Application of traditional Chinese medicine composition in preparation of medicine for treating and / or preventing thyroid diseases

Abstract

The invention belongs to the technical field of traditional Chinese medicine, and particularly relates to application of a traditional Chinese medicine composition in preparation of medicine for treating thyroiditis, and the traditional Chinese medicine composition is mainly prepared from codonopsis pilosula, radix astragali preparata, poria cocos, fried rhizoma atractylodis macrocephalae, prepared polygala tenuifolia, honey-fried licorice root, fried spina date seed, longan aril, angelica sinensis, jujube, elecampane and ginger. All the medicines in the traditional Chinese medicine composition conform to the principle of compatibility of monarch, minister, assistant and guide, compatibility is scientific, clinical cases are considered, pharmacodynamic tests show that the composition can remarkably improve the basic condition of mice suffering from thyroiditis, adjust the levels of thyroid hormones T3, T4 and TSH of the mice, reduce inflammatory factors TNF-alpha and IL-10 and inhibit inflammatory reaction, and clinical tests verify that the composition has a remarkable curative effect on thyroiditis. The traditional Chinese medicine composition can effectively relieve symptoms of patients with thyroiditis, is low in toxic and side effects and good in safety, and has a wide market prospect.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, and relates to a traditional Chinese medicine composition, its preparation method and new uses, specifically to a preparation method and new uses of Guipi Heji (a traditional Chinese medicine compound). Background Technology

[0002] Thyroid diseases and other endocrine and metabolic disorders are major health risks, imposing a significant medical burden on society and attracting increasing public attention. Data shows that thyroiditis accounts for approximately 15%-25% of all thyroid diseases, with women being more affected than men. Clinically, it can be broadly divided into chronic and acute types: chronic thyroiditis, represented by Hashimoto's thyroiditis, is autoimmune-mediated, has a prolonged course, and is often accompanied by hypothyroidism; acute thyroiditis, primarily subacute thyroiditis, is characterized by acute pain and cytokine storm, accounting for 15%-20% of all thyroiditis cases. Compared to other types, subacute thyroiditis, due to its significant symptoms, need for urgent intervention, and the inherent contradictions in treatment, has become a focus of clinical attention.

[0003] Subacute thyroiditis (SAT), a self-limiting disease related to the immune response following viral infection, resolves spontaneously in most cases, but the suffering it causes and its impact on quality of life cannot be ignored. With its rising incidence, its treatment has become an increasingly important concern. Modern medicine has not fully elucidated the pathogenesis of SAT, but it is generally believed to be related to viral infection and allergic reactions, while some studies show a close relationship with genetic factors. In terms of treatment, Western medicine focuses on symptom relief and thyroid function regulation. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to relieve pain and have some efficacy, but significant side effects and a high relapse rate are common. Long-term use of NSAIDs may cause liver and kidney toxicity, leading to symptoms such as fatigue and jaundice, severely affecting liver and kidney function. Gastrointestinal reactions are also common, such as nausea, vomiting, abdominal pain, and diarrhea, further exacerbating the suffering of already unwell patients. These side effects severely impact patients' quality of life and cause some patients to develop resistance to Western medical treatment.

[0004] Western medicine treatment has obvious limitations, while traditional Chinese medicine shows unique advantages. The advantages of traditional Chinese medicine in the treatment of subacute thyroiditis are becoming increasingly prominent. Traditional Chinese medicine classifies SAT into the categories of "goiter disease", "painful goiter", and "goiter swelling", and the understanding of its etiology and pathogenesis mainly focuses on two aspects: internal injury and external infection. Based on this, many treatment methods have been proposed by medical experts in past dynasties. For the qi and blood stagnation in front of the neck caused by exogenous wind-heat pathogens, some medical experts adopt the treatment method of dispersing wind and heat, reducing swelling and relieving pain, and select drugs with the effect of clearing heat and detoxifying, such as honeysuckle and forsythia; for the qi and blood stagnation and abnormal distribution of body fluids caused by emotional depression, some medical experts take the treatment idea of soothing the liver and regulating qi, promoting blood circulation and removing blood stasis, and commonly use medicinal materials such as bupleurum and turmeric. These treatment methods start from the overall perspective, combining disease differentiation and syndrome differentiation, and have achieved good results in clinical practice.

[0005] As a classic prescription, although there is no relevant report on the use of Guipi Mixture in the treatment of thyroid diseases, based on its ingredients and efficacy, it is expected to play a potential role in the treatment of subacute thyroiditis.

[0006] Guipi Mixture is composed of stir-fried atractylodes macrocephala, poria cocos, prepared polygala tenuifolia, longan aril, angelica sinensis, codonopsis pilosula, roasted astragalus membranaceus, stir-fried wild jujube seed, roasted licorice root, costus root, Chinese date, and ginger, and has the effects of replenishing qi and strengthening the spleen, nourishing blood and calming the mind. From the perspective of the etiology and pathogenesis of subacute thyroiditis, in the internal injury factor, emotional disorder leads to the liver losing its dredging function, qi stagnation transforming into fire, and the fire transforming body fluids into phlegm, which binds in the neck. This process may lead to qi and blood deficiency and disharmony of the spleen and stomach functions. Codonopsis pilosula and roasted astragalus membranaceus in Guipi Mixture can replenish qi and strengthen the spleen, providing power for the recovery of spleen and stomach functions. When the spleen and stomach functions are normal, qi and blood can be generated smoothly, which helps to improve the condition of qi and blood deficiency. Angelica sinensis has the effects of nourishing blood and promoting blood circulation, which can promote qi and blood circulation and relieve the problem of qi and blood stagnation. Stir-fried atractylodes macrocephala and poria cocos can strengthen the spleen and promote diuresis, preventing the endogenous generation of phlegm-dampness and avoiding the aggravation of the disease caused by the binding of phlegm pathogens in the neck. Costus root can promote qi circulation to relieve pain and strengthen the spleen and promote digestion, and can relieve the discomfort caused by qi stagnation.

[0007] At present, there is no relevant research or report on the use of Guipi Mixture in the treatment of thyroid diseases. However, from its ingredients, efficacy, and the etiology and pathogenesis of subacute thyroiditis and the treatment idea of traditional Chinese medicine, Guipi Mixture has certain potential value in the treatment of subacute thyroiditis. The inventor has carried out relevant clinical research and experimental research to explore the specific mechanism, efficacy, and safety of Guipi Mixture in the treatment of subacute thyroiditis, providing new ideas and methods for the treatment of subacute thyroiditis. Summary of the Invention

[0008] The present invention is a further development of the uses of the existing product "Guipi Mixture", and its new use is derived from the feedback of the company's employees. The employees reported that during the medication period, taking "Guipi Mixture" to regulate the sleep condition, the condition of thyroiditis was significantly relieved and the treatment period was shortened. Therefore, according to the employees' feedback, the applicant further studied its use in the treatment of thyroiditis.

[0009] The first object of the present invention is to provide the use of a traditional Chinese medicine composition in the treatment of thyroid diseases.

[0010] In some embodiments, the traditional Chinese medicine composition includes Codonopsis pilosula, stir-fried Atractylodes macrocephala, roasted Astragalus membranaceus, roasted Glycyrrhiza uralensis, Poria cocos, processed Polygala tenuifolia, stir-fried Ziziphus jujuba var. spinosa, Arillus longan, Angelica sinensis, Aucklandia lappa, Chinese date, and ginger.

[0011] The second object of the present invention is to provide the weight ratio of the traditional Chinese medicine composition: Codonopsis pilosula 45 - 100 parts by weight, stir-fried Atractylodes macrocephala 100 - 175 parts by weight, roasted Astragalus membranaceus 45 - 100 parts by weight Roasted Glycyrrhiza uralensis 15 - 55 parts by weight, Poria cocos 100 - 175 parts by weight, processed Polygala tenuifolia 100 - 175 parts by weight Stir-fried Ziziphus jujuba var. spinosa 45 - 100 parts by weight, Arillus longan 100 - 175 parts by weight, Angelica sinensis 100 - 175 parts by weight Aucklandia lappa 15 - 55 parts by weight, Chinese date 15 - 60 parts by weight, ginger 5 - 40 parts by weight.

[0012] In some embodiments, the traditional Chinese medicine composition is made from the following traditional Chinese medicine components in the following weight ratio: Codonopsis pilosula 68 parts by weight, stir-fried Atractylodes macrocephala 136 parts by weight, roasted Astragalus membranaceus 68 parts by weight Roasted Glycyrrhiza uralensis 34 parts by weight, Poria cocos 136 parts by weight, processed Polygala tenuifolia 136 parts by weight Stir-fried Ziziphus jujuba var. spinosa 68 parts by weight, Arillus longan 136 parts by weight, Angelica sinensis 136 parts by weight Aucklandia lappa 34 parts by weight, Chinese date 34 parts by weight, ginger 17 parts by weight.

[0013] The third object of the present invention is to provide the preparation method of the traditional Chinese medicine composition:

[0014] Stir-fried Atractylodes macrocephala, Aucklandia lappa, and Angelica sinensis are respectively distilled to extract volatile oils, and the medicinal residues are reserved.

[0015] The residue of Angelica sinensis was percolated with 50% ethanol as a solvent. The percolate was collected and the ethanol was recovered. The residue of Atractylodes macrocephala and Aucklandia lappa, along with the remaining nine herbs including Codonopsis pilosula, were decocted three times with water: 2 hours for the first decoction, 1.5 hours for the second decoction, and 1 hour for the third decoction. The decoctions were combined, filtered, and the filtrate was concentrated to an appropriate volume. This filtrate was then combined with the percolate, allowed to stand, filtered, and the filtrate was concentrated to approximately 1000 mL. 3 g of sodium benzoate was added, the mixture was cooled, and the volatile oil was added. Water was added to 1000 mL and mixed well to obtain the final product.

[0016] In some embodiments, the traditional Chinese medicine composition is prepared into a clinically acceptable dosage form after the addition of excipients.

[0017] In a preferred embodiment, the clinically acceptable dosage form is granules, tablets, pills, capsules, and microcapsules.

[0018] In a preferred embodiment, the clinically acceptable dosage form is an oral compound.

[0019] Specifically, the thyroid diseases mentioned include hyperthyroidism and thyroiditis.

[0020] In a preferred embodiment, the thyroiditis is acute thyroiditis, subacute thyroiditis, or chronic thyroiditis.

[0021] In a preferred embodiment, the thyroiditis is subacute thyroiditis.

[0022] The fourth object of the present invention is to provide the use of Guipi Heji as a medicine for treating thyroid diseases.

[0023] Specifically, this invention provides the use of Guipi Heji in the treatment of subacute thyroiditis.

[0024] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0025] (1) Pharmacodynamic tests show that the composition of the present invention can improve the basic condition of mice with thyroiditis, adjust the thyroid hormone level of mice, reduce the levels of T3 and T4, increase the level of TSH, and at the same time reduce the levels of inflammatory factors TNF-α and IL-10, thus inhibiting the inflammatory response.

[0026] (2) Clinical trials have verified that the present invention can effectively alleviate the symptoms of patients with thyroiditis, improve the TCM syndrome of patients with subacute thyroiditis, and the relief of the main symptoms is particularly prominent. The efficacy rate is better than that of the positive control group prednisolone acetate tablets. Attached Figure Description

[0027] Figure 1 The levels of TNF-α in the serum of mice in each group (compared to the model group) were measured. @ P <0.05,@@ P <0.01; compared with the positive group, # P <0.05, ## P <0.01; compared with the low-dose group of Guipi Heji, ^ P <0.05, ^^ P <0.01).

[0028] Figure 2 The levels of IL-10 in the serum of mice in each group (compared to the model group) were measured. @ P <0.05, @@ P <0.01; compared with the positive group, # P <0.05, ## P <0.01; compared with the low-dose group of Guipi Heji, ^ P <0.05, ^^ P <0.01). Specific Implementation

[0029] To make the objectives and technical solutions of this invention clearer, the following embodiments are provided for further explanation. However, the scope of protection of this invention is not limited to these embodiments; the embodiments are merely for illustrative purposes. Those skilled in the art should understand that any changes or equivalent substitutions that do not depart from the concept of this invention are included within the scope of protection of this invention.

[0030] Example 1: Mixture (Gui Pi Mixture) Codonopsis pilosula 68 parts by weight, stir-fried Atractylodes macrocephala 136 parts by weight, processed Astragalus membranaceus 68 parts by weight Prepared licorice root 34 parts by weight, Poria cocos 136 parts by weight, processed Polygala tenuifolia 136 parts by weight 68 parts by weight of stir-fried jujube seeds, 136 parts by weight of longan pulp, and 136 parts by weight of angelica root. 34 parts by weight of costus root, 34 parts by weight of jujube, and 17 parts by weight of ginger.

[0031] Preparation process: Stir-fry Atractylodes macrocephala, Aucklandia lappa, and Angelica sinensis to extract volatile oils by distillation. The residues are kept for later use. The Angelica sinensis residues are percolated with 50% ethanol as a solvent. The percolate is collected and the ethanol is recovered. The residues of Atractylodes macrocephala and Aucklandia lappa are decocted three times with water, the first time for 2 hours, the second time for 1.5 hours, and the third time for 1 hour. The decoctions are combined, filtered, and the filtrate is concentrated to an appropriate amount. It is then combined with the percolate, allowed to stand, filtered, and the filtrate is concentrated to about 1000 mL. 3g of sodium benzoate is added, cooled, and the above volatile oils are added. Water is added to 1000 mL and mixed well to obtain the final product.

[0032] Example 2: Mixture (100 vials) Codonopsis pilosula 45 parts by weight, stir-fried Atractylodes macrocephala 100 parts by weight, and processed Astragalus membranaceus 45 parts by weight Prepared licorice root 15 parts by weight, Poria cocos 100 parts by weight, processed Polygala tenuifolia 100 parts by weight 45 parts by weight of stir-fried jujube seeds, 100 parts by weight of longan pulp, and 100 parts by weight of angelica root. 15 parts by weight of costus root, 15 parts by weight of jujube, and 5 parts by weight of ginger.

[0033] Preparation process: Same as in Example 1.

[0034] Example 3: Mixture (100 vials) 100 parts by weight of Codonopsis pilosula, 175 parts by weight of stir-fried Atractylodes macrocephala, and 100 parts by weight of processed Astragalus membranaceus. Prepared licorice root 55 parts by weight, Poria cocos 175 parts by weight, processed Polygala tenuifolia 175 parts by weight 100 parts by weight of stir-fried jujube seeds, 175 parts by weight of longan pulp, and 175 parts by weight of angelica root. 55 parts by weight of costus root, 60 parts by weight of jujube, and 5-40 parts by weight of ginger.

[0035] Preparation process: Same as in Example 1.

[0036] Example 4: Granules (100 parts) Codonopsis pilosula 68 parts by weight, stir-fried Atractylodes macrocephala 136 parts by weight, processed Astragalus membranaceus 68 parts by weight Prepared licorice root 34 parts by weight, Poria cocos 136 parts by weight, processed Polygala tenuifolia 136 parts by weight 68 parts by weight of stir-fried jujube seeds, 136 parts by weight of longan pulp, and 136 parts by weight of angelica root. 34 parts by weight of costus root, 34 parts by weight of jujube, and 17 parts by weight of ginger.

[0037] Preparation process: The volatile oils of stir-fried Atractylodes macrocephala, Aucklandia lappa, and Angelica sinensis are extracted by distillation, and the residues are reserved. The Angelica sinensis residues are percolated with 50% ethanol as a solvent, the percolate is collected, and the ethanol is recovered. The residues of Atractylodes macrocephala and Aucklandia lappa are decocted three times with water along with the remaining nine herbs, including Codonopsis pilosula: 2 hours for the first decoction, 1.5 hours for the second decoction, and 1 hour for the third decoction. The decoctions are combined, filtered, and the filtrate is concentrated under reduced pressure to obtain an extract with a relative density of 1.10-1.15 (50℃). An appropriate amount of dextrin is added, mixed well, and granules of 1000g are prepared.

[0038] Example 5: Tablets (1500 servings) Codonopsis pilosula 68 parts by weight, stir-fried Atractylodes macrocephala 136 parts by weight, processed Astragalus membranaceus 68 parts by weight Prepared licorice root 34 parts by weight, Poria cocos 136 parts by weight, processed Polygala tenuifolia 136 parts by weight 68 parts by weight of stir-fried jujube seeds, 136 parts by weight of longan pulp, and 136 parts by weight of angelica root. 34 parts by weight of costus root, 34 parts by weight of jujube, and 17 parts by weight of ginger.

[0039] Preparation process: The above twelve ingredients are pulverized, with 220g of fine powder taken from Codonopsis pilosula, Poria cocos, and prepared licorice root. The remainder is reserved. The volatile oils of Angelica sinensis, stir-fried Atractylodes macrocephala, and Aucklandia lappa are extracted by distillation. The residue of Angelica sinensis is percolated with ginger using the percolation method described in the section on fluid extracts and extracts, with 50% ethanol as the solvent. The percolate is collected, and the ethanol is recovered. The residues of Atractylodes macrocephala and Aucklandia lappa, along with the remaining five ingredients including Polygala tenuifolia, Codonopsis pilosula, Poria cocos, and prepared licorice root, are decocted three times with water. The decoctions are filtered, the filtrates are combined, concentrated to an appropriate volume, and combined with the above percolate, concentrated into a thick paste. The fine powder of Codonopsis pilosula and other ingredients is added, mixed well, granulated, dried, and the volatile oil is added, mixed well, and pressed into 1500 tablets.

[0040] Example 6: Pills Codonopsis pilosula 68 parts by weight, stir-fried Atractylodes macrocephala 136 parts by weight, processed Astragalus membranaceus 68 parts by weight Prepared licorice root 34 parts by weight, Poria cocos 136 parts by weight, processed Polygala tenuifolia 136 parts by weight 68 parts by weight of stir-fried jujube seeds, 136 parts by weight of longan pulp, and 136 parts by weight of angelica root. 34 parts by weight of costus root, 34 parts by weight of jujube, and 17 parts by weight of ginger.

[0041] Preparation process: Grind the above twelve ingredients into a fine powder, sieve, and mix well. Add 800-900g of refined honey to the powder to make small honey pills, resulting in 1800 pills, each weighing 1g.

[0042] Alternatively, grind the above twelve ingredients into a fine powder, sift, and mix well. Add 800-900g of refined honey to the above powder to make large honey pills, thus obtaining 200 pills, each weighing 9g.

[0043] Example 7: Powder (100g) Codonopsis pilosula 68 parts by weight, stir-fried Atractylodes macrocephala 136 parts by weight, processed Astragalus membranaceus 68 parts by weight Prepared licorice root 34 parts by weight, Poria cocos 136 parts by weight, processed Polygala tenuifolia 136 parts by weight 68 parts by weight of stir-fried jujube seeds, 136 parts by weight of longan pulp, and 136 parts by weight of angelica root. 34 parts by weight of costus root, 34 parts by weight of jujube, and 17 parts by weight of ginger.

[0044] Preparation process: The above twelve ingredients are dried, pulverized into fine powder, passed through a 100-mesh sieve, and mixed evenly to obtain the final product.

[0045] Example 8: Capsules (100 capsules) Codonopsis pilosula 68 parts by weight, stir-fried Atractylodes macrocephala 136 parts by weight, processed Astragalus membranaceus 68 parts by weight Prepared licorice root 34 parts by weight, Poria cocos 136 parts by weight, processed Polygala tenuifolia 136 parts by weight 68 parts by weight of stir-fried jujube seeds, 136 parts by weight of longan pulp, and 136 parts by weight of angelica root. 34 parts by weight of costus root, 34 parts by weight of jujube, and 17 parts by weight of ginger.

[0046] Preparation process: Stir-fry Atractylodes macrocephala, Aucklandia lappa, and Angelica sinensis to extract volatile oils by distillation (retain the residue). The volatile oils are mixed with β-cyclodextrin to form an inclusion complex, which is then dried and pulverized for later use. Subsequently, the residue of Angelica sinensis is percolated with 50% ethanol, and the ethanol is recovered from the percolate to obtain a concentrated liquid. At the same time, the residues of Atractylodes macrocephala and Aucklandia lappa, along with the remaining 9 herbs, are decocted three times with water (for 2 hours, 1.5 hours, and 1 hour, respectively). The decoction is filtered and concentrated. Then, the concentrated decoction is combined with the percolate of Angelica sinensis, allowed to stand, filtered, and concentrated to a clear extract. Sodium benzoate is added and dried to obtain a dry extract powder. The dry extract powder is then mixed with the volatile oil inclusion complex and microcrystalline cellulose, granulated (or directly using the mixed powder), and then filled into empty capsules of appropriate specifications.

[0047] Comparative Example 1 (Mixed Solution) Codonopsis pilosula 30 parts by weight, stir-fried Atractylodes macrocephala 80 parts by weight, and processed Astragalus membranaceus 120 parts by weight Prepared licorice root 20 parts by weight, Poria cocos 80 parts by weight, and processed Polygala tenuifolia 136 parts by weight Stir-fried jujube seeds 68 parts by weight, longan pulp 200 parts by weight, angelica root 200 parts by weight 60 parts by weight of costus root, 20 parts by weight of jujube, and 10 parts by weight of ginger.

[0048] Preparation process: Same as in Example 1.

[0049] Comparative Example 2 (Mixed Solution) Codonopsis pilosula 68 parts by weight, stir-fried Atractylodes macrocephala 136 parts by weight, processed Astragalus membranaceus 68 parts by weight Prepared licorice root 34 parts by weight, Poria cocos 136 parts by weight, processed Polygala tenuifolia 136 parts by weight 68 parts by weight of stir-fried jujube seeds, 136 parts by weight of longan pulp, and 136 parts by weight of angelica root. Cyperus rotundus 34 parts by weight, jujube 34 parts by weight, ginger 17 parts by weight.

[0050] Preparation process: Stir-fry Atractylodes macrocephala, Cyperus rotundus, and Angelica sinensis to extract volatile oils by distillation, and set aside the residues; percolate the Angelica sinensis residues with 50% ethanol as solvent, collect the percolate, and recover the ethanol; decoct the residues of Atractylodes macrocephala and Cyperus rotundus with the remaining nine herbs, including Codonopsis pilosula, three times with water: 2 hours for the first time, 1.5 hours for the second time, and 1 hour for the third time. Combine the decoctions, filter, concentrate the filtrate to an appropriate volume, combine it with the above percolate, let it stand, filter, concentrate the filtrate to about 1000 mL, add 3g of sodium benzoate, cool, add the above volatile oils, add water to 1000 mL and mix well to obtain the final product.

[0051] Comparative Example 3 (Mixed Solution) Codonopsis pilosula 68 parts by weight, stir-fried Atractylodes macrocephala 136 parts by weight, processed Astragalus membranaceus 68 parts by weight Prepared licorice root 34 parts by weight, Poria cocos 136 parts by weight, processed Polygala tenuifolia 136 parts by weight 68 parts by weight of stir-fried jujube seeds, 136 parts by weight of prepared rehmannia root, and 136 parts by weight of angelica root. 34 parts by weight of costus root, 34 parts by weight of jujube, and 17 parts by weight of ginger.

[0052] Preparation process: Stir-fry Atractylodes macrocephala, Aucklandia lappa, and Angelica sinensis to extract volatile oils by distillation. The residues are kept for later use. The Angelica sinensis residues are percolated with 50% ethanol as a solvent. The percolate is collected and the ethanol is recovered. The residues of Atractylodes macrocephala and Aucklandia lappa are decocted three times with water, the first time for 2 hours, the second time for 1.5 hours, and the third time for 1 hour. The decoctions are combined, filtered, and the filtrate is concentrated to an appropriate amount. It is then combined with the percolate, allowed to stand, filtered, and the filtrate is concentrated to about 1000 mL. 3g of sodium benzoate is added, cooled, and the above volatile oils are added. Water is added to 1000 mL and mixed well to obtain the final product.

[0053] Comparative Example 4 Codonopsis pilosula 68 parts by weight, stir-fried Atractylodes macrocephala 136 parts by weight, processed Astragalus membranaceus 68 parts by weight Prepared licorice root 34 parts by weight, Poria cocos 136 parts by weight, processed Polygala tenuifolia 136 parts by weight 68 parts by weight of stir-fried jujube seeds, 136 parts by weight of longan pulp, and 136 parts by weight of Sichuan lovage rhizome. 34 parts by weight of costus root, 34 parts by weight of jujube, and 17 parts by weight of ginger.

[0054] Atractylodes macrocephala Koidz. stir-fried with bran, Aucklandia lappa Decne., and Angelica sinensis (Oliv.) Diels were separately distilled to extract volatile oils, and the medicinal residues were reserved. The medicinal residue of Angelica sinensis was percolated with 50% ethanol as the solvent, the percolate was collected, and the ethanol was recovered; the medicinal residues of Atractylodes macrocephala Koidz. stir-fried with bran and Aucklandia lappa Decne. and the other nine flavors such as Codonopsis pilosula (Franch.) Nannf. were decocted with water three times, 2 hours for the first time, 1.5 hours for the second time, and 1 hour for the third time. The decoction liquids were combined, filtered, the filtrate was concentrated to an appropriate amount, combined with the above percolate, allowed to stand, filtered, the filtrate was concentrated to about 1000 mL, 3 g of sodium benzoate was added, cooled, the above volatile oil was added, and water was added to 1000 mL and mixed evenly to obtain the product.

[0055] Comparative Example 5 (Powder) Codonopsis pilosula (Franch.) Nannf. 68 parts by weight, Atractylodes macrocephala Koidz. stir-fried with bran 136 parts by weight, Astragalus membranaceus (Fisch.) Bunge var. mongholicus (Bunge) P. K. Hsiao 68 parts by weight Glycyrrhiza uralensis Fisch. 34 parts by weight, Poria cocos (Schw.) Wolf 136 parts by weight, Polygala tenuifolia Willd. prepared 136 parts by weight Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow 68 parts by weight, Euphoria longana Lam. 136 parts by weight, Angelica sinensis (Oliv.) Diels 136 parts by weight Aucklandia lappa Decne. 34 parts by weight, Ziziphus jujuba Mill. 34 parts by weight, Zingiber officinale Rosc. 17 parts by weight.

[0056] Preparation process: The above twelve flavors were dried, pulverized into fine powder, passed through a 100-mesh sieve, mixed evenly, divided into doses, 5 g per package, taken 2 - 3 times a day.

[0057] I. Therapeutic effect of the composition of the present invention on murine thyroiditis

[0058] 1 Experimental materials

[0059] 1.1 Experimental animals

[0060] SPF-grade C57BL / 6 mice were selected, weighing 18 - 22 g, 6 - 8 weeks old, with half males and half females, 110 in total. The experimental animal license number: SCXK(Lu) 2022 0006, provided by Shandong Pengyue Experimental Animal Technology Co., Ltd. They were adaptively fed for 1 week under standard conditions before the experiment.

[0061] 1.2 Experimental drugs and reagents

[0062] 1.2.1 Drugs

[0063] Guipi Mixture (National Drug Approval Number Z37020303, Lunan Houpu Pharmaceutical Co., Ltd.), the traditional Chinese medicine compositions in Comparative Examples 1 - 5, Prednisone Acetate Tablets (National Drug Approval Number H34023845, Anhui Changhong Pharmaceutical Factory).

[0064] 1.2.2 Reagents

[0065] Thyroglobulin (Sigma); Freund's complete adjuvant, Freund's incomplete adjuvant (Sigma); T3, T4, TSH detection kits; IL-10, TNF-α detection kits; normal saline, etc.

[0066] 2 Experimental Methods

[0067] 2.1 Modeling

[0068] Establishment of a subacute thyroiditis model: A thyroid antigen-induced immunization method was used. Thyroglobulin was dissolved in physiological saline, mixed with an equal volume of Freund's complete adjuvant, and emulsified. Mice (excluding the normal control group) were intraperitoneally injected with 0.2 ml (containing 100 μg of thyroglobulin) per mouse. On day 14, a booster immunization was performed using an emulsion of thyroglobulin and Freund's incomplete adjuvant, at the same dose. The control group mice were intraperitoneally injected with an equal volume of physiological saline and Freund's adjuvant mixture (without thyroglobulin).

[0069] 2.2 Grouping and Dosing

[0070] After successful modeling (confirmed by detecting serum thyroid hormone levels and observing pathological changes in thyroid tissue), the mice were randomly divided into 11 groups of 10 mice each:

[0071] Control group: Administered an equal volume of normal saline by gavage once daily;

[0072] Model group: Administered an equal volume of physiological saline by gavage once daily;

[0073] Gui Pi He Ji: 0.45ml / kg (low dose), 0.9ml / kg (medium dose), 1.8ml / kg (high dose), hereinafter referred to as GPHE-L, GPHJ-M, and GPHJ-H respectively;

[0074] Comparative Examples 1-5: 0.9 ml / kg, weighed separately below;

[0075] Positive group: Prednisolone acetate tablets 0.039g / kg.

[0076] Experimental period: Based on the characteristics of the course of subacute thyroiditis and the results of previous preliminary experiments, the experimental period was set at 28 days. 2.3 Observation indicators and detection methods

[0077] 2.3.1 General Observation

[0078] During the experiment, the mice's mental state, activity level, food intake, water intake, and fur condition were observed daily; the mice were weighed once a week, and weight changes were recorded.

[0079] 2.3.2 Serological marker detection

[0080] After the experiment, mice were fasted for 12 hours but allowed free access to water. Blood was collected from the orbital sinus, and serum was separated by centrifugation (3000 r / min, centrifugation for 10 min). Serum thyroid hormone (T3, T4, TSH) levels were detected using enzyme-linked immunosorbent assay (ELISA), strictly following the kit instructions. Serum inflammatory cytokine (IL-10, TNF-α) levels were also detected using ELISA.

[0081] 3. Statistical Analysis

[0082] SPSS 22.0 statistical software was used for data analysis. Quantitative data were expressed as mean ± standard deviation (SD). The mean ± standard deviation (s) indicates that differences between groups were compared using one-way ANOVA. P <0.05 indicates that the difference is statistically significant.

[0083] 4 Experimental Results

[0084] 4.1 General condition of the mice

[0085] Table 1 General Conditions and Weight Changes ( (±s, n=10)

[0086] Compared with the model group, @ P <0.05, @@ P <0.01; compared with the positive group, # P <0.05, ## P <0.01; compared with the low-dose group of Guipi Heji, ^ P <0.05, ^^ P <0.01.

[0087] Table 1 shows that the mice in the model control group had slow weight gain, poor mental state, and significantly reduced food and water intake, indicating successful model establishment; the positive group showed some improvement. P <0.01); the traditional Chinese medicine composition of the present invention showed improvement in all dosage groups ( P <0.01), among which, the high-dose group was significantly better than the positive control group ( P <0.05) and all comparative examples (groups) P <0.01), the high-dose group was close to the level of the normal control group. The effects of comparative examples 4-5 were similar to those of the positive control group, while the effects of comparative examples 1-3 were slightly worse or significantly worse than those of the positive control group, indicating that the traditional Chinese medicine composition of the present invention can effectively improve the overall basic condition of mice with subacute thyroiditis.

[0088] 4.2 Thyroid hormone levels in each group of mice

[0089] Table 2. Thyroid hormone levels in mice of each group ( (±s, n=10)

[0090] Compared with the model group, @ P <0.05, @@ P <0.01; compared with the positive group, # P <0.05, ## P <0.01; compared with the low-dose group of Guipi Heji, ^ P <0.5, ^^ P <0.01.

[0091] As shown in Table 2, the levels of T3 and T4 in the model group were significantly increased ( P <0.01), TSH levels decreased significantly ( P <0.01), indicating successful model establishment; the positive control drug group can regulate thyroid hormone levels to a certain extent; the medium and high dose groups of the traditional Chinese medicine composition of this invention have significantly better regulatory effects than the positive control drug group and the groups in the comparative examples ( P <0.05), the thyroid hormone level in the high-dose group was close to that in the normal group. The regulatory effects of Comparative Examples 1-3 were similar to those of the positive control group, while the regulatory effects of Comparative Examples 4-5 were worse, indicating that the herbal composition of the present invention has a better effect on restoring thyroid function.

[0092] 4.3 Inflammatory factor levels

[0093] The levels of inflammatory factors in each group of mice are shown in the figure. Figure 1 and Figure 2 .Depend on Figure 1 and Figure 2 It can be seen that the levels of IL-10 and TNF-α were significantly increased in the model control group, indicating successful model establishment; the positive group showed a significant reduction in the levels of inflammatory factors (…). P <0.01); The efficacy of the medium and high dose groups of the traditional Chinese medicine composition of this invention in reducing inflammatory factors is significantly better than that of the positive control group and the comparative example ( P <0.05), the inflammatory factor levels in the high-dose group were close to those in the normal group. The reducing effect of the comparative examples 1-2 groups was similar to that of the positive control group, while the reducing effect of the comparative examples 3-5 was poor, indicating that the traditional Chinese medicine composition of the present invention has a significant advantage in inhibiting the inflammatory response.

[0094] In summary, the combination of traditional Chinese medicines in this invention is superior to the positive control group and all comparative examples in treating subacute thyroiditis. It shows significant advantages in improving the overall condition of mice, regulating thyroid hormone levels, and inhibiting inflammatory responses, and these effects are dose-dependent.

[0095] II. Clinical Data

[0096] 1. Materials and Methods

[0097] 1.1 Case Selection

[0098] (1) Diagnostic criteria: Western medicine meets the diagnostic criteria for SAT;

[0099] According to Traditional Chinese Medicine (TCM), the diagnosis of "gastritis" is as follows: 5 primary symptoms (swelling in the front of the neck, a foreign body sensation in the throat, fatigue, frequent sighing, and emotional distress); 3 secondary symptoms (spontaneous sweating, dry mouth and thirst, chest tightness or chest and rib pain); tongue appearance: pale red or with teeth marks, thin white or thin yellow coating; pulse appearance: wiry and thready pulse. If the patient meets at least 3 primary symptoms, or meets 2 primary symptoms and 1 secondary symptom, combined with the tongue and pulse, it is considered to be this syndrome.

[0100] (2) Inclusion criteria: meeting the above-mentioned diagnosis in both traditional Chinese and Western medicine; aged 18-65 years; stable condition; not having received other treatments before admission; mentally normal and able to cooperate with treatment; informed consent from the patient and family.

[0101] (3) Exclusion criteria: pregnant or lactating; those with acute suppurative thyroiditis; those with serious primary diseases; those allergic to the investigational drug; those who have recently taken other drugs that affect thyroid hormones and antibodies; those with mental illness or cognitive impairment.

[0102] (4) Elimination / dropout criteria: failure to take medication as required; serious adverse reactions during treatment; serious adverse reactions during treatment; unwillingness to continue participating in the study midway.

[0103] 1.2 Clinical Data

[0104] Eighty patients with SAT admitted between July 2024 and June 2025 were selected and randomly divided into two groups of 40 each. The control group consisted of 16 males and 24 females, aged 18–62 years (mean 41.35 ± 7.50 years), with a disease duration of 1–3 years (mean 1.51 ± 0.33 years) and a body mass index (BMI) of (20.05 ± 1.06) kg / m². 2 The observation group consisted of 12 males and 28 females, aged 19-60 years (mean 42.97 ± 8.12 years), with a disease duration of 1-3 years (mean 1.46 ± 0.35 years) and a BMI of (20.33 ± 1.02) kg / m². 2 There was no statistically significant difference between the two groups. P>0.05). This study was approved by the hospital's ethics committee.

[0105] 1.3 Treatment methods

[0106] Both groups of patients received routine treatment, appropriate exercise, and avoidance of overexertion. They were given a balanced diet, including fiber-rich vegetables and fruits such as celery and grapefruit. The control group received prednisolone acetate tablets (Anhui Changhong Pharmaceutical Factory, National Drug Approval Number H34023845) orally according to the instructions. The experimental group received the Gui Pi He Ji (a traditional Chinese medicine formula) of this invention. Both groups of patients were treated for 6 weeks.

[0107] 1.4 Comparison of Total Scores for TCM Syndromes

[0108] Traditional Chinese Medicine (TCM) Syndrome Scoring: The TCM symptom scoring method was used. Primary symptoms (neck swelling, a foreign body sensation in the throat, fatigue, frequent sighing, and emotional distress) were scored on a scale of 0, 2, 4, and 6 points respectively, based on severity. Secondary symptoms (spontaneous sweating, dry mouth and thirst, chest tightness or chest and rib pain) were scored on a scale of 0, 1, 2, and 3 points respectively. The sum of all scores was the total syndrome score. This scoring scale was assessed by two attending physicians during two follow-ups, combining the assessment with the patient's medical records. Changes in the patient's total TCM syndrome score before and after treatment were observed.

[0109] Table 3 Comparison of TCM syndrome scores before and after treatment in each group

[0110] As shown in Table 3, the total TCM syndrome score of the experimental group was significantly lower than that before treatment, and the effect was better than that of the control group.

[0111] 1.4 Comparison of clinical efficacy

[0112] Clinical control: The main symptoms described by traditional Chinese medicine have almost completely subsided, the physical signs (swelling and pain in the anterior neck) have returned to normal, and the syndrome score has decreased by ≥90%;

[0113] Significant improvement: Clinical symptoms and signs in Traditional Chinese Medicine showed significant improvement, with syndrome scores decreasing by >70% and <90%;

[0114] Effective: Clinical symptoms and signs in Traditional Chinese Medicine showed some improvement, with syndrome scores decreasing by >30% and <70%;

[0115] Ineffective: Symptoms show no change or worsening.

[0116] Overall effective rate = (number of clinically controlled cases + number of cases with significant effects + number of cases with effective results) / total number of cases × 100%.

[0117] After treatment, in the experimental group, 21 cases (52.5%) achieved clinical control, 11 cases (27.5%) showed significant improvement, 4 cases (10%) showed improvement, and 4 cases (10%) showed no improvement, with a total effective rate of 90%; in the positive group, 9 cases (22.5%) achieved clinical control, 5 cases (12.5%) showed significant improvement, 17 cases (42.5%) showed improvement, and 9 cases (22.5%) showed no improvement, with a total effective rate of 77.5%.

Claims

1. The use of a traditional Chinese medicine composition in the preparation of a drug for treating thyroid diseases, characterized in that, The aforementioned traditional Chinese medicine composition includes Codonopsis pilosula, stir-fried Atractylodes macrocephala, processed Astragalus membranaceus, processed Glycyrrhiza uralensis, Poria cocos, processed Polygala tenuifolia, stir-fried Ziziphus jujuba var. spinosa, longan pulp, Angelica sinensis, Aucklandia lappa, jujube, and ginger.

2. The use as described in claim 1, characterized in that, The traditional Chinese medicine composition is made from the following traditional Chinese medicine components in the following weight ratio: Codonopsis pilosula 45-100 parts by weight, stir-fried Atractylodes macrocephala 100-175 parts by weight, processed Astragalus membranaceus 45-100 parts by weight Prepared licorice root 15-55 parts by weight, Poria cocos 100-175 parts by weight, processed Polygala tenuifolia 100-175 parts by weight 45-100 parts by weight of stir-fried jujube seeds, 100-175 parts by weight of longan pulp, and 100-175 parts by weight of angelica root. 15-55 parts by weight of costus root, 15-60 parts by weight of jujube, and 5-40 parts by weight of ginger.

3. The use as described in claim 2, characterized in that, The traditional Chinese medicine composition is made from the following traditional Chinese medicine components in the following weight ratio: Codonopsis pilosula 68 parts by weight, stir-fried Atractylodes macrocephala 136 parts by weight, processed Astragalus membranaceus 68 parts by weight Prepared licorice root 34 parts by weight, Poria cocos 136 parts by weight, processed Polygala tenuifolia 136 parts by weight 68 parts by weight of stir-fried jujube seeds, 136 parts by weight of longan pulp, and 136 parts by weight of angelica root. 34 parts by weight of costus root, 34 parts by weight of jujube, and 17 parts by weight of ginger.

4. The use as described in any one of claims 1-3, characterized in that, The stir-fried Atractylodes macrocephala, Aucklandia lappa, and Angelica sinensis were distilled to extract volatile oils, and the residue was kept for later use.

5. The use as described in claim 4, characterized in that, The Angelica sinensis residue was percolated with 50% ethanol as a solvent, the percolate was collected, and the ethanol was recovered. The residues of Atractylodes macrocephala and Aucklandia lappa, along with the remaining nine herbs including Codonopsis pilosula, were decocted three times with water: 2 hours for the first decoction, 1.5 hours for the second decoction, and 1 hour for the third decoction. The decoctions were combined, filtered, and the filtrate was concentrated to an appropriate volume. This filtrate was then combined with the percolate, allowed to stand, filtered, and the filtrate was concentrated to approximately 1000 mL. 3 g of sodium benzoate was added, the mixture was cooled, and the volatile oil was added. Water was added to 1000 mL and mixed well to obtain the final product.

6. The use as described in claim 5, characterized in that, The traditional Chinese medicine composition is prepared into a clinically acceptable dosage form after adding excipients. Preferably, the clinically acceptable dosage form is granules, tablets, pills, capsules, and microcapsules; further, the clinically acceptable dosage form is an oral compound.

7. The use as described in any one of claims 1-6, characterized in that, The thyroid diseases mentioned include hyperthyroidism and thyroiditis.

8. The use as described in claim 7, characterized in that, The thyroiditis mentioned refers to acute thyroiditis, subacute thyroiditis, and chronic thyroiditis; further, the thyroiditis mentioned refers to subacute thyroiditis.

9. The use of Guipi Heji in the treatment of thyroid diseases.

10. The use of Guipi Heji in the treatment of subacute thyroiditis.

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