CN108686213A - Application of the cold sensation channel agonist in promoting body cold acclimatization ability - Google Patents
Application of the cold sensation channel agonist in promoting body cold acclimatization ability Download PDFInfo
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- CN108686213A CN108686213A CN201810760093.6A CN201810760093A CN108686213A CN 108686213 A CN108686213 A CN 108686213A CN 201810760093 A CN201810760093 A CN 201810760093A CN 108686213 A CN108686213 A CN 108686213A
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- cold
- channel agonist
- cold sensation
- sensation channel
- menthol
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- 230000035807 sensation Effects 0.000 title claims abstract description 59
- 230000001737 promoting effect Effects 0.000 title claims abstract description 7
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- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims abstract description 32
- 229940041616 menthol Drugs 0.000 claims abstract description 32
- WTEVQBCEXWBHNA-UHFFFAOYSA-N Citral Natural products CC(C)=CCCC(C)=CC=O WTEVQBCEXWBHNA-UHFFFAOYSA-N 0.000 claims abstract description 27
- 229940043350 citral Drugs 0.000 claims abstract description 24
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/11—Aldehydes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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Abstract
The invention belongs to food and medicine fields, are related to application of the cold sensation channel agonist in promoting body cold acclimatization ability.Cold sensation channel agonist includes TRPM8 agonists and/or TRPA1 agonists.TRPM8 agonists are selected from the one or more of menthol, citral, linalool, eugenol and eucalyptol.It is one or more that TRPA1 agonists are selected from cinnamic acid, mustard oil, allicin, capsiate, carvacrol, eugenol, pipering, gingerol, methyl salicylate, caryophyllus oil, citral and menthol.
Description
Technical field
The invention belongs to food and medicine fields, are related to cold sensation channel agonist in promoting body cold acclimatization ability
Using.
Background technology
The channel transient receptor potential (transient receptor potential, TRP) is a kind of positioned at cell membrane
On cationic channel, it includes multiple members, be generally divided into 7 subfamilies (TRPC, TRPA, TRPM, TRPV, TRPN,
TRPP and TRPML), it is the important molecule that body experiences external environment stimulation.TRPV subfamily members TRPV1 in TRP families,
TRPV2, TRPV3, TRPV4, TRPM subfamily member TRPM8 and TRPA subfamily member TRPA1 ion channels by valtage-gated,
And temperature and ligand can then realize the adjusting to passage switching by changing voltage, therefore these subfamilies are considered as temperature
The participant that perception and temperature are adjusted.Wherein, TRPM8 can perceive 8~28 DEG C of temperature, for perceiving nice and cool and behavior body temperature
It adjusts, also assists in the cryalgesia of the analgesic activity and certain neurons of cold mediation;TRPA1 can perceive 17 DEG C of temperature below, and
Participate in the pain sensation and cryalgesia allergy that perception mechanically and chemically induces.The two is receptor of the body to cold, is body creeping chill
Feel channel.
Cold environment threatens the health and work capacity of human body, and frostbite, hypothermia, immersion foot and trench foot etc. can be caused cold
Damage, can also promote the occurrence and development of hypertension, cerebral apoplexy and kinds cancer, meanwhile, it can also cause alertness, cognition energy
The different degrees of brain body work capacity such as power and the decline of accurate operation ability declines, and has seriously affected psychro-environment people's lives
And work.In physiological tolerance limit, human body for a long time in cold environment live by (generally 4~6 weeks), receives repeatedly medium strong
The cold stimulation of degree, human body may occur in which a series of variations, show as cold stress reaction (such as shiver with cold, skin vasoconstriction, increased heart rate
Deng) gradually weaken, metabolic heat production increases, heat dissipation capacity is reduced, cold-resistant and freezing tolerance is remarkably reinforced, and this variation is known as cold habit
Clothes, cold acclimatization can reduce the generation of Cold water stress, mitigate the degree of Cold water stress.The method for improving tolerance to cold effective at present be into
Row cold acclimatization is trained, and in standard GJB 2562-96, is taken exercise by long-distance running and/or cold water and/or cold air is tempered to improve people
Body tolerance to cold.Also there is research (referring to the Chinese patent application of Publication No. 106674305A) use with trans-ferulaic acid -4-
Beta-glucosidase improves the tolerance to cold of body as product made of active constituent.
Invention content
Present invention aims to cold sensation channel (TRPM8 and TRPA1) agonist to promote body cold acclimatization energy
Power.
In order to achieve the above object, the present invention uses following technical scheme:
Application of the cold sensation channel agonist in promoting body cold acclimatization ability, the cold sensation channel agonist include
TRPM8 agonists and/or TRPA1 agonists.
Preferably, the TRPM8 agonists are selected from one kind of menthol, citral, linalool, eugenol and eucalyptol
Or it is a variety of.
Preferably, the TRPA1 agonists are selected from cinnamic acid, mustard oil, allicin, capsiate, carvacrol, cloves
Phenol, pipering, gingerol, methyl salicylate, caryophyllus oil, citral and menthol are one or more.
Preferably, the cold sensation channel agonist is menthol.
Further preferably, the cold sensation channel agonist is the mixture of menthol and citral.
Preferably, by body is applied to by the product of active ingredient of cold sensation channel agonist.
By the product of active ingredient of cold sensation channel agonist it is cold sensation channel agonist agent solution preferably, described
Or drug, health products or food added with cold sensation channel agonist.
The present invention passes through safety natural component without side-effects -- and cold sensation channel agonist is applied to body, activates body
The channels TRPM8 and/or TRPA1, it is lasting to generate the cold feeling of simulation, be equivalent to body and carry out cold-resistant forging in cold environment
Refining, excitating organism generate cold acclimatization, improve tolerance to cold.It need not be as in standard GJB 2562-96 in cruel cold
In carry out cold-resistant training, it is only necessary to persistently apply cold sensation channel agonist, so that it may easily to realize the promotion of body tolerance to cold,
It is convenient and easy, there is huge social value and application prospect.
Specific implementation mode
The following is specific embodiments of the present invention, and technical scheme of the present invention will be further described, but the present invention is simultaneously
It is not limited to these embodiments.If without specified otherwise, the raw material employed in the embodiment of the present invention is commonly used in the art
Raw material, the method employed in embodiment, is the conventional method of this field.
Application of the cold sensation channel agonist of the present invention in promoting body cold acclimatization ability, wherein cold sensation channel swash
Dynamic agent includes TRPM8 agonists and/or TRPA1 agonists.TRPM8 agonists are selected from menthol, citral, linalool, cloves
Phenol and eucalyptol it is one or more.TRPA1 agonists are selected from cinnamic acid, mustard oil, allicin, capsiate, carvacrol, fourth
Fragrant phenol, pipering, gingerol, methyl salicylate, caryophyllus oil, citral and menthol are one or more.
Cold sensation channels of the TRPM8 and TRPA1 as body participates in the transmission of cold signal, mediates body cold sensation.Peppermint
The cool property compound such as alcohol, citral, linalool, eugenol and eucalyptol can activate TRPM8 cold sensations channel, generate nice and cool
Feel, to keep body perception cold;Cinnamic acid, mustard oil, allicin, capsiate, carvacrol, eugenol, pipering, ginger
The substances such as Capsaicin, methyl salicylate, caryophyllus oil, citral and menthol can activate TRPA1 cold sensations channel, can cause body
Chilly sensation.
The present invention activates TRPM8 and/or TRPA1 channels by cold sensation channel agonist, make body generate it is cold or
Cold and pain feeling is generated simultaneously, is simulated cold expoure, is equivalent to body and carries out cold resistant training, exactor in cold environment
Body generates cold acclimatization, improves tolerance to cold.
The cold sensation channel agonist of the present invention is preferably menthol.
The cold sensation channel agonist of the present invention is more preferably the mixture of menthol and citral.
Menthol and citral can stimulate the channels TRPM8 and TRPA1 simultaneously, and menthol is used alone or uses peppermint
The mixture of alcohol and citral has more preferably technique effect relative to other cold sensation channel agonists.
Preferably the mass percent ratio of menthol and citral is 60-80%:20-40%.
The present invention will be applied to body by the product of active ingredient of cold sensation channel agonist.This application can be mouth
Cold sensation channel agonist active ingredient can arbitrarily be carried the administration form in body by clothes, injection etc..
Can be that cold sensation channel agonist is dissolved in oil-based solvent using cold sensation channel agonist as the product of active ingredient
The cold sensation channel agonist agent solution of middle formation, wherein oil-based solvent can be the edible oils such as soybean oil, peanut oil, corn oil
Property substance, liquid quality fraction are configured according to actual conditions.It can also by the product of active ingredient of cold sensation channel agonist
For drug, health products or food added with cold sensation channel agonist, cold sensation channel agonist is added in the form of acceptable
It is added in any drug, health products or food.
Be the products application of active ingredient when the body using cold sensation channel agonist, cold sensation channel agonist effectively at
Divide and applied according to 30-80mg/kg weight, concrete numerical value is according to the age of life entity, constitution and required cold acclimatization energy to be achieved
Power is selected, and is continued using a period of time until cold acclimatization ability is improved.
Cold sensation channel agonist promotes the Effect study of body cold acclimatization ability.
1. material and method
1.1 experimental animal
Health male C57BL/6 mouse 200, weight 20-22g are cured by military medical research institute of Academy of Military Sciences environment
It learns and is provided with operation Institute for Medical Research.
1.2 laboratory sample
1st group of sample:The 5mg/ml oil solutions that linalool is configured to corn oil;
2nd group of sample:The 5mg/ml oil solutions that mustard oil is configured to corn oil;
3rd group of sample:The 5mg/ml oil solutions that menthol is configured to corn oil;
4th group of sample:The 5mg/ml oil solutions that menthol and citral are configured to corn oil, wherein per in 1ml solution
Contain 4mg menthols and 1mg citrals;
5th group of sample:The 5mg/ml oil solutions that menthol and citral are configured to corn oil, wherein per in 1ml solution
Contain 3mg menthols and 2mg citrals;
6th group of sample:The 5mg/ml oil solutions that menthol and citral are configured to corn oil, wherein per in 1ml solution
Contain 1mg menthols and 4mg citrals.
The castering action research of Mouse core body temperature under the conditions of 1.3 4 DEG C of cold sensation channel agonist pair cold expoures
100 healthy male C57BL/6 mouse are randomly divided into 10 groups:1-10 groups, wherein 1-6 groups are pressed respectively
It is molten that the daily gavage of 10ml/kg weight (dosage 50mg/kg) gives the cold sensation channel agonist oil in corresponding 1-6 groups sample
Liquid, continuous gavage 14 days, normal water diet in application;7th group and the 8th group is given by the daily gavage of 10ml/kg weight
Do not add the corn oil of cold sensation channel agonist, continuous gavage 14 days, normal water diet in application, the 8th group in
Daily gavage exposure 4 hours in 4 DEG C of low temperature chambers after 1 hour, continuous exposure 14 days;The mouse of 1-8 groups fills in last time
1 hour after stomach, 8 groups of mouse are exposed 4 hours in 4 DEG C of low temperature chambers, measure Mouse core body temperature.9th group and the 10th group daily
5g mouse grains are eaten in three times, wherein the menthol containing 0.2mg in the 9th group of every gram of mouse grain, continuous 14 days edible, in last
1 hour after secondary feeding, 2 groups of mouse are exposed 4 hours in 4 DEG C of low temperature chambers, measure Mouse core body temperature.
It the results are shown in Table 1.
The influence research of mouse survival time and survival rate under the conditions of the p- 5 DEG C of cold expoures of 1.4 cold sensation channel agonists
100 healthy male C57BL/6 mouse are randomly divided into 10 groups:11-20 groups, wherein 11-16 groups are pressed respectively
It is molten that the daily gavage of 10ml/kg weight (dosage 50mg/kg) gives the cold sensation channel agonist oil in corresponding 1-6 groups sample
Liquid, continuous gavage 14 days, normal water diet in application;17th group and the 18th group is given by the daily gavage of 10ml/kg weight
With it is no addition cold sensation channel agonist corn oil, continuous gavage 14 days, normal water diet in application, the 18th group
Exposure 4 hours, continuous exposure 14 days in 4 DEG C of low temperature chambers after daily gavage 1 hour;The mouse of 11-18 groups is in last
1 hour after secondary gavage, 8 groups of mouse are placed in -5 DEG C of low temperature chambers exposure, observe depositing for mouse survival time and cold expoure 4 hours
Motility rate.19th group and the 20th group eats 5g mouse grains in three times daily, wherein the peppermint containing 0.2mg in the 9th group of every gram of mouse grain
Alcohol, it is continuous 14 days edible, 1 hour after last time feeding, 2 groups of mouse are placed in exposure in -5 DEG C of low temperature chambers, observe mouse
Survival rate when time-to-live and cold expoure 4 hours.
It the results are shown in Table 2.
2. result
The body temperature of 1 different disposal group mouse of table
| Grouping | Given low (mg/kg) | Mouse core body temperature (DEG C) |
| 1st group | 50 | 34.3±0.5 |
| 2nd group | 50 | 34.1±0.4 |
| 3rd group | 50 | 36.0±0.2 |
| 4th group | 50 | 36.4±0.3 |
| 5th group | 50 | 37.2±0.4 |
| 6th group | 50 | 35.2±0.3 |
| 7th group | 0 | 32.1±0.6 |
| 8th group | 0 | 38.3±0.3 |
| 9th group | Edible 1mg menthols daily | 35.8±0.4 |
| 10th group | Edible 0mg menthols daily | 32.3±0.3 |
2 different disposal group mouse cold expoure survival condition of table
Although being above the 7th group it is found that the Mouse core temperature of 1-6 groups is less than the 8th group from Tables 1 and 2;11-
Although 16 groups of mouse survival time and 4h survival rates are less than the 18th group, it is above the 17th group, it is meant that, it presses daily
50mg/kg weight gavage cold sensation channel agonists pass through 14 days although 14 days mouse tolerance to cold of continuous gavage are less than
4 DEG C of cold resistant trainings mouse, but to be significantly better than without the small of cold resistant training also non-gavage cold sensation channel agonist
Mouse.In the mouse of gavage cold sensation channel agonist, the cold sensation channel agonist of daily gavage is 60% menthol and 40%
The mouse of citral, has best tolerance to cold, is secondly mouse and the filling of 80% menthol of gavage and 20% citral
The mouse of stomach menthol, and the mouse of daily 20% menthol of gavage and 80% citral shows less than daily gavage menthol
Mouse, illustrate menthol and citral with mass percent ratio for 60-80%:The mixture of 20-40% compositions, is applied to machine
Have the effect of being better than other cold sensation channel agonists in body, and menthol and citral with mass percent ratio for 60%:
The mixture of 40% composition has best cold-resistant effect.
9th group and the 19th group, the containing menthol mouse grain of feeding is not added with the 10th of the mouse grain of menthol relative to feeding
Group and the 20th group, tolerance to cold is greatly improved, further prove, by the product arbitrarily containing cold sensation channel agonist
The effect of cold acclimatization can be played by being applied to body also.
So when cold sensation channel agonist can extend survival of the animal (especially mammal) under the conditions of cold expoure
Between and improve survival rate, have and promote cold acclimatization, increase the effect of body tolerance to cold.
In place of this place embodiment is to the claimed non-limit of technical scope midrange, equally all wanted in the present invention
In the range of asking protection.
Specific embodiment described herein is only an example for the spirit of the invention.Technology belonging to the present invention is led
The technical staff in domain can do various modifications or supplement to described specific embodiment or substitute by a similar method, but simultaneously
The spirit or beyond the scope defined by the appended claims of the present invention is not deviated by.
It is skilled to this field although present invention has been described in detail and some specific embodiments have been cited
For technical staff, as long as it is obvious that can make various changes or correct without departing from the spirit and scope of the present invention.
Claims (7)
1. application of the cold sensation channel agonist in promoting body cold acclimatization ability, which is characterized in that the cold sensation channel
Agonist includes TRPM8 agonists and/or TRPA1 agonists.
2. application according to claim 1, which is characterized in that the TRPM8 agonists are selected from menthol, citral, virtue
Camphor tree alcohol, eugenol and eucalyptol it is one or more.
3. application according to claim 1, which is characterized in that the TRPA1 agonists are selected from cinnamic acid, mustard oil, big
Allicin, capsiate, carvacrol, eugenol, pipering, gingerol, methyl salicylate, caryophyllus oil, citral and menthol it is a kind of or
It is a variety of.
4. application according to claim 1, which is characterized in that the cold sensation channel agonist is menthol.
5. application according to claim 1, which is characterized in that the cold sensation channel agonist is menthol and citral
Mixture.
6. application according to claim 1, which is characterized in that will be using cold sensation channel agonist as the product of active ingredient
It is applied to body.
7. application according to claim 6, which is characterized in that described using cold sensation channel agonist as the production of active ingredient
Product are cold sensation channel agonist agent solution or drug, health products or food added with cold sensation channel agonist.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111296841A (en) * | 2020-04-27 | 2020-06-19 | 浙江大学 | Composition for preventing and treating cold injury, food containing composition and application |
| CN114917190A (en) * | 2022-06-13 | 2022-08-19 | 郑州味千生物技术有限公司 | Product for masking bitter taste |
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| CN1694693A (en) * | 2002-11-06 | 2005-11-09 | 花王株式会社 | Blood fluidity improving agent |
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| CN1694693A (en) * | 2002-11-06 | 2005-11-09 | 花王株式会社 | Blood fluidity improving agent |
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| CN114917190A (en) * | 2022-06-13 | 2022-08-19 | 郑州味千生物技术有限公司 | Product for masking bitter taste |
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