CN102349919B - Application of gingkolic acid in preparation of external preparation for treating osmidrosis - Google Patents
Application of gingkolic acid in preparation of external preparation for treating osmidrosis Download PDFInfo
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- CN102349919B CN102349919B CN 201110236658 CN201110236658A CN102349919B CN 102349919 B CN102349919 B CN 102349919B CN 201110236658 CN201110236658 CN 201110236658 CN 201110236658 A CN201110236658 A CN 201110236658A CN 102349919 B CN102349919 B CN 102349919B
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- gingkolic acid
- acid
- external preparation
- gingkolic
- preparation
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Abstract
The invention relates to application of gingkolic acid in preparation of an external preparation for treating osmidrosis. The gingkolic acid comprises ginkgoic acid, ginkgol, ginkgo diphenol and the like, and can be extracted from leaf, fruit, external exotesta, rhizome and other parts of ginkgo through a chemical separation method. The osmidrosis includes the osmidrosis of axillary part, foot part, perineum and other parts. The drug, cosmetic or disinfectant external preparation containing gingkolic acid for treating osmidrosis contains 0.001-80wt% of gingkolic acid and a pharmaceutically common external preparation matrix or acceptable carrier; and the preparation is any one pharmaceutically external dosage form. Pharmacological experiment researches show that the external preparation has the effects of inhibiting the growth and propagation of bacteria on skin surface and permeating into skin to destroy large sudoriferous gland, and inhibiting the generation of free fatty acid, ammonia nitrogen compound and other smelling substances in sweat. Clinical trial shows that the external preparation has significant treatment effect on the osmidrosis, has effective rate up to 100%, is safe to use and has no side effect.
Description
Technical field
The invention belongs to biological medicine and therapeutic make-up technique field, be specifically related to the purposes of gingkolic acid in the external preparation of preparation treatment fetid sweat.
Background technology
Fetid sweat can be divided into general fetid sweat and local fetid sweat, and the latter is comparatively common with bromhidrosis and foot odor.Bromhidrosis is a kind of common heritability skin metabolism disease, is commonly called as bromhidrosis, mainly shows as the armpit abnormal flavour, and some cases merges maschalephidrosis, and the order of severity varies with each individual.The sweat gland of human body comprises eccrine gland and apocrine gland, apocrine gland claims apocrine sweat gland, foul smell gland again, is distributed in positions such as axillary fossa, perineum, foot, groin and mammary areola, is positioned at corium and subcutaneous tissue intersection and subcutaneous tissue, be opened on hair follicle, Excreta is discharged skin surface along hair shaft.The apocrine gland liquid of just having discharged skin surface is creamy white, tasteless, contain protein, lipid, fatty acid, cholesterol, gluconic acid, compositions such as amine, the main cause of fetid sweat is the organic substance of excessive secretion in the perspiration drained of apocrine gland, be subjected to skin surface antibacterial (staphylococcus epidermidis, staphylococcus aureus, staphylococcus saprophyticus and gram negative bacilli diphtheroid, corynebacterium etc.) decomposition, produce six carbon to ten carbon short chain unsaturated fatty acids and micromolecule ammonia nitriding compound, as caproic acid, sad, different valerian element, butanoic acid and mercaptan, amine, metabolism products such as indole and produce unpleasant stink.Therefore destroy the key that apocrine gland is considered to the bromhidrosis radical cure.Because the secretory function of apocrine gland is subjected to the influence of androgen, the pubarche activity is degenerated to old, therefore bromhidrosis originates from adolescence, the between twenty and fifty phase is comparatively serious, makes the patient be subjected to physiology and psychological dual-pressure in social life, so thoroughly effective treatment is very important.
The method for the treatment of at present bromhidrosis disease clinically is a lot, roughly can be summarized as conservative treatment and operation method, and conservative treatment mainly comprises: external used medicine, injection, physiotherapy (microwave, freezing, electricity coagulates, laser) etc.The local topical medicine comprises topical application antibiotics, fragrant and deodorizing agent, antiperspirant, chemical hormone etc., its objective is to reduce skin of axillary fossa perspire, control bacterial invasion or hide niff, thus relief of symptoms; But at present there is the curative effect weak point of holding time in local application, easily recurrence, after part patient's drug withdrawal bounce-back more serious, can not reach the effect of real radical cure; Also multiple untoward reaction can occur, as anaphylaxiss such as agents area are rubescent, itch, and in various degree symptoms such as pachylosis, pigmentation, desquamation occur; The chemistry hormone causes sclerosis of the skin easily, and more refractory is treated later on, should avoid using this class medicine as far as possible.The subcutaneous injection botulinum toxin can suppress sweat gland secretion, but effect is subjected to the influence of individual variation, and it is not lasting to act on, and needs injection repeatedly; And be prone to injection site paraesthesia and stasis of blood purple, meeting forms antibody and influences therapeutic effect in the multiple injection body.The laser therapy method can cause the hot injury to skin and surrounding tissue in therapeutic process, and exists treatment not thorough, and there is the shortcoming of higher recurrent rate in postoperative.At present, remove the method that part armpit skin histology is the radical cure bromhidrosis disease used always by operation method, but the method can be brought wound and misery to the patient, the possibility that comprise pain, hemorrhage, infection of incisional wound, the cicatricial contracture influence is attractive in appearance and a series of complication such as function take place, even influence upper extremity function, still have certain relapse rate after the operation, so excision is not accepted by most of bromhidrosis patients.
For fear of the generation of this type of bad phenomenon, market demand develop a kind of derive from natural, effect significantly, the external preparation of the treatment fetid sweat of no obvious adverse reaction, to alleviate the patient suffering.Fetid sweat patient is numerous, and the external preparation product of developing this type for the treatment of fetid sweat has good potential applicability in clinical practice, is very useful and necessary to the patient.
Semen Ginkgo is the medicinal plants of China's preciousness, and the leaf of Semen Ginkgo, fruit and episperm etc. all have medicinal exploitation and be worth.According to the Compendium of Material Medica record, Semen Ginkgo property is sweet, bitter, flat, puckery; Have that relieving asthma and cough, leukorrhagia stopping are turbid, the merit of pain relieving; Cure mainly cough of cold type phlegm dyspnea, asthma, frequent micturition, leucorrhea with red and white discharge, rhagadia manus et pedis etc.It is found that in recent decades particularly and contain plurality of active ingredients in the Folium Ginkgo that main effective ingredient is flavonoid and terpene lactone chemical compound, has the function of control cardiovascular and cerebrovascular disease.China has the gingko episperm soak is used as pesticide morning among the people, and insects such as aphid, rice borer are had killing action.
Gingkolic acid is colourless or flaxen oily or powdered substance, is to be present in that a class has the component of important physiologically active in Folium Ginkgo, fruit and the episperm.Gingkolic acid involved in the present invention is alkyl or alkenyl phenol acid, according to whether being connected with carboxyl on the phenyl ring in the molecule, it is divided into ginkgoic acid and ginkgol two big classes.Ginkgoic acid is the salicylic acid molecule has saturated or unsaturated chain alkyl in phenyl ring C6 position series compound, can be divided into 5 kinds by chemical constitution, and side chain R is C
13H
27, C
15H
29, C
15H
31, C
17H
31And C
17H
33, corresponding molecular weight is respectively 320,346,348,372,374.Gingkolic acid comprises ginkgolic acid, hydroginkgoic acid, Semen Ginkgo eo-acid, the inferior acid of Semen Ginkgo, hydroginkgolinic acid, anacardic acid, ginkgol, Semen Ginkgo diphenol, Ginnol etc.Gingkolic acid (ginkgoic acid, ginkgol, Semen Ginkgo diphenol) structure See Figure.
The structure of gingkolic acid
Along with going deep into gradually that the separating Ginkgo phenolic acids material is studied, find that gingkolic acid has multiple biological activity.There are some researches show that gingkolic acid has good inhibition effect to external various bacteria, can suppress the growth of the former bacterium of part agricultural disease; Gingkolic acid has good inhibition effect to the growth of tumor cell line.About extraction, analysis and the antibacterial activity in vitro of gingkolic acid, anti-agriculture pathogen and protozoon, the existing bibliographical information of anti-tumor activity.Have not yet to see the report of the purposes of gingkolic acid in the external preparation of preparation treatment fetid sweat.Therefore, relevant gingkolic acid external preparation is prevented and treated the research and development of fetid sweat newtype drug, cosmetics, disinfectant, and to the abundant development and use of gingko resource, will produce huge social and economic benefit.
Summary of the invention
The new purposes that the purpose of this invention is to provide gingkolic acid, the i.e. purposes of gingkolic acid in the external preparation of preparation treatment fetid sweat.It has good deodorization effect, characteristics evident in efficacy, as not recur, use safety.
The object of the present invention is achieved like this:
The purposes of gingkolic acid in treatment fetid sweat, hyperhidrosis, chromhidrosis is provided.
The purposes of gingkolic acid in the external preparation of preparation treatment fetid sweat, hyperhidrosis, chromhidrosis is provided.
Described fetid sweat is armpit, foot, perineal position fetid sweat etc.
Described gingkolic acid comprises ginkgoic acid, ginkgol, Semen Ginkgo diphenol etc., can be by the Chemical Decomposition method, from the leaf of Semen Ginkgo, really, obtain the extract at position such as episperm, rhizome; Or to Folium Ginkgo, really, episperm, rhizome extract elaboration products and reclaim again in the remaining waste material in extracting the course of processing; Or from containing the each several part extract of this compounds, other plant obtains; Or the method by chemosynthesis obtains.Materials such as claimed this compounds of the present invention and pharmaceutically acceptable salt thereof, ester, solvate, crystal habit.
Medicine, cosmetics or the disinfectant external preparation of the treatment fetid sweat that contains gingkolic acid also are provided, contain gingkolic acid 0.001-80%, by weight percentage, and external preparation substrate or the external preparation acceptable carrier pharmaceutically used always.
Further, contain gingkolic acid 0.001-30%, by weight percentage.
Further, contain gingkolic acid 0.5-20%, by weight percentage.
By above-mentioned weight ratio scope get the principal agent gingkolic acid, external preparation substrate or acceptable carrier pharmaceutically commonly used prepares the gingkolic acid external preparation; And comprise medicine, cosmetics or the disinfectant external preparation that gingkolic acid and any combinations of substances are used for the treatment of fetid sweat.Described preparation is said exterior-applied formulation on any pharmaceutics, can be liquid preparation, cream cream, gel, powder, membrane, lotion, aerosol spray, transdermal absorption formulation, subcutaneous injection agent etc.
The invention has the beneficial effects as follows, the pharmacology pharmacodynamic experimental study shows, gingkolic acid external preparation of the present invention has and suppresses the breeding of skin surface bacterial growth, suppresses sweat gland secretion, infiltrates skin and destroy apocrine gland, inhibition and reduce the effect that free fatty acid and ammonia nitriding compound odor causing substance produce in the perspiration, but can not influence the sweat gland function of normal skin.Fetid sweat had significant therapeutical effect.The local irritation experimentation shows safety of the present invention, untoward reaction such as no skin irritation, allergy.Clinic trial result shows that the present invention has significant therapeutical effect to fetid sweat, and effective percentage reaches 100%, uses safety to have no side effect.
The specific embodiment
Below in conjunction with embodiment, the present invention is done to describe further.
Embodiment 1:
The gingkolic acid extraction process is as follows in the ginkgo nut episperm: the ginkgo nut episperm is stripped down, dry, with pulverizer it is pulverized.Accurately take by weighing a certain amount of gingko episperm through pulverizing, adding solid-liquid ratio is 80% ethanol of 1: 6 (W/V), under 60 ℃ of bath temperatures, stirring and leaching 2 times, (is annotated: behind the liquid feeding at each 4 hours extraction times, the beaker mouth seals with preservative film, to prevent the volatilization of ethanol).Lixiviate is used the nutsch filter sucking filtration after finishing, and collects filtrate.With rotary evaporation in vacuo instrument concentrated filtrate, condition is 55 ℃ of temperature, pressure 0.008-0.009MPa, concentrating under reduced pressure.In 60 ℃ of vacuum dryings, get gingkolic acid extractum, character is: light brown extractum, little smelly, be dissolved in alcohol, water insoluble; Weigh, and measure gingkolic acid content (mg/g).
Gingkolic acid assay: adopt the HPLC method to measure.The standard solution of gingkolic acid is between 100-1200 μ g/ml, and respective peaks area and gingkolic acid mass concentration have significant linear relationship, have worked out standard curve., filter the dissolving of gingkolic acid extractum with dehydrated alcohol (chromatographically pure).At column temperature: room temperature; Mobile phase: methanol-water (9: 1, v/v); Flow velocity 1ml/min; Sample size: 20 μ l; Detect wavelength 310nm; Analysis time: measure gingkolic acid content in the extractum under the 25min condition.Carry out qualitatively according to the retention time of standard specimen, calculate the content of gingkolic acid with external standard method.Gingkolic acid content is 637.17mg/g in the extractum.
Gingkolic acid extraction process and content assaying method are public method.
The preparation of gel: carbopol 10g is sprinkled upon 500ml distilled water surface, and swelling is spent the night.Take by weighing glycerol 60g, propylene glycol 120ml is added to respectively in the good carbopol of swelling, grinds evenly rapidly, obtains transparent gel-type vehicle.Get above-mentioned gingkolic acid extractum 40g, be dissolved in the 100ml95% alcoholic solution, slowly be added in the gel-type vehicle, stir.Slowly add triethanolamine 15ml again, mend distilled water to capacity 1000g, namely get faint yellow gingkolic acid gel 1000g, gingkolic acid content is 2.55% (W/W).Be sub-packed in 50 tubules every 20g.
Gel preparation technology is public method.
Embodiment 2:
The gingkolic acid extraction process is as follows in the Semen Ginkgo fruit Semen Ginkgo: with the Semen Ginkgo peeling, put into tissue mashing machine and pulverize.Accurately take by weighing a certain amount of Semen Ginkgo through pulverizing, adding solid-liquid ratio is 80% ethanol of 1: 10 (W/V), under 60 ℃ of bath temperatures, and stirring and leaching 2 times, each 4 hours extraction times, (annotate: behind the liquid feeding, the beaker mouth seals with preservative film, to prevent the volatilization of ethanol).After lixiviate finished, centrifugal (5000 rev/mins, 15 minutes) got supernatant.With rotary evaporation in vacuo instrument concentrated supernatant, condition is 55 ℃ of temperature, pressure 0.008-0.009MPa, and concentrating under reduced pressure, and in 60 ℃ of vacuum dryings, get gingkolic acid extractum, and character is: light brown extractum, and little smelly, be dissolved in alcohol, water insoluble.Weigh, and measure gingkolic acid content (mg/g).
Gingkolic acid assay: with embodiment 1.Gingkolic acid content is 475.38mg/g in the extractum.
The preparation of ointment: get above-mentioned gingkolic acid extractum 40g, be dissolved in the 100ml95% alcoholic solution, to wherein adding triethanolamine 50ml, heat to 70 ℃ again.Paraffin 300g, stearic acid 300g, propylene glycol 100ml are added stirring respectively melt, mend distilled water to capacity 1000g, stir to paste, namely get faint yellow gingkolic acid ointment 1000g, gingkolic acid content is 1.9% (W/W).Be sub-packed in 50 tubules every 20g.
Ointment preparation technology is public method.
Embodiment 3:
The gingkolic acid extraction process is as follows in the Folium Ginkgo: Folium Ginkgo is shredded, put into pulverizer with its pulverizing.Accurately take by weighing a certain amount of Folium Ginkgo through pulverizing, adding solid-liquid ratio is 80% ethanol of 1: 6 (W/V), under 60 ℃ of bath temperatures, stirring and leaching 2 times, (is annotated: behind the liquid feeding at each 4 hours extraction times, the beaker mouth seals with preservative film, to prevent the volatilization of ethanol).After lixiviate finished, centrifugal (5000 rev/mins, 15 minutes) got supernatant.With rotary evaporation in vacuo instrument concentrated supernatant, condition is 55 ℃ of temperature, pressure 0.008-0.009MPa, and concentrating under reduced pressure, and in 60 ℃ of vacuum dryings, get gingkolic acid extractum, and character is: light brown extractum, and little smelly, be dissolved in alcohol, water insoluble.Weigh, and measure gingkolic acid content (mg/g).
Gingkolic acid assay: with embodiment 1.Gingkolic acid content is 526.73mg/g in the extractum.
The preparation of tincture: get above-mentioned gingkolic acid extractum 80g, be dissolved in the 600ml95% alcoholic solution, again to wherein adding triethanolamine 50ml respectively, propylene glycol 200ml stirs, mend 95% alcoholic solution to capacity 1000ml, namely get faint yellow gingkolic acid tincture 1000ml, gingkolic acid content is 4.2% (W/V).Be sub-packed in 50 tubules every 20ml.
Tincture preparation technology is public method.
Embodiment 4:
Gingkolic acid extraction process and content assaying method get gingkolic acid extractum with embodiment 1 in the ginkgo nut episperm, and gingkolic acid content is 626.19mg/g.Get gingkolic acid extractum 80g, prepare gingkolic acid gel 1000g by embodiment 1 gel preparation technology, gingkolic acid content is 5% (W/W).Be sub-packed in 50 tubules every 20g.
Embodiment 5:
The gingkolic acid extraction process is with embodiment 2 in the Semen Ginkgo fruit Semen Ginkgo, and content assaying method gets gingkolic acid extractum with embodiment 1, and gingkolic acid content is 527.17mg/g.Get gingkolic acid extractum 10g, prepare gingkolic acid ointment 1000g by embodiment 2 ointment preparation technologies, gingkolic acid content is 0.53% (W/W).Be sub-packed in 50 tubules every 20g.
Embodiment 6:
The gingkolic acid extraction process is with embodiment 3 in the Folium Ginkgo, and content assaying method gets gingkolic acid extractum with embodiment 1, and gingkolic acid content is 529.11mg/g.Get gingkolic acid extractum 200g, prepare gingkolic acid tincture 1000ml by embodiment 3 tincture preparation technologies, gingkolic acid content is 10.6% (W/V).Be sub-packed in 50 tubules every 20ml.
Embodiment 7:
Gingkolic acid extraction process and content assaying method get gingkolic acid extractum with embodiment 1 in the ginkgo nut episperm, and gingkolic acid content is 628.23mg/g.Get gingkolic acid extractum 300g, prepare gingkolic acid tincture 1000ml by embodiment 3 tincture preparation technologies, gingkolic acid content is 18.85% (W/V).Be sub-packed in 50 tubules every 20ml.
Embodiment 8:
The gingkolic acid extraction process is with embodiment 3 in the Folium Ginkgo, and content assaying method gets gingkolic acid extractum with embodiment 1, and gingkolic acid content is 551.78mg/g.Get gingkolic acid extractum 200g, prepare gingkolic acid gel 1000g by embodiment 1 gel preparation technology, gingkolic acid content is 11% (W/W).Be sub-packed in 50 tubules every 20g.
Embodiment 9:
Gingkolic acid extraction process and content assaying method get gingkolic acid extractum with embodiment 1 in the ginkgo nut episperm, and gingkolic acid content is 663.62mg/g.Get gingkolic acid extractum 500g, prepare gingkolic acid tincture 1000ml by embodiment 3 tincture preparation technologies, gingkolic acid content is 33.2% (W/V).Be sub-packed in 50 tubules every 20ml.
Embodiment 10:
The gingkolic acid extraction process is with embodiment 2 in the Semen Ginkgo fruit Semen Ginkgo, and content assaying method gets gingkolic acid extractum with embodiment 1, and gingkolic acid content is 435.57mg/g.Get gingkolic acid extractum 1g, prepare gingkolic acid ointment 1000g by embodiment 2 ointment preparation technologies, gingkolic acid content is 0.044% (W/W).Be sub-packed in 50 tubules every 20g.
In order to the gingkolic acid external preparation that the top method is made, the pharmacology pharmacodynamic of being correlated with test, the experiment of local irritation safety evaluatio and clinic trial test.Be experimental data of the present invention below:
Influence to rat paw portion sweat gland secretion: the sweat gland excitation time, except sweat secretion increased, the visible sweat gland epithelial cell cavity of microscopically number increased.20 of rats are divided 2 groups at random, model control group and gingkolic acid gel group of the present invention, 10 every group.Each rat foot of gingkolic acid gel group of the present invention is coated with gingkolic acid gel of the present invention respectively outward, and each rat foot of model control group is outer respectively to be coated with physiological saline solution, every day 1 time, continuous 7 days.Last is smeared and was put to death rat in back 24 hours, neat ankle is blocked two hind legs, take off two sole of the foot portion meat lift skins and subcutaneous tissue 2-3 piece, the variation of respectively organizing in the rat paw sweat gland epithelial cell is observed in fixing, dehydration according to a conventional method, embedding, section, HE dyeing under the optical microscope.Cavity generation percentage rate=cavity sweat gland number/observation sweat gland is counted X100%.Experimental result sees Table 1.The result shows that gingkolic acid gel of the present invention can obviously reduce rat paw portion sweat gland cavity incidence rate, and sweat gland is had the obvious suppression effect.
The influence of table 1. pair rat paw portion sweat gland secretion
X ± s.n=10. compares with model group, * P<0.05, * * P<0.01.
The separation of application on human skin apocrine gland cell and external former be commissioned to train foster: get 5 of about 0.5cmX0.5cm sizes of apocrine gland tissue behind the bromhidrosis patient surgical operation, place the HBSS liquid that contains penicillin (100U/ml) and streptomycin (100 μ g/ml) repeatedly after the rinsing, in the 60mm culture dish, be cut into fritter about 1mm3 with eye scissors, add DMEM/F12 (1: 1) the liquid 3ml contain II Collagen Type VI enzyme (2mg/ml), hyclone (5%), penicillin (100U/ml) and streptomycin (100 μ g/ml), put in 37 ℃, 5%CO2 incubator and spend the night.Shift sweat gland next day and fill in the 60mm culture dish of 600 μ l sweat gland culture fluid in another, put under 37 ℃, 5%CO2 condition and cultivate; The sweat gland culture fluid as basic culture solution, is added hyclone (5%), recombinant human epidermal growth factor (10ng/ml), the former ammonia of triiodo thyroid (2ng/ml), half succinyl hydrocortisone (0.4 μ g/ml), insulin-transferrins-sodium selenite (1ml/100ml), penicillin (100U/ml), streptomycin (100 μ g/ml) with DMEM/F12 (1: 1).After treating that sweat gland is adherent, add about 2ml sweat gland culture fluid and continue to cultivate, later every 2-3d changes liquid 1 time, puts under 37 ℃, 5%CO2 condition and cultivates.
Going down to posterity of application on human skin apocrine gland cell cultivated and vitality test: after cultured skin sweat gland cells about 80% merges, and the feasible cultivation of going down to posterity.Centrifugal collecting cell, adopt tetramethyl azo azoles salt (MTT) colorimetric determination cell proliferation vigor, cell inoculation in 96 orifice plates (every porocyte number is 2 * 103), is established 6 drug dose groups, add gingkolic acid tincture 0 of the present invention respectively, 10,20,40,60,80,100 μ l, each dosage group is established 12 multiple holes; Cultivate after 3 days, the sucking-off culture fluid, add MTT solution 100 μ l in every hole in 37 ℃ of reactions 4 hours, discard MTT, every hole adds 100 μ l DMSO and vibrated 10 minutes, abundant dissolving crystallized thing, the 490nm place measures the absorbance A value, and experimental result is represented (experimental group A value/control group A value * 100) with cell proliferation rate.The result shows (seeing Table 2), compares with the blank group, and gingkolic acid tincture of the present invention can suppress the propagation of apocrine gland cell, and the apocrine gland cell is had tangible destruction.
The influence of table 2. pair apocrine gland cell proliferation
X ± s.n=12. compares with blank, * * P<0.01.
The local irritation experiment: get 8 of adult rabbit, male and female half and half, every animal sub-cage rearing was raised 3-4 days at laboratory condition earlier.Then rabbit spinal column both sides dorsal body setae is shaved off every lateral area 5 * 10cm with electric shaver-for women
2Whether scrutiny depilation district has redness and damage, if any abandoning it, can not test.Adopt the test method of multiple dosing, gingkolic acid external preparation of the present invention is smeared in the district in depilation, every day 2 times, smears continuously 7 days.Whether last is smeared after 24 hours with warm water flush away smear, observes the local skin reaction after 1,24,48,72 hour, as erythema, edema, desquamation, incrustation etc., have petechia, skin peptide coarse or poor etc., record time of origin and regression time.Experimental result shows, is smearing gingkolic acid external preparation of the present invention continuously after 7 days, and each rabbit skin does not all show tangible skin irritation and anaphylaxis.Show product safety of the present invention, have no adverse reaction.
The clinic trial test: on probation through the fetid sweat patient in order to the gingkolic acid external preparation that the top method is made, concrete case sees Table 3.All patients are coated with skin abnormal flavour place outward with the present invention, every day 1 time, continuous 5 days.The patient does not all use any other external preparation for skin medicine during treating.Efficacy assessment standard: recovery from illness: local lossless or hypohidrosis, no stink is followed up a case by regular visits to and was not had recurrence in 1 year; Effectively: local perspiration obviously reduces, and no stink or stink obviously alleviate, and recurrence (but before obviously being lighter than medication) is arranged after the drug withdrawal, needs intermittent use; Invalid: ephidrosis does not have minimizing, and stink does not have and alleviates.Cure rate=healing number/total case X100%; Effective percentage=(healing number+effective number)/total case X100%.The results are shown in Table 3.Clinic trial result shows that multiple fetid sweat patient uses gingkolic acid external preparation of the present invention all effective, and effective percentage reaches 100%; Cure rate is all above 95%.All patients untoward reaction such as skin irritation, allergy all do not occur during using the present invention.Therefore the present invention is a kind of external preparation of desirable treatment fetid sweat, and is evident in efficacy, safe and reliable.
The clinical effectiveness of table 3 gingkolic acid external preparation treatment of the present invention fetid sweat
Get bromhidrosis patient axillary secretions and do the antibacterial culture experiment: 30 routine patients get dorsal position, and two upper limb abductions, elbow in the wrong are after both hands place pillow.Dip in the cotton swab of the moistening mistake of normal saline and to get axillary secretions, send laboratory to do the antibacterial culture experiment in 10 minutes, 28 routine patients turn out the staphylococcus epidermidis growth, and 2 examples are turned out staphylococcus aureus growth.Preparation Carnis Bovis seu Bubali cream fluid medium: Carnis Bovis seu Bubali cream 0.3g, peptone 1.0g, sodium chloride 0.5g adds distilled water again to 100ml after adding a small amount of distilled water heat fused, and adjust pH to 7.2 filters, sterilization.Cotton swab dips in gets patient's axillary secretions, is inoculated in the test tube that contains Carnis Bovis seu Bubali cream soup body culture medium, and every pipe 1ml cultivated 24 hours in 37 ℃ of incubators, observed the bacterial growth situation.As liquid clarification in vitro, represent no bacterial growth; As be muddy, the expression antibacterial grows.Result of the test shows that the muddiness of liquid in vitro of axillary secretions inoculation illustrates that there is bacterial infection the patient oxter before the patient treatment; After the gingkolic acid external preparation of the present invention treatment, the clarification of liquid in vitro of patient's axillary secretions inoculation illustrates that gingkolic acid external preparation of the present invention can remove the oxter bacterial infection, has antibacterial action.
Get bromhidrosis patient axillary secretions and measure ammonia-nitrogen content, can reflect the amount of protein catabolite in the axillary secretions; What of organic acidic material mensuration axillary secretions pH value can react; And free content of fatty acid in the mensuration axillary secretions.With aseptic medicated napkin wiping bromhidrosis patient armpit, insert 25ml and do not have in the ammonia, measure solution acidity value, ammonia-nitrogen content and free fatty acid content.Measure the solution acidity value with pH meter.The nessler reagent photometry is one of standard method of measuring at present ammonia nitrogen.Get the 25ml color comparison tube, add the ammonia nitrogen standard and use liquid 0.00,0.25,0.5,1.0,2.0,3.0 4.0,5.0ml adds no ammonia and is diluted to scale, add the 0.5ml potassium sodium tartrate solution, 0.5ml nessler reagent, mixing, 10min develops the color in 25 ℃ of water-baths, with the 1cm cuvette at 420nm place colorimetric determination absorbance, with ammonia-nitrogen content to absorbance production standard curve.Nessler reagent: prepare with KI and HgI2, KOH according to the GB/T5750.5-2006 method.Sodium potassium tartrate tetrahydrate: take by weighing the 50g sodium potassium tartrate tetrahydrate and be dissolved in 100ml and do not have in the ammonia, add the NaOH5ml of 250g/L, heated and boiled is settled to 100ml to about 50ml after the cooling.Measure free fatty acid content with detection kit.Experimental result sees Table 4.The result shows that the present invention can reduce bromhidrosis patient armpit cleaning piece solution pH value, illustrates that the present invention can reduce the generation of oxter organic acid substance.The present invention can reduce the ammonia nitrogen compounds content of bromhidrosis patient armpit cleaning piece solution, illustrates that the present invention can obviously suppress the decomposition of oxter perspiration protein, reduces the generation of ammonia nitriding compound stink substance.Experimental result shows that also the present invention can reduce the free fatty acid content of bromhidrosis patient armpit cleaning piece solution, illustrates that the present invention can suppress steatolysis, reduces the catabolite free fatty acid content, thereby reduces the generation of odor causing substance.
Table 4 gingkolic acid external preparation of the present invention is to the influence of axillary secretions
X ± s.n=30. compares with model group, * P<0.05, * * P<0.01.
The present invention is compared with prior art: the present invention derives from natural precious medicinal plants Semen Ginkgo, from Folium Ginkgo, really, position extraction separation gingkolic acid such as episperm, be that effective ingredient is made preparation for external application to skin with the gingkolic acid, have disinfection, convergence hidroschesis, infiltrate skin and destroy apocrine gland, suppress the good action that odor causing substance produces; Fetid sweat is had significant radical cure effect, and curative effect is outstanding, use safety has no side effect, and has good potential applicability in clinical practice.
Claims (6)
1. gingkolic acid is prevented and treated purposes in the external preparation of fetid sweat, hyperhidrosis, chromhidrosis in preparation, and wherein gingkolic acid is the unique active component in the external preparation, contains the gingkolic acid of 0.5-20% by weight percentage in described external preparation.
2. the purposes of gingkolic acid as claimed in claim 1, described fetid sweat is armpit, foot or perineal position fetid sweat.
3. the purposes of gingkolic acid as claimed in claim 1, described external preparation is medicine, cosmetics or disinfectant external preparation.
4. the purposes of gingkolic acid as claimed in claim 1, described external preparation is liquid preparation, cream cream, gel, powder, membrane or aerosol spray.
5. the purposes of gingkolic acid as claimed in claim 1, described external preparation is lotion or transdermal absorption formulation.
6. as each described purposes among the claim 1-3, it is characterized in that described gingkolic acid is by the Chemical Decomposition method, from the leaf of Semen Ginkgo, really, obtain the extract of episperm, rhizome; Or to Folium Ginkgo, really, episperm, rhizome extract elaboration products and reclaim again in the remaining waste material in extracting the course of processing and obtain; Or the method by chemosynthesis obtains.
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EP3068366B1 (en) * | 2013-11-13 | 2020-07-15 | L'oreal | Use as a deodorant agent of a salified salicylic acid derivative, alone or in a mixture |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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US6086883A (en) * | 1993-12-03 | 2000-07-11 | Montana Limited | Extract from the leaves of Ginkgo biloba |
CN1747715A (en) * | 2003-04-07 | 2006-03-15 | 花王株式会社 | Deodorant agent |
CN1763209A (en) * | 2005-09-26 | 2006-04-26 | 江南大学 | Comprehensive utilization process for gingko episperm |
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US6086883A (en) * | 1993-12-03 | 2000-07-11 | Montana Limited | Extract from the leaves of Ginkgo biloba |
CN1747715A (en) * | 2003-04-07 | 2006-03-15 | 花王株式会社 | Deodorant agent |
CN1763209A (en) * | 2005-09-26 | 2006-04-26 | 江南大学 | Comprehensive utilization process for gingko episperm |
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EP3068366B1 (en) * | 2013-11-13 | 2020-07-15 | L'oreal | Use as a deodorant agent of a salified salicylic acid derivative, alone or in a mixture |
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