CN1327834C - Pharmaceutical composition for prevention and cure of skin pruritus - Google Patents
Pharmaceutical composition for prevention and cure of skin pruritus Download PDFInfo
- Publication number
- CN1327834C CN1327834C CNB2004100649282A CN200410064928A CN1327834C CN 1327834 C CN1327834 C CN 1327834C CN B2004100649282 A CNB2004100649282 A CN B2004100649282A CN 200410064928 A CN200410064928 A CN 200410064928A CN 1327834 C CN1327834 C CN 1327834C
- Authority
- CN
- China
- Prior art keywords
- luteolin
- skin
- pruritus
- skin pruritus
- histamine
- 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.)
- Expired - Fee Related
Links
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract
The present invention relates to an external local-application medical composition for preventing and curing skin pruritus caused by various reasons, which is mainly composed of a therapeutic effective amount of mignonette agent and pharmaceutical adjuvant and can comprise ledebouriella root volatile oil and an extract of matrine and/or densefruit pittany root-bark. The medical composition has no toxic or side effect and can be used for long term.
Description
Technical field
The present invention relates to come from the control skin pruritus pharmaceutical composition of Chinese medicine, be specially the partial smearing pharmaceutical composition that suppresses skin pruritus due to a variety of causes.
Background technology
Skin pruritus is a kind of chronic dermatosis that does not have former skin lesion, can be by stimulations such as some disease, medicine, cold, woolen knitwear allergy and take place, belong to the delayed ischemic neurological deficits dermatoses.It mainly shows as itches, and can show as locality or general, is paroxysmal, can last for hours at every turn, especially with night for very, pruritus very then is difficult to stand.It is one of the important symptom that comprises the inflammatory disease of the skin of allergic dermatitis, some systemic diseases (as uremia, obstructive jaundice, or AIDS etc.) also with the pruritus symptom.But a lot of pruritus do not have the obvious cause of disease and can study carefully among the crowd, especially in the old people, there is pruritus more than half not have cause specific, this may be because old people's skin xerosis cutis, degree of hydration is lower, easily produce and have the material (as cytokine) that the part causes the former character of itching, or some is caused the material sensitive of itching increase.But pruritus skin or neuropathic, it results from, and one or more cause and itch former material sensation teleneuron C fiber and cause.Histamine is that skin allergic reaction is (as rubella, drug eruption, contact dermatitis, allergic dermatitis and mosquito sting medicine) or the important medium of the caused skin pruritus of drying property skin, it causes the effect of itching and is confirmed by the antipruritic drug effect of low drowsiness property histamine H 1 receptor antagonist.Many endogenous chemical substances, as amine, proteolytic enzyme, nerve polypeptide, arachidonic acid metabolite or cytokine etc. all may become the part and cause the material of itching.So, cause the original qualitative diversity of itching, the interaction of skin hypersensitivity or inflammatory reaction and nerve conduction and Nervous and Mental Factors, and the local diversification that causes the former medium action pathway of itching (as histamine H 1, the outbreak of the participation pruritus that H2 and H3 receptor all can be in various degree; 5-hydroxy tryptamine can be respectively participates in the pathological process of pruritus by periphery and maincenter approach) make comparatively complicated that the etiology and pathology process of skin pruritus becomes, brought bigger difficulty for the skin pruritus clinical prevention.The medicine of the treatment skin pruritus card of existing clinical use is few and most certain toxic and side effects.As the amcinonide fluocinonide, can reduce the resistance against diseases of skin behind the abuse, the folliculitis that all fungus-caused tinea manuum, tinea pedis, tinea corporis, tinea cruris and suppurative bacterium cause, furuncle and phyma, impetigo etc. can make focus enlarge with the fluocinonide treatment, and the state of an illness increases the weight of.The life-time service fluocinonide can make epidermal tissue's attenuation, and skin elasticity weakens, and loses dermatoglyph or the colour of skin shoals.Sometimes also can impel xerosis cutis or ichthyosiform to change.Can cause skin pigmentation disorder and hirsutism.Facial medication person's skin pigmentation disorder is particularly evident, can be pigmentation such as chloasma sample, also can be hypopigmentation and forms white macula.The also normal clinically in addition antiallergic agent such as chlorphenamine that adopts is used for the treatment of, but can occur xerostomia after taking medicine mostly, phenomenons such as that drowsiness phenomenon, minority have is nauseating, vomiting.
Luteolin is the clear and definite known flavone compound of a kind of structure, extensively is present in the plant, and at Folium Perillae, content is higher in Caulis Lonicerae and some green vegetables, is found separation the fifties from eighties of last century, now can be manually semi-synthetic.Its biological activity people have also been carried out extensive studies, mainly concentrated on anti peroxidation of lipid, aspects such as mutation and inhibition tumor cell.
The problem to be solved in the present invention is research control a variety of causes or the comprehensive skin pruritus disease drug that produces of several reasons, and it has no side effect substantially, but life-time service, and have treatment and preventive effect simultaneously.
For addressing the above problem, the invention provides following technical scheme.
A kind of externally-applied medicinal composition of preventing and treating skin itching is characterized in that containing luteolin, and it mainly is made up of the luteolin and the pharmaceutic adjuvant of treatment effective dose.The externally-applied medicinal composition of described control skin itching, wherein content of luteolin is by weight 0.01%～1.0%; Wherein content of luteolin can be by weight 0.1%～0.5%.
The present invention prevents and treats the externally-applied medicinal composition of skin itching, except that containing the luteolin and pharmaceutic adjuvant for the treatment of effective dose, also can with other medicinal component assembly, as contain a kind of or two kinds of compositions that are selected from Radix Saposhnikoviae volatile oil, matrine, the Cortex Dictamni extract, promptly, make the externally-applied medicinal composition of control skin itching with luteolin and a kind of or two kinds of composition assembly that are selected from Radix Saposhnikoviae volatile oil, matrine, the Cortex Dictamni extract.In a word, the present invention includes luteolin all application in the external used medicine of preparation control skin itching.
The following experiment of the present invention shows that luteolin makes the partial smearing medicine and can effectively prevent and treat a variety of causes or a variety of causes skin pruritus due to comprehensive.It has no side effect substantially, but life-time service, and have treatment and preventive effect simultaneously.
Passive dermoreaction (PCA) is the immediate allergy of IgE mediation, and in this process, mast cells activation also discharges inflammatory mediator, and the some of them inflammatory mediator is main the causing former material of itching as histamine and proteolytic enzyme.Luteolin suppresses the outbreak of scratching where it itches that passive dermoreaction (PCA) is caused, and shows that the luteolin mechanism of action is and suppress mast cells activation and to cause the former medium of itching to discharge relevant.
Remove immune activation (IgE mediation), mastocyte also can directly be activated by non-immunologic mechanism by biological substance.Compound48/80 is the non-immune activation stimulant of a mastocyte, and has caused the pruritus reaction.Luteolin has effectively suppressed the pruritus outbreak due to the Compound48/80, and this results suggest all has tangible antagonism to luteolin to the pruritus outbreak due to mastocyte immunity or the non-immune activation.
Histamine, 5-hydroxy tryptamine and Compound 48/80 also are that topochemistry causes the former material of itching, subcutaneous injection histamine, and 5-hydroxy tryptamine and Compound 48/80 have caused the pruritus outbreak, and the luteolin partial smearing shows effective inhibitory action.This results suggest, luteolin are not only the inhibition that discharges by the activation to mastocyte in the process to the antipruritic outbreak, also have the facedown topochemistry to cause the effect of the former material of itching.
Allergic dermatitis is an inflammatory and allergic pathological process and with serious pruritus outbreak.Its dermoreaction has two different time phases.It mainly is mastocyte or the release of having a liking for participation of alkali granulocyte and inflammatory mediator mutually that speed is sent out; And it is tardy based on inflammatory cell and lymphocytic infiltration.We have made contact dermatitis and allergic dermatitis animal model, and the obvious inhibitory action of phase inflammatory outbreak when observing luteolin to two of dermatitis.Simultaneously luteolin also shows the inhibition to the vascular permeability inflammatory exudation due to PCA and the histamine, has affirmed the effective antiinflammatory action of luteolin, and this effect is and suppress the pruritus outbreak confidential relation is arranged.
Drying property dermatitis is on the low basis of skin hydration degree and the remarkable hypertrophy of phosphorus columnar epithelium occurs, visible hyperkeratosis of horny layer and parakeratosis, the skin corium proliferation of fibrous tissue, and with inflammatory reaction such as more amount lymphocyte and inflammatory cell infiltrations, its outbreak of scratching where it itches is relevant with the release that topochemistry causes the former material of itching.Also to cause itch former material and antiinflammatory action closely related with its antagonism chemistry to the inhibition of the variation of this pathological process and pruritus outbreak for luteolin.
The luteolin that the present invention prevents and treats in the pharmaceutical composition of skin pruritus can be any forms such as extractum of pure compound, thick purification product, extraction.And described luteolin can be from plant extraction separation, also can be synthetic or semisynthetic luteolin.The content of the luteolin in the pharmaceutical composition of the present invention does not have special restriction, as long as according to required suitable adjustment.Its qualitative character is that luteolin purity is 98%, and residual quantity of heavy metal is less than 5ppm, and persticide residue is less than 10ppm, and outward appearance is yellow or pale yellow powder, colourless or near colourless powder.Granularity is 100%～80%, and loss on drying is 5%.
Can contain Radix Saposhnikoviae volatile oil, matrine etc. in addition in the pharmaceutical composition of the present invention.The natural drug that is comprised does not have special restriction, especially to preventing and treating the effective Chinese medicine of skin pruritus for example Radix Saposhnikoviae, Cortex Dictamni, Radix Sophorae Flavescentis.The form of these medical herbs is through extracting extractum, volatile oil, powder or the crystallization of extraction or purification process, does not have other special restriction in addition.
Preparation of drug combination method of the present invention does not have special restriction, for example can use luteolin and other material dissolutions in solvent, to make the preparation method of mixed solution, also luteolin can be dissolved in water earlier, other material dissolution mixes two kinds of solution behind oil phase.In addition, can be used for making other composition (except that luteolin) of medicine of the present invention, only otherwise influence the performance of luteolin effect, can handle according to the suitable method of character and characteristics employing separately.
The specific embodiment
The used luteolin of the present invention is available from Shaanxi Plant Biotechnology Co., Ltd. of intelligent section, and luteolin purity is 98%, and residual quantity of heavy metal is less than 5ppm, and persticide residue is less than 10ppm, and outward appearance is yellow or pale yellow powder, colourless or near colourless powder.Granularity is 100%～80%, and loss on drying is 5%.Employed in addition luteolin should meet the standard (total number of bacteria less than 1000 grams, fungi count less than 100 grams should not detect escherichia coli) of Ministry of Public Health to the medicinal raw material defined.All the other adjuvants are commercial and meet standards of pharmacopoeia.
Embodiment 1
The luteolin ointment formulation
Prescription 1 consists of stearic acid (11.4% (w/w), down together), Oleum Arachidis hypogaeae semen (10%), Cera Flava (11.3%), Brij (0.5%), glycerol (11%), triethanolamine (0.8%) and water (50%), wherein luteolin content is 0.2% (purity is 98%), (can add matrine content is 2%), preparation method is that stearic acid, Oleum Arachidis hypogaeae semen, Cera Flava are mixed and heated to 80 ℃, and emulsifying agent, glycerol, water etc. are mixed and heated to 68 ℃, and two kinds of medicines are added the water mixings; Hybrid mode can be added to water by oil phase, also can be added to oil phase by water, gets final product behind the mixing.During use, get about 0.05 gram～0.1 gram and be applied to the skin pruritus part and get final product.
Embodiment 2
The prescription 2 that contains the luteolin ointment formulation consists of stearic acid (11.4% (w/w), down together), Oleum Ricini (10.0%), liquid paraffin (11.6%), polyoxyethylene nonylphenol ether (polyethenoxy ether class nonionic emulsifier, 0.5～0.3%), glycerol (12.2%), triethanolamine (1～0.8%) and water (52～50%), wherein luteolin content is 0.25% (purity is 98%).Preparation method is that liposoluble constituents such as stearic acid, Oleum Ricini, liquid paraffin, lanoline are mixed and heated to 80 ℃, and emulsifying agent, glycerol, water etc. are mixed and heated to 60 ℃; Hybrid mode can be added to water by oil phase, also can be added to oil phase by water, gets final product behind the mixing.During use, from packing container, take out about 0.05 gram～0.1 gram and be applied to the skin pruritus part and get final product.
Embodiment 3
The prescription 3 that contains the luteolin ointment formulation consists of stearic acid (12% (w/w), down together), hydrogenated vegetable oil (10%), vaseline (5.5%), paregal O-20 (oleic alcohol polyethylene glycols nonionic emulsifier, 0.3%), azone (1%), lanoline (4.7%), glycerol (16%), triethanolamine (0.1%) and water (47～50%), wherein luteolin content is 0.3% (purity is 98%), (can add Radix Saposhnikoviae volatile oil content 3～1%).Preparation method is stearic acid, hydrogenated vegetable oil, azone, and the lanoline mixing also is heated to 70 ℃, adds the Radix Saposhnikoviae volatile oil mixing; Emulsifying agent, water mix homogeneously such as glycerol, water are heated to 60 ℃, add the luteolin mixing; Hybrid mode is the water that oil phase is added to 1/3 amount, behind the mixing, remaining water is added and mixing again.During use, from packing container, take out 0.02 gram～0.04 gram and be applied to the skin pruritus part and get final product.
Embodiment 4
The prescription 4 that contains the luteolin ointment formulation consists of stearic acid (20.5% (w/w), down together), liquid paraffin (19.5%), paregal O-20 (0.7%), glycerol (14.2%) and water (45.7%), wherein luteolin content is 0.3% (purity is 80%), matrine content 0.1%, Cortex Dictamni water extraction extractum (Cortex Dictamni crude drug and extractum weight ratio are 1: 1) 0.2%.Preparation method is that stearic acid, Oleum Ricini, liquid paraffin, lanoline are mixed and heated to 80 ℃, and emulsifying agent, glycerol, water etc. are mixed and heated to 70 ℃, adds mixing behind luteolin, Cortex Dictamni extract, the matrine; Hybrid mode can be added to water by oil phase, also can be added to oil phase by water, gets final product behind the mixing.During use, from packing container, take out about 0.05 gram～0.1 gram and be applied to the skin pruritus part and get final product.
Embodiment 5
The prescription 5 that contains the luteolin ointment formulation consists of hard paraffin (12% (w/w), down together), Oleum Sesami (16%), liquid paraffin (10%), tween 80 (8%), glycerol (5%), triethanolamine (0.3%) and water (45～47%), wherein luteolin (98%) content is 0.4%.Preparation method is that hard paraffin, Oleum Sesami, liquid paraffin are mixed and heated to 60 ℃, and emulsifying agent, triethanolamine, glycerol, water etc. are mixed and heated to 68 ℃, adds mixing behind the luteolin; Hybrid mode can be added to water by oil phase, also can be added to oil phase by water, gets final product behind the mixing.During use, from packing container, take out about 0.05 gram～0.1 gram and be applied to the skin pruritus part and get final product.
Embodiment 6
Pharmacodynamics test
Luteolin (5,7,3 ', 4 '-kaempferol) available from Shaanxi Plant Biotechnology Co., Ltd. of intelligent section, purity is 98%.
Find by the pharmacodynamic study results of screening, in the preparation content of luteolin 0.01%～1.0%, all effective when (partial smearing 2～200 micrograms/point), present tangible dose-effect relationship, point out reliable medicine effect for treating effect.In the test ointment contained luteolin little, in, big three dose concentrations are respectively and contain 0.01%, 0.1%, 0.5% luteolin in the preparation by weight, promptly test dose is respectively 2,20,100 μ g/site, its part experimental data is as follows.
1, luteolin suppresses mice skin pruritus that passive cutaneous anaphylaxis, PCA causes
Rat anti ovalbumin (EA) the serum vein of 18 times of dilutions of 200 μ injects and carries out sensitization, and 20 μ l normal saline include EA 3mg and shave a mao back subcutaneous injection and attack after 24 hours, cause passive dermoreaction.In the experiment or institute's reagent product 30min partial smearing before antigen is attacked.The adjuvant partial smearing is as blank.Antigen is observed mice pruritus number of times after attacking immediately.And with the increase of azovan blue method observation mice vascular permeability (0.2ml of vein injection immediately normal saline includes the 1mg azovan blue after the antigen attack)
As shown in table 1, mice has caused skin pruritus with anti-EA serum vein sensitization and with the subcutaneous attack of antigen.The partial smearing luteolin has significantly suppressed the pruritus number of times.The partial smearing hydrocortisone has also effectively suppressed the pruritus outbreak.
Table 1, luteolin are to the influence of mice skin pruritus that passive cutaneous anaphylaxis, PCA causes (mean ± SD)
| Group | Dosage (μ g/site) | Number of animals (n) | Pruritus frequency n/60 min | Suppression ratio (%) |
| Blank group luteolin hydrocortisone | 2 20 100 100 | 10 10 10 10 10 10 | 46±21.8** 397±74.3 389±150.2 237±87.9** 183±61.5** 88±32.4** | 2 40.3 53.9 77.8 |
* P＜0.01 (comparing) with matched group
2. luteolin suppresses histamine, 5-hydroxyl color ammonia and Compoundm48/80 initiation dermoreaction
Mouse back is shaved hair, histamine, and 5-hydroxyl color ammonia or compound48/80 subcutaneous injection, institute's reagent thing topical application is the same.Observe mice pruritus attack times after the injection immediately.And the mice vascular permeability that causes with azovan blue method tissues observed amine increases (method is the same).
Subcutaneous injection histamine, 5-hydroxyl color ammonia or Compound 48/80 cause the reaction of mouse skin pruritus, and be wherein obvious with the Compound48/80 stimulation.Luteolin has effectively suppressed histamine, the caused skin pruritus outbreak of 5-hydroxy tryptamine, and is dose dependent, and same inhibitory action also can be observed in the skin pruritus model that Compound48/80 causes.Hydrocortisone has significantly suppressed histamine, the skin pruritus number of times that 5-hydroxyl color ammonia and Compound 48/80 cause.Topical application histamine H 1 receptor antagonist astemizole (hismanal) has suppressed the skin pruritus that histamine causes, and is same, and the opiate receptor antagonist naloxone also shows significant inhibitory effect to the skin pruritus outbreak that 5-hydroxy tryptamine causes.(table 2)
Table 2. luteolin is to histamine, and the influence of the mouse skin pruritus that 5-hydroxy tryptamine and Compound 48/80 are caused (mean ± SD)
| Group | Dosage (μ g/site) | Number of animals (n) | Histamine | Pruritus number of times (suppression ratio %) (n/60min) | |
| 5-hydroxy tryptamine | Compound 48/80 | ||||
| Matched group luteolin hydrocortisone astemizole naloxone | 2 20 100 100 100 | 10 10 10 10 10 10 | 158±28.3 89±31.4**(43.7) 95±35.6**(39.9) 75±24.6**(52.5) 49±17.5**(69.0) 61±24.3**(61.4) | 177±53.4 146±7.8(17.5) 99±13.5**(44.1) 77±15.9**(56.5) 46±14.8**(74.0) 68±9.4**(61.4) | 273±45.3 183±42.4**(33.0) 253±47.1(7.4) 163±55.1**(40.3) 154±23.6**(43.6) |
Material P＜0.01 (comparing) with matched group
3, vascular permeability increases reaction
But subcutaneous antigen is attacked the inflammatory reaction that the equal local vascular permeability of sensitized mice or local injection histamine increases.The partial smearing luteolin has effectively suppressed to increase inflammatory reaction by the caused vascular permeability of PCA or histamine.(table 3)
The influence that table 3 luteolin increases the caused skin heart permeability of PCA and histamine (mean ± SD)
| Group | Dosage (μ g/site) | Number of animals (n) | Azovan blue appears (mg) | |
| PCA reacts (suppression ratio %) | Histamine (suppression ratio %) | |||
| Matched group luteolin hydrocortisone | 2 20 100 100 | 10 10 10 10 10 | 0.21±0.04 0.20±0.05(4.8) 0.14±0.04**(33.3) 0.09±0.01**(57.1) 0.08±0.03**(61.9) | 1.09±0.38 0.70±0.25*(35.8) 0.51±0.12*(53.2) 0.39±0.11**(64.2) 0.34±0.08**(68.8) |
P＜0.05, * * P＜0.01 (comparing) with matched group
4, contact dermatitis and allergic dermatitis
201% 2,4-dinitrochlorobenzene (DNCB)-acetone soln spreads upon the mouse right ear both sides and causes contact dermatitis.Before the DNCB attack, back 30 partial smearing are subjected to reagent thing 20.Measure mouse right ear swelling degree to judge the inflammation degree.In the allergic dermatitis modelling process, 20 μ l 20%DNCB-acetone spread upon mouse right ear as sensitization, and partial smearing 200 μ l 0.5%DNCB-acetone are attacked the initiation allergic dermatitis after 10 days.Be subjected to application of reagent thing and ear swelling to judge same contact dermatitis.
Partial smearing DNCB has successfully made contact dermatitis and allergic dermatitis, and mouse right ear swelling is obvious.Different time sections is measured auris dextra swelling to observe the effect characteristics of luteolin after attack.Luteolin has significantly alleviated the ear swelling of model mice, and hydrocortisone also shows effective inhibitory action.See Table 4.
Table 4 luteolin is to the influence of contact dermatitis mice auricle swelling (mean ± SD)
| Group | Dosage (μ g/site) | Number of animals (n) | Auricle edema ratio (%) (suppression ratio %) | ||
| 2h | 4h | 24h | |||
| Matched group luteolin hydrocortisone | 2 20 100 100 | 10 10 10 10 10 | 11.2±7.5 10.6±7.6(5.4) 4.4±3.5**(60.3) 4.7±4.4**(57.8) 6.2±2.9**(44.4) | 22.10±9.6 12.33±8.5*(44.2) 11.63±6.4*(47.4) 8.7±7.9**(60.6) 7.5±5.0**(66.1) | 23.1±7.6 20.2±9.6 12.3±9.1**(46.8) 12.78±9.0**44.7) 6.6±4.8**(71.4) |
P＜0.05, * * P＜0.01 (comparing) with matched group
Table 5 luteolin is to the influence of allergic dermatitis mice auricle swelling (mean ± SD)
| Group | Dosage (μ g/site) | Number of animals (n) | Auricle edema ratio (%) (suppression ratio 100%) | ||
| 2h | 4h | 24h | |||
| Matched group luteolin hydrocortisone | 2 20 100 100 | 10 10 10 10 | 3.6±1.9 1.4±0.9**(61) 2.1±0.8*(41.6) 1.5±0.9**(58.3) 1.6±0.7**(55.6) | 3.7±2.0 1.5±0.8**(59.5) 2.2±0.7*(40.5) 1.5±0.9**(59.5) 1.3±0.9**(64.9) | 3.7±2.0 1.64±0.8**(57) 2.2±0.7*(40.5) 1.5±0.9**(59.5) 1.3±0.9**(64.9) |
* P＜0.05, * * P＜0.01 (with matched group relatively)
5. drying property dermatitis and pruritus outbreak
The mouse back unhairing, the about 2cm2 of area.2 of the absorbent cottons of the about 2cm2 of clip area.The slight anesthetized mice of ether is dipped in acetone ether mixed liquor (1: 1) with a slice absorbent cotton, is put in the plucked skin 60s in back, takes off, another sheet absorbent cotton is dipped in distilled water after, be put in same position 30s.Repeat every day 2 times, at 3 in 9 afternoons in the morning each once, so continuous 5 days.Mouse back is smeared tested medicine simultaneously, once a day, and continuous 5 days.After the last administration 30 minutes, observe mice pruritus attack times.Experiment finishes, and mice draws neck to put to death, and cuts skin of back, 3% formaldehyde fixed, and paraffin embedding is carried out pathology section examination.
Mouse back skin is smeared the local dehydration of acetone ether mixed liquor, causes drying property dermatitis model, causes the pruritus outbreak.Topical application can obviously alleviate the pruritus attack times, shows the effect (table 6) of significant inhibition pruritus.The pathological section result shows that normal mouse skin: the phosphorus columnar epithelium is normal, and horny layer is complete, and skin corium is loose, a small amount of lymphocytic infiltration that as seen is dispersed in; The model group mouse skin: the remarkable hypertrophy of phosphorus columnar epithelium, visible hyperkeratosis of horny layer and parakeratosis, the skin corium proliferation of fibrous tissue, visible more amount lymphocyte, neutrophil cell and eosinophilic granulocyte assemble; Luteolin group mouse skin phosphorus columnar epithelium is light～the moderate hypertrophy, and horny layer is as seen in a few regions keratinization, the slight hypertrophy of skin corium fibrous tissue, visible slight lymphocyte, neutrophil cell and eosinophilic granulocyte assemble, and pathological lesion obviously alleviates; Equally, fluocinonide also shows the good curing effect, the slight hypertrophy in phosphorus columnar epithelium subregion, and horny layer is complete, the slight hypertrophy of skin corium fibrous tissue, visible slight lymphocyte, neutrophil cell and eosinophilic granulocyte are dispersed in infiltration.
Table 6 luteolin is to the influence of drying property dermatitis skin pruritus that mice causes (mean ± SD)
| Group | Dosage (μ g/site) | Number of animals (n) | Pruritus frequency n/60min | Suppression ratio (%) |
| Blank group luteolin hydrocortisone | 2 20 100 100 | 10 10 10 10 10 10 | 8±5.5** 136±22.9 99±28.5* 98±18.6** 71±20.5** 46±9.8** | 27.2 27.9 47.8 66.2 |
P＜0.05; * P＜0.01 (comparing) with matched group
The present invention also uses and the similar test method of above-mentioned pharmacodynamics test, with luteolin respectively with Radix Saposhnikoviae volatile oil, matrine and/or the assembly of Cortex Dictamni extract, carried out pharmacodynamics test, also reach good prevention effect.
6. the different assembly of luteolin are to passive dermoreaction of mice and histamine, the inhibitory action of the skin itching reaction that 5-hydroxy tryptamine causes
The main assembly of ointment formulation: (1) .0.3% luteolin (purity 98%), 0.1% matrine (purity 98%, C
15H
24N
2O is available from Xi'an China collection biotechnology Co., Ltd); (2) .0.3% luteolin (purity 98%), 0.2% Cortex Dictamni water extraction extractum (Cortex Dictamni crude drug and extractum weight ratio are 1: 1); (3) 0.4% luteolins (purity 98%), 3% Radix Saposhnikoviae volatile oil (conventional water distillation and extraction).1,2 of pharmacodynamic experiment is identical among experimental technique and the embodiment 6.Partial smearing ointment formulation 20 micrograms.
By table 7 result as can be known, Chinese medicine (the matrine of luteolin and dispelling wind for relieving itching effect, Cortex Dictamni and Radix Saposhnikoviae) in effective ingredient carry out proportioning, to mast cell mediated (passive skin allergic reaction, PCA) or topochemistry cause the skin pruritus reaction that the former material of itching (histamine and 5-hydroxy tryptamine) causes and also show effective inhibitory action.
Table 7, to PCA, the influence of the mouse skin pruritus that histamine and 5-hydroxy tryptamine cause (mean ± SD)
| Group | Number of animals (n) | Pruritus number of times (suppression ratio %) (n/60min) | ||
| PCA | Histamine | 5-hydroxy tryptamine | ||
| Matched group luteolin+matrine luteolin+Cortex Dictamni luteolin+Radix Saposhnikoviae | 10 10 10 10 | 298±37.8 157±28.4**(47.3) 174±32.1**(41.6) 146±19.4**(51.0) | 154±30.4 94±11.2**(40.9) 112±16.7**(27.3) 86±18.2**(44.2) | 239±26.2 122±18.7**(48.9) 145±29.1(39.3) 157±34.8**(34.3) |
* P＜0.01 (comparing) with matched group
Claims (1)
1, luteolin is prevented and treated application in the external used medicine of drying property dermatitis in preparation.
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| CN1100633A (en) * | 1993-07-09 | 1995-03-29 | 吴羽化学工业株式会社 | Chondroprotective agents |
| CN1041279C (en) * | 1993-10-08 | 1998-12-23 | 栾兴志 | Medicine for curing dermatosis |
| CN1327831A (en) * | 2001-06-15 | 2001-12-26 | 姜莉蔚 | Chinese medicine for treating tinea and antipruritic |
| CN1606448A (en) * | 2001-12-07 | 2005-04-13 | 兰迪H·齐格勒 | Composition for treating lupus erythematosus |
| DE10308162A1 (en) * | 2003-02-26 | 2004-09-09 | Universitätsklinikum Freiburg | Process for the preparation of flavonoid-containing compositions and their use |
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