A traditional Chinese medicine composition for promoting nodule absorption after thermal ablation of benign thyroid nodules and its preparation method

Abstract

The present invention discloses a traditional Chinese medicine composition for promoting the absorption of benign thyroid nodules after thermal ablation, and a preparation method thereof. The composition is prepared from the following raw materials in parts by weight: 6-30 parts of peach kernel, 1-15 parts of saffron, 3-30 parts of angelica, 6-40 parts of Scrophularia, 3-15 parts of Chuanxiong, 5-45 parts of white peony root, 3-30 parts of Cyperus, and 3-20 parts of liquorice. The present invention targets the special period after radiofrequency ablation of benign thyroid nodules, which is mainly characterized by phlegm and blood stasis, but also by the "heat" evil caused by ablation. The pathogenesis is summarized as "phlegm and blood stasis blocking the meridians, and fire and heat are combined". The present invention adopts the principle of "activating blood circulation and resolving phlegm, and clearing heat and reducing fire" to formulate the "blood-activating and heat-clearing prescription" to promote better absorption of nodules and reduce clinical discomfort symptoms.

Description

Technical Field

[0001] The present invention relates to the field of thyroid nodule medicine and traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for promoting nodule absorption after thermal ablation of benign thyroid nodules and a preparation method thereof. Background Art

[0002] Thyroid nodules are scattered lesions caused by local abnormal growth of thyroid cells. Thyroid nodules have become a common clinical disease, and the incidence rate in women is higher than in men. Most thyroid nodules diagnosed clinically are benign, of which only 5% to 12% are malignant nodules.

[0003] Classic surgical thyroidectomy was once the standard treatment. With advances in medical technology and a growing demand for aesthetically pleasing results, thermal ablation of thyroid nodules has become increasingly common due to its proven efficacy, safety, and aesthetically pleasing appearance. While thermal ablation is safe and effective, it still suffers from limitations such as pain and discomfort in the surgical area, prolonged absorption of necrotic tissue in some patients (up to 32.5 months), and even long-term effects on thyroid function. The etiology and pathogenesis of goiter were first documented in the "Lüshi Chunqiu," which states: "Where there is light water, there are many bald and goitre-stricken people," suggesting that environmental and dietary factors may contribute to the development of nodules. Traditional medicine lacks a specific disease name for "thyroid nodules." Most physicians now classify these conditions, based on their clinical symptoms, as "goiter," "qi goiter," or "meat goiter." These conditions are treated according to their respective etiologies and pathogenesis, achieving some success. In clinical practice, reducing discomfort after thermal ablation, accelerating nodule absorption, and shortening the time it takes for nodules to resorb remain hot topics and challenges. Currently, the technologies related to thyroid nodule drugs, such as patent CN107029181A for a Chinese medicine composition, preparation method and application for nodular goiter, and CN109464623A for a Chinese medicine alcohol-lipid cold compress gel and preparation method for treating thyroid nodules, are relatively complex in formulation or use.

[0004] Radiofrequency ablation is a thermal destruction technology. The radiofrequency generator generates a high-frequency oscillating current, which is transmitted to the target tissue through the electrode needle, causing the polar molecules and ions in the surrounding tissue to vibrate and rub, and then convert into heat energy, thereby causing the local tissue cell proteins to undergo irreversible thermal coagulation and necrosis, and finally the necrotic tissue is absorbed, achieving the purpose of local inactivation of the lesion. Fire needle therapy is a treatment method that inserts the needle into the body surface after burning it red. According to the theory of traditional Chinese medicine, radiofrequency ablation is classified as the "fire needle" category of traditional Chinese medicine. Therefore, in this special period after radiofrequency ablation of benign thyroid nodules, phlegm and blood stasis are the main symptoms, but there is also the "heat" evil caused by ablation. In summary, its pathogenesis is characterized by "phlegm and blood stasis blocking the meridians, and fire and heat". In view of the above characteristics, the present invention has formed a traditional Chinese medicine solution through research. Summary of the Invention

[0005] The purpose of the present invention is to address the deficiencies in the prior art and provide an effective Chinese medicine composition and a preparation method thereof for promoting better absorption of benign thyroid nodules and reducing clinical discomfort symptoms after thermal ablation of benign thyroid nodules.

[0006] To achieve the above object, the technical solution provided by the present invention is:

[0007] A traditional Chinese medicine composition for promoting the absorption of benign thyroid nodules after thermal ablation, comprising the following raw materials in parts by weight: 6-30 parts of peach kernel, 1-15 parts of saffron, 3-30 parts of angelica, 6-40 parts of Scrophularia, 3-15 parts of Chuanxiong, 5-45 parts of white peony root, 3-30 parts of Cyperus rotundus, and 3-20 parts of liquorice.

[0008] Preferably, it is made from the following raw materials in parts by weight: 7-16 parts of peach kernel, 2-9 parts of saffron, 6-20 parts of angelica, 9-18 parts of Scrophularia, 6-12 parts of Chuanxiong, 6-15 parts of white peony root, 5-10 parts of Cyperus rotundus, and 2-10 parts of licorice.

[0009] As a further preferred embodiment, the invention is prepared from the following raw materials in parts by weight: 9 parts of peach kernel, 6 parts of saffron, 12 parts of angelica, 15 parts of Scrophularia, 9 parts of Chuanxiong, 9 parts of white peony root, 6 parts of Cyperus, and 3 parts of liquorice.

[0010] The present invention also protects a traditional Chinese medicine preparation for promoting the absorption of benign thyroid nodules after thermal ablation, characterized in that the traditional Chinese medicine preparation is prepared using the traditional Chinese medicine composition described in any one of claims 1-3.

[0011] The pharmaceutical preparation is prepared into oral liquid, tablets, pills, hard capsules, soft capsules or granules.

[0012] The present invention also provides a method for preparing a traditional Chinese medicine preparation for promoting nodule absorption after thermal ablation of benign thyroid nodules, characterized in that: the traditional Chinese medicine composition according to any one of claims 1 to 3 is used, each raw material is weighed according to weight, and crushed into a coarse granular mixture, the crushed mixture is added to water, and decocted for 25-35 minutes to obtain a decoction.

[0013] Preferably, the weight ratio of the crushed mixture to the added water is 1:3-5.

[0014] The decoction can be directly used as an oral liquid, or the decoction can be further processed to form a Chinese medicine preparation suitable for oral administration.

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] The present invention targets the special period after radiofrequency ablation of benign thyroid nodules, which is mainly characterized by phlegm and blood stasis, but also accompanied by the "heat" evil caused by ablation. The pathogenesis can be summarized as "phlegm and blood stasis blocking the collaterals, accompanied by fire and heat". The principle of "activating blood circulation and resolving phlegm, clearing away heat and reducing fire" is adopted to formulate the "blood-activating and heat-clearing prescription".

[0017] The pharmaceutical composition of the present invention has a relatively small number of raw materials, but is well formulated according to the principle, minister, assistant and guiding compatibility. Each of the medicinal ingredients is indispensable, and the combination has a significant synergistic effect:

[0018] In the formula, peach kernel and saffron promote blood circulation and dispel blood stasis, enter the blood system to dispel blood stasis, promote blood circulation, and relieve depression and resolve stagnation, serving as the main herbs. Angelica sinensis nourishes blood, promotes blood circulation, and relieves pain, while Scrophularia ningpoensis clears heat and cools blood, nourishes yin and reduces fire, and resolves toxins and resolves stagnation, serving as the assistant herbs. Cyperus rotundus is used to regulate qi and relieve depression, regulate menstruation, and relieve pain; Chuanxiong promotes blood circulation, promotes qi circulation, and relieves pain, and enters the blood system to regulate qi in the blood. Paeonia lactiflora clears heat from the blood, dispels blood stasis, and relieves pain; while liquorice harmonizes the other herbs, serving as the guiding herb. The combination of these herbs, while clearing heat and cooling blood, promoting blood circulation and removing blood stasis, also reduces swelling, resolves stagnation, and promotes qi circulation to relieve pain, can promote nodule absorption after ablation of benign thyroid nodules and reduce clinical discomfort. DETAILED DESCRIPTION

[0019] The above contents of the present invention are further described in detail below in the form of embodiments, but this should not be understood as the scope of the above subject matter of the present invention being limited to the following embodiments. All technologies implemented based on the above contents of the present invention fall within the scope of the present invention.

[0020] The experimental methods used in the following examples are conventional methods unless otherwise specified, and the reagents, methods and equipment used are conventional reagents, methods and equipment in the art unless otherwise specified.

[0021] Example 1

[0022] The present invention provides an oral Chinese medicine preparation for promoting better absorption of benign thyroid nodules after radiofrequency ablation for the treatment of nodules. The preparation is made of the following raw materials in parts by weight: 9 parts of peach kernel, 6 parts of saffron, 12 parts of angelica, 15 parts of Scrophularia, 9 parts of Chuanxiong, 9 parts of white peony root, 6 parts of Cyperus rotundus, and 3 parts of licorice.

[0023] Impurities and dust are removed from the component raw materials, and the weight is weighed according to the above total amount, and the mixture is crushed into coarse particles. Water is added to the crushed mixture (the weight ratio of the mixture to water is 1:4), and the mixture is decocted for 30 minutes. The resulting decoction is an oral Chinese medicine preparation for promoting better absorption of benign thyroid nodules after radiofrequency ablation. The obtained oral liquid preparation is packaged in vacuum plastic bags to obtain a finished product.

[0024] Example 2

[0025] The present invention provides an oral Chinese medicine preparation for promoting better absorption of benign thyroid nodules after radiofrequency ablation for the treatment of nodules. The preparation is made of the following raw materials in parts by weight: 10 parts of peach kernel, 3 parts of saffron, 12 parts of angelica, 15 parts of Scrophularia, 9 parts of Chuanxiong, 9 parts of white peony root, 6 parts of Cyperus rotundus, and 6 parts of licorice.

[0026] Impurities and dust are removed from the component raw materials, and the weight is weighed according to the above total amount, and the mixture is crushed into coarse particles. Water is added to the crushed mixture (the weight ratio of the mixture to water is 1:3.5), and the mixture is decocted for 27 minutes. The resulting decoction is an oral Chinese medicine preparation for promoting better absorption of benign thyroid nodules after radiofrequency ablation. The obtained oral liquid preparation is packaged in vacuum plastic bags to obtain the finished product.

[0027] Example 3

[0028] The present invention provides an oral Chinese medicine preparation for promoting better absorption of benign thyroid nodules after radiofrequency ablation for the treatment of nodules. The preparation is made of the following raw materials in parts by weight: 10 parts of peach kernel, 6 parts of saffron, 12 parts of angelica, 9 parts of Scrophularia, 9 parts of Chuanxiong, 12 parts of white peony root, 6 parts of Cyperus rotundus, and 6 parts of licorice.

[0029] Impurities and dust are removed from the component raw materials, and the weight is weighed according to the above total amount, and the mixture is crushed into coarse particles. Water is added to the crushed mixture (the weight ratio of the mixture to water is 1:4.5), and the mixture is decocted for 35 minutes. The resulting decoction is an oral Chinese medicine preparation for promoting better absorption of benign thyroid nodules after radiofrequency ablation. The obtained oral liquid preparation is packaged in vacuum plastic bags to obtain a finished product.

[0030] Comparative Example 1

[0031] The present invention provides an oral Chinese medicine preparation for promoting better absorption of benign thyroid nodules after radiofrequency ablation for the treatment of nodules. The preparation is made of the following raw materials in parts by weight: 8 parts of peach kernel, 9 parts of angelica, 12 parts of Scrophularia, 9 parts of Chuanxiong, 12 parts of white peony root, 6 parts of Cyperus rotundus, and 3 parts of licorice.

[0032] Impurities and dust are removed from the component raw materials, and the weight is weighed according to the above total amount, and the mixture is crushed into coarse particles. Water is added to the crushed mixture (the weight ratio of the mixture to water is 1:4), and the mixture is decocted for 30 minutes. The resulting decoction is an oral Chinese medicine preparation for promoting better absorption of benign thyroid nodules after radiofrequency ablation. The obtained oral liquid preparation is packaged in vacuum plastic bags to obtain a finished product.

[0033] Effect verification experiment:

[0034] Methods: 121 patients who underwent thyroid nodule ablation surgery at our hospital between October 2021 and October 2023 were randomly divided into an observation group, a control group I, and a control group II. The observation group included 42 patients (16 males and 26 females, with a mean age of 44.21±14.18 years); 18 patients had single nodules and 22 had multiple nodules; the mean nodule length was 2.13±1.65 cm (range, 1.11-4.6 cm). The control group included 40 patients (15 males and 25 females, with a mean age of 45.23±13.27 years); 16 patients had single nodules and 24 had multiple nodules; the mean nodule length was 2.42±1.09 cm (range, 1.0-4.2 cm). There were 39 cases in control group II, including 17 males and 22 females, with an average age of 42.69±12.20 years; 17 cases had single nodules and 23 cases had multiple nodules; the average nodule diameter was 2.22±1.19 cm (range, 1.0-4.5 cm). There was no statistically significant difference in baseline between the three groups (P>0.05).

[0035] Diagnostic criteria:

[0036] Western medicine diagnostic criteria conform to the 2023 edition of the "Guidelines for the Diagnosis and Treatment of Thyroid Nodules and Differentiated Thyroid Cancer" (Second Edition) published by the Chinese Society of Endocrinology. ① Color Doppler ultrasound reveals focal areas of abnormal thyroid echoes; ② Fine needle aspiration and cytology (FNAC) reveals benign conditions such as thyroid adenoma, cyst, or nodular goiter.

[0037] The diagnostic criteria of Traditional Chinese Medicine are consistent with the diagnosis of goiter in the "Surgery of Traditional Chinese Medicine" (3rd edition) edited by He Qinghu and Qin Guozheng: diffuse swelling or lumps on one or both sides of the throat in front of the neck, which are soft when pressed and seem to have accumulated air inside, or are soft and round, like a ball of meat, which can move up and down with swallowing and develop slowly.

[0038] Inclusion criteria

[0039] Inclusion criteria: ① Meet the Western medical diagnostic criteria for thyroid nodules and the Traditional Chinese Medicine diagnostic criteria for galls; ② Age 18 to 78 years (inclusive); ③ Diagnosis of benign thyroid nodules by imaging, fine needle aspiration cytology, or core needle biopsy, with ultrasound showing calcification and / or rich blood flow signals within the nodules; ④ Patients with protruding nodules that affect appearance or who have high requirements for postoperative aesthetics; ⑤ Patients who refuse surgical resection and require minimally invasive surgery; ⑥ Patients who require minimally invasive surgery due to excessive anxiety about thyroid nodules; ⑦ Informed consent: Volunteers who signed the informed consent form.

[0040] Exclusion criteria: ① Patients who have been clearly diagnosed with malignant tumors; ② Patients with severe damage to important organs, mental illness, obvious abnormalities in coagulation function and thyroid function, and pregnancy; ③ Other medical histories that, according to the researcher's judgment, reduce the possibility of enrollment or complicate enrollment, such as frequent changes in work environment, which may easily lead to loss to follow-up; ④ Subjects who are participating in clinical trials of other drugs or have just completed clinical trials of other drugs less than 3 months ago; ⑤ Subjects with allergic constitution or known allergies to the components of the Chinese medicine in this study.

[0041] method

[0042] Thermal ablation: With the patient's neck in hyperextension position, 1% lidocaine is locally injected through the skin and subcutaneously to the anterior thyroid capsule. Normal saline or 1% lidocaine is used to form an isolation zone between the thyroid capsule and surrounding tissues. The radiofrequency ablation power is adjusted to 30-35W. Mobile ablation is performed from deep to shallow and from dangerous to safe areas. After the initial ablation is completed, angiography is performed to evaluate the ablation inactivation range. If any uninactivated lesions are found in the nodule, they are marked and the uninactivated area is ablated again.

[0043] Observation group: Thyroid nodule thermal ablation treatment was performed in the same manner. On the second day after the ablation treatment, the patients were given the oral liquid preparation of Example 1, 1 dose per day, morning and evening, for 3 consecutive months.

[0044] Control group I: Thyroid nodule thermal ablation treatment was performed in the same manner. On the second day after the ablation treatment, the patients were given the oral liquid preparation of comparative example 1, 1 dose per day, morning and evening, for 3 consecutive months.

[0045] Control group II: Thyroid nodule thermal ablation treatment was performed in the same manner, and after thermal ablation, a placebo of Huoxueshengrefang was added (prepared by the hospital preparation room in accordance with the conventional composition of Chinese patent medicine placebo: pharmaceutical ingredients account for 10%, auxiliary materials are sucrose and sodium benzoate, and colorant caramel color, and its color, shape and taste are the same as Huoxueshengrefang, as comparative example 2), one dose per day, taken in the morning and evening, for three consecutive months.

[0046] Observation indicators

[0047] Thyroid nodule volume reduction rate: The volume reduction rate (VRR) of thyroid nodules was assessed by color ultrasound before surgery and at 1 month, 3 months, 6 months, and 12 months after surgery, as well as the blood flow of thyroid nodules detected by color ultrasound as the main evaluation indicators to observe the cure rate of thyroid nodules. The diameter of thyroid nodules in the two groups of patients was measured by color ultrasound and the volume was calculated to calculate the thyroid nodule volume reduction rate. VRR = (V0-V1) / V0×100% (V = πabc / 6, a, b, c are the maximum diameters of the three largest sections, respectively. V0 is the volume of the nodule before RFA treatment, and V1 is the volume of the nodule at each follow-up after RFA treatment.). The cure rate of thyroid nodules is divided into 4 levels. Cure (complete disappearance of nodule, complete blood flow blockage, no new lesions), marked effect (nodule VRR ≥ 75%, blood flow blockage ≥ 75%), effective (25% ≤ VRR < 75%; 25% ≤ blood flow blockage < 75%), ineffective (VRR < 25%, even recurrence; abundant blood flow inside and / or around the nodule).

[0048] Syndrome score: This score was developed based on the Qi stagnation and blood stasis syndrome scale with fire toxicity accumulation, according to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines." Symptoms (NRS pain score for anterior cervical pain, neck swelling, pharyngeal discomfort, hoarseness, sweating, and fatigue) were graded into four levels, with scores of 0, 1, 2, and 3, respectively, as shown in Table 2. The score was recorded on the first, seventh, 30th, 90th, and first year after surgery. The ratio of the score to the preoperative score was calculated and categorized into four levels: cured (≥95%), markedly effective (70%-95%), effective (30%-69%), and ineffective (<30%).

[0049] Cytokines: Peripheral venous fasting blood was collected from both groups of patients before surgery and on days 1, 7, and 30 after surgery. Serum was extracted by static centrifugation (30 min, 3500 rpm, 10 min). ELSA assays were performed according to the instructions in the manufacturer's instructions. The optical density (OD) of each well was measured at a wavelength of 450 nm using a microplate reader. The content of the corresponding marker in each test sample was calculated using the standard curve.

[0050] Safety evaluation: The patient's liver and kidney function was used as the safety indicator for evaluation, and the occurrence of adverse events such as hoarseness, bleeding, and infection during treatment was recorded.

[0051] SPSS 26.0 statistical software was used for statistical analysis. When comparing between groups, a normality test was performed first. If the data obeyed the normal distribution, they were expressed as mean ± standard deviation (x-±s). The two-sample t-test was used to compare the differences between the groups, and the chi-square test of counting data was used for the total effective rate.

[0052] Result Analysis

[0053] Table 2 shows the comparison of thyroid nodule reduction rate (VRR) among the three groups of patients. As shown in Table 2, the overall treatment effect of the observation group was better than that of the control group I and control group II, and the difference was statistically significant (P<0.05).

[0054] Table 2 Comparison of postoperative thyroid shrinkage rate (VRR) between the two groups (%)

[0055]

[0056] Note: Compared with 1 month after treatment, ▲▲ P<0.01; compared with the observation group, △△ P<0.01; compared with control group I, * P<0.05, ** P < 0.01;

[0057] Table 3 Comparison of the total effective rate of treatment between the two groups of patients (%)

[0058]

[0059] Note: Compared with the observation group, △ P<0.05; compared with control group I, * P < 0.05;

[0060] Table 4 Comparison of TCM syndrome scores after surgery in the two groups

[0061]

[0062] Note: Compared with 1 day after treatment, ▲▲ P<0.01; compared with the observation group, △ P<0.05, △△ P < 0.01;

[0063] Table 5 Comparison of cytokine indicators between the two groups of patients after surgery

[0064]

[0065] Note: Compared with before treatment, ▲ P<0.05, ▲▲ P<0.01; compared with the observation group, △ P<0.05, △△ P<0.01; compared with control group I, * P<0.05, ** P < 0.01;

[0066] During the treatment, no obvious liver and kidney function abnormalities were observed in the three groups of patients. Only one patient experienced hoarseness during ablation, and his voice returned to normal half an hour after the operation. No other adverse reactions were observed during follow-up.

[0067] As can be seen from the observation group, control group I, and control group II, the pharmaceutical composition of the present invention is well formulated according to the principle, minister, assistant, and guiding ingredients. Each of the medicinal ingredients is indispensable and the combination has a significant synergistic effect. The Chinese medicine composition of the present invention can effectively promote the absorption of nodules and reduce the patient's body's stress response. It also helps to reduce the occurrence of discomfort symptoms such as anterior neck pain and neck swelling in patients after surgery.

[0068] The above description is only a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Any simple modification, equivalent replacement and improvement made by any technician familiar with the profession to the above embodiment without departing from the scope of the technical solution of the present invention and based on the technical essence of the present invention shall still fall within the scope of protection of the technical solution of the present invention.

Claims

1. A Chinese medicine composition for promoting the absorption of benign thyroid nodules after thermal ablation, characterized in that: The invention is prepared from the following raw materials in parts by weight: 9 parts of peach kernel, 6 parts of saffron, 12 parts of angelica, 15 parts of Scrophularia, 9 parts of Chuanxiong, 9 parts of white peony root, 6 parts of Cyperus rotundus and 3 parts of liquorice.

2. A Chinese medicine preparation for promoting the absorption of benign thyroid nodules after thermal ablation, characterized in that: A Chinese medicine preparation prepared using the Chinese medicine composition according to claim 1.

3. The Chinese medicine preparation for promoting nodule absorption after thermal ablation of benign thyroid nodules according to claim 2, characterized in that: The pharmaceutical preparation is prepared into oral liquid, tablets, pills, hard capsules, soft capsules or granules.

4. A method for preparing a traditional Chinese medicine preparation for promoting nodule absorption after thermal ablation of benign thyroid nodules, characterized in that: The Chinese medicine composition according to claim 1 is used, and the raw materials are weighed according to weight, crushed into a coarse granular mixture, and the crushed mixture is added to water and boiled for 25-35 minutes to obtain a decoction.

5. The method for preparing the Chinese medicine preparation for promoting nodule absorption after thermal ablation of benign thyroid nodules according to claim 4, characterized in that: The weight ratio of the crushed mixture to the added water is 1:3-5.

6. The method for preparing the traditional Chinese medicine preparation for promoting nodule absorption after thermal ablation of benign thyroid nodules according to claim 4, characterized in that: The decoction can be taken directly as oral solution.

7. The method for preparing the traditional Chinese medicine preparation for promoting nodule absorption after thermal ablation of benign thyroid nodules according to claim 4, characterized in that: The decoction is further processed to form a Chinese medicine preparation suitable for consumption.

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