30 results about "Fotemustine" patented technology

The invention relates to anticancer sustained release injection which comprises sustained release microspheres and menstruum, wherein, the sustained release microspheres comprise anticancer active components and sustained release auxiliary material; the menstruum is special menstruum that contains suspending agent. The anticancer active components are fotemustine, nimustine, carmustine or combination of bendamustine and mitozolomide, docetaxel, etoposide, teniposide, vinblastine, anastrozole, tamoxifen, fluorouracil or mitomycin C; the sustained release auxiliary material is polylactic acid and polylactic acid copolymer, polyethylene glycol and polylactic acid copolymer of polyethylene glycol, terminal carboxyl group polylactic acid copolymer, EVAc, fatty acid and decanedioic acid copolymer, etc.; viscosity of the suspending agent is 100cp-3,000cp (at 25 DEG C-30 DEG C), and the suspending agent is selected from sodium carboxymethylcellulose, etc. The sustained release microspheres can also be made into sustained release implant; the injection or implant is injected or placed in or around tumor so as to reduce general reaction of the drug and selectively improve and keep local concentration for about 30-50 days. The anticancer sustained release injection can be used solely and can also promote anti-tumor effects of non-operative treatments, such as chemotherapy and/or radiotherapy, etc.

The invention relates to an anticancer slow-release gel injection and a preparation method thereof. The anticancer slow-release gel injection contains a taxane-like drug such as paclitaxel, docetaxel, hydroxypaclitaxel, epi-paclitaxel or deacetylpaclitaxel, a stine-like drug, an amphiphilic block polymer and a solvent. The composition exhibits the property of temperature-sensitive gelation, is a flowable liquid at the room temperature and turns into a stagnant and biodegradable water-insoluble gel in vivo in warm-blooded animals. The stine-like drug is selected from atrimustine, ambnmustine, nimustine, bendamustine, carmustine, elmustine, galamustine, fotemustine, estramustine, hesmustine, neptamustine, lomustine, semustine, ranimustine, semustine, tauromustine, tallimustine and spiromustine. The anticancer slow-release gel injection can release the drug slowly and locally around the tumor and retain the effective blood concentration for a plurality of weeks to a plurality of months, can not only kill tumor cells but also effectively inhibit tumor vessels, can reduce the general drug toxicity and can enhance the curative effect of chemotherapy particularly radioactive seed implantation.

The invention provides a fotemustine solid lipid nanoparticle for injection and oral administration. The nanoparticle is characterized in that a lipid material and an emulsifier are used to encapsulate the fotemustine to prepare the fotemustine solid lipid nanoparticle with small particle diameter, high encapsulation rate, good stability and low toxicity. The prepared fotemustine solid lipid nanoparticle improves the solubility and the stability of the fotemustine, reduces vascular stimulation of the fotemustine, and prolongs the circulating time of the medicament in blood, thereby improving the curative effect of medicaments, and ensuring that preparations made of the solid lipid nanoparticle have the characteristics of low toxicity, low fotemustine solid lipid nanoparticle with low stimulation and high efficiency. The invention also relates to a method for preparing the fotemustine solid lipid nanoparticle, which has simple preparation process and low cost, and is applicable to industrial production.

A new anticarcinogenic sustained-release injection consists of sustained-release microballoon sphere and menstruum; wherein, the sustained-release microballoon sphere comprises anticarcinogenic active ingredient and sustained-release accessory material; the menstruum is special menstruum containing suspending agent. The anticarcinogenic active ingredient is the combination of cytotoxic drugs of fotemustine, bendamustine, tallimustine, carmustinum, nimustine, lomustine, semustine or ranimustine and adriamycin, epirubicin, melphalan, 4H peroxide cyclophosphamide, actinomycin D, vinorelbine or nolvadex, etc.; the sustained-release accessory material is selected from polylactic acid and the multipolymer or mixture thereof, mono-methyl polyethyleneglycol, polyethyleneglycol or polylactic acid multipolymer, EVAc, the multipolymer of fatty acid and decanedioic acid, etc.; the viscosity of the suspending agent is 100cp-3000cp (at the temperature of 25 DEG C-30 DEG C), the suspending agent is selected from sodium carboxymethyl cellulose, etc. The sustained-release microballoon sphere also can be made into sustained-release implant which can be injected and placed in tumor or around tumor and can release medicine at the local parts of the tumor for 30 to 40 days; therefore, the anticarcinogenic sustained-release injection can be separately united together with non-operativetreatment such as chemo-treatment and/or radiation treatment, etc. for application.

Disclosed is a slow release injection containing platinum-group compounds and/or alkylating agents, which comprises slow release microspheres and dissolvent, the slow release microspheres include platinum-group compounds selected from Tegafur, Capecittabine, Pemetrexed, Carboplatin or Gemcitabine, and/or alkylating agent anticancer active constituents and slow release auxiliary materials, the dissolvent being conventional dissolvent or specific dissolvent containing suspension adjuvant. The viscosity of the suspension adjuvant is 100-3000cp (at 20-30 deg C), and is selected from sodium carboxymethylcellulose, the slow release auxiliary materials are selected from polyphosphate ester copolymers such as p(LAEG-EOP), p(DAPG-EOP), copolymer or blend of polyphosphate ester with PLA, Polifeprosan, poly(dodecanedioic acid-tetradecanedioic acid) or poly(fumaric acid-sebacylic acid). The alkylating agent is selected from Carmustine, Nimustine, Fotemustine, Lomustine or bendamustine. The anticancer composition can also be prepared into slow release implanting agent, for injection or placement in or around tumor with a period of effective concentration maintenance over 60 days, as well as the treatment effect of appreciably lowering general reaction of the drugs, and improving the treatment effect of the non-operative treatment methods such as chemotherapy.

The invention relates to anticancer sustained release injection which comprises sustained release microspheres and menstruum, wherein, the sustained release microspheres comprise anticancer active components and sustained release auxiliary material; the menstruum is special menstruum that contains suspending agent. The anticancer active components are fotemustine, nimustine, carmustine or combination of bendamustine and mitozolomide, docetaxel, etoposide, teniposide, vinblastine, anastrozole, tamoxifen, fluorouracil or mitomycin C; the sustained release auxiliary material is polylactic acid and polylactic acid copolymer, polyethylene glycol and polylactic acid copolymer of polyethylene glycol, terminal carboxyl group polylactic acid copolymer, EVAc, fatty acid and decanedioic acid copolymer, etc.; viscosity of the suspending agent is 100cp-3,000cp (at 25 DEG C-30 DEG C), and the suspending agent is selected from sodium carboxymethylcellulose, etc. The sustained release microspheres can also be made into sustained release implant; the injection or implant is injected or placed in or around tumor so as to reduce general reaction of the drug and selectively improve and keep local concentration for about 30-50 days. The anticancer sustained release injection can be used solely and can also promote anti-tumor effects of non-operative treatments, such as chemotherapy and/or radiotherapy, etc.

Disclosed is a slow release injection agent of anticancer composition containing nitrosourea drugs and synergistic agent, which comprises slow release microspheres and dissolvent, wherein the slow release microspheres comprise anti-cancer active constituents and slow release auxiliary materials, the dissolvent being conventional dissolvent or specific dissolvent containing suspension adjuvant. The viscosity of the suspension adjuvant is 100-3000cp (at 20-30 deg C), and is selected from sodium carboxymethylcellulose, the nitrosourea drugs are selected from Carmustine, Nimustine or Fotemustine, the synergistic agent can be selected from tetrazine drugs such as Mitozolomide or temozolomide and / or anticancer antibiotics such as Adriamycin, Aclarubicin, Epirubicin, mitomycin or pidorubicin, the slow release auxiliary materials are selected from polyphosphate ester copolymers such as p(LAEG-EOP), p(DAPG-EOP), copolymer or blend of polyphosphate ester with polylactic acid, Polifeprosan, sebacylic acid and PLGA. The anticancer composition can also be prepared into slow release implanting agent, for injection or placement in or around tumor with a period of effective concentration maintenance over 60 days, as well as the treatment effect of appreciably lowering general reaction of the drugs, and improving the treatment effect of the non-operative treatment methods such as chemotherapy.

Disclosed is a slow release injection containing antimetabolites and/or alkylating agents, which comprises slow release microspheres and dissolvent, the slow release microspheres include antimetabolites selected from Tegafur, Capecittabine, Pemetrexed, Carmofur or Gemcitabine, and/or alkylating agent anticancer active constituents and slow release auxiliary materials, the dissolvent being conventional dissolvent or specific dissolvent containing suspension adjuvant. The viscosity of the suspension adjuvant is 100-3000cp (at 20-30 deg C), and is selected from sodium carboxymethylcellulose, the slow release auxiliary materials are selected from polyphosphate ester copolymers such as p(LAEG-EOP), p(DAPG-EOP), copolymer or blend of polyphosphate ester with PLA, Polifeprosan, poly(dodecanedioic acid-tetradecanedioic acid) or poly(fumaric acid-sebacylic acid). The alkylating agent is selected from Carmustine, Nimustine, Fotemustine, Lomustine or bendamustine. The anticancer composition can also be prepared into slow release implanting agent, for injection or placement in or around tumor with a period of effective concentration maintenance over 50 days, as well as the treatment effect of appreciably lowering general reaction of the drugs, and improving the treatment effect of the non-operative treatment methods such as chemotherapy.

The slow released anticancer injection consists of slow released microsphere and solvent. The slow released microsphere includes effective anticancer component and slow releasing supplementary material, and the solvent is special solvent containing suspending agent. The effective anticancer component is composition of fotemustine, bendamustine, tallimustine and other cell toxicant medicines. The slow releasing supplementary material is polylactic acid and its copolymer, EVAc, etc. The .suspending agent is carboxymethyl cellulose sodium, etc. and has viscosity of 100-3000 cp at 20-30 deg.c. The slow released microsphere may be also prepared into slow released implanting agent. The present invention has raised local concentration for 30-40 days, and may be used alone or together with chemotherapy, radiotherapy and other non-operative treatment.

The invention relates to a preparation method for a fotemustine fat emulsion injection. The invention comprises the following steps: putting soybean oil, mid-chain oil, and oleic acid into a container, stirring the mixture to prepare an oil phase; adding a certain amount of water into a mixture of fotemustine, soybean phosphatide, and glycerin to prepare a water phase; adding the oil phase into the water phase, stirring uniformly, performing high-speed shearing, adjusting the pH to be neutral, homogenizing the mixture by a high-pressure homogenizer to prepare a drug-loaded fat emulsion, filtering, filling into an ampoule, injecting nitrogen, performing melt sealing and autoclaving. The injection emulsion of the invention has the advantages of high efficiency, large drug loading amount, no toxic and side effects, good stability, and convenient usage, and the preparation method is rapid and simple, and is applicable to large amount preparation and industrial production.

Disclosed is an anticancer slow release injection carrying tumor drug resistance reversal agents and reversal agent synergistic agent, which comprises slow release micro-balloons and dissolvent, wherein the slow release micro-balloons use slow release auxiliary materials as the carrying agent, the dissolvent being specific dissolvent containing suspension adjuvant. The anticancer active ingredient in the micro-balloons is reversal agent synergistic agent selected from Tipifarnib, Ronafarnib, Valspodar, and / or selected from monohydric camptothecine, Mitozolomide, docetaxel, Oxaliplatin, Eptaplatin, Ifosfamide, Lomustine, Estramustine, Fotemustine, Samostine or Teniposide, the slow release auxiliary materials are selected from Polifeprosan, di-aliphatic acid and sebacylic acid copolymer, poly(erucic aciddipolymer-sebacylic acid), poly(fumaric acid-sebacylic acid) and EVAc.

The invention provides a preparation method of fotemustine. The preparation method comprises the following steps: carrying out an aminolysis reaction between 1-amino ethyl diethyl phosphate and carmustine in a reaction medium to obtain a compound shown in a formula (II), wherein the reaction medium comprises water; and carrying out nitrosation on the compound shown in the formula (II) to obtain fotemustine. The method provided by the invention can prepare fotemustine with the yield being greater than 25% and the purity being higher than 99.73%. In addition, by using carmustine as a raw material to replace a highly toxic liquid reagent 2-chlorethyl isocyanate, environment-friendly synthesis of fotemustine is realized; therefore, the preparation method is more suitable for industrial production.

A new anticarcinogenic sustained-release injection consists of sustained-release microballoon sphere and menstruum; wherein, the sustained-release microballoon sphere comprises anticarcinogenic active ingredient and sustained-release accessory material; the menstruum is special menstruum containing suspending agent. The anticarcinogenic active ingredient is the combination of cytotoxic drugs of fotemustine, bendamustine, tallimustine, carmustinum, nimustine, lomustine, semustine or ranimustine and adriamycin, epirubicin, melphalan, 4H peroxide cyclophosphamide, actinomycin D, vinorelbine or nolvadex, etc.; the sustained-release accessory material is selected from polylactic acid and the multipolymer or mixture thereof, mono-methyl polyethyleneglycol, polyethyleneglycol or polylactic acid multipolymer, EVAc, the multipolymer of fatty acid and decanedioic acid, etc.; the viscosity of the suspending agent is 100cp-3000cp (at the temperature of 25 DEG C-30 DEG C), the suspending agent is selected from sodium carboxymethyl cellulose, etc. The sustained-release microballoon sphere also can be made into sustained-release implant which can be injected and placed in tumor or around tumor and can release medicine at the local parts of the tumor for 30 to 40 days; therefore, the anticarcinogenic sustained-release injection can be separately united together with non-operativetreatment such as chemo-treatment and/or radiation treatment, etc. for application.

The invention relates to a compound sustained-released injection containing a neovascularization inhibitor, which comprises sustained-release microspheres and menstruum; wherein, the sustained-release microspheres are composed of sustained-release excipients, the neovascularization inhibitor selected from marimastat or fumagillin, etc. and a cytotoxic drug selected from hydroxyl campto thecine, mitozolomide, 4-carboxyl temozolomide, docetaxel, oxaliplatin, hetaplatin, ifosfamide, lomustine, estramustine, fotemustine, samustine, etoposide, teniposide, vinblastine, anastrozole, fluorouracil or mitomycin C. The menstruum is special menstruum containing a suspending agent. The sustained-release excipients are selected from polifeprosan, polylactic acid, decanedioic acid polymer, such as poly (erucic acid dipolyme-decanedioic acid) and poly (allomaleic acid-decanedioic acid), etc. and EVAc, etc; the suspending agent, the viscosity of which is 100cp-3000cp (between 25 DEG C and 30 DEG C), is selected from carboxymethylcellulose sodium, etc. The sustained-release microspheres can also be prepared to be a sustained-release implant. The sustained-release implant is injected or deposited to the interior of tumour or around the tumour, which can improve the treatment effect of non-operative treatments, such as radio-chemotherapy, etc.

The invention provides a sustained-release injection which is an anti-tumor composite containing nitrosoureas drug and bortezomib. The sustained-release injection comprises a sustained-release microsphere and a solution medium, wherein the sustained-release microsphere comprises effective anti-tumor ingredient and sustained-release excipient, the solution medium is a common solution medium or a special solution medium containing a suspending drug. The suspending drug has the viscosity between 100cp and 3000cp (under twenty centi degrees to thirty centi degrees) and is selected from sodium carboxymethylcellulose and others; the nitrosoureas drug is selected from nimustine,bendamustine,carmustine,galamustine,fotemustine,ranimustine,samustine or lomustine; the sustained-release excipient is selected from polyphosphonate copolymer like p(LAEG-EOP)or p(DAPG-EOP), PLA, PLGA, polyphosphonate with PLA, polifeprosan, the polymer or blending polymer of ( erucic acid dipolymer-sebacic acid) or poly(boletic acid-sebacic acid); the anti-tumor composite can also be prepared to be a sustained-release implant which can maintain the effective concentration of drug over forty days for intratumor or tumor circumference injection or placement, can also reduce general reaction obviously and enhance the treatment effect of non-operative therapeutics such as chemotherapy and radiotherapy.

The invention relates to novel sustained-release injection for cancer therapy. The sustained-release injection comprises sustained-release microspheres and dissolvent, wherein the sustained-release microspheres comprise active ingredients for cancer therapy and sustained-release auxiliary materials, and the dissolvent is special dissolvent containing suspending agent. The active ingredients for cancer therapy are combination of fotemustine, bendamustine, tallimustine, carmustine, nimustine, lomustine, semustine or ranimustine with cytotoxic drug of adriacin, epidoxorubicin, melphalan, 4H- cyclophosphamide peroxide, actinomycin D, vinorelbine or tamoxifen; the sustained-release auxiliary materials comprise polylactic acid and the copolymer or mixture thereof, monomethyl polyethylene glycol, polyethylene glycol/polylactic copolymer, EVAc, fatty acid and decanedioic copolymer; the viscocity of the suspending agent is 100cp to 3000cp (at 25 to 30 DEG C), and the suspending agent is selected from sodium carboxymethyl cellulose; the sustained-release microspheres can also be produced into sustained-release implant, and by injecting or positioning the sustained-release agent in tumor or tumor margin, drug release in local part of tumor can be performed for approximately 30 to 40 days; therefore, the sustained-release injection can be applied in combination with non-operative treatment such as chemical treatment and/or radiation 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 selected from docetaxel, Fotemustine, 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.

The invention relates to a compound sustained-released injection containing a neovascularization inhibitor, which comprises sustained-release microspheres and menstruum; wherein, the sustained-release microspheres are composed of sustained-release excipients, the neovascularization inhibitor selected from marimastat or fumagillin, etc. and a cytotoxic drug selected from hydroxyl campto thecine, mitozolomide, 4-carboxyl temozolomide, docetaxel, oxaliplatin, hetaplatin, ifosfamide, lomustine, estramustine, fotemustine, samustine, etoposide, teniposide, vinblastine, anastrozole, fluorouracil or mitomycin C. The menstruum is special menstruum containing a suspending agent. The sustained-release excipients are selected from polifeprosan, polylactic acid, decanedioic acid polymer, such as poly (erucic acid dipolyme-decanedioic acid) and poly (allomaleic acid-decanedioic acid), etc. and EVAc, etc; the suspending agent, the viscosity of which is 100cp-3000cp (between 25 DEG C and 30 DEG C), is selected from carboxymethylcellulose sodium, etc. The sustained-release microspheres can also be prepared to be a sustained-release implant. The sustained-release implant is injected or deposited to the interior of tumour or around the tumour, which can improve the treatment effect of non-operative treatments, such as radio-chemotherapy, etc.

Disclosed is a slow release injection agent of anticancer composition containing nitrosourea drugs and alkaloid drugs, which comprises slow release microspheres and dissolvent, wherein the slow release microspheres comprise anti-cancer active constituents and slow release auxiliary materials, the dissolvent being conventional dissolvent or specific dissolvent containing suspension adjuvant. The viscosity of the suspension adjuvant is 100-3000cp (at 20-30 deg C), and is selected from sodium carboxymethylcellulose, the nitrosourea drugs are selected from Carmustine, Nimustine, Fotemustine, Lomustine or Bendamustine, the alkaloid drugs include Vincristine, Vinblastine, Vinorelbine, Vindesine and Vinrosidine, the slow release auxiliary materials are selected from polyphosphate ester copolymers such as p(LAEG-EOP), p(DAPG-EOP), copolymer or blend of polyphosphate ester with polylactic acid, Polifeprosan, sebacylic acid and PLGA. The anticancer composition can also be prepared into slow release implanting agent, for injection or placement in or around tumor with a period of effective concentration maintenance over 60 days, as well as the treatment effect of appreciably lowering general reaction of the drugs, and improving the treatment effect of the non-operative treatment methods such as chemotherapy.

The invention relates to a compound sustained-release injection containing neovascularization inhibitors, which comprises sustained-release microspheres and a solvent; wherein, the sustained-release microspheres comprise sustained-release auxiliary materials, neovascularization inhibitors which are selected from Marimastat or fumagillin, etc., and cytotoxic drugs which are selected from hydroxycamptothecine, Mitozolomide, 4-carboxy temozolomide, docetaxel, oxaliplatin, hetaplatin, isophosphamide, lomustine, estramustine, fotemustine, samustine, etoposide, teniposide, catharanthine, anastrozole, fluorouracil, or mitomycin C; the solvent is a special solvent containing a suspending agent. The sustained-release auxiliary materials are selected from decanedioic acid copolymers such as Polifeprosan, polylactic acid, poly (erucic acid dimmer-decanedioic acid) and poly (fumaric acid-decanedioic acid) and so on, EVAc, etc.; the viscosity of the suspending agent ranges from 100cp to 3000cp (when the temperature is 25 to 30 DEG C), and the suspending agent is selected from sodium carboxymethyl cellulose, etc. The sustained-release microspheres can also be made into a sustained-release implanting agent, and can increase the curative effects of the non-operative treatments such as radiotherapy and chemotherapy, etc. when being injected or put in or around tumors.

The invention relates to anticancer sustained release injection which comprises sustained release microspheres and menstruum, wherein, the sustained release microspheres comprise anticancer active components and sustained release auxiliary material; the menstruum is special menstruum that contains suspending agent. The anticancer active components are fotemustine, nimustine, carmustine or combination of bendamustine and mitozolomide, docetaxel, etoposide, teniposide, vinblastine, anastrozole, tamoxifen, fluorouracil or mitomycin C; the sustained release auxiliary material is polylactic acid and polylactic acid copolymer, polyethylene glycol and polylactic acid copolymer of polyethylene glycol, terminal carboxyl group polylactic acid copolymer, EVAc, fatty acid and decanedioic acid copolymer, etc.; viscosity of the suspending agent is 100cp-3,000cp (at 25 DEG C-30 DEG C), and the suspending agent is selected from sodium carboxymethylcellulose, etc. The sustained release microspheres can also be made into sustained release implant; the injection or implant is injected or placed in or around tumor so as to reduce general reaction of the drug and selectively improve and keep local concentration for about 30-50 days. The anticancer sustained release injection can be used solely and can also promote anti-tumor effects of non-operative treatments, such as chemotherapy and/or radiotherapy, etc.

The invention relates to a compound sustained-release injection containing neovascularization inhibitors, which comprises sustained-release microspheres and a solvent; wherein, the sustained-release microspheres comprise sustained-release auxiliary materials, neovascularization inhibitors which are selected from Marimastat or fumagillin, etc., and cytotoxic drugs which are selected from hydroxycamptothecine, Mitozolomide, 4-carboxy temozolomide, docetaxel, oxaliplatin, hetaplatin, isophosphamide, lomustine, estramustine, fotemustine, samustine, etoposide, teniposide, catharanthine, anastrozole, fluorouracil, or mitomycin C; the solvent is a special solvent containing a suspending agent. The sustained-release auxiliary materials are selected from decanedioic acid copolymers such as Polifeprosan, polylactic acid, poly (erucic acid dimmer-decanedioic acid) and poly (fumaric acid-decanedioic acid) and so on, EVAc, etc.; the viscosity of the suspending agent ranges from 100cp to 3000cp (when the temperature is 25 to 30 DEG C), and the suspending agent is selected from sodium carboxymethyl cellulose, etc. The sustained-release microspheres can also be made into a sustained-release implanting agent, and can increase the curative effects of the non-operative treatments such as radiotherapy and chemotherapy, etc. when being injected or put in or around tumors.

The invention relates to a combination containing fotemustine, which comprises an antitumor active ingredient, a thymus preparation and auxiliary materials, wherein the antitumor active ingredient is the fotemustine, the thymus preparation is an immunopotentiator, and the auxiliary materials comprise disodium hydrogen phosphate, hydrochloric acid, poloxamer, sorbitol, tween 80, mannitol and benzyl alcohol. By organically combining the immunopotentiator and the fotemustine which has favorable curative effect but larger toxicity, the invention effectively improves the drug effect, and greatly lowers the drug toxicity meanwhile.