CN107308185A - Pharmaceutical composition and liposome and its application - Google Patents
Pharmaceutical composition and liposome and its application Download PDFInfo
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- CN107308185A CN107308185A CN201710475665.1A CN201710475665A CN107308185A CN 107308185 A CN107308185 A CN 107308185A CN 201710475665 A CN201710475665 A CN 201710475665A CN 107308185 A CN107308185 A CN 107308185A
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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
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
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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
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/14—Liposomes; Vesicles
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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
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
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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
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
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- 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
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/41—Particular ingredients further characterized by their size
- A61K2800/413—Nanosized, i.e. having sizes below 100 nm
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Abstract
The present invention relates to cosmetic field, and in particular to pharmaceutical composition and liposome and its application.The pharmaceutical composition contains one or more and platinum in glabridin and the like.Effective active composition glabridin in the pharmaceutical composition of the present invention and the like has good cooperative effect between platinum, results in the whitening effect of Synergistic.Particularly, the liposome containing aforementioned pharmaceutical compositions shows especially low cytotoxicity, is easy to convey and applies.
Description
Technical field
The present invention relates to cosmetic field, and in particular to pharmaceutical composition and liposome and its application.
Background technology
Glabridin is one of Main Flavonoids constituents in glycyrrhiza glabra.It is in Cytochrome P450/NADPH oxidations system
Very strong Green Tea Extract oxidation is shown in system, free radical produced by substantially suppressing in internal metabolic processes,
Against the large biological molecule (low-density lipoprotein LDL, DNA) to oxidation-sensitive and cell membrane etc. by Free radicals injury.
Therefore, glabridin can be used as the whitening active ingredients commonly used in cosmetics.However, glabridin has certain cell toxicant
Property, so that cosmetics can not be used for heavy dose ofly.
The content of the invention
It is an object of the invention to provide a kind of pharmaceutical composition of whitening with Synergistic and liposome and its should
With.
To achieve these goals, one aspect of the present invention provides a kind of pharmaceutical composition, and it is sweet that the pharmaceutical composition contains light
One or more and platinum during grass is fixed and the like.
Second aspect of the present invention provides a kind of liposome containing aforementioned pharmaceutical compositions.
Third aspect present invention provides application of the above-mentioned liposome in whitening and oxidation resistant product is prepared.
Fourth aspect present invention provides the cosmetics containing above-mentioned liposome.
Effective active composition glabridin in the pharmaceutical composition of the present invention and the like has good between platinum
Good cooperative effect, results in the whitening effect of Synergistic.Particularly, the liposome performance containing aforementioned pharmaceutical compositions
Go out especially low cytotoxicity, be easy to convey and apply.
Embodiment
The end points and any value of disclosed scope are not limited to the accurate scope or value herein, these scopes or
Value should be understood to comprising the value close to these scopes or value.For number range, between the endpoint value of each scope, respectively
It can be combined with each other between the endpoint value of individual scope and single point value, and individually between point value and obtain one or more
New number range, these number ranges should be considered as specific open herein.
One aspect of the present invention provides a kind of pharmaceutical composition, and the pharmaceutical composition contains in glabridin and the like
One or more and platinum.
The present inventor is surprisingly had found, the one or more in glabridin and the like are combined with platinum
In use, resulting in whitening and the antioxidant effect of Synergistic.Although described glabridin and the like and platinum
Amount ratio can change in relative broad range, it is preferable that the weight ratio of described glabridin and the like and platinum is 10-
100：1, preferably 15-50：1.
Wherein, described glabridin and the like is preferably glabridin and/or licoflavone.
Wherein, the platinum refers to platinum, and preferably granularity is 5-200nm platinum particle.
Second aspect of the present invention provides a kind of liposome containing aforementioned pharmaceutical compositions.
According to the present invention, in the liposome, the content of aforementioned pharmaceutical compositions can change in relative broad range, it is considered to
Applied on as cosmetic composition, it is preferable that in the liposome, in terms of dry weight, the content of described pharmaceutical composition is
0.5-15 weight %.Under the conditions of satisfaction is somebody's turn to do, wherein, in the liposome, in terms of dry weight, described glabridin and the like
Content be preferably 0.5-10 weight %, the content of the platinum is preferably 0.01-0.1 weight %.
In accordance with the present invention it is preferred that, the liposome is formed by phosphatide, cholesterol and fatty acid compound.Wherein, institute
State the one or more in the aliphatic acid and its salt that fatty acid compound is preferably C8-C20.
Although the consumption for forming the phosphatide, cholesterol and fatty acid compound of the housing of liposome can be in wider model
Interior variation is enclosed, in order to obtain the liposome that stability is higher, it is preferable that the phosphatide, cholesterol and fatty acid compound
The weight ratio of consumption is 100：10-70：1-50, preferably 100：20-60：2-30, preferably 100：20-55：5-25, be preferably
100：25-45：8-20, more preferably 100：30-45：8-15.
According to the present invention, the phosphatide can be any phospholipids compounds of this area conventionally used for preparing liposome,
Can be natural phospholipid (lecithin, cephalin, cuorin etc.) or synthetic phospholipid, such as described phosphatide is soybean ovum
Phosphatide, hydrolecithin, phosphatidyl choline, phosphatidyl-ethanolamine, DSPC (DSPC), two myristoyl phosphorus
Phosphatidylcholine (DMPC), DOPE, DPPG, DPPC
(DPPC), DPPE, DSPC, diphosphatidylglycerol, phosphatidylserine and phosphorus
One or more in acyl inositol.In view of matching somebody with somebody between the phosphatide and the cholesterol of the present invention, fatty acid compound
Cooperation is used, it is preferable that the phosphatide is soybean lecithin, hydrolecithin, dimyristoyl phosphatidyl choline, two palmityl phosphorus
One or more in phosphatidylcholine and DSPC, more preferably dimyristoyl phosphatidyl choline, two palm fibres
One or more in palmitic acid phosphatidyl choline and DSPC.
According to the present invention, the fatty acid compound has certain modifying function for liposome, particularly with
Specific consumption is with that under the phosphatide and cholesterol cooperation of the invention of specific usage ratio, can be made stability-enhanced lipid
Body, and such liposome can be with higher entrapment efficiency entrapped drug, also beneficial to liposome in terms of cosmetics
Application.The fatty acid compound is the one or more in C8-C20 aliphatic acid and its salt, wherein, C8-C20 fat
The salt of fat acid can be its alkali metal salt, alkali salt etc..Preferably, the fatty acid compound be octanoic acid, Sodium Caprylate,
Potassium octanoate, calcium octoate, magnesium octoate, capric acid, sodium caprate, Capric acid potassium salt, capric acid calcium, capric acid magnesium, laurate, sodium laurate, laurate
Potassium, calcium laurate, Magnesium dilaurate, tetradecanoic acid, tetradecanoic acid sodium, potassium myristate, tetradecanoic acid calcium, tetradecanoic acid magnesium, palm fibre
It is palmitic acid acid, sodium palmitate, potassium palmitate, calcium palmitate, magnesium palmitate, stearic acid, odium stearate, potassium stearate, calcium stearate, hard
Fatty acid magnesium, oleic acid, enuatrol, potassium oleate, calcium oleate, magnesium oleate, linoleic acid, linoleic acid sodium, linoleic acid potassium, calcium linoleate, Asia
One or more in magnesium oleate, arachidic acid, arachidic acid sodium, arachidic acid potassium, arachidic acid calcium and arachidic acid magnesium, more preferably tristearin
One or more in sour sodium, potassium stearate, magnesium stearate, sodium palmitate, potassium palmitate, calcium palmitate and magnesium palmitate.
, for example can be with although described pharmaceutical composition can be configured at any position of the liposome according to the present invention
It is in the space of the hydrophobic grouping formation of phospholipid bilayer or in liposome center lumen body, it is preferable that institute
State glabridin and the like to be contained in the hydrophobic interlayer of the phospholipid bilayer of the liposome, the platinum is contained in
The middle part of the liposome (in center lumen body).
Wherein, the particle diameter of the liposome is 90-170nm, more preferably preferably 100-140nm, 100-130nm.
The present invention it is a kind of preferred embodiment in, the preparation method of the above-mentioned liposome containing pharmaceutical composition is excellent
Choosing includes：
(1) in organic solvent, by described glabridin and the like, phosphatide, cholesterol and fatty acid compound
Mixed；
(2) organic solvent in mixture obtained by step (1) is removed to obtain film-form residue；
(3) film-form residue formation liposome obtained by step (2) is caused in the presence of the aqueous solvent containing platinum；
Wherein, the fatty acid compound is the one or more in C8-C20 aliphatic acid and its salt.
It is in organic solvent, described glabridin and the like, phosphatide, courage is solid in step (1) according to the present invention
Alcohol and fatty acid compound are mixed, and can cause described glabridin and the like, phosphatide, cholesterol and aliphatic acid
Class compound dissolves in organic solvent, it is also possible that their fully contacts each other.Wherein, the glabridin and its similar
Thing, phosphatide, cholesterol and fatty acid compound species as described in above, will not be repeated here.
Preferably, the weight ratio of the consumption of the phosphatide, cholesterol and fatty acid compound is 100：10-70：1-50,
Preferably 100：20-60：2-30, preferably 100：20-55：5-25, preferably 100：25-45：8-20, more preferably 100：
30-45：8-15.
Wherein it is preferred to, the weight ratio of described glabridin and the like and phosphatide is 5-25：100, preferably 8-
20：100, more preferably 10-15：100.
According to the present invention, although the organic solvent, which can be used, can dissolve the glabridin substantially and its similar
The organic solvent that thing, phosphatide, cholesterol and fatty acid compound any kind of and being easy to remove, but for the ease of
Described glabridin and the like, phosphatide, cholesterol and fatty acid compound can be in more suitable solvent atmospheres
Obtain and preferably combine, to obtain the liposome that stability is higher, particle diameter is more suitable for, it is preferable that described to have in step (1)
Machine solvent is the mixture of the first organic solvent and the second organic solvent.Wherein, first solvent is methanol, ethanol, second two
One or more in alcohol, propane diols, isopropanol, n-butanol and ethyl acetate, preferably methanol, ethanol, isopropanol and acetic acid
One or more in ethyl ester, preferably methanol and/or ethanol.Second solvent be chloroform, dichloromethane, carbon tetrachloride,
One kind or many in one or more in ether and tetrahydrofuran, preferably chloroform, dichloromethane, carbon tetrachloride and ether,
Preferably chloroform and/or dichloromethane kind.
In accordance with the present invention it is preferred that, the weight ratio of first organic solvent and the second organic solvent is 100：10-100,
Preferably 100：30-90, more preferably 100：40-85.
According to the present invention, the consumption of the organic solvent can change in relative broad range, it is preferable that the organic solvent
Consumption make it that described glabridin and the like, phosphatide, the total concentration of cholesterol and fatty acid compound are 2-10 weights
Measure %, for example, preferably 2.5-6 weight %, 2.9-4.7 weight %.
According to the present invention, in step (2), the organic solvent in the mixture as obtained by by step (1) is removed, and just can be obtained
Film-form residue, so after step (3) adds water, so that it may promote the formation of liposome.
Wherein, the removing of the organic solvent can be carried out at reduced pressure conditions, it is preferable that in step (2), be removed organic molten
The temperature of agent is 50-100 DEG C.Mixture obtained by step (1) can be for example placed in reaction vessel by such process, using rotation
Turn evaporimeter to carry out at reduced pressure conditions, so that film-form residue just can be formed on reaction vessel wall.
According to the present invention, in step (3), the aqueous solvent containing platinum can be dispersion of the platinum in water,
Can be containing it is a small amount of other do not influence the present invention liposome shaping other solvents the aqueous solution and the dispersion of platinum,
It is preferred to use water.The platinum is as described above, is platinum, and preferably granularity is 5-200nm platinum particle.The platinum exists
Concentration in aqueous solvent can change in relative broad range, for the ease of the formation of liposome, it is preferable that in step (3), institute
State in the aqueous solvent containing platinum, the content of the platinum is 10-1000ppm (w/w), preferably 50-500ppm.
Preferably, in step (3), the weight ratio of the consumption of the phosphatide and the aqueous solvent containing platinum is 1：20-
100, preferably 1：30-80, more preferably 1：40-60.Using the aqueous solvent under the consumption, particle diameter can be obtained and be more suitable for
Liposome.
In accordance with the present invention it is preferred that, step (3) includes：By film obtained by the aqueous solvent containing platinum and step (2)
Shape residue is heated, and homogenization is then carried out again.
Wherein, the condition of the heating is preferably included：Temperature is 40-80 DEG C, and the time is 0.5-3h.At the homogeneous
The condition of reason is preferably included：First disperse 10-50min under 5,000-20,000rpm rotating speed, then in 500-1500bar and
High pressure homogenization 2-6 times under 20-60Hz frequency ultrasound.The homogeneous processing for example can be high-pressure homogeneous in IKA homogenizers, IKA
Carried out in machine.
Third aspect present invention provides application of the above-mentioned liposome in whitening and oxidation resistant product is prepared.
Fourth aspect present invention provides the cosmetics containing above-mentioned liposome.
Effective active composition glabridin in the pharmaceutical composition of the present invention and the like has good between platinum
Good cooperative effect, results in whitening and the antioxidant effect of Synergistic.Particularly, in the phosphatide using the present invention, courage
Sterol and the liposome of fatty acid compound formation are as under carrier, the lipid body surface containing aforementioned pharmaceutical compositions of gained
Reveal especially low cytotoxicity and stability, be easy to convey and apply.
The present invention will be described in detail by way of examples below.
In following examples and comparative example：
The platinum particle that the granularity that platinum particle is available from MIJI nanotech Co., LTD. is 5-200nm.
Glabridin is purchased from Qinghai Qinghaihu Pharmaceutical Co., Ltd..
Embodiment 1-31
The present embodiment is used to illustrate liposome of the present invention and preparation method thereof.
(1) phosphatide of the total consumptions of 10g, cholesterol, fatty acid compound and glabridin are dissolved in solvent (they
Species and each shared parts by weight are shown in Table 1)；
(2) resulting solution is subjected to decompression rotary evaporation in eggplant type bottle using Rotary Evaporators, decompression rotary evaporation
Condition includes：Temperature is 60 DEG C, and rotating speed is 90rpm, and the time is about 30min；To remove solvent, film-form residue is obtained；
(3) water (weight is 50 times of phosphatide, and the concentration of platinum particle is shown in Table 1) of the particle containing platinum is added to
Eggplant type bottle is stated to be contacted with film-form residue, and using Rotary Evaporators in rotary heating 1h under 65 DEG C, 90rpm；
(4) gained mixture is set into homogeneous about 10min under 10,000rpm in IKA homogenizers, then by IKA high pressures
Homogenizer obtains liposome in circulating homogeneous 3 times (total duration about 20min) under 1000bar and 50Hz；
Wherein, only in embodiment 2 (other embodiments all use operations described above parameter)：Step (2) decompression rotation
Turning the condition of evaporation includes：Temperature is 80 DEG C, and rotating speed is 100rpm, and the time is about 30min；The water of step (3) particle containing platinum
(weight is 60 times of phosphatide) is added to above-mentioned eggplant type bottle to be contacted with film-form residue, and using Rotary Evaporators in 55
DEG C, rotary heating 1.5h under 150rpm；In step (4) IKA homogenizers under 15,000rpm homogeneous 5min, then by IKA high pressures
Homogenizer obtains liposome in circulating homogeneous 3 times (total duration about 15min) under 1000bar and 50Hz frequencies.
Comparative example 1
Method according to embodiment 1, unlike, platinum particle and glabridin are not used, so as to obtain lipid
Body.
Comparative example 2
Method according to embodiment 1, unlike, glabridin is not used, so as to obtain liposome.
Comparative example 3
Method according to embodiment 1, unlike, platinum particle is not used, so as to obtain liposome.
Table 1
Test case 1
Glabridin assay：The glabridin titer of series concentration gradient is prepared by solvent of methanol, purple is utilized
Outer spectrophotometer determines the extinction of the glabridin standard liquid of various concentrations using methanol as reference liquid respectively under 280nm
Degree, makes glabridin concentration-absorbance standard curve.Appropriate liposome solutions are taken, are dissociated using micro-filtration centrifugal process
The aqueous solution of medicine, uses methanol dilution certain multiple, using ultraviolet specrophotometer at a wavelength of 280 nm, using methanol as reference
Liquid, the absorbance of determination sample solution.Liposome solutions, blank liposomes liquid solution are carried out with methanol and identical extension rate
Dilute and determine its absorbance, by glabridin standard curve conversion medicament contg, glabridin is calculated using formula (1)
Envelop rate.
Platinum assay：The platinum particles levels liquid of series concentration gradient is prepared by solvent of pure water, ultraviolet point is utilized
Light photometer determines the absorbance of the platinum particles levels solution of various concentrations using pure water as reference liquid respectively under 205nm, system
Make platinum particle concentration-absorbance standard curve.Appropriate liposome solutions are taken, certain multiple is diluted with water, ultraviolet point is utilized
Light photometer is under 205nm wavelength, using pure water as reference liquid, the absorbance of determination sample.Be tod with water and identical extension rate
Liposome solutions, blank liposomes liquid solution are diluted and determine absorbance, are contained by platinum particles levels curve conversion medicine
Amount, the envelop rate of platinum particle is calculated using formula (1)：
Envelop rate (%)=(1-WDo not wrap/WAlways) × 100% (1), wherein, WDo not wrapAnd WAlwaysThe free medicine of liposome is represented respectively
Amount and total amount of feeding.
As a result it is as shown in table 2：
Table 2
Test case 2
Measure the initial particle size of above-mentioned liposome, and survey after above-mentioned liposome is placed two weeks under room temperature (about 25 DEG C)
Its particle diameter is tried, it the results are shown in Table shown in 3.
Wherein, particle changing ratio is：(particle diameter-initial particle size after two weeks)/initial particle size × 100%.
Table 3
The liposome that can be seen that the present invention by the result of table 3 has more preferable stability, is placed by long-time
Afterwards, trend of some particle diameters even with reduction.
Test case 3：The external toxicity test to HACAT (people is epidermal cornified) cell is tested
The condition of culture of cell：By HACAT cell culture in the DMEM high glucose mediums containing 10 weight % hyclones,
37 DEG C, 5 weight %CO2Saturated humidity incubator is incubated.
Method of testing：Tissue Culture Flask is taken out, nutrient solution is absorbed, adds after PBS solution cleans cell and absorbs PBS solution；
Pancreatin (Trypsin-EDTA pancreatin, Gbico), cell dispersion are added to Tissue Culture Flask；1mL cell suspensions are taken to be used for cytometer
Number, adds cell suspension that 100 μ L have diluted in 96 orifice plates, it is 1.0 × 10 to make its concentration after calculating4Cells/well, puts
Enter CO2Incubator culture 24h；1 μ L samples solution (sample includes glabridin and above-mentioned liposome) is taken respectively in corresponding 96
In orifice plate, the sample solution concentration for making each hole is respectively that (consumption of liposome is so that the content of glabridin is set 10 μ g/mL for this
Put concentration), while setting blank well (95% ethanol for adding 1 μ L), cell culture well is put into incubator culture 48h；By 96
Orifice plate is toppled over after the culture medium containing sample, the CCK-8 reagents (JM754) that 100 μ L dilute 10 times is added per hole, in CO2Incubator
2~2.5h of middle culture；96 orifice plates are taken out, absorbance is determined at 450nm with ELIASA, cell survival is calculated according to below equation
Rate：
Cell survival rate=(TCS-dead cell number)/TCS * 100%.
It the results are shown in Table shown in 4.
Table 4
The liposome of the pharmaceutical composition formation of the present invention is can be seen that by the data of table 4 has relatively low toxicity, special
It is not to use under preferred liposome, toxicity is lower.
Test case 4：The external whitening function experiment test to B16 cells (melanocyte) of body
The condition of culture of cell：By B16 cell culture in the DMEM high glucose mediums containing 10 weight % hyclones, 37
DEG C, 5 weight %CO2Saturated humidity incubator is incubated.
Method of testing：Counted after B16 cells are peeled off from Tissue Culture Flask, add the cell suspension diluted in 6 holes
In plate, CO is put into2Incubator culture 24h；Original culture medium in 6 orifice plates is absorbed, the PBS of equivalent is added once per hole；
The DMEM solution that 1.98mL contains MSH (melanotropin, purchased from CALBIOCHBM companies) is added per hole, while setting blank well, i.e.,
Blank well adds the DMEM solution without MSH, and culture plate is put into CO2Incubator culture about 2.5h；Prepare certain density sample
Product solution, adds 20 μ L sample solution in 6 orifice plates per hole, while negative control (being only free of sample solution containing MSH) is set,
The concentration of sample solution in every hole is followed successively by 2 μ g/mL, culture plate is put into CO2Incubator culture 72h；Absorb in 6 orifice plates
Culture medium, is handled per recovery cell after the cell of hole into centrifuge tube with PBS once with the pancreatin of equivalent；Take 1/9~1/5
Above-mentioned cell liquid is into centrifuge tube and centrifugation discards liquid, adds 1 weight %triton X-100 (polyethylene glycol octyl phenyls
Ether) PBS solution, concussion, using BCA protein quantifications kit carry out total protein quantify；After remaining cell suspension is centrifuged
Liquid is discarded, with PBS, a certain amount of 1M NaOH is added according to protein quantification result, make solution total protein concentration identical,
2min is heated in 60 DEG C, toward 96 orifice plate loadings, OD values are determined under 405nm.
It the results are shown in Table shown in 5.
Table 5
The pharmaceutical composition that can be seen that the present invention by the data of table 5 results in the whitening effect of Synergistic, special
It is not to use under preferred liposome, whitening effect is more preferably.
The preferred embodiment of the present invention described in detail above, still, the present invention is not limited thereto.In the skill of the present invention
In art concept, technical scheme can be carried out a variety of simple variants, including each technical characteristic with it is any its
Its suitable method is combined, and these simple variants and combination should equally be considered as content disclosed in this invention, belong to
Protection scope of the present invention.
Claims (10)
1. a kind of pharmaceutical composition, it is characterised in that the pharmaceutical composition contain one kind in glabridin and the like or
A variety of and platinum.
2. composition according to claim 1, wherein, the weight ratio of described glabridin and the like and platinum is
10-100：1, preferably 15-50：1.
3. composition according to claim 1 or 2, wherein, described glabridin and the like be glabridin and/or
Licoflavone.
4. the composition according to any one in claim 1-3, wherein, the granularity of the platinum is the white of 5-200nm
Gold particle.
5. a kind of liposome of the pharmaceutical composition in 1-4 containing claim described in any one.
6. liposome according to claim 5, wherein, in the liposome, in terms of dry weight, described pharmaceutical composition contains
Measure as 0.5-15 weight %.
7. the liposome according to claim 5 or 6, wherein, the liposome is by phosphatide, cholesterol and fatty acid chemical combination
Thing is formed, wherein, the one or more in aliphatic acid and its salt that the fatty acid compound is C8-C20, the phosphatide,
The weight ratio of cholesterol and fatty acid compound is 100：10-70：1-50, preferably 100：20-60：2-30, be preferably
100：20-55：5-25, more preferably 100：25-45：8-20, is still more preferably 100：30-45：8-15；
Preferably, the phosphatide is soybean lecithin, hydrolecithin, phosphatidyl choline, phosphatidyl-ethanolamine, distearyl phosphorus
Phosphatidylcholine, dimyristoyl phosphatidyl choline, DOPE, DPPG, two palmityls
Phosphatidyl choline, DPPE, DSPC, diphosphatidylglycerol, phosphatidylserine
With the one or more in phosphatidylinositols, preferably soybean lecithin, hydrolecithin, dimyristoyl phosphatidyl choline,
One or more in DPPC and DSPC；
Preferably, the fatty acid compound be octanoic acid, Sodium Caprylate, potassium octanoate, calcium octoate, magnesium octoate, capric acid, sodium caprate,
Capric acid potassium salt, capric acid calcium, capric acid magnesium, laurate, sodium laurate, potassium laurate, calcium laurate, Magnesium dilaurate, tetradecanoic acid, 14
Alkanoic acid sodium, potassium myristate, tetradecanoic acid calcium, tetradecanoic acid magnesium, palmitic acid, sodium palmitate, potassium palmitate, calcium palmitate, palm fibre
Palmitic acid acid magnesium, stearic acid, odium stearate, potassium stearate, calcium stearate, magnesium stearate, oleic acid, enuatrol, potassium oleate, calcium oleate,
Magnesium oleate, linoleic acid, linoleic acid sodium, linoleic acid potassium, calcium linoleate, magnesium linoleate, arachidic acid, arachidic acid sodium, arachidic acid potassium, flower
One or more in raw acid calcium and arachidic acid magnesium, preferably odium stearate, potassium stearate, magnesium stearate, sodium palmitate, palm
One or more in sour potassium, calcium palmitate and magnesium palmitate.
8. the liposome according to any one in claim 5-7, wherein, described glabridin and the like is contained in
In the hydrophobic interlayer of the phospholipid bilayer of the liposome, the platinum is contained in the middle part of the liposome.
9. application of the liposome in whitening and oxidation resistant product is prepared in claim 5-8 described in any one.
10. the cosmetics containing the liposome described in any one in claim 5-8.
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| CN113318036A (en) * | 2021-06-30 | 2021-08-31 | 花安堂生物科技集团有限公司 | New application of artemisia plant extract water |
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