48 results about "Epothilones" patented technology

The present invention describes polymer nanoparticles with a cationic surface potential, in which both hydrophobic and hydrophilic pharmaceutically active substances can be encapsulated. The hydrophilic and thus water-soluble substances are encapsulated in the particle core by co-precipitation through ionic complexing with a charged polymer. Both therapeutic agents and diagnostic agents can be used as pharmaceutically active substances for encapsulation. The cationic particle surface permits stable, electrostatic surface modification with partially oppositely charged compounds, which can contain target-specific ligands for improving passive and active targeting.

The invention relates to a new process for concentrating epothilones in culture media, a new process for the production of epothilones, a new process for separating epothilones A and B and a new strain obtained by mutagenesis for the production of epothilones, as well as aspects related thereto. New crystal forms of epothilone B are also described.

The invention relates to a preparation method of epothilones B. In particularly, the invention provides a technique method to prepare epothilones B through adopting 100 to 500 liters fermentor to ferment and to separate epothilones B in large scale. The invention also relates to the preparation and application of epothilones B in preparation of gleevec resistance chronic myeloid leukemia treatment drug.

The present invention provides compounds of formula (I):

• • as described generally and in classes and subclasses herein. The present invention additionally provides pharmaceutical compositions comprising compounds of formula (I) and provides methods of treating cancer comprising administering a compound of formula (I).

Formulations comprising one or more epothilones together with a pharmaceutically acceptable carrier.

Recombinant host cells of the suborder Cystobacterineae, genus Stizmatella, containing recombinant expression vectors that encode heterologous epothilone polyketide synthase (PKS) genes and can produce epothilones at high levels are provided.

A process for extracting Epophilone from fermented liquid of myxobacterium includes mixed resin adsorption, solid and liquid extractions, molecular sieve chromatography, crystallizing and effiicent liquid-phase separation. Its advantages are high purity and extraction rate (more than 80%). The said Epophilone is an antineoplastic compound.

An anticancer composition containing neovascular inhibitor and epothilone and able to be made into slow-release implant or injection is composed of the slow-release microballs and solvent. Said slow-release microball consists of active anticancer component (neovascular inhibitor and/or epothilone) and slow-release additives (p (LAEG-EOP), p (DAPG-EOP), etc). Said solvent is an ordinary solvent or the special solvent containing the suspending aid.

The invention discloses an Epothilone freeze-dried compound which mainly contains the Epothilone, a solubilizer and a freeze-dried excipient; wherein, a preferable solubilizer is Carmowax 12-hydroxyl stearate. The product not only is simple in technique and is stable in quality, but also is low in side effect.

A slowly-release anticancer medicine in the form of injection or implant is disclosed. Said slowly-release injection is composed of a special solvent containing suspending aid and the slowly-release microballs consisting anticance medicine, iterstitial hydrolyte and slowly-releasing auxiliary. Said anticancer medicine is chosen from Epothilone A, Epothilone B, etc. Said interstitial hydrolyte is chosen from collagenase, relaxin, etc. Said slowly-releasing auxiliary is chosen from p(BHET-EOP/TC), p(LAEG-EOP), polyethanediol, etc.

The invention relates to a membrane extraction separation technique of epothilone, which comprises the following steps: filtering an epothilone a and b fermentation liquid through an organic membrane to obtain an organic membrane filtrate, and filtering the organic membrane filtrate through a ceramic membrane to obtain a ceramic membrane filtrate; eluting with a gel chromatographic column, sectionally collecting the eluates subjected to HPLC (high performance liquid chromatography) detection, concentrating the eluates through a nanofiltration membrane, eluting the concentrated solution by normal-phase silica gel chromatography, sectionally collecting the eluates subjected to HPLC detection, and crystallizing the collected eluates at low temperature to obtain the epothilone a and b crystal. The molecular weight cutoff of the organic membrane is 5000-6000. The molecular weight cutoff of the ceramic membrane is 1000-1500. The molecular weight cutoff of the nanofiltration membrane is 500-800. The crystallization temperature is -30 to -10 DEG C. The normal-phase chromatography is utilized to separate the epothilone a and b in the concentrated solution, thereby reducing the consumption of the organic solvent, simplifying the extraction process and lowering the cost.

The invention belongs to the technical field of biology, and particularly discloses a pretreatment method of epothilone B fermentation liquor. An inorganic salt is added into the fermentation liquor,so that resin and thalli are thoroughly separated, only the resin phase remains after the thalli are removed, the subsequent extract is reduced to 1/3 of the original mixture, an organic solvent for further extraction is saved, and impurities in the thalli are prevented from being introduced into the subsequent purifying process; and impurities with the retention time similar to that of epothiloneB are removed from the source. In addition, the separated resin phase does not need to be centrifuged or filtered by a plate frame and is directly loaded into a column without blocking a sieve plate,so that the column passing time is saved. According to the pretreatment method of the epothilone B fermentation liquor, the thalli and the resin are well separated, subsequent extraction steps are simplified, the usage amount of subsequent extraction organic solvents is reduced, the extraction efficiency and yield are improved, the universality is high, and the industrialization cost is low.

The invention provides a method for preparing epothilone B based on coupling of separation and fermentation of a molecularly imprinted membrane. The method comprises the following steps: carrying out early fermentation to obtain a seed culture solution, carrying out fermentation culture on the seed culture solution in a fermentation tank, filtering a fermentation solution by utilizing the molecularly imprinted membrane in the fermentation process, eluting a substance obtained through filtration, collecting the eluent and finally concentrating the eluent, thus obtaining epothilone B. The method has the beneficial effects that epothilone B is produced through fermentation by utilizing the fermentation tank and the specific adsorption separation and the fermentation process of the molecularly imprinted membrane are coupled, namely, the metabolite epothilone B is timely separated while producing epothilones B through fermentation, so that the concentration of epothilone B in the fermentation tank is maintained at a lower level, thus reducing feedback inhibition and product toxicity and increasing the fermentation yield; meanwhile, epothilone B is specifically separated by utilizing the molecularly imprinted membrane but other components are not separated to reduce the costs of downstream separation and purification; the method is beneficial for aftertreatment of the fermentation solution and refining of the products and has extensive application prospect in the industrial circles.

The invention discloses sorangium cellulosum highly producing epothilone D as well as a construction method and application of the sorangium cellulosum. The invention discloses construction of a recombinant sorangium cellulosum So ce M4 strain with an epoK gene knocked out by a TALEN technology for the first time. Tests prove that by knocking out the epoK gene in the sorangium cellulosum So ce M4strain by the TALEN technology, the yield of the epothilone D can be significantly increased, and meanwhile, the yield of epothilone B can be reduced, so that directed biosynthesis of epothilone in the sorangium cellulosum can be realized. The invention discloses the increase of the yield of the epothilone produced by the sorangium cellulosum by the TALEN for the first time, the TALEN technology is applied to increase of the yield of the epothilone D produced by the sorangium cellulosum, biosynthesis of the epothilone is promoted while the development of a sorangium cellulosum genetic engineering modification technology is promoted, and the application of the epothilone D in antitumor aspects is enlarged, which has quite important significance in development of biomedicine in China.