CN105816342A - Composition containing obacunone and method for using obacunone in skin whitening - Google Patents
Composition containing obacunone and method for using obacunone in skin whitening Download PDFInfo
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- CN105816342A CN105816342A CN201510013057.XA CN201510013057A CN105816342A CN 105816342 A CN105816342 A CN 105816342A CN 201510013057 A CN201510013057 A CN 201510013057A CN 105816342 A CN105816342 A CN 105816342A
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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
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
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- 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
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Abstract
The invention relates to a composition for partial usage and having melanin synthesis inhibition activity and tyrosinase inhibition activity, which contains 75-100% of pure obacunone, and the obacunone amount can effectively reduce melanin synthesis and/or inhibit tyrosinase activity. The invention also relates to a method for inhibiting melanin synthesis, inhibiting tyrosinase activity and whitening skin.
Description
Technical field
Describe the compositions including obacunone, and the tyrosinase activity in suppression skin and black
Purposes in the method for element synthesis and the method for skin-whitening.
Background technology
The colour of skin depends primarily on the melanic amount in skin.Melanin is brownish black color present in skin
Element.Owing to this pigment is dark, so melanin amount is the lowest, then causes the colour of skin the most shallow, and its amount be the highest,
Then cause the colour of skin the deepest.Melanin is by amino acid tyrosine being oxidized to dihydroxy in melanocyte
Phenylalanine and formed.This reaction is by tyrosinase catalysis.
The reason of excessive cutaneous pigmentation may be: the people hormone in vivo unrelated with ultraviolet is abnormal,
Genopathy etc.；Or the excessive melanin caused due to the radiation of excessive ultraviolet generates and melanin divides
Cloth is uneven.Skin has appropriate melanin have keep skin health and absorb the positive work of ultraviolet etc.
With.But, the melanin of excess causes negative effect, such as skin darkening and the non-homogeneous colour of skin.Therefore,
Many scientists have studied the suppression that melanin generates.
Due to tryrosinase this pivotal role in melanin is formed, develop effective skin-whitening group
The effort of compound, has concentrated on the function of suppression tryrosinase and the reagent of activity.Such as, carried
Go out numerous compositions, including various known tyrosinase inhibitors, especially, such as hydroquinone,
Vitamin C and its derivant, kojic acid, arbutin, glutathion, cysteine and Fructus Mori extract.
It is that they may cause skin irritation by a problem of synthesis skin-whitening agents such as hydroquinone or kojic acid
Or acute dermatitis.Therefore, have increasing need for being incorporated in compositions natural source, produce in the hope of solving synthesis
The undesirable aspect of some of product.
Summary of the invention
A kind of embodiment relates to the topical compositions of a kind of activity having and reducing B16 cell
(topical composition), it is substantially made up of following material: the obacunone that about 75-100% is pure,
Its amount can effectively reduce B16 cell；Cosmetically acceptable carrier；Optionally, one or more are changed
Cosmetic composition, it is selected from alcohol, fat, oil, surfactant, fatty acid, silicone oil, wetting agent
(humectant), humidizer (moisturizer), viscosity modifier, emulsifying agent, stabilizer, coloring
Agent and spice；And/or skin-whitening agents, its selected from tyrosinase inhibitor, free radical scavenger and it
Mixture.
Another embodiment relates to the topical compositions of a kind of activity having and reducing B16 cell, its
Being made up of following material: the obacunone that about 75-100% is pure, its amount can effectively reduce B16 cell；Change
Cosmetic acceptable carrier；Optionally, one or more cosmetic ingredients, its selected from alcohol, fat, oil,
Surfactant, fatty acid, silicone oil, wetting agent, humidizer, viscosity modifier, emulsifying agent, stable
Agent, coloring agent and spice；And/or skin-whitening agents, it is clear selected from tyrosinase inhibitor, free radical
Except agent and their mixture.
In described compositions, obacunone purifies from least one selected from the extract of following plant:
This plant is selected from Rutaceae Fructus Evodiae (Evodiarutaecarpia), favus skin (Dictamnicortex), closes Huang
Cypress (Phellodendriamurensis cortex), rutaceae Fructus Citri Sarcodactylis (Citrisarcodactylisfructus),
Fructus Aurantii Immaturus (Aurantiifrusctusimmaturus) and rutaceae Fructus Citri (Citrifructus).Described Wu Zhu
Cornel (Evodia) extract is relative to rutaecarpin (evodiamine), rutaecarpine (rutaecarpine)
Standardization is carried out with the content of at least one in limonin (limonine).In the composition, obacunone is
About 99.99% pure obacunone active substance.Said composition is preparation, selected from cream, ointment, foam,
Lotion, plaster, tablet, granule or Emulsion.In the composition, described obacunone and described skin
The weight ratio of whitening agent is about 100:1 to about 1:100.In the composition, B16 cell is reduced
Effective dose is about 10-1000mg.In the composition, obacunone constitutes the pact of described compositions
1-99wt%.Or, obacunone constitutes the about 1-75wt% of described compositions.Or, obacunone structure
Become the about 50-70wt% of described compositions.
Another embodiment relates to the topical compositions of a kind of activity for suppressing tryrosinase, substantially
On be made up of following material: at least about 90% pure obacunone, its amount can effectively suppress tryrosinase
Activity；Cosmetically acceptable carrier；Optionally, one or more cosmetic ingredients, its selected from alcohol,
Fat, oil, surfactant, fatty acid, silicone oil, wetting agent, humidizer, viscosity modifier, breast
Agent, stabilizer, coloring agent and spice；And/or skin-whitening agents, its selected from tyrosinase inhibitor,
Free radical scavenger and their mixture.
Another embodiment relates to the topical compositions of a kind of activity for suppressing tryrosinase, its
Being made up of following material: at least about 90% pure obacunone, its amount can effectively suppress the work of tryrosinase
Property；Cosmetically acceptable carrier；Optionally, one or more cosmetic ingredients, selected from alcohol, fat,
Oil, surfactant, fatty acid, silicone oil, wetting agent, humidizer, viscosity modifier, emulsifying agent,
Stabilizer, coloring agent and spice；And/or skin-whitening agents, selected from tyrosinase inhibitor, free radical
Scavenger and their mixture.
In the composition, obacunone purifies the extract from least one following plant, and this plant is selected from
Rutaceae Fructus Evodiae, favus skin, Cortex Phellodendri, rutaceae Fructus Citri Sarcodactylis, Fructus Aurantii Immaturus and rutaceae Fructus Citri.
Fructus Evodiae extract is relative to the content of at least one in rutaecarpin, rutaecarpine and limonin
Carry out standardization.In the composition, obacunone is about 99.99% pure obacunone active substance.This group
Compound is preparation, and it is selected from cream, ointment, foam, lotion, plaster, tablet, granule or Emulsion.
In the composition, described obacunone is about 100:1 to about with the weight ratio of described skin-whitening agents
1:100.In the composition, the effective dose of the activity of suppression tryrosinase is about 10-1000mg.?
In said composition, obacunone constitutes the about 1-99wt% of described compositions.Or, obacunone constitutes
The about 1-75wt% of described compositions.Or, obacunone constitutes the about 50-70wt% of described compositions.
Still another embodiment relates to a kind of topical compositions, and it includes cosmetically acceptable carrier peace treaty
The obacunone that 75-100% is pure, wherein obacunone constitutes the about 1-99wt% of described compositions.
Another embodiment relates to the method for skin whitening, and it includes compositions office specifically described herein
Portion is applied on skin, wherein be enough to the amount of obvious skin whitening and the persistent period apply described in combination
Thing.
Still another embodiment, in topical dermatological whitening cosmetic compound, selects containing one or more
From alcohol, fat, oil, surfactant, fatty acid, silicone oil, wetting agent, humidizer, viscosity adjustment
Cosmetic ingredient in agent, emulsifying agent, stabilizer, coloring agent and spice, is improved by U.S. of effective dose
The obacunone composition pure for about 75-100% of pale skin.
Another embodiment relates to topical compositions as herein described and has reduction melanin conjunction in manufacture
Purposes in the enamel of the activity become.
Further embodiment relates to topical compositions as herein described and has tryrosinase in manufacture
Enzyme inhibition activity enamel in purposes.
Accompanying drawing explanation
Fig. 1 depicts the curve chart of display obacunone cytotoxicity-CTG in B16F10 cell.
Fig. 2 depicts display and suppresses the enzyme of tryrosinase to live by the obacunone in B16F10 cell
The curve chart of property.
The curve chart that Fig. 3 describes shows and suppresses melanin by the obacunone in B16F10 cell
Synthesis.
Detailed description of the invention
Should be appreciated that the present invention is not limited to concrete compositions, method or scheme described in this article.
Additionally, unless otherwise defined, the implication that all technology used herein and scientific terminology have and basis
It is identical that the technical staff of field that the present invention belongs to is generally understood that.It will also be understood that term as used herein
It is only used for describing the purpose of particular, and is not intended to limit the scope of the present invention, the present invention's
Scope is defined solely by the appended claims.
The present invention is to be surprisingly found that based on following: obacunone has actively work as skin-whitening agents
With and there is no toxicity (Fig. 1) and melanin produce on and tyrosinase activity on provide suppression
Effect.As shown in Figure 2, the activity of tryrosinase is suppressed along with the increase of the dosage of obacunone；
As shown in Figure 3, melanin produces and is gradually lowered along with the increase of obacunone dosage or is suppressed.
Therefore, describe include purifying obacunone (present in an amount at least sufficient to realize reduction that melanin generates and/
Or the reduction of tyrosinase activity) compositions, and its use in skin-whitening or the method that brightens
On the way.
Definition
Term " compositions " refers to treat, improves, promotes, improves, manages, controls, keeps, excellent
Change, improve, reduce, suppress or prevent the spy relevant with native state, bioprocess or disease or disease
Determine the product of state.Term compositions include, but not limited to include the purification of effective dose compound,
The medicine (i.e. medicine (drug)) of extract, its at least one component or its mixture, nonprescription drugs (OTC),
Cosmetics, food, food ingredients or dietary supplement composition.Exemplary compositions include cream,
Astringent (cosmetic lotion), film (pack) or powder, or as Emulsion, lotion, liniment foam, sheet
Agent, plaster, granule or ointment.
Term used herein " extract " refers to solid-state, semifluid or liquid substance or preparation,
It includes that the active ingredient of Rutaceae Fructus Evodiae (Juss.) of plant material such as conc forms is (a kind of or many
Kind).The intention of term " extract " not only includes that (selected from water, 1 to 4 carbon is former by using solvent
Son lower alcohol such as methanol, ethanol, butanol, etc., ethylene, acetone, hexane, ether, chloroform, second
Acetoacetic ester, butyl acetate, dichloromethane, DMF (DMF), dimethyl sulfoxide
(DMSO), 1,3 butylene glycol, propylene glycol and combinations thereof) carry out the crude extract of preparation from plant,
But also include the crude extract in this solvent of a part.As long as extracting method can ensure that active ingredient
The extraction of (one or more) and preservation, the most any extracting method may be by.
The term " pure (purity the most by weight) " being connected with obacunone used herein refers to
By for physically by obacunone and the obacunone prepared by remaining plant extract Component seperation.Respectively
Kind purification process is known and can be for obtaining pure obacunone.Such as, the method for use can be as
Fractional distillation or affinity purification.As the result of purification process, obacunone can be at least about 10% pure (the most extremely
Few about 10wt% purity)；Or, at least about 20% is pure；Or, at least about 30% is pure；Or, extremely
About 40% is pure less；Or, at least about 50% is pure；Or, at least about 60% is pure；Or, at least about
70% is pure；Or, at least about 80% is pure；Or, at least about 90% is pure；Or, at least about 95% is pure；
Or, at least about 99% is pure；And preferably from about 75%-100% is pure.
Term compositions used herein, extract, extract mixtures, the component of extract and
/ or " effective dose " or " therapeutically effective amount " of activating agent or composition refer at dosage with on the persistent period
Be enough to realize the effective amount of expected result.Such as, " effective dose " or " therapeutically effective amount " refers to:
The compositions of the present invention, extract, extract mixtures, the component of extract and/or activating agent or one-tenth
The amount of part, when it is administered into experimenter (such as, mammal, such as people), be enough in experimenter
Realizing treatment such as suppresses B16 cell (i.e. melanin generation), the suppression activity of tryrosinase, skin beautiful
White and/or brighten, reduce or alleviate skin dark stain etc..Constitute " effective dose " or " treatment effectively treatment
(therapeutically effective treatment) " the compositions of the disclosure, extract, extract mixing
The amount of thing, the component of extract and/or activating agent or composition changes according to following factor: this activating agent
Or compound, the disease treated and its order of severity, administering mode, the persistent period for the treatment of maybe needs to control
The age of the experimenter treated, but his self know can also be considered by those skilled in the art routinely
Know and the disclosure determines.
Term " pharmaceutically acceptable " mean that medicine, medicament, extract or inert component, be
It is suitable for and the mankind and zootic contact tissue, and there is no too much toxicity, incompatibility, no
Stability, zest etc., it matches with rational interests/Hazard ratio.
Term " is administered (administer) ", " being administered (administered) ", " being administered (administers) "
" it is administered (administering) " and is defined as compositions being supplied to by approach as known in the art
Experimenter, route of administration include but not limited to intravenous, intra-arterial, oral, parenteral, oral cavity, locally,
In transdermal, rectum, intramuscular, subcutaneous, bone, saturating mucosa or intraperitoneal routes.In preferred embodiment
In, compositions topical routes is suitable.
Term used herein " experimenter " or " individual " include mammal, can give to it
Drug composition.The non-limitative example of mammal includes the mankind, non-human primates, rodent (bag
Include transgenic and nontransgenic mice) or similar animal.In some embodiments, experimenter is suckling
Animal, and in some embodiments, experimenter is people.
Obacunone
The fruit of Rutaceae Fructus Evodiae (Evodiarutaecarpa) BENTHAM (Rutaceae) can be used
EtOH extracts, thus obtains the extract (" Fructus Evodiae extract ") of Fructus Evodiae, this Fructus Evodiae
Extract can serve as the source of obacunone compound, and described obacunone compound is unique the present invention's
Compositions is useful.
Obacunone (C26H30O7) example arrangement show as follows:
Commercial, obacunone can be available from various sources, including ChemStrong Scientific Co., Ltd
Or Chengdu Biopurify Phytochemicals Ltd.Additionally, obacunone can purify carrying from plant
Take thing, including plant such as: Rutaceae Fructus Evodiae, tinea alba (Dictamnusdasycarpus Turcz.) (rue
Fragrant section) dry root bark, the dry tree of Cortex Phellodendri (Phellodendronamurense Rupr.) (section: Rutaceae)
Skin, the dry bark of wampee (Phellodendronchinense Schneid.) (section: Rutaceae), mandarin orange
Species Fructus Fortunellae Margaritae (Fortunella margarita), casimiroa edulis (Casimiroaedulis), Fructus Citri Sarcodactylis
(Citrisarcodactylisfructus), Fructus Aurantii Immaturus (Aurantiifrusctusimmaturus) and Fructus Citri
(Citrifructus).In some aspects, the flower of plant, head inflorescence or fruit or leaf are used as extract
Source.Upon extracting, extract can be standardized as activity mark's compound.Such as, Cortex Phellodendri
(cortex phellodendriamurensis) extract can be relative to berberine, palmatine, limonin
Standardization is carried out with the content of at least one in obacunone.
Various purification and extractive technique will be made below more being fully discussed or being known in the art
's.
Exemplary extraction process
In one example, useful extract and/or activation in unique compositions of the present invention
Compound can obtain by using organic solvent extraction technology.
In another example, use H2O、H2O-EtOH、H2O-MeOH or H2O-acetone etc.
As the solvent sequence fractional distillation of solvent, it is useful for can be used to obtain in unique compositions of the present invention
Extract and/or reactive compound.
Aquiferous ethanol always extracts (total hydro-ethanolic extraction) technology and can also be used for obtaining this
Bright unique compositions is useful extract and/or reactive compound.Generally, this is referred to as always carrying
Take.The extract produced in this process will comprise the various plant being present in extraction of substance
Chemical substance, it includes fat and the hydrotrope.After collecting extract solution, solvent is evaporated, from
And obtain extract.
Ethanol always extracts and also can use in the present invention.This technology uses ethanol rather than aquiferous ethanol,
As solvent.The extract that this extractive technique generates, in addition to water soluble compound, it is also possible to include fat
Dissolubility and/or lipophilic compound.
Can be used for obtaining extractive technique another of extract and/or the reactive compound used in the present invention
One example is that supercritical fluid carbon dioxide extracts (SFE).Material to be extracted during extracting at this
It is not exposed to any organic solvent.More properly, Extraction solvent is (> 31.3 DEG C in super critical condition. and
> 73.8 bars) and carbon dioxide, be with or without modifying agent.It will be recognized by those skilled in the art,
With transformation temperature and pressure condition, thus the best productivity of extract can be obtained.This technology produces fat
Dissolubility and/or the extract of lipophilic compound, hexane similar as above and ethyl acetate always carry
Take technology.
It will be recognized by those skilled in the art, also have many other extraction and purification process, Liang Zhe
This area is all known and is described in various patent and publication, can be used for obtaining for putting into practice this
The extract of invention and/or reactive compound.For example, it is possible to use in the embodiment of this invention in following ginseng
Examine the extraction process described in document (it introduces in this article): Murga et al. by quoting,
“Extraction of natural complex phenols and tannins from grape seeds by using
supercritical mixtures of carbon dioxide and alcohol.”J.Agric Food Chem.2000
August in year: 48 (8): 3408-12；Hong et al., " Microwave-assisted extraction of phenolic
Compounds from grape seed. " Nat Prod Lett.2001；15(3):197-204；
Ashraf-Khorassani et al., " Sequential fractionation of grape seeds into oils,
polyphenols,and procyanidins via a single system employing CO2-based fluids.”
J.Agric Food Chem., on May 5th, 2004；52(9):2440-4.
According to an example of the present invention, obacunone extract can be by extracting Fructus Evodiae with 70%EtOH
(Juss.) prepared by fruit.The moisture of final extract > 5.0%, thus the plant produced carries
Take the plant source (botanical) that thing has: the thick extraction ratio of finished product is 5-7:1.
Then obacunone extract can be relative to activity mark's thing content (such as rutaecarpin, Fructus Evodiae
The content of alkali, berberine, palmatine and limonin) analyze and standardization.
Then this obacunone active substance can be by solvent water from such as dichloromethane-water, ethyl acetate
-water, n-butanol-water system purify.
Or, this obacunone active substance can be by different chromatography such as macroporous resins, organosilicon tree
Fat, MCI resin, gel etc. purify.
It addition, this obacunone active substance can pass through preparative chromatography, half preparative chromatography, such as preparation
HPLC, half preparation HPLC etc. purify.
It addition, this obacunone active substance can be purified by high-speed countercurrent chromatography.
Compositions
Obacunone can be configured to compositions.Specifically, some embodiment relates to one and has black
The compositions of element synthesis-inhibitory activity, the amount of it obacunone included can effectively reduce B16 cell.
Some other embodiment relates to suppress the compositions of the enzymatic activity of tryrosinase, it Cortex Phellodendri included
The amount of ketone can effectively suppress the enzymatic activity of tryrosinase.Some other embodiment relates to skin-whitening
And/or the compositions of skin whitening, the amount energy whitening effect of it obacunone included or skin whitening.
Some compositions relates to reduce the group of the enzymatic activity of B16 cell and/or suppression tryrosinase
Compound, the amount of it obacunone included can effectively reduce B16 cell and/or the enzyme of suppression tryrosinase
Activity, wherein obacunone is at least about 75% pure.Or, in the composition, obacunone is at least about
80% is pure；Or, at least about 85% is pure；Or, at least about 90% is pure；Or, at least about 95% is pure；
Or, at least about 96% is pure；Or, at least about 97% is pure；Or, at least about 98% is pure；Or,
At least about 99% is pure；Or, in the composition, obacunone is about 99.99% pure.
Obacunone constitutes the pact at least 50wt%'s of described compositions, more preferably at least about compositions
The 65wt%'s of the 60wt% of 55wt%, at least about compositions, at least about compositions, at least about compositions
The 80wt% of the 75wt% of 70wt%, at least about compositions, at least about compositions, at least about compositions
85wt%, at least about the 95wt% of the 90wt% of compositions, at least about compositions, at least about combines
The 99wt% of thing.Or, obacunone constitutes the about 1-99wt% of described compositions；Or, obacunone
Constitute the about 1-90wt% of described compositions；Or, obacunone constitutes the pact of described compositions
1-75wt%；Or, obacunone constitutes the about 50-70wt% of described compositions.
In the composition, the amount of obacunone can be about 0.001% to about 10%.
Certainly, it will be recognized by those skilled in the art, the amount of the obacunone being incorporated in compositions, can
To depend on the standardized content of label.Such as, for the obacunone prepared by Fructus Evodiae extract
For, label can be rutaecarpin, rutaecarpine and/or limonin.Therefore, if by Huang
Cypress ketone is normalized into about the 40% of labelled compound, then the above-mentioned amount of obacunone will reduce 1/2nd.
Such as, obacunone extract can be normalized into about 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, 3.0%,
3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%,
9.0%, 9.5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,
The labelled compound content of 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%.
The pH of described compositions can be about 6.0 to about 8.0, or the pH of described compositions can
Being substantially neutral.In certain embodiments, the compositions of obacunone is used to have substantially neutral
pH。
Some embodiment relates to the compositions increasing skin-whitening or brightening.Said composition includes
The obacunone of effect amount, thus reduce melanin and produce and/or the enzymatic activity of suppression tryrosinase.This combination
Thing can include cosmetically acceptable carrier.
Some other embodiments relates to the method increasing skin-whitening or brightening, and it includes to include Huang
The compositions of cypress ketone extract is administered into experimenter, wherein said composition reduce or reduce melanin generate,
Pigmentation, or both have both at the same time.
The compositions of the present invention can be with topical.
The compositions of the present invention can carry out preparing in acceptable carrier, vehicle or excipient and
Can prepare, pack and identify for the skin-whitening of experimenter or the cosmetics brightened or medicinal usage.
In certain embodiments, obacunone constitutes the about 50-70wt% of described compositions, and carrier, matchmaker
Jie's thing or excipient constitute the about 50-30wt% of described compositions.
Generally, described compositions includes cosmetically acceptable carrier.It is applicable to all realities of the present invention
The example of the cosmetically acceptable carrier executing scheme includes, but not limited to water, glycerol, and various alcohol are such as
Ethanol, propanol, vegetable oil, mineral oil, silicone oil, aliphatic ether, fatty ester, fatty alcohol, glycol, poly-
Glycol or their combination in any.The method of preparation is as known in the art and is such as disclosed in
Remington's Pharmaceutical Sciences,Gennaro,Mack Publishing Co.,Easton Pa.,
In 1990, it is incorporated herein by reference.
In certain embodiments, compositions may further include one or more whitening agents thus improves
The whitening effect of compositions.The whitening agent thinking exemplary includes: all known whitening agents and future can
The whitening agent that can develop.Preferably, described whitening agent is selected from tyrosinase inhibitor, free radical scavenger
And mixture.The suitably example of tyrosinase inhibitor includes, but not limited to kojic acid and it spread out
Biology, arbutin and its derivant, Radix Glycyrrhizae extract and its derivant, ascorbic acid spreads out with it
Biology, and hydroquinone and its derivant.The suitably example of free radical scavenger includes, but not limited to
Radix Glycyrrhizae extract and its derivant, vitamin E and its derivant, vitamin A is derivative with its
Thing, vitamin C and its derivant, Herba Rosmarini Officinalis (Rosemary) extract and its derivant and
Superoxide dismutase.Preferably whitening agent is selected from kojic acid, the derivant of kojic acid, arbutin, arbutin
Derivant, Arctostaphylos ura-ursi extract, citron extract, Fructus Cucumidis sativi extract, vitamin C and its derivant,
The extract of Malpighia glabra L. (acerola cherry) and the fermented product of Malpighia glabra L..
The example of the nonexcludability of vitamin C derivatives is, such as, the Arrcostab of L-AA is such as
L-AA base cetylate, the different cetylate of L-AA base, L-AA base two Palmic acid
Ester, L-AA base isostearate, L-AA base distearate, L-AA base two
Isostearate, L-AA base myristinate, the different myristinate of L-AA base, L-resists
Bad hematic acid base 2-ethylhexanoate, L-AA base two-2-ethylhexanoate, L-AA based oleic acid
Ester and L-AA base dioleate；The phosphate ester of L-AA such as L-AA base-2-phosphoric acid
Ester and L-AA base-3-phosphate ester；The sulfuric ester of L-AA such as L-AA base-2-sulphuric acid
Ester and L-AA base-3-sulfuric ester；They salt with alkaline-earth metal such as calcium and magnesium.They can be single
Solely use or use in the mixture mode of two or more.
When obacunone mixes with any of whitening agent, obacunone is about with the ratio of known whitening agent
1:100 is to about 100:1, preferably from about 1:50 to about 50:1, more preferably from about 1:10 to about 10:1.Most preferably,
Obacunone is about 1:5 to about 5:1 with the ratio of known brightening agent.
The compositions of the present invention can be prepared with various forms.Such as, they can be in cosmetics system
The form of agent such as cream, astringent, film (pack) or powder, or be Emulsion, lotion, liniment foam, sheet
Agent, plaster, granule, aerosol spray, gel, mousse, brilliantine or ointment.In each preparation,
Various known conventional cosmetic composition can be introduced.For example, it is possible to the cosmetic ingredient included such as alcohol,
Fatty and oily, surfactant, fatty acid, silicone oil, wetting agent, humidizer, viscosity modifier, breast
Agent, stabilizer, coloring agent and spice.The compositions that some further embodiment relates to can be with suitable
Any convenient form for being applied topically on skin is prepared.Suitably Emulsion include oil-in-water,
Water-In-Oil and organosilicon bag aqueous emulsion.
Provide the skin lightening compositions of the type of a kind of improvement in certain embodiments, its bag
Containing skin-whitening agents, wherein improvements include adding obacunone.Said composition can include that cosmetics can
The carrier accepted.
Can be as desired to administration composition, every day, every day for several times or any makes results needed be able to reality
Existing suitable scheme.Compositions can be based on being continuously or intermittently administered.
Method
Compositions as herein described may be used for various cosmetics and/or medicinal application, including suppression or fall
Low melanin generates, and suppresses or reduces enzymatic activity and/or the skin-whitening of tryrosinase, brightens and brilliant white.
Some embodiment relates to the method for skin whitening, it include by above-described any compositions with
And their combination in any is applied topically on skin.
Some specific embodiment relates to the method for skin whitening, and it includes to include obacunone (its amount
Can effectively reduce B16 cell and/or suppression tryrosinase enzymatic activity) compositions locally apply
On skin.Compositions is applied with the amount and persistent period that be enough to obvious skin whitening.
In local skin whitening cosmetic compound, comprising one or more cosmetic ingredients, it is selected from
Alcohol, fat, oil, surfactant, fatty acid, silicone oil, wetting agent, humidizer, viscosity modifier,
Emulsifying agent, stabilizer, coloring agent and spice, improve and include that the obacunone of effective dose carrys out skin whitening.
In the method, the frequency that local applies will depend on a number of factors, raw including suppression melanin
The level of hope become and/or the level of hope of the enzymatic activity of suppression tryrosinase and obacunone are in compositions
In content.The most exemplary a kind of scheme includes being applied on skin twice every day, and apply in the morning
Once apply once with evening.
Embodiment
Embodiment 1: by B16F10 cell
(CTG) luminescent cell is deposited
Cytotoxicity/the peace of the obacunone that viability experiment (Luminescent Cell Viability Assay) is carried out
Full assessment
In order to measure the cell safety of obacunone, carry out following experiment.
Should(CTG) luminescent cell viability experiment (from Promega) is according to manufacture
The description of business is carried out, thus based on the ATP (for the indicant of metabolic active cells) existed
Quantitatively determine the quantity of survivaling cell in culture.Employ 99.99% in this experiment pure
Obacunone (with 100.00 μ g/mL, 33.333 μ g/mL, 11.111 μ g/mL, 3.704 μ g/mL,
1.235 μ g/mL, 0.412 μ g/mL, 0.137 μ g/mL, 0.046 μ g/mL, 0.015 μ g/mL) and hydrogen
Quinone (as reference, with identical gradient concentration).This experiment uses B16F10 cell to carry out.
According to the safety evaluation based on cell utilizing CTG to carry out, obacunone does not show cell
Toxicity (is shown in Table 1).
Table 1:
The results are shown in Fig. 1.
Embodiment 2: the agent of the enzymatic activity to tryrosinase carried out with obacunone in B16F10 cell
Amount dependency suppression
Whether have impact on the enzymatic activity of tryrosinase in order to measure obacunone, carry out following experiment.
At the 1st day, B16F10 cell is inoculated (plated) with the density plates of about 18,000 cell/ml
To 24 hole assay plate.Assay plate is at 37 DEG C, 5%CO2, incubation 24 hours under humidified condition.
2nd day, reference substance (arbutin) and test compound (obacunone) are added (in assay plate
Described compound is 5 μ l (ultimate densities: 1 ×)) on this plate and by this plate at 37 DEG C, 5%CO2、
Incubation 2 days the most again.
At the 5th day, plate is carried out imaging.At culture medium pail for used dressings (medium waste receptacle)
On carry out inverted plate shaking and to use the napkin of cleaning to wipe suction.Add 80 μ l 0.05mM PBS (0.1%
Triton-X) and by plate it is placed in refrigerator, continues 4 hours with-80 DEG C.Then by plate at thaw at RT
And it is repeated twice washing and freezing step.Then sample is transferred in the V base plate in 96-hole and with 3000
RPM centrifugal (span) 10 minutes.60 μ l supernatant samples are transferred in UV plate and by 140 μ l
Fresh 0.1%L-DOPA add in each hole.By plate 37 DEG C of incubations 1 hour.In temperature
At 475nm to read absorption value after educating.The supernatant samples of 5 μ l is transferred to another UV
To determine protein concentration with BCA in plate.
Being calculated as follows of the suppression percentage ratio of tyrosinase activity:
Suppression ratio %=[(A-B)/A] * 100
Wherein A is the absorption value of control sample (between the sample and do not have with tryrosinase)
Difference, and B is the absorption value of test specimen (between the sample and do not have with tryrosinase)
Difference (Diwakar G, Rana J, Scholten J D.Inhibition of melanin production by a
combination of Siberian larch and pomegranate fruit extracts.Fitoterapia,
2012；83:989-95).
The signal of maximum is obtained from the cell processed with L-DOPA；Bottom signal comes from unused
The cell that L-DOPA processed.
The B16F10 cells show processed with obacunone goes out the suppression to tyrosinase enzymatic activity improved
(wherein suppression ratio is 90.5% at 100 μ g/mL), for positive control arbutin, its
During with arbutin same concentrations, there is much better than suppression ratio (table 2 and table 3).
Result is shown in table 2 below and table 3.
Table 2. obacunone
Table 3. arbutin
As shown in Figure 2, the administration of obacunone result in the obacunone dosage to the enzymatic activity of tryrosinase
Dependency suppresses.
Embodiment 3: obacunone shows that the dose dependent that melanin produces reduces
In order to measure whether obacunone affects melanin generation, carry out following experiment.
Test the obacunone of 100ug/mL.Arbutin (known tyrosinase inhibitor) is used as
Positive control inhibitor in experiment.
Making obacunone be dissolved in DMSO and add in B16F10 cell, this B16F10 cell exists
Inoculate 24 hours with the density of 18,000 cells/mL in 24 orifice plates before process.Test compound
Ultimate density be 1 ×.The kytoplasm pH of the B16F10 cell in this experiment is about 5-7.Will be each
The obacunone of dosage adds in cell, in triplicate.Then by plate at 37 DEG C, 5%CO2, wet
Incubation 72 hours under conditions of profit.
At the 5th day, culture medium is removed from cell, add the NaOH of the 1M of 150 μ l to survey
Determine in each hole of plate and by plate 80 DEG C of incubations 30 minutes.After incubation, the solution of 140 μ l is turned
Move to test in UV plate and with 400nm signal.The solution of 5 μ l is transferred in UV plate also
The BCA reagent of 200 μ l is added in each hole.By plate 37 DEG C of incubations 20 minutes.At incubation
Absorption value is read afterwards at 562nm.
The signal of maximum is obtained under the effect of DMSO；Minimum letter is obtained in 200ug/mL arbutin
Number.
The inhibitory activity of sample is reported as the percentage ratio of the reduction that melanin produces, at 100%
For the comparison (UT) of reason.
It was found that cultivate at B16F10 after with obacunone (with 100mg/mL) incubation 72 hours
Melanin suppression ratio in cell is 77.8%, (sees table 4 He compared to for the positive control of arbutin
5).This shows, for interrupting the B16 cell in B16F10 cell, obacunone has excellent
Different effect.
Table 4. obacunone
Table 5. arbutin
Fig. 3 depicts result.It can be seen that use obacunone to make melanin produce in dose dependent
Reduce.
Therefore, it is expected to, aforementioned detailed description is considered as illustrative rather than restrictive, and
It should be understood that claim includes all equivalents, claim be intended to define the present invention spirit and
Scope.
Claims (26)
1. a topical compositions, its have reduce B16 cell activity, it is substantially by following
Material forms:
A) obacunone pure for about 75-100%, its amount can effectively reduce B16 cell；
B) cosmetically acceptable carrier；With
C) optional:
I) one or more cosmetic ingredients, its selected from alcohol, fat, oil, surfactant, fatty acid,
Silicone oil, wetting agent, humidizer, viscosity modifier, emulsifying agent, stabilizer, coloring agent and spice；With
/ or
Ii) skin-whitening agents, it is selected from tyrosinase inhibitor, free radical scavenger and their mixture.
2. a topical compositions, its have reduce B16 cell activity, it is by following material group
Become:
A) at least about 90% pure obacunone, its amount can effectively reduce B16 cell；
B) cosmetically acceptable carrier；With
C) optional:
I) one or more cosmetic ingredients, its selected from alcohol, fat, oil, surfactant, fatty acid,
Silicone oil, wetting agent, humidizer, viscosity modifier, emulsifying agent, stabilizer, coloring agent and spice；With
/ or
Ii) skin-whitening agents, it is selected from tyrosinase inhibitor, free radical scavenger and theirs is mixed
Compound.
3. the compositions of any one in claim 1-2, wherein said obacunone purifies from least one
Planting the extract of following plant, this plant is selected from Rutaceae Fructus Evodiae (Evodiarutaecarpia), favus skin
(Dictamnicortex), Cortex Phellodendri (Phellodendriamurensis cortex), rutaceae Fructus Citri Sarcodactylis
(Citrisarcodactylisfructus), Fructus Aurantii Immaturus (Aurantiifrusctusimmaturus) and rutaceae Fructus Citri
(Citrifructus)。
4. the compositions of claim 3, wherein said Fructus Evodiae extract is relative to rutaecarpin, Wu
The content of at least one in the Fructus Evodiae time alkali and limonin carrys out standardization.
5. the compositions of any one in claim 1-4, wherein said obacunone is about 99.99%
Pure obacunone active substance.
6. the compositions of any one in claim 1-5, described compositions is selected from following system
Agent: cream, ointment, foam, lotion, plaster, tablet, granule or Emulsion.
7. the compositions of any one in claim 1-2, wherein said obacunone is beautiful with described skin
The weight ratio of white agent is about 100:1 to about 1:100.
8. the compositions of any one in claim 1-7, wherein reduces the effective dose of B16 cell
It is about 10-1000mg.
9. the compositions of any one in claim 1-8, wherein said obacunone constitutes described
The about 1-99wt% of compositions.
10. the compositions of any one in claim 1-8, wherein said obacunone constitutes institute
State the about 1-75wt% of compositions.
The compositions of any one in 11. claim 1-8, wherein said obacunone constitutes institute
State the about 50-70wt% of compositions.
12. 1 kinds of topical compositions being used for suppressing the activity of tryrosinase, it is substantially by following thing
Matter forms:
A) obacunone pure for about 75-100%, its amount can effectively suppress the activity of tryrosinase；
B) cosmetically acceptable carrier；With
C) optional:
I) one or more cosmetic ingredients, its selected from alcohol, fat, oil, surfactant, fatty acid,
Silicone oil, wetting agent, humidizer, viscosity modifier, emulsifying agent, stabilizer, coloring agent and spice；With
/ or
Ii) skin-whitening agents, its be selected from tyrosinase inhibitor, free radical scavenger, and they
Mixture.
13. 1 kinds for suppressing the topical compositions of the activity of tryrosinase, it is made up of following material:
A) at least about 90% pure obacunone, its amount can effectively suppress the activity of tryrosinase；
B) cosmetically acceptable carrier；With
C) optional:
I) one or more cosmetic ingredients, its selected from alcohol, fat, oil, surfactant, fatty acid,
Silicone oil, wetting agent, humidizer, viscosity modifier, emulsifying agent, stabilizer, coloring agent and spice；With
/ or
Ii) skin-whitening agents, it is selected from tyrosinase inhibitor, free radical scavenger and theirs is mixed
Compound.
The compositions of any one in 14. claim 12-13, wherein said obacunone purifies certainly
The extract of at least one following plant, this plant be selected from Rutaceae Fructus Evodiae, favus skin, Cortex Phellodendri,
Rutaceae Fructus Citri Sarcodactylis, Fructus Aurantii Immaturus and rutaceae Fructus Citri.
The compositions of 15. claim 14, wherein said obacunone is relative to rutaecarpin, Fructus Evodiae
The content of at least one in secondary alkali and limonin carrys out standardization.
The compositions of any one in 16. claim 12-15, wherein said obacunone is about
99.99% pure obacunone active substance.
The compositions of any one in 17. claim 12-16, described compositions is selected from following
Preparation: cream, ointment, foam, lotion, plaster, tablet, granule or Emulsion.
The compositions of any one in 18. claim 12-13, wherein said obacunone and described skin
The weight ratio of skin whitening agent is about 100:1 to about 1:100.
The compositions described in any one in 19. claim 12-18, wherein can effectively suppress cheese ammonia
The amount of the activity of acid enzyme is about 10-1000mg.
The compositions of any one in 20. claim 12-19, wherein said obacunone constitutes
The about 1-99wt% of described compositions.
The compositions of any one in 21. claim 12-19, wherein said obacunone constitutes
The about 1-75wt% of described compositions.
The compositions of any one in 22. claim 12-19, wherein said obacunone constitutes
The about 50-70wt% of described compositions.
23. 1 kinds of topical compositions, it includes cosmetically acceptable carrier and at least 90% pure Huang
Cypress ketone, wherein said obacunone constitutes the about 1-99wt% of described compositions.
The method of 24. 1 kinds of skin whitening, it includes the compositions office any one of claim 1-23
Portion is applied on skin, wherein be enough to the amount of obvious skin whitening and the persistent period apply described in combination
Thing.
The topical compositions of any one in 25. claim 1-23 has reduction melanin in manufacture and closes
Purposes in the enamel of the activity become.
The topical compositions of any one in 26. claim 1-23 has the enzyme of tryrosinase manufacturing
Purposes in the enamel of inhibitory activity.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510013057.XA CN105816342A (en) | 2015-01-09 | 2015-01-09 | Composition containing obacunone and method for using obacunone in skin whitening |
| TW105100568A TW201630589A (en) | 2015-01-09 | 2016-01-08 | Compositions including obacunone and methods of using the same in skin whitening applications |
| PCT/CN2016/070544 WO2016110276A1 (en) | 2015-01-09 | 2016-01-11 | Topical composition containing obakunone and skin-whitening method using same |
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| CN201510013057.XA CN105816342A (en) | 2015-01-09 | 2015-01-09 | Composition containing obacunone and method for using obacunone in skin whitening |
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| Country | Link |
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| CN (1) | CN105816342A (en) |
| TW (1) | TW201630589A (en) |
| WO (1) | WO2016110276A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109998950A (en) * | 2019-03-04 | 2019-07-12 | 湖南商务职业技术学院 | A kind of sun-proof whitening cosmetic compound |
| CN113208959A (en) * | 2021-04-30 | 2021-08-06 | 广州市科能化妆品科研有限公司 | Composition for inhibiting melanin generation, whitening essence, and preparation method and application thereof |
| CN113318031A (en) * | 2021-06-21 | 2021-08-31 | 杭州友丽医疗科技(集团)有限公司 | Skin beautifying toner composition for removing chloasma, skin beautifying toner and preparation method thereof |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106265113A (en) * | 2015-05-14 | 2017-01-04 | 捷通国际有限公司 | The compositions comprising obacunone and the method using said composition in skin anti-aging is applied |
| CN115252630B (en) * | 2022-09-02 | 2024-02-09 | 深圳技术大学 | Application of phellodendron ketone in preparing medicine for preventing, improving or treating non-alcoholic fatty liver disease |
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| CN101695470A (en) * | 2009-10-27 | 2010-04-21 | 天津郁美净集团有限公司 | Composite for cosmetics, cosmetic product containing same and preparation method thereof |
| KR20120082047A (en) * | 2011-01-13 | 2012-07-23 | 강원대학교산학협력단 | A composition comprising obacunone for treating or preventing vascular disease |
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| CN102573787A (en) * | 2009-08-14 | 2012-07-11 | 株式会社爱茉莉太平洋 | Composition containing a natural extract |
| CN102357066B (en) * | 2011-10-26 | 2013-08-21 | 天津郁美净集团有限公司 | Cortex phellodendri extract and preparation method thereof |
| CN102614101B (en) * | 2012-04-25 | 2013-07-03 | 天津郁美净集团有限公司 | Cosmetic composition containing amur corktree bark extract and preparation method and application thereof |
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2015
- 2015-01-09 CN CN201510013057.XA patent/CN105816342A/en active Pending
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| CN101695470A (en) * | 2009-10-27 | 2010-04-21 | 天津郁美净集团有限公司 | Composite for cosmetics, cosmetic product containing same and preparation method thereof |
| KR20120082047A (en) * | 2011-01-13 | 2012-07-23 | 강원대학교산학협력단 | A composition comprising obacunone for treating or preventing vascular disease |
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| CN109998950A (en) * | 2019-03-04 | 2019-07-12 | 湖南商务职业技术学院 | A kind of sun-proof whitening cosmetic compound |
| CN113208959A (en) * | 2021-04-30 | 2021-08-06 | 广州市科能化妆品科研有限公司 | Composition for inhibiting melanin generation, whitening essence, and preparation method and application thereof |
| CN113318031A (en) * | 2021-06-21 | 2021-08-31 | 杭州友丽医疗科技(集团)有限公司 | Skin beautifying toner composition for removing chloasma, skin beautifying toner and preparation method thereof |
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| WO2016110276A1 (en) | 2016-07-14 |
| TW201630589A (en) | 2016-09-01 |
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