13 results about "Ibrutinib" patented technology

The invention discloses an ibrutinib monolaurinol sulfate crystal compound, a preparation method and application, the structural formula of the ibrutinib monolaurinol sulfate crystal compound is shown as a formula II, the ibrutinib monolaurinol sulfate crystal compound is a crystal compound or an amorphous compound, and the crystal compound exists in an anhydrous and solvent-free form. According to the crystal compound, good druggability of the ibrutinib is ensured, the bioavailability of oral absorption is remarkably improved, and meanwhile, the difference between preprandial and postprandial of the ibrutinib is reduced, so that gastrointestinal reaction and potential toxic and side effects can be reduced.

Discussed herein are pharmaceutical compositions containing Ibrutinib and processes for preparing them. The compositions may be utilized in the treatment of a variety of conditions including, without limitation, B-cell proliferative disorders such as non-Hodgkin lymphoma (diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma or burkitt lymphoma), Waldenstrom macroglobulinemia, plasma cell myeloma, chronic lymphocytic leukemia, lymphoma, or leukemia. These compositions are designed for oral ingestion. The compositions are contained within a capsule such as a standard or sprinkle or in a liquid formulation such as a suspension. In one embodiment, the pharmaceutical composition contains Ibrutinib, a salt, prodrug, or metabolite thereof, microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, and magnesium stearate. In another embodiment, the pharmaceutical composition contains Ibrutinib, a salt, prodrug, or metabolite thereof, microcrystalline cellulose, carboxymethylcellulose sodium, hydroxypropylmethylcellulose, citric acid monohydrate, disodium hydrogen phosphate, sucralose, sodium methyl parahydroxybenzoate, sodium ethyl parahydroxybenzoate, concentrated hydrochloric acid, sodium hydroxide, and water.

This invention provides an ibrutinib capsule formulation. Ibrutinib and a macromolecular polymer are prepared into a solid dispersion via hot melt extrusion. After pulverization, a certain amount of fatty acid glycerides and other excipients are added for granulation. A lubricant is added, the mixture is homogenized, and the granules are then filled into capsules. The ibrutinib capsules prepared by this invention exhibit high dissolution; when water is used as the dissolution medium, they dissolve rapidly without the addition of surfactants. Furthermore, the addition of fatty acid glycerides during granulation further improves bioavailability. The preparation method of the ibrutinib capsules provided by this invention does not require micronization, is simple to operate, does not use organic solvents, and has high safety.

Disclosed in the present invention are a crystalline compound of ibrutinib monododecyl sulfate, and a preparation method therefor and the use thereof. The structural formula of the crystalline compound is as represented by formula II. Ibrutinib monododecyl sulfate is a crystalline compound or an amorphous compound, and the crystalline compound is present in an anhydrous and solvent-free form. The crystalline compound ensures a good druggability of ibrutinib and also significantly improves the bioavailability thereof during oral absorption; moreover, the crystalline compound is also conducive to reducing the difference in the effect of ibrutinib before and after meals, thereby reducing gastrointestinal reactions and potential toxicity and side effects.

The invention discloses an ibrutinib pharmaceutical composition and preparation as well as a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations. In order to solve the problems of low bioavailability, large administration dosage, high side effect risk and the like of ibrutinib, the invention provides an ibrutinib pharmaceutical composition and preparation as well as a preparation method and application thereof, the pharmaceutical composition comprises an active substance ibrutinib monolauryl sulfate, a filler, a release regulator and / or other auxiliary materials, the other auxiliary materials comprise at least one of a lubricant, a disintegrating agent and a flow aid; the preparation is a capsule or a tablet. According to the preparation of the ibrutinib monolaurinol sulfate composition prepared by adopting granulation or direct mixing, the bioavailability is greatly improved, and the dosage is greatly reduced under the condition that the blood exposure is basically unchanged; meanwhile, relatively stable blood concentration can be maintained, and the preparation has the advantages of small toxic and side effects, convenience in taking, high bioavailability and the like.

A method of treating cancer includes a combination of a therapeutically effective amount of an illudin or an illudin analog thereof, derivative, or a pharmaceutically acceptable salt thereof; and a therapeutically effective amount of Bortezomib, Ibrutinib or an analog, derivative, or a pharmaceutically acceptable salt thereof. Compositions and kits of the same are included herein. The cancer may be refractory to Bortezomib and / or Ibrutinib

The invention belongs to the technical field of pharmaceutical analysis, and particularly relates to a method for separating, detecting and determining an initial raw material SM3 and impurities thereof of ibrutinib. The impurities comprise one or more of propionyl chloride, 3-chloropropionyl chloride and benzoyl chloride. A mobile phase is a phosphate buffer solution as a mobile phase A, acetonitrile is a mobile phase B, a chromatographic column adopts octadecylsilane chemically bonded silica as a filler, and linear gradient elution of high performance liquid chromatography is carried out after pre-column derivatization. And then, according to a chromatogram, an external standard method is adopted to calculate the impurities according to a peak area. The method has the characteristics of good separation degree, good durability, high sensitivity and good reproducibility.

The invention belongs to the technical field of biological medicine and molecular biology, and particularly relates to application of RNF20 in diagnosis and treatment of diffuse large B-cell lymphoma. Specifically, the RNF20 is remarkably and highly expressed in DLBCL cell lines and tissues, and the high expression of the RNF20 is closely related to poor prognosis of a patient; the RNF20 can play a tumor promoting role by promoting DLBCL cell proliferation, regulating and controlling a cell cycle, inhibiting cell apoptosis and positively regulating and controlling FUS protein expression, and the drug sensitivity of DLBCL cells to ibrutinib can be enhanced by knocking down the RNF20. In a word, the research result shows that the RNF20 can serve as a treatment target, a new thought and a new direction are provided for DLBCL prognosis evaluation and targeted therapy, and therefore the RNF20 has good practical application value.

The invention belongs to the technical field of pharmaceutical analysis, and particularly relates to a method for separating and determining ibrutinib SM3 and impurities thereof based on gas chromatography. The impurities comprise any one or more of acrylic anhydride, trichlorotoluene, propionyl chloride, 3-chloropropionyl chloride, benzoyl chloride, acrylic acid and benzoic acid; the ibrutinib SM3 and impurities jointly form a composition to be detected. According to the method, (5% phenyl)-diphenylmethylsiloxane is adopted as a chromatographic column of a stationary liquid, or other stationary liquids with the same polarity are adopted; the ibrutinib SM3 and impurities of the ibrutinib SM3 are separated by adopting temperature programming; the temperature programming setting is as follows: the initial temperature is 35 + / -5 DEG C and is maintained for 5 + / -1 minutes, and the temperature is raised to 210 + / -10 DEG C at the rate of 30 + / -5 DEG C / min and is maintained for 8 + / -2 minutes. The method provided by the invention can effectively separate, identify and quantify various related substances in ibrutinib SM3, and has the advantages of short separation time, strong specificity, high sensitivity and good durability.

The present invention relates to a solid oral pharmaceutical for Axitinib, Ibrutinib and / or Palbociclib (API) or any other Kinase Inhibitor API with a novel, well defined method to enhance solubility of active pharmaceutical ingredients (API) with low solubility in aqueous media and use those enhanced API in a new approach of preparing modified and / or sustained release pharmaceutical formulation for API which are regularly not suitable for sustained release formulations because of their low solubility. This invention is applicable for small molecule API (molecular weight < 1000) for which the solubility can be enhanced by formation of a e.g., Cyclodextrin Complex regardless which Cyclodextrin or derivate thereof is employed according to the method described in this invention. Axitinib, Ibrutinib and / or Palbociclib and other Kinase Inhibitors can be found for treatment of malign tumor diseases and others.

The invention belongs to the technical field of analytical chemistry, and particularly relates to a method for separating and determining enantiomer impurities in ibrutinib and related substances thereof. The method is a high performance liquid chromatography, and comprises the following steps: by taking amylose-tris [3, 5-dimethyl phenyl carbamate] derivative bonded silica gel as a chromatographic column filler and a mixed solution of methanol, tetrahydrofuran and normal hexane as a mobile phase, separating enantiomer impurities from ibrutinib and related substances thereof through elution; and then detecting in a detector to obtain a chromatogram. According to the method, enantiomer impurities can be well separated from a main peak of a test sample and other 10 known impurities possibly existing in the test sample within 30 minutes, and the method has the advantages of short analysis time, high sensitivity, strong specificity, good reproducibility and simplicity and feasibility in operation.

The invention discloses a targeting covalent activation prodrug compound and a preparation method and application thereof, the targeting covalent activation prodrug compound is named as Ibt-DOX, and the structural formula of the targeting covalent activation prodrug compound is shown in the specification. According to the invention, high affinity and irreversible inhibition capability of a classical targeting covalent inhibitor to Bruton's tyrosine kinase (BTK) are retained, and in-situ release of potent chemotherapeutic drugs is triggered by a targeting covalent binding process, so that high synergy of targeting covalent inhibition and local chemotherapy is realized; the direct killing capacity of the medicine on BTK high-expression B cell tumor cells is greatly improved, and the treatment effect of the medicine is obviously better than that of the medicine which is independently used or is simply combined with chemotherapy medicine.