoimmune thyroid disease. TSAb is its characteristic immune marker. Multiple abnormal genes and environmental factors are associated with its pathogenesis, showing a significant genetic predisposition. Patients with this disease experience immune dysfunction, which stimulates the thyroid gland, leading to abnormalities in thyroid function and related hormone secretion. Clinically, it is characterized by hypermetabolic syndrome, diffuse thyroid enlargement, Graves' ophthalmopathy (GO), and pretibial myxedema.

[0003] Chinese patent document CN105056137A discloses a traditional Chinese medicine composition for treating toxic diffuse goiter. This composition consists of the following herbs in parts by weight: 8-16 parts of Buddha's Hand Dew, 8-16 parts of Citron, 8-16 parts of Rose, 8-16 parts of Seaweed, 8-16 parts of Deer Antler Vegetable, 8-16 parts of Qiongzhi, 6-14 parts of Rose of the Month, 6-14 parts of Saffron, 6-14 parts of Turmeric, 8-16 parts of Atractylodes Macrocephala, 8-16 parts of Codonopsis pilosula, and 4-8 parts of Licorice. The combined effects of these herbs in this invention promote stagnation and resolve phlegm, invigorate blood circulation, remove blood stasis, soften and disperse nodules. It closely addresses the basic pathogenesis of Graves' disease of the Qi stagnation and phlegm accumulation type, demonstrating significant advantages in improving patients' clinical symptoms, signs, and thyroid function, with definite efficacy and few adverse reactions.

[0004] Chinese patent document CN105233084A discloses a traditional Chinese medicine for treating toxic diffuse goiter. The unique feature of this medicine is that it is mainly composed of the following ingredients in parts by weight: 10-20g of wild amaranth, 5-13g of scutellaria baicalensis, 5-15g of plantain seed, 5-15g of coix seed, 5-15g of fritillaria cirrhosa, 5-13g of senna, 10-20g of gentian root, 5-13g of codonopsis pilosula, 10-20g of sanguisorba officinalis, and 5-15g of celosia seed. This invention is effective, easily absorbed, has no adverse reactions, is safe and reliable, and has low cost. It has broad application prospects and market potential, and is worthy of clinical promotion and application. Patients can take it with peace of mind, and the overall effective rate reaches 97%.

[0005] There are many traditional Chinese medicine compositions for treating toxic diffuse goiter, but they all have some drawbacks, such as too many ingredients, difficulty in sourcing materials, high prices, and unclear efficacy and poor treatment results. Therefore, there is an urgent need for a traditional Chinese medicine composition that is effective in treating toxic diffuse goiter, has fewer ingredients, is practical to use, has high compliance, is safe and effective, and can also improve depressive and anxiety states. Summary of the Invention

[0006] The purpose of this invention is to address the shortcomings of existing technologies by providing a traditional Chinese medicine composition for treating toxic diffuse goiter and its application.

[0007] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating toxic diffuse goiter, the traditional Chinese medicine composition being made from the following raw materials in parts by weight: 7-11 parts of gardenia, 7-11 parts of vinegar-processed turtle shell, 7-11 parts of processed pinellia, 7-11 parts of bupleurum, and 4-8 parts of notoginseng.

[0008] As a preferred example, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 8-10 parts of gardenia, 8-10 parts of vinegar-processed turtle shell, 8-10 parts of processed pinellia, 8-10 parts of bupleurum, and 5-7 parts of notoginseng.

[0009] As another preferred example, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 9 parts gardenia, 9 parts vinegar-processed turtle shell, 9 parts prepared pinellia, 9 parts bupleurum, and 6 parts notoginseng.

[0010] As another preferred example, the traditional Chinese medicine composition is a traditional Chinese medicine composition that treats toxic diffuse goiter while improving the patient's depression and anxiety.

[0011] As another preferred example, the traditional Chinese medicine composition is a traditional Chinese medicine composition that treats toxic diffuse goiter while improving the patient's depression and anxiety state and preventing liver function damage and leukopenia.

[0012] As another preferred example, the medicine composition is in the form of tablets, capsules, granules, oral liquids, or syrups.

[0013] Secondly, the present invention provides a pharmaceutical composition for treating toxic diffuse goiter, the pharmaceutical composition comprising a traditional Chinese medicine composition and methimazole.

[0014] Thirdly, the present invention provides the application of traditional Chinese medicine compositions or pharmaceutical compositions in the preparation of drugs for treating toxic diffuse goiter.

[0015] Fourthly, the present invention provides the application of traditional Chinese medicine compositions or pharmaceutical compositions in the preparation of drugs for treating toxic diffuse goiter while improving patients' depression and anxiety.

[0016] Fifthly, the present invention provides the use of a traditional Chinese medicine composition or pharmaceutical composition in the preparation of a medicament for treating toxic diffuse goiter while improving the patient's depression and anxiety state and preventing liver function damage and leukopenia.

[0017] The advantages of this invention are:

[0018] The treatment principle of this invention is to invigorate blood circulation, dissipate stagnation, clear heat, and eliminate goiter. This formula uses Bupleurum as the chief herb, taking advantage of its ability to clear and drain the Lesser Yang fire, harmonize the Lesser Yang, and also to raise the sunken Yang Qi, restoring it to its proper place. Gardenia is added to clear stagnation and guide fire, thus reaching the lungs, invigorating the stomach, and clearing the Triple Burner. The formula follows Danxi's method of resolving stagnation of Qi, fire, phlegm, and dampness. When liver stagnation is released and the Qi of the Triple Burner flows smoothly, the disease naturally subsides; when Qi is obstructed, dampness accumulates and stagnates into phlegm, Pinellia is added to dispel dampness and resolve phlegm; when the disease course is prolonged, the ministerial fire is stagnant, and the heart fire flares upward, turtle shell, a yin-strengthening herb, is used to tonify kidney water and clear heart fire. Furthermore, there is the theory that prolonged illness often leads to blood stasis, obstructing the meridians, with Qi, phlegm, fire, and blood stasis intertwined; Panax notoginseng is added to invigorate blood circulation, unblock the meridians, dissipate stagnation, and eliminate masses to interrupt the process. The combination of these herbs clears and drains the fire of the heart and liver, directly addressing the pathogenesis.

[0019] This invention combines traditional Chinese medicine with a low dose of antithyroid drugs, resulting in faster improvement of thyrotoxicosis symptoms. It also improves patients' depression and anxiety, prevents liver damage and white blood cell count decline, and significantly reduces side effects. Detailed Implementation

[0020] The present invention will be further described below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the description of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0021] Example 1: A traditional Chinese medicine composition for treating toxic diffuse goiter (I)

[0022] Gardenia 9 parts, vinegar-processed turtle shell 9 parts, prepared Pinellia ternata 9 parts, Bupleurum chinense 9 parts, Panax notoginseng 6 parts.

[0023] Example 2: A traditional Chinese medicine composition for treating toxic diffuse goiter (II)

[0024] Gardenia 9 parts, vinegar-processed turtle shell 7 parts, prepared Pinellia 11 parts, Bupleurum 8 parts, Panax notoginseng 7 parts.

[0025] Example 3: A traditional Chinese medicine composition for treating toxic diffuse goiter (Part III)

[0026] Gardenia 7 parts, vinegar-processed turtle shell 11 parts, prepared Pinellia 8 parts, Bupleurum 10 parts, Panax notoginseng 6 parts.

[0027] Example 4: A traditional Chinese medicine composition for treating toxic diffuse goiter (IV)

[0028] Gardenia 11 parts, vinegar-processed turtle shell 8 parts, prepared Pinellia ternata 10 parts, Bupleurum chinense 9 parts, Panax notoginseng 4 parts.

[0029] Example 5: A traditional Chinese medicine composition for treating toxic diffuse goiter (V)

[0030] Gardenia 8 parts, vinegar-processed turtle shell 10 parts, prepared Pinellia ternata 9 parts, Bupleurum chinense 7 parts, Panax notoginseng 8 parts.

[0031] Example 6: A traditional Chinese medicine composition for treating toxic diffuse goiter (VI)

[0032] Gardenia 10 parts, vinegar-processed turtle shell 9 parts, prepared Pinellia ternata 7 parts, Bupleurum chinense 11 parts, Panax notoginseng 5 parts.

[0033] Example 7: A traditional Chinese medicine composition for treating toxic diffuse goiter (VII)

[0034] Gardenia 9 parts, vinegar-processed turtle shell 11 parts, prepared Pinellia ternata 8 parts, Bupleurum chinense 10 parts, Panax notoginseng 6 parts.

[0035] Example 8: A traditional Chinese medicine composition for treating toxic diffuse goiter (VIII)

[0036] Gardenia 7 parts, vinegar-processed turtle shell 8 parts, prepared Pinellia 10 parts, Bupleurum 9 parts, Panax notoginseng 4 parts.

[0037] Example 9: A traditional Chinese medicine composition for treating toxic diffuse goiter (IX)

[0038] Gardenia 11 parts, vinegar-processed turtle shell 10 parts, prepared Pinellia 9 parts, Bupleurum 7 parts, Panax notoginseng 8 parts.

[0039] Example 10: A traditional Chinese medicine composition for treating toxic diffuse goiter (X)

[0040] Gardenia 8 parts, vinegar-processed turtle shell 9 parts, prepared Pinellia ternata 7 parts, Bupleurum chinense 11 parts, Panax notoginseng 5 parts.

[0041] Example 11: A Traditional Chinese Medicine Composition for Treating Toxic Diffuse Goiter (XI)

[0042] Gardenia 10 parts, vinegar-processed turtle shell 7 parts, prepared Pinellia 11 parts, Bupleurum 8 parts, Panax notoginseng 7 parts.

[0043] Example 12 Clinical Trial

[0044] 1. Subjects: This study recruited 120 patients who were initially diagnosed with toxic diffuse goiter at the Thyroid Disease Clinic of Shanghai Municipal Hospital of Traditional Chinese Medicine between October 2022 and October 2023. Patients were randomly assigned to two groups using a randomized controlled trial. Nine patients dropped out, resulting in a total of 111 patients included in the statistical analysis. The experimental group consisted of 56 patients, and the control group consisted of 55 patients.

[0045] 2. Intervention methods:

[0046] Control group: Oral methimazole (Merck Hhealthcare KGaA), 10 mg / time, 3 times / day; after 3 weeks of continuous medication, the dosage was reduced by 5 mg / day each time according to thyroid function, liver function and white blood cell count; the medication was used for a total of 12 weeks.

[0047] Experimental group: low-dose methimazole 10mg / day combined with Ningyingfang (gardenia 9g, vinegar-processed turtle shell 9g, prepared pinellia 9g, bupleurum 9g, notoginseng 6g, medicinal materials sourced from Shanghai Wanshicheng Pharmaceutical Co., Ltd.), water decoction, 200ml / time, twice / day; the methimazole dosage reduction method was the same as the control group; the medication was used for 12 weeks.

[0048] 3. Observation indicators and methods:

[0049] ① The Traditional Chinese Medicine (TCM) syndrome scoring system assesses the severity of primary and secondary symptoms of excessive heart and liver fire. Asymptomatic cases receive 0 points, mild cases receive 1 point, moderate cases receive 2 points, and severe cases receive 3 points. Tongue and pulse are not scored. The total score is the sum of all scores, ranging from 0 to 24 points.

[0050] ② Thyroid function and related antibody levels were measured in serum before treatment and 12 weeks after treatment, including FT3 (pmol / L), FT4 (pmol / L), TSH (uIU / mL), TRAb (IU / L), TPOAb (IU / ml), and TgAb (U / ml).

[0051] ③ Emotional and Lifestyle Therapy Scales: Before and 12 weeks after treatment, the Self-Rating Depression Scale (SDS) and the Self-Rating Anxiety Scale (SAS) were used for self-assessment of subjective feelings of depression and anxiety (<50 points is normal, 50-59 is mild, 60-69 is severe, >70 is severe). The SF-36 Quality of Life Scale was used to evaluate the impact of treatment on patients' quality of life.

[0052] ④ Safety evaluation: Liver function and blood routine tests were monitored before treatment and at 3 and 12 weeks after treatment.

[0053] 4. Criteria for Evaluating Therapeutic Effect

[0054] The assessment was conducted using the nimodipine method, based on the TCM syndrome score: (pre-treatment score - post-treatment score) ÷ (pre-treatment score) × 100%. Complete remission: Symptoms and signs disappeared, and FT3, FT4, and TSH returned to normal. Significant effect: Symptoms and signs significantly improved, TCM syndrome score decreased by ≥70%, and FT3, FT4, and TSH did not reach normal values ​​but decreased by ≥20%. Effective: Symptoms and signs improved, TCM syndrome score decreased by ≥30%, and FT3, FT4, and TSH did not reach normal values ​​but decreased by ≥10%. Ineffective: The above criteria were not met.

[0055] 5 Statistical Methods

[0056] All data were processed by specialists using SPSS 26.0. For continuous data, when the data follow a normal distribution, the mean ± standard deviation is used. When data does not follow a normal distribution, the median interquartile range (M(Q1,Q3)) is used; qualitative data are expressed as percentages (e.g., %). Two-sample t-tests or Mann-Whitney U tests are used. For ordinal data, nonparametric rank-sum tests are used for comparisons between groups. For count data, Pearson chi-square tests are used if the criteria are met; otherwise, Pearson continuous-corrected chi-square tests or Fisher's exact test are used. All statistical tests are two-tailed, and the significance level is set at α = 0.05, meaning p < 0.05 is considered statistically significant.

[0057] 6 Research Results

[0058] 6.1 Comparison of TCM syndrome scores before and after treatment

[0059] There was no statistically significant difference in the total TCM syndrome scores between the two groups before treatment (P>0.05), indicating comparability. After treatment, the TCM syndrome scores in the treatment group were significantly lower (P<0.001), and the treatment group was significantly better than the control group (P<0.001). See Table 1 for details.

[0060] Table 1 Comparison of TCM syndrome scores before and after treatment in the two groups [scores, ]

[0061]

[0062] Note: ***P < 0.001 for comparisons between the two groups. ### Before and after treatment, P<0.001

[0063] 6.2 Comparison of clinical efficacy

[0064] The total effective rate in the experimental group (86.4%) was significantly higher than that in the control group (42.6%), and the difference in total effective rate between the two groups was statistically significant (P<0.001). See Table 2 for details.

[0065] Table 2 Comparison of clinical efficacy between the two groups [n(percentage, %)]

[0066]

[0067] Note: **P < 0.01 for comparisons between two groups.

[0068] 6.3 Comparison of serum FT3, FT4, and TSH changes before and after treatment in the two groups: Before treatment, there were no significant differences in baseline FT3, FT4, and TSH levels between the two groups (P>0.05); after 12 weeks of treatment, FT3 and FT4 levels in both the control and experimental groups decreased significantly compared to before treatment (P<0.01), while TSH levels increased significantly compared to before treatment (P<0.01); no significant differences were observed between the two groups. See Table 3 for details.

[0069] Table 3 Comparison of serum FT3, FT4, and TSH levels before and after treatment in the two groups (M(Q1,Q3))

[0070]

[0071] Note: ## Before and after treatment, P<0.01

[0072] 6.4 Comparison of serum TRAb, TPoAb, and TgAb changes before and after treatment in the two groups: Before treatment, there were no significant differences in baseline TRAb, TPoAb, and TgAb levels between the two groups (P>0.05); after 12 weeks of treatment, TRAb, TPoAb, and TgAb levels in the experimental group decreased significantly compared to before treatment (P<0.01); no significant differences were observed in the control group. See Table 4 for details.

[0073]

[0074] Note: **P < 0.01 for comparisons between two groups. ## Before and after treatment, P<0.01

[0075] 6.5 Comparison of SDS, SAS, and SF-36 scores between the two groups before and after treatment. Before treatment, there were no significant differences in the baseline scores of the SAS, SDS, and SF-36 scales between the two groups (P>0.05). After 12 weeks of treatment, the SDS and SAS scores in the experimental group improved compared to before treatment (P<0.01); the SDS and SAS scores in the experimental group decreased by 9.36±5.61 and 8.94±4.60 points respectively after treatment, which was significantly different from the control group (P<0.01). The SF-36 score in the experimental group significantly improved compared to before treatment (P<0.01); the score in the experimental group increased by 13.29±9.23 points after treatment, while the score in the control group decreased by 0.35±10.76 points, which was significantly different (P<0.05). See Table 5 for details. Table 5 Comparison of SDS, SAS, and SF-36 scores between the two groups before and after treatment.

[0076]

[0077] Note: **P < 0.01 for comparisons between two groups.## Before and after treatment, P<0.01

[0078] 6.6 Safety Evaluation: Liver function and blood routine indicators were re-examined after 3 weeks. In the control group, 2 cases showed a liver function increase >3 times, and methimazole was discontinued due to suspected drug-induced liver injury. In the control group, 12 cases of mild liver function impairment (AST or ALT <2 times) were treated with hepatoprotective drugs, compared to 2 cases in the treatment group. In the control group, 3 cases showed a decrease in white blood cell count (<3.0*10^6). 9 In addition to the use of the white blood cell-boosting drug Leukogen, no decrease in white blood cell count was observed in the experimental group.

[0079] See Table 6 for details.

[0080] Table 6. Adverse event incidence (n, %)

[0081]

[0082] Note: * P < 0.05 for comparisons between two groups, *** P < 0.001 for comparisons between two groups.

[0083] 7. Discussion

[0084] The difficulty in treating toxic diffuse goiter lies in the fact that antithyroid drugs can cause liver damage and decreased white blood cell count, and the side effects are dose-dependent.

[0085] In this invention, the addition of traditional Chinese medicine in combination with a small dose of anti-thyroid hormone reduces side effects and leads to faster improvement in thyrotoxicosis symptoms.

[0086] The above description is only a preferred embodiment of the present invention. It should be noted that those skilled in the art can make several improvements and additions without departing from the method of the present invention, and these improvements and additions should also be considered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for treating toxic diffuse goiter, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 7-11 parts Gardenia, 7-11 parts Vinegar-processed Turtle Shell, 7-11 parts Processed Pinellia, 7-11 parts Bupleurum, and 4-8 parts Panax notoginseng.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 8-10 parts of gardenia, 8-10 parts of vinegar-processed turtle shell, 8-10 parts of processed pinellia, 8-10 parts of bupleurum, and 5-7 parts of notoginseng.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 9 parts gardenia, 9 parts vinegar-processed turtle shell, 9 parts prepared pinellia, 9 parts bupleurum, and 6 parts notoginseng.

4. The traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The aforementioned traditional Chinese medicine composition is a traditional Chinese medicine composition that treats toxic diffuse goiter while improving the patient's depression and anxiety.

5. The traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The aforementioned traditional Chinese medicine composition is a combination of traditional Chinese medicines used to treat toxic diffuse goiter, improve patients' depression and anxiety, and prevent liver damage and leukopenia.

6. The traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The traditional Chinese medicine composition is in the form of tablets, capsules, granules, oral liquids, or syrups.

7. A pharmaceutical composition for treating toxic diffuse goiter, characterized in that, The pharmaceutical composition comprises the traditional Chinese medicine composition according to any one of claims 1-3 and methimazole.

8. The use of the traditional Chinese medicine composition according to any one of claims 1-3 or the pharmaceutical composition according to claim 7 in the preparation of a drug for treating toxic diffuse goiter.

9. The use of the traditional Chinese medicine composition according to any one of claims 1-3 or the pharmaceutical composition according to claim 7 in the preparation of a drug for treating toxic diffuse goiter while improving the patient's depressive and anxious state.

10. The use of the traditional Chinese medicine composition according to any one of claims 1-3 or the pharmaceutical composition according to claim 7 in the preparation of a medicament for treating toxic diffuse goiter while improving the patient's depression and anxiety state and preventing liver function damage and leukopenia.

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