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Fullerene and its use to maintain good health and to prolong the expected lifespan of mammals

a fullerene and composition technology, applied in the field of 60fullerene and stable biocompatible compositions, can solve the problems of reducing the biological properties of water-insoluble fullerenes, affecting the survival of mammals, and reducing the use of organic solvents, so as to avoid the use and prolong the lifespan of mammals. the effect of longevity

Inactive Publication Date: 2014-05-22
MOUSSA FATHI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a method for extending the lifespan of mammals by administering a composition containing fullerene dissolved in a carrier such as fats and oils. This method avoids the use of charge transfer complexes and organic solvents and ensures that the fullerene is not in situ aggregated. The resulting composition is stable and safe for use and can be added to food or nutritional compositions to promote longevity in mammals. The method is simple and effective, and avoids the drawbacks of previous methods.

Problems solved by technology

Some of these molecules are physiologically useful, but they can also result in pathological oxidative stress to cells and tissues.
However, excess production of free radicals, their production in inappropriate relative amounts or deficiencies in endogenous defences can have deleterious effects.
Availability of biocompatible aqueous solutions of Ceo and its derivatives that are insoluble in water have been major obstacles to toxicity and in vivo studies of this new family of compounds.
Biological properties of water-insoluble fullerenes are still misunderstood and to our knowledge there are no certified toxicology data about them.
Most of the fullerenes studied until now are water-soluble derivatives, since study of water-insoluble fullerenes, such as pristine Ceo, in biological medium proves difficult.
However, water-soluble fullerenes are difficult to synthesize and to purify.
However, Ceo has not been employed as an active ingredient to develop an in vivo treating method in this publication.
However, the authors failed to detect the fullerene inside the cells and these suspensions containing very low concentrations of fullerene (typically 0.1 mg per ml) were inadequate to perform in vivo studies, especially toxicity studies. and metabolic fate investigations ((J. Am. Chem. Soc. 1994, 116, 4517-4518).
Other vectorisation methods include the formation of inclusion complexes with cyclodextrins, calixarenes, tween-20, micelles, liposomes, and vesicles; however the Ceo concentrations reached by such methods are still very low (1 mg / mL at most) and inadequate to perform in vivo toxicity studies.
Further, these methods present another drawback because they generally necessitate a preliminary dissolution step of the fullerene in an organic solvent.
Another method, disclosed in J. Med. Chem. 2000, 43, 3186-3188 uses polyvinyl-pyrrolidone to solubilize C6o; however this vehicle can react with fullerene and the formed complex may cause harmful effects on mice embryos.
However, in such compositions the water-insoluble fullerene is not fully dissolved and their oral absorption was unknown.
Thus, the in vivo use of water-insoluble fullerenes as free radical scavengers through delivery thanks to a non-aqueous carrier is still not satisfactory.

Method used

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  • Fullerene and its use to maintain good health and to prolong the expected lifespan of mammals
  • Fullerene and its use to maintain good health and to prolong the expected lifespan of mammals
  • Fullerene and its use to maintain good health and to prolong the expected lifespan of mammals

Examples

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Effect test

example 1

Direct Dissolution of [60]Fullerene in a Vegetable Oil

[0021]In the stainless steel milling vessels of a Pulverisette 7 (Fritsch, Idar-Oberstein, Germany) or a similar device, add 8 mg of [60]fullerene and 10 mL of olive oil or 10 g of butter and 6 stainless steel balls (8 mm of diameter) (the milling vessels and the balls can be made out of any biocompatible metal or polymer such as stainless steel, tempered chrome steel, silicon nitride, corundum, tungsten carbide, agate, oxide of zirconium etc). Agitate the mixture during several hours (at 600 rpm for instance) until complete dissolution. The resulting homogenous solution or paste is then ready for use for oral administration or by any route of administration after appropriate sterilization. Sterilization may be achieved by filtration under vacuum (pore size: 0.2 μηL). The sterilized composition is stable for at least 1 month. It is also possible to dissolve water-insoluble fullerenes in natural or mineral oils without stirring ho...

example 2

Pharmacokinetics and Biodistribution of an Oily Solution after Oral and Intra-Peritoneal Administration in Rats

[0022]Pharmacokinetic studies were carried out with male Wistar rats (weighing 200-220 g). Rats were housed in individual cages and maintained in an air-conditioned room (22-25° C.) on a 12 h light / dark cycle with water and food available. The rats were acclimated for 7 days and they were fasted overnight but with access to water, before treatment.

[0023]Under general anesthesia, a catheter was introduced into the rat right jugular vein, positioned subcutaneously with the tip in the inter-scapular region. The prepared rats were then allowed to recover for 24 h, and the blood catheters were flushed with 0.9% NaCl solution containing 20 I U / ml of heparin to avoid possible clot obstruction. Before Ceo administration, the rats were fasted overnight but with access to water. The same single dose of Ceo (4 mg / kg) was delivered orally, by a gavages needle, or intra-peritoneally to ...

example 3

Ceo-Induced Protection of the Liver against Acute Toxicity of Carbon Tetrachloride (CCU) in Rats

[0025]Carbon tetrachloride is a classical hepatotoxicant that causes rapid liver damage progressing from steatosis to centrilobular necrosis. CCU intoxication in rodents is an important model for elucidation of the mechanism of action of hepatotoxic effects such as fatty degeneration, fibrosis, hepatocellular death, and carcinogenicity. These effects are consistent with the known induced metabolic activation of CCl4 to reactive intermediates, including CCl3″ and CCl02′ free radicals, and mobilization of intracellular calcium. Kupffer cells (liver resident macrophages) participate in the mechanism of toxicity of CCl4 in vivo by release of chemoattractants for neutrophils and a series of chemical mediators (cytokines). Both expression and synthesis of these cytokines are mainly modulated through redox-sensitive reactions. Further, involvement of reactive oxygen species and lipid peroxydatio...

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Abstract

A water-insoluble fullerene is at least partially dissolved in a biocompatible lipid carrier, especially a fat or an oil such as butter, olive oil, and liquid paraffin. When administered to mammals, the fullerene, most preferably [60]fullerene dissolved in olive oil, scavenges free radicals and prolongs life span in rats.

Description

[0001]This application claims benefit of Tunisian Provisional Application No. TN 2011 / 327 filed Jun. 30, 2011 the contents of which are incorporated herein by reference.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]The present invention concerns [60]fullerene and stable biocompatible compositions comprising [60]fullerene dissolved in a carrier. The present invention also relates to a method for increasing the expected lifespan (longevity) of a mammal, which comprises a step of administering [60]fullerene or a composition comprising a therapeutically effective amount of [60]fullerene. The present invention further concerns a method for preserving a mammal to damages caused by free radicals using said [60]fullerene or said composition.[0004]2. Description of Related Art[0005]Free radicals, such as oxygen radicals and other reactive oxygen / nitrogen / chlorine species (hydroxyl, nitric oxide radicals), are constantly formed in vivo. Some of these molecules are physiologi...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K33/44A23L3/358A23L29/00A23L33/00
CPCA23L3/358A61K33/44A23L33/10A23D7/0053A23D9/007A61K47/14A61K47/44A61P39/06
Inventor MOUSSA, FATHIABDERRABBA, MANEF
Owner MOUSSA FATHI
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