CN108514555A - Application of the β-carypohyllene in preparing the antipruritic drug of prevention external preparation for skin - Google Patents
Application of the β-carypohyllene in preparing the antipruritic drug of prevention external preparation for skin Download PDFInfo
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- CN108514555A CN108514555A CN201810611636.8A CN201810611636A CN108514555A CN 108514555 A CN108514555 A CN 108514555A CN 201810611636 A CN201810611636 A CN 201810611636A CN 108514555 A CN108514555 A CN 108514555A
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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
- A61K31/01—Hydrocarbons
- A61K31/015—Hydrocarbons carbocyclic
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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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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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Application the present invention relates to β carypohyllenes as sole active agent in preparing the antipruritic drug of prevention external preparation for skin.Drug described in the application is made of β carypohyllenes and medically acceptable auxiliary material, wherein mass percentage of the β carypohyllenes in drug is 1.5%~6%.Drug of the present invention, which has, prevents uredo effect, can be used for preventing pruitus.
Description
Technical field
The present invention relates to the pharmaceutical products containing organic effective component, and in particular to the medicine containing bicyclic sesquiterpenoids
Object.
Background technology
Uredo reason mainly has bite by mosquitos, eczema, heat-rash, drug allergy, geroderma itch or certain
Skin allergy caused by interior department disease, wherein most commonly seen with dermatitis caused by bite by mosquitos.Itch and is considered reduction
Pain, at present clear itching and pain is conducted by different nerve pathways, is the feeling that different mechanisms generate, but is itched
Mechanism of production is not yet elucidated, and is mainly considered the endogenous stimulus such as histamine in body, bradykinin, protease substance and is deposited
It is multiple stimulus responsive teleneurons (itch receptor) effect of epidermis dermis boundary, the impulsion of generation is along spinal cord thalamus
Beam, thalamus, the conduction of corticocerebral sequence, thus generate the consciousness of itching form.Either itch caused by which kind of reason, can
Cause the sense of discomfort of human body, and the mental hygiene of human body can be influenced.Currently, various types of antipruritic agents are often malicious on the market
Side effect is larger, is weakened for a long time using rear antipruritic effect.
Carypohyllene is a kind of bicyclic sesquiterpenoids, there is a α-, β-, γ-three kinds of isomers, and the double bond of β-carypohyllene is suitable
Formula isomers is known as isocaryophyllene (isocarophyllene), and standard GB/T 2760-2014 approval β-carypohyllenes are to allow to make
Food flavor." β-carypohyllene " is also known as β-Allyl-4,3-guaiacol, english common name β-Caryophyllene, and molecular weight is
204.36, character is colourless to micro- yellow oily liquids, has light cloves like fragrance.Boiling point 119~121 DEG C (1466Pa).
It is dissolved in ether and ethyl alcohol, it is not soluble in water.Natural product are present in caryophyllus oil, clove-stems oil, cassia zeylanicum oil, cinnamon leaves oil, smoke clothing
In the essential oils such as careless oil, thyme linaloe oil, papper oil, pimento oil.The chemical structural formula of β-carypohyllene is as follows：
Existing research prompt, the pharmacological research of carypohyllene find to protect with antimicrobial antiphlogistic, antifertility and terminal pregnancy, bone
Shield reduces the effects that blood glucose, there is not yet the report of antipruritic aspect.
Invention content
The technical problem to be solved in the present invention is to provide the new applications of β-carypohyllene, i.e., the new opplication in pharmacy.
The above-mentioned new opplication in pharmacy is that β-carypohyllene is antipruritic in preparation prevention external preparation for skin as sole active agent
Drug in application.
In above application, the β-carypohyllene may be used conventional method and be extracted from natural plants, can also be by
Synthesis or other methods are made.
In above application, the drug is made of β-carypohyllene and medically acceptable auxiliary material, wherein β-carypohyllene
Mass percentage in drug is 1.5%~6%, most preferably 6%.
In above application, the drug can be clinically acceptable ointment or liniment.
The present invention measures β-carypohyllene to the inhibiting effect itched, and experimental method is in conjunction with the embodiments as described below.
Description of the drawings
Fig. 1 is various concentration β-carypohyllene ointment to licking the song of the influence result of body number inhibiting rate in mouse 10min
Line chart.
Specific implementation mode
Test 1 (the antipruritic experiment of ointment)
1 experimental animal：KM mouse (are purchased from Traditional Chinese Medicine University Of Guangzhou's Experimental Animal Center, animal quality certification number：SCXK
(Guangdong) 2013-0020) 50, it is divided into 5 groups, every group 10, half male and half female, weight (22-28g).
2 cause substance of itching：4-aminopyridine (4-AP) normal saline solution (injection volume 1mg.kg-1, prepared sample concentration
For 0.2mg.mL-1)。
3 reagents：Diphenhydramine bulk pharmaceutical chemicals (are purchased from Henan Tian Fu Chemical Co., Ltd.s, purity 99%), and β-carypohyllene (is purchased from
Sigma companies, purity：98.5%).
4 evaluation indexes：After 20min is administered, mouse is observed immediately and licking in the latent time and 10min of Licking response occurs
Body number (medicine-feeding part or shaving area), it is more than 3s by counting twice to lick the body time.
The preparation of 5 samples
The preparation of 5.1 bare substrate ointment
Prescription：
Atoleine 15.0g, albolene 5.0g, stearic acid 10.0g, glycerin monostearate 5.0g, triethanolamine
0.2g, lauryl sodium sulfate 0.2g, Tween-80 5.0g, glycerine 12.5g, ethyl hydroxy benzoate 0.1g distill appropriate amount of water, altogether
100.0g。
Preparation method：
Atoleine, albolene, stearic acid, glycerin monostearate is taken to be placed in beaker, in 75 DEG C of water-baths, melting
Afterwards, that is, oil phase is made, for use.Triethanolamine, lauryl sodium sulfate, Tween-80, glycerine, ethyl hydroxy benzoate, water is taken to be placed in another
In beaker, in 75 DEG C of water-baths, water phase is made, for use in dissolving.
Kept for 75 DEG C, by oil phase plus water oil phase, stirring while adding, until emulsification is complete, taking-up is stirred to room temperature, that is, made
At bare substrate ointment.Make blank control group, it is spare.
It is prepared by 5.2 various concentration β-carypohyllene ointment：
Three parts of β-carypohyllene, respectively 6.09g, 3.05g, 1.52g are weighed, matrix used presses the place of bare substrate ointment
Side, is dissolved in oil phase, preparation method is same as above 5.1 by β-carypohyllene.A concentration of 60mgg is respectively prepared-1、30mg·g-1、15mg·
g-1β-carypohyllene ointment, make the high, medium and low dosage group of β-carypohyllene respectively, it is spare.
5.3 positive drugs are that (Hefei cube pharmacy share is limited for bagodryl hydrochloride ointment (self-control) and paeonol unguentum
Company, lot number：20161207).Wherein, the preparation method of bagodryl hydrochloride ointment (self-control) is as follows：
Bagodryl hydrochloride 6.06g is weighed, matrix used presses the prescription of bare substrate ointment, bagodryl hydrochloride is dissolved in
Water phase, preparation method are same as above 5.1, and a concentration of 60mgg is made-1Bagodryl hydrochloride ointment 100g make positive drug group, it is standby
With.
6 antipruritic pharmacodynamics experimental methods
KM mouse 50, half male and half female is taken to be divided into 5 groups, every group 10, number (1-1,1-2,1-3 ... 5-10) is weighed
Weight is divided into blank group, positive drug group, β-high, medium and low dosage group of carypohyllene ointment.
With shaver, dorsal portion shaving, shaving area are 2.0 × 2.0cm behind the mouse right side, are smeared respectively at shaving position
Each administration group ointment.Positive drug group, β-high, medium and low dosage group of carypohyllene ointment is respectively with Mice Body restatement dosage：
0.3g·kg-1、0.3g·kg-1、0.15g·kg-1、0.075g·kg-1, it is 0.14g (flat with mouse that each group, which smears ointment amount,
Equal weight is that 27g is calculated), after 20min, in position hypodermic injection 4-AP solution 0.14mL, mouse is observed and recorded immediately
The number that injection site is later licked in 10min, it is more than 3s by counting twice to lick the body time.Refer to as antipruritic pharmacodynamic evaluation
Mark.
7 experimental results
Pharmacodynamic evaluation licks body number with 10min and takes statistics analysis.
Inhibiting rate calculation formula：
Inhibiting rate (%)=(blank control group licks body number-medicine group and licks body number)/blank control group lick body number ×
100%
1 various concentration β of table-carypohyllene ointment to licked in itch mouse 10min body number influence (N=10)
Note：Compared with model group,*P ＜ 0.05,**P ＜ 0.01.2 various concentration β of table-carypohyllene ointment is to itch mouse
Comparison result between body times influence each group is licked in 10min
Note：" ++ " represents P ＜ 0.01, and "+" represents P ＜ 0.05, and "-" represents no significant difference.
By table 1 and 2 result of table it is found that the more commercially available paeonol unguentum of antipruritic effect of self-control bagodryl hydrochloride ointment is good,
In order to ensure that the consistency of matrix used in each sample in experiment, this experiment select self-control bagodryl hydrochloride ointment to act on positive drug
Object group.
For positive drug group compared with blank control group, difference is statistically significant, shows modeling success.β-carypohyllene ointment
High dose group is compared with blank control, and the inhibiting rate that body number is licked in itch mouse 10min is 55.0%, and difference has statistics
Meaning, and it is more significant；β-carypohyllene ointment high dose group compares no significant difference with positive drug group, shows that the two is stopped
Effect of itching is almost the same；In β-carypohyllene ointment, low dose group compared with blank control group, body time is licked in itch mouse 10min
Several inhibiting rates is respectively 38.2% and 22.9%, and difference has statistical significance.Show β-carypohyllene ointment itching-relieving action effect
Fruit is apparent.
β-carypohyllene ointment dosage is different, and antipruritic effect has difference, and is presented between dosage and antipruritic effect a certain amount of
Effect relationship.
8 β-carypohyllene dose-effect relationships are investigated
8.1 implementation
Empirically " 5.2 " preparation method under 1, prepares β-carypohyllene ointment of 5 kinds of various concentrations, and concentration is respectively
10mg·g-1、15mg·g-1、30mg·g-1、45mg·g-1、60mg·g-1.Empirically " 6 " method under 1 is every group tested small
Mouse is 10, and under the conditions of recording various concentration, β-carypohyllene ointment in itch mouse 10min to licking body number.With each dense
The inhibiting rate for licking body number in degree group in mouse 10min is ordinate, and a concentration of abscissa of β-carypohyllene ointment is mapped, seen
Examine dose-effect relationship.
8.2 dose-effect relationships investigate result
According to the experimental result recorded, with each concentration group to the inhibiting rate for licking body number in itch mouse 10min
For ordinate, a concentration of abscissa mapping of β-carypohyllene ointment, the result is shown in Figure 1 are smeared.
By the above experimental result it is found that β-carypohyllene administration concentration is from 10mgg-1Increase to 15mgg-1When to mouse
The influence that body number is licked in 10min is little；And administration concentration increases to 45mgg-1When to licking the shadow of body number in mouse 10min
Sound is larger；When administration concentration is from 45mgg-1Increase to 60mgg-1When, antipruritic effect be basically unchanged and with positive drug only
Effect of itching reaches unanimity.Thus illustrate, β-carypohyllene is to licking body number inhibiting rate in 10mgg in mouse 10min-1To 60mg
g-1Concentration range in increase with the increase of concentration, and antipruritic effect in a certain range be in dose-effect relationship.
Test 2 (the antipruritic experiments of liniment)
1 experimental animal：KM mouse (are purchased from Traditional Chinese Medicine University Of Guangzhou's Experimental Animal Center, animal quality certification number：SCXK
(Guangdong) 2013-0020) 50, it is divided into 5 groups, every group 10, half male and half female, weight (22-28g).
2 cause substance of itching：4-aminopyridine (4-AP) normal saline solution (injection dosage 1mgkg-1, prepared solution
A concentration of 0.2mgmL-1)。
3 reagents：Diphenhydramine bulk pharmaceutical chemicals (are purchased from Henan Tian Fu Chemical Co., Ltd.s, purity 99%), and β-carypohyllene (is purchased from
Sigma companies, purity：98.5%).
4 evaluation indexes：After 20min is administered, observes in mouse 10min lick body number (medicine-feeding part or shaving immediately
Area), licking the body time, to be more than 3s count twice by licking body.
The preparation of 5 samples
It is prepared by 5.1 vehicle solutions：Absolute ethyl alcohol 15mL, distilled water 33mL, Tween-80 2mL is measured respectively to be placed in
In the conical flask with cover of 100mL, shake up to get vehicle solution 50mL.
It is prepared by 5.2 various concentration β-carypohyllene liniment：β-carypohyllene 3.05g, 1.52g, 0.76g is weighed to be respectively placed in
In the conical flask with cover of 100mL, vehicle solution 50mL is added in precision, and it is respectively 60mgmL to shake up to get concentration-1、
30mg·mL-1、15mg·mL-1β-carypohyllene liniment 50mL.
It is prepared by 5.3 positive drug groups：Bagodryl hydrochloride 3.03g is weighed, is placed in the conical flask with cover of 100mL, it is accurate
Vehicle solution 50mL is added to make it dissolve, shakes up to get a concentration of 60mgmL-1 bagodryl hydrochlorides liniment 50mL.
6 experimental methods
KM mouse 50 are taken, are divided into 5 groups, every group 10, weighed weight, respectively blank control group, positive drug group, β-
The high, medium and low dosage group of carypohyllene liniment.
With shaver, dorsal portion shaving, shaving area are 2.0 × 2.0cm behind the mouse right side, are smeared respectively at shaving position
Each administration group liniment.Positive drug group, β-high, medium and low dosage group of carypohyllene liniment is respectively with Mice Body restatement dosage：
0.3g·mL-1、0.3g·mL-1、0.15g·mL-1、0.075g·mL-1, it is 0.14mL (average with mouse that each group, which smears liniment amount,
Weight is that 27g is calculated), after 20min, 4-AP solution 0.14mL are subcutaneously injected at the position, observe and record mouse 10min immediately
Interior later to lick the number of injection site, it is more than 3s by counting twice to lick the body time.As antipruritic pharmacodynamics evaluation index.
7 experimental results
Pharmacodynamic evaluation licks body number with 10min and takes statistics analysis.Inhibiting rate calculation formula：
Inhibiting rate (%)=(blank control group licks body number-medicine group and licks body number)/blank control group lick body number ×
100%
Experimental result is shown in Table 3
3 various concentration β of table-carypohyllene liniment to licked in itch mouse 10min body number influence (N=10)
Note：Compared with model group,*P ＜ 0.05,**P ＜ 0.01.
4 various concentration β of table-carypohyllene liniment is between comparison result licking body times influence each group in itch mouse 10min
Note：" ++ " represents P ＜ 0.01, and "+" represents P ＜ 0.05, and "-" represents no significant difference.
As may be known from Table 3 and Table 4, β-carypohyllene liniment difference compared with blank control group has statistical significance (P ＜
0.05), illustrate that β-carypohyllene liniment itching-relieving action is with obvious effects.
From the above data, compared with blank control group, β-carypohyllene liniment high dose group and positive drug group 10min
Interior itch inhibiting rate is respectively 61.2% and 62.0%, and difference all has statistical significance (P ＜ 0.01)；β-carypohyllene liniment is high
Dosage group compares no significant difference with positive drug group；Itch suppression in β-carypohyllene liniment middle dose group and low dose group 10min
Rate processed is respectively 39.5% and 22.5%, and difference has statistical significance (P ＜ 0.05).
Claims (4)
1. application of the β-carypohyllene as sole active agent in preparing the antipruritic drug of prevention external preparation for skin.
2. application according to claim 1, it is characterised in that：The drug is by β-carypohyllene and medically acceptable
Auxiliary material forms, and wherein mass percentage of the β-carypohyllene in drug is 1.5%~6%.
3. application according to claim 2, it is characterised in that：Mass percentage of the β-carypohyllene in drug
It is 6%.
4. according to the application described in right 1,2 or 3, which is characterized in that the drug is ointment or liniment.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810611636.8A CN108514555A (en) | 2018-06-14 | 2018-06-14 | Application of the β-carypohyllene in preparing the antipruritic drug of prevention external preparation for skin |
| PCT/CN2018/106886 WO2019237555A1 (en) | 2018-06-14 | 2018-09-21 | Application of β-caryophyllene to prepare external remedy for relieving skin itching |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810611636.8A CN108514555A (en) | 2018-06-14 | 2018-06-14 | Application of the β-carypohyllene in preparing the antipruritic drug of prevention external preparation for skin |
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| CN108514555A true CN108514555A (en) | 2018-09-11 |
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| WO (1) | WO2019237555A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110101688A (en) * | 2019-05-08 | 2019-08-09 | 广州中医药大学(广州中医药研究院) | α-carypohyllene is preparing the application in the antipruritic external drug of skin |
| WO2019237555A1 (en) * | 2018-06-14 | 2019-12-19 | 广州中医药大学 | Application of β-caryophyllene to prepare external remedy for relieving skin itching |
| CN112107563A (en) * | 2020-10-19 | 2020-12-22 | 中国科学院动物研究所 | Compound for influencing cold feeling of human and animal and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07215846A (en) * | 1994-01-28 | 1995-08-15 | Takeda Chem Ind Ltd | Antiallergic agent |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107746367B (en) * | 2017-11-07 | 2020-05-26 | 清华大学 | β -caryophyllene derivative and preparation method and application thereof |
| CN108514555A (en) * | 2018-06-14 | 2018-09-11 | 广州中医药大学(广州中医药研究院) | Application of the β-carypohyllene in preparing the antipruritic drug of prevention external preparation for skin |
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2018
- 2018-06-14 CN CN201810611636.8A patent/CN108514555A/en active Pending
- 2018-09-21 WO PCT/CN2018/106886 patent/WO2019237555A1/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07215846A (en) * | 1994-01-28 | 1995-08-15 | Takeda Chem Ind Ltd | Antiallergic agent |
Non-Patent Citations (3)
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| CÍCERA DATIANE DE MORAISOLIVEIRA-TINTINO: "Anti-inflammatory and anti-edematogenic action of the Croton campestris A. St.-Hil (Euphorbiaceae) essential oil and the compound β-caryophyllene in in vivo models", 《PHYTOMEDICINE》 * |
| 李明亚主编: "《临床药物治疗学》", 31 August 2015, 中国医药科技出版社 * |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019237555A1 (en) * | 2018-06-14 | 2019-12-19 | 广州中医药大学 | Application of β-caryophyllene to prepare external remedy for relieving skin itching |
| CN110101688A (en) * | 2019-05-08 | 2019-08-09 | 广州中医药大学(广州中医药研究院) | α-carypohyllene is preparing the application in the antipruritic external drug of skin |
| CN112107563A (en) * | 2020-10-19 | 2020-12-22 | 中国科学院动物研究所 | Compound for influencing cold feeling of human and animal and application thereof |
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| WO2019237555A1 (en) | 2019-12-19 |
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Application publication date: 20180911 |