CN110177541A - For preventing the external member and cosmetic system of skin aging - Google Patents

For preventing the external member and cosmetic system of skin aging Download PDF

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Publication number
CN110177541A
CN110177541A CN201880005071.7A CN201880005071A CN110177541A CN 110177541 A CN110177541 A CN 110177541A CN 201880005071 A CN201880005071 A CN 201880005071A CN 110177541 A CN110177541 A CN 110177541A
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skin
laser
composition
treatment
external member
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孙维那
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Priority claimed from PCT/KR2018/001019 external-priority patent/WO2018139835A1/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9789Magnoliopsida [dicotyledons]
    • AHUMAN NECESSITIES
    • A45HAND OR TRAVELLING ARTICLES
    • A45DHAIRDRESSING OR SHAVING EQUIPMENT; EQUIPMENT FOR COSMETICS OR COSMETIC TREATMENTS, e.g. FOR MANICURING OR PEDICURING
    • A45D44/00Other cosmetic or toiletry articles, e.g. for hairdressers' rooms
    • A45D44/02Furniture or other equipment specially adapted for hairdressers' rooms and not covered elsewhere
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/42Amides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/66Enzymes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/02Preparations for care of the skin for chemically bleaching or whitening the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/81Preparation or application process involves irradiation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/91Injection

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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Biophysics (AREA)
  • Cosmetics (AREA)

Abstract

For preventing the external member and cosmetic system of skin aging, it includes telomerase activating composition, dermis of skin irradiation laser, the composition and skin muscular sarcocyte irradiation laser for local fat removal comprising hyaluronidase, and the method for preventing human skin aging using the external member and system.The external member and cosmetic system for preventing skin aging is with resultant effect related with skin aging, although including instantaneous wrinkle improvement, skin repair, elasticity enhancing, wrinkle improvement, local fat removal and skin hydration improvement and the treatment time short lasting holding effect for being up to 1 year to 1.5 years.

Description

For preventing the external member and cosmetic system of skin aging
Technical field
The present invention relates to for preventing the external member and cosmetic system of skin aging comprising telomerase activating composition, skin Skin corium irradiates laser, swashing for the composition of local fat removal and the irradiation of skin muscular sarcocyte comprising hyaluronidase Light device, and the beauty method for preventing human skin aging using the external member and system.
Background technique
Human skin is passed at any time and is constantly changed, and the representative of this variation is the skin as caused by aging Function deteriorates and aesthetics deteriorates.Other than internal abiogenous aging, various environmental factors can also cause aging.Skin aging It is generally divided into Extrinsic aging caused by intrinsic aging as caused by inherent cause and external environmental factor as such as sunlight.
Exogen skin aging leads to the formation of wrinkle on skin.The typical factor for causing wrinkle includes fat accumulation, skin Lower muscle loss, active oxygen, ultraviolet light, collagenous biological synthesis reduction etc..That is, external physical or chemical factor, for example, it is high temperature, strong Ultraviolet light, physical abrasion (damage), acidic materials etc. cause the destruction of skin histology, this causes following collagen or bullet again The destruction of property protein structure, gelatin etc., leads to the formation of wrinkle.
Specifically, collagen is generated and is found in main in extracellular matrix by the fibroblast in skin Stromatin is the triple-helix structure for accounting for 30% important albumen of whole body protein by weight, and having firm.It is reported that glue Former major function include keep the compact degree of the machinery of skin, the cohesive force of connective tissue and resistance, the adhesion strength that keeps cell, It divides and breaks up with inducing cell.Known collagen and cumulative exposure are proportionally degraded in the time of ultraviolet light.Therefore, all The denaturation for leading to the collagenous fibres in the accumulation and dermis of skin of elastic material such as the external factor of ultraviolet light causes to wrinkle in skin The formation of line and the reduction of elasticity.
Although being difficult to adjust endogenous skin aging by manual method, the exogen skin compared with endogenous skin aging Skin aging is easier to control, such as removal active oxygen, proliferation fibroblast and stimulation collagenous biological synthesis etc..With to wrinkle The research for preventing and treat of line growth, the critical function of collagen is constantly identified in skin.Studies have shown that when passing through thorn Swash the collagen in skin to generate come when increasing collagenic supersession, dermal matrix ingredient increases, causes wrinkle to improve, elasticity enhancing, skin The compact equal such effect of skin.Emerging evaluation of wrinkle treatment include ultrasonic therapy, skin descale, laser lift-off, meat poisoning bar Verticillium toxin injection etc..However, they are still unsatisfactory with regard to therapeutic effect and for the duration.
The endogenous skin aging of genetic determination may due to chromosome damage or Skin Cell loss and occur.Especially Ground, due to fissional DNA replication dna mechanism, the telomere of end of chromosome plays the hereditary information that buffering shortens form in DNA Loss effect.As every wheel cells divide, chromosome loses the DNA of certain length.It is being more than a certain number of cells point After splitting, telomere becomes too short, eventually leads to cell division termination, subsequent cell death.On the other hand, it was reported that if telomere Remain it is long, then cell have the extended service life, this can be completed by Telomerase.Therefore, to Telomerase as anti- Only the strategy of the hereditary aging of cell is studied.
The prior art
Patent document
(patent document 1) 10-2014-0146074 South Korea patent application (on December 24th, 2014).
Summary of the invention
Technical problem
Present invention seek to address that the above problem.The external member that the object of the present invention is to provide a kind of for preventing skin aging and Cosmetic system is formed using stimulation collagen, stimulates telomerase activation, restored the loss of elasticity due to caused by skin aging, change Kind wrinkle, degrade undesired fat deposit and maintenance skin, and for preventing human skin using the external member and system The beauty method of aging can prevent or delay exogen skin aging and endogenous for preventing skin aging comprehensively Skin aging.The object of the invention is also to provide a kind of with shorter treatment time, the few intercurrent disease after treatment, instantaneous to wrinkle Line improves and the external member and cosmetic system for being used to prevent skin aging of skin repair effect and lasting therapeutic effect, and The beauty method of human skin aging is prevented for using the external member and system.
The present inventor is dedicated to developing a kind of for stimulating telomerase activation, restoring due to skin using stimulating collagen to be formed Loss of elasticity caused by skin aging improves wrinkle, and degrade undesired fat deposit and maintenance skin are prevent skin aging System, and it has been found that of the invention includes telomerase activating composition, dermis of skin irradiation laser, comprising hyaluronidase For local fat removal composition and skin muscular sarcocyte irradiation laser for preventing the external member and beauty of skin aging Appearance system, which has, can prevent or delay exogen skin aging and the comprehensive of endogenous skin aging to prevent skin aging Effect.
The present invention includes composition and the light source (laser) with certain frequency, by it is comprehensive prevent due to it is hereditary because Endogenous skin aging caused by element and the exogen skin aging due to caused by various factors and the skin recovery work for making aging Power prevents skin aging.
In the present invention, preventing skin aging includes that stimulation collagen generates, and induces collagen contraction and collagen remodeling, maintenance by In follow the string and caused by fat accumulation relaxation skin, enhancing skin elasticity and improve wrinkle.Prevent the skin aging from further including The local fat of undesired accumulation is removed or reduced by making the telomerase activating in Skin Cell, in the cell that reduces fat Fat, reduce oedema, prevent or delay endogenous skin aging.Prevent skin aging further include by improve pigmentation come Improve skin hydration, improve skin roughness and improves the colour of skin.That is, preventing skin aging from referring in the present invention, but it is not limited to, Improve or prevent one or more skin aging symptoms listed above.
Solution
Hereinafter, will be explained in detail according to the present invention includes A) telomerase activating composition, B) dermis of skin irradiation Laser, C) composition and D for local fat removal) skin muscular sarcocyte irradiation laser for preventing skin aging External member and cosmetic system and use its treatment method.
※ telomerase activating composition (A)
As used herein, term " Telomerase " refers to the enzyme for keeping telomere length, and the inhereditary material is by seeing chromosome end The repeated nucleotide sequences at end are constituted, for preventing cell ageing.Telomere protects chromosome to contaminate from damage or with other Colour solid fusion, and their length shortens as every wheel cells divide.It is being more than telomere change after a certain number of cell divisions Must be too short, cause cell division to terminate, subsequent cell death.
Therefore, Telomerase is for keeping cell to be in pre- by preventing the loss of cellular genetic material and hereditary information The enzyme of ageing phase.In the present invention, cell ageing, the telomerase activating group are prevented by using telomerase activating composition It closes object activation Telomerase (expression for increasing telomere albumen) and keeps telomere length long.
In the present invention, any composition that can activate Telomerase can be used as telomerase activating composition.This hair Bright telomerase activating composition is characterized in that it increases the table of the subunit protein of Skin Cell middle-end corpuscular protein complex Reach and/or keep the telomere length of chromosome in Skin Cell.
In the present invention, the subunit protein of telomere protein complexes is selected from TRF1 (telomere repetition factor 1), (end TRF2 Grain repetition factor 2), RAP1 (suppressing Activating protein-1), TIN2 (TERF1- interact nuclear factor 2), (telomere protects egg to POT1 It is white 1) and one of TPP1 (three peptidyl peptidases 1) or a variety of.
In one embodiment, telomerase activating composition of the invention includes Dendropanax morbifera Lev. extract, Kappaphycus alvarezii extract or their mixture are as active constituent.Of the invention Dendropanax morbifera Lev. extract or Kappaphycus alvarezii extract can pass through grinding Dendropanax morbifera Lev. bark or Kappaphycus alvarezii, then in solvent (water, C1To C6Alcohol or Organic solvent such as ethyl alcohol, methanol, hexane etc.) in precipitate and with hydrolysis enzymatic treatment with obtain extract prepare, but not limited to this.
In the present invention, telomerase activating composition can be with 0.00001 to 10% (w/w), 0.0001 to 5% (w/w) Or 0.001 to 3% (w/w) amount contain active constituent Dendropanax morbifera Lev. extract or Kappaphycus alvarezii extract.
In the present invention, telomerase activating composition can be used conventional carrier, diluent or excipient such as lubricant, moisten Agent, flavoring agent, emulsifier, suspending agent, preservative, surfactant etc. are prepared.In one embodiment, telomerase activating group Closing object is topical preparation.Specifically, can be formulated as essence, therapeutic agent, serum, lotion, creme, ampoule, lotion or Packaging, but not limited to this.According to its formula, in addition to active constituent Dendropanax morbifera Lev. extract or Except Kappaphycus alvarezii extract, above-mentioned composition also may include commonly used in each formula antioxidant, Stabilizer, solubilizer, vitamin, pigment, fragrance etc..
The example of the carrier, diluent and excipient includes but is not limited to lactose, dextrose, sucrose, D-sorbite, sweet Reveal alcohol, starch, gum arabic, alginate, gelatin, calcium silicates, polyvinylpyrrolidone, cellulose, water, syrup, hydroxyl Yl benzoic acid methyl esters, nipasol, xanthan gum, talcum powder, magnesium stearate, mineral oil etc..
In another embodiment, telomerase activating composition of the invention is cosmetic composition, and can be into One step includes the well-known substance to skin with useful effect in field of cosmetics composition.For example, can also comprise Herba Visci extract, cogongrass rhizome extractive, extract of soybean etc..Each extract of the invention can be through microorganism such as ferment Female or lactobacillus fermentation extract, but not limited to this.
As the preparation embodiment of telomerase activating composition of the invention, preparation contains 0.00056% (w/w's) The ampoule and creme (Tables 1 and 2) of Kappaphycus alvarezii extract.
The amount of telomerase activating composition of the invention to be administered in skin according to skin, composition formula, The variation such as administration time, but can suitably be selected by those skilled in the art.Specifically, the composition of single dose is 3 to 20cc, and And the composition can be applied 1 to 5 time daily as needed.
In the present invention, the application of telomerase activating composition can be with the ultrasonic laser for being 10 to 90Hz with frequency Treatment.Here, adjoint treatment refers to application telomerase activating composition simultaneously or after applying telomerase activating composition It is treated immediately with ultrasonic laser, irradiation continues 5 to 20 minutes.In one embodiment of the invention, inciting somebody to action After 10cc telomerase activating composition is applied to skin, irradiation frequency is ultrasonic laser 10 minutes of 30Hz.
※ dermis of skin irradiates laser (B)
Dermis of skin irradiation laser of the invention is the laser or RF (radio frequency) laser that frequency is 2 to 100Hz, and And it transfers thermal energy to corium or is transferred to corium and SMAS (superficial muscular aponeurotic system).Dermis of skin irradiation of the invention swashs Light device can be one or more lasers.For example, it is selected from, [laser that frequency is 2 to 9Hz], [frequency is 30 to 50Hz Laser] and [RF (35MHz to 45MHz) laser] one or more.
The dermis of skin irradiation laser that for wavelength of the invention be 1064nm and frequency is 2 to 9Hz gos deep into corium simultaneously Transferring heat energy, so that collagen be stimulated to generate.Irradiation time may be, but not limited to, and 1 to 10 minute.
The dermis of skin that frequency used in the present invention is 30 to 50Hz irradiates laser and uses high intensity focused ultrasound (HIFU) laser energy (65 DEG C of thermal energy) is transferred to deep dermis and SMAS.This causes the contraction of subepidermal muscle layer, Cause wrinkle to reduce, and facilitates the generation of collagen and elastin laminin.It is meanwhile if there is excess fat layer, then this Laser facilitates lipolysis.The laser can be operated according to the depth that laser wave reaches with two different modes.One In kind mode, laser wave reaches 3.5mm depth under the surface of the skin and shrinks skin corium, to reduce wrinkle and stimulation collagen It is generated with elastin laminin.In another mode, laser wave reaches 4.5mm depth under the surface of the skin, facilitates fatty in skin The lipolysis of layer.Treatment may include both any one of above two mode or both of which.Irradiation time can divide Wei not be 10 to 40 minutes, but not limited to this.
92W used in the present invention RF laser (35MHz to 45MHz) allow RF wave penetrate dermis of skin/fat deposit, Heat is generated in deep dermis and to which induced tissue is shunk and is recombinated.When laser generates heat in connective tissue, blood stream Dynamic and circulation increases, and causes tissue compact and improved dermatoglyph.The effect of this laser also resides in iuntercellular water and nocuousness Substance is discharged, and contoured skin in irradiation area is caused significantly to be tightened.The laser can irradiate 3 to 10 under monopolar mode Minute, but not limited to this.
The laser of the invention that energy is transmitted to deep dermis can be selected from the laser of above-mentioned three types.It It can be any combination selected from the laser of above-mentioned three types, or swashing for all three types can be used together Light device.
It is 1064nm by wavelength in the of the invention specific embodiment using dermis of skin irradiation laser treatment And frequency is the laser illumination 3 of 5Hz (GentleMax) or 5 minutes, then (laser wave reaches A under the surface of the skin in mode 3.5mm is deep) and Mode B (laser wave reaches 4.5mm depth under the surface of the skin) the indigo laser that irradiation frequency is 30 to 50Hz, divide Do not continue 10 or 20 minutes.Finally, frequency of use is RF laser illumination skin 6 minutes of 40.68MHz.
By to corium or to corium and SMAS transferring heat energy, dermis of skin irradiation laser of the invention can bring with One of lower variation is a variety of:
I) contraction and recombination of dermal tissue;
Ii) the contraction of skin muscular sarcocyte;
Iii) the generation of inducing collagen, elastin laminin or collagen and elastin laminin;
Iv) increase the blood flow and Lymphatic Circulation in skin connective tissue;With
V) water and harmful substance present in skin is discharged.
※ is used for the composition (C) of local fat removal
The composition for local fat removal of every single dose volume of the invention includes the transparent of 300IU to 600IU Matter acid enzyme, and local anesthetic, antihistaminic, lipolysis stimulant and collagen can be further included and generated in stimulant It is one or more.
Hyaluronidase is the water-soluble enzyme from mammal vas deferens or testicular secretion, it is characterised in that it passes through hydrolysis Glucose amine key between a kind of main cytoplasm of hyaluronic acid-and connective tissue is to dissolve the screen between key removal tissue Barrier and the effect for reducing the proliferation of fibrous tissue in tissue.It it is known that hyaluronidase reduces the swelling and oedema in tissue.
Using the characteristic of the substance in hyaluronic acid enzyme hydrolysis and dissolution skin histology, LLD (lipolysis leaching is widely used Ba Yinliu) to treat, wherein hyaluronidase is directly subcutaneously injected with the substance including the fiber in subcutaneous tissue of degrading, thus It is fat to reduce adipose tissue and mitigation to help to drain adipose tissue to promote Lymphatic Circulation.However, although above-mentioned treatment helps In reduction adipose tissue, but due to the hyaluronidase that it uses high dose (2000 to 15000IU), with various side effects It is related.
Cause allergic symptom, such as rubescent or itch, and fat using the existing LLD treatment of high dose hyaluronidase The excessive dissolution of tissue causes due to subcutaneous hemorrhage or bruise caused by being recessed.LLD treatment has the disadvantages that treatment is had to It frequently interrupts to handle these side effects, and repels because patient is due to pain, therefore, it is difficult to continuously be treated.
In addition, making it difficult to reduce the interval (interval about 5cm) between injection point using the hyaluronidase of high dose.Cause This, fat removal is focusing only on around injection point, causes the scrambling and skin of such as impression, relaxation and wrinkle of skin The significant decrease of elasticity, and therefore lead to being discontented with for patient.
After making great efforts to solve the above problems, the inventors discovered that, show that the minimum hyaluronic acid enzyme amount of effect is 300IU, And it was found that being higher than 600IU, fat cell is excessively hydrolyzed, and causes the concern to recess or subcutaneous hemorrhage.Therefore, by incite somebody to action this Hyaluronidase in the injectable composition for local fat removal of the single dose of invention is adjusted to 300IU to 600IU, Make by using the drug bring side effect to minimize, and the smallest volume can be used, fat is carried out to extensive region It removes.
In clinical test it has been shown that under the hyaluronidase activity of 300IU and the volume injected of 1cc, injection group The diameter for closing the range of scatter of object is about 1cm.Therefore, it is combined by being injected between 0.5 to 2cm injection point with narrow interval Object can promote uniform fat removal and be generated by the collagen of skin irritatin.
Most preferably, injectable composition of the invention is injected, is infused every time with giving the hyaluronidase of 300IU to 600IU Penetrate, single dose volume is 0.5 to 2cc, between injection point between be divided into 0.5 to 1.5cm.The daily dose of hyaluronidase is preferably 15,000IU or lower, and single dose volume and injection point can suitably be adjusted according to the IU of hyaluronidase.
Injectable composition of the invention can the 1cc volume injected based on the hyaluronidase containing 300IU between fixation Every injection 50 times, and injection site can be the fatty heap including abdomen, buttocks, thigh, shank, chin, forehead, arm etc. Long-pending any body region.
Injectable composition of the invention can also comprising local anesthetic with mitigate inject caused by pain, antihistaminic with Prevent anaphylaxis side effect, lipolysis stimulant fatty acid into mitochondria and to be degraded from the fatty rapid transport of degradation They and collagen stimulation agent.Therefore, injectable composition prevents allergic symptom for example rubescent or itch and pain and bruise, adds Fast fat removal, and excellently formed by collagen and keep skin elasticity.
It about above-mentioned local anesthetic, can be counted on the basis of the total weight of composition, the injectable composition includes weight It measures the amount that percentage is 0.08 to 0.4% and uses lidocaine.When the amount of local anesthetic is lower than 0.08%, analgesic activity is not It is satisfactory, and when the amount is higher than 0.4%, the duration extension of anesthesia and be uneconomic.
About other compositions, with the amount that weight percent is 0.01 to 0.02% contain antihistaminic skin stretching-sensitive (English: Peniramin, pheniramine), lipolysis stimulant L-carnitine is contained with the amount that weight percent is 0.01 to 4.0%, And collagen is contained with the amount that weight percent is 0.1 to 2.0% and generates stimulant vitamin C.
Composition of the invention can also be in the dosage range that injectable composition allows comprising selected from molten commonly used in injecting One or more substances of tonicity agents, nonionic surfactant, stabilizer, the preservative of liquid etc..Composition of the invention is also The total amount that can be 0.01 to 4.0% with weight percent includes fat-splitting agent such as phosphatidyl choline, aminophylline, caffeine Deng, and improve sanguimotor placental hormone component or pentoxifylline.
It is the case where for wherein giving the hyaluronidase of 300IU with the expectation daily dose of 15,000IU, respective at its The amount of mentioned component in preparation is determined in maximum daily dose.
In an embodiment of the injectable composition for local fat removal of the invention, every single dose volume note Penetrating composition includes that the hyaluronidase of 300IU to 600IU and base are counted on the basis of the total weight of injectable composition, the note Penetrate composition also and include the lidocaine that weight percent is 0.08 to 0.4% is as local anesthetic, weight percent 0.01 to 0.02% skin stretching-sensitive is divided as antihistaminic, the L-carnitine that weight percent is 0.01 to 4.0% as fat It solving the vitamin C that stimulant and weight percent are 0.1 to 2.0% and generates stimulant as collagen, remaining is salting liquid, and And the composition is with the every single dose injection of 0.5 to 2cc volume, between injection point between be divided into 0.5 to 1.5cm.
In the specific preparation embodiment for the injectable composition for local fat removal of the invention, preparation includes The hyaluronidase of 30,000IU to 60,000IU, the lidocaine of 210mg, the skin stretching-sensitive of 12mg, 660mg L-carnitine, With the composition of the ascorbic 100cc of 600mg.
※ skin muscular sarcocyte irradiates laser (D)
Skin muscular sarcocyte of the invention irradiates laser inside mouth towards face irradiation, and be frequency is 1 to 3.5Hz Laser, transfer its energy to skin muscular sarcocyte.Since this laser transfers its energy to muscle layer, it is to glue It is primary improve at, wrinkle and elasticity enhancing have the effect of it is fabulous.In particular, by irradiating laser towards face inside mouth Beam can effectively transfer its energy to skin muscular sarcocyte.
Specifically, which is painless, and with non-ablative, Noninvasive side in the case where no anesthesia Formula provides fuel factor to oral mucosa, to provide remodeling and tightening effect.In the mouth of the step treatment use laser beam provide by Energy is controlled, so that reaching the temperature of 45 to 70 DEG C or 45 to 65 DEG C ranges in dermis, this can lead to 30% wink of tissue When shrink.Organized layer deeper below is pulled to the instantaneous contract of dermis, generates and promotes effect.
Since above-mentioned laser treatment transmits energy by oral mucosa, it can protect epidermis and stimulates collagen weight Modeling and virgin rubber original shape are at (collagenesis) (lasting up to 6 months).In addition, this laser treatment has the following advantages that, It is not accompanied by bleeding or pain other than some warming senses in oral mucosa, and it does not influence the daily life after treatment It is living, because of the especially fast quick-recovery of oral mucosa.
In the of the invention specific embodiment using skin muscular sarcocyte irradiation laser treatment, from mouth inside direction The skin muscular sarcocyte that facial irradiation frequency is 1.8Hz or 3Hz irradiates laser 5 or 6 minutes.
By transferring thermal energy to skin muscular sarcocyte or being transferred to skin muscular sarcocyte and dermis, skin muscular of the invention Sarcocyte irradiation laser can bring one of following variation or a variety of:
I) collagen remodeling in skin muscular sarcocyte and virgin rubber original shape at;
Ii) the contraction of skin muscular sarcocyte;With
Iii) the tissue contracts of dermis.
Detailed embodiment of the invention explained below.
To achieve the purpose of the present invention, one aspect of the present invention provides a kind of for preventing the external member of skin aging, wraps Containing A) telomerase activating composition;B) dermis of skin irradiates laser;C) the use of the hyaluronidase comprising 300IU to 600IU In the composition of local fat removal;And D) skin muscular sarcocyte irradiation laser.
Moreover, according to the present invention for preventing the external member of skin aging from may further include frequency as 10 to 90Hz's Ultrasonic laser is administered simultaneously with application telomerase activating composition, or is stood after using telomerase activating composition Apply.
In external member of the invention, can not consider their sequence, for example, with the sequence, with reverse order or with Machine sequence carry out using above-mentioned elements A) to D) treat.
For example, external member of the invention can by [A), B), C) and D)], [A), B), D) and C)], [A), C), B) and D)], [A), C), D) and B)], [A), D), B) and C)], [A), D), C) and B)], [B), A), C) and D)], [B), A), D) and C)] [B), C), A) and D)], [B), D), A) and C)], [B), D), C) and A)], [C), A), B) and D)], [C), A), D) and B)] [C), B), A) and D)], [C), B), D) and A)], [C), D), A) and B)], [C), D), B) and A)], [D), A), B) and C)] [D), A), C) and B)], [D), B), A) and C)], [D), B), C) and A)], [D), C), A) and B)], or [D), C), B) and A)] Sequence use.
In addition, 1 to 10 circulation may be reused in external member of the invention, but not limited to this.It in each cycle, can be with Use above-mentioned elements A) treated to D), but regardless of they sequence how.
On the other hand, the present invention provides a kind of for preventing the cosmetic system of skin aging, and it includes A) telomerase activating Composition;B) dermis of skin irradiates laser;C) local fat that is used for of the hyaluronidase comprising 300IU to 600IU removes Composition;And D) skin muscular sarcocyte irradiation laser.
Telomerase, telomerase activating composition, dermis of skin irradiation laser, hyaluronidase, comprising 300IU extremely The hyaluronidase of 600IU irradiates laser for the composition of local fat removal and skin muscular sarcocyte of the invention As described above.
Cosmetic system according to the present invention can also include the ultrasonic laser that frequency is 10 to 90Hz, with application telomere Enzyme activation composition simultaneously or applied immediately after applying telomerase activating composition.
Cosmetic system of the invention includes following element.When using the cosmetic system, it can execute and use following element Treatment but regardless of they sequence how, for example, with the sequence, with reverse order or with random sequence:
I) the telomerase activating composition to be administered in skin;
Ii) the dermis of skin irradiation laser to be illuminated for continuing 3 to 60 minutes on the skin;
Iii) the composition for local fat removal, waits for being injected with 0.5 to 2cc single dose volume, injects 0.5 is divided into 1.5cm between point;With
Iv) skin muscular sarcocyte irradiates laser, waits for inside mouth towards face irradiation 3 to 10 minutes.
It is stood simultaneously or after with element i) treatment in addition, cosmetic system of the invention may also include with element i) treatment is used I.e. irradiation frequency is ultrasonic laser 5 to 20 minutes of 10 to 90Hz.
For example, cosmetic system of the invention can use in the following order: [i), ii), iii) and iv)], [i), ii), Iv) and iii)], [i), iii), ii) and iv)], [i), iii), iv) and ii)], [i), iv), ii) and iii)], [i), iv), Iii) and ii)], [ii), i), iii) and iv)], [ii), i), iv) and iii)], [ii), iii), i) and iv)], [ii), Iv), i) and iii)], [ii), iv), iii) and i)], [iii), i), ii) and iv)], [iii), i), iv) and ii)], [iii), Ii), i) and iv)], [iii), ii), iv) and i)], [iii), iv), i) and ii)], [iii), iv), ii) and i)], [iv), I), ii) and iii)], [iv), i), iii) and ii)], [iv), ii), i) and iii)], [iv), ii), iii) and i)], [iv), Iii), i) and ii)], or [iv), iii), ii) and i)].
In cosmetic system of the invention, above-mentioned ii) in dermis of skin irradiation laser be swashing for 5Hz selected from frequency One or more lasers of light device, the laser that frequency is 30 to 50Hz and RF laser.The laser that can be 5Hz by frequency Device irradiates 3 to 8 minutes, and by frequency is laser illumination 15 to 40 minutes of 30 to 50Hz.RF laser can be with The frequency of 40.68MHz is irradiated 4 to 10 minutes.
In addition, cosmetic system of the invention can be reused in 1 to 10 circulation, but not limited to this.It is followed each In ring, may be used the treatment of above-mentioned element i) to iv) but regardless of they sequence how.For example, using element i), Ii), iii) and treatment iv) can be carried out with the sequence, be divided into one week, and whole process is considered as one and follows Ring, treatment can repeat three circulations.
In of the invention one specific treatment embodiment, application contains the Kappaphycus of 0.00056% (w/w) Then the telomerase activating composition of alvarezii extract is irradiated 10 minutes with the ultrasonic laser that frequency is 30Hz.It connects down Come, as dermis of skin irradiate laser, frequency be 5Hz laser (GentleMax) irradiate 5 minutes, and in mode A and Mode B irradiates the laser that a kind of frequency of indigo laser-is 30 to 50Hz, continues 20 minutes respectively, then frequency of use is The RF laser illumination of 40.68MHz 6 minutes.Then, using the hyaluronic acid comprising 30,000IU to 60,000IU of 100cc Enzyme, the lidocaine of 210mg, the skin stretching-sensitive of 12mg, the L-carnitine of 660mg and the ascorbic of 600mg are used for local fat The composition of removal, each injection single dose volume 1cc at 50 points, between injection point between be divided into 1cm, between one week Every injection four times.Hereafter, laser 5 is irradiated towards the skin muscular sarcocyte that facial irradiation frequency is 1.8Hz or 3Hz inside mouth to divide Clock.
In another treatment embodiment of the invention, the Kappaphycus containing 0.00056% (w/w) of 3cc is applied Then the telomerase activating composition of alvarezii extract is irradiated 10 minutes with the ultrasonic laser that frequency is 30Hz.It connects down Come, as dermis of skin irradiate laser, frequency be 5Hz laser (GentleMax) irradiate 3 minutes, and in mode A and Mode B irradiates the laser that a kind of frequency of indigo laser-is 30 to 50Hz, continues 10 minutes respectively, then with monopolar mode It uses RF laser illumination 6 minutes of 90w.Then, the hyaluronic acid comprising 30,000IU to 60,000IU of 100cc is prepared Enzyme, the lidocaine of 210mg, the skin stretching-sensitive of 12mg, the L-carnitine of 660mg and the ascorbic of 600mg are used for local fat The composition of removal, and at 10 points each injection 1cc single dose volume, between injection point between be divided into 1cm.This Afterwards, it is irradiated laser 6 minutes inside mouth towards the skin muscular sarcocyte that facial irradiation frequency is 3Hz.
On the other hand, the present invention provides according to the present invention for preventing the external member and beauty of skin aging for using Appearance system prevents the beauty method of skin aging.
It is according to the present invention to be used to prevent the external member of skin aging and cosmetic system as described above.
Specifically, the present invention provides a kind of for preventing the beauty method of skin aging, wherein carries out following steps Its sequence is considered at least once and not:
I) the step of applying telomerase activating composition;
Ii the step of) irradiation dermis of skin irradiates laser 3 to 60 minutes;
Iii) with 0.5 to 2cc single dose volume come inject for local fat removal composition the step of, injection point Between between be divided into 0.5 to 1.5cm;With
Iv the step of) being irradiated laser 3 to 10 minutes inside mouth towards face irradiation skin muscular sarcocyte.
In addition, beauty method of the invention may also include, irradiation frequency is immediately simultaneously or after step i) with step i) 10 to 90Hz ultrasonic laser 5 to 20 minutes.
In the present invention, can execute above-mentioned steps but regardless of they sequence how, for example, with the sequence, with phase Reverse-order or with random sequence.For example, above-mentioned steps can carry out in the following order: [i), ii), iii) and iv)], [i), Ii), iv) and iii)], [i), iii), ii) and iv)], [i), iii), iv) and ii)], [i), iv), ii) and iii)], [i), Iv), iii) and ii)], [ii), i), iii) and iv)], [ii), i), iv) and iii)], [ii), iii), i) and iv)], [ii), iv), i) and iii)], [ii), iv), iii) and i)], [iii), i), ii) and iv)], [iii), i), iv) and ii)] [iii), ii), i) and iv)], [iii), ii), iv) and i)], [iii), iv), i) and ii)], [iii), iv), ii) and i)] [iv), i), ii) and iii)], [iv), i), iii) and ii)], [iv), ii), i) and iii)], [iv), ii), iii) and i)] [iv), iii), i) and ii)], or [iv), iii), ii) and i)].
Above-mentioned steps i) to iv) can be carried out by the same person, and when can be arranged suitable between the steps Between be spaced.Appropriate intervals between step can be 1 to 60 minute, 1 to 24 hour or 1 day to 2 weeks, this depends on skin Situation and the time treated next time.Time interval can be determined by those skilled in the art, and can be according to treatment Step and skin variation.
Step ii of the invention) in dermis of skin irradiation laser be selected from frequency be 5Hz laser, frequency 30 To the laser of 50Hz and one or more lasers of RF laser.It can be 3 to 8 points of laser illumination of 5Hz by frequency Clock, and by frequency be laser illumination 15 to 40 minutes of 30 to 50Hz.RF laser can irradiate 4 with the frequency of 40.68MHz To 10 minutes.
External member and cosmetic system according to the present invention for preventing skin aging has synthesis related with skin aging Effect, including the improvement of instantaneous wrinkle, skin repair, elasticity enhancing, wrinkle improve, local fat removal and skin hydration improve with Although and treatment time is short but is up to 1 year to 1.5 years lasting holding effect.Therefore, the present invention is in terms of preventing skin aging Have the effect of excellent.
Detailed description of the invention
Fig. 1 is shown with H2O2After inducing aging, at 0.25% or 0.5%Kappaphycus alvarezii extract The expression of fibroblast middle-end the corpuscular protein POT1 and TPP1 of reason.
Fig. 2 shows with H2O2After inducing aging, at 0.25% or 0.5%Kappaphycus alvarezii extract Telomere length in the fibroblast of reason.
Fig. 3 is shown using beta galactosidase dyeing external member (Sigma Senescent cell dyeing external member) with H2O2 It uses after induction aging and is measured in the fibroblast of 0.25% or 0.5%Kappaphycus alvarezii extract-treated Aging degree photo.
Fig. 4 shows the aging degree measured in clinical studies by Laser Scanning Confocal Microscope in beginning day and the 42nd day, Effect is prevented to skin aging to verify the composition comprising Kappaphycus alvarezii extract.
Fig. 5, which is shown, is starting the aging degree measured by 3D scanner of day and the 42nd day in clinical studies, to test Card prevents effect to skin aging comprising the composition of Kappaphycus alvarezii extract.
Fig. 6 is shown in clinical studies to measure the perception test at age for starting day and the 42nd day subject As a result, preventing effect to skin aging to verify the composition comprising Kappaphycus alvarezii extract.
Fig. 7, which is shown in, irradiates after laser illumination the elasticity for enhancing double chin and cheek region immediately with dermis of skin The photo of contoured skin.
Fig. 8 is the photo of the nasolabial groove wrinkle after irradiating laser treatment 1 time (session) with skin muscular sarcocyte.
Fig. 9 is grouped into test group for 1 week, 2 weeks, 3 weeks and 4 weeks after being shown in baseline and treatment and compares 90 in 1 to 8 The quantity of the collagenous fibres measured in the Skin biopsy of subject, with study comprehensively it is according to the present invention for preventing or Treat the external member of skin aging and the effect of cosmetic system.Represent test group A of the invention) telomerase activating composition, B) Dermis of skin irradiates laser, C) it is used for the composition and D of local fat removal) skin muscular sarcocyte irradiation laser treatment, and Control group receives only some treatments in these treatments.Specifically, control 1 receives treatment A;Control 2 receives treatment B;It is right Receive treatment C according to 3;Control 4 receives treatment D;Control 5 receives treatment A, B and C;Control 6 receives treatment A, B and D;Control 7 receives Treat A, C and D;Control 8 receives treatment B, C and D.
Figure 10 shows the subject after baseline and treatment in 1 week, 2 weeks, 3 weeks and 4 weeks test group and control 1 to 8 The skin elasticity of middle measurement improves.Skin is assessed using DermaLab USB elastic probe (Cortex Technology, Inc.) The variation of elasticity.
Figure 11 is shown through measurement test group and control 1 to 81 week, 2 weeks, 3 weeks and 4 weeks after baseline and treatment The effect improving wrinkles that wrinkle in subject determines.Use device (the Aramo TS, by Aram HUVIS of quantization wrinkle degree Co., South Korea, programming) assess the variation to corrugate.
Figure 12 show after baseline and treatment 1 week, 2 weeks, 3 weeks and 4 weeks it is tested in test group and control 1 to 8 The facial maintenance effect measured in person.Use the French sound section image (Les of the thickness of measurement facial area subcutaneous fat Jardinsde la Duranne, Aix en Provence, France) ultrasonic wave assessed.
Figure 13 shows 1 week, 2 weeks, the 3 weeks and 4 weeks subject in test group and control 1 to 8 after baseline and treatment The Activation of Telomerase effect of middle measurement.The blood sample from subject is analyzed by sandwich enzyme immune measuring method to measure telomere The amount of enzyme.
When Figure 14 is shown 1 week, 2 weeks, 3 weeks and 4 weeks after baseline and treatment test group and control 1 to 8 in by The skin hydration measured in examination person improves.Skin hydration is determined by the capacitor of measurement reflection water content, and the water content exists There is highest dielectric constant in skin.
Figure 15 is shown through measurement test group and control 1 to 81 week, 2 weeks, 3 weeks and 4 weeks after baseline and treatment The skin roughness that skin roughness in subject determines improves.Using diameter be 30mm Silver Mirror (beauty scope, 60 mirror of X) image of test zone is shot, and skin surface contours are converted into figure and number to obtain pachylosis angle value.
Figure 16 shows the subject after baseline and treatment in 1 week, 2 weeks, 3 weeks and 4 weeks test group and control 1 to 8 The variation of the pigmentation amount of middle measurement.RSA (Robo Skin Analyzer CS 50, In Forward.Inc., Japan) Allow to be combined pore, pigmentation, wrinkle, colour of skin etc. inspection, and the instrument is used to measure the change of pigmentation amount Change.
Invention mode
Illustrate how the present inventor studies to obtain the set for preventing skin aging below with reference to embodiment and embodiment Part and cosmetic system, and the beauty side for preventing human skin aging using external member according to the present invention and system Method.
Reference implementation example
Reference implementation example 1: preparing telomerase activating extract and verifies its effect
(1) telomerase activating extract is prepared
Telomerase activating composition is prepared using Kappaphycus alvarezii extract.Specifically, will Kappaphycus alvarezii grinding, then in solvent (water, C1To C6Alcohol or organic solvent such as ethyl alcohol, methanol, hexane etc.) Then hydrolase is added to obtain extract in middle precipitating.
(2) experiment in vitro of skin aging is prevented
Have studied Kappaphycus alvarezii extract prepared above prevents effect to skin aging in vitro. When Telomerase is activated, the telomere length of end of chromosome is maintained or extends in cell, to extend the service life of cell. In this respect, the aging of human fibroblasts (human fibroblast) is tested.
By human fibroblast cell line with 1800 cell/cm2Concentration be placed in 100-mm plate (Corning 100mm TC- Treated Culture Dish, Product#430167) in, and use and contained with the ultimate density of 0.25% or 0.5% The fibroblast culture medium of Kappaphycus alvarezii extract is handled.Then, by with H2O2(peroxidating 4 × 40 μM of hydrogen) 96 hours are handled to induce aging.Use pre- senescent fibroblast and as the use same procedure of control and It is induced after aging but does not have to the fibroblast that Kappaphycus alvarezii extract is handled, comparative group middle-end The length of grain and the expression of telomere albumen.
With POT1 and TPP1 in the test group of Kappaphycus alvarezii extract-treated (for protecting and keeping The telomere albumen of telomere length) expression remain it is high.In particular, as the Kappaphycus for being 0.5% with concentration When alvarezii extract-treated cell, the expression of above-mentioned albumen is maintained close to the level of normal pre- senescent fibroblast. In contrast, Kappaphycus alvarezii extract is being not used by induction aging in the expression of above two albumen It handles in the fibroblast of aging and is reduced to 68% and 82% (Fig. 1) respectively.
In addition, telomere shorten the result shows that, with concentration be 0.5% Kappaphycus alvarezii extract-treated As caused by aging about 65% telomere can be inhibited to shorten (Fig. 2).
Finally, aging is induced in fibroblast under conditions of same as described above and is dyed using beta galactosidase The aging degree of external member (Sigma senile cell dye external member) measurement the experimental results showed that, be 0.5% with concentration Cell ageing degree significantly reduces (Fig. 3) in the cell of Kappaphycus alvarezii extract-treated.
(3) experiment in vivo of skin aging is prevented
The healthy volunteer that average age is 59 ± 5 is divided into the placebo of 21 subjects and the survey of 24 subjects Examination group.For test group, the emulsion formulations of the Kappaphycus alvarezii extract comprising 3% are applied to subject Entire facial area skin (2 times a day).Use Laser Scanning Confocal Microscope (Vivascope 1500Trilaser- Mavig GmbH) and 3D scanner (Fringe projection, Eotech, France;With Optocat software analyze) to The skin surface situation that experiment starts the measurement of the same day (the 0th day) and the 42nd day is compared (Fig. 4 and Fig. 5).In this respect, aging Stage 1 indicates the state of most aging, and the stage 4 refers to the least young skin of senescence progress.
As a result, test group showed improved skin aging journey relative to the 0th day at the 42nd day compared with placebo Degree, as shown in Figure 4.58% subject shows the improvement in their skin stages, and 46% subject's table in test group Reveal the improvement from ageing phase 1 or 2 to the stage 3 or 4.
Fig. 5 shows the measured value of wrinkle depth in ocular, shows to change at the 42nd day relative to the 0th day wrinkle depth It has been apt to 27.9%.
It is surveyed in the perception for measuring the average age of above-mentioned subject based on the photo that they shoot before and after the experiment In examination, the average age of placebo is 62 years old, does not have difference before and after photo.In contrast, test group subject It is considered occurring younger 3 to 6 years old average.88% subject is considered seeming younger (Fig. 6) in test group.
Reference implementation example 2: adjoint treatment is carried out with telomerase activating composition and ultrasonic laser
(1) telomerase activating composition is prepared
Telomerase activating is prepared using the Kappaphycus alvarezii extract obtained in reference implementation example 1 to combine Object.Specifically, by the telomerase activating group comprising the Kappaphycus alvarezii extract prepared in reference implementation example 1 Close creme and ampoule that object is configured to the composition for having as follows.
The composition of 1 telomerase activating creme of table
Ingredient Content % (w/w)
Glycerol 8.0
Sunflower oil 3.2
Stearic acid 2.5
Mango seed butter 1.5
Kappaphycus alvarezii extract 0.0056
Yeast/fermentation Herba Visci extract 0.007
Lactic acid bacteria/fermentation extract of soybean 0.0036
Yeast/fermentation cogongrass rhizome extractive 0.0026
Purified water In right amount
The composition of 2 telomerase activating ampoule of table
Ingredient Content % (w/w)
Glycerol 22.0
Pyrrolidone sodium carboxylate 12.0
Xanthan gum 0.2
Citric acid 0.15
Kappaphycus alvarezii extract 0.0056
Yeast/fermentation Herba Visci extract 0.007
Lactic acid bacteria/fermentation extract of soybean 0.0036
Yeast/fermentation cogongrass rhizome extractive 0.0026
Purified water In right amount
(2) effect of the adjoint treatment carried out with telomerase activating composition and ultrasonic laser
By above-mentioned telomerase activating composition be applied in the form of topical formulations 24 test groups in reference implementation example 1 by After the skin of examination person, the ultrasonic laser that irradiation frequency is 10 to 90Hz is to promote for composition to be transferred in skin.
It specifically, will frequency after the above-mentioned telomerase activating composition of 10cc is applied to skin in the form of topical formulations Rate is set as laser (the Legato-Alma Lasers, Israel of 30Hz;And Sonopact-Medius, South Korea) to entire Facial area irradiates 10 minutes 1 to 2 time.
In this study, ultrasonic laser i) has dither effect (hammering-shock effect to the skin area through treating; Push-pull effect) and ii) cause the fuel factor as caused by the vibration in epidermal tissue and corium.In addition, its iii) it destroys by surpassing The keratinocyte for the degeneration that sound application generates, and effectively transmitted composition by promoting composition to penetrate into space between cells To corium.
Reference implementation example 3: laser illumination corium and collagen generate effect of stimulation
In this experiment, after treating described in reference implementation example 2, the laser illumination of corium is up to entirely Facial area and chin area.In this step, the glue in corium is stimulated using the laser for transferring its energy to deep dermis It is primary at.
In this reference implementation example, the laser illumination of corium is carried out using three kinds of lasers.Firstly, being by wavelength Laser (GentleMax-Candela, the U.S.) irradiation that 1064nm and frequency are 5Hz 5 minutes on a skin surface, so that swashing Light energy is goed deep into corium with transferring heat energy.
Next, using high intensity focused ultrasound (HIFU) by frequency be 30 to 50Hz laser (Indigo-K1MED, South Korea) laser energy (65 DEG C of thermal energy) is transferred to deep dermis and SMAS.The laser has Mode A and Mode B, and Treatment is formed by respectively irradiating 20 minutes under Mode A and Mode B.This causes the contraction of muscle layer under corium, causes to reduce wrinkle It is generated with stimulation collagen and elastin laminin.Meanwhile if 10 to 20mm depth there are excess fat layer, this swashs Light irradiates induced lipolysis and decomposes.
Finally, with the RF laser (40.68MHz of monopolar mode irradiation 92W;Tenor Laser-Alma laser, with color Column) 6 minutes.This allows RF wave to penetrate dermis of skin/fat deposit and generates heat in deep dermis, and induced tissue is shunk and recombination. As laser generates heat in connective tissue, blood flow and circulation increase, cause tissue compact and improve dermatoglyph.This Outside, iuntercellular water and noxious material is discharged, contoured skin in irradiation area is caused significantly to be thinned.
About experimental result, significantly reducing for wrinkle of skin can see immediately after laser illumination, and under double Bar and cheek region in skin elasticity enhancing, in face contour generate significant difference (Fig. 7).
Reference implementation example 4: the composition and its lipolysis effect for local fat removal comprising hyaluronidase
In this study, it is given to 40 (20 males and 20 women) volunteers and is used for office comprising hyaluronidase The composition of portion's fat removal, the volunteer had BMI selected from 20 years old or more in adult be 25 or higher abdominal obesity Patient, give the form of their abdomen area injection.It measures and according to the present invention is gone for local fat as described below The effect of the composition removed.
(1) injectable composition for local fat removal of the preparation comprising hyaluronidase
About hyaluronidase, using the Liporase Inj. of Daehan New Pharm Co., Ltd, (1500IU/ is small Bottle, contain 13.3mg lactose hydrous), the amount wherein listed in following table add lidocaine (Hanmi Pharm.Co., Ltd.), Pi Lamin (Peniramin, Yuhan Co.), L-carnitine (Dream Pharma) and vitamin-C (Daewoo Pharm Co., Ltd.) and be sufficiently mixed to prepare the injection solution composition of 100cc.
Ingredient of the table 3 for the composition of local fat removal
(2) the lipolysis effect for the composition of local fat removal
Compare the composition by giving the EXPERIMENTAL EXAMPLE 4 in upper table 3, by give the composition of embodiment 1 to 3 with And changed by the waistline of endocrinology, conventional edema therapeutic induction.In abdomen area between rib cage and pubis, 50 A point injects the composition of each 1cc, and 50 points are arranged in a manner of 1cm apart respective since navel.Above-mentioned note is repeated weekly It penetrates, continues surrounding, move injection point every time.1 week measurement waistline is reduced after completing above-mentioned treatment, and 1 upon completion of the treatment The moon measures waistline again.Record the average value of measured value.
For oedema existing conventional therapy endocrine therapy carry out surrounding, 30 times weekly, behind one week and one month The reduction of waistline is measured, and the results are shown in table 4.
Table 4
For statistical analysis, the distribution of measured value is obtained using statistics packet SPSS, and is assessed using paired t-test The influence that test injection reduces waistline.The analysis uses 95% confidence interval, is adjusted according to changes of weight.
In the studies above, using body fat analyzer Inbody body fat analysis shows average fat loss for 1.5 to 2kg。
According to table 4, observe -0.2 ± 1.2cm's of waistline in the comparative example 3 for being wherein given only saline solution Variation.However, in EXPERIMENTAL EXAMPLE 4, the difference of -9.4 ± 0.2cm for observing waistline for one week after four treatments, and And four times treatment after one month when difference remain -9.5 ± 0.4cm, show no yo yo effect.
On the other hand, in the comparative example 1 for the hyaluronidase for giving 250IU, [every wheel is treated to 50 points in total Give 12500IU;4 wheel treatment in total], the difference for treating latter week is -1.6 ± 0.6cm, and treats the difference of the latter moon For -1.2 ± 0.3cm, show worse effect more significant than the present invention.In the comparative example 2 for the hyaluronidase for giving 650IU In, [every wheel treatment gives 32500IU to 50 points in total;4 wheel treatment in total], due to recess and bruise after first time treats Interrupt treatment.
In the case where the endocrinology as edema therapeutic, the waistline as caused by removal oedema reduce it is not significant and It disappears after one month, clearly illustrates that the waistline obtained by using hyaluronidase reduces the result for being not only oedema removal It is the result of lipolysis.
As can be seen from the above results, it has proved that injectable composition of the invention has excellent in terms of local fat removal Different effect and the side effect substantially reduced and no yo yo effect.
In addition, compared with the high dose hyaluronidase injection composition of prior art KR10-2009-0111916A, to the greatest extent Pipe uses the hyaluronidase of relatively low-dose, but injectable composition of the invention is also shown with the side effect and improvement minimized Local fat removal effect.
(3) side effect of the composition for local fat removal is given in assessment
The injectable composition of EXPERIMENTAL EXAMPLE 1 to 4 and the injectable composition such as part above (2) of comparative example 1 to 3 In give like that, and the side effect observed in patients is listed in Table 5 below.
Table 5
* skin elasticity is determined using the tactile assessment of 5 subscales: 1: it is excessively poor, 2: it is poor, 3: it is general, 4: it is good, 5: very It is good.
As shown in table 5, local anesthetic or antihistaminic combination are free of using EXPERIMENTAL EXAMPLE 1 according to the present invention Object, compared with the high dose composition of comparative example 2, the significant side effect for reducing such as bruise or recess, but observe To pain and allergic reaction.In addition, containing local anesthetic and antihistaminic compared with EXPERIMENTAL EXAMPLE 1 or comparative example 2 The composition of EXPERIMENTAL EXAMPLE 2,3,4 show with significantly reduced anaphylaxis rubescent, swelling, scabies itching and pain.These Effect be considered as using the hyaluronidase of local anesthetic and antihistaminic and low dosage caused by.In addition, in reality In the case where testing embodiment 4, observe excellent skin elasticity, show potential skin elasticity improvement, this facilitate with The combination of other anti-aging treatments.
In addition, some patients generate slightly recessed due to the fat removal of lipolysis stimulant in EXPERIMENTAL EXAMPLE 3 It falls into and relaxes, be limited to high obesity patient and restore in a short time.
In EXPERIMENTAL EXAMPLE 4, generating stimulant comprising collagen allows the fast quick-recovery of skin elasticity, without being recessed Or relaxation.
Reference implementation example 5: skin muscular sarcocyte irradiates laser and its elastic reinforcing effect
In this experiment, 9 volunteers in the participant of the treatment for the step of having received reference implementation example 3 are subjected to swash The treatment of light device.In this step, when laser delivers power to muscle layer, improve in collagen generation, wrinkle and elasticity increases Strong aspect has the effect of fabulous.In particular, by the way that effectively energy can be passed towards face irradiation laser beam inside mouth It is handed to skin muscular sarcocyte.
It specifically, the use of wavelength is 2940nm and laser (Fotona Laser- that setpoint frequency is 3Hz Slovenia it) is irradiated entire facial area 5 minutes from oral mucosa towards face.The laser treatment is painless, and Fuel factor is provided to oral mucosa with non-ablative, non-invasive manner in the case where without anesthesia, to provide remodeling and tightening effect Fruit.By transmitting the energy that well controls to make the temperature for being 45 to 65 DEG C in dermis reach, in the mouth of the step Treatment may cause 30% instantaneous contraction of tissue.Pull to the moment contract of dermis tissue deeper below Layer generates and promotes effect.
Since above-mentioned laser treatment transmits energy by oral mucosa, it can protect epidermis and stimulate collagen weight Modeling and virgin rubber original shape are at (lasting up to 6 months).In addition, this laser treatment this have the advantage that, in addition in oral mucosa Some warming senses except be not accompanied by bleeding or pain, and since oral mucosa especially restores fastly, so without downtime.
In this experiment, 9 volunteers are carried out laser treatment 5 times, is divided into 1 month.As a result, all volunteers Perioral aging lines substantially reduce.Specifically, although the wrinkle scoring before MFWS (improvement Fitzpatrick wrinkle scale) treatment is 2.22, but the scoring after MFWS treatment is 0.69, shows that wrinkle index reduces about 69%.
It was furthermore observed that instantaneous performance goes out the effect of this step.It is only once treated using the frequency of 1.8Hz, it can be with That sees nasolabial groove wrinkle substantially reduces (Fig. 8).
Observe using above with reference to the A in embodiment) telomerase activating composition, B) dermis of skin irradiation laser, C) for local fat removal composition and D) skin muscular sarcocyte irradiation laser therapeutic effect conceive the present invention.Now Following embodiment the present invention is described in detail will be referred to.However, these embodiments are merely to illustrate the present invention, and should not be construed as with Any mode limits the present invention.
<embodiment>
The present inventor is determined by experiment compared with the effect observed in the single step in above-mentioned reference implementation example, When with A) telomerase activating composition, B) dermis of skin irradiates laser, C) composition and D for local fat removal) skin Skin muscle layer shows synergy when irradiating laser combined treatment, completes the present invention.In order to study according to this hair comprehensively The effect of the bright external member and cosmetic system for preventing or treating skin aging is used to prevent skin with based on according to the present invention The external member of skin aging and component-A of cosmetic system) telomerase activating composition, B) dermis of skin irradiation laser, C) For local fat removal composition and D) skin muscular sarcocyte irradiation laser various combination treat 90 subjects;And And determine collagen generation/contraction/remodeling effect;Elastic improvement;Effect improving wrinkles;Local fat removal and facial maintenance Effect;Telomerase activating effect;Colour of skin improvement;Satisfaction and side effect.The datail description of the research is as follows.
(1) subject selects
This research is in October, 2016 to November for preventing the external member of skin aging and the effect of system 90 40 to 50 years old male and female outpatient patients for having visited the clinic (South Korea Seoul) of Sonyouna doctor carry out 's.
The subject for including in this research is that those i) are apprised of purpose and research overview, research process and scheme require simultaneously Endorsed informed consent form, ii) health, with can be in the research phase including dermopathic acute or chronic disease and iii) Between carry out follow-up subject.
If subject belongs to any group of in the following group, these subjects are excluded:
1) pregnant woman or breast feeding women and Women of Childbearing Age,
2) dermopathic people is being treated using the topical formulations containing steroids,
3) there is sensitive or allergic skin people,
4) people with cutaneous lesions such as mole, acne, erythema, telangiectasis etc..
5) functional cosmetic product has been used to be used for the people that wrinkle improves in 3 months before the study began,
6) receive the people of the treatment to survey region in 6 months before the study began,
7) internal disease such as hypertension, diabetes, the people of Drugs Treatment on Thyroid Disease and with cancer are being taken or Disease or other infection diseases;Blood has related disorders;Or the people of autoimmune disease.
(2) method
Subject is grouped at random and with the component (A), (B), (C) and (D) of external member and cosmetic system of the invention no It is treated with combination.
(A) it applies telomerase activating composition: applying the Kappaphycus containing 0.00056% (w/w) of 3cc The telomerase activating composition of alvarezii extract, it is then a kind of by super with Legato (Alma laser, Israel)- Acoustic vibration promotes the ultrasonic laser of cosmetics penetrated deep into whole with 50% irradiation of the frequency of 30Hz and maximum power output A facial area 10 minutes 1 to 2 time.
(B) irradiate laser illumination with dermis of skin: irradiation frequency is 3 points of 5Hz or lower laser (GentleMax) Clock, and the indigo laser that A and Mode B irradiation frequency are 30 to 50Hz in mode continues 10 minutes respectively, then with monopole Mode was with RF Tenor laser illumination 10 minutes of 92W.
(C) composition for local fat removal of the injection comprising hyaluronidase: preparation and above-mentioned reference implementation example 4 The hyaluronidase comprising 30,000IU of the identical 100cc of EXPERIMENTAL EXAMPLE 4, the lidocaine of 210mg, 12mg skin draw The ascorbic composition for local fat removal of quick, 660mg L-carnitine and 600mg, and at 10 points The respectively 1cc volume of hyaluronidase of the injection comprising 300IU, between injection point between be divided into 1cm.
(D) skin muscular sarcocyte irradiates laser inside mouth towards the irradiation of face: irradiating integumentary musculature with the frequency of 3Hz The Fotona laser of layer is inside mouth towards face irradiation 6 minutes.
Primary following treatment carried out to each subject group, each subject group by 10 subject groups at.
Table 6 is used for the treatment of subject group
Treatment
Control 1 A
Control 2 B
Control 3 C
Control 4 D
Control 5 A+B+C
Control 6 A+B+D
Control 7 A+B+C
Control 8 B+C+D
Test group A+B+C+D
Determined at any time collagen generation/contraction/remodeling effect, skin elasticity reinforcing effect, effect improving wrinkles, by office Portion's fat removes caused facial maintenance effect, local fat removal/reduction of lipolysis/oedema, skin in fat cell Telomerase activating and colour of skin improvement in skin cell.
Embodiment 1: measurement collagen generation/contraction/remodeling effect
The skin biopsy sample of collection research subject is to measure the quantity of collagenous fibres.Specifically, by skin biopsy mark Originally it is fixed in 2.5% glutaraldehyde solution, is washed with 0.1M phosphate buffer (pH 7.4), and molten in 1% osmium tetroxide 2 hours are fixed after in liquid.Next, 50% ethyl alcohol of skin histology gradient to dehydrated alcohol is dehydrated, propylene oxide is used Infiltration, is then embedded in Epon resin compound.The thin measurement that cutting thickness is 1 μm is sliced to select interested region, Then it obtains ultra-thin section and is handled with tannic acid to enhance the resolution ratio of collagenous fibres, then use uranyl acetate and citric acid Lead carries out conventional dual dyeing.Then it using transmission electron microscope (JEOL 200CX, Japan) observation sample, is put with identical Big rate (X 40,000) shoots all images to compare the variation of collagenous fibres.As a result it is summarised in table 7 and in Fig. 9 using figure It represents.
The increase of 7 collagenous fibres par of table
As shown in table 7 and Fig. 9, test group (with combination A, B, C and D treatment) according to the present invention 1 week to 4 weeks after the treatment It shows collagenous fibres more better than all control groups and increases effect.Particularly, with the single treatment group treated with A, B, C or D In collagenous fibres increase the summation of effect compared to (4 weeks after treatment: fiber number increase by 58.5%), test group shows excellent Synergy (4 weeks after treatment: 127.0%).Moreover, test group show than with combination ABC treatment group and with D treatment The effect found in single therapy group summation (4 weeks after treatment: 61.4%), with combination ABD treatment group and with C treat list The summation of the effect found in one treatment group is (4 weeks after treatment: 61.4%), with the group of combination ACD treatment and with B treating single The summation of the effect found in treatment group is (4 weeks after treatment: 65.6%) and with the group of combination BCD treatment and with A treating single The summation of the effect found in treatment group is (4 weeks after treatment: 57.5%) better effect.Therefore, by combine all treatment A, B, C and D, beauty external member of the invention and cosmetic system show excellent collaboration effect in the quantitative aspects for increasing collagenous fibres Fruit.
Embodiment 2: elastic improvement is measured
Measure the skin elasticity of study subject.Specifically, using DermaLab USB elastic probe (Cortex Technology, Inc.) evaluation studies subject skin elasticity improve.The instruction of DermaLab USB spring probe is due to feeling emerging Change of skin caused by the suction in interesting region and puff duration and restoring force.Before carrying out the measurements, using special adhesive tape The probe of device is bonded to the left cheek of test subject.In view of causing skin fatigue degree in same position duplicate measurements It increases, each elasticity measurement position is using only once.Using the variation of application software (version 1.09) analyzing skin elasticity, this is answered It is the exclusive analysis program of DermaLab USB with software.In the parameter of measurement, analyzed using Young's modulus (E), poplar Family name's modulus (E) is bigger, shows that elasticity is higher.Young's modulus (E) is based on when skin surface increases 1.5mm i.e. in measurement probe The distance between two infrared detection lines when required power difference, and its measurement unit is MegaPascal (MPa).? Before treatment (baseline) and treatment after 1 week, 2 weeks, 3 weeks and 4 weeks progress elasticity measurement.As a result it is summarised in table 8, and in Figure 10 Make to graphically illustrate.
8 mean skin elasticity of table improves
As shown in table 8 and Figure 10, test group (with combination A, B, C and D treatment) according to the present invention 1 week to 4 after the treatment Show skin elasticity improvement more better than all control groups week.Particularly, with the single therapy treated with A, B, C or D Compared to (4 weeks after treatment: elasticity improves 46.01%), test group shows excellent the summation of the skin elasticity improvement of group Effect is (4 weeks after treatment: 81.50%).Moreover, test group is shown than the group with combination ABC treatment and single the controlling with D treatment The summation of the effect found in treatment group is (4 weeks after treatment: group 48.56%), with combination ABD treatment and single controlling with C treatment The summation of the effect found in treatment group is (4 weeks after treatment: group 36.35%), with combination ACD treatment and single controlling with B treatment The summation of the effect found in treatment group is (4 weeks after treatment: 47.25%) and with the group of combination BCD treatment and with A treating single The summation of the effect found in treatment group is (4 weeks after treatment: 47.82%) better effect.Hereby it has been demonstrated, that passing through treatment A, the organic assembling of B, C and D, of the invention external member and cosmetic system for preventing skin aging is in terms of skin elasticity improvement Show excellent synergy.
Embodiment 3: assessment effect improving wrinkles
Measure the effect improving wrinkles of study subject.For the qualitative assessment to corrugate, corrugated degree using quantization Device (Aramo TS, by Aram HUVIS Co., South Korea program).The Silver Mirror (x10 mirror) for being 30mm by diameter Head and the skin surface of area-of-interest be in close contact, and be depressed on skin using constant pressure perpendicular.Then, it uses The difference for the skin brightness that light from device head generates quantifies corrugation.The negativity model of thus obtained wrinkle of skin can To use software to convert the format that is positive, or different measurement line adjusting parameter values can be directed to.As for corrugation degree, 10~12 Value indicate twenties people normal corrugation.As a result it is summarised in table 9, and makes to graphically illustrate in Figure 11.
Table 9 averagely wrinkles
As shown in table 9 and Figure 11, test group (with combination A, B, C and D treatment) according to the present invention 1 week to 4 after the treatment Show effect improving wrinkles more better than all control groups week.Particularly, with the single treatment group treated with A, B, C or D The summation (4 weeks after treatment: wrinkle reduces -3.60) of effect improving wrinkles is compared, and test group shows excellent synergy and (controls 4 weeks after treatment: -6.81).Moreover, test group is shown than sending out with the group of combination ABC treatment and in the single therapy group of D treatment The summation of existing effect is (4 weeks after treatment: -3.67), with the group of combination ABD treatment and in the single therapy group of C treatment finding Effect summation (after treatment 4 weeks: -2.94), with the group of combination ACD treatment and in the single therapy group of B treatment finding The summation of effect is (after treatment 4 weeks: -3.90) and with the group of combination BCD treatment and in the single therapy group of A treatment finding The summation of effect is (4 weeks after treatment: -2.74) better effect.Therefore, of the invention by combining all treatment A, B, C and D External member and cosmetic system for preventing skin aging have excellent synergy in terms of wrinkle improvement.
Embodiment 4: assessment is by local fat removal and decrease in edema bring skin repair effect
Measure the skin repair effect by applying the composition generation for local fat removal etc. of study subject.Tool Body, use the thickness of the subcutaneous fat of the facial area of ultrasonic measurement study subject.Using French sound section image (English: SuperSonic Imagine, Les Jardins de la Duranne, Aix en Provence, France) device progress Measurement based on ultrasound.Tester and subject, which face each other, to be seated to measure the subcutaneous fat in cheek and chin area Thickness, and make the minimum pressure on Vltrasonic device correctly to measure thickness.By aqueous gel be applied to measurement site with Ultrasound is transmitted in help, and is measured at two positions using the high frequency linearity probe of 6.0MHz, and average value is then calculated.Knot Fruit is summarised in table 10, and makes to graphically illustrate in Figure 12.
The variation of fat thickness in 10 chin area of table
As shown in table 10 and Figure 12, test group (with combination A, B, C and D treatment) according to the present invention 1 week to 4 after the treatment It shows excellent fat thickness week and reduces effect.As can be seen that the effect is depended on comprising using C (to go for local fat The composition removed)-element of the invention treatment, and after the treatment 1 week it can be observed that significant synergy, holds Continue after treatment 4 weeks.
Embodiment 5: measurement telomerase activating effect
The telomerase activating degree of evaluation studies subject.Study subject is forbidden to use for 24 hours before its blood testing Caffeine, excess drug or metabolism regulators, and in 10 points of extraction blood samples of the morning after they sufficiently rest.Using sandwich The amount of enzyme immunoassay measurement sample telomerase.Specifically, the standard containing Telomerase or test sample are applied to painting There is the plate to Telomerase (TA) monoclonal antibody (MAb) with specificity, so that Telomerase is attached on plate.In order to quantify sample The amount of this telomerase, preparation are specifically bound to the polyclonal antibody of HRP (horseradish peroxidase) conjugation of Telomerase simultaneously It is applied to plate, causes its Telomerase relevant to plate in conjunction with sandwich.When all reactions are completed after incubation, wash off Remaining unreacted excess material on plate, and react substrate solution to determine the amount of the HRP combined.When substrate is anti-with HRP At once, it is hydrolyzed by the peroxidase activity of HRP, leads to showing for substrate solution color.By addition sulfuric acid terminate enzyme with This reaction between substrate, and color substrate solution is measured under the wavelength of 450nm with spectrophotometer, to obtain standard song Line is to calculate the concentration of Telomerase.As a result it is summarised in table 11, and makes to graphically illustrate in Figure 13.
11 telomerase activation of table improves
As shown in table 11 and Figure 13, test group (with combination A, B, C and D treatment) according to the present invention 1 week to 4 after the treatment Show Activation of Telomerase effect more better than all control groups week.Particularly, with the single treatment group treated with A, B, C or D For the summation of telomerase activation effect compared to (4 weeks after treatment: telomerase activation increases by 1.03), test group shows excellent association Same effect is (4 weeks after treatment: 1.20).Moreover, test group is shown than the group with combination ABC treatment and single the controlling with D treatment The effect found in treatment group summation (4 weeks after treatment: 1.02), with combination ABD treatment group and with C treat single therapy group The summation of the effect of middle discovery is (4 weeks after treatment: 1.01), with the group of combination ACD treatment and in the single therapy group of B treatment sending out The summation of existing effect is (4 weeks after treatment: 0.99) and with the group of combination BCD treatment and in the single therapy group of A treatment finding Effect summation (4 weeks after treatment: 1.01) better synergy.Therefore, by combining all treatment A, B, C and D, this hair The bright external member for being used to prevent skin aging and cosmetic system have excellent telomerase activating effect.
Embodiment 6: measurement colour of skin improvement
(1) skin hydration is measured
Measure the skin hydration of study subject.This is completed by the capacitor of measurement reflection water content, in skin Water has highest dielectric constant, is indicated by arbitrary unit (AU).It is transferred to and connects that is, skin hydration usually passes through measurement The capacitor for touching the weak current of the probe of skin surface determines.Since water content and capacitor are proportional to one another, skin hydration is got over Greatly, measured value is higher.Therefore, which can be substantially by applied cosmetics or drug (leading in electric scattered field Body track) influence under conditions of water content under test constantly cuticula in 30~40 μm of depth.In addition, the device has in spy Under different test condition, for example, assessing the only of skin hydration when probe keeps slight distance with skin and is not directly contacted with skin Special ability.The range of readings of the device is from minimum 0AU to 120AU.In this respect, the capacitor of solid is usually 7F (farad), and The capacitor of water is 81F.Then, if the weak current of 7F to 81F flows, capacitance difference will occur.120 are divided that difference by, is obtained The value of above-mentioned arbitrary unit (AU).According to the principle, when being measured by the device, the plastics for being typically free of any water are shown Capacitor with about 6~8AU, and 100% moisture will provide 120AU when measuring.That is, higher value is explained To indicate higher water content.When by diameter be 16mm probe be placed on skin surface be in close contact measuring point and with When constant pressure is vertically pressed on the skin, there is digital reading, and use the average value for carrying out 5 measurements within a certain area (middle section between cheekbone and chin, 4 × 4cm) is recorded.Reading indicates that hydration levels are good for 35~40,31~34 It indicates slightly to lack moisture, and 25~30 indicate exsiccosis.As a result it is summarised in table 12, and makes to figure in Figure 14 Out.
12 skin hydration of table improves
As shown in table 12 and Figure 14, test group (with combination A, B, C and D treatment) according to the present invention 1 week to 4 after the treatment Show skin hydration improvement more better than all control groups week.Particularly, with the single therapy treated with A, B, C or D The summation (4 weeks after treatment: skin hydration increases by 2.27) of skin hydration improvement in group is compared, and test group shows excellent Synergy (4 weeks after treatment: 7.39).Moreover, test group is shown than the group treated with combination ABC and the list treated with D The summation of the effect found in one treatment group is (4 weeks after treatment: group 2.71), with combination ABD treatment and single controlling with C treatment The effect found in treatment group summation (4 weeks after treatment: 3.56), with combination ACD treatment group and with B treat single therapy group The summation of the effect of middle discovery is (4 weeks after treatment: 2.32) and in the group of combination BCD treatment and the single therapy group with A treatment It was found that effect summation (4 weeks after treatment: 2.61) better synergy.Therefore, by combining all treatment A, B, C and D, The external member for being used to prevent skin aging of the invention and cosmetic system have excellent skin hydration improvement.
(2) measurement of skin roughness
For the skin roughness of evaluation studies subject, using the image of optical principle shooting test zone, and by skin Skin surface profile is converted into chart and number.The Silver Mirror (× 60 mirror) for the use of diameter being thus 30mm, and by the head of the device Portion is placed on the measuring point being in close contact with skin surface, and is vertically pressed on the skin using constant pressure, and use exists The average value of 5 measurements carried out in certain region (middle section between cheekbone and chin, 4 × 4cm) is recorded.Reading is 28~31 indicate that roughness is good, and 32~35 indicate that skin is slightly coarse, and 36~40 indicate pachylosis.As a result it is summarised in table In 13, and make to graphically illustrate in Figure 15.
13 skin roughness of table
As shown in table 13 and Figure 15, test group (with combination A, B, C and D treatment) according to the present invention 1 week to 4 after the treatment Show skin roughness reducing effect more better than all control groups week.Particularly, it is individually controlled with what is treated with A, B, C or D The summation (4 weeks after treatment: skin roughness reduces -2.17) of skin roughness reducing effect in treatment group is compared, test group table Reveal excellent synergy (4 weeks after treatment: -3.82).Moreover, test group shows the group than being treated with combination ABC and uses D The summation of the effect found in the single therapy group for the treatment of is (4 weeks after treatment: -2.55), with the group of combination ABD treatment and with C controlling The summation of the effect found in the single therapy group for the treatment of is (4 weeks after treatment: -2.21), with the group of combination ACD treatment and with B treating Single therapy group in the summation of effect that finds (4 weeks after treatment: being treated -1.75) and with the group of combination BCD treatment and with A Single therapy group in the summation of effect that finds (4 weeks after treatment: -3.56) better synergy.Therefore, by combining institute There are treatment A, B, C and D, there is excellent skin roughness to drop for the external member for being used to prevent skin aging of the invention and cosmetic system Low synergy.
(3) measurement of pigmentation and pore
Use RSA (Robo Skin Analyzer CS 50, In Forward.Inc., Japan) measuring study subject Pigmentation amount variation.RSA is the instrument for allowing to carry out pore, pigmentation, wrinkle, colour of skin etc. joint inspection.Its Can be by using the illumination of compact molding box and from identical angle shot photo, and there is high reproducibility.With the apparatus measures The pore of study subject and the variation of pigmentation amount, by image capture apparatus and image analysis computer system two parts group At instrument capture wrinkle, pigment, the colour of skin, the image information of pore etc., and directly generate result.Because it can be from three Different angle shot photos, therefore it to can be carried out accurate analysis.As a result it is summarised in table 14, and used in Figure 16 Chart is shown.
14 pigmentation of table reduces (%)
As shown in table 14 and Figure 16, test group (with combination A, B, C and D treatment) according to the present invention 1 week to 4 after the treatment It shows pigmentation more better than all control groups week and reduces effect.Test group show than with combination ABC treatment group and With D treatment single therapy group in find effect summation (4 weeks after treatment: -3.39), with combination ABD treat group and use C The summation of the effect found in the single therapy group for the treatment of is (4 weeks after treatment: -3.83), with the group of combination ACD treatment and with B controlling The summation of the effect found in the single therapy group for the treatment of is (4 weeks after treatment: -3.38) and with the group of combination BCD treatment and with A controlling (4 weeks after treatment: -3.26) significantly excellent synergy is (4 after treatment for the summation of the effect found in the single therapy group for the treatment of Week: -4.58).Therefore, by combining all treatment A, B, C and D, the external member and beauty for being used to prevent skin aging of the invention There is system significantly excellent cutaneous pigmentation to reduce synergy.
Embodiment 7: for change of skin and satisfaction after treating and the evaluation questionnaire of side effect
Evaluation questionnaire investigation is carried out with the satisfaction of study subject about changing after 4 weeks skin treatings after treatment.It asks Volume is by forming 8 problems of the self-assessment for investigating subject after treatment, 7 problems including assessing change of skin satisfaction With 1 problem of future usage intention.In addition, the unfavorable dermoreaction in observational study region, such as erythema, oedema, decortication, scabies Itch and shouting pain, and result is summarised in table 15.
Table 15
It can be noted that the external member or cosmetic system according to the present invention for preventing skin aging (is surveyed such as in table 15 Examination group-is treated with ABCD) highest satisfaction is obtained to all effect item purpose self-assessments.
The collagenous fibres shown in number increase, elasticity changes with embodiment 1 to 6 for the self-assessment of these effectiveness results Kind, wrinkle improvement, skin repair effect, hydration improvement, roughness improvement are consistent with the result that pigmentation improves, and show basis Of the invention external member or cosmetic system for preventing skin aging is by the inclusion of component A, B, C and D related to skin aging Various aspects have synergy.Therefore, it is used to prevent the combination ABCD of skin aging, external member from controlling with according to the present invention In the group for the treatment of, 80% subject indicates have future strong use to be intended to, and subject's expression in control group less than 30% will To have using intention.
Meanwhile each from C single therapy group, ABD combined therapy group, ACD combined therapy group and BCD combined therapy group One subject undergoes erythema, and combines each from C single therapy group, D single therapy group, ABD combined therapy group, ACD One subject for the treatment of group and BCD combined therapy group undergoes itch.However, being not significantly different between treatment group is to be worth note Meaning.
Those skilled in the art in the invention will be understood from the foregoing description, and the present invention can not depart from its technology Implement in other embodiments in the case where design or essential characteristic.In this respect, previous embodiment should be construed as only It is illustrative and be all non-limiting in any way.Therefore, protection scope of the present invention will by appended claims and Its equivalent determines.

Claims (23)

1. a kind of for preventing the external member of skin aging comprising
A) telomerase activating composition;
B) dermis of skin irradiates laser;
C) the composition for local fat removal of the hyaluronidase comprising 300IU to 600IU;With
D) skin muscular sarcocyte irradiates laser.
2. external member according to claim 1, wherein prevent skin aging be collagen generation, collagen contraction, collagen remodeling, Skin repair, skin elasticity enhancing, wrinkle improvement, local fat removal, the lipolysis in fat cell, decrease in edema, skin Telomerase activating, skin hydration in skin cell improve, in skin roughness improvement, cutaneous pigmentation improvement and colour of skin improvement It is one or more.
3. external member according to claim 1, wherein A) telomerase activating composition increase Skin Cell in telomere albumen The expression of the subunit protein of complex, the protein subunits of the telomere protein complexes be selected from TRF1 (telomere repetition factor 1), TRF2 (telomere repetition factor 2), RAP1 (suppressing Activating protein-1), TIN2 (TERF1- interaction nuclear factor 2), POT1 (telomere Protected protein 1) and one of TPP1 (three peptidyl peptidases 1) or a variety of.
4. external member according to claim 1, wherein A) telomerase activating composition include Dendropanax Morbifera Lev. extract, Kappaphycus alvarezii extract or their mixture are as active constituent.
5. external member according to claim 1, wherein A will be applied) telomerase activating composition and frequency of use be 10 to The ultrasonic laser treatment of 90Hz combines.
6. external member according to claim 1, wherein B) dermis of skin irradiation laser be selected from frequency be 2 to 100Hz One of laser and RF (radio frequency) laser are a variety of, transfer thermal energy to corium or are transferred to corium and SMAS (shallowly Table muscular aponeurotic system).
7. external member according to claim 6, wherein B) to be selected from frequency be swashing for 5Hz to dermis of skin irradiation laser The RF laser that the laser and frequency that light device, frequency are 30 to 50Hz are 35 to 45MHz it is one or more.
8. external member according to claim 1, wherein C) hyaluronidase comprising 300IU to 600IU for local rouge The composition of fat removal is injectable composition.
9. external member according to claim 8, wherein the injectable composition for local fat removal further includes local anaesthesia Agent, antihistaminic, lipolysis stimulant and collagen generate one of stimulant or a variety of.
10. external member according to claim 9, wherein the local anesthetic is lidocaine, and the antihistaminic is skin Stretching-sensitive, the lipolysis stimulant is L-carnitine, and it is vitamin C that the collagen, which generates stimulant,.
11. external member according to claim 10, wherein the injection combination for local fat removal of every single dose volume Object includes the hyaluronidase of 300IU to 600IU, is counted on the basis of the total weight of injectable composition, the injectable composition is also The lidocaine for being 0.08 to 0.4% comprising weight percent as local anesthetic, weight percent is 0.01 to 0.02% Skin stretching-sensitive as antihistaminic, L-carnitine that weight percent is 0.01 to 4.0% as lipolysis stimulant and again Vitamin C that percentage is 0.1 to 2.0% is measured as collagen generation stimulant, remaining is salting liquid, and the composition with 0.5 to 2cc single dose volume is injected, between injection point between be divided into 0.5 to 1.5cm.
12. external member according to claim 11, wherein for local fat removal injectable composition also with 0.01 to The total amount of 4.0 weight % includes one kind or more selected from phosphatidyl choline, aminophylline, caffeine, placental hormone and pentoxifylline Kind component.
13. external member according to claim 1, wherein D) skin muscular sarcocyte irradiation laser inside mouth towards face Portion's irradiation, and be the laser that frequency is 1 to 3.5Hz, skin muscular sarcocyte is transferred thermal energy to, or be transferred to integumentary musculature Layer and dermis.
14. external member according to claim 13, wherein irradiation D) skin muscular sarcocyte irradiation laser, so that in target skin Reach the temperature of 45 to 70 range in skin layers.
15. a kind of for preventing or treating the cosmetic system of skin aging comprising:
A) telomerase activating composition;
B) dermis of skin irradiates laser;
C) the composition for local fat removal of the hyaluronidase comprising 300IU to 600IU;With
D) skin muscular sarcocyte irradiates laser.
16. cosmetic system according to claim 15 further includes ultrasonic laser and A that frequency is 10 to 90Hz) Telomerase activating composition.
17. cosmetic system according to claim 15, wherein B) dermis of skin irradiation laser be selected from frequency be 2 to Laser and RF (radio frequency) laser of 100Hz it is one or more, transfer thermal energy to corium or be transferred to corium and SMAS。
18. cosmetic system according to claim 15, wherein C) for local fat removal composition be injection combination Object, and the composition for local fat removal also includes local anesthetic, antihistaminic, lipolysis stimulant and collagen Generate stimulant.
19. cosmetic system according to claim 18, wherein C) note for local fat removal of every single dose volume The hyaluronidase that composition includes 300IU to 600IU is penetrated, is counted on the basis of the total weight of injectable composition, the injection group Close object also include weight percent be 0.08 to 0.4% lidocaine as local anesthetic, weight percent be 0.01 to 0.02% skin stretching-sensitive is stimulated as antihistaminic, the L-carnitine that weight percent is 0.01 to 4.0% as lipolysis The vitamin C that agent and weight percent are 0.1 to 2.0% generates stimulant as collagen, remaining is salting liquid, and described Composition is injected with 0.5 to 2cc single dose volume, between injection point between be divided into 0.5 to 1.5cm.
20. cosmetic system according to claim 15, wherein D) skin muscular sarcocyte irradiation laser inside mouth towards face Portion's irradiation, and be the laser that frequency is 1 to 3.5Hz, it transfers thermal energy to skin muscular sarcocyte or is transferred to integumentary musculature Layer and dermis.
21. a kind of for preventing the beauty method of skin aging, wherein following steps progress is considered that its is suitable at least once and not Sequence:
I) the step of applying telomerase activating composition;
Ii the step of) irradiation dermis of skin irradiates laser 3 to 60 minutes;
Iii) part is used for inject with the interval between 0.5 to 1.5cm injection point and with 0.5 to 2cc single dose volume The step of composition of fat removal;With
Iv the step of) being irradiated laser 3 to 10 minutes inside mouth towards face irradiation skin muscular sarcocyte.
22. beauty method according to claim 21, further include with step i) simultaneously or after step i) immediately according to Radio frequency rate is ultrasonic laser 5 to 20 minutes of 10 to 90Hz.
23. beauty method according to claim 21, wherein step ii) in dermis of skin irradiation laser be selected from frequency Laser, the laser that frequency is 30 to 50Hz and the RF laser that rate is 5Hz it is one or more, wherein
The frequency is laser illumination 3 to 8 minutes of 5Hz,
The frequency is laser illumination 15 to 40 minutes of 30 to 50Hz, also,
The RF laser is irradiated 4 to 10 minutes with the frequency of 40.68MHz.
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