275 results about "Anthracycline" patented technology

The present invention relates to conjugates of therapeutically useful anthracyclines with carriers such as polyclonal and monoclonal antibodies, proteins or peptides of natural or synthetic origin; methods for their preparation, pharmaceutical composition containing them and use thereof in treating certain mammalian tumors.

Compositions which comprise an anthracycline agent, and a cytidine analog are encapsulated in liposomal carriers. The preferred anthracycline agent is selected from the group of daunorubicin, doxorubicin, and idarubicin, while the preferred cytidine analog is selected from the group of cytarabine, gemcitabine, or 5-azacytidine. The combination of the anthracycline agent and cytidine analog encapsulated in said liposomal carriers are useful in achieving a drug retention and a sustained drug release for each therapeutic agent.

There has been required a clinically applicable solid preparation for injection which contains a block copolymer composed of a hydrophilic polymer structure moiety and a hydrophobic polyamino acid structure moiety and an anthracycline anticancer agent. It is intended to provide a clinically applicable solid preparation for injection which contains a block copolymer composed of a hydrophilic polymer structure moiety and a hydrophobic polyamino acid structure moiety, an anthracycline anticancer agent, a saccharide and a base.

The application describes methods for screening subjects with breast cancer to determine if the breast cancer will be responsive to a breast cancer therapy including an anthracycline. The application also describes methods for treating subjects with breast cancer by screening them for the likelihood of the effectiveness of treating the cancer with a therapy including anthracycline and administering the therapy in subjects when it is found that anthracycline is likely to be effective.

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.

The invention relates to methods and kits for the prediction of a likely outcome of chemotherapy in a cancer patient. More specifically, the invention relates to the prediction of tumour response to chemotherapy based on measurements of expression levels of a small set of marker genes. The set of marker genes is useful for the identification of breast cancer subtypes responsive to taxane based chemotherapy, such as e.g. a taxane-anthracycline-cyclophosphamide-based (e.g. Taxotere (docetaxel)-Adriamycin (doxorubicin)-cyclophosphamide, i.e. (TAC)-based) chemotherapy.

The invention relates to a method for preparing a chitosan or sodium alginate-modified carbon nanotube-targeted slow release carrier in the technical field of nano materials, which comprises the following steps: preparing cut carbon nanotubes; preparing modified carbon nanotubes; preparing a modified carbon nanotube-targeted slow release carrier and adding aqueous solution of an anthracycline anticancer medicament; and subjecting the solution to supersonic treatment, stirring treatment and suction filtration, washing the product of the suction filtration, drying the product at room temperature under vacuum to obtain the chitosan or sodium alginate-modified carbon nanotube-targeted slow release carrier carrying the medicament. The method can realize an adriamycin carrying ratio of between 151 and 161 percent according to measurement.

A method of synthesizing 4-R-substituted anthracyclines and their corresponding salts from 4-demethyldaunorubicin includes the steps of treating 4-demethyldaunorubicin with a sulfonylating agent to form 4-demethyl-4-sulfonyl-R3-daunorubicin. 4-Demethyl-4-R3-sulfonyl-daunorubicin is then subject to a reducing agent in the presence of a transition metal catalyst in a temperature range of about 30° C. to about 100° C. in a polar aprotic solvent in an inert atmosphere. Protected 4-demethoxy-4-R-daunomycin then undergoes hydrolysis in a basic solution to form the 4-R-substituted anthracyclines. The novel method lacks the step of forming a stereospecific glycoside bond between aglycone and aminoglycoside. The method also increases the yield of the final product up to 30 to 40%.

Novel iron chelators exhibiting neuroprotective and good transport properties are useful in iron chelation therapy for treatment of a disease, disorder or condition associated with iron overload and oxidative stress, eg. a neurodegenerative or cerebrovascular disease or disorder, a neoplastic disease, hemochromatosis, thalassemia, a cardiovascular disease, diabetes, a inflammatory disorder, anthracycline cardiotoxicity, a viral infection, a protozoal infection, a yeast infection, retarding ageing, and prevention and / or treatment of skin ageing and skin protection against sunlight and / or UV light. The iron chelator function is provided by a 8-hydroxyquinoline, a hydroxypyridinone or a hydroxamate moiety, the neuroprotective function is imparted to the compound e.g. by a neuroprotective peptide, and a combined antiapoptotic and neuroprotective function by a propargyl group.

Methods and compositions are provided for treating proliferative disorders, wherein the composition comprises at least one compound according to Formula I:wherein R1 is selected from the group consisting of —OH, —NH2, —NH—CH2—CO2H, —NH—CH(CH3)—CO2H, and —NH—C(CH3)2—CO2H, or a pharmaceutically acceptable salt of such a compound; and an anthracycline, e.g. doxorubicin, or a pharmaceutically acceptable salt thereof, or a platin, e.g. oxaliplatin, or a pharmaceutically acceptable salt thereof.

The present invention relates to therapeutic conjugates with the ability to target various antigens. The conjugate contains a targeting antibody or an antigen-binding fragment thereof and an anthracycline chemotherapy drug. The targeting antibody and the anthracycline chemotherapy drug are linked via a linker that includes a hydrazide moiety.

The invention discloses a method for detecting antitumor drugs by constructing an electrochemical sensor with two ratios in a same system. The method specifically comprises the following steps that 1, the antitumor drugs and two electrochemical active substances are added into a phosphate buffer solution to prepare a mixed solution; 2, a bare glassy carbon electrode is taken as a working electrode to be placed in an electrolyte solution containing the mixed solution to be stabilized for a period of time, and then square wave voltammetry detection is conducted; 3, ratios (I1 and I2) of peak currents of the antitumor drugs with the different concentrations to peak currents of the other two electrochemical active substances with the different current peak positions are obtained, linear equations are constructed for the concentrations of the antitumor drugs according to I1 and I2, and then the electrochemical sensor with two ratios can be developed. The method is easy to operate, mild in condition and high in antijamming property, stability and sensitivity, can be used for efficient detection on the anthracycline antitumor drugs in serum and has an important application prospect in the fields of bioanalysis and clinical diagnosis.

Medical implants are provided which release an anthracycline, fluoropyrimidine, folic acid antagonist, podophylotoxin, camptothecin, hydroxyurea, and / or platinum complex, thereby inhibiting or reducing the incidence of infection associated with the implant.

Anthracycline analogs and their bioconjugates are useful as anticancer agents.

A method of treating the human body for cancer comprises administering an effective therapeutic amount of a Pegylated Liposomal form of the anthracycline Doxorubicin (“PLD”), in combination with an effective therapeutic amount of ET-743

The invention discloses an anthracycline liposome injection, including the injection and a frozen powder injection and a preparation process of the injection. The frozen liposome consists of the anthracycline or an anthracycline hydrochloride, compound neutral phospholipids, surfactant, negative-charge phospholipids, buffers, PH regulators and freezing protection agent. The preparation process includes the following steps: preparation of a hollow liposome, a homogenized liposome, an anthracycline lopsome and an anthracycline lopsome suspension; adding the freezing protection agent; constant volume; sterilization; sub-package; freezing and drying; storage, etc. The liposome injection can be preserved for 12 months under the room temperature with better stability. And the encapsulation rate can be above 95 percent and a granule diameter is between 30 and 300mm. The side effect is low and the technique is simple, thus being convenient for industrial production.

This invention pertains to pharmaceutical formulations which comprise (i) a drug (e.g., an amphiphilic drug) (e.g., an anthracycline) (e.g., doxorubicin) and (ii) a short-chain sphingolipid (e.g., a short-chain glycosphingolipid or a short-chain sphingomyelin) (e.g., N-octanoyl-glucosylceramide, referred to as C8-GlcCer) (e.g., N-hexanoyl-sphingomyelin, referred to herein as C6-SM), and which provide improved drug delivery and efficacy. The short-chain sphingolipidis selected from compounds of the following formula: wherein: R1 is independently: an O-linked saccharide group; or an O-linked polyhydric alcohol group; or: R1 is independently: an O-linked (optionally N-(C1-4alkyl)-substituted amino)-C1-6alkyl-phosphate group; or an O-linked (polyhydric alcohol-substituted)-C1-6alkyl-phosphate group; R2 is independently C3-9alkyl, and is independently unsubstituted or substituted; R3 is independently C7-19alkyl, and is independently unsubstituted or substituted; R4 is independently —H, —OH, or —O—C1-4alkyl; RN is independently —H or C1-4alkyl; the bond marked with an alpha (α) is independently a single bond or a double bond; if the bond marked with an alpha (α) is a double bond, then R5 is —H; if the bond marked with an alpha (α) is a single bond, then R5 is —H or —OH; the carbon atom marked (*) is independently in an R-configuration or an S-configuration; the carbon atom marked (**) is independently in an R-configuration or an S-configuration; and pharmaceutically acceptable salts, solvates, esters, ethers, chemically protected forms thereof. In one embodiment, the pharmaceutical formulation is a liposomal pharmaceutical formulation prepared using a mixture of lipids comprising, at least, vesicle-forming lipids (e.g., phospholipids) (e.g., phosphatidylcholines) (e.g., fully hydrogenated soy phosphatidylcholine (HSPC)) (e.g., dipalmitoyl-phosphatidylcholine (DPPC)) and said short-chain sphingolipid, and optionally cholesterol and optionally a vesicle-forming lipid which is derivatized with a polymer chain (e.g., a phosphatidylethanolamine (PE) which is derivatized with polyethyleneglycol (PEG)) (e.g., N-(carbonyl-methoxypolyethylene glycol 2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine sodium salt (MPEG2000-DSPE). The present invention also pertains to methods for the preparation and use of such formulations.

Medical implants are provided which release an anthracycline, fluoropyrimidine, folic acid antagonist, podophylotoxin, camptothecin, hydroxyurea, and / or platinum complex, thereby inhibiting or reducing the incidence of infection associated with the implant.

The present invention is a compound having the structurewhere:anthracycline is doxorubicin, daunorubicin or a derivative thereof;N is the 3' nitrogen of daunosamine;Ra is H or alkyl;X is, O, S, CRc2 or NRc where Rc is H or alkyl;Rb is alkyl or aryl;n is 1 to 6; andm is 0 to 6.Ra and Rc are preferably H, methyl, ethyl, propyl or butyl, although other alkyl substituents are usable. Rb is alkyl or aryl. The compound of the present invention as described above is activatable in vivo by esterases and spontaneous dehydration to form an aldehyde. The aldehyde may couple to nucleophiles of intracellular macromolecules. The compounds of the present invention are cytotoxically effective in the inhibition of human myeloma cells.

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.

This invention provides an aqueous / t-butanol solvent-system, facile reconstitute, submicron-reconsitiute preliposome-lyophilaye and method of its preparation and use.In one embodiment this entails a modified method for the preparation of a submicron and stable liposome formulation of the non-cross-resistant anthracycline Annamycin is described. The optimal lipid composition was DMPC:DMPG at a 7:3 molar ratio and the optimal lipid:drug weight ratio 50:1. The selected formulation is a preliposome lyophilized powder that contains the phospholipids, Annamycin, and 1.7 mg Tween 20 per mg of Annamycin. The liposome suspension is obtained on the day of use by adding normal saline at 37° C. (1 ml per mg Annamycin) and hand-shaking for one minute. The presence of Tween 20 is essential in shortening the reconstitution step (from >2 hours to 1 minute), avoiding the early formation of free drug crystals, and reducing the median particle size (from 1.5 μm to 0.15-0.20 μm) without destruction of the liposome vesicles. The chemical stability of the preliposome powder at room temperature was >3 months and the chemical and physical stability of the liposome suspension at room temperature >24 hours. The in vitro cytotoxicity of the formulation was equivalent to that prepared by the standard evaporation method. The results of the study indicate that small amounts of surfactant may be used to enhance the reconstitution step and reduce the liposome size of lyophilized liposome formulations of lipophilic drugs.

The invention relates to a method for screening anthracycline cardiotoxicity genes through mRNA expression profiles and competitive endogenesis RNA expression profiles jointly. The method includes the steps that expression values of a large quantity of genes are detected through mRNA and competitive endogenesis RNA expression profile chips, and the correlations of all the genes are ordered; the obtained mRNA feature genes and the obtained competitive endogenesis RNA feature genes are combined; a gene pool is subjected to further gene selection with a genetic algorithm; differential expression genes are selected by comparing the data between different samples of mRNA and competitive endogenesis RNA joint expression profiles of breast cancer patients, breast cancer AIC patients and able-bodied persons; the differential expression genes are predicted, and the genes with the scores larger than 140 and free energy smaller than 20 are selected as reliable target genes; genes with obvious differences are selected from the target genes, and constructed breast-cancer anthracycline cardiotoxicity attacking target genes are verified through the residual RNA. By means of the method, more reliable potential gene markers related to anthracycline cardiotoxicity can be selected as a candidate.

The invention relates to a polymer vesicle of a double-loading anthracycline ring medicine and a photosensitizer, having a bubble generation function, as well as preparation. A pH / temperature double-sensitive multifunctional polymer vesicle of hydrophilic inner cavity loaded anthracycline ring medicine and a hydrophobic film loaded photosensitizer, having the bubble generation function, is prepared by taking an amphiphilic triblock copolymer PCL-b-PEG-b-PCL as a material. The anthracycline ring medicine is wrapped with and loaded in the hydrophilic inner cavity by an ammonium hydrogen carbonate gradient active medicine loading method, ammonium hydrogen carbonate can be decomposed under the condition of low pH value or heating to generate carbon dioxide bubbles, the structure of the vesicleis broken and the wrapped medicines are released rapidly. After the medicines are delivered to the local part of tumor through EPR (enhanced permeability and retention) targeting, the therapeutic effect of the anthracene ring chemotherapeutic medicines on the tumor can be obviously improved under illumination. The polymer vesicle can serve as a medicine carrier to wrap and load hydrophilic and hydrophobic medicines simultaneously, has a stable structure, has high biocompatibility and degradability, and has a wide application prospect on the aspects of medicine delivery and controllable release and chemotherapeutic combined photothermal therapy on the tumor.

The invention provides a method for preparing an anthracycline antitumor antibiotic oleic acid compound and an oil-water double phase for preparing the compound and albumin, and the anthracycline antitumor antibiotic oleic acid compound is prepared into an albumin nanoparticle preparation. The albumin nanoparticle preparation prepared by the method is little in using amount of auxiliary materials, high in medicine-carrying dose and high in stability, and a preparation process is simple and is suitable for large-scale industrial production; and the albumin nanoparticle preparation has the tumor targeting and good clinical application value.

The invention relates to a tumor-targeted sound and light power medicine-carrying nanometer nano-micelle, and a preparation method and a purpose thereof. The medicine-carrying nanometer nano-micelle is structurally characterized in that porphyrins compounds and anthracyclines chemotherapeutic medicine form a nanometer composition through a pi-pi conjugation effect; and amphiphilic block copolymers with PEO (polyoxyethylene) or PEG (polyethylene glycol) hydrophilic segments cover nanometer compounds through the hydrophobic effect to form a hydrophilic case. The medicine-carrying nanometer nano-micelle is in a regular spherical form, and has the advantages of uniform distribution, stable property and high medicine carrying capacity; the medicine can be conveyed to the tumor focus in the targeted way and can be effectively enriched in the tumor tissue; under the ultrasound (illumination) condition, the treatment effect of the anthracyclines chemotherapeutic medicine on the tumor can be obviously enhanced; and the tumor drug resistance can be effectively reversed. Wide clinic application prospects can be realized in an aspect of combined tumor treatment by a sound (light) power therapy method and chemotherapy.

The present invention relates to the use of cardiac hormones, particularly natriuretic peptides, for diagnosing the risk of suffering from a cardiovascular complication, particularly heart disease or acute coronary syndrome, as a consequence of cardiotoxic medication, in particular chemotherapeutics, including anthracyclines. In particular, the invention relates to a method for diagnosing the risk of a patient who is going to receive cardiotoxic medication of suffering from a cardiovascular complication as a consequence of the cardiotoxic medication, comprising the steps of (a) taking a body fluid or tissue sample, and (b) measuring, preferably in vitro, the level of a cardiac hormone. Preferred cardiac hormones in the context of the present invention are ANP, NT-proANP, BNP, and NT-proBNP.

The use of radio-labeled antitumor drugs in the treatment of solid tumors by the method of administering a radio-labeled anticancer drug to a patient and imaging at least a part of the patient using Positron Emission Tomography imaging is described. The method can be used to monitor delivery of antitumor drugs to tumors, to predict the effectiveness of therapy with a particular antitumor drug or combination of antitumor drugs, to assess the effectiveness of modulators of cellular accumulation, to individualize therapy and to evaluate the effectiveness of antitumor drugs with respect to particular cancers. Particularly preferred drugs are labeled taxanes, e.g., 11C-paclitaxel and 11C-docetaxel, labeled anthracyclines, e.g., 11C-doxorubicin and 11C-epirubicin, and other radiolabeled drugs, e.g. 11C-topotecan, 11C-SN-38, and 11C-imatinib. The invention further describes antitumor drugs labeled with the radioactive label 11C and methods of preparing radio-labeled drugs.