CN102688155A - External composition - Google Patents
External composition Download PDFInfo
- Publication number
- CN102688155A CN102688155A CN2012100684308A CN201210068430A CN102688155A CN 102688155 A CN102688155 A CN 102688155A CN 2012100684308 A CN2012100684308 A CN 2012100684308A CN 201210068430 A CN201210068430 A CN 201210068430A CN 102688155 A CN102688155 A CN 102688155A
- Authority
- CN
- China
- Prior art keywords
- salt
- acid
- pqq
- glycol
- edta
- 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
Images
Landscapes
- Cosmetics (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides an external composition, containing the components as following: (a) pyrroloquinoline quinone or physiologically acceptable salt thereof; (b) EDTA or physiologically acceptable salt thereof; and (c) at least one compound with hydroxyl groups selected from polyols with 2 to 6 carbon atoms and 2 to 4 hydroxys and dibasic alcohol, the content of the compound with hydroxyl groups (c) is more than 5 part relative to the 1 weight part of pyrroloquinoline quinone or physiologically acceptable salt (a).
Description
Technical field
The present invention relates to comprise PQQ (following abbreviate as sometimes " PQQ ") or its physiologically acceptable salt and EDTA or its physiologically acceptable salt, be used as the topical composition of cosmetics, accurate medicine or medicine.
Background technology
Elastin laminin in vivo, corium and joint that is distributed widely in ligament, blood vessel wall, lung, skin etc. needs the organ of retractility.Elastin laminin plays gives elastic effect to the tissue of these organs, in skin in order to keep elastic force or to compact etc. and bring into play big effect.
Its amount slowly reduces known elasticity albumen owing to aging, ultraviolet, active oxygen or pressure etc.Known in skin,, slowly loses elastin laminin the elasticity of skin because reducing, produce wrinkle or lax, become an aged big reason.
Make as decomposition in the elastoser that elastin laminin reduces, with the dermal matrix that is present in skin in the relevant elastoser of decomposition of elastin laminin; Known from the elastoser of neutrophil cell with from fibroblastic elastoser; Wherein, the known elastin laminin of the formation and the elasticity of skin being kept relevant elastic fiber from fibroblastic elastoser decomposes.Therefore, prediction can obtain high anti-wrinkle effect through suppressing its activity.
Wherein, If pick-up metal in the compositions of cosmetics, medicine or food etc.; Then not only be harmful to, and can not keep for example utilizing the character of washing liquid (1otion) shape, emulsion form or the gelatinous compositions of preparations such as CVP Carbopol ETD2050 owing to the kind of metal.Therefore, often be combined with EDTA in these compositionss as chelating agen.
In addition, known EDTA adds in these compositionss as the aging-resistant active component elastase activity inhibited (patent documentation 1) sometimes.
In addition, PQQ is present in animal, plant and microorganism etc. widely in the biosphere, plays a role as obtaining the necessary redox coenzyme of energy.
Known PQQ has a lot of physiologically actives, can expect the application as the effective ingredient of medicine, cosmetics or food.As this physiologically active, the effect of removing of known activity oxygen and free radical, cell proliferation facilitation, ultra-violet absorption effect, nerve growth factor production facilitation, brain function improvement effect, hair regrowth, color improvement effect, melanin produce inhibition and whitening function, mitochondrion activation and antifatigue effect etc.
Patent documentation 1: TOHKEMY 2006-298812 number
Summary of the invention
The objective of the invention is to, provide to comprise PQQ or its physiologically acceptable salt (following abbreviate as sometimes " its salt ") and EDTA or its salt, have the excellent inhibiting topical composition of elastase activity.
The inventor studies in order to solve above-mentioned problem, obtains following discovery.
(i) PQQ or its salt have the elastase activity inhibitory action.
(ii), then can not obtain the elastase activity inhibitory action of the degree of predicting from the elastase activity inhibitory action that each composition has if in the compositions that comprises EDTA or its salt, cooperate PQQ or its salt.The elastase activity inhibitory action of EDTA or its salt decay on the contrary.
(iii) in the compositions that comprises EDTA or its salt and PQQ or its salt and then cooperate at least a hydroxy-containing compounds be selected from by in the group that carbon number is 2～6, hydroxyl value is 2～4 polyhydric alcohol and glycol ether constitutes; Making the content of this hydroxy-containing compounds is more than 5 weight portions with respect to PQQ or its salt 1 weight portion, thereby can bring into play the elastase activity inhibitory action that EDTA or its salt and PQQ or its salt have respectively effectively.
The present invention is based on above-mentioned discovery and accomplishes, and following topical composition is provided.
The 1st. a kind of topical composition; Comprise (a) PQQ or its physiologically acceptable salt, (b) EDTA or its physiologically acceptable salt and (c) be selected from by at least a hydroxy-containing compounds in the group that carbon number is 2～6, hydroxyl value is 2～4 polyhydric alcohol and glycol ether constitutes; With respect to PQQ or its physiologically acceptable salt (a) 1 weight portion, the content of hydroxy-containing compounds (c) is more than 5 weight portions.
The 2nd. like the 1st described topical composition,, contain EDTA or its physiologically acceptable salt (b) of 0.00001～500 weight portion with respect to PQQ or its physiologically acceptable salt (a) 1 weight portion.
The 3rd. like the 1st or the 2nd described topical composition,, contain PQQ or its physiologically acceptable salt (a) of 0.00001～10 weight % with respect to the total amount of compositions.
The 4th. any described topical composition as in the 1st～the 3rd, with respect to the total amount of compositions, contain EDTA or its physiologically acceptable salt (b) of 0.0001～3 weight %.
The 5th. like any described topical composition in the 1st～the 4th; Above-mentioned hydroxy-containing compounds (c) is for being selected from least a in the group that is made up of propylene glycol, 1,3 butylene glycol, dipropylene glycol, glycerol, isoamyl glycol, diglycerol, glycol monoethyl ether and diethylene glycol monoethyl ether.
The 6th. any described topical composition as in the 1st～the 5th, with respect to the total amount of compositions, contain the above-mentioned hydroxy-containing compounds (c) of 0.01～97 weight %.
The 7th. a kind of inhibition method; Through comprise (a) PQQ or its physiologically acceptable salt and (b) add in the compositions of EDTA or its physiologically acceptable salt (c) be selected from by carbon number be 2～6, at least a hydroxy-containing compounds in hydroxyl value is 2～4 polyhydric alcohol and glycol ether constitutes the group, suppress that (a) composition mixes the inhibiting reduction of elastase activity of (a) composition that causes with (b) composition, perhaps (a) composition mixes the inhibiting reduction of elastase activity of (b) composition that causes with (b) composition.
The 8th. like the 7th described method; Being added with (c) is selected from by the above-mentioned composition after at least a hydroxy-containing compounds in the group that carbon number is 2～6, hydroxyl value is 2～4 polyhydric alcohol and glycol ether constitutes; With respect to PQQ or its physiologically acceptable salt (a) 1 weight portion, contain EDTA or its physiologically acceptable salt (b) of 0.00001～500 weight portion.
The 9th. like the 7th or the 8th described method; Being added with (c) is selected from by the above-mentioned composition after at least a hydroxy-containing compounds in the group that carbon number is 2～6, hydroxyl value is 2～4 polyhydric alcohol and glycol ether constitutes; With respect to the total amount of compositions, contain PQQ or its physiologically acceptable salt (a) of 0.00001～10 weight %.
The 10th. like any described method in the 7th～the 9th; Being added with (c) is selected from by the above-mentioned composition after at least a hydroxy-containing compounds in the group that carbon number is 2～6, hydroxyl value is 2～4 polyhydric alcohol and glycol ether constitutes; With respect to the total amount of compositions, contain EDTA or its physiologically acceptable salt (b) of 0.0001～3 weight %.
The 11st. like any described method in the 7th～the 10th; Above-mentioned hydroxy-containing compounds (c) is for being selected from least a in the group that is made up of propylene glycol, 1,3 butylene glycol, dipropylene glycol, glycerol, isoamyl glycol, diglycerol, glycol monoethyl ether and diethylene glycol monoethyl ether.
The 12nd. like any described method in the 7th～the 11st, with above-mentioned hydroxy-containing compounds (c) so that to be selected from concentration by the total amount of the above-mentioned composition after at least a hydroxy-containing compounds in the group that carbon number is 2～6, hydroxyl value is 2～4 polyhydric alcohol and glycol ether constitutes be that the mode of 0.01～97 weight % is added in the above-mentioned composition with respect to being added with (c).
Because PQQ or its salt have multiple pharmacologically active, can expect to use as the active component of cosmetics, medicine or accurate medicine.In addition, the inventor finds that PQQ or its salt have the elastase activity inhibitory action, is to the wrinkle that minimizing caused of elastin laminin or lax etc. prevention or improves useful composition.
On the other hand, EDTA or its salt are desired to be coupled in cosmetics, medicine or the accurate medicine with the chelating agen form sometimes.In addition, known have an elastase activity inhibitory action, also adds for wrinkle or the lax prevention that waits or improvement sometimes.
Therefore, also desire is coupled to PQQ or its salt and EDTA or its salt in their topical composition together sometimes, at this moment, can expect that combination has both inhibiting excellent effect of elastase activity.Yet the inventor finds, in the compositions that is combined with PQQ or its salt and EDTA or its salt, can not get the additive effect that can be predicted by the elastase activity inhibitory action of each composition.Find that in addition compare with the situation of independent EDTA or its salt, the elastase activity inhibitory action dies down on the contrary.
Compositions of the present invention; Except PQQ or its salt and EDTA or its salt; Comprise at least a hydroxy-containing compounds that is selected from by in the group that carbon number is 2～6, hydroxyl value is 2～4 polyhydric alcohol and glycol ether constitutes; With respect to PQQ or its salt 1 weight portion, the content of this hydroxy-containing compounds is more than 5 weight portions, can bring into play the elastase activity inhibitory action that PQQ or its salt and EDTA or its salt have respectively effectively thus.Wherein, can bring into play effectively from fibroblastic elastase activity inhibitory action.
Thus, can improve the elastic force of skin effectively, skin given compacted or gloss, prevent or improve lax, wrinkle, the pachylosis or gloomy of skin.
Description of drawings
Fig. 1 is the also usefulness of expression through PQQ or its salt and EDTA or its salt, the figure that the elastase activity inhibitory action reduces.
Fig. 2 adds through glycol ether for expression, the figure that the elastase activity inhibitory action is recovered.
Fig. 3 adds the figure that the elastase activity inhibitory action is recovered for expression through polyhydric alcohol or glycol ether.
The specific embodiment
Below the present invention is specified.
Topical composition of the present invention comprises (a) PQQ or its salt, (b) EDTA or its salt and (c) is selected from by at least a hydroxy-containing compounds in the group that carbon number is 2～6, hydroxyl value is 2～4 polyhydric alcohol and glycol ether constitutes; With respect to PQQ or its salt (a) 1 weight portion, the content of hydroxy-containing compounds (c) is more than 5 weight portions.
PQQ or its salt
PQQ is present in the multiple organisms such as animal, plant and microorganism, therefore can from various biologies, extract.In addition, PQQ can buy commercially available article.
As the salt of PQQ, can enumerate alkali metal salts such as sodium salt and potassium salt, alkali earth metal salts such as calcium salt and magnesium salt etc.In the salt, be preferably sodium salt, potassium salt, calcium salt and magnesium salt.
With respect to the total amount of compositions, the PQQ in the compositions or the content of its salt are preferably more than the 0.00001 weight %, more preferably more than the 0.0001 weight %, further more preferably more than the 0.001 weight %.In addition, be preferably below the 10 weight %, more preferably below the 5 weight %, further more preferably below the 1 weight %.If in above-mentioned scope, then just can fully obtain the physiologically active of PQQ or its salt with the common consumption of cosmetics, accurate medicine or medicine external agent.In addition, if in above-mentioned scope, the favorable solubility in preparation then, the preparation as topical composition also forms excellent preparation in addition.
In addition, with respect to the total amount of compositions, the PQQ in the compositions or the content of its salt for example are preferably 0.00001～10 weight %, 0.0001～5 weight % more preferably, further 0.001～1 weight % more preferably.
EDTA or its salt
As the salt of EDTA, can enumerate Na salt (2Na salt, 3Na salt and 4Na salt), K salt (2K salt, 3K salt and 4K salt) and the CaNa salt (Ca2Na salt) etc. of EDTA.They can also be hydrate.Wherein, turn into high aspect consideration, be preferably the salt of EDTA, more preferably the Na salt of EDTA and K salt from chelating.
EDTA or its salt can use a kind of separately or combination is used two or more.
With respect to the total amount of compositions, the EDTA in the topical composition of the present invention or the content of its salt are preferably more than the 0.0001 weight %, more preferably more than the 0.001 weight %, further more preferably more than the 0.01 weight %.In addition, be preferably below the 3 weight %, more preferably below the 1 weight %, further more preferably below the 0.5 weight %.
With respect to the total amount of compositions, the EDTA in the topical composition of the present invention or the content of its salt for example are preferably 0.0001～3 weight %, 0.001～1 weight % more preferably, further 0.01～0.5 weight % more preferably.
If the content of EDTA or its salt in above-mentioned scope, then can fully obtain the elastase activity inhibitory action, when chelating turns usefulness into, form the difficult compositions that produces the stimulation of skin.
In addition, for the content of EDTA or its salt ratio, with respect to PQQ or its salt 1 weight portion, be preferably more than 0.00001 weight portion, more preferably more than 0.0001 weight portion, further more preferably more than 0.001 weight portion with respect to the content of PQQ or its salt.In addition, be preferably below 500 weight portions, more preferably below 100 weight portions, further more preferably below 10 weight portions.
For the content of EDTA or its salt ratio, with respect to PQQ or its salt 1 weight portion, for example be preferably 0.00001～500 weight portion, 0.0001～100 weight portion more preferably, further 0.001～10 weight portion more preferably with respect to the content of PQQ or its salt.
If the content of EDTA or its salt, when then can fully obtain elastase activity inhibitory action and chelating and turn usefulness into, forms and is difficult for the compositions of generation to the stimulation of skin in above-mentioned scope with respect to the ratio of the content of PQQ or its salt.
Polyhydric alcohol
When compositions of the present invention contains polyhydric alcohol as hydroxy-containing compounds, use that carbon number is 2～6, hydroxyl value is 2～4 polyhydric alcohol.
Specifically, can enumerate ethylene glycol, propylene glycol, 1, ammediol (trimethylene), 1,2-butanediol, 1; 3-butanediol, 2,3-butanediol, 1,4-butanediol (tetramethylene glycol), 2-butylene-1,4-glycol, 1; 5-pentanediol (pentamethylene glycol), 1, dihydroxylic alcohols such as 2-pentanediol, isoamyl glycol (isopentyl glycol), hexanediol and dipropylene glycol, trihydroxylic alcohols such as glycerol and trimethylolpropane; Diglycerol, tetramethylolmethane and 1,2, tetrahydroxylic alcohols such as 6-hexanetriol etc.
Wherein, be preferably propylene glycol, 1,3 butylene glycol, dipropylene glycol, glycerol, isoamyl two pure and mild diglycerols, more preferably propylene glycol, 1,3 butylene glycol, glycerol and diglycerol.
Glycol ether
When compositions of the present invention contains glycol ether as hydroxy-containing compounds,, specifically, can enumerate the glycol ether of glycols such as glycol monoethyl ether, ethylene glycol monoethyl ether and ethylene glycol ether as glycol ether,
The glycol ether of diethylene glycol classes such as diethylene glycol monomethyl ether, diethylene glycol monoethyl ether and diglycol monotertiary propyl ether,
The glycol ether of propandiols such as dihydroxypropane single-ether and propylene glycol monopropyl ether, and
The glycol ether of dipropylene glycol classes such as dipropylene glycol list ether and dipropylene glycol list propyl ether etc.
Wherein, be preferably the glycol ether of glycols and diethylene glycol class, more preferably glycol monoethyl ether and diethylene glycol monoethyl ether are preferably diethylene glycol monoethyl ether especially.
Be selected from and use a kind of separately or combination is used two or more by the hydroxy-containing compounds in the group that carbon number is 2～6, hydroxyl value is 2～4 polyhydric alcohol and glycol ether constitutes.
The content of polyhydric alcohol glycol ether
Total amount with respect to compositions; Be selected from by the content of at least a hydroxy-containing compounds in compositions in the group that carbon number is 2～6, hydroxyl value is 2～4 polyhydric alcohol and glycol ether constitutes and be preferably more than the 0.01 weight %; More preferably more than the 0.1 weight %, further more preferably more than the 0.5 weight %.If in above-mentioned scope, then can bring into play the elastase activity inhibitory action that PQQ or its salt and EDTA or its salt have effectively.
In addition, with respect to the total amount of compositions, the content of the above-mentioned hydroxy-containing compounds in the compositions is preferably below the 97 weight %, more preferably below the 50 weight %, further more preferably below the 30 weight %.If in above-mentioned scope, then form the compositions of good usability.
In addition, with respect to the total amount of compositions, the content of the above-mentioned hydroxy-containing compounds in the compositions for example is preferably 0.01～97 weight %, 0.1～50 weight % more preferably, further 0.5～30 weight % more preferably.
The polyhydric alcohol glycol ether is with respect to the ratio of PQQ or its salt
With respect to PQQ or its salt 1 weight portion, the total amount that is selected from by at least a hydroxy-containing compounds in the group that carbon number is 2～6, hydroxyl value is 2～4 polyhydric alcohol and glycol ether constitutes is to get final product more than 5 weight portions.In addition, be preferably more than 10 weight portions, more preferably more than 20 weight portions.If in above-mentioned scope, then can bring into play the elastase activity inhibitory action that PQQ or its salt and EDTA or its salt have effectively.
In addition, to the not restriction especially of total amount of above-mentioned hydroxy-containing compounds, yet, be preferably below 800 weight portions, more preferably below 500 weight portions, further more preferably below 300 weight portions with respect to PQQ or its salt 1 weight portion.If in above-mentioned scope, then can bring into play the elastase activity inhibitory action that PQQ or its salt and EDTA or its salt have effectively, this external enwergy obtains good usability.
With respect to PQQ or its salt 1 weight portion; The total amount that is selected from by at least a hydroxy-containing compounds in the group that carbon number is 2～6, hydroxyl value is 2～4 polyhydric alcohol and glycol ether constitutes for example is preferably 5 weight portions～800 weight portions; 10～500 weight portions more preferably, further 20～300 weight portions more preferably.
The preparation form
Topical composition of the present invention can be mixed together normally used base or carrier and additive as required in PQQ or its salt, EDTA or its salt and above-mentioned polyhydric alcohol and/or glycol ether and medicine, accurate medicine or the cosmetics, thereby can form the composition for external application of medicine, accurate medicine or used for cosmetic.
The form of the composition for external application that medicine is used does not limit especially, can enumerate for example liquid agent, suspending agent, Emulsion, cream, ointment, gel, liniment, lotion and aerosol etc.These preparations can prepare according to the method for revising to put down in writing in the Japanese Pharmacopoeia preparation general provisions for the 15th time etc.Wherein, be preferably liquid agent, suspending agent, Emulsion, cream, ointment, gel, lotion and aerosol, more preferably cream, Emulsion and gel.
When forming the composition for external application of accurate medicine or used for cosmetic, can form the form identical with said medicine.In addition, can enumerate sticker and the Formulation that medicinal liquid is infiltrated up to form in the non-woven fabrics etc.Wherein, be preferably liquid agent, suspending agent, Emulsion, cream, ointment, gel, lotion and Formulation, more preferably cream, Emulsion and gel.
As cream and Emulsion, when containing oiliness base and aqueous base, can be preferably the O/W type for w/o type or O/W type.
Do not contain under the situation of base of water, be preferably ointment and contain polyhydric alcohol and/or the glycol ether of above-mentioned explanation liquid agent as base.
Purposes during as the composition for external application that forms accurate medicine or used for cosmetic; Specifically; Can enumerate for example basic cosmetics such as astringent, emulsion, gel, cream, beautifying liquid, Sun block cosmetics, facial film, facial mask, hand cream, skin cream and emollient cream; Cleansing milk, cleansing product, the agent of shaving, bath foam, shampoo, hair conditioner and conditioning liquid washings such as (treatment) apply some make up; Lip such as lip gloss and lipstick applies some make up, color make-up cosmetics such as foundation cream and mascara, depilatory and bath shampoo etc.
Base or carrier
As base or carrier; For example can enumerate liquid paraffin, squalane, vaseline, gelled hydrocarbon (white oil and poly compound ointment base (プ ラ ス チ ベ one ス) etc.), ceresine, α-alkene through hydrocarbon such as oligomer and liquid paraffin,lights; Methyl polysiloxane, cross-linking type methyl polysiloxane, height gather methyl polysiloxane, annular siloxane, alkyl-modified siloxanes, the alkyl-modified siloxanes of cross-linking type, amino modified siloxanes, polyether modified siloxane, polyglycerol-modified siloxanes, cross-linking type polyether modified siloxane, cross-linking type alkyl, polyether modified siloxane, siloxanes alkyl chain, and modified polyether modified siloxane, siloxanes alkyl chain are total to silicone oil such as the polyglycerol-modified siloxanes of modification, polyether-modified side chain siloxanes, polyglycerol-modified side chain siloxanes, silicon Acrylote, phenyl modified siloxanes and silicone resin altogether; Higher alcohols such as spermol, cetostearyl alcohol, stearyl alcohol and tadenan; Sterols such as cholesterol, plant sterol and plant sterol hydroxy stearic acid ester; Jojoba oil, Ramulus et Folium Spiraeae Salicifolia seed oil, Oleum helianthi, Oleum Vitis viniferae, Chinese toon oil, squalane, shea oil and Rice plumule wet goods vegetable oil; Animal oil such as lanoline, Atlantic Ocean helmet breast Channa argus oil, squalane and house oil; Natural polymer derivants such as ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, JR-125 and acetylation hyaluronic acid; Synthetic high polymers such as polyvinylpyrrolidone, CVP Carbopol ETD2050 and acrylic acid alkyl methacrylate copolymer; Natural polymers such as carrageenin, alginic acid, cellulose, guar gum 、 Wen outer coffin seed, dextrin, zierane glue and hyaluronic acid; Polyvinyl butyral resin; Polyethylene Glycol; Two
alkane, butanediol adipate polyester, esters such as isopropyl myristate, myristic acid octyl group dodecyl ester, isopropyl palmitate, cetin, isononyl isononanoate, four (2 ethyl hexanoic acid) pentaerythritol ester, Jojoba oil and three (caprylic/capric) glyceride; Polysaccharide such as dextrin and maltodextrin; Lower alcohol such as ethanol and isopropyl alcohol, the carbon number of above-mentioned explanation are 2～6, hydroxyl value is 2～4 polyhydric alcohol, the glycol ether of above-mentioned explanation; Organic acid such as succinic acid, glycolic, gluconic acid and citric acid, and aqueous base such as water etc.
Wherein, preferred polyol, higher alcohol, hydrocarbon, esters, silicone oil and organic acid, more preferably polyhydric alcohol.
As the preferred example of the present composition, can enumerate the polyhydric alcohol that contains above-mentioned explanation liquid agent, lotion, cream, gel and Emulsion as base.
Base or carrier can use a kind of separately or combination is used two or more.
Additive
In the topical composition of the present invention; In the scope of not damaging effect of the present invention; Addible known additive in medicine, accurate medicine or the cosmetics can be added, for example antioxidant, surfactant, thickening agent, preservative agent, pH regulator agent, stabilizing agent, counter-stimulus, antiseptic, coloring agent, spice and pearling agent etc. can be added.
As antioxidant, can enumerate for example dibenzylatiooluene, Butylated hydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, ascorbic acid derivates, tocopherol, Tocopheryl derivatives, arabo-ascorbic acid and L-cysteine hydrochloride etc.
As surfactant; Can enumerate for example sorbitan fatty acid esters classes such as sorbitan list isostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan five (2 ethyl hexanoic acid) double glyceride and sorbitan four (2 ethyl hexanoic acid) double glyceride; Methyl glycol fatty acid ester classes such as propylene glycol monostearate; Castor oil hydrogenated derivants such as polyoxyethylene hydrogenated Oleum Ricini 40 (HCO-40), polyoxyethylene hydrogenated Oleum Ricini 50 (HCO-50), polyoxyethylene hydrogenated Oleum Ricini 60 (HCO-60) and polyoxyethylene hydrogenated Oleum Ricini 80; Polyoxyethylene sorbitan fatty acid esters classes such as polyoxyethylene (20) sorbitan monolaurate (polysorbate20), polyoxyethylene (20) sorbitan monostearate (polysorbate60), polyoxyethylene (20) dehydrated sorbitol mono-fatty acid ester (polysorbate80) and polyoxyethylene (20) sorbitan isostearate; Polyoxyethylene list coconut oil fat acid glyceride; The glycerol alkyl ether; Alkyl-glucoside; Polyoxyalkylene alkyl such as polyoxyethylene cetyl base ether; Amine such as stearylamine and oleyl amine; Siloxane type surfactants such as polyoxyethylene methyl polysiloxane copolymer, lauryl PEG-9 poly dimethyl siloxy ethyl polydimethylsiloxane and PEG-9 poly dimethyl siloxy ethyl polydimethylsiloxane, natural surfactants such as phospholipid, Buddhist Sha graceful (Surfactin) and saponin, fatty acid amide amine such as stearic acid diethylamino buserelin and stearic acid diethylamino propyl amides; Alkylamines such as three lauryl amines, dimethyl stearic amine and D2EHA di 2 ethylhexyl amine, betaines amphoteric surfactantes such as stearic acid dimethylaminopropyl amide and lauryl hydroxyl sulfo betaine etc.
As thickening agent, can enumerate for example cellulose thickeners such as guar gum, locust bean gum, carrageenin, hyaluronic acid, xanthan gum, polyvinyl alcohol, polyvinyl pyrrolidone, CVP Carbopol ETD2050, acrylic acid alkyl methacrylate copolymer, Polyethylene Glycol, bentonite, alginic acid, macrogol, sodium chondroitin sulfate, methylcellulose, ethyl cellulose, hydroxyethyl-cellulose, hydroxy methocel, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, carboxymethyl cellulose and NATROSOL 250 etc.
As antiseptic or preservative agent, can enumerate for example benzoic acid, sodium benzoate, dehydroactic acid, dehydro sodium acetate, p-Hydroxybenzoic acid isobutyl ester, p-Hydroxybenzoic acid isopropyl ester, butyl p-hydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, benzyl p-hydroxybenzoate, methyl parahydroxybenzoate, phenyl phenol, benzyl alcohol, methaform, sorbic acid and salt thereof, gluconic acid chlorhexidine, alkane diol and fatty acid glyceride etc.
As the pH regulator agent, can enumerate for example mineral acid (hydrochloric acid and sulphuric acid etc.), organic acid (lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid and sodium succinate etc.), inorganic base (potassium hydroxide and sodium hydroxide etc.) and organic base (triethanolamine, diisopropanolamine (DIPA) and triisopropanolamine etc.) etc.
As stabilizing agent, can enumerate for example sodium polyacrylate, dibenzylatiooluene and Butylated hydroxyanisole etc.
As counter-stimulus, can enumerate for example Radix Glycyrrhizae extract and sodium alginate etc.
Additive can use a kind of separately or combination is used two or more.
Other active component
Topical composition of the present invention can comprise other effective ingredient in the scope that does not hinder effect of the present invention.As the concrete example of effective ingredient, can enumerate the composition of for example preserving moisture, anti-inflammatory component, antimicrobial component, vitamins, peptide or derivatives thereof, aminoacid or derivatives thereof, cell-activating composition, aging resistance composition, blood circulation promoting composition, cutin softening composition, whitening composition, astringent component and ultraviolet protection and become to grade.
As the composition of preserving moisture; Can enumerate for example glycerol, 1; Polyhydric alcohol such as 3-butanediol, propylene glycol, Polyethylene Glycol and diglycerol trehalose; Macromolecular compounds such as hyaluronate sodium, Hirudoid, sodium chondroitin sulfate, collagen, elastin laminin, keratin, chitin and chitosan, aminoacid such as glycine, aspartic acid and arginine, nature moisturizing factor such as sodium lactate, carbamide and pyrrolidone sodium carboxylate; Lipids such as ceramide, cholesterol and phospholipid, plant extracts such as chamomile extract, Hamamelis virginiana extract, tea extract and Folium perillae extract etc.
As anti-inflammatory component, can enumerate the composition that for example derives from plant (for example Symphytum officinale), allantoin, glycyrrhizic acid or derivatives thereof, zinc oxide, pyridoxine hydrochloride, tocopherol acetas, salicylic acid or derivatives thereof and EACA etc.
As antibiotic or sterilization component; Can enumerate for example chlorhexidine, salicylic acid, benzalkonium chloride, ethacridine, iodine, resorcinol, ethanol, benzethonium chloride, adapalene, benzoyl peroxide, clindomycin, cresol, gluconic acid and derivant thereof, povidone iodine, potassium iodide, iodine, isopropyl methyl phenol, triclocarban, triclosan, plain No. 101 of sensitization, plain No. 201 of sensitization, p-Hydroxybenzoate, phenyl phenol, 1,2-pentanediol, alkane diol, fatty acid glyceride, Azelaic Acid, salt dialkylaminobenzoic acid diaminourea glycine, gluconic acid chlorhexidine and heap zinc phenolsulfonate etc.
As vitamins; Can enumerate for example retinoids such as retinol derivatives such as retinol, retinyl acetate and retinol cetylate, retinal, tretinoin, tretinoin methyl ester, tretinoin ethyl ester, retinol retinoic acid ester, d-Delta-Tocopherol retinoic acid ester, alpha-tocopherol retinoic acid ester and betatocopherol retinoic acid ester; Vitamin E classes such as d1-alpha-tocopherol, d1-alpha-tocopherol acetate, d1-alpha-tocofecol succinic acid ester and d1-alpha-tocofecol succinic acid calcium; Vitamin B2 classes such as riboflavin, FMN, flavin adenine dinucleotide (FAD), Riboflavine Tertrabutyrate, Riboflavin Tetrabutyrate, riboflavin 5 '-phosphate ester sodium and riboflavin four nicotinates; Nicotinic acid classes such as d1-Tocopheryl Nicotinate, nicotinic acid benzene methyl, methyl nicotinate, nicotinic acid Beta-Butoxy ethyl ester and nicotinic acid 1-(4-aminomethyl phenyl) ethyl ester; Vitamin c class such as ascorbigen-A, ascorbyl stearate, ascorbyl palmitate and L-Vitamin C dipalmitate; Vitamin D classes such as hesperidin methyl, vitamin D2 and gallbladder calcium ostelin; Vitamin K such as phylloquinone and farnoquinone class; 1 type of vitamin B such as dibenzoylthiamine element, dibenzoyl thiamine, thiamine salt hydrochlorate, thiamine cetyl hydrochlorate, thiamine rhodanate, thiamine lauryl hydrochlorate, thiamine nitrate, thiamine monophosphate, thiamine lysinate, thiamine triphosphate, thiamine phosplate phosphate, thiamine phosplate, thiamine bisphosphate, thiamine bisphosphate hydrochlorate, thiamine triguaiacyl phosphate and thiamine triguaiacyl phosphate monophosphate; 12 types of vitamin Bs such as vitamin B6 classes such as pyridoxine hydrochloride, acetic acid pyridoxol, pyridoxal hydrochloride, 5 '-pyridoxal 5-phosphate and hydrochloric acid pyridoxamine, cobalamin, hydroxocobalamin and deoxyadenosine cobalt amine; Folic acid such as folic acid and pteroylglutamic acid class; Nicotinic acid such as nicotinic acid and nicotiamide class; Pantothenic acid classes such as pantothenic acid, calcium pantothenate, pantothenylol (panthenol), D-pantetheine, D-pantethine, coenzyme A and pantothenylol ether; Biotin such as biotin and biotin complex of yeast. class; The vitamin c class of ascorbic acid derivates such as ascorbic acid, sodium ascorbate, hydroascorbic acid, ascorbic acid phosphoric acid esters sodium and magnesium L-ascorbyl-2-phosphate, and the vitaminoid action factors such as γ-Hi-Z, carnitine, ferulic acid, alpha-lipoic acid and orotic acid etc.
As the peptide or derivatives thereof, for example can enumerating, keratin decomposes peptide, hydrolysis of keratin, collagen, decomposes peptide, hydrolysis conchiolin, lactoprotein decomposition peptide, lactoalbumin hydrolysate, lauroyl lactoalbumin hydrolysate sodium, soybean protein decomposition peptide, hydrolyzed soybean protein, wheat protein, wheat protein decomposition peptide, hydrolyzed wheat protein, casein decomposition peptide and acylated peptide (palmityl oligopeptide, palmityl pentapeptide and palmityl tetrapeptide etc.) etc. from the collagen of fish, scarce collagen, gelatin, elastin laminin, elastin laminin decomposition peptide, collagen decomposition peptide, hydrolytic collagen, hydroxypropyl ammonium chloride hydrolytic collagen, elastin laminin decomposition peptide, the conchiolin held.
As the aminoacid or derivatives thereof, can enumerate for example betanin (trimethyl glycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, Beta-alanine, threonine, glutamic acid, glutamine, agedoite, aspartic acid, cysteine, cystine, methionine, leucine, isoleucine, valine, histidine, taurine, GABA, GABOB, carnitine, carnosine and creatine etc.
As the cell-activating composition; Can enumerate for example amino acids such as GABA and EACA, vitaminss such as retinol, thiamine, riboflavin, pyridoxine hydrochloride and pantothenic acid class, Alpha-hydroxy acids such as glycolic and lactic acid; Tannin; Flavonoid, saponin, plain No. 301 of allantoin and sensitization etc.
As the aging resistance composition, can enumerate for example pangamic acid, kinetins, ursolic acid, Rhizoma Curcumae Longae extract, sphingol derivant, silicon, silicic acid, N-methyl-L-serine and mevalonolactone etc.
As the blood circulation promoting action component, can enumerate the composition that for example derives from plant (for example Radix Ginseng, angelica keiskei koidzumi, arnica montana, Semen Ginkgo, Fructus Foeniculi, Rabdosia japonica (エ Application メ イ ソ ウ), オ ラ Application ダ カ シ, Flos Matricariae chamomillae, Anthemis nobilis, Radix Dauci Sativae, Radix Gentianae, Fructus Arctii, rice, Fructus Crataegi, Lentinus Edodes, Crataegus Oxyacantha, Juniperus communis L., Rhizoma Chuanxiong, Japanese Herba Swertiae bimaculatae, Herba thymi vulgaris, Flos Caryophylli, Pericarpium Citri Reticulatae, Radix Angelicae Sinensis, Semen Persicae, Pericarpium Citri tangerinae, Radix Dauci Sativae, Bulbus Allii, butchers broom, Fructus Vitis viniferae, Paeonia suffruticosa, Aesculus chinensis Bunge, Herba Melissae officinalis, Fructus Citri grandis, Semen Coicis, Herba Rosmarini Officinalis, Rosehips, Pericarpium Citri Reticulatae, Radix Angelicae Sinensis, Pericarpium Citri tangerinae, peach, Fructus Pruni, Semen Juglandis or corn) and glucityl Hesperidin etc.
As the cutin softening composition, can enumerate for example carbamide, salicylic acid, glycolic, fruit acid, phytic acid and iodine etc.
As whitening composition, can enumerate for example ascorbic acid and derivant, arbutin, tocopherol and tranamic acid etc.
As astringent component, can enumerate for example p-phenolsulfonic acid's zinc, zinc oxide, menthol and ethanol etc.
As the ultraviolet protection composition; Can enumerate for example p-methoxycinnamic acid 2-Octyl Nitrite, 2-[4-(lignocaine)-2-hydroxy benzoyl] hexyl-benzoate, 2; 4; 6-three [4-(the own oxygen carbonyl of 2-ethyl) anilino-]-1; 3,5-triazine, tert-butyl group methoxy dibenzoyl methylmethane, dibenzylidene oxo-imidazole alkane propanoic acid Octyl Nitrite, ethylhexyl triazinone, para-amino benzoic acid and derivant, ESCAROL 507 monooctyl ester, glycol salicylate, dihydroxy benaophenonel, titanium oxide and zinc oxide etc.
Other effective ingredient can use a kind of separately or combination is used two or more.
Method for using
Topical composition of the present invention is different and different according to state, age or the sex of using subject's skin etc., yet if for example following method gets final product.That is, (for example 1～5 time, preferred 1～3 time) coating for several times in 1 day (for example 0.05～5g) gets final product in right amount to skin.In addition, 1 of PQQ or its salt day consumption is for example with 0.0005～0.05g, preferred 0.001～0.02g, more preferably 0.002～0.01g comes coating composition to get final product.
In addition, the coating time for example is to get final product in 1～6 month, preferred 3～6 months.
Topical composition of the present invention goes for having lax, wrinkle, pachylosis or the gloomy people of skin.In addition, go for expecting the physiologically active of PQQ or its salt, have the people of various dermatosis or skin problem.In addition, in order to prevent skin problem, the people with normal skin also becomes suitable use object.
Other
The present invention comprises a kind of inhibition method; Through comprise (a) PQQ or its salt and (b) add in the compositions of EDTA or its salt (c) be selected from by carbon number be 2～6, at least a hydroxy-containing compounds in hydroxyl value is 2～4 polyhydric alcohol and glycol ether constitutes the group, suppress that (a) composition mixes the inhibiting reduction of elastase activity of (a) composition that causes with (b) composition, perhaps (a) composition mixes the inhibiting reduction of elastase activity of (b) composition that causes with (b) composition.
(a) composition in this method, (b) composition and (c) concrete example of composition; (a) composition, (b) composition and (c) preference of composition; (a) composition, (b) composition and (c) consumption of composition, (a) composition, (b) composition and (c) usage rate of composition, base that can contain in the compositions or carrier; The additive that can contain in the compositions, other effective ingredient that can contain in the compositions and the preparation form of compositions are like said to topical composition explanation of the present invention.
[embodiment]
Below enumerate embodiment the present invention is explained more specifically, but the present invention is not limited by these embodiment.
(1) elastase activity suppresses the test method of effect
Be described below the elastase activity suppression ratio from the HF is made an experiment.
Use contains the minimum essential medium (DMEM) of 10% hyclone will be from the SF (NHDF, Network ラ ボ ウ society system) of normal adult with 2 * 10
4The density of cells/well is inoculated into the 96 hole microwell plates (Corning) that cell culture is used, at 37 ℃, 5%CO
2Cultivated 24 hours in the incubator.After removing culture supernatant, add the 0.5%Triton X-100 aqueous solution of 50 μ l, use the liquid that at room temperature leaves standstill 30 minutes as crude enzyme liquid.
Add in the crude enzyme liquid in each hole (50 μ l) and be dissolved with one or more 0.1M Tris hydrochloride buffer (pH8.0) the solution 50 μ l of composition such as EDTA2Na (with the pure pharmaceutical worker's industry of light), PQQ2Na.Further; 0.1M Tris hydrochloric acid buffer solution (pH 8.0) the 100 μ l that will comprise the PMSF of 1.5mM and elastoser synthetic substrate succinyl-alanyl-alanyl-alanyl-paranitroanilinum of 5mM (ペ プ チ De institute system) add in each hole; Make that total amount is 200 μ l in the hole, under 37 ℃, left standstill 2 hours in the dark place.
The use extinction photometer is measured the absorbance of the 405nm that the paranitroanilinum that produces from fibroblastic elastin laminin enzyme hydrolysis forms.
The value of not adding the absorbance when receiving reagent agent (only buffer) is made as C ', and the value of adding the absorbance when receiving the reagent agent is made as S ', calculates the elastin laminin enzyme inhibition rate by following formula.
From fibroblastic elastin laminin enzyme inhibition rate (%)=(1-(S '/C ')) * 100
(2) also suppressing owing to PQQ or its salt and EDTA or its salt with the elastase activity that causes
The reduction of effect
The experimental liquid of forming shown in the preparation below table 1 is like (1) the said elastase activity suppression ratio of calculating.The elastase activity suppression ratio of the EDTA-2Na of reference example 1 is 100 o'clock relative value such as (A), (B) of table 1 and Fig. 1.
[table 1]
*: purified water comprises the Tris hydrochloride buffer.
Can know by table 1 and Fig. 1, the comparison that comparison through 1,2,3 of reference examples and reference example are 1,4,5, EDTA-2Na and PQQ have the elastase activity inhibitory action respectively, yet even with both and with the additive effect that also can not get expecting.
Moreover, can know, reduce through the elastase activity inhibitory action of also using PQQ, EDTA-2Na to have through the comparison of reference example 1,3 and the comparison of reference example 1,5.
(3) effect of glycol ether interpolation
The experimental liquid of forming shown in the preparation below table 2 is like (1) the said elastase activity suppression ratio of calculating.Elastase activity suppression ratio such as table 2 are with shown in Figure 2.
[table 2]
Can know by table 2 and Fig. 2; Though through and the elastase activity suppression ratio reduction with EDTA-2Na and PQQ-2Na; Yet through further cooperating ethoxydiglycol (diethylene glycol monoethyl ether) as glycol ether; The elastase activity suppression ratio improves, and the elastase activity that can give full play to EDTA-2Na and PQQ molecule suppresses effect.
(4) effect of polyhydric alcohol, glycol ether interpolation
The experimental liquid of forming shown in the preparation below table 3 is like (1) the said elastase activity suppression ratio of calculating.Elastase activity suppression ratio such as table 3 are with shown in Figure 3.
[table 3]
Can know by table 3 and Fig. 3, through cooperating EDTA-2Na and PQQ-2Na, and then as the dipropylene glycol of polyhydric alcohol, 1,3 butylene glycol or as the ethoxydiglycol of glycol ether, the elastase activity suppression ratio improves.
(5) hydroxy-containing compounds is with respect to the influence of the ratio of PQQ
Preparation below table 4 and the experimental liquid of forming shown in the table 5 are like (1) the said elastase activity suppression ratio of calculating.Only the elastin laminin enzyme inhibition rate under EDTA-2Na and the PQQ situation is that 100 o'clock relative value is shown in table 4 and table 5.
[table 4]
[table 5]
Can know at the cooperation ratio of polyhydric alcohol to surpass in 2 the scope, can obtain hydroxy-containing compounds and cooperate the elastase activity that brings to suppress the raising effect of effect with respect to PQQ.
Utilizability on the industry
Topical composition of the present invention comprises PQQ or its salt and EDTA or its salt, has excellent elastase activity inhibitory action, is useful as cosmetics, accurate medicine or medicine external agent etc. therefore.
Claims (5)
1. topical composition; Comprise (a) PQQ or its physiologically acceptable salt, (b) EDTA or its physiologically acceptable salt and (c) be selected from by at least a hydroxy-containing compounds in the group that carbon number is 2～6, hydroxyl value is 2～4 polyhydric alcohol and glycol ether constitutes; With respect to PQQ or its physiologically acceptable salt (a) 1 weight portion, the content of hydroxy-containing compounds (c) is more than 5 weight portions.
2. topical composition according to claim 1 with respect to PQQ or its physiologically acceptable salt (a) 1 weight portion, contains EDTA or its physiologically acceptable salt (b) of 0.00001～500 weight portion.
3. topical composition according to claim 1 and 2 with respect to the total amount of compositions, contains PQQ or its physiologically acceptable salt (a) of 0.00001～10 weight %.
4. according to any described topical composition in the claim 1～3,, contain EDTA or its physiologically acceptable salt (b) of 0.0001～3 weight % with respect to the total amount of compositions.
5. according to any described topical composition in the claim 1～4; Above-mentioned hydroxy-containing compounds (c) is for being selected from least a in the group that is made up of propylene glycol, 1,3 butylene glycol, dipropylene glycol, glycerol, isoamyl glycol, diglycerol, glycol monoethyl ether and diethylene glycol monoethyl ether.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2011-063949 | 2011-03-23 | ||
| JP2011063949 | 2011-03-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102688155A true CN102688155A (en) | 2012-09-26 |
Family
ID=46854004
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012100684308A Pending CN102688155A (en) | 2011-03-23 | 2012-03-15 | External composition |
Country Status (2)
| Country | Link |
|---|---|
| JP (2) | JP5401575B2 (en) |
| CN (1) | CN102688155A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107056778A (en) * | 2016-12-22 | 2017-08-18 | 上海宣创生物科技有限公司 | PQQ beet alkali salt |
| CN107496345A (en) * | 2017-09-01 | 2017-12-22 | 安庆徽云博冠化妆品科技有限公司 | A kind of protein chelates mildy wash and preparation method thereof |
| CN111440023A (en) * | 2020-03-17 | 2020-07-24 | 浙江丰瑜生态科技股份有限公司 | Slow-release water-soluble fertilizer containing humic acid |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014087990A1 (en) * | 2012-12-04 | 2014-06-12 | ロート製薬株式会社 | Composition for external application |
| JP6284730B2 (en) * | 2013-09-25 | 2018-02-28 | ロート製薬株式会社 | Composition for external use |
| JP2015063486A (en) * | 2013-09-25 | 2015-04-09 | ロート製薬株式会社 | External composition |
| JP6284729B2 (en) * | 2013-09-25 | 2018-02-28 | ロート製薬株式会社 | Composition for external use |
| CN109171787B (en) | 2018-08-27 | 2021-02-26 | 苏州瑞派宁科技有限公司 | Method and device for sampling pulse signal and computer program medium |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63152309A (en) * | 1986-08-11 | 1988-06-24 | Lion Corp | External preparation of skin |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03112912A (en) * | 1989-09-27 | 1991-05-14 | Sanko Seibutsu Kagaku Kenkyusho:Kk | Cosmetic composition |
| JPH0820512A (en) * | 1994-07-07 | 1996-01-23 | Mitsubishi Gas Chem Co Inc | Melanin production inhibitor and whitening dermal agent for external use |
| JP2006169225A (en) * | 2004-12-16 | 2006-06-29 | Koei Kogyo Kk | External agent for preventing skin aging |
| JP2006298812A (en) * | 2005-04-20 | 2006-11-02 | Mikimoto Pharmaceut Co Ltd | Antioxidant, skin lotion for anti-oxidization, elastase activity inhibitor and maillard reaction inhibitor |
| JP2009191043A (en) * | 2008-02-18 | 2009-08-27 | Shiseido Co Ltd | Elastase inhibitor |
| JP2009221154A (en) * | 2008-03-17 | 2009-10-01 | Pola Chem Ind Inc | Interleukin-6 production inhibitor |
| JP2009263279A (en) * | 2008-04-25 | 2009-11-12 | Oriza Yuka Kk | Elastase inhibitor |
| JP2010120904A (en) * | 2008-11-21 | 2010-06-03 | Mitsubishi Gas Chemical Co Inc | Hair-growing composition and method for growing hair by using the same |
| JP5672751B2 (en) * | 2010-04-07 | 2015-02-18 | 三菱瓦斯化学株式会社 | Liposomes containing pyrroloquinoline quinone |
| JP2012001507A (en) * | 2010-06-18 | 2012-01-05 | Osaka Prefecture Univ | Ptp1b inhibitor, and diabetes treatment agent, skin external pharmaceutical preparation and food containing the same |
-
2012
- 2012-03-15 CN CN2012100684308A patent/CN102688155A/en active Pending
- 2012-03-22 JP JP2012064661A patent/JP5401575B2/en active Active
-
2013
- 2013-10-04 JP JP2013208988A patent/JP5934164B2/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63152309A (en) * | 1986-08-11 | 1988-06-24 | Lion Corp | External preparation of skin |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107056778A (en) * | 2016-12-22 | 2017-08-18 | 上海宣创生物科技有限公司 | PQQ beet alkali salt |
| CN107056778B (en) * | 2016-12-22 | 2019-05-21 | 上海宣创生物科技有限公司 | Pyrroloquinoline quinone beet alkali salt |
| CN107496345A (en) * | 2017-09-01 | 2017-12-22 | 安庆徽云博冠化妆品科技有限公司 | A kind of protein chelates mildy wash and preparation method thereof |
| CN111440023A (en) * | 2020-03-17 | 2020-07-24 | 浙江丰瑜生态科技股份有限公司 | Slow-release water-soluble fertilizer containing humic acid |
Also Published As
| Publication number | Publication date |
|---|---|
| JP5401575B2 (en) | 2014-01-29 |
| JP2013256543A (en) | 2013-12-26 |
| JP5934164B2 (en) | 2016-06-15 |
| JP2012211129A (en) | 2012-11-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102688155A (en) | External composition | |
| JP5827052B2 (en) | Composition for external use | |
| JP6430109B2 (en) | Composition for external use | |
| WO2011129374A1 (en) | Composition for external use for complexion improvement | |
| CN103099800A (en) | External-use and oral-use composition comprising tranexamic acid | |
| JP4786630B2 (en) | Topical skin preparation | |
| CN101588787B (en) | Anti-wrinkle agent and ADAM inhibitor | |
| JP6632495B2 (en) | Antimicrobial composition | |
| CN104780902A (en) | Composition for external use | |
| JP2005306831A (en) | Skin care preparation for external use | |
| JP2005060234A (en) | External preparation for skin | |
| JP2020007375A (en) | Skin external composition | |
| JP5951277B2 (en) | External composition containing azelaic acid | |
| CN102670423A (en) | Elastinase activity inhibitor | |
| CN103458865A (en) | Composition for external application | |
| JP5960505B2 (en) | Composition for external use | |
| CN102846599A (en) | External-use composite | |
| JP6391927B2 (en) | Skin external composition | |
| JP2005060233A (en) | External preparation for skin | |
| WO2012008457A1 (en) | Composition for external application | |
| JP6329757B2 (en) | Composition for external use | |
| JP2012036174A (en) | Composition for external application | |
| JP6709585B2 (en) | Topical skin | |
| JP2024078351A (en) | DKK1 expression promoter | |
| JP2024110598A (en) | Skin preparations |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1174840 Country of ref document: HK |
|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120926 |
|
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1174840 Country of ref document: HK |