68 results about "Topotecan HCl" patented technology

A method of using an MMP inhibitor and optionally radiation therapy, and one or more antineoplastic agents of the topoisomerase class selected from the group consisting of irinotecan and topotecan, as a combination therapy for the treatment of neoplasia is disclosed.

Conjugates of transferrin, albumin and polyethylence glycol consisting of native or thiolated transferrin or albumin or of polyethylene glycol (MW between approximately 5,000 and 20,0000) with at least one HS-, HO- or H2N group and cytostatic compounds derived through maleinimide or N-hydroxysuccinimide ester compounds, such as doxorubicin, daunorubicin, epirubicin, idarubicin, mitoxandrone, chloroambucil, melphalan, 5-fluorouracyl, 5'-desoxy-5-fluorouridine, thioguanine, methotrexate, paclitaxel, docetaxel, topotecan, 9-aminocamptothecin, etoposide, teniposide, mitopodoside, vinblastine, vincristine, vindesine, vinorelbine or a compound of general formula A, B, C or D, where n=0-6, X=-NH2, -OH, -COOH, -O-CO-R-COR*, -NH-CO-R-COR*, where R is an aliphatic carbon chain with 1-6 carbon atoms or a substituted or unsubstituted phenylene group and R* H, phenyl, alkyl with 1-6 carbon atoms.

A method of preparing and using a sterile non-toxic pyrogen-free cold extract from the leaves of Nerium oleander as a supplementary medication to cancer chemo-, hormon and / or radiotherapy to restore and / or ameliorate the immune system of the patient and / or to decrease side effects and increase the antitumor effects of radiotherapy and chemotherapeutics, particularly when used in combination with taxol, adriamycin, cisplatin, 5-fluoro-uracil, alimta, cyclophosphamide, mitomycin-C, navelbine, taxotere and topotecan, respectively, and its use in the manufacture of a medicament for the treatment of one or more cancers of bladder, kidney, liver, ovary, pancreas, testicle, uterus, and vagina as well as pleuramesotheliomas and Hodgkin's lymphomas.

A topotecan liposomal composition which can be reconstituted from a lyophilized form to an injectable liposome suspension having selected liposome sizes in the size range between 0.05 and 0.25 microns, and between about 85-100% liposome-entrapped topotecan is disclosed.

A pharmaceutical composition comprising a solid unit dosage form comprising: one or more of pharmaceutically active ingredients selected from valacyclovir, olanzapine, voriconazole, topotecan, artesunate, amodiaquine, guggulosterone, ramipril, telmisartan, tibolone, atorvastatin, simvastatin, amlodipine, ezetimibe, fenofibrate, tacrolimus, valgancyclovir, valsartan, clopidrogel, estradiol, trenbolone, efavirenz, metformin, pseudoephedrine, verapamil, felodipine, valproic acid / sodium valproate, mesalamine, hydrochlorothiazide, levosulpiride, nelfinavir, cefixime and cefpodoxime proxetil in combination with a water insoluble polymer and / or a water soluble polymer. Methods for making the pharmaceutical composition are also disclosed.

Disclosed is an anti-cancer composition slow release injection which comprises slow release microspheres and dissolvent, the slow release microspheres comprise slow release auxiliary materials, Epothilone derivatives, glyoxaline piperazidine, Topo enzyme inhibitor combination selected from SN-38, CPT-11, HCPT, Topotecan, Irinotecan, Etoposide, Teniposide, Amrubicin, Valtaxin, XK469, AD312, ICRF-187 or ICRF-193, the dissolvent being specific dissolvent containing suspension adjuvant, the slow release auxiliary materials are selected from polylactic acid and its copolymer, polyethylene / polylactic acid, glycollic acid copolymer, aliphatic acid and sebacylic acid copolymer, the viscosity of the suspension adjuvant is 80-3000cp (at 20-30 deg C), and is selected from carboxymethylcellulose, The slow release microspheres can also be prepared into slow release implanting agent, for injection or placement in or around tumor with a release period of about 40 days. The slow release injection and slow release implanting agent can be used independently for effectively suppressing tumor accretion, or used in combination with non-operative methods such as chemotherapy and / or radiotheraphy with the function of improving their treatment effects.

The invention belongs to the field of pharmaceutical preparations, and relates to preparation of a novel target nano carrier and application of the novel target nano carrier in a camptothecin drug targeting delivery system. The system can be represented as PAMAM-HA / drug, wherein PAMAM is polyamide amine-amine arboraceous macromolecules of different generations, HA is hyaluronic acid of different molecular weights, and the drug is one or more of camptothecin anticancer drugs such as camptothecin, 10- hydroxycamptothecine, topotecan and the like. The carrier is used for wrapping the camptothecin drugs, and has the actions of prolonging the drug blood circulation time, improving the drug bioavailability, reducing the non-tumor part concentration of the drug, reducing the drug cytotoxicity, and simultaneously protecting the lactonic rings of the camptothecin drugs from damage, thereby improving the tumor treatment efficiency from multiple aspects. The nano carrier provided by the invention has important significance in promoting the safe delivery of the camptothecin drugs and the effective treatment of tumor.

A process for preparing topotecan.

Convection-enhanced delivery (CED) is used as a method to deliver a direct infusion of therapeutic agents to the central nervous centre thus circumventing the blood-blood barrier. A non-PEGylated liposomal composition comprising at least one saturated neutral phospholipid and at least one saturated anionic phospholipid and a therapeutic or diagnostic agent encapsulated therein is used to overcome toxicity associated with high peak drug concentration delivered locally CED as well as to increase tissue distribution volume for an improved sustained drug release. In one embodiment, the liposome composition comprises a molar ratio of DSPC:DSPG:CHOL of 7:2:1 and the therapeutic or diagnostic agent is selected from topotecan, conotoxin, gadodiamide or rhodamine, and is used in the treatment of epilepsy

This invention relates a method of treating hyperproliferative diseases. More particularly, the present invention relates to a method of treating hyperproliferative diseases, such as cancer, comprising the step of administering to a mammal in need of such treatment, either simultaneously or sequentially, (i) a therapeutically effective amount of a taxane derivative, a platinium coordination complex selected from the group consisting of carboplatin, tetraplatin, and topotecan, a nucleoside analog selected from the group consisting of gemcitabine hydrochloride and 5-FU, an anthracycline, a topoisomerase selected from the group consisting of etoposide, teniposide, amsacrine, topotecan, and Camptosar®, an aromatase inhibitor; and (ii) a therapeutically effective amount of an isothiazole derivative. The combinations of the present invention may optionally include an anti-hypertensive agent. This invention also relates to pharmaceutical compositions useful in the treatment of hyperproliferative diseases in mammals, containing such combinations. The present invention also relates to kits having a first compartment with a compound of formula 1 and a second compartment containing a taxane derivative, a platinum coordination complex, a nucleoside analog, an anthracycline, a topoisomerase inhibitor, or an aromatase inhibitor and a third compartment containing an anti-hypertensive agent.

New processes are disclosed for the preparation of camptothecin derivatives, such as, irinotecan and topotecan, as well as new intermediates and compounds related thereof.

Medical devices, and in particular implantable medical devices, may be coated to minimize or substantially eliminate a biological organism's reaction to the introduction of the medical device to the organism. The medical devices may be coated with any number of biocompatible materials. Therapeutic drugs, agents or compounds may be mixed with the biocompatible materials and affixed to at least a portion of the medical device. These therapeutic drugs, agents or compounds may also further reduce a biological organism's reaction to the introduction of the medical device to the organism. In addition, these therapeutic drugs, agents and / or compounds may be utilized to promote healing, including the formation of blood clots. Also, the devices may be modified to promote endothelialization. Various materials and coating methodologies may be utilized to maintain the drugs, agents or compounds on the medical device until delivered and positioned. In addition, the devices utilized to deliver the implantable medical devices may be modified to reduce the potential for damaging the implantable medical device during deployment. Medical devices include stents, grafts, anastomotic devices, perivascular wraps, sutures and staples. In addition, various polymer combinations may be utilized to control the elution rates of the therapeutic drugs, agents and / or compounds from the implantable medical devices.

The invention relates to a novel crystalline form of topotecan hydrochloride, and methods of making the same. The characteristic XRPD pattern and FT-IT patterns are shown in FIGS. 1 and 2.

The present invention relates to treatment of Trop-2 positive cancers with the combination of anti-Trop-2 ADC and a Rad51 inhibitor. Preferably the drug conjugated to the antibody is SN-38, and the ADC is sacituzumab govitecan. The ADC may be administered at a dosage of between 4 mg / kg and 16 mg / kg, preferably 4, 6, 8, 9, 10, 12, or 16 mg / kg. When administered at specified dosages and schedules, the combination of ADC and Rad51 inhibitor can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Surprisingly, the combination is effective to treat cancers that are refractory to or relapsed from irinotecan or topotecan.

The present invention relates to treatment of SCLC with therapeutic ADCs comprising a drug attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. Preferably, the drug is SN-38. More preferably, the antibody is an hRS7 antibody and the ADC is sacituzumab govitecan. The ADC may be administered at a dosage of between 4 mg / kg and 16 mg / kg, preferably 4, 6, 8, 9, 10, 12, or 16 mg / kg, mostly preferably 8 to 10 mg / kg. When administered at specified dosages and schedules, the ADC can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Surprisingly, the ADC is effective to treat cancers that are refractory to or relapsed from irinotecan or topotecan. Preferably, the ADC is administered as a combination therapy with one or more other anti-cancer treatments, such as carboplatin or cisplatinum.

The disclosed method rapidly identifies with desired accuracy AML patients, including elderly AML patients, likely to respond to treatment with a combination of a farnesyltransferase inhibitor and one or more of etoposide, teniposide, tamoxifen, sorafenib, paclitaxel, temozolomide, topotecan, trastuzumab and cisplatinum. In an embodiment, the improvements include the use of whole blood rather than the customary bone marrow sample, thus making the assay more accurate, rapid, less intrusive, less expensive as well as less painful. The method includes evaluation of a two-gene expression ratio (RASGRP1:APTX), which with a corresponding threshold, provides sufficient accuracy for predicting the response to the combination treatment. In the preferred embodiment the combination treatment combines tipifarnib (R115777, ZARNESTRA®) with etoposide. Further, the elderly AML patients identified as being likely responsive to the combination treatment with tipinifarb and etoposide have a complete recovery rate comparable to the best therapy available for younger patients.

The invention relates to a thermal sensitive liposome preparation containing camptothecin antineoplastic agents, which contains the camptothecin antineoplastic agents, common lipoid, a phase-change regulator and an optional long-circulating material, wherein the phase-change regulator accounts for 6-100% of the weight of liposome, the long-circulating material accounts for 0-40% of the weight of the liposome, and the weight ratio of the amptothecin antineoplastic agents to the liposome is 1:0.5-1:100. Since the liposome preparation is characterized by thermal sensitivity, when the tissues of a tumor are heated partially, the liposome is targeted to the position of the tumor and releases a lot of medicine at the position of the tumor, thereby improving the curative effect and reducing the overall toxic and side effect. The camptothecin antineoplastic agents of the inveition can include water-solubility derivatives, such as irinotecan and topotecan, and water-insolubility derivatives, such as hydroxycamptothecine, SN-38, 9-NC, and the like.

The present disclosure relates to a pharmaceutical composition, a health functional food composition, and a method for preventing or treating a brain disease or diabetes. The pharmaceutical composition, health functional food composition, and method includes at least one active ingredient that is chlorhexidine, thioguanosine, mebendazole, fenbendazole, colchicine, farnesol, trimethobenzamide hydrochloride, disulfuram, azathioprine, mebeverine hydrochloride, zaprinast, tosufloxacin hydrochloride, efavirenz, thiostrepton, probenecid, entacapone, harmine hydrochloride, flunisolide, thimerosal, hexestrol, sulfaquinoxaline sodium salt, monensin sodium salt, raloxifene hydrochloride, 2-chloropyrazine, or topotecan.

The invention provides a topotecan hydrochloride targeted liposome preparation and a preparation method of the topotecan hydrochloride targeted liposome preparation. According to the topotecan hydrochloride targeted liposome preparation, antitumor drug topotecan hydrochloride is encapsulated into a targeted long-circulating liposome modified by hydrophilic polymer polyethylene glycol and targeted ligand RGD cyclopeptide, and the lipsome is capable of prolonging the circulating time of the medicine in the body, thereby the tumor targeting is achieved, the curative effect is improved and the toxic and side effects are reduced.

The present invention relates to the use of dihalomethanes as reagents for the preparation of Topotecan{4-(S)-10(dimethylamino)-methyl-4-ethyl 4,9 dihydroxyl-H-pyrano[3'4':6,7]indolizino-[1,2-b]quinoline-3,14(4H,12H)dione} from 10-hydroxycamptothecin. The invention discloses the rationale use of dichloromethane under solid-liquid phase transfer catalysis, which can behave both as solvent and a reactant when it serves as a source for C-1 unit for amino-alkylation of 10-hydroxy-4-(S)camptothecin.

Therapeutic pharmaceutical compositions and methods of treatment of abnormal cell growth comprising a pyrimidine derivative or a pharmaceutically acceptable salt, solvate or prodrug thereof in combination with an oral camptothecin, an oral camptothecin derivative, an indolopyrrocarbazole derivative or a pharmaceutically acceptable salt, solvate or prodrug thereof for the treatment of cancer are described. In one embodiment of the present invention the oral camptothecin derivative is selected from the group consisting of 10-hydroxycamptothecin, 9-aminocamptothecin, 9-nitrocamptothecin, irinotecan, irinotecan salt, SN-38, CPT-11, and topotecan and the indolopyrrocarbazole derivative is edotecarin. In one embodiment the pyrimidine derivative is selected from the group consisting gemcitabine, MTA and capecitabine. In one preferred embodiment, the pyrimidine derivative is capecitabine and the camptothecin derivative is CPT-11.

This invention relates to a topotecan liposome and its preparation method. The preparation can be used as therapeutic drug of multiple tumours such as non-small cell lung cancer, liver cancer, stomach cancer, hematopathy, and lymphomata. The topotecan liposome is characterised in containing topotecan and at least one biologic receivable phospholipid at a weight ratio of 1:0.5. The phospholipid is selected from one of natural phospholipid, hydrogenated soybean phosphatide, and synthesized phospholipid. The liposome can also contain cholesterol and supported reagent. The supported reagent is selected from one of glucose, mannit, sucrose, sorbitol, dextran, lactose, and trehalose. The weight ratio of phospholipid and supported agent is 1:0.01-500. The preparation method comprise film dispersion, injection, ultrasonic dispersion, lyophilization, freeze thawing, forceful discharging, preparing with a viscolizer, and preparing through microjet under high pressure.

The present invention is directed to a method of inhibiting cancer cell growth, comprising administering a pharmaceutical composition to a subject in need thereof. The pharmaceutical composition comprises at least one camptothecin derivative or a pharmaceutically acceptable salt thereof; and at least one PEG phospholipid, and provides a sustained release of topotecan as an active ingredient.

New processes are disclosed for the preparation of camptothecin derivatives, such as, irinotecan and topotecan, as well as new intermediates and compositions thereof.

New uses for phenylketone carboxylate compounds and substituted aromatic compounds of Formula I, Formula I.1, Formula I.2, Formula IA, Formula IB, Formula IC and Formula II and their pharmaceutical acceptable salts for the treatment of cancer. The use of a combination of two of these compounds is described and the use of the combination of one of these compounds with an anticancer agent such as decarbazine, doxorubicin, daunorubicin, cyclophosphamide, busulfex, busulfan, vinblastine, vincristine, bleomycin, etoposide, topotecan, irinotecan, taxotere, taxol, 5-fluorouracil, methotrexate, gemcitabine, cisplatin, carboplatin and chlorambucil.

A process for preparing topotecan.

The invention provides a preparing method of a topotecan hydrochloride lipidosome nano preparation and the topotecan hydrochloride lipidosome nano preparation prepared by the same, wherein the method comprises the following steps: a), dissolving phospholipid, cholesterol and a modification material in ethanol to obtain an organic phase, injecting the organic phase into an aqueous solution containing a gradient regulator, stirring, and homogenizing to form a blank liposome; b) with adopting of a tangential flow filtration method, utilizing deionized water to replace the ionic gradient regulator in the aqueous phase outside the blank liposome, and thus forming an ion concentration gradient of the aqueous phases inside and outside the blank liposome; c) taking topotecan hydrochloride, mixing with the blank liposome formed in the step b), incubating under a temperature higher than a phospholipid phase transition temperature, and thus obtaining the topotecan hydrochloride liposome nano preparation. The method is simple to operate, has less time-consuming, has the quality easy to control, and is suitable for industrialized mass production.

The present invention generally relates to the fields of cancer therapy and cancer prevention. More particularly, the present invention generally relates to a diagnostic marker for predicting the efficacy of topoisomerase I (topo I) inhibitors in the treatment of cancers. More specifically, the present invention relates to methods, machines, computer systems, computable readable media and kits which can be used to identify and determine the effectiveness of topoisomerase I (topo I) inhibitors in the treatment of cancers, and in some embodiments, the level of sensitivity or resistance of a tumor cell to a topoisomerase I inhibitor, such as camptothecin (CPT), or CTP analogues such as topotecan and irinotecan and derivatives thereof. More specifically, the present invention related to methods, machines, computer systems, computable readable media and kits which can be used to determine the presence of phosphorylation of topoisomerase I polypeptide, in some embodiments phosphorylation at residue serine 10 (S10) of a topoisomerase I polypeptide, wherein the presence of phosphorylation, in particular the phosphorylation at serine 10 of a topoI polypeptide indicates a cancer is likely to be unresponsive to a topo I inhibitor, whereas the absence of phosphorylation, in particular, the absence of phosphorylation at residue serine 10 (S10) identifies a cancer is likely to be responsive to a topo I inhibitor. Other aspect of the present invention relate to phospho-serine 10 topoisomerase I antibodies and other protein binding moieties, and uses thereof.