33 results about "Tofacitinib" patented technology

The present invention relates to a monolithic tablet composition for oral administration of tofacitinib or a pharmaceutically acceptable salt thereof, without a functional coating.

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 present disclosure relates to oral compositions of Compound I or its derivatives. Several dosage ranges are disclosed, along with SAD, MAD, and PK data. Comparative data between Compound I, tofacitinib, ritrecitinib, and cyclosporin A are also disclosed. Methods of use for treating inflammatory conditions are also disclosed.

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.

One aspect of the present disclosure is directed to a method of delivering tofacitinib to or through a skin. Another aspect of the present disclosure is directed to a method of locally inhibiting activity of at least one of JAK-1, JAK-2, TYK-2, and JAK-3 within an epidermis layer, a dermis layer, a subcutaneous tissue layer, or a muscle tissue. Another aspect of the present disclosure is directed to a topical 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 beyond the skin

: The present invention provides a topical pharmaceutical composition comprising Janus kinase (JAK) inhibitors like Tofacitinib, Immunosuppressive agent like Tacrolimus, Fingolimod and statins like atorvastatin, Simvastatin, Fluvastatin, Lovastatin, Pitavastatin, Pravastatin and Rosuvastatin dissolved or dispersed in a pharmaceutically acceptable base together with other pharmaceutically acceptable excipients or in a dermatologically acceptable carrier, useful in the treatment of vitiligo. The inventive concept provided herein are methods and pharmaceutical compositions by preparing oral dosage forms like Topical liquid spray or Topical cream or Topical gel dosage form for the management of vitiligo and its associated disorders and accordingly performing preclinical study to prove the efficacy of the selected drug substances from the class of JAK inhibitors, statins and immunosuppressants.

The present invention relates to an improved process for preparation of tofacitinib (I) and pharmaceutically acceptable salt thereof. (I)

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 present disclosure relates to a pharmaceutical composition, a quasi-drug composition, or a cosmetic composition comprising: a tubulin inhibitor; and at least one compound selected from the group consisting of calcium, colchicine, tapinarof, fingolimod, tofacitinib, and pharmaceutically acceptable salts thereof as active ingredients for the prevention, alleviation, or treatment of skin diseases. The combination therapy of the present invention can be utilized as an active ingredient simultaneously exhibiting activities such as skin moisturizing, whitening, wrinkle alleviation, acne alleviation, skin barrier strengthening, or skin keratinocyte differentiation, in addition to preventing, treating, or alleviating skin diseases.

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 invention belongs to the field of pharmaceutical preparations, and particularly relates to a novel application of tofacitinib or a pharmaceutical composition containing the tofacitinib, and the tofacitinib exists in a medicine in the form of tofacitinib or pharmaceutically acceptable salt of the tofacitinib. The medicine can be prepared into an external preparation, including an external solution and an external semisolid, the external solution includes a solution, a foaming agent, a spray, a tincture and a liniment, and the external semisolid includes an ointment, a cream, a gel, a patch and an emplastrum; the external preparation can be a tofacitinib foaming agent and comprises the following components: tofacitinib or pharmaceutically acceptable salt thereof, a solvent, a humectant, a foam stabilizer, a surfactant, a pH regulator, an antioxidant and water, and the antioxidant comprises L-arginine and butylated hydroxytoluene.

Provided are a process for preparing (3R,4R)-1-benzyl-N,4-dimethylpiperidin-3-amine or a salt thereof, which is an intermediate useful for the preparation of tofacitinib, an intermediate used in the process, i.e., isopropanol solvate of methyl ((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)carbamate dibenzoyl-L-tartrate, an intermediate, having excellent stability, useful for the preparation of tofacitinib, i.e., (3R,4R)-1-benzyl-N,4-dimethylpiperidin-3-amine acetate, and a process for preparing tofacitinib or a pharmaceutically acceptable salt thereof.

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.

The present application relates to a compound preparation for treating alopecia areata, active ingredient A is a direct or indirect EPO receptor agonist, active ingredient B is tofacitinib or its pharmaceutically acceptable salt, and the EPO receptor agonist is preferably roxadustat. The beneficial effect is that roxadustat and tofacitinib or its pharmaceutically acceptable salt are both limited when used alone for alopecia areata treatment, but they act on different target points in the pathogenesis of alopecia areata respectively, so they are made into a compound preparation, the key signal pathway in the pathogenesis of alopecia areata is inhibited by roxadustat to compensate for the defect of tofacitinib in insufficient curative effect on moderate and severe patients from the etiology, and the hair repair effect of tofacitinib is improved from the symptom by the good hair growth promoting effect of roxadustat, the curative effects of the two are complementary, the alopecia areata is treated both from the etiology and the symptom, and the side effect risk can be reduced by appropriately reducing the dose of tofacitinib according to the synergistic effect.

To provide a tofacitinib-containing tablet with superior stability, which suppresses an increase of tofacitinib-related substances even when produced by a wet granulation process, and a method for producing the tofacitinib-containing tablet, as well as a method for improving the quality of a tofacitinib-containing tablet.SOLUTION: A tofacitinib-containing tablet comprises tofacitinib or a pharmaceutically acceptable salt thereof and a sugar alcohol, wherein the sugar alcohol is at least one selected from the group consisting of mannitol, erythritol, xylitol, sorbitol, maltitol, and isomalt.SELECTED DRAWING: None

The present invention relates to a film coated tablet formulation comprising tofacitinib or pharmaceutically acceptable salts thereof wherein tofacitinib or pharmaceutically acceptable salts thereof has a d (0.5) particle size less than 20 μm. Further, the present invention also relates to a simple, rapid, cost effective, time-saving and industrially convenient process.

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.

1. Name of the designed product: packaging box (tofacitinib sustained-release tablets). 2. Use of the designed product: the designed product is mainly used for packaging of medicines. 3. Design points of the designed product: combination of shape and pattern. 4. Picture or photo best indicating the design points: design 1 perspective view. 5. Design 1 is designated as the basic design.

The present invention provides a tofacitinib nano-microneedle preparation and its preparation method and application, which belong to the field of medical technology. The tofacitinib nano-microneedle preparation prepared by the present invention is a soluble microneedle, which can enable the drug to penetrate the stratum corneum of the skin, deliver the drug into the dermis, directly act on the hair follicle cells, and exert the therapeutic effect as soon as possible. Compared with traditional transdermal drug delivery techniques and injections such as ointments and skin patches, soluble microneedle drug delivery technology is more efficient, the variety of drugs is richer, and the length of the microneedle under the skin does not touch the skin pain nerve endings, does not cause pain, and the penetration depth of the soluble microneedle does not damage the capillary network, and the probability of bacterial infection is greatly reduced. After microneedle administration, the skin epidermis has only micron-level wounds, which can be healed within 24 to 48 hours. In actual use, the soluble microneedle does not require special operation, and the storage conditions are relatively mild.

The application is a preparation method of tofacitinib demethylated impurity, comprising the following steps: dissolving free tofacitinib raw material in a solvent, adding N-iodosuccinimide, adding a base catalyst, heating to initiate the reaction, and then stirring and reacting after the reaction is initiated; the reaction is detected by TLC, and the target compound is obtained after post-treatment and purification; the impurity compound can be used as an impurity reference substance in the detection standard of tofacitinib finished product, and is used for the quality control link of impurity qualitative and quantitative analysis in the production process of tofacitinib; the preparation method is novel, raw materials are easy to obtain, operation is simple, and the cost is low.

The invention discloses application of tofacitinib in preparation of a medicine for treating dry age-related macular degeneration, and belongs to the technical field of medicine application. The preclinical research proves that the tofacitinib can be used for effectively treating the dry AMD, and the effects of the tofacitinib are reflected in protecting the retina-choroid structure, maintaining the normal thickness of the retina-choroid, protecting the retinal pigment epithelium (RPE) structure, protecting the photoreceptor cell structure and protecting the choroid structure. In addition, tofacitinib can also play a therapeutic role by inhibiting expression of inflammatory factors in eye tissues. The tofacitinib disclosed by the invention has a remarkable treatment potential on the dry AMD, and a new drug choice and strategy are provided for clinical treatment of the dry AMD.

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.

A topical formulation comprising (a) a therapeutically effective amount of tofacitinib; (b) at least one solvent; and (c) optionally one or more other pharmaceutically acceptable excipients is provided. Also provided is a method for treating and / or preventing autoimmune diseases in a subject administering said topical formulation.

The invention provides methods related to combination therapies comprising an anti- alpha4beta7 antibody, e.g., vedolizumab, and. a pan-JAK inhibitor, e.g., tofacitinib, for treating inflammatory bowel disease, such as ulcerative colitis or Crohn's disease.

The invention discloses a JAK-STAT3 degradation agent and a preparation method and application thereof.The structure of the degradation agent is shown in the formula I. The compound can degrade JAK and STAT3 protein at the same time through the molecular glue effect, and compared with existing JAK-STAT3 inhibitors such as tofacitinib or ruxotinib, the degradation agent can directly down-regulate an IL6-JAK-STAT3 signal channel, and the degradation effect is good. According to the present invention, the compound can effectively inhibit the phosphorylation of STAT3, block the proliferation, the survival, the angiogenesis, the invasion, the metastasis and other processes of cancer cells, and reduce the levels of JAK1, JAK2, JAK3, STAT3 and pSTAT3, such that the compound has strong pathway inhibition activity compared with the traditional inhibitor.

The invention provides methods related to combination therapies comprising an anti- alpha4beta7 antibody, e.g., vedolizumab, and. a pan-JAK inhibitor, e.g., tofacitinib, for treating inflammatory bowel disease, such as ulcerative colitis or Crohn's disease.

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.