CN106420381A - Novel applications of artemisinin ingredients or composition of artemisinin ingredients in skin care - Google Patents
Novel applications of artemisinin ingredients or composition of artemisinin ingredients in skin care Download PDFInfo
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- CN106420381A CN106420381A CN201610639349.9A CN201610639349A CN106420381A CN 106420381 A CN106420381 A CN 106420381A CN 201610639349 A CN201610639349 A CN 201610639349A CN 106420381 A CN106420381 A CN 106420381A
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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
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
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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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
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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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/282—Artemisia, e.g. wormwood or sagebrush
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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
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/005—Antimicrobial preparations
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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
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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
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
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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
- A61Q19/08—Anti-ageing preparations
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
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Abstract
The invention relates to novel applications of the defined artemisinin ingredients or a composition of the artemisinin ingredients, namely, the novel applications in the skin care field of mammals. According to the novel applications, the bad state of the skin of the mammals is eliminated or alleviated so that the healthy and beauty of the skin are enhanced through the means of regulating the keratinization disorder, inhibiting hyperpigmentation, resisting cicatrization, delaying skin aging, maintaining the skin elasticity, resisting inflammation, stopping bleeding, easing pain, and resisting bacteria and skin parasites. The benefits are proved through the means of obviously preventing or alleviating the keratosis disease symptoms including acne, furfur and the like, preventing or reducing fine lines and wrinkles of the skin, and preventing or alleviating the grey yellow and dim color of the skin. The benefits are realized through the means of applying the artemisinin ingredients, the composition of the artemisinin ingredients, or the skin care compositions (including health products, household chemicals, and health care products or medicines) containing the artemisinin ingredients or the composition of the artemisinin ingredients to the mammals. The applications of the artemisinin ingredients or the composition of the artemisinin ingredients are expanded to the field of skin care, so that great contribution is made to the health undertaking of people.
Description
Technical field
The present invention relates to a kind of new opplication of defined artemisine composition or combinations thereof, i.e., in skin of mammal
The new opplication of skin nursing field includes：a）Prevention acted on by correcting dyskeratosis, postpone and/or treat mammal acne,
The keratosiss caused by dyskeratosis such as dandruff, desquamation prurituss, dry chap, psoriasises, scleroderma, perifollicular keratosises
Disease；b）By the lip of the softening of promotion cutinization or submissive mammal, skin, hair, refer to toenail, hoof etc., and promote suckling
Animal lip, skin, hair, refer to the renewal of toenail, hoof etc., adjust their oiliness and gloss；c）By anti-pigmentation
Promote skin lightening ruddy, prevention, delay and/or treatment mammal skin blackening, sallow dimness, mottle, acne print, Exposure to Sunlight are damaged
The appearance of the pigmentation symptom such as wound, inflammation damnification；d）By the effect prevention of anti-cicatrization, postpone and/or treat suckling to move
Thing scytitiss stimulate the cicatrix symptoms such as the cicatrix growth, acne print that the cicatrix that injury is caused grows, environmental stimuli injury is caused
Occur；e）Skin elasticity effect is kept to strengthen skin elasticity and gloss, prevention, delay and/or treatment suckling by slow down aging
Animal skin microgroove, wrinkle, sagging, atrophy, swelling, the appearance of corse sweat pore；f）Posted by antibacterium, antifungal, anti-skin
Infested effect keeps the cleaning of mammal skin, and prevention, delay and/or treatment antibacterial, funguses, dermatozoon etc. are caused
Mammal skin defective mode；G) by antiinflammatory, analgesia, hemostasis etc. effect elimination or alleviation scytitiss red and swollen heat pain,
The defective modes such as bleeding；h）By promoting keratinization, correcting dyskeratosis, anti-pigmentation, suppress cicatrization, delaying skin old
Change, keep skin elasticity, antiinflammatory, analgesia, hemostasis, antibacterium, antifungal, anti-dermatozoon etc. a series of to skin of mammal
The beneficial effect of skin, eliminates or alleviates mammal skin defective mode so as to provide enhanced skin health and beauty.
By by the skin care compositionss of the artemisine composition containing safe and effective amount or combinations thereof such as health-oriented products, day
Change product, health product or medicine etc. to be administered on the mammal for needing this kind of effect, these methods achievable and benefit.
Background technology
As the high speed development people of economy and society are also improved with beautiful requirement therewith to health, especially skin is protected
Reason receives more extensive concern, and the feature and safety of skincare product is put forward higher requirement.Perplex people at present
The skin problem of people masses is mainly：Acne, desquamation, the dimness blackening of skin sallow, sagging, the microgroove wrinkle that relaxes, residual cicatrix
Acne print, red and swollen heat pain etc..Therefore with facial cream, facial film, Cleansing Foam, bath oil, shampoo, skin ointments agent etc. as representative on market
Skin nursing products, with the addition of mostly to solve the active component of various skin problems.But these compositions are people mostly
Work synthesis source, advocates natural today nature is pursued, and the activity of the natural origin of the various skin problems of energy effectively solving becomes
Point, with extremely public expectation the features such as little of its green, environmental protection, safe, toxic and side effects and its consumption demand also exists
Constantly increase.
Arteannuin is the present that Chinese Traditional Medicine gives the people of the world, safeguards people from world to preventing and treating the infectious diseases such as malaria
People's health is significant.Slaughtering cry of a deer researcher within 2015 and Nobel prize's soul is obtained because of arteannuin, shows
Accreditation of the whole world to artemisine composition, is that China's traditional medicine culture goes to the world, recognizes process by the people of the world
In a monument.Artemisine composition has become the study hotspot of countries in the world at present, to its antitumor, parasiticide, controls
Treat the effect such as systemic lupus erythematosus (sle) to conduct in-depth research.But above research all launches around drug research,
For the elite that response country is deeply excavated in pools of traditional Chinese medicine, the unique advantage of Chinese medicine, propulsion Chinese medicine modern times are given full play to
Change, the call for promoting Chinese medicine to go to the world, applicant is carried out widely to artemisine composition in line with rigorous realistic attitude
Pharmacodynamics screening is studied, to making artemisine composition preferably be serviced by society.
Applicant carries out extensive Pharmacodynamics screening with artemisine composition or combinations thereof, and has surprisingly found that arteannuin
Constituents or combinations thereof have promotion keratinization on mammal skin, correct dyskeratosis, suppression pigmentation, suppression scar
Trace generation, delay skin aging, holding skin elasticity, elimination red and swollen heat pain, killing skin vermiform mite etc. have notable benefit
Skin care active.Therefore applicants have discovered that the artemisine composition of safe and effective amount or combinations thereof and containing safe and effective amount
Artemisine composition or combinations thereof skin care compositionss dermatosis or skin defective mode can be provided preventative or
Therapeutic treatment.For example, applicant has found that artemisine composition or combinations thereof have prevention, postpone and/or the treatment food in one's mouth
The hyperkeratotic conditions caused by dyskeratosis such as newborn animal acne, dandruff, psoriasises, scleroderma, perifollicular keratosises；Soften or
The lip of submissive mammal, skin, hair, refer to toenail, hoof etc., and promote mammal lip, skin, hair, refer to toenail, hoof etc.
Renewal, adjust their oiliness and gloss；Prevention, postpone and/or treatment mammal skin blackening, sallow dimness, mottle,
The appearance of the pigmentation symptom such as acne print, sun exposure damage, inflammation damnification；Prevention, delay and/or treatment mammal skin scar
Trace, the appearance of the cicatrix symptom such as acne print；Prevent, postpone and/or treat mammal skin microgroove, wrinkle, sagging, atrophy, swell
The appearance of swollen, corse sweat pore；Keep the cleaning of mammal skin, prevention, delay and/or treatment antibacterial, funguses, skin parasitism
Mammal skin defective mode caused by worm etc.；By promoting keratinization, correcting dyskeratosis, anti-pigmentation, suppression scar
Trace formation, delay skin aging, holding skin elasticity, antiinflammatory, analgesia, hemostasis, antibacterium, antifungal, anti-dermatozoon etc.
A series of effects beneficial to mammal skin, eliminate or alleviate mammal skin defective mode so as to provide enhanced skin
Skin health and beauty.The above innovation for finding to advance health-oriented products, daily chemical products, health product or medicine, and will be right
Public physical and mental healths and daily life produce far-reaching influence.
Content of the invention
The first aspect of the invention is to provide a kind of new opplication of defined artemisine composition or combinations thereof,
I.e. in the new opplication of skin care applications；The second aspect of the invention be to provide a kind of skin care compositionss its include safety and have
The artemisine composition of effect amount or combinations thereof and Dermatology and other active additives pharmaceutically acceptable and substrate；The present invention
The 3rd aspect be to provide a kind of eliminate or alleviate mammal skin defective mode with provide enhanced skin health with
Beautiful method, methods described includes to apply defined artemisine composition or combinations thereof or the present invention to mammal
Skin care compositionss.
Artemisine composition as herein described or combinations thereof refer to arteannuin and its derivant and correlative and they
Salt is included but is not limited to, arteannuin, dihydroarteannuin, artesunate, sodium artesunate, Artemether, arteether, arteannuin C13
Derivant, arteannuin C12Derivant, arteannuin C4Derivant, deoxidation bridge arteannuin structure related compound, demethylation arteannuin
Structure related compound, de- ketonic oxygen arteannuin structure related compound, steroid arteannuin structure related compound, lactams green grass or young crops
Artemisin structure related compound, open loop arteannuin structure related compound, 4,5- epoxy carbon for arteannuin structure related compound,
Arteannuin structure simplifies thing, other arteannuin structure related compounds and their salt；Or the group containing artemisine composition
Compound or extract are included but is not limited to, Chinese medicine Herba Artemisiae Annuae（ARTEMISIAE ANNUAE HERBA）And its product, plant Artemisia annua
（Artemisia annuaL.）And its product, other Compositae artemisias (Artemisia Linn. Sensu stricto, excl. Sect. Seriphidium Bess.) plant and its product, Herba Artemisiae Annuae tissue culture medium, artemisinin mother liquid etc.；Or be selected from
The arbitrary composition of mentioned component.The source of artemisine composition or combinations thereof can be synthesis or include naturally but do not limit
In natural product extraction, chemical complete synthesis, molecular design, biosynthesiss, histiocyte culture, fungal transformation, metabolic pathway
Etc. approach.
Skin as herein described refers to that the skin of mammal and its accessory organ include but is not limited to, skin, sweat gland, skin
Adipose gland, fingernail, toenail, hair, lip, epidermis, corium etc..
Skin care compositionss as herein described refer to the artemisine composition comprising safe and effective amount or combinations thereof and skin
Learn constituted with other active additives pharmaceutically acceptable and substrate various health-oriented products, cosmetics of everyday use, medicine, health product
Etc. including but is not limited to, Emulsion class cosmetics, watery class cosmetics, powder class cosmetics, cream kind cosmetics, aerosol class are made up
Product, hair based article, beauty class cosmetics, soaps, facial film, curative effect class cosmetics, sun-proof class cosmetics, tablet, powder, ball
Agent, ointment, membranous patch, gel, capsule, granule, effervescent, fumigant, slow releasing agent etc. and other skin nursings are used
Product.
Safe and effective amount as herein described refers to that the person skilled of this area is rationally judged using artemisine composition
Or combinations thereof be enough to produce significant beneficial effect, and the amount be enough to avoid serious untoward reaction again, that is, provide rational
Effective hazard ratio, its content is preferably from about 0.0001%～90%, even more preferably about 0.01%～35%, and most preferably about 1%～22% wherein
The percentage ratio is counted with composition quality as 100%.
Skin defective mode as herein described is referred to due to the skin life caused by the intrinsic factor of body or extrinsic factor
The state that reason health is weakened with aesthetic appearance is included but is not limited to, and abnormal cutaneous keratinization, desquamation prurituss, skin sallow are dark
Light, skin darkening, skin aging are lax, skin lines wrinkle, skin turgor are thickened, atrophoderma is sagging, corse sweat pore, skin
Inflammation is red and swollen, skin greasing is coarse, dry skin chap, dermatorrhagia pain, skin are caused by inflammation or environmental stimuli injury
Pigmentation, skin by inflammation or environmental stimuli injury cause cicatrix growth etc..The acne of such as mammal, dandruff,
The hyperkeratotic conditions caused by dyskeratosis such as psoriasises, scleroderma, perifollicular keratosises；Mammal lip, skin, hair,
Refer to dry and chap of the skin or the excess oiliness of toenail, hoof etc.；Mammal skin blackening, sallow dimness, mottle, acne print, sun exposure damage,
The appearance of the pigmentation symptom such as inflammation damnification；Mammal skin cicatrix, the appearance of the cicatrix symptom such as acne print；Skin of mammal
Skin microgroove, wrinkle, sagging, atrophy, the appearance of corse sweat pore；Mammal skin is drawn by antibacterial, funguses, dermatozoon etc.
Defective mode for rising etc..
Enhanced skin health as herein described is referred to as skin defective mode is mitigated or eliminated with beauty and makes skin
Physiological health and aesthetic appearance recover or further enhance including but not limited to,
a）By correcting dyskeratosis effect prevention, postponing and/or treat mammal acne, dandruff, desquamation prurituss, dry chap
Split, the hyperkeratotic conditions caused by dyskeratosis such as psoriasises, scleroderma, perifollicular keratosises；
b）By the lip of the softening of promotion cutinization or submissive mammal, skin, hair, refer to toenail, hoof etc., and promote suckling
Animal lip, skin, hair, refer to the renewal of toenail, hoof etc., adjust their oiliness and gloss；
c）Promote skin lightening ruddy by anti-pigmentation, prevention, delay and/or treatment mammal skin blackening,
The appearance of the pigmentation symptoms such as sallow dimness, mottle, acne print, sun exposure damage, inflammation damnification；
d）By the effect prevention of anti-cicatrization, postpone and/or treat the cicatrix that the injury of mammal skin inflammatory stimulus is caused
Cicatrix growth that growth, environmental stimuli injury are caused, the appearance of the cicatrix symptom such as acne print；
e）Skin elasticity effect is kept to strengthen skin elasticity and gloss by slow down aging, prevention, delay and/or treatment suckling are moved
Thing skin lines, wrinkle, sagging, atrophy, swelling, the appearance of corse sweat pore；
f）By antibacterium, antifungal, anti-dermatozoon effect keep mammal skin cleaning, prevention, postpone and/or
Mammal skin defective mode caused by treatment antibacterial, funguses, dermatozoon etc.；
G) eliminated by the effect such as antiinflammatory, analgesia, hemostasis or alleviate the defective modes such as scytitiss red and swollen heat pain, bleeding；
h）By promoting keratinization, correcting dyskeratosis, anti-pigmentation, suppression cicatrization, delay skin aging, keep skin
A series of works beneficial to mammal skin such as elasticity, antiinflammatory, analgesia, hemostasis, antibacterium, antifungal, anti-dermatozoon
With, eliminate or alleviate mammal skin defective mode so as to provide enhanced skin health and beauty.
Administration as herein described refers to include but is not limited to by various route of administration, partial smearing, Local out dressing, mouth
The mode such as taking, fumigate makes artemisine composition as herein described or combinations thereof or skin care compositionss as herein described act on skin
Skin.
Other active additives as herein described and substrate refer to known in the field in current skin protection cosmetics of everyday use, medicine
Applied in product, health product, healthy product or possible application the wide scope in addition to artemisine composition and combinations thereof
Other optional active additives and substrate are included but is not limited to, oily raw material, silty raw material, colloid raw material, solvent materials, water
Soluble polymer, preservative, thickening agent, acid-base class regulator, antioxidant, wetting agent, astringent, sunscreen, antibacterial, tune
Reason agent, cracking-off agent, opacifier, prurituss, frosting agent, surfactant, skin transferral agent, skin feeling agent, Skin Soothing Agent,
Skin healing agent, nourishing additive agent, trace element and hormoness additive, biological active substanceies additive, synthesis class nutrition add
Plus agent, bioactive peptide, natural extract, additive biology, quintessence oil, essence, spice, pigment, coloring agent, adhesive, disintegrating agent,
Filler, lubricant, wetting agent, osmotic pressure regulator, stabilizer, fluidizer, correctivess, suspending agent, coating material, figuration
Agent, absorbent, diluent, flocculant and deflocculant, filter aid, release blocker, microcapsule, microsphere, liposome etc. and he
Combination.
Dermatology as herein described refers to the compositionss and its contains component be applied to and suckling with pharmaceutically acceptable
Animal skin contacts, without excessive toxicity, incompatibility, unstability, atopic reaction etc.；Or be applied in process
Various route of administration are contacted with mammalian organism, anti-without excessive toxicity, incompatibility, unstability, allergia
Should wait.
The acceptable substrate of pharmacology as herein described refers to that described substrate will not produce impact to pharmacological experiment, can
With appropriate dispersion artemisine composition or combinations thereof, and as the negative control group in experiment.
By following non-limiting examples, specific embodiments of the present invention will be further described now and carry out
Illustrate, example is served only for explaining the present invention, is not intended to limit the scope of the present invention.Content described herein is only this
Basic explanation under spirit and range of condition, its object is to make those skilled in the art it will be appreciated that the present invention
Content is simultaneously implemented according to this, it is impossible to only limit the scope of the claims of the present invention with following examples, to according to technical solution of the present invention
Those of ordinary skill for, according to disclosed spirit, any equivalent transformation or modification are carried out to the present invention,
Protection scope of the present invention all should be belonged to.
Embodiment 1：The preparation of arteannuin protective skin cream.
Following component can be made into arteannuin protective skin cream by the existing production technology of protective skin cream.
| Component | Mass fraction % | Component | Mass fraction % |
| Dihydroarteannuin | 2.00 | Vaseline | 6.00 |
| Lanoline | 4.00 | American Avocado Tree oil | 4.00 |
| Hexadecanol | 2.00 | Essence | In right amount |
| Hexadecanol polyoxyethylene ether | 1.50 | Deionized water | Add to 100.00 |
Embodiment 2：The preparation of arteannuin shampoo.
Following component can be made into arteannuin shampoo by the existing production technology of shampoo.
| Component | Mass fraction % | Component | Mass fraction % |
| Arteannuin | 3.00 | Stearic acid | 5.00 |
| Sodium lauryl sulphate | 20.00 | Sodium hydroxide | 0.75 |
| Oleum Cocois single ethanol amide | 1.00 | Essence | In right amount |
| Propylene glycol monostearate | 2.00 | Deionized water | Add to 100.00 |
Embodiment 3:The preparation of Herba Artemisiae Annuae facial film.
Following component can be made into Herba Artemisiae Annuae facial film by the existing production technology of facial film.
| Component | Mass fraction % | Component | Mass fraction % |
| Herba Artemisiae Annuae extract | 10.00 | Glycerol | 5.00 |
| Polyvinylpyrrolidone | 2.00 | Ethanol | 10.00 |
| Carboxymethyl cellulose | 3.00 | Essence | In right amount |
| Polyethylene Glycol | 15.00 | Deionized water | Add to 100.00 |
Experimental example 1：Artemisine composition of the present invention or the antiinflammatory action of combinations thereof
Artemisine composition or combinations thereof are with the acceptable substrate dispersion of pharmacology.Kunming mouse 24 is taken, is randomly divided into 2
Group, i.e. matrix control group and 2% artemisine composition or combinations thereof group, each 12 per organizing.Dimethylbenzene 0.05mL is applied to mice
Auris dextra, administer locally to respectively at 15min, 30min, 45min after stimulation the substrate of each group equivalent and 2% artemisine composition or its
Compositionss, the disconnected neck of 60min puts to death animal, cuts left and right auricular concha, is taken at the same position of two ears with the card punch of diameter 8mm respectively
Lower auricle weighs quality, is compared with the calculating each group auricular concha swelling degree of poor quality of two auricles.
1. artemisine composition of table or the acutely inflamed impact of combinations thereof xylol induced mice auricular concha (mean ±
SD)
| Group | Number of elements | Swelling |
| Matrix control group | 12 | 55.8±3.27 |
| 2% artemisine composition or combinations thereof group | 12 | 22.5±2.96 |
P<0.01, compare with matrix control group
There is antiinflammatory action by the visible artemisine composition of table 1 or combinations thereof, there were significant differences with matrix control group.
Experimental example 2：Artemisine composition of the present invention or the analgesic activity of combinations thereof
Artemisine composition or combinations thereof are with the acceptable substrate dispersion of pharmacology.Kunming mouse 30 is taken, is randomly divided into 2
Group, i.e. matrix control group and 2% artemisine composition or combinations thereof group, each 15 per organizing.Administer locally to the substrate of each group equivalent
Cover with preservative film after 2% artemisine composition or combinations thereof administration, untie after immobilization with adhesive tape 30min, cleaned with normal saline
Medicine, then dry, newly to prepare immediately 2.5% formalin, 30 μ L is wiped to the right metapedes back of the body subcutaneous injection of mice with dry absorbent cotton.Injection first
After aldehyde, immediate record is licked per only mice first and licks the number of times for stinging right metapedes in the incubation period and 10min for stinging right metapedes.
2. artemisine composition of table or combinations thereof PARA FORMALDEHYDE PRILLS(91,95) cause the impact (mean ± SD) of mice pain
| Group | Number of elements | Incubation period/s | Sufficient number of times is licked in 10min |
| Matrix control group | 15 | 7.9±1.55 | 25.4±5.2 |
| 2% artemisine composition or combinations thereof group | 15 | 13.2±3.25 | 14.9±5.4 |
P<0.01, compare with matrix control group
There is analgesic activity by the visible artemisine composition of table 2 or combinations thereof, there were significant differences with matrix control group.
Experimental example 3：Artemisine composition of the present invention or the anastalsis of combinations thereof
Artemisine composition is with the acceptable solvent dispersion of pharmacology.Kunming mouse 24 is taken, is randomly divided into 2 groups, i.e. substrate
Matched group and 2% artemisine composition or combinations thereof group, each 12 per organizing.Mice is fixed in Mus cylinder, tail point portion 2cm soaks
Steep in 2% artemisine composition or combinations thereof solution or solvent, administration time 30min, after the 2h of interval, repeat administration 1 time.
After last dose 30min, cut with profit and cut off at tail point 1.5cm in mice, when starting meter record bleeding when blood flows out naturally
Between, drop of blood was drawn every 5 seconds with the cotton balls that oneself weighs in advance, until bleeding stops (depletion of blood when cotton balls is inhaled) naturally.Count as the following formula
Calculate each group animal bleeds amount:Amount of bleeding=band blood cotton balls weight one initial cotton balls weight (mg).
The anastalsis (mean ± SD) that 3. artemisine composition of table or combinations thereof dock to mice
| Group | Number of elements | Bleeding time/s | Amount of bleeding/mg |
| Matrix control group | 12 | 124.7±11.68 | 45.3±12.1 |
| 2% artemisine composition or combinations thereof group | 12 | 113.1±12.77 | 25.3±8.7 |
P<0.05, compare with matrix control group
There is anastalsis by the visible artemisine composition of table 3 or combinations thereof, there were significant differences with matrix control group.
Experimental example 4：Artemisine composition of the present invention or the antibacterial actions of combinations thereof
Antibacterial group has or not colony growth through cultivating observation after 48h, with the medicine least concentration of the aseptic elder that is born as medicine most
Low Mlc (MIC).
4. artemisine composition of table or combinations thereof are to common causative antibacterial minimum inhibitory concentration
| Strain name | MIC/g% |
| Staphylococcus aureuses | 1.1 |
| Propionibacterium acness | 0.9 |
| Bacillus pyocyaneus | 1.1 |
| Lactobacilluss | 1.0 |
By the visible artemisine composition of table 4 or combinations thereof to common causative antibacterial, especially cause the golden yellow of dermatosis
Staphylococcuses, propionibacterium acness, bacillus pyocyaneus have certain inhibitory action.
Experimental example 5：Artemisine composition of the present invention or the antifungic action of combinations thereof
Funguses group does not increase through cultivating the bacterium scope for observing dibbling after 72h, and tapers into drying, is bacterial strain by Drug inhibition
Least concentration (MIC).
5. artemisine composition of table or combinations thereof are to common skin funguses minimum inhibitory concentration
| Strain name | MIC/g% |
| Pityrosporum furfur | 0.9 |
| Candida albicans | 0.9 |
| Epidermophyton | 1.1 |
There is certain inhibitory action by the visible artemisine composition of table 5 or combinations thereof to common dermatophytess.
Experimental example 6：The anti-vermiform mite effect of artemisine composition of the present invention or combinations thereof
Artemisine composition or combinations thereof are with the acceptable substrate dispersion of pharmacology.Paste overnight method using adhesive tape to obtain
Human Demodex, is randomly divided into substrate group and 2% artemisine composition or combinations thereof group, per group 12.Inhaled with micropipettor
The substrate of equivalent and 2% artemisine composition or each 200 μ L medicinal liquid Deca of combinations thereof are taken on wave carrier piece, with push jack by medicinal liquid
Uniformly spread out, demodectic adhesive tape will be detected and be affixed on microscope slide, it is ensured that medicinal liquid is fully contacted with polypide.Then microscope slide is put
In growth cabinet (30 DEG C of temperature, humidity 75%), basis of microscopic observation vermiform mite death condition after 12h.Dead criterion:
Continuous Observation 1min under 400 power microscopes, demodicid mite body huge legendary turtle limb or the motionless person of sufficient pawl are tentatively judged as death, continue after 30min to see
Examine still motionless person and be defined as death.
6. artemisine composition of table or combinations thereof are to demodectic killing action
| Group | Number of elements | Dead number of elements | Mortality rate |
| Matrix control group | 12 | 0 | 0% |
| 2% artemisine composition or combinations thereof group | 12 | 10 | 83% |
There is significant killing action to vermiform mite by the visible artemisine composition of table 6 or combinations thereof.
Experimental example 7：Artemisine composition of the present invention or the keratinization adjustment effect of combinations thereof
Artemisine composition or combinations thereof are with the acceptable substrate dispersion of pharmacology.Take Kunming mouse 30, male and female half and half,
It is randomly divided into substrate group and 2% artemisine composition or combinations thereof group.2 groups of mices distinguish the substrate of partial smearing equivalent daily
Cover with preservative film after 2% artemisine composition or combinations thereof administration, untie after immobilization with adhesive tape 30min, cleaned with normal saline
Medicine, then wiped with dry absorbent cotton dry, continuous 21 days, two times a day.Animal was put to death in the 22nd day, at root of the tail 2cm, taking rat-tail table
Skin, fixes paraffin embedding with 10% formalin, and HE is dyeed, in the tail scale of light each mice of Microscopic observation.All scale epidermises
There is continuously rows of granular cell person, be referred to as the scale for having granular layer to be formed, granular cell is flat or rhombus cell in epidermis
Constituted, full of the cutin granule that thick deep basophilia, HE dyeing are transparent in avy blue in endochylema.Count rat-tail epidermis 100
Granular layer is had to form number in scale.
The impact (mean ± SD) that 7. artemisine composition of table or combinations thereof are formed to mice rat-tail granular cell
| Group | Number of elements | Rat-tail per 100 scales in granular layer form number |
| Matrix control group | 15 | 7.3±1.1 |
| 2% artemisine composition or combinations thereof group | 15 | 13.8±1.7 |
P<0.05, compare with matrix control group
Played the role of to promote keratinization, corrected dyskeratosis, with matrix control group by the visible artemisine composition of table 7 or combinations thereof
There were significant differences.
Experimental example 8：The delay skin aging effect of artemisine composition of the present invention or combinations thereof
Artemisine composition or combinations thereof are with the acceptable substrate dispersion of pharmacology.With people's normal skin fibroblast
（NHDF）Secondary Culture obtains the preferable culture fluid of cell concentration for testing.The cell of culture is inoculated into Tissue Culture Dish
In, cultivate 24h, whne cell growth to occupy culture dish area 80% when, suck culture medium, PBS one time, be subsequently adding
300（μL）PBS, is sealed with hyaline membrane, thinks 144mJ/cm2Exposure dose UVB irradiating cell 40s is clear with PBS immediately after irradiation
Wash one time, be inoculated in the culture fluid of 2% artemisine composition or combinations thereof and blank culture fluid respectively, cultivate at 37 DEG C
72h.Wherein 1ml culture fluid is taken, for suppressing collagen protein catabolic enzyme（MMP-L1）The measure of generation, 1mL is used for cell survival
The measure of power.The experiment is repeated 3 times.The collagen protein catabolic enzyme growing amount in culture fluid is determined using immune ELISA kit.
8. artemisine composition of table or inhibitory action of the combinations thereof to collagen protein catabolic enzyme
| Group | MMP-L1 pheron quality mean concentration | MMP-L1 enzyme generates suppression ratio |
| Blank control group | 0.17 | - |
| 2% artemisine composition or combinations thereof group | 0.07 | - |
| MMP-L1 enzyme generates suppression ratio | - | 58.8% |
Obvious suppression Skin Cell collagen protein is had to decompose zymogenesis by the visible artemisine composition of table 8 or combinations thereof,
With skin anti-aging and the function of strengthening skin elasticity.
Experimental example 9：Artemisine composition of the present invention or the anti-pigmentation of combinations thereof
Artemisine composition or combinations thereof are with the acceptable substrate dispersion of pharmacology.Cavia porcelluss 6 are taken, is gone per only back part of animal
Hair, takes 2 from region, and UVB is irradiated and irradiated from UVB light source, and irradiation total amount is 2500mJ/cm2, irradiate 2 area equation
Region start coating after one week, the substrate of partial smearing equivalent and 2% artemisine composition or combinations thereof respectively, continuous 21
My god, two times a day.With Multi-functional skin survey during respectively in UVB pre-irradiation, after irradiating 1 week, 2 weeks, 3 weeks and 4 weeks after 1 week and medication
The color change in each region of examination instrument measurement guinea pig back skin, carries out objective comparison.Biopsy divide as Microscopic observation after 4 weeks
Analysis.Dyeed with Schmorl method, high power lenses count per square millimeter of epidermis cell number containing melanin granule of per part of sample.With Imokawa
Method is dyeed, and high power lenses count per square millimeter of stratum basale number containing dopa-positive melanocytes of per part of sample.
9. artemisine composition of table or combinations thereof irradiate the impact (mean) of the measure of guinea pig skin color value to UVB
| Group | Pre-irradiation | After irradiation | Medication 1 week | Medication 2 weeks | Medication 3 weeks | Medication 4 weeks |
| Matrix control group | 30 | 59 | 59 | 58 | 60 | 58 |
| 2% artemisine composition or combinations thereof group | 31 | 58 | 56 | 51 | 47 | 41 |
P<0.05, medication is compared for 4 weeks with matrix control group
10. artemisine composition of table or combinations thereof have the pigmented inhibitory action of Cavia porcelluss (mean ± SD) to UVB
| Group | The melanocyte of the DOPA positive（Individual/mm2） | Cell containing melanin granule（Individual/mm2） |
| Matrix control group | 773.18±68.52 | 2801.13±180.72 |
| 2% artemisine composition or combinations thereof group | 566.97±82.67 | 2136.14±192.35 |
P<0.05, compare with matrix control group
By table 9,10 visible artemisine compositions or combinations thereof have resisting mammal pigmentation.
Experimental example 10：The anti-cicatrix of skin formation effect of artemisine composition of the present invention or combinations thereof
Artemisine composition or combinations thereof are with the acceptable substrate dispersion of pharmacology.12 Japan large ear rabbits are anaesthetized,
In bilateral rabbit ear veutro, lateral margin upper and lower parts do the square cutout of 2 diameter about 1cm, slit space 2.0cm, removal respectively
Rabbit ear skin and subcutaneous tissue and perichondrium, cartilage-preserving, gauze pressing stops blooding.Substrate group will be randomly divided into per only ear wound surface
With 2% artemisine composition or combinations thereof group, the gauze piece external application 5 of substrate or 2% artemisine composition or combinations thereof is soaked with
Minute simultaneously retains, rear gauze wrapping, adopts same method dressing within 3,6,9,12,15,18,21 days after surgery.Wound surface is after surgery
12 days visible wound granulation tissue growths, the whole scar healings of 28 days visible wound surface, healing starts to occur being higher by surface for latter 18 days
Hypertrophic cicatrix.Put to death animal within postoperative 50 days, specimen is cut, 10% formalin is fixed, cut into slices after paraffin embedding, HE is dyeed.
3 high power fields (× 200 times) being randomly selected in HE dyeing per a section, counts the fibroblast number in the constituent parts visual field, take
Meansigma methodss.Calculate scar hyperplasia index（Hypertrophic Index, HI）：HE staining tissue slides use micrometer under low power lens
Chi is measured, and calculates scar hyperplasia index by formula HI=A/B.The vertical height of A=cicatrix projection peak to credulous bone surface；B=
The vertical height of cicatrix periphery normal skin skin edge to credulous bone surface.
When 50 days, the visible substrate group wound healing district's groups of perusal are knitted apparently higher than surrounding normal skin, show as cicatrix
Central authorities are in papillae, and in pale red, matter is tough, and hypertrophy block is higher by surface.2% artemisine composition or the healing of combinations thereof group
Area is slightly above normal skin, and color and luster is thin.HE staining tissue slides observe visible substrate group cicatrix blood capillary proliferation substantially, become
Fiber finer karyon is big, intensive hypertrophy, be located at corium holostrome, collagen arrangement disorder.2% artemisine composition or combinations thereof group scar
Trace tissue is relatively thin, and surfacing, level are in order, fibroblast significantly reduces.
Anti- cicatrix of skin formation effect (mean ± SD) of 11. artemisine composition of table or combinations thereof
| Group | Scar hyperplasia index | Fibroblast number |
| Matrix control group | 3.18±0.86 | 86.01±2.87 |
| 2% artemisine composition or combinations thereof group | 1.79±0.77 | 39.78±2.63 |
P<0.05, compare with matrix control group
Resisting mammal cicatrix of skin is had to form effect by the visible artemisine composition of table 11 or combinations thereof.
Experimental example 11：Artemisine composition of the present invention or therapeutical effect of the combinations thereof to rabbit Acne Model
Artemisine composition or combinations thereof are with the acceptable substrate dispersion of pharmacology.Male New Zealand rabbits 22 are taken, random point
For substrate group and 2% artemisine composition or combinations thereof group.To preserved skin 2cm at 2 groups of new zealand rabbit ears medial surface syrinx openings
× 2cm scope, smears coal tar 1 time daily, each 0.5mL, continuous 2 weeks.After 2 weeks, take skin at 2 new zealand rabbit modelings and live
Inspection, pathology section examination, determine that model is formed.The left ear of 2 groups of animals distinguishes substrate and 2% arteannuin of partial smearing equivalent daily
Constituents or combinations thereof, continuous 14 days, two times a day.Perusal in 15th day is simultaneously lived in animal ears corresponding site bark fetching skin
Inspection, piece of tissue with 10% formalin fix, 10% nitric acid decalcification, paraffin embedding, section, HE is dyeed, tissues observed under the light microscopic
Learn and change.
Histology's criterion of experimental acne：(-) no acne, infundibulum only has loose keratinocyte；(+) hair follicle
The a small amount of keratinocyte being sticked together of infundibulum accumulation, funnel is not expanded；In (++) hair follicle, the cutin thromboembolism of moderate, stretches
Enter sebaceous gland duct, with the hypertrophy of sebaceous gland duct, funnel is expanded；In (+++) hair follicle, close cutin thromboembolism causes hair follicle
Severe is expanded, the obvious hypertrophy of sebaceous gland duct epithelium, and part sebaceous gland occurs dissolving time.
Perusal：Rabbit ear coating is after 2 weeks, it is seen that at Oleic acid, local organization is substantially coarse, thicken, hardening, and follicular orifice has
Black keratotic plug, in blackhead shape, when opening coal tar crust, it is seen that attachment hair follicle keratotic plug thereon, its lower visible open increase
Follicular orifice, follicular orifice swell in papulosquamous.After 2% artemisine composition or combinations thereof group medication 14 days, whole flap thickness
Thinning, pliability increases, and local follicular orifice keratotic plug and acne are reduced, and pimple flattens minimizing, has part keratotic plug to leave a little after coming off
The follicular orifice of shape depression.After substrate group medication 14 days, ear's still visible obvious hair follicle keratotic plug, follicular orifice bump pad is slightly put down.
Om observation：After modeling 2 weeks, it is seen that hyperkeratosiss, the hypergranulosis of epidermis and follicular epithelium, acanthosiss,
The hair follicle of adjacent expansion mutually merges, and follicular orifice and infundibulum are full of keratinization material, and extend to sebaceous gland, and follicular orifice keratotic plug is blocked up
Plug, infundibulum of hair follicle portion full of keratinization material and expands in gyalectiform, and dermis telangiectasis are obvious, and perifollicolar diffuses scattered
In inflammatory cell infiltration, based on small round cell, and a small amount of neutrophilic granulocyte.2% artemisine composition or combinations thereof group are used
After medicine 14 days, epidermis is slightly thickened, and follicular orifice is slightly expanded, and is had loose keratinization material filling on a small quantity, is had no that infundibulum of hair follicle portion expands
Big such as gyalectiform, less dermal inflammation cellular infiltration.After substrate group medication 14 days, it is seen that hyperkeratosiss, epidermis and follicular epithelium
Granular layer, spinous layer still hypertrophy substantially, follicular orifice and infundibulum still see keratinization material buildup, infundibulum expands such as gyalectiform, intradermal
There is more inflammatory cell infiltration.
There are correction dyskeratosis, resisting mammal Cuo by result above and the visible artemisine composition of table 12 or combinations thereof
The effect of skin ulcer.
12. artemisine composition of table or combinations thereof are histopathologic impact (mean) on rabbit experiment ear acne
P<0. 05, compare with matrix control group.
Claims (10)
1. a kind of new opplication of artemisine composition or combinations thereof, i.e. new opplication in mammal skin nursing field,
It is characterized in that described artemisine composition or combinations thereof refer to arteannuin and its derivant and correlative and their salt
Class is included but is not limited to, arteannuin, dihydroarteannuin, artesunate, sodium artesunate, Artemether, arteether, arteannuin C13Spread out
Biological, arteannuin C12Derivant, arteannuin C4Derivant, deoxidation bridge arteannuin structure related compound, demethylation arteannuin knot
Structure related compound, de- ketonic oxygen arteannuin structure related compound, steroid arteannuin structure related compound, lactams Herba Artemisiae Annuae
Plain structure related compound, open loop arteannuin structure related compound, 4,5- epoxy carbon are for arteannuin structure related compound, green grass or young crops
Artemisin structure simplifies thing, other arteannuin structure related compounds and their salt；Or the combination containing artemisine composition
Thing or extract are included but is not limited to, Chinese medicine Herba Artemisiae Annuae（ARTEMISIAE ANNUAE HERBA）And its product, plant Artemisia annua
（Artemisia annuaL.）And its product, other Compositae artemisias (Artemisia Linn. Sensu stricto, excl. Sect. Seriphidium Bess.) plant and its product, Herba Artemisiae Annuae tissue culture medium, artemisinin mother liquid etc.；Or be selected from
The arbitrary composition of mentioned component.
2. the skin care compositionss containing artemisine composition or combinations thereof such as health-oriented products, daily chemical products, health product or medicine
Deng the new opplication in mammal skin nursing field, it is characterised in that containing the as claimed in claim 1 of safe and effective amount
Artemisine composition or combinations thereof, and Dermatology and other active additives pharmaceutically acceptable and substrate.
3. artemisine composition as described in right 1～2 is arbitrary or combinations thereof or skin care compositionss are protected in mammal skin
The new opplication in reason field, it is characterised in that the source of artemisine composition or combinations thereof can be synthesis or naturally including but not
It is limited to, natural product extraction, chemical complete synthesis, molecular design, biosynthesiss, histiocyte culture, fungal transformation, metabolism are led to
The approach such as road.
4. artemisine composition as described in claims 1 to 3 is arbitrary or combinations thereof or skin care compositionss are in skin of mammal
The new opplication of skin nursing field, it is characterised in that the content of artemisine composition or combinations thereof in skin care compositionss is preferably
About 0.0001%～90%, even more preferably about 0.01%～35%, most preferably about 1%～22% wherein the percentage ratio be with compositionss
Quality is 100% meter.
5. artemisine composition as described in Claims 1 to 4 is arbitrary or combinations thereof or skin care compositionss are in skin of mammal
The new opplication of skin nursing field, it is characterised in that other active additives that can add and substrate refer to known in the field
At present skin protection cosmetics of everyday use, medicine, health product, applied in healthy product or possible application except artemisine composition and its group
Other optional active additives of wide scope beyond compound and substrate are included but is not limited to, oily raw material, silty raw material, glue
Matter raw material, solvent materials, water-soluble polymer, preservative, thickening agent, acid-base class regulator, antioxidant, wetting agent, convergence
Agent, sunscreen, antibacterial, conditioner, cracking-off agent, opacifier, prurituss, frosting agent, surfactant, skin transferral agent, skin
Skin sensory agent, Skin Soothing Agent, skin healing agent, nourishing additive agent, trace element and hormoness additive, biological active substanceies
Additive, synthesis class nourishing additive agent, bioactive peptide, natural extract, additive biology, quintessence oil, essence, spice, pigment,
Toner, adhesive, disintegrating agent, filler, lubricant, wetting agent, osmotic pressure regulator, stabilizer, fluidizer, correctivess, help
Suspension, coating material, excipient, absorbent, diluent, flocculant and deflocculant, filter aid, release blocker, microcapsule, micro-
Ball, liposome etc. and their combination.
6. artemisine composition as described in Claims 1 to 5 is arbitrary or combinations thereof or skin care compositionss are in skin of mammal
The new opplication of skin nursing field, it is characterised in that described skin care compositionss are included but is not limited to, health-oriented products, cosmetics of everyday use,
Medicine, health product, Emulsion class cosmetics, watery class cosmetics, powder class cosmetics, cream kind cosmetics, aerosol class cosmetics,
Hair based article, beauty class cosmetics, soaps, facial film, curative effect class cosmetics, sun-proof class cosmetics, tablet, powder, pill, soft
Unguentum, membranous patch, gel, capsule, granule, effervescent, fumigant, slow releasing agent etc. and other skin care implements.
7. artemisine composition as described in claim 1～6 is arbitrary or combinations thereof or skin care compositionss are in skin of mammal
The new opplication of skin nursing field, it is characterised in that described application refers to skin defective mode be mitigated or eliminated and makes the life of skin
Reason health is recovered with aesthetic appearance or is further enhanced including but not limited to,
a）By correcting dyskeratosis effect prevention, postponing and/or treat mammal acne, dandruff, desquamation prurituss, dry chap
Split, the hyperkeratotic conditions caused by dyskeratosis such as psoriasises, scleroderma, perifollicular keratosises；
b）By the lip of the softening of promotion cutinization or submissive mammal, skin, hair, refer to toenail, hoof etc., and promote suckling
Animal lip, skin, hair, refer to the renewal of toenail, hoof etc., adjust their oiliness and gloss；
c）Promote skin lightening ruddy by anti-pigmentation, prevention, delay and/or treatment mammal skin blackening,
The appearance of the pigmentation symptoms such as sallow dimness, mottle, acne print, sun exposure damage, inflammation damnification；
d）By the effect prevention of anti-cicatrization, postpone and/or treat the cicatrix that the injury of mammal skin inflammatory stimulus is caused
Cicatrix growth that growth, environmental stimuli injury are caused, the appearance of the cicatrix symptom such as acne print；
e）Skin elasticity effect is kept to strengthen skin elasticity and gloss by slow down aging, prevention, delay and/or treatment suckling are moved
Thing skin lines, wrinkle, sagging, atrophy, swelling, the appearance of corse sweat pore；
f）By antibacterium, antifungal, anti-dermatozoon effect keep mammal skin cleaning, prevention, postpone and/or
Mammal skin defective mode caused by treatment antibacterial, funguses, dermatozoon etc.；
G) eliminated by the effect such as antiinflammatory, analgesia, hemostasis or alleviate the defective modes such as scytitiss red and swollen heat pain, bleeding；
h）By promoting keratinization, correcting dyskeratosis, anti-pigmentation, suppression cicatrization, delay skin aging, keep skin
A series of works beneficial to mammal skin such as elasticity, antiinflammatory, analgesia, hemostasis, antibacterium, antifungal, anti-dermatozoon
With, eliminate or alleviate mammal skin defective mode so as to provide enhanced skin health and beauty.
8. a kind of elimination or alleviation mammal skin defective mode are to provide enhanced skin health and beautiful method, and which is special
Levying is that methods described includes the arbitrary described artemisine composition of right 1～7 or combinations thereof or shield to be applied to mammal
Skin compositionss.
9. pass through to apply artemisine composition or combinations thereof or the skin protection as described in claim 1～8 is arbitrary to mammal
Compositionss, to eliminate or alleviate mammal skin defective mode so as to obtain enhanced skin health and beauty.
10. artemisine composition as described in claim 1～9 is arbitrary or combinations thereof or skin care compositionss are in skin of mammal
The application of skin nursing field.
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Application publication date: 20170222 |