163 results about "Voriconazole" patented technology

The present invention relates to one kind of freeze dried voriconazole composition including voriconazole in effectively treating amount and hydroxypropyl-beta-cyclodextrin. Each of the preparation unit contains voriconazole in 50-400 mg, pregreably 200 mg and hydroxypropyl-beta-cyclodextrin of 5-40 time, preferably 15-25 times, weight of voriconazole.

The invention provides voriconazole phosphate ester for injection and a medicinal salt thereof and a preparation method for the voriconazole phosphate ester for injection and the medicinal salt thereof. The preparation method comprises the following steps: adding 5 to 98 percent water for injection in a liquid preparation container; adding 90 to 110 percent of the accurate formula dosage of voriconazole phosphate ester and the medicinal salt thereof in the container; stirring the mixture; slowly dropwise adding a pH value regulator; regulating pH to between 6.0 and 11; supplementing water to the full dosage and then adding 0.01 to 1.0 percent (weight in volume) medicinal carbon into the product; stirring the mixture for 15 to 60 minutes; using a sand filter stick to carry out rough filtration and decarburization on the obtained product, and using a 0.22mum millipore filter to carry out fine filtration on the product until the clarity is qualified; after determining that the content of the midbody is qualified, determining the filling quantity and subpackaging the finished product in the vial; adding the semi-plug; carrying out freezing and drying on the sample; controlling the moisture content between 1 and 8 percent; pressing the plug; and carrying out capping.

The invention discloses a voriconazole slow-release suppository and a preparation method thereof. The voriconazole slow-release suppository disclosed by the invention is prepared from voriconazole, a solubilizer, a slow-release material, an emulsifier, a dispersing medium and an excipient; and the preparation method disclosed by the invention comprises the following steps of: preparing slow-release microspheres by solubilizing the extremely indissolvable voriconazole, carrying out cast pouring and cooling to obtain the voriconazole slow-release suppository. The preparation method disclosed bythe invention is simple, the prepared suppository has a slow-release characteristic, the first pass effect generated by oral administration and the toxic action of intravenous administration for the organs of a whole body are avoided, and particularly for the patients of intensive care units, the patients with serious fungous infection and child and senile patients, the pain brought to the patients by frequent administration is reduced, the administration compliance is improved, and the curative effect of medicaments is improved.

The invention relates to a novel broad-spectrum antifungal medicine compound, a broad-spectrum antifungal medicine composition, an application of the compound or the composition in the preparation of a broad-spectrum antifungal medicine, and an application of the compound or the composition in the preparation of a medicine used for treating severe invasive infection (comprising Candida krusei) caused by invasive aspergillosis and / or Fluconazole-resistant Monilia and / or severe infection caused by Scedosporium and fusarium. The novel broad-spectrum antifungal medicine compound and the broad-spectrum antifungal medicine composition have extensive and strong antifungal activity and better dynamic property and safety. For deep mycotic infection, the novel broad-spectrum antifungal medicine compound and the broad-spectrum antifungal medicine composition are better than the original voriconazole in the aspects of the antibiotic activity and the medicine resistance and is better than amphotericin B in the aspects of safety and effectiveness; and compared with the formerly applied voriconazole, Fluconazole, itraconazole and amphotericin B, the novel broad-spectrum antifungal medicine compound and the broad-spectrum antifungal medicine composition have reinforced medicine effect, less adverse reaction and good safety.

The invention discloses a preparation method for voriconazole and a voriconazole intermediate. According to the invention, with a voriconazole condensate isomer as a raw material, 4-chloro-6-ethyl-5-fluoropyrimidine and 2'4'-difluoro-2-[1-(1H-1,2,4-triazolyl)]acetophenone are obtained through recovery under an acidic condition, and can be further used for preparation of the voriconazole. By adoption of the method provided by the invention, the utilization rates of raw and auxiliary materials for preparation of the voriconazole in the prior art can be greatly improved; and cost is reduced.

The invention discloses a freeze-dried voriconazole micelle preparation and a preparation method thereof. The freeze-dried voriconazole micelle preparation consists of the following components in part by weight: 1 part of voriconazole, 2 to 10 parts of cholate, 1.5 to 5 parts of phospholipid, and 1 to 10 parts of freeze-drying supporting agent. According to the preparation, the dissolubility of the voriconazole is increased, and the dissolution degree of the voriconazole in water is improved; and the preparation can be diluted into intravenous injection by using injection water for clinical use. The particle diameter of the prepared voriconazole micelles is between 10 and 100 nanometers, the particle diameter of most micelles is about 20 nanometers, the particle size is uniform, the frozen and dried voriconazole micelles are high in re-dissolution speed, a transparent and colorless solution is formed after the voriconazole micelles are re-dissolved, and the particle diameter has no obvious change, so the safety of clinical application is enhanced. According to the prepared freeze-dried voriconazole micelle preparation, because the voriconazole is wrapped inside by the mixed micelles, influence of light, heat and moisture is avoided, and the stability of the voriconazole in a long-term storage process is improved.

This invention involves Voriconazole derivatives. The invention also involves Voriconazole derivatives preparation methods, including the following steps : 2 - (5-fluoro-4-yl) acetate and ethanol for esterification, generate 2 -(5-fluoro-4-yl) ethyl acetate, in alkaline conditions takes reaction with methylation agent, generate 2 - (5-fluoro-4-yl) ethyl propionate; hydrolysis of 2 - (5-fluoro-4-yl) propionic acid, through split gain S-2 - (5-fluoro-4-yl) propionic acid; for chlorination to gain S-2 - (5-fluoro-4-yl) propionyl chloride; occurred Friedel-Crafts reaction, generating S-1 - 2, 4-difluoro-2 - (5-fluoro-4-yl) acetone; with 1-methyl - 1-H-1 ,2,4 - triazol under alkali conditions to take reaction to gain voriconazole and the series of voriconazole derivatives. The methods described in this invention has short routes, only use of a pair of enantiomers separation, the overall yield has been greatly improved, is a simple and easy method for synthesis of voriconazole and its derivatives.

The invention discloses a method for determining the concentrations of two anti-tumor drugs, metabolites and endogenous substances related to the activity of a metabolic enzyme in human plasma, whichcomprises the following steps: preprocessing, respectively taking voriconazole and bromouracil as internal standards, separating drug components in supernate by using high performance liquid chromatography in a preprocessed sample, performing drug targeting detection by using a high-resolution mass spectrum multi-reaction monitoring mode, and quantifying to realize the analysis and determination of the concentrations of the two anti-tumor drugs, the metabolites and the endogenous substances related to the activity of the metabolic enzyme in the plasma. The method has the advantages of rapidness, extremely high targeting property, high flux, high sensitivity, strong specificity, good precision and accuracy, good stability, high extraction recovery rate, no obvious matrix effect and dilutioneffect and the like. The method for determining the concentrations of two anti-tumor drugs, metabolites and endogenous substances related to the activity of the metabolic enzyme in the human plasma can be used for monitoring the blood concentration of irinotecan and metabolites thereof and the blood concentration of fluorouracil and endogenous substances related to the activity of the metabolic enzyme thereof clinically.

The present invention relates to pharmaceutical dosage forms which include an antifungal having poor solubility. The pharmaceutical dosage forms of the present invention further comprise non-spherical granules, which do not contain a coated core region and may be formed into pharmaceutically acceptable dosage forms. The antifungal active pharmaceutical ingredients include itraconazole, saperconazole, ketoconazole, voriconazole and fluconazole.

The invention relates to a Voriconazole dried suspension, comprising 5-15wt% of Voriconazole, 3-20wt% of suspending agent, 30-60wt% of filling agent, 20-50wt% of sweetening agent, 0.1-10wt% of PH regulator, 0.2-2wt% of lubricant, 0.1-2wt% of flavoring agent and 1-5wt% of opacifier. The Voriconazole dried suspension is a fine particle dosage form with more advantages than tablet and other solid dosage forms, has the advantages of large distribution area in gastrointestinal tract, fast absorption and high bioavailability, and can avoid the disadvantage of difficult swallowing of the tablet. Dried suspension is stored as solid, and is given through the mouth in suspension state, so as to be suitable for drugs with low water stability, and for children, the old and the patients who has difficult in swallowing.

The invention provides an ear drop which comprises voriconazole and one or more than one of its pharmaceutical salts, ambroxol and one or more than one of its pharmaceutical salts, and pharmaceutical adjuvants. The ear drop of the invention can effectively improve patient feeling of earache and ear fullness; the ear drop is prepared by the combination of ambroxol hydrochloride and voriconazole, and thus the application of the ear drop has significantly better effect than single application of a voriconazole ear drop or ambroxol hydrochloride, and has higher patient compliance than single application of a voriconazole ear drop, has a shorter treatment course; and it is concluded that the combination of a voriconazole ear drop and ambroxol hydrochloride for the ear drop has synergistic effect on disease cause elimination and function recovery.