10 results about "Apremilast" patented technology

The invention relates to the field of analytical chemistry, and particularly discloses a method for separating alprimilast intermediate 3 and impurities by high performance liquid chromatography, which adopts octadecylsilane chemically bonded silica as a filler, a dihydric phosphate solution as a mobile phase A and acetonitrile as a mobile phase B to carry out gradient elution, all known impurities and unknown impurities in the alprimilast intermediate 3 can be effectively separated, nine impurities are effectively separated in one chromatography, the separation degree between a main peak and an impurity IX reaches 3.87 and is larger than 1.5, the separation degree between other impurities is larger than 1.5, specificity is good, interference of a blank solvent and other unknown impurities is avoided, and the method is suitable for industrial production. The separation efficiency is high, the anti-interference capability is strong, the analysis speed is high, and the detection accuracy is high, so that the quality of alprimilast is effectively controlled.

The application discloses a compound inhalation powder aerosol and a preparation method thereof. The compound inhalation powder aerosol comprises apremilast or a pharmaceutically acceptable salt thereof and an efficacy enhancing substance, wherein the efficacy enhancing substance is nintedanib or a pharmaceutically acceptable salt thereof; and the amount of the efficacy enhancing substance is 0.1-10 times the amount of the apremilast or the pharmaceutically acceptable salt thereof. In the compound inhalation powder aerosol, the drug exposure of apremilast is greatly improved under the action of nintedanib, and a significant enhancement effect is exhibited. Meanwhile, nintedanib further improves efficacy. The powder aerosol is used for pulmonary inhalation administration, and apremilast or the pharmaceutically acceptable salt thereof and nintedanib or the pharmaceutically acceptable salt thereof are used for treating lung diseases, so that the drugs can be directly delivered to effective sites, the administration dose can be further effectively reduced or the drug utilization rate can be improved, the deposition rate can be improved, and the treatment effect can be greatly improved.

The application discloses a detection method for determining the residual amount of easily hydrolyzed impurities in apremilast, which comprises the following steps: using a high performance liquid chromatograph, adopting polysaccharide derivatives as a filler (CHIRALPAK IH, 4.6mm*150mm, 5um), adopting a n-hexane-tetrahydrofuran (65:35) mobile phase, a flow rate of 1.0ml per minute, a column temperature of 30 DEG C, a detection wavelength of 230nm, and a sample injection volume of 50ul. The application adopts the polysaccharide derivative filler to determine the easily hydrolyzed impurities in the apremilast, has high separation efficiency, strong anti-interference ability, fast analysis speed and high detection sensitivity, and can effectively control the quality of the apremilast by determining the amount of the easily hydrolyzed impurities in the apremilast.

The invention discloses an inhalation preparation for treating IPF diseases. The inhalation preparation is an aerosol inhalation liquid preparation, an inhalation aerosol, an inhalation powder aerosol or a soft aerosol. The inhalation preparation comprises an active drug, and the active drug is any one of apremilast, ibudilast, roflumilast, crisaborole and defamilast. A preparation process of an inhalation preparation is introduced into a traditional preparation, active ingredients of a traditional oral preparation are easily damaged in digestive tracts, the bioavailability is low, the liver first-pass effect is achieved, the effect is slow, and the inhalation preparation capable of remarkably improving IPF is prepared. Tests prove that the prepared inhalation preparation can effectively improve the bioavailability and improve the clinical use effect.

This invention provides an apremilast-loaded hydrogel of *Callicarpa nudiflora* vesicles, its preparation method, and its application, relating to the field of pharmaceutical formulation technology. This invention utilizes *Callicarpa nudiflora* vesicles to encapsulate apremilast and then reconstitute it into a hydrogel, preparing a drug that can be directly applied to the affected skin of psoriasis patients via local transdermal administration. The hydrogel achieves synergistic treatment of psoriasis through apremilast and *Callicarpa nudiflora* vesicles, improving efficacy.

An inhalation formulation for treating an IPF disease. The inhalation formulation is an aerosol inhalation liquid formulation, an inhalation aerosol, a dry powder inhaler or a soft mist inhaler. The inhalation formulation contains an active drug, and the active drug is any one of apremilast, ibudilast, roflumilast, crisaborole, and difamilast. A preparation process for the inhalation formulation is introduced into a conventional formulation. An active component in a conventional oral formulation is prone to being destroyed in the digestive tract, and has low bioavailability, a liver first pass effect, and a slow onset of action. An inhalation formulation capable of significantly alleviating IPF is prepared. Tests prove that the prepared inhalation formulation can effectively increase the bioavailability, and improve the clinical use effect.

To provide an apremilast solid preparation suppressed in increase of related substances with time and excellent in stability.SOLUTION: The apremilast solid preparation contains apremilast and an additive, wherein the additive contains at least one selected from the group consisting of low-substituted hydroxypropyl cellulose, crospovidone, glycerin fatty acid ester, hydrous silicon dioxide, and light anhydrous silicic acid. It is preferable that the additive does not contain at least one selected from the group consisting of a sodium salt, a calcium salt, and a magnesium salt.SELECTED DRAWING: None

The invention discloses a synthesis method of a psoriasis treatment drug apremilast, and belongs to the technical field of organic synthesis. The preparation method comprises the following steps: taking 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl) ethanone as an initial raw material, and carrying out reductive amination to obtain an intermediate 1; splitting the intermediate 1 by tartrate to obtain an intermediate 2; and finally, carrying out condensation reaction on the intermediate 2 and 3-acetamido phthalic anhydride to obtain apremilast. The invention develops a green and efficient synthesis process of apremilast, the preparation of a target product is realized through three-step reaction, the process breaks through the technical bottleneck that the traditional route depends on high-pressure hydrogenation conditions and noble metal catalysts (such as palladium on carbon), and the whole process adopts normal-pressure operation and mild temperature and avoids high-temperature reaction. The safety in industrial production is improved to a great extent, and the method is more suitable for industrial continuous production.

The present invention relates to a stable pharmaceutical formulation of solid dosage forms for oral administration comprising an immunosuppressive agent such as apremilast as the active ingredient. It also relates to a process for the preparation thereof.

The present application provides a pharmaceutical composition for treating psoriasis, which contains a certain amount of apremilast and choline-based ionic liquid, so that the medicine prepared therefrom can directly act on the skin surface, provide an effective concentration of apremilast at the action site, and increase the amount of apremilast penetrating into the skin. The present application also provides a preparation method of the pharmaceutical composition, and a medicine comprising the pharmaceutical composition.