CN103845280B - 20(R)-ginsenoside Rg3 preparation for external use, preparing method thereof and applications thereof - Google Patents
20(R)-ginsenoside Rg3 preparation for external use, preparing method thereof and applications thereof Download PDFInfo
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- CN103845280B CN103845280B CN201210501652.4A CN201210501652A CN103845280B CN 103845280 B CN103845280 B CN 103845280B CN 201210501652 A CN201210501652 A CN 201210501652A CN 103845280 B CN103845280 B CN 103845280B
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Abstract
The invention relates to different formulas comprising an active component 20(R)-ginsenoside Rg3 and a plurality of auxiliary materials, or relates to a plurality of preparations for external use prepared by adding other active components into the formulas. The formulas and the preparations for external use can be used for medicines or cosmetics, and can be used for treating dysmenorrhea and leucoderma through an external use administration manner.
Description
Technical field
The present invention relates to a kind of 20 (R)-ginsenoside Rg3 active component and multiple auxiliary materials combination formula, make various outer
Use preparation；External preparation formula of the present invention is not limited to a kind of active component of 20 (R)-ginsenoside Rg3s, or 20 (R)-people
Ginseng saponin Rg3 and other active components combination formula, these active component can be Radix Notoginseng, Aloe, Radix Glycyrrhizae, the Radix Polygoni Multiflori, Semen Ginkgo, black
Seed of Sesamum indicum L. extract, Rhizoma Zingiberis Recens extract, Semen Vitis viniferae extract, Punica granatum L. seed extract, plants essential oil, arbutin, vitamin C and its spread out
One kind in biological, Vitamin E and its derivant, two or more.The formula and its external preparation of the present invention can be used
In medicine exterior-applied formulation or cosmetics, can be used for treating vitiligo.
Background technology
Radix Ginseng is belonging to the plant of Araliaceae Panax, and in China, Korea, Japan are widely used, existing more than 2000 years
History, with prevention disease and prolongation life-span as main application target.According to《Sheng Nong's herbal classic》Record, Radix Ginseng has：' tonifying five ZANG-organses, peace
Nerve, determines soul, stop palpitate with fear, remove pathogenic factor, item Fructus Alpiniae Oxyphyllae, and long term usage is made light of one's life by commiting suicide macrobiosis ' effect.Modern medicine study shows Radix Ginseng
Primary efficacy and effect have：For the effect of central nervous system, anticancer antitumor action, Immunologic Functions, anti-sugar
The effect of urine disease, strengthens liver function effect, and cardiovascular and cerebrovascular vessel obstacle improves, anti arteriosclerosis effect, Blood pressure regulation, Yi Jigeng
Term obstacle and function of resisting osteoporosis, resisting fatigue, antioxidation suppress aging etc..
Principle active component of the ginsenoside as Radix Ginseng, is widely studied and uses, wherein with 20 (R)-ginsenosides
Rg3 is the most noticeable, its principle active component as Radix Ginseng, and safety is good, has been made into antitumor oral formulations
Clinic is applied to, is furtherd investigate as injection.
It is many using Radix Ginseng and its total saponins as the main active of external preparation in existing research, as Radix Ginseng and Radix Ginseng
Total saponins composition is all very complicated, and various functions composition mixes, and often produces some untoward reaction and clear without method interpretation
Chu, is also unfavorable for that the kind to the greatest extent of effect plays；And monomer saponin has the characteristics of effect is clear and definite, side effect is low, consumption is few, thus it is single
Body ginsenoside is applied especially to the more commercially valuable and healthy meaning of cosmetic product as external preparation main active
Justice.The present invention is using ginseng saponinses --- 20 (R)-ginsenoside Rg3s as main active, by with make with infiltration
Adjuvant and other active components formula, external preparation is made, had during they are applied to pharmaceutical preparation and cosmetics wide
Wealthy market prospect.
The content of the invention
The purpose of the present invention is for defect present in prior art, there is provided a kind of to contain 20 (R)-ginsenoside Rg3s
External preparation.By 20 (R)-ginsenoside Rg3 of active component and multiple auxiliary materials, 20 (R)-ginsenoside Rg3s and other activity
Composition and multiple auxiliary materials formula, make external preparation such as gel, cream, tincture, spray, cataplasma etc., further can open
Send out into determined curative effect, using safe drugs external preparation and cosmetics, such as by topical route administration, can send out at short notice
Wave curative effect, fast treating dysmenorrhea.
To realize the purpose of the present invention, one aspect of the present invention provides a kind of external preparation, including 20 (R)-ginsenosides
Rg3。
Wherein, the weight of 20 (the R)-ginsenoside Rg3 and the ratio of the gross weight of the external preparation are 0.01-10:
100；Preferably 0.1～10: 100, more preferably 1～10: 100.
Particularly, 20 described (R)-ginsenoside Rg3 purity are 1%～98%；Preferably 30～80%, it is further excellent
Elect 60% as.
Particularly, 20 described (R)-ginsenoside Rg3 purity >=1%, preferably >=30%, more preferably >=
60%, it is still more preferably >=80%, then is still more preferably >=98%.
Particularly, the external preparation also includes that Radix Notoginseng, Aloe, Radix Glycyrrhizae, the Radix Polygoni Multiflori, Semen Ginkgo, Semen Sesami Nigrum extract, Rhizoma Zingiberis Recenss are carried
Take thing, Semen Vitis viniferae extract, Punica granatum L. seed extract, plants essential oil, arbutin, vitamin C and its derivant or Vitamin E and its
Derivant.
Wherein, the external preparation is the gel containing 20 (R)-ginsenoside Rg3s, cream, tincture, spray or bar
Cloth agent.
Particularly, the adjuvant in the gel, cream, tincture or cataplasma preparation be water, glycerol, Propylene Glycol, ethanol,
Carbomer, arabic gum, hyaluronic acid, tragakanta, Polyethylene Glycol series, menthol, methylcellulose, starch, hexadecane
Base Polyethylene oxide (20) ether, glyceryl stearate, hexadecanol, squalane, octadecanol, dimethione methoxy cinnamic acid second
One or more in the own ester of base；Preferably carbomer hydrogel matrix.
Wherein, the external preparation is the rubber emplastrum containing 20 (R)-ginsenoside Rg3s or emplastrum, wherein described
Rubber emplastrum includes 20 (R)-ginsenoside Rg3s, host material, tackifier, softening agent and filler, wherein the substrate material
Expect for rubber；The tackifier selects Colophonium, esterase, hydrogenated rosin or nopinene；The softening agent is vaseline, sheep
Hair fat, liquid Paraffin or vegetable oil；The filler Zinc Oxide or Griffith's zinc white.；The emplastrum includes 20 (R)-ginsenosides
Rg3, host material, wherein the host material is acrylic resin, Oleum Verniciae fordii, oleum lini, Oleum sesami, Oleum Ricini, Colophonium, edible
Gelatin, Cera Flava, glycerol, maltose or Zinc Oxide.
Wherein, it is made up of following proportioning raw material per 100ml gels：
Wherein, it is made up of following proportioning raw material per 100ml emplastrumes：
Wherein, 20 described (R)-ginsenoside Rg3 purity are 1%～98%；Preferably 30～80%, further preferably
For 60%.
Particularly, 20 described (R)-ginsenoside Rg3 purity >=1%, preferably >=30%, more preferably >=
60%, it is still more preferably >=80%, then is still more preferably >=98%.
Another aspect of the present invention provides a kind of preparation method of external preparation, including by 20 (R)-ginsenoside of active component
Rg3 is mixed homogeneously with adjuvant, obtains final product.
Wherein, the weight of 20 (the R)-ginsenoside Rg3 and the ratio of the gross weight of the external preparation are 0.01-10:
100；Preferably 0.1～10: 100, more preferably 1～10: 100.
Particularly, 20 described (R)-ginsenoside Rg3 purity are 1%～98%；Preferably 30～80%, it is further excellent
Elect 60% as.
Particularly, 20 described (R)-ginsenoside Rg3 purity >=1%, preferably >=30%, more preferably >=
60%, it is still more preferably >=80%, then is still more preferably >=98%.
Particularly, the adjuvant is water, glycerol, Propylene Glycol, ethanol, carbomer, arabic gum, hyaluronic acid, Calculus Bovis from Northwest of China Millefolium
Glue, Polyethylene Glycol series, menthol, methylcellulose, starch, cetyl Polyethylene oxide (20) ether, glyceryl stearate, ten
One or more in six alcohol, squalane, octadecanol, dimethione ethylhexyl methoxy cinnamate, preferably blocks
Ripple nurse hydrogel matrix.
Particularly, also including addition Radix Notoginseng, Aloe, Radix Glycyrrhizae, the Radix Polygoni Multiflori, Semen Ginkgo, Semen Sesami Nigrum extract, Rhizoma Zingiberis Recens extract, Portugal
Grape seed extract, Punica granatum L. seed extract, plants essential oil, arbutin, vitamin C and its derivant or Vitamin E and its derivant,
Mix with 20 (R)-ginsenoside Rg3s, adjuvant.
Another aspect of the invention provides a kind of preparation method of 20 (R)-ginsenoside Rg3 gels, including order below
Carry out the step of：
1) get the raw materials ready according to following proportioning per 100ml gels：
2) card pool nurse is added in the deionized water of 50-60ml, after swelling, adds ginsenoside Rg3, EDTA-Na2, perfume (or spice)
Essence, propylparaben, methyl hydroxybenzoate, stir, and are subsequently added into the sodium hydroxide solution that mass percent concentration is 10%,
The pH value of mixed solution is adjusted to 5～7, is stirred, deionized water is subsequently adding to 100ml.
Another aspect of the invention provides a kind of preparation method of 20 (R)-ginsenoside Rg3 emplastrumes, including order below
Carry out the step of：
1) get the raw materials ready according to following proportioning per 100ml emplastrumes：
2) ginsenoside Rg3 is added in the deionized water of 10～20ml, mix homogeneously is subsequently added into EDTA-Na2 molten
Xie Hou, adjusts the pH value of mixed solution to 5～7 with sodium hydroxide solution, is subsequently adding essence, propylparaben, Metagin
Ester, in adding acrylic resin cream base, is eventually adding deionized water to 100ml, is fully mixed, be coated on backing nonwoven after being mixed
Emplastrum made by cloth.
Further aspect of the present invention provide a kind of external preparation containing 20 (R)-ginsenoside Rg3s prepare treatment dysmenorrhea,
Application in the medicine of vitiligo disease.
External preparation prepared by the present invention has the advantage that：
1st, external preparation prescription compatibility science of the present invention, formula are unique, and effect is definite, safe, quality controllable；
2nd, in external preparation of the present invention, 20 (R)-ginsenoside Rg3 of active component is directed through skin and acts on affected part, treats
Effect is notable, and medicine is effective rapid；
3rd, the preparation method of external preparation of the present invention is simple, and process conditions are gentle, and with low cost, expense is low；
4th, external preparation of the invention, can quickly eliminate dysmenorrhea by topical administration approach, good to treating vitiligo effect
It is good.
Specific embodiment
The beneficial effect of formula of the present invention is further described below by specific embodiment, these embodiment bags
The pharmacodynamics test of cream, tincture, emplastrum, gel made by combination formula of the present invention is included.These embodiments are only models
Example property, any restriction is not constituted to the scope of the present invention.It will be understood by those skilled in the art that without departing from this
The details of technical solution of the present invention and form can be modified or replaced under bright formula thinking, purposes scope, but these
Modification and replacement are each fallen within protection scope of the present invention.
1 Rg3 cream of embodiment
1st, prepare raw material according to following proportioning
1) prepare part A raw material according to following proportioning：
2) prepare part B raw material according to following proportioning：
2nd, under stirring respectively A, part B raw material are mixed, heat temperature raising remain 70 DEG C, after stirring,
It is while stirring part B mixed material to be added in the raw material of part A under conditions of 70 DEG C in keeping temperature, stirs
Afterwards, plus deionized water is to 100%, room temperature is cooled to, Rg3 emollient cream 100g, 20g/ bottles is obtained.
2 Rg3 cream of embodiment
1st, prepare raw material according to following proportioning
1) according to such as in proportioning preparation part A raw material：
2) according to such as in proportioning preparation part B raw material：
3) according to such as in proportioning preparation C portion raw material：
2nd, under stirring respectively A, part B raw material are mixed, heat and remain 70 DEG C, after stirring, protected
It is while stirring part B mixed material to be added in the raw material of part A under conditions of 70 DEG C to hold temperature, after stirring, then
C portion raw material is added, is added deionized water to 100% after mix homogeneously again, is cooled to room temperature, Rg3 sunscreen cream 100g, 20g/ is obtained
Bottle.
3 Rg3 gels of embodiment
1st, prepare raw material according to following proportioning
Full side finally adds deionized water to 100%.
2nd, by card pool nurse be added in deionized water, stirring swelling after, add ginsenoside Rg3, EDTA-Na2, essence,
Propylparaben, methyl hydroxybenzoate, after stirring, adjust mixing with the sodium hydroxide solution that mass percent concentration is 10%
The pH of solution is 6 (pH is also applied for the present invention for 5～7), stirs, adds deionized water to 100%, and Rg3 gels are obtained
Agent 100ml, 10g/.
4 Rg3 emplastrumes of embodiment
1st, prepare raw material according to following proportioning
2nd, ginsenoside Rg3 is mixed homogeneously with a small amount of water, it is after being subsequently added into EDTA-Na2 dissolvings, dense with mass percent
The pH for spending the sodium hydroxide solution regulation mixed solution for 10% is 6 (pH is also applied for the present invention for 5～7), then in stirring
Addition essence, propylparaben, methyl hydroxybenzoate under state, in adding acrylic resin cream base after being mixed, plus deionized water is extremely
100%, fully it is mixed, is coated on backing non-woven fabrics, makes plaster, agent 50 is pasted, 7cmX10cmX2 patches/bag.
5 Rg3 tinctures of embodiment
1st, prepare raw material according to following proportioning
2nd, ginsenoside Rg3, Radix Polygoni Multiflori extract, Semen Sesami Nigrum extract are taken, with addition deionized water after ethanol dissolving extremely
100%, obtain final product.
6 20 (R)-ginsenoside Rg3 of embodiment treats dysmenorrhea pharmacodynamic experiment
1. experiment material
1.1 medicines and reagent
20 (R)-ginsenoside Rg3 dysmenorrhea patch extractum, the pharmaceutical preparation of Dalian Fu Sheng natural drugs development corporation, Ltd. grind
Room offer, lot number are provided：20110901, specification：7cmX10cmX2 patches/bag.
Bare substrate is provided by Dalian pharmaceutical preparation research department of Fu Sheng natural drugs development corporation, Ltd., lot number：
20110901；Water is heated and softened before use, is made into respective concentration with bare substrate standby.
Positive drug：Jing oxazepans are pasted, Xi'an Kangping Medicines and Health Product factory；Lot number：20101215；Specification：3 patches/bag；
Diethylstilbestrol injection, Shanghai GM pharmaceutcal corporation, Ltd, lot number：20110321；
Oxytocin injections liquid, Nanjing biochemical-pharmaceutical factory, lot number：2011011；
Depilatory cream, Shanghai ADEL health products Co., Ltd, lot number：20110305.
1.2 animals female Kunming mouses, 12-16g, male mice in kunming, 18-22g；SD rats, 160-180g,
Male and female dual-purpose, purchased from Dalian Medical Univ's Experimental Animal Center, the certification of fitness number：SCXK(13)2002-0002.
1.3 instrument PB303-N electronic balances, Mettler-Toledo Instrument (Shanghai) Co., Ltd..PowerLab/8s, even
There is provided by Australian AD Instruments companies with software kit.
2. methods and resultses
The impact of rat dysmenorrhea model caused by 2.1 pairs of oxytocin
Female sd inbred rats 60, are randomly divided into 6 groups, i.e. blank control group, model group, positive drug control group, the high agent of Rg3
Amount group (Rg3 concentration 10%), middle dose group (Rg3 concentration 1%), low dose group (Rg3 concentration 0.1%), wherein, blank
Group：Not oxytocin injection uterotonic, sticks bare substrate (without any medicine in bare substrate)；Model group：Injection
Oxytocin is positive；Positive drug control group：Stick Jing oxazepan patch groups；The high, medium and low dosage groups of Rg3, stick high dose Rg3 respectively
(10%), middle dosage Rg3 (1%), low dosage Rg3 (0.1%).
In addition to blank control group, the equal subcutaneous injection diethylstilbestrol of each group rat, continuous 10 days, once a day, the 1st day and
Only, the 2nd～9 day injection 0.2mg/ is only for 10 days injection 0.8mg/；5th day starts, rat abdomen shaving, depilation, is pasted with sun respectively
Property comparison medicine Jing oxazepan patch, ginsenoside Rg3's dysmenorrhoea patch, paste medicine 3 × 2cm of scope2, immobilization with adhesive tape, once a day, continuous 7 days；
Blank control group and model group give equivalent distilled water.After last was to after diethylstilbestrol 1 hour, rats by intraperitoneal injection oxytocin
2u/ only, observes each group rat pain reaction in 30 minutes, and writhing response shrinks indent, trunk and hindlimb extension with rat abdomen,
Buttocks is uterine contraction dysmenorrhea index with side limbs inward turning, observe and record in 30 minutes each group rat dysmenorrhea writhing number of elements and
Average writhing number of times, calculates dysmenorrhea incidence rate, the results are shown in Table 1.
Impact of 1 ginsenoside Rg3 of table to rat dysmenorrhea model caused by oxytocin
Jing X2Inspection, compares * P ＜ 0.05, * * p ＜ 0.01, * * * ＜ 0.001 with bare substrate.
The impact of 2.2 pairs of oxytocin induced mice dysmenorrhea model
SD female mice 60, is randomly divided into 6 groups, i.e. blank control group, model group, positive drug control group, the high agent of Rg3
Amount group (Rg3 concentration 10%), middle dose group (Rg3 concentration 1%), low dose group (Rg3 concentration 0.1%), wherein, blank
Group：Not oxytocin injection uterotonic, sticks bare substrate (without any medicine in bare substrate)；Model group：Injection
Oxytocin is positive；Positive drug control group：Stick Jing oxazepan patch groups；The high, medium and low dosage groups of Rg3, stick high dose Rg3 respectively
(10%), middle dosage Rg3 (1%), low dosage Rg3 (0.1%).
In addition to blank control group, the equal subcutaneous injection diethylstilbestrol of each group mice, continuous 10 days, once a day, the 1st day and
Only, the 2nd～9 day injection 0.1mg/ is only for 10 days injection 0.2mg/；5th day starts, rat abdomen shaving, depilation, is pasted with sun respectively
Property comparison medicine Jing oxazepan patch, ginsenoside Rg3's dysmenorrhoea patch, paste medicine 3 × 2cm of scope2, immobilization with adhesive tape, once a day, continuous 7 days；
Blank control group and model group give equivalent distilled water.After last was to after diethylstilbestrol 1 hour, mouse peritoneal injection oxytocin
2u/ only, observes each group rat pain reaction in 30 minutes, and writhing response shrinks indent, trunk and hindlimb extension with mouse web portion,
Buttocks is uterine contraction dysmenorrhea index with side limbs inward turning, observe and record in 30 minutes the incubation period of mice dysmenorrhea writhing and
Writhing number of times, calculates dysmenorrhea incidence rate, the results are shown in Table 2.
Impact of 2 ginsenoside Rg3 of table to oxytocin induced mice dysmenorrhea model
Jing X2Inspection, compares * P ＜ 0.005, * * p ＜ 0.01, * * * p ＜ 0.001 with bare substrate.
Conclusion：20 (R)-ginsenoside Rg3 of above-mentioned experiment results proved can significantly inhibit the rat of oxytocin induction, mice
The generation of dysmenorrhea, substantially reduces pain writhing number of times in dysmenorrhea model rat caused by oxytocin, mice 30 minutes, extends dysmenorrhea and dive
Fu Qi, prompting can significantly improve dysmenorrhea symptom, the effect of Rapid reversal dysmenorrhea pain.
7 20 (R)-ginsenoside Rg3 of embodiment treats vitiligo pharmacodynamic experiment
1 materials and methods
1.1 laboratory animal：Cavia porcelluss, 250 ± 20g of body weight, male and female dual-purpose, purchased from Dalian Medical Univ's Experimental Animal Center,
The certification of fitness number：SCXK(13)2002-0002.
1.2 medicines and instrument
Hydrogen peroxide：Suzhou Zhen Ya chemical plant produces, lot number 20009303；
Ginsenoside Rg3's gel：Dalian Fu Sheng natural drugs development corporation, Ltd. provides, lot number 20110315, specification：
10g/；
Positive drug：(Main Ingredients and Appearance is halometasone 0.05% to Sicorten Plus, triclosan 1%) Novartis, lot number
200012；
7170A type automatic clinical chemistry analyzers, HIT.
1.3 experimental technique
1.3.1 prepare vitiligo animal model
Black or black colored hair (dark skin) Cavia porcelluss 60 are taken, and back black wool about 40cm are sloughed with sodium sulfide2.It is randomly divided into
6 groups, i.e. blank control group；Model control group；Positive controls (Sicorten Plus group)：Ginsenoside Rg3's gel low dose group
(Rg3 concentration 0.1%)：Middle dose group (Rg3 concentration 1%)：High dose group (Rg3 concentration 10%), wherein, blank control group：Apply
Smear equivalent distilled water；Model control group：Smear hydrogen peroxide modeling group (preparing vitiligo animal model group)；Positive controls：
Smear Sicorten Plus；Ginsenoside Rg3's low dose group smears Rg3 concentration 0.1%：Middle dose group smears Rg3 concentration 1%：High agent
Amount group smears Rg3 concentration 10%.Every group of Cavia porcelluss have one's hair cut device and Cavia porcelluss spinal column both sides are gone by depilatory (5% sodium sulfide) with electronic
Hair, goes hair-fields area to be about 100cm2, in addition to blank control group, other each group Cavia porcelluss smear 5% hydrogen peroxide in hair removal section,
Use 0.5ml every time, daily 2 times, continuous 50 days.Blank control group smears equivalent distilled water.During this period, each group Cavia porcelluss are used weekly
Sodium sulfide loses hair or feathers 1 time in the tested area in back.
1.3.2 treatment of ginsenoside Rg3's vitiligo gel to the pneumatic thing model of leucoderma
Blank control group and model group do not carry out any process, and positive controls smear Sicorten Plus treatment vitiligo；People
Ginseng saponin Rg3 gel low dose groups, middle dose group, high dose group smear ginsenoside Rg3's gel of corresponding dosage respectively,
Daily 2 times, continuous 50 days.During treatment, each group Cavia porcelluss are lost hair or feathers 1 time in the tested area in back with sodium sulfide weekly.
After treatment end, naked eyes gross examination of skeletal muscle treats leukodermic curative effect.
Curative effect determinate standard：With Cavia porcelluss agents area center 3cm2It is for an observation unit, excellent for tested area (3cm2) pigment base
This recovery is normal；It is good pigment area ＞ 50% occur for tested area；In be tested area's pigment area ＜ 50%, difference is for tested area's skin
Skin is in still pale or white macula shape；In terms of total effective rate adds " good " by " excellent ".
Anaesthetized with 20% urethane, acetylcholine esterase (ChE) activity is surveyed in ventral aorta blood drawing.And take in agents area center
1cm × 1cm skins, are fixed with neutral formalin, paraffin embedding, section, carry out melanin dyeing with ferrous sulfate lillie methods, with
Meaning 20 hair follicles of observation, calculating wherein have melanin hair follicle number and dermal melanin distribution situation.
1.3.3 Data Processing in Experiment experimental result represented with x ± s, using variance analyses and rank test.
2 results
2.1 perusals are shown in Table 3.
3 ginsenoside Rg3 of table treats leukodermic observation of curative effect (3cm2Observation unit)
The observation result table of table 3 shows：Blank control group compares difference (the P ＜ for having highly significant with model control group
0.01)；Sicorten Plus positive control drug group, ginsenoside Rg3's group total effective rate respectively 70%, 80%, 90%, it is right with blank
According to group comparing difference without significance (P ＞ 0.05).
2.2 histological observations are shown in Table 4, and " +++ " shows that epidermal basal cell and spinous layer have melanin；" ++ " shows epidermis base
Floor cells and spinous layer more than 1/2 have melanin；"+" shows that epidermal basal cell and spinous layer 1/2～1/3 have melanin；" ± " shows table
Scytoblastema floor cells and the accidental melanin of spinous layer；"-" shows epidermal basal cell and spinous layer without melanin.From table 4, blank
Group, Sicorten Plus positive controls, the basic, normal, high dosage group of ginsenoside Rg3 is compared with model group significant differences
(P ＜ 0.01)；Property (P ＜ 0.05) that ginsenoside Rg3's gel group compares with Sicorten Plus group that there were significant differences.
4 ginsenoside Rg3 of table is on the melanic impact of the pneumatic thing model skin of leucoderma
Note：* p ＜ 0.01, are compared with model group；△P ＞ 0.05, are compared with blank；ΔΔP ＜ 0.05 are right with the positive
According to comparing.
3 conclusion vitiligo are dermatology common diseases, and clinic is mainly shown as that dermal melanin is reduced.It is easy according to melanin
Cavia porcelluss dark skin is decolourized by the characteristics of by strong oxidizer hydrogen peroxide destroying, this test from 5% hydrogen peroxide.Continuous 50 days
Afterwards, the visible Cavia porcelluss dark skin of naked eyes is pale, some appearance white maculas, or even grows white hair at original black wool.Under skin biopsy mirror
It can be seen that, in spinous layer and hair follicle, melanin is reduced, some hair follicle internal upper parts are white, it is middle in yellow, pigment of the bottom in black
Change, shows that vitiligo model group is successfully prepared.After continuously being treated 50 days with ginsenoside Rg3's gel, ginsenoside Rg3's
Basic, normal, high dosage group is recovered substantially with Sicorten Plus group skin perusal pigment, is close to Normal group；Examine in histology
In looking into, the melanin hair follicle number of the basic, normal, high dosage group of ginsenoside Rg3 is significantly more than positive control (Sicorten Plus) group (P ＜
0.05), show that effect of ginsenoside Rg3's gel in terms of melanin hair follicle is recovered is better than Sicorten Plus.
Embodiment 8Rg3 external preparation toxicology test is studied
1 material
1.1 medicine
Ginsenoside Rg3's external preparation (cream, tincture, patch, gel), above-mentioned preparation Rg3 concentration are high dose
Group (30%), low dosage (0.1%) group, Dalian Fu Sheng natural drugs development corporation, Ltd. are developed and are provided, lot number：
20110816；
Positive drug：DNFB, Tianjin chemical reagent factory, lot number：20100511；
Sodium sulfide, Guangzhou Chemical Reagent Factory, lot number：20101105；
Acetone, Tianjin chemical reagent factory, lot number：20111029.
1.2 animal
Healthy 2.5 ± 0.3kg of new zealand rabbit, Kunming mouse 20 ± 2 are purchased from Dalian Medical Univ's laboratory animal
The heart, the certification of fitness number：SCXK(13)2002-0002.
2 experimental techniques
2.1 skin irritation test
Healthy new zealand rabbit (2.5 ± 0.3) kg 10 is taken, 24h is using electronic device and the depilatory (5% of having one's hair cut before test
Sodium sulfide) by rabbit spinal column both sides unhairing, go hair-fields area to be about 100cm2, 5 skin zero damages after unhairing 24h, are taken at random
Rabbit is as intact skin group；Damaged skin group is the disposable injection of hair removal section employing in other 5 depilation new zealand rabbits
Syringe needle will lose hair or feathers sterilization standardized " # " shape wound of skin, length and width about 5cm, with oozing of blood as degree.Respectively with outside ginsenoside Rg3
With preparation --- cream, tincture, gel (Rg3 concentration 30% is higher by 300 times than minimum effective dose 0.1%) uniform application
The back on the left of the rabbit, average thickness are about 1mm, observe the medication of each rabbit after administration respectively at 2h, 12h, 24h, 48h, 72h
Situation at skin；Ginsenoside Rg3's patch repeats above-mentioned experiment, and administering mode is docile and obedient, dosage 2x3cm2。
2.2 skin sensibiligens test health new zealand rabbit (2.5 ± 0.3) kg 30, male and female half and half.Before test
24h gives rabbit unhairing, and 6 groups are randomly divided into after unhairing 24h, i.e. intact skin high dose group (external preparation Rg3 concentration 30%), complete
It is whole skin low dose group (external preparation Rg3 concentration 0.1%), damaged skin high dose group (external preparation Rg3 concentration 30%), broken
Damage skin low dose group (external preparation Rg3 concentration 0.1%), intact skin matched group, damaged skin matched group.Damaged skin group
Using injection needleses head be in rabbit off hair sterilization skin on standardized " # " shape wound, length and width about 5cm, with oozing of blood as degree.
Intact skin matched group, damaged skin matched group difference apply bare substrate (not containing any medicine).Intact skin high dose group,
Damaged skin high dose group is left in rabbit with ginsenoside Rg3's external preparation (cream, or tincture, gel) uniform application respectively
Side back, average thickness are about 2mm, and intact skin low dose group, damaged skin low dose group use ginsenoside Rg3's external respectively
Preparation (cream, tincture, gel) uniform application back on the left of the rabbit, average thickness are about 1mm, aseptic with what is be of convenient length
Gauze and nonirritant immobilization with adhesive tape, every animal point cage are fed, and wash away residue with warm water after sticking 24h.Respectively at removal
1h after by reagent, 1 day, 2 days, 3 days, 7 days, observe and record the change of body weight, skin, hair, eye and the mucosa of animal, exhale
Suction, central nervous system, extremity activity and other poisoning manifestations.Ginsenoside Rg3's patch (high dose group Rg3%, low dose group
Rg30.1%) the above-mentioned experiment of repetition, administering mode are to stick, 2 × 3cm of dosage2。
2.3 Skin sensitization
Healthy Kunming white mice (20 ± 2) g 30, male and female half and half are randomly divided into ginsenoside Rg3's experimental group, blank right
According to group and positive controls, before administration, 24h is by back both sides symmetrical unhairing (3cm × 3cm).
Sensitization：By ginsenoside Rg3's experimental mice respectively with ginsenoside Rg3's external preparation (cream, or tincture, solidifying
Colloid) uniform application, average thickness is about 1mm, is applied to left dorsal hair removal section, with the sterile gauze being of convenient length with it is stingless
The immobilization with adhesive tape of sharp property, animal sub-cage rearing.Remove after 6h, residue is washed away with warm water.Take off on the left of blank control group mouse back
Commensurability bare substrate (not containing any medicine) is applied at hair；1%2,4- bis- is applied on the left of positive controls back part of animal at depilation
100 μ l of chloronitrobenzene acetone soln.It is repeated 1 times in the 7th day and the 14th day each group in addition.
Excite：Ginsenoside Rg3's experimental group after last sticks ginsenoside Rg3's (cream, or tincture, gel) 6h,
Remove them and residue is washed away with warm water, then ginsenoside Rg3's (cream, or tincture, gel) is applied to into right side depilation
Area, washes away medicine, observes at once after 6h, and is observed in 24h, 48h, 72h respectively and record skin allergy situation.It is positive right
Carry out exciting with same method with blank control group according to group and contact and observed and recorded.Sensitization degree is evaluated by scale.
Result of the test presses the scoring of skin wound repair standards of grading, calculates mean scores and is evaluated.Meanwhile, observe animal
Whether whole body allergy symptoms that asthma, astasia or shock etc. serious are had.Ginsenoside Rg3's patch is given in docile and obedient mode
Medicine, each step of the above-mentioned test of repetition, which is smeared and makes docile and obedient, 1 × 1cm of administration range into2。
3 experimental results
3.1 irritation test
After each rabbit medication, skin occurs without the red, abnormal phenomena such as swell, ooze out, and points out ginsenoside Rg3 equal to skin
Nonirritant reaction.
3.2 skin sensibiligens are tested
As a result show：Rabbit intact skin, damaged skin group contact ginsenoside Rg3's external preparation (cream, or tincture,
After gel, patch), the change of the body weight of animal, skin, hair, eye and mucosa, breathing, central nervous system, extremity activity
Exception is showed no, drug of topical application local has no the phenomenons such as erythema and edema, and consubstantiality left and right sides compares no abnormality seen reaction, compares indifference
Not.Illustrate ginsenoside Rg3's external preparation --- cream, or tincture, gel, patch to skin without acute toxic reaction.
3.3 Skin sensitization
As a result show：There are not the anaphylaxiss such as erythema, edema in ginsenoside Rg3's experimental group and blank control group.Sun
Property control administration 6h after, skin has erythema to be formed, and without edema, is 1.7 points by standards of grading, sensitization rate be 100%, 0h,
Still there is erythema when 24h, 48h, 72h, have no that edema occurs.Each group animal allergy meansigma methodss and sensitization rate result such as 5 institute of table
Show.Each group mice is showed no the serious whole body sensitivity response such as asthma, astasia or shock.Show ginsenoside Rg3's external
Preparation (cream, or tincture, gel, patch) is to skin without sensitivity response.
5 animal sensitivity response meansigma methodss of table and sensitization rate (n=10)
Claims (4)
1. the step of a kind of preparation method of external preparation, including order below is carried out：
1) get the raw materials ready according to following proportioning per 100ml gels：
2) carbomer is added in the deionized water of 50-60ml, 20 (R)-ginsenoside Rg3s of swelling rear addition, EDTA-Na2、
Essence, propylparaben, methyl hydroxybenzoate, stir, and are subsequently added into the sodium hydroxide that mass percent concentration is 10% molten
Liquid, adjusts the pH value of mixed solution to 5～7, stirs, be subsequently adding deionized water to 100ml.
2. preparation method as claimed in claim 1, is characterized in that described 20 (R)-ginsenoside Rg3 purity of raw material is 1%
～98%.
3. preparation method as claimed in claim 1 or 2, is characterized in that weight and 20 (the R)-people of 20 (R)-ginsenoside Rg3s
The ratio of the gross weight of ginseng saponin Rg3 and adjuvant is 0.01-10：100.
4. preparation method as claimed in claim 1 or 2, is characterized in that also including adding Radix Notoginseng, Aloe, Radix Glycyrrhizae, the Radix Polygoni Multiflori, silver
Fructus Pruni, Semen Sesami Nigrum extract, Rhizoma Zingiberis Recens extract, Semen Vitis viniferae extract, Megranate Seed P.E, plants essential oil, arbutin, vitamin C
And its one or more in derivant or Vitamin E and its derivant is mixed with 20 (R)-ginsenoside Rg3s, adjuvant.
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| CN1452629A (en) * | 2000-05-31 | 2003-10-29 | 科学技术振兴事业团 | Skin tissue regeneration prmoters comprising ginsenoside Rb1 |
| CN1569011A (en) * | 2003-07-24 | 2005-01-26 | 山东绿叶天然药物研究开发有限公司 | Application of 20(R)-ginsenoside-Rg3 in the preparing process of medicine for treating or preventing cardiovascular and cerebrovascular disease |
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| CN1883492B (en) * | 2006-05-22 | 2010-07-28 | 富力 | Water solution of 20(R)-ginsenoside Rg3 pharmaceutical composition and preparation method thereof |
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| CN1452629A (en) * | 2000-05-31 | 2003-10-29 | 科学技术振兴事业团 | Skin tissue regeneration prmoters comprising ginsenoside Rb1 |
| CN1569011A (en) * | 2003-07-24 | 2005-01-26 | 山东绿叶天然药物研究开发有限公司 | Application of 20(R)-ginsenoside-Rg3 in the preparing process of medicine for treating or preventing cardiovascular and cerebrovascular disease |
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| Title |
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| 人参果实汁液治疗白癜风初探;张理美;《山东医学高等专科学校学报》;20091231;第31卷(第6期);第417-418页 * |
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