CN108686213B - Application of cold sensory channel agonist in preparation of medicine for promoting cold habit taking capability of organism - Google Patents
Application of cold sensory channel agonist in preparation of medicine for promoting cold habit taking capability of organism Download PDFInfo
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- CN108686213B CN108686213B CN201810760093.6A CN201810760093A CN108686213B CN 108686213 B CN108686213 B CN 108686213B CN 201810760093 A CN201810760093 A CN 201810760093A CN 108686213 B CN108686213 B CN 108686213B
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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
-
- 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
-
- 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
-
- 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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- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The invention belongs to the field of food and medicine, and relates to application of a cold sensation channel agonist in promoting the cold habit of human bodies. Cold sensory channel agonists include TRPM8 agonists and/or TRPA1 agonists. The TRPM8 agonist is one or more selected from menthol, citral, linalool, eugenol and eucalyptol. The TRPA1 agonist is selected from one or more of cinnamaldehyde, mustard oil, allicin, capsaicine ester, carvacrol, eugenol, piperine, gingerol, wintergreen oil, clove oil, citral and menthol.
Description
Technical Field
The invention belongs to the field of food and medicine, and relates to an application of a cold sensation channel stimulant in preparation of a medicine for promoting the cold habit of taking by a human body.
Background
Transient Receptor Potential (TRP) channels are a class of cationic channels located on cell membranes and include a number of members, generally divided into 7 subfamilies (TRPC, TRPA, TRPM, TRPV, TRPN, TRPP and TRPML), which are important molecules for the body to sense external environmental stimuli. TRPV subfamily members TRPV1, TRPV2, TRPV3, TRPV4, TRPM subfamily members TRPM8 and TRPA subfamily members TRPA1 ion channels in the TRP family are voltage gated, whereas temperature and ligands can effect modulation of channel switching by changing voltage, and thus these subfamilies are considered to be participants in temperature sensing and temperature regulation. Wherein, the TRPM8 can sense the temperature of 8-28 ℃, is used for sensing cooling and behavioral thermoregulation, and also participates in the cold-mediated analgesia and the cold pain sense of some neurons; TRPA1 senses temperatures below 17 ℃ and is involved in sensing both mechanically and chemically induced pain and cold hyperalgesia. Both are receptors of the body to cold and are the channels of the body's cold sensation.
The cold environment threatens the health and the operation capability of a human body, can cause cold injuries such as frostbite, hypothermia, feet for soaking, trench feet and the like, can also promote the occurrence and the development of hypertension, cerebral apoplexy and various cancers, and can also cause the reduction of the operation capability of the brain body in different degrees such as the reduction of alertness, cognitive ability and fine operation capability, and the like, thereby seriously influencing the life and the work of people in the alpine environment. Within the physiological tolerance limit, a human body lives in a cold environment for a long time (generally 4-6 weeks), repeatedly receives cold stimulation with medium intensity, and can generate a series of changes on the human body, wherein the changes are shown as that cold stress reaction (such as chill, skin vasoconstriction, heart rate acceleration and the like) is gradually weakened, the metabolic heat production is increased, the heat dissipation capacity is reduced, and the cold resistance and the freezing resistance are obviously enhanced, and the changes are called as cold habitual clothes, which can reduce the occurrence of cold injury and the degree of cold injury. The current effective method for improving cold tolerance is to perform cold habit training, such as in the standard GJB 2562-96, and improve the cold tolerance of human body by long-distance running and/or cold water exercise and/or cold air exercise. There has also been a study (see chinese patent application publication No. 106674305 a) to improve cold tolerance of the body using a product prepared with trans-ferulic acid-4- β -glucoside as an active ingredient.
Disclosure of Invention
The present invention aims to use agonists of the cold sensory channel (TRPM8 and TRPA1) to promote the body's ability to habituate cold.
In order to achieve the purpose, the invention adopts the following technical scheme:
use of a cold sensory channel agonist comprising a TRPM8 agonist and/or a TRPA1 agonist in the manufacture of a medicament for promoting the cold habit of the body.
Preferably, the TRPM8 agonist is selected from one or more of menthol, citral, linalool, eugenol, and eucalyptol.
Preferably, the TRPA1 agonist is selected from one or more of cinnamaldehyde, mustard oil, allicin, capsaicinoids, carvacrol, eugenol, piperine, gingerol, wintergreen oil, clove oil, citral and menthol.
Preferably, the cold sensory channel agonist is menthol.
Further preferably, the cold sensory channel agonist is a mixture of menthol and citral.
Preferably, a product containing a cold sensory channel agonist as an active ingredient is administered to the body.
Preferably, the product containing the cold sensory channel agonist as an active ingredient is a cold sensory channel agonist solution or a pharmaceutical, health product or food to which a cold sensory channel agonist is added.
The cold feeling channel stimulant which is a natural component without side effect is applied to an organism, the TRPM8 and/or TRPA1 channel of the organism is activated, the cold feeling is simulated continuously, the cold feeling is similar to cold-resistant exercise of the organism in a cold environment, the organism is stimulated to generate cold habit clothes, and the cold-resistant capability is improved. The cold resistance training in harsh cold as in the standard GJB 2562-96 is not needed, and the cold resistance of the organism can be easily improved by only continuously applying the cold sensation channel agonist, so that the cold resistance training method is convenient and easy to implement, and has great social value and application prospect.
Detailed Description
The following are specific examples of the present invention and further describe the technical solutions of the present invention, but the present invention is not limited to these examples. The raw materials used in the examples of the present invention are those commonly used in the art, and the methods used in the examples are those conventional in the art, unless otherwise specified.
The use of a cold sensory channel agonist of the present invention in the manufacture of a medicament for promoting the ability of the body to habituate cold, wherein the cold sensory channel agonist comprises a TRPM8 agonist and/or a TRPA1 agonist. The TRPM8 agonist is one or more selected from menthol, citral, linalool, eugenol and eucalyptol. The TRPA1 agonist is selected from one or more of cinnamaldehyde, mustard oil, allicin, capsaicine ester, carvacrol, eugenol, piperine, gingerol, wintergreen oil, clove oil, citral and menthol.
TRPM8 and TRPA1 are used as cold sensing channels of the body, participate in the transmission of cold signals and mediate the cold sensing of the body. Cooling compounds such as menthol, citral, linalool, eugenol and eucalyptol can activate TRPM8 cold feeling channel to generate cool feeling, so that the body can sense cold; the substances such as cinnamaldehyde, mustard oil, allicin, capsaicine ester, carvacrol, eugenol, piperine, gingerol, wintergreen oil, clove oil, citral and menthol can activate TRPA1 cold feeling channel and cause cold feeling of organism.
The cold feeling channel agonist activates the TRPM8 and/or TRPA1 channel, so that the body generates cold or cold and pain feeling at the same time, cold exposure is simulated, the cold feeling channel agonist is equivalent to cold-resistant exercise of the body in a cold environment, the body is stimulated to generate cold habit clothes, and the cold-resistant capability is improved.
The cold sensory channel agonist of the present invention is preferably menthol.
The cold sensory channel agonist of the present invention is further preferably a mixture of menthol and citral.
Menthol and citral can stimulate both the TRPM8 and TRPA1 channels, with menthol alone or a mixture of menthol and citral having superior technical effects over other cold sensory channel agonists.
Preferably, the mass percentage ratio of the menthol to the citral is 60-80% to 20-40%.
The present invention applies a product containing a cold sensory channel agonist as an active ingredient to the body. The administration may be any administration form capable of bringing the active ingredient of the cold sensory channel agonist into the body, such as oral administration, injection, etc.
The product with the cold feeling channel stimulant as the effective component can be a cold feeling channel stimulant solution formed by dissolving the cold feeling channel stimulant in an oily solvent, wherein the oily solvent can be edible oily substances such as soybean oil, peanut oil, corn oil and the like, and the mass fraction of the solution is configured according to actual conditions. The product with the cold sensory channel stimulant as the active ingredient can also be a medicine, health-care product or food added with the cold sensory channel stimulant, and the cold sensory channel stimulant is added into any medicine, health-care product or food in an acceptable form.
When the product with the cold feeling channel stimulant as the active ingredient is applied to the body, the active ingredient of the cold feeling channel stimulant is applied according to the weight of 30-80mg/kg, the specific numerical value is selected according to the age and the physique of a living body and the cold habit taking ability required to be achieved, and the application is continued for a period of time until the cold habit taking ability is improved.
Research on the effect of the cold sensory channel agonist on promoting the body to learn the ability to take the cold.
1. Materials and methods
1.1 Experimental animals
200 healthy male C57BL/6 mice, weighing 20-22g, were provided by the military medical institute environmental medicine and work medicine institute of the military scientific institute.
1.2 Experimental samples
Group 1 samples: linalool is 5mg/ml oil solution prepared from corn oil;
group 2 samples: preparing 5mg/ml oil solution of mustard oil with corn oil;
group 3 samples: 5mg/ml oil solution prepared from menthol and corn oil;
group 4 samples: 5mg/ml oil solution of menthol and citral prepared with corn oil, wherein each 1ml solution contains 4mg of menthol and 1mg of citral;
group 5 samples: 5mg/ml oil solution of menthol and citral prepared with corn oil, wherein each 1ml solution contains 3mg of menthol and 2mg of citral;
group 6 samples: menthol and citral were formulated with corn oil as 5mg/ml oil solutions containing 1mg menthol and 4mg citral per 1ml solution.
1.3 study of the Effect of cold sensory channel agonists on the increase in core body temperature of mice under 4 ℃ Cold Exposure
100 healthy male C57BL/6 mice were randomly divided into 10 groups: groups 1-10, wherein the cold sensory channel agonist oil solutions in the samples of groups 1-6 were administered to the patients by gavage at a dose of 50 mg/kg/day of 10ml/kg body weight for 14 days with normal drinking water and diet during administration; performing gavage with 10ml/kg body weight in groups 7 and 8, administering corn oil without cold sensory channel agonist, continuously performing gavage for 14 days, wherein water and diet are normal during administration, and performing exposure in 4 deg.C low temperature chamber for 4 hours after performing gavage for 1 hour every day for 14 days; mice from groups 1-8 were exposed to 4 hours in a 4 ℃ cold chamber 1 hour after the last gavage, and the core body temperature of the mice was measured. Group 9 and group 10 were fed three times a day with 5g of rat chow, wherein each gram of rat chow in group 9 contained 0.2mg of menthol, for 14 consecutive days, and 2 mice were exposed to 4 hours in a 4 ℃ cold chamber 1 hour after the last feeding, and the core body temperature of the mice was measured.
The results are shown in Table 1.
1.4 Effect of Cold sensory channel agonists on survival time and survival Rate in mice exposed to Cold at-5 deg.C
100 healthy male C57BL/6 mice were randomly divided into 10 groups: groups 11-20, wherein groups 11-16 were separately gavaged with a solution of cold sensory channel agonist oil in the samples of the corresponding groups 1-6 at a dose of 50mg/kg body weight of 10ml/kg per day for 14 consecutive days with normal drinking water and diet during administration; performing gavage with 10ml/kg body weight in groups 17 and 18 per day, administering corn oil without cold sensory channel agonist, continuously performing gavage for 14 days, wherein water and diet are normal during administration, and performing exposure in 4 deg.C low temperature chamber for 4 hours after performing gavage for 1 hour per day for 14 days; mice from groups 11-18 were exposed 1 hour after the last gavage in a-5 ℃ cryostat, and mice were observed for survival and survival at 4 hours after cold exposure. Groups 19 and 20 received 5g of rat chow three times a day, with group 9 containing 0.2mg of menthol per gram of rat chow, for 14 consecutive days, and 2 mice were exposed in a-5 ℃ cryostat 1 hour after the last feeding, and observed for survival and survival at 4 hours of cold exposure.
The results are shown in Table 2.
2. Results
TABLE 1 body temperature of mice of different treatment groups
| Grouping | Gavage dosage (mg/kg) | Core body temperature (. degree. C.) of mouse |
| Group 1 | 50 | 34.3±0.5 |
| Group 2 | 50 | 34.1±0.4 |
| Group 3 | 50 | 36.0±0.2 |
| Group 4 | 50 | 36.4±0.3 |
| Group 5 | 50 | 37.2±0.4 |
| Group 6 | 50 | 35.2±0.3 |
| Group 7 | 0 | 32.1±0.6 |
| Group 8 | 0 | 38.3±0.3 |
| Group 9 | Daily consumption of 1mg menthol | 35.8±0.4 |
| Group 10 | Daily intake of 0mg menthol | 32.3±0.3 |
TABLE 2 Cold-exposure survival of mice in different treatment groups
As can be seen from tables 1 and 2, the core temperature of the mice in groups 1-6 was lower than that in group 8, but higher than that in group 7; although the survival time and 4h survival rate of the mice in groups 11-16 were lower than those in group 18 but higher than those in group 17, it means that the cold sensory channel agonist was gavaged at 50mg/kg body weight per day, and the mice that were continuously gavaged for 14 days had significantly better cold tolerance than the mice that had been cold-tolerant exercised at 4 ℃ for 14 days, but not had cold tolerance and had no gavaged cold sensory channel agonist. Among the mice with the perfused cold sensory channel agonist, the mice perfused daily with the cold sensory channel agonist of 60% menthol and 40% citral have the best cold tolerance, and the mice perfused daily with 80% menthol and 20% citral and the mice perfused with menthol, while the mice perfused daily with 20% menthol and 80% citral exhibit less than the mice perfused daily with menthol, indicating that the mixture of menthol and citral in the mass percentage ratio of 60-80%: 20-40% has the best cold tolerance when applied to the body than other cold sensory channel agonists, while the mixture of menthol and citral in the mass percentage ratio of 60%: 40% has the best cold tolerance.
The cold tolerance of the rats fed the diet containing menthol was greatly improved in groups 9 and 19 compared to the rats fed the diet of rats 10 and 20 to which no menthol was added, and it was further confirmed that any product containing a cold sensory pathway agonist applied to the body also exerts the cold habit.
Therefore, the cold sensory channel agonist can prolong the survival time of animals (especially mammals) under cold exposure conditions and improve the survival rate, and has the effects of promoting cold habit taking and increasing the cold tolerance of the body.
The embodiments herein are not exhaustive of the technical scope of the present invention, and are within the scope of the present invention.
The specific embodiments described herein are merely illustrative of the spirit of the invention. Various modifications or additions may be made to the described embodiments or alternatives may be employed by those skilled in the art without departing from the spirit or ambit of the invention as defined in the appended claims.
While the invention has been described in detail and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof.
Claims (1)
1. Use of a cold sensory channel agonist in the manufacture of a medicament for promoting the cold habit of the body, wherein the cold sensory channel agonist is a TRPM8 agonist and a TRPA1 agonist;
the TRPM8 agonist is menthol;
the TRPA1 agonist is citral;
in the cold sensory channel stimulant, the mass percentage ratio of menthol to citral is 60% and 40% respectively;
the medicine takes a cold sensory channel agonist as an active ingredient, and the using method of the medicine is as follows: when the medicine is applied to the body, the active ingredient of the cold sensory channel agonist is applied according to 30-80mg/kg body weight.
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| CN1694693A (en) * | 2002-11-06 | 2005-11-09 | 花王株式会社 | Blood fluidity improving agent |
| CN106674305A (en) * | 2016-12-27 | 2017-05-17 | 中国人民解放军第四军医大学 | Method for extracting monomer medicine for promoting cold acclimatization ability of organism, and application thereof |
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