CN109498604A - Geraniol new application prevents and treats the preparation and method of pruritus caused by non-disease - Google Patents
Geraniol new application prevents and treats the preparation and method of pruritus caused by non-disease Download PDFInfo
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- CN109498604A CN109498604A CN201811582011.XA CN201811582011A CN109498604A CN 109498604 A CN109498604 A CN 109498604A CN 201811582011 A CN201811582011 A CN 201811582011A CN 109498604 A CN109498604 A CN 109498604A
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- geraniol
- pruritus
- pharmaceutical composition
- itch
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
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Abstract
本发明公开了香叶醇或其药学上可接受的辅料用于制备预防和治疗瘙痒症的药物组合物的用途；及一种预防和治疗非疾病引起的瘙痒症的方法，用本发明提供的药物组合物或配制品进行个体给药；本发明提供了香叶醇或其药学上可接受的辅料用于制备预防和治疗瘙痒症的药物组合物的用途、及预防和治疗瘙痒症的配制品及方法。
The invention discloses the use of geraniol or its pharmaceutically acceptable excipients for preparing a pharmaceutical composition for preventing and treating pruritus; and a method for preventing and treating pruritus caused by non-diseases. The pharmaceutical composition or formulation is administered to individuals; the present invention provides the use of geraniol or its pharmaceutically acceptable adjuvant for preparing a pharmaceutical composition for preventing and treating pruritus, and a formulation for preventing and treating pruritus and method.
Description
Technical field
The present invention relates to biomedicine field more particularly to geraniol new applications, prevent and treat scabies caused by non-disease
Itch the preparation and method of disease.
Background technique
Itch be it is a kind of it is common make one to generate offending feeling, often occur together scratching, is many systemic diseases and skin
The cardinal symptom of skin disease can seriously affect the physical and mental health of patient, reduce quality of life.Severe pruritus is mostly by kidney, bile
Disease and drug side-effect cause, and chronic, serious itch is in addition to above-mentioned disease, also it occur frequently that in skins such as atopic dermatitis
Skin disease.Itch can directly be caused by skin chemical medium, can also be caused by the variation of physical factor (such as temperature), Jin Eryin
Play the peripheral nerve fiber even reaction of central nervous system.
The generation of itch is a complicated, multifactor effect as a result, complex genesis, and causes a disease there are many uncertain
Factor causes the treatment of this disease very intractable, and the course of disease is long, touching refractory.Clinical trials difficult still faces without effect method at present
Bed is mainly based on antihistamine H1 and bisfentidine, glucocorticoid, immunological regulation and local UV irradiation treatment, but Chang Yin
Occur adverse reaction can not prolonged application, have no progeny between treatment, itch recurs rapidly.
Geraniol (Geraniol), also known as " Geraniol " are a kind of naturally occurring non-annularity monoterpenes (Fig.1),
Pure and mild ether can be dissolved in.Geraniol is naturally present in yak Miao Ke Pelargonium fish pelargonium, He Shui section Cymbopogon cymbopogon distans, Lauraceae
The grey son in the fruit mountain storehouse of Litsea cubeb litsen tree, grass family lemongrass, the flower of rosaceae Rosa rose and the palm more than the 250 kinds of plants such as rare
In object, it is widely used in the fields such as drug, tobacco, food ingredient.
Modern medical research has found that geraniol has extensive pharmacological action, have anti-inflammatory, antibacterial, it is antimycotic, anti-oxidant,
A variety of pharmacological properties such as antitumor, can be with a variety of diseases such as Reduce allergy asthma, enteritis, Parkinson's disease, depression.China is
There is the listing of geraniol capsule and pill, is mainly used for the prevention and treatment of tracheobronchitis disease, shows that this monomer of geraniol can be used as medicine
The safety of object.Research is it is also shown that geraniol has antihistamine effect.In addition, research and this seminar early period in recent years
The study found that geraniol has significant analgesic activity.
The Chinese patent of Publication No. CN107595823A, the new application of geraniol provide geraniol and treat in preparation
Purposes in the drug of mastadenitis of cow and containing geraniol or pharmaceutical composition.Geraniol is used for mastadenitis of cow, medicine
Effect is clear；Geraniol belongs to pure natural preparation, handles without organic solvent, securely and reliably；Small toxicity is used for a long time without bad anti-
It answers；The invention can repair the breast tissue of infection, be suitable for acute, subacute and chronic milk cow clinical mastitis.
But there are no geraniol reports directly relevant to pruritus for the prior art.
The Chinese patent of Publication No. CN106726871A, sweet wormwood mosquito-expelling and antipruritic floral water and preparation method thereof, discloses
A kind of sweet wormwood mosquito-expelling and antipruritic floral water and preparation method thereof.The sweet wormwood mosquito-expelling and antipruritic floral water is according to the mass fraction by with the following group
It is grouped as: 65-85 parts of sweet wormwood extracting solution, 0.5-5.0 parts of aromatic oil from Chinese pepper, 0.5-3.0 parts of cinnamon oil, 1-4 parts of citronellal, spiceleaf
1-4 parts of alcohol, 1-4 parts of wintergreen, 1-5 parts of peppermint oil, 5-10 parts of isopropyl myristate.By the sweet wormwood extracting solution of formula ratio with match
The essential oil and remaining ingredient just measured are uniformly mixed, and sweet wormwood mosquito-expelling and antipruritic floral water is made in filtering.Sweet wormwood mosquito repellent of the invention
Antipruritus toilet water preparation mosquito repellent ability is strong, and scattering ratio 95.3%, antipruritic effect is good, can effectively alleviate scabies brought by mosquito bite
Itch and red and swollen, natural safety, long-time service has no toxic and side effect to human body, and preparation method is simple, is conducive to large-scale production.The patent,
Only use geraniol in the Chinese herbal medicine of compounding, but the effect of geraniol and the antipruritic mechanism of antipruritus toilet water and unknown
Really.
In conclusion there are no the direct relations of open geraniol and itch for the prior art, also without the height for itch
Imitate drug.
Summary of the invention
In view of the above technical problems, the present invention provides geraniols or its pharmaceutically acceptable auxiliary material to be used to prepare prevention
With the purposes of the pharmaceutical composition for the treatment of pruritus and the preparation and method of prevention and treatment pruritus.
The first aspect of the invention, provides geraniol or its pharmaceutically acceptable auxiliary material is used to prepare prevention and controls
Treat the purposes of the pharmaceutical composition of pruritus.
Preferably, described pharmaceutical composition is injection, oral, topical administration preparation；It is further preferred that the drug
Composition is hypodermic preparation.
Preferably, the auxiliary material includes corn oil.
Preferably, the pruritus includes histamine dependence itch, non-histamine dependence itch, allergic contact dermatitis
The chronic itch of chronic itch, xerodermia.
Preferably, daily administration dosage of the described pharmaceutical composition in terms of geraniol is not less than 15mg/kg.
Preferably, histamine dependence itch, non-histamine dependence itch are prevented and treated, compositions are in terms of geraniol
Daily administration dosage is not less than 25mg/kg；It is further preferred that being 25mg/kg, 50mg/kg, 100mg/kg, 200mg/kg.
Preferably, the chronic itch of allergic contact dermatitis, the chronic itch of xerodermia, compositions are prevented and treated
Daily administration dosage in terms of geraniol is not less than 30mg/kg；It is further preferred that being 200mg/kg.
The second aspect of the invention provides a kind of for preventing and treating the preparation of pruritus, the preparation
Including geraniol.
Preferably, the preparation includes stop itching spray agent, antipruritic medicated soap, antipruritic ointment.
The third aspect of the invention provides a kind of method for preventing and treating pruritus, with medicine group of the invention
It closes object or preparation carries out individual administration.
Preferably, pharmaceutical composition or the daily dosage of preparation are calculated as with geraniol not less than 15mg/kg.
Compared with prior art, technical solution of the present invention has the advantage that the new use the present invention provides geraniol
On the way, the purposes be itch caused by pruitus, including disease factor caused by treating and preventing a variety of causes and non-disease because
Itch caused by element；The present invention still further provides drug and preparation containing geraniol, for treating, preventing skin scabies
Itch, provides efficient drug, preparation and method to be antipruritic.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
Some embodiments of invention without any creative labor, may be used also for those of ordinary skill in the art
To obtain other drawings based on these drawings.
Fig. 1 is the result that 5 groups of mouse scratching number in the embodiment of the present invention 2 changes over time；
Fig. 2 is the result of 5 groups of mouse scratching number statistics in the embodiment of the present invention 2；
Fig. 3 is the result that 5 groups of mouse scratching number in the embodiment of the present invention 3 changes over time；
Fig. 4 is the result of 5 groups of mouse scratching number statistics in the embodiment of the present invention 3；
Fig. 5 is the result of 2 groups of mouse scratching number statistics in the embodiment of the present invention 4；
Fig. 6 is the result of 2 groups of mouse scratching number statistics in the embodiment of the present invention 5.
Specific embodiment
It is described further below with reference to technical effect of the attached drawing to design of the invention, specific structure and generation, with
It is fully understood from the purpose of the present invention, feature and effect.
Embodiment 1 prepares antipruritic agent composition
Geraniol is dissolved in corn oil, and using 4 kinds of different gradient administrations, wherein the dosage of geraniol is 25mg/
kg、50mg/kg、100mg/kg、200mg/kg。
2 geraniol of embodiment is for treating histamine dependence itch
1. Experimental Animals and reagent
Mouse: the SPF grade male C57BL/6 mouse that this experiment uses, 8-10 week old, weight 16-20g (Shanghai Si Laike
Experimental animal Co., Ltd).Rearing conditions are cleaning grade, 5-6/cage, any to supply water.Experimental animal complete randomized point
Group.
Reagent: corn oil, antipruritic agent composition prepared by embodiment 1, compound 48/80 (synthesis 48/80, article No.
C2313)。
2. the method for establishing histamine dependence itch model
Male C57BL/6 mouse is selected, the nape of the neck intracutaneous injection compound 48/80, mouse shows in 30min after modeling
The scratching behavior of work.
3. experimental method
Experimental group: establish 15min intraperitoneal injection different dosing dosage geraniol before histamine dependence itch model (25,50,
100,200mg/kg), histamine dependence itch model is established in the nape of the neck intracutaneous injection 48/80 after 15min.
Control group: establishing 15min intraperitoneal injection corn oil before histamine dependence itch model, and the nape of the neck is intradermal after 15min
Histamine dependence itch model is established in injection 48/80.
The number that mouse scratches injection site or coating position with hind leg is observed, mouse completion is injected from hind leg scratching is lifted
Position is primary scratching to hind leg overall process is put down, and observes 30min, every 10min counting is primary, and counts total scratching number.
4. result
Experimental data is indicated with mean ± standard error (mean ± SEM), is counted using SPSS16.0 software, using list
Analysis of variance (one way ANOVA).Think that difference has conspicuousness with P < 0.05.
As shown in Figure 1 and Figure 2, the shadow that intraperitoneal injection different dosing dosage geraniol causes mouse scratching behavior to 48/80
It rings, data show average value ± standard error (n=8), * * p < 0.01, * * * p < 0.001v.s. corn oil.As it can be seen that different dosing amount is fragrant
Leaf-alcohol causes mouse scratching behavior to have statistical difference compared with corn oil, to 48/80.Therefore, geraniol can significantly delay
Solve histamine dependence itch.
3 geraniol of embodiment is for treating non-histamine dependence itch experiment
1. Experimental Animals and reagent
Mouse: the SPF grade male C57BL/6 mouse that this experiment uses, 8-10 week old, weight 16-20g (Shanghai Si Laike
Experimental animal Co., Ltd).Rearing conditions are cleaning grade, 5-6/cage, any to supply water.Experimental animal complete randomized point
Group.
Reagent: corn oil, antipruritic agent composition prepared by embodiment 1,200ug/50ul chloroquine (Chloroquine,
CQ, article No. C6628).
2. establishing non-histamine dependence itch model
Male C57BL/6 mouse is selected, the nape of the neck intracutaneous injection chloroquine, significantly scratching occurs in mouse in 30min after modeling
Grab behavior.
3. administration
Experimental group: establish 15min intraperitoneal injection different dosing dosage geraniol before non-histamine dependence itch model (25,
50,100,200mg/kg), the nape of the neck intracutaneous injection chloroquine establishes non-histamine dependence itch model after 15min.
Control group: 15min intraperitoneal injection corn oil before non-histamine dependence itch model, the nape of the neck skin after 15min are established
Interior injection chloroquine establishes non-histamine dependence itch model.
The number that mouse scratches injection site or coating position with hind leg is observed, mouse completion is injected from hind leg scratching is lifted
Position is primary scratching to hind leg overall process is put down, and observes 30min, every 10min counting is primary, and counts total scratching number.
4. result
Experimental data is indicated with mean ± standard error (mean ± SEM), is counted using SPSS16.0 software, using list
Analysis of variance (one way ANOVA).Think that difference has conspicuousness with P < 0.05.
As shown in Figure 3, Figure 4, intraperitoneal injection different dosing dosage geraniol causes histamine dependent/non-dependent mouse model small
Mouse scratches the influence of behavior, and * * p < 0.01, * * * p < 0.001v.s. corn oil are as it can be seen that different dosing dosage geraniol and corn
Oil is compared, and causes mouse scratching behavior to have statistical difference CQ.Therefore, geraniol can significantly alleviate non-histamine dependence
Itch.
4 geraniol of embodiment is for treating the chronic itch of allergic contact dermatitis
1. Experimental Animals and reagent
Mouse: the SPF grade male C57BL/6 mouse that this experiment uses, 8-10 week old, weight 16-20g (Shanghai Si Laike
Experimental animal Co., Ltd).Rearing conditions are cleaning grade, 5-6/cage, any to supply water.Experimental animal complete randomized point
Group.
Reagent: corn oil, antipruritic agent composition prepared by embodiment 1,2,4-dinitrofluorobenzene (2,4-
Dinitrofluorobenzene, DNFB, article No. D1529)
2. construct the chronic itch model of ACD contact dermatitis: experiment first 3 days, mouse web portion, skin of neck shaving (2cm ×
2cm).DNFB is dissolved in acetone, 0.5%, 0.25% two kind of concentration is divided into.DNFB group: shift to an earlier date 5 days for 50 μ l 0.5%DNFB
Solution is applied to mouse web portion shaving position, this stage is the Sensitization stage；It is every at the 1st, 3,5,7 day respectively after 5 days
30 μ l 0.25%DNFB solution are applied to mouse neck shaving position by it, this stage is the Challenge stage；Last time is smeared
After medicine, record and scratching number of the mouse in 60min that count.
3. administration
Experimental group: geraniol (200mg/kg) is injected intraperitoneally in the Challenge stage once a day, and totally 7 days.
Control group: corn oil is injected intraperitoneally in the Challenge stage once a day, and totally 7 days.
The number that mouse scratches injection site or coating position with hind leg is observed, mouse completion is injected from hind leg scratching is lifted
Position is primary scratching to hind leg overall process is put down, and observes 60min.Blind Test after being recorded with DV, every 10min is counted once, and is united
Count total scratching number.
4. result
Experimental data is indicated with mean ± standard error (mean ± SEM), is counted using SPSS16.0 software, using t
It examines for statistical analysis.Think that difference has conspicuousness with P < 0.05.
As a result as shown in figure 5, influence of the intraperitoneal injection geraniol to the scratching behavior of DNFB model mice, data show average value
± standard error (n=8) * * p < 0.01v.s. corn oil.As it can be seen that geraniol causes mouse scratching row compared with corn oil, to DNFB
For with statistical difference.Therefore, geraniol can the chronic itch of significant Reduce allergy contact dermatitis.
5 geraniol of embodiment is for treating the chronic itch of xerodermia
1. Experimental Animals and reagent
Mouse: the SPF grade male C57BL/6 mouse that this experiment uses, 8-10 week old, weight 16-20g (Shanghai Si Laike
Experimental animal Co., Ltd).Rearing conditions are cleaning grade, 5-6/cage, any to supply water.Experimental animal complete randomized point
Group.
Reagent: corn oil, antipruritic agent composition prepared by embodiment 1, acetone/diethyl ether mixed liquor (1: 1) and water mixing
Liquid (AEW)
2. establishing the chronic model of itching of xerodermia: first 3 days of experiment, mouse skin of neck shaving (2cm × 2cm).By cotton
Flower is impregnated with acetone and ether mixed liquor (1:1), is wiped shaving position 30s with cotton, is then crossed with distilled water immersion rapidly
Cotton wipes shaving position 30s.Daily coating twice (9:00 and 17:00), is total to coating 5 days.After last time coating, record simultaneously
Count scratching number of the mouse in 60min.
3. administration
Experimental group: 15min intraperitoneal injection geraniol (200mg/kg) before daily modeling, totally 5 days.
Control group: 15min intraperitoneal injection corn oil before daily modeling, totally 5 days.
The number that mouse scratches injection site or coating position with hind leg is observed, mouse completion is injected from hind leg scratching is lifted
Position is primary scratching to hind leg overall process is put down, and observes 60min.Blind Test after being recorded with DV, every 10min is counted once, and is united
Count total scratching number.
4. result
Experimental data is indicated with mean ± standard error (mean ± SEM), is counted using SPSS16.0 software, using t
It examines for statistical analysis.Think that difference has conspicuousness with P < 0.05.
As a result as shown in fig. 6, chamber inject geraniol to xerodermia AEW model mice scratching behavior influence, * * p <
0.01v.s. corn oil.As it can be seen that geraniol causes mouse scratching behavior to have statistical difference compared with corn oil, to AEW.Cause
This, geraniol can significantly alleviate the chronic itch of xerodermia.
In conclusion the present invention gives geraniol and is treated, it was demonstrated that geraniol by preparing acute and chronic itch model
For the multiple types such as histamine dependence, histamine dependent/non-dependent severe pruritus and allergic contact dermatitis, xerodermia
Chronic itch etc. all there is good itching-relieving action.The present invention is that prevention and treatment itch verifies new method, creatively uses geraniol
In preparing antipruritic drug, which can be used for various types of itch in clinic, including acute and chronic itch, curative effect are true
It cuts, has broad application prospects and stronger practical application value.
The preferred embodiment of the present invention has been described in detail above.It should be appreciated that those skilled in the art without
It needs creative work according to the present invention can conceive and makes many modifications and variations.Therefore, all technologies in the art
Personnel are available by logical analysis, reasoning, or a limited experiment on the basis of existing technology under this invention's idea
Technical solution, all should be within the scope of protection determined by the claims.
Claims (10)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811582011.XA CN109498604A (en) | 2018-12-24 | 2018-12-24 | Geraniol new application prevents and treats the preparation and method of pruritus caused by non-disease |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811582011.XA CN109498604A (en) | 2018-12-24 | 2018-12-24 | Geraniol new application prevents and treats the preparation and method of pruritus caused by non-disease |
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| CN201811582011.XA Pending CN109498604A (en) | 2018-12-24 | 2018-12-24 | Geraniol new application prevents and treats the preparation and method of pruritus caused by non-disease |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009114139A2 (en) * | 2008-03-11 | 2009-09-17 | President And Fellows Of Harvard College | Methods, compositions, and kits for treating pain and pruritis |
| CN106995760A (en) * | 2017-04-21 | 2017-08-01 | 铜仁学院 | A kind of antianaphylactic anti-inflammatory camellia tea oil hair soap |
-
2018
- 2018-12-24 CN CN201811582011.XA patent/CN109498604A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009114139A2 (en) * | 2008-03-11 | 2009-09-17 | President And Fellows Of Harvard College | Methods, compositions, and kits for treating pain and pruritis |
| CN106995760A (en) * | 2017-04-21 | 2017-08-01 | 铜仁学院 | A kind of antianaphylactic anti-inflammatory camellia tea oil hair soap |
Non-Patent Citations (4)
| Title |
|---|
| R PALKAR等: "Cooling Relief of Acute and Chronic Itch Requires TRPM8 Channels and Neurons", 《JOURNAL OF INVESTIGATIVE DERMATOLOGY》 * |
| STANDER S等: "Novel TRPM8 agonist cooling compound against chronic itch: results from a randomized, double-blind, controlled, pilot study in dry skin", 《JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY》 * |
| 姚静: "《药用辅料应用指南》", 31 August 2011, 中国医药科技出版社 * |
| 李仪奎主编: "《中药药理实验方法学》", 31 October 2006, 上海科学技术出版社 * |
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Application publication date: 20190322 |