WO2023109573A1 - 一种治疗桥本甲状腺炎的中药组合物及其制备方法 - Google Patents

一种治疗桥本甲状腺炎的中药组合物及其制备方法 Download PDF

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WO2023109573A1
WO2023109573A1 PCT/CN2022/136849 CN2022136849W WO2023109573A1 WO 2023109573 A1 WO2023109573 A1 WO 2023109573A1 CN 2022136849 W CN2022136849 W CN 2022136849W WO 2023109573 A1 WO2023109573 A1 WO 2023109573A1
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chinese medicine
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thyroiditis
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葛明华
郑传铭
李清林
黄萍
张轶雯
王佳峰
蒋烈浩
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浙江省人民医院
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/481—Astragalus (milkvetch)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A61K36/076—Poria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/284—Atractylodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/487—Psoralea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A61K36/815—Lycium (desert-thorn)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A61K36/8994—Coix (Job's tears)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the invention belongs to the field of traditional Chinese medicines, and relates to a traditional Chinese medicine composition and a preparation method thereof, in particular to a traditional Chinese medicine composition for treating Hashimoto's thyroiditis and a preparation method thereof.
  • Hashimoto's thyroiditis also known as chronic lymphocytic thyroiditis and lymphoid goiter, is a common autoimmune disease of the thyroid gland, and its pathological features are diffuse lymphocytes and plasma cells in the thyroid gland. Sexual infiltration, destruction of thyroid follicles, new capillaries in glandular tissue, and eventually lead to hypothyroidism, clinical features are normal thyroid function, hyperthyroidism (hyperthyroidism) or hypothyroidism (hypothyroidism).
  • hypothyroidism hyperthyroidism
  • hypothyroidism hypothyroidism
  • the incidence of Hashimoto's thyroiditis is increasing year by year, and it is more common in women aged 30 to 50. The onset is insidious, the development is slow and the course of disease is long. , part of the onset with a sense of swelling of the face and limbs, this disease has become an important disease that affects health in some areas of our country.
  • the holistic theory of traditional Chinese medicine believes that the viscera, qi and blood of the human body are an organic whole, so the treatment of Hashimoto's thyroiditis should not only start from the lesion, but should grasp the root, start from the liver, spleen and kidney, and carry out corresponding qi-invigorating gain or dredging regulation, from Fundamentally improve the immunity of patients with Hashimoto's thyroiditis, relieve the symptoms of goiter, and strengthen the body.
  • different treatment methods are adopted for different stages, different courses, and different symptoms of Hashimoto's thyroiditis.
  • the object of the present invention is to provide a Chinese medicine composition for the treatment of Hashimoto's thyroiditis. Prepared from raw medicinal materials, it has the effects of invigorating qi and strengthening the exterior, invigorating the spleen and kidney, and can be used for the treatment of Hashimoto's thyroid disease with definite curative effect.
  • a traditional Chinese medicine composition for treating Hashimoto's thyroiditis made of the following traditional Chinese medicine components in parts by weight:
  • the preferred weight ratio of raw materials in the Chinese medicine composition is:
  • the preferred weight ratio of raw materials in the Chinese medicine composition is:
  • the Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizome is fried with bran, and the seed of coix is fried with bran.
  • Astragalus membranaceus is sweet and slightly warm, and has the effects of invigorating qi and raising yang, benefiting health and strengthening the surface, and diuresis to reduce swelling; Synergistic effect, better play the effect of invigorating qi and solidifying the surface, invigorating the spleen and replenishing qi, diuresis and expelling dampness, and combined into a monarch drug.
  • Poria cocos is sweet in taste and flat in nature, and it guides the heart, lung, spleen, and kidney meridian. Spleen exudates dampness, eliminates numbness and relieves diarrhea, clears away heat and expels pus; the above three herbs are combined to exert the effects of diuresis, swelling, spleen and dampness, and are ministerial medicines.
  • Psoralen is bitter and pungent, which can nourish the kidney and strengthen yang, consolidate essence and reduce urination, warm the spleen and stop diarrhea; Kidney meridian, can warm kidney and strengthen yang, dispel cold and dehumidify; Lycium barbarum is sweet and slightly cold, and has the effects of nourishing kidney and lung, nourishing liver and improving eyesight; the combination of the above four herbs has the effect of warming kidney and yang, strengthening muscles and strengthening bones. effect.
  • Another object of the present invention is to provide a kind of oral pharmaceutical preparation containing above-mentioned Chinese medicine composition and preparation method thereof, described Chinese medicine oral pharmaceutical preparation is in oral liquid, mixture, tablet, capsule, pill, micropill, granule kind of.
  • the preparation method of described Chinese medicine oral pharmaceutical preparation comprises the following steps:
  • step B Weigh the coarse grains of raw medicinal materials in step A according to the prescription amount, mix them evenly, add 6-10 times the amount of water to decoct, filter the decoction, concentrate under reduced pressure, and obtain an extract for future use;
  • step C Add ethanol to the extract obtained in step B to make the alcohol content reach 60%-70%, let stand and cool for 24-48 h, filter, recover the ethanol from the filtrate, concentrate to obtain a concentrated solution, and set aside;
  • step D Take the extract obtained in step C, add corresponding pharmaceutically acceptable excipients directly or after being concentrated, and make oral pharmaceutical preparations through conventional processes.
  • step B add 6-10 times the amount of water and decoct twice, the first time is 2-3 h, and the second time is 1-2 h
  • step B is decocted by adding water twice, adding 8 times the amount of water for 3 h for the first time, and decocting for 2 hours by adding 6 times the amount of water for the second time.
  • step B is concentrated under reduced pressure to an extract with a relative density of 1.10-1.15 at 50-60°C.
  • step C is concentrated under reduced pressure into an extract with a relative density of 1.21-1.28 at 50-60 °C;
  • step D includes but are not limited to water precipitation, filtration, concentration, drying, crushing, sieving, and the like.
  • the acceptable excipients described in step D include one or more of fillers, lubricants, preservatives, flavoring agents, disintegrants, binders, colorants, and dispersants.
  • the pharmaceutically acceptable excipients include but are not limited to lactose, starch, dextrin, powdered sugar, magnesium stearate, maltose, lemonade, tartaric acid, sodium hydroxide, aspartame, stevioside, sweetener Sucralose, protein sugar, acesulfame potassium, aspartame, sucralose, sodium benzoate, etc.
  • the oral pharmaceutical preparation is an oral liquid preparation
  • the preparation method comprises the following steps:
  • step B Weigh the coarse grains of raw medicinal materials in step A according to the prescription amount, mix well, add water to decoct 2 times, add 8-10 times the amount of water for the first time, decoct for 2-3 hours, and add 6-8 times the amount for the second time water, decoct for 1-2 h, combine the decoction liquid, filter, concentrate under reduced pressure to an extract with a relative density of 1.1-1.15 at 50-60 °C, and set aside;
  • step C Add ethanol to the extract obtained in step B to make the alcohol content reach 60%-70%, let it stand for 24-48 h, filter, recover ethanol from the filtrate and concentrate it to a relative density of 1.21-1.28 at 50-60 °C Concentrate, spare;
  • step D Take the concentrated solution obtained in step C, add purified water to prepare the total amount, add sodium benzoate, filter until the clarity is qualified, fill, sterilize, and pack to obtain an oral liquid preparation.
  • the oral pharmaceutical preparation is an oral solid preparation
  • the preparation method of the oral solid preparation includes the following steps:
  • step B Weigh the coarse grains of raw medicinal materials in step A according to the prescription amount, mix well, add water to decoct 2 times, add 8-10 times the amount of water for the first time, decoct for 2-3 hours, and add 6-8 times the amount for the second time water, decoct for 1-2 h, combine the decoction liquid, filter, concentrate under reduced pressure to an extract with a relative density of 1.10-1.15 at 50-60 °C, and set aside;
  • step C Add ethanol to the extract obtained in step B to make the alcohol content reach 60%-70%, let it stand for 24-48 h, filter, recover ethanol from the filtrate and concentrate it to a relative density of 1.21-1.28 at 50-60 °C Extract, spare;
  • step D Take the extract from step C, vacuum-dry it at a vacuum degree of -0.09MPa ⁇ -0.10Mpa, and 60°C, pulverize it into a fine powder, sieve it, add an appropriate amount of excipients, mix well, make granules, and dry. Further make oral solid preparations such as granules, tablets, capsules and pills.
  • the invention provides the use of the traditional Chinese medicine composition in preparing medicines for treating Hashimoto's thyroid disease, especially in preparing medicines for diseases such as hypothyroidism caused by Hashimoto's thyroiditis.
  • the traditional Chinese medicine composition of the present invention is prepared from 9 raw materials of Astragalus, Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Atractylodes Rhizoma Mulberry, Poria cocos, Poria cocos, coix seed, psoraleae, mulberry, wolfberry,
  • composition of the present invention can significantly reduce the levels of serum inflammatory cytokines IL-6 and IL-12 and the levels of serum thyroid autoantibodies TGAb and TPOAb in rats with Hashimoto's thyroiditis, and significantly improve thyroid secretory function. It has a good therapeutic effect on Hashimoto's thyroiditis, especially for the symptoms of hypothyroidism caused by Hashimoto's thyroiditis, and has broad clinical application prospects.
  • step B Weigh the coarse grains of raw medicinal materials in step A according to the prescription, mix well, add water to decoct 2 times, add 10 times the amount of water for the first time, decoct for 2 hours, add 8 times the amount of water for the second time, decoct for 1.5 hours , the decoctions were combined, filtered, concentrated under reduced pressure to an extract with a relative density of 1.10 at 50-60°C, and set aside;
  • step C Add ethanol to the extract obtained in step B to make the alcohol content reach 60%, let stand and cool for 24 h, filter, recover ethanol from the filtrate and concentrate it to an extract with a relative density of 1.21 at 50-60°C, and set aside;
  • step D Take the extract of step C, add purified water to the total amount of preparation, add sodium benzoate, filter until the clarity is qualified, fill, sterilize, and pack to obtain the mixture.
  • step B Weigh the coarse grains of raw medicinal materials in step A according to the prescription, mix well, add water to decoct twice, add 10 times the amount of water for the first time, decoct for 3 hours, add 8 times the amount of water for the second time, decoct for 1 hour, The decoction liquids were combined, filtered, concentrated under reduced pressure to an extract with a relative density of 1.15 at 50-60°C, and set aside;
  • step B Add ethanol to the extract obtained in step B to make the alcohol content reach 65%, let stand and cool for 36 h, filter, recover ethanol from the filtrate and concentrate it to an extract with a relative density of 1.25 at 50-60 ° C, and set aside;
  • step D Take the extract from step C, add 2 times the amount of purified water to the extract and let it stand for more than 48 hours, filter, add purified water to the filtrate to make up the total amount, add sodium benzoate, filter until the clarity is qualified, then fill, sterilize, and pack , to obtain oral liquid.
  • step B Weigh the coarse grains of raw medicinal materials in step A according to the prescription amount, mix well, add water to decoct twice, add 8 times the amount of water for the first time, decoct for 3 hours, add 6 times the amount of water for the second time, decoct for 2 hours , the decoctions were combined, filtered, concentrated under reduced pressure to an extract with a relative density of 1.15 at 50-60°C, and set aside;
  • step C Add ethanol to the extract obtained in step B to make the alcohol content reach 60%, let stand and cool for 48 h, filter, recover ethanol from the filtrate and concentrate it to an extract with a relative density of 1.24 at 50-60°C, and set aside;
  • step C extract, carry out vacuum drying under the condition of vacuum degree -0.09MPa ⁇ -0.10Mpa, 60 °C, pulverize into fine powder, sieve, add the sucrose powder of formula quantity, dextrin (weight ratio 5: 2 ), mixed evenly, made into granules, dried, and granulated to obtain granules.
  • step B Weigh the coarse grains of raw medicinal materials in step A according to the prescription, mix well, add water to decoct twice, add 8 times the amount of water for the first time, decoct for 2 hours, add 6 times the amount of water for the second time, decoct for 2 hours , the decoctions were combined, filtered, concentrated under reduced pressure to an extract with a relative density of 1.13 at 50-60°C, and set aside;
  • step B Add ethanol to the extract obtained in step B to make the alcohol content reach 70%, let stand and cool for 48 h, filter, recover ethanol from the filtrate and concentrate it to a concentrated solution with a relative density of 1.28 at 50-60 ° C, and set aside;
  • step D Take the concentrated solution obtained in step C, add purified water to prepare the total amount, add 0.25% aspartame, filter until the clarity is qualified, fill, sterilize, and pack to obtain the oral solution.
  • step B Weigh the coarse grains of raw medicinal materials in step A according to the prescription, mix well, add water to decoct 2 times, add 9 times the amount of water for the first time, decoct for 2 hours, add 7 times the amount of water for the second time, decoct for 2 hours , the decoctions were combined, filtered, concentrated under reduced pressure to an extract with a relative density of 1.10 at 50-60°C, and set aside;
  • step B Add ethanol to the extract obtained in step B to make the alcohol content reach 65%, let stand and cool for 36 h, filter, recover ethanol from the filtrate and concentrate it to an extract with a relative density of 1.25 at 50-60 ° C, and set aside;
  • step D Take the extract from step C, vacuum-dry it at a vacuum degree of -0.09MPa ⁇ -0.10Mpa, and 60°C, grind it into a fine powder, sieve it, add an appropriate amount of dextrin and 0.25% aspartame, and mix well , made into granules, dried, and granulated to obtain granules.
  • step B Weigh the coarse grains of raw medicinal materials in step A according to the prescription, mix them evenly, add water to decoct twice, add 10 times the amount of water for the first time, decoct for 2 hours, add 6 times the amount of water for the second time, decoct for 1 hour , the decoction liquid was combined, filtered, concentrated under reduced pressure to an extract with a relative density of 1.14 at 50-60°C, and set aside;
  • step B Add ethanol to the extract obtained in step B to make the alcohol content reach 70%, let stand and cool for 36 h, filter, recover ethanol from the filtrate and concentrate it to an extract with a relative density of 1.28 at 50-60 ° C, and set aside;
  • step D Take the extract from step C, vacuum-dry it at a vacuum degree of -0.09MPa ⁇ -0.10Mpa, and 60°C, pulverize it into a fine powder, sieve it, add an appropriate amount of starch and microcrystalline cellulose, granulate, and dry.
  • the capsules are filled to obtain capsules.
  • step B Weigh the coarse grains of raw medicinal materials in step A according to the prescription, mix well, add water to decoct twice, add 8 times the amount of water for the first time, decoct for 2.5 hours, add 7 times the amount of water for the second time, decoct for 1.5 hours , the decoctions were combined, filtered, concentrated under reduced pressure to an extract with a relative density of 1.12 at 50-60°C, and set aside;
  • step C Add ethanol to the extract obtained in step B to make the alcohol content reach 60%, let stand and cool for 48 h, filter, recover ethanol from the filtrate and concentrate it to an extract with a relative density of 1.25 at 50-60°C, and set aside;
  • step D Take the extract from step C, put it in a 60°C oven for drying, crush it into fine powder, sieve it, add the formula amount of starch, dextrin and sucrose (weight ratio 3:2:1), mix well, granulate, and dry , granulate, add 0.3% magnesium stearate, mix well, and compress into tablets to obtain tablets.
  • step B Weigh the coarse grains of raw medicinal materials in step A according to the prescription, mix well, add water to decoct twice, add 10 times the amount of water for the first time, decoct for 3 hours, add 8 times the amount of water for the second time, decoct for 1 hour , the decoctions were combined, filtered, concentrated under reduced pressure to an extract with a relative density of 1.11 at 50-60°C, and set aside;
  • step D Take the extract from step C, vacuum-dry it at a vacuum degree of -0.09MPa ⁇ -0.10Mpa, and 60°C, grind it into a fine powder, sieve it, add an appropriate amount of starch and micro-powder silica gel, mix well, granulate, and dry , capsule filling, to obtain capsules.
  • step B Weigh the coarse grains of raw medicinal materials in step A according to the prescription amount, mix well, add water to decoct twice, add 8 times the amount of water for the first time, decoct for 2.5 hours, add 7 times the amount of water for the second time, decoct for 2 hours , the decoctions were combined, filtered, concentrated under reduced pressure to an extract with a relative density of 1.11 at 50-60°C, and set aside;
  • step C Add ethanol to the extract obtained in step B to make the alcohol content reach 65%, let stand and cool for 24 h, filter, recover ethanol from the filtrate and concentrate it to an extract with a relative density of 1.24 at 50-60°C, and set aside;
  • step D Take the extract from step C, vacuum-dry it at a vacuum degree of -0.09MPa ⁇ -0.10Mpa, and 60°C, grind it into a fine powder, sieve it, add microcrystalline cellulose, dextrin, sodium carboxymethyl starch, Micropowder silica gel, mix thoroughly, add 52% (weight) of the prescription amount of ethanol solution with a concentration of 40% as a wetting agent and knead continuously to make a soft material, and the pore size of the extruder is 0.9
  • the sieve plate of mm is extruded into strips; turn on the spheronizer, select the rotating speed of 1210 rpm, put the strips in the spheronizer, and spheronize for 4 minutes, until the particles are rolled into pellets, take out the pellets and dry them at 41 °C, sieve Divide to get 20-30 mesh pellets.
  • step B Weigh the raw materials of step A according to the prescription amount, mix them evenly, add water to decoct 2 times, add 9 times the amount of water for the first time, decoct for 3 hours, add 6 times the amount of water for the second time, decoct for 1 hour , the decoctions were combined, filtered, concentrated under reduced pressure to an extract with a relative density of 1.12 at 50-60°C, and set aside;
  • step C Add ethanol to the extract obtained in step B to make the alcohol content reach 65%, let stand and cool for 24 h, filter, recover ethanol from the filtrate and concentrate it to an extract with a relative density of 1.21 at 50-60°C, and set aside;
  • step D Take the extract from step C, spray dry it at a vacuum degree of -0.09MPa ⁇ -0.10Mpa, grind it into fine powder, sieve it, add dextrin, mix it evenly, pelletize it, dry it, coat it, and polish it to get a pill .
  • step B Weigh the coarse grains of raw medicinal materials in step A according to the prescription amount, mix well, add water to decoct twice, add 9 times the amount of water for the first time, decoct for 2 hours, add 7 times the amount of water for the second time, decoct for 1.5 hours , filter the decoction, concentrate under reduced pressure to an extract with a relative density of 1.13 at 50-60°C, and set aside;
  • step C Add ethanol to the extract obtained in step B to make the alcohol content reach 70%, let stand and cool for 48 hours, filter, recycle the ethanol from the filtrate and concentrate it to an extract with a relative density of 1.24 at 60-70°C, and set aside;
  • step D take the extract of step C, carry out vacuum drying under the condition of vacuum degree -0.09MPa ⁇ -0.10Mpa, 60 °C, pulverize into fine powder, sieve, add microcrystalline cellulose, sodium carboxymethyl starch ( Weight ratio 5:2), mix well, add 95% ethanol to make soft material, granulate, dry, granulate, add 0.2% magnesium stearate and 0.2% talcum powder, mix well, press tablet, film-coat, Ready to get tablets.
  • the inventors conducted a pharmacodynamic study. It should be noted that the medicines selected in the pharmacodynamic test of the present invention are the medicines obtained from the representative formula and the preparation method of the present invention. The tests and results related to the medicines obtained by other formulations and preparation methods included in the present invention are limited by space, so they are not exhaustive here.
  • bovine thyroglobulin (1) Put 10 mg of bovine thyroglobulin into a 10 mL EP tube at the 4th week, add PBS slow-release solution to 10 mL, shake evenly, put 5 mL of the solution into another 10 mL EP tube, Then add 5 mL of Freund's complete immune adjuvant and shake well to form an emulsion.
  • the prepared bovine thyroglobulin concentration is 0.05%, that is, every 0.2 mL emulsifier contains 100 ⁇ g of bovine thyroglobulin.
  • Tg triglyceride
  • CFA complete Freund's adjuvant
  • the dosage of the low, medium and high dose groups of the traditional Chinese medicine composition was 10 mL/kg per rat per day.
  • Get the Chinese medicine composition granule, put into the measuring cylinder, add distilled water, leave standstill after stirring evenly with a glass rod, promptly obtain the daily required dosage of Chinese medicine composition low, middle and high dosage group is respectively 6.78g crude drug/ kg, 13.55g crude drug/kg, 27.10g crude drug/kg (converted according to body surface area, equivalent to 1/2, 1, and 2 times the daily dose of an adult in turn), put them in a 200mL glass bottle for storage (stir before gavage) evenly).
  • the daily dose of each rat in the positive control group was 10 mL/kg. Take 10 tripterygium glycosides tablets and put them into a mortar, grind them thoroughly with a grinding rod, put them into a measuring cylinder, add distilled water, and stir them evenly with a glass rod to get the daily dose of the positive control group.
  • the dose is 6.25 mg/kg (converted according to the body surface area, equivalent to the daily dosage for adults), put it into a 200 mL glass bottle for storage (stir well before gavage).
  • the normal control group and the model group were given the same amount of normal saline every day.
  • ELISA Enzyme-linked immunoassay
  • Enzyme addition Add 50 ⁇ L of enzyme-labeled reagent to each well, except for blank wells.
  • Termination Add 50 ⁇ L of stop solution to each well to stop the reaction (the blue color will turn yellow immediately).
  • SPSS 20.0 statistical software was used for analysis and processing. Experimental data are expressed as "mean ⁇ standard deviation In the form of ", one-way analysis of variance was used to compare the differences between groups. P ⁇ 0.05 indicated a statistical difference, and P ⁇ 0.01 indicated a very significant difference.
  • ELISA Enzyme-linked immunoassay
  • Serum TGAb and TPOAb are common autoantibodies in the serum of patients with autoimmune thyroid disease, which can fix complement and cytotoxicity, and participate in the destruction of thyroid cells.
  • the levels of serum TGAb and TPOAb in the model group rats were significantly increased ( P ⁇ 0.01); The levels of serum TGAb and TPOAb in rats in the high-dose group were significantly lower, and there was a significant difference ( P ⁇ 0.01); No significant change, no significant difference ( P > 0.05).
  • FT3 free triiodothyronine
  • FT4 free thyrox-ine
  • TSH thyroid stimulating hormone
  • composition of the present invention can significantly reduce the levels of serum inflammatory cytokines IL-6 and IL-12 and the levels of serum thyroid autoantibodies TGAb and TPOAb in rats with Hashimoto's thyroiditis, and significantly improve thyroid secretory function.
  • Hashimoto's thyroiditis has a good therapeutic effect, especially for the symptoms of hypothyroidism caused by Hashimoto's thyroiditis.

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Abstract

本发明属于中药领域，具体公开了一种治疗桥本甲状腺炎的中药组合物及其制备方法。所述中药组合物由黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材制成，药性平和、配伍精当、协同增效，能补气固表、健脾益肾。药效学实验表明，本发明组合物能显著降低桥本甲状腺炎大鼠的血清炎性细胞因子IL-6、IL-12水平和血清甲状腺自身抗体TGAb、TPOAb水平，并显著改善甲状腺分泌功能，对桥本甲状腺炎具有良好的治疗效果，尤其针对桥本甲状腺炎引起的甲状腺功能减退症状疗效确切，具有广阔的临床应用前景。

Description

一种治疗桥本甲状腺炎的中药组合物及其制备方法 技术领域
本发明属于中药领域，涉及一种中药组合物及其制备方法，具体涉及一种治疗桥本甲状腺炎的中药组合物及其制备方法。
 背景技术
桥本甲状腺炎（Hashimoto′s thyroiditis，HT）又称慢性淋巴细胞性甲状腺炎、淋巴性甲状腺肿，是一种常见的甲状腺自身免疫性疾病，其病理特征是甲状腺内淋巴细胞和浆细胞发生弥漫性浸润，甲状腺滤泡破坏，腺体组织内新生毛细血管，最终导致甲状腺功能下降，临床特征甲状腺功能正常、亢进（甲亢）或减退（甲减）。目前，桥本甲状腺炎的发病率呈逐年递增的趋势，多见于30～50岁女性，起病隐匿，发展缓慢病程较长，主要表现为甲状腺肿大，多数为弥漫性，少数可为局限性，部分以颜面、四肢肿胀感起病，该病已经成为我国部分地区影响健康的重要疾病病种。
 技术问题
目前，西医主要认为本病的发病与细胞、病毒、遗传、环境等因素有关。在治疗方面主要是根据患者甲状腺功能情况采取甲状腺激素替代治疗，但临床常存在激素副作用较大、停药后易复发。而手术及放射性治疗往往会发生低血糖及其他手术后遗症。而目前新型的疗法是基因治疗，已有研究证实其对免疫调节及病理改变过程具有决定性作用，但所需剂量较大。近年来的临床研究显示，中医药治疗本病有其独特的优势。
中医认为桥本甲状腺炎源于先天禀赋不足，后天肝脾失调而情志不舒，饮食水土不宜，产生气郁，痰凝，淤血等病理产物而发病，其主要病位与肝脾肾有关。中医整体论认为人体的脏腑气血是一个有机整体，所以治疗桥本甲状腺炎不能光从病变部位入手，应当抓住根本，从肝脾肾入手，进行相应的补气增益或疏泄调节，从根本上提高桥本甲状腺炎患者的机体免疫能力，缓解甲状腺肿大症状，培本固元。现代中医临床实践中，针对桥本甲状腺炎的不同时期、不同病程、不同病症，采用不同的治疗方法。
目前西医治疗上多采取注射甲状腺激素，虽然初期可以很明显地改善患者身体状况，但是随着病情深入，患者对于激素的依赖性增大，所需用量也会逐渐増大以致无效，并伴随不良现象，停药后容易复发，直至甲状腺功能低下。硒剂作为桥本病的辅助疗法，在临床治疗运用并不广泛，其副作用发生率也极大地限制了其临床运用。而运用糖皮质激素进行免疫调节治疗，也存在副作用大的问题，并且在如何合理使用方面尚存在争议，临床上缺乏一定的规范性。
近年来，在治疗桥本甲状腺炎方面，中医药取得了良好的疗效。中医的辨证施治具有一定的灵活性、副作用小、安全性高的特点。中医药治疗桥本甲状腺炎，从患者的体质出发，结合患者情志、外界环境等多方面因素，根据病情变化判断其症候特点，针对性进行个体化的用药。在治疗原发病的同时，提高患者的免疫力。中医药治疗桥本甲状腺炎疗效确切，具有疗效全面、稳定，副作用小、禁忌证少的优点。而且中医药治疗本病可弥补临床上单用西药治疗而造成的功能缓解和免疫缓解不同步的现象，也可减轻西医治疗存在的副作用，从而提高患者的依从性。
中医学强调整体观念，辨证论治，随着中医研究的深入，中药疗法治疗桥本甲状腺炎取得了很好的临床疗效。且中医药具有疗效可靠、剂型合理、副作用小的优势，因此开发治疗桥本甲状腺炎的中医药具有及其重要的意义。
 技术解决方案
本发明的目的是提供一种治疗桥本甲状腺炎的中药组合物，所述中药组合物由黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材制备而成，具有补气固表、健脾益肾之功效，可用于桥本甲状腺疾病的治疗，疗效确切。
一种治疗桥本甲状腺炎的中药组合物，由下列重量份的中药组分制成：
黄芪10-30重量份             白术10-30重量份           茯苓10-20重量份
猪苓10-20重量份             薏苡仁20-40重量份       补骨脂10-20重量份
桑寄生10-20重量份         枸杞子10-20重量份       仙茅5-20重量份。
所述中药组合物中原料的优选重量配比为：
黄芪10-20重量份             白术10-20重量份           茯苓10-15重量份
猪苓10-15重量份             薏苡仁25-35重量份       补骨脂10-15重量份
桑寄生10-15重量份         枸杞子10-15重量份       仙茅5-15重量份。
所述中药组合物中原料的优选重量配比为：
黄芪15重量份                  白术15重量份                茯苓12重量份
猪苓12重量份                  薏苡仁30重量份            补骨脂12重量份
桑寄生12重量份              枸杞子12重量份            仙茅9重量份。
优选地，所述白术为麸炒白术，薏苡仁为麸炒薏苡仁。
方中，黄芪味甘、微温，具有补气升阳、益卫固表、利水退肿之功效；白术味苦，甘，性温，可补气健脾、燥湿利水；黄芪与白术合用可以协同增效，更好的发挥补气固表、健脾益气、利水渗湿的功效，合为君药。
茯苓味甘、性平，归心、肺、脾、肾经，可利水渗湿，健脾和胃，宁心安神；猪苓味甘、淡，性平，具有利水渗湿的功效；薏苡仁健脾渗湿，除痹止泻，清热排脓；以上3味药合用，共同发挥利水消肿、健脾利湿的功效，是为臣药。
补骨脂味苦、辛，可以补肾壮阳、固精缩尿、温脾止泻；桑寄生味苦、性平，具有祛风湿、补肝肾、强筋骨的功效；仙茅辛，热，归肾经，能温肾壮阳、祛寒除湿；枸杞子味甘，微寒，具有滋肾润肺、补肝明目等功效；以上4味药合用，具有温肾助阳、强筋健骨之功效。
上述黄芪等9味中药，依据中医“君臣佐使”及“药对”配伍理论，遵循“虚者补之”、“急则治其标”的治疗理念进行组方配伍，诸药相合，协同增效，具有补气固表、健脾益肾之功效，针对多种原因导致的桥本甲状腺疾病均显示出确切的疗效。
本发明的另一个目的是提供一种含有上述中药组合物的口服药物制剂及其制备方法，所述中药口服药物制剂为口服液、合剂、片剂、胶囊剂、丸剂、微丸、颗粒剂中的一种。
所述的中药口服药物制剂的制备方法包括以下步骤：
A、取黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材，净选，分别粗碎，得原料药材粗颗粒，备用；
B、按处方量称取步骤A原料药材粗颗粒，混匀，加6-10倍量水煎煮，煎煮液滤过，减压浓缩，得浸膏，备用；
C、步骤B所得浸膏加入乙醇使含醇量达60%-70%，静置冷沉24-48 h，滤过，滤液回收乙醇，浓缩，得浓缩液，备用；
D、取步骤C所得浸膏，直接或经浓缩后加入相应的药学上可接受的辅料，经常规工艺制成口服药物制剂。
优选地，步骤B加6-10倍量水煎煮2次，第一次2-3 h，第二次1-2 h
进一步优选，步骤B加水煎煮2次，第一次加8倍量水煎煮3 h，第二次加6倍量水煎煮2h。
优选地，步骤B减压浓缩为50-60 ℃时相对密度为1.10-1.15的浸膏。
优选地，步骤C减压浓缩为50-60 ℃时相对密度为1.21-1.28的浸膏；
步骤D所述的常规工艺包括但不限于水沉、过滤、浓缩、干燥、粉碎、过筛等。
优选地，步骤D所述的可接受的辅料包括填充剂、润滑剂、防腐剂、矫味剂、崩解剂、粘合剂、着色剂、分散剂中的一种或几种。
优选地，所述药学上可接受的辅料包括但不限于乳糖、淀粉、糊精、糖粉、硬脂酸镁、麦芽糖、柠檬水、酒石酸、氢氧化钠、阿斯巴甜、甜菊苷、甜蜜素、蛋白糖、乙酰磺氨酸钾、阿司帕坦、三氯蔗糖、苯甲酸钠等。
在一种实施方式中，所述口服药物制剂是口服液体制剂，制备方法包括下列步骤：
A取黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材，净选，分别粗碎，得原料药材粗颗粒，备用；
B、按处方量称取步骤A原料药材粗颗粒，混匀，加水煎煮2次，第一次加8-10倍量水，煎煮2-3 h，第二次加6-8倍量水，煎煮1-2 h，煎煮液合并，滤过，减压浓缩至50-60 ℃下相对密度为1.1-1.15的浸膏，备用；
C、步骤B所得浸膏加入乙醇使含醇量达60%-70%，静置冷沉24-48 h，滤过，滤液回收乙醇并浓缩至50-60 ℃下相对密度为1.21-1.28的浓缩液，备用；
D、取步骤C所得浓缩液，加纯化水至配制总量，加入苯甲酸钠，过滤至澄清度合格后灌装，灭菌，包装，即得口服液体制剂。
在另一种实施方式中，所述的口服药物制剂是口服固体制剂，所述口服固体制剂的制备方法包括下列步骤：
A、取黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材，净选，分别粗碎，得原料药材粗颗粒，备用；
B、按处方量称取步骤A原料药材粗颗粒，混匀，加水煎煮2次，第一次加8-10倍量水，煎煮2-3 h，第二次加6-8倍量水，煎煮1-2 h，煎煮液合并，滤过，减压浓缩至50-60 ℃下相对密度为1.10-1.15的浸膏，备用；
C、步骤B所得浸膏加入乙醇使含醇量达60%-70%，静置冷沉24-48 h，滤过，滤液回收乙醇并浓缩至50-60 ℃下相对密度为1.21-1.28的浸膏，备用；
D、取步骤C浸膏，在真空度 -0.09MPa~-0.10Mpa，60 ℃条件下进行真空干燥，粉碎成细粉，过筛，加入适量赋形剂，混匀，制成颗粒，干燥，再进一步制成颗粒剂、片剂、胶囊剂、丸剂等口服固体制剂。
本发明提供所述中药组合物在制备治疗桥本甲状腺疾病药物中的用途，尤其在制备针对因桥本甲状腺炎引起的甲状腺功能减退等疾病药物中的用途。
本发明所述中药组合物由黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材制备而成，具有补气固表、健脾益肾的作用，适用于桥本甲状腺炎的治疗。药效学实验表明，本发明组合物能显著降低桥本甲状腺炎大鼠的血清炎性细胞因子IL-6、IL-12水平和血清甲状腺自身抗体TGAb、TPOAb水平，并显著改善甲状腺分泌功能，对桥本甲状腺炎具有良好的治疗效果，尤其针对桥本甲状腺炎引起的甲状腺功能减退症状疗效确切，具有广阔的临床应用前景。
 本发明的实施方式
为了使本领域技术人员充分了解和理解本发明所述技术方案，以下通过具体的实施例进一步说明本发明，但本领域技术人员应该知晓，本发明实施例并不以任何方式限制本发明。
实施例 1  合剂的制备
黄芪0.3 kg     白术0.3 kg      茯苓0.2 kg
猪苓0.1 kg     薏苡仁0.2 kg    补骨脂0.1 kg
桑寄生0.2 kg   枸杞子0.1 kg    仙茅0.2 kg
A、取黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材，净选，分别粗碎，得原料药材粗颗粒，备用；
B、按处方量称取步骤A原料药材粗颗粒，混匀，加水煎煮2次，第一次加10倍量水，煎煮2 h，第二次加8倍量水，煎煮1.5 h，煎煮液合并，滤过，减压浓缩至50-60℃下相对密度为1.10的浸膏，备用；
C、步骤B所得浸膏加入乙醇使含醇量达60%，静置冷沉24 h，滤过，滤液回收乙醇并浓缩至50-60 ℃下相对密度为1.21的浸膏，备用；
D、取步骤C浸膏，加纯化水至配制总量，加入苯甲酸钠，过滤至澄清度合格后灌装，灭菌，包装，即得合剂。
实施例 2  口服液的制备
黄芪0.1 kg     白术0.1 kg      茯苓0.1 kg
猪苓0.2 kg     薏苡仁0.4 kg    补骨脂0.2 kg
桑寄生0.1 kg   枸杞子0.2 kg    仙茅0.05 kg
A、取黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材，净选，分别粗碎，得原料药材粗颗粒，备用；
B、按处方量称取步骤A原料药材粗颗粒，混匀，加水煎煮2次，第一次加10倍量水，煎煮3 h，第二次加8倍量水，煎煮1h，煎煮液合并，滤过，减压浓缩至50-60 ℃下相对密度为1.15的浸膏，备用；
C、步骤B所得浸膏加入乙醇使含醇量达65%，静置冷沉36 h，滤过，滤液回收乙醇并浓缩至50-60 ℃下相对密度为1.25的浸膏，备用；
D、取步骤C浸膏，加入浸膏2倍量纯化水静置48 h以上，过滤，滤液加纯化水至配制总量，加入苯甲酸钠，过滤至澄清度合格后灌装，灭菌，包装，即得口服液。
实施例 3  颗粒剂的制备
黄芪0.15 kg     麸炒白术0.15 kg      茯苓0.12 kg
猪苓0.12 kg     麸炒薏苡仁0.3 kg     补骨脂0.12 kg
桑寄生0.12 kg   枸杞子0.12 kg        仙茅0.09 kg
A、取黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材，净选，分别粗碎，得原料药材粗颗粒，备用；
B、按处方量称取步骤A原料药材粗颗粒，混匀，加水煎煮2次，第一次加8倍量水，煎煮3 h，第二次加6倍量水，煎煮2 h，煎煮液合并，滤过，减压浓缩至50-60 ℃下相对密度为1.15的浸膏，备用；
C、步骤B所得浸膏加入乙醇使含醇量达60%，静置冷沉48 h，滤过，滤液回收乙醇并浓缩至50-60 ℃下相对密度为1.24的浸膏，备用；
D、取步骤C浸膏，在真空度-0.09MPa~-0.10Mpa，60 ℃条件下进行真空干燥，粉碎成细粉，过筛，加入配方量的蔗糖粉、糊精（重量比5∶2），混匀，制成颗粒，干燥，整粒，即得颗粒剂。
实施例 4  口服液的制备
黄芪0.15 kg     白术0.15 kg      茯苓0.12 kg
猪苓0.12 kg     薏苡仁0.3 kg     补骨脂0.12 kg
桑寄生0.12 kg   枸杞子0.12 kg    仙茅0.09 kg
A、取黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材，净选，分别粗碎，得原料药材粗颗粒，备用；
B、按处方量称取步骤A原料药材粗颗粒，混匀，加水煎煮2次，第一次加8倍量水，煎煮2 h，第二次加6倍量水，煎煮2 h，煎煮液合并，滤过，减压浓缩至50-60 ℃下相对密度为1.13的浸膏，备用；
C、步骤B所得浸膏加入乙醇使含醇量达70%，静置冷沉48 h，滤过，滤液回收乙醇并浓缩至50-60 ℃下相对密度为1.28的浓缩液，备用；
D、取步骤C所得浓缩液，加纯化水至配制总量，加入0.25%阿司帕坦，过滤至澄清度合格后灌装，灭菌，包装，即得口服液。
实施例 5  颗粒剂的制备
黄芪0.11 kg     麸炒白术0.11 kg      茯苓0.11 kg
猪苓0.18 kg     薏苡仁0.38 kg        补骨脂0.18 kg
桑寄生0.11 kg   枸杞子0.18 kg         仙茅0.06 kg
A、取黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材，净选，分别粗碎，得原料药材粗颗粒，备用；
B、按处方量称取步骤A原料药材粗颗粒，混匀，加水煎煮2次，第一次加9倍量水，煎煮2 h，第二次加7倍量水，煎煮2 h，煎煮液合并，滤过，减压浓缩至50-60 ℃下相对密度为1.10的浸膏，备用；
C、步骤B所得浸膏加入乙醇使含醇量达65%，静置冷沉36 h，滤过，滤液回收乙醇并浓缩至50-60 ℃下相对密度为1.25的浸膏，备用；
D、取步骤C浸膏，在真空度-0.09MPa~-0.10Mpa，60 ℃条件下进行真空干燥，粉碎成细粉，过筛，加入适量的糊精和0.25%阿司帕坦，混匀，制成颗粒，干燥，整粒，即得颗粒剂。
实施例 6  胶囊剂的制备
黄芪0.25 kg     白术0.25 kg      茯苓0.12 kg
猪苓0.12 kg     薏苡仁0.21 kg    补骨脂0.12 kg
桑寄生0.18 kg   枸杞子0.18 kg    仙茅0.07 kg
A、取黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材，净选，分别粗碎，得原料药材粗颗粒，备用；
B、按处方量称取步骤A原料药材粗颗粒，混匀，加水煎煮2次，第一次加10倍量水，煎煮2 h，第二次加6倍量水，煎煮1 h，煎煮液合并，滤过，减压浓缩至50-60 ℃下相对密度为1.14的浸膏，备用；
C、步骤B所得浸膏加入乙醇使含醇量达70%，静置冷沉36 h，滤过，滤液回收乙醇并浓缩至50-60 ℃下相对密度为1.28的浸膏，备用；
D、取步骤C浸膏，在真空度-0.09MPa~-0.10Mpa，60 ℃条件下进行真空干燥，粉碎成细粉，过筛，加入适量的淀粉、微晶纤维素，制粒、干燥，胶囊灌装，即得胶囊剂。
实施例 7  片剂的制备
黄芪0.18 kg     白术0.12 kg      茯苓0.14 kg
猪苓0.11 kg     薏苡仁0.33 kg    补骨脂0.14 kg
桑寄生0.11 kg   枸杞子0.14 kg    仙茅0.07 kg
A、取黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材，净选，分别粗碎，得原料药材粗颗粒，备用；
B、按处方量称取步骤A原料药材粗颗粒，混匀，加水煎煮2次，第一次加8倍量水，煎煮2.5 h，第二次加7倍量水，煎煮1.5 h，煎煮液合并，滤过，减压浓缩至50-60 ℃下相对密度为1.12的浸膏，备用；
C、步骤B所得浸膏加入乙醇使含醇量达60%，静置冷沉48 h，滤过，滤液回收乙醇并浓缩至50-60 ℃下相对密度为1.25的浸膏，备用；
D、取步骤C浸膏，置60 ℃烘箱进行干燥，粉碎成细粉，过筛，加入配方量的淀粉、糊精和蔗糖（重量比3∶2∶1），混匀，制粒，干燥，整粒，加入0.3%硬脂酸镁，混匀，压片，即得片剂。
实施例 8  胶囊剂的制备
黄芪0.2 kg        白术0.1 kg           茯苓0.18 kg
猪苓0.11 kg       麸炒薏苡仁0.28 kg    补骨脂0.15 kg
桑寄生0.12 kg     枸杞子0.11 kg         仙茅0.1 kg
A、取黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材，净选，分别粗碎，得原料药材粗颗粒，备用；
B、按处方量称取步骤A原料药材粗颗粒，混匀，加水煎煮2次，第一次加10倍量水，煎煮3 h，第二次加8倍量水，煎煮1 h，煎煮液合并，滤过，减压浓缩至50-60 ℃下相对密度为1.11的浸膏，备用；
C步骤B所得浸膏加入乙醇使含醇量60%，静置冷沉36 h，滤过，滤液回收乙醇并浓缩至50-60 ℃下相对密度为1.26的浸膏，备用；
D、取步骤C浸膏，在真空度-0.09MPa~-0.10Mpa，60 ℃条件下进行真空干燥，粉碎成细粉，过筛，加入适量的淀粉、微粉硅胶，混匀，制粒、干燥，胶囊灌装，即得胶囊剂。
实施例 9  微丸的制备
黄芪0.28 kg     白术0.14 kg      茯苓0.16 kg
猪苓0.14 kg     薏苡仁0.25 kg    补骨脂0.16 kg
桑寄生0.14 kg   枸杞子0.16 kg    仙茅0.12 kg
A、取黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材，净选，分别粗碎，得原料药材粗颗粒，备用；
B、按处方量称取步骤A原料药材粗颗粒，混匀，加水煎煮2次，第一次加8倍量水，煎煮2.5 h，第二次加7倍量水，煎煮2 h，煎煮液合并，滤过，减压浓缩至50-60 ℃下相对密度为1.11的浸膏，备用；
C、步骤B所得浸膏加入乙醇使含醇量达65%，静置冷沉24 h，滤过，滤液回收乙醇并浓缩至50-60 ℃下相对密度为1.24的浸膏，备用；
D、取步骤C浸膏，在真空度-0.09MPa~-0.10Mpa，60 ℃条件下进行真空干燥，粉碎成细粉，过筛，加入微晶纤维素、糊精、羧甲基淀粉钠、微粉硅胶，充分混匀，加入处方量52%（重量）的浓度为40%的乙醇溶液为润湿剂不断捏合，制成软材，经挤出机孔径为0.9 mm的筛板挤成条状物；打开滚圆机，选择转速1210 rpm，将条状物置滚圆机内，滚圆时间为4 min，至颗粒滚制成丸，取出微丸于41 ℃烘干，筛分即得20-30目的微丸。
实施例 10 丸剂的制备
黄芪0.12 kg     白术0.12 kg      茯苓0.15 kg
猪苓0.15 kg     薏苡仁0.36 kg    补骨脂0.11 kg
桑寄生0.11 kg   枸杞子0.15 kg    仙茅0.08 kg
A、取黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材，净选，分别粗碎，得原料药材粗颗粒，备用；
B、按处方量称取步骤A原料药材粗颗粒，混匀，加水煎煮2次，第一次加9倍量水，煎煮3 h，第二次加6倍量水，煎煮1 h，煎煮液合并，滤过，减压浓缩至50-60 ℃下相对密度为1.12的浸膏，备用；
C、步骤B所得浸膏加入乙醇使含醇量达65%，静置冷沉24 h，滤过，滤液回收乙醇并浓缩至50-60 ℃下相对密度为1.21的浸膏，备用；
D、取步骤C浸膏，在真空度-0.09MPa~-0.10Mpa，喷雾干燥，粉碎成细粉，过筛，加入糊精，混匀，制丸，干燥，包衣，抛光，即得丸剂。
实施例 11  片剂的制备
黄芪0.16 kg     白术0.20 kg      茯苓0.15 kg
猪苓0.15 kg     薏苡仁0.35 kg    补骨脂0.15 kg
桑寄生0.15 kg   枸杞子0.11 kg    仙茅0.15 kg
A、取黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材，净选，分别粗碎，得原料药材粗颗粒，备用；
B、按处方量称取步骤A原料药材粗颗粒，混匀，加水煎煮2次，第一次加9倍量水，煎煮2 h，第二次加7倍量水，煎煮1.5 h，煎煮液滤过，减压浓缩至50-60 ℃下相对密度为1.13的浸膏，备用；
C、步骤B所得浸膏加入乙醇使含醇量达70%，静置冷沉48h，滤过，滤液回收乙醇并浓缩至60-70 ℃下相对密度为1.24的浸膏，备用；
D、取步骤C浸膏，在真空度-0.09MPa~-0.10Mpa，60 ℃条件下进行真空干燥，粉碎成细粉，过筛，加入配方量的微晶纤维素、羧甲基淀粉钠（重量比5∶2），混匀，加95%乙醇制软材，制粒，干燥，整粒，加入0.2%硬脂酸镁和0.2%的滑石粉，混匀，压片，包薄膜衣，即得片剂。
为验证本发明中药组合物治疗桥本甲状腺炎的功效，发明人开展了药效学试验研究。需要说明的是，本发明药效学试验所选取的药品为本发明具有代表性的配方及其制备方法所得的药品。本发明所包含的其它配方及制备方法所得药品涉及的试验及其结果，限于篇幅，在此不一一穷举。
实验例 1  对桥本甲状腺炎大鼠血清炎性细胞因子的影响
1 实验材料
1.1 实验动物
健康SPF级SD大鼠60只，雌性，4-6周龄，体重为（120±20）g，由鲁南制药集团股份有限公司提供，实验动物合格证编号SYXK(鲁) 2018-0018。动物于专用实验室内分笼饲养，自然光照，自由摄食、饮水，室温控制在20-25 ℃，相对湿度控制在45%-65%，适应性喂养1周后进行试验。
1.2 仪器、试剂及药品
电子天平（YB502型，上海精密仪器仪表有限公司）；电子分析天平（AG285型，梅特勒托利多公司）；酶标仪（MK3型，芬兰Labsystems Multiskan MS公司）；洗板机（芬兰Labsystems Multiskan MS公司）；微量高速离心机（D3024型）；移液器（吉尔森P型移液器Pipetman）；隔水式恒温培养箱（GHP-9050型）；牛甲状腺球蛋白（bTg）（10 mg/支，批号：167771，购自上海羽朵生物科技有限公司）；弗氏完全免疫佐剂（CFA）（含卡介苗）（10 mg/支，批号：20160620，购自上海羽朵生物科技有限公司）；弗氏不完全免疫佐剂（IFA）（不含卡介苗）（10 mg/支，批号：20160801，购自上海羽朵生物科技有限公司）；血清IL-6、IL-12试剂盒（均购自武汉华联科生物技术有限公司）；碘化钠（批号：201607133，购买于上海羽朵生物科技有限公司）；受试药物为根据实施例3项下配方及制法所制得的颗粒剂样品；阳性对照药为雷公藤多苷片（批号：国药准字Z52020369，购自贵州汉方药业有限公司）。
2 实验方法
2.1 造模
2.1.1 碘化钠（NaI）的配制
用电子秤测量出0.64 g的NaI晶体，置于量筒中，加入部分蒸馏水后摇晃均匀，使NaI晶体充分溶解，最后在加蒸馏水至l L，配制出浓度为0.64 g/L的高碘水。
2.1.2 乳化剂的配制
（1）于第4周将10 mg牛甲状腺球蛋白放入10 mL EP管中，加PBS缓释液至10 mL，摇晃均匀后，将其中5 mL溶液放入另一个10 mL EP管中，然后加入5 mL弗氏完全免疫佐剂，充分摇晃成乳剂。配置的牛甲状腺球蛋白浓度为0.05%，即每0.2 mL乳化剂含有牛甲状腺球蛋白100 μg。
（2）第5周到第8周将10 mg牛甲状腺球蛋白放入10 mL EP管中，加PBS缓释液至10 mL，摇晃均匀后，将其中5 mL溶液放入另一个10 mL EP管中，然后加入5 mL弗氏不完全免疫佐剂，充分摇晃成乳剂。配置的牛甲状腺球蛋白浓度为0.05%，即每0.2 mL乳化剂含有牛甲状腺球蛋白100 μg。
2.1.3 动物模型的建立
取适应性饲养结束后的大鼠60只，随机分为以下6组，即空白对照组、模型组、阳性对照组、中药组合物低、中、高剂量组，每组10只大鼠。除空白对照组外，其余各组均给予浓度为0.64 g/L的高碘水，空白对照组给予等体积蒸馏水。
于第4周开始给予各组大鼠双足皮下多点注射由完全弗氏佐剂（CFA）充分乳化成油包水状的甘油三酯（Tg）（Tg：CFA=1:1），一共2次，中间间隔2天，作为初次免疫；于第5周开始大鼠后背皮下多点注射由弗氏不完全免疫佐剂（IFA）乳化的Tg，一共4次，中间间隔7天，作为加强免疫。第8周结束时成模。
2.2 给药
中药组合物低、中、高剂量组每日每只大鼠灌胃量为10 mL/kg。取中药组合物颗粒剂，放入量筒中，加入蒸馏水，用玻璃棒搅拌均匀后静置，即得到中药组合物低、中、高剂量组每日所需的给药剂量分别为6.78g生药/kg、13.55g生药/kg、27.10g生药/kg（按体表面积折算，依次相当于成人每日服药量的1/2、1、2倍），放入200mL玻璃瓶中保存（灌胃前搅拌均匀）。
阳性对照组每日每只大鼠灌胃量为10 mL/kg。取10片雷公藤多苷片放入研钵中，用研磨棒将其充分研碎，放入量筒中，加入蒸馏水，用玻璃棒搅拌均匀后，即得到阳性对照组每日所需的给药剂量为6.25 mg/kg（按体表面积折算，相当于成人每日服药量），放入200 mL玻璃瓶中保存（灌胃前搅拌均匀）。
正常对照组以及模型组每日给予等量生理盐水。
2.3 评价指标检测
2.3.1 大鼠血清炎性细胞因子IL-6、IL-12含量的检测
给药4周后，大鼠腹主动脉采血，在3000 rpm的条件下离心10 min，取血清并转移至新的EP管中。采用酶联免疫法（ELISA法）来检测血清中IL-6、IL-12的水平。
具体操作步骤如下：
1） 标准品的稀释与加样：
在酶标包被板上设标准孔，共5孔，在第一孔中加入100 μL标准品，再在第一孔加50 μL标准品稀释液，反复吹打混匀操作轻柔，勿触及孔底；
取第一孔100 μL加到第二孔，再加标准品稀释液50 μL至第二孔，混匀；
取第二孔50 μL，弃掉，再取50 μL到第三孔，向第三孔加标准品稀释液50 μL，混匀；
取第四孔50 μL加至第五孔中，再加标准品稀释液50 μL至第四孔，混匀后再取第四孔50 μL至第五孔，加标准品稀释液50 μL至第五孔，混匀，弃第五孔50 μL。稀释后各孔加样量都为50 μL，浓度分别为2.4 μmol/L、1.6 μmol/L、0.8 μmol/L、0.4 μmol/L、0.2 μmol/L，标准曲线以同法做复孔。
2）加样：分别设空白孔（空白对照孔不加样品及酶标试剂，其余各步操作相同）、待测样品孔。在酶标包被板上待测样品孔中先加样品稀释液40 μL，然后再加待测样品10 μL（样品最终稀释度为5倍）。将样品加于酶标板孔底部，尽量不触及孔壁，轻轻晃动混匀。
3）温育：用封板膜封板后置37 ℃温育30 min。
4） 配液：将30倍浓缩洗涤液用蒸馏水30倍稀释后备用。
5）洗涤：小心揭掉封膜，加蒸馏水洗涤，于滤纸上拍干，重复5次。
6） 加酶：每孔加入酶标试剂50 μL，空白孔除外。
7）温育：操作同上述步骤3）。
8）洗涤：操作同上述步骤5）。
9）显色：每孔先加入50 μL显色剂A，再加入50 μL显色剂B，轻轻震荡混匀，37 ℃避光显色15 min。
10）终止：每孔加终止液50 μL，终止反应（此时蓝色立转黄色）。
11）测定：以空白空调零，在加终止液后15 min以内，于450 nm波长依序测量各孔的吸光度（OD值）。
2.4 统计学方法
采用SPSS 20.0统计软件分析处理。实验数据以“均数±标准差
Figure 304760dest_path_image001
”形式表示，采用单因素方差分析进行组间差异比较，以 P＜0.05表示具有统计学差异， P＜0.01表示有极显著性差异。
3 实验结果
3.1 大鼠一般状态观察
第一周适应性喂养，所有动物饮食、饮水、二便、皮毛及活动情况等均正常。第4周初次免疫之后，大部分大鼠开始出现毛色粗糙或脱毛、倦怠嗜卧等现象，少数大鼠灌胃时出现情绪激动、烦躁易怒等现象。
3.2 对大鼠血清炎性细胞因子IL-6、IL-12水平的影响
表1  各组大鼠血清IL-6、IL-12水平
Figure 769371dest_path_image002
组别 IL-6（pg/mL） IL-12（pg/mL）
空白对照组 46.41±3.59 123.83±14.80
模型组 113.02±6.65 ## 205.10±18.01 ##
阳性药组 80.57±10.04 ** 166.14±23.72 **
低剂量组 87.65±5.21 ** 183.52±18.46 **
中剂量组 82.37±6.66 ** 175.09±21.73 **
高剂量组 74.97±3.16 ** 161.78±19.34 **
注：与正常对照组相比，“ ##”表示 P＜0.01；与模型组相比，“**”表示 P＜0.01。
如表1所示，与正常对照组相比，模型组大鼠血清IL-6、IL-12的水平明显升高，有显著性差异（ P＜0.01）；与模型组相比，中药组合物低、中、高剂量组大鼠血清IL-6、IL-12的水平明显降低，差异均有显著性（ P＜0.01）；与阳性对照组相比，中药组合物低、中、高剂量组大鼠血清IL-6、IL-12的水平无明显变化，无显著性差异（ P＞0.05）。这些表明本发明中药组合物能够通过显著降低桥本甲状腺炎大鼠的血清炎性细胞因子水平来发挥其治疗作用。
实验例 2  对桥本甲状腺炎大鼠血清甲状腺自身抗体的影响
1 实验材料
1.1 实验动物
健康SPF级SD大鼠60只，雌性，4-6周龄，体重为120±20g，由鲁南制药集团股份有限公司提供，实验动物合格证编号SYXK(鲁)2018-0018。动物于专用实验室内分笼饲养，自然光照，自由摄食、饮水，室温控制在20-25℃，相对湿度控制在45%-65%，适应性喂养1周后进行试验。
1.2 仪器、试剂及药品
电子天平（YB502型，上海精密仪器仪表有限公司）；电子分析天平（AG285型，梅特勒托利多公司）；酶标仪（MK3型，芬兰Labsystems Multiskan MS公司）；洗板机（芬兰Labsystems Multiskan MS公司）；微量高速离心机（D3024型）；移液器（吉尔森P型移液器Pipetman）；隔水式恒温培养箱（GHP-9050型）；牛甲状腺球蛋白（bTg）（10mg/支，批号：167771，购自上海羽朵生物科技有限公司）；弗氏完全免疫佐剂（CFA）（含卡介苗）（10mg/支，批号：20160620，购自上海羽朵生物科技有限公司）；弗氏不完全免疫佐剂（IFA）（不含卡介苗）（10mg/支，批号：20160801，购自上海羽朵生物科技有限公司）；血清甲状腺抗体TGAb（甲状腺球蛋白抗体）、TPOAb（甲状腺过氧化物酶抗体）药盒（均购自武汉华联科生物技术有限公司）；碘化钠（批号：201607133，购买于上海羽朵生物科技有限公司）；受试药物为根据实施例3项下配方及制法所制得的颗粒剂样品；阳性对照药为雷公藤多苷片（批号：国药准字Z52020369，购自贵州汉方药业有限公司）。
2 实验方法
2.1 造模和给药
同实验例1。
2.2 大鼠血清TGAb、TPOAb含量的检测
给药4周后，大鼠腹主动脉采血，在3000 rpm的条件下离心10 min，取血清并转移至新的EP管中。采用酶联免疫法（ELISA法）来检测血清中TGAb、TPOAb的水平。
具体操作步骤同实验例1。
2.3 统计学方法
同实验例1。
3 实验结果
表2  各组大鼠血清TGAb、TPOAb水平
Figure 80266dest_path_image002
组别 TPOAb（pg/mL） TGAb（pg/mL）
空白对照组 1502.57±290.27 15.04±1.27
模型组 3902.43±329.71 ## 32.81±1.95 ##
阳性药组 2362.97±180.62 ** 21.53±1.39 **
低剂量组 2608.62±230.62 ** 25.26±1.44 **
中剂量组 2426.54±214.32 * 22.27±1.75 **
高剂量组 2254.81±257.76 ** 20.95±1.02 **
注：与正常对照组相比，“ ##”表示 P＜0.01；与模型组相比，“*”表示 P＜0.05，“**”表示 P＜0.01。
血清TGAb、TPOAb是常见的自身免疫性甲状腺疾病患者血清中的自身抗体，具有固定补体和细胞毒作用，参与破坏甲状腺细胞。如表2所示，与正常对照组相比，模型组大鼠血清TGAb、TPOAb的水平明显升高，有显著性差异（ P＜0.01）；与模型组相比，中药组合物低、中、高剂量组大鼠血清TGAb、TPOAb的水平明显降低，有显著性差异（ P＜0.01）；与阳性对照组相比，中药组合物低、中、高剂量组的大鼠血清TGAb、TPOAb的水平无明显变化，无显著性差异（ P＞0.05）。这些表明，本发明中药组合物能够通过显著降低桥本甲状腺炎大鼠血清中甲状腺自身抗体TGAb、TPOAb水平来发挥其治疗作用。
实验例 3  对桥本甲状腺炎大鼠甲状腺功能的影响
1 实验材料
1.1 实验动物
健康SPF级SD大鼠60只，雌性，4-6周龄，体重为（120±20）g，由鲁南制药集团股份有限公司提供，实验动物合格证编号SYXK(鲁) 2018-0018。动物于专用实验室内分笼饲养，自然光照，自由摄食、饮水，室温控制在20-25 ℃，相对湿度控制在45%-65%，适应性喂养1周后进行试验。
1.2 仪器、试剂及药品
电子天平（YB502型，上海精密仪器仪表有限公司）；电子分析天平（AG285型，梅特勒托利多公司）；酶标仪（MK3型，芬兰Labsystems Multiskan MS公司）；洗板机（芬兰Labsystems Multiskan MS公司）；微量高速离心机（D3024型）；移液器（吉尔森P型移液器Pipetman）；隔水式恒温培养箱（GHP-9050型）；牛甲状腺球蛋白（bTg）（10 mg/支，批号：167771，购自上海羽朵生物科技有限公司）；弗氏完全免疫佐剂（CFA）（含卡介苗）（10 mg/支，批号：20160620，购自上海羽朵生物科技有限公司）；弗氏不完全免疫佐剂（IFA）（不含卡介苗）（10 mg/支，批号：20160801，购自上海羽朵生物科技有限公司）；血清FT3、FT4、TSH药盒（均购自武汉华联科生物技术有限公司）；碘化钠（批号：201607133，购买于上海羽朵生物科技有限公司）；受试药物为根据实施例3项下配方及制法所制得的颗粒剂样品；阳性对照药为雷公藤多苷片（批号：国药准字Z52020369，购自贵州汉方药业有限公司）。
2 实验方法
2.1 造模和给药
同实验例1。
2.2 甲状腺功能的检测
给药4周后，大鼠腹主动脉采血，在3000 rpm的条件下离心10 min，取血清并转移至新的EP管中。采用化学发光法检测血清游离三碘甲状腺原氨酸（Free triiodothyronine，FT3）、游离甲状腺素（Free thyrox-ine，FT4）以及促甲状腺激素（Thyroid hormone，TSH）水平。
2.3 统计学方法
同实验例1。
3 实验结果
表3  各组大鼠甲状腺功能比较
Figure 6634dest_path_image002
组别 FT3（pg/mL） FT4（pg/mL） TSH（μIU/mL）
空白对照组 5.21±0.36 17.45±3.15 3.69±1.64
模型组 32.14±1.28 ## 112.46±7.26 ## 0.19±0.01 ##
阳性药组 18.54±2.46 ** 94.62±5.44 ** 2.85±0.03 **
低剂量组 20.24±2.26 * 102.45±6.23 * 2.44±0.03 *
中剂量组 19.04±2.46 ** 95.82±3.12 ** 2.82±0.01 **
高剂量组 17.48±1.59 ** 93.02±4.16 ** 2.97±0.02 **
注：与正常对照组相比，“ ##”表示 P＜0.01；与模型组相比，“*”表示 P＜0.05，“**”表示 P＜0.01。
如表3所示，与正常对照组相比，模型组大鼠血清FT3、FT4的水平明显升高，TSH的水平明显降低，差异具有显著性（ P＜0.01）；与模型组相比，中药组合物不同剂量组大鼠血清FT3、FT4的水平明显降低，TSH的水平明显升高，差异具有显著性（ P＜0.01）；与阳性对照组相比，中药组合物低、中、高剂量组的大鼠血清FT3、FT4以及TSH的水平无明显变化，无显著性差异（ P＞0.05）。这些表明，本发明中药组合物能够通过显著改善桥本甲状腺炎大鼠的甲状腺分泌功能来发挥其治疗作用。
综上所述，本发明组合物能显著降低桥本甲状腺炎大鼠的血清炎性细胞因子IL-6、IL-12水平和血清甲状腺自身抗体TGAb、TPOAb水平，并显著改善甲状腺分泌功能，对桥本甲状腺炎具有良好的治疗效果，尤其针对桥本甲状腺炎引起的甲状腺功能减退症状疗效显著。

Claims (9)

  1. 一种治疗桥本甲状腺炎的中药组合物，其特征在于，由下列重量份的中药组分制成：
    黄芪10-30重量份           白术10-30重量份           茯苓10-20重量份
    猪苓10-20重量份           薏苡仁20-40重量份       补骨脂10-20重量份
    桑寄生10-20重量份       枸杞子10-20重量份       仙茅5-20重量份。
  2. 根据权利要求1所述的治疗桥本甲状腺炎的中药组合物，其特征在于，由下列重量份的中药组分制成：
    黄芪15重量份                白术15重量份                茯苓12重量份
    猪苓12重量份                薏苡仁30重量份            补骨脂12重量份
    桑寄生12重量份            枸杞子12重量份            仙茅9重量份。
  3. 根据权利要求1中所述的治疗桥本甲状腺炎的中药组合物，其特征在于，所述白术为麸炒白术，薏苡仁为麸炒薏苡仁。
  4. 一种由权利要求1-3任意一项所述中药组合物制成的口服药物制剂，其特征在于，所述口服药物制剂为口服液、合剂、颗粒剂、胶囊剂、丸剂、片剂中的一种。
  5. 一种如权利要求4所述的口服药物制剂的制备方法，其特征在于，包括下列步骤：
    A、取黄芪、白术、茯苓、猪苓、薏苡仁、补骨脂、桑寄生、枸杞子、仙茅9味原料药材，净选，分别粗碎，得原料药材粗颗粒，备用；
    B、按处方量称取步骤A原料药材粗颗粒，混匀，加6-10倍量水煎煮，煎煮液滤过，减压浓缩，得浸膏，备用；
    C、步骤B所得浸膏加入乙醇使含醇量达60%-70%，静置冷沉24-48 h，滤过，滤液回收乙醇，浓缩，得浓缩液，备用；
    D、取步骤C所得浸膏，直接或经浓缩后加入相应的药学上可接受的辅料，经常规工艺制成口服药物制剂。
  6. 根据权利要求5所述的口服药物制剂的制备方法，其特征在于，所述步骤B加6-10倍量水煎煮2次，第一次2-3 h，第二次1-2 h。
  7. 根据权利要求5所述的口服药物制剂的制备方法，其特征在于，步骤B减压浓缩为50-60 ℃时相对密度为1.10-1.15的浸膏。
  8. 根据权利要求5所述的口服药物制剂的制备方法，其特征在于，步骤C减压浓缩为50-60 ℃时相对密度为1.21-1.28的浸膏。
  9. 如权利要求1所述的中药组合物在制备治疗桥本甲状腺炎药物中的用途。
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