RU2789964C1 - Method for improving the condition of the skin and subcutaneous tissues - Google Patents

Abstract

FIELD: cosmetics.

SUBSTANCE: invention relates to the cosmetic and pharmaceutical industries and is a method for improving the condition of the skin and subcutaneous tissues. A method for improving the condition of the skin and subcutaneous tissues of the body and face, including the treatment of the skin with an inert gas, characterized in that krypton or its mixture with xenon is used as an inert gas by introducing krypton or its mixture with xenon and exposure for at least 15 minutes in the space between the skin and a product such as a stocking, sock, sleeve, face mask that ensures the creation of a sealed space above the selected area of the skin, containing at least one valve that provides the possibility of vacuuming the cavity and introducing gases into the cavity.

EFFECT: invention provides an improvement in blood supply and nutrition of the skin and subcutaneous tissues.

3 cl, 4 tbl, 4 ex

Description

The invention relates to the cosmetic and pharmaceutical industries and is a method for improving the condition of the skin and subcutaneous tissues.

There are many methods for correcting the manifestations of local edema and neuropathy and improving blood supply, both medicinal and physiotherapeutic, for example, drug electrophoresis, magnetotherapy, ultratonotherapy, local darsonvalization, ultrasound therapy (Nuvakhova M.B., Marchenkova L.A., 2017). All the described methods are aimed at improving microcirculation and blood supply and reducing the effects of local edema in the area of the affected skin.

An invention is known that relates to medicine, namely to cosmetology and physiotherapy (RF patent 2735464, A61M 5/142Yu publ. 02.11.2020). The procedure is carried out with the CarboxyPen apparatus by mesotherapeutic introduction of carbon dioxide, using mesotherapeutic needles, 30G on the Gage scale, from 6 to 13 mm long: intradermally or subcutaneously, at 3-10 points, to a depth of 3-6 mm. At the same time, from 2 to 5 ml of carbon dioxide is used per injection. The total amount of carbon dioxide per procedure is 10-20 ml. The course of treatment is 5-6 times a day. At the same time, carbon dioxide injections are carried out near areas of the skin where there are manifestations of edema and neuropathies, at a distance of 0.1-1 cm from them and along the behind-the-ear, submandibular and cervical collectors, at a distance of 0.1-1 cm from them.

A number of technical solutions have been identified from the prior art, which describe various methods for introducing inert gases in the treatment and prevention of various diseases.

There is a known method of introducing xenon into the human body during xenon therapy (RF patent 2706424, A61M 16/10, publ. 11/19/2019). To introduce into the body the amount of xenon necessary for the prevention and treatment of the disease, a xenon clathrate compound is used, which is a compound in which xenon molecules are located in the voids of the frame formed by the crystal lattice of ice, xenon clathrate is introduced into the gastrointestinal tract of the body through a dosage form carrier for taking inside.

Disadvantage - requires a special thermostable shell, low temperature storage.

A known method of xenon therapy, which is based on the inhalation of xenon, namely, the inhalation of a gas mixture of xenon and oxygen. For example, technical solutions (see RF patents No. 2446837, No. 2392011, No. 2339409, No. 2319515, No. 2305565).

But to carry out such therapy, trained specialists and special equipment are needed. Due to the nature of xenon absorption, the total duration of the procedure is 30-40 minutes.

A known method of increasing the transdermal permeability of medicinal or cosmetic preparations for external use, a method of introducing gaseous xenon into the skin (RF patent 2506944, A61K 9/00, A61K 33/00, A61P 17/00, A61P 19/00, A61P 21/00, A61K 8/00, A61Q 5/00, A61Q 19/00, published 02/20/2014). The invention relates to the cosmetic and pharmaceutical industries and is a method for increasing the transdermal permeability of therapeutic or cosmetic preparations for external use. The method includes introducing into the skin from 1.0 to 300.0 vol. % of gaseous xenon in the composition of an acceptable neutral carrier or medical or cosmetic product. The invention provides an increase in the effectiveness of medicinal or cosmetic products by increasing the transepidermal transport of bioactive compounds.

The disadvantage of the known solution is the inability to control the content of xenon in the composition of the external agent when it is applied to the skin.

The objective of the present invention is a method for improving the condition of the skin and subcutaneous tissues by improving the blood supply and nutrition of the skin and subcutaneous tissues, in various pathological conditions, including dystrophic phenomena, inflammatory manifestations.

The problem is solved by the fact that a method for improving the condition of the skin and subcutaneous tissues, including treatment of the skin with an inert gas, characterized in that krypton is used as an inert gas, or its mixture with xenon in various ratios by introducing/exposure to an inert gas or its mixture with xenon on the skin and exposure sufficient to improve the condition of the skin and subcutaneous tissues by means of a product that provides the creation of an airtight space above the selected area of the skin, containing at least one valve that provides the possibility of evacuating the cavity and introducing gases into the cavity (into the airtight space).

As a component of the mixture with krypton, xenon is used, with a quantitative ratio of not more than 99% in the mixture.

In the claimed technical solution, an inert gas or a mixture of an inert gas is injected through at least one valve located in the wall inside the product, such as a stocking, sock, sleeve, face mask, patch, mask for the forehead, chin, providing tight sealed contact around the perimeter of the product for the purpose of tight fixation with the skin and sealing the created space.

For local treatment of small skin areas, in the claimed technical solution, an inert gas or a mixture of inert gas is injected into a cap-type product with a diameter of 3 to 50 mm for local treatment of small skin areas.

Before the introduction of an inert gas or an inert gas mixture, the skin is treated with a lipophilic substance, which is chosen as liquid hydrocarbons (for example, vaseline, vaseline oil, etc.), higher carboxylic acids (for example, caprylic acid, alpha-lipoic acid, lauric acid , palmitic acid, etc.), natural waxes (for example, beeswax, carnauba, rose, jojoba, etc.), emollients of various chemical nature (for example, esters, fatty acids, fatty alcohols, fats, oils, squalane, silicones ).

Krypton is an inert monatomic gas without color, taste or smell. It is obtained as a by-product in the form of a krypton-xenon mixture in the process of air separation in industrial plants. In the process of air separation by the method of low-temperature rectification, a constant selection of the liquid oxygen fraction containing liquid hydrocarbons, krypton and xenon is performed (the selection of the oxygen fraction with hydrocarbons is necessary to ensure explosion safety). To extract krypton and xenon, hydrocarbons are removed from the sampled fraction in catalytic furnaces and sent to an additional distillation column to remove oxygen; silica gel (or other adsorbent). After cleaning the gas mixture from hydrocarbon residues and moisture, it is pumped into cylinders for transportation to the Kr and Xe separation unit (this is due to the fact that not every enterprise operating air separation plants has a Kr and Xe separation unit).

The use of krypton or its mixture with xenon as an inert gas in the claimed invention makes it possible to effectively improve the condition of the skin and subcutaneous tissues in order to improve blood supply, which leads to a decrease in the manifestation of the venous pattern on the limbs, an improvement in capillary subcutaneous circulation, an increase in skin elasticity, and a decrease in swelling under the eyes. , reduce manifestations in the form of rosacea.

It is known that krypton has excellent healing properties. Moreover, these properties are superior to xenon in a number of indicators. Considering that krypton is an order of magnitude cheaper than xenon, and the introduction of anesthesia at the earth's atmospheric pressure is impossible, it is relatively safe for widespread use, and it has prospects for use in many branches of medicine. Krypton has analgesic, antispasmodic, cardiotonic, neuroprotective, antistress, antihypoxic, immunostimulating, anti-inflammatory, anabolic, neurohumoral, myotonic, anticonvulsant, regenerative, tonic effects. The listed properties of krypton make it an effective tool for improving the athletic performance of athletes, since it increases the endurance and recovery of athletes after heavy physical exertion, improves reaction. In clinical practice, krypton has shown itself to be an effective treatment for post-stroke conditions. (B.M. Ovchinnikov, A.Yu. Perov, E.A. Sazanova, "Methods of krypton therapy for various disorders of cerebral circulation", Preprint INR RAS, No. 1232/2009).

Xenon is an inert noble gas, absolutely non-toxic, does not react with biological molecules, does not show mutagenic, teratogenic, cyto- and immunotoxic properties. It has been used in medicine since 1951 for inhalation anesthesia. When introduced into the body, the gas is completely eliminated within 4 hours (Sanders R.D., Franks N.P., Maze M. Xenon: no stranger to anaesthesia / Brit J Anaesthesia, 2003. - V. 91 (5). - P. 709-717 ). The therapeutic effect of gas has been shown in neurotoxicity of various genesis, Parkinson's disease, schizophrenia, cerebral ischemia [Burov N.E., Potapov V.N., Makeev G.N. Xenon in anesthesiology - M., Puls., 2000. - 356 p.; Abraini J.H., David H.N., Lemaire M. Potentially Neuroprotective and Therapeutic Properties of Nitrous Oxide and Xenon - Ann. N.Y. Acad. sci. 2005, 1053: P. 289-300]. Increasingly, gas is used in subnarcotic (small) doses for therapeutic anesthesia with neurotoxicity of various origins (Abraini J.H., David H.N., Lemaire M. Potentially Neuroprotective and Therapeutic Properties of Nitrous Oxide and Xenon - Ann. N.Y. Acad. Sci. 2005, 1053: P. 289-300). Xenon is effective in the composition of liposomes and when introduced into the vessels of the brain, this contributes to a significant acceleration of the restoration of brain tissue repair and a decrease in neurotoxicity after a stroke (Britton G.L., Kim H., Kee R.N. et al. In Vivo Therapeutic Gas Delivery for Neuroprotection with Echogenic Liposomes / Circulation 2010, 122(16): 1578-1587).

As the main mechanism of action of xenon, its effect on the systems of mediators that ensure the conduction of a nerve impulse, primarily the blockade of N-methyl-D-aspartate (NMDA) receptors, is considered. This signaling system was originally described for the central nervous system, but later it was also found in bone and hematopoietic tissues, pancreas, deep tissues (muscles, tendons, joints), nerve endings in the heart muscle, myocardiocytes (Skerry T.M., Alfredson H., Lorentzon R.J. Chronic tendon pain: no signs of chemical inflammation but high concentrations of the neurotransmitter glutamate. Implications for treatment / Curr Drug Targets, 2002. - V. 3. - P. 43-54). NMDA receptors have also been identified in the basal, spiny and granular layers of human skin - (Kinkelin I, Brocker E-B, Koltzenburg M. et al. Localization of ionotropic glutamate receptors in peripheral axons of human skin / Neurosci Lett, 2000. - V. 283 - P. 149-152; Nahm W.K., Philpot B.D., Adams M.M. et al. Significance of N-methyl-D-aspartate (NMDA) receptor-mediated signaling in human keratinocytes / J Cell Physiol, 2004. - V. 200 ( 2) - P. 309-317; Fischer M., Glanz D., William T. et al. N-methyl-D-aspartate-receptors influence the intracellular calcium concentration of keratinocytes / Experimental Dermatology, 2004. - V. 13 (8) - P. 512-519). Currently, NMDA receptors are considered as targets for the treatment of human skin diseases (Nahm W.K., Philpot B.D., Adams M.M. et al. Significance of N-methyl-D-aspartate (NMDA) receptor-mediated signaling in human keratinocytes / J Cell Physiol, 2004. - V. 200 (2. - P. 309-317). The effectiveness of the topical application of calcium channel antagonists, which accelerate the repair of the epithelial barrier, is associated with the impact on them (Fuziwara S., Inoue K., Denda M. NMDA-type glutamate receptor is associated with cutaneous barrier homeostasis / J. Invest. Dermatol, 2003, - V. 120. - P. 1023-1029). A decrease in the severity of hyperalgesia, inflammatory hyperemia and muscle pain in humans has been shown with local superficial intradermal administration of the NMDA antagonist ketamine and the opioid phentamine (Koppert W., Zeck S., Blunt J.A., Schmelz M. The Effects of Intradermal Fentanyl and Ketamine on Capsaicin-Induced Secondary Hyperalgesia and Flare Reaction / Anesth Analg, 1999 - V. 89 (6) - p. 1521-1527 Cairns B. E., Svensson P., Wang K. et al. Activation of Peripheral NMDA Receptors Contributes to Human Pain and Rat Afferent Discharges Evoked by Injection of Glutamate into the Masseter Muscle J Neurophysiol, 2003. - # 90. - P. 2098-2105).

Hyperactivation of NMDA receptors is the most important factor in the mechanisms of tissue damage during oxidative stress (Said S.I., Pakbaz H., Berisha H.I., Raza S. NMDA receptor activation: critical role in oxidant tissue injury / Free Radical Biology and Medicine, 2000. - V. 28 (8) - P. 1300-1302). In this regard, the above mechanism of action of xenon is directly related to another of its mechanisms - the ability to regulate the antioxidant status of the body. This phenomenon was revealed by Russian scientists in experiments on animals, in which, with the introduction of gas, a decrease in the activity of lipid peroxidation processes was noted (Burov N.E., Potapov V.I., Makeev G.N. Xenon in anesthesiology / M., Pulse, 2000. - 356 pp. The use of xenon in medicine, edited by N. I. Suslov, M. N. Shpisman, V. N. Potapov / Tomsk, 2008. - 300 p.).

It is known that xenon easily diffuses through a full-layer skin preparation (Transdermal delivery of xenon from lipophilic solution and water, doi: 10.7243/2053-5309-3-2), through artificial skin analogues - Strat-M membranes and has the properties of a transdermal enhancer. For example, the ability of xenon to regulate the transdermal diffusion of niacinamide was studied using a Strat-M artificial skin membrane analog model on Franz cells. In a transdermal diffusion study with a 5% solution of niacinamide, xenon was shown to act as an enhancer - it increases the rate of penetration of niacinamide through Strat-M membranes. Based on the data obtained, it was found that in a simplified biophysical model of Strat-M membranes, xenon has an amplifying effect based on the process of nucleation of heterogeneous xenon nucleation at interfaces in the microporous structures of the Strat-M membrane, initiating the phenomenon of hydrophobic superslip. (Petrov E., Verkhovskiy A. Xenon as a transdermal enhancer for niacinamide in Strat-M™ membranes. Med Gas Res.2022;12(1):24-27).

Examples of specific use of the invention are given below.

Example 1

To study the effect of krypton gas and krypton/xenon mixture on the arterial circulation of the lower extremities, six male and female volunteers, aged 48 to 65 years, were recruited. During the study, patients did not take oral and topical medications. Three subjects (group 1) had grade 1 ischemia in both legs: motor activity and sensitivity were preserved, but almost every day there was a feeling of numbness, coldness, and pain. The other three volunteers (group 2) were diagnosed with grade 2 ischemia in both legs: there is a periodic limitation of motor activity and sensitivity, accompanied by a symptom of intermittent claudication.

Daily procedure: All volunteers were put on stockings made of a gas-tight film with a valve to remove air between the wall of the stocking and the surface of the lower limb, followed by the introduction of krypton. The upper part of the stocking was fixed with a plaster around the lower limb. Previously, the surface of the skin of the lower extremities was treated with vegetable squalane. After dressing and fixing the stocking, the remaining air was sucked out through the valve using a large-capacity syringe (500 ml). Then, all volunteers were injected with krypton through the same valve on the left leg, also using a syringe in the amount of 1 liter; and on the right leg, a different mixture of krypton/xenon was injected, as shown in table. The exposure time was from 25 to 30 minutes.

The data are presented in table 1.

Table 1 - Effect of krypton gas and krypton/xenon mixture on the arterial circulation of the lower extremities Group 1 Left leg Krypton Krypton Krypton Right leg Krypton/Xenon = 1/99% Krypton/Xenon = 10/90% Krypton/Xenon = 50/50% Group 2 Left leg Krypton Krypton Krypton Right leg Krypton/Xenon = 1/99% Krypton/Xenon = 10/90% Krypton/Xenon = 50/50%

The described procedure was repeated for 7 days.

After the procedures, all volunteers noted a significant improvement in the condition in both lower extremities: the symptoms of numbness, coldness, and pain stopped. There was a possibility of a long walk. An ultrasound examination revealed a significant restoration of blood flow. Improvement was observed in both limbs.

Example 2

To study the effect of krypton gas and krypton/xenon mixture in venous circulation disorders of the lower extremities, four female volunteers, aged 45 to 55 years, were recruited. During the study, patients did not take oral and topical medications. In volunteers, symptoms were observed on both limbs: an increase in the pattern of veins on the skin, the appearance of spider veins (telangiectasia), rare pain sensations.

Daily procedure: All volunteers were put on stockings made of a gas-tight film with a valve to remove air between the wall of the stocking and the surface of the lower limb, followed by the introduction of krypton. The upper part of the stocking was fixed with a plaster around the lower limb. Previously, the surface of the skin of the lower extremities was washed and treated with jojoba oil. After dressing and fixing the stocking, the remaining air was sucked out through the valve using a large-capacity syringe (500 ml). Then, all volunteers were injected with krypton through the same valve on the left leg, also using a syringe in the amount of 1 liter; and on the right leg, a different mixture of krypton/xenon was injected, as shown in table. The exposure time was from 15 to 25 minutes.

The data are presented in table 2.

Table 2 - the effect of krypton gas and krypton/xenon mixtures in venous circulation disorders of the lower extremities Left leg Krypton Krypton Krypton Krypton Right leg Krypton/Xenon = 1/99% Krypton/Xenon = 10/90% Krypton/Xenon = 50/50% Krypton/Xenon = 80/20%

The described procedure was repeated for 7 days.

After the procedures, all volunteers noted a significant improvement in the condition in both lower extremities: the manifestation of the venous pattern decreased, the capillary subcutaneous circulation improved (the number of spider veins decreased).

Example 3

To study the effect of krypton gas and krypton/xenon mixture on the condition of the skin of the face and décolleté area, the study was carried out on three female volunteers aged 37 to 57 years.

Volunteers observed a dull complexion, sagging skin, dark circles under the eyes, fine wrinkles around the eyes, swelling of the lower eyelids, rosacea.

An analogue of a cosmetic mask made of non-woven material was formed from a gas-tight film, along the perimeter with a thin strip of double-sided adhesive tape, which ensures a snug fit of the film, while dividing into left and right parts. The film had a valve on each side. The skin was pre-washed. After fixing the film on the face, air was sucked off through the valve, and then krypton was injected into the area of the left side of the face in an amount of 100 ml, and a krypton/xenon mixture was injected into the area of the right side of the face, as shown in Table 1.

The data are presented in table 3.

Table 3 - the effect of krypton gas and krypton/xenon mixtures on the condition of the skin of the face and décolleté Left side of the face Krypton Krypton Krypton Right side of the face Krypton/Xenon = 1/99% Krypton/Xenon = 20/80% Krypton/Xenon = 40/60%

Exposure from 25 to 30 minutes. Daily for 10 days.

Result: the elasticity of the skin has increased, swelling under the eyes has decreased, dark circles have disappeared, manifestations in the form of rosacea have significantly decreased. The results obtained were visible on both sides of the face and practically did not differ from each other.

Example 4

To study the effect of krypton and a krypton/xenon mixture on the course of inflammatory manifestations on the skin in the form of acne, a test was carried out on 3 female volunteers aged 17 to 25 years.

Volunteers suffered from severe acne on the forehead, cheeks, and neck.

An analogue of a cosmetic mask made of non-woven material was formed from a gas-tight film, along the perimeter with a thin strip of double-sided adhesive tape, which ensures a snug fit of the film, while dividing into left and right parts. The film had a valve on each side. The skin was pre-washed. After fixing the film on the face, air was sucked off through the valve, and then krypton was injected into the left area of the face in an amount of 100 ml, and a mixture of gases - krypton/xenon was injected into the right area of the face, as shown in Table.

The results are presented in table 4.

Table 4 - the effect of krypton and a krypton/xenon mixture on the course of inflammatory manifestations on the skin in the form of acne Left half
faces Krypton Krypton Krypton Right half
faces Krypton/Xenon = 1/99% Krypton/Xenon = 40/60% Krypton/Xenon = 90/10%

Exposure from 20 to 30 minutes. Daily for 10 days.

Result: acne manifestations on both sides of the face significantly decreased, the effect was manifested in the rapid destruction of inflammatory elements, the release of comedones, there were no fresh rashes.

Claims (3)

1. A method for improving the condition of the skin and subcutaneous tissues of the body and face, including treating the skin with an inert gas, characterized in that krypton or its mixture with xenon is used as an inert gas by introducing krypton or its mixture with xenon and holding for at least 15 minutes in space between the skin and a product such as a stocking, sock, sleeve, face mask, providing the creation of an airtight space above the selected area of the skin, containing at least one valve that provides the possibility of evacuating the cavity and introducing gases into the cavity. 2. The method according to claim 1, characterized in that an inert gas or an inert gas mixture is introduced into the space above the skin through a valve formed by a cap-type product with a diameter of 5 to 50 mm, made of a material that provides close contact with the irregularities of the skin area along to your perimeter. 3. The method according to paragraphs. 1, 2, characterized in that before the introduction of an inert gas or a mixture of an inert gas, the skin is treated with a lipophilic substance.