CN112137908A - Application of phenethyl and styryl resorcinol glycoside compounds in melanin generation inhibitor - Google Patents
Application of phenethyl and styryl resorcinol glycoside compounds in melanin generation inhibitor Download PDFInfo
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- CN112137908A CN112137908A CN202011191248.2A CN202011191248A CN112137908A CN 112137908 A CN112137908 A CN 112137908A CN 202011191248 A CN202011191248 A CN 202011191248A CN 112137908 A CN112137908 A CN 112137908A
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- phenethyl
- styryl
- resorcinol
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- glycosides
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- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 title claims abstract description 55
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 239000003112 inhibitor Substances 0.000 title claims abstract description 19
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K8/60—Sugars; Derivatives thereof
- A61K8/602—Glycosides, e.g. rutin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
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- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
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- Saccharide Compounds (AREA)
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Abstract
The invention discloses an application of phenethyl and styryl resorcinol glycoside compounds in a melanin generation inhibitor, belonging to the technical field of biology. The invention aims to provide a plurality of active ingredients of skin care products with the functions of substantially lightening spots, whitening, reducing pigmentation and brightening skin, which can achieve the functions by inhibiting the mRNA expression of tyrosinase, inhibiting the tyrosinase activity pathway and reducing the generation of melanin. The recommended addition level of the compound as an active ingredient in the skin care product is 1% -10%.
Description
Technical Field
The invention relates to the technical field of biology, and in particular relates to a phenethyl and styryl resorcinol glycoside compound and application thereof in preparation of a melanin generation inhibitor.
Background
Most Asian women pay attention to the fair and beautiful skin of the Asian women, and in the development history of China, the modern whitening cosmetics are close to the development history of the modern whitening cosmetics, the Asian women go through a whitening stage depending on physical covering, wherein the Asian women are most commonly used with white powder and lead powder, but the Asian women can cause cyan marks on the skin after long-term use, so that the appearance is influenced; the skin is then transferred to the "bleaching stage" where the whitening is achieved by erosion, exfoliation of the stratum corneum, which if used for a long period of time, destroys the skin barrier and makes the skin sensitive. With the progress of science and technology, people continuously deepen the understanding of whitening, and the currently accepted melanin production pathway in the world is as follows: tyrosine → dopa acid → dopaquinone → dopachrome (or dihydroxyindole acid) → melanin oligomer → melanin, so we have entered the "synergistic whitening" stage of achieving the purpose of whitening by adding inhibitors such as melanin production, melanin transfer, tyrosinase, etc., and the ingredients that are excellent in this stage are: hydroquinone, kojic acid, Vc, and the like. However, these molecules are directed only to the downstream melanogenesis pathway, and the cells often have a large stimulation or side effect due to the stress pathological compensatory function.
The nature of the melanin biosynthetic pathway is formed by a series of enzymatic and non-enzymatic reactions, Tyrosinase (TYR) is a key enzyme in the process, and its abnormal over-expression also has a great influence on melanin production. The existing whitening substances mainly affect the activity of tyrosinase and have small influence on the expression quantity of the tyrosinase. The compound which can inhibit the activity of tyrosinase and the expression level of tyrosinase is searched, so that the inhibition effect on the generation of melanin can be greatly improved, and the whitening effect is improved. In addition, molecules with whitening activity, such as kojic acid, phenethyl resorcinol, etc., which are currently on the market, have the disadvantages of poor stability, large cytotoxicity and irritation. Although the stability of the lipid carrier can be improved by the lipid carrier technology, the irritation is not improved at all. Therefore, the finding of the compound which can inhibit the tyrosinase activity and remarkably inhibit the expression quantity of the tyrosinase, has good stability and small irritation and has important application significance.
Research shows that USF1 (upstream stimulating factor 1) is a key transcription regulator for tyrosinase synthesis, and our research finds that USF1 can promote tyrosinase expression by forming a transcription complex with regulatory interferon regulator 1(IRF1) under ultraviolet or inflammation induction. And proline 4 hydroxylase beta polypeptide (P4HB) can regulate ubiquitination of IRF1 so as to regulate tyrosinase expression. The activity of P4HB is enhanced, IRF1 ubiquitination is increased, so that the formation of IRF1/USF1 transcription complex is reduced, and the effect of inhibiting TYR transcription and expression is further exerted. The small molecules capable of enhancing the activity of P4HB are found to be capable of inhibiting the expression of TYR protein and well inhibiting the generation of melanin.
Disclosure of Invention
The invention aims to provide an application of phenethyl and styryl resorcinol glycoside compounds in melanin generation inhibitors, wherein the compounds have the advantages of remarkably improving melanin generation activity, having small irritation, inhibiting TYR activity and having a regulator of P4HB agonist activity, thereby playing double roles of inhibiting TYR protein synthesis and inhibiting TYR activity.
In order to achieve the purpose, the invention adopts the following technical scheme that the application of phenethyl and styryl resorcinol glycoside compounds in melanin generation inhibitors is characterized in that: the structural formula of the compound is shown as follows,
wherein R1 is pyranose monosaccharide, specifically any one of galactopyranose, arabinopyranose, glucopyranose and mannopyranose;
r2 is a single bond or a double bond.
Preferably, the compound is 1- (3, 5-dihydroxy) phenethyl-beta-D-arabinopyranoside (short for compound No. 1),the structural formula is
Preferably, the compound is 1- (3, 5-dihydroxy) phenethyl-beta-D-galactopyranoside (compound No. 2 for short), and the structural formula is shown in the specification
Preferably, the compound is 1- (3, 5-dihydroxy) styryl-beta-D-galactopyranoside (short for compound No. 3), and the structural formula is shown in the specification
Preferably, the compound is 1- (3, 5-dihydroxy) phenethyl-beta-D-mannopyranoside (compound No. 4 for short), and the structural formula is
Preferably, the compound is 1- (3, 5-dihydroxy) styryl-beta-D-mannopyranoside (compound No. 5 for short), and the structural formula is
Preferably, the compound is 1- (3, 5-dihydroxy) styryl-beta-D-glucopyranoside (compound No. 6 for short), and the structural formula is
The phenethyl and styryl resorcinol glycoside compounds can regulate ubiquitination degradation of IRF1 (interferon regulatory factor 1) by targeted combination of P4HB (prolyl hydroxylase beta polypeptide), and further inhibit formation of IRF1/USF1 transcription complex to regulate mRNA expression and protein expression of Tyrosinase (TYR), thereby inhibiting melanin generation.
The phenethyl and styryl resorcinol glycoside compounds can reduce melanin generation by inhibiting tyrosinase activity, and achieve the purposes of lightening spots, whitening, reducing pigmentation and brightening skin.
The phenethyl and styryl resorcinol glycoside compounds can achieve the purpose of whitening in a double way, namely inhibiting tyrosinase expression and inhibiting tyrosinase activity, and can effectively whiten the skin on the premise of ensuring low irritation.
The recommended addition amount of the phenethyl and styryl resorcinol glycoside compounds in the whitening cosmetics or medicines is 1-10%.
Furthermore, the phenethyl resorcinol glycoside compounds and the styryl resorcinol glycoside compounds are mainly in the form of aqueous paste or gel or liquid, preferably aqueous emulsion in the skin care products.
Preferably, the phenethyl and styryl resorcinol glycosides are formulated as aqueous lotions, water-in-oil or oil-in-water emulsions, oil or oleyl lotions, vesicular dispersions of anionic or nonionic amphiphilic lipids, aqueous gels, hydroalcoholic gels, alcogel or oleyl gels, solid sticks or aerosols.
The invention provides application of phenethyl and styryl resorcinol glycoside compounds in preparation of melanin generation inhibitors.
Compared with the prior art, the compound provided by the invention can inhibit the TYR activity, and has a regulator of P4HB agonistic activity, so that the compound plays a dual role in inhibiting the synthesis of TYR protein and the TYR activity; the phenethyl and styryl resorcinol glycoside compound has the advantages of remarkably improving the melanogenesis activity and having small irritation.
Description of the drawings:
FIG. 1 is a diagram of the mechanism of the phenylethyl and styryl resorcinol glycosides of the present invention for inhibiting tyrosinase mRNA expression;
FIG. 2 is a graph showing the effect of activity of phenethyl and styryl resorcinol glycosides P4HB of the present invention;
FIG. 3 shows the effect of the expression of the tyrmrRNA of the phenethyl and styryl resorcinol glycosides of the present invention;
FIG. 4 shows the inhibition of TYR activity by phenethyl and styryl resorcinol glycosides of the present invention;
FIG. 5 is a graph showing the effect of phenethyl and styryl resorcinol glycosides of the present invention on melanin production;
FIG. 6 shows the safety scores of phenethyl and styryl resorcinol glycosides of the present invention.
Detailed Description
The invention will be further explained with reference to specific embodiments, without however limiting the invention thereto, and within the knowledge of a person skilled in the art, numerous variations can be made without departing from the spirit of the invention.
In the following examples, unless otherwise specified, the methods used were conventional, and the reagents used were all commercially available.
Example 1 use of phenethyl and styryl resorcinol glycosides compounds as melanin production inhibitors, the compounds being at least one of 1- (3, 5-dihydroxy) phenethyl- β -D-arabinopyranoside, 1- (3, 5-dihydroxy) phenethyl- β -D-galactopyranoside, 1- (3, 5-dihydroxy) styryl- β -D-galactopyranoside, 1- (3, 5-dihydroxy) phenethyl- β -D-mannopyranoside, 1- (3, 5-dihydroxy) styryl- β -D-glucopyranoside, the structural formulas are respectively as follows:
wherein, the compounds No. 1, 2 and 4 are synthesized by the preparation method of the Organic Process reaction & Development 2007,11,1004-1009
The compound No. 3,5 and 6 is synthesized by the preparation method of reference Tetrahedron Asymmetry,2005,16,2625-2630, and the basic synthetic route is as follows
Example 2: phenethyl and styryl resorcinol glycoside compounds inhibit tyrosinase mRNA expression mechanism through P4HB pathway
As a result: see FIG. 1, the expression mechanism of tyrosinase mRNA is inhibited by phenethyl and styryl resorcinol glycosides.
As shown in fig. 1, a.p4hb reduced the promoter activity of TYR;
P4HB reduced protein expression of TYR;
irfs can interact with P4HB and USF1, possibly mediating the effect of P4HB on TYR expression;
P4HB inhibits protein expression of IRF 1;
in nuclei, P4HB interaction with IRF1 was significantly reduced following P4HB interference;
after the F.P4HB is interfered, the ubiquitination level of IRF1 can be reduced, and further the content of IRF1 is increased;
H. in the nucleus, P4HB can inhibit the protein expression of IRF 1;
G. the activity of a firefly luciferase reporter gene is enhanced by over-expressing IRF1 gene 1, which indicates that IRF1 can be combined with a TYR promoter to increase the transcriptional activity of TYR;
I. in the nucleus, after IRF1 interference, the interaction between USF and IRF1 is obviously weakened;
J. after overexpression of IRF1, co-localization of IRF1 and USF1 was significantly enhanced;
usf1 interaction with IRF1 can enhance TYR mRNA expression;
usf1 interaction with IRF1 enhanced the expression of TYR protein.
And (4) conclusion:
p4HB (prolyl hydroxylase beta polypeptide) can regulate mRNA expression and protein expression of Tyrosinase (TYR) by regulating ubiquitination degradation of IRF1 (interferon regulatory factor 1) and further inhibiting formation of IRF1/USF1 transcription complex, thereby inhibiting melanin generation.
Example 3: effect of phenethyl and styrylresorcinol glycosides on P4HB Activity and tyrosinase mRNA expression
The detection method comprises the following steps:
first, A375 cells were seeded in 96-well plates at 37 ℃ with 5% CO2Culturing in an incubator until cells adhere to the wall, transfecting P4HB reporter gene plasmids, continuously culturing for 24h, adding a compound No. 1-6 with proper concentration, and incubating for 2 h. The cells were digested and the transcriptional activity of the different transcription factors described above was determined according to the luciferase assay kit instructions.
A375 cells were inoculated into a 12-well plate, cultured at 37 ℃ in a 5% CO2 incubator for 24 hours, added with phenethyl and styryl resorcinol glycoside compounds (compound No. 1 to compound No. 6) at the same molar concentration, and then irradiated with UVB for 30min for induction after 377. After 30min, the cells were harvested and total RNA was extracted from the cells using RNeasy Mini kit and treated with ribonuclease-free to remove residual genomic DNA. Each 25. mu.L reaction contains 1.5. mu.g of total RNA and cDNA, and can be synthesized using a high-volume cDNA kit. qRT-PCR reactions were performed on Applied Biosystems ViiA 7 using gene specific primers and iTaq SYBR green. Relative gene expression was calculated using the standard curve method with GAPDH as an internal control. The primer sequences used were as follows:
TABLE 1 primer sequences of the genes in fluorescent quantitative PCR
As a result: see fig. 2 and 3, effects of phenethyl and styrylresorcinol glycoside compound P4HB activity and TYRmRNA expression;
and (4) conclusion:
in the 377-treated group, compared with the UV model group, the P4HB activity and the tyrosinase mRNA expression condition are hardly changed, which indicates that 377 has no capability of activating P4HB activity and has no capability of inhibiting tyrosinase mRNA expression. The compound No. 4 has obvious effects on activating P4HB activity and inhibiting tyrosinase mRNA expression, and the effect is most prominent.
Example 4 Effect of phenethyl and styryl Resorcinol glycosides on tyrosinase Activity
The inhibition of the tyrosinase activity of six phenethyl and styryl resorcinol glycoside compounds in A375 cells is determined by spectrophotometry. A375 cells were cultured in 24-well plates, treated with the same appropriate concentration of phenethyl and styryl resorcinol glycosides affecting tyrosinase for 72h, then trypsinized to collect cells, and washed 3 times with pre-cooled Phosphate Buffered Saline (PBS). Lysis buffer was prepared by mixing 0.1m sodium phosphate buffer (ph6.8) containing 0.1% triton x-100 with protease inhibitor. Cells were disrupted by sonication at 4 ℃ and centrifuged at 16000rpm for 30 min. Protein content was quantified using the BCA kit, and cell lysates were then adjusted to the same concentration of protein using lysis buffer. The solution including the cell extract, 2mg/mL levodopa (L-Dopa) and 0.1M sodium phosphate buffer (pH6.8) was mixed well and placed in a 96-well plate and incubated at 37 ℃ for 2 hours. Finally, absorbance was measured at 450nm using a full wavelength microplate reader.
As a result: see fig. 4, the inhibition rate of phenylethyl and styryl resorcinol glycosides on TYR activity;
and (4) conclusion: the phenethyl and styryl resorcinol glycoside compounds and 377 can inhibit the activity of tyrosinase, and the effect of the phenethyl and styryl resorcinol glycoside compounds from No. 1 to No. 6 is stronger than that of the compound 377, wherein the compound No. 4 has obvious effect of inhibiting the activity of tyrosinase compared with other five compounds and 377.
Example 5: effect of phenethyl and styryl resorcinol glycosides on melanogenesis
The detection method comprises the following steps:
this part of the experiment was performed in a375 cells, after cell attachment 1 μ L of 10 μ M α -MSH was added to each well and incubated for 24h, and after 48h treatment with the same concentration of phenethyl and styryl resorcinol glycosides and 377 the cells were harvested and washed twice with PBS, resuspended in 1M NaOH containing 10% dimethyl sulfoxide, and heated at 80 ℃ for 1 h. The final melanin content is expressed as the absorbance of the extract at 490 nm.
As a result: see FIG. 5, the effect of phenethyl and styryl resorcinol glycosides on melanin production;
and (4) conclusion: both phenethyl and styryl resorcinol glycoside compounds and 377 can inhibit melanin generation, and the capability of the compound No. 4 is obviously stronger than that of 377; compounds Nos. 1, 2, 3,5 and 6 showed equivalent effects to 377.
Example 6: skin irritation detection of phenethyl and styryl resorcinol glycoside compounds
The detection method comprises the following steps:
in order to further develop the application of the phenethyl and styryl resorcinol glycoside compounds in the anti-inflammatory and anti-aging skin care products, firstly, the safety of the phenethyl and styryl resorcinol glycoside compounds needs to be ensured, and six kinds of phenethyl and styryl resorcinol glycoside compound gel are firstly prepared in the experiment of the part, wherein the addition amount of the gel is 10 percent so as to observe the irritation of the gel to the skin.
Firstly, depilating the back of a mouse by using a depilatory cream, smearing corresponding medicines on the exposed part on the right side of the depilated skin every day, smearing common gel on the exposed part on the left side, taking pictures regularly during a test period, observing whether white spots, other skin irritation injuries or toxic phenomena can be caused, finding out professionals to judge whether the skin tested area has the allergic irritation phenomenon, and grading the safety level. (high allergy risk: 0; moderate allergy risk: 1 +; Low allergy risk: 2 +; No allergy risk; 3-4)
As a result: see fig. 6, the safety of phenethyl and styryl resorcinol glycosides is scored;
and (4) conclusion: the safety scores of the six phenethyl and styryl resorcinol glycoside compounds are all more than 3 points, and according to the scoring standard, the six compounds are all allergy-free substances and have good safety.
In conclusion, the six phenethyl and styryl resorcinol glycoside compounds can play a role in efficiently inhibiting tyrosinase expression and activity and/or inhibiting melanin generation under the condition of ensuring no stimulation or low stimulation, and have the potential of being used as raw materials of whitening cosmetics.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (10)
1. The application of phenethyl and styryl resorcinol glycoside compounds in melanin generation inhibitors is characterized in that: the structural formula of the compound is shown as follows,
wherein R1 is pyranose monosaccharide, specifically any one of galactopyranose, arabinopyranose, glucopyranose and mannopyranose;
r2 is a single bond or a double bond.
2. The use of phenethyl and styryl resorcinol glycosides of claim 1 in melanin production inhibitors, wherein: the compound is 1- (3, 5-dihydroxy) phenethyl-beta-D-arabinopyranoside, and the structural formula is shown in the specification
3. The use of phenethyl and styryl resorcinol glycosides of claim 1 in melanin production inhibitors, wherein: the compound is 1- (3, 5-dihydroxy) phenethyl-beta-D-galactopyranoseGlycoside, the structural formula of which is
4. The use of phenethyl and styryl resorcinol glycosides of claim 1 in melanin production inhibitors, wherein: the compound is 1- (3, 5-dihydroxy) styryl-beta-D-galactopyranoside, and the structural formula is
5. The use of phenethyl and styryl resorcinol glycosides of claim 1 in melanin production inhibitors, wherein: the compound is 1- (3, 5-dihydroxy) phenethyl-beta-D-mannopyranoside, and the structural formula is shown in the specification
6. The use of phenethyl and styryl resorcinol glycosides of claim 1 in melanin production inhibitors, wherein: the compound is 1- (3, 5-dihydroxy) styryl-beta-D-mannopyranoside, and the structural formula is
7. The use of phenethyl and styryl resorcinol glycosides of claim 1 in melanin production inhibitors, wherein: the compound is 1- (3, 5-dihydroxy) styryl-beta-D-glucopyranoside, and the structural formula is
8. Use of phenethyl and styryl resorcinol glycosides according to any one of claims 1-7 in melanogenesis inhibitors, wherein: the phenethyl and styryl resorcinol glycoside compound can regulate ubiquitination degradation of IRF1 (interferon regulatory factor 1) by targeted combination of P4HB (prolyl hydroxylase beta polypeptide), and further inhibit formation of IRF1/USF1 transcription complex to regulate mRNA expression and protein expression of Tyrosinase (TYR), so as to inhibit melanin generation; the phenethyl and styryl resorcinol glycoside compounds can also reduce melanin generation by inhibiting tyrosinase activity, and achieve the purposes of lightening spots, whitening, reducing pigmentation and brightening skin.
9. Use of phenethyl and styryl resorcinol glycosides according to any one of claims 1-7 in melanogenesis inhibitors, wherein: the phenethyl and styryl resorcinol glycoside compounds can achieve the purpose of whitening in two ways, namely inhibiting tyrosinase expression and inhibiting tyrosinase activity, and can effectively whiten the skin on the premise of ensuring low irritation; the recommended addition amount of the phenethyl and styryl resorcinol glycoside compounds in the whitening cosmetics or medicines is 1-10%.
10. Use of phenethyl and styryl resorcinol glycosides according to any one of claims 1-7 in melanogenesis inhibitors, wherein: the phenethyl and styryl resorcinol glycosides are used in skin care products mainly in the form of aqueous pastes or gels or liquids, and are specifically formulated as aqueous lotions, water-in-oil or oil-in-water emulsions, oil or oleyl lotions, vesicular dispersions of anionic or nonionic amphiphilic lipids, aqueous gels, hydroalcoholic gels, alcoholic or oleyl gels, solid sticks or aerosols.
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| CN1475492A (en) * | 2003-07-17 | 2004-02-18 | 中国人民解放军第二军医大学 | Salidroside derivatives and their preparation methods and uses |
| WO2017035775A1 (en) * | 2015-09-01 | 2017-03-09 | 拉芳家化股份有限公司 | Product containing rhodiola rosea extract and ginkgo biloba extract, preparation method therefor, and use thereof |
| CN110964066A (en) * | 2019-12-26 | 2020-04-07 | 上海澄穆生物科技有限公司 | Salidroside derivative, preparation method and application thereof in whitening cosmetics |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1475492A (en) * | 2003-07-17 | 2004-02-18 | 中国人民解放军第二军医大学 | Salidroside derivatives and their preparation methods and uses |
| WO2017035775A1 (en) * | 2015-09-01 | 2017-03-09 | 拉芳家化股份有限公司 | Product containing rhodiola rosea extract and ginkgo biloba extract, preparation method therefor, and use thereof |
| CN110964066A (en) * | 2019-12-26 | 2020-04-07 | 上海澄穆生物科技有限公司 | Salidroside derivative, preparation method and application thereof in whitening cosmetics |
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