CN107115218A

CN107115218A - A kind of nano-lipid carrier sun protection gel and preparation method thereof

Info

Publication number: CN107115218A
Application number: CN201710303781.5A
Authority: CN
Inventors: 周四元; 刘苗; 张邦乐; 宦梦蕾; 叶威良; 崔晗; 刘道洲; 成颖
Original assignee: Fourth Military Medical University FMMU
Current assignee: Fourth Military Medical University FMMU
Priority date: 2017-05-03
Filing date: 2017-05-03
Publication date: 2017-09-01

Abstract

The invention discloses a kind of nano-lipid carrier sun protection gel and preparation method thereof.The NLC gel are using sodium carboxymethylcellulose as matrix, and RES and Orangic sunscreen are wrapped in lipid carrier, through emulsification, ultrasonic NLC gel by liquid fat and solid grease composition lipid carrier jointly.Wherein liquid fat is Glycerin, mixed triester with caprylic acid capric acid, and solid grease is the wooden fruit ester of breast, and Orangic sunscreen is：4 methyl benzyl subunit camphors (Parsol5000), butylmethoxydibenzoylmethane (Parsol1789), ethylhexyl methoxy cinnamate (ParsolMCX).Experimental design of the present invention uses JMP7 softwares, and experimental result is analyzed with spss, and data are rigorous, reliable results；The solid matrix material of nano-lipid carrier reduces the photo-labile of RES and Orangic sunscreen；RES has uvioresistant and cytoprotection function concurrently, is also easy to produce photosensitized reaction for sunscreen product and phototoxic predicament provides new strategy.

Description

A kind of nano-lipid carrier sun protection gel and preparation method thereof

Technical field

The invention belongs to the carrier system technical field in cosmetics technology of preparing.It is related to a kind of while loading resveratrol Preparation method and its formulation optimization research with the nano carrier of Orangic sunscreen.

Background technology

China's western part highlands sunshine-duration is long, and ultraviolet radiation intensity is high, and human body skin is vulnerable to damage, in addition high Original is air-dried, dust storm big, the easy dehydration decortication of skin, has further aggravated damage of the ultraviolet to skin.Therefore daylight Property dermatitis turn into common disease.Ultraviolet irradiation intensity, time length and lesion reaction according to suffered by people, can be by sunburn point For " instantaneity sunburn " and " cumulative bad sunburn " two major classes.Instantaneity be in a short time skin by strong sunlight exposure institute Cause.The no such strong short-term reaction of instantaneity sunburn of cumulative bad sunburn, is caused by chronic phototoxic reaction.Such symptom is more Come across the people being often exposed under sunlight.Ultraviolet (UV) radiation in sunshine be a kind of environment of highly significant because Son, it mainly acts on the skin of people.According to wavelength size, the ultraviolet in sunshine can be divided into three classes：L) long wave ultraviolet Line (UVA), wavelength is 320~400nm, and almost all reaches ground, can penetrate corium；2) ultraviolet B radiation (UVB), wavelength is 280~320nm, can penetrate skin, most of reachable ground；3) short wave ultraviolet (UVC), wavelength is 200~280nm, Absorbed by ozone layer, it is impossible to reach ground.Found in the investigation to commercially available plateau sunscreen product：(1) most products By using w/o type emulsification system, while loading physics and chemical sun, product is greasy clouding, and officers and men in plateau make Sense of discomfort can be produced during with this class product.Such product moisture retention is poor simultaneously.(2) because strong illumination causes active component Stability degradation.(3) chemical sun part percutaneous absorbtion, can produce skin irritation.With use sun-screening agent personnel Increase, relevant sun-screening agent receives agent and causes the report of allergic phenomena and photoallergy more and more.(4) Commercial sunscreens gel is used Water miscible chemical sun, although with moisture-keeping function, but available sun-screening agent is restricted, and sun-proof result is also failed to understand It is aobvious, and surface-active contents are higher in prescription, it is larger to skin irritation.

Resveratrol is natural polyphenol class compound, and with significant antioxidation, dermal application resveratrol can Hydroderma, inflammation caused by suppressing UVB, can effectively improve training plateau officers and men because long-time is by intense UV rays irradiation Caused solar dermatitis.In vitro study shows, can resist being aoxidized caused by UVA rays using resveratrol before irradiation Stress.Research display：The binding site of resveratrol in skin is predominantly located at the keratinocyte of epidermis, and white black false hellebore Alcohol can protect HaCaT cells from NO releases SNP damage；Resveratrol also can be by suppressing 1L-1 β and NF- κ B and its Jie The MMPs expression led irradiates the light injury caused to human fibroblasts so as to suppress UVA.But neat resveratrol is in ultraviolet light Its cis-isomer, reduced activity, end-on light, thermally labile are converted under irradiation.Make resveratrol making in cosmetic field With being restricted.

NLC is that matrix material is cooled down and made after high-temperature heating using two kinds or two or more solid-liquids or admittedly .As the carrier of local medicine-applying system, NLC's has the advantage that：(1) particle diameter is small, and sticking effect is strong；(2) it can improve The stability of chemical sun；(3) there is scattering process to ultraviolet, radiation intensity of the ultraviolet to skin can be weakened, produce Diamagnetic outside line synergistic function；(4) excitant of the chemical sun to skin can be reduced；(4) addition of liquid fatty substance is caused Lattice defect, can accommodate more drug molecules, improve the carrying capacity of medicine, and reduction medicine is let out in storage process by exclusion Dew；(5) NLC support material has without using organic solvent in good biocompatibility, preparation process, to physical toxicity It is small.Hydrogel has the viscosity behavior of fluid, this enable it to skin good contact, and quality is salubrious, with good Water lock, moisture-keeping function, but its can only load water soluble anti-solarization agent, anti-solarization effect is poor.NLC is combined preparation nanometer with hydrogel Structured lipid carrier hydrogel, nano structured lipid carrier hydrogel overcomes while NLC and hydrogel advantage is remained NLC and hydrogel shortcoming.

If resveratrol and Orangic sunscreen are prepared as into nano structured lipid carrier gel, drugloading rate can be not only improved, Strengthen uvioresistant effect, reduce and smear number of times, and product can protect HacaT while sun-proof, moisture-keeping functions are had concurrently Cell, photosensitized reaction and phototoxic effect that reduction Orangic sunscreen is produced to skin.

The content of the invention

It is an object of the invention to provide a kind of nano-lipid carrier sun protection gel and preparation method thereof.Prepared with this method Sun protection gel can improve the photostability of resveratrol and Orangic sunscreen, the stimulation that reduction Orangic sunscreen is produced to skin Property, provide new approaches for the exploitation of sunscreen product.

The technical scheme is that：A kind of nano-lipid carrier sun protection gel, it is characterized in that pressing quality by following material Percentage is made：

Resveratrol 0.25~1.5%；Orangic sunscreen 7~9%；Complex lipid 8~16%；Composite emulsifier 2~ 5%；Carmethose 0.1~0.4%；Sodium Hyaluronate 0.2~0.3%；NeoloneTM MxP 0.5~2%；Glycerine 3 ~8%；Vitamin E 0.5~1%；Bisabolol 0.1~0.3%；Allantoin 0.1~0.25%；EDTA-2Na 0.05~ 0.2%；Remaining is deionized water；

Wherein, complex lipid is the wooden fruit ester of breast and pungent capric acid glycerine, and the wooden fruit ester of breast by quality ratio：Pungent capric acid glycerine= 5:1；

Orangic sunscreen is：4- methyl benzyl subunit camphors (Parsol5000), butylmethoxydibenzoylmethane (Parsol1789), ethylhexyl methoxy cinnamate (ParsolMCX), and Parsol5000 by quality ratio： Parsol1789：ParsolMCX=1:2:5；

Composite emulsifier is Olivem1000 and Olivem800, and Olivem 1000 by quality ratio:Olivem 800 =5:3.

A kind of preparation method of nano-lipid carrier sun protection gel, it is characterized in that using carmethose as matrix, liquid Grease and solid grease composition lipid carrier, resveratrol and Orangic sunscreen are wrapped in lipid carrier jointly, through emulsifying, It is ultrasonic to obtain NLC-gel.Wherein liquid fat is Glycerin, mixed triester with caprylic acid capric acid, and solid grease is the wooden fruit ester of breast, is tried by JMP Software for Design Test, data analysis is carried out using spss softwares, preferably goes out optimal prescription.

(1) preparation method of the nano structured lipid carrier gel：Weigh carmethose, the hyaluronic acid of recipe quantity Sodium, preservative, are uniformly dispersed with glycerine, are added deionized water and in quickly being stirred on magnetic stirring apparatus, are fully swelled, are made solidifying Gel matrix.The wooden fruit ester of the breast of recipe quantity, composite emulsifier, the wooden fruit fat of breast, vitamin E, bisabolol are collectively disposed at 80 DEG C again Parsol5000, Parsol1789, ParsolMCX are added after water-bath, heating and melting, treats that temperature is down to 50 DEG C, adds white black false hellebore Alcohol/Glycerin, mixed triester with caprylic acid capric acid dispersion liquid, is made oil phase.The allantoin, EDTA-2Na, deionized water of recipe quantity are weighed 80 in water-bath Dissolving DEG C is heated to, aqueous phase is made.Aqueous phase and oil phase are sheared into 5min respectively in 75 DEG C of oil baths, 2000r/min, simultaneously will Oil phase slowly adds to aqueous phase, 2000r/min shearing 5min with stable flow velocity, and in ultrasound 10min under 180W power, must receive Mizhi matter support dispersion (NLC).NLC dispersion liquid room temperatures are placed to 40 DEG C, added in gel-type vehicle, it is stirring while adding to equal It is even, obtain nano-lipid carrier gel (NLC-gel).

(2) formulation optimization method：Using absorbance as index, by single factor experiment, pungent certain herbaceous plants with big flowers acid glyceride and breast are investigated Wooden fruit ester rate of charge, resveratrol consumption, emulsifier, shear rate, ultrasonic power, shear time, ultrasonic time are to referring to Target influences, and filters out the significant factors of experiment.Reciprocation between investigation factor, to be tested using custom design When, the addition factor is reduced, optimal result of the test is obtained by minimum test number (TN) to reach.Designing and dividing with JMP On the basis of analysis prediction, the data obtained is inputted in spss, using single variable linear model analysis, Optimal Parameters.

JMP is that SAS companies are the Six Sigma statistical software that global customers are developed, and experimental design is JMP surging function One of, the current country yet there are no the report for being applied to cosmetic field.The NLC-gel is characterised by its rigorous prescription Optimization process.On the basis of single factor test and reciprocation is investigated, JMP7 design experiments are used, and result is entered by spss softwares Row homogeneity test of variance, the optimal prescription drawn is：RES consumptions are 1%, and shear time is 5min, and ultrasonic time is 10min. According to UVB Protection Assessments method in QB/T2410-1998, it is 2.358 ± 0.070 to survey its absorbance, shows that the NLC-gel has There is the effect of complete protectiving ultraviolet irradiation.RES, Parsol5000, Parsol1789, ParsolMCX encapsulating in said preparation Rate is respectively 33.36% ± 2.25,62.58% ± 3.02,61.13% ± 2.78,55.18% ± 1.03.It is further stable Property result of the test prompting, its shape, content, granularity, viscosity, pH can be kept under high temperature, high humidity and intense light conditions stably.Early stage In experiment, HPLC methods are established while determining the content of resveratrol and three kinds of Orangic sunscreens, its methodology result shows this Method is accurate, reliable, the quality evaluation available for NLC-gel.

The present invention constructs a kind of novel nano delivery system in technical field of cosmetic preparation, and this delivery system is nanometer Lipid carrier gel, the solid matrix material that carrier is collectively formed by liquid fat and solid grease wraps up resveratrol and had Machine sun-screening agent must carry medicinal gel.While the gel can play anti-sunlight function, it is possible to increase resveratrol and Orangic sunscreen Photostability.

The novelty of the present invention is：1. NLC is combined with hydrogel and prepares nano structured lipid carrier hydrogel, receive Rice structured lipid carrier hydrogel overcomes the shortcoming of NLC and hydrogel while NLC and hydrogel advantage is remained.2. The solid matrix material of nano-lipid carrier improves the photostability of resveratrol and Orangic sunscreen.3. resveratrol has concurrently Uvioresistant and cytoprotection function, are also easy to produce photosensitized reaction for sunscreen product and phototoxic predicament provide new strategy.4. it is real Test design and use JMP7 softwares, experimental result is analyzed with spss, and data are rigorous, reliable results.

Brief description of the drawings

Fig. 1 is particle diameter distribution (DLS) figure of nano-lipid carrier sun protection gel.

Fig. 2 is the potential image of nano-lipid carrier sun protection gel.

Fig. 3 is that device is portrayed in prediction.

Under Fig. 4 is high temperature, high humidity and intense light conditions, the content of nano-lipid carrier sun protection gel respectively at 0 day, 5 days and The variation diagram of 10 days, wherein, n=3.

Under Fig. 5 is high temperature, high humidity and intense light conditions, the granularity of nano-lipid carrier sun protection gel respectively at 0 day, 5 days and The variation diagram of 10 days, wherein, n=3.

Under Fig. 6 is high temperature, high humidity and intense light conditions, the viscosity of nano-lipid carrier sun protection gel respectively at 0 day, 5 days and The variation diagram of 10 days, wherein, n=3.

Under Fig. 7 is high temperature, high humidity and intense light conditions, the pH of nano-lipid carrier sun protection gel is respectively at 0 day, 5 days and 10 It variation diagram, wherein, n=3.

Fig. 8 be UVA and UVB irradiation under the conditions of, RES, Parsol5000, Parsol1789, ParsolMCX bulk drug Content respectively in the variation diagram of 0h, 1h, 2h and 3h days, wherein, n=3.

Fig. 9 be under the conditions of UVA and UVB irradiations, RES in ultra light sun block lotion, Parsol5000, Parsol1789, ParsolMCX content respectively in the variation diagram of 0h, 1h, 2h and 3h days, wherein, n=3.

Figure 10 be under the conditions of UVA and UVB irradiations, RES in nano-lipid carrier sun protection gel, Parsol5000, Parsol1789, ParsolMCX content respectively in the variation diagram of 0h, 1h, 2h and 3h days, wherein, n=3.

Embodiment

A kind of prescription of nano-lipid carrier sun protection gel is as follows：0.1g sodium carboxymethylcelluloses, 0.3g Sodium Hyaluronates, 1ml NeoloneTM MxP, 8ml glycerine, the wooden fruit ester of 12.5g breasts, 2.5g Olivem1000,1.5g Olivem800,0.5g dimensions Raw element E, 0.1g bisabolol, 1g Parsol5000,2g Parsol1789,5g ParsolMCX, 1g resveratrol, 2.5g are pungent Glycerol decanoate, 0.2g allantoins, 0.1g EDTA-2Na, deionized water 61.7g.

The preparation method of above-mentioned nano-lipid carrier sun protection gel is as follows：Weigh the carmethose, transparent of recipe quantity Matter acid sodium, NeoloneTM MxP, are uniformly dispersed with glycerine, add deionized water, in quickly being stirred on magnetic stirring apparatus, fully It is swelled, gel-type vehicle is made；Again by the wooden fruit ester of the breast of recipe quantity, Olivem1000, Olivem800, vitamin E, bisabolol Addition Parsol5000, Parsol1789, ParsolMCX after 80 DEG C of water-baths, heating and melting is collectively disposed at, treats that temperature is down to 50 DEG C, the dispersion liquid of resveratrol and Glycerin, mixed triester with caprylic acid capric acid is added, oil phase is made；Recipe quantity allantoin, EDTA-2Na are weighed, is added Deionized water, 80 DEG C are heated to dissolving in water-bath, and aqueous phase is made；By aqueous phase and oil phase respectively at 75 DEG C of oil baths, 2000r/min Middle shearing 5min, while oil phase is slowly added into aqueous phase with stable flow velocity, 2000r/min shears 5min, and in 180W work( Ultrasound 10min under rate, obtains nano-lipid carrier dispersion liquid (NLC)；NLC dispersion liquid room temperatures are placed to 40 DEG C, gel base is added It is stirring while adding to uniform in matter, obtain nano-lipid carrier gel (NLC-gel).

The formulation optimization of nano-lipid carrier sun protection gel and its quality evaluation

1 purpose：Determine optimum preparation scheme and its quality evaluation

2 research methods：

The sign of 2.1 nano-lipid carrier sun protection gels

Weigh appropriate NLC-gel, diluted with deionized water, vortex oscillation makes it be uniformly dispersed, with nano particle size and Zeta potentiometric analyzers determine NLC-gel particle diameter and current potential.

2.2 entrapment efficiency determination

Using gel column SephadexG-25, nanoparticle is separated using deionized water as eluant, eluent in free drug, is occurred Start to collect after blue-opalescent, opalescence disappears after 16ml, precision measures collection liquid 5ml, is demulsified with methanol, HPLC-PDA methods are determined Content after demulsification, content accounts for the percentage of total amount as envelop rate using after demulsification.

Envelop rate=(medication amount of parcel/medicine total amount) × 100%

The evaluation of 2.3 UVB protective actions

According to QB/T2410-1998, the UVB sun-proof results of sun care preparations are evaluated using ultraviolet absorptivity method.Will be medical Adhesive tape is cut on the ㎝ of 1 ㎝ × 4 rectangle, the surface that sticking veneer is attached to quartz cell printing opacity side.After ultraviolet preheating, setting inspection Survey wavelength：280nm、290nm、300nm、310nm、320nm.Precision weigh (8 ± 0.2) ㎎, take after medical latex fingerstall, will Sample application is uniform, claims 5 parallel samples.Room temperature is placed after 30min, and testing sample is placed in sample arm, another to post The quartz cell of adhesive tape is placed in reference light paths.Determine the A of five wavelength of 280nm, 290nm, 300nm, 310nm, 320nm_i, will survey Definite value seeks arithmetic mean of instantaneous valueFive parallel samples of sequentially determining, willSeek the purple of arithmetic mean of instantaneous value, as sample Outer absorbance

2.4 formulation optimization

Using absorbance as index, by single factor experiment, pungent certain herbaceous plants with big flowers acid glyceride and the wooden fruit ester rate of charge of breast, white lamb's-quarters are investigated Reed alcohol dosage, the influence of emulsifier, shear rate, ultrasonic power, shear time, ultrasonic time to index, are filtered out The significant factors of experiment.Based on the custom design experimental method in JMP softwares, Optimal Parameters.Friendship between prior investigation factor Interaction, when being tested using custom design, to reduce the addition factor, to reach the effect for reducing number of times.With absorbance Envelop rate with 4 kinds of active ingredient is evaluation index, preferably optimum composition and preparation technology.

2.5 quality evaluation

2.5.1 outward appearance

2.5.2 assay

By nano-lipid carrier gel dispersion in deionized water, it is demulsified with methanol, HPLC method detection levels.

2.5.2 pH measure weighs appropriate NLC-gel, and deionized water dilutes, and vortex oscillation makes it be uniformly dispersed, with essence Close pH meter is determined, and instrument is corrected with pH4.0 and pH6.86 phosphate-buffered salt.

2.5.3 the measure of viscosity

Two level adjusters are adjusted, until the bubble at the top of viscosimeter is in middle position.Appropriate NLC-gel is weighed, is revolved Dynamic crane knob, makes viscosimeter slowly decline, rotor is gradually immersed among fluid to be measured, until mark and liquid on rotor Untill face is equal.Under " measurement " key, stepper motor starts rotation, can simultaneously measure after appropriate time (reading is substantially constant) and work as Preceding rotor, the viscosity number under the rotating speed and percentage meter scale.

：Relative viscosity；K：Coefficient (K=1000) M：Determine the moment of torsion that revolution is produced；ω：Angular speed (ω=6r/ Min) rotor number：No. 1

2.5.4 storage stability evaluation

According to 2015 editions《Chinese Pharmacopoeia》Four general rules《Material medicine and preparation stability test direction principle》To nanometer The stability of lipid sun-prevention gel carries out experimental study.

2.5.6 ultraviolet stability evaluation

Appropriate nano-lipid carrier sun protection gel is weighed in measuring cup, quartz plate is covered on bottleneck, is hung down away from light source The straight ㎝ of distance 20, it is respectively 280.0 μ w/cm to measure UVA and UVB intensity through illumination photometer²±28μw/cm²And 172 μ w/cm²± 17.2μw/cm², and respectively at 1h, 2h, 3h sampling, HPLC methods survey its content, observe the change of content under different irradiation times. Meanwhile, using bulk drug and self-control sunscreen as two kinds of controls, test method is ibid.Make by oneself in the grease of sunscreen containing only liquid Grease (Glycerin, mixed triester with caprylic acid capric acid), i.e., do not form the lipid carrier with skeleton structure, its prescription with solid grease (breast wood fruit ester) Amount and preparation technology are equal to nano-lipid carrier sun protection gel.

3 experimental results：

The sign of 3.1 nano-lipid carrier sun protection gels

The average grain diameter of nano-lipid carrier sun protection gel is 184.8nm, and zeta current potentials are -51.57mV.As a result see Fig. 1, Fig. 2.

3.2 envelop rate

Resveratrol, Parasol5000, Parasol 1789, ParasolMCX in nano-lipid carrier sun protection gel Envelop rate be respectively 33.36% ± 2.25,62.58% ± 3.02,61.13% ± 2.78,55.18% ± 1.03.As a result carry Show the nano-lipid carrier gel of this patent design has higher envelop rate on the premise of containing plurality of active ingredients.

3.3 the evaluation of UVB protective actions

The absorbance of nano-lipid carrier sun protection gel is 2.358 ± 0.070, is commented according to UVB protection in QB/T2410-1998 Valency method, points out the nano-lipid carrier sun protection gel of this patent design to have the effect of complete protectiving ultraviolet irradiation.

3.4 formulation optimization results

According to single factor experiment result, when the significant factors of influence absorbance are resveratrol dosage (A), shearing Between (B), ultrasonic time (C).According to custom design principle, each factor set 3 levels (A1, A2, A3 be respectively 0.05g, 0.25g, 1g, B1, B2, B3 are respectively 5min, 10min, 20min, and C1, C2, C3 are respectively 1min, 5min, 10min).It is interactive to examine Examining does not have reciprocation between result prompting resveratrol consumption and shear time, shear time has obvious friendship with ultrasonic time Interaction, resveratrol usage amount there may exist reciprocation with ultrasonic time.Factors A, B, C, A × C, B × C are added, is added Plus effect absorbance and the envelop rate of 4 kinds of active ingredient, go out 15 groups of experiments with JMP custom designs, by the data obtained typing Analysis, with least square method carry out models fitting, by prediction portray device draw optimal prescription be A1B1C3, as a result see Fig. 3.

On the basis of being designed with JMP and analyzing prediction, the data obtained is inputted in spss, using single variable linear mould Type analysis, using each index as dependent variable, factor A, B, C, A × C, B × C are immobilisation factor, examine intersubjective effect, are used The homogeneity test of variance that Tukey HSD methods are compared two-by-two.As a result point out：The inspection of effect between one-way analysis of variance main body Test in result constructed overall model F statistics be followed successively by (according to absorbance, resveratrol, Parsol5000, Parsol1789, ParsolMCX order)：5.571st, 765.169,6.271,38.268,45.329, corresponding P values are almost For 0, it is believed that the linear effects of overall fitting are very good.

For index absorbance, influences of factor A, B, A × C, B × C to absorbance all highly significants, factor C is to extinction There was no significant difference for angle value.And further comparative result two-by-two shows, the average difference between A1 and A3 is maximum, B3 and B1 Between average difference it is maximum, the average difference between C2 and C1 is maximum.Therefore, for index absorbance, optimal combination It should be A1B3C2.

For index resveratrol envelop rate, influences of A, B, C, A × C, B × C to resveratrol envelop rate all shows very much Write.And further comparative result two-by-two shows, the average difference between A3 and A1 is maximum, and shear time is it of B1 and B2 Between average difference it is maximum, ultrasonic time is maximum for the average difference between C2 and C1.Therefore, for index resveratrol Envelop rate, optimal combination should be A3B1C2.

For index Parsol5000 envelop rate, factor A, C, A × C, B × C influence on Parsol 5000 envelop rate Highly significants, factor B does not have a significant impact to Parsol 5000 envelop rate.And further comparative result table two-by-two Bright, the average difference between A1 and A3 is maximum, and shear time is maximum for the average difference between B3 and B2, and ultrasonic time is Average difference between C3 and C1 is maximum.Therefore, for index Parsol 5000 envelop rate, optimal combination should be A1B3C3。

For index Parsol1789 envelop rate, factor A, C, A × C, B × C influence on Parsol 1789 envelop rate Highly significants, factor B does not have a significant impact to Parsol 1789 envelop rate.And further comparative result table two-by-two Bright, A1 is maximum for the average difference between % and A3, and shear time is maximum for the average difference between B1 and B3, when ultrasonic Between for the average difference between C3 and C1 it is maximum.Therefore, for index Parsol 1789 envelop rate, optimal combination should For A1B1C3.

For index ParsolMCX envelop rate, factor A, B, C, A × C, B × C influence on Parsol MCX envelop rate All highly significants.And further comparative result two-by-two shows, the average difference between A1 and A3 is maximum, and shear time is B1 Average difference between B3 is maximum, and ultrasonic time is maximum for the average difference between C3 and C1.Therefore, for index Parsol MCX envelop rate, optimal combination should be A1B1C3.

In summary, optimum combination should be A1B1C3.I.e. resveratrol dosage is 1g, and shear time is 5min, ultrasound Time is 10min.It is consistent with the result that device is portrayed in prediction.Measured absorbance is 2.358 ± 0.070, according to QB/T2410- UVB Protection Assessments method in 1998, shows that the NLC-gel has the effect of complete protectiving ultraviolet irradiation.Resveratrol, Parasol5000, Parasol1789, ParasolMCX envelop rate are respectively 33.36% ± 2.25,62.58% ± 3.02, 61.13% ± 2.78,55.18% ± 1.03.Further stability test result prompting, its shape, content, granularity, viscosity, PH can keep stable under high temperature, high humidity and intense light conditions.

3.5 quality evaluation

3.5.1 outward appearance

The nano-lipid carrier sun protection gel of this patent design is gluey for milky, and uniform and smooth, no lamination is not done Dry up or liquefy, stretchability is good.

3.5.2 assay

Resveratrol, Parasol5000, Parasol 1789, ParasolMCX in nano-lipid carrier sun protection gel Content 101.38% ± 1.36,102.98% ± 0.89,99.67% ± 1.31,95.25% ± 0.07.

3.5.2 pH measure

The mean ph value of nano-lipid carrier sun protection gel is 6.31 ± 0.08.According to QB/T-2286-1997, milky lotion The pH value limitation scope of liquid is 4.5~8.5.As a result the pH value of the nano-lipid carrier gel of prompting this patent design meets moisturizing The physical and chemical index of emulsion.

3.5.3 the measure of viscosity

Measurement result shows the viscosity of nano-lipid carrier sun protection gel between 15~20Pas.3.5.4 storage-stable Property evaluate

Storage stability structure is shown in Fig. 4~Fig. 7.As a result show, under influence factor experimental condition, nano-lipid carrier is prevented The content of solarization gel, viscosity, granularity, pH do not occur significant difference, and its shape does not also change.Point out this patent design Nano-lipid carrier sun protection gel have good stability.

3.5.5 ultraviolet stability evaluation

As a result show, bulk drug 1h after UVA irradiates, RES, Parsol5000, Parsol1789, ParsolMCX's Content has conspicuousness reduction, after UVB1h is penetrated, and RES, Parsol5000, ParsolMCX content have conspicuousness drop It is low, and Parsol1789 content has no change.Because 320~360nm and 280~320nm ripples of the RES in UVA and UVB Duan Jun has absorption；Though Parsol5000 and ParsolMCX are potent UVB absorbents, its respectively UVA 320~350nm and 320~360nm has different degrees of absorption；And Parsol1789 is UVA absorbents, do not absorbed in UVB wave bands, therefore contain No conspicuousness change is measured, Fig. 8 is as a result seen.

Ultra light sun block lotion after UVA irradiations 2h, RES and Parsol1789, content have conspicuousness reduction, by UVB Penetrate after 2h, RES content has after conspicuousness reduction, UVB irradiations 3h, and RES, Parsol5000, ParsolMCX content have aobvious The reduction of work property, and Parsol1789 content does not have conspicuousness change.As a result prompting matrix can prevent resveratrol and organic Sun-screening agent produces light degradation, but result is shown in Fig. 9.

Nanometer lipid sun-prevention gel is after UVA irradiations 3h, and RES, Parsol5000 and ParsolMCX content are showed no Conspicuousness changes, and only Parsol178 content reduces 2.0% after irradiation 3h；After being irradiated through UVB, Parsol5000, Conspicuousness change does not occur for Parsol1789, ParsolMCX content, and RES content reduces 3.9%.Show nanometer Resveratrol and Orangic sunscreen in lipid carrier sun protection gel can be stablized in UVA and UVB irradiation 2h, and light drop does not occur Solution.As a result point out, compared with the UV stable evaluation result of bulk drug and ultra light sun block lotion, said preparation can significantly improve RES With the photostability of Orangic sunscreen, Figure 10 is as a result seen.

4 conclusions：

Formulation optimization result shows that resveratrol consumption is 1%, and shear time is 5min, when ultrasonic time is 10min, Measured absorbance is 2.358 ± 0.070, shows that there is the nano-lipid carrier sun protection gel complete protectiving ultraviolet to shine The effect penetrated.RES, Parsol5000, Parsol1789, ParsolMCX envelop rate is respectively 33.36% ± 2.25, 62.58% ± 3.02,61.13% ± 2.78,55.18% ± 1.03.Storage stability result prompting said preparation is stable, is easy to storage Deposit；Ultraviolet stability result prompting this patent design nano-lipid carrier sun protection gel can effectively improve RES, Parsol5000, Parsol1789 and ParsolMCX photostability, with certain market prospects.

Claims

1. a kind of nano-lipid carrier sun protection gel, it is characterized in that being made up by mass percentage of following material：

Resveratrol 0.25~1.5%；Orangic sunscreen 7~9%；Complex lipid 8~16%；Composite emulsifier 2~5%；Carboxylic Methylcellulose sodium 0.1~0.4%；Sodium Hyaluronate 0.2~0.3%；NeoloneTM MxP 0.5~2%；Glycerine 3~8%； Vitamin E 0.5~1%；Bisabolol 0.1~0.3%；Allantoin 0.1~0.25%；EDTA-2Na 0.05~0.2%；Its Remaining is deionized water；

Wherein, complex lipid is：Newborn wood fruit ester and pungent capric acid glycerine, and the wooden fruit ester of breast by quality ratio：Pungent capric acid glycerine=5: 1；

Composite emulsifier is：Olivem1000 and Olivem800, and Olivem 1000 by quality ratio:Olivem 800=5: 3。

2. nano-lipid carrier sun protection gel as claimed in claim 1, it is characterized in that, specific preparation method is as follows：Weigh place Carmethose, Sodium Hyaluronate, the NeoloneTM MxP of side's amount, are uniformly dispersed with glycerine, add deionized water, Yu Ci Quickly stir, be fully swelled on power agitator, gel-type vehicle is made；Again by the wooden fruit ester of the breast of recipe quantity, Olivem1000, Olivem800, vitamin E, bisabolol be collectively disposed at after 80 DEG C of water-baths, heating and melting add Parsol5000, Parsol1789, ParsolMCX, treat that temperature is down to 50 DEG C, add the dispersion liquid of resveratrol and Glycerin, mixed triester with caprylic acid capric acid, oil is made Phase；Recipe quantity allantoin, EDTA-2Na are weighed, deionized water is added, 80 DEG C are heated to dissolving in water-bath, and aqueous phase is made；Will Aqueous phase and oil phase in 75 DEG C of oil baths, 2000r/min respectively at shearing 5min, while oil phase is slowly added into water with stable flow velocity Phase, 2000r/min shearing 5min, and in ultrasound 10min under 180W power, obtain nano-lipid carrier dispersion liquid (NLC)；Will NLC dispersion liquid room temperatures are placed to 40 DEG C, are added in gel-type vehicle, stirring while adding to uniform, obtain nano-lipid carrier gel (NLC-gel)；

Wherein resveratrol consumption is 1%, and shear time is 5min, and when ultrasonic time is 10min, measured absorbance is 2.358, resveratrol, Parasol5000, Parasol1789, ParasolMCX envelop rate be respectively 33.36%, 62.58%th, 61.13%, 55.18%.