CN114159448A - Application of steroid substance in preparation of preparation for improving attention - Google Patents

Application of steroid substance in preparation of preparation for improving attention Download PDF

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CN114159448A
CN114159448A CN202111505699.3A CN202111505699A CN114159448A CN 114159448 A CN114159448 A CN 114159448A CN 202111505699 A CN202111505699 A CN 202111505699A CN 114159448 A CN114159448 A CN 114159448A
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attention
estratetraene
androstadiene
improving
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黄艳
胡立平
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Shenzhen Institute of Advanced Technology of CAS
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Shenzhen Institute of Advanced Technology of CAS
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Priority to PCT/CN2022/137660 priority patent/WO2023104166A1/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/007Pulmonary tract; Aromatherapy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system

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Abstract

The invention provides the use of a steroid comprising androstadiene and/or estratetraene in the manufacture of an attention-promoting formulation. The steroid substance provided by the invention has stronger sex pertinence; under the same circumstances, estratetraene odour acts mainly on men and androstadiene odour acts mainly on women. The steroid substance stimulates the sense of smell in a gas diffusion mode to improve attention and sense of smell stimulation, and has quick response and easy implementation. In addition, in operation, the invention can realize the effect of attention improvement only by filling the environment with estratetraene/androstadiene with a certain concentration.

Description

Application of steroid substance in preparation of preparation for improving attention
Technical Field
The invention belongs to the technical field of cognition improvement, and particularly relates to an application of a steroid substance in preparation of a preparation for improving attention.
Background
First, note that function is a function underlying human cognitive processing. The processing of the current task related information and the suppression of the task unrelated information are all attention-derived effects. Essential oils such as peppermint, lavender, tangerine, etc. are often used to improve the attention of an individual. Second, many methods of improving attention have a long onset, e.g., a long adjustment period is required to improve attention through cognitive training or exercise.
CN107095920A discloses a rose fragrant smoked compound plant essential oil, which is prepared from the following raw materials in percentage by weight: 60-80% of honeysuckle essential oil, 6-10% of rose essential oil and the balance of geranium essential oil, chamomile essential oil, lavender essential oil, olive oil, sandalwood and frankincense; according to the invention, when the attention of an individual is not paid, various essential oil molecules are dispersed in the air in a heating mode by using various incense instruments and the aroma reaches the brain through olfaction, so that the attention is focused, but the sex-specific and quick-acting characteristics are not achieved.
CN113350340A discloses the use of hydroxypiperone hydrochloride in the preparation of a medicament for improving attention-alertness. The usage amount of the oxypeperisone hydrochloride is 2.5-20 mg/kg. The invention verifies that the hydroxypipropidone hydrochloride can improve the reaction accuracy, reduce the error times and reduce the impulsive reaction to a certain extent through the test on a rat 5-CSRTT behavioral model, thereby playing the roles of improving the attention and enhancing the behavior control. However, this component only validates the experiments on the behavioral model of rat 5-CSRTT, and does not achieve attention enhancement with effect on only a single sex.
Therefore, how to improve attention for a specific sex and shorten the period of attention improvement is the focus of current research.
Disclosure of Invention
In view of the deficiencies of the prior art, it is an object of the present invention to provide a use of a steroid substance for the preparation of an attention-enhancing formulation. Compared with other attention level improving methods, the method adopting two pheromones for improving the attention level has the characteristics of sex pertinence and quick response.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the present invention provides the use of a steroid comprising androstadiene and/or estratetraene in the manufacture of an attention-promoting formulation.
In the present invention, the use of said androstadiene for the preparation of a preparation for improving the attention of women.
In the invention, the application of the estratetraene in preparing the preparation for improving the attention of men is provided.
In the present invention, the steroid substance stimulates the sense of smell by means of gas diffusion to raise attention.
In the present invention, the attention level of an individual is raised by gas olfactory stimulation, AND the gases used are androstadiene (AND, androsta-4, 16-dien-3-one) AND estratetraene (EST, estra-1,3,5(10),16-tetra en-3-ol). Wherein the androstadiene odor environment is effective for females and the estratetraene odor environment is effective for males. These two substances are steroid substances, considered "quasi-human sex pheromones", commonly found in sweat.
One of the starting points of the invention is that attention of individuals of different sexes is promoted through androstadiene and estratetraene, and the invention has strong human group pertinence. Secondly, another point of view of the present invention is how to act on an individual quickly. The present invention rapidly increases the level of attention of an individual through olfactory stimulation, i.e., through a gaseous scent. In general, the method of using two quasi-pheromones for attention level has the characteristics of gender specificity and rapid onset of action compared with other methods of improving attention level.
Androstadiene and estratetraene were original as odors to raise attention levels, and the inventors performed experiments with neurological evidence. Previous studies have reported a number of effects of androstadiene and estratetraene on gender perception and emotional perception of individuals. For example, in the estratetraene setting, men are more likely to perceive a neutral lattice human figure as a woman. Behavior and electroencephalogram experiments show that the estratetraene odor can improve the attention of male individuals and has no effect on females; the androstadiene odor can improve the attention of female individuals and has no effect on men. This increase in attention appears to be an enhancement to the processing of task related information and an enhancement to the inhibition of extraneous information.
In addition, it is particularly noted that the present invention provides a method for increasing attention levels by using androstadiene and estratetraene as olfactory stimuli to act on men or women. And is therefore not limited to a particular gas release method or choice as solvent for the dissolution of estratetraene or androstadiene.
In the present invention, the steroid substance has a diffusion concentration of 0.1 to 10. mu. mol/m2For example, it may be 0.1. mu. mol/m2、0.5μmol/m2、1μmol/m2、1.5μmol/m2、2μmol/m2、2.5μmol/m2、3μmol/m2、3.5μmol/m2、4μmol/m2、4.5μmol/m2、5μmol/m2、5.5μmol/m2、6μmol/m2、7μmol/m2、8μmol/m2、9μmol/m2、10μmol/m2Etc., preferably 1 to 5. mu. mol/m2
In a second aspect, the present invention provides a method for improving attention, including the following steps:
(1) dissolving the steroid substance of the first aspect in a volatile solvent to obtain a solution;
(2) volatilizing the solution obtained in the step (1), and stimulating smell by a gas diffusion mode to improve attention.
In the present invention, in step (1), the volatile solvent includes any one of ethanol, propylene glycol, glyceryl caprylate, tripropylene glycol monomethyl ether or glyceryl triacetate, or a combination of at least two thereof.
In the present invention, the concentration of the steroid substance in the solution is 1500. mu. mol/L, and may be, for example, 100. mu. mol/L, 200. mu. mol/L, 300. mu. mol/L, 400. mu. mol/L, 500. mu. mol/L, 600. mu. mol/L, 700. mu. mol/L, 800. mu. mol/L, 900. mu. mol/L, 1000. mu. mol/L, 1100. mu. mol/L, 1200. mu. mol/L, 1400. mu. mol/L, 1500. mu. mol/L, or the like.
In the present invention, the solution is volatilized in a manner including free volatilization and/or assisted volatilization.
Preferably, the temperature of the free volatilization is 0-40 ℃, for example, can be 0 ℃,5 ℃, 10 ℃, 15 ℃, 20 ℃, 25 ℃, 30 ℃, 35 ℃, 40 ℃ and so on.
Preferably, the auxiliary volatilization adopts a high-frequency electronic oscillation mode.
Preferably, the frequency of the high-frequency electronic oscillation is 1-3MHz, and may be, for example, 1MHz, 1.2MHz, 1.4MHz, 1.6MHz, 1.8MHz, 2MHz, 2.2MHz, 2.4MHz, 2.6MHz, 2.8MHz, 3MHz, or the like.
In the present invention, in the step (2), the amount of the solution is 5 to 50mL/m2For example, it may be 5mL/m2、6mL/m2、7mL/m2、8mL/m2、9mL/m2、10mL/m2、15mL/m2、20mL/m2、25mL/m2、30mL/m2、35mL/m2、40mL/m2、45mL/m2、50mL/m2And the like.
Preferably, in the step (2), the volatilization time is 1-20min, such as 1min, 2min, 3min, 4min, 5min, 6min, 7min, 8min, 9min, 10min, 12min, 14min, 16min, 18min, 20min and the like, preferably 5-10 min.
Compared with the prior art, the invention has the following beneficial effects:
(1) according to the invention, estratetraene and androstadiene gas are adopted, which respectively play a role in paying attention to different sexes in a targeted manner, so that the sex pertinence is strong, under the same environment, the estratetraene smell mainly plays a role in males, and the androstadiene smell mainly plays a role in females;
(2) the invention adopts a method of attention level of estratetraene and androstadiene pheromone, and has the characteristics of quick response and easy implementation through olfactory stimulation;
(3) the method is simple and easy to operate, and the attention improvement effect can be realized only by filling the environment with estratetraene/androstadiene with a certain concentration.
Drawings
Fig. 1 is a graph of the ERP variation of individual resistance to interference for men and women in the androstatetraene gas environment provided in example 1.
Fig. 2 is a graph of the ERP variation of individual resistance to interference for men and women in the estratetraene gas environment provided in example 4.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.
The following examples and comparative examples, where no specific techniques or conditions are indicated, can be performed according to the techniques or conditions described in the literature in the art or according to the product specifications. The reagents or apparatus used are conventional products commercially available from a formal channel or may be prepared by the prior art, without reference to the manufacturer.
Example 1
The embodiment provides a method for improving attention, which includes the following steps:
(1) dissolving 500 mu mol of androstadiene in 1L of propylene glycol to obtain 500 mu mol/L of androstadiene propylene glycol solution;
(2) 50mL of androstadiene in propylene glycol was placed in a incense machine at 10m2The solution is continuously volatilized for 6min in a high-frequency electronic oscillation mode of 2Mz, and the smell is stimulated in a gas diffusion mode to improve the attention of women.
The above scheme is subjected to effect verification in empirical research. In the experiment, a woman is required to complete an attention task in an androstadiene gas environment, and simultaneously electroencephalogram (EEG) is carried out, and the result shows that the brain pays more attention to the corresponding change of related electroencephalogram components.
Example 2
The embodiment provides a method for improving attention, which includes the following steps:
(1) dissolving 800 mu mol of androstadiene in 1L of propylene glycol to obtain 800 mu mol/L of androstadiene propylene glycol solution;
(2) 50mL of androstadiene in propylene glycol was placed in a incense machine at 10m2The solution is continuously volatilized for 5min in a high-frequency electronic oscillation mode of 1Mz, and the smell is stimulated in a gas diffusion mode to improve the attention of women.
The above scheme is subjected to effect verification in empirical research. In the experiment, a woman is required to complete an attention task in an androstadiene gas environment, and simultaneously electroencephalogram (EEG) is carried out, and the result shows that the brain pays more attention to the corresponding change of related electroencephalogram components.
Example 3
The embodiment provides a method for improving attention, which includes the following steps:
(1) dissolving 200 mu mol of androstadiene in 1L of propylene glycol to obtain a propylene glycol solution of 200 mu mol/L androstadiene;
(2) 50mL of androstadiene in propylene glycol was placed in a incense machine at 10m2The solution is continuously volatilized for 10min in a 3Mz high-frequency electronic oscillation mode, and the smell is stimulated in a gas diffusion mode to improve the attention of women.
The above scheme is subjected to effect verification in empirical research. In the experiment, a woman is required to complete an attention task in an androstadiene gas environment, and simultaneously electroencephalogram (EEG) is carried out, and the result shows that the brain pays more attention to the corresponding change of related electroencephalogram components.
Example 4
The embodiment provides a method for improving attention, which includes the following steps:
(1) dissolving 500 mu mol of estratetraene in 1L of propylene glycol to obtain 500 mu mol/L of estratetraene propylene glycol solution;
(2) 50mL of estratetraene in propylene glycol was placed in a incense machine and placed at 10m2The solution is continuously volatilized for 6min in a high-frequency electronic oscillation mode of 2Mz, and the olfaction is stimulated in a gas diffusion mode to improve the attention of the male.
The above scheme is subjected to effect verification in empirical research. In the experiment, men are required to complete attention tasks in an estratetraene gas environment and simultaneously carry out electroencephalogram (EEG), and the result shows that the brain pays more attention to the corresponding change of related electroencephalogram components. Specifically, compared with the smell of the snuff clove oil, the amplitude of the tested electroencephalogram Pd component (representing the attention suppression function) of the male subjected to the snuff estratetraene is increased, which shows that the attention suppression is better performed on the interference stimulation, namely the attention capability is improved. In contrast, the female syringomy oil and androstadiene odors did not notice ingredient differences.
Example 5
The embodiment provides a method for improving attention, which includes the following steps:
(1) dissolving 700 mu mol of estratetetraene in 1L of propylene glycol to obtain a propylene glycol solution of 700 mu mol/L of estratetetraene;
(2) 50mL of estratetraene in propylene glycol was placed in a incense machine and placed at 10m2The solution is continuously volatilized for 8min in a high-frequency electronic oscillation mode of 1.5Mz, and the olfaction is stimulated in a gas diffusion mode to improve the attention of men.
The above scheme is subjected to effect verification in empirical research. In the experiment, men are required to complete attention tasks in an estratetraene gas environment and simultaneously carry out electroencephalogram (EEG), and the result shows that the brain pays more attention to the corresponding change of related electroencephalogram components.
Example 6
The embodiment provides a method for improving attention, which includes the following steps:
(1) dissolving 100 mu mol of estratetraene in 1L of propylene glycol to obtain a propylene glycol solution of 100 mu mol/L of estratetraene;
(2) 50mL of estratetraene in propylene glycol was placed in a incense machine and placed at 10m2The solution is continuously volatilized for 10min in a high-frequency electronic oscillation mode of 3Mz, and the olfaction is stimulated in a gas diffusion mode to improve the attention of the male.
The above scheme is subjected to effect verification in empirical research. In the experiment, men are required to complete attention tasks in an estratetraene gas environment and simultaneously carry out electroencephalogram (EEG), and the result shows that the brain pays more attention to the corresponding change of related electroencephalogram components.
Example 7
This example provides a method for improving attention, which is different from example 1 only in that the volatile solvent is ethanol, and the other steps are the same as example 1.
The above scheme is subjected to effect verification in empirical research. In the experiment, a woman is required to complete an attention task in an androstadiene gas environment, and simultaneously electroencephalogram (EEG) is carried out, and the result shows that the brain pays more attention to the corresponding change of related electroencephalogram components.
Example 8
This example provides a method of improving attention, which is different from example 2 only in that the volatile solvent is glyceryl caprylate, and the other steps are the same as example 2.
The above scheme is subjected to effect verification in empirical research. In the experiment, men are required to complete attention tasks in an estratetraene gas environment and simultaneously carry out electroencephalogram (EEG), and the result shows that the brain pays more attention to the corresponding change of related electroencephalogram components.
Example 9
This example provides a method of improving attention, which differs from example 1 only in that the concentration of androstadiene in the solution is 10. mu. mol/L, and the other steps are the same as in example 1.
The above scheme is subjected to effect verification in empirical research. In the experiment, a woman is required to complete an attention task in an androstadiene gas environment, and simultaneously electroencephalogram (EEG) is carried out, and the result shows that the brain pays more attention to the corresponding change of related electroencephalogram components.
Example 10
This example provides a method of improving attention, which is different from example 2 only in that the concentration of estratetraene in the solution is 10. mu. mol/L, and the other steps are the same as example 2.
The above scheme is subjected to effect verification in empirical research. In the experiment, men are required to complete attention tasks in an estratetraene gas environment and simultaneously carry out electroencephalogram (EEG), and the result shows that the brain pays more attention to the corresponding change of related electroencephalogram components.
Example 11
The embodiment provides a method for improving attention, which includes the following steps:
(1) dissolving 500 mu mol of androstadiene in 1L of propylene glycol to obtain 500 mu mol/L of androstadiene propylene glycol solution;
(2) 50mL of androstadiene propylene glycol solution is smeared on the inner side of the arms of a female, and the attention of the female can be improved by stimulating the sense of smell after the self-diffusion of gas at 25 ℃ is found out for 15 min.
The above scheme is subjected to effect verification in empirical research. In the experiment, a woman is required to complete an attention task in an androstadiene gas environment, and simultaneously electroencephalogram (EEG) is carried out, and the result shows that the brain pays more attention to the corresponding change of related electroencephalogram components.
Example 12
The embodiment provides a method for improving attention, which includes the following steps:
(1) dissolving 500 mu mol of estratetraene in 1L of propylene glycol to obtain 500 mu mol/L of estratetraene propylene glycol solution;
(2) 50mL of estratetraene propylene glycol solution is smeared on the inner side of the male arm, and the attention of the male can be improved by stimulating the sense of smell after 15min through an autonomous gas diffusion mode.
The above scheme is subjected to effect verification in empirical research. In the experiment, men are required to complete attention tasks in an estratetraene gas environment and simultaneously carry out electroencephalogram (EEG), and the result shows that the brain pays more attention to the corresponding change of related electroencephalogram components.
Comparative example 1
The present comparative example provides a method of improving attention, the method comprising the steps of:
(1) dissolving 1g of peppermint essential oil in 1L of propylene glycol to obtain 1g/L of peppermint propylene glycol solution;
(2) 50mL of peppermint in propylene glycol solution was placed in a incense machine and placed at 10m2In the space range of (2), the solution is continuously volatilized for 6min in a high-frequency electronic oscillation mode of 2Mz, and gas passes throughThe body diffusion mode stimulates the sense of smell to improve the attention of women.
The results show that: mint odor can improve the performance of women in completing their attention tasks.
Comparative example 2
The present comparative example provides a method of improving attention, the method comprising the steps of:
(1) dissolving 1g of peppermint essential oil in 1L of propylene glycol to obtain 1g/L of peppermint propylene glycol solution;
(2) 50mL of peppermint in propylene glycol solution was placed in a incense machine and placed at 10m2The solution is continuously volatilized for 6min in a high-frequency electronic oscillation mode of 2Mz, and the olfaction is stimulated in a gas diffusion mode to improve the attention of the male.
The results show that: mint odor can improve the performance of men completing their attention tasks.
In comparative examples 1 and 2, the mint odor, while improving the performance of the individual in completing the attention task, was not gender specific.
Test example
And (3) testing items: examples 1, 4 provide methods of improving attention;
the test method comprises the following steps: the participating males (20) and females (20) complete an attention task and record brain electrical signals. The task process requires that the task be tried to shield as much as possible from the disturbances caused by color and shape variations.
The ability of an individual to resist interference is one of the key aspects in assessing attention control ability; the electroencephalogram Pd component is a direct electroencephalogram index for evaluating the individual interference capability. The experiment shows that the androstadiene can improve the attention capacity of women (the Pd component is increased) and has no obvious influence on the attention level of men.
Fig. 1 is a graph of the ERP variation of individual resistance to interference in the androstatetraene gas environment provided in example 1 for men and women, as shown in fig. 1, the magnitude of the attention component varies in the case of androstadiene gas environments for men and women in contrast. The data show that women showed a greater Pd composition than the control conditions, while men did not differ significantly in the two gas conditions. Research results show that the androstadiene can improve the attention capacity of women and has very weak effect on men.
Fig. 2 is a graph of ERP changes in resistance to interference in men and women in the estratetraene gas environment provided in example 4, and as shown in fig. 2, men induced a greater Pd component in the estratetraene gas environment than in the control conditions (solvent only), i.e. increased control ability, was noted, and appeared to be better able to eliminate interference. In contrast, women have no difference between the two gas environments. The research result shows that the estratetraene can improve the attention ability of men and has no obvious influence on the attention level of women.
The above results indicate that the sex-like pheromones estratetraene and androstadiene are able to boost the attention capacity of men or women with respect to sex, but are not effective in the other sex.
The applicant states that the present invention is illustrated by the above examples of the use of the steroid substances of the invention in the preparation of a formulation for enhancing attention, but the present invention is not limited to the above examples, i.e. it is not intended that the present invention necessarily relies on the above examples for its practice. It should be understood by those skilled in the art that any modification of the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific modes, etc., are within the scope and disclosure of the present invention.

Claims (10)

1. Use of a steroid comprising androstadiene and/or estratetraene in the manufacture of an attention-promoting formulation.
2. Use according to claim 1, wherein the androstadiene is used in the preparation of a preparation for improving the attention of a female.
3. Use according to claim 1 or 2, wherein the estratetraene is used in the manufacture of a formulation for improving male attention.
4. Use according to any one of claims 1 to 3, wherein the steroid substance stimulates olfaction by means of gas diffusion to increase attention.
5. Use according to claim 4, wherein the steroid substance has a diffusion concentration of 0.1-10 μmol/m2Preferably 1 to 5. mu. mol/m2
6. A method of improving attention, the method comprising the steps of:
(1) dissolving the steroid substance of claim 1 in a volatile solvent to form a solution;
(2) volatilizing the solution obtained in the step (1), and stimulating smell by means of gas diffusion to improve attention.
7. The method for improving attention according to claim 6, wherein in the step (1), the volatile solvent comprises any one or a combination of at least two of ethanol, propylene glycol, glyceryl caprylate, tripropylene glycol monomethyl ether or glyceryl triacetate, and is preferably propylene glycol.
8. The method for improving attention according to claim 6 or 7, wherein the concentration of the steroid substance in the solution in step (1) is 100-1500 μmol/L.
9. A method for improving attention according to any one of claims 7-8, wherein in step (2), the solution is volatilized in a manner that includes free volatilization and/or assisted volatilization;
preferably, the temperature of the free volatilization is 0-40 ℃;
preferably, the auxiliary volatilization adopts a high-frequency electronic oscillation mode;
preferably, the frequency of the high-frequency electronic oscillation is 1-3 MHz.
10. The method for improving attention according to any one of claims 7 to 9, wherein in the step (2), the amount of the solution is 5 to 50mL/m2
Preferably, in the step (2), the volatilization time is 1-20min, preferably 5-10 min.
CN202111505699.3A 2021-12-10 2021-12-10 Application of steroid substance in preparation of preparation for improving attention Pending CN114159448A (en)

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