113 results about "Melphalan" patented technology

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.

Shown and described are the synthesis of more potent forms of C-Mel, a prodrug used in Antibody-Directed Enzyme Prodrug Therapy, that releases the clinically used anticancer alkylating agent melphalan extracellularly. Shown and described are the synthesis of a variety of melphalan analogues with the intention to promote facile intracellular drug access. Esters, amides, and peptides of melphalan are shown. Cephalosporin prodrugs of the most interesting melphalan derivatives were synthesized and evaluated for potency, toxicity, therapeutic window, plasma stability, and solubility.

The present invention is in the field of drug delivery, and specifically, cationic liposome-based drug delivery. In embodiments, this invention provides methods of making ligand-targeted (e.g., antibody- or antibody fragment-targeted) liposomes useful for the delivery of liposomes to tumors, including brain tumors. In embodiments, the liposomes deliver temozolomide across the blood-brain barrier for treatment of primary or metastatic brain tumors. Additional cancers that can be treated with the liposomes include neuroendocrine tumors, melanoma, prostate, head and neck, ovarian, lung, liver, kidney, breast, urogenital, gastric, colorectal, cervical, vaginal, angiosarcoma, liposarcoma, rhabdomyosarcoma, choriocarcinoma, pancreatic, retinoblastoma and other types of cancer. In another embodiment the liposomes deliver melphalan for the treatment of multiple myeloma, other tumors of the blood or other solid tumors. In still other embodiments the liposomes can deliver other drugs such as pemetrexed or irinotecan for treatment of cancer or drugs including atropine for treatment of organophosphate poisoning.

The invention relates to a melphalan freeze-dried powder injection and a preparing method thereof. The prepared melphalan freeze-dried powder injection is used for treating multiple myeloma, oophoroma, polycythemia vera, local malignant melanoma and soft tissue sarcoma. The melphalan freeze-dried powder injection contains melphalan, utilizes the mixed solvent composed of the tert-butyl alcohol and the injection water in the preparation process, wherein the concentration of the melphalan in the mixed solvents is 10-25 mg / ml; and the volume ratio of the solvents is: 5-50% of tert-butyl alcohol and the balance of injection water. The preparation process comprises the following steps: measuring tert-butyl alcohol, adding injection water, mixing evenly, cooling to 2-15 DEG C, heat preserving, adding melphalan, stirring and dripping 0.5 mol hydrochloric acid to dissolve, filtering, filling, plugging, disking, freeze-drying, pressing plug, out box, tying and packing after quality test qualification.

The present disclosure relates to the field of oncology, more particularly to the field of melanoma. Provided are methods of treating melanoma, particularly advanced cutaneous melanoma, with a combination of pharmaceutical agents comprising MDM4-specific antagonists (such as an inhibitor of the MDM4-p53 interaction or a molecule that decreases MDM4 protein stability) or MDM4-MDM2 dual inhibitors (i.e., molecules that disrupt the interactions between p53 and MDM2 and p53 and MDM4) and one or more chemotherapeutic agents such as for example alkylating agents (i.e., Dacarbazine (DITC) or melphalan), alkylating-like agents (i.e., cisplatin or carboplatin) or mitotic inhibitors (taxanes docetaxel or paclitaxel) and PI3K-AKT, B-RAF and MEK inhibitors. Further provided are pharmaceutical formulations of MDM4-specific antagonists (be it an inhibitor of the MDM4-p53 interaction or a molecule that decreases MDM4 protein stability) or MDM4-MDM2 dual inhibitors (i.e., molecules that disrupt the interactions between p53 and MDM2 and p53 and MDM4) and a pharmaceutical formulation of one or more chemotherapeutic agents such as for example alkylating agents (i.e., Dacarbazine (DITC) or melphalan), alkylating-like agents (i.e., cisplatin or carboplatin) or mitotic inhibitors (taxanes docetaxel or paclitaxel) and B-RAF and MEK inhibitors.

The present invention is directed to pharmaceutical compositions comprising melphalan and a cyclodextrin derivative, and methods of making and using the same.

The present disclosure relates to the field of oncology, more particularly to the field of melanoma. Provided are methods of treating melanoma, particularly advanced cutaneous melanoma, with a combination of pharmaceutical agents comprising MDM4-specific antagonists (such as an inhibitor of the MDM4-p53 interaction or a molecule that decreases MDM4 protein stability) or MDM4-MDM2 dual inhibitors (i.e., molecules that disrupt the interactions between p53 and MDM2 and p53 and MDM4) and one or more chemotherapeutic agents such as for example alkylating agents (i.e., Dacarbazine (DITC) or melphalan), alkylating-like agents (i.e., cisplatin or carboplatin) or mitotic inhibitors (taxanes docetaxel or paclitaxel) and PI3K-AKT, B-RAF and MEK inhibitors. Further provided are pharmaceutical formulations of MDM4-specific antagonists (be it an inhibitor of the MDM4-p53 interaction or a molecule that decreases MDM4 protein stability) or MDM4-MDM2 dual inhibitors (i.e., molecules that disrupt the interactions between p53 and MDM2 and p53 and MDM4) and a pharmaceutical formulation of one or more chemotherapeutic agents such as for example alkylating agents (i.e., Dacarbazine (DITC) or melphalan), alkylating-like agents (i.e., cisplatin or carboplatin) or mitotic inhibitors (taxanes docetaxel or paclitaxel) and B-RAF and MEK inhibitors.

The invention refers to new alkylating di- and tripeptides based on a melphalan unit, and one or two additional amino acids or amino acid derivatives, which can be used in the treatment of carcinogenic diseases. Further, the invention refers to a a pharmaceutical composition comprising the alkylating peptides of the invention.

The present invention relates generally to methods for treating cancer. In one respect, the present invention relates to a method of treating a hematological cancer (e.g., multiple myeloma, leukemia, lymphoma) comprising administering to a patient in need thereof a therapeutically effective amount of a histone deacetylase inhibitor, for example, a histone deacetylase (HDAC) inhibitor as described herein, for example, PXD-101. In another respect, the present invention relates to a method of treating cancer (e.g., solid tumour cancer, e.g., rectal cancer, colon cancer, ovarian cancer; hematological cancer, e.g., multiple myeloma, leukemia, lymphoma) comprising administering to a patient in need thereof, a first amount of a histone deacetylase (HDAC) inhibitor, for example, a histone deacetylase inhibitor as described herein, for example, PXD-101, and a second amount of an other chemotherapeutic agent, for example, an other chemotherapeutic agent selected from: an antibody against VEGF, Avastin®, an antibody against CD20, rituximab, bortezomib, thalidomide, dexamethasone, vincristine, doxorubicin, and melphalan, wherein the first and second amounts together comprise a therapeutically effective amount.

The present invention is solid tumor treating medicine composition and belongs to the field of medicine technology. The medicine composition contains melphalan in effective anticancer amount and medicinal supplementary material. The medicinal supplementary material is mainly biocompatible, degradable and absorbable polymer, and during the degradation and absorption of the polymer, melphalan is released slowly to local tumor part to lower the systemic toxic reaction and to maintain local medicine concentration. The present invention has enhanced treating effect. The solid tumor includes cerebral tumor, liver cancer, lung cancer, esophagus cancer, gastric cancer, etc.

Synthesis of antineoplastic Melphalan is carried out by esterification reacting, amino-protection reacting, hydrogenation reducing, hydroxyethylation reacting, chlorination reacting, de-protection reacting, taking chlorinating agent, absolute alcohol protecting carboxyl and pyrocarbonic di-tert-butyl protecting amino, hydrolyzing by hydrochloric acid to obtain final product. It's cheap, efficient and non-toxic, has gentle reactive condition and can be used for industrial production. It's cheap, convenient, efficient and non-toxic and can be used for industrial production.

The invention discloses a preparation method of a gold nano-composite targeting drug delivery system. The preparation method comprises the following steps: sequentially adding a chloroauric acid solution and a silver nitrate solution into a hexadecyl ammonium bromide solution, mixing uniformly, then sequentially adding an ascorbic acid solution and a gold nano-particle seed solution, and centrifuging to obtain a gold nano-bar; adding ethyl orthosilicate to obtain a mesoporous silicon oxide nano-material; adding 3-aminopropyl triethylsilane to obtain aminated GNRs@mSiO2; adding a thionyl chloride solution of melphalan to obtain aminated GNRs@mSiO2-MEL; and adding HA-RGD to obtain GNRs@mSiO2-HA-RGD-MEL. According to the preparation method, gold nano-particles with an effect of photothermal therapy are effectively combined with an anti-cancer drug, namely melphalan, thereby realizing combined therapy of tumor thermotherapy and chemotherapy and increasing the therapeutic effect; and by utilizing mesoporous silicon oxide ducts for efficiently loading drugs, the drug loading capacity can be increased.

The invention discloses a preparation method of a targeted graphene oxide binary medicine loading composite modified by HA / RGD. The method includes the following steps of conducting functional modification on graphene oxide through ADH to obtain aminated graphene oxide GO-ADH, coupling an METH connection bridge to HA through an amido bond in a covalent mode, conducting dialyzing and freeze-drying after stirring is conducted for 4-6 hours to obtain HA-METH, adding the obtained GO-ADH to obtain GO-HA-METH, adding sulfhydrylated RGD to obtain a GO-HA-RGD composite, dropwise adding a solution containing melphalan and a solution containing adriamycin, and conducting centrifuging, washing and freeze-drying to obtain MEL / DOX-GO-HA-RGD. The preparation method is easy to operate and mild in experimental condition. The whole carrier system is high in medicine loading amount, long-acting slow release can be achieved, pH sensitivity is achieved, the release rate under the low-pH-value environment is high, and the whole carrier system is suitable for micro environments of tumor tissue and has important clinical significance.

The invention discloses a beta-lactamase-RGD-fusion protein and a preparation method thereof. The amino acid sequence of the recombinant beta-lactamase-RGD-fusion protein comprises a protein sequence which is derived from beta-lactamase and a sequence which comprises short peptide RGD. The recombinant beta-lactamase-RGD-fusion protein not only has the structure and the function of the beta-lactamase, but also has cell adhesion activity, so that the fusion protein can be positioned at the place of the tumor, thereby having better target. The beta-lactamase-RGD-fusion protein can be used for the treatment of the antibody guide enzyme prodrug, can be used for treating a series of solid tumors such as breast cancer and the like jointly with the cephalosporins prodrug, and has better effect than single melphalan and low toxicity.

Described herein are methods of treating multiple myeloma with clinically proven safe and effective amounts of an antibody that specifically recognizes CD38 with bortezomib, melphalan, and prednisone. Also described are methods of selling or offering for sale an antibody that specifically recognizes CD38 or pharmaceutical compositions thereof with bortezomib, melphalan, and prednisone.

The invention relates to the fields of natural medicines and medicinal chemistry, and provides chlormethine fructus evodiamine derivatives, and a preparation method and application thereof. In particular, the invention relates to a preparation method for introducing DNA alkylating agent melphalan derivatives at N-13 site of evodiamine, and application to preparation of anti-tumor medicines. The structure of the evodiamine splicing melphalan derivatives and pharmaceutically acceptable salt is shown in a general formula I shown in the description, wherein n, m and p are described in the claims and the description.

Disclosed are a receptor-mediated quantum dot tracing targeted drug delivery system, a preparation method thereof and application. The targeted drug delivery system comprises polyethylene glycol, hyaluronic acid, quantum dots and melphalan complex which are abbreviated as PEG-HA-QDs-MEL. The PEG is connected with HA amide in a dewatered and condensed manner, the water-soluble CdTe / CdS quantum dots are connected into the HA, and finally, the PEG, the HA and the QDs are prepared with the MEL complex to obtain the targeted drug delivery system. The component content of the PEG-HA-QDs-MEL includes, by weight, 30-100 parts of the MEL, 600-1500 parts of the PEG, 200-500 parts of the HA, 5-50 parts of the CdTe / CdS quantum dots, 20-50 parts of DCC (dicyclohexylcarbodiimide), 1-10 parts of DMAP (dimethylamino-pyridine), 100-500 parts of succinic anhydride, 20-50 parts of NHS, 20-50 parts of EDC (carbodiimide) and 10-100 parts of sodium bisulfite. The targeted drug delivery system is applied to preparing antitumor drugs.

This invention provides a process of making 4-(bis-(2-hydroxyethyl)amino)-L-phenylalanine of the formulaby hydroxyethylation, in a regioselective manner, of the aromatic amino group rather than the glycinic amino group.

The present invention is directed to pharmaceutical compositions comprising melphalan and a cyclodextrin derivative, and methods of making and using the same.

The present invention relates to methods for the treatment of metastatic cancer. Methods of treating metastatic cancer by administration of a set of drugs overcome multiple mechanisms of melphalan resistance and hypersensitize cancer cells to melphalan are described. The methods involve the administration of drug(s) that induce oxidative stress in cancer cells, in conjunction with melphalan on a defined schedule.

The invention relates to a temperature-controlled sustained-release injection containing an alkylating agent and a preparation method thereof, the temperature-controlled sustained-release injection comprises effective anti-cancer amount of the alkylating agent, an amphiphilic block copolymer, a solvent and a certain amount of drug release regulator, wherein, the mixture of the amphiphilic block copolymer and a solvent without organic solvent has the temperature-sensitive gelatinization feature, which is flowable liquid in the environment that is lower than the body temperature and can be automatically converted to the water-insoluble gel that can not flow and be biodegradable for absorption in an endotherm, and the water-insoluble gel can allow the contained angiogenesis inhibitor to have the local sustained release in a tumor and maintain the effective drug concentration for a plurality of weeks to a plurality of months. The sustained-release gel injection can be injected in the tumor or the tumor periphery or be arranged in the postoperative tumor cavity, thus significantly reducing the systemic reaction of the drug and being used for the treatment of the tumors in different stages. The alkylating agent is selected from cyclophosphamide, melphalan, leukeran, 4H-cyclophosphamide peroxide, norcantharidin, mannosulfan, treosulfan, ritrosulfan, ethoglucid, pipobroman, piposulfan, pumitepa, uredepa, azatepa and so on.

Certain toxic compounds (T) such as, for example, compounds based upon diphtheria toxin, ricin toxin, pseudomonas exotoxin, .alpha.-amanitin, pokeweed antiviral protein (PAP), ribosome inhibiting proteins, especially the ribosome inhibiting proteins of barley, wheat, corn, rye, gelonin and abrin, as well as certain cytotoxic chemicals such as, for example, melphalan and daunomycin can be conjugated to certain analogs of gonadotropin-releasing hormone to form a class of compounds which, when injected into an animal, destroy the gonadotrophs of the animal's anterior pituitary gland. Hence such compounds may be used to sterilize such animals and / or to treat certain sex hormone related diseases.

The invention relates to the fields of natural drugs and medicinal chemistry, relates to an enmein diterpene-melphalan derivative as well as a preparation method and application thereof and specifically relates to a preparation method of a melphalan derivative with a DNA alkylating agent induced on a 14-OH or 6, 14-OH site in a mother nucleus structure of enmein diterpene and application of the melphalan derivative to an antitumor drug. The structures of enmein diterpene-melphalan derivative and pharmaceutically acceptable salt thereof are shown as the general formula I or the general formulaII, wherein n is described as the claims and the specification.

The present invention relates to clinically proven subcutaneous pharmaceutical compositions comprising anti-CD38 antibodies and methods of their uses in combination with bortezomib, melphalan and prednisone.

The present invention relates generally to methods for treating cancer. In one respect, the present invention relates to a method of treating a hematological cancer (e.g., multiple myeloma, leukemia, lymphoma) comprising administering to a patient in need thereof a therapeutically effective amount of a histone deacetylase inhibitor, for example, a histone deacetylase (HDAC) inhibitor as described herein, for example, PXD-101. In another respect, the present invention relates to a method of treating cancer (e.g., solid tumor cancer, e.g., rectal cancer, colon cancer, ovarian cancer; hematological cancer, e.g., multiple myeloma, leukemia, lymphoma) comprising administering to a patient in need thereof, a first amount of a histone deacetylase (HDAC) inhibitor, for example, a histone deacetylase inhibitor as described herein, for example, PXD-101, and a second amount of an other chemotherapeutic agent, for example, an other chemotherapeutic agent selected from: an antibody against VEGF, AVASTIN® (bevacizumab), an antibody against CD20, rituximab, bortezomib, thalidomide, dexamethasone, vincristine, doxorubicin, and melphalan, wherein the first and second amounts together comprise a therapeutically effective amount.

The present invention relates to methods and sets of drugs for the effective treatment of metastatic cancer and the administration of a set of drugs that overcome mechanisms of resistance to DNA-damaging agents, thereby sensitizing cancer cells to said DNA-damaging agents. The methods involve the administration of a set of drugs comprising melphalan, BCNU, hydroxocobalamin, and ascorbic acid. In a preferred embodiment, ethanol is also added to the set of drugs and bone marrow toxicity is reversed with an infusion of bone marrow stem cells. The methods also involve the depletion of GSH in tumors and the selective delivery of drugs to solid tumors. The methods also involve preventing the loss of catalase function and preventing oxidant-induced hemolysis and / or methemoglobin formation in subjects treated with oxidant drugs or agents that generate hydrogen peroxide, wherein said methods comprise the systemic administration of ethanol.

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.

The invention provides a medicine composition for treating tumors and an application thereof. The medicine composition is composed of acriflavine or pharmaceutically acceptable salts thereof, melphalan or pharmaceutically acceptable salts thereof, and a medicinal carrier, wherein the molar ratio of the acriflavine to the melphalan is 1:100 to 1:10, and the tumors comprise blood tumors and solid tumors. The forms of the medicine comprise single preparations prepared from acriflavine or melphalan respectively, or a compound preparation prepared from acriflavine and melphalan. The medicine composition provided by the invention has the effects of improving the curative effect on tumors, the toxicity of the medicine composition can be reduced, and the growth speeds of the tumors can be slowed down.

An anticarcinogenic slow release formulation carrying an anticancer drug and a synergist is a slow release injection or a slow release implant, and the slow release injection is made from slow release microspheres and a dissolvant. The slow release microspheres comprise anticancer active components and a slow adjuvant, and the dissolvant is a special dissolvant containing a suspending agent which is selected from sodium carboxymethyl cellulose and the like, and the viscosity of the suspending agent is 80cp-3,000cp (at room temperature). The anticancer active components are alkylating agents such as melphalan, ifosfamide and the like, purine analogues such as O6-BG and the like, and / or hormones anticancer drugs selected from triptorelin, goserelin, leuprorelin and a composition selected from epothilone (A-F) and derivatives thereof; the slow release adjuvant is chosen from one of or the copolymer or the mixture of polylactic acid and a copolymer thereof, polifeprosan and the copolymer or the mixture of polylactic acid and sebacic acid copolymer; the slow release implant and the slow release injection are injected or put in tumors or around the tumors, which is beneficial to diffusing the drug in the solid tumors, maintaining high concentration, reducing drug tolerance, being capable of mutual synergy and enhancing curative effects of chemotherapy and / or radiotherapy.