Medicine for resisting hashimoto thyroiditis disease and preparation method thereof

Abstract

The invention relates to the technical field of medicine component extraction, and discloses a medicine for resisting hashimoto thyroiditis disease, the medicine comprises an active component and an auxiliary material, the active component is an andrographis paniculata general flavone extract, andrographis paniculata general flavone is used as a main component, and the andrographis paniculata general flavone can reduce exudation of capillary walls, so that the medicine can be used for preventing and treating the hashimoto thyroiditis disease. The andrographis paniculata total flavone extract has an anti-inflammatory effect, is especially effective for symptoms such as upper respiratory tract and diarrhea caused by bacteria and viruses, shows strong antibacterial and antiviral capabilities, can inhibit ADP-induced human platelet aggregation, shortens the dissolution time of euglobulin, and has a good anti-inflammatory effect. The andrographis paniculata extract has a certain protective effect on myocardial injury caused by isoprenaline and experimental myocardial infarction ischemic injury, and the andrographis paniculata extract can enhance the function of phagocytes and improve the staphylococcus aureus phagocytosis capacity of peripheral blood leukocytes, and is used for enhancing immunity and overcoming immunity diseases.

Description

Technical Field

[0001] The invention relates to the technical field of drug component extraction, in particular to a drug capable of resisting Hashimoto's thyroiditis and a preparation method thereof. Background Art

[0002] Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis, is a chronic autoimmune disease with its own thyroid tissue as an antigen. It was first reported by Hashimoto of Kyushu University in Japan based on histological characteristics, so it is also named Hashimoto's thyroiditis. It is the most common thyroid inflammation in clinical practice. It is more common in middle-aged women, with a high incidence age of 40 to 50 years old, and there are also many cases in children.

[0003] At present, Western medicine mainly uses thyroxine replacement therapy, immunotherapy and surgery to relieve local thyroid symptoms, but the effect on the patient's systemic symptoms is not good. Among them, the most conventional treatment is hormone replacement therapy, but hormones have no immunomodulatory effect, cannot reduce the titer of thyroid autoantibodies, and patients need to take medication for life. Secondly, patients need to have continuous physical examinations and adjust the dosage of hormones according to the indicators of thyroid function. There are many adverse reactions, and discontinuation of medication is prone to recurrence. Therefore, seeking new effective drugs for Hashimoto's thyroiditis has obvious social and economic value.

[0004] As a traditional Chinese medicinal material, Andrographis paniculata has the effects of clearing away heat and detoxifying, cooling blood and reducing swelling. In recent years, studies have found that Andrographis paniculata total flavonoid extract has significant anti-inflammatory, antioxidant and immunomodulatory effects. However, there is currently a lack of specific applications of Andrographis paniculata total flavonoid extract in anti-inflammatory drugs on the market, especially in the treatment of inflammatory diseases such as Hashimoto's thyroiditis. Therefore, it is of great significance to develop an anti-inflammatory drug containing Andrographis paniculata total flavonoid extract. Summary of the invention

[0005] In view of the deficiencies in the prior art, the present invention provides a drug having an anti-Hashimoto's thyroiditis effect and a preparation method thereof.

[0006] To achieve the above object, the present invention provides the following technical solution: a drug having the effect of resisting Hashimoto's thyroiditis, the drug comprising an active ingredient and excipients, wherein the active ingredient is a total flavonoid extract of Andrographis paniculata.

[0007] Preferably, the auxiliary materials include but are not limited to fillers, binders, lubricants, disintegrants and necessary drug synergistic ingredients.

[0008] Preferably, the filler is lactose and starch or one of them, the binder is hypromellose, the lubricant is magnesium stearate, and the disintegrant is cross-linked polyvinylpyrrolidone.

[0009] A method for preparing a drug for treating Hashimoto's thyroiditis comprises the following steps:

[0010] a. Prepare materials: 60% ethanol, refined suet oil and Andrographis paniculata raw materials,

[0011] b. Material handling:

[0012] (1) removing impurities from the raw medicinal material of Andrographis paniculata, picking leaves, spraying, watering, slightly moistening, shredding, and drying the leaves;

[0013] (2) Take refined mutton fat and heat it to melt, add the Andrographis paniculata silk treated as above, and stir-fry over low heat until the surface shows a uniform glossy luster. When the Andrographis paniculata silk turns slightly yellow, take it out and let it cool. The weight ratio of Andrographis paniculata to refined mutton fat is 5:1.

[0014] c. Extraction: Take an appropriate amount of processed Andrographis paniculata silk and add 60% ethanol for extraction, with a solid-liquid ratio of 1:20;

[0015] d. Concentration: The drug solution in step c is concentrated to 1 mL of drug solution containing 1 g of crude drug, and purified using HPD300 macroporous resin to obtain the Andrographis paniculata total flavonoids extract;

[0016] e. Mixing the Andrographis paniculata total flavonoids extract with auxiliary materials, and then adopting appropriate preparation technology to prepare the medicine containing the Andrographis paniculata total flavonoids extract.

[0017] Preferably, the extraction method in step c is not limited to cold soaking, percolation, microwave-assisted extraction, Soxhlet extraction, hot reflux extraction, supercritical extraction, etc., and combinations such as cold soaking-percolation, cold soaking-ultrasound, cold soaking-Soxhlet extraction, cold soaking-hot reflux extraction.

[0018] Preferably, the specific concentration step of step d is: adding water to dilute the medicinal solution to make 0.1g of crude drug per 1mL of medicinal solution; then passing through an HPD300 macroporous adsorption resin column at a flow rate of 4BV / h, first washing with 5 times the column volume of water, and then eluting with 7 times the column volume of 50% ethanol, the elution flow rate is 4BV / h, and then collecting the eluate, recovering ethanol under reduced pressure, filtering, adding 3% gelatin solution to the filtrate until no precipitation is produced, and then adding ethanol until the alcohol content reaches 80%, and finally leaving it overnight, filtering, and recovering ethanol under reduced pressure to obtain the Andrographis paniculata total flavonoids extract.

[0019] Preferably, the form of the pharmaceutical preparation in step e is prepared according to demand, and the types of pharmaceutical preparations include: tablets, sugar-coated tablets, film-coated tablets, enteric-coated tablets, capsules, hard capsules, soft capsules, oral liquids, lozenges, granules, granules, pills, powders, pastes, pills, suspensions, powders, solutions, injections, suppositories, ointments, plasters, creams, sprays, drops and patches.

[0020] Preferably, after the ethanol is recovered under reduced pressure, an appropriate amount of activated carbon is added for decolorization, and the product is filtered again to obtain a clarified Andrographis paniculata total flavonoids extract.

[0021] Preferably, the specific steps of the microwave-assisted extraction are:

[0022] (1) Weighing a certain amount of processed Andrographis paniculata silk, placing it in an extraction inner tank, and determining the specific amount according to production requirements, and at the same time, preparing an appropriate amount of ethanol solution as an extraction solvent;

[0023] (2) Add a certain amount of 60% ethanol solution into the extraction inner tank, with a solid-liquid ratio of 1:20;

[0024] (3) placing the extraction inner tank in a microwave extraction device, setting the microwave pressure to 1 atm, and performing microwave-assisted extraction;

[0025] (4) After the extraction is completed, the extract is collected, and after the extraction tank is cleaned with a small amount of extract, the extract is combined and transferred to a centrifuge tube;

[0026] (5) Centrifugal separation: centrifuge the extract to remove solid impurities and particles therein, centrifugal speed: 13000 rad / min, centrifugal time: 45 min;

[0027] (6) Volume adjustment and shaking: Transfer the supernatant after centrifugation to a volumetric flask, adjust the volume to the mark with ethanol solution, and shake to obtain the extract.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] 1. The present invention uses Andrographis paniculata total flavonoids as a main component. Andrographis paniculata total flavonoids can reduce the exudation of capillary walls and have an anti-inflammatory effect. Andrographis paniculata total flavonoids extract is particularly effective for symptoms such as upper respiratory tract and diarrhea caused by bacteria and viruses, showing its powerful antibacterial and antiviral capabilities. Andrographis paniculata total flavonoids has a significant improvement effect on myocardial tissue morphological damage and electrocardiogram abnormalities, has a significant antagonistic effect on acute myocardial infarction, has a preventive and therapeutic effect on coronary thrombotic myocardial infarction, can also inhibit ADP-induced human platelet aggregation, shorten euglobulin lysis time, and has a certain protective effect on myocardial damage caused by isoproterenol and experimental myocardial infarction ischemic damage. Andrographis paniculata extract can enhance phagocyte function, improve the ability of peripheral blood leukocytes to phagocytose Staphylococcus aureus, and is used to strengthen immunity and overcome immune diseases.

[0030] 2. The total flavonoids of Andrographis paniculata in the present invention have low toxicity, and the Andrographis paniculata toxicity is very small. After Andrographis paniculata extract is used as medicine, it usually does not cause serious adverse reactions and has high safety.

[0031] 3. The extraction process of the total flavonoids of Andrographis paniculata in the present invention is mature and has high extraction efficiency: by optimizing the extraction conditions, such as extraction temperature, ethanol mass fraction, etc., the extraction efficiency of the total flavonoids of Andrographis paniculata can be significantly improved, and the extracted total flavonoids of Andrographis paniculata can maintain good stability under appropriate storage conditions and are not prone to deterioration or degradation. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] none DETAILED DESCRIPTION

[0033] The technical solutions in the embodiments of the present invention will be described clearly and completely below.

[0034] Example:

[0035] A drug with anti-Hashimoto's thyroiditis effect, comprising an active ingredient and excipients, wherein the active ingredient is an Andrographis paniculata total flavonoids extract.

[0036] As a further technical solution of the present invention, the auxiliary materials include but are not limited to fillers, binders, lubricants, disintegrants and necessary drug synergistic ingredients, the filler is lactose and starch or one of them, the binder is hypromellose, the lubricant is magnesium stearate, and the disintegrant is cross-linked polyvinylpyrrolidone.

[0037] A method for preparing a drug for treating Hashimoto's thyroiditis comprises the following steps:

[0038] a. Prepare materials: 60% ethanol, refined suet oil and Andrographis paniculata raw materials,

[0039] b. Material handling:

[0040] (1) removing impurities from the raw medicinal material of Andrographis paniculata, picking leaves, spraying, watering, slightly moistening, shredding, and drying the leaves; the Andrographis paniculata shreds can be further processed according to a subsequent extraction method, such as grinding into powder;

[0041] (2) Take refined mutton fat and heat it to melt, add the Andrographis paniculata silk treated as above, and stir-fry over low heat until the surface shows a uniform glossy luster. When the Andrographis paniculata silk turns slightly yellow, take it out and let it cool. The weight ratio of Andrographis paniculata to refined mutton fat is 5:1.

[0042] c. Extraction: Take an appropriate amount of processed Andrographis paniculata silk and add 60% ethanol for extraction, with a solid-liquid ratio of 1:20;

[0043] d. Concentration: The drug solution in step c is concentrated to 1 g of crude drug in 1 mL of drug solution, and purified by HPD300 macroporous resin to obtain the total flavonoids extract of Andrographis paniculata. The specific concentration steps are: dilute the drug solution with water to dilute it to 0.1 g of crude drug per 1 mL of drug solution; then pass it through an HPD300 macroporous adsorption resin column at a flow rate of 4 BV / h, first wash it with 5 times the column volume of water, then elute it with 7 times the column volume of 50% ethanol, the elution flow rate is 4 BV / h, then collect the eluate, recover ethanol under reduced pressure, filter it, add 3% gelatin solution to the filtrate until no precipitation is generated, then add ethanol until the alcohol content reaches 80%, finally leave it overnight, filter it, recover ethanol under reduced pressure, and obtain the total flavonoids extract of Andrographis paniculata;

[0044] e. Mix the Andrographis paniculata total flavonoids extract with excipients, and then adopt an appropriate preparation process to prepare a drug containing the Andrographis paniculata total flavonoids extract. The drug preparation form is prepared according to demand, and the drug types include: tablets, sugar-coated tablets, film-coated tablets, enteric-coated tablets, capsules, hard capsules, soft capsules, oral liquids, lozenges, granules, granules, pills, powders, pastes, pills, suspensions, powders, solutions, injections, suppositories, ointments, plasters, creams, sprays, drops and patches, preferably oral dosage forms, such as: capsules, tablets, oral liquids, granules, pills, powders, pills, pastes, etc.

[0045] As a further technical solution of the present invention, the extraction method in step c is not limited to cold soaking, percolation, microwave-assisted extraction, Soxhlet extraction, hot reflux extraction, supercritical extraction, etc., and a combination such as cold soaking-percolation, cold soaking-ultrasound, cold soaking-Soxhlet extraction, cold soaking-hot reflux extraction, preferably microwave-assisted extraction, which is time-saving, consumes less solvent, and has the highest total flavonoid extraction efficiency (microwave-assisted extraction is to grind the raw materials into powder first, and during the extraction process, microwave energy will selectively heat certain areas or components in the Andrographis paniculata powder, making it easier to separate flavonoids from the matrix and enter the ethanol solution);

[0046] The specific steps of microwave-assisted extraction are:

[0047] (1) Weighing a certain amount of processed Andrographis paniculata silk, placing it in an extraction inner tank, and determining the specific amount according to production requirements, and at the same time, preparing an appropriate amount of ethanol solution as an extraction solvent;

[0048] (2) Add a certain amount of 60% ethanol solution into the extraction inner tank, with a solid-liquid ratio of 1:20;

[0049] (3) placing the extraction inner tank in a microwave extraction device, setting the microwave pressure to 1 atm, and performing microwave-assisted extraction;

[0050] (4) After the extraction is completed, the extract is collected, and after the extraction tank is cleaned with a small amount of extract, the extract is combined and transferred to a centrifuge tube;

[0051] (5) Centrifugal separation: centrifuge the extract to remove solid impurities and particles therein, centrifugal speed: 13000 rad / min, centrifugal time: 45 min;

[0052] (6) Volume adjustment and shaking: Transfer the supernatant after centrifugation to a volumetric flask, adjust the volume to the mark with ethanol solution, and shake to obtain the extract.

[0053] As a further technical solution of the present invention, after the ethanol is recovered under reduced pressure, an appropriate amount of activated carbon is added for decolorization, and the product is filtered again to obtain a clarified Andrographis paniculata total flavonoids extract.

[0054] The present invention uses total flavonoids of Andrographis paniculata as a main component. The total flavonoids of Andrographis paniculata can reduce the exudation of capillary walls and has an anti-inflammatory effect. The total flavonoids extract of Andrographis paniculata is particularly effective for symptoms such as upper respiratory tract and diarrhea caused by bacteria and viruses, showing its strong antibacterial and antiviral capabilities. The total flavonoids of Andrographis paniculata has a significant improvement effect on myocardial tissue morphological damage and electrocardiogram abnormalities, has a significant antagonistic effect on acute myocardial infarction, has a preventive and therapeutic effect on coronary thrombotic myocardial infarction, can also inhibit ADP-induced human platelet aggregation, shorten the euglobulin lysis time, and has a certain protective effect on myocardial damage caused by isoproterenol and experimental myocardial infarction ischemic damage. The Andrographis paniculata extract can enhance the function of phagocytes and improve the ability of peripheral blood leukocytes to phagocytose Staphylococcus aureus, and is used to strengthen immunity and overcome immune diseases.

[0055] The total flavonoids of Andrographis paniculata have low toxicity. The extract of Andrographis paniculata usually does not cause serious adverse reactions after being used as medicine, and has high safety (animal experimental results have shown that the total flavonoids extract of Andrographis paniculata has a significant effect on the treatment of Hashimoto's thyroiditis in rats with Hashimoto's thyroiditis. The total flavonoids extract of Andrographis paniculata has good safety and efficacy, and can effectively treat Hashimoto's thyroiditis);

[0056] The extraction process of total flavonoids from Andrographis paniculata is mature and has high extraction efficiency: by optimizing the extraction conditions (such as using microwave-assisted extraction, which saves time, consumes less solvent, and has the highest extraction efficiency of total flavonoids, and it is better to grind the raw materials into powder. During the extraction process, microwave energy will selectively heat certain areas or components in the Andrographis paniculata powder, making it easier to separate flavonoids from the matrix and enter the ethanol solution), the extraction efficiency of total flavonoids from Andrographis paniculata can be significantly improved. The extracted total flavonoids from Andrographis paniculata can maintain good stability under appropriate storage conditions and are not prone to deterioration or degradation.

[0057] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the above embodiments, it is obvious to those skilled in the art that the features thereof are equivalently replaced. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A drug for treating Hashimoto's thyroiditis, characterized in that: The medicine comprises active ingredients and excipients, wherein the active ingredient is the Andrographis paniculata total flavonoids extract.

2. The drug for treating Hashimoto's thyroiditis according to claim 1, characterized in that: The auxiliary materials include but are not limited to fillers, binders, lubricants, disintegrants and necessary drug synergistic ingredients.

3. The drug for treating Hashimoto's thyroiditis according to claim 2, characterized in that: The filler is lactose and starch or one of them, the binder is hypromellose, the lubricant is magnesium stearate, and the disintegrant is cross-linked polyvinylpyrrolidone.

4. A method for preparing a drug for treating Hashimoto's thyroiditis according to claim 1, characterized in that: The following steps are involved: a. Prepare materials: 60% ethanol, refined suet oil and Andrographis paniculata raw materials, b. Material handling: (1) removing impurities from the raw medicinal material of Andrographis paniculata, picking leaves, spraying, watering, slightly moistening, shredding, and drying the leaves; (2) heating and melting refined suet, adding the processed andrographis paniculata silk, and frying over a low heat until the surface is uniformly glossy and shiny and the andrographis paniculata silk turns slightly yellow, taking out and cooling, wherein the weight ratio of andrographis paniculata to refined suet is 5:1; c. Extraction: Take an appropriate amount of processed Andrographis paniculata silk and add 60% ethanol for extraction, with a solid-liquid ratio of 1:20; d. Concentration: The drug solution in step c is concentrated to 1 mL of drug solution containing 1 g of crude drug, and purified using HPD300 macroporous resin to obtain the Andrographis paniculata total flavonoids extract; e. Mixing the Andrographis paniculata total flavonoids extract with auxiliary materials, and then adopting appropriate preparation technology to prepare the medicine containing the Andrographis paniculata total flavonoids extract.

5. A method for preparing a drug for treating Hashimoto's thyroiditis according to claim 4, characterized in that: The extraction method in step c is not limited to cold soaking, percolation, microwave-assisted extraction, Soxhlet extraction, hot reflux extraction, supercritical extraction, etc., and combinations such as cold soaking-percolation, cold soaking-ultrasound, cold soaking-Soxhlet extraction, cold soaking-hot reflux extraction.

6. A method for preparing a drug for treating Hashimoto's thyroiditis according to claim 4, characterized in that: The specific concentration steps of step d are: adding water to dilute the drug solution to make each 1 mL of the drug solution contain 0.1 g of the crude drug; then passing the solution through an HPD300 macroporous adsorption resin column at a flow rate of 4 BV / h, first washing with 5 times the column volume of water, then eluting with 7 times the column volume of 50% ethanol, the elution flow rate is 4 BV / h, then collecting the eluate, recovering the ethanol under reduced pressure, filtering, adding 3% gelatin solution to the filtrate until no precipitation is generated, then adding ethanol until the alcohol content reaches 80%, finally leaving it overnight, filtering, and recovering the ethanol under reduced pressure to obtain the Andrographis paniculata total flavonoids extract.

7. A method for preparing a drug for treating Hashimoto's thyroiditis according to claim 4, characterized in that: The pharmaceutical preparation form in the step e is prepared according to demand, and the pharmaceutical types include: tablets, sugar-coated tablets, film-coated tablets, enteric-coated tablets, capsules, hard capsules, soft capsules, oral liquids, lozenges, granules, granules, pills, powders, pastes, pills, suspensions, powders, solutions, injections, suppositories, ointments, plasters, creams, sprays, drops and patches.

8. A method for preparing a drug for treating Hashimoto's thyroiditis according to claim 6, characterized in that: After the ethanol is recovered under reduced pressure, an appropriate amount of activated carbon is added for decolorization, and the product is filtered again to obtain a clarified Andrographis paniculata total flavonoids extract.

9. A method for preparing a drug for treating Hashimoto's thyroiditis according to claim 5, characterized in that: The specific steps of the microwave-assisted extraction are: (1) Weighing a certain amount of processed Andrographis paniculata silk, placing it in an extraction inner tank, and determining the specific amount according to production requirements, and at the same time, preparing an appropriate amount of ethanol solution as an extraction solvent; (2) Add a certain amount of 60% ethanol solution into the extraction inner tank, with a solid-liquid ratio of 1:20; (3) placing the extraction inner tank in a microwave extraction device, setting the microwave pressure to 1 atm, and performing microwave-assisted extraction; (4) After the extraction is completed, the extract is collected, and after the extraction tank is cleaned with a small amount of extract, the extract is combined and transferred to a centrifuge tube; (5) Centrifugal separation: centrifuge the extract to remove solid impurities and particles therein, centrifugal speed: 13000 rad / min, centrifugal time: 45 min; (6) Volume adjustment and shaking: Transfer the supernatant after centrifugation to a volumetric flask, adjust the volume to the mark with ethanol solution, and shake to obtain the extract.