48 results about "Clofarabine" patented technology

A process for making clofarabine comprising: fluorinating a compound of formula VII

wherein each R⁴ is independently a hydroxy protecting group, OR⁶ is a leaving group, with a fluorinating agent in the presence of guanidine carbonate to give a compound of formula VIII:

The present invention relates to a preparation method of clofarabine, comprising mixture of 2-adenine chlorine and the compound of formula I. the reaction is done under mild conditions and an appropriate temperature; the basically pure compound of the formula III can be prepared after separation. The high-purity clofarabine can be got through hydrolysis under alkaline conditions.

The invention discloses a preparing process of clorfarabine raw medicine, specifically provides steps of the process, material ratio and reaction condition of each step. The process is easy to implement, low in cost. The main material 2-chloro inosine is easy to get. The inventive process is beneficial to extensive industrial production of clorfarabine.

The present invention relates to a Clofarabine freeze drying powder and the preparation method, which comprises Clofarabine and at least one biological acceptable excipient. Wight ratio of the Clofarabine and the excipient is from one to 10 till one to 50. The excipient is selected from one kind of mannitol and lactose. The optional choice is the mannitol. The preparation method is as following. The Clofarabine is melted with the injection water and the excipient is added. Followed by well mixing , filtration, packaging, adding stopper and loading in the plate. The freeze dryer is opened in advance. The platelayer is cooled with the heat conduction oil until temperature of the platelayer increases till minus 40 DEG Cto minus 50 DEG C. The Clofarabine solution packaged in the sterile silin bottle can be sent to the freeze dryer quickly.The box door is shut and the plate temperature is kept at minus 40 DEG Cto minus 50 DEG C and the box temperature is decreased. When the sample temperature reaches minus 40 DEG C, The plate cooling is stopped and the condenser is opened. At the same time the product temperature is maintaineed by cooling for 3 hours. When the temperature of the condenser reaches minus 40 DEG, the vacuum system is opened. After temperature holding, four steps of heating, sublimation, drying, plugging, box pressing and opening sealing can be started.

The invention relates to a synthesis method of clofarabine, a midbody thereof and a preparation method of the midbody. The synthesis method comprises the steps of: 1) a compound I is reacted with strong lewis acid and water in dichloromethane respectively to generate a compound II; 2) the compound II is jointly reacted with PBSF and Et3N.3HF in methylbenzene and triethylamine to be taken as a fluorination agent, and is fluoridized by adding Et3N with proper amount to generate a compound III; 3) the compound III is reacted with hydrogen bromide to generate a compound IV; 4) the compound IV is condensed with 2-arprinocide and ROM to generate a compound V; and 5) the compound V is reacted with lithium hydroxide to prepare the clofarabine. After the synthesis method is used, the strong lewis acid which can be dissolved in the methylene dichloride is taken as a rearrangement agent, so that the complex step of feeding HBr or Hcl gas is eliminated; and as raw materials for the fluoridation are low in price and are relatively stable to water, the strict water-free operation does not need, and equipment can not be corroded, so that the synthesis method is safe to use. The preparation totalyield is improved to 18.3%.

The invention belongs to a chemical synthesis drug process, particularly relating to a new synthesizing process of antineoplastic agent clofarabine, which has cheap, easily obtained original raw materials, moderate condition in the reaction and no device specially required, and can be applied to industrial production. In the method, a new synthesizing intermediate is adopted to carry out systemization, therefore, the invention also relates to a novel intermediate in use of the method.

The invention provides a clofarabine pharmaceutical composition freeze-dried powder injection which is prepared by freeze-drying 10-30 parts by weight of clofarabine, 100-300 parts by weight of mannitol, 20-60 parts by weight of sodium bicarbonate, pH regulator and water for injection. The clofarabine pharmaceutical composition freeze-dried powder injection is a white or almost white loose mass or powder with good stability and good product redissolution property. The invention also provides a preparation method of the clofarabine pharmaceutical composition freeze-dried powder injection with simple method and strong operability.

The invention discloses a method for purifying clofarabine by a chromatographic column. The method adopts an inverse macroporous adsorption resin as a chromatographic column packing material to prepare the chromatographic column, adds a crude product water solution of the clofarabine with a concentration of between 0.001 and 0.025 weight percent into the chromatographic column, then performs the elution by pure water first, then orderly uses pure water/organic solution mixed liquids with the gradually reduced volume ratios as eluents for gradient elution, and collects and concentrates the eluents with qualified purity. The purification method ensures that the purity of a clofarabine product reaches more than 99.8 percent and the yield reaches more than 90 percent, has simple operation, and is suitable for industrial mass production.

This invention relates to methods of treating or preventing an autoimmune disorder comprising the administration of clofarabine or a pharmaceutically acceptable salt, hydrate, solvate, clathrate, prodrug or metabolite thereof to a patient in need of such treatment. The invention further relates to methods of treating or preventing an autoimmune disorder comprising the administration of clofarabine or a pharmaceutically acceptable salt, hydrate, solvate, clathrate, prodrug or metabolite thereof and an additional therapeutic agent to a patient in need of such treatment.

The invention discloses a clofarabine and methotrexate double-medicine preparation and a preparation method thereof. The clofarabine and methotrexate double-medicine preparation is prepared from the effective components of clofarabine and methotrexate according to the molar ratio of (0.8-1.2):(0.8-1.2), wherein the clofarabine serves as main medicine, the methotrexate serves as auxiliary medicineand targeting molecules, the methotrexate and the clofarabine are connected through the hydrogen-bond effect to form micelle, and the micelle is freeze-dried under vacuum. The grain diameter of the clofarabine and methotrexate double-medicine nano-micelle is 100-200 nm, the stability of the preparation obtained after freeze-drying is good, a good responsiveness release characteristic is achieved after the preparation is injected into the human body, it is proved through the cytotoxicity test that compared with pure double-medicine use of the clofarabine and the methotrexate, a higher tumor suppression effect is achieved, and the preparation is suitable for serving as an intravenous injection preparation, and has the advantages of being high in targeting performance, long in circulation andlow in toxicity and achieving synergistic treatment.

A slow release anticancer injection carrying clofarabine and a synergist thereof comprises slow release microspheres and a solvent, wherein the slow release microspheres comprise effective anticancer ingredients and slow release adjuvants, and the solvent is a special solvent containing a suspending agent. The effective anticancer ingredients comprise clofarabine and a clofarabine synergist selected from phosphoinositol-3-kinase inhibitor, pyrimidine analogues and/or DNA repairase inhibitor; the slow release adjuvants comprise biocompatible polymers such as polylactic acid (PLA) and copolymer thereof, polylactic acid-polyethylene glycol (PEG)-COOH copolymers, fatty acid dimmer-sebacic acid copolymers, polys(erucic acid dimmer-sebacic acid), polys(fumaric acid-sebacic acid), polifeprosan, polylactic acid and EVAc; the suspending agent has viscosity of 100-3,000cp (at 20-30 DEG C) and is selected from sodium carboxymethyl cellulose, etc. The effective anticancer ingredients and the slow release microspheres can also be made into slow release implant, and the slow release injection and implant can be injected into tumor or around tumor to effectively inhibit tumor growth and remarkably strengthen the effect of non-surgery treatments as chemotherapy or the like.

A compound anti-cancer sustained-release injection containing clofarabine is composed of sustained-release microspheres and a solvent, wherein, the sustained-release microspheres comprise anti-cancer effective components and sustained-release excipients, the anti-cancer effective components are composed of the clofarabine and a clofarabine synergist which is selected from anti-tumor antibiotics and/or anti-metabolism drugs, the solvent is the special solvent containing a suspending agent; the sustained-release excipients are selected from polylactic acid/glycolic acid copolymer, monomethyl polyethylene glycol/polylactic acid, polyethylene glycol/polylactic acid, terminal carboxyl polylactic acid, terminal carboxyl polylactic acid/glycolic acid copolymer, EVAc, copolymer of fatty acid and sebacic acid and so on; the viscosity of the suspending agent is 80cp to 3000cp ( at 20 DEG C to 30 DEG C ), and the suspending agent is selected from carboxymethyl cellulose and so on; the sustained-release microspheres can further be made into a sustained-release implant which is injected or arranged in a tumor or the tumor periphery, and the local drug release can approximately last 30 to 50 days. The independent application of the sustained-release injection and the sustained-release implant can effectively inhibit the tumor growth, and the combined application with chemotherapy drugs and/or radiotherapy and other non-surgical therapies, and also can significantly enhance the efficacy.

This invention relates to methods of treating or preventing lupus comprising the administration of clofarabine or a pharmaceutically acceptable salt, hydrate, solvate or clathrate thereof to a patient in need of such treatment. The invention further relates to methods of treating or preventing lupus comprising the administration of clofarabine or a pharmaceutically acceptable salt, hydrate, solvate or clathrate thereof and an additional therapeutic agent to a patient in need of such treatment.

Disclosed is an anticancer slow release injection containing clofarabine and cytotoxic drugs, which comprises slow release micro-balloons and dissolvent, wherein the slow release microballoons comprise anti-cancer active constituents and slow release auxiliary materials, the dissolvent being specific dissolvent containing suspension adjuvant. The anticancer active constituents include clofarabine and cytotoxic drugs, the cytotoxic drugs are selected from anti-taxone, alkylating agent, Topo enzyme inhibitor and/or plant alkaloid, The slow release auxiliary materials are selected from polylactic acid and glycollic acid copolymer, polyethylene glycol and polylactic acid copolymer, PLA-COOH copolymer, EVAc, aliphatic acid and sebacylic acid copolymer, The viscosity of the suspension adjuvant is 100-3000cp (at 25-30 deg C),and is selected from sodium carboxymethylcellulose.

Disclosed is an anticancer slow release injection carrying both clofarabine and its synergistic agent, which comprises slow release micro-balloons and dissolvent, wherein the slow release microballoons comprise anti-cancer active constituents and slow release auxiliary materials, the dissolvent being specific dissolvent containing suspension adjuvant. The anticancer effective ingredients include clofarabine and its synergistic agents selected from phosphoinositide-3-enzyme inhibitor, pyrimidine analog and /or DNA restoring enzyme inhibitor, the slow release auxiliary materials are selected from polylactic acid and copolymer, polyethylene glycol, PLA-COOH copolymer, di-aliphatic acid and sebacylic acid copolymer, poly(erucic aciddipolymer-sebacylic acid), poly(fumaric acid-sebacylic acid), Polifeprosan, poly(lactic acid) and EVAc, the viscosity of the suspension adjuvant is 100-3000cp (at 20-30 deg C), and is selected from sodium carboxymethylcellulose.

Disclosed is an anticancer slow release injection carrying both clofarabine and cytotoxic drugs, which comprises slow release micro-balloons and dissolvent, wherein the slow release microballoons comprise anti-cancer active constituents and slow release auxiliary materials, the dissolvent being specific dissolvent containing suspension adjuvant. The anticancer active constituents include clofarabine and cytotoxic drugs selected from adriamycin, pidorubicin, Melphalan, 4-hydroperoxycyclophosphamide, actinomycin D, Vinorelbine, Tamoxifen, Tallimustine, Atrimustine, Semustine and ranimustine, the slow release auxiliary materials are selected from polylactic acid and copolymer, monomethyl polyethylene glycol, polyethylene glycol and polylactic acid copolymer, EVAc, aliphatic acid and sebacylic acid copolymer, The viscosity of the suspension adjuvant is 100-3000cp (at 25-30 deg C), and is selected from sodium carboxymethylcellulose.

The invention discloses a clofarabine compound anticancer slow-release injection which is an anticancer slow-release injection and consists of slow-release microspheres and solvent; wherein, the slow-release microspheres comprise anticancer effective ingredients and slow-release auxiliary materials; the solvent is a special solvent containing a suspending agent; the anticancer effective ingredients are combination of the clofarabine and a clofarabine synergist which is selected from antitumor antibiotics and/or antimetabolic drugs; the slow-release auxiliary materials are selected from one or combination of copolymer of racemic polyactic acid and copolymer thereof, copolymer of monomethyl polyethylene glycol or polyethylene glycol or carboxyl-terminated polyactic acid and polyactic acid, copolymer of bi-fatty acid and sebacic acid, poly-(erucic acid dimmer-sebacic acid), poly-(fumaric acid-sebacic acid), polifeprosan and EVAc; the suspending agent has 80cp-3000cp of viscosity; the slow-release microspheres also can be made into a slow-release implant, is injected or placed in tumor or around the tumor, and release drugs for about 40 days; the slow-release injection and the slow-implant can be applied separately so as to suppress the tumor growth or is applied with the non-operative treatment of chemoradiotherapy, and the like, in a combining way, so as to enhance the curative effect thereof significantly.

The invention belongs to pharmaceutical technical field, and provides a method for separating and purifying Clofarabine, the method comprises the following steps: a step of dissolving and filtering, a step of separating and purifying by high performance preparative liquid chromatography, a step of recovering products and the like, wherein the step of separating and purifying employs inverse high performance preparative liquid chromatography, the mobile phase is an acetonitrile solution, and an UV detector carries out on-line detection. The method of the invention has the advantages of simple operation, high separation efficiency, stable technology and low cost, and separation with high purify of mass Clofarabine can be realized, the purity is more than 99.8% and the yield is more than 98%.