35 results about "Lonidamine" patented technology

Lonidamine or a lonidamine analog is administered with one or more additional anti-cancer agents or surgery or radiation to treat cancer or is administered alone or in combination to treat cancer, optionally in a sustained release formulation, and improve patient outcome.

Lonidamine derivatives can be useful in methods of treating, inhibiting, and / or preventing polycystic kidney disease (PKD). Accordingly, lonidamine derivatives can be administered in a therapeutically effective amount for inhibiting, and / or preventing polycystic kidney disease (PKD) in the subject. This can include administering a therapeutically effective amount of the lonidamine derivatives for inhibiting CFTR and / or Hsp90 or biological pathway thereof. Also, the method can include administering the lonidamine derivatives in a therapeutically effective amount for inhibiting ErbB2, Src, Raf-1, B-Raf, MEK, Cdk4, NKCC1, or combinations thereof. For example, the therapeutically effective amount of the lonidamine derivatives can be configured so as to provide a concentration in or adjacent to a kidney cell of about 0.25 uM or more or less.

The invention discloses a co-delivery nano-carrier of drugs and genes, a preparation method and an application thereof; and particularly relates to a co-delivery nano-carrier TCPL-siRNA-PPX which can carry a chemotherapeutic drug and a genetic drug simultaneously. The drug delivery system is composed of a polymer prodrug carrier TCPL, siRNA and a multifunctional polyanionic polyer PPX through electrostatic adsorption among the components in a self-assembly manner. The co-delivery nano-carrier can achieve targetedly delivery of the drug and the gene to the same tumor cell, release the siRNA at the cytoplasm, silence Bcl-2 protein, promote apotosis and relieve inhibition of the Bcl-2 on lonidamine, and can deliver the chemotherapeutic drug, lonidamine, which is mitochondrion-acted to mitochondria so that the chemotherapeutic drug and the gene can synergistically trigger the apotosis of a mitochondrial pathway and kill tumor cells cooperatively. Through in-vivo and in-vitro activity evaluation, the drug delivery system is proved to be better than drug delivery carriers which deliver single components respectively at the same time, can significantly improve the anti-cancer activity of the drug and the gene and has a definite synergistic treatment effect.

Novel compounds useful for inhibiting spermatogenesis and cancer treatment, and in particular as inhibitors of heat shock proteins and / or elongation factor 1 alpha.

A method for treatment or prophylaxis of benign prostatic hyperplasia by administration of lonidamine or a lonidamine analog is provided. Also provided are unit dosage forms of lonidamine or an analog, useful for such treatment and prophylaxis.

The invention discloses a nano-carrier for drug and gene co-delivery and a preparation method and application thereof, and particularly relates to a co-delivery nano-carrier TCPL-siRNA-PPX for simultaneously carrying a chemotherapeutic drug and a gene-based drug. A polymeric prodrug carrier TCPL, siRNA and a multifunctional polyanionic polymer PPX are self-assembled by electrostatic adsorption between ingredients to form the drug delivery system; a drug and a gene can be targeted to be delivered to the same tumor cell, and moreover, siRNA is released in cytoplasm to silence the Bc1-2 protein, promoting apoptosis and releasing the inhibition of Bcl-2 on lonidamine; the chemotherapeutic drug acting on mitochondria, lonidamine, is delivered to the mitochondria; both cooperatively trigger the apoptosis of the mitochondrial pathway, jointly killing the tumor cell. By in-vitro and in-vivo activity evaluation, the invention proves that the system is better than the simultaneous delivery of each single component, can remarkably increase anti-cancer activity, and has a definite synergistic treatment effect.

Fertility management can include: administering to the subject one or more doses of a compound according to Formula I so as to reduce fertility in the subject. Fertility management can also include administering an effective amount of the compound to: impair Sertoli cell function in a male subject; inhibit spermatogenesis in the subject; reduce testis weight in the subject; reduce ovary weight in a female subject; reduce serum progesterone in the female subject; impair ovarian follicle function in the female subject; causing reversible fertility in the subject. In order to return fertility, the method can include ceasing administration of the compound to the subject so as to return fertility in the subject. The compound can be administered for irreversibly sterilizing the subject.

Lonidamine derivatives can be useful in methods of treating, inhibiting, and / or preventing polycystic kidney disease (PKD). Accordingly, lonidamine derivatives can be administered in a therapeutically effective amount for inhibiting, and / or preventing polycystic kidney disease (PKD) in the subject. This can include administering a therapeutically effective amount of the lonidamine derivatives for inhibiting CFTR and / or Hsp90 or biological pathway thereof. Also, the method can include administering the lonidamine derivatives in a therapeutically effective amount for inhibiting ErbB2, Src, Raf-1, B-Raf, MEK, Cdk4, NKCC1, or combinations thereof. For example, the therapeutically effective amount of the lonidamine derivatives can be configured so as to provide a concentration in or adjacent to a kidney cell of about 0.25 uM or more or less.

The invention relates to superparamagnetic electric conductive gamma-iron oxide / polyaniline-lonidamine (gamma-Fe2O3 / PAn-Lon) and a preparation method thereof. The method comprises the following steps of: mixing aniline and a hydrochloric acid solution to obtain a mixed solution which contains sodium dodecyl benzene sulfonate, adding gamma-Fe2O3, stirring, and adding ammonium persulfate, wherein the molar ratio of the ammonium persulfate to the aniline is 1:1; reducing by using ammonia water to obtain eigen polyaniline, washing by using water, and drying in vacuum to obtain gamma-Fe2O3 / PAn; and adding the gamma-Fe2O3 / PAn into a Lon acidic solution, stirring, performing suction filtering by using a vacuum pump, washing by using water, and drying in vacuum to obtain the gamma-Fe2O3 / PAn-Lon. The defects that the treatment effect cannot be limited in the specific cancerous cell, tissue or organ and normal tissue is damaged are overcome; and by the gamma-Fe2O3 / PAn-Lon, the treatment effect can be limited in the specific cancerous cell, tissue or organ, the normal tissue is not damaged, and the specific pathological cell is identified through electric conductivity of an organism in an organism microenvironment, so that the Lon can better enter a lesion site, and the toxic and side effects of the Lon on healthy tissue are reduced.

The invention relates to the fields of chemical pharmacy and pharmaceutic preparation, in particular relating to a compound Lonidamine amorphous multielement solid dispersion and a preparation method thereof. The solid dispersion in the invention is characterized by being prepared from Lonidamine, a surfactant and a solid dispersion carrier, wherein the Lonidamine is dispersed in the solid dispersion carrier in an amorphous mode. The Lonidamine amorphous multielement solid dispersion in the invention has the advantages of non-toxic auxiliary materials, no pollution and simple and convenient operation, and greatly improves the solubility of the Lonidamine, thus enhancing the bioavailability and ensuring good thermodynamic stability of preparations.

Poly-N-(2-hydroxypropyl)methacrylamide-lonidamine macromolecule prodrug and preparation method thereof. The invention discloses a compound represented by the general structural formula (I), wherein m=10-500 and n=10-500. The PHPMA-LND macromolecular prodrug synthesized by the present invention can not only increase the water solubility and half-life of the small molecule drug LND, and has a high drug delivery rate, but also can effectively control the release of its drug in the human body, reduce the number of times patients take medicine, and reduce its side effects.

The invention discloses a synthetic method of anti-tumor medicament lonidamine. The synthetic method comprises the following steps: taking 2,4-dichloromethylbenzene and phenylhydrazine as a starting raw material, performing acetylation on the phenylhydrazine, then reacting with hydroxylamine hydrochloride and chloral hydrate to generate N- acetylamino oximino acetylaniline, further performing rearrangement, cyclocondensation and hydrolysis under the catalysis of concentrated sulfuric acid to generate 1H-indazole-3-carboxylic acid; and enabling the 2,4-dichloromethylbenzene and N-bromosuccinimide (NBS) to react to generate 2,4-dichlorobenzyl bromide, and then reacting with the 1H-indazole-3-carboxylic acid to generate the lonidamine. The synthetic method disclosed by the invention has the characteristics of simple instruments and equipment required for the synthetic method, easiness in getting the raw materials, low cost, high yield and the like. During the reaction process, the industrial three wastes are simple to process, and the synthetic method is green and environment-friendly; and the obtained product has the advantages of stable quality, low content of single impurity and higher quality in comparison with the similar products in the industry, and is more suitable for large-scale industrial production.

The invention discloses a Prussian blue nano-particle coated with zinc glutamate loaded with triphenylphosphine-lonidamine and a preparation method thereof, comprising a Prussian blue nano-core whose surface is coated with at least A zinc glutamate layer, the surface of the outermost zinc glutamate layer has a load layer loaded with triphenylphosphine-lonidamine, and the load layer is covered with a tumor cell membrane layer. The present invention has the ability to target tumor cells, has a long circulation time in the body, and can gather in mitochondria and cause dysfunction, reduce the synthesis of ATP, down-regulate the synthesis of various heat shock proteins, and cause cell apoptosis at the same time, effectively enhancing the low-temperature light therapy of tumors. Efficacy of heat therapy.

The present invention discloses an application of a hexokinase inhibitor to preparation of a medicine for preventing and treating the Alzheimer disease. It is proposed that the hexokinase inhibitor, especially lonidamine and 3-bromopyruvic acid can improve the cognitive level of an Alzheimer disease model mouse, remove A beta and reduce A beta aggregation, the hexokinase inhibitor has the obviousanti-Alzheimer disease progression effect, and a basis is provided for the hexokinase inhibitor, especially the lonidamine and the 3-bromopyruvic acid to preparation of the medicine for preventing andor treating the Alzheimer disease.

The invention relates to a preparation method of 1H-indazole-3-carboxylic acid derivatives, grasetron and lonidamine. The 1H-indazole-3-carboxylic acid derivative is a compound with the structure of formula (1) and formula (2), and the main structural feature is that it has a 1H-indazole-3-carboxylic acid amide skeleton and a 1H-indazole-3 ‑Carboxylate backbone. The 1H-indazole-3-carboxylic acid derivative can be synthesized from simple anthranilamide or anthranilate as a starting material. 1H-indazole-3-carboxylic acid derivatives are key intermediates in the synthesis of various drugs, such as granisetron, lonidamine, etc. The 1H-indazole-3-carboxylic acid derivatives and drug molecules granisetron and lonidamine involved in the present invention have simple synthesis methods, mild reaction conditions, fast reaction speed, high yield and easy purification.