CN118459325B - Preparation method of raspberry ketone and derivative thereof and application of raspberry ketone and derivative thereof in oil control cosmetics - Google Patents
Preparation method of raspberry ketone and derivative thereof and application of raspberry ketone and derivative thereof in oil control cosmetics Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
- C07C49/24—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing hydroxy groups
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
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- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
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Abstract
The invention discloses a preparation method of raspberry ketone and a derivative thereof and application of the raspberry ketone and the derivative thereof in oil control cosmetics, belonging to the field of cross application of organic synthesis technology and cosmetics. The preparation method takes a monochloromethylbenzene derivative and propylene oxide as raw materials, and synthesizes raspberry ketone and a derivative thereof shown in the following formula under the action of magnesium metal and Sarrett reagents. The invention also provides application of the raspberry ketone derivative prepared by the preparation method as an oil control component in preparation of oil control cosmetics. The preparation method avoids the use of explosive sources such as hydrogen and the like, is simpler and safer, and has higher yield compared with the prior art. Experiments show that the raspberry ketone derivative has the effects of controlling oil and inhibiting skin grease secretion, can be used as an oil control component in cosmetics, and expands the new application of the raspberry ketone derivative in the field of cosmetics.
Description
Technical Field
The invention belongs to the field of cross application of organic synthesis technology and cosmetics, and particularly relates to a preparation method of raspberry ketone and a derivative thereof and application of raspberry ketone and derivative thereof in oil control cosmetics.
Background
Raspberry ketone is an organic compound with raspberry aroma and fruit aroma, is widely used as essence in the food industry at the earliest time, and has aroma-enhancing and sweet-increasing effects in the cosmetic industry in recent years. As the structure is similar to that of the p-hydroxyacetophenone, the anti-microbial agent can be used as a novel preservative in various cosmetics, and has the remarkable effects of safety, no toxicity, no harm, no sensitization and good antibacterial property. Through searching, research reports on oil control are not found at present.
Meanwhile, most of the existing methods for synthesizing raspberry ketone are carried out by condensing and hydrogenating hydroxybenzaldehyde and acetone (such as CN109678689A, CN1097729A, and the like), or carrying out hydrogenation reduction on anisaldehyde to obtain anisyl acetone (such as CN1478768A, CN 101717328B), and the method of catalytic hydrogenation is not needed at last although the adopted raw materials are different. The target substance is synthesized by means of biological fermentation and the like, and the substance is converted by the action of enzymes in a microbial strain body to obtain the required substance, and the method has low conversion rate (such as CN 108753852B, CN 112391418B). In addition, raspberry ketone is extracted from raspberry plants by a plant extraction mode, the extraction rate is low, a large amount of plants are needed, more three wastes (waste gas, waste water and solid waste) are generated in the extraction process, and the environmental treatment pressure (such as CN 103553893A) is increased.
CN102584554a discloses a method for preparing raspberry ketone in acidic ionic liquid, which uses phenol and butenone as initial raw materials, uses acidic ionic liquid which has good thermal stability and is difficult to volatilize and can be recycled as catalyst and reaction solvent, and carries out selective addition reaction to synthesize raspberry ketone, but the yield of raspberry ketone prepared by the method is only 20-65%, and cannot meet the requirement of industrial production. CN104193607a discloses a synthesis method of raspberry ketone, which uses fennel acetone as starting material, in the presence of acetic acid medium and catalyst alkylphenol, dropwise adding bromohydric acid at 103-108 ℃ to make demethylation reaction, extracting reactant with ethyl acetate, and distilling to obtain raspberry ketone product with content of more than 99.5%. However, the yield of the raspberry ketone is lower than about 61-85%, and the raspberry ketone is not suitable for industrial production.
The chemical method of organic synthesis is most directly effective to obtain the target substance raspberry ketone and the derivative thereof. The existing chemical method uses hydrogen, which has relatively high cost and certain potential safety hazard, and the poor treatment can cause explosion, thus being a potential hazard source. Although the non-hydrogenation method is used for avoiding the danger of hydrogen, the synthesis process is complex and cannot be industrially implemented. It is therefore very challenging to develop efficient, safe, non-hydrogenated synthesis of raspberry ketone and its derivatives and to meet the needs of industrial production.
Disclosure of Invention
In order to solve the technical problems, the invention provides a preparation method of raspberry ketone and a derivative thereof and application of the raspberry ketone and the derivative thereof in oil control cosmetics. The invention adopts the monochloromethylbenzene derivative and the epoxypropane as raw materials, synthesizes the raspberry ketone derivative efficiently and safely under the action of organic auxiliary agent metal magnesium and Sarrett (Sha Ruite) reagent (chromic anhydride-bipyridine complex formed by chromic anhydride and pyridine), verifies the effect of inhibiting skin grease secretion through experiments, and expands the new application of the raspberry ketone derivative in the field of cosmetics.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
In a first aspect, the invention provides a preparation method of raspberry ketone and derivative thereof, which takes monochloromethylbenzene derivative and propylene oxide as raw materials, and synthesizes the raspberry ketone and derivative thereof shown in formula (I) under the action of magnesium metal and Sarrett reagent;
（I），
wherein R represents a mono-substituted phenyl group or a poly-substituted phenyl group;
r is selected from-OH OR-OR 1, wherein R 1 represents a substituted OR unsubstituted C1-C3 alkane.
The shape of the magnesium metal in the present invention is a filament from which surface oxides are removed.
Because magnesium reacts with water severely and Sha Ruite reagents decompose when meeting water, the whole reaction process of the invention needs to be carried out under the protection of inert gas in an anhydrous environment.
The synthetic route of the invention is as follows:
。
in an embodiment, the preparation method comprises the following steps:
S1, reacting a monochloromethylbenzene derivative with magnesium metal to obtain a reaction solution;
S2, adding propylene oxide into the reaction liquid obtained in the step S1 for reaction, quenching the reaction after the reaction is finished, filtering the reaction liquid, and removing the solvent from the filtrate to obtain residues;
S3, carrying out oxidation reaction on the residues obtained in the step S2 and Sha Ruite reagent, and treating to obtain the raspberry ketone and the derivative thereof.
Preferably, the monochloromethylbenzene derivative in step S1 has the following structure:
，
Wherein R represents a mono-substituted phenyl group or a poly-substituted phenyl group;
r is selected from-OH OR-OR 1, wherein R 1 represents a substituted OR unsubstituted C1-C3 alkane.
Preferably, the solvent for the reaction in step S1 is anhydrous tetrahydrofuran, the reaction temperature is 0-5 ℃, and the reaction time is 7-9h.
Preferably, the molar ratio of the monochloromethylbenzene derivative to the magnesium metal in step S1 is from 1:1.8 to 2.2, more preferably 1:2.
Preferably, the reaction in step S2 is: propylene oxide is added dropwise, heating is carried out, and the reaction is carried out for 6-7h at 30 ℃ after the completion of the dropwise addition.
Further preferably, the temperature of the heating does not exceed 30 ℃.
Preferably, the molar ratio of the oxypropane to the monochloromethylbenzene derivative in step S2 is from 1:0.85 to 1.15, more preferably 1:1.
Preferably, the quenching reaction in step S2 is: acid was added dropwise until a white fine solid appeared, and the addition was completed.
Preferably, the solvent for the oxidation reaction in step S3 is dichloromethane, the reaction temperature is 25 ℃, and the reaction time is 5-7h.
Preferably, the molar ratio of Sha Ruite reagent to propylene oxide is 1.1-1.3:1; further preferably 1.2:1.
Preferably, the processing in step S3 is: extracting the reaction liquid after the oxidation reaction with water, drying, removing water and filtering the organic phase, and removing the solvent to obtain the residual white solid, namely the target substance.
In a second aspect, the invention also provides the raspberry ketone derivative with oil control effect prepared by the preparation method.
The raspberry ketone derivative has the structure that:
，
wherein R represents a mono-substituted phenyl group or a poly-substituted phenyl group;
R is selected from-OH OR-OR 1, wherein R 1 represents a substituted OR unsubstituted C1-C3 alkane;
Preferably is 。
In a third aspect, the present invention provides the use of a raspberry ketone derivative as an oil control ingredient in the preparation of an oil control cosmetic.
The raspberry ketone derivative has the structure that，
Wherein R represents a mono-substituted phenyl group or a poly-substituted phenyl group;
R is selected from-OH OR-OR 1, wherein R 1 represents a substituted OR unsubstituted C1-C3 alkane;
Preferably is 。
The raspberry ketone derivative can inhibit the expression of key genes for sebum synthesis, so as to reduce the lipid synthesis of sebocytes and achieve the effect of controlling oil.
Preferably, the key gene is at least one of SREBP1 gene, FAS gene and SCD1 gene.
The oil control cosmetics in the present invention include, but are not limited to, facial cleanser, shampoo, facial mask, astringent, cream emulsion, gel, powder, mud, wax base, spray or aerosol.
In a fourth aspect, the present invention provides an oil control cosmetic comprising a raspberry ketone derivative having the structure。
Preferably, the raspberry ketone derivative accounts for 0.2% -1% of the quality of the oil control cosmetic.
The beneficial effects of the invention are as follows:
(1) The invention prepares the format reagent of the aromatic methyl benzene derivative through the reaction of the monochloromethyl benzene derivative and the magnesium metal, then reacts with propylene oxide to acidify to form the hydroxybutyl benzene derivative, and then uses Sha Ruite reagent to oxidize the hydroxy of the secondary alcohol into ketone with high selectivity, finally obtains the raspberry ketone and the derivative thereof with high purity. The method changes the previous mode of synthesizing the target object by reducing double bonds through catalytic hydrogenation, avoids using explosive sources such as hydrogen and the like, and has simpler and safer preparation method. Compared with the prior art, the preparation method has higher yield and is suitable for industrial production.
(2) The substance obtained by the reaction in the step 1 does not need complex treatment, and excessive magnesium metal is taken out, recovered and stored in a dry environment, and the surface oxide film is removed before reuse. After the reaction is finished, the reaction device is not required to be removed, a constant-pressure dropping funnel is additionally arranged to perform the operation of the next step, meanwhile, excessive Sha Ruite reagents react to form chromic anhydride bipyridine salt which exists in the water phase, and the chromic anhydride bipyridine salt can be dried, dehydrated and alkalized and then used. The excessive materials used in the preparation process can be recycled and simply treated and then reused, and continuous synthesis operation can be realized by skillfully using the construction of a simple device in the reaction treatment process, so that a feasible operation method is provided for cost reduction, and a good technical foundation is laid for industrial production.
(3) Experiments prove that: the raspberry ketone derivative provided by the invention has good safety, and can inhibit the expression of SREBP1, FAS and SCD1 genes so as to reduce the lipid synthesis of sebocytes and achieve the effect of controlling oil.
(4) The oil control cosmetic prepared by using the raspberry ketone derivative as an oil control component has good safety, can effectively inhibit skin grease secretion, and has good oil control effect.
Drawings
FIG. 1 shows the growth of SZ95 human sebaceous cells after treatment with the synthesized raspberry ketone derivative of the invention in different concentration gradients;
FIG. 2 shows the expression of essential sebum synthesis genes of SZ95 strain of human sebaceous gland cells after treatment with the raspberry ketone derivatives of the invention in different concentration gradients;
FIG. 3 is a comparison of sebum amounts of forehead skin before and after use of the facial cleanser composition provided in example six;
FIG. 4 is a graph showing sebum secretion inhibiting effects of a mask composition sample provided in example eight;
Fig. 5 is a graph showing the degree of satisfaction of the oil control effect of the emulsion composition sample provided in example nine.
Detailed Description
The following examples are presented only to aid in understanding the method of the present invention and its core ideas. It should be noted that it will be apparent to those skilled in the art that various modifications and adaptations of the invention can be made without departing from the principles of the invention and these modifications and adaptations are intended to be within the scope of the invention as defined in the following claims. The following description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described herein.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
Embodiment one: preparation of raspberry ketone
When the R group is para-monosubstituted hydroxyl-OH, the synthetic target is the structure of raspberry ketone.
The total reaction process is as follows:
The 14.549 g substance A p-hydroxybenzyl chloride solid (the mass of the substance is 0.1: 0.1 mol, the mass fraction is 98%, the same applies below) is weighed into a100 mL three-mouth bottle, 40 mL anhydrous THF (anhydrous tetrahydrofuran) is added, a stirring device and a thermometer are arranged, and the mixture is placed in an ice water bath (0 ℃); and weighing 4.862 g metal magnesium strips (0.2 mol), polishing the surface oxide film by using sand paper, cutting the surface oxide film into filaments, rapidly placing the filaments into a three-mouth bottle, replacing the gas in the reaction device by using inert gas high-purity nitrogen or high-purity argon for three times, reducing the flow rate, and continuously slightly introducing the inert gas. The reaction was continued at 8 h f with ice water bath temperature and gradual dissolution of the magnesium strip was observed.
After the reaction is finished, the redundant magnesium strips are rapidly taken out by forceps, and the substance B generated by the reaction is dissolved in a solvent without treatment for the next step. Adding a constant-pressure dropping funnel device, adding 5.814 g propylene oxide liquid (0.1 mol, 99.9%) weighed in advance into the funnel, slightly and continuously introducing the liquid after the liquid is replaced by inert gas for three times, removing the ice water bath device, starting to slowly drop propylene oxide, heating properly, and maintaining the reaction at the temperature of below 30 ℃ for 6 h after the dropping is completed. Slowly dripping 8.33 mL new concentrated hydrochloric acid into the reaction device to quench the reaction, wherein white fine solid appears, stirring for about 10 min after dripping is completed, filtering to remove magnesium chloride generated, washing a filter cake three times by using 10 mL anhydrous THF once, recovering solvent from the residual filtrate by a rotary evaporator, and weighing 16.013 g after drying.
All solids from the previous step were added to a 250 mL three-necked flask, 70 mL dichloromethane solvent was added, and a constant pressure dropping funnel was added. The 29.851 g Sha Ruite reagent (0.12 mol) and 50 mL dichloromethane solvent were weighed to give a mixed solution, which was added to the funnel, replaced three times with inert gas, and the slight addition was continued. The temperature was maintained at 25℃and added dropwise. After the completion of the dropwise addition, the reaction was continued to be carried out for 5 h, after the completion of the reaction, the reaction solution was extracted with 100. 100 ml water, the organic phase was separated, dried with anhydrous sodium sulfate, the dried organic phase was separated by filtration, the solvent was recovered by rotation, white needle-like solid was precipitated, 15.017 g was obtained after drying, the yield was 94.9%, and the purity was tested to be 98.15%.
The raspberry ketone structure information is verified as follows:
1H NMR(DMSO-d6): δ(ppm) = 2.10(3H, CH3), 2.78(t, 2H, CH2), 2.80(t, 2H, CH2), 6.65 - 6.71(m, 2H, ArH), 6.96 - 7.02(m, 2H, ArH) , 9.06(s, 1H, OH);13C NMR(DMSO-d6): δ(ppm) = 28.7(1C, CH2), 29.8(1C, CH3), 43.1(1C, CH2), 115.8(2C, ArC), 130.2(2C, ArC), 133.9(1C, ArC), 155.7(1C, ArC), 206.7(1C, CO).
embodiment two: preparation of raspberry ketone derivative
When the R group is para-hydroxy-OH substitution and meta-OCH 2CH3 substitution, the synthetic target substance is the structure of the raspberry ketone derivative.
The total reaction process is as follows:
19.235 g of substance D, namely parahydroxy-m-ethoxy benzyl chloride solid (0.1 mol, 97%) is weighed into a 100mL three-mouth bottle, 50mL anhydrous THF is added, a stirring device and a thermometer are arranged, and the mixture is placed in an ice water bath; and weighing 4.859 g metal magnesium strips (0.2 mol), polishing the surface oxide film by using sand paper, cutting the surface oxide film into filaments, rapidly placing the filaments into a three-mouth bottle, replacing the gas in the reaction device by using inert gas high-purity nitrogen or high-purity argon for three times, reducing the flow rate, and continuously slightly introducing the inert gas. Maintaining the temperature of the ice-water bath for reaction 9 h, gradual dissolution of the magnesium strip was observed.
After the reaction is finished, the redundant magnesium strips are rapidly taken out by forceps, and the substance E generated by the reaction is dissolved in a solvent and can be used for the next step without treatment. Adding a constant-pressure dropping funnel device, adding 5.832 g propylene oxide liquid (0.1 mol, 99.9%) weighed in advance into the funnel, slightly and continuously introducing the liquid after the liquid is replaced by inert gas for three times, removing the ice water bath device, starting to slowly drop propylene oxide, heating properly, and maintaining the reaction at the temperature of below 30 ℃ for 7 h after the dropping is completed. Slowly dripping 8.41 mL new concentrated hydrochloric acid into the reaction device to quench the reaction, wherein white fine solid appears, stirring for about 10 min after dripping is completed, filtering to remove magnesium chloride generated, washing a filter cake three times by using 10 mL solvent THF once, recovering the solvent from the residual filtrate by a rotary evaporator, and weighing 20.224 g after drying.
All solids from the previous step were added to a 250 mL three-necked flask, 85 mL dichloromethane solvent was added, and a constant pressure dropping funnel was added. The 29.823 g Sha Ruite reagent (0.12 mol) and 60 mL dichloromethane solvent were weighed to give a mixed solution, which was added to the funnel, replaced three times with inert gas, and the slight addition was continued. The temperature is maintained at 25 ℃, the dripping is carried out, the reaction is continued to be carried out for 6 h after the dripping is completed, after the reaction is completed, 100 ml water is used for extracting the reaction liquid, the organic phase is separated, anhydrous sodium sulfate is dried, the organic phase is filtered out, the solvent is recovered by rotation, white needle-like solid is separated out, 19.053 g is obtained after the drying, and the yield is 95.1 percent and the purity is tested to be 97.36 percent.
The structural information of the raspberry ketone derivative is verified as follows:
1H NMR(DMSO-d6): δ(ppm) = 1.42(t, 3H, CH3), 2.24(s, 3H, CH3), 2.68(t, 2H, CH2), 2.83(t, 2H, CH2), 4.13(q, 2H, CH2), 6.59(m, 1H, ArH), 6.65 - 6.71(m, 2H, ArH), 9.83(s, 1H, OH);13C NMR(DMSO-d6): δ(ppm) = 14.8(1C, CH3), 29.0(1C, CH2), 30.1(1C, CH3), 43.5(1C, CH2), 64.9(1C, CH2), 113.3(1C, ArC), 115.1(1C, ArC), 121.8(1C, ArC), 132.6(1C, ArC), 146.0(1C, ArC), 148.3(1C, ArC), 207.8(1C, CO).
Embodiment III: cytotoxicity test for detecting raspberry ketone derivative on human sebaceous gland cell SZ95 strain
Human sebaceous gland cell SZ95 strain is cultivated. After the cells with good growth condition and density of about 80% -90% of one dish of p60 are digested, counting, mixing 3X 10-5 cells with DMEM culture medium, adding the mixture into 96-well cell culture plates, culturing at the temperature of 37+/-1 ℃ and CO 2 5.0.0% +/-1%, replacing the culture medium after 12-16 hours, adding raspberry ketone derivative prepared in the second embodiment of the invention with the final concentration of 0, 50-100 mu M, 200 mu M, 500 mu M, 1000 mu M and 2000 mu M respectively, and repeating 6 wells for each concentration. After 48h, the viability of the cells was tested using CCK8 kit to test the toxicity of different concentrations of raspberry ketone derivative to sebaceous gland cells cultured in vitro.
The results are shown in FIG. 1.
The results show that the raspberry ketone derivative has no influence on the growth and proliferation of cells of the SZ95 strain of the human sebaceous gland cells when the concentration of the raspberry ketone derivative is 50 mu M, 100 mu M and 200 mu M, and has better safety.
Embodiment four: sebum synthesis experiment of raspberry ketone derivative for inhibiting sebaceous gland cell SZ95
Primers GAPDH (internal control), SREBP1, FAS, SCD1 (synthesized by Bio Inc.) were designed using NCBI and Primer Blast, respectively, as shown in Table 1.
TABLE 1
RNA of human sebaceous cell SZ95 strain treated with raspberry ketone derivative (prepared in example II) for 48 hours at 0. Mu.M, 50. Mu.M, 100. Mu.M and 200. Mu.M was extracted using RNA extraction kit, respectively. RNA concentration and purity were detected by NANO-400A ultra-micro nucleic acid analyzer. The reverse transcription reaction system was formulated on ice according to the reverse transcription kit instructions. After reverse transcription of RNA into cDNA on a PCR instrument according to the instructions on the kit, a real-time fluorescent quantitative PCR (RT-PCR) reaction system was formulated on ice: taking RT-PCR SYBR Green 5 mu L, 0.2 mu L of each of the upstream primer and the downstream primer, 1 mu L of cDNA of a sample and 3.6 mu L of double distilled water (ddH 2 O) from a special 96-well plate for fluorescent quantitative PCR; RT-PCR reaction conditions for Bio-rad: pre-denaturation at 95℃for 2 min, denaturation at 95℃for 10s, annealing/extension at 60℃for 30s,40 cycles. Based on the Ct values obtained, the results were statistically analyzed by 2 "-DELTA.Ct calculation analysis, after repeating the test three times, as shown in FIG. 2.
The genes involved in lipid synthesis are responsible for the relative quantification of mRNA of the major transcription factors regulating cholesterol/fatty acid metabolism, sterol response element binding protein (SREBP 1), fatty Acid Synthase (FAS), stearoyl-coa desaturase 1 (SCD 1).
The results showed that at the gene transcription level, 50 μm raspberry ketone derivatives inhibited the expression of SREBP1, FAS and SCD1 genes at 42.0%, 31.9% and 39.7%, respectively; 100 μm raspberry ketone derivative inhibited the expression of SREBP1, FAS and SCD1 genes at 62.9%, 71.0%, 62.8%, respectively; 200. Mu.M raspberry ketone derivatives inhibited the expression of SREBP1, FAS and SCD1 genes by 72.8%, 75.8%, 81.3%, respectively.
The experiment shows that the raspberry ketone derivative inhibits the expression of key genes for sebum synthesis so as to reduce the lipid synthesis of sebocytes and achieve the effect of controlling oil.
The oil control effect achieved by the raspberry ketone derivative prepared in example two of the present invention will be described in detail below by taking different cosmetics as examples.
Fifth embodiment: shampoo containing raspberry ketone derivative
Shampoo described in table 2 was prepared according to the following preparation method.
[ Preparation method ]
1) Weighing the components of the phase A, heating to 85 ℃, and uniformly stirring;
2) After the material is completely dissolved and uniformly stirred, starting to cool and reducing the temperature;
3) And adding the weighed phase B when the temperature is lower than 45 ℃, uniformly stirring, and discharging.
TABLE 2
Wherein,
Sodium laureth sulfate, water, available from the Nanlichen industry Co., ltd;
water, sodium lauroyl amphoacetate, sodium chloride, purchased from guangzhou flower fine chemical company, inc;
Water, sodium lauroyl sarcosinate, phenoxyethanol, available from the Guangzhou flower fine chemical company, inc.;
cocoamidomethyl MEA, glycerol, available from the fine chemical company, florist, guangzhou;
guar hydroxypropyl trimethylammonium chloride, water, available from Guangzhou curie chemical technology, inc;
Polyquaternium-10, available from Rongdao chemical Co., guangzhou;
PPG-3 octyl ether, available from Bai Li Xin International trade (Guangzhou) Co., ltd;
Polyquaternium-7, water, sodium benzoate, available from Guangzhou Mega trade development Co.
[ Performance test ]
The oil control properties of the shampoo composition samples provided in examples 1 to 6 and comparative example 1, respectively, were tested as follows.
350 Volunteers, whose scalp was rated oily or mixed oil, were divided into 7 groups of 50 persons each, between 20 and 45 years of age. And labeled as examples 1-6 and comparative example 1. The samples of the shampoo compositions provided in examples 1-6 and comparative example 1 were then used 1 time every 2 days for each volunteer and test feedback of each volunteer on product safety and oil control efficacy was recorded after 28 days for each volunteer using the shampoo composition samples provided in examples 1-6 and comparative example 1, respectively, and the oil control effects of the shampoo compositions provided in examples and comparative examples were analyzed as shown in table 3.
The oil control efficacy criteria are as follows:
Is very effective: the oil control effect is very good, the oil output of the scalp is obviously reduced, the hair is fresh and fluffy after the use, and the oil output speed is obviously delayed.
The method is effective: has certain oil control effect, reduces the oil output of the scalp, and ensures that the hair is fresh after the scalp is used, and has certain delay of the oil output speed
Invalidation: no change before and after use
TABLE 3 Table 3
From the data in Table 3, it is shown that the shampoo compositions of examples 2,3 and 4 containing 0.2%, 0.4% and 1% of the raspberry ketone derivative of the invention have effective oil control percentages of 94%, 92% and 90%, respectively, which means that the shampoo compositions containing the raspberry ketone derivative at a concentration of 0.2% -1% have excellent oil control effect on scalp, and hair achieves refreshing and fluffy effects, effectively improving the health condition of scalp.
Example six: facial cleanser containing raspberry ketone derivative
The facial cleanser described in table 4 was prepared according to the following preparation method.
[ Preparation method ]
1) Weighing the components of the phase A, heating to 85 ℃, and uniformly stirring;
2) After the material is completely dissolved and uniformly stirred, starting to cool and reducing the temperature;
3) And adding the B phase and the C phase which are completely dissolved in advance when the temperature is below 45 ℃, uniformly stirring, and discharging.
TABLE 4 Table 4
Wherein,
Polyethylene glycol-14M, available from the company of the chemical industry, inc. In the guangzhou;
Potassium cocoyl glycinate, available from guangzhou macrodiversity fine chemical company, inc;
disodium lauryl sulfosuccinate, water, available from Guangzhou macrogol fine chemical Co., ltd;
Lauryl hydroxysulfobetaine, sodium chloride, water, available from the international trade (guangzhou) company, berlin;
PEG-150 distearate, available from Guangzhou macrogol fine chemical Co., ltd;
PEG-100 stearate, glyceryl stearate, available from Bai Hao Co., ltd.
[ Performance test ]
The oil control properties of the samples of the facial cleanser compositions provided in examples 7-12 and comparative example 2, respectively, were tested as follows.
280 Male or female volunteers between the ages of 20 and 45 and rated as oily or mixed oil-biased skin were divided into 7 groups of 40. And are labeled as examples 7-12 and comparative example 2. The volunteers of examples 7-12 and comparative example 2 were then given 1 time per day using the facial cleanser composition samples provided in the respective examples and comparative examples, respectively. The sebum amount of the skin surface of the forehead of the volunteer before and after using the product was tested using a sebum tester Sebumeter SM 815 for 14 days. Differences between initial values and corresponding measured values of the test areas were calculated, and differences at different time points were statistically analyzed to analyze the oil control effect of the facial cleanser compositions provided in examples and comparative examples, and the mean (integer) of test results of 280 volunteers is shown in fig. 3.
When the test data are normally distributed, adopting a t-test method to carry out statistical analysis; and when the test data are in non-normal distribution, adopting a rank sum test method to carry out statistical analysis. The statistical methods all used a two-tailed test, test standard α=0.05. p <0.05 indicates statistical significance, indicating that the product has oil control effect.
As can be seen from a comparison of the results of fig. 3, the samples of the facial cleanser compositions provided in examples 8, 9 and 10, which contained 0.2%, 0.4% and 1% of raspberry ketone derivatives, were able to significantly reduce the sebum level of the forehead skin. After using the facial cleanser composition samples provided in examples 6-2, 6-3 and 6-4 on day 14, the average values of sebum measurements were 18, 13, 9, respectively, and the statistical analysis results of the differences at different time points were p <0.05.
The facial cleanser composition containing the raspberry ketone derivative with the concentration of 0.2% -1% has good oil control effect on facial skin, and the oil output of the skin is reduced, so that the skin barrier is effectively improved, the water-oil state and the skin surface microecology are balanced.
Embodiment seven: toning lotion containing raspberry ketone derivative
The lotions described in table 5 were prepared according to the following preparation method.
[ Preparation method ]
1) Weighing the components of the phase A, heating to 85 ℃, and uniformly stirring;
2) After the material is completely dissolved and uniformly stirred, starting to cool and reducing the temperature;
3) And adding the weighed phase B when the temperature is lower than 45 ℃, uniformly stirring, and discharging.
TABLE 5
Wherein,
Glycerol, purchased from hongzhou, honest daily chemical company, inc;
glycerol glucomannan, available from Shenzhen Biotechnology Co., ltd;
sodium hyaluronate, available from Guangzhou Heya biochemical Co., ltd;
Allantoin, available from Guangzhou, bai Hao Bo Co., ltd., product number 101015.
[ Performance test ]
The oil control properties of the samples of the cosmetic water compositions provided in examples 13 to 18 and comparative example 3 were respectively tested as follows.
280 Male or female volunteers between the ages of 20 and 45 and rated as oily or mixed oil-biased skin were divided into 7 groups of 40. And are labeled as examples 13-18 and comparative example 3. The volunteers of examples 13 to 18 and comparative example 3 were then used 2 times per day using the samples of the water composition provided in examples 13 to 18 and comparative example 3, respectively, and the use conditions of the volunteers of different groups were registered at 28 days after the use of the water to evaluate the safety and oil control efficacy of the products.
The oil control efficacy of the product was evaluated by calculating satisfaction, and the results are shown in table 6.
Satisfaction evaluation: the method is characterized in that the method is divided into 1 and 2, wherein the method is divided into 3 and 4, and the method is divided into 1 and 2, and the method is divided into 3 and 4, and the method is divided into 5 and 5, wherein the statistical score is equal to or more than 4, and the number of people is effective, and the satisfaction calculating method is as follows: satisfaction = (satisfaction + very satisfied)/total number of persons involved in evaluation 100%
Statistical analysis: binomial distribution test analysis of differences using SPSS set the expected satisfaction to 50% and using 95% confidence intervals, p <0.05 indicates that the differences are statistically significant.
Oil control efficacy: compared with the expected value of satisfaction of 50%, the difference after a period of time is statistically significant, and the sample is judged to have the oil control effect, otherwise, the sample is judged not to have the oil control effect.
TABLE 6
The data in Table 6 are analyzed to show that the examples 14, 15 and 16, which contain 0.2%, 0.4% and 1% of raspberry ketone derivative, are effective in improving skin oil-out and gloss, moisturizing and controlling skin, refreshing skin and controlling oil, and reducing skin oil yield. After 28 consecutive days of use of the samples of the cosmetic water compositions provided in examples 14, 15 and 16, 90.00%, 95.00% and 92.5% of subjects respectively considered a reduction in skin oil output, and the statistical analysis results were p <0.05 compared to before the use of the samples.
The cosmetic water composition containing raspberry ketone derivative with concentration of 0.2% -1% has effect of reducing facial skin grease secretion, and can effectively improve facial skin health.
Example eight: mask containing raspberry ketone derivative
The mask described in table 7 was prepared according to the following preparation method.
[ Preparation method ]
1) Weighing the components of the phase A, heating to 85 ℃, and uniformly stirring;
2) After the material is completely dissolved and uniformly stirred, starting to cool and reducing the temperature;
3) And (3) when the temperature is lower than 45 ℃, adding all the raw materials of the phase B in sequence, uniformly stirring, and discharging.
TABLE 7
Wherein,
Glycerol glucomannan, available from Shenzhen Biotechnology Co., ltd;
Carbomers available from new material stock, inc. of Tiancigao, guangzhou;
Xanthan gum, available from guangzhou city wanlu chemical company, inc;
sodium hyaluronate, available from Guangzhou Heya biochemical Co., ltd;
Allantoin, available from baobao limited, guangzhou, cat No. 101015;
arginine, available from Shanghai lion technology development Co.
[ Performance test ]
The oil control properties of the mask composition samples provided in examples 19 to 24 and comparative example 4 were respectively tested as follows.
280 Male or female volunteers between the ages of 20 and 45 and rated as oily or mixed oil-biased skin were divided into 7 groups of 40. And are labeled as examples 19-24 and comparative example 4. The volunteers of examples 19-24 and comparative example were then asked to try out samples of the mask compositions provided in examples 19-24 and comparative example 4, respectively. The oil control effect was calculated using a Sebumeter in SM 815 at day 0 (baseline) and 28 on the sebum content of the face (forehead, left and right cheeks).
As shown in fig. 4.
Wherein, oil control effect (%) = (S0-S28)/s0×100% (S0 is sebum measurement at baseline, S28 is sebum measurement after 28 days), and a significant difference (p < 0.05) after a period of use compared to baseline indicates oil control effect.
As can be seen from a comparison of the results of fig. 4, the mask composition samples provided in examples 20, 21 and 22, which contained 0.2%, 0.4% and 1% of raspberry ketone derivatives, were effective in inhibiting sebum secretion from the forehead, left cheek and right cheek of the skin. After using the mask composition samples provided in examples 20, 21 and 22 on day 28, subjects with 72.0%, 75.2% and 82.0%, respectively, considered a reduction in skin oil output from the forehead; subjects with 84.6%, 82.4% and 83.3% respectively considered reduced skin oil delivery to the left cheek; subjects with 86.6%, 81.4% and 82.3% respectively considered a reduction in skin oil delivery to the forehead, and the statistical analysis results were p <0.05 compared to baseline.
The mask composition containing the raspberry ketone derivative with the concentration of 0.2-1% has the effects of inhibiting the secretion of facial skin grease, can effectively balance the skin water and oil conditions, and can effectively control the oil.
Example nine: emulsion containing raspberry ketone derivative
The emulsions described in table 8 were prepared according to the following preparation method.
[ Preparation method ]
1) Weighing the components in the phase A, adding the components into an oil pan, stirring and heating to 85 ℃;
2) Weighing the raw materials in the phase B, adding the raw materials into a water pot, stirring and heating to 85 ℃;
3) Adding the completely dissolved phase A in the step 1) and uniformly stirring, adding the completely dissolved phase B, homogenizing for 5-20 minutes, and then starting to cool;
4) And (3) when the temperature is lower than 45 ℃, adding all the raw materials of the phase C in sequence, uniformly stirring, and discharging.
TABLE 8
Wherein,
C14-22 alcohol, C12-20 alkyl glucoside, available from Guangzhou, bai Hao Bo Co., ltd., cat# 36198W;
PEG-100 stearate, glyceryl stearate, available from Bai Hao Corp., guangzhou, inc., cat# 38364A;
Ethylhexyl palmitate, available from Guangzhou Ning, inc. of chemical industry, inc.;
Isononyl isononanoate, available from Shenzhen good Biotechnology Co., ltd;
cetylstearyl alcohol, available from honest daily chemical company, inc. In guangzhou;
A polydimethyl siloxane, which is a polymer of a vinyl alcohol, purchased from Shenzhen products Biotechnology Co.
Glycerol glucoside, available from Shenzhen Biotechnology Co., ltd;
Carbomers available from new material stock, inc. of Tiancigao, guangzhou;
Xanthan gum, available from guangzhou city wanlu chemical company, inc;
sodium hyaluronate, available from Guangzhou Heya biochemical Co., ltd;
Allantoin, available from Guangzhou, bai Hao Bo Co., ltd., product number 101015.
[ Performance test ]
The oil control properties of the emulsion composition samples provided in examples 25 to 30 and comparative example 5, respectively, were tested as follows.
280 Male or female volunteers between the ages of 20 and 45 and rated as oily or mixed oil-biased skin were divided into 7 groups of 40. And are labeled as examples 25-30 and comparative example 5. The oil control effect of the products was then evaluated after 28 days using the emulsion composition samples provided in examples 25-30 and comparative example 5 on the left side of the volunteers of examples 25-30 and comparative example 5, respectively, and clear water as a blank on the right side of the volunteers.
The oil control efficacy was evaluated by statistical satisfaction, and the results are shown in fig. 5, as in example seven.
Comparing the data of FIG. 5, it can be seen that the emulsion composition samples provided in examples 26, 27 and 28, which contained 0.2%, 0.4% and 1% of raspberry ketone derivative, were effective in significantly reducing the amount of oil delivered to the skin. After 28 consecutive days of use of the emulsion composition samples provided in examples 26, 27 and 28, 90.00%, 97.5.00% and 97.5% of subjects, respectively, considered a reduction in skin oil output, and the statistical analysis results were p <0.05 compared to before the use of the samples.
The emulsion composition containing raspberry ketone derivative with the concentration of 0.2% -1% is effective in inhibiting the secretion of facial skin grease and can effectively improve the water-oil balance of facial skin.
The invention has been further described with reference to specific embodiments, which are exemplary only and do not limit the scope of the invention in any way. It will be understood by those skilled in the art that various changes and substitutions of details and forms of the technical solution of the present invention may be made without departing from the spirit and scope of the present invention, but these changes and substitutions fall within the scope of the present invention.
Claims (4)
1. A preparation method of raspberry ketone and derivative thereof is characterized in that the raspberry ketone and derivative thereof in formula (I) is synthesized by taking monochloromethyl benzene derivative and propylene oxide as raw materials under the action of magnesium metal and Sha Ruite reagent;
（I），
wherein R represents mono-OR poly-substitution, R is selected from-OH OR-OR 1, wherein R 1 represents unsubstituted C1-C3 alkane;
the monochloromethylbenzene derivative has the following structure:
，
Wherein R represents mono-OR poly-substitution, R is selected from-OH OR-OR 1, wherein R 1 represents unsubstituted C1-C3 alkane;
The preparation method comprises the following steps:
S1, reacting a monochloromethylbenzene derivative with magnesium metal to obtain a reaction solution;
S2, adding propylene oxide into the reaction liquid obtained in the step S1 for reaction, quenching the reaction after the reaction is finished, filtering the reaction liquid, and removing the solvent from the filtrate to obtain residues;
s3, carrying out oxidation reaction on the residues obtained in the step S2 and Sha Ruite reagent, and treating to obtain the raspberry ketone and the derivative thereof;
the quenching reaction in step S2 is: dripping acid until white fine solid appears, and finishing dripping;
the process in step S3 is: extracting the reaction liquid after the oxidation reaction with water, drying, removing water and filtering the organic phase, and removing the solvent to obtain the residual white solid, namely the target substance.
2. The preparation method according to claim 1, wherein the solvent for the reaction in the step S1 is anhydrous tetrahydrofuran, the reaction temperature is 0-5 ℃, and the reaction time is 7-9h.
3. The method according to claim 1, wherein the reaction in step S2 is: propylene oxide is added dropwise, heating is carried out, and the reaction is carried out for 6-7h at 30 ℃ after the completion of the dropwise addition.
4. The preparation method according to claim 2, wherein the solvent for the oxidation reaction in step S3 is methylene chloride, the reaction temperature is 25 ℃, and the reaction time is 5-7h.
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