CN104069322A - Pharmaceutical composition with facial whitening and spot lightening effects and preparation method and application thereof - Google Patents
Pharmaceutical composition with facial whitening and spot lightening effects and preparation method and application thereof Download PDFInfo
- Publication number
- CN104069322A CN104069322A CN201410248234.8A CN201410248234A CN104069322A CN 104069322 A CN104069322 A CN 104069322A CN 201410248234 A CN201410248234 A CN 201410248234A CN 104069322 A CN104069322 A CN 104069322A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- skin
- whitening
- light speckle
- speckle effect
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
The invention discloses a pharmaceutical composition with facial whitening and spot lightening effects and a preparation method and application thereof. The raw materials of the pharmaceutical composition disclosed by the invention are natural active extracts, thereby being free of irritation to skin. The pharmaceutical composition with facial whitening and spot lightening effects is prepared from the following raw materials of rubia yunnanensis, firethorn fruits, coleus forskohlii, mulberry, cuckoopint and saxifrage, wherein the percentage by mass of any component is not greater than 40% of the total mass. The pharmaceutical composition disclosed by the invention is novel and reasonable in formula and simple in preparation method. Cell experiments, animal experiments and human experiments prove that the pharmaceutical composition is remarkable in facial whitening and spot lightening effects, safe, free of irritation or sensitization to skin and good in social and economic benefits.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation method thereof, particularly a kind of used for cosmetic pharmaceutical composition with the light speckle effect of face whitening and preparation method thereof, is suitable for the cosmetics that make an addition to cream class, white class, newborn class, liquid class (except perfume).
Background technology
As the saying goes " one white hide three ugly ", great beauty, face are white as a jade, are yearned for by people from ancient times.Nails is always advocated pale skin, and skin whitening is that each girl pursues." Chinese Skin typology " report of being presided over by the Dermatology expert De of life science institute of L'Oreal-professor La Xiali is pointed out: " comparing with European women; Chinese women is in ageing processes of skin; what first show is mottle problem, and pigmentation can increase along with the increase at age ".Therefore in China, freckle removing and whitening articles for use are in great demand always, and its sales volume is constantly created new peak, have become one of main flow kind of skin protection cosmetics at present.Whitening chemicals refer to the formation by acting on dermal melanin, certain stage of metabolic pathway, control, check melanin generates, thereby reduce skin colourity or alleviate pigmentation, take and reach the chemicals of the natural or synthetic that skin-whitening is object.The domestic and international whitening chemicals for cosmetics are mainly hydroquinone, kojic acid, fruit acid, arbutin and vitamin C derivatives etc. at present, hydroquinone and mercury salt can reach rapid whitening effect, but its toxic and side effects is large, life-time service can cause the permanent decolouring of skin and contact dermatitis.Life-time service kojic acid has cytotoxicity, and can increase the incidence rate of the gonad cell chromosome interchange and chromosomal aberration, but kojic acid derivative whitening function is stronger, and toxic and side effects is less, and current skin-lightening cosmetic is many as effective ingredient; Arbutin action temperature and, but using dosage is excessive, have a toxic and side effects similar with kojic acid.Vitamin C derivatives has poor stability and the shortcoming such as expensive.(Nerya?O，Musa?R，Khatib?s，eta1.Chalcones∞potent?tyrosinasc?inhibitors：the?effect?ofhydroxyl?positions?and?numbers[J].Phytochemistry，，2004,65：1389-1395)
Due to synthetic chemistry goods, there is the safety problems such as zest, anaphylaxis, and plant whitening product not only has pure natural property, the popularity in source, wide in variety nontoxic, the advantage such as have no side effect, still the various functions such as antibacterial, the sebum of tool and cutin adjusting, enhancing body local immunity, so each cosmetics company drops into huge sum of money development of new plant whitening product one after another.(Smit N, Vicanova J, Pavel S.The hunt for natural skin whitening agents[J] .Int J Mol Sci, 2009,10 (12): 5326-5349; Kamakshi R.Fairness via formulations:a review of cosmetic skin-Iightening ingredients[J] .J Cosmet Sci, 2012,63 (1): 43-54) the existing 2,000 years history of Chinese medicine beauty treatment, accumulated rich experience, at present, in Japan, containing the cosmetics of natural Chinese medicinal herb, accounted for the more than 50% of whole Cosmetic Market.Therefore, the research of this respect is the focus of cosmetic field research and development always.(Shu Shumiao, Xiao Feng, Pan Qin. the progress of whitening Chinese medicament and plant amedica. external medical plant amedica fascicle, 2007,22 (6): 252-255) as patent 200810024411.9, this patent discloses a kind of Chinese medicine composition and application thereof with whitening function, this Chinese medicine composition by Radix Scutellariae, Rhizoma Polygoni Cuspidati, Cortex Moutan extract is composite forms.As patent 200910192274.4, this patent discloses a kind of whitening and spot eliminating cream and preparation method thereof, active component is Chinese medicine extraction liquid, and Chinese medicine is comprised of the component of following Chinese medicine percent: Rhizoma Gymnadeniae 5～55%, Flos Ginseng 15～35%, Flos Albiziae 5～15%, Flos Lonicerae 5～15%, Flos Rosae Rugosae 15～20%, Flos Chrysanthemi 5～10%.As patent 201010261392.9, this patent discloses a kind of compositions for the light speckle of face whitening, plant extraction lightening compositions and has had the compositions of whitening function, said composition comprises the spermidine derivant of effective dose, and beauty treatment or the upper acceptable vehicle of pharmacology.
Summary of the invention
The object of the invention is, in order to overcome weak point of the prior art, provides a kind of medical composition and its use with the light speckle effect of face whitening.
The pharmaceutical composition with the light speckle effect of face whitening of the present invention, take Radix Rubiae Yunnanensis, firethorn fruit, Coleus forskohlii Briq., Fructus Mori, Trillium tschonoskii Maxim and Herba Saxifragae to prepare as raw material, and the weight percentage of arbitrary component is all no more than 40% of total amount;
The pharmaceutical composition with the light speckle effect of face whitening is to prepare with the raw material of following mass fraction: 1～60 part of Radix Rubiae Yunnanensis, 1～60 part of firethorn fruit, 1～60 part of Coleus forskohlii Briq., 1～60 part, Fructus Mori, 1～60 part of Trillium tschonoskii Maxim, 1～60 part of Herba Saxifragae.
The pharmaceutical composition with the light speckle effect of face whitening is to prepare with the raw material of following mass fraction: 1～50 part of Radix Rubiae Yunnanensis, 1～50 part of firethorn fruit, 1～50 part of Coleus forskohlii Briq., 1～50 part, Fructus Mori, 1～50 part of Trillium tschonoskii Maxim, 1～50 part of Herba Saxifragae.
Preferably, described in there is the pharmaceutical composition of the light speckle effect of face whitening, be to prepare with the raw material of following parts by weight:
1～40 part of Radix Rubiae Yunnanensis
1～40 part of firethorn fruit
1～40 part of Coleus forskohlii Briq.
1～40 part, Fructus Mori
1～40 part of Trillium tschonoskii Maxim
1～40 part of Herba Saxifragae
Preferably, described in there is the pharmaceutical composition of the light speckle effect of face whitening, be to prepare with the raw material of following parts by weight:
2～35 parts of Radix Rubiae Yunnanensis
2～35 parts of firethorn fruits
2～35 parts of Coleus forskohlii Briq.s
2～35 parts, Fructus Mori
2～35 parts of Trillium tschonoskii Maxims
2～35 parts of Herba Saxifragaes
Preferably, described in there is the pharmaceutical composition of the light speckle effect of face whitening, be to prepare with the raw material of following parts by weight:
8～30 parts of Radix Rubiae Yunnanensis
8～30 parts of firethorn fruits
8～30 parts of Coleus forskohlii Briq.s
8～30 parts, Fructus Mori
10～30 parts of Trillium tschonoskii Maxims
10～30 parts of Herba Saxifragaes
Most preferred, be to prepare with the raw material of following parts by weight:
10 parts of Radix Rubiae Yunnanensis
10 parts of firethorn fruits
10 parts of Coleus forskohlii Briq.s
10 parts, Fructus Mori
10 parts of Trillium tschonoskii Maxims
10 parts of Herba Saxifragaes
Most preferred, be to prepare with the raw material of following parts by weight:
8 parts of Radix Rubiae Yunnanensis
8 parts of firethorn fruits
8 parts of Coleus forskohlii Briq.s
12 parts, Fructus Mori
12 parts of Trillium tschonoskii Maxims
12 parts of Herba Saxifragaes
Most preferred, be to prepare with the raw material of following parts by weight:
8 parts of Radix Rubiae Yunnanensis
8 parts of firethorn fruits
8 parts of Coleus forskohlii Briq.s
15 parts, Fructus Mori
15 parts of Trillium tschonoskii Maxims
15 parts of Herba Saxifragaes
Most preferred, be to prepare with the raw material of following parts by weight:
8 parts of Radix Rubiae Yunnanensis
10 parts of firethorn fruits
10 parts of Coleus forskohlii Briq.s
12 parts, Fructus Mori
12 parts of Trillium tschonoskii Maxims
12 parts of Herba Saxifragaes
Most preferred, be to prepare with the raw material of following parts by weight:
8 parts of Radix Rubiae Yunnanensis
8 parts of firethorn fruits
8 parts of Coleus forskohlii Briq.s
10 parts, Fructus Mori
10 parts of Trillium tschonoskii Maxims
15 parts of Herba Saxifragaes
The preparation method with the pharmaceutical composition of the light speckle effect of face whitening of the present invention, comprises the following steps:
(1) each above-mentioned raw material being placed in to volumetric concentration is that 20%～80% ethanol soaks 2～48 hours, and the ethanol consumption that soaks use be 10～200 times of each raw material gross weight, and filtration, obtains soak;
Preferably, the soak with ethanol that filtration residue is 20%～80% by volumetric concentration again 2～48 hours, merges the solution after soaking, and obtains soak.
(2) soak is concentrated into 2～5% of former weight, and concentrated solution macroporous resin adsorption, then the ethanol of using volumetric concentration 5～95% eluting repeatedly, collect eluent, is the described pharmaceutical composition with the light speckle effect of face whitening;
Preferably, the volumetric concentration of ethanol is 40%～95%;
Described macroporous resin adopts the XAD-2 type macroporous resin of U.S. Rohm and Haas Company (US) Independenec Mall West, Philadelphia, Pennsy Lvania 1, XAD-2 type macroporous resin is that to take styrene and propionic ester be monomer, adding Ethenylbenzene is cross-linking agent, and toluene, dimethylbenzene are porogen, and their polymerizations that is cross-linked with each other have formed porous skeleton structure.The concentrated method of soak is conventional concentrating under reduced pressure.
Evidence, the pharmaceutical composition with the light speckle effect of face whitening of the present invention, the multiple action such as has, and can be used in preparation and suppresses the cosmetics of pigmentation skin care and the curative drug of skin;
The invention still further relates to a kind of skin care cosmetics, described in comprising, there is the pharmaceutical composition of the light speckle effect of face whitening and the adjuvant that cosmetic field is used;
The invention still further relates to a kind of curative drug of skin, comprise the pharmaceutical composition with the light speckle effect of face whitening described in claim and medically acceptable carrier.
Especially can, for the preparation of skin care cosmetics, comprise cream, emulsion, astringent, gel, facial film, liniment or lotion; But be not limited to above-mentioned dosage form, can be according to method known in skin care item industrial circle, aforementioned pharmaceutical compositions is made to various external preparation after by known method degerming.
During preparation skin care cosmetics, can be by the extracting solution compositions making, through being evaporated to 10%～50% of former weight, obtain composition concentrated solution, mix mutually with the substrate of known cosmetics and medicine or adjuvant, carrier, additive, according to conventional method, be prepared, wherein, described composition concentrated solution accounts for 5%～10% of cosmetics gross weight.
The present invention is according to tcm theory, from a large amount of natural drugs, having selected Radix Rubiae Yunnanensis, firethorn fruit, Coleus forskohlii Briq., Fructus Mori, Trillium tschonoskii Maxim and Herba Saxifragae is raw material, prepared the described compositions with the light speckle effect of face whitening, wherein, described Radix Rubiae Yunnanensis is selected the dry root of Rubiaceae Rubia plants Radix Rubiae yunnanensis Rubia yunnanensis (Franch) Diels, and firethorn fruit selects the evergreen wild undershrub of Rosaceae Maloideae Pyracantha to plant the not fruit of Pyracanthafortuneana (Maxim.) Li; Coleus forskohlii Briq. is selected the labiate Coleus plant (dried floral of Coleus forskohlii (Wild) Briq; Fructus Mori is selected the dry fruit ear of moraceae plants Mulberry Morus alba L.; Trillium tschonoskii Maxim is selected the dry root of Liliaceae Trillium plant Trillium tschonoskii Maxim; Herba Saxifragae is selected the herb of saxifragaceae plant Herba Saxifragae Saxifragga stolonifera Curt..
According to < < Chinese Pharmacopoeia > > and document, record:
Radix Rubiae Yunnanensis is Yunnan specialty medical material, and it is the root of Rubiaceae Rubia plants Radix Rubiae yunnanensis Rubia yunnanensis (Franch) Diels, has another name called Yunnan Herba Salviae Chinensis, Radix Rubiae Yunnanensis, little red medicine.< < Yunnan Chinese herbal medicine > > records its energy " promoting the flow of QI in the collateral by warming the meridian is taken good care of QI and blood ".The effect that Radix Rubiae Yunnanensis has promoting the flow of QI in the collateral by warming the meridian, promoting blood circulation by removing wind, softening the hard mass removing mass and nourishes blood and enrich blood, Radix Rubiae Yunnanensis clinical practice is extensive, and toxic and side effects is little, is used for the treatment of the various diseases such as anemofrigid-damp arthralgia, subcutaneous nodule, traumatic injury and bloody sputum.Modern study confirms that Radix Rubiae Yunnanensis has significant therapeutic effect to psoriasis, can improve skin activity, and have anticancer function.
Firethorn fruit is the fruit of evergreen wild undershrub plant Pyracanthafortuneana (Maxim.) Li of Rosaceae Maloideae Pyracantha, firethorn fruit has another name called Fructus Pyracanthae (Fructus Pyracanthae Fortuneanae), torch fruit etc., is mainly distributed in mountain region and the hilly country in the regions such as China southeast, southwest and northwest.Firethorn fruit edible, the sweet acid of nature and flavor, has the effects such as spleen invigorating removing food stagnancy, promoting the production of body fluid to quench thirst.Firethorn fruit extract is rich in the flavone compounds such as rutin and hyperin, also contains in addition aminoacid, plurality of inorganic salt and trace element etc.Once reported that firethorn fruit had significant whitening function abroad, and successfully developed skin-lightening cosmetic as raw material.
Coleus forskohlii Briq. is the labiate Coleus plant (flower of Coleus forskohlii (Wild) Briq, Coleus forskohlii Briq. is defined as rare plant by domestic botanist, the wild Coleus forskohlii Briq. Domestic Resources of China is very rare, and Ta China is only distributed on the hillside, wilderness of 2300 meters of area, northeast height above sea level in Yunnan Province Wild plant.Coleus forskohlii Briq. is called as catholicon at Gu Yindu, among the people with herb decoction in India for a long time, for the sick treatment such as heart disease, stomachache, disordered breathing, insomnia, spasm, evident in efficacy.Coleus forskohlii Briq. is found to treat glaucoma and dermatosis in recent years, thereby causes scientist's extensive concern.Coleus forskohlii Briq. chemical composition is various, and separated chemical composition mainly contains terpenoid, flavone, sterol, volatilization wet goods.
Fructus Mori is the dry fruit ear of moraceae plants Mulberry Morus alba L., and the traditional Chinese medical science thinks that Fructus Mori sweet in the mouth is sour, and cold nature, enters the heart, liver, kidney channel, is strengthening by means of tonics, the good fruit of the heart nourishing and intellengence improving.There is the YIN nourishing of enriching blood, promoting the production of body fluid to quench thirst, the effect such as intestine moistening is dry, cures mainly deficiency of YIN-blood and having a dizzy spell of causing, tinnitus cardiopalmus, irritated insomnia, soreness of the waist and knees, early whitening of beard and hair, the xerostomia of quenching one's thirst, the diseases such as constipation with dry stool.
Trillium tschonoskii Maxim is the dry root of Liliaceae Trillium plant Trillium tschonoskii Maxim, have another name called Rhizoma Trillii Tschonoskii, mainly be grown in the hillside sylvan life thick grass of about height above sea level 2000m, function tranquillizing and allaying excitement, promoting blood circulation and hemostasis, removing toxic substances, cure mainly have a dizzy spell, hypertension, neurasthenia.Trillium tschonoskii Maxim is rich in multiple steroidal saponin and aminoacid, is the important source material of extracting steroidal saponin.
Herba Saxifragae is the herb of saxifragaceae plant Herba Saxifragae Saxifragga stolonifera Curt..Micro-bitter, acrid, cold, slightly poisonous, dispel the wind, heat clearing away, removing pathogenic heat from blood and toxic substance from the body.Control rubella, eczema, otitis media, erysipelas, cough, spits blood, lung abscess, metrorrhagia, haemorrhoids.In recent years, it is found that in Herba Saxifragae and be rich in arbutin, effectively the active degree of check melanin blast cell, just as giving melanin hypnosis, has whitening, the effect of light speckle.
At present, there is not yet both at home and abroad the compositions of Radix Rubiae Yunnanensis, firethorn fruit, Coleus forskohlii Briq., Fructus Mori, Trillium tschonoskii Maxim and Herba Saxifragae extract for thering is the relevant report of the light speckle effect of face whitening.
In sum, the inventor has read lot of documents, according to the ultimate principle of skin-whitening agents, utilizes cell model to carry out high flux screening, finally finds to have the pharmaceutical composition of remarkable skin whitening function.Pharmaceutical composition of the present invention confirms that through human clinical trial effect is remarkable, and safety is good.Related composition has that effect is clear and definite, safety good, without any side effects and in cosmetic formulations stable feature; Comparing with existing like product, have effect outstanding feature, is a kind of novel compositions with effective natural drug extract of the light speckle effect of face whitening.
The specific embodiment
Embodiment 1
At room temperature, get each 10 kilograms of Radix Rubiae Yunnanensis, firethorn fruit, Coleus forskohlii Briq., Fructus Mori, Trillium tschonoskii Maxim and Herba Saxifragaes, with 600 kilograms of immersions of ethanol of volumetric concentration 70%, extract, soak time is 24 hours, residue extracts with 600 kilograms of immersions of ethanol of volumetric concentration 70% for 24 hours again, then the solution after soaking is merged, after 200 object strainer filterings, 20 times of concentrating under reduced pressure, again by macroporous resin on concentrated solution, with the ethanol elution of volumetric concentration 50%, in the eluent of collection, contain needed effective ingredient, i.e. pharmaceutical composition in prescription of the present invention.
Embodiment 2
At room temperature, get 8 kilograms of Radix Rubiae Yunnanensis, 8 kilograms of firethorn fruits, 8 kilograms of Coleus forskohlii Briq.s, 12 kilograms, Fructus Mori, 12 kilograms of 12 kilograms of Trillium tschonoskii Maxims and Herba Saxifragaes, with 1200 kilograms of immersions of ethanol of volumetric concentration 50%, extract, soak time is 24 hours, residue extracts with 1200 kilograms of immersions of ethanol of volumetric concentration 50% for 24 hours again, then the solution after soaking is merged, after 200 object strainer filterings, 40 times of concentrating under reduced pressure, again by macroporous resin on concentrated solution, ethanol elution by volumetric concentration 40%, in the eluent of collecting, contain needed effective ingredient in prescription of the present invention, it is pharmaceutical composition.
Embodiment 3
At room temperature, get 8 kilograms of Radix Rubiae Yunnanensis, 8 kilograms of firethorn fruits, 8 kilograms of Coleus forskohlii Briq.s, 15 kilograms, Fructus Mori, 15 kilograms of 15 kilograms of Trillium tschonoskii Maxims and Herba Saxifragaes, with 1000 kilograms of immersions of ethanol of volumetric concentration 80%, extract, soak time is 24 hours, residue extracts with 1000 kilograms of immersions of ethanol of volumetric concentration 80% for 24 hours again, then the solution after soaking is merged, after 200 object strainer filterings, concentrate 25 times, again by macroporous resin on concentrated solution, ethanol elution by volumetric concentration 60%, in the eluent of collecting, contain needed effective ingredient in prescription of the present invention, it is pharmaceutical composition.
Embodiment 4
At room temperature, get 8 kilograms of Radix Rubiae Yunnanensis, 10 kilograms of firethorn fruits, 10 kilograms of Coleus forskohlii Briq.s, 12 kilograms, Fructus Mori, 12 kilograms of 12 kilograms of Trillium tschonoskii Maxims and Herba Saxifragaes, with 2000 kilograms of immersions of ethanol of volumetric concentration 30%, extract, soak time is 24 hours, residue extracts with 2000 kilograms of immersions of ethanol of volumetric concentration 30% for 24 hours again, then the solution after soaking is merged, after 200 object strainer filterings, concentrate 50 times, again by macroporous resin on concentrated solution, ethanol elution by volumetric concentration 50%, in the eluent of collecting, contain needed effective ingredient in prescription of the present invention, it is pharmaceutical composition.
Embodiment 5
At room temperature, get 8 kilograms of Radix Rubiae Yunnanensis, 8 kilograms of firethorn fruits, 8 kilograms of Coleus forskohlii Briq.s, 10 kilograms, Fructus Mori, 15 kilograms of 10 kilograms of Trillium tschonoskii Maxims and Herba Saxifragaes, with 1200 kilograms of immersions of ethanol of volumetric concentration 60%, extract, soak time is 24 hours, residue extracts with 1200 kilograms of immersions of ethanol of volumetric concentration 60% for 24 hours again, then the solution after soaking is merged, after 200 object strainer filterings, concentrate 30 times, again by macroporous resin on concentrated solution, ethanol elution by volumetric concentration 80%, in the eluent of collecting, contain needed effective ingredient in prescription of the present invention, it is pharmaceutical composition.
Embodiment 6
The liquid that embodiment 1 is obtained adopts concentrating under reduced pressure, is concentrated into 10%～50% of former weight, obtains pharmaceutical composition concentrated solution, for the preparation of the essence with the light speckle effect of face whitening,, the percentage by weight of component is as follows:
Production technology: under stirring, A and B are heated to respectively to 70 ℃ mutually, to all dissolving mix homogeneously, then under 70 ℃ of conditions, B is added to A mutually in, to forming W/Q type Emulsion.After stirring, be cooled to room temperature and get final product.
Embodiment 7
Pharmaceutical composition has the cell experiment research report of the light speckle effect of face whitening: in following experiment, the compositions of drug extract used is the pharmaceutical composition of embodiment 1.
1 materials and methods
1.1 reagent and instrument RPMI1640, Gibco company product; Hyclone (FBS), Hangzhou Ilex purpurea Hassk.[I.chinensis Sims company product; B-16 mouse black-in tumor cell, Chinese Academy of Sciences's cell provides, and vitamin C is provided by Beijing Berry Lai Si Biochemics Inc., meets cosmetic material medicine standard; L-GLUTAMINE, levodopa (L-Dopa), dimethyl sulfoxide (DMSO), trypsin, TritonX-100, is Sigma product, Thiazolyl blue (MTT), Serva product; CO
2incubator, U.S. Barnstead company; TDL-40B centrifuge, Anting Scientific Instrument Factory, Shanghai; Tissue Culture Plate, U.S. Greiner product; DG5031 enzyme-linked immunosorbent assay instrument, East China Electronics Co., Ltd pipe factory product.
1.2 method
1.2.1 the strain of cell culture B-16 melanoma cells is purchased from cell institute of the Chinese Academy of Sciences, treats that Growth of Cells, to fusion state, goes down to posterity through 0.25% trypsinization, is inoculated in 25cm
2in culture bottle, with RPMI1640 culture fluid, be placed in 37 ℃ of CO
2incubator, 5%CO
2saturated humidity environment is cultivated.Same passage cell is taken from experiment each time, and initial inoculation cell concentration is 10
5left and right.After cell inoculation 6h, add tested whitening agent, respectively establish 5 dosage groups, in the 2nd day, change identical pastille culture fluid, harvesting after continuous culture 3d, expects blue dyeing counting total cellular score with tongue, then cell is tested for following.
1.2.2 reagent preparation is got whitening extract 0.5g of the present invention with experiment grouping and first with 1ml DMSO, is dissolved, and adds freshly prepared RPMI-1640 and is diluted to that final concentration is 5,0.5,0.05,0.005,0.0005g/L, and the final concentration of DMSO is lower than 1%.Vitamin C directly adds culture fluid to be diluted to final concentration, and diluted concentration is respectively 10
-1, 10
-2, 10
-3, 10
4,10
-5mol/L.Blank group only adds dilution medicine corresponding solvent used.
1.2.3 tyrosinase activity suppression ratio detects and take L-Dopa as substrate, with reference to the method for Maeda etc., measures cell tyrosinase activity.Adjust melanocyte density, with 10
4individual/hole is inoculated in 96 orifice plates, changes liquid after 6h, and every hole adds the drug solution of 200 μ l, and each concentration arranges 4 multiple holes, and matched group adds fresh medium to replace drug solution, 5%CO
2hatch (liquid is changed once in centre) after 3d for 37 ℃, abandoning supernatant, PBS washes 3 times, every hole adds 45 μ l1%TritonX-100 solution, 10min is with dissolved cell in concussion, and every hole adds the L-Dopa of 0.01mol/L, hatches 60min for 37 ℃, in 450nm wavelength place colorimetric, with blank well zeroing, at enzyme-linked immunosorbent assay instrument, survey each hole absorbance, each experiment repeats 3 times.Tyrosinase activity suppression ratio=(each concentration mean light absorbency value of 1-÷ matched group mean light absorbency value) * 100%, is used SPSS13.0 carry out curve fitting and calculate IC
50value.
1.2.4 the synthetic suppression ratio of melanocyte detects the method mensuration that melanin content adopts Victoria, adjusts melanocyte density, with 5 * 10
5individual/hole is inoculated in 6 orifice plates, changes liquid after 6h, and every hole adds the drug solution of 1ml, and each concentration arranges 3 multiple holes, and matched group adds fresh medium to replace drug solution, 5%CO
2hatch (liquid is changed once in centre) after 3d for 37 ℃, abandoning supernatant, every hole adds 0.25% pancreatin 1ml to digest 2min under room temperature, adds 4ml culture fluid to end digestion, blows and beats into single cell suspension, get 20 μ l and make cell counting, the centrifugal 5min of all the other cell suspension 1500r/min, abandons supernatant, adds 1m11N NaOH solution, concussion 5min, after 80 ℃ of heating in water bath 1h, be transferred to 96 orifice plates, every hole adds 100 μ l, select 405nih wavelength, with blank well zeroing, on enzyme-linked immunosorbent assay instrument, survey absorbance, each experiment repeats 3 times.Melanocyte synthesizes suppression ratio (%)=[1-(medicine hole absorbance ÷ medicine porocyte density) ÷ (control wells absorbance ÷ control wells cell density)] * 100%, uses SPSS13.0 carry out curve fitting and calculate IC
50value.
1.2.5MTT colorimetric determination cell increment suppression ratio is got the B-16 cell of exponential phase of growth, through digestion, disperses to prepare single cell suspension, adjusts cell concentration, and cell is seeded to 96 porocyte culture plates, and initial cell inoculum density is 10
5individual/hole, amount of liquid 200 μ l/ holes, hatch 6h after cell attachment, suck culture fluid, add and contain variable concentrations medicine culture fluid, and each concentration arranges 6 multiple holes, continues to cultivate 3d (liquid is changed once in centre).While measuring cell proliferation rate, to every hole, add 0.5%MTT storage liquid 20 μ l, put CO
2incubator continues to cultivate 4h.Now MTT is converted into first for (formazan) through mitochondrial membrane succinate dehydrogenase, under microscope, inside and outside visible cell, have a large amount of aubergine acicular crystal, carefully draw culture fluid, every hole adds 200 μ 1DMSO, culture plate jolting 10min, makes first replace crystallization to dissolve completely.Put immediately microplate reader in 570nih photometry absorption value, each experiment repeats 3 times, with following formula, calculates and respectively organizes cell proliferation inhibition rate.Cell proliferation inhibition rate (%)=(1-experimental group 570/ matched group 570) * 100%, is used SPSS13.0 carry out curve fitting and calculate IC
50value.
1.2.6 statistical analysis is to the IC in each group
50value adopts SPSS to carry out variance analysis, carries out the comparison between sample average.
Result
The in-vitro evaluation of table 1 pharmaceutical composition to whitening function
Note: with the comparison of vitamin C group, * P<0.05, * * P<0.01.
Result of study shows that (referring to table 1) pharmaceutical composition of the present invention and vitamin C all have inhibitory action to intracellular tyrosine enzymatic activity and melanogenesis, and there is dose-dependence, the increase suppression ratio with dosage improves, and the effect of pharmaceutical composition of the present invention will significantly be better than vitamin C (P<0.05 or P<0.01).And pharmaceutical composition of the present invention suppresses the value-added IC of cell
50close with vitamin C, this illustrates that pharmaceutical composition cell of the present invention safety is good.
Adopt the pharmaceutical composition with the light speckle effect of face whitening of other embodiment to test, result also proves to have identical effect.
Embodiment 8
Pharmaceutical composition has the clinical experimental study report of the light speckle effect of face whitening: in following clinical trial, the compositions of drug extract used is the essence with the light speckle effect of face whitening (Zhong He international bio company limited product) prepared by the cosmetic formulations of embodiment 6.
1. materials and methods
The selection of 1.1 tested objects
Altogether include 20 female volunteers of 24～42 years old in, inclusive criteria: skin type belongs to IV type, unglazed allergies, without cosmetic allergic contact dermatitis history.。Exclusion standard: known to being subject to the composition allergy sufferers in trial product; Psychotic; Person within period of pregnancy, age of sucking or the later six months of giving a birth; There are serious hepatorenal disease, autoimmune disease (as systemic lupus erythematosus (sle), rheumatoid arthritis), HIV the infected: in nearly 12 months, be diagnosed as cutaneous tumor curer; Using and/or in first 14 days of test oral or external the medicine (glucocorticoid, immunosuppressant and antiallergic agent) of test forbidding; Using or testing and within first 1 month, used other like products person.
1.3 test instrunments adopt Lab colorimeter system spectrophotometer (Minolta spectrophotometer CM-2002) to measure the variation of skin color.
1.4 test index L=116 (Y/Y
n)
1/3-16; A=500[(X/X
n)
1/3(y/yn)
1/3]; B=200[(Y/Y
n)
1/3-(Z/Z
n)
1/3]; C
ab=(a
2+ b
2)
1/2; Hab=arctg (b/a), in formula, L, a, b are the coordinate figure of three-dimensional cartesian coordinate system system; X, Y, Z are the tristimulus values of XYZ colour system; The tristimulus values that Xn, Yn, Zn are persect reflecting diffuser.L: be brightness, be worth greatlyr, color is deflection white more, otherwise, deflection black.A: be red, green product ,+a is red direction, and-a is green direction.B: be yellow, blue product ,+b is yellow direction, and-b is blue direction.C: be saturation, in order to represent the deep or light of color of object surface.H: be hue angle, represent colored characteristic of dividing mutually each other.In Lab colorimeter system, with difference Δ L, Δ a, the Δ b of coordinate L, a, b, represent two kinds of aberration △ E between stimulation
ab, i.e. distance between the colour space two color dot.△E
ab＝[(ΔL)
2+(Δa)
2+(Δb)
2]
1/2。In formula: due to/E
ab, be the aggregative index of L, a, b, represented that the solid of colourity changes, so be to evaluate the more suitable index that the colour of skin changes.
1.5 smearing method tested objects are used continuously, after washing one's face, at face, smear the essence (Zhong He international bio company limited product) with the light speckle effect of face whitening before sleeping in every morning, evening, and applying amount is to be slightly shown in smear layer.Cervical region is not coated with cosmetics, is used as own control.
Testing time before making to apply some make up 1d, use after the 30th, 60,90d uses spectrophotometer to measure the variation of skin color.Follow-on test 3 times, averages.
Test position forehead (place between the eyebrows top 2cm); Left and right buccal (cheekbone back lower place 1cm); Cervical region (Adam's apple below 2cm)
1.6. safety evaluatio carries out untoward reaction evaluation to experimenter when further consultation, and whether inquiry experimenter's target site former symptom increases the weight of or occur new skin lesion, as symptoms such as pruritus, dry, desquamation, twinge, redness, desquamations and whether hinder daily life.Severe: untoward reaction hinders daily routines, and experimenter's subjective symptoms is remarkable, is impatient at, and needs to stop using; Moderate: untoward reaction hinders daily life, and experimenter's subjective symptoms is obvious, but can stand, and need not stop using and be subject to trial product; Slight: can react by Intolerance, experimenter occasionally can experience.To there is the experimenter of untoward reaction, doctor carries out patch test to it. to determine the cause effect relation of untoward reaction and test products.Responsible doctor thinks that experimenter is not suitable for continuing test, or experimenter requires to stop, and stops this experimenter's test, and records stop reason and time.
1.7. statistical procedures adopts SSPS11.5 software to carry out self front and back paired t-test.
2. result
2.1 different parts show the color difference table 2 of pharmaceutical composition different time, buccal aberration raises after using pharmaceutical composition of the present invention, after using 90d, buccal aberration occurs that significance changes (P<0.05), and the variation at all the other positions is without significance (P>0.05).
Table 2 different parts makes the comparison of pharmaceutical composition different time aberration Δ E
Note: relatively front with use, * P<0.05.
2.2 use the data show of the change list 3 of different time skin of cheek color value, use L-value and the b value of buccal after pharmaceutical composition 30,60 of the present invention, 90d all to raise, relatively front with use, difference has significance (P<0.05), and a value all has the attenuating (P<0.01) of utmost point significance after use 60,90d.C value occurs that after using 60d significance raises (P<0.05), there are no significant in the whole process of the test variation (P>0.05) of h value.This absolutely proves, volunteer is after using pharmaceutical composition of the present invention, and a value of its cervical region declines, and L-value continues to rise, and the rising of b value, shows that the colour of skin changes to HUANGBAI(sic) direction; C value raises after this brand skin-lightening cosmetic is used in explanation continuously colour of skin HUANGBAI(sic) saturation is increased; H value changes little, illustrates that the variation of the colour of skin is more consistent.
Table 3 makes the comparison of pharmaceutical composition different time skin of cheek color value
Note: relatively front with use, * P<0.05, * * P<0.01.
Before and after Product Safety assessment treatment, all there is not untoward reaction, without 1 routine patient, come off.There is not the Adverse Event relevant to this test products in whole research process.
Adopt the pharmaceutical composition with the light speckle effect of face whitening of other embodiment to carry out clinical trial, result also proves to have identical effect.
Embodiment 9
The skin irritation test research report with the pharmaceutical composition of the light speckle effect of face whitening: by animal experiment, observe the zest of the light speckle drugs with function of face whitening compositions to rabbit skin that have of the present invention.In following experiment, the compositions of drug extract used is the pharmaceutical composition of embodiment 4.
1 animal
16 regular grade adult healthy new zealand rabbits, male and female half and half, 2.5kg～3.5kg, buys in Guangdong Medical Lab Animal Center, and laboratory animal production licence number is SCXK (Guangdong) 2008-0002, the animal quality certification number: Guangdong 2012A008.Raise in Animal House F4 room, new southern drug safety assessment centers general area (the experimental animal room quality certification number: 0060590.), duration of test, 20 ℃ 2～22 ℃ of room temperatures, humidity 40%～67%, illumination 12h/12h round the clock light and shade replaces.The pharmaceutical composition that the pharmaceutical composition using in this experiment is the embodiment of the present invention 1, concentration is 1.0g crude drug/mL.
2 methods
According to the < < of Ministry of Health of the People's Republic of China cosmetics health standard (version in 2007) > >, adopt consubstantiality self left and right sides matching type, left side gives blank substrate (normal saline), and right side gives the pharmaceutical composition of 1.0g/mL.Before administration, prepare: 24h before administration, adopts mao method of shaving to remove family rabbit back spinal column both sides by hair, left and right each the about 3cm * 3cm of unhairing scope, application area 2.5cm * 2.5cm, not injured skin.Administration: get the about 0.5mL of tested material and spread upon on the skin of right side, left side is coated with normal saline in contrast, smears 1 time, continuously 14d every day.From second day, will be by hair before smearing at every turn.The double-deck hospital gauze sheet that medicinal liquid 0.5mL is soaked into 2.5cm * 2.5cm, is covered in plucked skin, covers one deck template, then fixes with nonirritant adhesive plaster and fixing band.After fixing about 4h, remove tested material, with warm water, remove residual tested material.Observed result after one hour.3 results
Under this experiment condition, the pharmaceutical composition of smearing continuously 1.0g/mL reacts (specifically in Table 4) to rabbit skin nonirritant in 14 days.
Table 41.0.g/mL pharmaceutical composition is to rabbit irritation test result repeatedly
Embodiment 10
There is the hypersensitive experimentation report of the pharmaceutical composition of the light speckle effect of face whitening: by animal experiment, observe the sensitization of the light speckle drugs with function of face whitening compositions to Hartley guinea pig skin that have of the present invention.The pharmaceutical composition that the pharmaceutical composition using in this experiment is the embodiment of the present invention 5.
1 animal
Select 50 of regular grade Hartley Cavia porcelluss, male and female half and half, weight range 180～250g, buys in Guangdong Medical Lab Animal Center, and laboratory animal production licence number is SCXK (Guangdong) 2008-0002, the animal quality certification number: Guangdong 2012A016.Raise in Animal House F4 room, new southern drug safety assessment centers general area (the experimental animal room quality certification number: 0060590.), duration of test, 20 ℃～22 ℃ of room temperatures, humidity 40%～67%, illumination 12h/12h round the clock light and shade replaces.By number Cavia porcellus is carried out to skin dyeing, with saturated picric acid solution (yellow) dye marker units, with 2% silver nitrate solution (coffee color) dye marker tens; By sex, separately raise, each cage box is put 5 Cavia porcelluss, and cage box is outer labelled, indicates special topic numbering, animal classification, group, sex, route of administration, cage number, number of animals and estimates to test the information such as commencement date and deadline.The pharmaceutical composition that the pharmaceutical composition using in this experiment is the embodiment of the present invention 1, concentration is 1.0g crude drug/mL.
2 methods
According to national < < medicine registration management way > >, < < chemicals zest, anaphylaxis and hemolytic investigative technique guideline > >.Be divided at random negative control group, positive controls, pharmaceutical composition group, 10 Cavia porcelluss of negative control group wherein, all the other respectively organize 20 Cavia porcelluss.Each organizes Cavia porcellus male and female half and half.Successively induce sensitization to contact experiment with exciting, the eluting phase of 10 days of being separated by between two experiments.Induction exposure experimental technique is front 24h preserved skin, cut off each 2cm * 2cm. region, Cavia porcellus spinal column both sides by hair.Positive controls: get 2.5%2, the acetone soln 0.2g of 4-dinitro-chloro-benzene, use respectively two-layer gauze (2.5cm * 2.5cm) and one deck antistaling film to cover, with non-stimulated gauze, cover 6h, remove covering, with warm water, remove residual given the test agent, the 7th day and the 14th day, in kind repeat once; In negative control treated animal same area, be coated with distilled water 0.4ml, pharmaceutical composition group is coated with 0.5ml.By same step, carry out Induction exposure.Exciting contact is after last is to tested material sensitization contact 14 days (testing the 28th day), at experimental group and negative control group guinea pig back preserved skin place coating 0.5ml, package and fixing, after 6h, remove tested material, observe at once, then in 24h, 48h, 72h, again observe skin allergy situation.The acetone soln 0.2g of 2.5%2,4-dinitro-chloro-benzene for positive controls, negative control treated animal same area is coated with distilled water 0.4ml.After sensitization 1h, 24h and excite after 24h and 48h observe administration local skin erythema, edema and other abnormal responses.By skin allergy standards of grading, skin erythema and edema are marked, and calculate the anaphylaxis incidence rate of each group, by skin hypersensitivity evaluation criterion judgement anaphylaxis occurrence degree.Anaphylaxis incidence rate=(number of animals/this treated animal sum that occurs skin erythema, edema or systemic anaphylaxis in group) * 100%.
3 results:
Excite contact experiment rear 24, 48h, by the professional who does not know experiment content according to < < chemicals zest, anaphylaxis and hemolytic investigative technique guideline > > pass judgment on whether occur sensitization of skin reaction (table 5), sensitivity response scoring >=2 timesharing, judge that this animal skin sensitivity response is positive, calculate sensitization rate (>=2 minutes number of animals/these treated animal sum * 100%), and press < < chemicals zest, in anaphylaxis and hemolytic investigative technique guideline > >, sensitization of skin reaction test grade scale is judged the sensitization intensity (table 6) of pharmaceutical composition of the present invention to guinea pig skin.
Table 5 sensitization of skin extent of reaction standards of grading
First calculate to put each observing time and respectively organize integral mean value, then calculate and observe every animal integral mean value interior every day in time limit, by < < chemicals zest, anaphylaxis and hemolytic investigative technique guideline > >, evaluate.By following formula, calculate every animal average integral every day.
Table 6 sensitization of skin extent of reaction grade scale
Excite rear 24h, 48h, the Cavia porcellus of negative control group, pharmaceutical composition group excites position skin all not occur erythema, edema situation, does not also occur other abnormal response, and anaphylaxis incidence rate is 0, and anaphylaxis evaluation is and has no skin allergy.
Excite rear 24h, positive controls Cavia porcellus excites position skin all to occur erythema, and anaphylaxis incidence rate is 100%, and anaphylaxis is evaluated as extremely strong sensitization.Excite rear 48h, positive controls Cavia porcellus excites position skin still all to have erythema, and anaphylaxis incidence rate is 100%, and anaphylaxis evaluation is still extremely strong sensitization.
4 conclusions
Under this experiment condition, pharmaceutical composition Hartley guinea pig skin is carried out to 3 sensitization and excite for 1 time after have no skin allergy.
Claims (9)
1. the pharmaceutical composition with the light speckle effect of face whitening, is characterized in that: take Radix Rubiae Yunnanensis, firethorn fruit, Coleus forskohlii Briq., Fructus Mori, Trillium tschonoskii Maxim and Herba Saxifragae prepares as raw material, and the weight percentage of arbitrary component is all no more than 40% of total amount.
2. the pharmaceutical composition with the light speckle effect of face whitening according to claim 1, it is characterized in that, it is to prepare with the raw material of following mass fraction: 1～60 part of Radix Rubiae Yunnanensis, 1～60 part of firethorn fruit, 1～60 part of Coleus forskohlii Briq., 1～60 part, Fructus Mori, 1～60 part of Trillium tschonoskii Maxim, 1～60 part of Herba Saxifragae.
3. the pharmaceutical composition with the light speckle effect of face whitening according to claim 2, it is characterized in that, it is to prepare with the raw material of following mass fraction: 1～50 part of Radix Rubiae Yunnanensis, 1～50 part of firethorn fruit, 1～50 part of Coleus forskohlii Briq., 1～50 part, Fructus Mori, 1～50 part of Trillium tschonoskii Maxim, 1～50 part of Herba Saxifragae.
4. according to the preparation method of the pharmaceutical composition with the light speckle effect of face whitening described in claim 1～3 any one, it is characterized in that comprising the following steps:
The first step: it is that 20%～80% ethanol soaks that each above-mentioned raw material is placed in to volumetric concentration, and the ethanol consumption that soaks use be 10～200 times of each raw material gross weight, and filtration, obtains soak:
Second step: soak is concentrated into 2～5% of former weight, concentrated solution macroporous resin adsorption, then the ethanol elution that is 5～95% by volumetric concentration, collect eluent, is the described pharmaceutical composition with the light speckle effect of face whitening.
5. the preparation method of the pharmaceutical composition with the light speckle effect of face whitening according to claim 4, is characterized in that: in the first step, the described soak with ethanol time is 2～48 hours; Or each raw material first uses soak with ethanol 2～48 hours, residue is used soak with ethanol 2～48 hours again, merges the solution after soaking, and obtains soak.
6. the preparation method with the pharmaceutical composition of the light speckle effect of face whitening according to claim 4, is characterized in that: in second step, described eluting is 40%～95% by the volumetric concentration of ethanol.
7. according to the purposes of the pharmaceutical composition with the light speckle effect of face whitening described in claim 1～3 any one, it is characterized in that: for the preparation of the curative drug of skin care cosmetics or skin.
8. skin care cosmetics, comprise the adjuvant that the pharmaceutical composition with the light speckle effect of face whitening described in claim 1～3 any one and cosmetic field are used.
9. the curative drug of skin, comprises the pharmaceutical composition with the light speckle effect of face whitening described in claim 1～3 any one and medically acceptable carrier.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410248234.8A CN104069322A (en) | 2014-05-29 | 2014-05-29 | Pharmaceutical composition with facial whitening and spot lightening effects and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410248234.8A CN104069322A (en) | 2014-05-29 | 2014-05-29 | Pharmaceutical composition with facial whitening and spot lightening effects and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104069322A true CN104069322A (en) | 2014-10-01 |
Family
ID=51591188
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410248234.8A Pending CN104069322A (en) | 2014-05-29 | 2014-05-29 | Pharmaceutical composition with facial whitening and spot lightening effects and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104069322A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106924111A (en) * | 2017-03-13 | 2017-07-07 | 广州市嘉美化妆品有限公司 | A kind of light spot liquid of face |
| CN107157838A (en) * | 2017-06-05 | 2017-09-15 | 云南摩尔农庄生物科技开发有限公司 | A kind of antioxidant composition containing walnut peel extract |
| CN107485020A (en) * | 2017-08-18 | 2017-12-19 | 武汉华士特工业生物技术开发有限公司 | A kind of oral liquid with whitening function and preparation method thereof |
| CN107496658A (en) * | 2017-09-19 | 2017-12-22 | 广州青岚生物科技有限公司 | A kind of clarification process and method of quality control of the pharmaceutical composition that there is the light spot for the treatment of face whitening to act on |
| CN107714557A (en) * | 2017-11-24 | 2018-02-23 | 重庆工商大学 | Method and the application of tyrosinase inhibitor are extracted in a kind of fruit from Pyracantha |
| CN108143683A (en) * | 2018-01-12 | 2018-06-12 | 福建师范大学 | A kind of plant composition with white-skinned face function and preparation method thereof |
| CN110522835A (en) * | 2019-07-19 | 2019-12-03 | 江西中医药大学 | Pharmaceutical composition and the preparation method and application thereof with lung mescenchymal stem cell directed differentiation effect in regulation pulmonary fibrosis microenvironment |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1927240A (en) * | 2006-09-06 | 2007-03-14 | 北京润德康医药技术有限公司 | Traditional Chinese medicine mask composition for depigmenting |
| CN102648952A (en) * | 2011-02-25 | 2012-08-29 | 上海天龙药业有限公司 | Traditional Chinese medicine composition with spot removing function |
| CN103083210A (en) * | 2013-01-25 | 2013-05-08 | 王恩瀚 | Medicine composition with skin whitening effect as well as preparation method and application thereof |
-
2014
- 2014-05-29 CN CN201410248234.8A patent/CN104069322A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1927240A (en) * | 2006-09-06 | 2007-03-14 | 北京润德康医药技术有限公司 | Traditional Chinese medicine mask composition for depigmenting |
| CN102648952A (en) * | 2011-02-25 | 2012-08-29 | 上海天龙药业有限公司 | Traditional Chinese medicine composition with spot removing function |
| CN103083210A (en) * | 2013-01-25 | 2013-05-08 | 王恩瀚 | Medicine composition with skin whitening effect as well as preparation method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| 张松伟: "盘龙云海11年快速发展之谜", 《中国消费者报》 * |
| 张目 等: "几种中药的美白作用研究", 《香料香精化妆品》 * |
| 胡艺: "近年国内外护肤养发植物药开发与研制简述", 《中国中医药信息杂志》 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106924111A (en) * | 2017-03-13 | 2017-07-07 | 广州市嘉美化妆品有限公司 | A kind of light spot liquid of face |
| CN107157838A (en) * | 2017-06-05 | 2017-09-15 | 云南摩尔农庄生物科技开发有限公司 | A kind of antioxidant composition containing walnut peel extract |
| CN107157838B (en) * | 2017-06-05 | 2020-12-08 | 云南摩尔农庄生物科技开发有限公司 | Antioxidant composition containing walnut green husk extract |
| CN107485020A (en) * | 2017-08-18 | 2017-12-19 | 武汉华士特工业生物技术开发有限公司 | A kind of oral liquid with whitening function and preparation method thereof |
| CN107496658A (en) * | 2017-09-19 | 2017-12-22 | 广州青岚生物科技有限公司 | A kind of clarification process and method of quality control of the pharmaceutical composition that there is the light spot for the treatment of face whitening to act on |
| CN107714557A (en) * | 2017-11-24 | 2018-02-23 | 重庆工商大学 | Method and the application of tyrosinase inhibitor are extracted in a kind of fruit from Pyracantha |
| CN107714557B (en) * | 2017-11-24 | 2021-07-09 | 重庆工商大学 | Method for extracting tyrosinase inhibitor from pyracantha fruit and application of tyrosinase inhibitor |
| CN108143683A (en) * | 2018-01-12 | 2018-06-12 | 福建师范大学 | A kind of plant composition with white-skinned face function and preparation method thereof |
| CN108143683B (en) * | 2018-01-12 | 2020-09-11 | 安徽花吟姿生物科技有限公司 | Plant composition with whitening effect and preparation method thereof |
| CN110522835A (en) * | 2019-07-19 | 2019-12-03 | 江西中医药大学 | Pharmaceutical composition and the preparation method and application thereof with lung mescenchymal stem cell directed differentiation effect in regulation pulmonary fibrosis microenvironment |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104069322A (en) | Pharmaceutical composition with facial whitening and spot lightening effects and preparation method and application thereof | |
| CN103083210A (en) | Medicine composition with skin whitening effect as well as preparation method and application thereof | |
| CN101829034B (en) | External Chinese medicinal composition with functions of blackening hair and dressing hair and preparation method thereof | |
| CN103385843B (en) | Speckle-removing composition, preparation method thereof and applications thereof | |
| CN102641233B (en) | Rhodiola crenulata facial mask with whitening and moisturizing effects | |
| CN104707032B (en) | A kind of whitening spot-removing Chinese medicine face cream and preparation method thereof | |
| CN102988264B (en) | Folium Ginkgo freckle removing and whitening frost and preparation method thereof | |
| CN104784507A (en) | Traditional Chinese medicine composition with multiple cosmetic effects and application | |
| CN103721144A (en) | Natural plant hair blackening solution and preparation method thereof | |
| CN101579027A (en) | Health-care tea for reducing and stabilizing blood pressure | |
| CN101708048B (en) | Health-care food and preparation method thereof | |
| CN109662904A (en) | It is a kind of to have effects that the skin care compositions of whitening antioxidation and its application and preparation method | |
| CN102973802B (en) | Drug composite for treating sensitive skin and preparation method thereof | |
| KR100564108B1 (en) | Cosmetic composition comprising plant extract having anti-aging effect | |
| CN104083635A (en) | A pharmaceutical composition with skin nourishing and moisturizing functions and a preparing method and applications thereof | |
| CN106728340A (en) | Chinese medicine composition with hair care effect and its preparation method and application | |
| CN110151866A (en) | A kind of nutritional supplement for improving eyesight and preparation method thereof and purposes | |
| CN106361668A (en) | Acne removing paste and preparation method thereof | |
| CN103540496B (en) | Traditional Chinese medicine life-cultivating and health-preserving wine and preparation method thereof | |
| CN102920913B (en) | Anti-spot beautifying composition and preparation method thereof | |
| CN104814916A (en) | Moisturizing essence and preparing method thereof | |
| CN108057106A (en) | A kind of Chinese medicine blackening agent and preparation method | |
| CN103341139A (en) | Chinese medicine composition as well as preparation method and use thereof | |
| CN105194487A (en) | Whitening and beautifying traditional Chinese medicine composition and facial mask and preparation method | |
| CN104771349A (en) | Skin care product containing plant extract and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20170216 Address after: 510000 Guangdong, Conghua, suburban street, No., cross river road, No. -6 (plant 3) on the third floor of building two Applicant after: Guangzhou Green Biological Technology Co., Ltd. Address before: 510000, Guangzhou, Panyu District, Inner Ring Road West University Hospital building, building, building, building 5, Applicant before: Wang Enhan |
|
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20141001 |