12 results about "Tofacitinib" patented technology

The present invention relates to a pharmaceutical composition, quasi-drug composition, or cosmetic composition for the prevention, improvement, or treatment of skin diseases, comprising as an active ingredient a tubulin inhibitor and one or more compounds selected from the group consisting of calcium, colchicine, tapinarof, fingolimod, tofacitinib, and pharmaceutically acceptable salts thereof. The combination therapy of the present invention can be used as an active ingredient that simultaneously exhibits activities such as skin moisturizing, whitening, wrinkle improvement, acne relief, skin barrier strengthening, or keratinocyte differentiation, along with the prevention, treatment, or improvement of skin diseases.

The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of a tofacitinib key intermediate. According to the present invention, the diphenyl glycolic acid tropine ester is adopted as the starting material, and the diphenyl glycolic acid tropine ester is obtained under the action of the photosensitizer and the perchlorate in cooperation with the irradiation of the high-pressure mercury lamp, such that the technology has characteristics of simple preparation, no use of the expensive catalyst, safety, environmental protection, and avoiding of the risk of the standard exceeding of the heavy metal content, and is suitable for the large-scale production.

Disclosed are methods of accelerating development of new hair follicles in pluripotent stem cell-derived skin organoids. In particular, disclosed are methods of accelerating development of new hair follicles in skin organoids by adding one or more growth factors, such as FGF10, FGF20, BIO, ruxolitinib, tofacitinib, LDN193189, vitamin E, GDNF, retinoic acid, or IGF2. The growth factors are added to a culture of skin organoid at critical windows of time of the skin organoid development, such as after (or upon) the formation of epidermis and dermis in the skin organoid.

The invention discloses a preparation method for catalytic synthesis of a tofacitinib intermediate through chiral quaternary ammonium salt ion pairs. The invention specifically provides a preparation method of a compound 4, which comprises the following step: in an aprotic solvent, in the presence of an alkaline reagent and a chiral catalyst I, carrying out a reaction as shown in the specification on a compound 2 and a compound 3 to generate the compound 4. According to the preparation method disclosed by the invention, the use of a highly toxic reagent is avoided, the pollution is small, the synthesis route is simplified, the safety is high, the process cost is reduced, and meanwhile, the yield and ee value of the preparation method are relatively high.

The present invention relates to long-acting parenteral formulations of tofacitinib comprising of tofacitinib or its fatty acid salts along with pharmaceutically acceptable excipients.

The name of the invention is tofacitinib surface delivery using ionic liquids. One aspect of the present disclosure is directed to a method of delivering tofacitinib to or through the skin. Another aspect of the present disclosure is directed to a method of locally inhibiting the activity of at least one of JAK-1, JAK-2, TYK-2, and JAK-3 within the epidermal layer, dermis layer, subcutaneous tissue layer, or muscular tissue. Another aspect of the present disclosure is directed to a surface composition comprising tofacitinib, or a pharmaceutically acceptable salt thereof, and an ionic liquid in an amount sufficient to allow a therapeutically effective amount of tofacitinib to reach a target depth within or outside the skin.

An imine reductase mutant and the use thereof in the preparation of a tofacitinib chiral amine building block. By means of an enzymatically coupled coenzyme regeneration system, the imine reductase mutant can efficiently catalyze racemic 1-benzyl-4-methylpiperidin-3-one as a substrate to undergo dynamic kinetic resolution and asymmetric reductive amination, so as to accurately synthesize a tofacitinib chiral amine building block (3R,4R)-1-benzyl-N-4-dimethylpiperidin-3-amine. Compared with conventional resolution methods, the technology has the significant advantages of simple operation, mild reaction conditions, environmental friendliness, high product yield, low cost, etc., and exhibits excellent application prospects in the synthesis of tofacitinib chiral amine intermediates.

The present disclosure relates to oral compositions of Compound I or a derivative thereof. Several dosing ranges are disclosed along with SAD, MAD and PK data. Comparative data between Compound I, Tofacitinib, Ritlecitinib, and Cyclosporine A are also disclosed. Methods of use for treating an inflammatory condition are also disclosed.

The application belongs to the technical field of pharmaceutical preparations, and particularly relates to a self-emulsifying nanometer preparation of tofacitinib and a preparation method thereof. The tofacitinib free base is mixed with diethylene glycol monoethyl ether, and is dissolved by heating and oscillation; then polyoxyethylene 40 hydrogenated castor oil and glyceryl monocaprylate are added, and are uniformly stirred to obtain a drug-containing SEDDS solution; the SEDDS solution is added dropwise into magnesium aluminosilicate to obtain a SEDDS solidified powder. The method significantly improves the solubility and stability of the tofacitinib free base, simplifies the production process, improves the bioavailability and safety of the drug, provides various preparation forms, and meets the medication needs of different patients.

The invention relates to an application of tofacitinib in preparation of a medicine for treating inflammatory knee osteoarthritis, and relates to the technical field of biological medicine.Clinical patients are screened, different administration comparison is carried out, continuous treatment is carried out for one year, and clinical symptom evaluation, inflammatory factor detection and safety evaluation are carried out in the treatment period; iconography detection and evaluation before and after treatment find that in middle-aged and elderly inflammatory knee osteoarthritis patients with poor or intolerant curative effect on NSAIDs, tofacitinib (5 mg is adjusted to 5 mg twice a day and once a day if necessary) can significantly relieve pain, improve joint functions and life quality, reduce inflammatory factor level and delay joint structure degeneration, and the tofacitinib is good in safety and free of toxic and side effects. And no serious adverse reaction occurs. The discovery provides a practical basis for clinical application of tofacitinib in the patients, and the tofacitinib has a good application prospect.

The invention belongs to the technical field of medicine synthesis, and particularly relates to a synthesis method of a tofacitinib key intermediate. According to the method, N-((3R, 4R)-1-benzyl-4-methylpiperidine-3-yl)-N-methyl-7H-pyrrolo [2, 3-d] pyrimidine-4-amine is taken as a starting material, under the action of N, N-diisopropylethylamine and 1-chloroethyl chloroformate, debenzylation is carried out through a one-pot method, conditions are mild, aftertreatment purification is simple and easy to operate, energy consumption is low, working hours are short, and the method is suitable for large-scale production.

The invention relates to a preparation method of a tofacitinib perhydrogenated impurity. The preparation method comprises the following step: under an alkaline condition, carrying out substitution reaction on a compound shown in a formula II and a compound shown in a formula III to prepare a compound shown in a formula IV. And debenzylating the compound in the formula IV to prepare the tofacitinib perhydrogenated impurity (a compound in a formula V). The preparation method provided by the invention is simple to operate, convenient to purify, high in yield and good in experimental repeatability, and provides a basis for quality research of tofacitinib.