A traditional Chinese medicine preparation for treating hashimoto's thyroiditis and a preparation method thereof

Abstract

This invention provides a traditional Chinese medicine preparation for treating Hashimoto's thyroiditis and its preparation method, belonging to the field of traditional Chinese medicine pharmaceutical technology. The preparation is made from Curcuma zedoaria, oyster shell, Eclipta prostrata, Ligustrum lucidum, Sargassum, processed Aconitum carmichaelii, Cremastra appendiculata, Duchesnea indica, Hedyotis diffusa, Artemisia capillaris, Oroxylum indicum, and cinnamon. The formula is meticulously formulated, closely addressing the core pathogenesis of Hashimoto's thyroiditis: "phlegm and blood stasis, spleen and kidney deficiency, and nutritional imbalance." It focuses on "eliminating masses and dispersing nodules, promoting qi and blood circulation," fully embodying the TCM diagnostic and treatment approach of "differentiating syndromes and treating accordingly, addressing both the root cause and symptoms." This invention's preparation has a good therapeutic effect on Hashimoto's thyroiditis, effectively improving thyroid autoimmune disorders, regulating thyroid function, and alleviating symptoms of local thyroid inflammation in experimentally induced Hashimoto's thyroiditis rats. Further clinical observation studies have found that this preparation significantly improves the overall effective rate of clinical treatment for Hashimoto's thyroiditis patients, providing a new approach to the treatment of this condition.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine pharmaceutical technology, specifically to a traditional Chinese medicine preparation for treating Hashimoto's thyroiditis and its preparation method. Background Technology

[0002] Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is an autoimmune disease whose pathogenesis mainly involves abnormal responses of cellular and humoral immunity. Its core pathological features include diffuse lymphocytic infiltration of thyroid tissue, destruction of follicular structure, and interstitial fibrosis. Serologically, it is characterized by abnormally elevated titers of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). Clinically, many patients are asymptomatic in the early stages. As the disease progresses, typical features such as hypothyroidism and goiter may appear. A few patients may also experience neck pain or a feeling of pressure.

[0003] Currently, Western medicine lacks a radical cure for HT (hysterosalpingography). Clinical treatment primarily relies on thyroid hormone replacement therapy. However, this method only provides exogenous thyroid hormone supplementation and maintains thyroid function homeostasis; it cannot suppress abnormal autoimmune responses, reduce thyroid autoantibody levels, or reverse inflammatory damage and fibrotic lesions in thyroid tissue. Furthermore, it requires long-term medication, leading to poor adherence. Therefore, effectively intervening in the pathological process of HT and improving patients' long-term prognosis has become an urgent clinical challenge.

[0004] Traditional Chinese medicine (TCM) possesses unique advantages in treating Hashimoto's thyroiditis. TCM classifies HT under the category of "goiter," with its core pathogenesis often involving liver qi stagnation, phlegm and blood stasis, and spleen and kidney deficiency. The disease affects the liver, spleen, and kidneys, and treatment is based on the principles of resolving phlegm and dissipating nodules, promoting qi and blood circulation, and soothing the liver and regulating qi. However, existing TCM compound formulas and prepared medicines still suffer from several shortcomings, including insufficient targeted formulation, often focusing solely on regulating qi and dissipating nodules, failing to address the multiple pathogenesis factors of liver qi stagnation, spleen deficiency, phlegm accumulation, and blood stasis, resulting in generally unsatisfactory efficacy. Therefore, developing a TCM preparation with precise formulation, stable efficacy, and the ability to specifically regulate immunity and improve clinical symptoms is of great significance for the clinical treatment of Hashimoto's thyroiditis. Summary of the Invention

[0005] (a) Technical problems to be solved

[0006] In view of the shortcomings of the prior art, the present invention provides a traditional Chinese medicine preparation for treating Hashimoto's thyroiditis and its preparation method.

[0007] (II) Technical Solution

[0008] To achieve the above objectives, the present invention provides the following technical solution:

[0009] On one hand, the present invention provides a traditional Chinese medicine preparation for treating Hashimoto's thyroiditis, the preparation being made from the following raw materials in parts by weight: Curcuma zedoaria 8-26 parts, oyster shell 8-26 parts, Sargassum fusiforme 3-20 parts, Cremastra appendiculata 5-25 parts, Duchesnea indica 5-25 parts, Hedyotis diffusa 4-21 parts, Artemisia capillaris 4-21 parts, Eclipta prostrata 3-20 parts, Ligustrum lucidum 3-20 parts, processed Aconitum carmichaelii 3-12 parts, Cinnamomum cassia 5-25 parts, and Oroxylum indicum 4-21 parts.

[0010] Specifically, the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: Curcuma zedoaria 13-21 parts, oyster shell 13-21 parts, seaweed 5-15 parts, Cremastra appendiculata 10-20 parts, Duchesnea indica 10-20 parts, Hedyotis diffusa 8-16 parts, Artemisia capillaris 8-16 parts, Eclipta prostrata 5-15 parts, Ligustrum lucidum 5-15 parts, processed Aconitum carmichaelii 3-8 parts, cinnamon 10-20 parts, and Oroxylum indicum 8-16 parts.

[0011] Specifically, the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 18 parts of Curcuma zedoaria, 18 parts of oyster shell, 10 parts of Sargassum, 15 parts of Cremastra appendiculata, 15 parts of Duchesnea indica, 12 parts of Hedyotis diffusa, 12 parts of Artemisia capillaris, 10 parts of Eclipta prostrata, 10 parts of Ligustrum lucidum, 5 parts of processed Aconitum carmichaelii, 15 parts of Cinnamomum cassia, and 12 parts of Oroxylum indicum.

[0012] Secondly, the present invention provides a method for preparing a traditional Chinese medicine preparation for treating Hashimoto's thyroiditis, characterized in that the traditional Chinese medicine preparation is prepared into an oral dosage form by adding excipients according to conventional traditional Chinese medicine manufacturing methods, and the oral dosage form includes pills, powders, granules, oral liquids, decoctions, and tablets.

[0013] Specifically, a method for preparing a decoction of traditional Chinese medicine for treating Hashimoto's thyroiditis includes the following steps:

[0014] (1) Weigh all the medicinal materials according to the above weight proportions, clean them, and separate the prepared aconite, oyster shell and cinnamon. Soak the remaining medicinal materials in water for 30-40 minutes.

[0015] (2) Put the prepared aconite and oyster into a pot, add 8-10 times the amount of water, bring to a boil over high heat, then simmer over low heat for 30-60 minutes. Then pour the soaked herbs into the simmered liquid, bring to a boil, and continue to simmer over low heat for 20-30 minutes. Add cinnamon 5-8 minutes before turning off the heat.

[0016] (3) After decocting, filter while hot. Add 6-8 times the amount of water to the dregs and decoct again for 20-30 minutes. Filter and combine the two decoctions to obtain the final product.

[0017] Thirdly, the present invention provides the application of the aforementioned traditional Chinese medicine preparation in the preparation of a drug for treating Hashimoto's thyroiditis.

[0018] The pharmacological effects of each traditional Chinese medicine in the herbal preparation of this invention are as follows:

[0019] Curcuma zedoaria: The dried rhizome of Curcuma zedoaria, Curcuma szedoaria, or Curcuma aromatica, all belonging to the ginger family. It has a pungent and bitter taste, and is warm in nature. It enters the liver and spleen meridians. It has the effects of promoting qi circulation, breaking up blood stasis, eliminating stagnation, and relieving pain. It is used for abdominal masses, amenorrhea due to blood stasis, chest pain, and abdominal distension due to food stagnation.

[0020] Oyster: The shell of the Pacific oyster, Dalian Bay oyster, or near-river oyster (all belonging to the Ostreidae family). It has a salty taste and slightly cold nature. It enters the liver, gallbladder, and kidney meridians. It has the effects of calming the mind, nourishing yin and suppressing yang, and softening and dispersing masses. It is used for palpitations, insomnia, dizziness, tinnitus, scrofula, phlegm nodules, and abdominal masses. Calcined oyster shell has astringent and consolidating properties, and can neutralize acid and relieve pain. It is used for spontaneous sweating, night sweats, seminal emission, metrorrhagia, leukorrhea, stomach pain, and acid reflux.

[0021] Seaweed: The dried thallus of Sargassum fusiforme or Sargassum fusiforme, belonging to the Sargassum family. It has a bitter and salty taste and is cold in nature. It enters the liver, stomach, and kidney meridians. It has the effects of resolving phlegm, softening hard masses, dissipating nodules, promoting diuresis, and reducing swelling. It is used for goiter, scrofula, testicular swelling and pain, and edema due to phlegm retention.

[0022] *Cremastra appendiculata*: The dried pseudobulb of *Cremastra appendiculata*, *Cremastra yunnanensis*, or *Cremastra yunnanensis*, all belonging to the Orchidaceae family. It has a sweet and slightly pungent taste and is cool in nature. It enters the liver and spleen meridians. It has the effects of clearing heat and detoxifying, resolving phlegm and dissipating nodules. It is used for carbuncles, boils, scrofula, snake and insect bites, and abdominal masses.

[0023] Duchesnea indicum: The whole herb of Duchesnea indicum, a plant belonging to the genus Duchesnea in the family Rosaceae. It has a sweet and bitter taste and is cold in nature. It enters the lung, liver, and large intestine meridians. It has the effects of clearing heat and detoxifying, dispersing blood stasis and reducing swelling. It is used for colds with fever, cough, infantile febrile convulsions, sore throat, diphtheria, jaundice-type hepatitis, bacterial dysentery, amoebic dysentery, and menorrhagia.

[0024] *Salvia splendens*: The dried aerial parts of *Salvia splendens*, a plant in the Lamiaceae family. It has a bitter and pungent taste, and is neutral in nature. It enters the stomach, liver, and lung meridians. It has the effects of promoting blood circulation and removing blood stasis, clearing heat and dampness, and dispersing nodules and reducing swelling. It is used for jaundice-type hepatitis, cancer, nephritis, leukorrhea, dysmenorrhea, lymph node tuberculosis, and elephantiasis; externally, it is used to treat facial nerve paralysis, mastitis, and boils.

[0025] Liu Ji Nu: The dried whole herb of *Liu Ji Nu*, a plant in the Scrophulariaceae family. It is bitter and cold in nature. It enters the spleen, stomach, liver, and gallbladder meridians. It has the effects of promoting blood circulation and removing blood stasis, regulating menstruation and relieving pain, cooling the blood, stopping bleeding, clearing heat and promoting diuresis. It is used for traumatic injuries, external bleeding, amenorrhea due to blood stasis, irregular menstruation, postpartum pain due to blood stasis, abdominal masses, bloody dysentery, hematuria, damp-heat jaundice, edema and abdominal distension, and excessive leukorrhea.

[0026] Eclipta prostrata: The dried aerial parts of Eclipta prostrata, a plant in the Asteraceae family. It has a sweet and sour taste, and is cold in nature. It enters the kidney and liver meridians. It has the effects of nourishing the liver and kidneys, cooling the blood, and stopping bleeding. It is used for liver and kidney yin deficiency, loose teeth, premature graying of hair, dizziness and tinnitus, soreness and weakness of the lower back and knees, yin deficiency and blood heat causing hematemesis, epistaxis, hematuria, bloody dysentery, metrorrhagia, and external bleeding.

[0027] Privet fruit: The dried, ripe fruit of the privet plant (Ligustrum lucidum), a member of the Oleaceae family. It has a sweet and bitter taste, and is cool in nature. It enters the liver and kidney meridians. It nourishes the liver and kidneys, improves eyesight, and darkens hair. It is used for liver and kidney yin deficiency, dizziness and tinnitus, soreness and weakness of the lower back and knees, premature graying of hair, blurred vision, internal heat and thirst, and night sweats.

[0028] Prepared aconite root: A processed product of the fibrous root of Aconitum carmichaelii, a plant in the Ranunculaceae family. It has a pungent and sweet taste, and is very hot in nature. It enters the heart, kidney, and spleen meridians. It has the effects of restoring yang and rescuing from collapse, tonifying fire and assisting yang, dispelling cold and relieving pain. It is used for collapse due to yang deficiency, cold limbs and weak pulse, insufficient heart yang, chest pain, vomiting and diarrhea due to deficiency and cold, cold pain in the epigastrium and abdomen, kidney yang deficiency, impotence and cold uterus, edema due to yin cold, external pathogenic factors due to yang deficiency, and cold-dampness arthralgia.

[0029] Cinnamon: The dried bark of the cinnamon tree (Cinnamomum cassia), a plant in the Lauraceae family. It has a pungent and sweet taste and is very hot in nature. It enters the kidney, spleen, heart, and liver meridians. It has the effects of tonifying fire and assisting yang, guiding fire back to its source, dispelling cold and relieving pain, and warming and unblocking the meridians. It is used for impotence and cold uterus, cold pain in the lower back and knees, kidney deficiency causing shortness of breath, upward floating of deficient yang, dizziness and red eyes, cold pain in the heart and abdomen, vomiting and diarrhea due to deficiency and cold, abdominal pain due to cold hernia, dysmenorrhea, and amenorrhea.

[0030] Oroxylum indicum: The dried, mature seeds of the Oroxylum indicum plant (family Bignoniaceae). It tastes bitter and sweet, and is cool in nature. It enters the lung, liver, and stomach meridians. It has the effects of clearing the lungs and relieving sore throat, soothing the liver and harmonizing the stomach. It is used for cough due to lung heat, sore throat, hoarseness, and liver and stomach pain.

[0031] (III) Beneficial Effects

[0032] This invention provides a traditional Chinese medicine preparation for treating Hashimoto's thyroiditis and its preparation method. The preparation is made from Curcuma zedoaria, oyster shell, Eclipta prostrata, Ligustrum lucidum, Sargassum, processed Aconitum carmichaelii, Cremastra appendiculata, Duchesnea indica, Hedyotis diffusa, Artemisia capillaris, Oroxylum indicum, and cinnamon. The formula is carefully formulated, closely addressing the core pathogenesis of Hashimoto's thyroiditis, namely "phlegm and blood stasis, spleen and kidney deficiency, and nutritional imbalance." It focuses on "eliminating masses and dispersing nodules, promoting qi and blood circulation," fully embodying the TCM diagnostic and treatment approach of "differentiating syndromes and treating accordingly, addressing both the root cause and the symptoms." Curcuma zedoaria and oyster shell are the principal herbs. Curcuma zedoaria is pungent and warm, which can disperse blood stasis, eliminate masses and dissipate nodules, and resolve lumps in the front of the neck. It can also regulate qi and relieve depression, and alleviate symptoms of depression and chest and rib pain. Oyster shell is salty and can soften hard masses, which can resolve phlegm and turbidity masses in the front of the neck. When combined with curcuma zedoaria, one is warm and the other is cold, which can enhance the effect of softening hard masses and dissipating nodules, and also restrain the drying effect of curcuma zedoaria, so as to avoid depletion of body fluids. The formula uses seaweed, *Cremastra appendiculata*, *Duchesnea indica*, *Heliotropium indicum*, and *Artemisia capillaris* as assistant herbs. Seaweed excels at resolving phlegm, softening hard masses, and promoting diuresis to reduce swelling, thus assisting the principal herb in resolving phlegm and turbidity in the neck. *Cremastra appendiculata* is cooling in nature, resolving phlegm and dissipating nodules, while also clearing internal heat, relieving neck pain and throat discomfort. *Duchesnea indica* is cold in nature, clearing heat stagnation, and its sour taste has astringent properties, assisting the principal herb in promoting blood circulation and removing blood stasis, while also clearing internal heat caused by phlegm and blood stasis. *Heliotropium indicum* is pungent and bitter, promoting blood circulation, clearing the meridians, and dissipating nodules, while its neutral nature prevents excessive blood circulation from depleting vital energy. *Artemisia capillaris* warms and promotes blood circulation, assisting the principal herb in breaking up blood stasis and dissipating nodules, relieving pain caused by neck lumps. The combination of these five herbs, considering both cold and hot properties, strengthens the core efficacy of the principal herb in resolving masses and dissipating nodules, while also addressing other symptoms such as phlegm-heat and spleen deficiency. The formula uses Eclipta prostrata, Ligustrum lucidum, processed Aconitum carmichaelii, Cinnamomum cassia, and Oroxylum indicum as adjuvant herbs. Eclipta prostrata nourishes Yin and benefits the kidneys, cools the blood and stops bleeding. Ligustrum lucidum nourishes the liver and kidneys, improves eyesight and darkens hair. The two herbs complement each other, protecting the Yin of the liver and kidneys, restraining the dryness of the pungent and warm herbs, and preventing the depletion of Yin fluids, while nourishing the body's vital energy. Processed Aconitum carmichaelii restores Yang and rescues from collapse, tonifies fire and assists Yang, dispels cold and relieves pain. Cinnamomum cassia tonifies fire and assists Yang, dispels cold and relieves pain, warms the meridians and unblocks the vessels. The two herbs together warm and tonify kidney Yang, dispel cold and unblock the vessels, which can help the circulation of Qi and blood, resolve phlegm and dissipate blood stasis, and enhance the function of the spleen and stomach. Oroxylum indicum is cool in nature, which can help clear internal heat, relieve symptoms such as foreign body sensation in the throat and throat discomfort, and at the same time can soothe the liver and regulate Qi, relieve emotional depression and chest and rib pain. Its sweet and cool nature can also restrain the excessive heat of processed Aconitum carmichaelii and Cinnamomum cassia, and prevent excessive warming and drying from depleting Yin fluids. The five auxiliary herbs serve both assisting and restraining functions, focusing on harmonizing Yin and Yang, protecting the spleen and kidneys, and mitigating the antagonistic effects of the principal and assistant herbs, thus achieving "attacking the pathogenic factors without harming the body's vital energy, and supporting the body's vital energy without aiding the pathogenic factors." Cinnamon serves as the guiding herb, its warm and penetrating nature enabling it to guide all the herbs in the formula directly to the affected area. At the same time, it harmonizes the cold and heat, deficiency and excess of the entire formula, restrains the cold nature of Curcuma zedoaria and Sargassum, and moderates the harshness of Aconitum carmichaelii. This ensures that the entire formula is balanced in terms of cold and heat, and combines attacking and tonifying effects, avoiding the excessive use of any single herb and ensuring the coordinated efficacy of the overall formula.

[0033] The traditional Chinese medicine preparation of this invention has a good therapeutic effect on Hashimoto's thyroiditis. It can effectively improve thyroid autoimmune disorders, regulate thyroid function, and reduce local inflammatory reactions in rats with experimental Hashimoto's thyroiditis. Further clinical observation studies have found that the traditional Chinese medicine preparation of this invention can significantly improve the overall effective rate of clinical treatment for patients with Hashimoto's thyroiditis. Its specific efficacy is reflected in three aspects: First, it effectively regulates the serum FT3, FT4, and TSH levels, corrects thyroid dysfunction, and improves symptoms related to hypothyroidism; second, it significantly reduces serum TGAb and TPOAb levels, reduces thyroid autoimmune damage, and delays disease progression; third, it significantly reduces the TCM syndrome score, effectively relieving clinical discomfort symptoms such as neck discomfort, depression, cold intolerance, and fatigue, addressing both local lesions and systemic conditioning, providing a new approach to the treatment of Hashimoto's thyroiditis. Attached Figure Description

[0034] Figure 1 The serum levels of IL-6, IFN-γ, and TNF-α in rats from each group were compared. Note: * P<0.05, ** P<0.01.

[0035] Figure 2 This study compares serum FT3, FT4, and TSH levels before and after treatment in two groups of patients. Note: * P<0.05, ** P<0.01.

[0036] Figure 3 This study compares serum TPOAb and TGAb levels before and after treatment in two groups of patients. Note: * P<0.05, ** P<0.01. Detailed Implementation

[0037] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0038] Example 1

[0039] A traditional Chinese medicine preparation for treating Hashimoto's thyroiditis, the preparation being made from the following raw materials in parts by weight: 18 parts Curcuma zedoaria, 18 parts Oyster shell, 10 parts Sargassum, 15 parts Cremastra appendiculata, 15 parts Duchesnea indica, 12 parts Lysimachia christinae, 12 parts Artemisia capillaris, 10 parts Eclipta prostrata, 10 parts Ligustrum lucidum, 5 parts processed Aconitum carmichaelii, 15 parts Cinnamomum cassia, and 12 parts Oroxylum indicum.

[0040] Example 2

[0041] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 8 parts of Curcuma zedoaria, 8 parts of oyster shell, 3 parts of Sargassum, 5 parts of Cremastra appendiculata, 5 parts of Duchesnea indica, 4 parts of Hedyotis diffusa, 4 parts of Artemisia capillaris, 3 parts of Eclipta prostrata, 3 parts of Ligustrum lucidum, 3 parts of processed Aconitum carmichaelii, 5 parts of Cinnamomum cassia, and 4 parts of Oroxylum indicum.

[0042] Example 3

[0043] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 26 parts of Curcuma zedoaria, 26 parts of oyster shell, 20 parts of Sargassum, 25 parts of Cremastra appendiculata, 25 parts of Duchesnea indica, 21 parts of Hedyotis diffusa, 21 parts of Artemisia capillaris, 20 parts of Eclipta prostrata, 20 parts of Ligustrum lucidum, 12 parts of processed Aconitum carmichaelii, 25 parts of Cinnamomum cassia, and 21 parts of Oroxylum indicum.

[0044] Example 4

[0045] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 23 parts of Curcuma zedoaria, 21 parts of oyster shell, 18 parts of Sargassum, 22 parts of Cremastra appendiculata, 23 parts of Duchesnea indica, 18 parts of Hedyotis diffusa, 18 parts of Artemisia capillaris, 16 parts of Eclipta prostrata, 16 parts of Ligustrum lucidum, 9 parts of processed Aconitum carmichaelii, 22 parts of Cinnamomum cassia, and 16 parts of Oroxylum indicum.

[0046] Example 5

[0047] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 10 parts of Curcuma zedoaria, 10 parts of oyster shell, 5 parts of Sargassum, 7 parts of Cremastra appendiculata, 7 parts of Duchesnea indica, 8 parts of Hedyotis diffusa, 6 parts of Artemisia capillaris, 5 parts of Eclipta prostrata, 5 parts of Ligustrum lucidum, 6 parts of processed Aconitum carmichaelii, 7 parts of Cinnamomum cassia, and 7 parts of Oroxylum indicum.

[0048] Example 6

[0049] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 15 parts of Curcuma zedoaria, 16 parts of oyster shell, 10 parts of Sargassum, 12 parts of Cremastra appendiculata, 12 parts of Duchesnea indica, 12 parts of Hedyotis diffusa, 10 parts of Artemisia capillaris, 12 parts of Eclipta prostrata, 15 parts of Ligustrum lucidum, 8 parts of processed Aconitum carmichaelii, 9 parts of Cinnamomum cassia, and 10 parts of Oroxylum indicum.

[0050] Example 7

[0051] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 12 parts of Curcuma zedoaria, 12 parts of oyster shell, 8 parts of Sargassum, 10 parts of Cremastra appendiculata, 10 parts of Duchesnea indica, 8 parts of Hedyotis diffusa, 10 parts of Artemisia capillaris, 8 parts of Eclipta prostrata, 9 parts of Ligustrum lucidum, 7 parts of processed Aconitum carmichaelii, 10 parts of Cinnamomum cassia, and 9 parts of Oroxylum indicum.

[0052] Experimental Example 1

[0053] 1. Materials and Methods

[0054] 1.1 Laboratory Animals

[0055] Thirty-six SPF-grade female SD rats, 6-8 weeks old and weighing 160-180 g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. and housed in an SPF-grade animal experimental center (temperature 22±2℃, relative humidity 50±10%, 12-hour light-dark cycle), with free access to food and water, and were acclimatized for 1 week.

[0056] 1.2 Experimental Drugs

[0057] The composition of each group of drugs is shown in Table 1 below:

[0058] Table 1. Composition of each prescription drug

[0059]

[0060] Preparation method: Weigh the Chinese herbs according to the corresponding proportions, separate the prepared aconite, oyster shell, and cinnamon, and soak the remaining herbs in water for 30 minutes; put the prepared aconite and oyster shell into a pot, add 10 times the amount of deionized water, bring to a boil over high heat, then simmer over low heat for 30 minutes, then pour the soaked herbs into the decocted liquid, bring to a boil, and continue to simmer over low heat for 20 minutes, add cinnamon 5-8 minutes before turning off the heat; filter while hot after decoction, add 8 times the amount of deionized water to the dregs, repeat the decoction once, combine the two filtrates, and concentrate them into an aqueous decoction containing 1 g / mL of raw herbs using a rotary evaporator, store at 4℃, warm to room temperature and shake well before use.

[0061] 1.3 Experimental Methods

[0062] 1.3.1 Animal modeling, grouping, and drug administration

[0063] A rat model of Hashimoto's thyroiditis was established using the "iodine excess + thyroid antigen immunization" method. After one week of acclimatization, six rats were randomly selected as the normal control group, and the rest were used as the model group for treatment. The rats in the model group drank deionized water containing 0.05% NaI for seven consecutive weeks. On days 1 and 4 of week 4, porcine thyroglobulin (pTg, 100 μg / injection) completely emulsified with Freund's complete adjuvant (CFA) was injected subcutaneously at multiple sites on the back of the rats. From weeks 5 to 8, booster immunizations were performed weekly, with the injection method and dosage consistent with the initial immunization. At week 8, tail vein blood was collected from the rats, and serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels were measured using enzyme-linked immunosorbent assay (ELISA). A significantly higher antibody level in the model group than in the normal control group (P<0.05) was considered a successful model establishment.

[0064] Rats that successfully developed the model were randomly divided into a model control group and a formulation AD group, with 6 rats in each group. Immediately after grouping, drug intervention was administered. The normal control group and the model control group were given an equal volume of physiological saline by gavage daily. The formulation AD group was given the corresponding decoction of the formulation by gavage daily at a dose of 15 g / kg body weight, with a volume of 15 mL / kg body weight. The administration was continued for 4 weeks. During the administration period, the model group and all intervention groups continued to drink deionized water containing 0.05% NaI, while the normal control group drank ordinary deionized water.

[0065] 1.3.2 Sample Collection

[0066] After the last administration, the rats were fasted for 12 h, blood was collected from the orbital cavity, centrifuged at 3500 rpm for 10 min at 4℃, and the serum was separated and stored at -20℃.

[0067] 1.3.3 Thyroid autoantibody markers

[0068] Serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) levels were detected using ELISA.

[0069] 1.3.4 Thyroid function indicators

[0070] Serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured using ELISA.

[0071] 1.3.5 Inflammatory markers

[0072] Serum levels of interleukin-6 (IL-6), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were detected using ELISA.

[0073] 1.4 Statistical Methods

[0074] All data in this study were analyzed using GraphPad Prism 8.0 statistical software. Quantitative data were expressed as mean ± standard deviation. One-way ANOVA was used for comparisons between groups, with P < 0.05 considered statistically significant.

[0075] 2 Results

[0076] 2.1 Thyroid antibody levels

[0077] The results of serum TPOAb and TGAb levels in each group of rats are shown in Table 2. Compared with the normal control group, the serum TPOAb and TGAb levels in the model control group were significantly increased, and the difference was statistically significant (P<0.01). Compared with the model control group, the serum TPOAb and TGAb levels in the AD group were significantly decreased, and the difference was statistically significant (P<0.05 or P<0.01).

[0078] Table 2 Comparison of thyroid antibody levels in different groups of rats (U / mL)

[0079]

[0080] Note: Compared with the normal control group. ## P<0.01; compared with the model control group, * P<0.05, ** P<0.01.

[0081] 2.2 Thyroid function

[0082] The results of serum TSH, FT3, and FT4 levels in each group of rats are shown in Table 3. Compared with the normal group, the serum TSH level in the model control group was significantly increased, while the FT3 and FT4 levels were significantly decreased, with extremely statistically significant differences (P<0.01). Compared with the model control group, the serum TSH level in the AD group was significantly decreased (P<0.01), while the FT3 and FT4 levels showed varying degrees of increase.

[0083] Table 3 Comparison of thyroid function indicators among different groups of rats

[0084]

[0085] Note: Compared with the normal control group. ## P<0.01; compared with the model control group, * P<0.05, ** P<0.01.

[0086] 2.3 Inflammatory markers

[0087] The results of serum IL-6, IFN-γ, and TNF-α levels in each group of rats are as follows: Figure 1 As shown, compared with the normal control group, the serum levels of IL-6, IFN-γ, and TNF-α in the model control group rats were significantly increased, and the differences were statistically significant (P<0.01); compared with the model control group, the serum levels of IL-6, IFN-γ, and TNF-α in the AD group rats showed a decreasing trend, and the differences were statistically significant (P<0.05 or P<0.01).

[0088] 3. Conclusion

[0089] The above experimental results indicate that the traditional Chinese medicine preparation of this invention has the effects of improving thyroid autoimmune disorders, regulating thyroid function, and reducing local thyroid inflammation in rats with experimental Hashimoto's thyroiditis. Specifically, it reduces serum TPOAb and TGAb levels, improves abnormal changes in TSH, FT3, and FT4, and downregulates the levels of pro-inflammatory factors such as IL-6, IFN-γ, and TNF-α. Further analysis revealed that formulation D showed the most significant overall improvement effect on the above indicators, indicating a synergistic effect among the raw materials in the traditional Chinese medicine preparation of this invention.

[0090] Experimental Example 2

[0091] 1. Clinical Data

[0092] 1.1 General Information

[0093] Eighty patients with Hashimoto's thyroiditis were selected as the study subjects and randomly divided into a control group and a treatment group, with 40 patients in each group. The control group consisted of 8 males and 32 females, aged 21-62 years, with a mean age of (43.65 ± 10.36) years and a mean disease duration of (22.98 ± 6.23) months. The treatment group consisted of 9 males and 31 females, aged 21-64 years, with a mean age of (44.78 ± 13.45) years and a mean disease duration of (20.70 ± 5.03) months. There were no statistically significant differences in gender, age, disease duration, or other general characteristics between the two groups (P > 0.05), indicating comparability and suitability for further clinical observation.

[0094] 1.2 Diagnostic Criteria

[0095] Western medicine diagnostic criteria: Referring to the diagnostic criteria for Hashimoto's thyroiditis in the "Guidelines for the Diagnosis and Treatment of Thyroid Diseases in China", and combining the patient's clinical symptoms, thyroid function test results and thyroid ultrasound examination results, it is determined that the patient meets the diagnosis of hypothyroidism Hashimoto's thyroiditis.

[0096] Traditional Chinese Medicine Diagnostic Criteria: These criteria were developed with reference to the diagnostic standards for the liver-stagnation and phlegm-retention syndrome of Hashimoto's thyroiditis in the "Guidelines for Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Hashimoto's Thyroiditis" and the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines." Main symptoms: Swelling in the anterior neck, localized tightness and discomfort, a foreign body sensation in the throat, as if phlegm is obstructing the throat, difficulty swallowing, and inability to cough it up; symptoms fluctuate with emotional state. Secondary symptoms: Irritability or depression, chest and rib or lower abdominal distension, frequent sighing. Tongue and pulse: Pale or dark tongue with a white or greasy coating, and a wiry and slippery pulse.

[0097] 1.3 Inclusion Criteria

[0098] Patients must meet the above-mentioned Western and Traditional Chinese Medicine diagnostic criteria; be between 18 and 70 years old, regardless of gender; have not received thyroid-related drug treatment in the past 3 months; have normal cognitive function and be able to cooperate in completing treatment, examinations, and follow-up work; and have obtained informed consent from the patient and their family by signing an informed consent form.

[0099] 1.4 Exclusion Criteria

[0100] Women who are breastfeeding or pregnant; those with thyroid cancer, malignant thyroid nodules, or other thyroid-related diseases; those with a history of mental illness, cognitive impairment, or inability to cooperate in completing the study; those allergic to the drugs used in this study; those with serious chronic diseases and dysfunction of vital organs such as the heart, liver, kidneys, and brain; those who have received other related treatments within the past 3 months; and those with other autoimmune diseases.

[0101] 2. Treatment methods

[0102] Both groups of patients received continuous treatment for 12 weeks. During the treatment period, patients were instructed to maintain a regular schedule, avoid overexertion, strictly adhere to a low-iodine diet, and have their thyroid function monitored regularly.

[0103] 2.1 Control Group

[0104] Levothyroxine sodium tablets [specification: 50μg / tablet, manufacturer: Merck Pharmaceuticals (Jiangsu) Co., Ltd.] are administered orally on an empty stomach every morning. The initial dose is 25μg once a day. The dose may be adjusted as appropriate based on the patient's thyroid function monitoring results.

[0105] 2.2 Treatment Group

[0106] In addition to the treatment given to the control group, the patient was given the following traditional Chinese medicine preparation of this invention (prescription composition: Curcuma zedoaria 18 g, Ostrea gigas 18 g, Sargassum fusiforme 10 g, Cremastra appendiculata 15 g, Duchesnea indica 15 g, Hedyotis diffusa 12 g, Artemisia capillaris 12 g, Eclipta prostrata 10 g, Ligustrum lucidum 10 g, Aconitum carmichaelii (processed) 5 g, Cinnamomum cassia 15 g, Oroxylum indicum 12 g). One dose per day, decocted in water, taken twice daily, morning and evening, warm, after meals.

[0107] 3. Observation of therapeutic effects

[0108] 3.1 Thyroid hormone levels

[0109] Fasting venous blood samples were collected from patients before and after treatment to measure serum levels of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH).

[0110] 3.2 Thyroid antibody levels

[0111] Fasting venous blood was collected from patients before and after treatment to detect serum thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) levels.

[0112] 3.3 Traditional Chinese Medicine Syndrome Scoring

[0113] Based on the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs," the primary and secondary symptoms, as well as tongue and pulse diagnosis, were scored before and after treatment. Symptoms were categorized into four levels based on severity: none, mild, moderate, and severe. Primary symptoms were scored 0, 2, 4, and 6 points respectively; secondary symptoms were scored 0, 1, 2, and 3 points respectively; and tongue and pulse diagnosis were scored 0 and 1 points respectively, depending on whether the symptoms matched the TCM syndrome. A higher total score indicates a more severe TCM syndrome presentation.

[0114] 3.4 Clinical efficacy

[0115] Based on relevant clinical guidelines and research standards, and combined with thyroid function, thyroid antibody levels, and TCM syndrome scores, clinical efficacy was divided into four levels: cured, significantly effective, effective, and ineffective.

[0116] 1. Cured: Thyroid function returns to normal, TGAb and TPOAb levels drop to the normal range, TCM syndrome score decreases by ≥90%, and the anterior neck mass and clinical symptoms completely disappear;

[0117] 2. Significant effect: Thyroid function basically returns to normal, TGAb and TPOAb levels decrease by ≥50% compared with before treatment, TCM syndrome score decreases by 60%-89%, the anterior neck mass shrinks significantly, and clinical symptoms are significantly relieved;

[0118] 3. Effective: Thyroid function improved compared to before treatment, TGAb and TPOAb levels decreased by 20%-49% compared to before treatment, TCM syndrome scores decreased by 30%-59%, the anterior neck mass shrank, and clinical symptoms were relieved.

[0119] 4. Ineffective: Thyroid function, TGAb, and TPOAb levels show no improvement or even worsen; TCM syndrome score decreases by <30%; anterior neck mass shows no change or increases; clinical symptoms do not improve or even worsen.

[0120] The overall clinical effective rate = (number of cured cases + number of cases with significant improvement + number of cases with improvement) / total number of cases × 100%.

[0121] 3.5 Statistical Methods

[0122] All data from this study were analyzed using GraphPad Prism 8.0 statistical software. Quantitative data were expressed as mean ± standard deviation. Paired t-tests were used for comparisons within groups before and after treatment, and independent samples t-tests were used for comparisons between groups. Categorical data were expressed as percentages (%), and comparisons between groups were performed using... Test. A p-value < 0.05 is considered statistically significant.

[0123] 4 Results

[0124] 4.1 Thyroid function

[0125] Serum FT3, FT4, and TSH levels before and after treatment in both groups of patients are as follows: Figure 2 As shown in the figure. Before treatment, there were no statistically significant differences in serum FT3, FT4, and TSH levels between the two groups (P>0.05). After treatment, serum TSH levels in both groups were significantly lower than before treatment (P<0.01), with a greater decrease in the treatment group than in the control group, and the difference between the groups was statistically significant (P<0.01). Serum FT3 and FT4 levels in both groups were significantly higher than before treatment (P<0.01), with a greater increase in the treatment group than in the control group, and the difference between the groups was statistically significant (P<0.01).

[0126] 4.2 Thyroid antibody levels

[0127] Serum TGAb and TPOAb levels before and after treatment in both groups of patients are as follows: Figure 3 As shown, before treatment, there was no statistically significant difference in serum TGAb and TPOAb levels between the two groups (P>0.05); after treatment, serum TGAb and TPOAb levels in both groups were significantly lower than before treatment (P<0.01), and the treatment group was lower than the control group, with statistically significant differences between the groups (P<0.01).

[0128] 4.3 Traditional Chinese Medicine Syndrome Scoring

[0129] The results of TCM syndrome scores before and after treatment in the two groups are shown in Table 4. Before treatment, there was no statistically significant difference in TCM syndrome scores between the two groups (P>0.05); after treatment, the TCM syndrome scores of both groups were significantly lower than before treatment (P<0.01), and the score of the treatment group was lower than that of the control group, with a statistically significant difference between the groups (P<0.01).

[0130] Table 4 Comparison of TCM syndrome scores before and after treatment in the two groups of patients

[0131]

[0132] 4.4 Clinical efficacy

[0133] As shown in Table 5, the total clinical effective rate of the control group was 77.50%, while that of the treatment group was 95.00%, which was significantly higher than that of the control group.

[0134] Table 5 Comparison of clinical efficacy between the two groups of patients

[0135]

[0136] 5. Conclusion

[0137] This study evaluated the clinical efficacy of the traditional Chinese medicine preparation of this invention by observing changes in thyroid function, thyroid autoantibody levels, and TCM syndrome scores before and after treatment in the treatment group and the control group. The results showed that the TCM preparation of this invention significantly improved the overall effective rate of clinical treatment for Hashimoto's thyroiditis, effectively regulated serum FT3, FT4, and TSH levels, corrected thyroid dysfunction, reduced serum TGAb and TPOAb levels, alleviated thyroid autoimmune damage, and simultaneously reduced TCM syndrome scores, alleviating clinical symptoms and providing a new approach for the clinical treatment of Hashimoto's thyroiditis.

[0138] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A traditional Chinese medicine preparation for treating Hashimoto's thyroiditis, characterized in that, The traditional Chinese medicine preparation is made from the following raw materials in parts by weight: Curcuma zedoaria 8-26 parts, oyster shell 8-26 parts, Sargassum fusiforme 3-20 parts, Cremastra appendiculata 5-25 parts, Duchesnea indica 5-25 parts, Hedyotis diffusa 4-21 parts, Artemisia capillaris 4-21 parts, Eclipta prostrata 3-20 parts, Ligustrum lucidum 3-20 parts, processed Aconitum carmichaelii 3-12 parts, Cinnamomum cassia 5-25 parts, and Oroxylum indicum 4-21 parts.

2. The traditional Chinese medicine preparation for treating Hashimoto's thyroiditis according to claim 1, characterized in that, The traditional Chinese medicine preparation is made from the following raw materials in parts by weight: Curcuma zedoaria 13-21 parts, Oyster shell 13-21 parts, Sargassum fusiforme 5-15 parts, Cremastra appendiculata 10-20 parts, Duchesnea indica 10-20 parts, Hedyotis diffusa 8-16 parts, Artemisia capillaris 8-16 parts, Eclipta prostrata 5-15 parts, Ligustrum lucidum 5-15 parts, processed Aconitum carmichaelii 3-8 parts, Cinnamomum cassia 10-20 parts, and Oroxylum indicum 8-16 parts.

3. The traditional Chinese medicine preparation for treating Hashimoto's thyroiditis according to claim 1, characterized in that, The traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 18 parts of Curcuma zedoaria, 18 parts of oyster shell, 10 parts of Sargassum, 15 parts of Cremastra appendiculata, 15 parts of Duchesnea indica, 12 parts of Hedyotis diffusa, 12 parts of Artemisia capillaris, 10 parts of Eclipta prostrata, 10 parts of Ligustrum lucidum, 5 parts of processed Aconitum carmichaelii, 15 parts of Cinnamomum cassia, and 12 parts of Oroxylum indicum.

4. The method for preparing a traditional Chinese medicine preparation for treating Hashimoto's thyroiditis as described in any one of claims 1 to 3, characterized in that, The traditional Chinese medicine preparation is prepared into an oral dosage form by adding excipients according to conventional traditional Chinese medicine manufacturing methods. The oral dosage form includes pills, powders, granules, oral liquids, decoctions, and tablets.

5. The use of the traditional Chinese medicine preparation according to any one of claims 1 to 3 in the preparation of a medicament for treating Hashimoto's thyroiditis.

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