61 results about "Chlorambucil" patented technology

A stent having a drug eluting formulation has three components: 1) Anti-neointimal hyperplasia or anti-restenosis agent 2) Main polymer 3) Additive polymer The anti-neointimal hyperplasia or anti-restenosis agent includes, but not limited to, Paclitaxel, Taxol, Rapamycin, Tacrolimus, Actinomycin D, Methotrexate, Doxorubicin, cyclophosphamide, and 5-fluorouracil, 6-mercapatopurine, 6-thioguanine, cytoxan, cyclosporine, cytarabinoside, cis-platin, chlorambucil, busulfan, and any other drug that can inhibit cell proliferation, and combinations thereof. The main polymer includes, but not limited to, polystyrene, parylene and polyurethane. The additive polymer includes, but not limited to, polyethylene glycol capped with diisocyanate moiety (NCO-PEG). TABLERatio between three components without solvent%ComponentformulationAgent1-10%Main polymer80-98% Additive1-19%polymer9.0 g of parylene, 0.6 g of tacrolimus, 0.4 g of NCO-PEG and 0.01 g of triethylene amine were dissolved in 90 g of tetrahydrofuran. The resulting mixture was heated at 40° C. for 30 minutes and cooled to room temperature. To the solution was added 0.1 g of pH 8.0 aqueous solution and mixed thoroughly. The resulting solution is applied to bare metal stents for coating.

The invention discloses a light-sensitive targeted anti-tumor predrug for killing tumor cells in response to hydrogen peroxide as well as a preparation method and application of the light-sensitive targeted anti-tumor predrug. A hydrogen peroxide-light stimulated drug and fluorescence double-release system is designed and synthesized by taking hydrogen peroxide as a target molecule released by the drug as well as boric acid ester as a response group. The determination of the fluorescence of the predrug (CM-1) finds that the predrug (CM-1) can well release fluorescence in response to hydrogen peroxide; meanwhile, compared with other light-sensitive drugs, the predrug has relatively good stability and targeting property; a research for determining the anti-tumor activity of the predrug by virtue of an MMT method finds that the compound (CM-1) has the anti-tumor activity higher than that of chlorambucil, namely that the targeting property of the compound (CM-1) is higher than that of chlorambucil; the intake condition of cells to the drug is explored according to the fluorescence characteristic of coumarin, and an experiment result shows that the predrug can be digested by cells. According to the predrug, an effectively research tool is provided for drug release in cell researches.

The invention discloses design and application of a drug and fluorescence dual-release system based on glutathione and photo-stimulation and designs and synthesizes a glutathione and photo-stimulation-based drug and fluorescence dual-release system. The glutathione and photo-stimulation-based drug and fluorescence dual-release system takes target molecules released by the drug of glutathione and 2, 4-dinitrobenzene sulfonyl chloride as response groups. Detection of the fluorescence performance of a prodrug (CM-2) shows that the prodrug (CM-2) can well respond to the glutathione to release fluorescence; meanwhile, compared with other photosensitive drugs, the prodrug is higher in stability and targeting property; measurement of antineoplastic activity research through an MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) method shows that the antineoplastic activity of the compound (CM-2) is higher than that of chlorambucil and accordingly shows that the targeting property of the compound (CM-2) is higher than that of the chlorambucil; the drug ingestion situation of cells is researched according to the fluorescence characteristics of coumarins, and experimental results show that the prodrug can be ingested by cells. The glutathione and photo-stimulation-based drug and fluorescence dual-release system provides an effective research tool for drug release of cell research.

The invention relates to a synthesis process of an antineoplastic drug chlorambucil. The synthesis process comprises the following steps: (1) amino protection reaction; (2) acylation reaction; (3) reduction reaction; (4) carboxyl protection reaction; (5) substitution reaction; (6) chlorination reaction; and (7) deprotection reaction. According to the synthesis process, the amino group is protected by use of acetic anhydride, and then acylation, reduction, carboxyl protection, substitution, chlorination and aqueous hydrochloric acid solution hydrolysis are performed to obtain the chlorambucil. The synthesis process of the antineoplastic drug chlorambucil has the characteristics of low cost, mild reaction conditions, low toxicity, convenience in process operation, and suitability for industrial production.

The invention discloses an enhancement tumor cell medicament screening method and its application mainly for effectively overcoming the multidrug resistance to improve the anti-cancer drug treatment effect in a tumor chemotherapy process. The invention screens an inhibitor which can effectively inhibiting the induction action through luciferase activity detection by using an Nrf2 as a cell drug screen platform of a molecular target and a tBHQ as an Nrf2 inducer, and the inhibitor is a medicament of the enhancement tumor cell. The medicament obtained by the screen is a small molecular compound ZDAK02 (coralyne sulfoacetate coralyne thioacetate). The combined use of the medicament of the invention with the anti-cancer drug Chlorambucil or anti-cancer drug oxaliplatin can enhance the toxicity of the anti-cancer drug to the cancer cells and be helpful for easing even reversing the multidrug resistance to the anti-cancer drugs.

The invention belongs to the field of biomedicine and discloses a tumor-targeting lipophilic positive ion-chlorambucil compound and a preparation method and application to an albumin nano-drug. The compound is of the structure shown in the formula (I), wherein Y is F, Cl, Br or I, and n is 0 or a natural number between 1 and 10. Cancer cell mitochondria serve as therapeutic targets of the compound and the albumin nano-drug of the compound, targeted cancer therapy is achieved, the problems of poor anti-cancer drug selectivity and multi-drug resistance are solved, and the cancer cell clearance effect is achieved in a cell apoptosis or death induction mode. Please see the formula in the description.

The invention belongs to the field of compound preparation, and specifically discloses a preparation method of an anti-tumor medicine chlorambucil. The preparation method comprises the steps of performing a Vilsmeier reaction on a raw material N,N-dihydroxyethylaniline and phosphorus oxychloride and DMF so as to prepare 4-[bi(2-chloroethyl)amino]benzaldehyde, then performing a witting reaction on4-[bi(2-chloroethyl)amino]benzaldehyde and methoxymethyl triphenylphosphonium chloride so as to prepare 4-[bi(2-chloroethyl)amino]-BETA-methoxystyrene, reacting under an acid condition so as to obtain4-[bi(2-chloroethyl)amino]phenylacetaldehyde, and finally, reacting with Meldrum's acid in triethylamine and formic acid systems so as to prepare a target product. The raw material N,N-dihydroxyethylaniline is cheap, has a wide source and is easy to obtain; the whole reaction process has high yield, production conditions are mild, the steps are short, and post treatment and purification are easyto operate, so that the preparation method is applicable to commercial large scale production, and meets the rapidly growing market demands.

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.

The invention provides a preparation method and application of oligopeptide hydrogel, and a medicinal composition. The obtained oligopeptide hydrogel has a good targeting tumor suppression effect or in-vivo imaging effect. The preparation method of the oligopeptide hydrogel includes the steps of mixing oligopeptide with an antibody in a water solution, and assembling the oligopeptide and the antibody into the hydrogel under the enzymatic action at the temperature of 2-6 DEG C, wherein the oligopeptide can form the hydrogel under the enzymatic action, and the antibody has a targeting effect ontumor cells. The capping groups of the oligopeptide are groups having an antitumor effect or in-vivo imaging effect; preferably, the antitumor groups are chlorambucil, and the groups with the in-vivoimaging effect are Cy5.5; more preferably, the sequence of the oligopeptide is X-GDFDFpDY, and the X is chlorambucil or Cy5.5; preferably, the antibody is antiHER2.

The invention discloses a chlorambucil derivative with a structure as shown in a formula I, II or III and pharmaceutically acceptable salts thereof, wherein the formula is described in the specification. The invention also relates to a preparation method for the chlorambucil derivative, a preparation of the chlorambucil derivative and application of the chlorambucil derivative.

The invention relates to antitumor application of chlorambucil-polydopamine prodrug nanoparticles, and concretely relates to a mild photothermal therapy-chemotherapy combined tumor alete treatment technology based on the chlorambucil-polydopamine prodrug nanoparticles. The nanoparticles can realize spatiotemporal manipulation in an antitumor effect in order to achieve accurately-positioned tumor ablation, and passive targeting action of the prodrug nanoparticles on tumor parts can be achieved by the enhanced permeation and retention(EPR) effect; the mild photothermal effect can enhance the expansion of tumor blood vessels and the permeability of cell membrane effectively promote the accumulation and penetration of the nanoparticles in tumors and the endocytosis of tumor cells; and photothermal therapy can induce the antitumor immunity in order to improve the effect of chemotherapy, so synergistic antitumor effects are generated in the photothermotherapy-chemotherapy combined therapy. The application provides a new way for precise cancer treatment, and has a potential clinical application prospect.

The invention relates to preparation of an enzymatic chlorambucil-polypeptide hydrogel and application in resisting cancer. The enzymatic chlorambucil-polypeptide hydrogel is prepared from folding phosphopeptides into alpha-helical configuration through catalytic specificity of alkaline phosphatase, and has the effect on remarkably improving the activity of an anti-tumor medicine. According to the application, the polypeptide sequence is CRB-G<D>F<D>F<D>Y and CRB-G<D>F<D>Fp<D>Y.

The invention discloses a preparation method and application of a polypeptide drug conjugate with tumor targeting. The polypeptide drug conjugate with the tumor targeting structurally comprises tumortargeting peptide WA1, a non-splitting connector and a cytotoxicity anti-tumor drug. The preparation method of the polypeptide drug conjugate (PDC-WA1) with the tumor targeting adopts a Fmoc solid-phase synthesis method and comprises the following main synthesis steps of: taking Fmoc-Ala-Wang resin as a raw material, after the tumor targeting peptide is synthesized, connecting the synthesized tumor targeting peptide with Fmoc-Acp-OH and chlorambucil in sequence, and carrying out purification by HPLC to obtain the polypeptide drug conjugate with the tumor targeting and anti-tumor activity. Thepreparation method has the advantages of low production cost, low environment pollution, few reaction by-products and low purification difficulty and is simple in reaction operation.

A library of glycosylated chlorambucil analogs which are useful as anti-tumor and / or anti-metastatic agents is disclosed. The glycosylated chlorambucil analogs have the general formulawhereinrepresents a reducing sugar moiety.

The invention relates to a double-receptor targeting drug delivery system realizing the synergistic effect of phototherapy and chemotherapy, as well as preparation and applications of the double-receptor targeting drug delivery system. The system is a compound containing hyaluronic acid, polylactic acid, polypeptide, and chlorambucil / chlorin e6, wherein the molecular weight of polylactic acid is 8000Da, specifically, the compound comprises the following components in parts by weight: 100-2000 parts of hyaluronic acid, 1500-10000 parts of polylactic acid, 21-450 parts of N,N'-dicyclohexylcarbodiimide, 12-240 parts of N-hydroxy succinimide, 1-30 parts of polypeptide, 20-400 parts of 1-(3-(Dimethylaminopropyl)-3-ethylcarbodiimide, 100-1000 parts of chlorambucil, and 50-600 parts of chlorin e6. The double-receptor targeting drug delivery system has the beneficial effects that (1) the synergistic effect of phototherapy and chemotherapy is realized; (2) the multiple targeting properties are realized; (3) the good blood stability is realized; (4) the system has small toxicity and high safety.

The invention discloses a meningeoma nursing medicine and a preparation method thereof. The nursing medicine is a formula formed by combining traditional Chinese medicine and western medicine, wherein the western medicine comprises the following components: dichloro diethylamine, cyclophosphamide, ifosfamide, melphalan, chlorambucil, thiotepa, mitomycin, busulfan, lomustine, carmustine, temozolomide and carboplatin. The traditional Chinese medicine comprises the following components: Oldenlandia diffusa, dangshen, honey-fried licorice root, fructus forsythiae, realgar, edible tulip, Schisandra chinensis, ginseng, soroseris, beautyberry leaf, radix curcumae, hawthorn, pheretima, gastrodia elata, Minoru thorns, Rehmannia Glutinosa, Ligusticum wallichii, Angelica sinensis, Polygonum cuspidatum, bamboo leaf, radix semiaquilegiae, red flower, white paeony root, pubescent holly root, fried monkshood, herba eupatorii, ambergris, fingered citron, Radix Aucklandiae, radix scutellariae, radix bupleuri and serrate rabdosia herb; the meningeoma nursing medicine has the advantages of obvious treatment effect, low disease relapsing rate and low side effect.

The invention discloses a radioactive-nuclide-labeled compound, namely a carbonyl-technetium-labeled chlorambucil complex as well as a preparation method and an application thereof. The preparation method of the carbonyl-technetium-labeled chlorambucil complex comprises chlorambucil (CB) and L-histidine (L-His) are coupled so as to obtain novel ligand His-CB, and then the ligand and [<99m>Tc(CO)3(H2O)]<+> intermediate are reacted, thereby obtaining the carbonyl-technetium-labeled chlorambucil complex. The carbonyl-technetium-labeled chlorambucil complex disclosed by the invention has the advantages of better tumor ingestion and detention effects, rapid removal of normal tissues and organs and good target / non-target ratio, and can be used for SPECT (single photon emission computed tomography) imaging diagnosis of tumor.

The invention relates to a synthesis method of a light controlled-release compound. The above lead compound is composed of a BODIPY parent nucleus and chlorambucil, and light controlled-release drug,photodynamic therapy and chemotherapy are integrated in the same molecular structure. The invention also discloses an application of the compound in tumor treatment. The lead compound is simple in structure and small in molecular weight, has a determined chemical structure, is easy to prepare, purify and further modify, and has the remarkable characteristics of low toxicity to mice and the like, so that the basic requirements of clinical medication are met. Proved by in-vitro and in-vivo experiments, the lead compound has an accurate controlled-release chemotherapeutic drug chlorambucil undervisible light radiation, and the optical radiation time and the drug release amount are in a positive correlation relationship, so that the chemotherapeutic drug and singlet oxygen are accurately released by a single molecule through optical stimulation, and the synergistic treatment of chemotherapy / photodynamic therapy of living tumors is realized. Therefore, the lead compound for photodynamic therapy cooperated with photocontrolled-release chemotherapy has a good application prospect in the aspect of tumor therapy.

The invention belongs to the technical field of artemisinin derivatives, and particularly relates to an artemisinin-chlorambucil ester compound and a preparation method thereof. In order to solve the problems that the tumor effect of artemisinin needs to be improved, the toxic and side effects of chlorambucil are large and the like, artemisinin-chlorambucil ester with a novel structure is designed and synthesized according to a pharmacophore splicing principle, and the structure of the artemisinin-chlorambucil ester compound is represented and determined by 1H NMR, 13C NMR and HRMS-ESI. The compound has good anti-tumor activity, and the toxic and side effects of chlorambucil are reduced. The preparation method is simple, the obtained derivative is high in anti-tumor activity and low in toxic and side effects, a novel medicine is provided for tumor resistance, and the derivative has good application value.

The invention provides a compound synthesized from a targeting antitumor drug F16 and chlorambucil, and a synthesis route and preparation method for the compound. The compound uses mitochondria as a target for treatment of cancers, overcomes the problems of low selectivity and multi-drug resistance of antitumor drugs and achieves the effect of removal of cancer cells through cell apoptosis.

The present invention relates to immunotherapies that are based on depletion of CD37-positive cells such as B-cells. The present invention provides methods for reduction of CD37-positive cells such as B-cells in an individual / patient using a combination of CD37 antibody / antibodies and chlorambucil. The combination of CD37 antibodies and chlorambucilis shown to have a synergistic effect. The application further provides materials and methods for treatment of diseases involving aberrant B-cell activity.

The invention relates to a chlorambucil multi-targeting medicine carrying system and a preparation method and application thereof in the aspect of anti-tumor medicines. The chlorambucil multi-targeted medicine carrying system is prepared by mixing a PEG-HA-CHL (polyethylene glycol-hyaluronic acid-chlorambucil) component with an Fe3O4 magnetofluid component in weigh ratio of 1:(1-5), wherein the PEG-HA-CHL comprises the following components in parts by weight: 20-100 parts of chlorambucil, 500-1500 parts of PEG, 100-500 parts of HA, 10-50 parts of DCC (dicyclohexylcarbodiimide), 1-10 parts of DMAP (dimethylamino pyridine), 100-500 parts of butanedioic anhydride, 10-50 parts of EDC (dichloroethane) and 20-100 parts of sodium hydrogensulfite. The invention has the advantages of intelligent medicine release, multiple targeting and better reverse medicine resistance, controlled medicine release, better blood circulation stability, better invisibility and wide applicability.

The invention discloses compound particles for treating retinal vasculitis and a preparation method thereof. The compound particles for treating the retinal vasculitis are prepared from cortisol, prednisone, chlorambucil, an antilymphocyte antibody, rifampicin, thin-leaf sphagnum fermented powder, moxisylyte, aesculin, lecithin, anisodine, zinc gluconate, cod liver oil, dl-alpha tocopherol, inosine, wheat germ oil and magnet powder. The compound particles combine with a variety of pharmaceutical ingredients, achieve anti-inflammatory, anti-bacterial, liver-protecting, eyesight-improving and body immunity regulating effects through combined action and have the remarkable effect of treating the retinal vasculitis. In addition, the compound particles have small side effects, do not produce the adverse effect on the eyesight and the bodies of patients after long-term taking and are wide in application prospect.

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.

The invention relates to a method for preparing a chlorambucil-dopamine conjugate and prodrug nanoparticles of the chlorambucil-dopamine conjugate. The method comprises the steps of: synthesizing 2,2-dimethyl-1,3-benzodioxole-5-propionic acid, then synthesizing 2-(2-hydroxyethyl)dithioxo)ethyl-2,2-dimethyl-1,3-benzodioxole-5-ethyl propionate, then synthesizing ((2-(2,2-dimethyl-1,3-benzodioxole)-5-propionyl)oxy)ethyl)-4-(4-(bis(2-chloroethyl)amino)phenyl)methyl butyrate, then synthesizing the chlorambucil-dopamine conjugate, and finally synthesizing the prodrug nanoparticles of the chlorambucil-dopamine conjugate. A simple and effective route is provided for preparation of the chlorambucil-dopamine conjugate and the prodrug nanoparticles of the chlorambucil-dopamine conjugate, and an experimental platform is provided for acquisition of a polymer drug carrier which has near-infrared light absorption, reduction response and integrated photothermal therapy and chemotherapy.

The invention discloses an oligo (ethylene glycol) modified chlorambucil medicine. The structural formula of the short-chain polyethylene glycol modified chlorambucil medicine is shown as a formula I; and in the formula I, the number-average molar mass of oligo (ethylene glycol) (OEG) segments is 198-1,998. The medicine is an amphiphilic anti-cancer medicine, can be self-assembled to form nanoparticles in water or a buffer solution, has long blood circulation time, can target tumors through ultra permeability and enhanced permeation and retention (EPR) effect and can effectively target cancer tissues through the EPR effect of the tumors; and compared with other chlorambucil medicine systems, the chlorambucil medicine has the advantages of high medicine loading rate, high druggability and the like and is expected to be used for clinical treatment of various tumors.

The invention belongs to the field of natural medicines and discloses a compound medicinal composition with anti-lymphoma effect and its application. The active ingredient of the compound pharmaceutical composition is composed of chlorambucil and wogonin in a molar ratio of 1:1 to 1:10. The combination of the two drugs has a strong synergistic effect on treating lymphoma.

This document relates to an aqueous composition comprising chlorambucil and human serum albumin, wherein the chlorambucil and the human serum albumin in the aqueous composition have a ratio by weightfrom about 1:10 to about 1:2000, wherein the aqueous composition comprises at least one water-miscible organic solvent. This document also relates to a solid composition comprising chlorambucil and human serum albumin. This document also relates to a liquid pharmaceutical composition comprising the solid composition comprising the chlorambucil and the human serum albumin, and a pharmaceutically acceptable carrier.

A library of glycosylated chlorambucil analogs which are useful as anti-tumor and / or anti-metastatic agents is disclosed. The glycosylated chlorambucil analogs have the general formulawhereinrepresents a reducing sugar moiety.

The invention relates to a synthesis process of an antineoplastic drug chlorambucil. The synthesis process comprises the following steps: (1) amino protection reaction; (2) acylation reaction; (3) reduction reaction; (4) carboxyl protection reaction; (5) substitution reaction; (6) chlorination reaction; and (7) deprotection reaction. According to the synthesis process, the amino group is protected by use of acetic anhydride, and then acylation, reduction, carboxyl protection, substitution, chlorination and aqueous hydrochloric acid solution hydrolysis are performed to obtain the chlorambucil. The synthesis process of the antineoplastic drug chlorambucil has the characteristics of low cost, mild reaction conditions, low toxicity, convenience in process operation, and suitability for industrial production.