210 results about "Capecitabine" patented technology

The present invention provides a medicinal composition having an excellent antitumor activity. That is, it provides a medicinal composition comprising a sulfonamide compound, a sulfonate compound or a salt of them, which is represented by the following formula: (wherein ring A represents an aromatic ring which may have a substituent group; ring B represents a 6-membered unsaturated hydrocarbon ring which may have a substituent group etc.; ring C represents a 5-membered hetero-ring containing one or two nitrogen atoms, and the ring C may have a substituent group; W represents a single bond or -CH=CH-; X represents -NH- etc.; and Y represents a carbon atom or a nitrogen atom; and Z represents -NH- etc.), particularly N-(3-chloro-1H-indol-7-yl)-4-sulfamoylbenzenesulfonamide or a salt thereof, combined with at least one substance selected from (1) irinotecan hydrochloride trihydrate; (2) mitomycin C; (3) 5-fluorouracil; (4) cisplatin; (5) gemcitabine hydrochloride; (6) doxorubicin; (7) taxol; (8) carboplatin; (9) oxaliplatin; (10) capecitabine; and (11) a salt of the above-mentioned (1) to (10).

Evidence demonstrating that elevated expression of dUTPase protects breast cancer cells from the expansion of the intracellular uracil pool, translating to reduced growth inhibition following treatment with 5-FU is provided. The implementation of in silica drug development techniques to identify and develop small molecule inhibitors of dUTPase are reported. As 5-FU and the oral 5-FU pro-drug capecitabine remain central agents in the treatment of a variety of malignancies, the clinical utility of a small molecule inhibitor to dUTPase represents a viable strategy to improve the clinical efficacy of these mainstay chemotherapeutic agents.

Methods of treating patients having metastatic or unresectable locally advanced HER2 positive cancer, e.g., breast cancer, with the antibody-drug conjugate trastuzumab-MCC-DM1 are provided, wherein the patients have received extensive prior treatment, e.g., with an anthracycline, a taxane, capecitabine, lapatinib, and trastuzumab.

Methods of treating a human body for cancer are provided. In one aspect, a therapeutic amount of capecitabine is administered in combination with ET-743 in a dose range between 0.75 and 1.4 mg / m2 for Et-743. In a related aspect, an effective therapeutic amount of ET-743 is administered in combination with capecitabine in a dose range between 1500 to 2500 mg / m / day for capecitabine.

The invention provides, in a general sense, a new labeling strategy employing compounds that are are N2S2 chelates conjugated to a targeting ligand, wherein the targeting ligand is a disease cell cycle targeting compound, a tumor angiogenesis targeting ligand, a tumor apoptosis targeting ligand, a disease receptor targeting ligand, amifostine, angiostatin, monoclonal antibody C225, monoclonal antibody CD31, monoclonal antibody CD40, capecitabine, a COX-2 inhibitor, deoxycytidine, fullerene, herceptin, human serum albumin, lactose, leuteinizing hormone, pyridoxal, quinazoline, thalidomide, transferrin, or trimethyl lysine. The present invention also pertains to kits employing the compounds of interest, and methods of assessing the pharmacology of an agent of interest using the present compounds.

The invention provides the use of a combination of an mTOR inhibitor and capecitabine in the treatment of cancer.

The present invention provides a method for treating tumors or tumor metastases in a patient, comprising administering to the patient simultaneously or sequentially a therapeutically effective amount of an EGFR kinase inhibitor and capecitabine combination, with or without additional agents or treatments, such as other anti-cancer drugs or radiation therapy. The invention also encompasses a pharmaceutical composition that is comprised of an EGFR kinase inhibitor and capecitabine combination in combination with a pharmaceutically acceptable carrier. A preferred example of an EGFR kinase inhibitor that can be used in practicing this invention is the compound erlotinib HCl (also known as TARCEVA®).

The present invention provides a medicinal composition having an excellent antitumor activity. That is, it provides a medicinal composition comprising a sulfonamide compound, a sulfonate compound or a salt of them, which is represented by the following formula: (wherein ring A represents an aromatic ring which may have a substituent group; ring B represents a 6-membered unsaturated hydrocarbon ring which may have a substituent group etc.; ring C represents a 5-membered hetero-ring containing one or two nitrogen atoms, and the ring C may have a substituent group; W represents a single bond or -CH=CH-; X represents -NH- etc.; and Y represents a carbon atom or a nitrogen atom; and Z represents -NH- etc.), particularly N-(3-chloro-1H-indol-7-yl)-4-sulfamoylbenzenesulfonamide or a salt thereof, combined with at least one substance selected from (1) irinotecan hydrochloride trihydrate; (2) mitomycin C; (3) 5-fluorouracil; (4) cisplatin; (5) gemcitabine hydrochloride; (6) doxorubicin; (7) taxol; (8) carboplatin; (9) oxaliplatin; (10) capecitabine; and (11) a salt of the above-mentioned (1) to (10).

The invention discloses a preparation method of capecitabine. The method comprises the following steps: based on D-ribose serving as a starting raw material, carrying out hydroxyl protection, 5-site tosylation, iodine substitution, hypophosphorous acid deiodination and acetylation so as to obtain the key intermediate 12,3-tri-O-acetyl-5-deoxy-beta-D-ribofuranose; carrying out glycosylation on the key intermediate and 5-fluorocytosine; and finally, carrying out N-4 site acylation and deprotection so as to obtain the capecitabine. In the method, a metal catalyst dose not need to be used for participating in reaction, the reaction condition is mild, and the yield is high, thus the method is economical and effective as well as suitable for industrial production on a large scale.

The invention relates to a preparation method of capecitabine and an intermediate thereof. The material conversion rate is high with less side reaction under the condition that bicarbonate is used as alkali by changing the reaction condition of synthesizing a compound of a formula I by a 5'-deoxidized-5-gemcitabine derivative and chloroformic acid n-amyl ester. Meanwhile, the applicant researches and finds that: Since 5-deoxidized-tri-O-acetyl-D-ribose prepared by using inosine reactrion substituted by iodine and protected by hydroxyl is adopted, the post-treatment process is simplified, and the yield is improved. The 5-deoxidized-tri-O-acetyl-D-ribose is a material for synthesizing the compound of the formula I while the compound of the formula I is a significant intermediate of capecitabine. The whole capecitabine synthesis process has high yield and low cost.

The invention relates to a multiparticulate modified release composition comprising a fluorocytidine derivative, preferably capecitabine, and a modified release component comprising a modified release coating, a modified release matrix material, or both. Following oral delivery, the composition in operation delivers the fluorocytidine derivative in a pulsatile manner at about six to about twelve hours after administration.

A combination of a 4-anilino-3-cyanoquinoline compound (e.g. HKI-272, SKI-606, EKB-569) and a capecitabine compound in the treatment of a neoplasm is provided. Regimens, kits, and methods for treatment of neoplasm, including breast cancer including metastatic breast cancer, and lung cancer, using this combination, optionally in combination with other anti-neoplastic agents, or immune modulators are also described.

The invention discloses a capecitabine oral sustained-release preparation and a preparation method thereof. The oral sustained-release preparation comprises the following components by weight percentage: 1) 50 to 90 percent of capecitabine, or pharmaceutically acceptable salt thereof, or ester derivative thereof, and 2) 10 to 50 percent of pharmaceutically acceptable accessories which comprise 4 to 44 percent of pharmaceutically acceptable sustained-release accessory. The preparation adopts the marketed pharmaceutical accessories, has high content of pharmaceutically active components (the weight percentage is more than 50 percent), and can release for 12 to 24 hours in a sustained mode.

The invention relates to fluorine contained miazines compound N-4 position alkyl oxygen carbonyl acidylating method, and its use in composing antineoplastic medicine-capecitabine. The invention has the advantages of avoiding using severe toxicity reagent such as, chloro formate, or phosgene etc, stable and easily gaining raw material, easy industrialization operation etc.

A combination of a 4-anilino-3-cyanoquinoline compound (e.g. HKI-272, SKI-606, EKB-569) and a capecitabine compound in the treatment of a neoplasm is provided. Regimens, kits, and methods for treatment of neoplasm, including breast cancer including metastatic breast cancer, and lung cancer, using this combination, optionally in combination with other anti-neoplastic agents, or immune modulators are also described.

The invention relates to a new method for continuously operating to synthesize capecitabine, which is characterized in that 5-flucytosine is subjected to acylation, condensation and hydrolysis to synthesize the capecitabine. The invention has the advantages of reasonable reaction sequence, continuous operation of three steps, operation simplification, high yield, low cost and less pollution.

The invention relates to the use of alkylphosphocholines in combination with antimetabolites for the treatment of multiple myeloma, colon cancer or renal cancer. Preferred alkylphosphocholines are described by the Formula II.A particularly effective treatment includes administering a combination of perifosine and capecitabine.

The invention provides a paclitaxel and diazepinocarbazole compound combined pharmaceutical composition, which comprises active ingredients and pharmaceutically acceptable excipients. The paclitaxel and diazepinocarbazole compound combined pharmaceutical composition is characterized in that the active ingredients are composed of gemcitabine and a diazepinocarbazole compound as shown in the formulaI or pharmaceutically acceptable salts thereof; and mass ratio of gemcitabine to the diazepinocarbazole compound or the pharmaceutically acceptable salts in the active ingredients is (2-8): 1. The pharmaceutical composition has good anticancer curative effect but low toxic or side effect. As the diazepinocarbazole compound is sensitive to gemcitabine, the diazepinocarbazole compound and gemcitabine are combined to produce a synergistic effect. Thereby, clinical dosage of capecitabine is reduced, toxic or side effect caused by large dosage of capecitabine is decreased, and safety index of clinic treatment is raised. The paclitaxel and diazepinocarbazole compound combined pharmaceutical composition has a good clinical application prospect.

The invention discloses nanoscale capecitabine and a preparation method thereof, relating to an antitumor drug capecitabine. In order to further improve the targeted treatment function, further improve the bioavailability, reduce the toxic and side effects and improve the treat effect, the invention firstly aims at providing a novel nanoscale capecitabine particle which is characterized by taking silicon dioxide aerogel as a carrier of the capecitabine; the invention secondly aims at providing a preparation method of the nanoscale capecitabine particle; and the preparation method is characterized by comprising the steps of: dissolving the capecitabine in absolute ethyl alcohol, adding the silicon dioxide aerogel according to a proportion, drying after complete adsorption, adding purified water and sending into an emulsifying machine for emulsification, homogenizing through a high-pressure homogenizer, and drying the obtained homogenate to obtain the nanoscale capecitabine particle. The nanoscale capecitabine has extremely high bioavailability for oral administration.

The invention provides a method of treating a subject with cancer, particularly leukemia, lymphoma, solid cancer such as colorectal cancer, gastric cancer, bladder cancer, non-small cell lung cancer, and breast cancer, comprising administering to the subject a compound of formulae (I) 40 or (Ia) in combination with an antimetabolite such as methotrexate, pemetrexed, cytarabine or nelarabine, or 5-fluorouracil, or capecitabine or their derivatives.

The invention discloses a method for preparing an anticancer medicine capecitabine and a hydroxyl derivative key intermediate thereof, and belongs to the technical field of pharmaceutical chemistry. The method is characterized in that: N-[(p-pentyloxy)carbonyl]-5-flurocytosin is taken as an initial raw material, and is subjected to five steps of chemical reactions to form the capecitabine. The preparation method has the advantages of reasonable sequence, readily available raw materials, mild reaction conditions, high process controllability, high yield and low cost. The crude intermediate has high purity, complicated purification treatment is avoided, the capecitabine obtained in a later stage can reach the standard of United States Pharmacopeia, and the method is more suitable for industrial production.

The invention discloses a synthesis method of antineoplastic medicine capecitabine, belonging to the technical field of pharmaceutical chemistry. The method takes xylose as raw material, and the capecitabine can be obtained through eight-step chemical reaction. The synthetic route uses the raw material which can be easily obtained and is low in price, has short reaction time, simple operation and high yield, and is easy for industrial production.

The invention relates to a preparation method of 2'3'-di-O-acetyl-5'-desoxy-5-fluoro-N4-(pentyloxycarbonyl)cytidine, belonging to the technical field of medicine. The compound is an important intermediate of Capecitabine. The preparation method comprises the following step: by using anhydrous sodium carbonate or anhydrous potassium carbonate as alkali, quaternary ammonium salt as a phase-transfer catalyst and 4-substituted-pyridine as a catalyst, carrying out amidation reaction on 2'3'-di-O-acetyl-5'-desoxy-5-fluorocytidine and amyl chloroformate to obtain the 2'3'-di-O-acetyl-5'-desoxy-5-fluoro-N4-(pentyloxycarbonyl)cytidine. The invention adopts the anhydrous sodium carbonate or anhydrous potassium carbonate instead of the high-toxicity organic alkali pyridine, and obtains ideal yield and product purity. The method has the advantages of accessible raw materials, low cost, small environmental hazard, high safety and reliability, short reaction time and good product quality.

The invention discloses a method for carrying out carbalkoxylation acylation on fluorouracil compound with an active coupling agent, and applications thereof in synthesizing capecitabine. The method comprises the steps of carrying out N-4 site acylation reaction of coupling agent shown as the formula (1) and fluorouracil complex shown as the formula (8), introducing active carbonyl at N-4 site to obtain acylate, directly reacting the acylate with alcohol or phenol without separation, and carrying out N-4 site carbalkoxylation acylation reaction, thus obtaining carbalkoxylation acylate of fluorouracil compound. The carbalkoxylation acylation method can be used for preparing capecitabine. The method conducts acylation and carbalkoxylation acylation on cytidine by adopting coupling agent and alcohol or phenol, thus avoiding use of chlorocarbonic ester or phosgene acylating agent, being used for preparing capecitabine, and being stable and easy to obtain raw materials, high in product purity, safe and environment-friendly for operation environment, and easy for industrial operation.

The invention discloses a kit for simultaneously detecting capecitabine and its metabolite in blood plasma. The capecitabine and its metabolite are respectively capecitabine, 5'-deoxy-5-gemcitabine, 5'-deoxy-5-floxuridine, 2'-deoxy-5-floxuridine, 5-fluorouracil, and 5-fluoro-5,6-dihydrouracil; the kit also comprises the following reagents: an eluate, contrast mother liquor, a mixed internal standard solution, a weak solution, an extract, and quality control liquid. The invention also discloses an application of the kit for simultaneously detecting capecitabine and its metabolite in blood plasma in preparation of a kit for diagnosing or screening hematology of malignant tumors. The kit has the advantages of high sensitivity, high specificity, and high accuracy for simultaneously detecting capecitabine and its metabolite in blood plasma, and a pre-processing process is simple.

The invention belongs to the technical field of medicine preparation and relates to a synthetic method of capecitabine. The method comprises the following steps: 1) condensation reaction: reacting 2', 3'-bi-O-acetyl-5'-deoxy-5-fluoro-cytidine with halo n-amyl formate in the presence of an acid applying agent and a dimethylamino-pyridine catalyst to prepare N-pentyloxy carbonyl-2' 3'-bi-O-actyl-5'-deoxy-5-fluoro-cytidine; and 2) hydrolysis reaction: carrying out hydrolysis reaction on N-pentyloxy carbonyl-2' 3'-bi-O-actyl-5'-deoxy-5-fluoro-cytidine in the presence of an inorganic base to prepare the final product capecitabine. Compared with the prior art, the method provided by the invention has the advantages that by taking the inorganic base as the acid applying agent, use of a lot of organic bases is avoided and therefore the yield is improved, the production cost lowered, the environmental pollution is reduced, the physical health of the worker is ensured, and industrial production is facilitated.

The present invention provides cancer treatment preparations of excellent targetability. The sugar chain-modified liposomes of the present invention, which contain an aromatase inhibitor, anti-androgenic agent, lyase inhibitor, GnRH agonist, GnRH antagonist, anti-angiogenic agent, tyrosine kinase inhibitor, serine-threonine kinase inhibitor, antibody having an anticancer activity, ansamitocin, capecitabine, celmoleukin, docetaxel hydrate, gemcitabine hydrochloride, oxaliplatin, prednisolone, tegafur-uracil mixtures, zinostatin stimalamer or arsenic trioxide may be used as cancer treatment preparations having an excellent targetability.

The invention discloses a capacitabine dispersible tablet and a preparation method thereof. The formula of the dispersible tablet is as follows: the proportion of a main drug of capacitabine ranges from 70%-80%; the proportion of an adhesive of polyvinylpyrrolidone K30 ranges from 3%-7%; the proportion of a disintegrating agent of cross-linked sodium carboxymethyl cellulose ranges from 3%-7%; and the proportion of a filling agent of microcrystalline cellulose ranges from 10%-20%.

The invention discloses application of HM-3 and platinum, paclitaxel or capecitabine medicine for preparing a solid tumor medicine, belonging to the field of medicines for treating tumor. Platinum, paclitaxel or capecitabine antimetabolites serve as active components and accompanied by a pharmaceutically acceptable carrier to be prepared into various pharmaceutically acceptable preparations. A plurality of experiments show that an integrin blocker HM-3 is clear in target; the integrin blocker HM-3 is reasonably used together with the platinum, paclitaxel or capecitabine for effectively suppressing growth of tumors in lung cancer, liver cancer, stomach cancer, breast cancer, cervical cancer, ovarian cancer, intestinal cancer, and the like. The combined medicine serves as a medicine and is capable of effectively treating tumors; the combined medicine is scientific, reasonable, feasible and effective, so that the treatment spectrum for treating the tumors is greatly expanded; the toxic and side effects are reduced; the HM-3 and platinum, paclitaxel or capecitabine medicine is prominent in social value and market value.