A61K38/41

METHOD OF OBTAINING A PHARMACOLOGICALLY ACTIVE LIPOSOMAL CYTOCHROME C AND NITRIC OXIDE COMPLEX

The invention relates to pharmaceutical industry and discloses a method of obtaining a new pharmacologically active liposomal agent containing substances that exhibit specific pharmacological activity on peripheral vessels and cavernous bodies of a mammal. More particularly, the invention relates to a method of obtaining a pharmacologically active liposomal cytochrome c containing nitric oxide. The new liposomal agent acts as a donor of the key biologically active substancenitric oxide (NO).

A method of obtaining a pharmacologically active liposomal cytochrome c and nitric oxide complex comprises the treatment of the liposomal cytochrome c emulsion with gaseous nitric oxide (NO) until liposomal cytochrome c is completely reconstituted and the addition of an S-nitroso compound to the liposomal cytochrome c emulsion.

Nanostructures comprising cobalt porphyrin-phospholipid conjugates and polyhistidine-tags

The present disclosure provides nanostructures (e.g., monolayer or bilayer nanostructures) comprising porphyrins with cobalt chelated thereto such that the cobalt metal resides within monolayer or bilayer in the porphyrin macrocycle. The nanostructures can have presentation molecules with a histidine tag attached thereto, such that at least a part of the his-tag is within the monolayer or bilayer and coordinated to the cobalt metal core and the presentation molecules are exposed to the outside of the nanostructures. The nanostructures can further comprise a cargo. The nanostructures can be used to deliver the cargo to an individual.

Nanostructures comprising cobalt porphyrin-phospholipid conjugates and polyhistidine-tags

The present disclosure provides nanostructures (e.g., monolayer or bilayer nanostructures) comprising porphyrins with cobalt chelated thereto such that the cobalt metal resides within monolayer or bilayer in the porphyrin macrocycle. The nanostructures can have presentation molecules with a histidine tag attached thereto, such that at least a part of the his-tag is within the monolayer or bilayer and coordinated to the cobalt metal core and the presentation molecules are exposed to the outside of the nanostructures. The nanostructures can further comprise a cargo. The nanostructures can be used to deliver the cargo to an individual.

COMPOSITIONS AND METHODS FOR NEURALGENESIS

The present invention relates to novel compositions and methods to produce 3D organ equivalents of the brain (i.e. mini-brains). The invention also relates to methods of using human induced pluripotent stem cells, a combination of growth and other soluble factors and gyratory shaking. Cells from healthy or diseased donors or animals can be used to allow testing different genetic backgrounds. The model can be further enhanced by using genetically modified cells, adding micro-glia or their precursors or indicator cells (e.g. with reporter genes or tracers) as well as adding endothelial cells to form a blood-brain-barrier.

COMPOSITIONS AND METHODS FOR NEURALGENESIS

The present invention relates to novel compositions and methods to produce 3D organ equivalents of the brain (i.e. mini-brains). The invention also relates to methods of using human induced pluripotent stem cells, a combination of growth and other soluble factors and gyratory shaking. Cells from healthy or diseased donors or animals can be used to allow testing different genetic backgrounds. The model can be further enhanced by using genetically modified cells, adding micro-glia or their precursors or indicator cells (e.g. with reporter genes or tracers) as well as adding endothelial cells to form a blood-brain-barrier.

ENCAPSULATED CELLS PRODUCING CYTOCHROME P450 AND METHODS OF USE THEREOF
20180271794 · 2018-09-27 ·

Disclosed herein are methods and compositions to treat solid tumors. In one embodiment, the method of treating a solid tumor in a patient includes administering at the tumor site a therapeutically effective amount of cytochrome P450 producing cells encapsulated in a capsule and administering a prodrug which is activated by cytochrome P450, wherein the prodrug is administered at least three or more cycles, and wherein each cycle comprises three consecutive daily administration.

RECOMBINANT ADENO-ASSOCIATED VIRAL VECTORS FOR TREATING BIETTI CRYSTALLINE DYSTROPHY

The present disclosure provides a recombinant adeno-associated vector comprising a codon-optimized sequence encoding CYP4V2 linked to selected gene expression regulatory sequences and its use in treating Bietti Crystalline Dystrophy (BCD).

COMPOSITIONS AND METHODS FOR THE TREATMENT OF CARBOXYHEMOGLOBINEMIA

Described herein is a new antidote for the rapid elimination of carbon monoxide from hemoglobin, including brain, heart, and red cell hemoglobin. The disclosed therapy involves the use of modified human globins, particularly neuroglobins modified at residue 64 and cytoglobins modified at residue 81, which bind carbon monoxide with extremely high affinity. The monomeric mutant globins are infused into blood, where they rapidly and irreversibly sequester carbon monoxide, and thus limit toxic effects of carbon monoxide on cellular respiration and oxygen transport and utilization.

COMPOSITIONS AND METHODS FOR THE TREATMENT OF CARBOXYHEMOGLOBINEMIA

Described herein is a new antidote for the rapid elimination of carbon monoxide from hemoglobin, including brain, heart, and red cell hemoglobin. The disclosed therapy involves the use of modified human globins, particularly neuroglobins modified at residue 64 and cytoglobins modified at residue 81, which bind carbon monoxide with extremely high affinity. The monomeric mutant globins are infused into blood, where they rapidly and irreversibly sequester carbon monoxide, and thus limit toxic effects of carbon monoxide on cellular respiration and oxygen transport and utilization.

METHOD OF PRODUCING OF PHARMACOLOGICALLY ACTIVE LIPOSOMAL COMPOSITION CONTAINING CYTOCHROME C, AND LIPOSOMAL COMPOSITION OBTAINED BY THIS METHOD

This invention relates to pharmaceutics and a method of producing of liposomal composition containing cytochrome c and the pharmacologically active liposomal composition obtained by this method, which can be used as a means of polyfunctional pharmacotherapy, especially for ophthalmology, hematology and cardiology.

A method of producing of liposomal composition containing cytochrome c, the method includes preparing mixture of solutions of lipids in an organic solvents, drying in vacuum the mixture and emulsifying it in aqueous medium containing cytochrome c, adding of cryoprotectant, homogenization of the emulsion, filtration and freeze-drying, and according to the invention the lipids are egg or soybean phosphatidylcholine with one or two of lipids from the group consisting of dipalmitoylphosphatidylglycerol, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol or dioleoyloxypropy trimethylammonium, whereas the ratio of phosphatidylcholine:to other lipids is 0.3-2.0:1, thereby to prepare the mixture of solutions of lipids, phosphatidylcholine is dissolved in ethyl alcohol, and other lipidsin chloroform and a volume ratio in a mixture of solutions of ethyl alcohol:chloroform is 1:1.5-2.5, emulsification is performed at a weight ratio of cytochrome c to lipids of 1:11.4-18.5 adding a cryoprotectant solution to the aqueous medium, and the cryoprotectant is selected from lactose, trehalose, sucrose oligosaccharides, wherein the said solution contains 60-80% of total cryoprotectant, and homogenization with step-by-step increasing pressure from 300 to 800 atm, after its completion a solution of selected cryoprotectant is added to emulsion, wherein solution contains 40-20% of total cryoprotectant, and the weight ratio of lipids mixture to cryoprotectant is 1:5.5-7.2.

It is claimed a liposomal composition containing cytochrome c, lipids and cryoprotectant, which is performed according to the method above, and the composition includes egg or soybean phosphatidylcholine in mixture with one or two of lipids from the group consisting of dipalmitoylphosphatidylglycerol, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol or dioleoyloxypropy trimethylammonium, and cryoprotectant is selected from lactose, trehalose, sucrose oligosaccharides, wherein the weight ratio of cytochrome c:phosphatidylcholine:other lipids:cryoprotectant is 1:2.9-8.6:4.3-15.7:78.6-102.8 and percentage content ratio is (0.81-1.06)%:(3.03-8.26)%:(4.13-9.88)%:(78.67-83.30)% respectively.