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CN-122005686-A - External application medicine for subacute thyroiditis acute stage and preparation method thereof

CN122005686ACN 122005686 ACN122005686 ACN 122005686ACN-122005686-A

Abstract

The invention provides an external application medicine for subacute thyroiditis acute stage and a preparation method thereof, wherein the external application medicine comprises active ingredients, a percutaneous absorption promoter, an antioxidant and a gel matrix, the active ingredients are Chinese herbal compound extracts, non-steroidal anti-inflammatory drugs and an immunomodulator in a specific weight ratio, the percutaneous absorption promoter is a compound system of paeoniflorin oleate, sasanquasapogenin and menthol, resveratrol and curcumin are added as the antioxidant, the gel matrix is a compound system of carboxymethyl chitosan and sodium alginate, the synergistic treatment of the three-in-one of anti-inflammatory, immunoregulation, resolving hard mass and relieving pain is realized, the transdermal efficiency is high, the biocompatibility is good, the targeting effect on thyroid focus is realized, the neck swelling and pain in subacute thyroiditis acute stage is rapidly relieved, the inflammation index is reduced, and the safety is high.

Inventors

  • WU YINGPING
  • WANG MIN
  • YE WENJING
  • YANG WENKUI

Assignees

  • 广东省中医院海南医院

Dates

Publication Date
20260512
Application Date
20260409

Claims (10)

  1. 1. A topical application medicine for subacute thyroiditis acute stage is characterized by comprising active ingredients, percutaneous absorption promoters, antioxidants and gel matrixes, wherein the active ingredients comprise (1-3) of a traditional Chinese medicine compound extract, (0.5-2) of a non-steroidal anti-inflammatory agent and an immunomodulator, the weight ratio of the antioxidants is (3-8) of resveratrol and curcumin, the total addition amount is 0.8-1.2% of the total weight of the active ingredients, and the gel matrixes are prepared by compounding carboxymethyl chitosan and sodium alginate according to the weight ratio of (1-3) to 1.
  2. 2. The external application medicine according to claim 1, wherein the Chinese herbal compound extract comprises the following raw materials, by weight, 30-40 parts of selfheal, 25-35 parts of dandelion, 20-30 parts of radix paeoniae rubra, 15-25 parts of radix scrophulariae, 25-35 parts of radix ranunculi ternati and 10-20 parts of vinegar-processed frankincense.
  3. 3. The external application medicine according to claim 1, wherein the non-steroidal anti-inflammatory drug is any one of diclofenac sodium, ketoprofen or flurbiprofen axetil, and the non-steroidal anti-inflammatory drug is micronized and has a particle size of 1-5 μm.
  4. 4. The external application medicine according to claim 1, wherein the immunomodulator is one or more of total glucosides of paeony, triptolide and dipotassium glycyrrhizinate, and the immunomodulator is coated by nano liposome, the average particle size is 50-200nm, and the encapsulation rate is more than or equal to 85%.
  5. 5. The external application medicine according to claim 1, wherein the percutaneous absorption promoter is prepared by compounding paeoniflorin oleate, sasanquasapogenin and menthol according to the weight ratio of (3-5): 1 (2-3): 3-8% of the total weight of active components, wherein the paeoniflorin oleate is a fat-soluble modified product of paeoniflorin, and the sasanquasapogenin is prepared by desugaring and purifying sasanqua seed extract.
  6. 6. The external application medicine according to claim 5, wherein paeoniflorin oleate is prepared by modification of esterification reaction of paeoniflorin and oleic acid, the specific modification method comprises the steps of mixing paeoniflorin and oleic acid according to a molar ratio of 1 (1-1.5), adding a solvent and a catalyst, stirring at a constant temperature of 60-80 ℃ for reaction for 4-6 hours, and performing water washing, reduced pressure distillation and column chromatography purification after the reaction is finished to prepare paeoniflorin oleate.
  7. 7. The external application medicine according to claim 5, wherein the desugarization purification method comprises the steps of crushing camellia seed extract, adding deionized water which is 5-8 times of the extract in weight, stirring and dissolving, adjusting the pH value to 4.5-5.5, adding beta-glucosidase accounting for 2-5% of the extract in weight, carrying out enzymolysis at a constant temperature of 45-55 ℃ for 2-3 hours, inactivating enzymes, centrifuging to obtain supernatant, adding absolute ethyl alcohol which is 3-5 times of the volume into the supernatant, standing and precipitating for 2-4 hours, filtering and concentrating, purifying, collecting target eluting components, and freeze-drying to obtain the camellia sapogenin.
  8. 8. A method for preparing the external application medicine according to any one of claims 1 to 7, comprising the steps of: S1, pretreatment: a) The preparation method of the traditional Chinese medicine compound extract comprises the steps of weighing selfheal, dandelion, red paeony root, figwort root, catclaw grass and vinegar-processed frankincense according to parts by weight, extracting by adopting a supercritical CO 2 extraction process after pretreatment, collecting extract liquid, concentrating under reduced pressure, and freeze-drying to obtain the traditional Chinese medicine compound extract dry powder; b) Pretreating an immunoregulator, namely preparing the immunoregulator into a nano liposome wrapper by adopting a film dispersion-ultrasonic method, homogenizing under high pressure, and freeze-drying to obtain nano liposome-wrapped immunoregulator dry powder; s2, preparing an active component premix, namely uniformly mixing the traditional Chinese medicine compound extract dry powder, the non-steroidal anti-inflammatory drug subjected to micronization treatment and the immunoregulator dry powder wrapped by the nano liposome according to the weight ratio, adding the percutaneous absorption enhancer, and stirring at constant temperature until the active component premix is completely dispersed; S3, preparing a composite gel matrix, namely weighing carboxymethyl chitosan and sodium alginate according to the mass ratio, respectively adding purified water for full swelling, uniformly mixing the two swelling solutions, adding a cross-linking agent for constant-temperature stirring reaction, and preparing uniform and transparent composite gel matrix sol; s4, forming the application medicine, namely adding the active component premix and the antioxidant into the composite gel matrix sol, stirring uniformly after vacuum defoaming, coating the mixture on a medical non-woven fabric backing layer, covering a polyethylene anti-sticking layer, and performing constant-temperature shaping, slicing and sterile packaging to obtain the external application medicine.
  9. 9. The method of claim 8, wherein, In the step S1 a), the raw materials are crushed and then pass through a 80-100-mesh sieve, supercritical CO 2 is extracted by taking absolute ethyl alcohol as entrainer, the weight ratio of the absolute ethyl alcohol to the traditional Chinese medicine raw materials is 1:1-2, the extraction pressure is 20-30MPa, the extraction temperature is 40-50 ℃ and the extraction time is 1.5-2.5h, the vacuum degree of reduced pressure concentration is 0.06-0.08MPa, the temperature is 45-55 ℃, and the concentration is carried out until the extract liquid has no alcohol taste; Dissolving lecithin and cholesterol in absolute ethyl alcohol according to a mass ratio of 4-6:1, adding an immunomodulator, stirring until the mixture is completely dissolved, removing an organic solvent by reduced pressure rotary evaporation to form a uniform lipid film, adding a phosphate buffer solution for hydration after vacuum drying, carrying out ultrasonic treatment, carrying out high-pressure homogenization, carrying out ultrasonic frequency 30-50kHz, power 150-300W, temperature 35-45 ℃ and ultrasonic duration 15-25min, homogenizing pressure 60-90MPa, homogenizing temperature control at 30-40 ℃, carrying out cyclic homogenization for 2-4 times, passing through a microporous filter membrane of 0.22 mu m, preparing a nano liposome suspension, and carrying out freeze drying to obtain dry powder; In the step S2, the constant-temperature stirring temperature is 35-45 ℃, the stirring rotating speed is 30-50r/min, and the stirring time is 20-30min; In the step S3, the swelling temperature of the carboxymethyl chitosan and the sodium alginate is 40-50 ℃ and the swelling time is 2-4h, the cross-linking agent is calcium gluconate, the adding amount is 0.5-2% of the total mass of the carboxymethyl chitosan and the sodium alginate, the constant temperature reaction temperature is 35-45 ℃, and the reaction time is 15-30min; In the step S4, the coating thickness is 0.3-0.5mm, the constant temperature setting temperature is 40-50 ℃, and the setting time is 30-60min.
  10. 10. Use of a topical application medicament as claimed in any one of claims 1 to 7 for the manufacture of a medicament for the treatment of neck pain, fever caused by subacute thyroiditis.

Description

External application medicine for subacute thyroiditis acute stage and preparation method thereof Technical Field The invention relates to the technical field of medicinal preparations, in particular to an external application medicament for subacute thyroiditis in an acute stage and a preparation method thereof. Background Subacute thyroiditis, also called subacute granulomatous thyroiditis, (pseudo) giant cell thyroiditis, noninfectious thyroiditis, transitional thyroiditis, viral thyroiditis, deQuervain thyroiditis, granulomatous thyroiditis or giant cell thyroiditis, and the like, is a clinically common thyroiditis disease, and is mostly related to upper respiratory tract virus infection such as Coxsackie virus, influenza virus, EB virus, and the like, and the disease course is mainly divided into an acute stage (thyrotoxicosis stage), a remission stage (hypothyroidism stage) and a recovery stage. The acute phase is the stage with the most severe symptoms and highest treatment rate of patients, and the core clinical manifestations are severe pain, diffuse/nodular enlargement and obvious tenderness of thyroid gland areas, pain can radiate to the lower jaw, behind the ear, throat and throat, and simultaneously, systemic inflammatory reactions such as fever, hypodynamia and the like are accompanied, and transient thyrotoxicosis symptoms such as palpitation, tremble hands, hyperhidrosis and the like caused by the massive release of thyroid hormone seriously affect the life quality of the patients. Currently, clinical first-line therapy relies mainly on oral non-steroidal anti-inflammatory drugs or glucocorticoids. Although these drugs are effective in controlling symptoms, long-term or large-dose use often accompanies systemic side effects such as gastrointestinal damage, sodium retention, elevated blood sugar, etc., and there is a risk of recurrence after withdrawal, patient compliance is poor, disease progression cannot be fundamentally blocked, and some patients progress to permanent hypothyroidism. In recent years, topical treatment has been shown to be advantageous in soft tissue inflammatory diseases as a strategy capable of reducing systemic exposure and increasing drug concentration at the target site. However, the traditional Chinese medicine composition still has a plurality of defects that the active ingredients are single, and the traditional Chinese medicine composition or the single medicine composition is only contained, so that the synergistic effect of anti-inflammatory and analgesic effects, immunoregulation and stagnation-resolving and detumescence can not be realized at the same time, the treatment effect is limited, and particularly, a large amount of active oxygen free radicals generated by acute-phase inflammation outbreak can cause oxidative stress damage to thyroid follicular cells, and the key pathological link is often ignored in the existing external treatment. In addition, the traditional Chinese medicine external preparation has the theoretical basis of clearing heat and detoxicating, resolving hard mass and relieving pain in the aspect of treating goiter and carbuncle (methylene inflammation), but often has the problems of low transdermal efficiency of active ingredients, short local detention time of focus, single treatment target point and the like, and is difficult to rapidly relieve acute pain and inflammation. The preparation has poor matrix adaptability, the existing external gel and paste have the problems of poor adhesiveness, easy displacement, poor air permeability, easy clothes pollution and the like, and the patient has poor application compliance. Therefore, there is a need to develop an external compound preparation which can penetrate through skin barrier, realize high-efficiency enrichment in thyroid focus area and simultaneously exert multiple synergistic effects of anti-inflammatory, immunoregulation, antioxidation and direct analgesia, so as to overcome the defects of large systemic side effect of the existing oral treatment and insufficient curative effect of the traditional external medicine. Disclosure of Invention In view of the above, the present invention proposes an external application medicine for subacute thyroiditis in the acute phase and a preparation method thereof, which solves the above problems. The technical scheme of the invention is that the external application medicine for subacute thyroiditis acute stage comprises active ingredients, percutaneous absorption promoters, antioxidants and gel matrixes, wherein the active ingredients comprise (1-3) of traditional Chinese medicine compound extracts, (0.5-2) of non-steroidal anti-inflammatory drugs and immunomodulators, the weight ratio of the antioxidants is (3-8) of resveratrol and curcumin, the total additive amount is 0.8-1.2% of the total weight of the active ingredients, and the gel matrixes are prepared by compounding carboxymethyl chitosan and sodium alginate according to the weight ra