CN106420792A - Micro-nucleic acid acne-removing compound - Google Patents
Micro-nucleic acid acne-removing compound Download PDFInfo
- Publication number
- CN106420792A CN106420792A CN201610840261.3A CN201610840261A CN106420792A CN 106420792 A CN106420792 A CN 106420792A CN 201610840261 A CN201610840261 A CN 201610840261A CN 106420792 A CN106420792 A CN 106420792A
- Authority
- CN
- China
- Prior art keywords
- acne
- nucleic acids
- small nucleic
- seq
- positive
- 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
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
- A61K8/606—Nucleosides; Nucleotides; Nucleic acids
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/008—Preparations for oily skin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Dermatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Birds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a micro-nucleic acid acne-removing compound which comprises the following components by weight percent: 0.001-0.5% of micro-nucleic acid molecules and 99.50-99.999% of cosmetic accessories or externally applied agent accessories, wherein the length scope of the micro-nucleic acid molecules is 17-100bp, and the micro-nucleic acid molecules come from saccharomyces cerevisiae or candida tropicalis or synthetic double-chain RNA molecules. The micro-nucleic acid acne-removing compound can be used for removing and preventing facial acnes.
Description
Technical field
The invention belongs to cosmetics and drug world, specifically, relate to a kind of acne-removing composition, especially comprise double-strand
The acne-eliminating cosmetic of small nucleic acids molecule and anti-acne medicine.
Background technology
Whelk, has another name called acne, small pox etc., formal name used at school acne, is a kind of chronic inflammatory skin of pilosebaceous unit
Disease, is apt to occur in teenager, and clinical manifestation is damaged as feature with the acne, papule, warts, the polymorphy skin such as tubercle that are apt to occur in face.
Acne is the hair follicle sebum gland disease that many factors comprehensive function causes, and acne occurs main and hypersteatosis, follicular orifice
The factors such as hyperkeratosis, propionibacterium acnes propagation, excessive immune reaction are closely related.After adolescing, male sharp in human body
The level of element particularly testosterone raises rapidly, promote sebaceous glands to grow and produce a large amount of sebum, simultaneously pilosebaceous duct
Dyskeratosis causes catheter blockage, dyssebacia, is to lead acnegenic initial factors, abnormal furfur and filiform and fat
Matter mixed-stacking, forms horn plug i.e. micro mist thorn.Multiple-microorganism especially propionibacterium acnes amount reproduction, acne in hair follicle
The lipase that Propionibacterium produces decomposes sebum and generates free fatty, and chemotactic inflammatory cell and medium, finally induce and add simultaneously
Hyperphlogosis reacts.According to acne lesions character and the order of severity, acne is divided into 3 degree, 4 grades clinically, is specially:1 grade (light
Degree), only acne;2 grades (moderate), outside gumming thorn, also has some inflamed papules;3 grades (moderate), outside gumming thorn, also more
Inflamed papules or warts;4 grades (severe), in addition to having acne, inflamed papules and warts, goes back nodosity, tumour or scar.
The medicine of current acne treatment and method are a lot, but lack effective treatment method, and part treatment method makes
Product side effect big, curative effect is inconspicuous, the length course for the treatment of, easily recur, cure the symptoms, not the disease.The common method of acne treatment and existence
Many problems, including:(1) local topical medicine, tretinoin, benzoyl peroxide, antibiotics (clindamycin, erythromycin,
Chloramphenicol etc.), azelaic acid, sulphur lotion etc..But Tretinoin self stability is poor, and local excitation is more typically, has and makees compared with first mate
With greatly limit its application in clinic;Benzoyl peroxide is a kind of very effective local antibiotic preparation, but because passing
Controlling agent is easily generated local excitation, also limit its clinical practice.(2) oral antibiotic, first-selected Tetracyclines (minocycline,
Doxycycline etc.), being secondly macrolides (erythromycin), though being the effective means for the treatment of acne, but in use going out
Existing resistance problems is but on the rise.(3) oral isotretinoin, for serious acne.(4) anti-androgen therapy, as being administered orally
Contraceptive Compound Cyproterone Acetate Tablets, it is adaptable to Nv Xingzhong, severe acne patient, with the too high performance of androgen levels (as
Crinosity, seborrhea etc.) or Stein-Leventhal syndrome.(5) oral glucocorticoid, is mainly used in fulminant or polymerism Cuo
Sore.(6) other treatment, such as PDT (PDT), tartaric acid therapy, laser therapy etc..Current clinical treatment is mainly according to acne
3 degree, 4 grades carry out classification treatment, but be extremely difficult to Expected Results.
Although acne is a kind of skin disease, but can have a strong impact on the study of patient, work, motion, interpersonal relationships and society
Life, the physical and mental health of infringement patient.Therefore in the urgent need to exploitation one safely and effectively product for resolving poxes.
Content of the invention
In order to overcome the drawbacks described above of existing treatment acne technology, small nucleic acids is applied to cosmetics and external application by the present invention
Medicine, develops notable, the safe novel skincare product of anti-acne effect and medicine.
Therefore, first purpose of the present invention is to provide a kind of small nucleic acids molecule comprising there is acne result for the treatment of
Acne-removing composition, including cosmetics and medicine.
Second object of the present invention is to provide a kind of method preparing above-mentioned acne-eliminating cosmetic and anti-acne medicine.
For reaching above-mentioned purpose, the present invention adopts the following technical scheme that.
A kind of acne-removing composition, is made up of the component of following percentage by weight:Small nucleic acids molecule 0.001-0.5%, cosmetic
Product auxiliary material or externally applied drug auxiliary material 99.50-99.999%, wherein the length range of small nucleic acids molecule is 17~100bp.
Selectively, above-mentioned small nucleic acids molecular origin is in saccharomyces cerevisiae or candida tropicalis, i.e. saccharomyces cerevisiae total serum IgE or
Candida tropicalis total serum IgE.
Alternatively, above-mentioned small nucleic acids molecule is the double stranded rna molecule of Prof. Du Yucang.
Preferably, the double stranded rna molecule of above-mentioned Prof. Du Yucang be the one in following two class double stranded rna molecules or
The two or more mixture of person, is made up of positive-sense strand and antisense strand respectively:
First kind small nucleic acids molecule,
Positive-sense strand:5’-UAGGUACUUCGAGAAGCCUAGUANn-3’(SEQ ID NO:1),
Antisense strand:5’-UACUAGGCUUCUCGAAGUACCUANn-3’(SEQ ID NO:2);
Equations of The Second Kind small nucleic acids molecule,
Positive-sense strand:5’-AGGUACUUCGAGAAGCCNn-3’(SEQ ID NO:3),
Antisense strand:5’-GGCUUCUCGAAGUACCUNn-3’(SEQ ID NO:4),
Wherein, N is cytidine C, guanosine G, adenosine A, uridine U, dideoxycytosine core
Glycosides dC, NSC 22837 dG, deoxyadenosine dA or deoxythymidine dT;N represents the number of N, and n is
The integer of 0~2.
In a preferred embodiment, first kind small nucleic acids molecule is made up of following positive-sense strand and antisense strand:
Positive-sense strand:5’-UAGGUACUUCGAGAAGCCUAGUA-3’(SEQ ID NO:5),
Antisense strand:5’-UACUAGGCUUCUCGAAGUACCUA-3’(SEQ ID NO:6);Or
Positive-sense strand:5’-UAGGUACUUCGAGAAGCCUAGUAdTdT-3’(SEQ ID NO:15),
Antisense strand:5’-UACUAGGCUUCUCGAAGUACCUAdTdT-3’(SEQ ID NO:16);And
Equations of The Second Kind small nucleic acids molecule is made up of following positive-sense strand and antisense strand:
Positive-sense strand:5’-AGGUACUUCGAGAAGCC-3’(SEQ ID NO:7),
Antisense strand:5’-GGCUUCUCGAAGUACCU-3’(SEQ ID NO:8);Or
Positive-sense strand:5’-AGGUACUUCGAGAAGCCdTdT-3’(SEQ ID NO:13),
Antisense strand:5’-GGCUUCUCGAAGUACCUdTdT-3’(SEQ ID NO:14).
Preferably, above-mentioned acne-removing composition is acne-eliminating cosmetic, and above-mentioned cosmetic and percentage by weight are:Base oil
Fat 2.5-15%, NMF 1-20%, antioxidant 0.01-1.0%, thickener 0.1-2.0%, emulsifying agent 0.1-3%, plant
Oil-control factor 1-5%, skinfeel improver 0.1-2%, metal-chelator 0-0.5%, essence 0.1-0.5%, remaining for water such as
Deionized water, purified water, distilled water or distilled water etc..
Alternatively, above-mentioned acne-removing composition is anti-acne medicine, and described anti-acne pharmaceutical dosage form is ointment, emulsifiable paste
Agent, creme, liniment, aqua, lotion, gel, plastics or spray, described externally applied drug auxiliary material is selected from and is used for keeping little
The pharmaceutically acceptable auxiliary material of nucleic acid molecules stability, promotion small nucleic acids molecule percutaneous absorbtion dermal osmosis accelerator, be used for
Prepare pharmaceutically acceptable filler and excipient, water such as deionized water, purified water, the distilled water or double of external-use drug form
Steam water etc..
Preferably, above-mentioned basic grease is jojoba oil, dimethicone or their mixture.
Preferably, above-mentioned NMF be glycerine, 1,3-BDO, 1,2-pentanediol, 1,2-hexylene glycol/pungent glycol, transparent
Matter acid, glycerol caprylate or their two or more mixtures.
Preferably, above-mentioned antioxidant is fat soluble vitamin E acetate, sodium phytate or their mixture.
Preferably, above-mentioned thickener is acryloyldimethyl taurine amine/VP copolymer, xanthans or theirs is mixed
Compound.
Preferably, mentioned emulsifier is cetostearyl alcohol olive oil acid esters, sorb smooth olive oil acid esters or theirs is mixed
Compound.
Preferably, the above-mentioned plant oil-control factor is European horse-chestnut seed extract, medicine extracts of Salvia officinalis leaves, meadow pine (horse
Tail grass) extract, farfara extract, rosemary leaf extract, Flos Chrysanthemi (Europe medicine chrysanthemum) extract, sweet mary (lemon balm) leaf
Extract or their two or more mixtures.
Preferably, above-mentioned skinfeel improver is silicon body.
Preferably, above-mentioned metal-chelator is disodium ethylene diamine tetraacetate.
In a preferred embodiment, above-mentioned acne-eliminating cosmetic consists of the following components in percentage by weight:Flash
Bar oil 1-10%, dimethicone 1-5%, glycerine 2-10%, 1,3 butylene glycol 1-10%, 1,2-pentanediol 0.1-5%, 1,2-
Hexylene glycol/pungent glycol 0.1-2%, hyaluronic acid 0.01-5%, glycerol caprylate 0.1-1%, fat soluble vitamin E acetate
0.1-0.5%, acryloyldimethyl taurine amine/VP copolymer 0.1-1.0%, xanthans 0.1-1%, sodium phytate 0.01-
0.5%th, cetostearyl alcohol olive oil acid esters/sorb smooth olive oil acid esters 0.1-3%, plant oil-control factor 1-5%, silicon body
0.1-2%, disodium ethylene diamine tetraacetate 0-0.5%, small nucleic acids 0.001-0.5%, essence 0.1-0.5%, balance of deionization
Water.
A kind of method preparing above-mentioned acne-eliminating cosmetic, comprises the steps:
1) A phase mixture configuration, weighs following components mixing respectively:Jojoba oil, dimethicone, glycerine, 1,3-fourth
Glycol, 1,2-pentanediol, 1,2-hexylene glycol/pungent glycol, glycerol caprylate, fat soluble vitamin E acetate, acryloyldimethyl
Taurine amine/VP copolymer, xanthans, sodium phytate, cetostearyl alcohol olive oil acid esters, sorb smooth olive oil acid esters, ethylenediamine
Tetraacethyl disodium, deionized water;
2) B phase mixture configuration, weighs following components mixing respectively:Hyaluronic acid, silicon body, deionized water;
3) C phase mixture configuration, weighs following components mixing respectively:Small nucleic acids, the plant oil-control factor, essence, glycerine and
Deionized water;
4) take A phase mixture under the rotating speed of 30-45rpm, be stirred and heated to 85 DEG C, be incubated 30 minutes, open vacuum and change
Stirring is maximum speed 72rpm, homogeneous 5 minutes, changes mixing speed to 30-45rpm, is cooled to 60 DEG C;
5) add B phase mixture, open vacuum, maximum speed 72rpm stirring, homogeneous 2 minutes, change mixing speed to 30-
45rpm, is cooled to 50 DEG C;
6) add C phase mixture, open vacuum, maximum speed 72rpm stirring, homogeneous 2 minutes, change mixing speed to 30-
45rpm, continue cooling, change after 3 minutes stirring low speed to 20-30rpm, be cooled to 25-40 DEG C of blowing, obtain acne-eliminating cosmetic.
The acne-eliminating cosmetic of the present invention can be efficiently used for the dispelling and prevent of face acnes, skin oil-control, moisturizing, taste
Support and repair, and safety non-toxic;The anti-acne medicine of the present invention can be efficiently used for the treatment of face acnes.
Brief description
Fig. 1 is the propionibacterium acnes (Propionibacterium acnes) (amplifying 1000 times) under microscope and observing
Gram's staining photo.
Fig. 2 is that the normal propionibacterium acnes (Propionibacterium acnes) (puncture Anaerobic culturel) cultivated shines
Piece.
Fig. 3 is small nucleic acids suppression propionibacterium acnes growth photo, in figure "+" access bacterial classification;"-" does not connect bacterial classification;A is not for
Process group (is not added with small nucleic acids);B is erythromycin;C is 40mg/mL small nucleic acids;D is 80mg/mL small nucleic acids;E is that 120mg/mL is little
Nucleic acid.
Fig. 4 is small nucleic acids suppression propionibacterium acnes growth photo, in figure "+" access bacterial classification;"-" does not connect bacterial classification;A is not for
Process group (is not added with small nucleic acids);B is 80mg/mL small nucleic acids;C is 90mg/mL small nucleic acids;D is 100mg/mL small nucleic acids;E is
110mg/mL small nucleic acids.
Fig. 5 is the column diagram showing small nucleic acids suppression Escherichia coli Growth, and wherein ordinate is OD600Relative light absorption value, horizontal
Coordinate is different disposal group.
Fig. 6 is the photo of cylinder plate method detection small nucleic acids suppression Escherichia coli Growth result.
Fig. 7 is the gel electrophoresis of the saccharomyces cerevisiae M-dsRNA and candida tropicalis M-dsRNA of RNase digestion method purifying
Figure, in figure:M is RNA Marker;1 is candida tropicalis total serum IgE;2 is little for the candida tropicalis through RNase T1 separation
dsRNA;3 is saccharomyces cerevisiae total serum IgE;4 is the little dsRNA of saccharomyces cerevisiae separating through RNase T1.
Fig. 8 is the column diagram expressing change that real-time quantitative PCR detection small nucleic acids affects sebocyte cell based intracellular cvtokine.
Fig. 9 is the photo showing small nucleic acids acne-eliminating cosmetic trial effect I.
Figure 10 is the photo showing small nucleic acids acne-eliminating cosmetic trial effect II.
Figure 11 is the photo showing small nucleic acids acne-eliminating cosmetic trial effect III.
Detailed description of the invention
Addition to many kinds of substance referred to herein, content and concentration, wherein said percentage composition, except special instruction
Outward, weight/mass percentage composition is all referred to.
For convenience, hereinafter, term " double chain acid molecule ", " small nucleic acids ", " small nucleic acids molecule ", " RNA ",
" RNA molecule ", " double-stranded RNA ", " double stranded rna molecule " or " dsRNA " can exchange, and the meaning that they represent is identical with scope.
Wherein, RNA is positive-sense strand and the duplex structure of antisense strand annealing formation.
For convenience, the acne-eliminating cosmetic comprising small nucleic acids molecule of the present invention is referred to as " small nucleic acids acne-eliminating cosmetic "
Or " small nucleic acids cosmetics ".The anti-acne medicine comprising small nucleic acids molecule of the present invention be referred to as " small nucleic acids anti-acne medicine " or
Person's " small nucleic acids medicine ".
Research discovery, derives from saccharomyces cerevisiae and the RNA of candida tropicalis, especially small nucleic acids molecule have anti-acne and live
Property.In saccharomyces cerevisiae total serum IgE and candida tropicalis total serum IgE, length range is the anti-acne of the small nucleic acids molecule of 17~100bp
Activity is especially notable, and they are all double stranded rna molecules.
The small nucleic acids acne-eliminating cosmetic of the present invention and anti-acne medicine can comprise a kind of small nucleic acids molecule and such as make wine ferment
Female total serum IgE, candida tropicalis total serum IgE, described first kind small nucleic acids molecule or described Equations of The Second Kind small nucleic acids molecule;Also may be used
To comprise the mixture of two or more small nucleic acids molecule, i.e. saccharomyces cerevisiae total serum IgE, candida tropicalis total serum IgE, the described first kind
The mixture of arbitrary proportions arbitrarily two or more in small nucleic acids molecule and described Equations of The Second Kind small nucleic acids molecule.
In the small nucleic acids acne-eliminating cosmetic of the present invention and anti-acne medicine, the weight percentage lower limit of small nucleic acids is about
0.001%, preferably about the 0.005%th, the 0.01%th, the 0.015%th, the 0.02%th, the 0.025%th, the 0.03%th, the 0.035%th, the 0.04%th,
0.045% or 0.05%;The weight percentage upper limit is about 0.5%, preferably about the 0.48%th, the 0.45%th, the 0.42%th,
0.40%th, the 0.38%th, the 0.35%th, 0.32% or 0.3%.If the weight percentage of small nucleic acids is below about 0.001%, then dispel
Acne effect cannot get fully demonstrating;If the weight percentage of small nucleic acids greater than about 0.5%, then product cost is too high, may
Production marketing can be affected.
Should be understood that term " about " herein or " about " refer to that this represented number can have ± error the model of 10%
Enclose or domain of walker.
Preferably, the small nucleic acids anti-acne medicine of the present invention is further included in anti-acne aspect has association with above-mentioned small nucleic acids molecule
Same-action but the other drug active component that do not affects small nucleic acids stability and physiologically active, such as tretinoin, benzoyl peroxide
Formyl, antibiotics (clindamycin, erythromycin, chloramphenicol etc.), azelaic acid, sulphur etc., the consumption of these active constituents of medicine
Should be limited in not causing allergic scope.
As external used medicine, its formulation should be suitable for keeping the stability of small nucleic acids molecule, promote that small nucleic acids molecule is percutaneous
Absorption i.e. Cutaneous permeation, preferably aqueous dosage forms, be such as ointment, cream, creme, liniment, aqua, lotion, gel,
Plastics or spray etc..The preparation method of these formulations is well known to those skilled in the art.Those skilled in the art
Can be according to the suitable pharmaceutically acceptable externally applied drug auxiliary material of dosage form selection, including filler and excipient.
In above-mentioned aqua, liniment, cream, ointment, lotion, gel etc., as long as the host pharmacy being used
The host of upper permission then has no particular limits, and can enumerate for example water-soluble host, oiliness host, emulsion host.According to
Need, it is possible to use one kind or two or more such host.
As water-soluble host, such as polyethylene glycol (macrogol), ethanol, glycerine can be enumerated, pharmaceutically allow
Glycols (such as propane diols, butanediol) etc..Wherein, from the viewpoint of the solubility of the compounds of this invention is good, preferably medicine
The glycols allowing on.
As oiliness host, can enumerate for example from mineral vaseline or paraffin, make polyethylene tree with atoleine
Compound ointment bases (plastibase) obtained from fat gel, from biological beeswax etc..
As emulsion host, such as lanolin, stearyl alcohol etc. can be enumerated.Under the occasion using emulsion host, excellent
Emulsifying agent is added in choosing further, as such emulsifying agent, can enumerate such as polyoxyethylene hardened castor oil, monostearate sweet
Grease etc..
Ointment, cream, creme, gel and lotion generally comprise matrix, such as white petrolatum, yellow petrolatum, lanolin, white
Beeswax, cetanol, stearyl alcohol, stearic acid, hydrogenated oil and fat, Ultralube W 389 (gelatedhydrocarbon), polyethylene glycol, liquid stone
Wax, saualane etc.;Antioxidant, such as Tocopheryl derivatives, L-AA, dibutyl hydroxy toluene, butylated hydroxy anisole
Deng;Preservative, such as p-hydroxybenzoate etc.;NMF, such as glycerine, propane diols, Sodium Hyaluronate etc.;Surfactant, as
Polyoxyethylene deriv, fatty glyceride, sucrose fatty ester, fatty acid esters of sorbitan, methyl glycol fatty acid ester, ovum
Phosphatide etc.;And thickener, such as carboxyl vinyl polymer, xanthans, carboxymethylcellulose calcium, sodium carboxymethylcellulose, hydroxypropyl
Base cellulose, hydroxypropyl methyl cellulose etc..Furthermore, it is possible to be added as needed on stabilizer, preservative, sorbefacient, pH
Conditioning agent and other suitable additives.
The preparation of solution or form of emulsion can contain as the solvent of carrier mass, emulsifying agent or demulsifier, as water,
Ethanol, isopropanol, ethyl carbonate, ethyl acetate, phenmethylol, Ergol, propane diols, 1,3-butyl glycol are oily, fatty
Acid glyceride, polyethylene glycol or fatty acid esters of sorbitan etc..
The preparation of suspensions can contain as liquid diluent such as water, ethanol or the propane diols of carrier mass;Suspension
Such as ethoxylated isostearyl alcohols (ethoxylatedisosteatrylalcohol), polyoxyethylene sorbitan ester and polyoxyethylene
Isosorbide Dinitrate;And microcrystalline cellulose, inclined aluminium hydroxide (aluminummetahydroxide), bentonite, agar, Huang
Alpine yarrow glue etc..
Plastics can comprise such as methacrylate copolymer, hydroxypropyl cellulose, hydroxypropyl methyl fiber
The film forming agents such as element, methylcellulose, ethyl cellulose, polyvinyl alcohol.The plastics that the present invention provides is that small nucleic acids dissolves or divides
Dissipate in the solvent containing filmogen, apply the liquid preparation for external application forming film after putting affected part on the skin.
Further, above-mentioned solution, emulsion, the preparation of suspensions can also be attached on macromolecular material for
Prepare facial mask.
Spray may be embodied in the preparation of ointment, cream, creme, gel, suspension, aqua and lotion and made
Matrix, as white petrolatum, yellow petrolatum, lanolin, cera alba, cetanol, stearyl alcohol, stearic acid, hydrogenated oil and fat, Ultralube W 389,
Polyethylene glycol, atoleine, saualane etc.;Antioxidant, as Tocopheryl derivatives, L-AA, dibutyl hydroxy toluene,
Butylated hydroxy anisole etc.;Preservative, such as p-hydroxybenzoate etc.;NMF, such as glycerine, propane diols, Sodium Hyaluronate etc.;
Surfactant, as polyoxyethylene deriv, fatty glyceride, sucrose fatty ester, fatty acid esters of sorbitan, the third two
Alcohol fatty acid ester, lecithin etc.;Thickener, such as carboxyl vinyl polymer, xanthans, carboxymethylcellulose calcium, carboxymethyl cellulose
Element sodium, hydroxypropyl cellulose, hydroxypropyl methyl cellulose etc..Different stabilizer, buffer, flavor enhancement, suspension can be added
Agent, emulsifying agent, aromatic, preservative, solubilizer and other suitable additives.Especially, propellant can also be comprised such as
CFC, propane/butane or dimethyl ether.
In one embodiment, the small nucleic acids anti-acne medicine of the present invention is cream, is that small nucleic acids is dissolved in emulsion
The preparation being formed in type matrix.Its preparation method uses method conventional in the art, such as follows the steps below:
(1) oil phase is prepared:Weigh oleaginous base component and be heated to 50 DEG C~100 DEG C fusings, stir evenly, insulation;
(2) aqueous phase is prepared:Weigh surfactant, transdermal enhancer is dissolved in aqueous matrix, and be heated to 50 DEG C~
100 DEG C, stir evenly, insulation;
(3) above-mentioned oil phase is slowly added in above-mentioned aqueous phase, stirs 10~90 minutes;
(4) after being cooled to 45 DEG C~60 DEG C, add small nucleic acids, continue stirring;
(5) treat that temperature is down to room temperature, obtain cream.
Wherein, described oleaginous base component is selected from vaseline, paraffin, atoleine, silicone oil, beeswax, stearic acid, wool
The two or more combinations of any one or arbitrary proportion in fat, glycerin monostearate;Described aqueous matrix component selected from glycerine,
The two or more combinations of any one or arbitrary proportion in propane diols, ethanol, water;Described surfactant is sweet selected from monostearate
Grease, triethanolamine, lauryl sodium sulfate, polysorbate, aliphatic acid sorb are smooth, appointing in poloxamer, lecithin, gelatin
A kind of two or more combinations of or arbitrary proportion;Described transdermal enhancer is in Laurocapram, polyethylene glycol, menthol
The two or more combinations of any one or arbitrary proportion.
In another embodiment, the small nucleic acids anti-acne medicine of the present invention is ointment, be small nucleic acids with oil or
The uniform semi-solid external preparation that water-soluble base is mixed.Its preparation method uses method conventional in the art, than
As followed the steps below:
(1) weigh oleaginous base component and be heated to 50 DEG C~100 DEG C fusings, stir evenly, insulation;
(2) add small nucleic acids and transdermal enhancer in above-mentioned oleaginous base, stir evenly and get final product.
Wherein, described oleaginous base component is selected from vaseline, paraffin, liquid paraffin, silicone oil, beeswax, stearic acid, lanolin
The two or more combinations of any one or arbitrary proportion;Described transdermal enhancer is selected from Laurocapram, polyethylene glycol, menthol
In the two or more combinations of any one or arbitrary proportion.
In another embodiment, the small nucleic acids anti-acne medicine of the present invention is gel, is that small nucleic acids is made with auxiliary material
The glop with gel characteristic or semisolid preparation.Its preparation method uses method conventional in the art, such as presses
Carry out according to following steps:
(1) within 24 hours, make it fully swelling the immersion of gel-type vehicle component wet with solvent;Under agitation add three ethanol
Amine, regulates pH to 6.0~8.0, forms residuite standby;
(2), after separately weighing the dissolving of small nucleic acids aqueous matrix component, join in above-mentioned gel-type vehicle, stir evenly;
(3) add transdermal enhancer, aqueous matrix component is added to enough, stirs evenly and get final product.
Wherein, described gel-type vehicle component selected from carbomer, cellulose derivative, alginate, tragacanth, gelatin,
The two or more combinations of any one or arbitrary proportion in starch;Described aqueous matrix component is selected from glycerine, propane diols, water, second
The two or more combinations of any one or arbitrary proportion in alcohol;Described transdermal enhancer is selected from Laurocapram, polyethylene glycol, thin
The two or more combinations of any one or arbitrary proportion in lotus alcohol.
In another embodiment, the small nucleic acids anti-acne medicine of the present invention is spray, is small nucleic acids and proper auxiliary materials
Solution or emulsion or suspension, be filled in special device, the used time can be in vaporific ejection.Its preparation method uses this area
The method of middle routine, such as follows the steps below:
(1) weigh small nucleic acids aqueous matrix component to dissolve, stir evenly;
(2) add transdermal enhancer, aqueous matrix component is added to enough, stirs evenly, be filled in sprayer unit and get final product.
Wherein, described aqueous matrix component selected from glycerine, propane diols, water, two of any one or arbitrary proportion in ethanol
Plant combination of the above;Described transdermal enhancer is selected from Laurocapram, polyethylene glycol, any one or arbitrary proportion in menthol
Two or more combinations.
Below in conjunction with specific embodiment, the present invention is described in further details.Should be understood that following example are only used for
The bright present invention is not for restriction the scope of the present invention.
Embodiment
Saccharomyces cerevisiae total serum IgE in the present invention, candida tropicalis total serum IgE, first kind small nucleic acids molecule and the first kind are little
The preparation of nucleic acid molecules and order-checking are all completed by Biomics Bioisystech Co., Ltd.Embodiment is given following volume respectively
Number:
1. candida tropicalis total serum IgE, numbering BMX;
2. saccharomyces cerevisiae total serum IgE, numbering BMX01;
3. one of first kind small nucleic acids molecule, numbering BM06, sequence is:
Positive-sense strand:5’-UAGGUACUUCGAGAAGCCUAGUAdTdT-3’(SEQ ID NO:15),
Antisense strand:5’-UACUAGGCUUCUCGAAGUACCUAdTdT-3’(SEQ ID NO:16);
4. the two of first kind small nucleic acids molecule, numbering BM05, sequence is:
Positive-sense strand:5’-UAGGUACUUCGAGAAGCCUAGUA-3’(SEQ ID NO:5),
Antisense strand:5’-UACUAGGCUUCUCGAAGUACCUA-3’(SEQ ID NO:6);
5. one of Equations of The Second Kind small nucleic acids molecule, numbering BM01, sequence is:
Positive-sense strand:5’-AGGUACUUCGAGAAGCCdTdT-3’(SEQ ID NO:13),
Antisense strand:5’-GGCUUCUCGAAGUACCUdTdT-3’(SEQ ID NO:14);
6. the two of Equations of The Second Kind small nucleic acids molecule, numbering BM02, sequence is:
Positive-sense strand:5’-AGGUACUUCGAGAAGCC-3’(SEQ ID NO:7),
Antisense strand:5’-GGCUUCUCGAAGUACCU-3’(SEQ ID NO:8).
Wherein, BM05 is the backbone sequences of first kind small nucleic acids molecule;BM02 is the trunk sequence of Equations of The Second Kind small nucleic acids molecule
Row.
Embodiment 1
1st, experiment material and instrument:
Propionibacterium acnes (Propionibacterium acnes, ATCC 6919):The multiple auspicious biology in Shanghai;Improvement
GAM broth bouillon:Biochemistry is ground in Shanghai;Hemin, vitamin K1:Upper sea valley grinds biology;37 DEG C of constant incubators:Hundred
Ao Maike is biological;Superclean bench:Suzhou Decontamination Equipment Plant.
2nd, experiment packet:
Small nucleic acids BMX concentration is respectively:40mg/mL、80mg/mL、120mg/mL;Positive control:With commercially available erythromycin
Ointment does positive control, and concentration is 40mg/mL;Without bacterial classification comparison:Do not inoculate the culture medium of propionibacterium acnes;Untreated right
According to:The culture medium of inoculation propionibacterium acnes, but it is not added with small nucleic acids process.
3rd, experimental procedure:
It after nutrient broth medium by specification is configured, with 115 DEG C/15min of autoclaving, is cooled to 50 DEG C
When, add hemin 5 μ g/mL and 1 μ g/mL vitamin K1, take 4mL and move in teat glass, with sterile film sealing cooling
To room temperature, the small nucleic acids of above-mentioned process group is added to mix, standby after culture medium solidifying.
By propionibacterium acnes dry powder with sterilized water dissolving after, with the transfer needle after aseptic process dip rear percutaneous puncture-inoculation in
In the culture medium of teat glass, after inoculation, cover about 1mL liquid culture medium again on teat glass culture medium top, treat that its cooling is solidifying
Gu it after, is placed in after 37 DEG C of constant incubators cultivate 72h observation of taking pictures.
4th, experimental result
1) as Fig. 1 Gram's staining result shows, bacterial growth form meets propionibacterium acnes.
2) as Fig. 2 cultivation results shows, the propionibacterium acnes puncturing Anaerobic culturel is raw along puncturing route in the medium
Long.
3) as Fig. 3 result shows, positive control erythromycin completely inhibit the growth of propionibacterium acnes;Small nucleic acids concentration
When 80mg/mL, part inhibits the growth of propionibacterium acnes;Small nucleic acids concentration, when 120mg/mL, completely inhibit Cuo
The growth of sore Propionibacterium.
Result shows, the small nucleic acids molecule of the present invention has the activity of suppression propionibacterium acnes.
Embodiment 2
1st, experiment material and instrument:
Propionibacterium acnes (Propionibacterium acnes, ATCC 6919):The multiple auspicious biology in Shanghai;Improvement
GAM broth bouillon:Biochemistry is ground in Shanghai;Hemin, vitamin K1:Upper sea valley grinds biology;37 DEG C of constant incubators:On
Sea new talent;Superclean bench:Suzhou Decontamination Equipment Plant.
2nd, experiment packet:
Small nucleic acids BMX concentration is respectively:80mg/mL、90mg/mL、100mg/mL、110mg/mL、120mg/mL;Positive right
According to:Doing positive control with commercially available erythromycin ointment, concentration is 40mg/mL;Without bacterial classification comparison:Do not inoculate propionibacterium acnes
Culture medium;Untreated control:The culture medium of inoculation propionibacterium acnes, but it is not added with small nucleic acids process.
3rd, experimental procedure:
It after nutrient broth medium by specification is configured, with 115 DEG C/15min of autoclaving, is cooled to 50 DEG C
When, add hemin 5 μ g/mL and 1 μ g/mL vitamin K1, take 4mL and move in teat glass, with sterile film sealing cooling
To room temperature, the small nucleic acids of above-mentioned process group is added to mix, standby after culture medium solidifying.
By propionibacterium acnes dry powder, after dissolving with sterilized water, dip rear percutaneous puncture-inoculation with the transfer needle after aseptic process
In the culture medium of teat glass, cover about 1mL liquid culture medium again on teat glass culture medium top after inoculation, treat that it cools down
It after solidification, is placed in after 37 DEG C of constant incubators cultivate 72h observation of taking pictures.
4th, experimental result
As Fig. 4 result shows, 1) bacteriostasis of RNA molecule BMX is concentration dependent, and i.e. the higher fungistatic effect of concentration is more
By force.2) RNA molecule BMX concentration completely inhibit the growth of propionibacterium acnes when 110mg/mL.
Embodiment 3
1st, experiment material and instrument:
Escherichia coli (Escherichia coli):Hundred Ao Maike are biological;LB fluid nutrient medium:Hundred Ao Maike are biological;37
DEG C constant-temperature table:Intelligence city, Shanghai;Superclean bench:Suzhou Decontamination Equipment Plant.
2nd, experiment packet:
Small nucleic acids BMX concentration is respectively:40mg/mL、80mg/mL、120mg/mL;Positive control:Make of ampicillin
Positive control, concentration is 100 μ g/mL;Without bacterial classification comparison:Do not inoculate colibacillary culture medium;Untreated control:Inoculation large intestine
The culture medium of bacillus, but it is not added with small nucleic acids process.
3rd, experimental procedure:
By LB fluid nutrient medium (1% (W/V) Tryptone (tryptone), 0.5% (W/V) Yeast (yeast extract),
1% (W/V) NaCl, pH=7.0) after configuration is good, with 121 DEG C/20min of autoclaving, taking 4mL moves in teat glass, by nothing
After mycoderm sealing is cooled to room temperature, the small nucleic acids of above-mentioned process group is added to mix standby.
Strain Escherichia coli is inoculated in the culture medium of teat glass, is placed in 37 DEG C of constant-temperature table overnight incubation, with purple
Outer spectrophotometer measures OD at 600nm wavelength600Light absorption value, and statistical disposition result.
4th, experimental result
As Fig. 5 result shows, 1) the small nucleic acids BMX of variable concentrations all has the colibacillary effect of suppression.2) small nucleic acids is dense
Degree is 80 and completely inhibit colibacillary growth during 120mg/mL.
Embodiment 4
1st, experiment material and instrument:
Escherichia coli (Escherichia coli):Biomics Bioisystech Co., Ltd;LB solid medium:Hundred is difficult to understand
Mai Ke Bioisystech Co., Ltd;37 DEG C of constant-temperature tables:Intelligence city, Shanghai;Superclean bench:Suzhou Decontamination Equipment Plant.
2nd, experiment packet:
Small nucleic acids BMX concentration is respectively:40mg/mL、80mg/mL、120mg/mL;Positive control:Make of ampicillin
Positive control, concentration is 100 μ g/mL;Without bacterial classification comparison:Do not inoculate colibacillary culture medium;Untreated control:Inoculation large intestine
The culture medium of bacillus, but it is not added with small nucleic acids process.
3rd, experimental procedure:
((yeast soaks configuration LB solid medium for 1% (W/V) Tryptone (tryptone), 0.5% (W/V) Yeast
Cream), 1% (W/V) NaCl, 1.5% (W/V) Agar (agar), pH=7.0), with high pressure steam sterilization 121 DEG C/20 min, note
Enter 10-15mL in glass serum plate, standby after its natural coagulation.It is spread evenly across LB after strain Escherichia coli is diluted
Solid culture primary surface, after bacterium solution absorbs and does, places 4 Oxford cups symmetrically in each media surface.At Oxford cup
In be separately added into the small nucleic acids of above-mentioned variable concentrations, be placed in 37 DEG C of constant incubators and cultivate 24h, observe bacterial growth situation.
4th, experimental result
As Fig. 6 result shows, 1) the small nucleic acids BMX of variable concentrations all plays the role of to suppress Escherichia coli Growth.2) small nut
Acid concentration is 80 and completely inhibit colibacillary growth during 120mg/mL.
Embodiment 5
Yeast rna separates and identifies
1st, yeast total serum IgE:Saccharomyces cerevisiae total serum IgE (Biomics Bioisystech Co., Ltd), candida tropicalis total serum IgE
(Biomics Bioisystech Co., Ltd).
2nd, main agents and material:RNase T1 (Fermentas company of the U.S.), RNA Marker (RL1000, TaKaRa
Company), the glycogen (the auspicious neat biotechnology in Shanghai) polluting without RNase, other biochemical reagents are all purchased from the raw work in Shanghai.
3rd, key instrument:Superclean bench (SW-CJ-2F Suzhou Decontamination Equipment Plant);Low temperature refrigerator (-80 DEG C, DF-
U4086S, SANYO GS);Electrophoresis apparatus (Bio-Rad, the U.S.);Gel imaging system (Biosens, the U.S.);Uv-spectrophotometric
Meter and analysis work station (Shimadzu Shimadazi, Japan) etc..
4th, process yeast total serum IgE with RNaseT1 and isolate dsRNA.Reaction system is as follows:The liquid of 200 μ L contains 20 μ L (20
μg)RNA;10μL(10U)RNase T1;20 μ L 10 × TE Buffer (10mM Tris-HCl, 1mM EDTA, pH=8.0),
150 μ L sterilized waters.37 DEG C of reaction 30min, add 20 μ L EDTA (250mM) stopped reactions, 72 DEG C of heating 20min inactivators.Take 5 μ
L electrophoretic analysis.And with take l μ L yeast dsRNA add 99 μ L 1 × TE Buffer (l00 times dilutes), ultraviolet specrophotometer
Detection OD260And OD280Ratio (this value is dsRNA between 1.8~2.0).
5th, electrophoretic analysis digestion product:
The little dsRNA of yeast after separation through 15% polyacrylamide gel electrophoresis testing result as it is shown in fig. 7, separate ferment
Female little dsRNA length is distributed mainly on below 100bp, without DNA and other single stranded RNA findings.In figure:M is RNA Marker;1
For candida tropicalis total serum IgE;2 is the little dsRNA of candida tropicalis separating through RNase T1;3 is saccharomyces cerevisiae total serum IgE;4
For the little dsRNA of saccharomyces cerevisiae separating through RNase T1.
6th, UV spectrophotometer measuring:Record separated candida tropicalis and the OD of the little dsRNA of saccharomyces cerevisiae260With
OD280Ratio is respectively 1.91 and 1.89, it was demonstrated that be dsRNA.
Embodiment 6
Impact on TLR family and inflammatory factor after small nucleic acids stimulation sebocyte cell
1st, experiment material and instrument
People's sebocyte cell:Biomics Bioisystech Co., Ltd, Poly (I:C):U.S. Sigma-Aldrich is public
Department;Small nucleic acids BM01, BM06, BMX:Biomics Bioisystech Co., Ltd;6 porocyte culture plates:U.S. Corning is public
Department;RISOTMRNA extracts reagent:Biomics Bioisystech Co., Ltd;EzOmicsTMOne-Step qPCR Kit:Hundred is difficult to understand
Mai Ke Bioisystech Co., Ltd;ABI StepOnePlus real-time fluorescence quantitative PCR instrument (American AB I company).
2nd, experiment packet:
Small nucleic acids process group:BM01,50nM;BM06,50nM;Poly(I:C), 10ng/ml;BMX, 2.5 μ g;At She Zhiing
Reason group compares.
3rd, cell process:Spreading 6 orifice plates, before transfection, cell confluency degree is about 50%, processes cell with above-mentioned small nucleic acids.
4th, real-time quantitative PCR (Real time quantity PCR, RT-qPCR) detection
Cell uses RISO after processing 48hTMRNA extracts reagent, extracts cell total rna to specifications, is examined by RT-qPCR
Survey the mrna expression level of genes of interest in cell.
With the expression of gene mRNA in gene-specific primer detection sample, expand house-keeping gene GAPDH simultaneously and make
For internal reference comparison.Each sample amplifying target genes and reference gene GAPDH simultaneously, each reaction do 3 parallel.Use One-
Step qPCR kit carries out quantitative reaction, sets up following reaction system:2 μ L RNA templates, 2 × Master Mix of 12.5 μ L,
5 ' ends primer (10 μM) and 3 ' ends primer (10 μM) each 0.5 μ L, 50 × SYBR Green I Solution of 0.5 μ L, use DEPC
Process water and supply system to 25 μ L.It after mixing, is placed on real-time PCR reaction.Required primer is by hundred Ao Maike
Bioisystech Co., Ltd synthesizes, and sequence is as follows:
IL4 detection primer:
Upstream primer:5’-ATGAGAAGGACACTCGCTGC-3’(SEQ ID NO:9);
Downstream primer:5’-CCAACGTACTCTGGTTGGCT-3’(SEQ ID NO:10).
GAPDH primer:
Upstream primer:5’-GAAGGTGAAGGTCGGAGTC-3’(SEQ ID NO:11);
Downstream primer:5’-GAAGATGGTGATGGGATTTC-3’(SEQ ID NO:12).
Reaction condition:42 DEG C of reverse transcription 30min, 95 DEG C of denaturations 5min, 95 DEG C of denaturation 20sec, 58 DEG C of annealing 30sec,
72 DEG C extend 30sec, circulate 45 times.And do solubility curve reaction:95 DEG C/5min, 58 DEG C/5min, heat up with 0.5 DEG C/5sec
To 95 DEG C.
5th, statistical disposition
With the analysis of SPSS 14.0 statistical software, continuous data mean value ± SD represents, the significance test of many group differences
With one-way analysis of variance, compare between two groups with t inspection, P<0.05 expression difference is statistically significant.
6th, experimental result
As shown in Figure 8, compared with untreated fish group, press down the expression of inflammatory cytokines IL4 under the effect of small nucleic acids in
Notable rise (P<0.05).
Embodiment 7
A kind of small nucleic acids acne-eliminating cosmetic, this cosmetics consist of the following components in percentage by weight:Jojoba oil is the 2%th,
Dimethicone the 1%th, glycerine the 7.5%th, 1,3 butylene glycol the 5%th, 1,2-pentanediol the 2%th, 1,2-hexylene glycol/pungent glycol is the 0.5%th, saturating
Bright matter acid the 0.02%th, glycerol caprylate the 0.3%th, fat soluble vitamin E acetate the 0.2%th, acryloyldimethyl taurine amine/VP
Copolymer the 0.65%th, xanthans the 0.15%th, sodium phytate the 0.1%th, cetostearyl alcohol olive oil acid esters/sorb smooth olive oil acid esters
1%th, the plant oil-control factor the 2%th, silicon body the 0.5%th, small nucleic acids (BMX) the 0.25%th, essence the 0.15%th, balance of deionized water.
Embodiment 8
A kind of small nucleic acids acne-eliminating cosmetic, this cosmetics consist of the following components in percentage by weight:Jojoba oil is the 2%th,
Dimethicone the 1%th, glycerine the 7.5%th, 1,3 butylene glycol the 5%th, 1,2-pentanediol the 2%th, 1,2-hexylene glycol/pungent glycol is the 0.5%th, saturating
Bright matter acid the 0.02%th, glycerol caprylate the 0.3%th, fat soluble vitamin E acetate the 0.2%th, acryloyldimethyl taurine amine/VP
Copolymer the 0.65%th, xanthans the 0.15%th, sodium phytate the 0.1%th, cetostearyl alcohol olive oil acid esters/sorb smooth olive oil acid esters
1%th, the plant oil-control factor the 2%th, silicon body the 0.5%th, small nucleic acids (BMX01) the 0.5%th, essence the 0.15%th, balance of deionized water.
Embodiment 9
A kind of small nucleic acids acne-eliminating cosmetic, this cosmetics consist of the following components in percentage by weight:Jojoba oil is the 2%th,
Dimethicone the 1%th, glycerine the 7.5%th, 1,3 butylene glycol the 5%th, 1,2-pentanediol the 2%th, 1,2-hexylene glycol/pungent glycol is the 0.5%th, saturating
Bright matter acid the 0.02%th, glycerol caprylate the 0.3%th, fat soluble vitamin E acetate the 0.2%th, acryloyldimethyl taurine amine/
VP copolymer the 0.65%th, xanthans the 0.15%th, sodium phytate the 0.1%th, cetostearyl alcohol olive oil acid esters/sorb smooth olive oil acid esters
1%th, the plant oil-control factor the 2%th, silicon body the 0.5%th, small nucleic acids (BM01) the 0.003%th, essence the 0.15%th, balance of deionization
Water.
Embodiment 10
A kind of small nucleic acids acne-eliminating cosmetic, this cosmetics consist of the following components in percentage by weight:Jojoba oil is the 2%th,
Dimethicone the 1%th, glycerine the 7.5%th, 1,3 butylene glycol the 5%th, 1,2-pentanediol the 2%th, 1,2-hexylene glycol/pungent glycol is the 0.5%th, saturating
Bright matter acid the 0.02%th, glycerol caprylate the 0.3%th, fat soluble vitamin E acetate the 0.2%th, acryloyldimethyl taurine amine/VP
Copolymer the 0.65%th, xanthans the 0.15%th, sodium phytate the 0.1%th, cetostearyl alcohol olive oil acid esters/sorb smooth olive oil acid esters
1%th, the plant oil-control factor the 2%th, silicon body the 0.5%th, small nucleic acids (BM06) the 0.001%th, essence the 0.15%th, balance of deionization
Water.
Embodiment 11
A kind of small nucleic acids acne-eliminating cosmetic, this cosmetics consist of the following components in percentage by weight:Jojoba oil is the 2%th,
Dimethicone the 1%th, glycerine the 7.5%th, 1,3 butylene glycol the 5%th, 1,2-pentanediol the 2%th, 1,2-hexylene glycol/pungent glycol is the 0.5%th, saturating
Bright matter acid the 0.02%th, glycerol caprylate the 0.3%th, fat soluble vitamin E acetate the 0.2%th, acryloyldimethyl taurine amine/VP
Copolymer the 0.65%th, xanthans the 0.15%th, sodium phytate the 0.1%th, cetostearyl alcohol olive oil acid esters/sorb smooth olive oil acid esters
1%th, the plant oil-control factor the 2%th, silicon body the 0.5%th, small nucleic acids (BM06) the 0.003%th, essence the 0.15%th, balance of deionization
Water.
Embodiment 12
The method of preparation embodiment 7-11 small nucleic acids acne-eliminating cosmetic, specific as follows:
1) A phase mixture configuration, weighs following components mixing respectively:Jojoba oil the 2%th, dimethicone the 1%th, glycerine
7%th, 1,3 butylene glycol the 5%th, 1,2-pentanediol the 2%th, 1,2-hexylene glycol/pungent glycol the 0.5%th, glycerol caprylate the 0.3%th, oil-soluble
Vitwas E the 0.2%th, acryloyldimethyl taurine amine/VP copolymer the 0.65%th, xanthans the 0.15%th, sodium phytate
0.1%th, cetostearyl alcohol olive oil acid esters/sorb smooth olive oil acid esters 1%, balance of deionized water;
2) B phase mixture configuration, weighs following components mixing respectively:Hyaluronic acid the 0.02%th, deionized water the 3%th, silicon bullet
Body 0.5%;
3) C phase mixture configuration, weighs following components mixing respectively:Glycerine the 0.5%th, small nucleic acids 0.001-0.5%, go
Ionized water the 3%th, the plant oil-control factor the 2%th, essence 0.15%;
4) take A phase under the rotating speed of 30-45rpm, be stirred and heated to 85 DEG C, be incubated 30 minutes, open vacuum and change stirring and be
Maximum speed 72rpm, homogeneous 5 minutes, change mixing speed to 30-45rpm, be cooled to 60 DEG C;
5) add B phase, open vacuum, maximum speed 72rpm stirring, homogeneous 2 minutes, change mixing speed to 30-45rpm, cooling
To 50 DEG C;
6) adding C phase, opening vacuum, maximum speed 72rpm stirs, homogeneous 2 minutes, change mixing speed to 30-45rpm, continuation
Cooling, change after 3 minutes stirring low speed to 20-30rpm, be cooled to 25-40 DEG C of blowing, obtain small nucleic acids acne-eliminating cosmetic.
Embodiment 13
Tried out by the small nucleic acids acne-eliminating cosmetic of embodiment of the present invention 7-11, specific as follows:
1st, experimental subjects:Age distribution is in the masculinity and femininity of 15~33 years old (average age 22.9 years old).Face and neck neck
There is acne in various degree at position, inducement has that hormone secretion is vigorous, endocrinopathy, drug administration, cosmetics improper use etc..
2nd, experimental technique:After morning and evening every day net face, uniform application small nucleic acids acne-eliminating cosmetic is in affected part, it is possible to full face or neck
Neck position uniform application.It within two weeks, is an observation cycle.
3rd, acne is divided into (by three degree of level Four classification of acne general in the world) by the order of severity:
1) I (slightly):Acne are major determinant, can have a small amount of papule and useless fellow, and total focus number is less than 30;
2) II (moderate):Having acne, and having papule and the useless fellow of moderate quatity, total focus number is between 31-50;
3) III (sub-severe):Having substantial amounts of papule and useless fellow, total focus number, between 51-100, has big inflammation once in a while
Property damage, tubercle be less than 3;
4) IV (severe):Predominantly tubercle, tumour or acne conglobata.Total focus number is more than 100, and disease damage number exists
More than 100, tubercle or tumour are more than 3.
4th, therapeutic evaluation classification (with reference to Ministry of Public Health's dermatosis treating medicine guideline of clinical investigations):"-" (invalid), skin damages and disappears
Move back<20% or increase the weight of;"+" (effectively), skin damages and disappears>20%~60%;" ++ " (effective), skin damages and disappears>60%;" +++ " (fullys recover from an illness
More), skin damages and disappears.
5th, result for the treatment of is as follows:
6th, Fig. 9-11 shows representative patient's anti-acne effect photo (before using and comparing after using).From these
After photo is it can be seen that use the acne-eliminating cosmetic of the present invention to smear skin two weeks, the symptom of acne spots originally is all obvious
Mitigate, have the acne of patient almost to disappear.
Embodiment 14
A kind of small nucleic acids anti-acne medicine, this medicine is cream, composed of the following components:Small nucleic acids BMX 1g, stearic acid
40g, glycerin monostearate 40g, vaseline 20g, atoleine 70g, glycerine 50g, triethanolamine 3g, lauryl sodium sulfate
3g, Laurocapram 2g, Purified Water q. s, full dose 1000g.
The method preparing this small nucleic acids anti-acne medicine is as follows:
(1) oil phase:Accurately weigh stearic acid, glycerin monostearate, that heating in water-bath put by vaseline, atoleine is molten
Changing, stirring evenly, insulation is at about 75 DEG C;
(2) aqueous phase:Accurately weigh glycerine, triethanolamine, Laurocapram, lauryl sodium sulfate and water, in a water bath
Heating stirring and dissolving, and it is heated to 75 DEG C.
(3) it is slowly added into above-mentioned oil phase in aqueous phase, after stirring 15 minutes, be kept stirring for.
(4) it is cooled to about 55 DEG C, adds the small nucleic acids BMX of recipe quantity, continue stirring.
(5) treat that temperature is down to room temperature, obtain emulsifiable paste.
Embodiment 15
A kind of small nucleic acids anti-acne medicine, this medicine is cream, composed of the following components:Small nucleic acids BM06 1g, stearic acid
40g, glycerin monostearate 40g, vaseline 20g, atoleine 70g, glycerine 50g, triethanolamine 3g, lauryl sodium sulfate
3g, Laurocapram 2g, Purified Water q. s, full dose 1000g.
The method preparing this small nucleic acids anti-acne medicine is as follows:
(1) oil phase:Accurately weigh stearic acid, glycerin monostearate, that heating in water-bath put by vaseline, atoleine is molten
Changing, stirring evenly, insulation is at about 75 DEG C;
(2) aqueous phase:Accurately weigh glycerine, triethanolamine, Laurocapram, lauryl sodium sulfate and water, in a water bath
Heating stirring and dissolving, and it is heated to 75 DEG C.
(3) it is slowly added into above-mentioned oil phase in aqueous phase, after stirring 15 minutes, be kept stirring for.
(4) it is cooled to about 55 DEG C, adds the small nucleic acids BM06 of recipe quantity, continue stirring.
(5) treat that temperature is down to room temperature, obtain emulsifiable paste.
Embodiment 16
A kind of small nucleic acids anti-acne medicine, this medicine is gel, composed of the following components:Small nucleic acids BM01 1g, carbomer
10g, propane diols 50g, glycerine 50g, triethanolamine 10ml, ethanol 20ml, Laurocapram 5g, Purified Water q. s, full dose
1000g.
The method preparing this small nucleic acids anti-acne medicine is as follows:
By glycerine, propane diols joins makes it soak in carbomer, and adds about 500ml purified water, and standing 24h makes it fill
Divide swelling;Under agitation add triethanolamine, regulate pH to 6.5-7.5, form residuite standby;Separately weigh small nucleic acids
BM01, joins in above-mentioned gel, stirs evenly;It is eventually adding Laurocapram, add purified water extremely enough, stir evenly, obtain gel.
Embodiment 17
Tried out by the small nucleic acids anti-acne medicine of embodiment of the present invention 14-16, specific as follows:
1st, experimental subjects:Age distribution is in the masculinity and femininity of 18~33 years old (average age 23.5 years old).Face and neck neck
There is acne in various degree at position, inducement has that hormone secretion is vigorous, endocrinopathy, drug administration, cosmetics improper use etc..
2nd, experimental technique:After morning and evening every day net face, uniform application small nucleic acids acne-eliminating cosmetic is in affected part, it is possible to full face or neck
Neck position uniform application.It within two weeks, is an observation cycle.
3rd, acne is divided into (by three degree of level Four classification of acne general in the world) by the order of severity:
1) I (slightly):Acne are major determinant, can have a small amount of papule and useless fellow, and total focus number is less than 30;
2) II (moderate):Having acne, and having papule and the useless fellow of moderate quatity, total focus number is between 31-50;
3) III (sub-severe):Having substantial amounts of papule and useless fellow, total focus number, between 51-100, has big inflammation once in a while
Property damage, tubercle be less than 3;
4) IV (severe):Predominantly tubercle, tumour or acne conglobata.Total focus number is more than 100, and disease damage number exists
More than 100, tubercle or tumour are more than 3.
4th, therapeutic evaluation classification (with reference to Ministry of Public Health's dermatosis treating medicine guideline of clinical investigations):"-" (invalid), skin damages and disappears
Move back<20% or increase the weight of;"+" (effectively), skin damages and disappears>20%~60%;" ++ " (effective), skin damages and disappears>60%;" +++ " (fullys recover from an illness
More), skin damages and disappears.
5th, result for the treatment of is as follows:
Anti-acne medicine | Number of cases | Recovery from illness | Effective | Effectively | Invalid | Total effective rate |
Embodiment 14 small nucleic acids anti-acne medicine | 25 | 11 | 9 | 2 | 3 | 88.00% |
Embodiment 15 small nucleic acids anti-acne medicine | 19 | 9 | 7 | 1 | 2 | 89.47% |
Embodiment 16 small nucleic acids anti-acne medicine | 20 | 8 | 8 | 1 | 3 | 85.00% |
In sum, acne-eliminating cosmetic and the anti-acne medicine of the present invention can be efficiently used for dispelling of face acnes, and
Safety non-toxic, has wide commercial promise.
Claims (10)
1. an acne-removing composition, is made up of the component of following percentage by weight:Small nucleic acids molecule 0.001-0.5%, cosmetics
Auxiliary material or externally applied drug auxiliary material 99.50-99.999%, wherein small nucleic acids molecule is selected from saccharomyces cerevisiae total serum IgE, the false silk ferment in the torrid zone
One or more kinds of mixtures in female total serum IgE, following two class double stranded rna molecules, respectively by positive-sense strand and antisense strand
Composition:
First kind small nucleic acids molecule,
Positive-sense strand:5’-UAGGUACUUCGAGAAGCCUAGUANn-3’(SEQ ID NO:1),
Antisense strand:5’-UACUAGGCUUCUCGAAGUACCUANn-3’(SEQ ID NO:2);
Equations of The Second Kind small nucleic acids molecule,
Positive-sense strand:5’-AGGUACUUCGAGAAGCCNn-3’(SEQ ID NO:3),
Antisense strand:5’-GGCUUCUCGAAGUACCUNn-3’(SEQ ID NO:4),
Wherein, N be cytidine C, guanosine G, adenosine A, uridine U, deoxycytidine dC,
NSC 22837 dG, deoxyadenosine dA or deoxythymidine dT;N represents the number of N, and n is 0~2
Integer.
2. acne-removing composition as claimed in claim 1, it is characterised in that first kind small nucleic acids molecule is by following positive-sense strand and anti-
Justice chain composition:
Positive-sense strand:5’-UAGGUACUUCGAGAAGCCUAGUA-3’(SEQ ID NO:5),
Antisense strand:5’-UACUAGGCUUCUCGAAGUACCUA-3’(SEQ ID NO:6);Or
Positive-sense strand:5’-UAGGUACUUCGAGAAGCCUAGUAdTdT-3’(SEQ ID NO:15),
Antisense strand:5’-UACUAGGCUUCUCGAAGUACCUAdTdT-3’(SEQ ID NO:16);And
Equations of The Second Kind small nucleic acids molecule is made up of following positive-sense strand and antisense strand:
Positive-sense strand:5’-AGGUACUUCGAGAAGCC-3’(SEQ ID NO:7),
Antisense strand:5’-GGCUUCUCGAAGUACCU-3’(SEQ ID NO:8);Or
Positive-sense strand:5’-AGGUACUUCGAGAAGCCdTdT-3’(SEQ ID NO:13);
Antisense strand:5’-GGCUUCUCGAAGUACCUdTdT-3’(SEQ ID NO:14).
3. acne-removing composition as claimed in claim 1 or 2, it is characterised in that described acne-removing composition is acne-eliminating cosmetic, institute
State cosmetic and percentage by weight is:Basic grease 2.5-15%, NMF 1-20%, antioxidant 0.01-1.0%,
Thickener 0.1-2.0%, emulsifying agent 0.1-3%, plant oil-control factor 1-5%, skinfeel improver 0.1-2%, metal-chelator
0-0.5%, essence 0.1-0.5%, remaining be water;Or
Described acne-removing composition is anti-acne medicine, described anti-acne pharmaceutical dosage form be ointment, cream, creme, liniment, aqua,
Lotion, gel, plastics or spray, described externally applied drug auxiliary material is selected from the medicine for keeping small nucleic acids stability of molecule
Learn acceptable auxiliary material, promotion small nucleic acids molecule percutaneous absorbtion dermal osmosis accelerator, for preparing the medicine of external-use drug form
Learn acceptable filler and excipient, water.
4. acne-removing composition as claimed in claim 3, it is characterised in that described basic grease is jojoba oil, dimethyl-silicon
Oil or their mixture.
5. acne-removing composition as claimed in claim 3, it is characterised in that described NMF be glycerine, 1,3-BDO, 1,2-
Pentanediol, 1,2-hexylene glycol/pungent glycol, hyaluronic acid, glycerol caprylate or their two or more mixtures.
6. acne-removing composition as claimed in claim 3, it is characterised in that described antioxidant is fat soluble vitamin E acetic acid
Ester, sodium phytate or their mixture.
7. acne-removing composition as claimed in claim 3, it is characterised in that described thickener is acryloyldimethyl taurine
Amine/VP copolymer, xanthans or their mixture.
8. acne-removing composition as claimed in claim 3, it is characterised in that described emulsifying agent is cetostearyl alcohol olive oleic acid
Ester, sorb smooth olive oil acid esters or their mixture;
The described plant oil-control factor be European horse-chestnut seed extract, medicine extracts of Salvia officinalis leaves, meadow pine (gulfweed) extract,
Farfara extract, rosemary leaf extract, Flos Chrysanthemi (Europe medicine chrysanthemum) extract, sweet mary (lemon balm) leaf extract or
Their two or more mixtures;
Described skinfeel improver is silicon body;
Described metal-chelator is disodium ethylene diamine tetraacetate.
9. acne-removing composition as claimed in claim 3, it is characterised in that cosmetics are by following components in percentage by weight group
Become:Jojoba oil 1-10%, dimethicone 1-5%, glycerine 2-10%, 1,3 butylene glycol 1-10%, 1,2-pentanediol 0.1-
5%th, 1,2-hexylene glycol/pungent glycol 0.1-2%, hyaluronic acid 0.01-5%, glycerol caprylate 0.1-1%, fat soluble vitamin E
Acetate 0.1-0.5%, acryloyldimethyl taurine amine/VP copolymer 0.1-1.0%, xanthans 0.1-1%, sodium phytate
0.01-0.5%, cetostearyl alcohol olive oil acid esters/sorb smooth olive oil acid esters 0.1-3%, plant oil-control factor 1-5%, silicon
Body 0.1-2%, disodium ethylene diamine tetraacetate 0-0.5%, small nucleic acids 0.001-0.5%, essence 0.1-0.5%, balance of go
Ionized water.
10. the method preparing acne-eliminating cosmetic as claimed in claim 3, comprises the steps:
1) A phase mixture configuration, weighs following components mixing respectively:Jojoba oil, dimethicone, glycerine, 1,3 butylene glycol,
1,2-pentanediol, 1,2-hexylene glycol/pungent glycol, glycerol caprylate, fat soluble vitamin E acetate, acryloyldimethyl ox sulphur
Acid amide/VP copolymer, xanthans, sodium phytate, cetostearyl alcohol olive oil acid esters, sorb smooth olive oil acid esters, ethylenediamine tetrem
Acid disodium and deionized water;
2) B phase mixture configuration, weighs following components mixing respectively:Hyaluronic acid, silicon body, deionized water;
3) C phase mixture configuration, weighs following components mixing respectively:Small nucleic acids, the plant oil-control factor, essence, glycerine and go from
Sub-water;
4) take A phase mixture under the rotating speed of 30-45rpm, be stirred and heated to 85 DEG C, be incubated 30 minutes, open vacuum and change stirring
For maximum speed 72rpm, homogeneous 5 minutes, change mixing speed to 30-45rpm, be cooled to 60 DEG C;
5) add B phase mixture, open vacuum, maximum speed 72rpm stirring, homogeneous 2 minutes, change mixing speed to 30-45rpm, cold
But to 50 DEG C;
6) add C phase mixture, open vacuum, maximum speed 72rpm stirring, homogeneous 2 minutes, change mixing speed to 30-45rpm, continue
Continuous cooling, changes stirring low speed to 20-30rpm, is cooled to 25-40 DEG C of blowing, obtains acne-eliminating cosmetic after 3 minutes.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610840261.3A CN106420792A (en) | 2016-09-21 | 2016-09-21 | Micro-nucleic acid acne-removing compound |
PCT/CN2017/101023 WO2018054229A1 (en) | 2016-09-21 | 2017-09-08 | Micro-nucleic acid acne-removing composition |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610840261.3A CN106420792A (en) | 2016-09-21 | 2016-09-21 | Micro-nucleic acid acne-removing compound |
Publications (1)
Publication Number | Publication Date |
---|---|
CN106420792A true CN106420792A (en) | 2017-02-22 |
Family
ID=58166652
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610840261.3A Pending CN106420792A (en) | 2016-09-21 | 2016-09-21 | Micro-nucleic acid acne-removing compound |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN106420792A (en) |
WO (1) | WO2018054229A1 (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2018054229A1 (en) * | 2016-09-21 | 2018-03-29 | 百奥迈科生物技术有限公司 | Micro-nucleic acid acne-removing composition |
CN111616979A (en) * | 2019-02-28 | 2020-09-04 | 科丝美诗株式会社 | Composition comprising mixture of nucleic acid fragments and application thereof |
CN111956519A (en) * | 2020-07-17 | 2020-11-20 | 重庆珂蓝健康管理集团有限公司 | Small nucleic acid skin care product capable of quickly and safely removing freckles |
CN113749962A (en) * | 2021-09-17 | 2021-12-07 | 孔冰冰 | Preparation method of small nucleic acid acne and freckle removing composition |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115337233B (en) * | 2022-06-24 | 2023-05-30 | 广州环亚化妆品科技股份有限公司 | Gel mask with mild acne removing effect and preparation method thereof |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102935238A (en) * | 2012-07-27 | 2013-02-20 | 水爱生物科技(南通)有限公司 | Application of yeast M-dsRNA as TLR3 agonist, and yeast M-dsRNA preparation method |
CN103221540A (en) * | 2010-09-20 | 2013-07-24 | 百奥迈科生物技术有限公司 | The application of highly conserved domain sequences from viral genome as template to design therapeutic slirNAS |
US20150132342A1 (en) * | 2013-11-08 | 2015-05-14 | The Regents Of The University Of California | Novel immune activators: substitute 4-aminoquinazolines |
CN104739686A (en) * | 2013-12-28 | 2015-07-01 | 大连美乐生物技术开发有限公司 | Anti-acne cream and preparation method thereof |
CN105748353A (en) * | 2016-03-09 | 2016-07-13 | 广州千百度化妆品有限公司 | Cosmetic composition with acne treatment function and preparation method thereof |
CN105769643A (en) * | 2016-01-27 | 2016-07-20 | 广东芭薇生物科技股份有限公司 | Water moisturizing cream and preparation method thereof |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106420792A (en) * | 2016-09-21 | 2017-02-22 | 百奥迈科生物技术有限公司 | Micro-nucleic acid acne-removing compound |
-
2016
- 2016-09-21 CN CN201610840261.3A patent/CN106420792A/en active Pending
-
2017
- 2017-09-08 WO PCT/CN2017/101023 patent/WO2018054229A1/en active Application Filing
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103221540A (en) * | 2010-09-20 | 2013-07-24 | 百奥迈科生物技术有限公司 | The application of highly conserved domain sequences from viral genome as template to design therapeutic slirNAS |
CN102935238A (en) * | 2012-07-27 | 2013-02-20 | 水爱生物科技(南通)有限公司 | Application of yeast M-dsRNA as TLR3 agonist, and yeast M-dsRNA preparation method |
US20150132342A1 (en) * | 2013-11-08 | 2015-05-14 | The Regents Of The University Of California | Novel immune activators: substitute 4-aminoquinazolines |
CN104739686A (en) * | 2013-12-28 | 2015-07-01 | 大连美乐生物技术开发有限公司 | Anti-acne cream and preparation method thereof |
CN105769643A (en) * | 2016-01-27 | 2016-07-20 | 广东芭薇生物科技股份有限公司 | Water moisturizing cream and preparation method thereof |
CN105748353A (en) * | 2016-03-09 | 2016-07-13 | 广州千百度化妆品有限公司 | Cosmetic composition with acne treatment function and preparation method thereof |
Non-Patent Citations (1)
Title |
---|
MCLNTURFF,J. E. 等: "The Role of Toll-Like Receptors in the Pathophysiology of Acne", 《SEMINARS IN CUTANEOUS MEDICINE AND SURGERY》 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2018054229A1 (en) * | 2016-09-21 | 2018-03-29 | 百奥迈科生物技术有限公司 | Micro-nucleic acid acne-removing composition |
CN111616979A (en) * | 2019-02-28 | 2020-09-04 | 科丝美诗株式会社 | Composition comprising mixture of nucleic acid fragments and application thereof |
CN111956519A (en) * | 2020-07-17 | 2020-11-20 | 重庆珂蓝健康管理集团有限公司 | Small nucleic acid skin care product capable of quickly and safely removing freckles |
CN113749962A (en) * | 2021-09-17 | 2021-12-07 | 孔冰冰 | Preparation method of small nucleic acid acne and freckle removing composition |
Also Published As
Publication number | Publication date |
---|---|
WO2018054229A1 (en) | 2018-03-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN106420792A (en) | Micro-nucleic acid acne-removing compound | |
Mir-Palomo et al. | Inhibition of skin inflammation by baicalin ultradeformable vesicles | |
CN109715183A (en) | The new beauty and make-up and/or nutrition and health care or dermatological use of yeast extract | |
CN109310626A (en) | The purposes of Gram-negative kind treatment atopic dermatitis | |
KR20210013080A (en) | Composition for the treatment of skin conditions | |
JP2021504390A (en) | Methods and topical compositions for modifying the skin microbiome | |
WO2017087640A1 (en) | Probiotic treatment of skin diseases, disorders, and infections: formulations, methods and systems | |
CN112512540A (en) | Compositions for treating skin conditions | |
CN108852865A (en) | A kind of fullerene topical composition | |
CN111743830A (en) | Acne-removing composition and application thereof | |
CN117045523A (en) | High-content azelaic acid composition and preparation method thereof | |
CN104784223A (en) | Composition with itching removing function and preparation method thereof | |
JP2006290873A (en) | Aquaporin expression promoter | |
CN108542805A (en) | Anti-acne compound essential oil preparation and its preparation method and application | |
WO2021138599A1 (en) | Cosmetic compositions | |
CN102166254A (en) | Oil-in-water type spearmint oil nano emulsion and method for preparing same | |
KR101841118B1 (en) | Composition for skin external application comprising extract of scenedesmus sp. | |
CN103800401B (en) | Granulation promoting healing ointment | |
EP3378475A1 (en) | Composition and kit for the use in the prevention of recurrent onychomycosis | |
JP2003231626A (en) | Atp production promoter | |
CN112402335A (en) | Water-bursting powder and preparation method thereof | |
KR101326164B1 (en) | External Composition for Skin Having Antibacterial Activities | |
KR20080063005A (en) | Cosmetic composition containing piceatannol and vitamin a (retinoids) | |
CN107519119A (en) | A kind of snake gall anti-acne essence cream and preparation method thereof | |
KR20160020038A (en) | Cosmetic Composition containing Frangipani Oil or Fermented Frangipani Oil |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170222 |