268 results about "Bortezomib" patented technology

The present invention relates to a chemotherapeutic cancer treatment in which compounds of Formula Ia′, Ib′, Ic′, or II′ (referred to as a group as BH3Is) are administered to a mammal for the treatment of B-cell Lymphoma or other hematopoietic cancers, including diseases associated with MCL-1. In another aspect, the invention provides a method for treating particular types of hematopoietic cancers, such as B-cell lymphoma, using a combination of one or more compounds selected from the group consisting of compounds or Formula Ia, Ib, Ic, or II in combination with other therapies, for example, a class of therapeutics known as 26S proteosome inhibitors, such as, for example, Bortezomib. In another aspect the present invention relates to autoimmune treatment with pharmaceutical compositions comprising one or more compounds of Formula Ia′, Ib′, Ic′, or II′. In another aspect, this invention relates to methods for identifying compounds, for example, compounds of the BH3 mimic class, that have unique in vitro properties that predict in vivo efficacy against B-cell lymphoma tumors and other cancers as well as autoimmune disease.

Disclosed herein are compositions and methods for treating neoplastic diseases. Included are compositions and methods that are effective against multiple myeloma cells resistant to conventional and bortezomib treatment. Furthermore, combination treatment with two different proteosome inhibitors is shown to be synergistic for treating multiple myeloma.

The invention relates to the synthesis of boronic ester and acid compounds. More particularly, the invention provides improved synthetic processes for the large-scale production of boronic ester and acid compounds, including the peptide boronic acid proteasome inhibitor bortezomib.

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 bortezomib 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 bortezomib 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 erlitinib HCl (also known as Tarceva™).

The invention belongs to the technical field of medicine, in particular to the field of chemical pharmacy, and particularly relates to a freeze-dried composition containing bortezomib and a preparation method of the freeze-dried composition. The freeze-dried composition and the preparation method aim at overcoming main medicine dissolution difficulty and oxygen environment sensitivity in an environment. A mixed solvent comprising mannitol and tert butyl alcohol is used, so that a dissolution rate of bortezomib is increased significantly, and the dissolution rate of bortezomib can be increased further through an addition sequence of materials. A nitrogen filled environment is used, so that liquid preparation time is shortened greatly, the contact of main medicine components with an aerobic environment is avoided effectively, and contents of relevant substances and total impurities in a final finished product are reduced.

The invention provides a synthetic method of proteasome inhibitor bortezomib and analogs.

This application relates to combination therapies including triciribine and related compounds and bortezomib and derivatives thereof analogs and compositions with reduced toxicity for the treatment and prevention of tumors, cancer, and other disorders associated with abnormal cell proliferation.

The present invention discloses intermediates of chiral alpha-amino boric acid esters, chiral alpha-amino boric acid esters and salts thereof, and key intermediates for the synthesis of bortezomib. The invention also discloses a preparation method for the intermediates of the alpha-amino boric acid esters, and a method for synthesis of the bortezomib by using chiral alpha-amino boric acid esters and salts thereof and using a convergent strategy. According to the present invention, the bortezomib synthesis process route is low in cost, key intermediates are low in production cost, and operations are simple, very easy for industrial production.

The invention discloses a medicinal composition for treating non-small cell lung cancer. The medicinal composition comprises a target medicament, a chemotherapeutic medicament and a traditional Chinese medicament, wherein the target medicament is one or more of bortezomib, imatinib, gefitinib and sunitinib; the chemotherapeutic medicament is one or more of 5-fluorouracil, carboplatin, epirubicin, adriamycin and fludarabine; and the traditional Chinese medicament is one or more of salvia miltiorrhiza, astragalus membranaceus, sappanwood, Chinese pulsatilla root and portulaca oleracea. The medicinal composition has a remarkable synergetic treatment effect when being used for treating the non-small cell lung cancer, and can be used for remarkably strengthening the cancer-inhibition effect compared with treatment of a single medicament, so that the medicament dosage can be reduced, and the toxic and side effects of chemotherapeutic medicaments can be reduced.

The invention belongs to the field of synthesizing medicaments, and discloses a method for synthesizing bortezomib. In the method, 3-methyl butyraldehyde and R-(+)-1-phenylethylamine are used as initiative materials, and the [(1R)-3-methyl-1-[[(2S)-1-oxygen-3-phenyl-2[(pyrazine formyl) amino] propyl]amino]butyl]-boric acid is obtained by condensation, selective boric acid ester addition, hydrogenation deprotection, chiral condensation with L-phenylalanine, condensation with 2-carboxyl-piperazine and boric acidification. The synthesis method has the advantages of readily available raw materials, higher yield of the whole reaction route, mild reaction conditions, easy operation, lower production cost and the suitability for industrialized production.

The invention belongs to the pharmaceutical and chemical fields and particularly relates to a synthetic method of high-purity bortezomib and an intermediate of the high-purity bortezomib. According to the invention, N-(2- pyrazine carbonyl)-L-phenylalanine benzyl ester is obtained from condensation reaction between 2-pyrazine carboxylic acid and L-phenylalanine benzyl ester; then the product is catalyzed and hydrogenated; and then the product is condensed and hydrolyzed with the hydrochloride of (aR,3aS,4S,6S,7aR)-hexahydro-3a,8,8-trimethyl-alpha-(2-methyl propyl)-4,6-methano-1,3,2- benzodioxoborane-2-methylamine or trifluoroacetate so that the bortezomib is obtained. The preparation process disclosed by the invention has the advantages of simplicity in operation, high purity and low cost. The bortezomib obtained through the method disclosed by the invention is in the form of white powder or crystals, the content is 99.8% or higher, and the total content of SS- and RR-isomers is not greater than 0.1%.

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 invention provides a bortezomib pharmaceutic composition, and aims to solve the technical problem that the stability and dissolubility of the bortezomib are poor. The pharmaceutic composition contains bortezomib and amino acid in the mass ratio of 1:(2-100). By using the bortezomib pharmaceutic composition for injection, the dissolubility of the bortezomib can be effectively improved, and the effect is equivalent or superior to that of the products in the market. The bortezomib pharmaceutic composition is safe and non-irritant, the preparation cost is low, the preparation method is simple, and the stability is superior to that of the existing bortezomib preparation. The bortezomib pharmaceutic composition is favorable for industrial production.

We describe a bis-benzylidine piperidone, RA190, which covalently binds to the ubiquitin receptor RPN13 (ADRM1) in the 19S regulatory particle and inhibits proteasome function, triggering rapid accumulation of polyubiquitinated proteins. Multiple myeloma lines, even those resistant to bortezomib, were sensitive to RA190 via ER stress-related apoptosis. RA190 stabilized targets of human papillomavirus (HPV) E6 oncoprotein, and preferentially killed HPV-transformed cells. After p.o. or i.p. dosing of mice, RA190 distributed to plasma and major organs excepting brain, and potently inhibited proteasome function in skin and muscle. RA190 administration i.p. profoundly reduced growth of multiple myeloma and ovarian cancer xenografts, and oral RA190 treatment retarded HPV+ syngeneic mouse tumor growth, without impacting spontaneous HPV-specific CD8+ T cell responses, suggesting its therapeutic potential. The bis-benzylidine piperidone RA190 is a new orally-available proteasome inhibitor. Multiple myeloma, cervical and ovarian cancers are particularly sensitive to RA190.

The invention belongs to the technical field of medicines and particularly relates to a drug composition of bortezomib and a preparation method thereof. The drug composition disclosed by the invention contains bortezomib, tert butyl alcohol, sodium chloride and an excipient in the mass ratio of 1:0.5:(1-5):(5-20). The drug composition adopts freeze-dried powder injection or water injection, preferably the freeze-dried powder injection. The drug composition contains tert butyl alcohol and sodium chloride besides the conventional excipient; through adding tert butyl alcohol, bortezomib can be rapidly dissolved and rapidly reacted with polyalcohol excipients such as mannitol to form more stable borate, so that the stability problem of the bortezomib freeze-dried powder injection per se is solved; and through adding the drug active constituent i.e. sodium chloride, the normal physiological and biochemical activities and functions in vivo are fully guaranteed.

The invention provides a nanometer drug-loading system as well as a preparation method and an application thereof. The nanometer drug-loading system comprises a drug-loading nano-micelle core, a poly-dopamine shell, and bortezomib connected to the poly-dopamine shell, wherein drug-loading nano-micelles are nano-micelles formed by encapsulating chemical anti-cancer drugs by polyethylene glycol-distearoyl phosphoethanolamine. The preparation method of the nanometer drug-loading system comprises the following steps: forming the drug-loading nano-micelles; forming the poly-dopamine shell outside the drug-loading nano-micelles; and connecting bortezomib to the poly-dopamine shell. The nanometer drug-loading system has the grain diameter smaller than 50nm, is high in stability, has a tumor enrichment effect, and realizes simultaneous delivery of bortezomib and other chemical anti-cancer drugs; poly-dopamine has a photothermal effect, can assist chemotherapeutic medicines in treatment, has the synergy of combined treatment of chemotherapy and thermal therapy, and therefore, the nanometer drug-loading system has a wide medical application prospect.

Multi-dose formulations for bortezomib are presented in which bortezomib has significantly improved stability. Especially preferred formulations include those in which bortezomib is in a liquid form suitable for injection, wherein the solvent system predominantly comprises propylene glycol. In other preferred aspects, bortezomib is present as a Lewis donor-acceptor complex with a hetero-bifunctional Lewis base.

A bortezomib composition includes bortezomib and boric acid in a mass ratio of boric acid to bortezomib is from 1:1 to 10:1. The composition is a solid, and may be prepared by forming a liquid mixture including a solvent, bortezomib and boric acid, and lyophilizing the liquid mixture.

The present invention provides a synthetic process for producing bortezomib using a novel intermediate. The present invention also provides a process for purifying bortezomib anhydride, and a new crystalline polymorph of bortezomib anhydride.

The present invention relates to a method of treating cancer in a subject in need thereof, by administering to a subject in need thereof a first amount of a histone deacetylase (HDAC) inhibitor such as suberoylanilide hydroxamic acid (SAHA), or a pharmaceutically acceptable salt or hydrate thereof, and a second amount of one or more anti-cancer agents, including Bortezomib. The HDAC inhibitor and the anti-cancer agent may be administered to comprise therapeutically effective amounts. In various aspects, the effect of the HDAC inhibitor and the anti-cancer agent may be additive or synergistic.

The invention provides a freeze-drying process for preparation of bortezomib for injection, and according to the process, after subpackage of a bortezomib liquor, freeze-drying is performed, main features of a pre freezing stage comprise two times of annealing, in a sublimation drying stage, drying is kept for 30-40h at -30 DEG C. The bortezomib for injection prepared by the process is not spurted from a bottle, has full and complete appearance, good solubility, qualified clear degree and high safety, and is suitable for industrial production.

The present application provides a process for the preparation of Bortezomib, its intermediates and process for crystalline forms of Bortezomib.