It is known to science, that the disturbance of microcirculation is at the basis of premature ageing. UV radiation is one of the major reasons for premature ageing. It leads to the disturbance of microcirculation, as well as degranulation of mast cells with the extrication of more than 30 biologically active substances, including histamine and serotonin, which increase vessel penetrability and deteriorate the microcirculation disturbance. UV radiation pathogen action on skin is that in most biological structures UV energy causes the opening of chemical bonds and ionization of photo reactive molecules, what leads to the damage of proteins and amino acids. The appearance of signs of ageing, in the first place on open areas of skin, are directly connected with UV radiation. UV radiation leads to certain degenerative processes, as a result of the latter the skin becomes dry, coarse and there is a greater chance of wrinkle formation, epidermis atrophy, hyperkeratosis appearance, collagen degenerative changes and the protective function of keratin layer is impaired. There occurs the accumulation of a large amount of oxidants, free radicals, and the activation of lipid peroxidation under the effect of free radicals leads to further damage of epidermal barrier, significant lesion of cell membranes in epidermis as well as derma. Alongside with that, UV radiation actively affects microcirculation in derma. At the beginning of the process, micro vessel dilation and their filling with blood takes place. Within several minutes (from 6 to 90 minutes) blood filling is substituted by persistent contraction of micro vessels and stasis (blood flow seizure) as a result of which nutrition of derma is deteriorated. Further on, paralytic dilation of some microhemocirculation vessels occurs on the background of blood flow seizure and a continuous spasm (lumen narrowing) in others, as a result there is a significant decrease in the number of functioning capillaries. At microscopy, there can be distinctly observed immobile aggregated and adhesived or sladged (closely located in respect of other elements and capillary endothelium) erythrocytes, thrombocytes, leukocytes which simply stuff the capillaries (marginal state of formed elements of blood). Apart from sladging effect, diapedesis can be observed – the extrication of formed elements of blood from vessels into the surrounding tissues and micro hemorrhage. Another characteristic feature of UV radiation is the slump in the number of mast cells in dozens times. The reduction of the number of mast cells occurs on the account of their degranulation, at this, biologically active substances are extricated, what causes further pathologic increase in vessel penetrability. As a result, the capillary does not function and, if the blood flow is not restored, the process can become irreversible, the number of capillaries will decrease and it deteriorates the state of skin. It imminently causes premature ageing.
Vascular diseases of skin are some of the most common kinds of skin pathology, characterized by chronic and recurrent course and are hardly cured by classic therapy. An effective control over skin vascular system could solve many of the problems of clinical dermatology and cosmetology.
Most commonly, the disturbance in skin microcirculation is the development of the inflammatory reaction, the first three stages of which are characterized by reactivity, penetrability of vascular wall, liquid exudation and vascular blood cell diapedesis.
Hexapeptide 20 is a new preparation, which restores and supports microcirculation and lymph flow in skin. Lymph micro vessels are capable of opiodergic regulation, and tyrosine-containing peptides, the analogies of leu-encephaline, are a powerful direct-action lymph flow stimulators.
THE EFFECT OF PEPTIDE ON LYMPH STIMULATION
The protector activity of the Hexapeptide 20, the analogy to encephalin, its vasoprotector activity, which prevents (prophylactic activity) or reduces (medicative activity) the disturbances in microcirculation and vessel penetrability in subcutaneous fat, as well as its effect which results in the increase of the number of mast cells in damage area, was proved.
Besides, the dosage of Hexapeptide 20 does not exceed 0,0004 mkg/kg. In cosmetology the recommended dosage for application on the regulated area is 100 mkg/ml. Hexapeptide 20 possesses the highest lymph-stimulating activity among all known lymph-stimulators and it has no unwanted side-effects (diapedesis of erythrocytes and leukocytes, micro hemorrhage, blood stasis in separate vessels). Hexapeptide 20 causes activation of the wall and valve of the lymph vessel, what is supported by intensive lymph flow. The activation of lymph flow speed at Hexapeptide 20 application is caused by an intensive contraction of lymphangions. The major result of movement activation of the wall and valve of the lymph vessel is the increase in the speed of lymph flow. In comparison with other peptides, Hexapeptide 20 affected this parameter in the highest degree.
The generalization of screening of opioid peptides for revealing lymph stimulating activity enabled to claim that the activation of lymph flow and movement of the wall and valve of lymph vessel is primarily connected with the activation of δ-opiate receptors. Thus, the highest lymphotrophic activity was witnessed in the antagonist of δ-opioid receptors, the analogy to leu-encephalin Hexapeptide 20.
Table: The effect of peptides* on microhemo- and microlymphcirculation.
|№||Peptide name||n||Dosage(mkg/kg)||Lymph micro vessel activation||Microhemocirculation disturbance|
|Wall||Valve||Lymph flow||Blood flow decrease||Hemorrhage reactions||Stasis|
|1.||DAGO||12||0.04 — 0,4 4.0 — 1200.0||+ —||+ —||++ —||— —||— —||— —|
|2.||DSLET||5||4,0 — 40,0 400,0 — 3600,0||— —||— —||— +||— —||— —||— —|
|3.||Dinorphin (1-13)||11||0,04 — 3200,0||—||—||±||—||—||—|
|4.||Dalargin||20||0,004 — 40.0||++||++||++||+||+++||+|
|5.||DAGP-amid (an.dalargin)||6||4,0 — 40,0||—||+||++||—||—||—|
|6.||Hexapeptide 20||34||0,0004 — 40,0 400,0 — 200,0||+ —||+ —||+++ +||— —||— —||— —|
|7.||ß-endorphin||10||0,0004 — 4.0 40,0 — 200,0||— —||— —||— +||— +||— +++||— +|
Note: (..*)- The table features major changes in microcirculation, observed in the range of peptide dosage indicated. n – the number of applications; (+) – weak; (++)- average; (+++) – high activity; (-) – absence of peptide effect.
THE EFFECT OF THE PEPTIDE ON MICROCIRCULATION
The microcirculation in the subcutaneous fat of a laboratory rat was estimated
Implanting a chamber into the skin or extraction of subcutaneous fat by means of non-chamber method is always accompanied by traumatism of a number of micro vessels, located along the skin incision and in the area of biomicroscopy. At this, the decrease in blood flow speed and stasis in separate vessels are witnessed. In all the experiments (100%) within first minutes after the application, improved the state of microhemocirculation.
The improvement consisted of:
- the increase in blood flow speed in capillary micro vessels, venulae and arteriolae,
- the blood flow restoration in venulae with recent stasis,
- the increase in the number of functioning micro vessels,
- the restoration of the correct blood flow direction in vessels where is was retrograde.
The action time of Hexapeptide 20 was abrupt. Within 1-6 minutes it started to give a positive effect on microcirculation. In most cases the effect progressed within the duration of the experiment, which ended on the background of effective blood flow in all micro vessels of the 2nd and 3rd vascular layers. In the check experiments without Hexapeptide 20 application, the disturbances in microcirculation remained within 3 hours of the experiment duration and their state was constantly deteriorating.
The results of Hexapeptide 20 effect after UV radiation of skin and subcutaneous fat of a laboratory rat
The main criterion was the development of stasis in micro vessels in response to UV radiation. At estimating the efficiency of Hexapeptide 20, the number of micro vessels with restored blood flow after stasis was examined. This is the toughest criterion, which characterizes the irreversible disturbances of microcirculation. Local UV radiation in the conditions of biomicroscopy through the objective without lenses and maximum radiation area (S = 7,0 mm2), caused irreversible microhemocirculation disturbances, which occurred within 30 minutes, on average. Hexapeptide 20 was applied 30 minutes after UV radiation. In all the experiments without an exception (100%) Hexapeptide 20 caused microcirculation improvement in vessels. Often (80% of tests) primary blood flow restoration was witnessed in venulae (including major venulae), more rarely – in the first place in arteriolae and capillaries (20% of tests). Such consistency and frequency can be explained primarily by a high density of venular system. Within 2-3 minutes after the Hexapeptide 20 application the restoration of blood flow in the vessels with stasis was witnessed. Within 1 minute after Hexapeptide 20 application there could be clearly observed slow blood circulation in venulae, reversed blood flow direction, which within 5-20 minutes was substituted by the increase and restoration of speed and direction of blood flow. Within 1 hour after Hexapeptide 20 application intensive blood flow was witnessed in these vessels. Micro vessels, which preserved a slow blood flow after UV radiation, reacted to the Hexapeptide 20 by the increase and restoration of blood flow speed. In these micro vessels, the highest intensity of blood flow was witnessed in arteriolae. Without Hexapeptide 20 application the area of microcirculation disturbance did not decrease, but increased. Alongside with blood flow restoration Hexapeptide 20 removed progressing dilatation and venulae plethora, and not only restoration of venulae lumen took place, but also their reduction in comparison with the original diameter.
Pic. 1. The change of diameter of venulae and arteriolae of subcutaneous fat in response to UV radiation within 30 minutes (S — 7,0 mm2) in conditions of biomicroscopy. White column – arteriolae, black – venulae. x-axle shows the time in minutes after the seizure of UV radiation; y-axle – the change in diameter in % to the original, which was taken as 100%. * — Р < 0,01; ** — Р < 0,001.
Thus, Hexapeptide 20 is the most effective blood flow stimulator, capable of restoring the blood flow in microcirculation after damaging factor, as well as the most effective lymph flow stimulator
HEXAPEPTIDE 20 AS A MAST CELL PROTECTOR
During degranulation, mast cells extricate different inflammation mediators (histamine, serotonin, bradikinin, etc.), which significantly affect the state of vascular tonus. Prophylactic introduction of Hexapeptide 20 at inter-skin UV radiation provided protective effect on the number of mast cells in subcutaneous fat, their number exceeded 5 times the number of cells in experiments without the peptide application. Hemorrhage manifestations were significantly reduced and in some experiments were absent. They could be manifested in the way of a single vascular erythrocyte diapedesis. Hemorrhage was never witnessed. The degree of mast cell degranulation can be connected with the reduction of hemorrhage reactions on the level of micro vessels. Thus, Hexapeptide 20 showed protective activity towards mast cells (at this, mast cells did not extricate active mediators, changing the physical features of the vessels).
The medication effect of Hexapeptide 20 was in maintaining the original or increased level of microcirculation index, starting from the very first minutes after the application. Hexapeptide 20 turned out to be an effective vasoprotector and a mast cell protector, capable of quick restoring the blood flow in vessels, even in those where the disturbances had an irreversible character, on the background of already developed deep disturbances in microcirculation. The application of Hexapeptide 20 in dermatology and cosmetology is a new approach to the treatment and prophylactics of various skin diseases as it is a significant skin care preparation, an inhibitor to the process of ageing.
THE APPLICATION OF THE HEXAPEPTIDE 20 IN COSMETOLOGY
A unique peptide Hexapeptide 20 helps to cope with microcirculation disturbance, to prevent premature and delay genetically determined ageing. It restores the disturbed microcirculation and facilitates mast cell stabilization, thus preventing mast cell degranulation and impeding the extrication of biologically active substances by mast cells. As a result, microcirculation is restored and micro capillaries function and do not perish. It facilitates the flow of nutrients into skin and improves the complexion, wrinkles vanish and edemas under eyes are reduced. Hexapeptide 20 restores microcirculation by regulating vascular tonus and not only restores the flow of blood and nutrients into superficial and deep layers of skin, but also improves the blood flow-out. Another significant feature of Hexapeptide 20 is a powerful lymph stimulating effect. Hexapeptide 20 has the highest lymph stimulating activity among all known lymph stimulators and causes no side-effects. The lymph flow activation by Hexapeptide 20 is caused by an intensive contraction of lymphangions. Another essential feature of Hexapeptide 20 is an immune modulating effect.
- increases blood flow speed in micro capillaries,
- restores the blood flow in vessels with stasis,
- increases the number of functioning micro vessels,
- restores the correct blood flow direction in vessels where it was retrograde
- improves blood outflow and prevents succulence formation,
- possesses a powerful lymph stimulating effect,
- stabilizes mast cells and prevents their degranulation,
- possesses immune modulating and desintoxicating activities.
The application of Hexapeptide 20 in cosmetology is a significant skin care measure, a new approach to the therapy of age-related changes of skin, an inhibitor to the process of ageing.
Copyright© Terekhova T. 07.08.2020