Traditional Chinese medicine composition for treating nodules and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating nodules and a preparation method thereof. The traditional Chinese medicine composition is prepared from radix bupleuri, angelica sinensis, radix paeoniae alba, poria cocos, roasted rhizoma atractylodis macrocephalae, mint, salvia chinensis, spina gleditsiae, bulbus fritillariae thunbergii, selfheal, seaweed, kelp, pericarpium citri reticulatae viride, trichosanthes kirilowii maxim, rhizoma pleionis, oriental wormwood and malt. Through reasonable compatibility, the monarch drug, the ministerial drug, the adjuvant drug and the conductant drug cooperate properly, so that the overall efficacy of the prescription is more remarkable, and the prescription has a remarkable effect on treating thyroid nodules and breast nodules.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating nodules and a preparation method thereof. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] Nodules are palpable, localized, round, oval or irregular shaped solid skin lesions. Nodules can be inflammatory or non-inflammatory and can involve the epidermis, dermis or subcutaneous tissue. They can vary in size from millet to cherry or larger, and can fuse to form plaques. Nodules can appear in many different parts of the body, such as the lungs, thyroid, breast, skin, etc.

[0004] Thyroid nodules (TNS) are tissue masses in the thyroid tissue after abnormal proliferation of thyroid cells. They may be single or multiple, and may be solid or cystic in texture. The disease has various causes, which may be due to iodine deficiency, excessive proliferation of normal thyroid tissue, degeneration, history of radiation exposure, genetics, thyroid inflammation, etc. There is no age limit for the patients with thyroid nodules, but epidemiological statistics show that the prevalence of women is 3.83 times that of men, and the incidence rate is higher in people with a history of radiation exposure and a family history of thyroid nodules. Thyroid nodules are often found in the absence of symptoms, even when the thyroid function is normal. Only a small number of thyroid nodules will progress to other thyroid diseases. As the nodule progresses, patients may feel neck pain, a foreign body sensation in the throat, or a sense of pressure, and some people may even develop neck edema.

[0005] Breast nodules, often described as breast masses or breast lumps, are not necessarily breast tumors. They are the result of cancerous or non-cancerous growth of cells in the breast. Possible factors causing breast nodules include breast infection or injury, endocrine hormone level disorders, gene mutations, etc. Breast nodules can be caused by a variety of lesions, including breast infection, fat necrosis, fibrocystic changes, fibroadenomas, simple cysts, intraductal papilloma and malignant tumors. Among these lesions, malignant lesions are characterized by the formation of irregularly shaped, unclear borders and hard texture nodules in the breast. The symptoms of breast nodules vary depending on whether they are benign or malignant, and not all people's breast nodules can be touched. The symptoms of benign lesions are mostly unilateral or bilateral multiple nodules with clear nodule contours and good mobility. Malignant lesions are mostly unilateral and single, with unclear nodule boundaries, hard texture, poor mobility, adhesion to the skin, rapid growth, no obvious pain, and some nodules are accompanied by nipple discharge and nipple retraction.

[0006] Chinese patent with publication number CN109568477A discloses a pharmaceutical composition for treating thyroid nodules, which is a preparation prepared from the following raw materials in weight ratio: 9-15 parts of Cyperus rotundus, 9-15 parts of white peony root, 16-24 parts of Sargassum, 8-12 parts of Bupleurum, 12-18 parts of Kelp, 30-45 parts of Fritillaria, 8-12 parts of Pinellia, 5-7 parts of Citrus aurantium, 8-12 parts of Tangerine peel, 12-18 parts of Angelica sinensis, 8-12 parts of Chuanxiong, 8-12 parts of Forsythia suspensa, 12-18 parts of raw oyster, and 7-11 parts of Prunella vulgaris.

[0007] The traditional Chinese medicine compositions disclosed in the prior art have limited effects in treating thyroid nodules and breast nodules. The present invention is dedicated to providing a new traditional Chinese medicine composition with proper compatibility and significant efficacy. Summary of the invention

[0008] In order to overcome the shortcomings of the prior art, the present invention provides a new traditional Chinese medicine composition for treating thyroid nodules and breast nodules, which is composed of the following traditional Chinese medicines: bupleurum, angelica, white peony root, poria, stir-fried atractylodes, mint, caltrop, gleditsia thorn, thunbergii, selfheal, seaweed, kelp, green peel, trichosanthes, sagittaria, capillaris, and malt.

[0009] According to traditional Chinese medicine theory, the dosage of the drug needs to be adjusted according to its properties, interactions with other drugs, the patient's constitution and other factors to ensure efficacy and safety. The weight ratio of the Chinese medicine composition is: 5-15 parts by weight of bupleurum, 5-15 parts by weight of angelica, 5-15 parts by weight of white peony root, 15-25 parts by weight of Poria, 10-20 parts by weight of stir-fried Atractylodes macrocephala, 3-8 parts by weight of mint, 10-20 parts by weight of Lithospermum officinale, 10-20 parts by weight of Gleditsia sinensis, 5-15 parts by weight of Fritillaria thunbergii, 15-25 parts by weight of Prunella vulgaris, 12-18 parts by weight of Sargassum, 12-18 parts by weight of Kelp, 4-8 parts by weight of Citrus aurantium, 3-7 parts by weight of Trichosanthes, 2-8 parts by weight of Trichosanthes, 12-25 parts by weight of Artemisia capillaris, and 10-22 parts by weight of malt.

[0010] The "monarch, minister, assistant and envoy" in Chinese medicine prescriptions is an important concept in traditional Chinese medicine theory. It refers to the interaction and coordination between different drugs in the prescription to achieve the best therapeutic effect. The core of this theory is to achieve comprehensive conditioning and treatment of diseases through the mutual coordination of drugs.

[0011] Among them: the main medicines are Prunella Vulgaris, Seaweed, Ipomoea batatas, and Kelp.

[0012] Prunella Vulgaris: Mainly used to clear away heat and purge fire, soothe the liver and disperse nodules, and is effective for thyroid nodules.

[0013] Seaweed: softens and disperses lumps, reduces swelling and promotes diuresis, and has good effects on thyroid and breast nodules.

[0014] Lithospermum officinale: Disperses nodules and reduces swelling, acts directly on nodules, and enhances the efficacy of the overall prescription.

[0015] Kelp: It has the effect of softening and dispersing nodules and can dissolve nodules.

[0016] Among them, the assistant medicines are angelica, white peony root, Poria, stir-fried Atractylodes macrocephala, and Fritillaria thunbergii.

[0017] Angelica: replenishes blood and activates blood circulation, regulates Qi and blood, and has an auxiliary effect on promoting blood circulation and removing blood stasis in nodules.

[0018] White Peony Root: Nourishes blood and softens the liver, relieves pain, and helps to harmonize Qi and blood.

[0019] Poria: It promotes diuresis and strengthens the spleen, helps eliminate dampness, and improves the environment for the formation of nodules.

[0020] Fried Atractylodes macrocephala: strengthens the spleen and dries dampness, reducing the impact of dampness on nodules.

[0021] Fritillaria thunbergii: resolves phlegm and dissipates nodules, improves phlegm-dampness nodules.

[0022] Among them, the adjuvant drugs are bupleurum, gleditsia thorn, green tangerine peel, trichosanthes, and aralia.

[0023] Bupleurum: Soothes the liver and relieves depression, helps regulate qi stagnation and blood stasis, and has a relieving effect on the qi stagnation type of nodules.

[0024] Gleditsia sinensis: dispels stagnation and reduces swelling, dredges the meridians, and is used to enhance the efficacy of the drug's dispersing function.

[0025] Qingpi: regulates Qi and soothes the liver, improves Qi stagnation, and assists in untangling knots.

[0026] Trichosanthes: It can relieve chest tightness and resolve nodules, and is helpful for nodules caused by phlegm and dampness.

[0027] Rhizoma Cigu: Disperses nodules and reduces swelling, promotes qi and activates blood circulation, and assists in the treatment of nodules.

[0028] Among them, the ingredients are mint, wormwood and malt.

[0029] Mint: Soothes wind and relieves exterior symptoms, enhances the overall effect of the prescription, and harmonizes the medicinal properties.

[0030] Artemisia capillaris: It can eliminate dampness and reduce jaundice, regulate the accumulation of dampness and heat, and help improve the dampness and heat problems of nodules.

[0031] Malt: helps digestion, strengthens the spleen, and enhances digestion and absorption of drugs.

[0032] This Chinese medicine composition directly acts on thyroid and breast nodules through the main drug's heat-clearing, stagnation-dispelling, swelling-removing and diuresis effects. The auxiliary drug replenishes blood and activates blood circulation, regulates qi and blood, and the adjuvant drug is used to improve qi stagnation, blood stasis and dampness. The overall prescription harmonizes the efficacy of the drug by making the drug dispel wind and relieve exterior symptoms, remove dampness and reduce jaundice, ensuring that the prescription can dissipate nodules while regulating the internal environment and reducing side effects.

[0033] The preparation method of the above-mentioned Chinese medicine composition is:

[0034] (1) Wash and slice the thorns of Gleditsia sinensis, add 6 to 8 times the amount of 60% to 80% ethanol, boil for 1 to 3 hours, filter, and obtain filtrate A; add 4 to 6 times the amount of 60% to 80% ethanol and 0.01 to 0.05 times the amount of lecithin to the residue, boil for 1 to 3 hours, filter, and obtain filtrate B; combine filtrate A and filtrate B, place in a water bath at 30°C to 80°C for rotary evaporation, remove the solvent, and obtain concentrated product A;

[0035] (2) Wash and treat radix bupleuri, angelica, white peony root, poria, stir-fried atractylodes, mint, calanthe, fritillaria thunbergii, herba selfhei, seaweed, kelp, tangerine peel, trichosanthes, saussurea lancea, capillaris, and malt, add 6 to 8 times the amount of water, boil for 2 to 5 hours, filter, and obtain filtrate C; add 4 to 6 times the amount of water to the residue, boil for 2 to 5 hours, filter, and obtain filtrate D; combine filtrate C and filtrate D, and concentrate to an appropriate amount to obtain a medicinal solution;

[0036] (3) Mix the concentrated product A with the drug solution and filter to obtain the product.

[0037] To ensure the removal of the solvent, the rotary evaporation temperature in step (1) is gradually increased from 30°C to 80°C.

[0038] It should be noted that the above-mentioned Chinese medicine composition can be prepared into a common preparation with pharmaceutically acceptable excipients, and the preparation is one of decoction, tablet, granule, pill, and oral liquid; the pharmaceutically acceptable excipient includes at least one of filler, disintegrant, lubricant, preservative, and flavoring agent.

[0039] Compared with the prior art, the technical effects of the present invention are:

[0040] The Chinese medicine composition of the present invention has reasonable compatibility, and the synergistic effects of the main medicine, the auxiliary medicine, the adjuvant medicine and the guiding medicine are proper, so that the overall efficacy of the prescription is more significant, and has a significant effect in treating thyroid nodules and breast nodules.

[0041] The preparation process of the Chinese medicine composition of the present invention is optimized, and the Gleditsia sinensis thorns are processed separately by the alcohol extraction method, so that the effects of dispersing nodules, reducing swelling and unblocking meridians are improved, the nodule dispersing function of the medicinal effect is enhanced, and the medicinal effect of the Chinese medicine composition of the present invention is remarkable. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 These are the statistical results after two courses of treatment.

[0043] Figure 2 is the change rate of the maximum diameter of thyroid nodules in each group of patients.

[0044] Figure 3is the change rate of mammary nodule diameter in each group of rats.

[0045] Figure 4 It is the expression of the content of estradiol (E2) in rat serum.

[0046] Figure 5 It is the expression of progesterone (P) content in rat serum. DETAILED DESCRIPTION

[0047] In order to make the purpose and technical solution of the present invention clearer, the present invention is further described below in conjunction with embodiments, but the protection scope of the present invention is not limited to these embodiments, and the embodiments are only used to explain the present invention. It should be understood by those skilled in the art that any changes or equivalent substitutions that do not deviate from the concept of the present invention are included in the protection scope of the present invention.

[0048] Optimization of Gleditsia sinensis treatment

[0049] The flavonoid content in the concentrated product was determined by colorimetric method with rutin as reference. Accurately pipette 2 mL of sample into a 25 mL volumetric flask, titrate to 6 mL with distilled water, add 1 mL of 5% sodium nitrite, shake well and let stand for 6 minutes, add 1 mL of 10% aluminum nitrate, shake well and let stand for 6 minutes, then add 10 mL of 4% sodium hydroxide solution, add distilled water to the scale, shake well and let stand for 15 minutes. Repeat three times, use blank reagent as reference, and measure absorbance A at 510 nm wavelength with an enzyme marker.

[0050] Group A: Wash and slice the soapberry thorns, add 7 times the amount of 70% ethanol, boil for 2 hours, filter to obtain filtrate A, add 5 times the amount of 70% ethanol and 0.01 times the amount of lecithin to the residue, boil for 2 hours, filter to obtain filtrate B, combine filtrate A and filtrate B, place in a water bath at 30℃~80℃ for rotary evaporation, 30℃, 5min-35℃, 10min-40℃, 15min-50℃, 15min-60℃, 10min-70℃, 15min-75℃, 10min, 80℃, until there is no distillate, remove the solvent to obtain a concentrated product.

[0051] Group B: Wash and slice the soapberry thorns, add 7 times the amount of 70% ethanol, boil for 2 hours, filter to obtain filtrate A, add 5 times the amount of 70% ethanol and 0.03 times the amount of lecithin to the residue, boil for 2 hours, filter to obtain filtrate B, combine filtrate A and filtrate B, place in a water bath at 30℃~80℃ for rotary evaporation, 30℃, 5min-35℃, 10min-40℃, 15min-50℃, 15min-60℃, 10min-70℃, 15min-75℃, 10min, 80℃, until there is no distillate, remove the solvent to obtain a concentrated product.

[0052] Group C: Wash and slice the soapberry thorns, add 7 times the amount of 70% ethanol, boil for 2 hours, filter to obtain filtrate A, add 5 times the amount of 70% ethanol and 0.05 times the amount of lecithin to the residue, boil for 2 hours, filter to obtain filtrate B, combine filtrate A and filtrate B, place in a water bath at 30℃~80℃ for rotary evaporation, 30℃, 5min-35℃, 10min-40℃, 15min-50℃, 15min-60℃, 10min-70℃, 15min-75℃, 10min, 80℃, until there is no distillate, remove the solvent to obtain a concentrated product.

[0053] Group D: Wash and slice the soapberry thorns, add 7 times the amount of 70% ethanol, boil for 2 hours, filter to obtain filtrate A, add 5 times the amount of 70% ethanol to the residue, boil for 2 hours, filter to obtain filtrate B, combine filtrate A and filtrate B, place in a water bath at 30℃~80℃ and rotary evaporation at 30℃, 5min—35℃, 10min—40℃, 15min—50℃, 15min—60℃, 10min—70℃, 15min—75℃, 10min, 80℃, until there is no distillate, remove the solvent to obtain a concentrated product.

[0054] Group E: Wash and slice the soapberry spines, add 7 times the amount of 70% ethanol, boil for 2 hours, filter to obtain filtrate A, add 5 times the amount of 70% ethanol and 0.1 times the amount of lecithin to the residue, boil for 2 hours, filter to obtain filtrate B, combine filtrate A and filtrate B, place in a water bath at 30℃~80℃ for rotary evaporation, 30℃, 5min-35℃, 10min-40℃, 15min-50℃, 15min-60℃, 10min-70℃, 15min-75℃, 10min, 80℃, until there is no distillate, remove the solvent to obtain a concentrated product.

[0055] Group F: Wash and slice the soapberry thorns, add 7 times the amount of 70% ethanol, boil for 2 hours, filter to obtain filtrate A, add 5 times the amount of 70% ethanol and 0.03 times the amount of polysorbate 80 to the residue, boil for 2 hours, filter to obtain filtrate B, combine filtrate A and filtrate B, place in a water bath at 30℃~80℃ for rotary evaporation, 30℃, 5min—35℃, 10min—40℃, 15min—50℃, 15min—60℃, 10min—70℃, 15min—75℃, 10min, 80℃, until there is no distillate, remove the solvent to obtain a concentrated product.

[0056] The flavonoid content of the concentrated products obtained from Groups A to F was tested, and the results are shown in Table 1.

[0057] Table 1 Flavonoid content of each group of products

[0058]

[0059] Gleditsia sinensis thorns contain a large number of flavonoid compounds, such as quercetin, kaempferol, isoquercetin, etc., which have multiple biological activities. Experiments have found that 60% to 80% ethanol is more efficient in extracting flavonoids, and the extracted residues are subjected to secondary extraction. Since the flavonoid components in the residues are relatively small and difficult to extract, the inventors use lecithin to increase the surface wettability of Chinese herbal medicines, enhance the solubility of drug components in ethanol, extract more effective ingredients, and screen out the appropriate amount of lecithin.

[0060] Example 1 Decoction

[0061] Components:

[0062] 10g of Bupleurum, 10g of Angelica, 10g of White Peony, 20g of Poria, 15g of stir-fried Atractylodes, 6g of Menthus, 15g of Lithospermum officinale, 15g of Gleditsia sinensis, 10g of Fritillaria thunbergii, 20g of Prunella Vulgaris, 15g of Sargassum, 15g of Kelp, 6g of Citrus aurantium, 6g of Trichosanthes, 6g of Trichosanthes, 20g of Artemisia Capillaris, and 15g of Malt.

[0063] Preparation method:

[0064] (1) Wash and slice the thorns of Gleditsia sinensis, add 7 times the amount of 70% ethanol, boil for 2 hours, filter, and obtain filtrate A; add 5 times the amount of 70% ethanol and 0.03 times the amount of lecithin to the residue, boil for 2 hours, filter, and obtain filtrate B; combine filtrate A and filtrate B, place in a water bath at a temperature of 30°C to 80°C for rotary evaporation, 30°C, 5min-35°C, 10min-40°C, 15min-50°C, 15min-60°C, 10min-70°C, 15min-75°C, 10min, 80°C, until there is no distillate, remove the solvent, and obtain concentrated product A;

[0065] (2) Wash and treat radix bupleuri, angelica, white peony root, poria, stir-fried atractylodes, mint, calanthe, fritillaria thunbergii, herba prunellae, seaweed, kelp, tangerine peel, trichosanthes, saussurea lancea, capillaris, and malt, add 7 times the amount of water, decoct for 4 h, filter to obtain filtrate C, add 5 times the amount of water to the residue, decoct for 3 h, filter to obtain filtrate D, combine filtrate C and filtrate D, and concentrate to 150 ml to obtain a medicinal solution;

[0066] (3) Mix the concentrated product A with the drug solution and filter to obtain the product.

[0067] Example 2 Decoction

[0068] Components:

[0069] Bupleurum 5g, Angelica 5g, White Peony 5g, Poria 15g, Stir-fried Atractylodes 10g, Menthus 3g, Lithospermum 10g, Gleditsia 10g, Fritillaria 5g, Prunella Vulgaris 15g, Sargassum 12g, Kelp 12g, Citrus aurantium 4g, Trichosanthes 3g, Psoralea corylifolia 2g, Capillaris 12g, and Malt 10g.

[0070] Preparation method:

[0071] (1) Wash and slice the thorns of Gleditsia sinensis, add 6 times the amount of 60% ethanol, boil for 1 hour, filter, and obtain filtrate A; add 4 times the amount of 60% ethanol and 0.01 times the amount of lecithin to the residue, boil for 1 hour, filter, and obtain filtrate B; combine filtrate A and filtrate B, place in a water bath at a temperature of 30°C to 80°C for rotary evaporation, 30°C, 10min-35°C, 15min-40°C, 10min-50°C, 10min-60°C, 15min-70°C, 20min-75°C, 15min, 80°C, until there is no distillate, remove the solvent, and obtain concentrated product A;

[0072] (2) Wash and treat radix bupleuri, angelica, white peony root, poria, stir-fried atractylodes, mint, calanthera, fritillaria thunbergii, herba selfhei, seaweed, kelp, tangerine peel, trichosanthes, rhizoma aconitifolia, capillaris, and malt, add 6 times the amount of water, decoct for 2 h, filter to obtain filtrate C, add 4 times the amount of water to the residue, decoct for 2 h, filter to obtain filtrate D, combine filtrate C and filtrate D, and concentrate to 150 ml to obtain a medicinal solution;

[0073] (3) Mix the concentrated product A with the drug solution and filter to obtain the product.

[0074] Example 3 Decoction

[0075] Components:

[0076] Bupleurum 15g, Angelica 15g, White Peony 15g, Poria 25g, Stir-fried Atractylodes 20g, Menthus 8g, Lithospermum 20g, Gleditsia 20g, Fritillaria 15g, Prunella Vulgaris 25g, Sargassum 18g, Kelp 18g, Citrus aurantium 8g, Trichosanthes 7g, Psoralea corylifolia 8g, Artemisia capillaris 25g, and malt 22g.

[0077] Preparation method:

[0078] (1) Wash and slice the thorns of Gleditsia sinensis, add 8 times the amount of 80% ethanol, boil for 3 hours, filter, and obtain filtrate A; add 6 times the amount of 80% ethanol and 0.05 times the amount of lecithin to the residue, boil for 1 to 3 hours, filter, and obtain filtrate B; combine filtrate A and filtrate B, place in a water bath at a temperature of 30°C to 80°C for rotary evaporation, 30°C, 10min-35°C, 20min-40°C, 10min-50°C, 20min-60°C, 10min-70°C, 10min-75°C, 20min, 80°C, until there is no distillate, remove the solvent, and obtain concentrated product A;

[0079] (2) Wash and treat radix bupleuri, angelica, white peony root, poria, stir-fried atractylodes, mint, lycopodiella ciliata, fritillaria thunbergii, herba prunellae, seaweed, kelp, tangerine peel, trichosanthes, rhizoma atractylodis macrocephalae, capillaris, and malt, add 8 times the amount of water, boil for 5 h, filter, and obtain filtrate C; add 6 times the amount of water to the residue, boil for 5 h, filter, and obtain filtrate D; combine filtrate C and filtrate D, and concentrate to 150 ml to obtain a medicinal solution;

[0080] (3) Mix the concentrated product A with the drug solution and filter to obtain the product.

[0081] Example 4 Granules

[0082] Components:

[0083] 10g of Bupleurum, 10g of Angelica, 10g of White Peony, 20g of Poria, 15g of stir-fried Atractylodes, 6g of Menthus, 15g of Lithospermum officinale, 15g of Gleditsia sinensis, 10g of Fritillaria thunbergii, 20g of Prunella Vulgaris, 15g of Sargassum, 15g of Kelp, 6g of Citrus aurantium, 6g of Trichosanthes, 6g of Trichosanthes, 20g of Artemisia Capillaris, and 15g of Malt.

[0084] Preparation method:

[0085] (1) Wash and slice the thorns of Gleditsia sinensis, add 7 times the amount of 70% ethanol, boil for 2 hours, filter, and obtain filtrate A; add 5 times the amount of 70% ethanol and 0.03 times the amount of lecithin to the residue, boil for 2 hours, filter, and obtain filtrate B; combine filtrate A and filtrate B, place in a water bath at a temperature of 30°C to 80°C for rotary evaporation, 30°C, 5min-35°C, 10min-40°C, 15min-50°C, 15min-60°C, 10min-70°C, 15min-75°C, 10min, 80°C, until there is no distillate, remove the solvent, and obtain concentrated product A;

[0086] (2) Wash and treat radix bupleuri, angelica, white peony root, poria, stir-fried atractylodes, mint, calanthe, fritillaria thunbergii, herba prunellae, seaweed, kelp, tangerine peel, trichosanthes, saussurea lancea, capillaris, and malt, add 7 times the amount of water, boil for 4 h, filter, and obtain filtrate C; add 5 times the amount of water to the residue, boil for 3 h, filter, and obtain filtrate D; combine filtrate C and filtrate D, and concentrate to an appropriate amount to obtain a medicinal solution;

[0087] (3) The concentrated product A is mixed with the drug solution, filtered, concentrated to a relative density of 1.45, and appropriate amounts of starch and sucrose are added to make a soft material, granulated, dried, and granulated to obtain the product.

[0088] Example 5 Tablets

[0089] Components:

[0090] 10g of Bupleurum, 10g of Angelica, 10g of White Peony, 20g of Poria, 15g of stir-fried Atractylodes, 6g of Menthus, 15g of Lithospermum officinale, 15g of Gleditsia sinensis, 10g of Fritillaria thunbergii, 20g of Prunella Vulgaris, 15g of Sargassum, 15g of Kelp, 6g of Citrus aurantium, 6g of Trichosanthes, 6g of Trichosanthes, 20g of Artemisia Capillaris, and 15g of Malt.

[0091] Preparation method:

[0092] (1) Wash and slice the thorns of Gleditsia sinensis, add 7 times the amount of 70% ethanol, boil for 2 hours, filter, and obtain filtrate A; add 5 times the amount of 70% ethanol and 0.03 times the amount of lecithin to the residue, boil for 2 hours, filter, and obtain filtrate B; combine filtrate A and filtrate B, place in a water bath at a temperature of 30°C to 80°C for rotary evaporation, 30°C, 5min-35°C, 10min-40°C, 15min-50°C, 15min-60°C, 10min-70°C, 15min-75°C, 10min, 80°C, until there is no distillate, remove the solvent, and obtain concentrated product A;

[0093] (2) Wash and treat radix bupleuri, angelica, white peony root, poria, stir-fried atractylodes, mint, calanthe, fritillaria thunbergii, herba prunellae, seaweed, kelp, tangerine peel, trichosanthes, saussurea lancea, capillaris, and malt, add 7 times the amount of water, boil for 4 h, filter, and obtain filtrate C; add 5 times the amount of water to the residue, boil for 3 h, filter, and obtain filtrate D; combine filtrate C and filtrate D, and concentrate to an appropriate amount to obtain a medicinal solution;

[0094] (3) The concentrated product A is mixed with the drug solution, filtered, and concentrated to a relative density of 1.45, and appropriate amounts of starch, microcrystalline cellulose, sucrose, and sodium starch glycolate are added, granulated, dried, and granulated, and appropriate amounts of magnesium stearate are added, and tablets are pressed to obtain the product.

[0095] Example 6 Oral Liquid

[0096] Components:

[0097] 10g of Bupleurum, 10g of Angelica, 10g of White Peony, 20g of Poria, 15g of stir-fried Atractylodes, 6g of Menthus, 15g of Lithospermum officinale, 15g of Gleditsia sinensis, 10g of Fritillaria thunbergii, 20g of Prunella Vulgaris, 15g of Sargassum, 15g of Kelp, 6g of Citrus aurantium, 6g of Trichosanthes, 6g of Trichosanthes, 20g of Artemisia Capillaris, and 15g of Malt.

[0098] Preparation method:

[0099] (1) Wash and slice the thorns of Gleditsia sinensis, add 7 times the amount of 70% ethanol, boil for 2 hours, filter, and obtain filtrate A; add 5 times the amount of 70% ethanol and 0.03 times the amount of lecithin to the residue, boil for 2 hours, filter, and obtain filtrate B; combine filtrate A and filtrate B, place in a water bath at a temperature of 30°C to 80°C for rotary evaporation, 30°C, 5min-35°C, 10min-40°C, 15min-50°C, 15min-60°C, 10min-70°C, 15min-75°C, 10min, 80°C, until there is no distillate, remove the solvent, and obtain concentrated product A;

[0100] (2) Wash and treat radix bupleuri, angelica, white peony root, poria, stir-fried atractylodes, mint, calanthe, fritillaria thunbergii, herba prunellae, seaweed, kelp, tangerine peel, trichosanthes, saussurea lancea, capillaris, and malt, add 7 times the amount of water, boil for 4 h, filter, and obtain filtrate C; add 5 times the amount of water to the residue, boil for 3 h, filter, and obtain filtrate D; combine filtrate C and filtrate D, and concentrate to an appropriate amount to obtain a medicinal solution;

[0101] (3) Mix the concentrated product A with the drug solution, filter, and concentrate to a relative density of 1.05 to 1.15, add appropriate amounts of sucrose, honey, and sodium benzoate, sterilize, and fill to obtain the product.

[0102] Comparative Example 1 Decoction

[0103] Components:

[0104] 10g of Bupleurum, 10g of Angelica, 10g of White Peony, 20g of Poria, 15g of stir-fried Atractylodes, 6g of Menthus, 15g of Lithospermum officinale, 15g of Gleditsia sinensis, 10g of Fritillaria thunbergii, 20g of Prunella Vulgaris, 15g of Sargassum, 15g of Kelp, 6g of Citrus aurantium, 6g of Trichosanthes, 6g of Trichosanthes, 20g of Artemisia Capillaris, and 15g of Malt.

[0105] Preparation method:

[0106] Wash and treat bupleurum, angelica, white peony root, poria, stir-fried atractylodes, mint, calanthe, gleditsia thorn, thunbergia thunbergii, selfheal, seaweed, kelp, green peel, trichosanthes, saussurea, capillaris, and malt, add 7 times the amount of water, boil for 4 hours, filter to obtain filtrate A, add 5 times the amount of water to the residue, boil for 3 hours, filter to obtain filtrate B, combine filtrate A and filtrate B, concentrate to 150 ml, filter to obtain.

[0107] Comparative Example 2 Decoction

[0108] Components:

[0109] 10g of Bupleurum, 10g of Angelica, 10g of White Peony, 20g of Poria, 15g of stir-fried Atractylodes, 6g of Menthus, 15g of Lithospermum officinale, 15g of Gleditsia sinensis, 10g of Fritillaria thunbergii, 20g of Prunella Vulgaris, 15g of Sargassum, 15g of Kelp, 6g of Citrus aurantium, 6g of Trichosanthes, 6g of Trichosanthes, 20g of Artemisia Capillaris, and 15g of Malt.

[0110] Preparation method:

[0111] (1) Wash and slice the thorns of Gleditsia sinensis, add 7 times the amount of 70% ethanol, decoct for 2 hours, filter, and obtain filtrate A; add 5 times the amount of 70% ethanol to the residue, decoct for 2 hours, filter, and obtain filtrate B; combine filtrate A and filtrate B, place in a water bath at 30°C to 80°C for rotary evaporation, 30°C, 5min-35°C, 10min-40°C, 15min-50°C, 15min-60°C, 10min-70°C, 15min-75°C, 10min, 80°C, until there is no distillate, remove the solvent, and obtain concentrated product A;

[0112] (2) Wash and treat radix bupleuri, angelica, white peony root, poria, stir-fried atractylodes, mint, calanthe, fritillaria thunbergii, herba prunellae, seaweed, kelp, tangerine peel, trichosanthes, saussurea lancea, capillaris, and malt, add 7 times the amount of water, decoct for 4 h, filter to obtain filtrate C, add 5 times the amount of water to the residue, decoct for 3 h, filter to obtain filtrate D, combine filtrate C and filtrate D, and concentrate to 150 ml to obtain a medicinal solution;

[0113] (3) Mix the concentrated product A with the drug solution and filter to obtain the product.

[0114] Comparative Example 3 Decoction

[0115] Components:

[0116] 10g of Bupleurum, 10g of Angelica, 10g of White Peony, 15g of stir-fried Atractylodes, 6g of Menthus, 15g of Angelica Dahurica, 15g of Gleditsia sinensis, 10g of Fritillaria thunbergii, 15g of Sargassum, 15g of Kelp, 6g of Citrus aurantium, 6g of Licorice, 6g of Tripterygium wilfordii, 20g of Artemisia capillaris, and 15g of malt.

[0117] Preparation method:

[0118] (1) Wash and slice the thorns of Gleditsia sinensis, add 7 times the amount of 70% ethanol, boil for 2 hours, filter, and obtain filtrate A; add 5 times the amount of 70% ethanol and 0.03 times the amount of lecithin to the residue, boil for 2 hours, filter, and obtain filtrate B; combine filtrate A and filtrate B, place in a water bath at a temperature of 30°C to 80°C for rotary evaporation, 30°C, 5min-35°C, 10min-40°C, 15min-50°C, 15min-60°C, 10min-70°C, 15min-75°C, 10min, 80°C, until there is no distillate, remove the solvent, and obtain concentrated product A;

[0119] (2) Wash and treat radix bupleuri, angelica, white peony root, stir-fried atractylodes, mint, angelica dahurica, fritillaria thunbergii, seaweed, kelp, green peel, liquorice, saussurea ovata, capillaris, and malt, add 7 times the amount of water, decoct for 4 h, filter to obtain filtrate C, add 5 times the amount of water to the residue, decoct for 3 h, filter to obtain filtrate D, combine filtrate C and filtrate D, and concentrate to 150 ml to obtain a medicinal solution;

[0120] (3) Mix the concentrated product A with the drug solution and filter to obtain the product.

[0121] King medicine:

[0122] Seaweed and kelp: Mainly target nodules, have the effect of softening and dispersing nodules and can dissolve nodules.

[0123] Minister medicine:

[0124] Angelica and white peony root: regulate blood circulation, nourish liver and kidney, assist the role of the main medicine, and relieve the discomfort caused by nodules. Artemisia capillaris: has the effect of clearing away heat and dampness, helping to improve the symptoms related to nodules.

[0125] Adjuvant:

[0126] Stir-fried Atractylodes macrocephala and malt: Strengthen the spleen and stomach, help digestion and absorption of drugs, and enhance the overall therapeutic effect. Peppermint and Angelica dahurica: Clear away heat and relieve symptoms, relieve symptoms caused by nodules, and harmonize the efficacy of drugs.

[0127] Drug:

[0128] Qingpi and Shancigu: Soothe the liver and regulate qi, coordinate the effects of drugs, promote the efficacy of drugs to reach relevant parts, and improve nodule symptoms. Licorice: coordinate various drugs, reduce the toxic side effects of drugs, and enhance the overall effect of the prescription.

[0129] This prescription is designed to dissipate nodules, regulate internal organs, and clear away heat and detoxify.

[0130] Comparative Example 4 Decoction

[0131] Components:

[0132] 12g of Cyperus rotundus, 12g of white peony root, 20g of seaweed, 10g of Bupleurum chinense, 15g of Kelp, 35g of Fritillaria thunbergii, 10g of Pinellia ternata, 6g of Citrus aurantium, 10g of Tangerine peel, 15g of Angelica sinensis, 10g of Chuanxiong, 10g of Forsythia suspensa, 15g of raw oyster, and 9g of Prunella vulgaris.

[0133] Preparation method: According to the above raw material ratio, first put Fritillaria thunbergii and raw oyster into a casserole and add 3000ml of water. After boiling for half an hour over high heat, add Cyperus rotundus, White Peony Root, Seaweed, Bupleurum Root, Pinellia Tuber, Citrus Reticulata, Angelica Sinensis, Chuanxiong, Forsythia suspensa, Kelp, and Prunella Vulgaris. Boil over high heat, then continue to boil over low heat until about 150-200ml, and pour the boiled liquid into a clean container. Add 1500ml of water to the remaining drug residue, first boil over high heat, then boil over low heat until 150-200ml is left. The two liquids are mixed to 300-400ml, and concentrated to 150ml.

[0134] Explanation of the prescription of monarch, minister, assistant and envoy:

[0135] King medicine:

[0136] Seaweed: It has a significant softening and dispersing effect, and is the main drug for treating nodules. Kelp: Similar to seaweed, it has the effect of dispersing nodules, softening and dispersing nodules, and is one of the main drugs in prescriptions. Fritillaria thunbergii: It has the effect of resolving phlegm and dispersing nodules, and can help dissipate nodules, especially in cases of coughing with a lot of phlegm.

[0137] Minister medicine:

[0138] Cyperus rotundus: soothes the liver and regulates qi, regulates qi stagnation, and guides the drug to the lesion. Chaihu: soothes the liver and relieves depression, regulates qi, and helps dissipate nodules. Chenpi: regulates qi and strengthens the spleen, helps digestion and absorption of drugs, and improves qi.

[0139] Adjuvant:

[0140] White peony root: harmonizes the Ying and Wei, relieves the discomfort caused by nodules, and can enhance the blood-tonifying effect when combined with angelica. Angelica: nourishes the blood, harmonizes the Qi and blood, and enhances the overall efficacy. Chuanxiong: activates blood circulation and removes blood stasis, promotes blood circulation, and harmonizes the Qi and blood when combined with angelica and white peony root. Prunella vulgaris: clears heat and detoxifies, softens and disperses nodules, and enhances the effect of dissipating nodules. Forsythia: clears heat and detoxifies, reduces swelling and disperses nodules, and helps relieve inflammation of nodules.

[0141] Drug:

[0142] Qingpi: Soothes the liver and regulates qi, promotes the efficacy of the medicine, and harmonizes the whole prescription. Pinellia: Resolves phlegm and disperses nodules, helps the medicine reach the lesion, and relieves nodular symptoms.

[0143] Comprehensive conditioning aims to dissipate nodules, soothe the liver and regulate qi, promote blood circulation and remove blood stasis, clear away heat and detoxify, and promote the full effect of the medicine.

[0144] Verification of the effect of the Chinese medicine composition of the present invention on treating thyroid nodules

[0145] Clinical Data

[0146] Case selection: 200 outpatients were randomly divided into treatment group A, treatment group B, treatment group C and control group, each group had 50 cases, including 10 males and 50 females, aged between 30 and 60 years old. Ultrasound confirmed that the diameter of the largest solid nodule was between 10 and 25 mm.

[0147] Treatment

[0148] Treatment group A, treatment group B, and treatment group C respectively took the Chinese medicine preparations provided in Examples 1 to 3 of the present invention, once in the morning and once in the evening, with 60 days as a course of treatment.

[0149] The control group took 50 μg of levothyroxine once a day.

[0150] Efficacy criteria

[0151] Cured: The discomfort symptoms completely disappeared and the thyroid nodules were found to have shrunk.

[0152] Effectiveness: Symptoms of discomfort were alleviated and examination showed that thyroid nodules had shrunk.

[0153] Ineffective: No change in discomfort symptoms or size of thyroid nodules.

[0154] Treatment results:

[0155] The statistical review results after 60 days of treatment were as follows: in treatment group A, 35 cases were cured, 10 cases were effective, 5 cases were ineffective, and the total effective rate was 90.0%; in treatment group B, 33 cases were cured, 9 cases were effective, 8 cases were ineffective, and the total effective rate was 84.0%; in treatment group C, 36 cases were cured, 8 cases were effective, 6 cases were ineffective, and the total effective rate was 88.0%; in the control group, 15 cases were cured, 12 cases were effective, 23 cases were ineffective, and the total effective rate was 54%.

[0156] Figure 1 The results are statistically analyzed after two courses of treatment. The treatment effects of treatment groups A, B, and C were significantly better than those of the control group, and the symptoms were better controlled.

[0157] Changes in thyroid nodule size

[0158] At the initial diagnosis before treatment, color Doppler blood flow imaging was used to detect the maximum diameter of the patients' thyroid nodules in each group. For patients with multiple nodules, the largest one was observed, and the initial data were statistically analyzed. The maximum diameter of the thyroid nodules was measured again after one and two courses of treatment, and the change rate of the maximum diameter of the thyroid nodules was calculated and then statistically analyzed for each group.

[0159] Figure 2 The maximum diameter change rate of thyroid nodules in each group of patients showed that the Chinese medicine composition of the present invention can effectively reduce the size of thyroid nodules. After one course of treatment, the maximum diameter change rate of thyroid nodules in treatment group A, treatment group B, and treatment group C was significantly different from that in the control group, P < 0.01; after two courses of treatment, the maximum diameter change rate of thyroid nodules in treatment group A, treatment group B, and treatment group C was significantly different from that in the control group, P < 0.01.

[0160] Statistical processing

[0161] SPSS 22.0 software was used to perform statistical analysis on the data. The measurement data were expressed as (x±s). One-way analysis of variance was used for comparison among multiple groups, and independent sample T test was used for analysis between two groups. P<0.05 was considered statistically significant.

[0162] Verification of the effect of the Chinese medicine composition of the present invention on treating breast hyperplasia nodules

[0163] It should be noted that the following experimental studies are all carried out on the basis of acute toxicity tests and long-term toxicity tests to prove the safety of the drugs, and the dosages used in the experimental studies are all within the safe dosage range.

[0164] Drugs and Dosages

[0165] The dosage of the decoctions obtained in Examples 1 to 3 and Comparative Examples 1 to 4 was 13.5 ml / kg, and the decoctions were administered twice a day.

[0166] Experimental animals

[0167] Female non-pregnant SD rats, SPF grade, 180-220 g, experimental animal license number: SYXK(Lu)20180008, were adaptively fed under standard conditions for 1 week before the experiment.

[0168] Modeling method and grouping

[0169] Several rats were intramuscularly injected with estradiol benzoate at a dose of 0.5 mg / kg / d, and progesterone was intramuscularly injected at a dose of 4 mg / kg / d after 25 days of administration, for a total of 5 days. The modeling was checked on the 31st day. The rats with successful modeling were randomly divided into Example 1 group, Example 2 group, Example 3 group, Comparative Example 1 group, Comparative Example 2 group, Comparative Example 3 group, Comparative Example 4 group, and model group, with 10 rats in each group. 10 rats in the blank group were not treated.

[0170] Drug administration

[0171] The rats in each treatment group were given corresponding drugs by gavage, and the rats in the blank group and model group were given an equal amount of normal saline by gavage, twice a day, for 21 days.

[0172] Statistical processing

[0173] SPSS 22.0 software was used to perform statistical analysis on the data. The measurement data were expressed as (x±s). One-way analysis of variance was used for comparison among multiple groups, and independent sample T test was used for analysis between two groups. P<0.05 was considered statistically significant.

[0174] Observation indicators and experimental results

[0175] Changes in mammary gland diameter in rats

[0176] Before and after drug administration, color Doppler blood flow imaging was used to detect the maximum diameter of rat mammary nodules. For patients with multiple nodules, the largest one was observed and the initial data were statistically analyzed. The data were measured again 21 days after drug administration, and the diameter change rate was calculated and statistically analyzed.

[0177] Figure 3 It is the change rate of the diameter of the mammary nodules of each group of rats. It shows that the Chinese medicine composition of the present invention has a good therapeutic effect on mammary hyperplasia nodules in rats. Compared with the model group rats, there are significant differences in Example 1-3 groups, P < 0.01; compared with the comparative example 3 group rats, there are significant differences in Example 1-3 groups, P < 0.01; compared with the comparative example 4 group rats, there are significant differences in Example 1-3 groups, P < 0.01.

[0178] Expression of serum estradiol (E2) and progesterone (P) in rats

[0179] Blood was collected, serum was separated, and serum estradiol (E 2 ) and progesterone (P) content.

[0180] Figure 4 Estradiol (E 2 ) content expression, Figure 5 Expression of progesterone (P) content in rat serum. Estradiol is one of the main female sex hormones, which plays an important role in the development and maintenance of breast tissue. High levels of estradiol may stimulate the proliferation of breast tissue and increase the risk of breast nodules. Progesterone has a regulatory effect on breast tissue and usually works together with estrogen to affect the structure and function of the breast. Changes in progesterone levels may affect the formation and changes of breast nodules. Figures 4-5 The results showed that the Chinese medicine composition of the present invention has an effect on rat serum estradiol (E 2 ) and progesterone (P) play an excellent positive role in the regulation. Compared with the model group rats, the Example 1-3 groups have significant differences, P < 0.01; compared with the comparative example 3 group rats, the Example 1-3 groups have significant differences, P < 0.01; compared with the comparative example 4 group rats, the Example 1-3 groups have significant differences, P < 0.01.

Claims

1. A Chinese medicine composition for treating nodules, characterized in that: The Chinese medicine composition is composed of the following Chinese medicines: bupleurum, angelica, white peony root, tuckahoe, stir-fried atractylodes, mint, calanthe, thorn of gleditsia, fritillaria thunbergii, selfheal, seaweed, kelp, green peel, trichosanthes, sagittaria, capillaris, and malt.

2. The Chinese medicine composition according to claim 1, characterized in that: The Chinese medicine composition consists of the following Chinese medicines: 5-15 parts by weight of bupleurum, 5-15 parts by weight of angelica, 5-15 parts by weight of white peony root, 15-25 parts by weight of Poria, 10-20 parts by weight of stir-fried Atractylodes macrocephala, 3-8 parts by weight of peppermint, 10-20 parts by weight of celery, 10-20 parts by weight of Gleditsia sinensis, 5-15 parts by weight of Fritillaria thunbergii, 15-25 parts by weight of Prunella vulgaris, 12-18 parts by weight of Sargassum, 12-18 parts by weight of Kelp, 4-8 parts by weight of Citrus aurantium, 3-7 parts by weight of Trichosanthes, 2-8 parts by weight of Psoralea corylifolia, 12-25 parts by weight of Artemisia capillaris, and 10-22 parts by weight of malt.

3. The Chinese medicine composition according to claim 1, characterized in that The Chinese medicine composition consists of the following Chinese medicines: 10 parts by weight of bupleurum, 10 parts by weight of angelica, 10 parts by weight of white peony root, 20 parts by weight of Poria, 15 parts by weight of stir-fried Atractylodes macrocephala, 6 parts by weight of peppermint, 15 parts by weight of Lithospermum officinale, 15 parts by weight of Gleditsia sinensis, 10 parts by weight of Fritillaria thunbergii, 20 parts by weight of Prunella vulgaris, 15 parts by weight of Sargassum, 15 parts by weight of Kelp, 6 parts by weight of Citrus aurantium, 6 parts by weight of Trichosanthes kirilowii, 6 parts by weight of Psoralea corylifolia, 20 parts by weight of Artemisia capillaris, and 15 parts by weight of malt.

4. The Chinese medicine composition according to claim 1, characterized in that: The nodule is a thyroid nodule.

5. The Chinese medicine composition according to claim 1, characterized in that: The nodule is a breast nodule.

6. A method for preparing the Chinese medicine composition according to claim 1, characterized in that: The method comprises the following steps: (1) Wash and slice the thorns of Gleditsia sinensis, add 6 to 8 times the amount of 60% to 80% ethanol, boil for 1 to 3 hours, filter, and obtain filtrate A; add 4 to 6 times the amount of 60% to 80% ethanol and 0.01 to 0.05 times the amount of lecithin to the residue, boil for 1 to 3 hours, filter, and obtain filtrate B; combine filtrate A and filtrate B, place in a water bath at 30°C to 80°C for rotary evaporation, remove the solvent, and obtain concentrated product A; (2) Wash and treat radix bupleuri, angelica, white peony root, poria, stir-fried atractylodes, mint, calanthe, fritillaria thunbergii, herba selfhei, seaweed, kelp, tangerine peel, trichosanthes, saussurea lancea, capillaris, and malt, add 6 to 8 times the amount of water, boil for 2 to 5 hours, filter, and obtain filtrate C; add 4 to 6 times the amount of water to the residue, boil for 2 to 5 hours, filter, and obtain filtrate D; combine filtrate C and filtrate D, and concentrate to an appropriate amount to obtain a medicinal solution; (3) Mix the concentrated product A with the drug solution and filter to obtain the product.

7. The method according to claim 6, characterized in that In the step (1), the rotary evaporation temperature is gradually increased from 30°C to 80°C.

8. The method according to claim 6, characterized in that The added amount of the lecithin is 0.03 times of the filter residue.

9. A preparation made from the Chinese medicine composition according to claim 1, characterized in that: The preparation is one of decoction, tablet, granule, pill and oral liquid.

10. The preparation according to claim 9, characterized in that The preparation further comprises pharmaceutically acceptable excipients, and the pharmaceutically acceptable excipients include at least one of a filler, a disintegrant, a lubricant, a preservative, and a flavoring agent.

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