49 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 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.

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.

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.

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%.