KR102116050B1 - Chalcogenide-based particles for promoting collagen production, preparation method thereof, and a pharmaceutical composition for preventing or treating skin aging or skin damage containing the same as an active ingredient - Google Patents

Abstract

A chalcogenide-based particle for promoting collagen production, and a pharmaceutical composition for preventing or treating skin aging or skin damage containing the same as an active ingredient, and furthermore, a cosmetic composition comprising the above-mentioned colcogenide-based particle, And relates to a substrate related to this, the chalcogenide-based particles for promoting collagen production, that is, the new NIR emitting material does not contain a heavy metal, as a non-toxic substance harmless to the body, near infrared (NIR) wavelength band, about 1100 nm-1400 It can emit near-infrared rays at a wavelength of nm, from which it can promote collagen production and adipocyte production excellently. As an active ingredient of the pharmaceutical composition for preventing or treating skin aging, and for treating skin damage (wound) It is useful as, and surprisingly, the chalcogenide-based particles of the present invention are characterized by having absorption wavelengths from ultraviolet, visible, and near-infrared regions, and are also useful as active ingredients of drugs for preventing skin damage. It may be provided as an external preparation, or may be provided as a cosmetic for preventing skin aging, improving wrinkles, and regenerating skin.
In addition, the chalcogenide-based particles for promoting collagen production are provided as a substrate containing the same, and have an effect that can be usefully used as a part of a product or device used for cosmetic purposes or therapeutic purposes. .

Description

Calcogenide-based particles for promoting collagen production, pharmaceutical methods for preventing or treating skin aging or skin damage containing them as an active ingredient and methods thereof, and a pharmaceutical composition for preventing or treating skin aging or skin damage containing the same as an active ingredient}

A chalcogenide-based particle for promoting collagen production, and a pharmaceutical composition for preventing or treating skin aging or skin damage containing the same as an active ingredient, and furthermore, a cosmetic composition comprising the above-mentioned colcogenide-based particle, And related descriptions.

With the recent improvement in medical technology and public health benefits, the advent of an ultra-aging society has led to an improvement in the quality of life and the desire to maintain youth. Many studies have been conducted in various fields to delay and prevent aging, which is the first appearance on the skin, and various products such as anti-aging cosmetics and medicines as well as industrial and personal medical devices have been made.

The skin consists of the epidermis, dermis and subcutaneous tissue. The dermis is a layer between the epidermis and the subcutaneous tissue, and there are blood vessels, collagen, elastin fibers, pores, granulomas, sebaceous glands, sweat glands, various sensory nerves, fibroblasts, and macrophages that do not exist in the epidermis. do.

Here, collagen occupies the largest portion of the dermis, along with elastin. When the dermis has a problem, wrinkles occur and skin elasticity disappears, and skin aging progresses. Collagen is known to play the most important role in skin regeneration, skin moisture, wound healing and wrinkle improvement, and is produced from fibroblasts. As aging progresses, the water-containing function of collagen decreases and wrinkles increase. Collagen also acts as a wound-healing agent by filling the wound area with continuous collagen production of fibroblasts when a wound is formed.

Current treatment methods for skin wrinkle improvement and wound healing can be largely divided into treatment with medicines and treatment with instruments.

Among them, light treatment devices using light have been noticeably popularized and are still being studied. This is because the value of each wavelength individually or in combination is very high because the effect on the body is different for each wavelength range while using light of various wavelengths. For example, blue light is generally clinically known to reduce acne, remove acne when combined with red light, and reduce wounds often associated with acne treatment. Yellow light and tan light are clinically known to help reduce fine lines and wrinkles, hot flashes and help restore sun damaged skin. Green light is clinically known to help reduce and eliminate sun and aging spots, alleviate freckles and also promote brighter skin conditions and overall radiance of the skin.

On the other hand, red light and near-infrared have been used to increase collagen production, reduce redness, enlarged capillaries and damage to the skin, as well as to reduce wrinkles and fine lines. In particular, the wavelength of the band of 630 nm or more among the near infrared rays has an effect of suppressing the growth and inflammation of bacteria, and the wavelength of the band of 780 nm-15000 nm has the effect of collagen production and elastin regeneration (non-patent document 1), pruritus It has the effect of improving the blood flow, improving the blood flow, and regenerating the cells and forming nitric oxide in the body, thereby improving the biological activity and immunity by the antioxidant action.

On the other hand, the effect achieved from the wavelength of the band of 780 nm-15000 nm is that the light can penetrate effectively to the dermis below the epidermis or deeper than that level. A wavelength range of about 1100 nm-1400 nm, which is a safe therapeutically recommended range, except for wavelength bands that may have an undesirable effect, for example, heating dermis-containing water components or negatively affecting hemoglobin, In this range, it can give the best collagen production and fat cell stimulation, so it has the highest utilization value for the purpose of beauty or treatment such as skin aging prevention, skin regeneration, and wound healing (Non-Patent Document 2).

J Drugs Dermatol. 2009; 8: 708-712 J Biomed Opt. 2015 Mar; 20 (3): 030901.

One aspect of the present invention is to provide a NIR emitting material capable of emitting near infrared rays having a wavelength of about 1100 nm-1400 nm, preferably as a component suitable for beauty or treatment such as anti-aging skin, skin regeneration, and wound healing.

Another aspect of the present invention is to provide the NIR luminescent material, while at the same time providing an environmentally friendly, preferably non-toxic material harmless to the body of a mammal or human.

Another aspect of the present invention is to provide a method of manufacturing the NIR light-emitting material.

Another aspect of the present invention is to provide a pharmaceutical composition for the prevention of skin aging, or the treatment of skin aging or skin wounds, including the NIR luminescent material as an active ingredient.

Another aspect of the present invention is to provide a cosmetic composition for preventing skin aging, improving wrinkles, or improving skin wounds, including the NIR emitting material as an active ingredient.

Another aspect of the present invention is to provide an external preparation for skin or an ointment containing the NIR emitting material.

Another aspect of the present invention is to provide a substrate comprising the NIR emitting material.

In order to achieve the above object,

According to one aspect of the invention,

At least one near-infrared emitting metal; And

Chalcogenide-based particles for promoting collagen production, including one or more chalcogen (chalcogen) elements.

Also according to another aspect of the invention,

A method for producing a chalcogenide-based particle for promoting collagen production is provided, comprising: adding a metal salt containing at least one near-infrared emitting metal in at least one chalcogen element in an organic solvent to prepare a metal precursor solution.

Furthermore, according to another aspect of the present invention,

Provided is a pharmaceutical composition for preventing or treating skin aging or skin damage comprising the chalcogenide particles as an active ingredient.

Also according to another aspect of the invention,

Provided is a cosmetic composition for preventing or improving skin aging or skin damage comprising the chalcogenide particles as an active ingredient.

Furthermore, according to another aspect of the present invention,

An external skin preparation or ointment comprising the chalcogenide-based particles as an active ingredient is provided.

Also according to another aspect of the invention,

A substrate comprising the chalcogenide-based particles is provided.

The chalcogenide-based particles for promoting collagen production, that is, the new NIR luminescent material, does not contain heavy metals and is a non-toxic material harmless to the body, and emits near infrared rays having a near infrared (NIR) wavelength range of about 1100 nm to 1400 nm. It can be excellently promote collagen production and adipocyte production therefrom, and is useful as an active ingredient of a pharmaceutical composition for the prevention or treatment of skin aging, and for the treatment of skin damage (wound), and furthermore, surprisingly, the present invention The chalcogenide particles of the UV, visible light, near-infrared region has an absorption wavelength, it is useful as an active ingredient of a drug for preventing skin damage, it can be provided as an ointment or an external preparation for skin, or It can also be used as a cosmetic for skin anti-aging, wrinkle improvement, and skin regeneration.

In addition, the chalcogenide-based particles for promoting collagen production are provided as a substrate containing the same, and have an effect that can be usefully used as a part of a product or device used for cosmetic purposes or therapeutic purposes. .

1 is a graph showing the mRNA expression level of HaCaT (Keratinocytes cell line) cells using a commercially available near-infrared (500-3000nm) emitting halogen lamp.
Figure 2 is a graph showing the light absorption spectrum (A) and near infrared (λmax = 1250 nm) emission spectrum (B) of the chalcogenide particles.
3 is a photograph of a chalcogenide-based particle and a chalcogenide-based particle doped with an alkali metal taken by a transmission electron microscope (TEM).
Figure 4 is a photograph of the microstructure of the HaCaT cells cultured by untreated (A), Example 1 (B) and Example 2 (C).
5 is a graph showing mRNA expression levels of col1A1, TBF-b1, and TiMP according to concentrations of chalcogenide particles treated in HaCaT cells cultured in Example 1 (A) and Example 2 (B).
6 is a graph showing cell viability by concentration of chalcogenide particles treated in HaCaT cells cultured in Example 1 (A) and Example 2 (B).

Hereinafter, the present invention will be described in detail.

The following description should be understood as an example to aid the understanding of the present invention, and the spirit or scope of the present invention is not limited from the following description.

In one aspect of the invention,

At least one near-infrared emitting metal; And

Chalcogenide-based particles for promoting collagen production, including one or more chalcogen (chalcogen) elements.

In one embodiment of the present invention, the near-infrared light emitting metal may be a metal that can emit light in a wavelength range of near infrared region, for example, 650 nm or more, or, for example, light in a wavelength range of 200 nm-1000 nm. It may be a metal that absorbs first and emits light in the near-infrared region as emitted light.

In another embodiment of the present invention, the near-infrared light emitting metal may be one selected from the group consisting of Group IIA metal, Group IIIA metal, Group IVA metal, transition metal and lanthanide metal, specifically magnesium, calcium, strontium, Barium, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, gallium, germanium, yttrium, zirconium, molybdenum, ruthenium, silver, cadmium, indium, tin, platinum, gold, lead, lanthanum, Cerium, proseodymium, neodymium, samarium, europium, gadolium, terbium, dysprosium, ytterbium and ruthesium.

In another embodiment of the present invention, the near-infrared light emitting metal is selected from the group consisting of cadmium (Cd), lead (Pb), silver (Ag), iron (Fe), copper (Cu), and tin (Sn). It may be one or more.

On the other hand, in one aspect of the present invention, the near-infrared light emitting metal may be understood to be a metal that does not contain a heavy metal, or alternatively, it may be understood to be a metal harmless to the human body.

On the other hand, in one aspect of the present invention, the near-infrared light emitting metal has a property of absorbing a wavelength of 200 nm-1000 nm, for example, a metal that absorbs light in the visible light region and emits near infrared rays. In order to emit, it is possible to emit near-infrared light only with natural light in real life, without a separate light exposure step before use.

Of course, since it can absorb light in the region of UV and short wavelengths that can be harmful to the human body, it also has the advantage of absorbing light in the wavelength band harmful to the human body and preventing damage to the skin and scalp, among exposure light such as natural light. .

In another aspect of the present invention, the chalcogen element includes one or more selected from the group consisting of sulfur (S), selenium (Se), and tellurium (Te).

In one aspect of the present invention, the chalcogenide-based particles for promoting collagen production can not only prevent or improve aging and skin damage of the skin, but also have an effect of skin regeneration.

In one embodiment of the present invention, in the experimental example carried out in the present invention, using the chalcogenide-based particles for promoting collagen production of the present invention, it was found that the effect of skin regeneration in cell line experiments, especially collagen production is remarkable The increase was shown by experiment. In addition to this, the chalcogenide-based particles of the present invention can significantly increase the production of adipocytes and elastin with an effective effect on skin regeneration and recovery.

It is thought that the above-described effect is caused by the chalcogenide-based particles for collagen production of the present invention emitting light in the near-infrared region and reaching the dermal layer of the skin to thereby promote collagen production, fat cell production, and the like. do. Particularly, the chalcogenide-based particles of the present invention can emit light without irradiating light in a specific area. In other words, light is emitted in the near-infrared area only by being exposed to natural light even without light irradiation such as UV. It can be done, it is more useful.

In one embodiment of the present invention, in the experimental example carried out in the present invention, using the chalcogenide-based particles for promoting collagen production of the present invention, as a result of analyzing the absorption spectrum, light of a large region of 200 nm-1000 nm band It can be absorbed without limitation, it was confirmed that it can emit near-infrared rays only by exposure to natural light. Thus, the chalcogenide-based particles of the present invention can emit near-infrared rays without irradiating light in a specific region, thereby preventing damage or aging to the skin or scalp, and exhibiting the effect of skin regeneration.

In one embodiment of the present invention, the emitted light of the chalcogenide particles can be understood as light in the near infrared region, for example, 1000 nm-1800 nm, 1000 nm-1500 nm, 1000 nm-1400 nm, 1100 nm-1400 nm, or can be understood as light of about 1250 nm, provided that the present invention is not limited as long as it emits light in the region of the present invention that can promote collagen production, prevention of skin aging or damage, and skin regeneration. Is included in.

On the other hand, in another embodiment of the present invention, it can be understood that the wavelength band of the emitted light should be capable of stimulating by transmitting light to a location or region capable of promoting collagen production when exposed to the skin or scalp, for example It should be possible to transmit light near or above the dermal layer.

On the other hand, in another embodiment of the present invention, the wavelength band of the emitted light may be preferred in light of a wavelength band capable of minimizing unnecessary skin irritation, damage, etc. when exposing the skin or scalp, or irritating at a level that is completely absent. That is, for example, the light emitted from the skin, or hemoglobin, melanin, etc., there is little or no damage, emission light may be preferred. For example, it may be desirable to use light of a wavelength range of 1000-1400 nm, which is preferred in a conventional NIR device.

In one embodiment of the present invention, as in the experimental example of the present invention, the chalcogenide-based particles of the present invention in which the wavelength range of emitted light is confirmed to be around 1250 nm, exhibits a very preferable emitted light from the above-mentioned point of view. Without heating the contained water, without damaging hemoglobin, melanin, etc., it can promote collagen production, promote the production of fat cells, elastin, etc., prevent skin damage or aging, and show the effect of skin regeneration More useful effects are achieved.

In another aspect of the invention, the chalcogenide-based nanoparticles for promoting collagen production may be doped with alkali metal ions.

In one embodiment of the present invention, as shown in the experimental example conducted in the present invention, as a result of doping the collagen production promoting chalcogenide-based particles with alkali metal ions, surprisingly, excellent optical properties of up to 20 to 30 times appear, It was also confirmed that it has an effect of up to 30 times in collagen production. Thus, in particular, the chalcogenide-based particles of the present invention doped with alkali metal ions may be provided as a better component in terms of preventing skin aging or damage and skin regeneration.

Meanwhile, the alkali metal ion may be at least one selected from lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), and francium (Fr).

In another aspect of the present invention, the chalcogenide-based particles for promoting collagen production may be chalcogenide-based silver nanoparticles containing silver (Ag) and chalcogen (chalcogen) elements, and the chalcogenide-based silver nanoparticles The particles may be doped with alkali metal ions.

Here, the chalcogen element may be one or more selected from sulfur (S), selenium (Se) and tellurium (Te), and the alkali metal ion is lithium (Li), sodium (Na), potassium (K) , Rubidium (Rb), cesium (Cs), and francium (Fr).

In addition, if necessary, other metals other than silver (Ag) may be used, and the type of metal is 1 selected from the group consisting of Group IIA metals, Group IIIA metals, Group IVA metals, transition metals, and lanthanide metals. May be magnesium, calcium, strontium, barium, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, gallium, germanium, yttrium, zirconium, molybdenum, ruthenium, silver, cadmium, Indium, tin, platinum, gold, lead, lanthanum, cerium, proseodymium, neodymium, samarium, europium, gadolium, terbium, dysprosium, ytterbium and ruthesium can be used.

In one aspect of the present invention, the average diameter of the chalcogenide-based particles may be 4 nm-1000 nm, but only to promote collagen production, prevention of skin aging or damage, and effects of skin regeneration to be seen in the present invention. The size of the particles that can represent, alternatively, the emitted light in the near infrared region is included in the scope of the present invention without limitation.

In another aspect of the present invention, a metal salt containing one metal is dissolved in an organic solvent containing one chalcogen element selected from the group consisting of sulfur (S), selenium (Se) and tellurium (Te). To prepare a metal precursor solution (step 1); And

A method for manufacturing a chalcogenide-based metal nanoparticle is provided, including; (step 2) preparing a nanoparticle of a chalcogenide metal by irradiating ultrasound to the metal precursor solution of step 1;

Hereinafter, a method of manufacturing the chalcogenide-based metal nanoparticles will be described in detail.

In the method of manufacturing the chalcogenide-based metal nanoparticles, the step 1 is a metal salt containing one metal selected from the group consisting of sulfur (S), selenium (Se), and tellurium (Te). It is a step of preparing a metal precursor solution by dissolving it in an organic solvent containing a chalcogen element.

In this case, the metal is not particularly limited, IIA group metal, IIIA group metal, IVA group metal, transition metal, lanthanide group metal, etc. may be used, preferably magnesium, calcium, strontium, barium, titanium, vanadium, Chromium, manganese, iron, cobalt, nickel, copper, zinc, gallium, germanium, yttrium, zirconium, molybdenum, tungsten, ruthenium, silver, cadmium, indium, tin, platinum, gold, lead, lanthanum, cerium, prose Odymium, neodymium, samarium, europium, gadolinium, terbium, dysprosium, ytterbium, and ruthesium can be used. More preferably, iron, copper, silver, gadolinium, and europium can be used.

In addition, the salt of the metal salt is not particularly limited, preferably nitrate, carbonate, chloride, phosphate, borate, oxide, sulfonate, sulfate, stearate, myristate, acetate, acetylacetonate, and these Hydrates, mixtures of these, etc. can be used.

The method of manufacturing a chalcogenide-based metal nanoparticle according to the present invention can use a metal salt that is inexpensive and non-toxic as a metal salt. Therefore, the method of manufacturing a chalcogenide-based metal nanoparticle according to the present invention has the advantage of being eco-friendly, economical, and capable of mass production.

Furthermore, the organic solvent containing one chalcogen element selected from the group consisting of sulfur (S), selenium (Se) and tellurium (Te),

Thiol-based organic solvents such as C _6-8 arylthiol, straight or branched C _1-20 alkylthiol, straight or branched C _1-20 alkenylthiol and straight or branched C _1-20 alkynylthiol;

C _6-8 aryl selenol, straight or branched C _1-20 alkyl selenol, straight or branched C _1-20 alkenyl selenol, and straight or branched C _1-20 alkynyl selenol; Organic solvents;

C _6-8 aryltelurol, straight or branched C _1-20 alkyltelurol, straight or branched C _1-20 alkenyltelurol, straight or branched C _1-20 alkynyltelurol, etc. ; Can be used.

Preferably, C _1-20 of the organic solvent linear or branched C _1-20 alkyl thiol, celecoxib C _1-20 straight or branched chain alkyl of play, linear or branched can be used alkyl rurol Tel.

More preferably, methanethiol, 1-propanethiol, 2-propanethiol, butanethiol, pentanethiol, octanethiol, dodecanethiol, methane selenol, 1-propane selenol, 2-propane selenol as the organic solvent , Butane selenol, pentane selenol, octane selenol, dodecane selenol, methanetellurol, 1-propanetellurol, 2-propanetellurol, butanetellurol, pentanetellol, octanetellol, dodecanetellol, etc. Can be used.

In the method of manufacturing the chalcogenide-based metal nanoparticles, the step 2 is a step of manufacturing nanoparticles of the chalcogenide metal by irradiating ultrasound to the metal precursor solution of step 1.

At this time, the ultrasonic irradiation is not particularly limited, it is preferable to irradiate with an intensity of 2 to 200 kHz. In addition, although irradiation time is not specifically limited, Preferably, it can irradiate for 0.1 hour to 12 hours. More preferably, it can be irradiated at 20 kHz intensity for 5 minutes to 60 minutes, and most preferably, irradiated at 20 kHz intensity for 10 minutes to 30 minutes.

When the ultrasonic irradiation is irradiated with an intensity of less than 2 kHz, there is a problem that the nanoparticles are not manufactured due to insufficient ultrasonic irradiation, and when irradiated with an intensity of more than 200 kHz, the nanoparticles aggregate to form an aggregate Problems may arise.

Therefore, in order to prepare the chalcogenide-based metal nanoparticles of the present invention, it is preferable to irradiate with an intensity of 2 to 200 kHz.

Furthermore, the method for producing a chalcogenide-based metal nanoparticle according to the present invention after performing step 2,

Depositing nanoparticles in the metal precursor solution (step a); And

The step of drying and heat-treating the nanoparticles of step a (step b); may be further performed.

At this time, the step of depositing the nanoparticles in the metal precursor solution of step a is not particularly limited, but may be precipitated by precipitating the nanoparticles using an organic solvent.

Specifically, when an excessive amount of an organic solvent is added to the metal precursor solution to precipitate the nanoparticles formed in the metal precursor solution obtained in step 2, metal oxide nanoparticles are precipitated. The metal oxide nanoparticles precipitated in the metal precursor solution can be separated by centrifugation, and the nanoparticles can be recovered by performing centrifugation three or more times.

Here, the organic solvent is not particularly limited as long as it is an organic solvent for precipitating nanoparticles. Ethanol, methanol, acetone, isopropyl alcohol, ethyl acetate may be used, and ethyl in terms of yield of chalcogenide-based metal nanoparticles. Acetate is more preferred.

In addition, by performing the step of drying and heat treatment of the nanoparticles of step b, in particular, by performing heat treatment (annealing), it is possible to increase the crystallinity of the nanoparticles.

At this time, the drying is not particularly limited, it is preferable to perform a temperature of 50 to 80 ℃, the drying time is preferably from 3 to 12 hours.

In addition, the heat treatment is not particularly limited, but may be performed at a temperature of 100 to 600 ° C, preferably at a temperature of 150 to 300 ° C.

When the heat treatment is performed at a temperature of less than 150 ° C., there may occur a problem that crystallinity is not sufficiently imparted to the nanoparticles. Problems may arise in manufacturing monodispersed nanoparticles by changing and forming aggregates. Here, the heat treatment time is not particularly limited, but is preferably performed for 3 to 12 hours.

Furthermore, the heat treatment of step b may produce the desired nanoparticles by creating an atmosphere using nitrogen, argon, oxygen, hydrogen gas, etc., depending on the nanoparticles to be produced.

The method of manufacturing a chalcogenide-based metal nanoparticle according to the present invention uses only an organic solvent and a metal salt containing chalcogen to combine chalcogen with a metal through ultrasonic irradiation, so the conventional method of manufacturing a chalcogenide-based metal nanoparticle Compared to this, the risk of performing the manufacturing process has been significantly reduced, and the desired chalcogenide-based metal nanoparticles can be produced simply and easily.

In addition, by preparing nanoparticles through ultrasonic irradiation, it is possible to manufacture nanoparticles with a yield close to about 100% by preventing a phenomenon in which the yield is lowered when compared with the conventional production of nanoparticles using a surfactant. .

Therefore, the method of manufacturing the chalcogenide-based metal nanoparticles according to the present invention uses a non-toxic metal salt as a raw material and is an eco-friendly and simple and easy time for the chalcogenide-based metal nanoparticles having a uniform particle shape and size. Not only can it be produced in high yield, but mass production is also possible.

In one embodiment of the present invention, the step of preparing a metal precursor solution by dissolving a silver salt and an alkali metal salt in an organic solvent containing a chalcogen element (step 1); And

Irradiating ultrasound to the metal precursor solution of step 1 (step 2); A method of manufacturing the chalcogenide-based silver nanoparticles doped with an alkali metal containing the present invention is provided.

Here, the salt of the salt of the silver salt and the alkali metal salt of step 1 are independently nitrate, carbonate, chloride, phosphate, borate, oxide, sulfonate, sulfate, stearate, myristate, acetate, acetylacetonate, and Hydrates and mixtures thereof.

Further, the amount of the alkali metal salt based on 0.1 mmol of the silver salt may be contained within the range of 0.01-0.1 mmol, preferably within the range of 0.02-0.08 mmol, and more preferably within the range of 0.03-0.07 mmol It may be, and most preferably it may be contained in an amount of 0.05 mmol.

If the alkali metal salt is less than 0.01 mmol, the photoreactivity improvement effect may not be sufficient, and when it exceeds 0.1 mmol, a significant photoreactivity improvement effect may not be exhibited.

Furthermore, the organic solvent of step 1,

C _6-8 arylthiol, straight or branched C _1-20 alkylthiol, straight or branched C _1-20 alkenylthiol and straight or branched C _1-20 alkynylthiol A thiol-based organic solvent;

With C _6-8 arylselenol, straight or branched C _1-20 alkylselenol, straight or branched C _1-20 alkenylselenol and straight or branched C _1-20 alkynylselenol A selenol-based organic solvent selected from the group consisting of; And

C _6-8 aryltelurol, straight or branched chain C _1-20 alkyltelurol, straight or branched C _1-20 alkenyltelurol, straight or branched C _1-20 alkynyltelurol It may be characterized in that it is one kind of an organic solvent selected from the group consisting of;

Preferably, as the thiol-based organic solvent, methanethiol, pentathiol, 1-propanthiol, 2-propanthiol, butanethiol, pentathiol, octanethiol, 1-dodecanethiol, or the like can be used.

In addition, the ultrasound of step 2 may be characterized by being irradiated with an intensity of 2 to 200 kHz.

Specifically, the ultrasonic intensity of step 2 may be irradiated within a time range of 1 hour to 12 hours at an intensity of 2 to 200 kHz, and preferably irradiated within a time range of 5 minutes to 1 hour at an intensity of 20 kHz. And, more preferably, it can be irradiated within a time range of 10 minutes to 30 minutes with an intensity of 20 kHz.

If the ultrasonic waves are irradiated with an intensity of less than 2 kHz, there is a problem that the nanoparticles are not manufactured because the ultrasonic irradiation is not sufficiently performed, and when irradiated with an intensity of more than 200 kHz, the nanoparticles aggregate to form an aggregate. Can occur.

Furthermore, after performing step 2, depositing chalcogenide silver nanoparticles in the metal precursor solution (step a); And

Drying and heat-treating the chalcogenide-based silver nanoparticles of step a (step b); You can do more.

Hereinafter, the manufacturing method will be described in detail step by step.

The step a is a step of depositing the chalcogenide silver nanoparticles in the metal precursor solution after performing step 2 above.

Specifically, after performing the step 2, if an excessive amount of ethyl acetate is added to the metal precursor solution to precipitate chalcogenide silver nanoparticles in the metal precursor solution, the nanoparticles precipitate. The nanoparticles precipitated in the metal precursor solution can be separated by centrifugation, and centrifugation can be performed three or more times to recover nanoparticles.

The step b is a step of drying and heat-treating the chalcogenide-based silver nanoparticles of step a, and the crystallinity of the nanoparticles is increased through heat treatment.

The drying temperature of step b is not particularly limited, but may be performed at a temperature of 30 to 150 ° C, preferably at a temperature of 50 to 120 ° C, and more preferably at a temperature of 70 to 100 ° C It can be carried out, most preferably at a temperature of 80 ℃.

The drying time of step b is not particularly limited, but may be performed for 3 to 20 hours, preferably 5 to 18 hours, more preferably 10 to 15 hours, and most Preferably it can be carried out for 12 hours.

The heat treatment temperature of step b is not particularly limited, but may be performed at a temperature of 100 to 600 ° C, and preferably at a temperature of 150 to 300 ° C.

When the heat treatment is performed at a temperature of less than 150 ° C, a problem that crystallinity is not sufficiently imparted to the nanoparticles may occur, and when the heat treatment is performed at a temperature exceeding 600 ° C, the nanoparticles are decomposed due to the decomposition of sulfur by high temperature. Problems may occur in preparing monodispersed nanoparticles by changing properties and forming aggregates.

In addition, the heat treatment in step b may be used to produce an atmosphere by using nitrogen, argon, oxygen, and hydrogen gas, etc. according to the nanoparticles to be produced, thereby producing desired nanoparticles.

In another aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating skin aging or skin damage containing the chalcogenide particles for promoting collagen production as an active ingredient.

In one embodiment of the present invention, the pharmaceutical composition is contained as an active ingredient, from the characteristics indicated by the chalcogenide-based particles for promoting collagen production, that is, as described above, the wavelength light of the near-infrared region band from the emission light , It has the effect of promoting collagen production, promoting fat cells, and elastin production, and thus can prevent or treat skin aging or damage.

In another embodiment of the present invention, it can be understood that the pharmaceutical composition exhibits an effect of preventing or treating skin aging or damage by applying it to the skin or scalp, such as a skin ointment.

In another embodiment of the present invention, the pharmaceutical composition may further include at least one other component effective for skin aging or damage, in addition to the chalcogenide-based particles for promoting collagen production.

In addition, the pharmaceutical composition may further include a pharmaceutically acceptable additive, wherein the pharmaceutically acceptable additive is starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, calcium hydrogen phosphate , Lactose, mannitol, syrup, gum arabic, pregelatinized starch, corn starch, powdered cellulose, hydroxypropyl cellulose, opadry, sodium starch glycolate, carnauba lead, synthetic aluminum silicate, stearic acid, magnesium stearate, aluminum stearate, Calcium stearate, white sugar, dextrose, sorbitol and talc can be used. The pharmaceutically acceptable additive according to the present invention is preferably included in 0.1 to 90 parts by weight based on the composition, but is not limited thereto.

That is, the composition of the present invention may be administered in various forms, oral and parenteral, during actual clinical administration. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc. It can be prepared using. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient such as starch, calcium carbonate, sucrose, and e.g. (Sucrose), lactose (Lactose) or gelatin can be prepared by mixing. In addition, lubricants such as magnesium stearate talc may be used in addition to simple excipients. Liquid preparations for oral use include suspensions, intravenous solutions, emulsions and syrups, and may include various excipients, such as wetting agents, sweetening agents, fragrances, preservatives, etc. . Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. As the non-aqueous solvent and suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin butter, and glycerogelatin may be used.

The composition of the present invention may be administered parenterally according to a desired method, and it is preferable to select a method for external application to the skin when parenterally administered. The dosage range varies according to the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate, and disease severity.

The composition according to the invention is administered in a pharmaceutically effective amount. In the present invention, "a pharmaceutically effective amount" means an amount sufficient to treat the disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is the type of patient's disease, severity, and activity of the drug , Sensitivity to the drug, time of administration, route of administration and rate of discharge, duration of treatment, factors including co-drugs and other factors well known in the medical field. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with a conventional therapeutic agent, and may be administered single or multiple. Considering all of the above factors, it is important to administer an amount that can achieve the maximum effect in a minimal amount without side effects, which can be easily determined by those skilled in the art.

Specifically, the effective amount of the compound according to the present invention may vary depending on the patient's age, sex and body weight, and is generally administered daily or every other day from 0.1 mg to 100 mg, preferably 0.5 mg to 10 mg per kg of body weight. Alternatively, it may be administered in 1 to 3 times a day. However, since the dosage may be increased or decreased depending on the route of administration, the severity of obesity, sex, weight, and age, the above dosage does not limit the scope of the present invention in any way.

In another aspect of the present invention, there is provided a skin external preparation for preventing or treating skin aging or skin damage containing the chalcogenide particles for promoting collagen production as an active ingredient.

In another aspect of the present invention, there is provided a cosmetic composition for improving skin aging or skin damage containing the chalcogenide particles for promoting collagen production as an active ingredient.

In another aspect of the invention, the chalcogenide-based particles for promoting collagen production increase or promote the expression of col1A1, TiMP, and TGF-b1, from which promote collagen production, promote adipocyte production, promote elastin production, etc. It has the effect of improving, preventing, or treating skin aging, or damage, by raising factors effective for the same skin regeneration.

In one embodiment of the present invention, as shown in the following experimental example, it was confirmed that the expression of col1A1, TiMP, and TGF-b1 is increased from the chalcogenide-based particles provided by the present invention, and particularly, from this, collagen production It was found that this was significantly increased. In addition, it was confirmed that the alkali metal doped chalcogenide-based particles have an excellent effect of about 20 to 30 times.

In one aspect of the present invention, the chalcogenide-based particles for promoting collagen production are preferably used as raw materials for cosmetics, bath products, soaps, pharmaceutical ointments, animal medicines or pack products.

That is, the treatment agent for skin aging or skin damage containing the chalcogenide-based particles for promoting collagen production of the present invention as an active ingredient is a solution, suspension, spray, patch, patch, cream, ointment, gel, tablet Or it can be prepared as a pill.

Solutions include, in addition to the active ingredients, conventional excipients, such as solvents, solubilizers and emulsifiers, such as water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1, 3-butylene glycol, dimethylformamide, oils, especially cottonseed oil, peanut oil, camellia oil, aloe vera, glycerin, natural corn seed oil, olive oil, castor oil, almond oil and sesame oil, glycerol, glycerol form alcohol, tetihydro Furfuryl alcohol, polyethylene glycol and fatty acid esters of sorbitan, or mixtures of these substances, and may include methyl or propyl-p-hydroxybenzoate or sorbic acid as a preservative.

Suspension agents include conventional excipients in addition to the active ingredients, such as liquid diluents (e.g. water, ethyl alcohol and propylene glycol, polyethylene glycol), and suspensions (e.g. ethoxylated isostearyl alcohol, polyoxyethylene sorbitol, sorbitan Esters, cellulose derivatives and hydrogenated edible oils), microcrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth, injectable esters such as ethyl oleate or mixtures of these substances.

Ointments, creams and gels, in addition to the active ingredients, are usually excipients, such as animal and vegetable fats, wax paraffin, starch, targacanth, cellulose derivatives, polyethylene glycols, silicones, bentonite, silicic acid, talc and zinc oxide, or these substances. It may contain a mixture of.

In addition, in general, a method of applying to the affected area may be used, and a preferred method of administration may be selected according to the formulation.

The daily dosage of the composition of the present invention is determined depending on the subject to be administered, the method of administration, and the symptoms, but the dosage needs to be changed, in particular, the constitutional specificity and weight of the object to be treated, the type and depth of disease, the nature of the formulation, The nature of the drug administration and the duration or interval of administration may be changed.

In order to effectively treat skin aging or skin damage, it is important to select a suitable external formulation. The chalcogenide-based particles for promoting collagen production of the present invention may be appropriately diluted and applied directly to the skin, and the present invention provides an ointment that can effectively apply the agent for treating aging or skin damage to the affected area.

In one aspect of the present invention, the ointment of the present invention can be prepared by combining the therapeutic agent described above with an inorganic substance and then coating it with a fat-soluble base. The inorganic material is preferably used materials having excellent antibacterial, anti-inflammatory, and epidermal regeneration effects, and specific examples thereof include zinc oxide, zinc carbonate, and iron oxide.

In addition, it may be desirable to further use a ceramic carrier that can safely impregnate the therapeutic agent of the present invention. As the ceramic carrier, zeolite, talc, gypsum, sand powder and mixtures thereof can be preferably used. Such a ceramic carrier is excellent in impregnation of water-soluble components and can smoothly supply water-soluble components to the skin.

In one aspect of the present invention, the cosmetic composition of the present invention, or a cosmetic or dermatological or dermatological composition, includes various forms, such as an anhydrous composition containing an organic solvent such as oil or alcohol; Or hydrated forms such as aqueous based solutions, serums, gels, creams, lotions, toners, mousses, sprays, ointments, essences, pastes; Or in solid form, such as sticks, microcapsules; Any cosmetic product for hands, face, lips, hair or body, such as color cosmetic compositions, such as foundation, blush, eyeshadow, concealer, lip gloss, lip balm, lipstick, mascara and the like; As well as hair care products such as shampoos, conditioners, masks, serums, styling lotions and balms; It can be found as sun care products, hair removal, exfoliants, etc. The NIR-emitting material can be dispersed in the aqueous or non-aqueous phase of the composition.

In another aspect of the invention, chalcogenide-based particles useful in the composition may be used in the form of particles, but alternatively also vesicles; Microspheres, such as hollow microspheres; It will be understood that it can be encapsulated or captured in any delivery system known for use with cosmetic and / or dermatological ingredients, including but not limited to liposomes and the like.

Examples of hollow microspheres that can be used are obtained by polymerization of homopolymers or copolymers of ethylenically unsaturated monomers, or one or more ethylenically unsaturated monomers to form copolymers of ethylenically unsaturated monomers and one or more organic groups. Are those comprising at least one synthetic polymer. Examples of suitable ethylenically unsaturated monomers are, for example, vinylidene chloride, vinyl chloride, acrylonitrile, acrylic acid and its corresponding C1-C20 aliphatic or aromatic esters, methacrylic acid and its corresponding C1-C20 aliphatic. Or aromatic esters, acrylamide, methacrylamide, vinyl pyrrolidone, alkenes such as styrene, ethylene, propylene, butylene, methylpentene, 1,3-butadiene and the like. Polymeric shells of hollow microspheres are also suitable synthetic polymers, such as polyester, polyamide, polyphthalamide, polyimide, polycarbonate, polyketone, cellulose acetate, polysulfone, polyphenylene sulfide, polyphenylene jade Seed, polylactic acid, polyvinylpyrrolidone, polystyrene, polyacrylonitrile, polyacrylamide, polymethylmethacrylate, polyacrylate, and copolymers of the polymers listed above.

Preferred examples of hollow microspheres that can be used are those having a deformable polymeric shell composed of a copolymer of vinylidene chloride, acrylonitrile, and methylmethacrylate and an expandable fluid composed of isobutane or isopentane, which Commercially available under the trade name of Expancel® from Expancel, Inc. of Duluth, Georgia. Expansel® hollow microspheres are available in a variety of forms, such as dry, wet, unexpanded or pre-expanded forms. Both dry, unexpanded microspheres (Expansel® DU) and dry, expanded microspheres (Expansel® DE) can be used in the present invention to capture and stabilize NIR luminescent materials.

Encapsulation can be used to provide controlled or delayed release of the chalcogenide-based particles, or it can prevent the divergence of NIR luminescent material to the skin, scalp or hair, without interfering with NIR light emission entirely. . Preferably, the microspheres are significantly larger, without adversely affecting the physical and / or chemical properties of the captured NIR luminescent chalcogenide-based particles relating to or associated with their desired activity in cosmetic or topical compositions, Vesicles, liposomes, etc. can impart improved structural and spatial stability.

The microspheres can be coated or otherwise surface-treated with a film-forming material that forms a liquid-impermeable film for each microsphere. In this way, the microspheres are sealed from the solvent in the surrounding environment, which can potentially re-swell the polymeric shell of the microspheres and cause the trapped NIR emitting chalcogenide-based particles to shed early. Any material that can form a liquid-impermeable film that is hydrophilic or hydrophobic can be used. Suitable materials include film-forming materials such as natural or synthetic homopolymers or copolymers composed of ethylenically unsaturated monomers comprising acrylic acid, methacrylic acid or its C1-C10 alkyl esters, ethylene, propylene, or vinylpyrrolidone; Silicone gums, which are organosiloxanes having a viscosity generally in the range of about 200,000 to 10,000,000 centipoise at room temperature; Animal, plant, silicone or mineral waxes; Organic esters or hydrocarbon oils, or silicone resins, such as trimethylsiloxysilicate or poly-methylsilsesquioxane; Cellulose polymers; Fatty acids (e.g., fatty carboxylic acids having from about 6 to 40 carbon atoms, which can be liquid, solid or semi-solid at room temperature), fatty alcohols (e.g. liquid, solid, or semi-solid at room temperature) Alcohols having 6 to 50 carbon atoms), and inorganic materials. By way of example, the film-forming material may be an alkyl silicone polymer, such as a fatty alkylmethylsiloxane, such as cetyl dimethicone, stearyl dimethicone, or behenyl dimethicone, or other modified siloxane, such as typically dimethicone copolyol or Polyoxyalkylene silicones referred to as cetyl dimethicone copolyols.

On the other hand, in another aspect of the present invention, the composition of the present invention may contain additional cosmetic and / or dermatologically acceptable ingredients, including those described below.

A suitable serum or gel will generally contain about 1-99% water, and optionally about 0.001-30% aqueous phase thickener.

Other ingredients mentioned herein may be present in the percentage ranges described.

A typical skin cream or lotion comprises about 5-98% water, 1-85% oil, and about 0.1-20% of one or more surfactants. Preferably the surfactant is nonionic, and may be in the form of a silicone or organic nonionic surfactant.

Typical color cosmetic compositions, such as foundations, blushes, eye shadows, etc., are preferably about 0.1-65% in addition to about 5-98% water, 1-85% oil, and about 0.1-20% of one or more surfactants. % Particulate (pigment, or a combination of pigment and powder).

In addition, when the composition is in the form of an aqueous solution, dispersion or emulsion, the aqueous phase in addition to water may contain one or more aqueous phase structuring agents, ie agents that increase the viscosity of the composition or thicken the aqueous phase. This is particularly preferred when the composition is in the form of a serum or gel. The aqueous phase structuring agent must be compatible with NIR-releasing chalcogenide-based particles and also with other ingredients in the formulation.

In one aspect of the present invention, a substrate including the chalcogenide-based particles for promoting collagen production is provided.

Here, the substrate is the effect of the chalcogenide system for promoting collagen production, that is, irradiation of the near-infrared emission light to the skin or scalp, promoting collagen production, promoting fat cells or elastin, or preventing skin aging or damage, or skin If the emitted light can be irradiated to the skin or scalp even if it directly or directly or non-contacts the skin or scalp while exhibiting the above-mentioned useful effects such as the effect of regeneration, it is included without limitation, for example, as described above. It can be included and acts as a cosmetic product in an embedded form, and these examples are included in the above description or can be understood as including the above description.

In one embodiment of the present invention, a comb comprising the substrate may be considered, and a part of the comb includes the chalcogenide-based particles for promoting collagen production of the present invention, from which the comb is obtained by the user, scalp or skin. When used in, it can be understood that the effect achieved from the emitted light of the above-described chalcogenide-based particles may appear.

In another embodiment of the present invention, a mask including the substrate may be considered, and a part of the mask includes the chalcogenide-based particles for promoting collagen production of the present invention, and the mask includes natural light, artificial light, UV, etc. The present invention absorbs light in a wavelength range of 200 nm-1000 nm that can be absorbed by the chalcogenide particles of the present invention, and irradiates near-infrared rays to the skin or scalp with emitted light, from which the chalcogenide particles described above are also It can be understood that the effect achieved from the emitted light of can appear.

In another embodiment of the present invention, a mask pack comprising the substrate can be considered, and it can be understood that the effect achieved from the emitted light of the chalcogenide-based particles of the present invention may also be exhibited as the mask.

On the other hand, the above specific example is only one exemplary explanation, the collagen production promoting collagen production particles of the present invention promotes collagen production indicated, promotes the production of fat cells or elastin, prevention of skin aging or damage, skin regeneration If the effect of can be exhibited, it will be readily understood by those skilled in the art that it can be included and used in conventionally used cosmetic products and cosmetic products without special restrictions.

On the other hand, the chalcogenide particles contained in the substrate may be located on the surface of the substrate, or therein so as to irradiate the emitted light to the skin, hair, or scalp, the skin or scalp exposed to the emitted light If possible, it should be understood that there are no restrictions on location.

Hereinafter, the present invention will be described in detail by production examples, examples, and experimental examples.

However, the following preparation examples, examples, and experimental examples are only illustrative of the present invention, and the contents of the present invention are not limited thereto.

<Production Example 1> Chalcogenide particles (5 nm silver sulfide (Ag ₂ S) Preparation of nanoparticles)

0.5 mmol of silver nitrate was placed in a container containing 10 mL of 1-dodecanethiol, a metal precursor solution was prepared while stirring, and then ultrasonic waves of 20 kHz (50%) intensity were irradiated for 10 minutes using an ultrasonic irradiator.

Upon irradiation with the ultrasonic waves, it was observed that the solution that was initially transparent turned to black-brown with time, which means that the silver sulfide nanoparticles were successfully synthesized. The resulting nanoparticles were precipitated by adding excess ethyl acetate to the mixed solution in which the silver sulfide nanoparticles were prepared, followed by centrifugation to separate the nanoparticles from the supernatant to remove the supernatant. The above washing process was repeated at least three times, and the precipitate was dried at 80 ° C. for 12 hours to obtain silver sulfide nanoparticles having a size of 5 nm in a yield of about 100%. When acetone is used for precipitation of nanoparticles, about 50% of precipitation occurs, when ethanol, methanol, and isopropyl alcohol are used, about 70% of precipitation occurs, and when ethyl acetate is used There is about 100% precipitation, resulting in a higher yield.

<Production Example 2> Preparation of chalcogenide particles (5nm Li doped silver sulfide (Ag2S) nanoparticles)

0.1 mmol of silver nitrate and 0.05 mmol of lithium carbonate were placed in a container containing 10 mL of 1-dodecanethiol to prepare a metal precursor solution while stirring, and then ultrasonic waves of 20 kHz (50%) intensity were irradiated for 10 minutes using an ultrasonic irradiator. .

Upon irradiation with the ultrasonic waves, it was observed that the solution that was initially transparent turned to black-brown with time, which means that the silver sulfide nanoparticles were successfully synthesized. The resulting nanoparticles were precipitated by adding excess ethyl acetate to the mixed solution in which the silver sulfide nanoparticles were prepared, followed by centrifugation to separate the nanoparticles from the supernatant to remove the supernatant. The above washing process was repeated at least three times, and the precipitate was dried at 80 ° C. for 12 hours to obtain silver sulfide nanoparticles doped with Li having a size of 5 nm.

<Example 1> Treatment of chalcogenide particles 1

The present invention was performed as follows to treat the chalcoid-based particles to actual skin cells, to confirm near-infrared luminescence, and to observe changes in the cells.

<1-1> Surface modification of chalcogenide particles

After dispersing 0.1 g of chalcogenide particles prepared in Preparation Example 1 in 10 mL of chloroform, 500 μL was collected from the dispersed solution, and then dispersed in 5 mL of Chloroform, followed by 200 μL MPA solution (in Methanol, pH = 12-12.5) and stirred for 30 minutes. After stirring by adding 5 mL of distilled water to the solution, only the supernatant was collected and used for HaCaT cell treatment.

<1-2> Cell culture

HaCaT cell line was purchased from Korea Cell Line Bank, and RNA Extraction Kit was purchased from NtRON Biotechnology and used.

Specifically, the cell culture was 37 ° C, 95% air and 5 in Dulbecoo's modified Eagle's medium (DMEM) containing 100 U / mL penicillin and 100 μg / mL streptomycin supplemented with fetal bovine serum with HaCaT 10% heat inactivated. % CO ₂ was incubated under atmospheric conditions.

<Example 2> Treatment of chalcogenide particles 2

The present invention was performed as follows to treat the chalcoid-based particles to actual skin cells, to confirm near-infrared luminescence, and to observe changes in the cells.

<2-1> Surface modification of chalcogenide particles

After dispersing the alkali metal doped chalcogenide particles 0.1g prepared in Preparation Example 2 in 10 mL of chloroform and then collecting 500 μL from the dispersed solution and dispersing it in 5 mL of Chloroform, 200 μL MPA The solution (in Methanol, pH = 12-12.5) is added and stirred for 30 minutes. After stirring by adding 5 mL of distilled water to the solution, only the supernatant was collected and used for HaCaT cell treatment.

<2-2> Cell culture

HaCaT cell line was purchased from Korea Cell Line Bank, and RNA Extraction Kit was purchased from NtRON Biotechnology and used.

Specifically, the cell culture was 37 ° C, 95% air and 5 in Dulbecoo's modified Eagle's medium (DMEM) containing 100 U / mL penicillin and 100 μg / mL streptomycin supplemented with fetal bovine serum with HaCaT 10% heat inactivated. % CO ₂ was incubated under atmospheric conditions.

<2-3> Cell Counting

Cells inoculated at a density of 2 X 10 ⁵ cells / well in a 6-well culture dish were cultured for 24 hours, and then treated with the chalcogenide-based particles doped with alkali metal of <2-1>. 10 μL of cell suspension was mixed with 10 μL of trypan blue dye (0.4%) (WELGENE) and only viable cells were measured using a cellometer (Nexcelom bioscience).

<Experimental Example 1> Evaluation of the effect of promoting collagen production according to light irradiation

In order to self-evaluate the light of different wavelengths for irradiation type and collagen generation, the experiments were conducted as follows.

Specifically, atmosphere of 37 ° C., 95% air and 5% CO ₂ in DMEM (Dulbecoo's modified Eagle's medium) containing 100 U / mL penicillin and 100 μg / mL streptomycin supplemented with fetal bovine serum inactivated with 10% heat. After culturing HaCaT under conditions, it was mixed with 10 μL of a cell suspension and 10 μL of trypan blue dye (0.4%) (WELGENE) to measure only living cells using a cytometer (Nexcelom bioscience).

Then, the cultured HaCaT was irradiated with a commercially available near-infrared emission irradiator (open world infrared IR-2014 large diameter infrared irradiator, infrared wavelength: 750 nm (± 10%)) and fluorescent lamp, respectively, and each cell was separated at 10-minute intervals. The collagen production index shown in, that is, changes in mRNA expression of col1A1, TGF-b1, and TiMP were observed, and the results are shown in FIG. 1.

As shown in FIG. 1, when irradiated with a normal fluorescent lamp on pure HaCaT, it was confirmed that there was no significant difference in the expression level of mRNA regardless of the lapse of time, and the expression level was maintained constant.

On the other hand, when irradiated with near-infrared, as expected, it was confirmed that the mRNA expression level of the collagen production indicators, col1A1, TGF-b1, and TiMP is significantly increased.

Therefore, as previously known, when irradiating near-infrared rays on skin cell lines such as HaCaT, the mRNA expression of col1A1, TGF-b1, and TiMP is significantly increased, and it is confirmed that collagen production is significantly promoted. Could.

<Experimental Example 2> Evaluation of optical properties of chalcogenide particles

In order to evaluate whether the chalcogenide-based particles according to the present invention exhibit optical properties suitable for exhibiting the effect of promoting collagen production, they were tested as follows.

Specifically, for each chalcogenide-based particle used in Examples 1 and 2, light absorption and emission spectra were measured using a SolidSpec-3700 model from Shimadzu, and the results are shown in FIG. 2. .

As shown in Fig. 2, the UV absorption spectrum of each of the chalcogenide nanoparticles used in Examples 1 and 2 was confirmed that the particles absorbed light in a wide area ranging from 200 to 1000 nm, especially alkali. It was confirmed that the chalcogenide particles of Example 2 doped with metal exhibited a remarkable light absorption rate compared to Example 1.

On the other hand, in the emission spectrum, it was confirmed that the chalcogenide particles of Example 1 and Example 2 commonly have a maximum wavelength at 1250 nm and emit light in a wavelength range around this. In particular, as in Example 2, when the alkali metal is doped, it can be seen that the intensity of the near-infrared light emitting light increases as the amount of light absorption increases.

Therefore, the present invention, the chalcogenide particle absorbs light in a wide range of 200-1000 nm, and is a particle that emits near-infrared rays in the wavelength range of 1100-1400 nm, for the purpose of skin aging prevention, skin regeneration, skin wound recovery, etc. It can be seen that it can be used as an active ingredient, from which it can be provided as a pharmaceutical composition for the use of medicines such as external preparations for skin, ointments, etc., it can also be used as a cosmetic composition for cosmetic purposes, as well as the chalcogenide As a substrate containing particles, it can be seen that it can be used as a device, a product, etc. to improve the condition of the skin, especially for the purpose of medical, cosmetic, and the like.

<Experimental Example 3> Evaluation of the shape of the chalcogenide particles

In order to evaluate the shape of the chalcogenide-based particles of the present invention, experiments were conducted as follows.

Specifically, in order to analyze the chalcogenide-based nanoparticles that emit near infrared rays used in Examples 1 and 2, JOEL LTD. It was observed using a transmission electron microscope (TEM) of JEM-2100F (HR) model name of the company, and the results are shown in FIG. 3.

As shown in FIG. 3, it was confirmed that both the Example 1 and Example 2 chalcogenide particles used in the present invention were nanoparticles having a uniform shape without aggregation due to a size of about 5 nm.

From this, it was confirmed that the chalcogenide-based nanoparticles used in Examples 1 and 2 and the chalcogenide-based nanoparticles doped with an alkali metal had a uniform size of 5 nm and a spherical shape at the same level. Did.

<Experimental Example 4> Shape evaluation of HaCaT cells treated with chalcogenide particles

In order to evaluate the shape of the HaCaT treated with the chalcogenide-based particles of the present invention, experiments were conducted as follows.

Specifically, in order to evaluate and analyze the shape of each untreated HaCaT and each of the HaCaT cells treated with the chalcogenide particles according to Examples 1 and 2, using a Leica ICC50 HD model from Leica The structure was observed, and the results are shown in FIG. 4.

As shown in FIG. 4, unlike the untreated HaCaT, the HaCaT treated by Example 1 and Example 2 is confirmed to have chalcogenide particles distributed in the cells.

<Experimental Example 5> Evaluation of the effect of promoting collagen production by treatment with chalcogenide particles

In order to evaluate the efficacy of promoting collagen production in skin cells according to the present invention chalcogenide-based particle treatment, experiments were conducted as follows.

Specifically, after performing as in Example 1 and Example 2, after extracting RNA using RNA Extraction Kit from Intron Biotechnology Inc. in each HaCaT cell, based on the extracted RNA, iScript ™ cDNA from Bio-Rad Laboratories CDNA was synthesized using the Synthesis Kit. Synthesized cDNA was performed by real-time PCR using SYBR Green Master Mix (TaKaRa). Real-time PCR was performed using Applied Biosystems of Carlsbad, and the results are shown in FIG. 5.

As shown in FIG. 5, as the treatment concentration of Example 1 chalcogenide-based particles in HaCaT cells increased, the mRNA expression level of col1A1, TBF-b1, and TiMP increased by up to 3 times compared to the untreated group of chalcogenide-based particles. It was observed to increase to.

In addition, when the alkali metal-doped Example 2 chalcogenide-based particles were treated, mRNA expression levels of col1A1, TBF-b1, and TiMP increased up to 20 to 30 times as compared to the untreated group as the concentration of the particles increased. It was observed to increase.

Therefore, the present invention, the chalcogenide-based particles can significantly increase the mRNA expression rate of the collagen production indicators col1A1, TBF-b1, and TiMP, and in particular, up to 30 times the bar, preventing skin aging, skin regeneration , It can be seen that it is an active ingredient that can be used for the purpose of skin wound recovery, etc., from which it can be provided as a pharmaceutical composition for the use of medicines such as external preparations for skin, ointments, etc., it can also be used as a cosmetic composition for cosmetic purposes It can be seen that, as a substrate containing the chalcogenide particles, in particular, it can be used as a device, a product, etc. to improve the condition of the skin for the purpose of medical, cosmetic, etc.

<Experimental Example 6> Evaluation of cytotoxicity of chalcogenide particles

In order to evaluate the cytotoxicity of the chalcogenide-based iva of the present invention, it was tested as follows.

Specifically, using the Epoch Microplate Spectrometer from BioTek, the survival rates of HaCaT cells treated with Example 1 and Example 2 chalcogenide particles were analyzed, and the results are shown in FIG. 6.

As can be seen in Figure 6, even if the concentration of chalcogenide-based particles in the cell is increased to 30%, it can be seen that the cell viability before and after particle treatment is well maintained at around 100%.

Therefore, it can be seen that the chalcogenide-based particles of the present invention do not significantly affect the survival rate of skin cells such as HaCaT cells.

From Experimental Examples 1-6 described above, it can be seen that the chalcogenide-based particles of the present invention can promote collagen production from emitting near-infrared rays, and are particularly non-toxic substances for skin cells, and furthermore, the present invention cal From the wavelength band emitted by the kozinide-based particles, preferably 1100-1400, more preferably 1200-1300, up to 1250 nm, it is most preferable not only for promoting collagen production but also for producing adipocytes in the dermis. As it exhibits emitted light, it can be usefully provided as a pharmaceutical composition for preventing or treating skin aging and skin wounds (damage) containing it as an active ingredient, and can also be usefully used as a component in cosmetics, beauty products, and devices. You can see that there is.

In addition, by doping the chalcogenide particles with an alkali metal, surprisingly, excellent optical properties of up to 20 to 30 times appear, and even in the production of collagen, it was confirmed that there is an effect of up to 30 times, and a better active ingredient can be provided. And

Furthermore, since the present invention has a feature capable of absorbing light in the range of absorption wavelengths of the chalcogenide particles from ultraviolet rays of 200 to 1000 nm from visible and near-infrared regions, it can be judged that the skin protection effect is also excellent. , It can be seen that even by exposing the chalcogenide-based particles of the present invention to ordinary light, the above-described excellent effects, such as skin protection, skin regeneration, and anti-aging effects, may be exhibited.

Claims (12)

Silver (Ag), which is a near-infrared emitting metal; And chalcogen (chalcogen) element sulfur (S); A cosmetic composition for promoting collagen production, containing the chalcogenide-based particles as an active ingredient.
delete delete According to claim 1,
The chalcogenide particle is a cosmetic composition for promoting collagen production, characterized in that further doped with lithium (Li), an alkali metal ion.
delete According to claim 1,
The cosmetic composition for promoting collagen production, characterized in that the average diameter of the chalcogenide particles is 4 nm-1000 nm.
According to claim 1,
The chalcogenide-based particle is a cosmetic composition for promoting collagen production, characterized in that absorbing light of 200 nm-1000 nm.
According to claim 1,
The chalcogenide particles are 1100 nm-1400 nm cosmetic composition for promoting collagen production, characterized in that it emits light.
Silver (Ag), which is a near-infrared emitting metal; And chalcogen (chalcogen) element sulfur (S); A pharmaceutical composition for the prevention or treatment of skin damage or wound healing, containing the chalcogenide-based particles as an active ingredient.
According to claim 1,
The cosmetic composition for promoting collagen production is a cosmetic composition for improving wrinkles or improving skin wounds.
Silver (Ag), which is a near-infrared emitting metal; And chalcogen (chalcogen) element sulfur (S); A cosmetic or cosmetic article comprising chalcogenide particles.
The method of claim 11,
A cosmetic or cosmetic article, wherein the chalcogenide particles irradiate near-infrared emission light to the skin, hair or scalp.

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