29 results about "Axitinib" patented technology

A pharmaceutical composition for prevention or treatment of a disease or disorder characterized by chronic inflammation, associated with angiogenesis and fibrosis. The pharmaceutical composition includes a multi-target inhibitor, multi-phase modulator, or multi-kinase inhibitor, such as axitinib, nintedanib, pirfenidone, riociguat, sorafenib, sunitinib, lenvatinib, regorafenib, ponatinib, or pazopanib.

The application belongs to the field of medicine, and particularly relates to application of axitinib in preparation of a medicine for treating plexiform neurofibroma. In the medicine, axitinib serves as the only effective component or one of the effective components. When axitinib serves as one of the effective components in the medicine, the effective components further include a MEK inhibitor. The MEK inhibitor is selected from one of selumetinib and trametinib. The application proves that axitinib can play a role in inhibiting plexiform neurofibroma (pNF) by targeting OTUD3, an important gene for promoting pNF progression. Moreover, axitinib is a drug that has been used for clinical treatment, and has good safety. The research result of the application shows that the combination use of axitinib and the MEK inhibitor can improve the inhibitory effect on neurofibroma.

The present invention relates to a sustained-release biodegradable ophthalmic implant containing axitinib dispersed in a hydrogel for the long-term treatment of retinal diseases.

This invention belongs to the field of biopharmaceutical technology and provides the use of vitamin C (VC) in combination with a tyrosine kinase inhibitor for the treatment of clear cell renal cell carcinoma. This combination of VC and a tyrosine kinase inhibitor is used to prepare a drug for treating clear cell renal cell carcinoma. Tyrosine kinase inhibitors include sunitinib and axitinib. When VC concentrations range from 0.039 mM to 0.625 mM and sunitinib concentrations range from 0.78 μM to 6.25 μM, the two agents synergistically inhibit tumor cell proliferation. When VC concentrations range from 0.039 mM to 0.625 mM and axitinib concentrations range from 0.39 μM to 3.13 μM, the two agents synergistically inhibit tumor cell proliferation. In this application, the combination of VC and a tyrosine kinase inhibitor can treat clear cell renal cell carcinoma and effectively inhibit tumor cell colony formation. This novel combination therapy provides new insights for clinical treatment.

The present application provides an acesulfame implant which is stable, safe and can achieve at least 6 months of sustained release, can effectively treat various eye diseases including but not limited to glaucoma, cataract, retinal vein obstruction (RVO), uveitis, diabetic macular edema (DME) and age-related macular degeneration (wAMD and nAMD), etc., avoids repeated administration, reduces the formation of side effects, reduces the cost of drug use, and meets the high stability required by drug preparation in production, storage and transportation, has good application prospect, and meets the unmet clinical needs.

The invention relates to a predictive gene expression signature of response to antiangiogenic drugs, such as axitinib, in gastro-enteric-pancreatic and pulmonary neuroendocrine tumours. The signature is formed by the gene expression of three genes (SPP1, ATXN7 and REXO1L2P), which is converted by means of a bioinformation packet into a unique score that can predict which patients will benefit from treatment with the drug, this benefit being understood as longer survival without progression and larger tumour volume reductions in response to treatment.

The application discloses a preparation method of an intermediate of Axitinib. The application specifically discloses a preparation method of a compound as shown in formula III, which comprises the following steps: adding a reaction solution containing a compound as shown in formula I into a reaction solution containing a compound as shown in formula IX, and carrying out a substitution reaction as shown in the following formula III. The preparation method of the intermediate of Axitinib can avoid using expensive reagents, save cost, and significantly improve the yield of the compound III, and is beneficial to industrial production.

The present application relates to the technical field of medicine, and particularly relates to a method for preparing a key intermediate 2-methylthio-N-methyl benzamide of axitinib medicine. The existing method for synthesizing 2-methylthio-N-methyl benzamide generally uses dangerous chemicals, has low process safety, and has poor stability of raw materials, and thus cannot meet the requirements of green chemistry and safe production. In view of the above problems, the present application provides a method for preparing a key intermediate 2-methylthio-N-methyl benzamide of axitinib medicine, which directly synthesizes 2-methylthio-N-methyl benzamide through one-step reaction by taking 2-methylbenzo[d] isothiazole-3(2H)-ketone as raw material and taking sodium sulfide nonahydrate as a key additive. The synthesis route is short, and the operation steps are few, and high-risk reagents such as sodium borohydride, trimethylaluminum and dimethylaminothiocarbonyl chloride used in the existing method are completely avoided.

The present invention relates to an ocular implant comprising an amorphous solid dispersion (ASD) comprising a tyrosine kinase inhibitor (TKI), such as axitinib, and a polymer excipient. Further, the invention relates to methods of treatment using the ocular implant of the invention comprising the amorphous solid dispersion (ASD) in treating an ocular disease. According to the present invention, ocular diseases are treated by injecting an amorphous solid dispersion (ASD) or an ocular implant comprising the ASD into the eye, wherein the ocular implant releases the TKI. Moreover, the invention relates to processes for preparing an amorphous solid dispersion (ASD) and an ocular implant of the invention comprising an ASD.

The present invention relates to a composition comprising a molecular assembly in which axitinib is physically associated, and to a preparation method therefor.

The application discloses a preparation method of an intermediate of Axitinib and an intermediate of Axitinib as shown in formula VI. The application provides a preparation method of a compound as shown in formula VII, which comprises the following steps: performing ring formation reaction on a compound of formula VI in the presence of a base and a solvent to obtain the compound of formula VII. The Axitinib synthesis route provided by the application has the advantages of less steps, low cost, high purity of a synthesis product and no introduction of toxic substances.

A composition containing a molecular association in which axitinib is physically bound and a method for preparing the composition are disclosed. The composition contains a molecular association in which axitinib is physically bound, a solubilizer, a stabilizer, and an additive. The additive may include any one or more selected from a buffer, an osmotic pressure regulator, and a pH adjuster.

The present invention relates to a sustained release biodegradable ocular implant containing axitinib dispersed in a hydrogel for use in the treatment of retinal diseases for an extended period of time.

This invention belongs to the field of crystalline drug molecule technology, specifically relating to a method for preparing and applying axitinib-fumaric acid-acetic acid cocrystal. The axitinib-fumaric acid-acetic acid cocrystal provided by this invention comprises one molecule of axitinib, one molecule of fumaric acid, and one molecule of acetic acid as its basic crystalline unit. It exhibits significant improvements in stability, solubility, and permeability. The preparation method is simple to operate, has good reproducibility, and is suitable for industrial production.

In a process of making Axitinib, a palladium catalyst is added to a mixture of 2-vinylpyridine and the protected intermediate of formula (III) to form protected-Axitinib of formula (IV).In the formulas, P is a protective group and X is I, Cl, Br, or trifluoromethanesulfonate. The palladium catalyst is prepared separately, before being added to the reaction mixture, and is made from a mixture of a palladium source, a ligand, and a base in a suitable solvent. By adding the palladium catalyst to this protected intermediate, the process can use lower amounts of palladium and can have faster reaction times.

The present invention relates to a molecular assembly which is a novel axitinib polymorph in which axitinib is physically bound.

Disclosed herein is an ophthalmic composition of an active ingredient that is poorly soluble in water. The ophthalmic composition comprises cyclodextrin, axitinib, and water, and is a clear solution having a pH of less than about 5.5. In accordance with embodiments of the present disclosure, the ophthalmic composition is a clarified solution that does not contain any water-insoluble precipitates therein.

This invention relates to the field of pharmaceutical intermediate synthesis technology, specifically disclosing a method for preparing 6-iodoinazole. The method uses 6-aminoinazole as a starting material, and in the presence of sodium thiosulfate pentahydrate and nitrate, it reacts with... N The reaction of -iodosuccinimide with 6-iodoindazole yields a highly efficient synthesis of 6-iodoindazole. The preparation method of this invention has the advantages of readily available raw materials, mild reaction conditions, simple operation, high product yield, and good purity. It can be mass-produced industrially, providing an efficient and feasible technical route for the preparation of intermediates for the anticancer drug axitinib, and solving the problems of high cost, complex processes, and poor environmental friendliness in existing 6-iodoindazole preparation methods.

The invention belongs to the technical field of medicines, and discloses a liposome for resisting angiogenesis and down-regulating PD-L1 protein as well as a preparation method and application of the liposome. According to the invention, the active targeting liposome which is modified by NGR and is co-loaded with axitinib and siRNAPD-L1 is prepared by a film dispersion method and a lipid co-extrusion method. The method is simple in preparation process, low in cost, good in stability and high in repeatability. On one hand, Axi / siRNAPD-L1-coated NGR-Lipo inhibits tumor microangiogenesis, reshapes a tumor vascular system, normalizes tumor vessels, inhibits tumor metastasis and improves a tumor immunosuppression microenvironment; on the other hand, PD-L1 protein on the surfaces of tumor cells is silenced, tumor immune escape is relieved, and tumor immunotherapy is enhanced. The Axi / siRNAPD-L1 coated NGR-Lipo realizes an enhanced anti-tumor effect by combining an anti-angiogenesis therapy and an immune checkpoint blocking therapy. The preparation process of the liposome is simple and rapid, is easy for large-scale and industrial production, and also has a better development prospect in the aspect of clinical application transformation.

The invention discloses a preparation method of a drug intermediate 6-iodoindazole. The method comprises the following steps: by taking 6-nitroindazole as a raw material, in an acetic acid solvent, in the presence of iodized salt and strong acid, firstly heating and stirring for pretreatment, then cooling the system to 0 DEG C, and then adding a sodium nitrite aqueous solution for reaction to obtain the target product 6-iodoindazole. The method provided by the invention has the advantages of easily available raw materials, high reaction selectivity, less three wastes, high total yield (87%) and the like, is safe and simple to operate, effectively overcomes the defects of harsh conditions, serious pollution and high cost of the traditional diazotization method, and provides a technical route with great industrial prospects for large-scale production of the key intermediate of the anti-cancer drug axitinib.

The invention relates to the technical field of organic chemistry, and particularly discloses a benzene ring stereoisosteric modified bicyclo [1.1. 1] pentane compound as well as a preparation method and application thereof, the technical core is that triplet-state carbene is inserted into bicyclo [1.1. 1] butane (BCB) under a photosensitive condition, and a new path for synthesizing C2-substituted BCP is developed. The spanning from a two-dimensional plane to a three-dimensional structure is realized by replacing a disubstituted benzene ring in a drug skeleton (such as Sonidegi and axitinib) with BCP. According to the bioisostere modification, the water solubility and metabolic stability of molecules are improved by utilizing an sp3 skeleton, the limitation that a benzene ring is easily oxidized by P450 enzyme is overcome, the compound is successfully endowed with remarkable cytotoxic activity, and experiments prove that by adjusting charge distribution and spatial conformation, the cytotoxic activity of the compound is remarkably improved. Important guidance is provided for development of active molecules with new purposes, and the project is funded by key support projects of Guangming advanced research institutes of Southern Science and Technology Universities.

The invention relates to a sustained release biodegradable ocular implant containing axitinib dispersed in a hydrogel for the treatment of a retinal disease for an extended period of time.

The present invention relates to a solid oral pharmaceutical for Axitinib, Ibrutinib and / or Palbociclib (API) or any other Kinase Inhibitor API with a novel, well defined method to enhance solubility of active pharmaceutical ingredients (API) with low solubility in aqueous media and use those enhanced API in a new approach of preparing modified and / or sustained release pharmaceutical formulation for API which are regularly not suitable for sustained release formulations because of their low solubility. This invention is applicable for small molecule API (molecular weight < 1000) for which the solubility can be enhanced by formation of a e.g., Cyclodextrin Complex regardless which Cyclodextrin or derivate thereof is employed according to the method described in this invention. Axitinib, Ibrutinib and / or Palbociclib and other Kinase Inhibitors can be found for treatment of malign tumor diseases and others.

The invention relates to a sustained release biodegradable ocular implant containing axitinib dispersed in a hydrogel for the treatment of a retinal disease for an extended period of time.

The present invention relates to compositions comprising molecular associates physically bound with axitinib and methods of making the same.

The application belongs to the technical field of crystal form drug molecules, and particularly relates to an axitinib oxalate crystal form and a preparation method and application thereof. The axitinib oxalate crystal form provided by the application is composed of one molecule of axitinib, one molecule of oxalic acid and two molecules of water as a basic unit of the crystal form, has high solubility, good stability, a simple preparation method, good reproducibility and is suitable for industrialized production.

The invention relates to a molecular association compound which is a novel axitinib polymorphic substance, and axitinib is physically combined.

The present invention relates to a use of Axitinib and analogs thereof in the preparation of a blood-brain barrier permeability regulator. The blood-brain barrier permeability regulator can reduce blood-brain barrier permeability, and promote recovery of a blood-brain barrier function from a pathologically impaired state to a state close to a physiological barrier. Axitinib and an analog thereof reduce blood-brain barrier permeability by inhibiting the vascular endothelial cell growth factor-phosphatidylinositol kinase-protein kinase B signaling pathway and reducing the degree to which a blood-brain barrier tight junction protein Claudin-5 / Occludin is down-regulated. The blood-brain barrier permeability regulator can be used in the treatment of a disease related to causing a change in blood-brain barrier permeability.

The invention relates to the field of pharmaceutical preparations and pharmaceutical crystal forms, in particular to a crystal form alpha of axitinib, a pharmaceutical composition containing the crystal form alpha of axitinib and application of the crystal form alpha of axitinib. The axitinib crystal form alpha provided by the invention has excellent solubility, stability, hygroscopicity and flowability, and both the axitinib crystal form alpha and the pharmaceutical composition containing the axitinib crystal form alpha have remarkably improved bioavailability. The preparation method of the crystal form alpha is simple, good in repeatability, high in yield, easy to operate, green, environmentally friendly, small in needed solvent amount and beneficial to recycling, the reagent cost can be effectively reduced, and large-scale production is easy to achieve.