WO2018097527A1 - Composition for skin whitening or wound treatment, containing liquid plasma - Google Patents

Composition for skin whitening or wound treatment, containing liquid plasma Download PDF

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Publication number
WO2018097527A1
WO2018097527A1 PCT/KR2017/012771 KR2017012771W WO2018097527A1 WO 2018097527 A1 WO2018097527 A1 WO 2018097527A1 KR 2017012771 W KR2017012771 W KR 2017012771W WO 2018097527 A1 WO2018097527 A1 WO 2018097527A1
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WIPO (PCT)
Prior art keywords
composition
growth factor
skin
liquid plasma
plasma
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PCT/KR2017/012771
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French (fr)
Korean (ko)
Inventor
김철호
강성운
Original Assignee
아주대학교산학협력단
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Priority claimed from KR1020170110760A external-priority patent/KR101979105B1/en
Priority claimed from KR1020170110761A external-priority patent/KR102006784B1/en
Application filed by 아주대학교산학협력단 filed Critical 아주대학교산학협력단
Priority to US16/464,180 priority Critical patent/US11759407B2/en
Publication of WO2018097527A1 publication Critical patent/WO2018097527A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/30—Insulin-like growth factors (Somatomedins), e.g. IGF-1, IGF-2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin

Definitions

  • the present invention relates to a composition for skin whitening or wound healing comprising liquid plasma. More specifically, the present invention relates to a cosmetic composition for skin whitening containing a liquid plasma as an active ingredient, and a pharmaceutical composition for treating or preventing skin pigmentation diseases.
  • the present invention comprises a pharmaceutical composition for treating wounds, a quasi-drug composition, nutraceutical composition, and administering the composition to the subject or applying to the skin of the subject comprising a liquid plasma and growth factors as an active ingredient. It relates to a wound treatment method.
  • the composition comprising the liquid plasma and the growth factor of the present invention is excellent in wound healing effect by inducing proliferation of fibroblasts, and may be usefully applied to medicines including skin external preparations for wound treatment.
  • Melanogenesis is a defense mechanism against melanocyte melanocytes (melanocytes) that stimulate the production of melanin, which increases melanogenesis, which is transferred to keratinocytes and accumulated in the skin epidermis.
  • melanin protects the skin
  • hyperpigmentation of the skin causes blemishes, freckles, darkening of the skin after skin inflammation, and senile pigment spots. It may also result.
  • the melanin production process is made by tyrosinase, an amino acid called tyrosinase, which is transformed into dopa and dopaquinone, followed by a non-enzymatic oxidation reaction. It is known that spots, blotch, etc. are produced.
  • Korean Patent Publication No. 2005-0509848 discloses a whitening cosmetic containing a keratone derivative isolated from the previous issue.
  • Korean Patent Publication No. 2005-0479741 discloses a whitening cosmetic containing a glucose acylated derivative.
  • hydroquinone is once recognized for its effects, but its use is generally limited because of its sensitivity.
  • Ascorbic acid is easily oxidized, and the cosmetics blended with it cause discoloration and deodorization.
  • the substances derived from plant extracts have a great difference in efficacy depending on the origin of the plant, making it difficult to maintain homogeneity of the product. The disadvantage is that the synthesis efficiency is very low.
  • Skin acts as a protective barrier to the body and is the body's primary line of defense against disease, and the epidermis provides a barrier to microbial invasion.
  • Wound healing is a complex process that generally involves three stages: inflammation, proliferation, and remodeling. The first step involves clotting to achieve haemostasis, and supplementation of neutrophils to destroy bacteria and necrotic tissue, followed by supplementation of macrophages. During the second stage, angiogenesis occurs, where endothelial cells enter the wound site, while fibroblasts enter the wound site and help to produce granulation tissue.
  • Wound closure refers to the complete closure of the skin clinically, keratinocyte (fibroblast), fibroblast (endothelial cell), macrophage (macrophage), platelet (platelet) It is a complex process in which different kinds of cells interact and regulate. Each process is regulated by a complex signaling network regulated by many growth factors, cytokines and chemokines.
  • Wounds need to be treated quickly to reduce the risk of secondary infection.
  • the inflammatory response persists during wound healing, normal wound healing is delayed because the progression from the inflammatory phase to the proliferative phase is not made. For this reason, the development of wound treatment methods that do not induce an inflammatory response is actively progressing.
  • the present invention relates to a skin whitening or wound healing composition comprising a liquid plasma, and the present inventors have made diligent efforts to develop a method for the fundamental treatment of pigmentation of the skin.
  • the liquid plasma inhibits tyrosinase activity and melanin biosynthesis. It has been confirmed that it can be used for skin whitening because it shows an inhibitory effect, and the present inventors have made diligent efforts to develop a method for the fundamental treatment of wounds, and as a result, liquid plasma and epidermal growth factor (fibroblast) in fibroblasts ( Epidermal growth factor (EGF) was confirmed that the regeneration of fibroblasts was promoted to complete the present invention.
  • fibroblast epidermal growth factor
  • EGF epidermal growth factor
  • the present invention has been made to solve the problems of the prior art, and relates to a composition for skin whitening or wound treatment comprising a liquid plasma.
  • One object of the present invention is to provide a composition for skin whitening that exhibits excellent whitening effect through tyrosinase activity inhibitory effect and melanin biosynthesis inhibitory effect, and also excellent liquidity in terms of stability.
  • Another object of the present invention to provide a cosmetic composition for skin whitening containing the composition for skin whitening comprising the liquid plasma.
  • Another object of the present invention to provide a pharmaceutical composition for the treatment or prevention of pigmentation diseases containing a composition for skin whitening comprising the plasma.
  • Another object of the present invention is to provide a pharmaceutical composition for wound treatment comprising liquid plasma and growth factors as an active ingredient.
  • Another object of the present invention to provide a quasi-drug composition for wound treatment comprising a liquid plasma and growth factors as an active ingredient.
  • Another object of the present invention to provide a health care food composition for wound treatment comprising a liquid plasma and growth factors as an active ingredient.
  • Yet another object of the present invention is to provide a wound healing method comprising administering to a subject a composition comprising a liquid plasma and a growth factor as an active ingredient.
  • Yet another object of the present invention is to provide a wound healing method comprising applying to the skin of an individual a composition comprising a liquid plasma and a growth factor as an active ingredient.
  • non thermal plasma treated solution refers to the generation of high density high energy plasma in a liquid, which can be prepared by exposure to atmospheric nonthermal plasma (NTP) at atmospheric pressure.
  • NPS nonthermal plasma
  • liquid plasma may be used interchangeably with the term “plasma-conditioned liquid material” and the term “liquid material” may be used without limitation in the form of a liquid, but preferably Preferably water, saline, buffer, or medium, most preferably medium.
  • culture media refers to a medium capable of supporting cell growth and survival in vitro , and refers to a conventional medium used in the art appropriate for the culture of cells. It includes everything. Depending on the type of cells, medium and culture conditions can be selected.
  • the basal medium used for culturing the cells is preferably a cell culture minimum medium (CCMM), and generally includes a carbon source, a nitrogen source and a trace element component.
  • CCMM cell culture minimum medium
  • Such cell culture basal media include, for example, Dulbeco's Modified Eagle's Medium (DMEM), Minimal Essential Medium (MEM), Basic Medium Eagle (BME), RPMI1640, F-10, F-12, (Minimal Essential Medium), GMEM ( Glasgow's Minimal Essential Medium), Iscove's Modified Dulbecco's Medium, but are not limited to these.
  • whitening refers to the ability of the skin to be continuously exposed to ultraviolet light to increase melanocytes and thereby prevent excessive deposition of melanin pigment on the skin, or to thin the previously deposited melanin pigment. . As a result, it is possible to suppress the production of blemishes and freckles caused by excessive deposition of melanin pigment.
  • growth factor refers to a polypeptide that promotes the division, growth and differentiation of several cells, and refers to epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA), insulin-like growth Factor-1 (IGF-1), transforming growth factor- ⁇ (TGF- ⁇ ) or fibroblast growth factor (FGF), but is not limited thereto.
  • EGF epidermal growth factor
  • PDGF-AA platelet derived growth factor-AA
  • IGF-1 insulin-like growth Factor-1
  • TGF- ⁇ transforming growth factor- ⁇
  • FGF fibroblast growth factor
  • treatment means any action that improves or beneficially alters skin pigmentation, wounds, and other symptoms thereof by using liquid plasma according to the present invention.
  • Those skilled in the art will be able to determine the exact criteria for skin pigmentation, and determine the degree of improvement, improvement and treatment, with reference to data provided by the Korean Medical Association.
  • prevention means any action that inhibits or delays skin pigmentation, wounds, and other symptoms caused by using the liquid plasma according to the present invention. It will be apparent to those skilled in the art that the compositions herein having a therapeutic effect on skin pigmentation diseases or wounds can be prevented using the liquid plasma according to the invention before the initial symptoms or symptoms of skin pigmentation or wounds appear.
  • the term "pharmaceutical composition” means a composition to be administered for a specific purpose.
  • the pharmaceutical composition of the present invention includes a liquid plasma prepared by irradiating a plasma to a liquid substance as an active ingredient, and may include a protein and a pharmaceutically acceptable carrier, excipient or diluent involved therein.
  • Said "pharmaceutically acceptable" carrier or excipient means that which has been approved by the governmental regulatory authority, or listed in government or other generally approved pharmacopoeia for use in vertebrates, and more particularly in humans. do.
  • the pharmaceutical compositions of the invention may be in the form of suspensions, solutions or emulsions in oily or aqueous carriers, and may be prepared in the form of solids or semisolids.
  • the pharmaceutical compositions of the present invention may include formulating agents such as suspending, stabilizing, dissolving and / or dispersing agents and may be sterilized.
  • the pharmaceutical composition may be stable under the conditions of manufacture and storage, and may be preserved against the contaminating action of microorganisms such as bacteria or fungi.
  • the pharmaceutical compositions of the present invention may be in sterile powder form for reconstitution with a suitable carrier prior to use.
  • the pharmaceutical compositions may be in unit-dose form, in microneedle patches, in ampoules, or in other unit-dose containers, or in multi-dose containers.
  • the pharmaceutical composition may be stored in a freeze-dried (freeze-dried) state, which requires the addition of a sterile liquid carrier, eg, water for injection just before use.
  • a sterile liquid carrier eg, water for injection just before use.
  • Immediately injectable solutions and suspensions may be prepared as sterile powders, granules or tablets.
  • the pharmaceutical compositions of the present invention can be formulated or included in the form of microspheres in a liquid.
  • the pharmaceutical compositions of the present invention may comprise their pharmaceutically acceptable compounds and / or mixtures at concentrations between 0.001 and 100,000 U / kg.
  • the pharmaceutical compositions of the present invention may include suitable excipients, preservatives, suspending agents, additional stabilizers, dyes, buffers, antibacterial agents, antifungal agents, and isotonic agents, for example, sugars or sodium chloride.
  • suitable excipients such as used herein, the term "stabilizer” refers to a compound that is optionally used in the pharmaceutical compositions of the present invention to increase shelf life.
  • the stabilizer can be a sugar, an amino acid, or a polymer.
  • the pharmaceutical composition of the present invention may include one or more pharmaceutically acceptable carriers, and the carrier may be a solvent or a dispersion medium.
  • pharmaceutically acceptable carriers include water, saline, ethanol, polyols (eg glycerol, propylene glycol and liquid polyethylene glycols), oils, and suitable mixtures thereof.
  • sterilization techniques applied to the pharmaceutical compositions of the present invention include filtration through bacteria-inhibiting filters, terminal sterilization, incorporation of sterile preparations, irradiation, sterile gas irradiation, heating, vacuum drying and freeze drying. do.
  • administration means introducing the composition of the present invention to a patient in any suitable manner, and the route of administration of the composition of the present invention may be administered via any general route as long as it can reach the desired tissue.
  • the method of treatment of the present invention may comprise administering the pharmaceutical composition in a pharmaceutically effective amount.
  • the effective amount is defined as the type of disease, the severity of the disease, the type and amount of the active ingredient and other ingredients contained in the composition, the type and formulation of the patient and the age, body weight, general health condition, sex and diet, time of administration, route of administration And various factors, including the rate of secretion of the composition, the duration of treatment, and the drugs used concurrently.
  • the "cosmetic composition” is a composition for improving or improving skin pigmentation, wound, and other symptoms caused thereby.
  • Cosmetic composition comprising the composition of the present invention as an active ingredient, lotion, nutrition lotion, nutrition essence, massage cream, beauty bath additives, body lotion, body milk, bath oil, baby oil, baby powder, shower gel, shower cream, sun Screen lotion, sunscreen cream, suntan cream, skin lotion, skin cream, sunscreen cosmetic, cleansing milk, depilatory (cosmetic), face and body lotion, face and body cream, skin whitening cream, hand lotion, hair lotion, Cosmetic Cream, Jasmine Oil, Bath Soap, Water Soap, Beauty Soap, Shampoo, Hand Cleanser (Hand Cleaner), Medicated Soap (Non-Medical), Cream Soap, Facial Wash, Hair Rinse, Makeup Soap, Tooth Whitening Gel, Toothpaste, etc.
  • composition of the present invention may further comprise a suitable carrier, excipient or diluent commonly used in the preparation of cosmetic compositions.
  • Carriers, excipients or diluents that may be further added to the cosmetic compositions of the present invention include purified water, oils, waxes, fatty acids, fatty acid alcohols, fatty acid esters, surfactants, humectants, thickeners, antioxidants, viscosity stabilizers, kills Rating agents, buffers, lower alcohols, and the like.
  • a whitening agent, a moisturizing agent, vitamins, sunscreens, perfumes, dyes, antibiotics, antibacterial agents, antifungal agents may be included as necessary.
  • the oil may be hydrogenated vegetable oil, castor oil, cottonseed oil, olive oil, palm oil, jojoba oil, avocado oil, wax, wax, carnauba, candelilla, montan, ceresin, liquid paraffin, lanolin Can be used.
  • Stearic acid, linoleic acid, linolenic acid, oleic acid may be used as the fatty acid, and cetyl alcohol, octyldodecanol, oleyl alcohol, pantenol, lanolin alcohol, stearyl alcohol, hexadecanol may be used as fatty acid alcohol.
  • isopropyl myristate, isopropyl palmitate, butyl stearate may be used as the fatty acid ester.
  • surfactants cationic surfactants, anionic surfactants and nonionic surfactants known in the art can be used, and surfactants derived from natural products are preferred as much as possible.
  • it may include a hygroscopic agent, a thickener, an antioxidant, and the like, which are widely known in the cosmetic field, and their types and amounts are known in the art.
  • step (a) filling the plasma generating apparatus with a carrier gas; (b) generating a plasma by supplying a voltage of 0.5 kV to 20 kV and a frequency of 10 to 30 kHz to the plasma generator; And (c) irradiating the generated plasma to a liquid material, wherein the carrier gas in step (a) is selected from the group consisting of nitrogen, helium, argon, and oxygen. It provides a method for producing a liquid plasma, characterized in that any one or more selected, the liquid material in the step (c) provides a method for producing a liquid plasma which is water, saline, buffer, or medium.
  • liquid plasma composition comprising a liquid plasma prepared by any one or more of the above methods.
  • a pharmaceutical composition for the prevention or treatment of skin pigmentation disease comprising the liquid plasma composition as an active ingredient, wherein the skin pigmentation disease is spots, freckles, black spots, birthmarks, It provides a pharmaceutical composition for the prevention or treatment of skin pigmentation disease, characterized in that any one or more selected from the group consisting of pigmentation by drugs, pigmentation after inflammation, and hyperpigmentation occurring in dermatitis.
  • a method for preventing or treating skin pigmentation disease comprising administering the pharmaceutical composition to an individual, wherein the skin pigmentation disease is a blemish, freckles, black spots, birthmarks, It provides a method for preventing or treating skin pigmentation disease, characterized in that any one or more selected from the group consisting of pigmentation by drugs, pigmentation after inflammation, and hyperpigmentation occurring in dermatitis.
  • a cosmetic composition for skin whitening comprising the liquid plasma composition as an active ingredient.
  • the pharmaceutical composition provides a pharmaceutical composition for wound treatment further comprising a growth factor
  • the growth Factors include epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA), insulin-like growth factor-1 (IGF-1), transforming growth factor- ⁇ (TGF- ⁇ ) or fibroblast growth factor
  • EGF epidermal growth factor
  • PDGF-AA platelet derived growth factor-AA
  • IGF-1 insulin-like growth factor-1
  • TGF- ⁇ transforming growth factor- ⁇
  • FGF fibroblast growth factor
  • a wound treatment method comprising administering the pharmaceutical composition to a subject, wherein the wound is a wound that is skin damage caused by cuts, peels, rashes, inflammations, ulcers, or scratches.
  • the wound is a wound that is skin damage caused by cuts, peels, rashes, inflammations, ulcers, or scratches.
  • the composition provides a quasi-drug composition for wound treatment further comprising a growth factor, the growth factor Epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA), insulin-like growth factor-1 (IGF-1), transforming growth factor- ⁇ (TGF- ⁇ ) or fibroblast growth factor ( FGF) provides a quasi-drug composition for wound treatment.
  • EGF Epidermal growth factor
  • PDGF-AA platelet derived growth factor-AA
  • IGF-1 insulin-like growth factor-1
  • TGF- ⁇ transforming growth factor- ⁇
  • FGF fibroblast growth factor
  • Cosmetic composition for skin whitening comprising a liquid plasma according to the present invention
  • the composition for the treatment or prevention of pigmentation diseases shows an excellent inhibitory effect on tyrosinase activity and melanin biosynthesis
  • whitening cosmetic composition skin pigmentation
  • the composition comprising a liquid plasma and a growth factor according to the present invention can promote the regeneration of fibroblasts. Therefore, it is expected that the composition comprising the liquid plasma and the growth factor according to the present invention can promote the healing of wounds.
  • FIG. 1A and 1B illustrate a method of manufacturing a liquid plasma (NTS) according to the present invention.
  • Figure 2 shows the pigment formation inhibitory effect of the liquid plasma according to the present invention in Zebrafish.
  • Figure 3 shows the pigmentation inhibitory effect in the human tissue skin of the liquid plasma according to the present invention.
  • 4a and 4b show the effect of inhibiting tyrosinase activity in the human tissue skin of liquid plasma according to the present invention.
  • Figure 5 shows the results of the toxicity effect in the Melanocyte of the liquid plasma according to the present invention.
  • 6a and 6b show the effect of reducing the Melanogenesis marker in the human melanocyte of the liquid plasma according to the present invention.
  • Figure 7 shows the wound healing effect of the liquid plasma according to the present invention.
  • Figure 8 shows the cytotoxicity effect of the liquid plasma according to the present invention.
  • Human foreskin tissue was cultured in Transwell (DMEM high glucose + 4% FBS), and the liquid plasma was treated with 1min / 1ml. After incubation for 3 days, the fixation was observed through Fontana-masson staining. As a result, it was confirmed that the epidermal stain was lighter than that of the control group in the liquid plasma treated Human Tissue skin.
  • Example 1-2 Liquid plasma ( NTS ) And the growth factor comprising the growth factor
  • Example 2-1 Zebrafish Pigmentation inhibitory effect
  • the fertilized eggs collected from zebrafish male and female were put into zebrafish fertilized egg culture medium (Egg water, 0.2 g sea slat / L) and generated for 24 hours, and then the liquid plasma prepared in Example 1 was treated.
  • the fertilized egg corion was punched out with tweezers, and the fertilized egg showing the toxicity of the sample was removed after 24 hours. After complete removal, the samples of the same concentration were processed again. After 48 hours of sample treatment, the degree of pigmentation of the sample treated group compared to the control group was observed by a stereo microscope and confirmed, and the results are shown in FIG. 2.
  • zebra fish treated with liquid plasma were found to inhibit the formation of pigments compared to the control.
  • Example 2-2 Inhibitory Effect of Pigmentation on Human Tissue Skin
  • Example 1 After incubating human foreskin tissue in Transwell (DMEM high glucose + 4% FBS), the liquid plasma prepared in Example 1 was treated with 1min / 1ml. After culturing for 3 days and fixed, the degree of pigment formation was observed through Fontana-masson stain, and the results are shown in FIG. 3.
  • epidermal staining was lighter than that of the control group in the human plasma tissue treated with liquid plasma.
  • the human foreskin sample was seeded with 2 ⁇ 10 6 in a 60 mm dish, and then treated with 1 min / 1 ml of the liquid plasma prepared in Example 1. After 24 hours of incubation and fixation, Western blot, PCR, tyrosinase activity and melanin content were measured, and the results are shown in FIGS. 4A and 4B.
  • Example 2-4 In melanocyte Toxic effect verification
  • Example 5 After treating the liquid plasma prepared in Example 1 to the human melanocyte, the cytotoxicity was confirmed by time, and the results are shown in FIG. 5.
  • liquid plasma according to the present invention does not exhibit toxicity in human melanocyte.
  • Example 2-5 Human in melanocyte Melanogenesis marker reduction effect
  • liquid plasma according to the present invention was confirmed to reduce melanogenesis markers in human melanocyte, which was confirmed to reduce the RNA level of Tyrosinase as well as protein level.
  • Example 3-1 Check the effect of wound healing
  • the wound treatment effect did not appear in the group treated with liquid plasma alone, but the wound treatment effect was confirmed in the group treated with EGF alone.
  • the wound treatment effect was confirmed in the group treated with EGF alone.
  • a significant wound healing effect was observed than when treated with EGF alone.
  • composition according to the present invention was confirmed that there is no fibroblast cytotoxicity.
  • composition containing the liquid plasma as an active ingredient is excellent in the skin whitening and skin pigmentation disease treatment or prevention effect.
  • composition comprising the liquid plasma and growth factors of the present invention is excellent in wound healing by inducing proliferation of fibroblasts, and may be usefully applied to medicines including skin external preparations for wound treatment.

Abstract

The present invention relates to a composition for skin whitening or wound treatment, containing liquid plasma. More particularly, the present invention relates to a cosmetic composition for skin whitening and a pharmaceutical composition for treating or preventing skin pigmentation disorders, both of which contain liquid plasma as an active ingredient. In addition, the present invention relates to: a pharmaceutical composition, a quasi-drug composition, and a functional health food composition, all of which are for wound treatment and contain, as active ingredients, liquid plasma and growth factors; and a wound treatment method comprising a step of administering the compositions to a subject or applying the compositions to the skin of the subject. The composition, of the present invention, containing liquid plasma and growth factors induces the proliferation of fibroblasts so as to have an excellent wound treatment effect, thereby being useful by being applied to pharmaceutical products, including an external use skin preparation for wound treatment, and the like.

Description

액상 플라즈마를 포함하는 피부미백 또는 상처치료용 조성물Skin whitening or wound treatment composition comprising liquid plasma
본 발명은 액상 플라즈마를 포함하는 피부미백 또는 상처치료용 조성물에 관한 것이다. 보다 구체적으로, 본 발명은 액상 플라즈마를 유효성분으로 함유하는 피부 미백용 화장료 조성물, 및 피부 색소 침착 질환의 치료 또는 예방용 약제학적 조성물에 관한 것이다. 또한 본 발명은 액상 플라즈마 및 성장인자를 유효성분으로 포함하는 상처 치료용 약제학적 조성물, 의약외품 조성물, 건강기능식품 조성물, 및 상기 조성물을 개체에 투여하는 단계 또는 개체의 피부에 도포하는 단계를 포함하는 상처 치료 방법에 관한 것이다. 본 발명의 액상 플라즈마 및 성장인자를 포함하는 조성물은 섬유아세포의 증식을 유도함으로써 상처 치료 효능이 뛰어나, 상처 치료를 위한 피부 외용제를 비롯한 의약품 등에 적용되어 유용하게 사용될 수 있을 것이다.The present invention relates to a composition for skin whitening or wound healing comprising liquid plasma. More specifically, the present invention relates to a cosmetic composition for skin whitening containing a liquid plasma as an active ingredient, and a pharmaceutical composition for treating or preventing skin pigmentation diseases. In another aspect, the present invention comprises a pharmaceutical composition for treating wounds, a quasi-drug composition, nutraceutical composition, and administering the composition to the subject or applying to the skin of the subject comprising a liquid plasma and growth factors as an active ingredient. It relates to a wound treatment method. The composition comprising the liquid plasma and the growth factor of the present invention is excellent in wound healing effect by inducing proliferation of fibroblasts, and may be usefully applied to medicines including skin external preparations for wound treatment.
피부흑화(melanogenesis)는 멜라닌 색소생성세포(melanocyte)에서 자외선 등의 자극에 대한 방어기작으로 멜라닌 생성활동이 증가되고 이로 말미암아 만들어진 다량의 멜라닌이 각질형성세포(keratinocyte)로 전이되어 피부표피층에 축척된 결과이다. 비록 멜라닌이 피부보호작용을 하나 피부의 과색소침착은 기미, 주근깨, 피부염증 후의 피부흑화, 노인성 색소반점 등을 일으키며 이로 인해 당사자에게 미용상의 불편뿐만 아니라 정신적으로 부정적인 영향을 미쳐 사회활동에 불편을 초래하기도 한다. 멜라닌 생성 과정은 아미노산의 일종인 티로신(tyrosine)에 티로시나제(tyrosinase)라는 효소가 작용하여 도파(DOPA), 도파퀴논(dopaquinone)으로 바뀐 후 비효소적인 산화 반응을 거쳐 만들어 지며, 이것이 피부 내에 이상 침착하여 기미, 검버섯 등이 생기는 것이라고 알려져 있다. 이와 같은 색소침착, 기미, 반점 등의 완화, 예방 및 치료에는 멜라닌 생성을 억제하는 물질, 예를 들면 하이드로퀴논(hydroquinone), 알부틴, 비타민 C 및 그 유도체 등이 개발되어 이를 함유한 미백화장료가 공개되었으며, 한국 특허공고번호 제 2005-0509848호에는 전호로부터 분리된 케락톤 유도체를 함유한 미백화장료가 공개되어 있고. 또한, 한국특허공고번호 2005-0479741호에는 글루코오스 아실화 유도체를 함유한 미백화장료가 공개되어 있다. 이 중, 하이드로퀴논은 일단 효과가 인정되고 있지만 감작성이 있기 때문에 일반적으로 사용이 제한되고 있다. 아스콜빈산은 쉽게 산화되어, 이를 배합한 화장료는 변색, 변취되는 문제를 야기하고, 식물추출물 유래의 물질들은 식물의 산지에 따라 효능의 차이가 심하여 제품의 균질성이 유지되기 어렵고, 글루코오스 아실화 유도체는 합성 효율이 매우 낮은 단점이 있다.Melanogenesis is a defense mechanism against melanocyte melanocytes (melanocytes) that stimulate the production of melanin, which increases melanogenesis, which is transferred to keratinocytes and accumulated in the skin epidermis. The result is. Although melanin protects the skin, hyperpigmentation of the skin causes blemishes, freckles, darkening of the skin after skin inflammation, and senile pigment spots. It may also result. The melanin production process is made by tyrosinase, an amino acid called tyrosinase, which is transformed into dopa and dopaquinone, followed by a non-enzymatic oxidation reaction. It is known that spots, blotch, etc. are produced. To alleviate, prevent, and treat pigmentation, blemishes, and spots, substances that inhibit melanin production, such as hydroquinone, arbutin, vitamin C, and derivatives thereof, have been developed and whitening cosmetics containing them are disclosed. Korean Patent Publication No. 2005-0509848 discloses a whitening cosmetic containing a keratone derivative isolated from the previous issue. In addition, Korean Patent Publication No. 2005-0479741 discloses a whitening cosmetic containing a glucose acylated derivative. Among these, hydroquinone is once recognized for its effects, but its use is generally limited because of its sensitivity. Ascorbic acid is easily oxidized, and the cosmetics blended with it cause discoloration and deodorization. The substances derived from plant extracts have a great difference in efficacy depending on the origin of the plant, making it difficult to maintain homogeneity of the product. The disadvantage is that the synthesis efficiency is very low.
한편, 피부는 신체를 보호하는 방어막 역할을 수행하고 질환에 대한 신체의 일차 방어선이며, 표피(epidermis)가 미생물 침입에 대한 장벽을 제공한다. 따라서 상처, 화상, 찰과상 및 피부에 대한 기타 손상의 치료에서 일차적인 목적은 감염을 예방하기 위한 신속한 봉합(closure) 및 상처 치유이다. 상처 치유는 일반적으로, 염증(inflammation), 증식(proliferation) 및 재형성(remodelling)의 3가지 단계를 수반하는 복잡한 과정이다. 첫 번째 단계는 지혈(haemostasis)을 달성하기 위한 응고(clotting), 그리고 세균 및 괴사 조직을 파괴하기 위한 호중구의 보충, 그 이후에 대식세포의 보충을 수반한다. 두 번째 단계 동안, 혈관신생(angiogenesis)이 발생하고, 이때 내피 세포가 상처 부위로 들어가고, 이와 동시에 섬유아세포가 상처 부위로 들어가고 육아 조직(granulation tissue)을 생산하는데 도움을 준다. 육아 조직의 형성은 재상피화(reepithelialisation)가 일어날 수 있도록 한다. 최종 단계 동안, 콜라겐 생산과 파괴의 수준이 균등해지고, 그리고 치유된 상처는 최대 강도를 달성하기 위하여 천천히 변경된다. 상처 치유는 이들 과정 중에서 임의의 한 가지가 적절하게 또는 시기 적절한 방식으로 기능하지 않을 때, 지연되거나 손상된다. 이것은 만성적인 상처를 유발할 수 있는데, 이러한 상처는 개인에게 중요한 문제일 뿐만 아니라 비용이 많이 드는 임상적 문제점일 수 있다. Skin, on the other hand, acts as a protective barrier to the body and is the body's primary line of defense against disease, and the epidermis provides a barrier to microbial invasion. Thus the primary objectives in the treatment of wounds, burns, abrasions and other damage to the skin are rapid closure and wound healing to prevent infection. Wound healing is a complex process that generally involves three stages: inflammation, proliferation, and remodeling. The first step involves clotting to achieve haemostasis, and supplementation of neutrophils to destroy bacteria and necrotic tissue, followed by supplementation of macrophages. During the second stage, angiogenesis occurs, where endothelial cells enter the wound site, while fibroblasts enter the wound site and help to produce granulation tissue. The formation of granulation tissue allows for re-epithelialization. During the final stage, the level of collagen production and destruction is evened, and the wound healed is slowly changed to achieve maximum strength. Wound healing is delayed or damaged when any one of these processes does not function properly or in a timely manner. This can lead to chronic wounds, which can be an important problem for an individual as well as an expensive clinical problem.
상기 상처 치유(wound closure)는 임상적으로 피부가 완전하게 봉합되는 것을 의미하며, 각질세포(keratinocyte), 섬유모세포(fibroblast), 혈관내피세포(endothelial cell), 대식세포(macrophage), 혈소판(platelet) 등 여러 종류의 세포가 상호작용하며 조절하는 복잡한 과정이다. 각각의 과정은 많은 성장인자(growth factor), 사이토카인(cytokine) 및 케모카인(chemokine)이 조절하는 복잡한 신호전달망에 의해 조절된다.Wound closure refers to the complete closure of the skin clinically, keratinocyte (fibroblast), fibroblast (endothelial cell), macrophage (macrophage), platelet (platelet) It is a complex process in which different kinds of cells interact and regulate. Each process is regulated by a complex signaling network regulated by many growth factors, cytokines and chemokines.
상처는 빠르게 치료해야 2차 감염의 위험을 줄일 수 있다. 또한, 상처치료 과정에서 염증반응이 지속되면 염증기에서 증식기로의 진행이 이루어지지 않아 정상적인 상처치유가 지연된다. 이러한 이유로 염증반응을 유도하지 않는 상처 치료방법의 개발이 활발하게 진행되고 있다.Wounds need to be treated quickly to reduce the risk of secondary infection. In addition, if the inflammatory response persists during wound healing, normal wound healing is delayed because the progression from the inflammatory phase to the proliferative phase is not made. For this reason, the development of wound treatment methods that do not induce an inflammatory response is actively progressing.
이에 본 발명의 출원인들은 본 발명을 완성하였다. 액상 플라즈마를 포함하는 피부미백 또는 상처치료용 조성물에 관한 것으로, 본 발명자들은 피부의 색소 침착의 근본적인 치료를 위한 방법을 개발하기 위하여 예의 노력한 결과, 액상 플라즈마가 티로시나아제 활성을 저해 효과 및 멜라닌 생합성을 억제효과를 나타내므로 피부 미백에 이용될 수 있음을 확인하였고, 또한 본 발명자들은 상처의 근본적인 치료를 위한 방법을 개발하기 위하여 예의 노력한 결과, 섬유아세포(fibroblast)에 액상 플라즈마 및 상피세포 성장인자(epidermal growth factor. EGF)를 처리하는 경우 섬유아세포의 재생이 촉진됨을 확인하여 본 발명을 완성하기에 이르렀다. Applicants of the present invention thus completed the present invention. The present invention relates to a skin whitening or wound healing composition comprising a liquid plasma, and the present inventors have made diligent efforts to develop a method for the fundamental treatment of pigmentation of the skin. As a result, the liquid plasma inhibits tyrosinase activity and melanin biosynthesis. It has been confirmed that it can be used for skin whitening because it shows an inhibitory effect, and the present inventors have made diligent efforts to develop a method for the fundamental treatment of wounds, and as a result, liquid plasma and epidermal growth factor (fibroblast) in fibroblasts ( Epidermal growth factor (EGF) was confirmed that the regeneration of fibroblasts was promoted to complete the present invention.
선행기술Prior art
1. 국제공개특허 WO20161675161. International Publication WO2016167516
본 발명은 상기와 같은 종래 기술상의 문제점을 해결하기 위해 안출된 것으로, 액상 플라즈마를 포함하는 피부미백 또는 상처치료용 조성물에 관한 것이다.The present invention has been made to solve the problems of the prior art, and relates to a composition for skin whitening or wound treatment comprising a liquid plasma.
그러나 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업계에서 통상의 지식을 가진 자에게 명확하게 이해될 수 있을 것이다.However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problem, another task that is not mentioned will be clearly understood by those skilled in the art from the following description.
이하, 본원에 기재된 다양한 구체예가 도면을 참조로 기재된다. 하기 설명에서, 본 발명의 완전한 이해를 위해서, 다양한 특이적 상세사항, 예컨대, 특이적 형태, 조성물, 및 공정 등이 기재되어 있다. 그러나, 특정의 구체예는 이들 특이적 상세 사항 중 하나 이상 없이, 또는 다른 공지된 방법 및 형태와 함께 실행될 수 있다. 다른 예에서, 공지된 공정 및 제조 기술은 본 발명을 불필요하게 모호하게 하지 않게 하기 위해서, 특정의 상세사항으로 기재되지 않는다. "한 가지 구체예" 또는 "구체예"에 대한 본 명세서 전체를 통한 참조는 구체예와 결부되어 기재된 특별한 특징, 형태, 조성 또는 특성이 본 발명의 하나 이상의 구체예에 포함됨을 의미한다. 따라서, 본 명세서 전체에 걸친 다양한 위치에서 표현된 "한 가지 구체예에서" 또는 "구체예"의 상황은 반드시 본 발명의 동일한 구체예를 나타내지는 않는다. 추가로, 특별한 특징, 형태, 조성, 또는 특성은 하나 이상의 구체예에서 어떠한 적합한 방법으로 조합될 수 있다.Hereinafter, various embodiments described herein are described with reference to the drawings. In the following description, for a thorough understanding of the present invention, various specific details are described, such as specific forms, compositions, processes and the like. However, certain embodiments may be practiced without one or more of these specific details, or in conjunction with other known methods and forms. In other instances, well known processes and manufacturing techniques have not been described in particular detail in order to not unnecessarily obscure the present invention. Reference throughout this specification to "one embodiment" or "embodiment" means that a particular feature, form, composition or characteristic described in connection with the embodiment is included in one or more embodiments of the invention. Thus, the context of “in one embodiment” or “embodiment” expressed at various places throughout this specification does not necessarily represent the same embodiment of the invention. In addition, particular features, forms, compositions, or properties may be combined in any suitable manner in one or more embodiments.
본 발명의 하나의 목적은 티로시나아제 활성억제효과 및 멜라닌 생합성 억제효과를 통해 우수한 미백효과를 나타내며, 안정성 면에서도 우수한 액상 플라즈마를 포함하는 피부 미백용 조성물을 제공하는 것이다. One object of the present invention is to provide a composition for skin whitening that exhibits excellent whitening effect through tyrosinase activity inhibitory effect and melanin biosynthesis inhibitory effect, and also excellent liquidity in terms of stability.
본 발명의 다른 목적은 상기 액상 플라즈마를 포함하는 피부 미백용 조성물을 함유하는 피부 미백용 화장료 조성물을 제공하는 것이다. Another object of the present invention to provide a cosmetic composition for skin whitening containing the composition for skin whitening comprising the liquid plasma.
본 발명의 또 다른 목적은 상기 플라즈마를 포함하는 피부 미백용 조성물을 함유하는 색소 침착 질환의 치료 또는 예방용 약제학적 조성물을 제공하는데 있다.Another object of the present invention to provide a pharmaceutical composition for the treatment or prevention of pigmentation diseases containing a composition for skin whitening comprising the plasma.
또한 본 발명의 다른 하나의 목적은 액상 플라즈마 및 성장인자를 유효성분으로 포함하는 상처 치료용 약제학적 조성물을 제공하는 것이다. Another object of the present invention is to provide a pharmaceutical composition for wound treatment comprising liquid plasma and growth factors as an active ingredient.
본 발명의 다른 하나의 목적은 액상 플라즈마 및 성장인자를 유효성분으로 포함하는 상처 치료용 의약외품 조성물을 제공하는 것이다.Another object of the present invention to provide a quasi-drug composition for wound treatment comprising a liquid plasma and growth factors as an active ingredient.
본 발명의 또 다른 하나의 목적은 액상 플라즈마 및 성장인자를 유효성분으로 포함하는 상처 치료용 건강기능식품 조성물을 제공하는 것이다.Another object of the present invention to provide a health care food composition for wound treatment comprising a liquid plasma and growth factors as an active ingredient.
본 발명의 또 다른 하나의 목적은 액상 플라즈마 및 성장인자를 유효성분으로 포함하는 조성물을 개체에 투여하는 단계를 포함하는 상처 치료 방법을 제공하는 것이다.Yet another object of the present invention is to provide a wound healing method comprising administering to a subject a composition comprising a liquid plasma and a growth factor as an active ingredient.
본 발명의 또 다른 하나의 목적은 액상 플라즈마 및 성장인자을 유효성분으로 포함하는 조성물을 개체의 피부에 도포하는 단계를 포함하는, 상처 치료 방법을 제공하는 것이다.Yet another object of the present invention is to provide a wound healing method comprising applying to the skin of an individual a composition comprising a liquid plasma and a growth factor as an active ingredient.
본 명세서에서 사용된 용어 "액상 플라즈마(non thermal plasma treated solution, NTS)"는 고밀도 고에너지 플라즈마를 액체 속에서 발생시키는 것을 의미하며, 대기압의 상온 비열 플라즈마(nonthermal plasma, NTP)에 노출시켜 제조될 수 있다. 상기 용어 “액상 플라즈마”는 용어 “플라즈마 처리된 액상 물질(plasma-conditioned liquid material)"과 상호교환적으로 사용될 수 있고, 상기의 “액상 물질”은 액상 형태의 물질은 제한없이 사용 가능하나, 바람직하게는 물, 식염수, 완충액, 또는 배지이고, 가장 바람직하게는 배지이다.As used herein, the term "non thermal plasma treated solution (NTS)" refers to the generation of high density high energy plasma in a liquid, which can be prepared by exposure to atmospheric nonthermal plasma (NTP) at atmospheric pressure. Can be. The term "liquid plasma" may be used interchangeably with the term "plasma-conditioned liquid material" and the term "liquid material" may be used without limitation in the form of a liquid, but preferably Preferably water, saline, buffer, or medium, most preferably medium.
본 명세서에서 사용된 용어 "배지(culture media)"는 인 비트로(in vitro)에서 세포 성장 및 생존을 지지할 수 있게 하는 배지를 의미하고, 세포의 배양에 적절한 당 분야에서 사용되는 통상의 배지를 모두 포함한다. 세포의 종류에 따라 배지와 배양조건을 선택할 수 있다. 세포의 배양에 사용되는 기본배지는 바람직하게는 세포 배양 최소 배지(cell culture minimum medium: CCMM)로, 일반적으로 탄소원, 질소원 및 미량원소 성분을 포함한다. 이런 세포 배양 기본 배지에는 예를 들면, DMEM(Dulbeco's Modified Eagle's Medium), MEM(Minimal essential Medium), BME(Basal Medium Eagle), RPMI1640, F-10, F-12,(Minimal essential Medium), GMEM(Glasgow's Minimal essential Medium), Iscove's Modified Dulbecco's Medium 등이 있으나, 이로 제한되지 않는다. As used herein, the term "culture media" refers to a medium capable of supporting cell growth and survival in vitro , and refers to a conventional medium used in the art appropriate for the culture of cells. It includes everything. Depending on the type of cells, medium and culture conditions can be selected. The basal medium used for culturing the cells is preferably a cell culture minimum medium (CCMM), and generally includes a carbon source, a nitrogen source and a trace element component. Such cell culture basal media include, for example, Dulbeco's Modified Eagle's Medium (DMEM), Minimal Essential Medium (MEM), Basic Medium Eagle (BME), RPMI1640, F-10, F-12, (Minimal Essential Medium), GMEM ( Glasgow's Minimal Essential Medium), Iscove's Modified Dulbecco's Medium, but are not limited to these.
본 명세서에서 사용된 용어 "미백"은 피부가 자외선에 지속적으로 노출되어 멜라닌 세포가 증가하고 그로 인해 피부에 멜라닌 색소가 과도하게 침착되는 것을 방지하거나, 기존에 침착된 멜라닌 색소를 엷게 하는 기능을 일컫는다. 이에 따라, 과도한 멜라닌 색소의 침착으로 생기는 기미나 주근깨의 생성을 억제할 수 있다.As used herein, the term "whitening" refers to the ability of the skin to be continuously exposed to ultraviolet light to increase melanocytes and thereby prevent excessive deposition of melanin pigment on the skin, or to thin the previously deposited melanin pigment. . As a result, it is possible to suppress the production of blemishes and freckles caused by excessive deposition of melanin pigment.
본 명세서에서 사용된 용어 "성장인자"는 여러 세포의 분열, 성장 및 분화를 촉진하는 폴리펩티드를 의미하며, 상피세포 성장인자(EGF), 혈소판 유래 성장인자-AA(PDGF-AA), 인슐린 유사 성장인자-1(IGF-1), 형질 전환 성장인자-β(TGF-β) 또는 섬유아세포 성장인자(FGF)를 포함하나, 이에 제한되는 것은 아니다.As used herein, the term "growth factor" refers to a polypeptide that promotes the division, growth and differentiation of several cells, and refers to epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA), insulin-like growth Factor-1 (IGF-1), transforming growth factor-β (TGF-β) or fibroblast growth factor (FGF), but is not limited thereto.
본 발명의 일 구체예에서 "치료”란, 본 발명에 따른 액상 플라즈마를 이용하여 피부 색소침착, 상처, 및 이로 인한 다른 증세를 호전시키거나 이롭게 변경하는 모든 행위를 의미한다. 본원이 속하는 기술분야에서 통상의 지식을 가진 자라면, 대한의학협회 등에서 제시된 자료를 참조하여 피부 색소침착의 정확한 기준을 파악하고, 개선, 향상 및 치료된 정도를 판단할 수 있을 것이다.In one embodiment of the present invention, "treatment" means any action that improves or beneficially alters skin pigmentation, wounds, and other symptoms thereof by using liquid plasma according to the present invention. Those skilled in the art will be able to determine the exact criteria for skin pigmentation, and determine the degree of improvement, improvement and treatment, with reference to data provided by the Korean Medical Association.
본 발명의 일 구체예에서 “예방”이란, 본 발명에 따른 액상 플라즈마를 이용하여 피부 색소 침착, 상처, 및 이로 인한 다른 증세를 억제 또는 지연시키는 모든 행위를 의미한다. 피부 색소침착 질환 또는 상처에 치료효과가 있는 본원의 조성물은 피부 색소침착 또는 상처의 초기증상 또는 증상이 나타나기 전에 본 발명에 따른 액상 플라즈마를 이용하여 이러한 질환을 예방할 수 있다는 것은 당업자에게 자명할 것이다.In one embodiment of the present invention, "prevention" means any action that inhibits or delays skin pigmentation, wounds, and other symptoms caused by using the liquid plasma according to the present invention. It will be apparent to those skilled in the art that the compositions herein having a therapeutic effect on skin pigmentation diseases or wounds can be prevented using the liquid plasma according to the invention before the initial symptoms or symptoms of skin pigmentation or wounds appear.
본 명세서에 있어서 “약학조성물”이란, 특정한 목적을 위해 투여되는 조성물을 의미한다. 본 발명의 목적상, 본 발명의 약학조성물은 플라즈마를 액상 물질에 조사하여 제조한 액상 플라즈마를 유효성분으로 포함하는 것이며, 이에 관여하는 단백질 및 약학적으로 허용 가능한 담체, 부형제 또는 희석제를 포함할 수 있다. 상기의 "약학적 허용될 가능한" 담체 또는 부형제는 정부의 규제부에 의해 승인된 것이나, 또는 척추 동물, 그리고 보다 특별하게는 인간에게 사용을 위한 정부 또는 기타 일반적으로 승인된 약전에서 리스트된 것을 의미한다.As used herein, the term "pharmaceutical composition" means a composition to be administered for a specific purpose. For the purposes of the present invention, the pharmaceutical composition of the present invention includes a liquid plasma prepared by irradiating a plasma to a liquid substance as an active ingredient, and may include a protein and a pharmaceutically acceptable carrier, excipient or diluent involved therein. have. Said "pharmaceutically acceptable" carrier or excipient means that which has been approved by the governmental regulatory authority, or listed in government or other generally approved pharmacopoeia for use in vertebrates, and more particularly in humans. do.
비경구적인 투여를 위해 본 발명의 약학조성물은 유성 또는 수성 담체에 있는 현탁액, 용액 또는 에멀젼의 형태로 될 수 있고, 고체 또는 반고체의 형태로 제조될 수 있다. 또한, 본 발명의 약학조성물은 현탁제, 안정화제, 용해제 및/또는 분산제와 같은 제형화제를 포함할 수 있고, 멸균될 수 있다. 상기 약학조성물은 제조 및 저장의 조건 하에서 안정할 수 있고, 세균이나 곰팡이와 같은 미생물의 오염 작용에 대해 보존될 수 있다. 대안적으로, 본 발명의 약학조성물은 사용 전에 적절한 담체와 재구성을 위해 멸균 분말 형태일 수 있다. 약학조성물은 단위-복용량 형태로, 마이크로니들 패치에, 앰플에, 또는 기타 단위-복용량 용기에, 또는 다-복용량 용기에 존재할 수 있다. 대안적으로, 약학적 조성물은 단지 멸균 액체 담체, 예를 들어 사용 바로 전에 주사용 물의 부가함을 요하는 동결-건조된(냉동건조) 상태로 보관될 수 있다. 즉시 주사용액 및 현탁액은 멸균 분말, 그래뉼 또는 타블렛으로 제조될 수 있다.For parenteral administration, the pharmaceutical compositions of the invention may be in the form of suspensions, solutions or emulsions in oily or aqueous carriers, and may be prepared in the form of solids or semisolids. In addition, the pharmaceutical compositions of the present invention may include formulating agents such as suspending, stabilizing, dissolving and / or dispersing agents and may be sterilized. The pharmaceutical composition may be stable under the conditions of manufacture and storage, and may be preserved against the contaminating action of microorganisms such as bacteria or fungi. Alternatively, the pharmaceutical compositions of the present invention may be in sterile powder form for reconstitution with a suitable carrier prior to use. The pharmaceutical compositions may be in unit-dose form, in microneedle patches, in ampoules, or in other unit-dose containers, or in multi-dose containers. Alternatively, the pharmaceutical composition may be stored in a freeze-dried (freeze-dried) state, which requires the addition of a sterile liquid carrier, eg, water for injection just before use. Immediately injectable solutions and suspensions may be prepared as sterile powders, granules or tablets.
몇몇 비 제한적인 실시형태에 있어서, 본 발명의 약학조성물은 제형화되어 질 수 있고, 또는 액체 속에 미립구의 형태로 포함될 수 있다. 어떤 비 제한적인 실시형태에 있어서, 본 발명의 약학조성물은 이들의 약학적으로 허용될 수 있는 화합물 및/또는 혼합물을 0.001 내지 100,000 U/kg 사이의 농도로 포함할 수 있다. 또한 어떤 비 제한적인 실시형태에 있어서, 본 발명의 약학조성물은 적절한 부형제는 보존제, 현탁제, 추가적인 안정화제, 염료, 완충제, 항균제, 항진균제, 및 등장화제, 예를 들어, 설탕 또는 염화나트륨을 포함할 수 있다. 여기서 사용된 것으로, 용어 "안정화제"는 보존 수명을 증가하기 위해 본 발명의 약학조성물에 선택적으로 사용된 화합물을 언급한다. 비-제한적인 실시에 있어서, 안정화제는 당, 아미노산, 또는 폴리머일 수 있다. 또한 본 발명의 약학조성물은 하나 또는 그 이상의 약학적으로 허용될 수 있는 담체를 포함할 수 있고, 상기 담체는 용매 또는 분산 배지일 수 있다. 약학적으로 허용될 수 있는 담체의 비-제한적인 예는 물, 식염수, 에탄올, 폴리올 (예, 글리세롤, 프로필렌 글리콜 및 액체 폴리에틸렌 글리콜), 오일, 및 이들의 적절한 혼합물을 포함한다. 본 발명의 약학조성물에 적용되는 멸균 기술의 비-제한적인 예는 세균-억제 필터를 통한 여과, 터미날 멸균화, 멸균 제제의 합체, 방사선 조사, 멸균 가스 조사, 가열, 진공 건조 및 동결 건조를 포함한다.In some non-limiting embodiments, the pharmaceutical compositions of the present invention can be formulated or included in the form of microspheres in a liquid. In certain non-limiting embodiments, the pharmaceutical compositions of the present invention may comprise their pharmaceutically acceptable compounds and / or mixtures at concentrations between 0.001 and 100,000 U / kg. Also in certain non-limiting embodiments, the pharmaceutical compositions of the present invention may include suitable excipients, preservatives, suspending agents, additional stabilizers, dyes, buffers, antibacterial agents, antifungal agents, and isotonic agents, for example, sugars or sodium chloride. Can be. As used herein, the term "stabilizer" refers to a compound that is optionally used in the pharmaceutical compositions of the present invention to increase shelf life. In a non-limiting implementation, the stabilizer can be a sugar, an amino acid, or a polymer. In addition, the pharmaceutical composition of the present invention may include one or more pharmaceutically acceptable carriers, and the carrier may be a solvent or a dispersion medium. Non-limiting examples of pharmaceutically acceptable carriers include water, saline, ethanol, polyols (eg glycerol, propylene glycol and liquid polyethylene glycols), oils, and suitable mixtures thereof. Non-limiting examples of sterilization techniques applied to the pharmaceutical compositions of the present invention include filtration through bacteria-inhibiting filters, terminal sterilization, incorporation of sterile preparations, irradiation, sterile gas irradiation, heating, vacuum drying and freeze drying. do.
본 명세서에 있어서 “투여”란, 어떠한 적절한 방법으로 환자에게 본 발명의 조성물을 도입하는 것을 의미하며, 본 발명의 조성물의 투여경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 투여될 수 있다. 경구 투여, 복강 내 투여, 정맥 내 투여, 근육 내 투여, 피하 투여, 피내 투여, 비내 투여, 폐내 투여, 직장내 투여, 강내 투여, 복강 내 투여, 경막 내 투여가 이루어질 수 있으나, 본 발명의 약학조성물은 피부 위에 도포하거나 피하 또는 피내에 주사하는 형태로 제공되는 것이 가장 바람직하나, 이에 제한되는 것은 아니다.As used herein, "administration" means introducing the composition of the present invention to a patient in any suitable manner, and the route of administration of the composition of the present invention may be administered via any general route as long as it can reach the desired tissue. have. Oral administration, intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, intranasal administration, pulmonary administration, rectal administration, intraluminal administration, intraperitoneal administration, intradural administration, Most preferably, the composition is provided in the form of an application on the skin or subcutaneous or intradermal injection.
본 발명의 치료 방법은 상기 약학조성물을 약제학적 유효량으로 투여하는 것을 포함할 수 있다. 본 발명에서 유효량은 질환의 종류, 질환의 중증도, 조성물에 함유된 유효 성분 및 다른 성분의 종류 및 함량, 제형의 종류 및 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 조성물의 분비율, 치료 기간, 동시 사용되는 약물을 비롯한 다양한 인자에 따라 조절될 수 있다.The method of treatment of the present invention may comprise administering the pharmaceutical composition in a pharmaceutically effective amount. In the present invention, the effective amount is defined as the type of disease, the severity of the disease, the type and amount of the active ingredient and other ingredients contained in the composition, the type and formulation of the patient and the age, body weight, general health condition, sex and diet, time of administration, route of administration And various factors, including the rate of secretion of the composition, the duration of treatment, and the drugs used concurrently.
본 명세서에 있어서 “화장료 조성물”이란, 피부 색소침착, 상처, 및 이로 인한 다른 증세를 호전시키거나 개선을 위한 조성물이다. 본 발명의 조성물을 유효성분으로 포함하는 화장료조성물은 화장수, 영양로션, 영양에센스, 마사지 크림, 미용목욕물첨가제, 바디로션, 바디밀크, 배스오일, 베이비오일, 베이비파우더, 샤워겔, 샤워크림, 선스크린로션, 선스크린크림, 선탠크림, 스킨로션, 스킨크림, 자외선차단용 화장품, 크렌징밀크, 탈모제(화장용), 페이스 및 바디로션, 페이스 및 바디크림, 피부미백크림, 핸드로션, 헤어로션, 화장용크림, 쟈스민오일, 목욕비누, 물비누, 미용비누, 샴푸, 손세정제(핸드클리너), 약용비누(비의료용), 크림비누, 페이셜워시, 헤어린스, 화장비누, 치아미백용 겔, 치약 등의 형태로 제조될 수 있다. 이를 위해 본 발명의 조성물은 화장료조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 또는 희석제를 더 포함할 수 있다. 본 발명의 화장료 조성물 내에 더 추가될 수 있는 담체, 부형제 또는 희석제로는 정제수, 오일, 왁스, 지방산, 지방산 알콜, 지방산 에스테르, 계면활성제, 흡습제(humectant), 증점제, 항산화제, 점도 안정화제, 킬레이팅제, 완충제, 저급 알콜 등이 포함되지만, 이에 제한되는 것은 아니다. 또한, 필요에 따라 미백제, 보습제, 비타민, 자외선 차단제, 향수, 염료, 항생제, 항박테리아제, 항진균제를 포함할 수 있다. 상기 오일로서는 수소화 식물성유, 피마자유, 면실유, 올리브유, 야자인유, 호호바유, 아보카도유가 이용될 수 있으며, 왁스로는 밀랍, 경랍, 카르나우바, 칸델릴라, 몬탄, 세레신, 액체 파라핀, 라놀린이 이용될 수 있다. 지방산으로는 스테아르산, 리놀레산, 리놀렌산, 올레산이 이용될 수 있고, 지방산 알콜로는 세틸알콜, 옥틸도데칸올, 올레일알콜, 판텐올, 라놀린알콜, 스테아릴 알콜, 헥사데칸올이 이용될 수 있으며 지방산 에스테르로는 이소프로필미리스테이트, 이소프로필 팔미테이트, 부틸스테아레이트가 이용될 수 있다. 계면활성제로는 당업계에 알려진 양이온 계면활성제, 음이온 계면활성제 및 비이온성 계면활성제가 사용가능하며 가능한 한 천연물 유래의 계면활성제가 바람직하다. 그 외에도 화장품 분야에서 널리 알려진 흡습제, 증점제, 항산화제 등을 포함할 수 있으며, 이들의 종류와 양은 당업계에 공지된 바에 따른다.In the present specification, the "cosmetic composition" is a composition for improving or improving skin pigmentation, wound, and other symptoms caused thereby. Cosmetic composition comprising the composition of the present invention as an active ingredient, lotion, nutrition lotion, nutrition essence, massage cream, beauty bath additives, body lotion, body milk, bath oil, baby oil, baby powder, shower gel, shower cream, sun Screen lotion, sunscreen cream, suntan cream, skin lotion, skin cream, sunscreen cosmetic, cleansing milk, depilatory (cosmetic), face and body lotion, face and body cream, skin whitening cream, hand lotion, hair lotion, Cosmetic Cream, Jasmine Oil, Bath Soap, Water Soap, Beauty Soap, Shampoo, Hand Cleanser (Hand Cleaner), Medicated Soap (Non-Medical), Cream Soap, Facial Wash, Hair Rinse, Makeup Soap, Tooth Whitening Gel, Toothpaste, etc. It may be prepared in the form of. To this end, the composition of the present invention may further comprise a suitable carrier, excipient or diluent commonly used in the preparation of cosmetic compositions. Carriers, excipients or diluents that may be further added to the cosmetic compositions of the present invention include purified water, oils, waxes, fatty acids, fatty acid alcohols, fatty acid esters, surfactants, humectants, thickeners, antioxidants, viscosity stabilizers, kills Rating agents, buffers, lower alcohols, and the like. In addition, a whitening agent, a moisturizing agent, vitamins, sunscreens, perfumes, dyes, antibiotics, antibacterial agents, antifungal agents may be included as necessary. The oil may be hydrogenated vegetable oil, castor oil, cottonseed oil, olive oil, palm oil, jojoba oil, avocado oil, wax, wax, carnauba, candelilla, montan, ceresin, liquid paraffin, lanolin Can be used. Stearic acid, linoleic acid, linolenic acid, oleic acid may be used as the fatty acid, and cetyl alcohol, octyldodecanol, oleyl alcohol, pantenol, lanolin alcohol, stearyl alcohol, hexadecanol may be used as fatty acid alcohol. And isopropyl myristate, isopropyl palmitate, butyl stearate may be used as the fatty acid ester. As surfactants, cationic surfactants, anionic surfactants and nonionic surfactants known in the art can be used, and surfactants derived from natural products are preferred as much as possible. In addition, it may include a hygroscopic agent, a thickener, an antioxidant, and the like, which are widely known in the cosmetic field, and their types and amounts are known in the art.
본 발명의 일 구체예에서, (a) 플라즈마 발생 장치에 캐리어 가스를 충진하는 단계; (b) 상기 플라즈마 발생 장치에 0.5kV 내지 20kV의 전압 및 10 내지 30kHz의 주파수를 공급하여 플라즈마를 발생시키는 단계; 및 (c) 상기 발생된 플라즈마를 액상 물질에 조사하는 단계를 포함하는 액상 플라즈마의 제조 방법을 제공하고, 상기 (a) 단계에서의 캐리어 가스는 질소, 헬륨, 아르곤, 및 산소로 구성되는 그룹으로부터 선택되는 어느 하나 이상인 것을 특징으로 하는 액상 플라즈마의 제조 방법을 제공하며, 상기 (c) 단계에서의 액상 물질은 물, 식염수, 완충액, 또는 배지인 액상 플라즈마의 제조 방법을 제공한다.In one embodiment of the present invention, (a) filling the plasma generating apparatus with a carrier gas; (b) generating a plasma by supplying a voltage of 0.5 kV to 20 kV and a frequency of 10 to 30 kHz to the plasma generator; And (c) irradiating the generated plasma to a liquid material, wherein the carrier gas in step (a) is selected from the group consisting of nitrogen, helium, argon, and oxygen. It provides a method for producing a liquid plasma, characterized in that any one or more selected, the liquid material in the step (c) provides a method for producing a liquid plasma which is water, saline, buffer, or medium.
본 발명의 다른 구체예에서, 상기 중 어느 하나 이상의 방법으로 제조된 액상 플라즈마를 포함하는 액상 플라즈마 조성물을 제공한다.In another embodiment of the present invention, there is provided a liquid plasma composition comprising a liquid plasma prepared by any one or more of the above methods.
본 발명의 또 다른 구체예에서, 상기의 액상 플라즈마 조성물을 유효성분으로 포함하는 피부 색소 침착 질환의 예방 또는 치료용 약학조성물을 제공하고, 상기 피부 색소 침착 질환은 기미, 주근깨, 흑색점, 모반, 약물에 의한 색소 침착, 염증 후 색소 침착, 및 피부염에서 발생하는 과색소 침착으로 구성되는 그룹으로부터 선택되는 어느 하나 이상인 것을 특징으로 하는 피부 색소 침착 질환의 예방 또는 치료용 약학조성물을 제공한다.In another embodiment of the present invention, there is provided a pharmaceutical composition for the prevention or treatment of skin pigmentation disease comprising the liquid plasma composition as an active ingredient, wherein the skin pigmentation disease is spots, freckles, black spots, birthmarks, It provides a pharmaceutical composition for the prevention or treatment of skin pigmentation disease, characterized in that any one or more selected from the group consisting of pigmentation by drugs, pigmentation after inflammation, and hyperpigmentation occurring in dermatitis.
본 발명의 또 다른 구체예에서, 상기의 약학조성물을 개체에 투여하는 단계를 포함하는 피부 색소 침착 질환의 예방 또는 치료 방법을 제공하고, 상기 피부 색소 침착 질환은 기미, 주근깨, 흑색점, 모반, 약물에 의한 색소 침착, 염증 후 색소 침착, 및 피부염에서 발생하는 과색소 침착으로 구성되는 그룹으로부터 선택되는 어느 하나 이상인 것을 특징으로 하는 피부 색소 침착 질환의 예방 또는 치료 방법을 제공한다.In another embodiment of the present invention, there is provided a method for preventing or treating skin pigmentation disease, comprising administering the pharmaceutical composition to an individual, wherein the skin pigmentation disease is a blemish, freckles, black spots, birthmarks, It provides a method for preventing or treating skin pigmentation disease, characterized in that any one or more selected from the group consisting of pigmentation by drugs, pigmentation after inflammation, and hyperpigmentation occurring in dermatitis.
본 발명의 또 다른 구체예에서, 상기 약학조성물의 피부 색소 침착 질환의 예방 또는 치료 용도를 제공한다.In another embodiment of the present invention, there is provided a use of the pharmaceutical composition for the prevention or treatment of skin pigmentation disease.
본 발명의 또 다른 구체예에서, 상기 액상 플라즈마 조성물을 유효성분으로 포함하는 피부 미백용 화장료 조성물을 제공한다.In another embodiment of the present invention, it provides a cosmetic composition for skin whitening comprising the liquid plasma composition as an active ingredient.
본 발명의 또 다른 구체예에서, 상기 액상 플라즈마 조성물을 유효성분으로 포함하는 상처 치료용 약학조성물을 제공하고, 상기 약학조성물은 성장인자를 추가로 포함하는 상처 치료용 약학조성물을 제공하며, 상기 성장인자는 상피세포 성장인자(EGF), 혈소판 유래 성장인자-AA(PDGF-AA), 인슐린 유사 성장인자-1(IGF-1), 형질 전환 성장인자-β(TGF-β) 또는 섬유아세포 성장인자(FGF)인 것인 상처 치료용 약학조성물을 제공하며, 상기 상처는 자상, 박피, 발진, 염증, 궤양, 또는 스크레치에 의한 피부 손상인 상처 치료용 약학조성물을 제공한다.In another embodiment of the present invention, to provide a pharmaceutical composition for wound treatment comprising the liquid plasma composition as an active ingredient, the pharmaceutical composition provides a pharmaceutical composition for wound treatment further comprising a growth factor, the growth Factors include epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA), insulin-like growth factor-1 (IGF-1), transforming growth factor-β (TGF-β) or fibroblast growth factor It provides a pharmaceutical composition for treating wounds (FGF), wherein the wound provides a pharmaceutical composition for treating wounds that is skin damage caused by cuts, peels, rashes, inflammations, ulcers, or scratches.
본 발명의 또 다른 구체예에서, 상기의 약학조성물을 개체에 투여하는 단계를 포함하는 상처 치료 방법을 제공하고, 상기 상처는 자상, 박피, 발진, 염증, 궤양, 또는 스크레치에 의한 피부 손상인 상처 치료 방법을 제공한다.In another embodiment of the present invention, there is provided a wound treatment method comprising administering the pharmaceutical composition to a subject, wherein the wound is a wound that is skin damage caused by cuts, peels, rashes, inflammations, ulcers, or scratches. Provide a method of treatment.
본 발명의 또 다른 구체예에서, 상기 약학조성물의 상처 치료 용도를 제공한다.In another embodiment of the present invention, there is provided a wound treatment use of the pharmaceutical composition.
본 발명의 또 다른 구체예에서, 상기 액상 플라즈마 조성물을 유효성분으로 포함하는 상처 치료용 의약외품 조성물을 제공하고, 상기 조성물은 성장인자를 추가로 포함하는 상처 치료용 의약외품 조성물을 제공하며, 상기 성장인자는 상피세포 성장인자(EGF), 혈소판 유래 성장인자-AA(PDGF-AA), 인슐린 유사 성장인자-1(IGF-1), 형질 전환 성장인자-β(TGF-β) 또는 섬유아세포 성장인자(FGF)인 것인 상처 치료용 의약외품 조성물을 제공한다.In another embodiment of the present invention, to provide a quasi-drug composition for wound treatment comprising the liquid plasma composition as an active ingredient, the composition provides a quasi-drug composition for wound treatment further comprising a growth factor, the growth factor Epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA), insulin-like growth factor-1 (IGF-1), transforming growth factor-β (TGF-β) or fibroblast growth factor ( FGF) provides a quasi-drug composition for wound treatment.
이하 상기 본 발명을 단계별로 상세히 설명한다.Hereinafter, the present invention will be described in detail step by step.
본 발명에 따른 액상 플라즈마를 포함하는 피부 미백용 화장료 조성물, 색소 침착 질환의 치료 또는 예방용 조성물은 뛰어난 티로시나아제 활성을 저해 효과 및 멜라닌 생합성을 억제효과를 나타내므로 미백용 화장료 조성물, 피부 색소 침착 질환의 치료 또는 예방용 약제학적 조성물로 유용하게 이용될 수 있을 것으로 기대된다. 또한 본 발명에 따른 액상 플라즈마 및 성장인자를 포함하는 조성물은 섬유아세포의 재생을 촉진시킬 수 있다. 따라서, 본 발명에 따른 액상 플라즈마 및 성장인자를 포함하는 조성물은 상처의 치유를 촉진시킬 수 있을 것으로 기대된다. Cosmetic composition for skin whitening comprising a liquid plasma according to the present invention, the composition for the treatment or prevention of pigmentation diseases shows an excellent inhibitory effect on tyrosinase activity and melanin biosynthesis, whitening cosmetic composition, skin pigmentation It is expected to be usefully used as a pharmaceutical composition for the treatment or prevention of diseases. In addition, the composition comprising a liquid plasma and a growth factor according to the present invention can promote the regeneration of fibroblasts. Therefore, it is expected that the composition comprising the liquid plasma and the growth factor according to the present invention can promote the healing of wounds.
도 1a 와 도 1b 는 본 발명에 따른 액상 플라즈마(NTS)의 제조방법을 나타낸 도면이다.1A and 1B illustrate a method of manufacturing a liquid plasma (NTS) according to the present invention.
도 2는 본 발명에 따른 액상 플라즈마의 Zebrafish에서의 색소 형성 억제 효과를 나타낸다. Figure 2 shows the pigment formation inhibitory effect of the liquid plasma according to the present invention in Zebrafish.
도 3은 본 발명에 따른 액상 플라즈마의 Human Tissue skin에서의 색소 형성 억제 효과를 나타낸다. Figure 3 shows the pigmentation inhibitory effect in the human tissue skin of the liquid plasma according to the present invention.
도 4a 와 도 4b 는 본 발명에 따른 액상 플라즈마의 Human Tissue skin에서 티로시나아제 활성 억제 효과를 나타낸다. 4a and 4b show the effect of inhibiting tyrosinase activity in the human tissue skin of liquid plasma according to the present invention.
도 5는 본 발명에 따른 액상 플라즈마의 Melanocyte에서 독성 효과 검증 결과를 나타낸다. Figure 5 shows the results of the toxicity effect in the Melanocyte of the liquid plasma according to the present invention.
도 6a 와 도 6b 는 본 발명에 따른 액상 플라즈마의 Human melanocyte에서 Melanogenesis marker 감소 효과를 나타낸다.6a and 6b show the effect of reducing the Melanogenesis marker in the human melanocyte of the liquid plasma according to the present invention.
도 7은 본 발명에 따른 액상 플라즈마의 상처 치료 효과를 나타낸다.Figure 7 shows the wound healing effect of the liquid plasma according to the present invention.
도 8은 본 발명에 따른 액상 플라즈마의 cytotoxicity 효과를 나타낸다.Figure 8 shows the cytotoxicity effect of the liquid plasma according to the present invention.
Human foreskin tissue를 Transwell(DMEM high glucose + 4% FBS)에서 culture한 후, 액상 플라즈마를 1min/1ml로 처리하였다. 3일간 배양한 후 고정하여 Fontana-masson stain을 통해 색소 형성 정도를 관찰한 결과, 액상 플라즈마로 처리된 Human Tissue skin에서 대조군에 비해 epidermal의 염색이 옅게 나타남이 확인되었다. Human foreskin tissue was cultured in Transwell (DMEM high glucose + 4% FBS), and the liquid plasma was treated with 1min / 1ml. After incubation for 3 days, the fixation was observed through Fontana-masson staining. As a result, it was confirmed that the epidermal stain was lighter than that of the control group in the liquid plasma treated Human Tissue skin.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로서, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .
실시예Example 1. 액상  1. Liquid 플라즈마의Plasma 제조 Produce
실시예Example 1-1. 액상  1-1. Liquid 플라즈마(NTS)의Of plasma (NTS) 제조 Produce
배지로서 F12(10% FBS 24ug/ml 3-isobutyl-1-methylxanthine, 80nM 12-O-tetradecanoyl Phorbor 13-acetate(TPA), 1.2g/ml bFGF, 0.1ug/ml cholera toxin)를 각각 10ml을 용기에 담고, 헬륨과 산소를 캐리어 가스로 이용하여 플라즈마를 4KV의 세기로 배지로부터 1cm 의 거리를 두고 ml당 1분의 조건으로 처리 액상 플라즈마("플라즈마 처리된 배지")를 완성하였다. 상기 액상 플라즈마의 제조방법을 도 1(a)에 나타내었다.10 ml each of F12 (10% FBS 24ug / ml 3-isobutyl-1-methylxanthine, 80nM 12-O-tetradecanoyl Phorbor 13-acetate (TPA), 1.2g / ml bFGF, 0.1ug / ml cholera toxin) The plasma was subjected to a treatment liquid plasma (“plasma treated medium”) at a condition of 1 minute per ml at a distance of 1 cm from the medium at 4 KV intensity using helium and oxygen as the carrier gas. The method of manufacturing the liquid plasma is shown in FIG.
실시예Example 1-2. 액상  1-2. Liquid 플라즈마plasma (( NTSNTS ) 및 성장인자를 포함하는 조성물의 제조) And the growth factor comprising the growth factor
본 발명에 따른 액상 플라즈마와 성장인자의 상처 치료에 미치는 효과를 알아보기 위하여, 배지로서 DMEM High Glucose + 10 % FBS 및 성장인자로서 EGF를 이용하여 섬유아세포에서 세포 이동(cell migration) 효과를 평가하였다. 우선 전압 15kV 및 주파수 15kHz의 전원이 공급되고 캐리어 가스로는 질소 가스를 이용하는 플라즈마 발생장치를 이용하여 상기 배지에 플라즈마를 처리하여 액상 플라즈마("플라즈마 처리된 배지")를 완성하였다. 상기 액상 플라즈마의 제조방법을 도 1(b)에 나타내었다.In order to examine the effect of liquid plasma and growth factor on wound healing according to the present invention, the effect of cell migration in fibroblasts was evaluated using DMEM High Glucose + 10% FBS as a medium and EGF as a growth factor. . First, power was supplied at a voltage of 15 kV and a frequency of 15 kHz, and the plasma was treated with a plasma generator using nitrogen gas as a carrier gas to complete a liquid plasma (“plasma treated medium”). The method of manufacturing the liquid plasma is shown in FIG. 1 (b).
실시예Example 2. 액상  2. Liquid 플라즈마의Plasma 피부 미백 효과 확인 Check the skin whitening effect
실시예Example 2-1.  2-1. Zebrafish에서의Zebrafish 색소 형성 억제 효과 Pigmentation inhibitory effect
제브라 피쉬 암수로부터 채취한 수정란을 제브라피쉬 수정란 배양배지 (Egg water, 0.2 g sea slat/ L)에 넣고 24시간 발생 시킨 후, 실시예 1에서 제조한 액상 플라즈마를 처리하였다. 샘플 처리 시 코리온(chorion)의 샘플 투과 정도를 증가 시키기 위해 수정란의 코리온을 핀셋으로 구멍을 내어 처리 하였고, 샘플 처리 후 24시간 이후 샘플의 독성이 나타난 수정란은 제거 하고, 나머지 수정란의 코리온을 완전 제거 후 다시 동일 농도의 샘플을 처리 하였다. 샘플 처리 48 시간 이후에 대조군 대비 샘플 처리군의 색소 발생 정도를 Stereo　현미경으로 관찰하여 확인하고, 그 결과를 도 2에 나타내었다. The fertilized eggs collected from zebrafish male and female were put into zebrafish fertilized egg culture medium (Egg water, 0.2 g sea slat / L) and generated for 24 hours, and then the liquid plasma prepared in Example 1 was treated. In order to increase the degree of permeation of the corion, the fertilized egg corion was punched out with tweezers, and the fertilized egg showing the toxicity of the sample was removed after 24 hours. After complete removal, the samples of the same concentration were processed again. After 48 hours of sample treatment, the degree of pigmentation of the sample treated group compared to the control group was observed by a stereo microscope and confirmed, and the results are shown in FIG. 2.
도 2를 참고하면 액상 플라즈마로 처리된 제브라 피쉬의 경우 대조군에 비해 색소의 형성이 억제됨이 확인되었다. Referring to FIG. 2, zebra fish treated with liquid plasma were found to inhibit the formation of pigments compared to the control.
실시예Example 2-2. Human Tissue skin에서의 색소 형성 억제 효과 2-2. Inhibitory Effect of Pigmentation on Human Tissue Skin
Human foreskin tissue를 Transwell(DMEM high glucose + 4% FBS)에서 culture한 후, 실시예 1에서 제조된 액상 플라즈마를 1min/1ml로 처리하였다. 3일간 배양한 후 고정하여 Fontana-masson stain을 통해 색소 형성 정도를 관찰하고, 그 결과를 도 3에 나타내었다. After incubating human foreskin tissue in Transwell (DMEM high glucose + 4% FBS), the liquid plasma prepared in Example 1 was treated with 1min / 1ml. After culturing for 3 days and fixed, the degree of pigment formation was observed through Fontana-masson stain, and the results are shown in FIG. 3.
도 3을 참고하면 액상 플라즈마로 처리된 Human Tissue skin에서 대조군에 비해 epidermal의 염색이 옅게 나타남이 확인되었다. Referring to FIG. 3, it was confirmed that epidermal staining was lighter than that of the control group in the human plasma tissue treated with liquid plasma.
실시예Example 2-3. Human Tissue skin에서 티로시나아제 활성 억제 효과 2-3. Inhibitory Effect of Tyrosinase Activity on Human Tissue Skin
Human foreskin sample을 60mm dish에 2X106으로 seeding 한 후, 실시예 1에서 제조된 액상 플라즈마 1min/1ml로 처리하였다. 24시간 배양후 고정하여 Western blot, PCR, tyrosinase의 활성도 및 melanin content를 측정하고, 그 결과를 도 4a 와 도 4b 에 나타내었다. The human foreskin sample was seeded with 2 × 10 6 in a 60 mm dish, and then treated with 1 min / 1 ml of the liquid plasma prepared in Example 1. After 24 hours of incubation and fixation, Western blot, PCR, tyrosinase activity and melanin content were measured, and the results are shown in FIGS. 4A and 4B.
도 4로부터 알 수 있듯이 액상 플라즈마로 처리된 Human Tissue skin에서 tyrosinase 및 MITF, melanin content 가 유의성 있게 감소함이 확인되었다. As can be seen from Figure 4 it was confirmed that the tyrosinase and MITF, melanin content significantly reduced in the human Tissue skin treated with liquid plasma.
실시예Example 2-4.  2-4. Melanocyte에서In melanocyte 독성 효과 검증 Toxic effect verification
Human melanocyte에 실시예 1에서 제조한 액상 플라즈마를 처리후 시간별로 세포독성을 확인하여 그 결과를 도 5에 나타내었다. After treating the liquid plasma prepared in Example 1 to the human melanocyte, the cytotoxicity was confirmed by time, and the results are shown in FIG. 5.
도 5로부터 알 수 있듯이 본 발명에 따른 액상 플라즈마는 human melanocyte에서 독성을 나타내지 않는 것을 확인되었다. As can be seen from Figure 5 it was confirmed that the liquid plasma according to the present invention does not exhibit toxicity in human melanocyte.
실시예Example 2-5. Human  2-5. Human melanocyte에서in melanocyte MelanogenesisMelanogenesis marker 감소 효과 marker reduction effect
Human melanocyte에 실시예 1에서 제조한 액상 플라즈마를 처리후, 시간별로 Melanogenesis marker들의 감소효과를 확인하여 그 결과를 도 6a 와 도 6b 에 나타내었다.After treating the liquid plasma prepared in Example 1 to the human melanocyte, the effect of reducing the Melanogenesis markers was confirmed by time, and the results are shown in FIGS. 6A and 6B.
도 6에서 알 수 있듯이 본 발명에 따른 액상 플라즈마는 human melanocyte에서 melanogenesis marker들을 감소시키는 것이 확인되었고, 이는 protein level 뿐만 아니라 Tyrosinase의 RNA Level 또한 감소시키는 것을 확인하였다.As can be seen in Figure 6, the liquid plasma according to the present invention was confirmed to reduce melanogenesis markers in human melanocyte, which was confirmed to reduce the RNA level of Tyrosinase as well as protein level.
실시예Example 3. 액상  3. Liquid 플라즈마의Plasma 상처 치료 효과 확인 Check the effect of wound healing
실시예Example 3-1. 상처 치료 효과 확인 3-1. Check the effect of wound healing
상기 실시예 1에서 제조된 액상 플라즈마에 EGF를 각각 10ng/ml 및 30ng/ml 양으로 pretreat 하고, 사람 유래의 섬유아세포(Fibroblast) 세포주(1X105 cell)를 seeding하여 1시간 후에 세포 이동 결과를 wound healing assay로 평가하였다. 한편, 비교예로서 액상 플라즈마 및 EGF 각각에 섬유아세포를 seeding한 후 세포 이동을 확인하였다. 그 결과를 도 7에 나타내었다. Pretreat EGF in amounts of 10 ng / ml and 30 ng / ml, respectively, in the liquid plasma prepared in Example 1, and seed the human-derived fibroblast cell line (1 × 10 5 cells) to wound the cell migration result after 1 hour. It was evaluated by a healing assay. On the other hand, as a comparative example, after seeding the fibroblasts in each of the liquid plasma and EGF, cell migration was confirmed. The results are shown in FIG.
도 7을 참고하면, 비교예로서 액상 플라즈마만을 단독 처리한 군에서는 상처 치료 효과가 나타나지 않았지만, EGF만을 단독 처리한 군에서는 상처 치료 효과가 확인되었다. 액상 플라즈마 및 EGF를 모두 처리한 군에서는 EGF만을 단독 처리하였을 때보다 현저한 상처 치료 효과가 확인되었다. Referring to FIG. 7, as a comparative example, the wound treatment effect did not appear in the group treated with liquid plasma alone, but the wound treatment effect was confirmed in the group treated with EGF alone. In the group treated with both liquid plasma and EGF, a significant wound healing effect was observed than when treated with EGF alone.
실시예Example 3-2.  3-2. cytotoxicitycytotoxicity 확인 Confirm
본 발명에 따른 액상 플라즈마 및 EGF를 포함하는 조성물이 섬유아세포에 cytotoxicity를 나타내는지 알아보기 위하여 cell viability 결과를 MTT로 확인하였다. 그 결과를 도 8에 나타내었다. In order to determine whether the composition comprising the liquid plasma and EGF according to the present invention exhibits cytotoxicity in fibroblasts, the cell viability result was confirmed by MTT. The results are shown in FIG.
도 8을 참고하면, 본 발명에 따른 조성물이 섬유아세포 cytotoxicity는 없는 것으로 확인되었다. Referring to Figure 8, the composition according to the present invention was confirmed that there is no fibroblast cytotoxicity.
이제까지 본 발명에 대하여 그 바람직한 실시예들을 중심으로 살펴보았다. 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자는 본 발명이 본 발명의 본질적인 특성에서 벗어나지 않는 범위에서 변형된 형태로 구현될 수 있음을 이해할 수 있을 것이다. 그러므로 개시된 실시예들은 한정적인 관점이 아니라 설명적인 관점에서 고려되어야 한다. 본 발명의 범위는 전술한 설명이 아니라 특허청구범위에 나타나 있으며, 그와 동등한 범위 내에 있는 모든 차이점은 본 발명에 포함된 것으로 해석되어야 할 것이다.So far I looked at the center of the preferred embodiment for the present invention. Those skilled in the art will appreciate that the present invention can be implemented in a modified form without departing from the essential features of the present invention. Therefore, the disclosed embodiments should be considered in descriptive sense only and not for purposes of limitation. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the scope will be construed as being included in the present invention.
본 발명은 액상 플라즈마를 유효성분으로 함유하는 조성물은 피부 미백, 및 피부 색소 침착 질환의 치료 또는 예방 효과가 우수하다.The composition containing the liquid plasma as an active ingredient is excellent in the skin whitening and skin pigmentation disease treatment or prevention effect.
또한 본 발명의 액상 플라즈마 및 성장인자를 포함하는 조성물은 섬유아세포의 증식을 유도함으로써 상처 치료 효능이 뛰어나, 상처 치료를 위한 피부 외용제를 비롯한 의약품 등에 적용되어 유용하게 사용될 수 있을 것이다.In addition, the composition comprising the liquid plasma and growth factors of the present invention is excellent in wound healing by inducing proliferation of fibroblasts, and may be usefully applied to medicines including skin external preparations for wound treatment.

Claims (20)

  1. (a) 플라즈마 발생 장치에 캐리어 가스를 충진하는 단계;(a) filling a carrier gas into a plasma generating device;
    (b) 상기 플라즈마 발생 장치에 0.5kV 내지 20kV의 전압 및 10 내지 30kHz의 주파수를 공급하여 플라즈마를 발생시키는 단계; 및(b) generating a plasma by supplying a voltage of 0.5 kV to 20 kV and a frequency of 10 to 30 kHz to the plasma generator; And
    (c) 상기 발생된 플라즈마를 액상 물질에 조사하는 단계를 포함하는, 액상 플라즈마의 제조 방법.(c) irradiating the generated plasma to a liquid material.
  2. 제 1항에 있어서, The method of claim 1,
    상기 (a) 단계에서의 캐리어 가스는 질소, 헬륨, 아르곤, 및 산소로 구성되는 그룹으로부터 선택되는 어느 하나 이상인 것을 특징으로 하는, 액상 플라즈마의 제조 방법.The carrier gas in the step (a) is any one or more selected from the group consisting of nitrogen, helium, argon, and oxygen, the method of producing a liquid plasma.
  3. 제 1항에 있어서, The method of claim 1,
    상기 (c) 단계에서의 액상 물질은 물, 식염수, 완충액, 또는 배지인, 액상 플라즈마의 제조 방법.The liquid material in the step (c) is water, saline, buffer, or medium, the method of producing a liquid plasma.
  4. 제 1항 내지 제 3항 중 어느 하나 이상의 방법으로 제조된 액상 플라즈마를 포함하는, 액상 플라즈마 조성물.A liquid plasma composition comprising a liquid plasma prepared by at least one method of claim 1.
  5. 제 4항의 액상 플라즈마 조성물을 유효성분으로 포함하는, 피부 색소 침착 질환의 예방 또는 치료용 약학조성물.A pharmaceutical composition for preventing or treating skin pigmentation disease, comprising the liquid plasma composition of claim 4 as an active ingredient.
  6. 제 5항에 있어서, The method of claim 5,
    상기 피부 색소 침착 질환은 기미, 주근깨, 흑색점, 모반, 약물에 의한 색소 침착, 염증 후 색소 침착, 및 피부염에서 발생하는 과색소 침착으로 구성되는 그룹으로부터 선택되는 어느 하나 이상인 것을 특징으로 하는, 피부 색소 침착 질환의 예방 또는 치료용 약학조성물.The skin pigmentation disease is any one or more selected from the group consisting of blemishes, freckles, black spots, birthmarks, pigmentation by drugs, pigmentation after inflammation, and hyperpigmentation occurring in dermatitis Pharmaceutical compositions for the prevention or treatment of pigmentation diseases.
  7. 제 5항의 약학조성물을 개체에 투여하는 단계를 포함하는, 피부 색소 침착 질환의 예방 또는 치료 방법.A method of preventing or treating skin pigmentation disorders comprising administering the pharmaceutical composition of claim 5 to an individual.
  8. 제 7항에 있어서,The method of claim 7, wherein
    상기 피부 색소 침착 질환은 기미, 주근깨, 흑색점, 모반, 약물에 의한 색소 침착, 염증 후 색소 침착, 및 피부염에서 발생하는 과색소 침착으로 구성되는 그룹으로부터 선택되는 어느 하나 이상인 것을 특징으로 하는, 피부 색소 침착 질환의 예방 또는 치료 방법.The skin pigmentation disease is any one or more selected from the group consisting of blemishes, freckles, black spots, birthmarks, pigmentation by drugs, pigmentation after inflammation, and hyperpigmentation occurring in dermatitis Method of preventing or treating pigmentation disease.
  9. 제 5항의 약학조성물의 피부 색소 침착 질환의 예방 또는 치료 용도.Use of the pharmaceutical composition of claim 5 for the prevention or treatment of skin pigmentation diseases.
  10. 제 4항의 액상 플라즈마 조성물을 유효성분으로 포함하는, 피부 미백용 화장료 조성물.A cosmetic composition for skin whitening comprising the liquid plasma composition of claim 4 as an active ingredient.
  11. 제 4항의 액상 플라즈마 조성물을 유효성분으로 포함하는, 상처 치료용 약학조성물.The pharmaceutical composition for wound treatment, comprising the liquid plasma composition of claim 4 as an active ingredient.
  12. 제 11항에 있어서,The method of claim 11,
    상기 약학조성물은 성장인자를 추가로 포함하는, 상처 치료용 약학조성물.The pharmaceutical composition further comprises a growth factor, pharmaceutical composition for wound treatment.
  13. 제 12항에 있어서,The method of claim 12,
    상기 성장인자는 상피세포 성장인자(EGF), 혈소판 유래 성장인자-AA(PDGF-AA), 인슐린 유사 성장인자-1(IGF-1), 형질 전환 성장인자-β(TGF-β) 또는 섬유아세포 성장인자(FGF)인 것인, 상처 치료용 약학조성물.The growth factor is epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA), insulin-like growth factor-1 (IGF-1), transforming growth factor-β (TGF-β) or fibroblasts Growth factor (FGF), wound pharmaceutical composition for treatment.
  14. 제 11항에 있어서,The method of claim 11,
    상기 상처는 자상, 박피, 발진, 염증, 궤양, 또는 스크레치에 의한 피부 손상인, 상처 치료용 약학조성물.The wound is wound, skin peeling, rash, inflammation, ulcers, or damage to the skin by scratch, pharmaceutical composition for wound treatment.
  15. 제 11항의 약학조성물을 개체에 투여하는 단계를 포함하는, 상처 치료 방법.A method of treating wounds, comprising administering the pharmaceutical composition of claim 11 to a subject.
  16. 제 15항에 있어서,The method of claim 15,
    상기 상처는 자상, 박피, 발진, 염증, 궤양, 또는 스크레치에 의한 피부 손상인, 상처 치료 방법.And the wound is skin damage by cuts, peels, rashes, inflammation, ulcers, or scratches.
  17. 제 11항의 약학조성물의 상처 치료 용도.Use of the pharmaceutical composition of claim 11 for wound healing.
  18. 제 4항의 액상 플라즈마 조성물을 유효성분으로 포함하는, 상처 치료용 의약외품 조성물.The quasi-drug composition for wound treatment comprising the liquid plasma composition of claim 4 as an active ingredient.
  19. 제 18항에 있어서,The method of claim 18,
    상기 조성물은 성장인자를 추가로 포함하는, 상처 치료용 의약외품 조성물.The composition further comprises a growth factor, the quasi-drug composition for wound treatment.
  20. 제 19항에 있어서,The method of claim 19,
    상기 성장인자는 상피세포 성장인자(EGF), 혈소판 유래 성장인자-AA(PDGF-AA), 인슐린 유사 성장인자-1(IGF-1), 형질 전환 성장인자-β(TGF-β) 또는 섬유아세포 성장인자(FGF)인 것인, 상처 치료용 의약외품 조성물.The growth factor is epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA), insulin-like growth factor-1 (IGF-1), transforming growth factor-β (TGF-β) or fibroblasts It is a growth factor (FGF), the quasi-drug composition for wound treatment.
PCT/KR2017/012771 2016-11-25 2017-11-13 Composition for skin whitening or wound treatment, containing liquid plasma WO2018097527A1 (en)

Priority Applications (1)

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KR20160158678 2016-11-25
KR10-2016-0158673 2016-11-25
KR20160158673 2016-11-25
KR10-2016-0158678 2016-11-25
KR10-2017-0110760 2017-08-31
KR10-2017-0110761 2017-08-31
KR1020170110760A KR101979105B1 (en) 2016-11-25 2017-08-31 Composition for skin-whitening comprising non thermal plasma treated solution
KR1020170110761A KR102006784B1 (en) 2016-11-25 2017-08-31 Composition for treating wound comprising non thermal plasma treated solution

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101101321B1 (en) * 2008-11-03 2012-01-02 주식회사 엠씨티티 cell delivery vehicle composition having a hydrogel form for healing wounds
JP2014212839A (en) * 2013-04-23 2014-11-17 沖野　晃俊 Method for caring biological cells and epidermis and the like using atmospheric pressure plasma, and device for caring biological cells and epidermis and the like using atmospheric pressure plasma
WO2015191843A1 (en) * 2014-06-13 2015-12-17 Advanced Plasma Therapies, Inc. Veterinary methods for using nitric oxide in a plasma state to treat medical conditions and diseases in animals
KR101635718B1 (en) * 2016-01-29 2016-07-01 김민기 Apparatus for hairdressing and beautycare using plasma
KR101657063B1 (en) * 2015-04-09 2016-09-13 아주대학교산학협력단 Liquid type plasma for preventing and treating of cancer

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Publication number Priority date Publication date Assignee Title
KR101101321B1 (en) * 2008-11-03 2012-01-02 주식회사 엠씨티티 cell delivery vehicle composition having a hydrogel form for healing wounds
JP2014212839A (en) * 2013-04-23 2014-11-17 沖野　晃俊 Method for caring biological cells and epidermis and the like using atmospheric pressure plasma, and device for caring biological cells and epidermis and the like using atmospheric pressure plasma
WO2015191843A1 (en) * 2014-06-13 2015-12-17 Advanced Plasma Therapies, Inc. Veterinary methods for using nitric oxide in a plasma state to treat medical conditions and diseases in animals
KR101657063B1 (en) * 2015-04-09 2016-09-13 아주대학교산학협력단 Liquid type plasma for preventing and treating of cancer
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