31 results about "Tamibarotene" patented technology

The invention discloses a tamibarotene cyclodextrin or cyclodextrin derivative clathrate which is prepared from tamibarotene and cyclodextrin or a cyclodextrin derivative, the molar ratio of tamibarotene to cyclodextrin or cyclodextrin derivative is 1:1-1:100, and the preparation method is as follows: the cyclodextrin or cyclodextrin derivative is added to a solvent to produce a solution or suspension, and then the tamibarotene is added for stirring, grinding or ultrasonic mixing to obtain the tamibarotene cyclodextrin or cyclodextrin derivative clathrate; or the cyclodextrin or cyclodextrin derivative is put in a colloid mill or mortar, a solvent is added for stirring to make a paste, then the tamibarotene is added into the paste for grinding for 1-5 hours to obtain a homogeneous thick paste, and the tamibarotene cyclodextrin or cyclodextrin derivative clathrate is obtained by filtration, concentration or freeze drying. The invention also discloses a tamibarotene-containing composition. The tamibarotene cyclodextrin or cyclodextrin derivative clathrate improves the solubility and dissolution rate of the tamibarotene, has good water solubility, less vascular stimulation, quick disintegration, higher bioavailability and other characteristics.

The invention belongs to the technical field of medicine pharmaceutical synthesis, and particularly relates to a method for catalytically synthesizing tamibarotene through an acenaphthene imidazole n-heterocyclic carbine allyl palladium chloride compound, aiming at providing a novel synthesis method of tamibarotene. The method comprises the following steps of: by taking a novel acenaphthene imidazole n-heterocyclic carbine allyl palladium chloride compound with high catalytic activity as a catalyst; performing amide carbonylation coupled reaction under carbon monoxide in order to directly synthesize a key precursor of tamibarotene by such one step; and then simply hydrolyzing to obtain the target compound, namely, tamibarotene. According to the method, the catalyst adopted has high catalytic performance, so that the catalytic coupling reaction brings high yield; and the catalyst is naturally easily synthesized, the raw materials adopted in the synthetic line are easily available, so that such synthetic line has high competitive advantages and high utility value in industrial production.

The present invention provides a practical preparation form of Tamibarotene and dosage form thereof, which exhibit high absorptivity by the body with minimized toxicity, and which are safe and stable without any risk of contamination. It is provided a Tamibarotene capsule preparation which encapsulates a composition comprising an oil component as its base and Tamibarotene as an active ingredient dissolved in the base. It is preferred that the oil component be propylene glycol fatty acid esters or polyethylene glycols. It is also preferred that the Tamibarotene capsule preparation comprise 0.1-50 mg / mL of the Tamibarotene based on the oil component.

The invention discloses preparation of tamibarotene-cytarabine conjugate, nano pharmacosomes and an anti-tumor application of the tamibarotene-cytarabine conjugate and nano pharmacosomes. The tamibarotene-cytarabine conjugate is prepared by coupling the carboxyl of tamibarotene with four locations of amino groups of cytarabine. The tamibarotene-cytarabine conjugate has a proper amphipathy, can form a nanoscale dispersive self-assembly transfer system in water and has good anti-tumor activity in vitro and vivo.

The present invention aims to provide a growth inhibitor for cancer stem cells resistant to existing anticancer drug therapies, which growth inhibitor acts on the cells through growth inhibition and apoptosis. The growth inhibitor for cancer stem cells contains a retinoid agonist, preferably tamibarotene, alone or in combination with a rexinoid agonist, preferably bexarotene, as an effective component(s). The growth inhibitor for cancer stem cells enhances the effects of various anticancer drugs when the growth inhibitor is used in combination with the anticancer drugs.

The invention discloses a method for preparing dispersible tablets of tamibarotene. The process in the method adopts the solvent deposition method, and the dispersible tablets of tamibarotene, prepared by the method, are good in stability, high in content uniformity and also high in dissolution rate; the method is operated according to the requirements of the Chinese Pharmacopoeia on the dissolution rate of the dispersible tablets, and the dispersible tablets are completely disintegrated within 3 minutes and can pass the No 2 screen(24 meshes), so that the dispersible tablets can enhance the absorption in the human body and improve the biological utilization rate; the preparation method is simple in operation and causes little pollution; by dissolving the tamibarotene in the organic solvents and depositing the tamibarotene in the auxiliary materials, the dust problem in operation can be solved, the caused pollution can be lessened, the untoward reactions of operators are avoided; and the mixed powder of raw materials and auxiliary materials, prepared by the method, can be tabletted directly, so that the cost is saved, and the requirement for being suitable for industrialized production is met.

The invention relates to a medicine analyzing method and particularly relates to a method for measuring impurities in tamibarotene and a preparation thereof by using high performance liquid chromatography. Octadecyl silane bonding silica gel is used as a filling agent, a phosphoric acid buffer solution with a volume ratio of water to phosphoric acid being 2000:1-2000:5 is used as a mobile phase A, acetonitrile is used as a mobile phase B, and a gradient elution process is adopted to establish a sensitive, exclusive and comprehensive tamibarotene impurity detecting and analyzing method. The method can be adopted to effectively detect changes of impurities in production and storage processes of the tamibarotene, and has important practical significance to medicine quality control.

The invention provides an orally taken tamibarotene solid preparation. The solid preparation comprises tamibarotene, disintegrating agent, filling agent and lubricating agent, wherein the weight of the tamibarotene is 1%-2% of the weight of the solid preparation, the weight of the filling agent is 70%-90% of the weight of the solid preparation, the weight of the disintegrating agent is 8%-25% of the weight of the solid preparation and the weight of the lubricating agent is 0.5%-0.6% of the weight of the solid preparation. The orally taken tamibarotene solid preparation prepared according to the invention has high dissolution rate, content uniformity and stability, is beneficial to the promotion of the bioavailability of human body and is more suitable for clinical application. The invention also provides a preparation method and an application of the solid preparation.

The invention belongs to the technical field of medicine pharmaceutical synthesis, and particularly relates to a method for catalytically synthesizing tamibarotene through an acenaphthene imidazole n-heterocyclic carbine allyl palladium chloride compound, aiming at providing a novel synthesis method of tamibarotene. The method comprises the following steps of: by taking a novel acenaphthene imidazole n-heterocyclic carbine allyl palladium chloride compound with high catalytic activity as a catalyst; performing amide carbonylation coupled reaction under carbon monoxide in order to directly synthesize a key precursor of tamibarotene by such one step; and then simply hydrolyzing to obtain the target compound, namely, tamibarotene. According to the method, the catalyst adopted has high catalytic performance, so that the catalytic coupling reaction brings high yield; and the catalyst is naturally easily synthesized, the raw materials adopted in the synthetic line are easily available, so that such synthetic line has high competitive advantages and high utility value in industrial production.

The invention discloses a synthesis method for the (I) Linarotene (I), a leukemia treatment drug. The invention mainly proposes a novel synthetic route with the steps as follows: the aniline, and p-chlorocarbonyl benzoic methyl ester are used as the raw materials; the intermediate is the p-chlorocarbonyl benzoic methyl ester and can do the cyclization with the 2,5 - dichloro-2 ,5 - dimethyl hexaneunder the anhydrous condition to get the intermediate 4-[(5,6,7,8-tetrahydrocannabinol-5,5,8,8- tetramethyl-2-naphthalene) carbamoyl] methyl benzoate. After the hydrolysis, the 4-[(5,6,7,8-tetrahydrocannabinol-5,5,8,8- tetramethyl-2-naphthalene) carbamoyl] benzoate (I) can be made, that is, the Linarotene. The synthetic route is simple; the operation is convenient and conducive to the environmental protection; the invention is suitable for the industrial production.

The invention provides a multiple target point type Tamibarotene derivative as well as a preparation method and an application thereof. Particularly, RAR (retinoic acid receptor) agonist Tamibarotene is connected with antineoplastic drug hydroxycarbamide, fluorouracil and lenalidomide on sales through ester bonds or amido bonds respectively to obtain three multiple target point mutual prodrugs. The invention provides a method for preparing the compound and the application of the compound in preparing antineoplastic drugs, particularly drugs for curing various leukemias. The invention further relates to a drug combination of the compound.

The present invention comprises ternary compositions of tamibarotene and / or ammonium lactate in Pemulen for treatment of effects of aging.

The invention discloses a synthesis method of 5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthylamine. The synthesis method comprises the following steps: the 5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthoamide reacts with sodium hydroxide in a high boiling point solvent; a protective group of the amino group is removed at temperature between 100 DEG C and 200 DEG C; a reaction solution is deposited with water and filtered; a solid product obtained is recrystallized to obtain the 5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthylamine. The method is environmentally friendly,has little pollution, low cost, simple operation, high safety, high reaction yield and high transformation rate reaching more than 80 percent and requires no adoption of expensive Pd-C catalysts and no catalytic hydrogenation. If necessary, the obtained 5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthylamine can be condensed and hydrolyzed to obtain tamibarotene.

The invention relates to the field of medicinal chemistry, and discloses a nitric oxide donor type tamibarotene derivative, a preparation method and application thereof. More specifically, the present invention provides a compound shown in general structural formula (I), wherein the definition of R is shown in the description of this patent. Rotin is a kind of multi-target compound obtained by hybridizing various linking groups with ester bonds or amide bonds, and is suitable as an antitumor drug for treating various leukemias.

The invention provides a water-soluble prodrug of tamibarotene, and a preparation method and applications thereof and belongs to the technical fields of organic compound synthesis and medical applications. The water-soluble prodrug of tamibarotene has favorable water solubility and suitable drug crystal form, and therefore, is suitable to be used as a raw material for medical preparations and especially suitable for preparing injections. Particularly, the invention provides medical acceptable salts of tamibarotene DMEA ester, which have the general formula (I), wherein HA is HCl, H2SO4, HNO3,H3PO4, HOAc, paratoluenesulfonic acid, maleic acid, succinic acid, citric acid or L(+)-tartaric acid.