CN100508952C

CN100508952C - Freezing-dried and non-freezing-dried hydroquinone mono-propionate beautifying effect nanometer emulsion and preparation method thereof

Info

Publication number: CN100508952C
Application number: CNB2007102022433A
Authority: CN
Inventors: 丁宇; 丁克祥; 朱晓亮
Original assignee: Individual
Current assignee: Individual
Priority date: 2007-10-24
Filing date: 2007-10-24
Publication date: 2009-07-08
Anticipated expiration: 2027-10-24
Also published as: CN101167696A

Abstract

The invention discloses freeze-drying, non freeze-drying hydroquinone monocarbonylate nano-emulsions for beauty treatment and a process for preparation. The freeze-drying nano-emulsions contain the following materials by weight proportion: hydroquinone monocarbonylate 0.5-4 parts, vitamin E 0.2-2.0 parts, isopropyl myristate 8-18 parts, octanoic acid capric acid triacetate 0.1-1.0 parts, octanoic acid capric acid glycedol 32-40 parts, polyglycerol fatty acid esters 10-14 parts, double distilled water 35-45 parts, manna sugar 15-25 parts, aminoacetic acid1-6 parts. The non freeze-drying nano-emulsions contain the following materials by weight proportion: monocarbonylate 0.5-4 parts, vitamin E 0.2-2.0 parts, isopropyl myristate 8-18 parts, octanoic acid capric acid triacetate 0.1-1.0 parts, octanoic acid capric acid glycedol 32-40 parts, polyglycerol fatty acid esters 10-14 parts, double distilled water 35-45 parts. The invention has the advantages of simple preparation method, easy practical operation and industrialization, stable quality of products, prolonged storage time, and effective and quick preparation. The whole process for preparion can be finished in less than 30 minutes. No special apparatus is needed. Great progress has been made in saving energy and materials, and reducing the environmental contamination.

Description

Lyophilizing, non-freezing-dried hydroquinone mono-propionate beautifying effect nanometer emulsion and preparation method thereof

Technical field

The present invention relates to the bio-pharmaceutical preparation technique through being applied to the preparation of skin-color disposition disease and beauty treatment brightening, dispelling spots, dispelling product after improveing, refer in particular to a kind of freeze-dried type and non-freeze-dried type hydroquinone mono-propionate beautifying effect nanometer emulsion and preparation method thereof.

Background technology

Along with improving constantly of the progress of the development of society and science and technology and people's material, culture, spiritual life level, all personages' that like to be beautiful pursuit is not only in aesthetic health care, also becomes the important content that the modern society people pursue high-quality, high-grade life.Wherein, the skin whitening speckle dispelling has become the focus of current beautifying health cosmetics.

Yet a kind of beautifying health cosmetics of advantages of good skin brightening, dispelling spots, dispelling in use not only will have no side effect safely and makes skin that comfort be arranged, and product also must have good stable and effect.And these important prerequisites, not only substrate prescription and the technological process with skin whitening spot-eliminating beauty treatment cosmetics is relevant, and with the characteristic of interpolation functional component and carrier thereof and they close association such as influence to Transdermal absorption.In the past, though have been noted that the stability of functional component and the problem of Transdermal absorption, do not show great attention to as yet and take notice of that can the structure of functional component and physicochemical property promote its Transdermal absorption or whether can make the problem of its real performance useful effect by suitable carriers actually.Specifically, be exactly whether functional component in these skin whitening spot-eliminating beauty treatment cosmetics can make it see through that the keratodermatitis barrier reaches corresponding site of action and stable the keeping certain effect time at these positions by suitable carriers.

In fact, causing some skin whitening spot-removal function composition can not give full play to its main cause that biological action and physiologic function should be arranged concludes mainly and is: the histological structure of skin uniqueness, barrier action and defense function; Physicochemical properties such as shape, structure, molecular weight size and hydrophobicity; Bio information conduction, transhipment and absorbing path; Targeting, amalgamation, dissolubility and intermiscibility; Action pathway and bioavailability; Action time and dosage, half-life, effect duration; With the area size and the time of contact skin; The diversity that individual percutaneous absorbs etc.Among these reasons, at first, most important one be exactly the barrier function of skin.

On normal human skin histology and physiology, keratinocyte and stratiform lipid and substrate have been formed the cuticular layer of skin, and being considered to skin whitening spot-removal function composition, the lipotropy of these cuticular layers and hypotonicity be difficult to transdermal major obstacle, it is mainly by cholesterol, saturated free fatty of long-chain and ceramide are formed in the ratio of 1:1:1, and be arranged in the flat stratiform, can strictly limit exogenous material, comprise protein, water, sugar, lipid, vitamin, inorganic ions or cosmetic industry any material that becomes to grade passes through, and comprises that the skin whitening spot-removal function becomes to grade all can't or to be difficult to bring into play due biological action by complete keratodermatitis barrier.

In fact, in horny layer of epidermis, exist potential two passages: the one, between every 3-10 horn cell bundle, there is the crack (width〉0.1 μ m) of broad; The 2nd, the passage (average pore size 30nm) that the even narrow permeability that exists between each horn cell is relatively poor, the latter is the main thoroughfare of carrier.Therefore, make skin whitening spot-removal function composition can bring into play its effect and advantage, must make them can see through this road barrier of epidermis effectively; Bring into play its biological agent and advantage and will make these skin whitening spot-removal function compositions see through epidermal barrier, break through following approach unless adopt some effective ways: promptly reversibility ground changes flat Keratinocytic folded in order collection arrangement architecture in the keratodermatitis, increase the epidermis cell gap, and make the complete fluidisation of its lipoids; The binding ability of nitrogen substance and water improves cuticular hydration in the enhancing skin surface keratin; Effectively sebum noble cells on interior sebum of dissolving skin sebaceous gland duct or the lumen of gland wall reduces hydrophobicity in the sebaceous gland duct; By expansion and soften cuticle, thereby make the opening of sweat gland, hair follicle become the big skin whitening spot-removal function composition Transdermal absorption that promotes; When promoting its transdermal, suppress velocity of blood flow, it is increased in local skin concentration.

In order to realize this goal, a large amount of research staff are not only carrying out deep discussion and well-designed aspect the prescription of the beauty and make-up product of skin whitening speckle dispelling and the technological process, and in the kind of solvent, the allotment of substrate, short skin whitening spot-removal function composition transdermal, a large amount of scientific researches have been carried out in aspects such as adjusting percutaneous mechanism of absorption, and attempt or developed the targeting vector and the movement system of a series of skin functional components.For example, in skin whitening spot-eliminating beauty treatment cosmetics, be added with the natural medicine that is beneficial to short skin functional component Transdermal absorption, as adding terpenoid: comprise monoterpene, sesquiterpene, triterpenoid compound; Quintessence oil: comprise Oleum menthae, Oleum Caryophylli, oil of rosemary, Oleum Rosae Rugosae, Jasmin oil, Essential lavender oil, Laurel wet goods; Alkaloid; Lactone; Other: is as menthol and Borneolum Syntheticum etc.Add the synthesising preparation that some help short skin whitening spot-removal function composition Transdermal absorption in addition, as organic acid and esters thereof: comprise fatty acid, fatty acid ester, amino-acid ester, lactams ester, cholinester etc.; Pyrrolidinone compounds; Phospholipid and phosphoric acid salt; Amide-type; Enzyme etc.Wherein pass by the most frequently used have dimethyl sulfoxide, sodium tetradecyl sulfate, laurocapram, lauric acid, cocoa butter, Oleum Terebinthinae, shark alkane etc., and laurocapram has become the object of reference of some new short transdermal agents.The possible mechanism of these short Transdermal absorption synthesising preparations is by the lipid of dissolving skin surface, makes epidermal protein qualitative change, simultaneously, by to modes such as functional component solubilising or hydrotropies, increasing its permeability that passes the keratodermatitis barrier and their diffusion and distributions in each layer of epidermis, thereby reach the purpose that promotes the functional component Transdermal absorption.And the mechanism of the short Transdermal absorption of laurocapram also may and cuticular layer between the lipid of matter have an effect, to increase its flowability, to reduce the diffusional resistance of natural functional component and bioactive substance etc.

Yet, although above-mentioned short skin penetrant is promoting to have brought into play certain effect aspect the skin whitening spot-removal function composition Transdermal absorption, but because the source difference of above-mentioned skin whitening spot-removal function composition, its physicochemical property also has nothing in common with each other, and some is a water solublity, and some is fat-soluble, some is pure dissolubility, also some is that water oil is two molten or two insoluble, and therefore, the dissolubility and the stability that solve between above-mentioned short skin penetrant and the skin whitening spot-removal function composition are all very difficult; And, the molecular weight of some functional component is little, the molecular weight of some functional component is big, molecular structure and form be obvious difference also, depend merely on the passive transdermal effect of above-mentioned short skin penetrant, still be not enough to make skin whitening spot-removal function composition Transdermal absorption and the maximum biological action of performance smoothly, some functional component even still can't Transdermal absorption and its due biological action of performance.Particularly along with above-mentioned short skin penetrant great majority are chemosynthesis or semi-synthetic preparation, increasing or use as working concentration are too frequent, and the cost of product is increased, and, the irritated rate and the zest of skin are strengthened, and toxic and side effects is more obvious; Simultaneously skin whitening spot-removal function material mostly all to heat, to pH value, to illumination, to the oxidation reaction sensitivity, therefore, even above-mentioned short skin penetrant can promote the functional component Transdermal absorption, but because the unstability of skin whitening spot-removal function composition, in the implementation process of concrete formulated product, make these functional component inactivations again easily and can't bring into play its corresponding effect.

In order to overcome above-mentioned shortcoming and defect, there is the scholar liposome (Liposome) technology to be applied in the skin whitening spot-eliminating beauty treatment cosmetics having proposed in recent years.Liposome is a kind of carrier of short functional component Transdermal absorption preferably, it is to seal the hollow spheres body that forms by bimolecular lamellar lipid membrane, diameter is between 100-1000nm, because of its constituent and structure and biomembrane and cell membrane fairly similar, more easily make skin whitening spot-removal function composition see through the keratodermatitis barrier and enter subcutaneous.Liposome is encapsulated in this functional component in the middle of the thin film of class lipid bilayer, and form superminiature spheroid carrier preparation naturally, it promotes the mechanism of Transdermal absorption to have following several: 1. hydration: it can increase horny layer humidifying and hydration, make that structure changes between horn cell, the skin functional component can enter intercellular substance by effects such as diffusions.2. fusion: the phospholipid of liposome and the lipid layer in the epidermal barrier merge, and the horny layer lipid is formed and structural change, thereby barrier action is taken a turn for the worse, and the liposome that is encapsulated with the skin activity material can pass through smoothly; Or the phospholipid of liposome and epidermis lipid barrier form little bubble structure when producing fusion, and functional component is passed through between the little bubble structure to the skin internal penetration; 3. penetration: the external special construction of liposome is the transdermal horny layer directly, and can be penetrated into deep skin, even reach blood vessel, and can directly enter skin lower floor through sebaceous gland, sweat gland even hair follicle, to realize the Transdermal absorption effect of functional component.

Though, liposome truly has as skin whitening spot-removal function composition carrier system and is beneficial to its biological effect of performance, and performance application promise in clinical practice aspect skin whitening freckle dispelling aesthetic health care cosmetics, but it is as carrier formulation, remain and still have to be overcome and solution in some problems: liposome is in preparation process, with an organic solvent too much, particularly organic solvents such as chloroform (chloroform), methanol use too much, not only cause cost to raise, and very big to preparation person's health effect, cause serious environmental pollution etc. simultaneously; The preparation of liposome is based on phospholipid (soybean phospholipid and lecithin) and cholesterol, phospholipid (soybean phospholipid and lecithin) cost an arm and a leg (about 5000 yuan/kilogram), not only increase product cost greatly, make the product cost price higher, and, very difficult, time-consuming, bothersome, the effort of its dissolving in preparation process, very trouble operates also; Although functional component is good by liposome, the surface has been completed into a kind of lipoids structure, therefore, when preparation water solublity skin whitening spot-eliminating beauty treatment essence, but be difficult to mix, and, also there is certain problem with the intermiscibility of other preparation; In addition, when practical application, the long-term stability of liposome is preserved certain difficulty, and after placing a period of time, by the skin whitening spot-removal function composition of liposome still automatically seepage with overflow, less stable loses the parcel meaning; The preparation of functional component liposome is influenced by several factors and disturbs, and the operating technology of liposome still can not make liposome very high to the envelop rate of functional component especially at present, and in fact the envelop rate of Zhi Bei functional component liposome is lower; Because of the physicochemical property of liposome itself adds the problem of technological operation itself, comparatively speaking, the particle diameter of liposome is still bigger, and skewness, and this has also influenced the performance of its effect; Liposome still belongs to passive carrier, and its targeting is still limited, and therefore, action effect also is subjected to certain influence; And liposome also has an important defective to be, skin whitening spot-removal function composition is often to thermo-responsive, and the functional component liposome still can't be realized and coupling and the preparation of skin whitening spot-eliminating beauty treatment cosmetics under low temperature or room temperature at present.

For this reason, recent a kind of new carrier formulation---the nano-emulsion (nanoemulsion) that 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 the 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.

The method for preparing at present nano-emulsion mainly is divided into high energy emulsion process and low-energy emulsification method.The high energy emulsion process prepares nano-emulsion as the term suggests be to carry out the nano-emulsion preparation by the energy that various forms produces, and usually it is divided into three kinds of methods, i.e. shear agitation method, high pressure homogenizer homogenate method and supersound method.The shear agitation method can be controlled particle diameter well, and the prescription composition can have a lot of selections.High pressure homogenizer homogenate method is most widely used in commercial production, and general high pressure homogenizer operating pressure is 50-100MPa, and new its pressure of improved high pressure homogenizer can be up to 350MPa.Supersound method is reducing aspect the particle diameter very effectively, adopt the probe Ultrasound Instrument usually, but this method only is fit to the preparation small amount of sample, and the heating of in use popping one's head in can produce iron filings and go forward side by side into medicinal liquid, so the influence of quality to medicinal liquid of should noting popping one's head in.In addition, the dispersion of nano-emulsion also is subjected to the influence of supersonic frequency and ultrasonic time, and the hydrophobicity of polymerization single polymerization monomer is strong more, and required ultrasonic time is long more.

And the low-energy emulsification legal system is equipped with nano-emulsion is the physicochemical property of utilizing its system, makes the dispersion of emulsion droplet can spontaneous generation nano-emulsion.The low-energy emulsification legal system is equipped with nano-emulsion and is divided into the phase transition temperature emulsion process usually and changes emulsion process mutually.The phase transition temperature emulsion process is used more extensive in commercial production, it is a characteristic of utilizing the dissolubility of polyoxyethylene-type non-ionic surface active agent to change along with variation of temperature, with water with oil phase is disposable is mixed in together, when temperature raises, hydrogen bond on the surfactant molecule comes off, the polyoxyethylene chain dehydration, and the molecule hydrophobicity strengthens, spontaneous curvature becomes negative value, forms aqueous reverse micelle (w/o type Emulsion); When temperature was reduced to phase transition temperature, surfactant spontaneously made curvature approach zero, and formed layer structure; When temperature further reduced, middle a part layer of surfactant produced very big forward curvature, forms trickle oiliness micelle (O/W type Emulsion), and emulsion droplet forms the process of nano-emulsion in the phase transition temperature method that Here it is.The phase transition temperature emulsion process makes full use of surfactant molecule low-down interfacial tension when phase transition temperature and promotes emulsifying, for non-ionic surface active agent, by changing the temperature of system, O/W type Emulsion when the w/o type Emulsion when impelling high temperature becomes low temperature, and in cooling procedure, system becomes lowest surface tension from zero curvature, has promoted the formation of fine dispersion oil droplet.In addition, except temperature, other parameters such as salinity and pH value also can exert an influence to emulsifying.Because the coalescent speed of emulsion droplet is very fast, so although emulsifying effectiveness is fine when phase transition temperature, but the nano-emulsion of preparing is extremely unstable, but can or be heated to 25-30 ℃ by quick cooling, obtain the Emulsion (O/W or w/o type) of dynamic stability, it can reach very little particle diameter and very narrow particle size distribution range; If heating or refrigerative speed are fast inadequately, the merging of emulsion droplet will become major trend, thereby forms polydisperse thick Emulsion.And change the emulsifying rule mutually is continuously water to be added among the oil phase, during beginning, because the oil phase surplus forms w/o type Emulsion, but along with the increase of water ratio, has constantly changed wherein surfactant curvature, and water droplet coalesces together gradually; At the Emulsion phase inversion point, surfactant forms layer structure, and this moment, the surface tension minimum helped to form very little dispersion emulsion droplet.After the Emulsion phase inversion point, along with the further increase of water, O/W type Emulsion forms, and emulsion droplet forms the process of nano-emulsion in Here it is the phase transition method.Changing in the emulsion process floating forming process of dripping mutually needs short chain surfactants, and it forms flexible monolayer at oil-water interfaces, causes the formation at the transformation temperature nano-emulsion.During this transfer, surfactant produces lowest surface tension, and this helps to form fine emulsion droplet.

The volume that the principal element that influences the nano-emulsion type has oil phase and a water is both viscosity differences and the kind of surfactant when.Wherein, surfactant is the most important to the formation and the character of nano-emulsion, its molecule generally is to be made of nonpolar, lipophilic hydrocarbon chain and polar, hydrophilic group two parts, have not only oleophylic but also hydrophilic amphipathic characteristic, this kind molecule has and can reach in the inner critical nature that forms micelle of solution by oriented adsorption on various interfaces, has the surface tension that reduces the interface, the type of decision nano-emulsion, produce interfacial tension gradient, cause static and steric hindrance repelling effect etc.In the selection of surfactant, what at first need to consider is exactly its hydrophile-lipophile balance (HLB) value, as select HLB surfactant between 8～18, then it will form O/W type nano-emulsion, select the surfactant between 3～6 then easily to form the w/o type nano-emulsion.In most systems, forming the stabilized nano breast needs the participation of cosurfactant, its effect has following characteristics: increase the interfacial film flowability: when generating nanoemulsions, the interface bends, need interfacial tension and interfacial pressure work done, and when big drop is dispersed into droplet, needing interface deformation to reform, these need the interface bending energy.Add cosurfactant, can reduce the interface rigidity, increase the interface flowability, required interface bending energy when reducing nanoemulsions and generating makes the easy spontaneous generation of nanoemulsions; The HLB value of reconciliation statement surface-active agent: when forming nanoemulsions, for making surfactant that a large amount of absorption be arranged on oil/water surface, must be with the suitable surfactant of HLB value, if the HLB value of surfactant is improper, available cosurfactant is adjusted to desired value.Reduce interfacial tension: for single surfactant, usually before reducing to zero, interfacial tension reached CMC (in solution, forming the required least concentration of micelle), add different cosurfactants, interfacial tension is further reduced, even be negative value, this moment, the interface expansion generated intact drop, cause more surfactant and cosurfactant in Interfacial Adsorption, thereby greatly reduce the concentration of surfactant and cosurfactant in the system solution, interfacial tension be again on the occasion of, generated nanoemulsions.

Yet, nano-emulsion also exists such or such problem in actual application at present: treating in skin-color disposition disease and the skin whitening spot-eliminating beauty treatment cosmetics at present, the application that successfully hydroquinone mono-propionate is re-dubbed lyophilizing or non-lyophilizing nano-emulsion still belongs to blank; The fabricating technology of successful lyophilizing or non-freezing-dried hydroquinone mono-propionate beautifying skin effect nanometer also belongs to blank; How to select lower emulsifying agent of toxicity and co-emulsifier and hydroquinone mono-propionate coupling, thereby reduce the toxicity and the skin irritation of lyophilizing or non-freezing-dried hydroquinone mono-propionate nano-emulsion; 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 the stability and the non-oxidizability of hydroquinone mono-propionate nano-emulsion; How to determine the best lyophilizing or the prescription and the preparation technology of non-freezing-dried hydroquinone mono-propionate beautifying skin nano-emulsion; How to make in lyophilizing or the non-freezing-dried hydroquinone mono-propionate beautifying skin nano-emulsion functional component bring into play better brightening, dispelling spots, dispelling effect and advantage; How to select and definite skin whitening spot-eliminating beauty treatment nano-emulsion in kind and the application dose or the concentration of functional component, or the like all be a unsolved difficult problem.

Summary of the invention

The objective of the invention is to be improved, innovate, a kind of lyophilizing, non-freezing-dried hydroquinone mono-propionate beautifying effect nanometer emulsion and preparation method thereof are provided at shortcoming that exists in the background technology and problem.

Lyophilizing nano-emulsion of the present invention is made by following component that (consumption is a weight portion: hydroquinone mono-propionate 0.5-4.0, vitamin E 0.2-2.0, isopropyl myristate 8-16, sad capric acid triglyceride 0.1-1.0, sad capric acid polyethyleneglycol glyceride 32-40, polyglyceryl fatty acid ester 10-14, distilled water 35-45, mannitol 15-25, glycine 1-6.

The non-lyophilizing nano-emulsion of the present invention is made (consumption is a weight portion) by following component: hydroquinone mono-propionate 0.5-4.0, vitamin E 0.2-2.0, isopropyl myristate 8-16, sad capric acid triglyceride 0.1-1.0, sad capric acid polyethyleneglycol glyceride 32-40, polyglyceryl fatty acid ester 10-14, distilled water 35-45.

Optimum weight proportioning of the present invention is (freeze-dried type): hydroquinone mono-propionate 2.0, vitamin E 0.5, isopropyl myristate 9, sad capric acid triglyceride 0.5, sad capric acid polyethyleneglycol glyceride 36, polyglyceryl fatty acid ester 12, distilled water 40, mannitol 17, glycine 3.

Optimum weight proportioning of the present invention is (a non-freeze-dried type): hydroquinone mono-propionate 2.0, vitamin E 0.5, isopropyl myristate 9, sad capric acid triglyceride 0.5, sad capric acid polyethyleneglycol glyceride 36, polyglyceryl fatty acid ester 12, distilled water 40.

The principles of formulating prescriptions of the present invention: the activity of hydroquinone mono-propionate energy restraint of tyrosinase, reduce skin dopachrome and melanic formation and deposition, skin whitening or speckle dispelling there are positive effect.Hydroquinone mono-propionate is the derivant of hydroquinone, though relatively stable than hydroquinone in theory, still not really stable in actual applications.The concentration that it is used in the skin ointment cream is generally 3.0%-3.5%, this concentration was added after one month not only makes the product variable color, and color is deepened gradually, have a strong impact on the outward appearance and the quality of product, what is more important, add prolonged application behind this concentration hydroquinone mono-propionate, have certain skin irritation and cytotoxicity; And owing to improved the nano-emulsion dosage form, making the hydroquinone mono-propionate concentration of using in the hydroquinone mono-propionate nano-emulsion only is 1.5%-2.0%, and product is more stable, and it is little to have toxicity, and is safe in utilization a little less than the zest, and technology is simple, is easy to large-scale production; The particle diameter that adds nano-emulsion is minimum, and dispersibility is also fabulous, and it is easier that hydroquinone mono-propionate is soluble in the aqueous phase, and has improved the stability of hydroquinone mono-propionate, and its bioavailability is higher.But owing to have some amido links and ester bond in the nano-emulsion; the liquid nano breast is easy to hydrolysis and is difficult for preserving; therefore; it can be prepared into the lyophilizing nano-emulsion during long preservation; and mannitol is as freeze drying protectant; glycine then is used to increase lyophilizing effect and outward appearance, can improve protective capability and redispersion performance to nano-emulsion simultaneously.

The preparation method of the non-freeze-dried type hydroquinone mono-propionate beautifying effect nanometer emulsion of the present invention is:

1) by non-lyophilizing nano-emulsion proportioning raw materials,, places container jointly with isopropyl myristate, vitamin E and hydroquinone mono-propionate and sad capric acid triglyceride; After raw material shakes up in the container, place immediately on the liquid flash mixer and fully mix, making wherein, hydroquinone mono-propionate is dissolved as oil phase (A) fully;

2) in sad capric acid polyethyleneglycol glyceride: polyglyceryl fatty acid ester equals the ratio of 3:1, places among another container; After shaking up, place immediately and carry out abundant mix homogeneously on the liquid flash mixer, make it to form S/C mixture (B);

3) again in oil phase (A): S/C mixture (B): the ratio of pure distilled water (C)=15:45:40, get the S/C mixture (B), the pure distilled water (C) that form behind sad capric acid polyethyleneglycol glyceride and the abundant mix homogeneously of polyglyceryl fatty acid ester respectively and add according to this in oil phase (A) container;

4) at ambient temperature, select the time constant-temperature magnetic stirring apparatus for use, and with 200rpmmin ^-1Rotating speed magnetic agitation 30min, can obtain the hydroquinone mono-propionate nano-emulsion that can use for the skin whitening speckle dispelling; As the muddy no opalescence of prepared hydroquinone mono-propionate nano-emulsion, available S/C mixture (B) slowly drips until meeting the requirements.

The preparation method of freeze-dried type hydroquinone mono-propionate beautifying effect nanometer emulsion of the present invention is:

5) mannitol and the glycine with corresponding proportion adds 4 respectively) in, and it is dissolved fully.Take out after again this being placed-20 ℃ of refrigerator pre-freeze 12h, place-50 ℃ environment to keep 3.5h then, reach after the pre-freeze effect, place freezer dryer to start vacuum system again, the freeze drying box internal pressure is evacuated to 7Pa, and keeps this vacuum; Allow this hydroquinone mono-propionate nano-emulsion sample be warming up to-20 ℃ naturally, insulation 8h makes wherein most of moisture distillation; At last, slowly temperature is risen to 0 ℃, by hot plate this hydroquinone mono-propionate nano-emulsion sample temperature slowly is heated to 30 ℃ again, remove residual moisture, obtain lyophilization hydroquinone mono-propionate nano-emulsion lyophilizing nano-emulsion at the vacuum state lower cover.This freezing-dried hydroquinone mono-propionate nano-emulsion outward appearance is white in color or faint yellow bulk spongy solid.

Beneficial effect of the present invention:

Outstanding innovative point of the present invention is that beauty functions composition hydroquinone mono-propionate is successfully combined application with the nano-emulsion technology, and the skin hydroquinone mono-propionate beautifying effect nanometer emulsion (containing lyophilized formulations) of formation is unprecedented.And the preparation composition of hydroquinone mono-propionate beautifying effect nanometer emulsion of the present invention is simplified, and product is stable, and accelerate action time, shorten the course of treatment, effect improves, and the nano-emulsion particle diameter trickle, be evenly distributed, be easy to Transdermal absorption, with low cost, preparation technology is simple, and practical operation is easy, preparation is fast efficient, do not need special instruments and equipment, all the deadline only can form product in 30 minutes, was easy to extensive industrialization.Specifically, the beneficial effect that hydroquinone mono-propionate beautifying effect nanometer emulsion embodied that adopts the technology of the present invention to prepare mainly shows as:

1, the stability to illumination improves greatly.Respectively bark fetching skin beauty treatment nano-emulsion product and traditional beauty treatment essence product, and place glass ground joint flat bottle respectively placed under daylight lamp and the natural light Continuous irradiation 30 days, simultaneously by sampling in 0,5,10,15,30 day.Through measuring index of correlation, find that the beautifying skin nano-emulsion product that adopts the technology of the present invention to prepare is higher than the beauty treatment essence stability of traditional handicraft preparation.

2, to the sensitivity tests under condition of different temperatures: difference bark fetching skin beauty treatment nano-emulsion product and traditional beauty treatment essence product, 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 beautifying skin nano-emulsion product that adopts the technology of the present invention to prepare is higher than the beauty treatment essence product stability of traditional handicraft preparation.

3, to the stability test that is exposed in the air and room temperature is deposited naturally: difference bark fetching skin beauty treatment nano-emulsion product and traditional beauty treatment essence product, 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 beautifying skin nano-emulsion product that adopts the technology of the present invention to prepare is higher than the beauty treatment essence product stability of traditional handicraft preparation.Room temperature stability is observed: difference bark fetching skin beauty treatment nano-emulsion product and traditional beauty treatment essence product, 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 beautifying skin nano-emulsion product that adopts the technology of the present invention to prepare is higher than the beauty treatment essence product stability of traditional handicraft preparation.

4, high speed centrifugation separation test: respectively bark fetching skin beauty treatment nano-emulsion product and traditional beauty treatment essence product, and place respectively high speed centrifuge supporting centrifuge tube, with 10000-16000rpmmin ^-1The centrifugal 30min of speed, through measuring index of correlation, find that the beautifying skin nano-emulsion product that adopts the technology of the present invention to prepare is higher than the beauty treatment essence product stability of traditional handicraft preparation.

5, emulsion droplet particle size determination: distinguish bark fetching skin beauty treatment nano-emulsion product and traditional beauty treatment essence product, and measure its particle diameter respectively with full-automatic determining instrument (Ma Erwen particle size determination instrument).Found that beautifying skin nano-emulsion product cut size is all at nanoscale and most about 20 nanometers; And traditional beauty treatment essence product cut size is most of at the 1-100 micron substantially at micron order.As seen, beautifying skin nano-emulsion emulsion droplet particle diameter is much smaller than the beauty treatment essence emulsion droplet particle diameter of traditional handicraft preparation; Moreover, the centralized particle diameter of beauty treatment nano-emulsion, uniformity is better.

6, combination of beauty functions composition and dissolubility thereof: respectively according to technology of the present invention--beautifying skin nano-emulsion preparation method and traditional beauty treatment essence preparation method, under identical condition beauty functions composition of the same race (as hydroquinone mono-propionate) is carried out dissolubility test, the saturation solubility of finding the beautifying skin nano-emulsion is apparently higher than traditional beauty treatment essence product; Under the kindred circumstances, respectively according to technology of the present invention--beautifying skin nano-emulsion preparation method and traditional beauty treatment essence preparation method, multiple beauty functions composition with same kind under identical condition carries out dissolubility test, and the saturation solubility of finding the beautifying skin nano-emulsion is also apparently higher than traditional beauty treatment essence product; And, respectively according to technology of the present invention--beautifying skin nano-emulsion preparation method and traditional beauty treatment essence preparation method, with same kind but the multiple beauty functions composition of different physicochemical properties (as hydroquinone mono-propionate, VC ethylether, arbutin) carries out dissolubility test, the saturation solubility that draws the beautifying skin nano-emulsion equally is also apparently higher than traditional beauty treatment essence product under identical condition.Therefore, the effectiveness of its product also obviously improves.

7, bioactive test.Respectively according to technology of the present invention--beautifying skin nano-emulsion preparation method and traditional beauty treatment essence preparation method, beauty functions composition (as SOD) with biologically active of the same race under identical condition is mixed with SOD nano-emulsion and SOD essence respectively, under identical storage condition, measure the SOD activity respectively respectively at placing 30 days front and back, found that the SOD activity in the SOD nano-emulsion is active obviously high than the SOD in the SOD essence.

8, percutaneous diffusion test: because nano-emulsion has obviously improved the dissolubility of insoluble drug at aqueous phase, and because the particle diameter and the skin histology affinity of nano-emulsion, the percutaneous diffusion rate of beauty functions composition or bioactive substance is obviously increased, and Transdermal absorption is obviously accelerated.As with can treat the skin acne the beauty functions composition---the percutaneous release result of quadracycline shows, quadracycline needs about 12 hours in the percutaneous absorbability (during the skin diffusion peak) that cosmetics coagulate in the agent, percutaneous absorbability in cosmetics Emulsion (during the skin diffusion peak) needs about 24 hours, and the percutaneous absorbability (during the skin diffusion peak) in the beauty treatment nano-emulsion only needs about 5-6 hour.As seen, the drug diffusion speed of beauty functions composition---quadracycline in the beauty treatment nano-emulsion is obviously high.

9, effectiveness of application.The result of the newborn essence clinic trial of non-nano with the dosage functional component of the same type that the beautifying effect nanometer emulsion of using the present invention's development and traditional handicraft are prepared shows that the former is than the high 15-25% of latter's effective percentage.

10, application safety property testing.Adopt beauty treatment nano-emulsion technology of preparing of the present invention, make its functional component add concentration and reduce greatly, access times also obviously reduce, and the chemosynthesis or the semi-synthetic material of short dermal osmosis are rejected substantially, and the safety of application is improved.And, adopt the beautifying effect nanometer emulsion of the present invention's preparation, its molecule or the emulsion droplet particle diameter overwhelming majority are in nanoscale (between the 10-80 nanometer), therefore, the beauty functions composition re-uses after finishing the preparation of beauty treatment nano-emulsion, feels fine and smooth, smooth, moist, comfortable more.

Simultaneously, under the identical or better situation of result of use, reduced the application concentration of beautifying skin functional component in cosmetics (containing essence), reduce the interpolation concentration of traditional method, this makes the contingent skin irritation of functional component, anaphylaxis, toxic and side effects reduce greatly on the one hand, and safety then improves greatly; On the other hand, the minimizing of beauty functions composition consumption has reduced resource consumption and waste, and product cost is reduced greatly.In addition, which kind of type cosmetics no matter tradition cosmetics 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 beautifying effect nanometer emulsion of the present invention is simplified, with low cost, preparation technology is simple, practical operation is easy, preparation is fast efficient, do not need special instruments and equipment, do not need the external world that energy is provided, do not need heating, and, be mixed with only 30 minutes whole deadlines of product.Therefore, make the industrialization technology level, amount of product throughput, quality, safety, effect etc. of new type of cosmetic preparation all obviously improve and improve, and, in energy, raw-material saving, reduce environmental pollution etc. sizable progress is also arranged.Especially the nanometer of improving looks can be according to the needs of aesthetic health care and damage property problem skin treating, arbitrarily coupling some have Synergistic but physicochemical property difference, dissolubility is different, molecular weight is not of uniform size functional component, make the skin beauty health-care effect more remarkable.

The present invention has following effect and function:

1, the stability of functional component hydroquinone mono-propionate in skin whitening spot-eliminating beauty treatment cosmetics.If the functional component hydroquinone mono-propionate can not keep stable in skin whitening spot-eliminating beauty treatment cosmetics and at the effect duration stable existence, its product can't be ensured the quality of products naturally.And beauty functions composition hydroquinone mono-propionate is being used nano-emulsion technology preparation of the present invention, and the effect nanometer emulsion of its formation then can improve its stability significantly, prolongs its effect duration greatly, and the perusal outward appearance is limpid, transparent, attractive in appearance.

2, the combination of functional component hydroquinone mono-propionate and vitamin E and in skin whitening spot-eliminating beauty treatment cosmetic formulations the reasonability of ratio.If the combination of functional component hydroquinone mono-propionate and vitamin E because of preparation technology make its can't be in skin whitening spot-eliminating beauty treatment cosmetics composite and reasonability compound proportion be affected, its product can't guarantee its effect naturally.And functional component hydroquinone mono-propionate and vitamin E are when application nano-emulsion technology of the present invention is prepared, then can be according to prescription or composite needs, appropriate design or add any functional component or functional component, and the beautifying effect nanometer emulsion that forms can keep its good stable equally, and improves or strengthen its action effect greatly.

3, functional component hydroquinone mono-propionate and the vitamin E dissolubility in skin whitening spot-eliminating beauty treatment cosmetics directly influences its preparation and effect.Usually, in cosmetics preparation and use, has only certain density functional component, perhaps the functional component of different solubility characteristics is worked in coordination with the better skin beauty health-care effect of competence exertion, but remain in certain difficulty because of of the solution of traditional cosmetics technology of preparing to the complete solubility problem of beauty functions composition, cause dissolving bad because of its functional component, product stability and working concentration reduce, perhaps different deliquescent functional components can't Synergistics and can't be reached corresponding dosage effect or mutual aid synergism, and product can't guarantee its curative effect naturally.And functional component hydroquinone mono-propionate and vitamin E adopt nano-emulsion technology of the present invention to prepare, because the flowability and the favorable dispersibility of the nano-emulsion of the present invention's preparation, can increase the dissolubility of functional component hydroquinone mono-propionate and vitamin E greatly, and can promote different deliquescent beauty functions compositions to dissolve each other and be total to moltenly, make this nano-emulsion have better action effect.

4, functional component hydroquinone mono-propionate and the vitamin E concentration in skin whitening spot-eliminating beauty treatment cosmetics.The really advantage of its effect of performance need be prepared, preserves and be used to the functional component hydroquinone mono-propionate usually under low temperature or room temperature, but present conventional cosmetics preparation technique adopts mostly and carries out water and oil phase emulsifying under the 70-80 ℃ of condition, this not only causes its content to descend greatly, and efficacy effect obviously reduces, even loses its due action effect.And prepare under 25 ℃ of left and right sides conditions of nano-emulsion technology employing room temperature of the present invention, make the hydroquinone mono-propionate with skin whitening freckle dispelling aesthetic health care effect of interpolation be able to a large amount of preservations, bioavailability also obviously improves, and can bring into play its due action effect effectively like this.

5, functional component hydroquinone mono-propionate and the vitamin E percutaneous absorbability in skin whitening spot-eliminating beauty treatment cosmetics.Skin whitening spot-eliminating beauty treatment cosmetics want really to bring into play and reach conditioning, improve the effect of cutaneous pigmentation situation and skin whitening freckle dispelling aesthetic health care, it is important whether functional component hydroquinone mono-propionate in these cosmetics and vitamin E can see through the keratodermatitis barrier and reach corresponding site of action and keep certain effect time at these positions.And functional component hydroquinone mono-propionate and vitamin E will be realized these effects, need assistance such as some effective auxiliary agents, media, carrier, just might see through epidermal barrier and enter their due biological actions of performance in the skin, and existing traditional cosmetics technology of preparing and prescription great majority are to add some traditional short skin penetrants, not only product efficacy can't guarantee, and too much chemosynthesis or semisynthetic short skin penetrant add too much, also skin irritation might take place.And the hydroquinone mono-propionate effect nanometer emulsion of the present invention's preparation is because its particle diameter is little, particle size distribution is even, add that emulsifying is good, good with the intermiscibility of skin barrier structure, therefore, the easier epidermis that sees through of its functional component absorbs, even penetrable holostrome skin, make the aesthetic health care effect meeting of its skin whitening speckle dispelling better.

6, the functional component hydroquinone mono-propionate safety of in skin whitening spot-eliminating beauty treatment cosmetics, using.Be not that all beauty functions compositions all do not have skin irritation, 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 skin beauty health-care is used, 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, its functional component hydroquinone mono-propionate adds concentration and can reduce greatly, and access times also obviously reduce, and the chemosynthesis or the semi-synthetic material of short dermal osmosis are rejected substantially, and the safety of application is improved.

7, the comfortableness after the functional component hydroquinone mono-propionate is prepared through cosmetics is most important.But according to present traditional cosmetics preparation technology, its molecular particle size is mostly about micron order, and the beautifying effect nanometer emulsion that adopts the present invention to prepare, its molecule or the emulsion droplet particle diameter overwhelming majority are in nanoscale (between the 10-80 nanometer), therefore, the functional component hydroquinone mono-propionate re-uses after finishing the preparation of beauty treatment nano-emulsion, feels fine and smooth, smooth, moist, comfortable more.

8, functional component and related raw material convenient sources, good and cheap also most important.Under the prerequisite of guaranteeing safe in utilization and action effect basically identical, adopt domestic raw material to substitute imported raw material as far as possible, perhaps domestic purchase import packing easily raw material, so not only reduce cost of material or produce and consume, and could guarantee that so also raw material sources are convenient, finished product low price and preparation of product are also simple and convenient.Hydroquinone mono-propionate effect nanometer emulsion of the present invention adopts domestic raw material and functional component substantially, and its result compares the effect unanimity with the like product for preparing with imported raw material.

9, specific aim or the targeting in skin whitening spot-eliminating beauty treatment cosmetics, used of functional component hydroquinone mono-propionate.Specific aim that the functional component hydroquinone mono-propionate is used in cosmetics or targeting are also extremely important.Present traditional cosmetics technology of preparing still can only guarantee to contain relevant beauty functions composition, but be not all pointed or targeting of beauty functions composition, even added the Transdermal absorption that some short skin penetrants also can only increase functional component, also can't make functional component performance targeting.And the hydroquinone mono-propionate effect nanometer emulsion that adopts the present invention to prepare, owing to functional component can be combined on a certain carrier, and this carrier has certain specific aim and targeting, therefore, can realize the specific aim and the targeting of beauty functions composition, make its effect more special and direct, then corresponding effect will be more obviously with efficient.

10, functional component hydroquinone mono-propionate effectiveness of application in skin whitening spot-eliminating beauty treatment cosmetics.Functional component skin whitening speckle dispelling effectiveness of application and its mutual aid concertedness and synergy in skin whitening spot-eliminating beauty treatment cosmetics is closely related.Present traditional cosmetics technology of preparing still can only guarantee to add relevant beauty functions composition, can both not bring into play the advantage of the collaborative and synergy of mutual aid but be all beauty functions composition at cosmetics, have mutual aid beauty functions composition collaborative and synergy and may not necessarily reach the expected design effect yet even added some.And the beautifying effect nanometer emulsion that adopts the present invention to prepare, because common influences such as its dispersibility, flowability, uniformity, stability, percutaneous absorbability, specific aim or targeting reach and the area of contact skin increases, prolong action time, make the mutual aid concertedness and the synergy of the later functional component of compatibility more obvious, then practical application effect will be more obviously with efficient.

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 the cosolvent of functional component hydroquinone mono-propionate, and vitamin E is then as the antioxidant and the synergetic effect additive of hydroquinone mono-propionate.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 skin whitening spot-eliminating beauty treatment used for cosmetic nano-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 skin whitening spot-eliminating beauty treatment used for cosmetic 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 external preparation for skin brightening, dispelling spots, dispelling nano-emulsion.

Beauty functions composition of the present invention is a hydroquinone mono-propionate, and it is the derivant of hydroquinone.Owing to hydroquinone is met light or is exposed to and is easy to be oxidized to 1,4-benzoquinone in the sky G﹠W and becomes brown, especially all the more so in alkaline solution, metal ion is sneaked in addition, and particularly ferrum and copper ion play in its redox reaction process and accelerate the catalysed promoted effect.Therefore, preparation in the past or physical holding of the stock or when using similar preparation, many disadvantages such as variable color often occurs, go bad, cannot say for sure to deposit.Though hydroquinone mono-propionate is more stable than the physicochemical property of hydroquinone, overlong time, excessive concentration, oxidation is obvious excessively, the variable color of hydroquinone mono-propionate, the rotten skin irritation etc. that reaches still can occur.The preparation principle of hydroquinone mono-propionate nano-emulsion is drawn the pseudo-ternary phase diagram of hydroquinone mono-propionate nano-emulsion 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 hydroquinone mono-propionate being dissolved among the oil phase isopropyl myristate, and under the effect of compositions such as S/C mixture that sad capric acid polyethyleneglycol glyceride and polyglyceryl fatty acid ester form and distilled water and participating in, formation hydroquinone mono-propionate nano-emulsion naturally.In hydroquinone mono-propionate nano-emulsion preparation prescription, isopropyl myristate is as oil phase, and sad capric acid polyethyleneglycol glyceride is as emulsifying agent, and polyglyceryl fatty acid ester is a co-emulsifier, and distilled water is as water.Select for use mannitol as freeze drying protectant, and select for use glycine to increase the outward appearance of lyophilizing effect and protection lyophilized formulations and improve the performance of its redispersion.

Different functional components has different physicochemical properties, and actual concentration of adding is also variant, and therefore, the prescription of the nano-emulsion of preparation is also had nothing in common with each other.In general, the basis of prescription is oil phase, water, emulsifying agent (surfactant), co-emulsifier (cosurfactant), and the functional component of prescription then carries out prescription according to the actual needs of skin beauty health-care and treatment damage capacitive problem skin.During preparation, can it be dissolved in the corresponding phase liquid respectively earlier according to the dissolubility of beauty functions composition.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 water-in-oil type (W/O) nano-emulsion are: determine each prescription from pseudo-three-phase diagram after, earlier with hydrophilic emulsifier and co-emulsifier mixed as requested, stir at normal temperatures, add a certain proportion of oil phase again, after continuing to stir, the water phase titration promptly gets water-in-oil type (W/O) nano-emulsion till muddy liquid becomes clear.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.

Analysis and Identification of the present invention:

1, the naked eyes outward appearance is observed: blank nanoemulsions appearance colorless or light blue slightly, clear, visible opalescence, have certain fluidity.Hydroquinone mono-propionate nano-emulsion appearance colorless or faint yellow slightly, clear, visible opalescence, has certain fluidity.

2, the electron microscopic morphology of nano-emulsion is observed: respectively get a blank nano-emulsion and hydroquinone mono-propionate nano-emulsion respectively, place on the copper mesh that is covered with the Formvar film, treat that nature dries after, directly observe with transmission electron microscope; Simultaneously, with the 2-3% Sodium phosphotungstate copper mesh of the nano-emulsion that is loaded with hydroquinone mono-propionate is carried out negative staining 30min.Concrete grammar is: the Sodium phosphotungstate drips of solution with 2-3% is added on the stencil plate earlier, in addition the hydroquinone mono-propionate nano-emulsion is 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.

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 below the 100nm, and particle size distribution should concentrate in certain following particle size range of 100nm, and current potential is to be measured.

4, the mensuration of hydroquinone mono-propionate in the nano-emulsion: precision takes by weighing hydroquinone mono-propionate or the freezing-dried hydroquinone mono-propionate nano-emulsion is an amount of, puts respectively in the 25mL measuring bottle, and adding butanediol or propylene glycol are diluted to scale and shake up, as need testing solution; The freezing-dried hydroquinone mono-propionate nano-emulsion need add Triton X-100 breakdown of emulsion, and hydroquinone mono-propionate wherein to be measured is discharged fully.The assay of hydroquinone mono-propionate and related substance check that assay carries out assay with reference to its quality standard and content assaying method.

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.

Preparation points for attention of the present invention:

1, 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.

2, when this patent of invention of practice is carried out other functional component nano-emulsion preparation, as the ratio of selecting oil phase that the present invention designs, water, emulsifying agent, co-emulsifier occurs when muddy, can estimate again according to pseudo-three-phase diagram on the one hand, simultaneously can adopt titrating mode, i.e. water phase titration or emulsifying agent/co-emulsifier mixture carries out titration.Titration with dropper or syringe all can, one after another drop ofly slowly carry out.In the titration process, agitator is operate as normal still, and until titration preparation till the transparent fully and clarification, this moment is accrued calculates true titration institute consumption accurately, and writes down it, so that reference when preparing once more.Simultaneously, should readjust the ratio of oil phase, water, emulsifying agent, co-emulsifier according to percentage ratio.

3, when this patent of invention of practice is carried out other functional component nano-emulsion preparation, molten or water-soluble or pure molten or water oil is double molten because functional component may be an oil, therefore, during actual the preparation, should be according to the dissolution characteristics of this functional component, earlier solid or liquid functional component are dissolved among the homophase.As functional component is water-soluble solid or liquid, among then earlier this functional component being soluble in the aqueous phase; As functional component is oil-soluble solid or liquid, then this functional component is dissolved among the oil phase earlier; As functional component is pure dissolubility solid or liquid, then earlier this functional component is dissolved among the pure agent, is dissolved among oil phase or water or emulsifying agent/co-emulsifier system again, afterwards, carries out the nano-emulsion preparation according to the design's ratio again.If muddiness still appears in process for preparation, then available alcohol carries out titration, and last reuse emulsifying agent/co-emulsifier system is adjusted.Equally, titration with dropper or syringe all can, one after another drop ofly slowly carry out, in the titration process, agitator is operate as normal still, till titration is prepared transparent fully and clarified, this moment is accrued calculates true titration institute consumption accurately, and writes down it, so that reference when preparing once more.Simultaneously, according to percentage ratio, readjust the ratio of oil phase, water, emulsifying agent, co-emulsifier.

4, the emulsifying agent/co-emulsifier system high-quality high-grade that designs owing to patent of the present invention, and raw material is French import, and cost of material is more expensive, and the source is not very convenient.Therefore, with the preferably high-end or high priced line of this raw material preparation effect nanometer emulsion, particularly can be used for preparing cost an arm and a leg, precious rare biological effect composition nano-emulsion.

5, according to the technical matters and the preparation method of patent of the present invention, also can select other emulsifying agents/co-emulsifier system, but preferably once emulsifying agent/co-emulsifier system and the oil phase and the water of coupling, and preferably select colourless, tasteless, odorless, transparent and high safety, to the non-irritating emulsifying agent of skin/co-emulsifier system.Like this, not only can substitute import reagent, convenient sources, and can reduce cost greatly.Certainly, when selecting new emulsifying agent/co-emulsifier system and oil phase and water, need grope and calculate aforementioned proportion earlier equally.For example, the home-made polyethylene castor oil hydrogenated of moral, tween 80, Span4 etc.

6, the external preparation for skin nano-emulsion select then mainly by isopropyl myristate as oil phase, sad capric acid polyethyleneglycol glyceride is as emulsifying agent, polyglyceryl fatty acid ester is a co-emulsifier, distilled water is as water.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 the external preparation for skin nano-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 external preparation for skin effect nanometer emulsion.

7, the excipient of freeze-drying prods generally can be divided into crystal type and non-crystalline type.The form of excipient and quantity have determined the outward appearance and the heavy dispersibility of lyophilizing nano-emulsion.Freeze-drying prods by the excipient gained of non-crystalline type mostly is the thickness foamer, generally should not adopt; And add the crystal type excipient, after moisture is removed by distillation in freezing dry process, the nanometer emulsion droplet can be evenly dispersed in excipient around and among the crystalline space, form outward appearance freeze-dried products preferably.In addition, if dispersion effect is good, during excipient was soluble in the aqueous phase rapidly during redissolution, emulsion droplet also was dispersed in aqueous phase thereupon uniformly, formed the constant effect nanometer emulsion of quality.

8, theoretically, use mannitol should be better as the excipient effect, and this may be that emulsion droplet is dispersed between the crystalline lamella because the crystallization of mannitol is a featheriness, therefore obtains outward appearance freeze-dried products preferably.The amount of mannitol is big more, produces more crystallization space, so the dispersion of nanometer emulsion droplet is more even, and heavy dispersibility is good more.Certainly, also can use glycine separately, or albumin, preferably mannitol and glycine being share, eutectic temperature is higher relatively, can effectively keep the shape in the sample freeze-drying process, reduces the shrinkage of sample, improves freeze drying rate, shortens freeze-drying time.Mannitol can add earlier when the preparation of nano breast during as excipient.As the nano-emulsion for preparing adds again, dissolve difficult relatively, possible time expand.

9, the dispose procedure of functional component in the nanoemulsions system depends on the concentration of these functional components in the nanoemulsions system to a great extent.Theoretically, the concentration of functional component in carrier is high more, discharges just fast more, therefore, the concentration of functional component in carrier can not be too low, otherwise the functional component molecule can intensively be adsorbed on the liquid film of emulsifying agent or surfactant composition on the one hand, thereby cause diffusion hindered; On the other hand, functional component concentration is low, and the system concentration difference is little, and diffusion is just slow, causes the bioavailability of functional component to reduce.

10, nano-emulsion characteristics the most outstanding than other system are exactly can the solubilising functional component.No matter be water miscible functional component or fat-soluble functional component, in nanoemulsions, can reach very big solubilizing amount.The solubilising of functional component in the droplet of nanoemulsions has crucial meaning for the slow release and the controlled release of functional component.Because the functional component in the droplet wants to discharge, must pass through the interfacial film formed by emulsifying agent or surfactant molecule earlier, this process is normally slow, and the total concentration of functional component in the droplet of nanoemulsions can reach very high.

11, the functional component solubilising is in nanoemulsions, can reach and reduce the medication number of times, slowly discharge the purpose of medicine, and O/W type nano-emulsion is the good carrier of fat-soluble functional component, it singly is not the effect of emulsifying agent or surfactant to the solubilising of functional component, has more the effect of its kernel oil phase.

12, nano-emulsion good transdermal and its unique texture and to the remarkable solubilising of functional component and form the over-saturation system thereby to increase inside and outside the skin factors such as Concentraton gradient of functional component relevant.Therefore, functional component content can be much higher than the amount of conventional hydroquinone mono-propionate dissolubility in IPM in the preparation hydroquinone mono-propionate nano-emulsion.

Though 13, 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, and 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.

14, the principal element that influences the nano-emulsion type has the kind of the volume ratio of oil-water, both viscosity differences and emulsifying agent or surfactant.Wherein, emulsifying agent or surfactant are the most important to the formation and the character of nano-emulsion, its molecule generally is to be made of nonpolar, lipophilic hydrocarbon chain and polar, hydrophilic group two parts, have not only oleophylic but also hydrophilic amphipathic characteristic, this kind molecule have can be on various interfaces oriented adsorption and in the inner critical nature that forms micelle of solution, have the surface tension that reduces the interface, decision nano-emulsion type, produce interfacial tension gradient, cause static and steric hindrance repelling effect etc.

What 15, at first need in the selection of emulsifying agent or surfactant to consider is exactly its hydrophile-lipophile balance (HLB) value, as select HLB emulsifying agent or surfactant between 8～18, then it will form O/W type nano-emulsion, select emulsifying agent or surfactant between 3～6 then easily to form the w/o type nano-emulsion.

16, the emulsifying agent Labrasol of the present invention's selection is mainly derived from plant, and its HLB value is 14, is applicable to the nonionic adjuvant of the high HLB value of functional component.Co-emulsifier PlurolOleiqueCC497 with two kinds of surfactants mixing energy formation by a certain percentage hybrid films, can make more stable effect nanometer emulsion mainly as the Emulsion that helps of nonionic emulsifier and nano-emulsion.

17, the design of this hydroquinone mono-propionate effect nanometer emulsion adopts drafting pseudo-ternary phase diagram method to carry out, selection is mixed in proportion water and oil phase and is prepared into binary liquid, as volumetric solution binary liquid is carried out titration with the S/C mixed liquor simultaneously, in titration process, only need like this to observe the once phase-change process, reduced the error that twice phase transformation occur when carrying out titration as volumetric solution and produce with water or oil phase.

18, in view of the content that reduces emulsifying agent or surfactant (reducing skin irritation and production cost) as far as possible, guarantee certain oil content (keeping certain hydroquinone mono-propionate drug loading), guarantee taking all factors into consideration of certain water content principles such as (reducing the nano-emulsion viscosity), the ratio design alternative hydroquinone mono-propionate IPM mixed liquor of each composition of hydroquinone mono-propionate nano-emulsion during Km=3: pure distilled water: (S/C)=15%:40%:45%, the optimum content of hydroquinone mono-propionate is defined as 2% in the nano-emulsion.

19, in the titration process of preparation hydroquinone mono-propionate nano-emulsion, adopt perusal to have or not opalescence, and get rid of gel or the liquid crystal area that forms in conjunction with Zeta potential and particle size determination method, the result is comparatively accurate.If by origin software processes experimental data and prepare the method for pseudo-ternary phase diagram then more accurately quick.

20, by patent component design of the present invention and Technology, though the hydroquinone mono-propionate nano-emulsion quality of preparation is first-class,, cost an arm and a leg because wherein part material adopts France to make, and it is not very convenient to originate, and suggestion is used in being applied in expensive goods or preparation biological preparation nano-emulsion.

21, cosmetics or prepare some common cosmetics essences as being used in still can adopt following prescription to carry out by method for designing of the present invention and Technology: (1) oil phase: with isopropyl palmitate (9%); (2) water: with deionized water or distilled water (45%); (3) emulsifying agent (tween 80)/co-emulsifier (propylene glycol) mixture: 46%.Wherein, tween 80 accounts for 67% in emulsifying agent/co-emulsifier mixture, and propylene glycol accounts for 33% in emulsifying agent/co-emulsifier mixture, and Pei Zhi nano-emulsion actual cost is low like this, and effect is good equally.

22, in order to adapt to everyone age, skin type, individual variation and seasonal variety and the region is cold and hot, it is wet etc. to do, also can be by related advisory in the technology of the present invention thinking and the points for attention, the nano-emulsion of design and preparation water-in-oil type (W/O) or oil-in-water type (O/W), and can suitably adjust the configuration proportion of oil phase, water and emulsifying agent/co-emulsifier mixture, make it to be mixed with dissimilar nano-emulsions.Certainly, this ratio also should design by pseudo-three-phase diagram, and need in actual process for preparation, to adjust and grope, up to the nano-emulsion of being prepared be transparent, clarify, have opalescence, good fluidity, good dispersion, particle size distribution evenly, the nano-particle diameter is less than 80nm, be preferably in about 20-30nm, and colourless, tasteless, nonirritant etc.

The specific embodiment

Embodiment one: non-freeze-dried type hydroquinone mono-propionate nano-emulsion

Each raw material optimum weight proportioning is: hydroquinone mono-propionate 2.0, vitamin E 0.5, isopropyl myristate 9, sad capric acid triglyceride 0.5, sad capric acid polyethyleneglycol glyceride 36, polyglyceryl fatty acid ester 12, pure distilled water 40.

The preparation method of non-freezing-dried hydroquinone mono-propionate beautifying effect nanometer emulsion: 1) take by weighing the isopropyl myristate (IPM) of 9 gram weight respectively, 0.5 the vitamin E of gram weight, 2.0 the hydroquinone mono-propionate of gram weight, 0.5 the sad capric acid triglyceride of gram weight place among the 250mL conical flask jointly.2) with this 250mL conical flask earlier with have gentle hands jog even after, place immediately on the liquid flash mixer and fully mix, till wherein hydroquinone mono-propionate dissolves fully.In the time of can not dissolving fully as hydroquinone mono-propionate, this conical flask can be placed and carry out the water proof heating on the electric furnace or place 60 ℃ of left and right sides constant water bath box heating until dissolving fully as oil phase (A).3) according to sad capric acid polyethyleneglycol glyceride: the ratio of polyglyceryl fatty acid ester=3:1 accurately takes by weighing the sad capric acid polyethyleneglycol glyceride of 36 gram weight and the polyglyceryl fatty acid ester of 12 gram weight, and both is placed among another container.4) same, with this container earlier with the have gentle hands jog even after, place immediately and carry out abundant mix homogeneously on the liquid flash mixer, make it to form S/C mixture (B) 48 grams.5) accurately measure the pure distilled water of 40mL (C) with graduated cylinder.6) again in oil phase (A): S/C mixture (B): the ratio of pure distilled water (C)=15:45:40, get the S/C mixture (B) that forms behind the sad capric acid polyethyleneglycol glyceride of 45 grams and the abundant mix homogeneously of polyglyceryl fatty acid ester respectively, the pure distilled water (C) of 40 grams add this preparation method step 2 according to this) in (A) 250mL conical flask in, mix homogeneously gently.7) under 25 ℃ of conditions of room temperature, select JB-3A type time constant-temperature magnetic stirring apparatus for use, and with the rotating speed magnetic agitation 30min of 200rpm/min, can obtain can be for the hydroquinone mono-propionate nano-emulsion of skin whitening spot-eliminating beauty treatment used for cosmetic.8) as the muddy no opalescence of prepared hydroquinone mono-propionate nano-emulsion, available S/C mixture (B) or pure distilled water slowly drip until forming transparent, clarification, opalescence is arranged, good fluidity, good dispersion, particle size distribution is even, the nano-particle diameter is at the nano-emulsion of 10-80nm, and censorship is until conforming to quality requirements.9) above-mentioned up-to-standard nano-emulsion is used ceramic ultrafilter or rustless steel bacteria filter filter, and need be carried out packing and gland according to product specification simultaneously less than 100,000 molecular weight.

* 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 two: freeze-dried type hydroquinone mono-propionate nano-emulsion

The optimum weight proportioning of each raw material of freeze-dried type is: hydroquinone mono-propionate 2.0, vitamin E 0.5, isopropyl myristate 9, sad capric acid triglyceride 0.5, sad capric acid polyethyleneglycol glyceride 36, polyglyceryl fatty acid ester 12, pure distilled water 40, mannitol 17, glycine 3.

The preparation method of freeze-dried type hydroquinone mono-propionate beautifying effect nanometer emulsion: 1) take by weighing the isopropyl myristate (IPM) of 9 gram weight respectively, 0.5 the vitamin E of gram weight, 2.0 the hydroquinone mono-propionate of gram weight, 0.5 the sad capric acid triglyceride of gram weight place among the 250mL conical flask jointly.2) with this 250mL conical flask earlier with have gentle hands jog even after, place immediately on the liquid flash mixer and fully mix, till wherein hydroquinone mono-propionate dissolves fully.In the time of can not dissolving fully as hydroquinone mono-propionate, this conical flask can be placed and carry out the water proof heating on the electric furnace or place 60 ℃ of left and right sides constant water bath box heating until dissolving fully as oil phase (A).3) according to sad capric acid polyethyleneglycol glyceride: the ratio of polyglyceryl fatty acid ester=3:1 accurately takes by weighing the sad capric acid polyethyleneglycol glyceride of 36 gram weight and the polyglyceryl fatty acid ester of 12 gram weight, and both is placed among another container.4) same, with this container earlier with the have gentle hands jog even after, place immediately and carry out abundant mix homogeneously on the liquid flash mixer, make it to form S/C mixture (B) 48 grams.5) accurately measure the pure distilled water of 40mL (C) with graduated cylinder.6) again in oil phase (A): S/C mixture (B): the ratio of pure distilled water (C)=15:45:40, get the S/C mixture (B) that forms behind the sad capric acid polyethyleneglycol glyceride of 45 grams and the abundant mix homogeneously of polyglyceryl fatty acid ester respectively, the pure distilled water (C) of 40 grams add this preparation method step 2 according to this) in (A) 250mL conical flask in, mix homogeneously gently.7) under 25 ℃ of conditions of room temperature, select JB-3A type time constant-temperature magnetic stirring apparatus for use, and with the rotating speed magnetic agitation 30min of 200rpm/min, can obtain can be for the hydroquinone mono-propionate nano-emulsion of skin whitening spot-eliminating beauty treatment used for cosmetic.8) as the muddy no opalescence of prepared hydroquinone mono-propionate nano-emulsion, available S/C mixture (B) or pure distilled water slowly drip until forming transparent, clarification, opalescence is arranged, good fluidity, good dispersion, particle size distribution is even, the nano-particle diameter is at the nano-emulsion of 10-80nm, and censorship is until conforming to quality requirements.9) take by weighing the mannitol of 17 gram weight and the glycine of 3 gram weight respectively, directly be added in the above-mentioned up-to-standard nano-emulsion, place immediately on the liquid flash mixer and fully mix, after making it to dissolve fully, use ceramic ultrafilter or rustless steel bacteria filter to filter, and need carry out packing according to product specification simultaneously less than 100,000 molecular weight.10) with 9) place-20 ℃ of refrigerator pre-freezes, take out behind the 12h, place-50 ℃ environment to keep 3.5h then, reach after the pre-freeze effect, place freezer dryer to start vacuum system, the freeze drying box internal pressure is evacuated to 7Pa, and keeps this vacuum; Allow this hydroquinone mono-propionate nano-emulsion sample be warming up to-20 ℃ naturally, insulation 8h makes wherein most of moisture distillation; At last, slowly temperature is risen to 0 ℃, by hot plate this hydroquinone mono-propionate nano-emulsion sample temperature slowly is heated to 30 ℃ again, remove residual moisture, obtain lyophilization hydroquinone mono-propionate nano-emulsion lyophilizing nano-emulsion at the vacuum state lower cover.This freezing-dried hydroquinone mono-propionate nano-emulsion outward appearance is white in color or faint yellow bulk spongy solid.

* remarks: all implementation steps and operating process are carried out in the aseptic environments in cleaning as far as possible, 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

[claim 1] a kind of lyophilizing, non-freezing-dried hydroquinone mono-propionate beautifying effect nanometer emulsion is characterized in that the freeze-dried type nano-emulsion is to be made by the following weight parts proportion raw material:

Hydroquinone mono-propionate 2.0, vitamin E 0.5, isopropyl myristate 9, sad capric acid triglyceride 0.5, sad capric acid polyethyleneglycol glyceride 36, polyglyceryl fatty acid ester 12, distilled water 40, mannitol 17, glycine 3;

Non-freeze-dried type nano-emulsion is to be made by the following weight parts proportion raw material:

Hydroquinone mono-propionate 2.0, vitamin E 0.5, isopropyl myristate 9, sad capric acid triglyceride 0.5, sad capric acid polyethyleneglycol glyceride 36, polyglyceryl fatty acid ester 12, distilled water 40.
[claim 2] is characterized in that may further comprise the steps according to the preparation method of the described non-freezing-dried hydroquinone mono-propionate beautifying effect nanometer emulsion of claim 1:

1) by non-lyophilizing nano-emulsion proportioning raw materials,, places container jointly with isopropyl myristate, vitamin E and hydroquinone mono-propionate and sad capric acid triglyceride; After raw material shakes up in the container, place immediately on the liquid flash mixer and fully mix, making wherein, hydroquinone mono-propionate is dissolved as oil phase (A) fully;

2) in sad capric acid polyethyleneglycol glyceride: polyglyceryl fatty acid ester equals the ratio of 3:1, places among another container; After shaking up, place immediately and carry out abundant mix homogeneously on the liquid flash mixer, make it to form S/C mixture (B);

3) getting the S/C mixture (B), the pure distilled water (C) that form behind sad capric acid polyethyleneglycol glyceride and the abundant mix homogeneously of polyglyceryl fatty acid ester respectively adds in oil phase (A) container according to this;

4) at ambient temperature, select the time constant-temperature magnetic stirring apparatus for use, and with 200rpmmin ^-1Rotating speed magnetic agitation 30min, can obtain the hydroquinone mono-propionate nano-emulsion that can use for the skin whitening speckle dispelling; As the muddy no opalescence of prepared hydroquinone mono-propionate nano-emulsion, available S/C mixture (B) slowly drips until meeting the requirements.
[claim 3] is characterized in that may further comprise the steps according to the preparation method of the described freezing-dried hydroquinone mono-propionate beautifying effect nanometer emulsion of claim 1:

1) by non-lyophilizing nano-emulsion proportioning raw materials,, places container jointly with isopropyl myristate, vitamin E and hydroquinone mono-propionate and sad capric acid triglyceride; After raw material shakes up in the container, place immediately on the liquid flash mixer and fully mix, making wherein, hydroquinone mono-propionate is dissolved as oil phase (A) fully;

2) in sad capric acid polyethyleneglycol glyceride: polyglyceryl fatty acid ester equals the ratio of 3:1, places among another container; After shaking up, place immediately and carry out abundant mix homogeneously on the liquid flash mixer, make it to form S/C mixture (B);

3) getting the S/C mixture (B), the pure distilled water (C) that form behind sad capric acid polyethyleneglycol glyceride and the abundant mix homogeneously of polyglyceryl fatty acid ester respectively adds in oil phase (A) container according to this;

4) at ambient temperature, select the time constant-temperature magnetic stirring apparatus for use, and with 200rpmmin ^-1Rotating speed magnetic agitation 30min, can obtain the hydroquinone mono-propionate nano-emulsion that can use for the skin whitening speckle dispelling; As the muddy no opalescence of prepared hydroquinone mono-propionate nano-emulsion, available S/C mixture (B) slowly drips until meeting the requirements;

5) mannitol and the glycine with corresponding proportion adds 4 respectively) in, and it is dissolved fully; Take out after again this being placed-20 ℃ of refrigerator pre-freeze 12h, place-50 ℃ environment to keep 3.5h then, reach after the pre-freeze effect, place freezer dryer to start vacuum system again, the freeze drying box internal pressure is evacuated to 7Pa, and keeps this vacuum; Allow this hydroquinone mono-propionate nano-emulsion sample be warming up to-20 ℃ naturally, insulation 8h makes wherein most of moisture distillation; At last, slowly temperature is risen to 0 ℃, by hot plate this hydroquinone mono-propionate nano-emulsion sample temperature slowly is heated to 30 ℃ again, remove residual moisture, obtain lyophilization hydroquinone mono-propionate nano-emulsion lyophilizing nano-emulsion at the vacuum state lower cover; This freezing-dried hydroquinone mono-propionate nano-emulsion outward appearance is white in color or faint yellow bulk spongy solid.