CN101849890B

CN101849890B - Synchronous repair and sunscreen composite nano emulsion for skin injury from ultraviolet A radiation and ultraviolet B radiation and method for preparing same

Info

Publication number: CN101849890B
Application number: CN2010101809246A
Authority: CN
Inventors: 杨永鹏; 朱晓亮; 董萍; 丁克祥; 左夏林; 丁宇
Original assignee: Individual
Current assignee: Individual
Priority date: 2010-05-18
Filing date: 2010-05-18
Publication date: 2011-12-28
Anticipated expiration: 2030-05-18
Also published as: CN101849890A

Abstract

The invention relates to a synchronous repair and sunscreen composite nano emulsion for skin injury from ultraviolet A radiation and ultraviolet B radiation and a method for preparing the same. The product is prepared from the following raw materials in percentage by mass: 9.0 to 13 percent of isopropyl myristate, 25.0 to 33 percent of caprylocaproyl macrogolglyceride, 8.5 to 15 percent of polyglyceryl fatty acid ester, 33 to 46 percent of triple distilled water, 0.002 to 0.004 percent of superoxide dismutase, 0.25 to 0.4 percent of glutathione, 1 to 3 percent of vitamin E, 1.5 to 3 percent of coenzyme Q10, 0.8 to 1.6 percent of 1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-diketone, 2.0 to 5.0 percent of ethylhexyl methoxycinnamate, 0.6 to 2.0 percent of 4-methyl benzylidene camphor, 0.03 to 0.2 percent of ethylene diamine tetraacetic acid, 0.05 to 0.3 percent of citric acid and 0.5 to 2.0 percent of sodium citrate. The composite nano emulsion greatly improves the stability, safety and sunscreen effect of the sunscreen functional ingredient, can prevent the skin from being further damaged by the ultraviolet radiation and synchronously achieve the repair effect while serving as sunscreen.

Description

Middle long wave ultraviolet skin injury is repaired and sun-proof composite nano-emulsion and preparation method synchronously

Technical field

The present invention relates to be applied to preparation sun-proof and that repair product after the improvement of preparation novel form technology process the reparation synchronously of long wave ultraviolet skin injury and sun-proof composite nano-emulsion and preparation method thereof in referring in particular to.

Background technology

Atmospheric ozone layer has stopped in the sunlight 99% ultraviolet radiation, has protected the tellurian all things on earth creature to avoid the injury of intensive ultraviolet.Since the reported first antarctic ozone cavities in 1985, the atmospheric ozone consume has become one of current global environmental problem.Be discharged into the chemical stability height of the chloro-fluoro-carbon kind chemical compound in the environment, the holdup time was 40～150 years in atmosphere.After these chemical compounds arrive stratosphere by the troposphere, be subjected to the high-energy ultraviolet radiation and decompose, decompose the chlorine atom and the ozone molecule reaction that produce, consume ozone molecule.Consequently, a chlorine atom consumes thousands of ozone molecules, and atmospheric ozone layer is seriously damaged, and the solar ultraviolet irradiation intensity increases.It is predicted, the every minimizing 1% of ozone content, UV sunlight intensity just increases by 2%, and skin carcinoma patient will increase by 3%.In recent years, along with the consume of ozone layer ozone, people's sun-proof consciousness and sense of self-protection strengthen, sun care preparations also become in a lot of people's lives necessary.

The solar ultraviolet wave band is divided disunity, but all is divided into four parts substantially.Common has: 400～320nm is long wave ultraviolet (a UVA wave band); 320～280nm is ultraviolet B radiation (a UVB wave band); 280～200nm is short wave ultraviolet (a UVC wave band); 200～100nm is vacuum ultraviolet (a UVD wave band); Pigmentation at once occurs after the UVA irradiation, pigmentation 1-2h after irradiation arrives the peak, and 3-4h disappears gradually.It is pigmentation that skin is subjected to according to the main reflection in back, and UVA accelerates skin metabolism.The UV radiation that the overwhelming majority arrives earth surface is UVA.The UVA radiation can be divided into 2 classes again: UVAII 320-340; UVAI340-400.Because UVAI and UVAII wavelength are very long, they can penetrate into dermis of skin, cause collagen protein and elastic fiber injured.Elastic fiber makes skin be shaped, and delimits and crooked function.Elastic fiber is injured will to produce wrinkle and the final skin premature aging that produces.The radiating injury of UVA can than UVB darker penetrate into epidermis and corium.The UVA light intensity is more steady, but it is at all times.It is forever to exist that UVA is radiated between equator and the latitude 60, seldom is subjected to height above sea level, the influence of time in season and a day.And it can penetrate glass and water.The biological chemical structure of skin and the change of organizational structure after long-term sunlight is exposed to the sun, photoaging that Here it is.It is dry that the skin of photoaging seems, keratinization is coarse, spottiness, and wrinkle is dark.

UVB claims " outdoor ultraviolet " again, as long as suitable coverage can isolate, it is the main cause that causes general red, inflammation of skin and sunburn; UVA can reflect into indoor, be called " indoor ultraviolet " again, it can go deep into skin corium, can destroy collagen, elastic fibers even fibroblast, so UVA still can not excite pigment synthetic and make the colour of skin " blackening ", cause skin " wear out " especially and the main chief culprit of microgroove generation.UVB is stronger to the physiological action of human body, causes tardy melanin pigmentation, and melanin pigmentation starts from shining back 48-72h.UVB can make skin produce and be permitted the polyphyly material, and important health care is arranged.7-dehydrocholesterol in the skin is converted into vitamin D3 after UVB (wavelength 280nm) irradiation, vitamin D3 is the important substance of calcium metabolism in the body.Because wave band is short, high-octane UVB light penetrates horny layer, enters epidermis.UVB light also can make skin produce erythema, is most active ultraviolet for the radiation of burning just.UVB can reduce enzyme and non-oxydasis agent in the skin rapidly, has hindered the free radical resisting ability thus, and many is that free radical is to be tanned by the sun by sunlight to cause.This also is considered to because the potential cause of the skin carcinoma of the impaired initiation of DNA, removes therefore that to tan by the sun the free radical that causes by sunlight also be a sun-proof importance.

UVC is isolated under the protection of ozone layer when entering atmosphere.The UVC wavelength is short, the energy of the nucleoprotein of biological cell and this wave band of ribonucleic acid strong absorption, and nucleic acid (DNA) has strong absorption for the ultraviolet of wavelength 250-260nm, makes material degeneration such as microbial nucleic acids, and is disruptive to organism and microorganism.Therefore, UVC is usually used in sterilization treatment, and many with the wavelength of 253.7nm as ultraviolet sterilization, ultraviolet sterilizing lamp commonly used in the Cosmetic Manufacture is promptly based on this principle.

The wavelength of UVD band ultraviolet is extremely short, and high-octane vacuum ultraviolet can produce a large amount of ozone, and the oxidisability of ozone is very strong, and good sterilization and deodorization are arranged.From the histology, the characteristics of photoaging skin are exactly a large amount of elastic fibers of degenerating to occur, and the elastic fiber of degeneration finally goes bad and is unbodied material.Along with chronic aging, elastic fiber quantity and thickness increase on a small quantity, and ultrastructure has MC.In the skin of photoaging, be that collagen protein has reduced with what Elastic tissue formed distinct contrast.The collagenase of having evidence suggests the UV photopolymerization initiation, collagenase hydrolysis glue connects tissue, causes destroying, and wrinkle occurs.For general aging, the degraded of the more stable and obstruction enzyme of sophisticated collagen changes very tricklely, and the appearance of deep layer wrinkle is seldom arranged.Significantly the photoaging symptom is tanned by the sun up to light and could be occurred in a lot of years of back, so photoaging is one of pathology that least draws attention.To more than 40 year old, when photoaging symptom over fifty years old occurs, just have destructive skin histology impaired, and in fact this just begun at 15 years old.Because ultraviolet is omnipresent, and is all-pervasive, it is necessary therefore using sun-proof and repairing skin care item.

Can make human body skin avoid solar radiation effectively by the following method: absorb UV light, light scattering, luminous reflectance suppresses free radical or does not contact sunlight to be exposed to the sun.Usual way is the UV light absorber and suppresses free radical.Many sunscreen productses all over the world contain the UVB sunscreen, the erythema that the UVB sunscreen can avoid UVB light to be exposed to the sun and to produce.The protection efficient of these sunscreen productses can be weighed with spf value.Spf value is high more, and is just better to the protection of UVB so.Some generation can protect skin to avoid the shortwave part (UVAII:320-340nm) of UVA wavelength, but does not protect the long wave part (UVA:340-400nm) of UVA wavelength, and this part long wave can deeper penetrate into corium generation microgroove and wrinkle.Be used in the UVA organic sunscreen agent in sunscreen products and the skin care item at present, can only be protected from UVA short wavelength, be i.e. the injury of UVAII wavelength (320-340).UVAI light is the ultraviolet of tool deep layer penetrance, therefore can the bottommost layer of skin be damaged.The UV light sky that some is not intercepted advances skin thoroughly, produce free radical, and pair cell has a negative impact.Nearest research proves that effectively some vitamin such as vitamin E and vitamin C are antioxidants, can strengthen the function of UV sunscreen, provides the wide spectrum of the best sun-proof, prevents the infringement of environment and too early skin aging.

Sunscreen can be divided into physical sunscreen agent and chemical sunscreen on mechanism.The physical sunscreen agent mainly is by reflection, masks ultraviolet and reaches sun-proof purpose.Chemical sunscreen then is by absorbing ultraviolet, making it be converted into heat and discharge, to reach sun-proof effect.The present sunscreen cream of less pure physics on the market, common product all is the product mix in conjunction with physics and chemical sunscreen, these products are exactly the advantage that combines physical sunscreen agent and chemical sunscreen.The main component of physical sunscreen agent is titanium dioxide and zinc oxide, and zinc oxide can be used to treat diseases such as eczema, dermatitis at department of dermatologry, thus based on the product of this sunscreen, non-stimulated, be fit to responsive skin matter and use, relatively safety.Certainly not being the physical sunscreen product just 100% can be irritated because in the sunscreen cream except sunscreen, also have other adjunct ingredient, some people may also can be to these composition allergy, re-uses after therefore the people of responsive skin matter still needs to test.Simultaneously, the sun-proof spectrum of physical sunscreen agent is wider, so sun-proof ability is more intense.But, because physics, the chemical property of these two kinds of materials determine it can only be mixed with butyrous unguentum and use that so this sunscreen cream is relatively more oily, thick and heavy clouding, butyrous skin uses just may feel comfortable inadequately.Product quality based on chemical sunscreen is relatively finer and smoother, is put on and feels salubriouser on the skin, is more suitable for oily skin, may cause allergy but deficiency is some product.And under action of ultraviolet radiation, can decompose, fission, also promptly so-called " light degradation ", different sunscreen has different light degradation rates, and photodegradation has reduced chemical sunscreen to the Ultraviolet rays protection effect.According to test, the different monooctyl ester of chemical sunscreen methoxy cinnamic acid that in sun care preparations, uses at present, after through the radiation of 10 times of minimum erythema ultraviolet dosages, nearly nearly 70% light degradation.The light degradation of chemistry sunscreen is the problem that formulator is had a headache very much.Because light degradation, the chemical sunscreen that must add higher dosage in the prescription has sufficiently high SPF when having guaranteed to use.To the investigation in the sun care preparations in the market, find that there is such or such problem in sun-proof functional component, the situation of summary is as follows.

Deficiency and the following introduction of problem that physical sunscreen agent and chemical sunscreen and dosage form thereof are used:

1. the quality of physical sunscreen agent: the physical sunscreen agent be meant can uv reflectance additive, inorganic compound normally.A lot of people think that the sunscreen that adds the physics sunscreen is comparatively safe, and some producer even " physical sunscreen " are as the attraction.1. shortcoming: some shortcoming of physical sunscreen agent is bad as: skin sense, feel, and particularly the product of high SPF must add a large amount of titanium dioxide, zinc oxide etc., is a problem in the skin uniform spreading; Use as the powder body dosage form in addition, stop up pore easily.2. advantage: physical sunscreen agent biggest advantage is can light degradation, and its mechanism is uv reflectance, itself is inert, does not also have the problem of skin absorbs, and this also is that everybody thinks the reason of physical sunscreen agent than chemical sunscreen safety.

2. the quality of chemical sunscreen: 1. shortcoming: under action of ultraviolet radiation, can decompose, fission, also promptly so-called " light degradation ", call it by the fine-sounding name of: light stability is not high.Different sunscreen has different light degradation rates, and photodegradation has reduced chemical sunscreen to the Ultraviolet rays protection effect.According to test, the different monooctyl ester of chemical sunscreen methoxy cinnamic acid that in sun care preparations, uses at present, sun-proof result is fine, but after through the radiation of 10 times of minimum erythema ultraviolet dosages, nearly nearly 70% light degradation.Therefore chemical sunscreen light degradation is the problem that formulator is had a headache very much.Because light degradation, the chemical sunscreen that must add higher dosage in the prescription has sufficiently high SPF when having guaranteed to use.On the other hand, after chemical sunscreen infiltrates through skin, the micromolecule after the degraded, to skin, body toxic side effect whether, this problem is very troubling always.Though official represents safety through strict test,, the micromolecule after in fact sunscreen decomposes still has zest to human body, particularly the product of high spf value.2. advantage: still, chemical sunscreen still has its strong point, and chemical sunscreen is dissolved in oil phase, even under the big situation of addition, use feeling should than physical sunscreen agent will, sensation is light saturating and other skin care item difference are little.On the other hand, different chemical sunscreen ultraviolet signature absworption peak differences can compositely be used, and reaches synergism.But at present a lot of sun care preparationss, composition is single, does not have the wide spectrum effect.The common chemical sunscreen is described below: 1. o-aminobenzoa class, salicylic acid esters are the absorbent of UVB, and absorption efficiency is low, and is big to the zest of skin, but cheap, comparatively commonly used in the product at home; 2. Methoxycinnamate, absorbent properties are good, can absorb UVB preferably in alcoholic solution; 3. benzophenone and derivant thereof have the certain absorption effect to UVA, UVB, and to light and thermally stable, but absorbance is low, and oxygen resistence is general, need add antioxidant, and be the most commonly used with oxybenzone, but certain phototoxicity is arranged; 4. methane Derivatives be fit to the SPF (sun protection factor) high product, but light stability is poor, degraded significantly behind the ultra-vioket radiation, and bigger to the zest of skin, sensitization is strong, is restricted so use; 5. Camphora series is the most commonly used with UVINUL MBC95, and is better to the assimilation effect of UVA, stability and chemical inertness better, skin absorbs is few, stimulate little, no phototoxicity and mutagenicity, poor to ultraviolet absorptance benzophenone and derivant thereof.In a word, chemical absorbent is the optical effect of ultra-violet absorption value importantly, can defend erythema, anti-sunburn, effect such as tanned, often skin is had than strong stimulation and damage but dosage is excessive, and may cause the decline of epidermis, so its consumption is all restricted, be the effect of the scattering of physics radiation and the physical sunscreen agent is emphasized, sun-proof result is more weak and influence the secretion of sebaceous gland and sweat gland.

3. the deficiency of current sunscreen product dosage form

Skin-protection product all must be made the form that is suitable for various application before supplying with use, this form is called the dosage form of administration, is called for short preparation.In application, use and reach the skin effect of the best for convenience,, also can be processed into different dosage forms with a kind of product and use according to the purposes difference of skin-protection product.For the requirement of preparation, require product to make different dosage forms after, can make things convenient for consumer to use, uses comfortablely, increased the stability of product simultaneously, minimizing toxic and side effects, and effect will get well, also be convenient to product storage, transport and carry.The dosage form that the antitan agent product is commonly used has powder, ointment, Emulsion, membrane etc. in the market, and the physical sunscreen agent often is prepared into powder, spreads upon sun-proof position during use, utilizes the principle of reflection to reach sun-proof result.But the physical sunscreen dosage form, skin sense, feel are bad, and are problems in the skin uniform spreading; The powder body dosage form is used in addition, stops up pore easily.Chemistry sunscreen ointment commonly used, emulsion dosage form.Chemistry sunscreen light stability is not high, and different sunscreen has different light degradation rates, and photodegradation has reduced chemical sunscreen to the Ultraviolet rays protection effect.On the other hand, the micromolecule after the chemical sunscreen degraded, easier of skin generation zest.And current dosage form fails to address these problems, and we remove to seek the novel sunscreen of discovery or solve these problems with a kind of new dosage form with regard to needs for this.

Researcher is arranged at present by detecting sunscreen, find that sunscreen can absorb and to cause in the ultraviolet that the wavelength that the people produces acute dermatitis (erythema) and skin burn is that the ultraviolet B radiation (UVB) of 290～320nm and the wavelength of skin darkening are the long wave ultraviolet (UVA) of 320～400nm.In sun care preparations but add too much UV absorbent, easily skin being produced stimulates, make skin allergy, photosensitive, play erythema, chafing, aging and blackening etc.Therefore, " cosmetics health standard " done restriction to the kind and the use amount of sunscreen, and content is about 1%～10% in cosmetics.The side effect of sun care preparations is except dermoreaction such as contact dermatitis, contact allergy and photosensitivity, and professional medical information has report, and sunscreen can influence the synthetic of vitamin D, causes observable vitamin D ₃Reduce.Life-time service SPF is 29 sun care preparations, has obtained same conclusion after 2 years.Because sun care preparations is put the area that is coated with on the skin on skin big, and bear burning sun and tan by the sun, therefore, guarantee that security of products is extremely important.Have research to detect 380 parts of sunscreen products altogether in 4 years, disqualification rate is 9.2%.Wherein repeatedly skin irritation test: in (degree) zest account for 2.9% (this rank is a substandard product), gently (degree) zest 66.3%, nonirritant 30.8%; Skin allergic reaction test: moderate sensitization accounts for 2.4%, slight sensitization 4.0%, weak sensitization 5.0%, do not see skin allergic reaction 88.7%, and moderate sensitization and slight sensitization are substandard product; Skin Phototoxicity experiment result there is no the skin phototoxicity.The sample that detects in 4 years has 9.2% toxicology disqualified upon inspection, has illustrated that the part sun care preparations has potential insecurity.In 3 toxicological tests, the disqualification rate the highest (6.3%) of skin allergic reaction test; Secondly repeatedly skin irritation test (2.9%).

Therefore, a kind of advantages of good skin sun care preparations in use not only will have sun-proof result, and wants safety and comfort, and product is stable.Certainly these are not only relevant with the physicochemical characteristics of sun-proof functional component, also with the carrier that uses very big relation are arranged.Problem in the face of sunscreen sensitization can only reduce the content of sunscreen in cosmetics, and low content adds the instability of sunscreen, and photolysis causes the effect of sun care preparations to reduce more.How to make the sunscreen better application in cosmetics, keep the sunscreen good stable and reduce its anaphylaxis, and reach good effect that this just becomes the problem of formulator overriding challenge.

For this reason, a kind of novel carriers-nano-emulsion (nanoemulsion) that in cosmetic industry, has been born again.Nano-emulsion is begun one's study from the forties in 20th century by Schulman, just has medicinal nano breast to come out up to late 1990s, and nano-emulsion is just really used also thing in recent years in pharmaceutical formulation.Nano-emulsion is celebrated with atomic grain, the emulsion droplet particle diameter that it is made up of oil phase, water, emulsifying agent and co-emulsifier is about the transparent or semitransparent liquid between 10～100nm, its emulsion droplet is dispersed in the another kind of liquid and forms dispersion system of colloid, has certain opalescence, it is spherical that its emulsion droplet mostly is greatly, and size is more even, good fluidity, can not make it layering through heating or autoclaving or centrifugalize yet, belong to the thermodynamically metastable fixed system usually.Two fundamental differences of nano-emulsion and common emulsion are: at first, the formation of ordinary emulsion generally needs the external world that energy is provided, and the formation of nano-emulsion is spontaneous; Secondly, ordinary emulsion is a thermodynamic unstable system, in depositing process, will take place coalescent and finally be divided into oil, water is biphase, and nano-emulsion is a thermodynamic stable system, can not take place coalescent.

Yet at present nano-emulsion is sun-proof and repair the problem that also exists in the cosmetic applications synchronously: still do not have precedent at applying nano breast at present at home and abroad as carriers sun-proof and that repair cosmetics synchronously; How to select lower emulsifying agent of toxicity and co-emulsifier and prescription sunscreen coupling, thereby reduce the toxicity and the sensitization of skin of product; How to reduce the consumption of emulsifying agent and co-emulsifier; How to determine the emulsifying agent and the co-emulsifier of optimum matching, improve functional component stability in the product; How to determine best prescription and preparation technology; Reparation synchronously of long wave ultraviolet skin injury and sun-proof composite Nano Ruzhong functional component are brought into play better anti-sunlight function and advantage in how making; How to select better and determine that the kind of functional component is come compatibility and application dose or concentration in this product, or the like all be a unsolved difficult problem.Work of the present invention be exactly determine good in the long wave ultraviolet skin injury repair synchronously and sun-proof composite nano-emulsion prescription, the ratio of each component in nano-emulsion and preparation method thereof.

Summary of the invention

For overcome exist in the current background technology shortcoming: (1) chemical sunscreen can decompose under action of ultraviolet radiation, fission, and light stability is not high, as, benzophenone and derivant oxygen resistence thereof are general, need add antioxidant; Methane Derivatives be fit to the SPF (sun protection factor) high product, but light stability is poor, degraded significantly behind the ultra-vioket radiation, and bigger to the zest of skin, sensitization is strong.(2) at present a lot of sun care preparationss, composition is single, does not reach the effect of opposing while UVA and UVB, does not have the wide spectrum effect.(3) at present in the sunlight screening skin-protecting product, the ultra-violet absorption agent content is higher, and too much UV absorbent, and easily skin being produced stimulates, make skin allergy, photosensitive, play erythema, chafing, aging and blackening etc.(4) present sunscreen product, when playing anti-sunlight function, but the free radical that can not cause producing to ultraviolet is synchronously removed, and reaches the effect of reparation.

The objective of the invention is to be improved, innovate, the reparation synchronously of a kind of middle long wave ultraviolet skin injury and sun-proof composite nano-emulsion and preparation method thereof are provided at shortcoming that exists in the background technology and problem.

2. technical scheme of the present invention

(1) reparation synchronously of long wave ultraviolet skin injury and sun-proof composite nano-emulsion are made (consumption is a mass percent) by following component among the present invention: isopropyl myristate 9.0%～13%, sad capric acid polyethyleneglycol glyceride 25.0%～33%, polyglyceryl fatty acid ester 8.5%～15%, triple distillation water 33%～46%, superoxide dismutase 0.002%～0.004%, glutathion 0.25%～0.4%, vitamin E 1%～3%, coenzyme Q10 1.5%～3%, 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1,3-diketone 0.8%～1.6%, the different monooctyl ester 2.0%～5.0% of methoxy cinnamic acid, 4 methyl benzylidene camphor 0.6%～2.0%, disodiumedetate 0.03%～0.2%, citric acid 0.05%～0.3%, sodium citrate 0.5%～2.0%.

(2) preferred mass percentage ratio of the present invention is: isopropyl myristate 7.9%, sad capric acid polyethyleneglycol glyceride 31.5%, polyglyceryl fatty acid ester 10.5%, triple distillation water 38.497%, superoxide dismutase 0.003%, glutathion 0.3%, vitamin E 2%, coenzyme Q10 2%, 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1,3-diketone 1.3%, the different monooctyl ester 3.6% of methoxy cinnamic acid, 4 methyl benzylidene camphor 1.2%, disodiumedetate 0.1%, citric acid 0.1%, sodium citrate 1.0%.

(3) principles of formulating prescriptions of the present invention:

1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1, the 3-diketone is the most effective fat-soluble UVA filtering agent, safety of being sold by the drugs approved by FDA sales counter and effective UVA sunscreen, it can very effective blocking-up UVA, thereby can improve the spf value of sunscreen product.The composite best results of 4 methyl benzylidene camphor p-methoxycinnamic acid monooctyl ester, and 4 methyl benzylidene camphor can increase its stability in product, can significantly improve the SPF index.Human body skin is played extremely effectively protection and repair.Octyl methoxycinnamate is very safe oil-soluble UVB lightscreening agent, and higher UVB extinction coefficient are arranged, and also is one of sunscreen that utilization rate is the highest in the global range, and it more can not cause allergic reaction than other chemical analysis.Skin ductility is good, and life-time service can effectively reduce sunburn, erythema etc., is used with other lightscreening agent, can protect skin to avoid photo-aging, suppresses the formation of skin surface mottle.

Ultraviolet can cause skin to produce free radical, and unnecessary free radical just can damage body by multiple channel, for example oxygen-derived free radicals can cause lipid peroxidation, lipid peroxide meeting and protein cross, produce insoluble protein, this variation is the most obvious with collagen protein in the connective tissue, and it can cause collagen to become tough, contraction in length, make skin lose expansive force is so-called wrinkle; In addition, lipid peroxide can resolve into materials such as malonaldehyde under oxidasic effect, and generates xanthein with the PHOSPHATIDYL ETHANOLAMINE commissure, and then to form purple brown matter with materials such as protein, nucleic acid be so-called senile plaque.Purple brown in fact matter not only appears at face, other positions such as brain, the heart, liver etc. also occur in vivo.And SOD is super oxyradical scavenger, can effectively prevent or delay the generation of said process to the continuous supplemented with exogenous SOD of body by suitable approach.SOD is widely used in cosmetics both at home and abroad, shows, effects such as crease-resistant, speckle dispelling, the element that discolors are not only arranged, also have the effect of antiinflammatory, sun-proof, delaying decrepitude of skin through clinical verification and life-time service.It is reported and all add a certain amount of SOD in the superior cosmetics of states such as America and Europe, Japan.At present the domestic market occurs contain the SOD cosmetics have multiple, as big precious SOD, SOD compound enzyme cosmetic cream etc.The clinical research that SOD compound enzyme cosmetic cream is done shows, SOD compound enzyme cosmetic cream is 88.68% to treatment wrinkle effective percentage, the freckle effective percentage is 87.80%, the acne effective percentage is 94.74%, the pigmentation effective percentage is 91.84%, total effective rate is 90.17%, has compared significant difference with matched group.The SOD molecular weight is about 32000, and can it by skin absorbs, and the Shanghai The 2nd Army Medical College is coated with test outside carrying out with 125I labelling SOD, and the result shows that SOD can be by skin absorbs.According to these results, the SOD cosmetics should be good.

Glutathion be belong to contain sulfydryl, the small-molecule peptide material, have two kinds of important antioxidations and integrate Detoxication.Glutathion is the tripeptides by glutamic acid, cysteine and glycine be combined into, and its molecular weight is 307.33.Current research shows that glutathion can be corrected the imbalance of acetylcholine, acetylcholine esterase, plays anti-allergic effects, also can prevent skin aging and pigmentation, reduces melanic formation, improves the skin oxidation resistance and makes skin produce gloss.

Coenzyme Q10 has another name called " ubiquinone ", it is a kind of intravital fat-soluble natural vitamins material of multiple biology that is present in, it is the Natural antioxidant that cell self produces, and can improve organic immunity, is the metabolic important active substances of indispensable participation in the human body.Its dominant mechanism is the carrier of electronic cell and proton, participates in protein and lipid metabolism, is that Cellular respiration and metabolism are the necessary activator of human body cell produce power.It is the natural micromolecule that a kind of human skin itself just exists, can quicken cell and upgrade, and the activated cell activity, thus promote the ability of cellular uptake nutrition greatly.In skin care item, add coenzyme Q10, can help other nutrient in the Skin Cell active absorption skin care item effectively, make the skin protection composition rest on skin surface no longer simply, really realize the composition effect (effect from outside to inside) of skin care item.Coenzyme Q10 to aging resistance, reduce wrinkle, recover skin gloss elasticity, aspect such as whiten has original effect; and can effectively replenish cellular energy, delaying skin aging, repair damage that the radical pair cell causes, protect fragile skin, simultaneously to promoting the cellular metabolism function, remove blood rubbish, effectively suppress melanin, improving obscure skin etc. certain effect is arranged.

Vitamin E (Vitamin E; VE) be a kind of fatsoluble vitamin with extensive physiological action; also be a kind of advantages of good skin nutrient and oil-soluble small molecule antioxidant; it is nutrition and conditioning skin effectively; and interrupt the chain reaction of free radical rapidly; the protection cell membrane stability prevents lipid peroxidation on the film.VE also has the connective tissue of keeping elasticity, promotes the sanguimotor effect of blood vessel.Also the scalable hormone is normally secreted in vivo, and acid is plain in the control volume consumes, and protects functions such as mucocutaneous, thereby makes the skin moisturizing fitness, is full of youthful vigor.VE prevents that to keeping skin metabolism skin aging from playing crucial effects, also can prevent the facial dark brown spot that produces, and also is the accumulation of lipoid brown pigment, promotes the blood circulation of terminal blood vessel, makes skin that abundant nutrition supply be arranged, and keeps gloss to moisten.

Disodiumedetate (EDTA-Na ₂) be a kind of important chelating agent, be used for the metal ion and the separating metal of complex system, help and the effectiveness that keeps functional component.Citric acid and two hydration trisodium citrates can be formed good buffer system, and it is relatively stable to keep nano-emulsion system pH value, and help functional component and effectively bring into play.And citric acid belongs to the alpha hydroxy acid class, itself also has certain pigment dissolving and removes effect, and skin is had must beautification function.

(4) preparation method of reparation synchronously of long wave ultraviolet skin injury and sun-proof composite nano-emulsion among the present invention

1. take by weighing disodiumedetate, superoxide dismutase, glutathion according to formula ratio and place container, add again after triple distillation water dissolves, add citric acid and sodium citrate more successively, and with this solution as water (I).

2. according to formula ratio, take by weighing isopropyl myristate, place another container, add vitamin E, coenzyme Q10, UVB sunscreen 4 methyl benzylidene camphor successively, UVA sunscreen 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1,3-diketone, above material is ultrasonic concussion dissolving in tepidarium, add the different monooctyl ester of UVB sunscreen methoxy cinnamic acid again, also place ultrasonic the making it of ultrasonator concussion to dissolve fully, and with this solution as oil phase (II).

3. in sad capric acid polyethyleneglycol glyceride (S): the ratio of polyglyceryl fatty acid ester (C)=3: 1 (weight ratio) places among the other container; Fully mix homogeneously makes it to form emulsifying agent/co-emulsifier (S/C) mixture (III).

4. according to oil phase (II): S/C (III): the ratio of water (I)=18%: 42%: 40% (mass percent), the phase (I) of fetching water respectively earlier, S/C mixture (III) place container.

5. after above-mentioned water (I), S/C mixture (III) two liquid phases fully being mixed, again at ambient temperature or in the natural room temperature, put it into and shake in the ultrasonator also about ultrasonic 2min, perhaps under 25 ℃ of conditions of room temperature or in the natural room temperature, start the time constant-temperature magnetic stirring apparatus, with 200rpmmin ^-1Rotating speed magnetic agitation 5min, then, in this container, directly add oil phase (II) again, and with whole system in ultrasonator about ultrasonic 10min, perhaps under 25 ℃ of conditions of room temperature or in the natural room temperature, start the time constant-temperature magnetic stirring apparatus, with 200rpmmin ^-1Rotating speed magnetic agitation 20min.The long wave ultraviolet skin injury is repaired and sun-proof composite nano-emulsion synchronously in can forming.

(5) usage and dosage: the time spent, reparation synchronously of long wave ultraviolet skin injury and sun-proof composite nano-emulsion an amount of (about diameter 1.5cm) are applied to face in getting.

(6) storage: airtight, put shady and cool dry place and preserve.

3. beneficial effect of the present invention

Outstanding innovative point of the present invention is with sun-proof functional component 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1, the 3-diketone successfully combines application with the nano-emulsion carrier technique, the long wave ultraviolet skin injury is repaired and sun-proof composite nano-emulsion synchronously in the formation, and this is unprecedented.After sun-proof functional component combined with the nano-emulsion carrier and uses, the stability of sunscreen improved.The preparation composition of reparation synchronously of long wave ultraviolet skin injury and sun-proof composite nano-emulsion is simplified among the present invention, but wide spectrum is sun-proof.The nano-emulsion particle diameter is trickle, be evenly distributed, sense organ is fine.Simultaneously, the present invention integrate sun-proof with repair the skin injury that ultraviolet causes, in the time of sun-proof and can reach the effect of skin repair.The present invention is with low cost in addition, and preparation technology is simple, and practical operation is easy, and preparation is fast efficient, does not need special instruments and equipment, and all the deadline only can form product in 30 minutes, was easy to extensive industrialization.Specifically, the beneficial effect that middle long wave ultraviolet skin injury is repaired synchronously and sun-proof composite nano-emulsion embodied that adopts the technology of the present invention to prepare mainly shows as:

3.1 the stability of product efficacy composition improves greatly

1. the stability of illumination improves greatly: the long wave ultraviolet skin injury is repaired and sun-proof composite Nano milk product and product emulsion (under identical condition prescription functional component of the present invention being mixed with) synchronously in getting respectively, and place glass ground joint flat bottle respectively, placed under daylight lamp and the natural light Continuous irradiation simultaneously 30 days, by sampling in 0,5,10,15,30 day.Through measuring index of correlation, find that the middle long wave ultraviolet skin injury that adopts the technology of the present invention to prepare is repaired synchronously and the middle long wave ultraviolet skin injury of sun-proof composite Nano milk product is repaired synchronously and ultra light sun block lotion product light stability is higher.

2. the experiment of the sensitivity under condition of different temperatures: the long wave ultraviolet skin injury is repaired and sun-proof composite Nano milk product and product emulsion synchronously in getting respectively, and place glass ground joint flat bottle respectively, placed 0 ℃, 4 ℃, 25 ℃, 40 ℃, 60 ℃, 80 ℃ temperature simultaneously following 30 days, by sampling in 0,5,10,15,30 day.Through measuring index of correlation, find that the middle long wave ultraviolet skin injury that adopts the technology of the present invention to prepare is repaired synchronously and the middle long wave ultraviolet skin injury of sun-proof composite Nano milk product is repaired synchronously and the ultra light sun block lotion product stability is higher.

3. be exposed to the stability experiment of depositing naturally with room temperature in the air: the long wave ultraviolet skin injury is repaired and sun-proof composite Nano milk product and product emulsion synchronously in getting respectively, and place glass beaker respectively, (the room temperature condition temperature is 20-25 ℃ to place air at room temperature simultaneously, relative humidity is 50%-75%), expose 30 days, by sampling in 0,5,10,15,30 day.Through measuring index of correlation, find that the middle long wave ultraviolet skin injury that adopts the technology of the present invention to prepare is repaired synchronously and the middle long wave ultraviolet skin injury of sun-proof composite Nano milk product is repaired synchronously and the ultra light sun block lotion product stability is higher.Room temperature stability is observed: the long wave ultraviolet skin injury is repaired and sun-proof composite Nano milk product and product emulsion synchronously in getting respectively, and place glass ground joint flat bottle respectively, place natural room temperature air (the room temperature condition temperature is 25-32 ℃, and relative humidity is 40-80%) to deposit sampling in 30 days simultaneously.Through measuring index of correlation, find that the middle long wave ultraviolet skin injury that adopts the technology of the present invention to prepare is repaired synchronously and sun-proof composite Nano milk product is higher than the ultra light sun block lotion product stability of traditional handicraft preparation.

4. high speed centrifugation separation test: the long wave ultraviolet skin injury is repaired and sun-proof composite Nano milk product and product emulsion synchronously in getting respectively, and place respectively high speed centrifuge supporting centrifuge tube, with 16000rpmmin ^-1The centrifugal 30min of speed, through measuring index of correlation, find that the middle long wave ultraviolet skin injury that adopts the technology of the present invention to prepare is repaired synchronously and sun-proof composite Nano milk product is higher than the ultra light sun block lotion product stability of traditional handicraft preparation.

3.2 the prescription reasonability of product improves greatly: the sad capric acid polyethylene glycol glycerol fat and the polyglyceryl fatty acid ester that adopt France from natural plants, to extract in this product, and the ratio of they and the shared nano-emulsion system nearly 90% of pure water, therefore, glue and sticking, oily but not greasy, dense and not thick, particularly they are little to the zest of skin, safety is good, few side effects, free of toxic effects.Our sunscreen 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1 of selecting for use in addition, the 3-diketone is the most effective fat-soluble UVA filtering agent, and effect is better than many physical action compositions, and can protect cell and immune system.Safety of being sold by the drugs approved by FDA sales counter and effective UVA sunscreen, it can very effective blocking-up UVA, thereby can improve the spf value of sunscreen product.The composite use of filtering agent of it and UVB can improve the effect of sunscreen product, in it and the composite best results of 4 methyl benzylidene camphor p-methoxycinnamic acid monooctyl ester.4 methyl benzylidene camphor can increase its stability in product.Reparation composition such as superoxide dismutase in the product, vitamin E etc. can be strengthened the function of UV sunscreen when playing anti-sunlight function, provide the wide spectrum of the best sun-proof.Buffer system in the prescription helps to keep the pH value of nano-emulsion simultaneously, improves the stability of system, guarantees sun-proof result.

3.3 product has dual function: the present invention integrate sun-proof with repair the skin injury that ultraviolet causes, in the time of sun-proof and can reach the effect of skin repair.Cause that for ultraviolet skin produces unnecessary free radical good scavenging action is arranged, prevented that radical pair skin from further losing, formula for a product functional component of the present invention plays extremely effectively protection and repair to human body skin.

Improve 3.4 the sun-proof result of product is compared greatly with mill run: the result of the non-nano milk product clinic trial with the dosage functional component of the same type that the composite nano-emulsion of using the present invention's development and traditional handicraft are prepared shows that the SPF (sun protection factor) of reparation synchronously of middle long wave ultraviolet skin injury and sun-proof composite nano-emulsion improves greatly.

3.5 the sense organ and the comfort of product improve greatly: nanoemulsions as two kinds of immiscible liquid according to a certain percentage, under the combined effect of surfactant and cosurfactant, form naturally thermodynamically stable, isotropic, good fluidity, as clear as crystal, glittering and translucent, trickle xanchromatic, slightly opalescent dispersion arranged, have good sense organ, and actual comfort is splendid.

3.6 the sun-proof functional component of product improves greatly in the dissolubility of carrier: the middle long wave ultraviolet skin injury according to technology preparation of the present invention is repaired and sun-proof composite nano-emulsion synchronously, under identical condition with beauty functions composition of the same race (as 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1, the 3-diketone) carries out dissolubility test, find that the saturation solubility of functional component in the nano-emulsion carrier is apparently higher than traditional emulsion carriers product, its mechanism is concentration and the dosage that nano-emulsion can improve the sun-proof functional component in the unit volume solvent greatly, no matter be water miscible sun-proof functional component, still oil-soluble sun-proof functional component can reach solubilizing amount to greatest extent in nanoemulsions.

3.7 security of products improves greatly.Adopt nano-emulsion technology of preparing of the present invention, under the identical or better situation of result of use, reduced 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1, the application concentration of the sun-proof functional component of 3-diketone in product, reduce the addition of traditional method, this makes the contingent skin irritation of functional component on the one hand, anaphylaxis, toxic and side effects reduces greatly, thereby safety improves greatly, on the other hand, 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1, the stability of the sun-proof functional component of 3-diketone in the nano-emulsion carrier improves greatly, reduce sun-proof functional component and be degraded to micromolecule, reduced the sensitization of sunscreen, the safety that has improved sunscreen to skin.

3.8 this product cost lowers, technology is simple, be beneficial to environmental protection: which kind of type sunscreen product no matter traditional sunscreen product technology produce, owing to need to use plurality of raw materials, its oil phase and water-phase component complexity, technological process is loaded down with trivial details, production cycle is longer, particularly oil phase and water must just can be finished emulsifying etc. under hot conditions, and the preparation composition of the composite nano-emulsion of the present invention preparation simplify, with low cost, preparation technology is simple, practical operation is easy, preparation efficiently fast, does not need special instruments and equipment, does not need the external world energy to be provided, not to need to heat.

4. the present invention has following effect and function:

4.1 improve the stability of sun-proof functional component in sunlight screening skin-protecting product.There is cracked shortcoming in the chemistry sunscreen in application, can decompose under action of ultraviolet radiation, fission, and light stability is not high.Different sunscreen has different light degradation rates, and photodegradation has reduced chemical sunscreen to the Ultraviolet rays protection effect.According to test, the different monooctyl ester of chemical sunscreen methoxy cinnamic acid that in sun care preparations, uses at present, after through the radiation of 10 times of minimum erythema ultraviolet dosages, nearly nearly 70% light degradation, therefore chemical sunscreen light degradation is the problem that formulator is had a headache very much.Because light degradation, sufficiently high SPF is arranged in the time of must adding the chemical sunscreen assurance use of higher dosage in the prescription.And use nano-emulsion technology preparation of the present invention, the effect nanometer emulsion of its formation then can improve the stability of sunscreen significantly, reduces the degradation rate of sunscreen greatly.

4.2 improve the safety of sun-proof functional component in application.The sunscreen that has causes skin allergy easily.Can cause photoallergy and contact dermatitis as PABA (para-amino benzoic acid), and easy and whitening composition reaction, cross allergy formed.Other are such as symptoms such as mottle generation, skin pruritus, rednesses, all with the penetrance of chemical sunscreen and zest not without responsibility.The process that chemistry is sun-proof also is a kinds of oxidation reaction in fact, can generate the unwanted refuse of various skin equally, rests on the flesh table.Theoretically, no matter which kind of functional component, surpassing its using dosage or repeatedly repeatedly the time, all might cause the abnormal response of skin; Particularly the biomacromolecule material of some chemosynthesis materials or heterologous is all the more so.Therefore, these functional components are when using, if do not adopt relevant preparation or vehicle treated, its product can't guarantee its safety naturally, even serious skin irritation or allergy or skin injury occur.And after adopting nano-emulsion of the present invention to handle, sun-proof functional component in the product adds concentration and can reduce greatly, access times also obviously reduce, in addition because nano-emulsion itself also has certain antibacterial action, need not add chemical preservative just can prevent product rotten, and can certain inhibitory or killing effect be arranged to the certain micro-organisms that skin surface exists, the safety of application is improved.

4.3 improve the compatibility of functional component in product.Functional component according to its water solublity or oil-soluble be wrapped in different mutually in, make that the functional component in the homophase not can not influence each other, improved the stability of prescription, make inconsistent functional component also can in same prescription, use.When using nano-emulsion technology of the present invention preparation, then can be according to the needs of reality prescription, appropriate design or add any functional component or functional component, and the sun-proof effect nanometer emulsion that forms can keep its good stable, and improve or strengthen its action effect greatly.

4.4 improve the dissolubility of functional component.Preparation must ultra light sun block lotion or during sun care preparations, and functional component must reach in product must concentration, and sun-proof functional component could be brought into play sun-proof effect on skin.Traditional suntan lotion is ancient sun care preparations dosage form, and oil film is thinner, and being difficult for lasting maintenance and water solublity sun-prevention component can not add, and the oil-soluble constituent concentration is lower.Chang Yong ultra light sun block lotion and cream frost in the market, most of a kind of dosage form can only be held a kind of functional component of character, can not hold water solublity and oil-soluble composition simultaneously.And use nano-emulsion technology of preparing of the present invention, and can promote different deliquescent functional component solubilisings, improve the dissolubility of functional component in product.

4.5 improve the sense organ comfortableness of product.Nanoemulsions as two kinds of immiscible liquid according to a certain percentage, under the combined effect of surfactant and cosurfactant, form naturally thermodynamically stable, isotropic, good fluidity, as clear as crystal, glittering and translucent, trickle xanchromatic, slightly opalescent dispersion is arranged, have good perception.Its molecule or the emulsion droplet particle diameter overwhelming majority are in nanoscale (between 10～100 nanometers), and therefore, the product efficacy composition re-uses after preparing by the nano-emulsion technology, feels fine and smooth, smooth, moist, comfortable more.

4.6 improve the mobility of prescription.A kind of good product needed also will change prescription according to practical situation in the face of different consumer groups, as oily skin with regard to inapplicable butyrous sun care preparations.The product of the application of the invention preparation, comprise that mainly four of oil phase, water, surfactant and cosurfactants are mutually, by this four phase liquid and hydrophile-lipophile balance value difference, can obtain oil-in-water type nanoemulsions (O/W), water-in-oil type nanoemulsion liquid (W/O) and doubly-linked ideotype nanoemulsions as required.Adjust and change conveniently because of its dosage form, therefore can prepare different sun-proof reparation nano-emulsions in actual applications according to the physicochemical property of season, skin type and functional component.

4.7 improved the reasonability of formula for a product.In order to improve the stability of functional component and product, the prescription functional component mutual aid that we select is collaborative, has improved stability each other simultaneously mutually.Sunscreen 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1, the 3-diketone is the most effective fat-soluble UVA sunscreen, with UVB sunscreen 4 methyl benzylidene camphor and the composite best results of the different monooctyl ester sunscreen of methoxy cinnamic acid.4 methyl benzylidene camphor can increase its stability in product.While EDTA-Na ₂, sodium citrate-citric acid buffer system improved the stability of nano-emulsion product, the prescription of product is very reasonable.The present invention has added antioxidant content in order to remove the free radical that is produced by ultraviolet radiation skin in sunscreen formulas in addition, can in time remove free radical, avoids ultraviolet that skin is further lost.The present invention reaches the effect of reparation synchronously in sun-proof.

4.8 reduced the complexity of production.Middle long wave ultraviolet skin injury by the present invention's preparation is repaired and sun-proof composite nano-emulsion synchronously, and preparation technology is terse, technical operation is simple, saves time to save trouble; And whole process of preparation does not need specific apparatus and equipment, laborsaving saving money; And, carry out this product preparation can be under normal temperature condition the sun-proof effect nanometer emulsion system of spontaneous formation, do not need electric power and other energy, but both energy savings and cost are free from environmental pollution again.

4.9 nanoemulsions of the present invention belongs to the thermodynamically metastable fixed system as a kind of drug-supplying system (TDDS) carrier, is using genus initiative still aspect the antitan agent reparation skin care item.In the application aspect the cosmetics, can drive the application of nano-emulsion aspect other subject by the present invention.

4.10 nano-emulsion technology of the present invention is to prepare under the temperature conditions about 25 ℃, the activity of therefore thermo-labile for protection, high temperature functional component and content, particularly protected protein class, peptide class, enzyme, cell growth factor subclass isoreactivity material have important value (as the superoxide dismutase in the present invention's prescription).Application in other field provides a kind of good method for these functional components.

5. the know-why of nano-emulsion preparation of the present invention:

As oil phase, sad capric acid polyethyleneglycol glyceride is as emulsifying agent by isopropyl myristate in the present invention, and polyglyceryl fatty acid ester is a co-emulsifier, and distilled water is as water.And sad capric acid triglyceride are as functional component 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1, the cosolvent of sunscreen such as 3-diketone, disodiumedetate (EDTA-Na ₂) be a kind of important chelating agent, be used for the metal ion and the separating metal of complex system, help and the effectiveness that keeps functional component.Lemon acid and two hydration trisodium citrates can be formed good buffer system, and it is relatively stable to keep nano-emulsion system pH value, and help functional component and effectively bring into play.Because the sad capric acid polyethyleneglycol glyceride of emulsifying agent helps the mutual blending of oil phase isopropyl myristate and water distilled water and forms emulsion droplet, and the co-emulsifier polyglyceryl fatty acid ester also is the essential condition that sun-proof effect nanometer emulsion forms.Particularly because polyglyceryl fatty acid ester and the special separately physicochemical property of sad capric acid polyethyleneglycol glyceride, the co-emulsifier polyglyceryl fatty acid ester can be inserted in the limitans with the sad capric acid polyethyleneglycol glyceride of emulsifying agent, form complex condensed film, to improve the coagulability and the compliance of film, and can increase dissolubility with sad capric acid polyethyleneglycol glyceride, and further reduce interfacial tension, help forming more stable composite nano-emulsion.Sad capric acid polyethyleneglycol glyceride often is subjected to the restriction of dissolubility, and polyglyceryl fatty acid ester can make the dissolubility of sad capric acid polyethyleneglycol glyceride increase, the easier further dispersion of emulsion droplet, particularly sad capric acid polyethyleneglycol glyceride and polyglyceryl fatty acid ester are in isopropyl myristate and the further a large amount of absorption of distilled water boundary, both are reduced the concentration in continuous phase, interfacial tension become again on the occasion of, make it progressively to form stable middle long wave ultraviolet skin injury and repair synchronously and sun-proof composite nano-emulsion.

Main sun-proof effective component of the present invention is 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1, the 3-diketone.1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1, the 3-diketone is the most effective fat-soluble UVA filtering agent, and effect becomes to assign to better than many physical actions, and can protect cell and immune system.Safety of being sold by the drugs approved by FDA sales counter and effective UVA sunscreen, it can very effective blocking-up UVA, thereby can improve the spf value of sunscreen product.Middle long wave ultraviolet skin injury is repaired synchronously and the preparation principle of sun-proof composite nano-emulsion is drawn the pseudo-ternary phase diagram of various sun-proof functional component nano-emulsions in the prescription and nano-emulsion region area relative value size is carried out computational analysis by origin7.0 software.Owing to can make oil phase and water blending and form the nanometer emulsion droplet by emulsifying agent and co-emulsifier, and co-emulsifier can be inserted in the limitans of emulsifying agent, make it to form complex condensed film, improve the coagulability and the compliance of film, and can increase the dissolubility of emulsifying agent, further reduce interfacial tension, more stable after helping nano-emulsion and forming.Consider that emulsifying agent is subjected to the restriction of dissolubility, and co-emulsifier can make the dissolubility of emulsifying agent increase, the easier dispersion of emulsion droplet, particularly emulsifying agent and co-emulsifier are in oil phase and the further a large amount of absorption of aqueous phase interface, both are reduced the concentration in continuous phase, interfacial tension become again on the occasion of, make it progressively to form stabilized nano breast more.Meanwhile manage by 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1, oil-soluble sunscreen such as 3-diketone are dissolved among the oil phase isopropyl myristate, and under the effect of water soluble ingredients such as S/C mixture that sad capric acid polyethyleneglycol glyceride and polyglyceryl fatty acid ester form and distilled water and participating in, long wave ultraviolet skin injury reparation and sun-proof composite nano-emulsion synchronously in forming naturally.

During preparation, can it be dissolved in the corresponding phase liquid respectively earlier according to the dissolubility of functional component.After oil phase, emulsifying agent, co-emulsifier have been determined, can find out the nano-emulsion zone by pseudo-three-phase diagram, thereby determine their consumptions separately.In oil phase, water, emulsifying agent, four components of co-emulsifier, generally emulsifying agent and consumption thereof can be fixed, three summits of oil phase, water, three ingredients constitute equilateral triangles of co-emulsifier make phasor at constant temperature.Common way is: oil phase, emulsifying agent, the co-emulsifier mixed solution of definite composition are carried out titration with water.Whether with dropper carry out titration when adding water at every turn, stir simultaneously, examining then is transparent nano-emulsion or muddy nano-emulsion.Adding after water makes nano-emulsion reach complete equipilibrium, nano-emulsion should be transparent, clarification, flow and have opalescent liquid.Certainly, also can be with emulsifying agent and co-emulsifier mixed solution a summit as equilateral triangle, then oil phase and water are formed pseudo-three-phase diagram as two other summit of equilateral triangle.

The concrete preparation method and the basic step of oil-in-water type (O/W) nano-emulsion are: select oil phase and oleophilic emulsifier earlier, and according to certain ratio this oleophilic emulsifier is dissolved in the oil phase, constantly stir, make it to mix fully; This mixing material is slowly added aqueous phase, constantly stir; As the consumption of known co-emulsifier, then it directly can be added aqueous phase, as not know the consumption of co-emulsifier, the above-mentioned oil-water mixture body of then available this co-emulsifier titration promptly gets the oil-in-water type nano-emulsion till becoming clear.

6. Analysis and Identification of the present invention:

6.1 the naked eyes outward appearance is observed: blank nanoemulsions appearance colorless or light blue slightly, clear, visible opalescence, have certain fluidity.In the long wave ultraviolet skin injury repair synchronously and sun-proof composite nano-emulsion appearance colorless or faint yellow slightly, clear, visible opalescence, have certain fluidity.

6.2 the electron microscopic morphology of nano-emulsion is observed: the Sodium phosphotungstate drips of solution with 2-3% is added on the stencil plate earlier, in addition reparation synchronously of middle long wave ultraviolet skin injury and sun-proof composite nano-emulsion are added drop-wise to the copper mesh front, go too much sample liquid with the filter paper suction, the copper mesh face down is covered dye liquor drips, negative staining 30min takes out copper mesh, draws too much dye liquor with filter paper, with copper mesh face up place glass dish to dry 2 hours naturally after, under transmission electron microscope, carry out form observation and take a picture.The common atrament of the common form of the Electronic Speculum of nano-emulsion is the nano-emulsion droplet, and nano-emulsion negative staining form whiteness then is the nano-emulsion droplet, and background is a black.

6.3 nano-emulsion size, distribution and potential measurement: adopt the Ma Erwen assay method, get nano-emulsion 2ml and inject the test cup, measure size and the distribution and the zeta current potential of nano-emulsion particle by particle size analyzer.Usually, the mean diameter of nano-emulsion particle is between 10～100nm, and reparation synchronously of middle long wave ultraviolet skin injury and sun-proof composite nano-emulsion centralized particle diameter meet the characteristics of nano-emulsion about 60nm.

6.4 1-in the nano-emulsion (4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1, the mensuration of 3-diketone: reparation synchronously of long wave ultraviolet skin injury and sun-proof composite nano-emulsion were an amount of during precision took by weighing, put respectively in the 25mL measuring bottle, adding butanediol or propylene glycol are diluted to scale and shake up, as need testing solution.1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1, the assay of sun-proof functional components such as 3-diketone and related substance check that assay carries out assay with reference to its quality standard and content assaying method, by detecting 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1, the 3-diketone accounts for 1.2% of total content, meets the restriction that " cosmetics health standard " done the sunscreen use amount.

6.5 the evaluation of nano-emulsion type: adopt staining to identify that the cardinal principle of the type of nano-emulsion is to judge the type of nano-emulsion by tonyred (oiliness dyestuff) and methylene blue (water-soluble dye) red or blue diffusion speed in nano-emulsion: water-soluble dye in the diffusion of O/W nano-emulsion soon, because O/W nano-emulsion continuous phase is water, water-soluble dye is faster than spreading at oil phase at water, as a same reason, oil-soluble dyes are fast in the diffusion of W/O nano-emulsion.Being tested and appraised composite nano-emulsion of the present invention is the oil-in-water type nano-emulsion.

7. preparation points for attention of the present invention:

7.1 used container must strictly according to the rules clean and sterilization during the product preparation, preferably adopting strong acid to soak back water dashes, clear water washes clean again, dry with distilled water immersion the back, place again after the baking oven high-temperature sterilization drying standby, but the materials such as antiseptic that preparation process is avoided contacting heavy metal and Fe ion and contained release formaldehyde, equipment application of pure rustless steel, compositions such as prescription water must not be brought metal ion into, in order to avoid influence product quality and stability.

7.2 incomplete same because of the quality standard of present sun-proof functional component of the same race and raw material, particularly there is some difference for content and purity, therefore, when carrying out the product preparation, the quality and the source of the hig diligence raw material of being sure to.After in the end determining formula material and preparation method, do not change raw material sources and quality more in principle, in order to avoid influence product quality, stability and result of use.

7.3 prepare in strict accordance with above-mentioned dosage and method.When carrying out this product preparation, should add according to above-mentioned flow sequence, its additive capacity must require accurate, and, sun-proof functional component of various oil-solubles or additive raw material addition sequence can not be made mistakes in the oil phase process for preparation, and could add a kind of raw material down after the raw material that must wait a kind of adding fully dissolves again,, influence the preparation of whole nano-emulsion system in order to avoid muddiness occurs.

7.4 when preparation composite nano-emulsion of the present invention, need select and definite S/C mass ratio (km value), and definite S/C mass ratio (km value) 1,2,3,4, be to carry out the oily biphase binary liquid test of titration water and last definite by ability after the pseudo-ternary phase diagram analysis, only, be only comparatively ideal km value determining and calculating the km value that obtains maximum nano-emulsion zone.Above-mentioned preparation method determines that by testing Km value has been 3, but actual when carrying out the product preparation, surfactant (S) and cosurfactant in this ratio still must be after mixing also will be more abundant mixing, prepare effect and quality in order to avoid influence.

7.5 oil phase Semen Myristicae isopropyl ester (IPM) is at the sun-proof functional component of dissolved oil dissolubility (1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1, dissolution velocity when 3-diketone and 4 methyl benzylidene camphor is slower usually, for increasing work efficiency or dissolution velocity, under situation with good conditionsi, can adopt ultrasonic shake and a little the mode of heat to quicken the dissolving of functional component or additive, make sure to keep in mind not use the method for high-temperature digestion, in order to avoid destroy functional component.

7.6 because the proportion or the different relation of density of liquid solution, when carrying out the product preparation, the capacity of selected preparation container must be a bit larger tham the product volume of actual preparation, as prepare the 100g product, need to select the preparation container of 150-200mL, like this, both be convenient to each composition and fully mixed and dissolve, also be convenient to ultrasonic concussion or stirring and evenly mixing, and be unlikely to overflow outward.

7.7 though blank nano-emulsion itself has the characteristics of certain bacteria growing inhibiting, but owing in the formula for a product other interpolation antiseptic is not arranged, so when carrying out the product preparation, except that the preparation container must carry out strictness cleaning and sterilization, also should be during concrete the preparation in strict accordance with rule of operation, under aseptic condition and according to the sterile working, require to operate as far as possible, avoid product nano-emulsion product to be polluted, influence product quality.

7.8 the product that preparation is finished don't fail to lucifuge be packed, also place cool place, drying, ventilation, lucifuge place to preserve as far as possible.In addition, after product uses at ordinary times, need not place low temperature or refrigerator to preserve, but must seal tightly, be positioned over natural room temperature and get final product.

7.9 the ratio of oil phase, water, emulsifying agent, co-emulsifier is very crucial, the ratio of the oil phase of the present invention design, water, emulsifying agent, co-emulsifier is only decided at a certain or two kinds of functional components, during other effect nanometer emulsion of reality preparation, can suitably adjust the ratio of oil phase, water, emulsifying agent, co-emulsifier according to the concrete condition that occurs in the process for preparation, but had better not surpass 5% up and down, the ratio of adjusting 2-3% usually gets final product.

Though 7.10 nano-emulsion belongs to the thermodynamically metastable fixed system, temperature is too high and cross the low stability that then directly has influence on it, emulsifying agent mainly is distributed in water during low temperature, then mainly is distributed in oil phase during high temperature.The rising of temperature because the lipophile of emulsifying agent increases, hydrophilic weakens, forms reverse micelle, so the hydrophilic group of nonionic emulsifier weakens with the HYDROGEN BOND INTENSITY that water forms, even ruptures, and will cause emulsifying agent to be separated out from aqueous solution, promptly produces the cloud point phenomenon.Temperature reduces, because the hydrophilic of nonionic emulsifier is greater than lipophile, it and water form positive micelle, therefore, also will produce similar cloud point phenomenon.Have only the system of working as to be in certain medium temperature, nonionic emulsifier then can form the stratiform micelle, thereby really reaches balance, and system is also kept balance and stable.Therefore, the effect nanometer emulsion that requires to prepare is preserved at normal temperatures.

Description of drawings

Fig. 1. the preparation technology's flow process and the technology path of reparation synchronously of middle long wave ultraviolet skin injury and sun-proof composite nano-emulsion.

The specific embodiment

Middle long wave ultraviolet skin injury is repaired and sun-proof composite nano-emulsion synchronously

Each raw material preferred mass percentage ratio is: isopropyl myristate 7.9%, sad capric acid polyethyleneglycol glyceride 31.5%, polyglyceryl fatty acid ester 10.5%, triple distillation water 38.497%, superoxide dismutase 0.003%, glutathion 0.3%, vitamin E 2%, coenzyme Q10 2%, 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1,3-diketone 1.3%, the different monooctyl ester 3.6% of methoxy cinnamic acid, 4 methyl benzylidene camphor 1.2%, disodiumedetate 0.1%, citric acid 0.1%, sodium citrate 1.0%.

The preparation method (100g is an example with preparation) of reparation synchronously of middle long wave ultraviolet skin injury and sun-proof composite nano-emulsion:

1) accurately takes by weighing disodiumedetate 0.1g respectively with analytical balance, superoxide dismutase 0.003g, glutathion 0.3g places through among the 100mL conical flask of decontamination, add again after 38.497g triple distillation water fully dissolves, add 0.1g citric acid and 1.0g sodium citrate more successively, the dissolving of above material can place the CQ-10 ultrasonator to carry out ultrasonic concussion accelerate dissolution, more than every kind add and to add time a kind of material again after material all needs to dissolve fully, clearly be labeled as water (I) 40g with colored marking pen, and with this solution as water.

2) accurately take by weighing the isopropyl myristate of 7.9g weight with analytical balance, place another through among the 50mL conical flask of decontamination, add the 2g vitamin E successively, the 2g coenzyme Q10,1.2g oil-soluble UVB sunscreen 4 methyl benzylidene camphor, 1.3g fat-soluble UVA sunscreen 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1, the 3-diketone, above material is ultrasonic concussion dissolving in tepidarium, add the different monooctyl ester of 3.6g oil-soluble UVB sunscreen methoxy cinnamic acid again, also place ultrasonic the making it of ultrasonator concussion to dissolve fully, and with clear oil phase (II) 18g that is labeled as of marking pen.

3) according to the sad capric acid polyethyleneglycol glyceride (S) that has designed in advance: the ratio of polyglyceryl fatty acid ester (C)=3: 1 (weight ratio), accurately take by weighing sad capric acid polyethyleneglycol glyceride of 31.5g and 10.5g polyglyceryl fatty acid ester respectively, and both are placed among the clean conical flask of 50mL of the 3rd process decontamination; Add a cover, and this conical flask placed rapidly on the liquid flash mixer, open the liquid flash mixer, and it is transferred to the II shelves, fully mix homogeneously makes it to form emulsifying agent/co-emulsifier (S/C) mixture, behind the 3-5min, the closing liquid flash mixer takes off conical flask, and with clear S/C mixture (III) 42g that is labeled as of marking pen.

4) according to oil phase (II): S/C (III): the ratio of water (I)=18%: 42%: 40% (mass percent), fetch water respectively earlier phase (I) 40g, S/C mixture (III) 42g place among the 4th the clean conical flask of the 200mL through decontamination.

5) above-mentioned water (I), S/C mixture (III) two liquid phases are fully mixed after, again under 25 ℃ of conditions of room temperature or in the natural room temperature, put it into and shake in the ultrasonator also about ultrasonic 2min, perhaps under 25 ℃ of conditions of room temperature or in the natural room temperature, start the time constant-temperature magnetic stirring apparatus, with 200rpmmin ^-1Rotating speed magnetic agitation 5min, then, in this container, directly add oil phase (II) 18g again, and with whole system in ultrasonator about ultrasonic 10min, perhaps under 25 ℃ of conditions of room temperature or in the natural room temperature, start the time constant-temperature magnetic stirring apparatus, with 200rpmmin ^-1Rotating speed magnetic agitation 20min.

6) close ultrasonator or time constant-temperature magnetic stirring apparatus, take off the 200mL conical flask, observe its outward appearance colourless in this way, limpid transparent, fluidity and good dispersion, obviously visible opalescence person is arranged, be among the 100g long wave ultraviolet skin injury and repair synchronously and sun-proof composite nano-emulsion.

7) long wave ultraviolet skin injury among this 100g is repaired synchronously and sun-proof composite nano-emulsion is sub-packed in rapidly among the lucifuge glass container of different size, added a cover, sterilization, packing, and place to preserve among drying, ventilation, the shady and cool room temperature and get final product.

8) according to International or National or enterprise's relevant criterion and requirement, stochastic sampling from above-mentioned packing product, and carry out the related system that national departments concerned requires and detect, after waiting to judge or estimating it and meet national relevant regulations and standard, promptly can be used as launch and sell.

* remarks: all implementation steps and operating process are all carried out in the aseptic environments in cleaning, and operator should carry out in strict accordance with sterile working's rules.

Embodiment of the present invention only is the description that preferred implementation of the present invention is carried out; be not that design of the present invention and scope are limited; do not breaking away under the preceding topic of design philosophy of the present invention; engineers and technicians make technical scheme of the present invention in this area various modification and improvement; all should fall into protection scope of the present invention; the technology contents that the present invention asks for protection all is documented in claims.

Claims

1. the long wave ultraviolet skin injury is repaired and sun-proof composite nano-emulsion synchronously in one kind, and it is characterized in that being used for reparation synchronously of long wave ultraviolet skin injury and sun-proof composite nano-emulsion is to be made by the raw material of following mass percent:

2. the long wave ultraviolet skin injury is repaired synchronously and sun-proof composite nano-emulsion in according to claim 1, it is characterized in that it is made up of the raw material of following mass percent:

Oil phase 18%, emulsifying agent and co-emulsifier mixture 42%, water 40%.

3. the long wave ultraviolet skin injury is repaired and sun-proof composite nano-emulsion synchronously in according to claim 2, it is characterized in that described oil phase is isopropyl myristate, vitamin E, coenzyme Q10,4 methyl benzylidene camphor, 1-(4-tert-butyl-phenyl)-3-(4-methoxyphenyl) propane-1,3-diketone, the different monooctyl ester of methoxy cinnamic acid.

4. the long wave ultraviolet skin injury is repaired and sun-proof composite nano-emulsion synchronously in according to claim 2, it is characterized in that described water is triple distillation water, superoxide dismutase, glutathion, disodiumedetate, citric acid, sodium citrate.