42 results about "Thyroid hormones" patented technology

The invention discloses a group of blocking monoclonal antibodies of an SH1 homologous cluster fully human thyrotropin receptor (TSHR) (a TSH receptor, TSHR) as well as a preparation method and application of the blocking monoclonal antibodies of the SH1 homologous cluster fully human thyrotropin receptor (TSHR). The method comprises the following steps: sorting plasma cells and memory single B cells for specifically recognizing TSHR in peripheral blood of a patient with high TSH receptor blocking antibody (TBAb) titer by using flow cytometry, cloning antibody light and heavy chains in vitro and performing recombinant expression, and performing antibody property screening verification by using hTSHR-CHO cells. The blocking monoclonal antibody specifically targeting the human TSHR is obtained. The fully human TSH receptor blocking monoclonal antibody disclosed by the invention can be specifically combined with TSHR, and can effectively block signal transduction after the TSH is combined with the receptor; the synthesis and secretion of thyroid hormone are inhibited; expression and fibrosis of effector cell orbital fibroblasts TSHR for inhibiting thyroid-related eye diseases are remarkably relieved, and wide application prospects are achieved in treatment of Graves' diseases and diseases such as thyroid eye diseases caused by hyperthyroidism.

The invention discloses a group of blocking monoclonal antibodies of a CHK36 homologous cluster fully human TSH receptor (TSHR) as well as a preparation method and application of the blocking monoclonal antibodies. The method comprises the following steps: sorting plasma cells and memory single B cells for specifically recognizing TSHR in peripheral blood of a patient with high TSH-blocking antibody (TBAb) titer by using flow cytometry, cloning antibody light and heavy chains in vitro and performing recombinant expression, and performing antibody property screening verification by using hTSHR-CHO cells, so as to obtain the TSHR-TBAb-TSHR-TBAb. The blocking monoclonal antibody specifically targeting the human TSHR is obtained. The fully human TSH receptor blocking monoclonal antibody disclosed by the invention can be specifically combined with TSHR, and can effectively block signal transduction after the TSH is combined with the receptor; the synthesis and secretion of thyroid hormone are inhibited; according to the present invention, with the application of the compound, the expression and the fibrosis of the effector cell orbit fibroblast TSHR inhibiting the thyroid-related eye disease can be significantly reduced, and the wide application prospect is provided in the treatment of Graves' disease (Graves' disease, GD) and diseases caused by hyperthyroidism, such as thyroid eye disease (thyroid eye disease, TED), and the like.

The invention belongs to the field of biological medicines, and particularly relates to 4-quinazolinone compounds serving as thyroid hormone beta receptor agonists and application of the 4-quinazolinone compounds. The invention discloses a thyroid hormone beta receptor agonist as shown in a formula (I), relates to a 4-quinazolinone compound and a preparation method thereof, and further relates to a pharmaceutical composition containing the compound and application. The compound or the pharmaceutical composition provided by the invention can be used for preventing, treating or relieving diseases regulated by thyroid hormone beta receptors, especially for treating non-alcoholic fatty liver diseases.

The invention relates to an application of a DIO1 gene in a liver in controlling the body color of a turbot, and belongs to the field of molecular biology, and the application method is as follows: the turbot with golden body color is obtained by overexpressing the DIO1 gene in the liver of the turbot; the amino acid sequence of the protein coded by the DIO1 gene is as shown in SEQ ID NO. 1. The invention discovers that the gene expression level change in the liver can cause the change of the blood hormone level by influencing the thyroid hormone pathway in the turbot for the first time, thereby influencing the color formation of the skin; therefore, the formation of the target body color of the scophthalmus maximus can be controlled by controlling the gene expression level, so that the market value of the scophthalmus maximus is improved.

The present invention discloses a composition for treating hypothyroidism. The formula includes: placenta, antler, Pseudostellaria baicalensis, Salvia miltiorrhiza, and Herba Lycopodii. The prescription of the present invention is demonstrated to have therapeutic effects on hypothyroidism from both traditional Chinese medicine and modern medicine perspectives: from the perspective of traditional Chinese medicine, the efficacy of the present invention in replenishing qi and blood, regulating yin and yang, tonifying kidney essence, filling the marrow sea, and unblocking meridians is unique in treating goiter. From the perspective of modern medicine: Panlushending Jiawei Decoction has the effects of promoting cell reproduction, differentiation, and repairing damaged cells, and is also anti-apoptotic. It also has the effects of promoting the regeneration of vascular endothelial cells, forming new blood vessels, increasing blood flow rate, increasing blood supply, and increasing the secretion and synthesis of thyroid hormones. It can also increase the level of free hormone reabsorption from the intestine and lower the concentration of antibodies.

Solid orodispersible compositions in the form of thin films for the oral administration of thyroid hormones are described, characterized by a high stability, and by the bioavailability of the active ingredient for oral absorption. The film compositions described are designed for rapid disintegration in the mouth, for sublingual administration, or to be held in the mouth for longer times before they disintegrate, but in any case without being mucoadhesive films. All the examples described are characterized by being thin and flexible and are suitable for administration even to patients who are not conscious, dysphagic or otherwise unable to swallow.

The present invention relates to a compound that acts as a thyroid hormone beta receptor agonist and its use, and further relates to a compound represented by formula (1) or a pharmaceutically acceptable form thereof, a pharmaceutical composition comprising the same, and a method for preparing the same. The compound or pharmaceutical composition described herein can be used to prepare a medicament for preventing, treating, or alleviating diseases regulated by thyroid hormone beta receptors. #imgabs0#

Provided are a set of fully human TSH receptor (TSHR)-blocking monoclonal antibodies targeting a CHK36 homolog cluster, a preparation method therefor, and an application thereof. The method comprises the following steps: using flow cytometry to sort plasma cells and single memory B cells that specifically recognize TSHR in peripheral blood of a patient with a high titer of TSH-blocking antibodies (TBAb), performing in vitro cloning of antibody light and heavy chains and performing recombinant expression, and using hTSHR-CHO cells to perform screening and validation of antibody properties to obtain a blocking monoclonal antibody that specifically targets human TSHR. The fully human TSH receptor-blocking monoclonal antibodies specifically bind to a TSHR, and effectively block signal transduction after a TSH binds to a receptor, inhibit the synthetic secretion of thyroid hormones, and significantly reduce and inhibit TSHR expression and fibrosis in orbital fibroblasts of effector cells associated with thyroid-related ocular diseases. The fully human TSH receptor-blocking monoclonal antibodies have broad application prospects in the treatment of Graves' disease (GD) and other diseases caused by hyperthyroidism, such as thyroid eye disease (TED).

The invention relates to pyridazinone or pyridazine compounds as well as derivatives and pharmaceutical compositions thereof. Specifically, the invention provides a pyridazinone or pyridazine compound as shown in a formula (I) or (Ia) or a stereoisomer, a tautomer, an enantiomer, a diastereoisomer, a resonator, a pharmaceutically acceptable salt, a hydrate, a solvate or a crystal form of the pyridazinone or pyridazine compound. The compound shown in the formula (I) or (Ia) has excellent agonistic effect and pharmacodynamic performance on a thyroid hormone beta receptor.

The present application provides a novel thyroid hormone β receptor agonist of formula (I) having better activity, selectivity or safety and the use thereof for preventing or treating diseases related to the action of β receptor agonists, including, for example, obesity, hyperlipidemia, hypercholesterolemia, diabetes, liver diseases (fatty liver, NASH, NAFLD, etc.), cardiovascular diseases (atherosclerosis, etc.), thyroid diseases (hypothyroidism, thyroid cancer, etc.), and the like.

The present invention relates to a polycyclic thyroid hormone β receptor agonist and use thereof, in particular, to a compound represented by formula (1) or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising same, a preparation method therefor, and use thereof. The compound or the pharmaceutical composition of the present invention can be used for preparing a drug for preventing, treating, or relieving diseases regulated by the thyroid hormone β receptor.

The present application relates to a kind of thyroid hormone interferent high-sensitivity screening method, belong to new pollutant screening method technical field.The present application is based on the biological recognition performance of polypeptide and the peroxidase-like activity of nano gold combined with polypeptide material, based on this, a kind of thyroid hormone interferent screening method under medium alkaline condition can guarantee the activity of polypeptide and also can play the enzyme activity of nano gold.The dopamine can be catalyzed by nano gold under medium alkaline condition and quickly generate red product.Once interferent combines specific recognition polypeptide, occupies the enzyme activity recognition site of nano gold, reduces enzyme activity, in dopamine color system, different absorbance values are shown, so as to show the thyroid hormone interference toxic effect, reach the purpose of recognizing thyroid hormone interferent.The method does not need to use a large amount of organic solvent, and toxicity evaluation of thyroid hormone interferent can be realized by absorbance determination, with the advantages of simple preparation, low cost, high sensitivity.

The invention relates to a polymorphic form of a compound capable of serving as a thyroid hormone beta receptor modulator, a preparation method and application of the polymorphic form and a pharmaceutical composition containing the polymorphic form. The polymorphic form is applied to preparation of drugs for treating various thyroid-related diseases.

Disclosed in the present invention is a thyroid hormone β receptor agonist, which is a compound having a structure represented by formula (I), an optical isomer thereof, or a pharmaceutically acceptable salt thereof.

Hyperthyroid diarrhea refers to hyperthyroid diarrhea, which is mostly intractable diarrhea, due to excessive thyroid hormone causing increased intestinal peristalsis excitability and diarrhea when the thyroid function is increased, which is caused by endocrine metabolic disorder leading to gastrointestinal function disorder. The present application studies and observes the treatment effect of kaempferol coupling derivative JC-1 on diarrhea of hyperthyroid model mice, and provides a new drug treatment option for diarrhea type colon dysfunction.

The invention discloses application of sitagliptin in preparation of a medicine for treating Graves eye diseases, and belongs to the field of biological medicine. The invention discloses the application of sitagliptin in preparation of the medicine for treating Graves eye diseases for the first time, and sitagliptin can improve expression of CD4 + CTL cytotoxic functional molecules and improve eye symptoms, extraocular muscle thickening and fibrosis, orbit fat neogenesis and orbit T lymphocyte infiltration of mice; the mouse spleen CD4 + CTL cell proportion is improved; in addition, the thyroid hormone level, thyroid hyperplasia and hypertrophy and lymphocyte infiltration of mice can be improved. Sitagliptin is a clinically common hypoglycemic drug, and is perfect in safety database, small in side effect and easy to popularize clinically. Therefore, the experimental result of the invention fully supports the new application of sitagliptin in treating Graves eye diseases, and is a new direction worthy of exploration for treating Graves eye diseases due to strong clinical operability.

The present invention relates to a delivery system of thyroid hormones comprising lipid or polymeric nanoparticles, preferably comprising a targeting agent for the TRCP6 receptor. Such a delivery system can be used in the treatment of diabetic cardiomyopathy or diabetic nephropathy.

The present disclosure provides methods and a device for thyroxine delivery. This device is designed for subcutaneous implantation to ensure continuous delivery of thyroxine. It features a reservoir regulated by an embedded microprocessor with advanced signal software. The software triggers a precision pump to release a specific dose of thyroxine at regular intervals. This system enhances patient compliance and maintains optimal metabolic control.

The present invention provides a preparation method for Resmetirom and an intermediate I thereof. In the method, by means of a continuous process, there is no need to separate the intermediate and perform post-reaction work-up, thereby saving a plurality of procedures and operation time; and the work-up is simple and efficient, and the use of a highly polluting reagent pyridine is avoided. Moreover, by adjusting a material feeding order, the reaction can be promoted and the color of a product can be effectively improved. The entire process is simple to operate and cost-effective, uses a green and environmentally friendly reagent, and is suitable for large-scale industrial production.

The present disclosure provides methods of treating a medulloblastoma in a subject in need comprising administering T3 to the subject. The present disclosure also provides methods of inhibiting proliferation of medulloblastoma cells in a subject in need by administering T3 to the subject. Moreover, the present disclosure provides uses of T3 for treating medulloblastoma and the manufacture of a medicament for treating medulloblastoma.

The invention provides a culture medium and a culture method of a hiPSC-derived thyroid organ, and belongs to the technical field of thyroid organ culture. The invention relates to a culture method of a hiPSC-derived thyroid organ. The culture method comprises the following steps: (1) putting a resuscitated hiPSC-derived thyroid organ into a proliferation culture medium for culturing; and (2) when the thyroid organoid is cultured in the step (1) until the size of the thyroid organoid is 120-150 microns, replacing the proliferation culture medium with a differential culture medium, and continuously culturing. Sodium iodide with a specific concentration is added during thyroid organoid culture, so that the secretion amount of in-vitro thyroxine T4 of the organoid reaches 5ng / ml and is far higher than that (0.023 ng / ml) in the prior art. The invention provides a culture medium and a culture method capable of obviously promoting the maturity of the thyroid organoid, and the culture medium and the culture method have a wide application prospect.

Provided are a group of fully human thyrotropin receptor (TSHR) (TSH receptor, TSHR) blocking monoclonal antibodies belonging to a SH1 homocluster, a preparation method therefor, and a use thereof. The method comprises the following steps: using flow cytometry to sort plasma cells and individual memory B cells, which specifically recognize TSHR, from peripheral blood of a patient having a high TSH receptor blocking antibody (TBAb) titer, cloning antibody light and heavy chains in vitro, followed by recombinant expression, and performing antibody characteristic screening and verification by using hTSHR-CHO cells, thereby obtaining blocking monoclonal antibodies that specifically target human TSHR. The fully human TSH receptor blocking monoclonal antibodies can specifically bind to TSHR, thereby enabling effective blockage of signal transduction after TSH binds to the receptor, inhibiting the synthesis and secretion of thyroid hormones, and significantly reducing and suppressing the expression of TSHR and fibrosis in orbital fibroblasts, the effector cells in thyroid-related eye diseases. The present invention has broad application prospects in the treatment of Graves' diseases and diseases caused by hyperthyroidism, such as thyroid eye diseases.

The invention belongs to the field of biological medicine, and particularly relates to an oxazolone compound and a preparation method, a pharmaceutical composition and application thereof. The invention provides a compound as shown in a formula (I) or a stereoisomer, a geometric isomer, a tautomer, a deuterated compound, a nitrogen oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or prodrugs of the stereoisomer, the geometric isomer, the tautomer, the deuterated compound, the nitrogen oxide, the solvate, the metabolite and the pharmaceutically acceptable salt of the compound as shown in the formula (I), and also provides a preparation method of the compound. The invention also relates to application of the compound in preparation of drugs for thyroid hormone receptor mediated diseases. According to the compound, good THR-beta agonist activity is maintained, selectivity to THR-alpha and druggability of the compound are improved, and certain activity is shown in an in-vitro molecular level experiment.

Methods of treatment of medulloblastoma by administering thyroid hormone (T3) to a subject are provided herein.

The invention relates to the technical field of in-vitro diagnosis, in particular to a thyroid hormone detection kit and a thyroid hormone detection method. Wherein the thyroid hormone comprises at least one of triiodothyronine and tetraiodothyronine; the thyroid hormone detection kit comprises (i) a cyclodextrin reserve reagent; ii) an antibody capture reagent; iii) an antibody detection reagent; and, iv) a signalling agent. According to the kit and the detection method, the T3 and T4 detection signal intensity can be improved, the detection limit is reduced, and the accuracy and reliability of low-concentration sample detection are improved.

The invention provides application of thyroxine and a thyroxine receptor inhibitor in preparation of a medicine for regulating primordial follicle activation, and belongs to the technical field of biology. It is found that thyroxine can promote primordial follicle activation, the thyroxine receptor inhibitor inhibits primordial follicle activation, and the thyroxine receptor inhibitor can serve as a medicine for adjusting primordial follicle activation of a patient suffering from premature ovarian insufficiency and has a good application prospect.

The invention provides application of SLC16A10 in diagnosis and treatment of psoriasis, and relates to the technical field of biological medicines. The research of the inventor finds that SLC16A10 can participate in metabolism of arachidonic acid in keratinocytes by adjusting the homeostasis of thyroid hormones so as to promote the occurrence and development of psoriasis; the SLC16A10 represents a promising therapeutic target for treating psoriasis drip, and can improve the curative effect of the existing immune targeted therapeutic drug; comprehensive in-vitro and in-vivo experiments prove that the severity and excessive inflammation of psoriasis can be relieved by down-regulation of the SLC16A10; in addition, the SLC16A10 can induce one of sequelae of psoriasis, namely post-inflammation hypopigmentation, by inhibiting melanogenesis. Research results of the invention show that the SLC16A10 has potential as a psoriasis diagnosis biomarker and a treatment target.

This invention provides a mesenchymal stem cell culture medium, its preparation method, and its application. The mesenchymal stem cell culture medium of this invention includes a basal culture medium and functional additives. The functional additives include: recombinant human albumin, recombinant transferrin, recombinant bone morphogenetic protein; recombinant insulin or insulin-like growth factor, recombinant fibroblast growth factor, recombinant epidermal growth factor, recombinant platelet-derived growth factor; thyroid hormones, ethanolamine, carnitine, glucocorticoid regulators, retinoic acid compounds; heparin sodium, signal-regulating lipids, cholesterol, DL-α-tocopherol acetate, linolenic acid, oleic acid, stearic acid; prolactin F68, and Tween 80. The mesenchymal stem cell culture medium of this invention does not contain immunogenic proteins or blood products derived from animals or humans. All components can be supplied with GMP-compliant raw materials and the process can be controlled, ensuring the controllability, safety, and reproducibility of the culture process.

The present disclosure belongs to the field of medicines. Disclosed in the present invention are a thyroid hormone β receptor agonist, a crystalline form, a preparation method and the use. The compound is a compound having a structural formula as represented by formula (I) or a pharmaceutically acceptable salt thereof. The X-ray powder diffraction pattern of a crystal form A of the compound of formula (I) comprises characteristic peaks at 6.10 ± 0.20°, 12.08 ±0.20° and 16.49±0.20° 2θ, as determined by means of using Cu-Ka radiation, The present invention develops a new 2-pyridone derivative. The compound has high agonistic activity and selectivity for the thyroid hormone β receptor, and can be used for treating metabolic diseases, particularly for treating diseases related to thyroid hormone receptor. The present invention also studies a series of crystal forms of the compound. The crystal form A compound has the advantages of good stability, low hygroscopicity, and small heat influence.

The invention belongs to the technical field of traditional Chinese medicine, and particularly relates to application of a traditional Chinese medicine composition in preparation of medicine for treating thyroiditis, and the traditional Chinese medicine composition is mainly prepared from codonopsis pilosula, radix astragali preparata, poria cocos, fried rhizoma atractylodis macrocephalae, prepared polygala tenuifolia, honey-fried licorice root, fried spina date seed, longan aril, angelica sinensis, jujube, elecampane and ginger. All the medicines in the traditional Chinese medicine composition conform to the principle of compatibility of monarch, minister, assistant and guide, compatibility is scientific, clinical cases are considered, pharmacodynamic tests show that the composition can remarkably improve the basic condition of mice suffering from thyroiditis, adjust the levels of thyroid hormones T3, T4 and TSH of the mice, reduce inflammatory factors TNF-alpha and IL-10 and inhibit inflammatory reaction, and clinical tests verify that the composition has a remarkable curative effect on thyroiditis. The traditional Chinese medicine composition can effectively relieve symptoms of patients with thyroiditis, is low in toxic and side effects and good in safety, and has a wide market prospect.