CN109419633A - A kind of liquid crystal slow-releasing system containing Cannador or cannabidiol - Google Patents
A kind of liquid crystal slow-releasing system containing Cannador or cannabidiol Download PDFInfo
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- CN109419633A CN109419633A CN201710741421.3A CN201710741421A CN109419633A CN 109419633 A CN109419633 A CN 109419633A CN 201710741421 A CN201710741421 A CN 201710741421A CN 109419633 A CN109419633 A CN 109419633A
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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
- A61K8/0295—Liquid crystals
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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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/347—Phenols
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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
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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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- 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
- A61K2800/10—General cosmetic use
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Abstract
The present invention provides a kind of liquid crystal slow-releasing systems of high concentration active material containing Cannador or cannabidiol, it solves the cosmetics containing Cannador or cannabidiol or external preparation rate of release is too fast, the active constituent of high concentration generates the defect of stimulation to skin, the present invention also provides Cannadors or cannabidiol to prepare the application in cosmetics simultaneously, wherein the cosmetics are the cosmetics with liquid crystal slow-releasing system.
Description
Technical field
The present invention relates to cosmetic fields, and in particular to a kind of to contain the high concentration of Cannador or cannabidiol activity
The liquid crystal slow-releasing system of substance.
Background technique
The transmitting of cosmetic industry ingredient, refer to the effective component in cosmetics act on skin surface or enter epidermis or
Corium, and the process gathered and played a role at the position.For example, the UV absorbent in sunscreen product should be trapped in skin table
Face plays a part of to absorb and reflect ultraviolet light；Whitening agent in whitening product often acts on the basal layer in epidermis, blocks black
The generation of element；And the effect of anti-aging product ingredient then often acts on the fibroblast of skin corium, makes skin high resilience.
Studies have shown that contain a large amount of nutritional ingredient in skin care item in the market, however no matter the kind of these nutriments
Why are class and effect, if skin cannot effectively absorb, all can cause to bear to skin.And skin surface cosmetics nutritional ingredient
Surplus exactly causes the one of the major reasons of " skin oxidative ", and skin can be made premature aging occur, and metabolic function is degenerated, skin
Become drying, sensitivity, wrinkle, color spot, dark sore etc..Studies have shown that the anti-wrinkle cream nutritional ingredient there are about 90% is superfluous, not only cannot
Play the role of anti-aging, the aging of skin can be accelerated instead.For these cosmetic compositions analysis shows: wherein dimension life
The content of element, grease and amino acid has severely exceeded, and the surplus of these nutriments can contain cell division and neoblast
It generates, becomes the breeding ground of parasitic bacteria growth and breeding, to the very harmful of skin.Be used for a long time fat content up to 11% it is anti-
Wrinkle frost will accelerate the aging of Skin Cell, and our usually used cosmetics fat contents are averagely up to 15%.It is various
These all illustrate that we should more pay attention to the research of cosmetic industry ingredient " Transfer Technology ", establish more scientific, effective transmitting
System, the exploitation and application of whitening and anti-aging and other functional ingredient are just significant.
It is more to the transmitting transdermal study of drug both at home and abroad at present, it is concentrated mainly on drug permeation properties, pharmacokinetics
Several aspects such as analysis, the selection of penetrating agent, also get more and more attention in the transmission system research of cosmetics.Transport vehicle master
It to include microcapsules, liposome, nanoparticle (nanosphere, nanoemulsions, solid lipid nano granule), carrier and liquid crystal.
Liquid crystal, that is, liquid crystal (Liquid Crystal, LC), refers to Cucumber in molten condition or is dissolved by the solvent
Later, although losing the rigidity of solid matter, the easy mobility of liquid is obtained, maintains each of partiallycrystalline states material molecule
Anisotropy ordered arrangement forms a kind of intermediate state of some properties for having crystal and liquid concurrently, this to be converted from solid-state to liquid
Existing ordered orientation fluid is known as liquid crystal in the process.
Liquid crystal structure is the mesomorphic state between crystal and liquid, existing mobility and continuity as liquid,
And its molecule remains the distinctive regularly arranged mode of solid crystals, there is birefringence specific to anisotropic crystal.
There are many liquid crystal type, and liquid crystal can be divided into two major classes according to Production conditions (situation) difference: thermotropic liquid crystal (thermotropic LC)
With lysotropic liquid crystal (lyotropic LC).
Thermotropic liquid crystal refers to by single compound or the liquid crystal formed by the homogeneous mixture of a few compounds, usually one
Determine the substance for just showing liquid crystalline phase in temperature range, liquid crystalline phase is caused by temperature change.Lysotropic liquid crystal is a kind of comprising solvent
The binary of the liquid crystal that two or more compounds including compound are formed, usually Amphi-pathic compound and polar solvent composition or
Multicomponent system.Lysotropic liquid crystal is the liquid crystalline phase occurred when solute molecule concentration is in a certain range in the solution, liquid crystalline phase by
Concentration changes and causes, and wherein the liquid crystal of water and surfactant composition is one kind most commonly seen in lysotropic liquid crystal.
The formation of surfactant liquid crystal and the special construction of surfactant molecule are closely bound up.Surfactant molecule
With the no special molecular structure of other substances, one end of molecule is hydrophilic radical, and the other end is lipophilic group, has amphiphilic
Property.When the concentration of surfactant in the solution critical micelle concentration (cmc) below when, be in the form of monomer or to be adsorbed on
Form on interface exists；When concentration in the solution reaches cmc or more, molecule micella with system free energy reduce and by
Gradually formed；If molecular concentration continues to increase, further association is formed liquid crystal by micella.The formation of surfactant liquid crystal mainly according to
Rely the interaction between parents' molecule, the electrostatic force between polar group and the Van der Waals force between hydrophobic grouping.Theoretically
Surfactant liquid crystal can form 18 kinds of different structures, but common only 3 kinds: layered liquid crystal, Hexagonal liquid crystal and vertical
Square shape liquid crystal.
Now mainly there are six major class using more liquid crystal emulsifier.It is lecithin lipid, glucose glycoside, sucrose ester respectively
Class, phosphoric acid ester, olive esters and stearoyl class etc..Wherein natural liquid crystal emulsifier has glucose glycoside, sucrose ester
Class and olive esters.
In cosmetics, according to its formation condition, liquid crystal can be divided into layered liquid crystal, hexagonal crystal shape liquid crystal and cubic liquid
It is brilliant.Wherein, layered liquid crystal structure is most commonly seen.The key point that the facial treatment milk of liquid crystal structure system is different from ordinary emulsion is
One layer of stable liquid crystalline phase protective layer can be formed on lotion oil-water interfaces.It so forms liquid crystal structure and depends primarily on use
Liquid crystal emulsifier, emulsifier need to could form liquid crystal emulsifier containing parents' molecule, and being mainly characterized by one end in molecule is parent
The polar group of water, it can be miscible with the raw material of water or other polar groups, and the other end is the hydrocarbon chain or hydrophobic of oleophylic
Group can be dissolved in most of hydro carbons or nonpolar solvent.The emulsion of liquid crystal system compares ordinary emulsion.It is big with four
Advantage: first is that forming liquid crystal protective layer, the stability of formula can be improved；Second is that its result is similar to human skin barrier function, tool
There is efficient moisture-retention effect；Third is that liquid crystal protective layer can slow down the release of active constituent；Fourth is that having excellent salubrious skin sense.
Patent CN1222848A provides ascorbic dedicated transmission system, by being crosslinked non-emulsified siloxanes dissolution dimension
The method of raw element C, solves the problems, such as that the molten water of vitamin C is oxidizable, improves cosmetic result, for other skin effective components
Be transmitted without and be related to.
Patent CN104000747A discloses liquid crystal emulsified gel mask composition, composition include oil, liquid crystal emulsifier,
Polyalcohol, gelation macromolecule, skin effective component and excess water, in the composition containing various oil soluble skins effectively at
Point, reduce percutaneous moisture loss.But stimulation of the high concentration active constituent to skin is not solved, do not have yet
The liquid crystal slow-releasing system of the open high concentration active material containing Cannador or cannabidiol.
Summary of the invention
The present invention solves the cosmetics containing Cannador or cannabidiol or external preparation rate of release is too fast, high
The active constituent of concentration generates the defect of stimulation to skin, provides a kind of high concentration hemp extraction based on liquid crystal slow-releasing system
The delivery system of object or cannabidiol.
To achieve the goals above, the present invention adopts the following technical solutions:
First aspect present invention provides Cannador or cannabidiol and is preparing the application in cosmetics, wherein institute
Contain liquid crystal slow-releasing system in the cosmetics stated.
Cannabidiol (CBD) of the present invention can be chemosynthesis product, biosynthetic products, plant extracts or
It is prepared using other modes.Preferably, cannabidiol of the present invention is plant extracts, the plant extract portion
Position can be the shell of the stalk core of hemp Cannabis sativa L., flower, leaf, root and/or seed.
In one embodiment of the invention, it is containing active matter by mass percentage in the Cannador
50%-99%；Preferably, containing active matter in the Cannador by mass percentage is 60%-99%；Preferably,
Containing active matter in the Cannador by mass percentage is 95%-99%.Heretofore described active matter is to go
Except the cannabinoids substance of tetrahydrocannabinol, the active matter is selected from cannabidiol, cannabinol, hemp phenol terpene, hemp cyclic terpene
One or more of phenol, cannabidivarin, tetrahydrocannabinol, cannabigerol ester；Preferably, the active matter is
Cannabidiol.
In another embodiment of the present invention, by mass percentage containing the big of 1%-99% in the Cannador
Numb diphenol.Preferably, by mass percentage containing the cannabidiol of 50%-99% in Cannador of the present invention.More
Preferably, by mass percentage containing the cannabidiol of 60%-99% in the Cannador.It is particularly preferred, this hair
By mass percentage containing the cannabidiol of 95%-99% in the bright Cannador.
Contain Cannador by mass percentage in cosmetics of the present invention or cannabidiol is 0.01%-6%；
Preferably, contain Cannador by mass percentage in the cosmetics or cannabidiol is 0.4%-6%
Cosmetics of the present invention are selected from aerosol spray, creme, lotion, facial cleanser, dispersion, foam, coagulate
Glue, smoothing toner, toner, toner, mousse, ointment, powder, patch, pomade, solution, hand are rodlike by pump spray, cooperation
The product form that product form, the cooperation hygenic towelette of object composition form.
Liquid crystal slow-releasing system of the present invention includes liquid crystal emulsifier, fatty alcohol, polyalcohol, grease, water.
Preferably, further include skin supplement ingredient in liquid crystal slow-releasing system of the present invention, the skin-nourishing at
It is selected from hemp-seed oil, retinol, retinyl palmitate, retinyl acetate, retinol phosphate, Co-Q10, elastic egg
White, collagen, hyaluronic acid, ceramide, collagen, caffeine, chitosan, ascorbic acid, ascorbic acid glucoside,
α-bisabol, tocopherol, fertility alcohol acetic ester, arbutin, niacinamide, adenosine, retinyl acetate, vitamin A. D. E and product
Avenge the combination of one or more of careless extract.
It in an embodiment of the invention, further include hemp-seed oil in liquid crystal slow-releasing system of the present invention.This
Field technical staff be appreciated that hemp-seed oil have effects that it is anti-oxidant, remove free radical, while there is humectant, pre-
The effect that anti-chafing and treatment skin lesion, drying and help are healed.It is added when in liquid crystal system of the present invention
After hemp-seed oil, hemp-seed oil can have the function that skin nutrition jointly with cannabidiol, while enhance cannabidiol
The effect of absorbing, promoting cannabidiol.
It in an embodiment of the invention, further include centella extraction in liquid crystal slow-releasing system of the present invention
Object.Gotu Kola P.E of the present invention can also be obtained by commercially available acquisition by this field general extraction methods,
Such as it is obtained by solvent extraction method.Preferably, the Gotu Kola P.E can be prepared via a method which to obtain: by accumulated snow
Blade of grass drying and crushing is concentrated into medicinal extract after being extracted with methanol or ethyl alcohol, and medicinal extract is soluble in water, and insoluble matter is obtained by filtration, dry
To obtain the final product.It will be understood by those skilled in the art that the Gotu Kola P.E can compact epidermis and corium coupling part, skin can be made
Skin limbers up, and helps to solve cutis laxa phenomenon, keeps skin smooth flexible, help promotes collagen shape in skin corium
At regenerating fibrin, reconnect is got up, and achievees the effect that skin compact smooth.
The second aspect of the present invention provides a kind of liquid crystal slow-releasing system containing Cannador or cannabidiol, packet
Include Cannador or cannabidiol, liquid crystal emulsifier, fatty alcohol, polyalcohol, grease, water.
In one embodiment of the invention, it is containing active matter by mass percentage in the Cannador
50%-99%；Preferably, containing active matter in the Cannador by mass percentage is 60%-99%；Preferably,
Containing active matter in the Cannador by mass percentage is 95%-99%.Heretofore described active matter is to go
Except the cannabinoids substance of tetrahydrocannabinol；The active matter is selected from cannabidiol, cannabinol, hemp phenol terpene, hemp cyclic terpene
One or more of phenol, cannabidivarin, tetrahydrocannabinol, cannabigerol ester；Preferably, the active matter is
Cannabidiol.
In another embodiment of the present invention, by mass percentage containing the big of 1%-99% in the Cannador
Numb diphenol.Preferably, by mass percentage containing the cannabidiol of 50%-99% in Cannador of the present invention.More
Preferably, by mass percentage containing the cannabidiol of 60%-99% in the Cannador.It is particularly preferred, this hair
By mass percentage containing the cannabidiol of 95%-99% in the bright Cannador.
Contain Cannador by mass percentage in cosmetics of the present invention or cannabidiol is 0.01%-6%；
Preferably, contain Cannador by mass percentage in the cosmetics or cannabidiol is 0.4%-6%
Cannador of the present invention is to extract to obtain by hemp plant, the extract part packet of the hemp plant
Include the shell of stalk core, flower, leaf, root and/or seed；The Cannador can be the different plant parts of hemp plant point
The combination for indescribably taking the extract or extract to be formed is also possible to different plant parts of hemp plant or combinations thereof simultaneously
It extracts, the combination of obtained extract or extract.Preferably, Cannador of the present invention is hemp leaf extract.
Cannador of the present invention is to extract to obtain by general extraction methods, is preferably obtained by solvent extraction
It arrives.The Extraction solvent is selected from water, low mass molecule alcohol or its aqueous solution, acetic acid esters, ketone, ether or lower boiling hydrocarbons；Described is low
Molecule alcohol includes methanol, ethyl alcohol, butanol or propyl alcohol；The acetic acid esters includes methyl acetate or ethyl acetate；The ketone packet
Include acetone；The ether includes methyl ether or ether；The lower boiling hydrocarbons includes aliphatic hydrocarbon, aromatic hydrocarbon or hydrogenate hydrocarbon.It is preferred that
, the Extraction solvent is selected from water or ethanol solution.
In one embodiment of the invention, the Cannador can obtain by the following method:
1) raw material are heated to reflux using or mixtures thereof Extraction solvent；
2) it is filtered to remove residue；
3) it extracts；
4) adjusting pH value is 2-4；
5) it is extracted with Extraction solvent, then removes solvent；
6) chromatographic isolation is carried out, Cannador is obtained；
Preferably, hemp extract part is heated using or mixtures thereof 3-10 times of Extraction solvent measured in the step 1)
Reflux at least 1 hour；Extractant described in step 3) is to contain 20wt% second in the Cannador extracting method
The sodium hydrate aqueous solution of alcohol；PH adjusting agent is the mixed liquor of extract liquor and 5% sulfuric acid solution in the step 4)；Described is big
The flowing phase mixture that chromatographic isolation described in step 6) is applied in nettle extract extracting method is by methanol/water and acetic acid or second
Alcohol/water and acetic acid composition.
It should be noted that " 3-10 times is measured " etc. in the application describes, refer to that the volume of the Extraction solvent of use is to mention
3-10 times of position quality is taken, for example, hemp extract part is 1g, the dosage of Extraction solvent is 3mL-10mL.
In one particular embodiment of the present invention, the Cannador can obtain by the following method:
1) raw material are crushed to 10-40 mesh, obtain powder；
2) gained powder Extraction solvent cold soaking is extracted, obtains extracting solution；
3) by resulting extracting liquid decoloration；
4) it is concentrated under reduced pressure to get Cannador medicinal extract.
Preferably, it in the step 2), is extracted 1-3 times with the ethyl alcohol cold soaking of 4-8 times of amount, 30%-60%, each 0.5-2
Hour；Decoloration is decolourized using 0.1-1wt% activated carbon adsorption in the step 3)；Reduced pressure under the conditions of 70 DEG C is dense
Being reduced to relative density is 1.01-1.03.
Preferably, containing liquid crystal emulsifier in the liquid crystal slow-releasing system by mass percentage is 2%-9%；It is further excellent
Choosing, containing liquid crystal emulsifier in the liquid crystal slow-releasing system by mass percentage is 2%-5%；Most preferably, the liquid crystal
Containing liquid crystal emulsifier in slow-releasing system by mass percentage is 2%；The liquid crystal emulsifier is selected from cholesterol, hydrogenation lecithin
One or more of rouge, alkyl glucoside, ceramide, stereth, stearate；Preferably alkyl glucosides
Glycosides.
Preferably, containing fatty alcohol in the liquid crystal slow-releasing system by mass percentage is 3%-10%；Further preferably
, containing fatty alcohol in the liquid crystal slow-releasing system by mass percentage is 3%-5%；Quality is pressed in the liquid crystal slow-releasing system
It is 3.5% that percentage, which contains fatty alcohol,；The fatty alcohol is selected from cetostearyl alcohol, behenyl alcohol, nonyl alcohol, laruyl alcohol, nutmeg
One or more of alcohol, oleyl alcohol, sub- oleyl alcohol, castor-oil plant alcohol, arachidic alcohol, behenyl alcohol or sinapinic alcohol；Preferably cetearyl alcohol
Alcohol Huo behenyl alcohol.
Preferably, containing polyalcohol in the liquid crystal slow-releasing system by mass percentage is 2%-8%；Further preferably
, containing polyalcohol in the liquid crystal slow-releasing system by mass percentage is 4%-6%；Most preferably, the liquid crystal sustained release
Containing polyalcohol in system by mass percentage is 5%；The polyalcohol be selected from propylene glycol, glycerol, butanediol, polyethylene glycol,
One or more of hexylene glycol, xylitol, polypropylene glycol, D-sorbite；Preferably butanediol.
Preferably, containing grease in the liquid crystal slow-releasing system by mass percentage is 0.01%-9%；Further preferably
, containing grease in the liquid crystal slow-releasing system by mass percentage is 1%-8%；Most preferably, the liquid crystal slow-releasing system
In by mass percentage containing grease be 7%；Preferably, the grease includes solid or semisolid grease, liquid fat；Into
One step is preferred, and the solid or semisolid grease is higher melting-point solid or semisolid grease, described higher melting-point solid
Body or semisolid grease are selected from the combination of one or more of mango seed ester, shea butter, vaseline, and the liquid crystal is slow
It releases and contains solid or semisolid grease in system by mass percentage for 0.01%-3%；It is further preferred that the liquid crystal is slow
Releasing in system by mass percentage is 0.5%-1.5%, most preferably, the liquid crystal sustained release containing solid or semisolid grease
Containing solid or semisolid grease in system by mass percentage is 1%；The liquid fat is preferably the lower liquid oil of polarity
Rouge, the lower liquid fat of polarity be selected from one or both of ethylhexyl palmitate, carbonic acid dioctyl ester, monoglyceride with
On combination, containing liquid fat be by mass percentage 0.01%-6% in the liquid crystal slow-releasing system, it is further preferred that
Containing liquid fat in the liquid crystal slow-releasing system by mass percentage is 5%-6%, most preferably, the liquid crystal slow-releasing system
In by mass percentage containing liquid fat be 6%.
It in one embodiment of the invention, further include skin supplement ingredient in the liquid crystal slow-releasing system, the liquid crystal
Containing skin supplement ingredient in slow-releasing system by mass percentage is 0.01%-2%, it is preferred that in the liquid crystal slow-releasing system
It is by mass percentage 1%-2% containing skin supplement ingredient.It is furthermore preferred that the skin supplement ingredient is hemp-seed oil,
Wherein containing hemp-seed oil in the liquid crystal slow-releasing system by mass percentage is 1%-2%.
In one particular embodiment of the present invention, the liquid crystal sustained release containing Cannador or cannabidiol
System includes following components and content by mass percentage:
In one particular embodiment of the present invention, the liquid crystal sustained release containing Cannador or cannabidiol
System includes following components and content by mass percentage:
It is furthermore preferred that the liquid crystal slow-releasing system containing Cannador or cannabidiol includes by mass percentage
Following components and content:
Liquid crystal slow-releasing system of the present invention prevents light and heat to work by the way that high concentration active material cladding is got up
The degradation of property substance, while can control the slow release of active constituent and the infiltration of active constituent can be promoted.For sensitive work
Property substance, can control directly contacting for these substances and skin using liquid crystal slow-releasing system, reduce the stimulation to skin, play
The effect of sustained release.The rate of release of active constituent in liquid crystal can also be adjusted by the interaction of liquid crystal and cuticula
Section reduces transmitting of the active constituent being dissolved in oil droplet between interface, realizes the lasting release of active constituent, is that skin is abundant
It is absorbed and utilized.
Detailed description of the invention
Hereinafter, carrying out the embodiment that the present invention will be described in detail in conjunction with attached drawing, in which:
Fig. 1: in vitro in transdermal experiment, with the extension of time, the cannabidiol of non-liquid crystal slow-releasing system sample A is accumulated
Transmitance situation of change；
Fig. 2: in vitro in transdermal experiment, with the extension of time, the cannabidiol of non-liquid crystal slow-releasing system sample B is accumulated
Transmitance situation of change；
Fig. 3: in vitro in transdermal experiment, with the extension of time, the cannabidiol of non-liquid crystal slow-releasing system sample C is accumulated
Transmitance situation of change；
Fig. 4: in vitro in transdermal experiment, with the extension of time, the cannabidiol accumulation of liquid crystal slow-releasing system sample E is saturating
Cross rate situation of change；
Fig. 5: in vitro in transdermal experiment, with the extension of time, the cannabidiol accumulation of liquid crystal slow-releasing system sample F is saturating
Cross rate situation of change；
Fig. 6: in vitro in transdermal experiment, with the extension of time, the cannabidiol accumulation of liquid crystal slow-releasing system sample G is saturating
Cross rate situation of change；
Fig. 7: the quantity of the liquid crystal of polarized light microscope observing liquid crystal slow-releasing system sample E and the image of distribution；
Fig. 8: the quantity of the liquid crystal of polarized light microscope observing liquid crystal slow-releasing system sample F and the image of distribution；
Fig. 9: the quantity of the liquid crystal of polarized light microscope observing liquid crystal slow-releasing system sample G and the image of distribution.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiment is only section Example of the invention, rather than all.Based in the present invention
Embodiment, every other embodiment obtained by those of ordinary skill in the art without making creative efforts, all
Belong to the scope of protection of the invention.
The preparation of 1 Cannador of embodiment
(1) raw material (hemp stalk core, cannabis, marihuana) is cleaned and is air-dried；
(2) raw material after above-mentioned air-dry are crushed, rear 40 mesh of mistake；
(3) it by gained powder, is extracted 2 times, every time 1.5 hours with the ethyl alcohol cold soaking of 6 times of amounts, 45%；
(4) combined extract is decolourized through 0.5wt% activated carbon adsorption；
Under the conditions of (5) 70 DEG C of temperature, relative density 1.02 is concentrated under reduced pressure into get Cannador medicinal extract.
According to above-mentioned preparation method,
When raw material are marihuana, Cannador 1A is obtained；
When raw material are cannabis, Cannador 1B is obtained；
When raw material are hemp stalk core, Cannador 1C is obtained；
When raw material are marihuana and cannabis, Cannador 1D is obtained；
It is wherein 50% containing active matter content in Cannador 1A, the content of cannabidiol is in active matter
90%.
The preparation of 2 Cannador of embodiment
(1) raw material (marihuana, hemp stalk core, cannabis) are heated to reflux 1 hour using the ethyl alcohol of 9 times of amounts；
(2) it is filtered to remove residue, removes solvent under vacuum condition；
(3) medicinal extract of acquisition is heated about 40 minutes at about 125 DEG C of temperature；
(4) chromatographic isolation is then carried out, wherein flowing phase mixture is made of ethanol/water and acetic acid to get hemp extraction
Object.
According to above-mentioned preparation method,
When raw material are marihuana, Cannador 2A is obtained；
When raw material are cannabis, Cannador 2B is obtained；
When raw material are hemp stalk core, Cannador 2C is obtained；
When raw material are marihuana and cannabis, Cannador 2D is obtained；
It is wherein 80% containing active matter content in Cannador 2A, the content of cannabidiol is in active matter
92%.
The preparation of 3 Cannador of embodiment
(1) raw material (marihuana, hemp stalk core, cannabis) are heated to reflux 1.5 hours using the ethyl alcohol of 7 times of amounts；
(2) it is filtered to remove residue；
(3) it is at least extracted twice with 5% sodium hydrate aqueous solution, wherein contains 20wt%'s in sodium hydrate aqueous solution
Ethyl alcohol；
(4) extract liquor is mixed with 5% sulfuric acid solution so that pH value 3；
(5) it is then extracted twice using aliphatic hydrocarbon, removes solvent under cryogenic vacuum；
(6) chromatographic isolation is then carried out, wherein flowing phase mixture is made of ethanol/water and acetic acid to get hemp extraction
Object.
According to above-mentioned preparation method,
When raw material are marihuana, Cannador 3A is obtained；
When raw material are cannabis, Cannador 3B is obtained；
When raw material are hemp stalk core, Cannador 3C is obtained；
When raw material are marihuana and cannabis, Cannador 3D is obtained；
It is wherein 99% containing active matter content in Cannador 3A, the content of cannabidiol is in active matter
95%.
The preparation of 4 liquid crystal slow-releasing system of embodiment
It is formulated (mass percent): hemp leaf extract (the Cannador 1A obtained in embodiment 1) 0.4%, alkyl
2%, behenyl alcohol 3.5% of glucoside, butanediol 5%, vaseline 1%, monoglyceride 6%, moisturizing to 100%.
Preparation method: oily phase (hemp leaf extract, alkyl glucoside, behenyl alcohol, vaseline, monoglyceride) is accurately weighed, and is stirred
It mixes and is heated to 70 DEG C -75 DEG C, insulated sterilizing；Accurately weigh water phase (butanediol, water) with another container, be heated with stirring to 75 DEG C-
80 DEG C, insulated sterilizing；During the oil phase is added to the aqueous phase, after homogeneous 3-5min, is stirred at low speed using blender and be cooled to room temperature, obtained
Liquid crystal slow-releasing system containing hemp leaf extract, is denoted as product 1.
The preparation of 5 liquid crystal slow-releasing system of embodiment
It is formulated (mass percent): hemp leaf extract (the Cannador 1A obtained in embodiment 1) 0.6%, alkyl
3%, behenyl alcohol 5% of glucoside, butanediol 4%, vaseline 2%, monoglyceride 4%, hemp-seed oil (containing 10% active constituent)
1%, moisturizing to 100%.
Preparation method: oily phase (hemp leaf extract, alkyl glucoside, behenyl alcohol, vaseline, monoglyceride, hempseed are accurately weighed
Oil), and 70 DEG C -75 DEG C are heated with stirring to, insulated sterilizing；Water phase (butanediol, water), agitating and heating are accurately weighed with another container
To 75 DEG C -80 DEG C, insulated sterilizing；During the oil phase is added to the aqueous phase, after homogeneous 3-5min, is stirred at low speed using blender and be cooled to room
Temperature obtains the liquid crystal slow-releasing system containing hemp leaf extract, is denoted as product 2.
The preparation of 6 liquid crystal slow-releasing system of embodiment
It is formulated (mass percent): hemp leaf extract (the Cannador 1A obtained in embodiment 1) 2%, alkyl Portugal
4%, behenyl alcohol 6% of glucosides, butanediol 6%, vaseline 0.5%, monoglyceride 5%, hemp-seed oil (containing 10% active constituent)
2%, moisturizing to 100%.
Preparation method: it is identical as 5 preparation method of embodiment, it is denoted as product 3.
The preparation of 7 liquid crystal slow-releasing system of embodiment
It is formulated (mass percent): hemp leaf extract (the Cannador 2A obtained in embodiment 2) 0.01%, alkyl
2%, behenyl alcohol 3% of glucoside, butanediol 8%, vaseline 0.01%, monoglyceride 0.01%, Gotu Kola P.E (trade name
CENTELLA ASIATICA EXTRACT (WS) CH is bought in Sabinsa Corporation) 1.5%, lactic acid 0.8%, it mends
Water is to 100%.
Preparation method: oily phase (hemp leaf extract, alkyl glucoside, behenyl alcohol, vaseline, monoglyceride, centella are accurately weighed
Extract), and 70 DEG C -75 DEG C are heated with stirring to, insulated sterilizing；With another container accurately weigh water phase (butanediol, lactic acid,
Water), 75 DEG C -80 DEG C are heated with stirring to, insulated sterilizing；During the oil phase is added to the aqueous phase, after homogeneous 3-5min, blender low speed is used
Stirring is cooled to room temperature, obtains the liquid crystal slow-releasing system containing hemp leaf extract, is denoted as product 4.
The preparation of 8 liquid crystal slow-releasing system of embodiment
It is formulated (mass percent): hemp leaf extract (the Cannador 3A obtained in embodiment 3) 6%, alkyl Portugal
9%, behenyl alcohol 10% of glucosides, butanediol 2%, vaseline 3%, monoglyceride 6%, Gotu Kola P.E (trade name CENTELLA
ASIATICA EXTRACT (WS) CH is bought in Sabinsa Corporation) 0.01%, lactic acid 0.01%, moisturizing is extremely
100%.
Preparation method: it is identical as 7 preparation method of embodiment, it is denoted as product 5.
The preparation of 9 liquid crystal slow-releasing system of embodiment
It is formulated (mass percent): hemp leaf extract (the Cannador 1A obtained in embodiment 1) 3%, alkyl Portugal
5.5%, behenyl alcohol 6.5% of glucosides emulsifier, butanediol 5%, vaseline 1.5%, monoglyceride 3%, Gotu Kola P.E (quotient
The name of an article CENTELLA ASIATICA EXTRACT (WS) CH is bought in Sabinsa Corporation) 0.75%, lactic acid
0.4%, moisturizing to 100%.
Preparation method: it is identical as 7 preparation method of embodiment, it is denoted as product 6.
Cannador Transdermal absorption is tested in 10 liquid crystal slow-releasing system of embodiment
This experiment passes through hemp in comparative liquid crystal slow-releasing system and existing common non-liquid crystal slow-releasing system formula (creme)
The Transdermal absorption situation of extract tests the sustained release release performance of liquid crystal slow-releasing system.Wherein, non-liquid crystal slow-releasing system formula is adopted
With existing common cosmetic, specific sample formulations are referring to table 1.In addition, due in this experiment Cannador it is main
Ingredient is cannabidiol (CBD), while in view of instrument detection limit and measurement accuracy rate, therefore is detected main in Cannador
The content of ingredient CBD is wanted to calculate transmitance.
One, experimental method
1, the preparation of mouse skin
Rat is broken after neck execution, and the hair of abdomen is shaved off with hair cutter, coats depilatory cream, scrapes off depilatory cream after placing 5min,
It is cleaned with physiological saline, peels skin of abdomen, cleared subcutaneous fat is cleaned, is laid on preservative film and wraps up, in -20
DEG C refrigerator cold-storage, it is spare, it is no more than 7d.
2, Franz diffusion cell Transdermal absorption is tested
Rat skin is fixed between the two upper and lower chambers of Franz diffusion cell, cuticula upward, acceptance pool (diffusion area
2cm2, volume 12mL) and physiological saline is contained, and acceptable solution is just contacted with skin corium, and 5mL sample is contained in sample cell.In constant temperature
Constant speed (180rmin is kept at (37 DEG C ± 0.1) DEG C-1) be stirred continuously.Later in 2,4,6,8,10,12, take respectively for 24 hours
0.5mL acceptable solution is ready for testing in next step in EP pipe, and supplements the acceptable solution of equivalent.
The acceptable solution for taking each sample each period respectively, using the concentration of sample in liquid phase detection method detection acceptable solution.Root
According to formula, Percutaneous permeability Q (mg/cm can be calculated2), then transmitance is calculated by Percutaneous permeability.
Note: wherein Q: Percutaneous permeability, S: transdermal diffusion area (diffusion cell R=0.8cm, S=2cm2)V1: Franz expands
Dissipate the volume (V of pond acceptance pool1=12mL), ρnMass fraction (mg/mL) ρ of acceptable solution when being sampled for n-thiFor i-th sampling
When acceptable solution mass concentration (mg/mL), V2For sampling amount.
Liquid crystal slow-releasing system compares the infiltration enhancing rate formula of non-liquid crystal slow-releasing system:
Permeate enhancing rate=(liquid crystal system transmitance-non-liquid crystal system transmitance)/non-liquid crystal system transmitance
3, sample formulations
The preparation formula of table 1 liquid crystal slow-releasing system and non-liquid crystal slow-releasing system
Table 2 different moments each sample transmitance
Two, detection method
Using octadecylsilane chemically bonded silica as filler (C18,4.6 × 150mm, 5 μm of chromatographic column), with acetonitrile-water
(70:30) is mobile phase, and Detection wavelength 210nm, flow velocity 1mL/min, column temperature is 25 DEG C.
The preparation of reference substance solution: taking CBD reference substance 15.0mg, accurately weighed, sets in 100mL measuring bottle, with chromatographic grade first
Alcohol dissolves and is diluted to scale, shakes up, and precision measures the above-mentioned solution of 5mL, sets in 50mL measuring bottle, is settled to quarter with hplc grade methanol
Degree, shakes up, and nylon membrane is crossed, as reference substance solution.
The preparation of test solution: taking 100 μ L acceptable solutions in 1.5mLEP pipe, adds 900 μ L of hplc grade methanol,
Fullyd shake on oscillator sufficiently to extract, after static 15min, be centrifuged 1min in 10000r/min centrifuge, with 2mL without
Bacterium syringe takes supernatant liquor, crosses nylon66 fiber (0.45 μm) film, spare as test solution.
It is tested according to chromatographic condition setting and its parameter, records the area at peak.
Three, experimental result
If attached drawing 1 and the comparison of attached drawing 4 can be seen that the 0-4h after experiment starts, slope is lower in Fig. 4, shows to possess liquid
The cosmetics of crystal system sample E maintain extremely low skin permeation rate when starting, and ensure that the extremely strong slow-release capability of liquid crystal system.And
When experimental period is in 4-6h, slope obviously becomes larger, i.e., infiltration rate has great promotion.Finally, after testing 6h,
Infiltration rate reverts to and the comparable stage of non-liquid crystal system sample A；Meanwhile by attached drawing 2 and attached drawing 5 to when 3 He of attached drawing
The comparison of attached drawing 6 also has same effect.Thus it proves, the more non-liquid crystal sustained release of formula of liquid crystal slow-releasing system of the present invention
System compares and is able to maintain extremely strong slow-release capability.
In addition, by Fig. 1-6 and table 2 it is found that the transmitance of non-liquid crystal slow-releasing system sample B be 6.1%, liquid crystal slow-releasing system
The transmitance of sample F is 6.6%, is computed the transmitance for learning the more non-liquid crystal slow-releasing system sample B of liquid crystal slow-releasing system sample F
There is 8.2% or so considerable degree of promotion, likewise, the more non-liquid crystal slow-releasing system sample A of liquid crystal slow-releasing system sample E
Transmitance promotes 7.8%, and the transmitance of the more non-liquid crystal slow-releasing system sample C of liquid crystal slow-releasing system sample G promotes 6.1%.Thus
It proves, the transmitance of the formula of the more non-liquid crystal slow-releasing system of formula of liquid crystal slow-releasing system of the present invention to Cannador
It is promoted.
As shown in Table 2, after the active matter content variation of Cannador in liquid crystal slow-releasing system, liquid of the present invention
Brilliant slow-releasing system formula can still be maintained slow-release capability and promote transmitance.
11 polarized light microscopy of embodiment observes liquid crystal emulsified system
Liquid crystal slow-releasing system sample E, sample F, the sample G for taking a small amount of embodiment 10 to prepare are placed on glass slide, with lid glass
Piece gently flattens, and uses the quantity and distribution of polarized light microscope observing product liquid crystal.As a result as Figure 7-9, marihuana extracts
Object isoreactivity substance/functional component is successfully coated among system.And desired liquid crystal emulsified system is formd, from
And reached the lasting release of active constituent, the purpose utilized is fully absorbed for skin.
The experiment of 12 human-body safety of embodiment
The relevant regulations of the human safety method of inspection in this agreement with experimental " cosmetics safety technical specification ".
Necessary toxicology is completed before this test to examine, inspection result is qualification.
Human skin patch-skin closure type patch test
1. test objective
Detection tested material causes the Potential feasibility of human skin adverse reaction.
2. test material
2.1 test products
6 kinds of liquid crystal slow-releasing systems involved in embodiment 4-9 select the formula of every kind of product to carry out test human body peace respectively
Full property test), totally 6 products.
2.2 patch material
Area is no more than 50mm2, depth about 1mm qualified spot tester material.
3. the selection of subject
Satisfactory society volunteer 180, the age 20-45 years old, male 60, was divided into 6 groups by product, often by female 120
Group 30 is tried out the formula in embodiment 4-9 in listed 6 class products by group, wherein every group of 10 males, 20 women respectively.
4. test method
4.1 take tested products 0.020mL-0.025mL (liquid) respectively, are put into the small interior of spot tester.
4.2 control wells are without any processing.
4.3 will be pasted on the back or forearm song side of subject added with the spot tester of tested material with low sensitization adhesive tape, use hand
The light pressure of the palm is allowed to equably be pasted on skin, continues for 24 hours.
4.4 after removing tested material spot device 30min (after impression disappearance after), for 24 hours with 48h press 3 standard sight skin of table
Skin reaction.
3 skin closure type patch test dermoreaction grade scale of table
5. test result
Negative reaction is presented in the test result of all products, it was demonstrated that and consumer safety provided by the invention is guaranteed,
The adverse reactions such as skin irritation, sensitization (easy allergic human population or to the crowd of this product allergy except) will not be generated；
The preferred embodiment of the present invention has been described above in detail, still, during present invention is not limited to the embodiments described above
Detail within the scope of the technical concept of the present invention can be with various simple variants of the technical solution of the present invention are made, this
A little simple variants all belong to the scope of protection of the present invention.
It is further to note that specific technical features described in the above specific embodiments, in not lance
In the case where shield, can be combined in any appropriate way, in order to avoid unnecessary repetition, the present invention to it is various can
No further explanation will be given for the combination of energy.
In addition, various embodiments of the present invention can be combined randomly, as long as it is without prejudice to originally
The thought of invention, it should also be regarded as the disclosure of the present invention.
Claims (15)
1. Cannador or cannabidiol are preparing the application in cosmetics, wherein the cosmetics are to be sustained with liquid crystal
The cosmetics of system.
2. application according to claim 1, which is characterized in that the Cannador is hemp leaf extract, described big
Containing active matter in nettle extract by mass percentage is 50%-99%, and the active matter is the big of removal tetrahydrocannabinol
Numb phenolic substances；Preferably, the active matter is selected from cannabidiol, cannabinol, hemp phenol terpene, cannabichromene, secondary hemp
One or more of diphenol, tetrahydrocannabinol, cannabigerol ester.
3. application according to claim 1, which is characterized in that contain 1%- by mass percentage in the Cannador
99% cannabidiol；Preferably, by mass percentage containing the cannabidiol of 50%-99% in the Cannador.
4. application according to claim 1, which is characterized in that mentioned by mass percentage containing hemp in the cosmetics
It takes object or cannabidiol is 0.01%-6%.
5. application according to claim 1, which is characterized in that the liquid crystal slow-releasing system includes liquid crystal emulsifier, rouge
Fat alcohol, polyalcohol, grease, water.
6. application according to claim 5, which is characterized in that further include hemp-seed oil in the liquid crystal slow-releasing system.
7. a kind of liquid crystal slow-releasing system containing Cannador or cannabidiol, which is characterized in that including Cannador or
Cannabidiol, liquid crystal emulsifier, fatty alcohol, polyalcohol, grease, water.
8. liquid crystal slow-releasing system according to claim 7, which is characterized in that in the Cannador by mass percentage
It is 50%-99% containing active matter, the active matter is the cannabinoids substance for removing tetrahydrocannabinol, the active matter
In cannabidiol, cannabinol, hemp phenol terpene, cannabichromene, cannabidivarin, tetrahydrocannabinol, cannabigerol ester
One or more；Preferably, the active matter is cannabidiol.
9. liquid crystal slow-releasing system according to claim 7, which is characterized in that press quality hundred in the liquid crystal slow-releasing system
Divide than being 0.01%-6% containing Cannador or cannabidiol.
10. liquid crystal slow-releasing system according to claim 7, which is characterized in that liquid crystal emulsified in the liquid crystal slow-releasing system
Agent is selected from one or both of cholesterol, hydrolecithin, alkyl glucoside, ceramide, stereth, stearate
More than；Preferably, liquid crystal emulsifier is alkyl glucoside in the liquid crystal slow-releasing system.
11. liquid crystal slow-releasing system according to claim 7, which is characterized in that fatty alcohol selects in the liquid crystal slow-releasing system
From cetostearyl alcohol, behenyl alcohol, nonyl alcohol, laruyl alcohol, myristyl alcohol, oleyl alcohol, sub- oleyl alcohol, castor-oil plant alcohol, arachidic alcohol, behenyl alcohol or mustard
One or more of sub- alcohol；Preferably cetostearyl alcohol Huo behenyl alcohol.
12. liquid crystal slow-releasing system according to claim 7, which is characterized in that polyalcohol selects in the liquid crystal slow-releasing system
From one or both of propylene glycol, glycerol, butanediol, polyethylene glycol, hexylene glycol, xylitol, polypropylene glycol, D-sorbite with
On；Preferably butanediol.
13. liquid crystal slow-releasing system according to claim 7, which is characterized in that grease is selected from the liquid crystal slow-releasing system
Solid grease or semisolid grease, liquid fat.
14. liquid crystal slow-releasing system according to claim 7, which is characterized in that further include big in the liquid crystal slow-releasing system
Flaxseed oil, wherein containing hemp-seed oil in the liquid crystal slow-releasing system by mass percentage is 1%-2%.
15. liquid crystal slow-releasing system according to claim 7, which is characterized in that by mass percentage include following components and
Content:
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Cited By (5)
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| WO2021018936A1 (en) | 2019-07-29 | 2021-02-04 | Echo Pharmaceuticals B.V. | Treatment of inflammatory skin conditions |
| WO2021018934A1 (en) | 2019-07-29 | 2021-02-04 | Echo Pharmaceuticals B.V. | Treatment of sebaceous gland disorders |
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Cited By (6)
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| WO2021018936A1 (en) | 2019-07-29 | 2021-02-04 | Echo Pharmaceuticals B.V. | Treatment of inflammatory skin conditions |
| WO2021018934A1 (en) | 2019-07-29 | 2021-02-04 | Echo Pharmaceuticals B.V. | Treatment of sebaceous gland disorders |
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