| Arbutin is a kind of natural active substances isolated from a variety of genus, its chemical name is 4-hydroxyphenyl-β-D- glucopyranoside(referred β- arbutin). β- arbutin is reported that its mechanism of eliminating the pigment, tyrosinase inhibitors and having skin whitening effect.In the 1990 s,β- arbutin was first introduced as a cosmetic whitening agent by Shiseido Cosmetics Corporation.It is often as an advanced cosmetic ingredient, for removing skin freckles, age spots,and melisma.Lemon(Citrus lemon(L) Burm.F.) is Rutaceae Citrus small evergreen tree, rich in essential oil. Due to nourishing, pigmentation, whitening and other effects,it is often as a functional ingredient application for moisturizing, cream, whitening toner water. In addition,for its good effect through the skin and better penetration enhancement,it is often used as a natural penetration enhancers, widely used in cosmetics, medicine and so on.In this paper, β- arbutin is the main active substance,Lemon volatile oil is an auxiliary whitening permeation enhancers.Screen compound prescription and prepare both whitening and Transdermal the double effect special cosmetics.While reducing the amount of externalβ- arbutin, increasing the natural penetration enhancement,there has be a synergistic function.This provides a theoretical basis for future industrial production. The main contents are as follows:(1) Establish a determination method for measuring the content of β- arbutin by HPLC and limonene in lemon volatile by GC,and determinate of the two materials, respectively.(2) Single factor experiment for fresh lemon peel :the impact of soak time, solid-liquid ratio and extraction time for the amount of lemon volatile oil,Adopting box-Behnken Design(BBD) Design Optimizates of extraction process of volatile oil of lemon.(3) In vitro percutaneous permeation test method to investigate the lemon volatile oil its own transdermal identities and the promotion β- arbutin transdermal performance,and filter out the amount of volatile oil and β- arbutin.(4) Orthogonal design method to optimize of the cream formulations, respectively, the amount of oil phase emulsifier, oily base, aqueous base and deionized water as a four factors test.Carry out the four factors and three levels test L9(3)4; control the quality of cream, and investigate formability, stability; in vitro percutaneous penetration study,investigate β- arbutin penetration rate in cream, and enhancing rate ER.(5) Determinate cream whitening effect in biochemical methods.In the guinea pig skin irritation study, according to "2007 edition cosmetics Specifications" skin irritation test score standard and skin tissue sections, preliminarily investigate the whitening cream skin irritation.Results:(1) Establish a method to detect β- arbutin by HPLC, the content of β-arbutin material was 95.0%. The method is a good specificity, precision RSD is 1.50%,repeatability RSD is 0.50%, recoveries rate RSD is 1.57%, the stability of 24 h, RSD is0.38%, which results are good, stable and feasible. Limonene was determined in lemon volatile oil by internal standard method.The result is that the average percentage of limonene in lemon was 33.72%. precision RSD is 4%, repeatability RSD is 1.13%,recoveries RSD is 1.3%, the stability at 24 h, RSD is 1.08%, these results are good, stable and feasible.(2) Optimization of lemon volatile oil extraction process as follows: solid-liquid ratio(ml /g) is10:1 the distillation time 3.35 h, soak time 5h, under this condition, the extraction rate of volatile oil is 2.28%.(3) In lemon volatile oil itself penetration test: in this experimental system penetration rate of limonene in a concentration-dependent manner, the amount of cumulative permeation per unit area between 2-24 h shows obvious regularity: 5.0%> 3.0%> 1.0 %;indicating lemon volatile oil has a high skin permeability. Lemon essential oil to promote β-arbutin vitro transdermal penetration test: ① under equal amounts of β- arbutin,compare the enhancing rate ER, both transdermal penetration capacity: 3.0% Azone> 2.0% Azone>3.0% volatile oil> 2.0% volatile oil> 1.0% Azone> 1.0% volatile oil. 3.0% oil and 3.0%azone ER are 1.9465、1.9687 respectively, for the small gap, 3.0% volatile oil is choosen as whitening cream transdermal penetration enhancers. ② 3.0% volatile oil as transdermal penetration enhancers, concentrations of 1.0%, 2.0% and 3.0% β- arbutin enhancing rate is respectively 1.9499、1.9005、1.9315. Further calculated: comparing with 3.0% β- arbutin conventional amounts, add 3.0% lemon volatile oil can reduce the amount of 1.45% of β-arbutin.(4) Pharmaceutical formulations orthogonal test L9(3) 4. The results showed that the optimum formulation in 100 g formulation composition :deionized water 85 g, glycerin 9g,polyethylene glycol glyceryl oleate 3g, polyethylene glycol-7- stearate 2g, glyceryl stearate2 g, dimethicone 3g, beeswax 1.5g, carbomer 0.15 g, xanthan gum 0.25 g, lemon volatile oil3.0g, β- arbutin 1.962 g. This combination cream is physical stability, the particles is uniformly fine. Penetration rate of transdermal penetration enhancers: 5.2227 ug ? cm-2 ?h-1, negative group: 3.3782 ug ? cm-2 ? h-1, the ER is 1.55. Lemon volatile oil can effectively promote β- arbutin percutaneous absorption in whitening cream description.(5) In the whitening experiment, the optimum conditions is: L- tyrosine solution 0.8m L, tyrosinase 0.40 m L, water bath time 10 min, reaction time 5 min. In the preferred reaction system,measuring tyrosinase inhibition of whitening cream: prelimary inhibition rate: LA cream>LA lemon volatile oil negative >LA β- arbutin negative; inhibition rate: LA cream> LA lemon volatile oil negative >LA β-arbutin negative; maximum inhibition rate:LA cream ≈LA lemon volatile oil negative >LA β-arbutin negative. Indicating that Lemon volatile oil has a certain synergy in β- arbutin whitening cream. In irritation test, the results as follows: ① sample tests by an independent statistical analysis, in the concentration of3% there is no significant difference in the intact skin with the matrix control group of intact skin, p> 0.05.On damaged skin p <0.05, there is a significant difference in the 3%concentration in the matrix blank group, shows little irritation in breakage mild skin.p<0.05, there is a significant difference at 5% and 8% concentration,compared with matrix blank group,indicating that both concentration of frost irritate the integrity and broken skin. ② skin biopsy analysis, 3% volatile oil preparation make the skin stratum loosen,however consistent epidermis, uniform thickness, there is no damage to the dermis and hair follicles. High concentrations of volatile oil preparation on integrity and damaged skin cause the cuticle broken off, the skin not coherent, non-uniform thickness, change hair follicles form in the dermis and prevent its growth, and result in hair follicles overflow.Conclusions:(1) Whitening cream recipe( 100g) : lemon volatile oil 3.0g, β- arbutin1.962 g,deionized water 75 g, glycerin 9g, polyethylene glycol glyceryl oleate 3g,polyethylene glycol-7- stearate 2g, glyceryl stearate 2g, dimethicone 3g, beeswax 1.5g,carbomer 0.15 g, xanthan gum 0.25 g.This combination is physical stability, cream particles uniformly fine.The LA cream is good inhibition of tyrosinase, and has a good function of whitening. It can be developed as a special cosmetic.(2) In LA scream lemon volatile oil is able to play a better penetration enhancement effect on β- arbutin, 3% concentration of lemon essential oil is the same with concentration of nitrogen-one. 3% lemon volatile oil as transdermal penetration enhancers added LA cream can reduce the usage of β- arbutin and effectively promote its security. |
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