CN101534842B - Composition comprising hyaluronic acid and/or its salts for treatment of atopic dermatitis - Google Patents
Composition comprising hyaluronic acid and/or its salts for treatment of atopic dermatitis Download PDFInfo
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- CN101534842B CN101534842B CN2007800410606A CN200780041060A CN101534842B CN 101534842 B CN101534842 B CN 101534842B CN 2007800410606 A CN2007800410606 A CN 2007800410606A CN 200780041060 A CN200780041060 A CN 200780041060A CN 101534842 B CN101534842 B CN 101534842B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/347—Phenols
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Abstract
Provided is a composition for prevention and treatment of atopic dermatitis, comprising hyaluronic acid and/or a salt thereof, and preferably resveratrol. The composition has therapeutic effects on amelioration and treatment of atopic dermatitis which is an allergic disease.
Description
Technical field
The present invention relates to a kind of compositions that comprises hyaluronic acid and/or its salt for prevention and treatment atopic dermatitis, and a kind of pharmaceutical composition that comprises the said composition for the treatment of effective dose.
Background technology
Atopic dermatitis is the chronic disease of deep layer, and it is with serious pruritus and follow-up inflammation consecutive infection.In the westerner, the sickness rate of atopic dermatitis is higher, and particularly about 10% child suffers from this disease, and is presented in recent years that its sickness rate increases gradually.In Korea S, the outbreak of atopic dermatitis has begun to increase fast year by year equally.Yet, since height more rate and the cause of disease fail to set forth clear, most of therapeutic scheme major parts of having carried out are the symptom treatments to disease.According to nearest publication, atopic dermatitis is caused by dysimmunity, has attempted new pharmacotherapy with the treatment atopic dermatitis.
Dysimmunity is characterised in that and shows as allergy that this is that health is to exaggerative or inappropriate immunoreation of foeign element.The anaphylaxis that is 1 type allergy is caused by antigenic specificity IgE antibody, but making the experimenter contact identical antigen may cause also and may not cause allergic reaction, vary with each individual.Because this reason, anaphylaxis are called atopy (atopy), refer to the idiosyncratic reaction (idiosyncratic reaction) of health.The example of atopic diseases can comprise allergic rhinitis, asthma, food anaphylaxis, atopic dermatitis etc.
The concrete mechanism of action that causes the antigenic specificity IgE antibody-like of anaphylactic disease outbreak will be described below.T assists (Th) cell to be responsible for immunologic function in vivo, and is divided into Th1 cell and Th2 cell, and they show the antagonistic substance that mutual balance and secretion are confronted with each other.Yet, because T assists (Th) cell to account for leading differentiation towards Th2, in the patient of atopic dermatitis, observed the unbalance of Th1/Th2.That is to say, in Th2 type cell, increase the secretion that relates to anaphylactoid eosinophilic granulocyte of stimulation IgE antibody generation and the secretion of interleukin (IL)-4, IL-5 and IL-10, and in the cell of Th1 type, reduced the secretion of the material that suppresses the IgE generation.The IgE level that increases causes the activation of basophilic granulocyte and mastocyte.The combination of IgE and IgE receptor (Fc ε RI), anaphylactogen is combined the follow-up crosslinked of complex with Fc ε RI/IgE subsequently, causes the activation of basophilic granulocyte and mastocyte, and therefore this cause a process that is called as threshing.At this moment, go out for example biological active substances of histamine at cell exocrine, therefore cause for example symptom of atopic dermatitiss such as strong pruritus, erythema, edema, inflammation.In fact, 80～90% atopic dermatitis patients demonstrates the serum IgE level of increase, and the serum IgE level of known this increase has high probability (the Cellular and MolecularImmunology of the anaphylactic disease of causing, people such as Abbas, the 2nd edition, Saunders, Philadelphia; With Journalof Dermatological Science, 36,1-9,2004).
Simultaneously, in the treatment of atopic dermatitis (it is a kind of anaphylactic disease), be extensive use of steroid and hydryllin medicine at present.A kind of severe case relates to the administration of immunosuppressant.Regrettably, these medicines only demonstrate temporary transient curative effect and are very easy to occur for example disadvantageous side effect such as osteoporosis, ischemic necrosis, arteriosclerosis, glaucoma, tumorigenicity.Therefore, press for the novel therapeutic medicament of developing a kind of remission for atopic dermatitis and treatment, and it can provide efficient and lasting therapeutic effect, and have MIN adverse side effect.
As mentioned above, because the IgE antibody-like has served as the main amboceptor of atopic dermatitis, play the effect of antipruritic and anti-inflammatory so suppress the excessive secretion of IgE antibody, thereby the effect of anti-atopic dermatitis can be provided.That is to say, have the material that suppresses the IgE activity and can overcome the problem that is caused by above-mentioned steroid, hydryllin and immunosuppressant, and the more basic methods of the basic reason that influences atopic dermatitis can be provided, therefore this disease be demonstrated excellent therapeutic effect.
In this case, the present inventor has been found that the compositions that comprises hyaluronic acid and/or hyaluronate and preferably comprise resveratrol, has demonstrated significant effect in the alleviation of atopic dermatitis and treatment.Based on this fact, the present invention has proposed the compositions for prevention and treatment atopic dermatitis, and it comprises hyaluronic acid and/or hyaluronate.
Hyaluronic acid (HA) is the heteropolysaccharide of alternately being made up of the residue of D-glucuronic acid and N-acetylglucosamine.HA is for having 2 * 10
5The straight chain polymer of the molecular weight that Da is above.HA is the biomaterial of finding in multiple body fluid and tissue (for example connective tissue of bovine eye, cockscomb, animal, Placenta Hominis and umbilical cord).In the cartilage in joint and eyes, found especially the HA of high concentration, so it is used to various medical applications, for example the auxiliary injection agent of injectable anti-arthritic, eye surgery, xerophthalmia medicine etc.In addition, have the hyaluronic enzyme of degraded family in vivo, and HA absorbs the water of himself weight hundred times and forms gel in water.Therefore the HA gel that forms has very high viscosity, therefore this slowed down release rate of drugs, so in drug delivery system (DDS) field, carried out a large amount of explorations and research (referring to JP 1989-287041, USP 5416071 and US2003/0064105) energetically about hyaluronic application.Hyaluronic add captures moisture to be forming gel, and therefore is used for various cosmetic uses, for example cosmetic humectant, be used for reducing (KR2005-0048287, KR 2004-0024004 and the KR 2003-0061447) such as cosmetics additives of wrinkle.
Yet not having the alleviation of example report hyaluronic acid and/or hyaluronic acid salt pair atopic dermatitis and treatment is that treatment is effective.In addition, as far as we know, in this area, go back nobody at present and attempt to comprise the compositions of hyaluronic acid and/or hyaluronate and resveratrol for prevention and treatment atopic dermatitis.
Summary of the invention
Technical problem
Therefore, an object of the present invention is to address the above problem the technical problem that does not also have solution with other.
As for address the above problem carry out multiple deeply and the result of thorough research experiment, the present inventor has been found that the compositions that comprises hyaluronic acid and/or hyaluronate has significant effect to prevention and treatment atopic dermatitis.Find to have realized the present invention based on these.
Technical scheme
According to a technical scheme of the present invention, can realize above-mentioned and other purpose by the compositions that comprises hyaluronic acid and/or hyaluronate that is provided for preventing and treat atopic dermatitis.
In order to confirm that above-mentioned composition is to prevention and the therapeutic effect of atopic dermatitis, as institute in the EXPERIMENTAL EXAMPLE below is illustrational, the present inventor uses the animal model of atopic dermatitis, has carried out the measurement of ear swelling test and blood IgE level.The result confirms that above-mentioned compositions display is to the excellent therapeutic effect of atopic dermatitis.
Hyaluronic acid (HA) is naturally occurring biopolymer and is colourless and transparent linear polysaccharide that it has high viscosity and 5 * 10
4～13 * 10
6The molecular weight of Da, and the monosaccharide that comprises alternating N-acetyl-D-glycosamine and D-glucuronic acid is as repetitive.By conventional method known in the art, for example sour dissolving, alkali dissolution, neutral dissolving and enzyme dissolving can be extracted and the purification hyaluronic acid from diversified organism and tissue (for example vitreous humor, knuckle synovia, cockscomb etc.).
As limiting hereinbefore, compositions of the present invention can adopt hyaluronic acid and hyaluronate.The preferred example of described hyaluronate can comprise, but be not limited to: hyaluronate sodium, potassium hyaluronate, hyaluronic acid ammonium, calcium hyauronate, hyaluronic acid magnesium, Curiosin, Cobalt hyaluronate. and combination arbitrarily thereof.Hyaluronate sodium more preferably.
Depend on extraction and purification process, method of testing etc., hyaluronic acid or its salt can have the various molecular weights scope.When molecular weight increases, even a spot of hyaluronic acid or its salt also may form gel.For example, when hyaluronic molecular weight be 1 * 10
6During Da, hyaluronic preferred content is greater than 2wt% in hyaluronic acid compositions, is 3 * 10 and work as hyaluronic molecular weight
6During Da, preferred content is greater than 0.5wt%.
Simultaneously, the molecular weight of the hyaluronic acid in the compositions of hyaluronic acid and/or its salt or its salt and content should be enough in order to form hyaluronic acid derivatives.Therefore, hyaluronic molecular weight is preferably 2 * 10
5More than the Da, and more preferably 1 * 10
6～1 * 10
7Da, and based on the gross weight of compositions, hyaluronic preferred content scope is 0.5～50wt%.
In the preferred embodiment of the present invention, except hyaluronic acid and/or its salt, above-mentioned compositions can also further comprise resveratrol.
The research of carrying out according to the inventor, though hyaluronic acid and/or hyaluronate and resveratrol can demonstrate the curative effect to atopic dermatitis separately, but compare with each chemical compound of independent use, find that being used in combination of they produced unexpected improvement curative effect.More specifically, the special combination of hyaluronic acid and/or hyaluronate and resveratrol has produced the curative effect of remarkable excellence by the interaction partners atopic dermatitis of complementarity, and does not cause the competitive reaction between the two.These true will be hereinafter embodiment and EXPERIMENTAL EXAMPLE in the checking that experimentizes.
Resveratrol for have 3,5,4 '-polyphenol antioxidation agent of resveratrol structure, and extensively be present in gymnosperm and the dicotyledon.Though resveratrol can exist simultaneously with the form of free and glucosides, it mainly exists with the form of glucosides, and wherein, the resveratrol of non-saccharic composition is attached to (J.Prog.Phytochem., 6,203-209,1980) on the saccharic composition.Known resveratrol has active anticancer for example, antioxidant activity, anti-inflammatory activity, cholesterol reducing activity, to multiple beneficial effect (Mol.Nutr.Food Res., 49,405-430,2005 of preventive effect of cardiovascular disease etc.; Biomed.Pharmacother.; 56,84-87,2002; AJH, 18,864-870,2005; With Food Chemistry, 101,449-457,2007).Therefore, multi-purpose feasibility has been carried out a large amount of explorations and research, for example: influenza emits aging resistance and skin whitening component (KR2004-0101665 and KR 2005-0039927) and the functional health care food (KR 2006-0015737) etc. of agent (KR 2005-0071627), cosmetics.
Resveratrol exists with two kinds of isomeric form; Trans-resveratrol and cis-resveratrol., wherein, transisomer is more stable in nature form.Owing to the primary stage of the trans-resveratrol inhibition cancer formation of reporting natural generation is arranged and has active anticancer (Science, 275,218-220,1997), actively developed a large amount of explorations and research at the purposes of resveratrol.
According to the present invention, in the cis and transisomer of resveratrol, be preferably the trans-resveratrol that is present in occurring in nature (trans-3,5,4 '-resveratrol).As the source of resveratrol, can use the extract that contains resveratrol, the resveratrol that from the plant variety of any appropriate, obtains or synthetic resveratrol.The exemplary of these plant varieties can comprise gymnosperm and dicotyledon.Preferably, can from following plants, extract and purified resveratrol: fruit, skin, seed, stem and the leaf of Fructus Vitis viniferae (particularly European grape (Vitis vinifera), muscat (Vitis rotundifolia) and fox grape (Vitis labrusca)), Rhizoma Polygoni Cuspidati (Polygonumcuspidatum), Eucalyptus, PiceameyeriRehd. Et Wils., Lapland pine (Scottish pine), Semen arachidis hypogaeae and Bulbus Lilii etc.
As the raw material of resveratrol, the extract of above-mentioned plant variety can use separately and use with its combination in any, perhaps can use the extract that contains small amount of resveratrol in addition.The preferred highly purified purified resveratrol extract that has above 90% that uses.
The content of resveratrol can be preferably at 0.01～50wt%, and more preferably in the scope of 0.01～10wt%.
Preferably, described compositions can be the pharmaceutically acceptable carrier that comprises more than one or the pharmaceutical composition of excipient.
If necessary, in order to increase the dissolubility of resveratrol, this pharmaceutical composition can further comprise for example other composition of solvent, oil, emulsifying agent etc.These other materials can use separately or with its compositions, and selection that can be easy and suitable in the preparation of said composition.
The example of the solvent that can use in the present invention comprises: water, ethanol, isopropyl alcohol, 1,3 butylene glycol, propylene glycol, glycerol etc.
The oil of Shi Yonging can be for being selected from least a in Semen Maydis oil, Oleum sesami, Oleum Gossypii semen, soybean oil, Oleum Arachidis hypogaeae semen, monoglyceride, Diglyceride and triglyceride, mineral oil, Squalene, Jojoba oil, olive oil, evening primrose oil, borage oil, Oleum Vitis viniferae and the combination in any thereof in the present invention.
As for emulsifying agent, can use for example lecithin, organic monoglyceride, sorbitan fatty acid ester, polyoxyethylene fatty acid ester, sorbitan stearate etc.
Yet the above-mentioned material that provides only is used for illustration, and therefore also can use other suitable material.
In addition, described compositions can preferably be prepared the cosmetic composition that becomes acceptable carrier on the cosmetics that comprise more than one or excipient.That is, said composition can be prepared into the compositions that is used for prevention and treatment atopic dermatitis of cosmetics form or cosmetics additive form.Acceptable carrier or excipient can be identical or different with pharmaceutically acceptable carrier or excipient on the cosmetics.
When needs use compositions of the present invention as cosmetic material, can only add said composition itself or use with other cosmetic composition, perhaps can suitably use according to other conventional method.Cosmetics comprise, but are not limited to aftershave lotion, washing liquid, facial cream, beauty treatment Liniment (pack) and colour cosmetic (color cosmetic).
Cosmetic composition can be mixed with the compositions of various ways, example gel, emulsifiable paste, ointment etc.According to required combination dosage form, by adding conventional softening agent, emulsifying agent and thickening agent or other material known in the art, use known method,, can suitably prepare gel, emulsifiable paste, ointment type compositions.
For example, by adding for example softening agent of trimethylolpropane, Polyethylene Glycol and glycerol, for example the solvent of propylene glycol, ethanol and different hexadecanol and pure water can prepare gel type composition.
For example, the cream type compositions can prepare by adding following material: aliphatic alcohol, for example octadecanol, tetradecanol, tadenan, EICOSANOL, the pure and mild 2-Methylpentadecane alcohol of isooctadecane; Emulsifying agent, for example lipid (for example lecithin, phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, Phosphatidylserine, phosphatidylinositols and derivant thereof), tristerin, sorbitan cetylate, sorbitan stearate etc.; Natural fat and oil, for example American Avocado Tree oil, almond oil, babassu oil, borage oil, Flos Camelliae Japonicae wet goods; Lipid composition, for example ceramide, cholesterol, fatty acid, phytosphingosine, lecithin etc.; The solvent of propylene glycol etc. for example; And pure water.
For example, can prepare the ointment type compositions by adding softening agent, emulsifying agent and for example wax of microwax, paraffin, ceresine, Cera Flava, spermaceti, vaseline etc.
Technical scheme provides the pharmaceutical preparation that is used for preventing and/or treating atopic dermatitis according to another preferred, and it comprises above-mentioned composition as active component and more than one pharmaceutically acceptable carrier or excipient.
Therefore, if necessary, above-mentioned preparation can comprise pharmaceutically acceptable carrier, diluent, excipient or its combination in any.These components are conducive to active component and enter organic administration.
Carrier is defined as the chemical compound that is conducive to target compound or material target approach cell or tissue.Although the type to carrier has no particular limits, according to required dosage form, carrier can be preferably the conventional carrier that uses in this area, for example be selected from least a in the following material: solid carrier, for example starch, lactose, mannitol, carboxymethyl cellulose, corn starch and inorganic salt; Liquid-carrier, for example distilled water, normal saline, D/W, alcohol (for example ethanol, propylene glycol and Polyethylene Glycol); And oiliness carrier, for example various animal and plant oil, white vaseline, paraffin and wax.
The example of excipient can comprise the filler of for example lactose, sucrose, mannitol and Sorbitol, corn starch, wheaten starch, rice starch, potato starch, gelatin, Tragacanth, methylcellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose and/or the cellulosic material of polyvinylpyrrolidone (PVP) for example.
Of the present invention one preferred embodiment in, pharmaceutical dosage form can be a kind of injection preparation.By conventional method known in the art, use aseptic aqueous solution, nonaqueous solvent, suspending agent, Emulsion or lyophilized products as matrix material (base material) compositions to be made injection preparation.
Of the present invention another preferred embodiment in, pharmaceutical dosage form can be a kind of oral formulations.By conventional method known in the art, this oral formulations can be mixed with capsule, suspending agent, Emulsion, syrup or aerosol form.
Perhaps, described pharmaceutical dosage form can comprise for example other dosage form of suppository.
The specific embodiment
Now, with reference to the following examples the present invention will be described in further detail.Provide these embodiment only to be used for illustrating the present invention, and the scope that can not be construed as limiting the invention and essence.
Embodiment 1: the preparation of hyaluronic acid derivatives
Be 3 * 10 with the molecular weight of 1g
6The hyaluronate sodium of Da is dissolved in the pure water of surplus to the concentration of 1% (w/w), has therefore prepared hyaluronic acid derivatives.
Comparing embodiment 1: the preparation of resveratrol solution
Resveratrol (purity: greater than 99%, available from Sigma) be dissolved in the ethanol to 0.1% (w/w) concentration with the preparation resveratrol solution.
EXPERIMENTAL EXAMPLE 1: mice ear test
In order to confirm medicine to prevention and the therapeutic effect of atopic dermatitis, use the ear swelling model to experimentize as the animal model of atopic dermatitis.Described ear swelling model is a kind of animal model, wherein use a kind of hapten (a kind of be attached on the protein and form the low molecular weight substance of anaphylactogen thus) to make the ear allergy of mice to induce atopic reaction, and measure the thickness of ear swelling as time goes by to confirm therapeutic effect (the Journal ofDermatological Science to atopic dermatitis, 36,1-9,2004; With Journal of DermatologicalScience, 37,159-167,2005).
This experiment is adopted Balb/C mice (male, 5 weeks are big) and as haptenic 2, and 4-dinitro-1-chlorobenzene (DNCB, Sigma).Each animal groups is made up of 5 mices.The acetone soln of the 1%DNCB of 30 μ l is applied on the auris dextra of mice to cause the anaphylaxis of ear.After one week, every day, the solution with the 1%DNCB of 30 μ l was applied to animal on one's body to cause atopic dermatitis.Simultaneously, twice of every day the resveratrol solution of the comparing embodiment 1 of the hyaluronic acid derivatives of the embodiment 1 of 30 μ l and 30 μ l is applied on the auris dextra of every group of mice.Before carrying out the DNCB anaphylaxis and at first day and the 3rd day that induces atopic reaction, use digital micrometer (Digitrix, NSK, Japan) thickness of measurement animal ear.Following table 1 has provided the result who obtains like this, and it is presented at induces the atopic reaction increase of the thickness of ear afterwards.
The ear thickness (μ m) that [table 1] increases
| First day | The 3rd day | |
| Contrast | 117.8 | 187.8 |
| Embodiment 1 | 123.6 | 143.4 |
| Comparing embodiment 1 | 146.2 | 170.4 |
Remarkable increase as shown in table 1, that contrast (treatment) group shows the ear thickness of animal along with the passage of the time of inducing atopic reaction.At the 3rd day, compare with the mice of inducing atopic reaction of contrast (treatment) group, the increase degree of the ear thickness of the mice of inducing atopic reaction in embodiment 1 and the comparing embodiment 1 is little as can be seen, thereby shows that this medicine is to the inhibition of ear swelling.Especially, when comparing with matched group, the value added of the ear thickness of the mice in embodiment 1 demonstrates the marked difference greater than 40 μ m, thereby confirmed the inhibition of hyaluronic acid derivatives to the excellence of atopic dermatitis, and further confirmed to be better than the inhibition with the comparing embodiment 1 of resveratrol treatment.Hyaluronic acid and resveratrol all have therapeutic effect to atopic dermatitis as can be known from these results, and particularly hyaluronic acid has remarkable result to the treatment atopic dermatitis.
Embodiment 2: comprise the preparation of the hyaluronic acid derivatives of resveratrol
Be 3 * 10 with the molecular weight of 1g
6The hyaluronate sodium of Da is dissolved in the pure water of surplus with the concentration of 1% (w/w), has prepared hyaluronic acid derivatives thus.Then, resveratrol (purity: greater than 99%, available from Sigma) is joined in the hyaluronic acid derivatives body to the concentration of 0.1% (w/w), prepared the hyaluronic acid derivatives that comprises resveratrol thus.
EXPERIMENTAL EXAMPLE 2: induce atopic dermatitis at the mice back
In order to confirm to comprise the hyaluronic acid derivatives of resveratrol to the therapeutic effect of atopic dermatitis, carry out the animal model as atopic dermatitis of inducing of atopic dermatitis at the back of mice.It is a kind of animal model that mouse back is induced the dermatitis model, wherein the hapten anaphylaxis is carried out at the back after the depilation of animal, carry out atopy subsequently and induced for 4～5 weeks, smeared curative drug several days at the back of animal, and the IgE level in the measurement blood is to confirm therapeutic effect (the Journal of Dermatological Science to atopic dermatitis, 36,1-9,2004).This animal model is a kind of useful model, because by measuring blood IgE horizontal survey medicine to the inhibition of IgE level, can more directly confirm therapeutic effect to atopic dermatitis by it.
This experiment is adopted Balb/C mice (male, 5 weeks are big) and as haptenic 2, and 4-dinitro-1-chlorobenzene (DNCB, Sigma).Each animal groups is made up of 5 mices.(acetone: olive oil=3: 1) solution spreads upon on the back after the depilation of mice to cause the hapten anaphylaxis with the acetone of the 1%DNCB of 200 μ l.After one week, once the solution of the 0.5%DNCB of 200 μ l is spread upon every three days animal on one's body 5 weeks to cause atopic dermatitis thus.Finish induce atopic dermatitis after, embodiment 1 and the hyaluronic acid derivatives of embodiment 2 and the (composition: prednival acetas (Prednisolone Valerate Acetate) of the Lidomex emulsifiable paste as steroid medicine of 200 μ l with each 200 μ l, Sama Pharmaceutical Co., Ltd., Korea) be applied to last 5 day of back that mice is brought out dermatitis twice (over against according to) every day.Matched group is not treated.Before dispenser, and after dispenser second day, the 5th day, blood collected from the afterbody of mice.Isolate serum, use Mouse IgE ELISA (AlphaDiagnostic International) to measure blood IgE level then.Based on the IgE level of the blood before the dispenser, calculate the blood IgE level after mice is carried out Drug therapy.The gained result is as shown in table 2 below.
[table 2]
| The 2nd day | The 5th day | |
| Contrast | 44.1 | 17.6 |
| Over against shining (Lidomex) | 34.2 | 13.3 |
| Embodiment 1 | 30.0 | 12.8 |
| Embodiment 2 | 25.8 | 10.5 |
As can be seen from Table 2, its confirmation is compared with matched group, and the gel of steroid medicine Lidomex and embodiment 1 and 2 demonstrates inhibition to the IgE higher level the mice of inducing dermatitis.More allow the people surprised be, compare with the steroid medicine that is used at present the atopy treatment, the hyaluronic acid derivatives that comprises resveratrol of the hyaluronic acid derivatives of embodiment 1 and embodiment 2 is obviously more outstanding on the horizontal inhibition of IgE.As previously described, from inferring this medicine to the direct therapeutic effect of atopic dermatitis to the inhibition degree of IgE level.Therefore, as can be seen, compare with the steroid medicine, the medicine among the embodiment 1 and 2 demonstrates the therapeutic effect good to atopic dermatitis simultaneously.
Especially, treatment at second day, the gel of embodiment 2 demonstrates than matched group and exceeds the horizontal inhibition of about IgE more than 20% and exceed the horizontal inhibition of about IgE more than 10% than the Lidomex group, thereby shows that the hyaluronic acid derivatives that comprises resveratrol of embodiment 2 has notable therapeutic effect to atopic dermatitis.Result from above-mentioned EXPERIMENTAL EXAMPLE 1 only uses the anti-atopic dermatitis effect of resveratrol demonstration than only using hyaluronic weak effect as can be seen.Yet, from the result table 2 as can be seen, compare with each chemical compound of independent use, find resveratrol and the hyaluronic therapeutic effect that has produced remarkable improvement that is used in combination, this is because the complementarity interaction between them causes.
In a word, comprise hyaluronic pharmaceutical preparation and can more effectively treat atopic dermatitis than conventional anabolic agent.Combination had produced notable therapeutic effect to atopic dermatitis when especially, the result showed hyaluronic acid and resveratrol.
Embodiment 3: comprise the preparation of resveratrol and hyaluronic gel
The molecular weight that mixes 1% (w/w) is 3 * 10
6The propylene glycol of the glycerol, 3% (w/w) of the resveratrol, 5% (w/w) of the hyaluronate sodium of Da, 0.1% (w/w) and the pure water of surplus are with the preparation gel.
Embodiment 4: comprise the preparation of resveratrol and hyaluronic emulsifiable paste
The molecular weight that mixes 1% (w/w) is 3 * 10
6The propylene glycol of the ceramide, 3% (w/w) of the sorbitol acid anhydride stearate of the resveratrol, 2.5% (w/w) of the hyaluronate sodium of Da, 0.1% (w/w), the Camellia oil, 0.1% (w/w) of 5% (w/w) and the pure water of surplus are with the preparation emulsifiable paste.
Embodiment 5: comprise the preparation of resveratrol and hyaluronic ointment
Mixing the molecular weight that comprises 1% (w/w) is 3 * 10
6The sorbitol acid anhydride stearate of the glycerol, 1% (w/w) of the resveratrol, 5% (w/w) of the hyaluronate sodium of Da, 0.1% (w/w) and the vaseline of surplus are with preparation ointment.
Industrial applicibility
Find out significantly that from above description the compositions that comprises hyaluronic acid and/or its salt according to the present invention can be mixed with pharmaceutical composition, cosmetic composition or the pharmaceutical preparation for prevention and treatment atopic dermatitis.Especially, further resveratrol is attached to and plays in the above-mentioned composition the significant prevention of atopic dermatitis and therapeutic effect.
Claims (14)
1. compositions that is used for preventing and/or treating atopic dermatitis, said composition comprises hyaluronic acid and/or hyaluronate, and it further comprises: based on the gross weight of described compositions, the resveratrol of content in the scope of 0.01～50wt%.
2. compositions according to claim 1, wherein, described hyaluronate is selected from hyaluronate sodium, potassium hyaluronate, hyaluronic acid ammonium, calcium hyauronate, hyaluronic acid magnesium, Curiosin, Cobalt hyaluronate. and combination arbitrarily thereof.
3. compositions according to claim 2, wherein, described hyaluronate is hyaluronate sodium.
4. compositions according to claim 1, wherein, described hyaluronic molecular weight is 2 * 10
5More than the Da.
5. compositions according to claim 1, wherein, based on the gross weight of described compositions, described hyaluronic content is 0.5～50wt%.
6. compositions according to claim 1, wherein, described resveratrol is trans-resveratrol.
7. compositions according to claim 1, wherein, the purity of described resveratrol is greater than 90%.
8. according to any described compositions in the claim 1～7, wherein, described compositions is the pharmaceutical composition that comprises pharmaceutically acceptable carrier or excipient.
9. according to any described compositions in the claim 1～7, wherein, described compositions is the cosmetic composition that comprises acceptable carrier on the cosmetics or excipient.
10. compositions according to claim 9, wherein, described cosmetic composition is formulated into gel-type.
11. compositions according to claim 9, wherein, described cosmetic composition is formulated into cream type.
12. compositions according to claim 9, wherein, described cosmetic composition is formulated into ointment type.
13. a pharmaceutical preparation that is used for prevention and treatment atopic dermatitis, said preparation comprises as the described compositions of the claim 1 of active component and more than one pharmaceutically acceptable carrier or excipient.
14. preparation according to claim 13, wherein, described preparation is injection or oral formulations.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2006-0127123 | 2006-12-13 | ||
| KR1020060127123A KR100927579B1 (en) | 2006-12-13 | 2006-12-13 | Composition Comprising Hyalruronic Acid and/or their Salt for Treatment of Atopic Dermatitis |
| KR1020060127123 | 2006-12-13 | ||
| PCT/KR2007/006486 WO2008072905A1 (en) | 2006-12-13 | 2007-12-12 | Composition comprising hyaluronic acid and/or its salts for treatment of atopic dermatitis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101534842A CN101534842A (en) | 2009-09-16 |
| CN101534842B true CN101534842B (en) | 2013-07-03 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007800410606A Active CN101534842B (en) | 2006-12-13 | 2007-12-12 | Composition comprising hyaluronic acid and/or its salts for treatment of atopic dermatitis |
Country Status (3)
| Country | Link |
|---|---|
| KR (1) | KR100927579B1 (en) |
| CN (1) | CN101534842B (en) |
| WO (1) | WO2008072905A1 (en) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008094910A2 (en) * | 2007-01-30 | 2008-08-07 | Cypress Pharmaceutical, Inc. | Hyaluronate compositions |
| KR20100102531A (en) * | 2009-03-11 | 2010-09-24 | 주식회사 엘지생명과학 | Composition for treating atopic dermatitis |
| GB2502029B (en) * | 2011-02-09 | 2018-02-21 | Forward Scout Entpr Pty Ltd | Cosmetic or pharmaceutical formulation comprising hyaluronate crosspolymer and one or more of; azelaic acid, or derivative, and natural oils |
| TWI446915B (en) * | 2011-07-12 | 2014-08-01 | Holy Stone Healthcare Co Ltd | Composition for use in treating and preventing mucosa related disease |
| ES2665254T3 (en) | 2011-07-12 | 2018-04-25 | Holy Stone Healthcare Co., Ltd. | Compositions comprising hyaluronic acid for treatment and prevention of mucosal related diseases |
| EP3302409B1 (en) | 2015-06-05 | 2021-04-21 | Tomcat International Limited | Process and composition for stimulating hyaluronic acid synthesis |
| FR3036956B1 (en) * | 2015-06-05 | 2019-12-20 | President And Fellows Of Harvard College | METHOD OF STIMULATING THE SYNTHESIS OF HYALURONIC ACID |
| CA2896038C (en) | 2015-07-03 | 2022-08-09 | Glycobiosciences Inc. | Polymer matrix compositions comprising a high concentration of bio-fermented sodium hyaluronate and uses thereof |
| US10722436B2 (en) | 2015-08-10 | 2020-07-28 | Mary Kay Inc. | Topical compositions |
| CN110123795A (en) * | 2018-02-09 | 2019-08-16 | 上海睿泰生物科技股份有限公司 | Load purposes of the human pluripotent stem cells excretion body of resveratrol on preparation treatment skin disease drug |
| KR20210003168A (en) * | 2018-04-18 | 2021-01-11 | 이콤 메디칼 게엠베하 | High molecular weight hyaluronic acid for enhancing epithelial survival and restructuring body surface |
| CN109045279B (en) * | 2018-09-10 | 2020-01-21 | 因之彩生物科技（武汉）有限公司 | External composition, application thereof and external therapeutic agent |
| KR102289551B1 (en) | 2019-07-17 | 2021-08-13 | 주식회사 제이투케이바이오 | A skin-care agent containing hyaluronic acid complex |
| CN110237091A (en) * | 2019-07-27 | 2019-09-17 | 海南希睿达生物技术有限公司 | A kind of hyaluronic acid maintenance biomembrane can be used for children |
| RU2710074C1 (en) * | 2019-10-02 | 2019-12-24 | Общество с ограниченной ответственностью "МедикалСайнс" | Hydrogel water-soluble composition based on hyaluronic acid and polyvalent metal ions and a method for production thereof |
| WO2023104843A1 (en) | 2021-12-09 | 2023-06-15 | Beiersdorf Ag | Topical preparation for enhancing skin condition |
| DE102022202547A1 (en) | 2021-12-09 | 2023-06-15 | Beiersdorf Aktiengesellschaft | Topically applicable preparation to improve the condition of the skin |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020173472A1 (en) * | 1998-01-09 | 2002-11-21 | Pezzuto John M. | Pharmaceutical formulations of resveratrol |
| CN1602198A (en) * | 2001-12-12 | 2005-03-30 | 乌尔萨法姆药物两合公司 | Pharmaceutical composition for use in ophthalmology and rhinology |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5872109A (en) * | 1995-02-07 | 1999-02-16 | Shiseido Company, Ltd. | Anti-inflammatory agent |
| JPH10287550A (en) * | 1997-04-10 | 1998-10-27 | Nippon Rideia Oririi Kyokai | Preparation for external use for skin |
-
2006
- 2006-12-13 KR KR1020060127123A patent/KR100927579B1/en active IP Right Grant
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2007
- 2007-12-12 CN CN2007800410606A patent/CN101534842B/en active Active
- 2007-12-12 WO PCT/KR2007/006486 patent/WO2008072905A1/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020173472A1 (en) * | 1998-01-09 | 2002-11-21 | Pezzuto John M. | Pharmaceutical formulations of resveratrol |
| CN1602198A (en) * | 2001-12-12 | 2005-03-30 | 乌尔萨法姆药物两合公司 | Pharmaceutical composition for use in ophthalmology and rhinology |
Also Published As
| Publication number | Publication date |
|---|---|
| KR100927579B1 (en) | 2009-11-23 |
| WO2008072905A1 (en) | 2008-06-19 |
| KR20080054627A (en) | 2008-06-18 |
| CN101534842A (en) | 2009-09-16 |
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