Biologically active substances, method for obtaining and...

Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution... – Containing or obtained from cactaceae

Reexamination Certificate

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C424S777000, C424S078030, C424S439000, C514S885000

Reexamination Certificate

active

06737086

ABSTRACT:

The present invention relates to the biochemical field, and more precisely to biological compounds of vegetable origin.
The present invention relates to new biologically active substances extracted from the fruits of plants with a CAM metabolism, method for obtaining them and pharmaceutical, cosmetic and/or nutritional compositions containing them.
The compositions of the present invention are intended to accelerate and amplify the synthesis of heat shock proteins (or stress proteins) of the cells of living beings. In fact, the stress or aggression conditions are of a nature which alters the quality and synthesis of proteins. Eucaryotes have had to develop metabolic routes intended to preserve their structure.
Plants with a CAM metabolism principally belong to the Cactaceae, Crassulaceae and Saxifragaceae families, which form the only entity capable of developing this type of metabolism.
These plants are particularly adapted to severe climatic conditions and have a particular chlorophyll metabolism which results in a carbon cycle, called CAM (“Crassulaceae Acid Metabolism”).
Certain plants are capable of living under stressful conditions (notably plants living in the arid areas of hot or cold deserts or in high-altitude areas), and having a particular metabolism for incorporating CO
2
, called CAM. Plants of the Cactaceae, Crassulaceae and Saxifragaceae families are well adapted to these heat shock conditions. The synthesis of biological substances which activate or amplify the expression of heat shock proteins is above all abundant in fruit during its formation; the maturation of fruit occurs above all during a period when the temperature returns to normal. The fruit being very exposed to the heat, there is every reason to think that it uses means to protect its protein syntheses.
This protection measure could also be found in other living species.
Among the plants with a CAM metabolism, there can be mentioned in particular the Cactaceae. Cactaceae constitute a family of dicotyledonous plants, commonly called cactus, appreciated for their curious shapes and their brilliantly coloured flowers. One of the most wide-spread genera of the Cactaceae family is constituted by the Opuntias. The
Opuntia ficus
-
indica
or prickly pear (Cactaceae family) is formed of flat articles, with an oval shape, “flat cactus cladodes”, the surfaces of which are sprinkled with areola. Each of these contains a dormant shoot apex, protected by bristles, barbs or glochidia (characteristic of the genus), thorns; they thus constitute the homology of buds. On young shoots, the areola are accompanied by small fleshy leaves, which rapidly fall.
The growth and proliferation of living organisms presumes a high autonomy not only to restore genetic material, guaranteeing the perennity of the species, but also to repair lesions to their body, in order to preserve their integrity. These two necessities require complementary biological systems.
Various mechanisms used by cells to ensure the intact preservation of genetic resources have already been discovered; by way of example, there can be mentioned the protein p 53 system. Similarly, mechanisms exist to ensure the structural conformity of proteins developed from the transcription of information contained in the genome. These synthesis protection mechanisms use various processes and, among these, the synthesis of what are called “heat shock proteins”, in spite of the fact that they do not respond in a unique fashion to heat stresses.
The term stress must be taken in its wide sense; it includes stress of various origins, such as temperature rise (from where the name heat shock proteins is derived), oxidizing stress, UV radiation, viral or bacterial infections, or stress resulting from various stimuli such as nutritional deprivation, mechanical aggression or metabolic shock. This is why heat shock proteins are synthesized by the cells to respond to both aggression of a chemical origin (poisons, etc.), of physical origin (ionizing radiation, osmolarity, pH, etc.), of biological origin (cytokines), or mechanical origin.
Heat shock proteins (HSP's) are proteins responsible for protecting the cell, and more particularly its protein syntheses, from aggression of any origin. With age, the capacities for protein synthesis reduce considerably and consequently the ability to respond to aggression is less and less adaptive. This results in the death of numerous cells, lack of protection and a reduction in cell capital, which produces, in particular at the level of mammalian skin, a reduction in the number of keratinocytes available to protect the dermis. Time, exposure to the sun and temperature variations induce aggressions which attack the cells. The skin of the young human adult is particularly well adapted to rapidly respond to aggression as it is capable of synthesizing large quantities of heat shock proteins in order to protect the conformation of the proteins during synthesis. With age, heat shock protein synthesis capacities diminish.
Protection of the skin from the sun is one of the care products in greatest demand by consumers and the most recommended by consultants. Variability in the protective ozone layer, the search for summer warmth, the possibility of travel to the tropics have considerably increased the risk of the appearance of skin disorders resulting from exposure to the sun and thermal aggression. Nowadays, protection against UV and IR radiation exists with different filtering or reflection indices, but there are no products to be applied to the skin to protect it against excessive heat or cold.
The body uses heat shock proteins in order to prevent damage caused by numerous types of aggression: aggressions of external origin (photoluminous, thermal radiation, chemical or biological compounds), but also aggressions of internal origin (hyperthermia, hypothermia, variation in biological parameters, such as for example osmolarity, concentration of certain substances, etc.).
The heat shock proteins are also called stress proteins, shock proteins; scientific terminology refers to them as HSP's. These proteins can also be called, in certain cases, chaperone proteins and, in other cases, glucose regulated proteins (GRP's).
Heat shock proteins (HSP's) include a very large number of molecules. In order to simplify their naming, it is therefore agreed to define them specifically by their molecular weight, expressed in kilodaltons (kDa). Different groups of HSP's can thus be identified: hsp 110′s (110 kDa), hsp 90′s (90 kDa), hsp 70′s (70 kDa) which represent the largest family of hsp's; hsp 60′s (60 kDa), hsp 47′s (47 kDa) and small hsp's (i.e. between 16 and 40 kDa).
The heat shock proteins constitute a large molecular family involved in maintaining the spatial conformation of proteins. For this reason, when the temperature rises, the spatial structure of proteins is modified (this is the same phenomenon as the coagulation of albumin in an acid medium).
The large number of HSP's results from the fact that they act with a specificity which depends on the cell type, their destination or also the type of stress. Each member of the HSP family thus has a quite precise function and the intervention points are very numerous. The HSP's apply not only to the post-translational stages forming part of a normal synthesis function and of the proteins' life, such as the setting up of the conformation and their transport, but also at the level of the events which alter protein synthesis by intervening in the selection of metabolic routes: restoration, destruction and elimination of modified substrates. Certain HSP's have an action which develops during thermal aggression, others only play their roles in the presence of a chemical risk.
There is therefore a large number of shock proteins, each adapted to a specific protection mechanism.
These substances, of protein type, are coded by genes for which the chromosome location has only been established for a few of these. It should be noted that

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