37 results about "Dianhydrogalactitol" patented technology

The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of glioblastoma multiforme. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N⁷ methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide; the drug acts independently of the MGMT repair mechanism.

The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to substituted hexitols such as dianhydrogalactitol and diacetyldianhydrogalactitol.

An improved analytical method for analysis of dianhydrogalactitol preparations provides a method for determining the purity of dianhydrogalactitol and detecting impurities in preparations of dianhydrogalactitol, as well as identifying any such impurities. The method employs high performance liquid chromatography (HPLC), in particular, HPLC with evaporative light scattering detection (ELSD); the HPLC can be followed by tandem mass spectroscopy. The method can further comprise the step of performing preparative HPLC collection of at least one specific substance peak present in a preparation of dianhydrogalactitol.

An improved analytical method for analysis of dianhydrogalactitol preparations provides a method for determining the purity of dianhydrogalactitol and detecting impurities in preparations of dianhydrogalactitol, as well as identifying any such impurities. The method employs high performance liquid chromatography (HPLC), in particular, HPLC with evaporative light scattering detection (ELSD); the HPLC can be followed by tandem mass spectroscopy. The method can further comprise the step of performing preparative HPLC collection of at least one specific substance peak present in a preparation of dianhydrogalactitol.

The present invention provides an efficient method of synthesizing and purifying dianhydrohexitols such as dianhydrogalactitol. In general, as applied to dianhydrogalactitol, the method comprises: (1) reacting dulcitol with a concentrated solution of hydrobromic acid at a temperature of about 80° C. to produce dibromogalactitol; (2) reacting the dibromogalactitol with potassium carbonate in t-butanol to produce dianhydrogalactitol; and (3) purifying the dianhydrogalactitol using a slurry of ethyl ether to produce purified dianhydrogalactitol. Another method produces dianhydrogalactitol from dulcitol; this method comprises: (1) reacting dulcitol with a reactant to convert the 1,6-hydroxy groups of dulcitol to an effective leaving group to generate an intermediate; and (2) reacting the intermediate with an inorganic weak base to produce dianhydrogalactitol through an intramolecular S_N2 reaction. Other methods for the synthesis of dianhydrogalactitol from dulcitol are described.

Methods and compositions suitable for the treatment of malignancies such as recurrent glioma and progressive secondary brain tumor are disclosed. These methods employ a hexitol derivative such as dianhydrogalactitol, a derivative or analog of dianhydrogalactitol, diacetyldianhydrogalactitol, or a derivative or analog of diacetyldianhydrogalactitol. The compositions can include such hexitol derivatives.

Methods and compositions suitable for the treatment of malignancies in subjects with a germline deletion polymorphism that blocks the activity of thymidine kinase inhibitors in triggering apoptosis in tumor cells or in subjects having a mutation in or a dysregulation of the AHI1 gene are disclosed. These methods employ an alkylating hexitol derivative such as dianhydrogalactitol, a derivative or analog of dianhydrogalactitol, diacetyldianhydrogalactitol, a derivative or analog of diacetyldianhydrogalactitol, dibromodulcitol, and a derivative or analog of dibromodulcitol. The compositions can include such alkylating hexitol derivatives. The methods can further include administration of a BH3 mimetic, and the compositions can further include a BH3 mimetic. In subjects having a dysregulation of the AHI1 gene, the methods can further include the administration of an agent modulating the expression or activity of the AHI1 gene or AHI1 protein, and the compositions can further include such an agent.

The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to substituted hexitols such as dianhydrogalactitol and diacetyldianhydrogalactitol.

The present invention is directed to methods for treatment of malignancies in companion animals employing dianhydrogalactitol, diacetyldianhydrogalactitol, and dibromodulcitol, as well as analogs and derivatives thereof, in addition to a method to improve the efficacy and/or reduce the side effects of the administration of a therapeutic agent selected from the group consisting of dianhydrogalactitol, a derivative of dianhydrogalactitol, diacetyldianhydrogalactitol, a derivative of diacetyldianhydrogalactitol, dibromodulcitol, and a derivative of dibromodulcitol to a veterinary subject, the method comprising the steps of: (1 (identifying at least one factor or parameter associated with the efficacy and/or occurrence of side effects of the administration of the therapeutic agent to the veterinary subject; and (2) modifying the factor or parameter to improve the efficacy and/or reduce the side effects of the administration of the therapeutic agent to the veterinary subject.

The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of non-small-cell lung carcinoma (NSCLC) and ovarian cancer, as well as other types of malignancy, including brain metastases of NSCLC. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N7 methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is activeagainst tumors that are refractory to temozolomide, cisplatin, and tyrosine kinase inhibitors; the drug acts independently of the MGMT repair mechanism. Dianhydrogalactitol can be used together withother anti-neoplastic agents and can possess additive or super-additive effects.

The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of non-small-cell lung carcinoma (NSCLC) and for the treatment of glioblastoma multiforme (GBM). Dianhydrogalactitol acts as an alkylating agent on DNA that creates N7 methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide; the drug acts independently of the MGMT repair mechanism.

An improved analytical method for analysis of dianhydrogalactitol preparations provides a method for determining the purity of dianhydrogalactitol and detecting impurities in preparations of dianhydrogalactitol, as well as identifying any such impurities. The method employs high performance liquid chromatography (HPLC), in particular, HPLC with evaporative light scattering detection (ELSD); the HPLC can be followed by tandem mass spectroscopy. The method can further comprise the step of performing preparative HPLC collection of at least one specific substance peak present in a preparation of dianhydrogalactitol.

Methods and compositions employing dianhydrogalactitol or a derivative or analog of dianhydrogalactitol together with a vascular endothelial growth factor (VEGF) inhibitor or other anti-neoplastic agents can be used for treatment of glioma. In particular, methods and compositions according to the invention can decrease the invasiveness of gliomas. Further disclosed are methods of using the compositions for treating a malignancy that has failed a VEGF inhibitor treatment.

The invention belongs to the field of medicines, and discloses application of combination of dianhydrogalactitol and an autophagy inhibitor in anti-melanoma drug preparation. The anti-melanoma drug contains the dianhydrogalactitol and an autophagy inhibitor, wherein the autophagy inhibitor is selected from 3-MA; and the anti-melanoma drug is a compound drug prepared from the dianhydrogalactitol and the autophagy inhibitor. The autophagy inhibitor disclosed by the invention inhibits autophagy of melanoma cells induced by the dianhydrogalactitol; and the dianhydrogalactitol induces autophagy ofthe melanoma cells so as to counteract antagonism of melanoma to the treatment of the dianhydrogalactitol caused by autophagy, thereby significantly enhancing therapeutic effects of the dianhydrogalactitol on the melanoma. The combination of the dianhydrogalactitol and the autophagy inhibitor can very well inhibiting autophagy induced by single use of the dianhydrogalactitol, so that the combination of the dianhydrogalactitol and the autophagy inhibitor has significant curative effects on the melanoma; and moreover, the effects of the combination of the dianhydrogalactitol and the autophagy inhibitor is significantly better than effects of single use of the dianhydrogalactitol and the autophagy inhibitor. Thus, synergistic effects of the combination of the dianhydrogalactitol and the autophagy inhibitor are proven.