132 results about "Lenalidomide" patented technology

Methods of treating, preventing or managing leukemias are disclosed. The methods encompass the administration of an immunomodulatory compound of the invention known as Revlimid® or lenalidomide. The invention further relates to methods of treatment using this compound with chemotherapy, radiation therapy, hormonal therapy, biological therapy or immunotherapy. Pharmaceutical compositions and single unit dosage forms suitable for use in the methods of the invention are also disclosed.

Methods of treating or managing specific cancers, including non-Hodgkin's lymphoma, by the administration of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione are disclosed. Methods of using gene and protein biomarkers as a predictor of non-Hodgkin's lymphoma response to treatment with 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione are also disclosed.

The present invention relates to improved processes for preparing 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione (I) (lenalidomide) and its intermediate 3-(1-oxo-4-nitro-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione. The present invention further relates to improved processes for preparing lenalidomide crystalline form A, use of said crystalline form A as an active pharmaceutical ingredient or as an intermediate in the preparation of further crystalline or amorphous forms of lenalidomide, compositions comprising lenalidomide crystalline form A and their use in the treatment of disease.

The invention discloses a method for preparing lenalidomide (3-(7-amino-3-oxo-1H-isoindole-2-base) piperidine-2,6-diketone). Two intermediates of the lenalidomide are 2-halomethyl-3-nitro-benzoic acidmethyl ester and 3-aminopiperidine-2,6-diketone. The invention discloses methods for preparing the two intermediates and preparing the lenalidomide by using the two intermediates. The method has novel process, short procedures, high reaction yield, low production cost, and larger implementation value and social and economic benefits.

The invention relates to an anticancer slow-release gel injection which contains slow-release microspheres containing an angiogenesis inhibitor, an amphiphilic block polymer, a solvent and a slow-release agent, wherein the composition of the amphiphilic block polymer and the non-organic solvent exhibit the property of temperature-sensitive gelation. After the in vivo injection, the injection turns into a stagnant and biodegradable water-insoluble gel and the gel slowly releases the drug contained therein for a plurality of weeks to a plurality of months. After the intratumoral or peritumoral injection, the anticancer slow-release gel injection can significantly reduce the general drug reactions and is used for treating tumors of different stages. The angiogenesis inhibitor is selected from SU5416, SU6668, bosutinib, sprycel, erlotinib, vandetanib, gefitnib, canertinib, lapatinib, lestaurtinib, masitinib, vatalanib, mubritinib, tandutinib, nilotinib, marimastat, nilotinib, pelitinib, telatinib, sunitinib, sorafenib, zarnestra, sirolimus, imatinfb, lenalidomide and thalidomide.

The invention relates to a lenalidomide derivative and a use thereof as a medicine, and in particular relates to a compound shown as a formula (I), a solvate, a hydrate, a stereoisomer or pharmaceutically acceptable salt thereof. The invention further relates to a pharmaceutical composition comprising the compound, and the use of the compound in preparing medicines for preventing or treating malignant tumors, in particular malignant tumors in the blood-lymphatic system. Compared with lenalidomide, the compound provided by the invention has a longer half-life period and can be used for preparing long-acting preparations.

The invention discloses a composite for treating myelodysplastic syndrome. The composite comprises the following components: lenalidomide, a carrier, a solubilizing agent, a disintegrating agent, a lubricating agent, a flow aid and an adhesive, wherein the carrier is a mixture of any one or several of a high-molecular water-soluble polymer, a water-soluble small molecule compound, a hydrophilic auxiliary material and an inorganic carrier; the solubilizing agent is a mixture of one or several of lauryl sodium sulfate, poloxamer, beta. cyclodextrin and a derivative thereof, polysorbate and polyoxyethylene alkyl ether. The invention also provides a preparation method of the composite, and the preparation method comprises the steps of grinding, mixing, dry granulation, total mixing and tabletting or capsule filling. The preparation method disclosed by the invention effectively enhances the water solubility and bioavailability of the lenalidomide; the dry granulation preparation process simplifies the preparation steps, reduces the cost, saves the energy resources, reduces the labor expenditure and realizes the energy conservation and environment protection in production.

The invention discloses a method for preparing lenalidomide. The method comprises the following steps: firstly, etherifying 2-methyl-3-nitrobenzoic acid to obtain 2-methyl-3-nitrobenzoic acid methyl ester, brominating to obtain 2-brooethyl-3-nitrobenzoic acid methyl ester, reacting L-glutamine and tert-butyl dicarbonate to obtain N-Boc glutamic acid, acquiring 3-amino-2,6-piperidine diketone protected by Boc from N-Boc-glutamic acid in the presence of a condensing agent and a catalyst, further reacting with acid to prepare 3-amino-2,6-piperidine diketone hydrochloride, reacting 3-amino-2,6-piperidine diketone with 2-brooethyl-3-nitrobenzoic acid methyl ester so as to obtain 3-(4-nitryl-1,3 dihydro-1-oxo-2 hydrogen-isobenzazole-2-yl) piperidine-2,6-diketone, and finally reducing, thereby obtaining lenalidomide. The method disclosed by the invention is high in product yield.

The invention discloses a method for simultaneously detecting multiple anti-tumor drugs in a blood sample. A pretreated sample to be detected is detected by adopting ultra-high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The pretreatment process comprises the following steps: adding serum into a mixed solution of methanol and acetonitrile, oscillating and centrifuging,taking out the centrifuged supernatant, drying, dissolving the dried powder into a methanol aqueous solution, and filtering to obtain a sample to be detected. The method can be used for simultaneously detecting 13 kinds of anti-tumor drugs such as methotrexate, 5-fluorouracil, apatinib, busulfan, carboplatin, cyclophosphamide, docetaxel, gemcitabine, imatinib, illinotecan, lenalidomide, oxaliplatin, paclitaxel and the like in blood.

The invention discloses an immunomodulator slow-release preparation and a preparation method thereof. A lenalidomide slow-release tablet is composed of a slow-release layer and an optional quick-release layer, wherein the slow-release layer contains active ingredients of lenalidomide and a slow-release framework material simultaneously; the quick-release layer does not contain the slow-release framework material. The lenalidomide slow-release tablet disclosed by the invention is capable of slowly and uniformly releasing medicines by virtue of the slow-release framework material, so as to reduce the release speed, delay the time to peak, prolong the action time of lenalidomide, and provide a uniform and constant blood concentration. Moreover, The lenalidomide slow-release tablet disclosed by the invention is simple in prescription and excellent in quality stability; the preparation process is simple to operate, free from special treatment and production equipment, low in production cost, and beneficial to batch-enlarged industrial production for the product; the preparation method is high in yield, the granulation and crushing procedures are simple and practicable to operate, the intermediate material is good in stability, flowability, compressibility and content uniformity, and completely meets the requirements of tabletting, and the surface of the prepared tablet is smooth and beautiful.

The invention provides novel anti-cancer precursor medicaments using NGR(NO2) as a targeting carrier. The novel anti-cancer precursor medicaments are prepared by designing and synthesizing a 5-fluorouracil precursor medicament, a lenalidomide precursor medicament, a cytarabine precursor medicament, an epirubicin precursor medicament and a dasatinib precursor medicament. According to the initial research on the anti-tumor activity of the 5-fluorouracil precursor medicament, the 5-fluorouracil precursor medicament can inhibit the invasion and metastasis of tumor cells and the growth of solid tumors. The 5-fluorouracil precursor medicament is modified in both effectiveness and preparation compared with the 5-fluorouracil serving as a parent medicament and is widely applicable. Concretely, the invention mainly relates to three aspects: (1) design and antiangiogenic effect of a novel tumor-targeted tripeptide NGR(NO2); (2) preparation of anti-cancer precursor medicaments by coupling the tumor-targeted tripeptide NGR(NO2) and 5 anti-cancer medicaments through covalent bonds; and (3) antitumor and antiangiogenic medical use of the novel 5-fluorouracil precursor medicament.

The invention discloses a novel preparation method of lenalidomide. Glutarimide and 4-nitro-isoindolin-1-one are used as raw materials of the lenalidomide. The lenalidomide is prepared by (1) performing bromination in the alpha position of the carbonyl of the glutarimide to obtain 3; (2) condensing 4-nitro-isoindolin-1-one and the 3 to obtain 4; and (3) subjecting the 4 to reduction to obtain 5, namely the lenalidomide. The preparation method has easily available raw materials, short steps, simple operation, high reaction yield and low production cost, and is environmental friendly. The preparation method has large implement value and social and economic benefit.

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

The invention relates to a pharmaceutical composition containing lenalidomide, and a preparation method thereof. The pharmaceutical composition is prepared from the lenalidomide, a thinning agent, a disintegrating agent, a lubricating agent and an optional pharmaceutically acceptable carrier. The pharmaceutical composition containing the lenalidomide provided by the invention has favorable stability and drug dissolution rate, the product quality can be controlled, and the preparation method is simple in process, high in operability and suitable for industrialized mass production.

The invention relates to fatty acid lenalidomide derivatives; compositions comprising an effective amount of a fatty acid lenalidomide derivative; and methods for treating or preventing a metabolic disease comprising the administration of an effective amount of a fatty acid lenalidomide derivative.

A method of identifying a subject having chronic lymphocytic leukemia (CLL) who is likely to be responsive to a treatment compound, comprising obtaining a first sample and a second sample from the subject having CLL; administering 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione (Compound A) to the first sample and administering lenalidomide to the second sample; determining the level of a biomarker in the first sample and determining the level of the biomarker in the second sample; and diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the first sample is different from the level of the biomarker in the second sample.

The invention relates to the field of drug synthesis, and particularly relates to a preparation method of a lenalidomide intermediate and lenalidomide. The compound is a drug for treating multiple myeloma. The method comprises the steps of adopting 2-bromomethyl-3-nitrobenzoate and 3-amino-2,6-piperidione hydrochloride as reaction substrates and an inorganic base as an acid-binding agent and obtaining a white to almost white key intermediate 3-(4-nitro-1-oxo-1,3-dihydro-2H-isoindole-2-yl) piperidine-2,6-diketone of the lenalidomide through simple post-treatment; and adopting a mixed solvent of an organic solvent and water as a reaction solvent and carrying out catalytic hydrogenation in the presence of palladium on carbon to prepare the lenalidomide (II). The process route is low in production cost, and a product is high in purity and friendly to environment, and has relatively great implement value and social and economical benefits.

The invention provides a method for synthesizing lenalidomide, belongs to the field of anti-tumor and anti-leukemia medicines in organic synthesis, and particularly relates to the method for synthesizing lenalidomide. To solve the problems of low yield, low purity, environmental pollution caused by massive harmful waste, excessive cost for environment-friendly treatment, easily occurred risk of violent explosive, degradation caused by long reacting time at high temperature and low catalyst recycling frequency in a traditional lenalidomide synthesis reaction, the method comprises the following steps: 1, adding a lenalidomide precursor nitro compound into an organic solvent, adding an activated carbon catalyst having a Pd loading capacity of 10 percent, then leading the mixture serving as a material I into a pre-heating module of a microchannel reactor; and 2, respectively pumping preheated material I and a material II hydrogen into a reaction module of the microchannel reactor into a reactor, collecting outflowing reaction liquid, and treating to obtain the lenalidomide. The method is environment-friendly, and has the advantages of high reaction yield, high purity and good economical efficiency.

The invention discloses a method for refining a crude lenalidomide product. The method comprises the following steps of: (1) adding the crude lenalidomide product to a mixed solution of isopropanol and water; (2) heating, after the crude lenalidomide product is completely dissolved, adding activated carbon and nanometer ceramic powder and carrying out heat preservation for the first time; (3) filtering when the solution is hot, and cooling filtrate till crystals precipitate; and (4) carrying out heat preservation for the second time, carrying out suction filtering after the crystal precipitation is finished, and finally drying. Due to adoption of the technical scheme, the method for refining the crude lenalidomide product has the beneficial effects of low isopropanol toxicity, high safety, simpleness in process, no need of special equipment and environment requirements, suitability for industrial production, high product content and high refining yield; and the purify of the lenalidomide is remarkably improved.