73 results about "Caspofungin" patented technology

The present invention provides Caspofungin and salts thereof substantially free of Caspofungin C₀ and salts thereof. The present invention also provides processes for the preparation of said Caspofungin and salts thereof and processes for the determination of the amount of Caspofungin C₀ and salts thereof present in Caspofungin and salts thereof. The present invention further provides pharmaceutical compositions comprising said Caspofungin and salts thereof.

The present invention relates to pharmaceutical compositions comprising a pharmaceutically acceptable salt of caspofungin as active ingredient being useful for the prevention and/or treatment of fungal infections. Said compositions additionally comprise specific bulking agents and small amounts or no amounts of an additional pH modifier and may be in a liquid or solid form, e.g. may be lyophilized compositions. Said compositions show good stability and reduced amounts of sub-visible particulate matter formed in solutions which are reconstituted from the lyophilized product.

This invention relates to a method of treating otitis externa, and in particular otitis externa of fungal etiology, using topical medication, including antifungal agents such as, for example fluconazole, voriconazole, itraconazole, clotrimazole, amphotericin B, caspofungin (Cancidas®), micafungin (Mycamine®), terbinafine, naftifine, butenafine, amorolfine, ravuconazole, posaconazole, flucytosine, econazole, enilaconazole, miconazole, oxiconazole, saperconazole, sulconazole, terconazole, tioconazole, nikkomycin Z, anidulafungin (LY303366), nystatin, pimaricin, griseofulvin, ciclopirox, haloprogin, tolnaftate, and undecylenate.

The invention relates to a method for purifying a caspofungin precursor pneumocandin B0 component, and the method comprises the following steps of: carrying out reversed-phase column chromatography on a PB0 component crude product, collecting and carrying out reduced-pressure concentration to obtain a semi-pure product; carrying out normal phase column chromatography on the PB0 semi-pure product obtained in the step 1 to obtain high-purity PB0 component; and carrying out positive and negative phase liquid phase analysis, wherein the chromatographic purity is more than 95%. Compared with the prior art, the method has the beneficial effects that a normal phase column and a reversed-phase column are used for purifying the PB0 component, so that the purification steps are simple, the purification effect is good, the requirements for equipment are low, large-scale production is realized, and the production feasibility is high; and particularly, the PB0 component separated by the method is high in yield, but is lower in cost.

The invention relates to a preparation method of caspofungin. The preparation method comprises the following steps: using p-thiocresol to replace hydroxide radicals of pneumocandins B0, then reducing acylamino groups by using a reducing agent, and finally using ethidene diamine to replace p-sulfonyl toluene, thus obtaining the caspofungin. According to the preparation method disclosed by the invention, an appropriate solvent is adopted for crystallizing and separating an intermediate, repeated separation and purification operation for chromatographic column preparation in the prior art is avoided, the reaction time is shortened, degradation of the intermediate is avoided, the operation is simplified, high-purity and high-yield caspofungin is obtained, and the preparation method is particularly suitable for industrial production.

The invention discloses a genetic recombination strain for producing pneumocandins B0, a breeding method and applications. The bacterial strain classification name of the genetic recombination strain is Glarea lozoyensis Q45; the preservation registration number is CCTCC NO: M2014416; and the preservation date is September 14, 2014. The method for breeding the strain includes the steps that an original strain is manufactured into a protoplast; a mutation library composed of a plurality of mutant strains is obtained through ion implantation and lithium chloride processing; the mutation library is manufactured into a protoplast again; random fusion is carried out on the protoplasts after ion implantation inactivation and heat inactivation are carried out; fermentation screening is carried out on high-yield genetic recombinant bacteria; and protoplast preparation and fusion and fusant screening are carried out on the screened genetic recombinant bacteria, and therefore the genetic recombination strain is obtained. The genetic recombination strain is excellent in performance and stable in production capacity; the yield of the pneumocandins B0 obtained through fermentation is 6 g/L; in addition, by-products are few; the post-extraction difficulty of the pneumocandins B0 is reduced; the application to high-quality caspofungin preparation is facilitated; and the genetic recombination strain has the important industrial value.

The invention discloses an echinocandin antifungal agent caspofungin containing medicinal composition, which contains cane sugar used as an excipient. The medicinal composition provide by the invention has good stability.

The invention relates to a drug composition, containing caspofungin or pharmaceutically acceptable salts thereof, and a lactate buffering agent in a pharmaceutically acceptable amount. By addition of the lactate buffering agent, the composition greatly decreases generation of caspofungin degradation product, greatly raises stability of caspofungin, and is convenient for preservation and clinic usage, thereby raising usage security of caspofungin.

The invention discloses a method for detecting antifungal drugs in serum by an ultra-high performance liquid chromatography-tandem mass spectrometry technology. The antifungal drug is prepared from fluconazole (FCZ), voriconazole (VCZ), voriconazole N-oxide (OVCZ), posaconazole (PCZ), itraconazole (ICZ), hydroxyl itraconazole (HICZ) and caspofungin (CPF). The method includes: detecting the contentof the antifungal drug in the pretreated serum by adopting ultra-high performance liquid chromatography tandem mass spectrometry, performing quantifying by utilizing a mass spectrum isotope internalstandard method, establishing a calibration curve by taking the concentration ratio of a standard substance to an internal standard substance as an X axis and the peak area ratio of the standard substance to the internal standard substance as a Y axis, and calculating the concentration of a target drug in the serum; the method is high in sensitivity, high in specificity, accurate and simple in pretreatment process, separation and detection of seven common antifungal drugs are completed at the same time within 5.0 min, the accuracy and precision basically meet the requirements, and a simple andrapid detection method is provided for clinical antifungal drug concentration monitoring.

The invention provides a method for separating and purifying Pneumocandins B0, which comprises the steps of acidifying and extracting a broth, separating a leaching solution by resin adsorption, concentrating, and then drying to obtain the Pneumocandins B0. The obtained product with high purity is a good raw material to prepare antifungal drug Pneumocandins B0. The prepared end product has the advantages of high yield, low production cost, and simple operation, and is especially suitable for industrial production.

The invention belongs to the technical field of medicines, and particularly relates to a synthesis method of caspofungin. The synthesis method comprise the following steps: mixing a compound shown asformula II and thionyl chloride dissolved in a solvent A to form a compound shown as formula III, mixing the compound shown as the formula III without purification and ethidene diamine dissolved in asolvent B to form a compound shown as formula IV, mixing the compound shown as the formula IV and a borane complex to form a compound shown as formula I. The synthesis method replaces virulent and malodorous thiol or thiophenol compound with an irritating odor with thionyl chloride, and avoids using highly corrosive acid; formed cyclic sulphite facilitates configuration retention of a reactant; atthe same time, an ethidene diamine group is directly introduced into cyclic sulphite without the purification since cyclic sulphite has properties that cyclic sulphite is easy to remove and does notchange a chiral configuration of the reactant; a reaction procedure is shortened; the number of times of the purification for preparation is reduced; and the purity and yield are improved.

The invention provides a pharmaceutical composition of a freeze-dried powder injection containing caspofungin or pharmaceutically acceptable salts of the caspofungin, and a preparation method of the pharmaceutical composition. The composition contains caspofungin or pharmaceutically acceptable salts of the caspofungin, a pH modifier and pharmaceutically acceptable auxiliary materials, wherein the pharmaceutically acceptable auxiliary materials are one or more of cane sugar, mannitol, newtol and sorbitol; and the pH modifier is one or more of appropriate lactic acid, sodium hydroxide and potassium hydroxide, so that the pH value of the pharmaceutical composition is kept within an acceptable range.

The present disclosure concerns methods and formulations for delivery of hydrophobic agents (such as ubiquinone or poorly soluble drugs) for therapeutic and bioanalytical use. It further concerns use of lipopeptides (e.g. caspofungin) or surfactants to solubilize hydrophobic agents and thus increase their bioavailability. Also described are therapeutic methods for the treatment of conditions that benefit from such hydrophobic agents. The present disclosure further relates to methods of identifying drug candidates for treatment of ubiquinone deficiency.

The invention discloses a liquid pharmaceutical composition containing echinocandin antifungal agent caspofungin, wherein the pharmaceutical composition containing carbohydrate as a stabilizer. The pharmaceutical composition provided by the invention has good stability.

The invention provides a method for separating and purifying caspofungin or its salt, which comprises the following steps: separating caspofungin or its pharmaceutically acceptable salt in a reversed column chromatography, then recrystallizing, and drying to obtain caspofungin or its pharmaceutically acceptable salt with high purity. The prepared end product has the advantages of high purity and low production cost, the medicine quality is increased, operation is simple, and the method is suitable for industrial production.

The invention discloses a preparation method of a high-purity and high-yield caspofungin impurity CO. The preparation method comprises step1, an intermediate I is prepared from solids containing pneumocandins BO and CO; step 2, a crude product of an intermediate II is prepared from the intermediate I, chromatography purification and separation are performed with a reversed-phase chromatography method and a normal-phase chromatography method, and the intermediate II is obtained; step3, a crude product of the caspofungin impurity CO is prepared from the intermediate II, chromatographic separation is performed with a reversed phase chromatography method, and the high-purity caspofungin impurity CO is obtained. By means of a specific combination and purification method of raw materials, the caspofungin impurity CO with HPLC (high performance liquid chromatography) purity higher than 97% can be obtained, and a way is provided for preparation of the caspofungin impurity CO. The purity of the product obtained with the method can completely meet the requirements, and a process is relatively simple.

The invention discloses an application of a kind of small molecule compounds as an adjuvant in the preparation of antifungal drugs. After 51,520 small molecule compounds in a national compound sample bank are subjected to high-throughput screening, the result shows that when small molecule compounds as shown in a formula I to a formula X independently act on a candida albicans biological membrane, the inhibition ratio is almost zero, but when the small molecule compounds are used with conventional antifungal drugs such as amphotericin B, fluconazole or caspofungin, the remarkable synergism is achieved, the efficacy of the conventional antifungal drugs is improved by 30% or above, the use dosage of the conventional antifungal drugs is reduced, and the inhibiting effect of the antifungal drugs to drug resistance fungi is improved.

The invention relates to an application of caspofungin in preparation of a medicine for treating ischemia/reperfusion injury. The caspofungin is used for treating ischemia/reperfusion injury, particularly myocardial tissue ischemia, and more particularly has a protective effect on myocardial ischemia/reperfusion, so that the myocardial ischemia/reperfusion injury can be remarkably reduced.

The invention belongs to the technical field of medicine, and more specifically relates to applications of traditional Chinese medicine sanguisorba officinalis in preparing an antifungal drug synergist. It is confirmed by in vivo experiments that sanguisorba officinalis possesses synergistic effects with routine antifungal drugs such as fluconazole, miconazole, caspofungin, and amphotericin B; with regard to drug resistance funguses, when the antifungal drugs are combined with sanguisorba officinalis, drug dose of the routine antifungal drugs can be reduced obviously, inhibiting effects of the routine antifungal drugs on funguses can be improved to different degrees, effects of the antifungal drugs on the drug resistance funguses can be recovered, and inhibiting effects on the drug resistance funguses are improved. Novel applications of traditional Chinese medicine sanguisorba officinalis are provided; clinical fungus drug resistance can be widely observed, and drug resistant degree becomes higher, drug dose of the antifungal drugs can be reduced, medical cost is reduced for patients, and drug toxic and side effects are reduced.

The invention belongs to the technical field of medicines, and particularly relates to a caspofungin intermediate and a synthesis method thereof. The synthesis method of the intermediate comprises thefollowing steps of: mixing a compound as shown in a formula II and thionyl chloride dissolved in a solvent A to obtain a compound as shown in a formula III. The method replaces thiol or thiophenol compound with high toxicity, foul smell and pungent smell with the thionyl chloride so as to avoid the use of strong corrosive acid, and the formed cyclic sulfite is favorable for maintaining the configuration of a reactant; and meanwhile, the method utilizes the property that the thionyl chloride is easy to leave and does not change the chiral configuration of the reactant, directly introduces ethylenediamine groups without purification, shortens the reaction steps, reduces the times of preparation and purification, and improves the yield and purity.