CN114903881B - Application of N-acetyl-N' -caffeoyl butanediamine in preparation of preparation for preventing and treating insomnia and related diseases - Google Patents
Application of N-acetyl-N' -caffeoyl butanediamine in preparation of preparation for preventing and treating insomnia and related diseases Download PDFInfo
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- CN114903881B CN114903881B CN202210620665.7A CN202210620665A CN114903881B CN 114903881 B CN114903881 B CN 114903881B CN 202210620665 A CN202210620665 A CN 202210620665A CN 114903881 B CN114903881 B CN 114903881B
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- ZINBYEVHNDIYBV-UHFFFAOYSA-N 3-(3,4-dihydroxyphenyl)prop-2-enamide Chemical compound NC(=O)C=CC1=CC=C(O)C(O)=C1 ZINBYEVHNDIYBV-UHFFFAOYSA-N 0.000 description 1
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- YIBXWXOYFGZLRU-UHFFFAOYSA-N syringic aldehyde Natural products CC12CCC(C3(CCC(=O)C(C)(C)C3CC=3)C)C=3C1(C)CCC2C1COC(C)(C)C(O)C(O)C1 YIBXWXOYFGZLRU-UHFFFAOYSA-N 0.000 description 1
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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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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- 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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
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- A61P25/24—Antidepressants
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- 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 discloses an application of N-acetyl-N' -caffeoyl butanediamine in preparing health-care food and medicine for preventing and treating insomnia, anxiety and depression. The experimental result shows that in the dosage range of 1-100mg/kg given to experimental animals, N-acetyl-N' -caffeoyl butanediamine can obviously reduce the activity times of insomnia mice, shorten the sleep latency period of the insomnia mice, prolong the sleep time of the insomnia mice, and obviously call back the index level of neurotransmitters such as 5-HT, 5-HIAA, GABA, glu and the like in brain tissues of the insomnia mice, and the neurotransmitters are closely related to mental diseases such as insomnia, anxiety and depression.
Description
Technical Field
The invention relates to the technical field of medicine preparation, in particular to application of N-acetyl-N' -caffeoyl butanediamine in preparation of a preparation for preventing and treating insomnia, anxiety, depression and related diseases.
Background
Insomnia is one of the more common symptoms in life and is closely related to life and work of people. The occurrence of insomnia is related to various factors such as age, sex and disease, and the prevalence of insomnia increases with age. In recent years, social employment pressure is increased, economic demands are increased increasingly, living habits of people are changed, and incidence of insomnia is increased in the social environment. Insomnia not only causes anxiety, depression and other emotions to the patient, but also causes various diseases to occur. Therefore, it is becoming particularly important to develop drugs for treating insomnia naturally. The current clinical drugs for treating insomnia mainly comprise barbiturates, benzodiazepines and non-benzodiazepine sedative hypnotics; melatonin drugs; orexin receptor antagonists; 5-HT2A receptor antagonists; antipsychotic, antidepressant, antiepileptic drugs, etc. These are all chemical synthetic drugs, and have many adverse reactions, and drug resistance and dependence can be generated after long-term use. In recent years, some newly discovered sedative hypnotic traditional Chinese medicine active monomers are also used for researching on treating and improving sleep disorder related diseases. Such as syringic acid, isoliquiritigenin and the like, have proved to have remarkable improving effect on sleep disorder.
Therefore, the search for active monomer ingredients with sedative-hypnotic effects from natural medicines, which can be used for preventing and treating insomnia, anxiety and depression, is a problem to be solved by those skilled in the art.
Disclosure of Invention
In view of this, the present invention provides the use of N-acetyl-N' -caffeoylbutanediamine in the preparation of a formulation for the prevention and treatment of insomnia, anxiety, depression and related disorders.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
use of N-acetyl-N '-caffeoylbutanediamine in the preparation of a formulation for the prevention and treatment of insomnia, anxiety, depression and related disorders, said N-acetyl-N' -caffeoylbutanediamine having the structure:
N-acetyl-N' -caffeoylbutanediamine of formula C 15 H 20 N 2 O 4 Molecular weight 292.14, english full name (E) -2-propenamide, N- [4- (acrylamino) butyl]-3- (3, 4-dihydroxyphenyl) -, or 2-propenamide, N- [4- (acetylamino) butyl ]]-3- (3, 4-dihydroxyphenyl) -, or (E) -N- (4-acetylbutylyl) -3- (3, 4-acetylphenyl) acrylamide, or N- (4-acetylbutylyl) -3- (3, 4-acetylphenyl) acrylamide english abbreviation (E) -N-acetyl-N '-caffeoyl putricine, or N-acetyl-N' -caffeoyl putricine, is a caffeic acid amide that we have isolated from medlar. There are few reports of the current research on N-acetyl-N '-caffeoylbutanediamine, and there is no report on the biological activity of N-acetyl-N' -caffeoylbutanediamine. The invention discovers N-acetyl through animal experimentsThe base-N' -caffeoyl butanediamine has remarkable sedative hypnotic effect. Further, the compound can be developed into a medicament for preventing and treating insomnia, anxiety and depression, and has great clinical application value.
As a preferable technical scheme of the invention, the preparation is any one of powder, tablets, capsules, emulsion, pills and granules.
As a preferable technical scheme of the invention, the preparation is any one of an oral dosage form, an external patch and an injection.
Another object of the present invention is to provide a medicament containing N-acetyl-N' -caffeoylbutanediamine.
As a preferred technical scheme of the invention, the daily application dosage of the medicine is 1-100mg/kg calculated by N-acetyl-N' -caffeoyl butanediamine.
Compared with the prior art, the application of the N-acetyl-N' -caffeoyl butanediamine in preparing medicaments for preventing and treating insomnia, anxiety and depression and the pharmaceutical composition have the following beneficial effects:
(1) N-acetyl-N' -caffeoyl butanediamine can obviously reduce the number of autonomous activities of insomnia mice.
(2) N-acetyl-N' -caffeoyl butanediamine can significantly shorten sleep latency of insomnia mice.
(3) The N-acetyl-N' -caffeoyl butanediamine can obviously prolong the sleeping time of insomnia mice.
(4) N-acetyl-N' -caffeoylbutanediamine can call back the transmitter level of 5-HT, 5-HIAA, GABA, glu and the like of brain tissues of insomnia mice.
The invention proves that the N-acetyl-N' -caffeoyl butanediamine has sedative hypnotic effect for the first time, and can be used for preparing medicaments for preventing and treating insomnia, anxiety and depression.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required to be used in the embodiments or the description of the prior art will be briefly described below, and it is obvious that the drawings in the following description are only embodiments of the present invention, and that other drawings can be obtained according to the provided drawings without inventive effort for a person skilled in the art.
FIG. 1 is the effect of N-acetyl-N '-caffeoylbutanediamine on the voluntary locomotor activity test of mice, wherein 2 is N-acetyl-N' -caffeoylbutanediamine; G. z, D for the high, medium and low dose groups respectively; in comparison with the set of models, ** p<0.01， *** p< 0.001；
FIG. 2 is a graph showing the effect of N-acetyl-N '-caffeoylbutanediamine on sleep latency in mice (2 is N-acetyl-N' -caffeoylbutanediamine; G, Z, D shows the high, medium and low dose groups, respectively; compared to the normal control group, ### p<0.001the method comprises the steps of carrying out a first treatment on the surface of the In comparison with the set of models, * p<0.05， *** p<0.001）；
FIG. 3 shows the effect of N-acetyl-N '-caffeoylbutanediamine on sleep time in mice (2N-acetyl-N' -caffeoylbutanediamine; G, Z, D shows the high, medium and low dose groups, respectively; compared to the normal control group, # p<0.05the method comprises the steps of carrying out a first treatment on the surface of the In comparison with the set of models, ** p<0.01， *** p<0.001）；
FIG. 4 shows the effect of N-acetyl-N '-caffeoylbutanediamine on 5-HT in mouse brain tissue (2 is N-acetyl-N' -caffeoylbutanediamine; G, Z, D shows the high, medium and low dose groups, respectively; compared to the normal control group, ### p<0.001the method comprises the steps of carrying out a first treatment on the surface of the In comparison with the set of models, ** p<0.01， *** p<0.001）；
FIG. 5 shows the effect of N-acetyl-N '-caffeoylbutanediamine on 5-HIAA in mouse brain tissue (2 is N-acetyl-N' -caffeoylbutanediamine; G, Z, D shows the high, medium and low dose groups, respectively; compared to the normal control group, ### p<0.001the method comprises the steps of carrying out a first treatment on the surface of the In comparison with the set of models, ** p<0.01， *** p<0.001）；
FIG. 6 is a graph showing the effect of N-acetyl-N '-caffeoylbutanediamine on GABA in mouse brain tissue (2 is N-acetyl-N' -caffeoylbutanediamine; G, Z, D shows the high, medium and low dose groups, respectively; compared to the normal control group, ## p<0.01the method comprises the steps of carrying out a first treatment on the surface of the In comparison with the set of models, ** p<0.01， *** p<0.001）；
FIG. 7 shows the effect of N-acetyl-N '-caffeoylbutanediamine on Glu in mouse brain tissue (2 is N-acetyl-N' -caffeoylbutanediamine; G, Z, D shows the high, medium and low dose groups, respectively; compared to the normal control group, # p<0.05the method comprises the steps of carrying out a first treatment on the surface of the In comparison with the set of models, * p<0.05， ** p<0.01， *** p<0.001）；
FIG. 8 is a graph showing the effect of N-acetyl-N '-caffeoylbutanediamine on Glu/GABA ratio in mouse brain tissue (2 is N-acetyl-N' -caffeoylbutanediamine; G, Z, D shows the high, medium and low dose groups, respectively; compared to the normal control group, ## p< 0.01the method comprises the steps of carrying out a first treatment on the surface of the In comparison with the set of models, * p<0.05， ** p<0.01， *** p<0.001）。
description of the embodiments
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Examples
Exploring the effect of N-acetyl-N' -caffeoylbutanediamine on insomnia, anxiety or depression in mice
Pharmacodynamics evaluation of sleep improvement effect of N-acetyl-N' -caffeoylbutanediamine is carried out by adopting a model of insomnia, anxiety or depression of mice caused by injection of p-chlorophenylalanine (PCPA). And observing the sedative hypnotic effect of the N-acetyl-N' -caffeoylbutanediamine on the insomnia mice by using the behavioral evaluation methods such as the record of the number of times of autonomous activities of the mice, the record of the weight, the experiment of inducing the sleep of the mice by using sodium pentobarbital and the like. Brain tissue was taken to measure neurotransmitter 5-HT, 5-HIAA, GABA, glu levels, and the possible mechanisms of N-acetyl-N' -caffeoylbutanediamine to improve sleep, anxiety or depression were investigated.
1. Experimental animal
Healthy SPF grade male ICR mice (18-22 g) were supplied by the university of Ningxia medical science animal center (laboratory animal license number SCXK (university of Ningxia medical science) 2020-0001). The animals are adaptively fed into SPF standard laboratories, and the feeding conditions of all groups of animals are the same: ambient temperature (25 ℃), relative humidity (50% -60%). Can feed and feed water freely.
Experimental method
ICR mice were fed adaptively for 3 days prior to receiving the molding, and the day prior to molding was randomly divided into 6 groups of a normal control group, a model group, a positive drug group (melatonin), and an N-acetyl-N' -caffeoylbutanediamine group (low dose group 1mg/kg/d, medium dose group 10mg/kg/d, and high dose group 100 mg/kg/d), each group of 10 animals. After adaptive feeding, modeling is carried out continuously for 2 days, normal control groups are given normal saline (0.1 mL/10 g/d), PCPA suspension is injected into the abdominal cavity of the other groups (400 mg/kg/d), mice are continuously active in the daytime within 28-30h after injection, feeding is reduced, aggressiveness is enhanced, and modeling success is indicated.
After successful modeling, normal control and model groups were given equal volumes of normal saline (0.1 mL/10 g/d), and the positive drug group melatonin was given at 10mg/kg/d and N-acetyl-N' -caffeoylbutanediamine was given at 1, 10 and 100mg/kg/d, respectively. Each group of mice was dosed at 8:00-12:00 am daily for 7 consecutive days.
3. Observation index
The invention adopts SPSS 18.0 to carry out data analysis and statistics, the obtained results are represented by mean value + -standard deviation (X + -S), and the difference between groups is compared by single factor analysis of variance (one-way ANOVA)Data processing is carried out, and the variability has statistical significancep<0.05 as standard.
Number of autonomous activities
The number of independent activities of each mouse within 5min was recorded after successful molding and half an hour after 7 th day of dosing, respectively. Mice were placed in the apparatus for 3min prior to each recording. (the results are shown in Table 1 and FIG. 1)
TABLE 1 influence of N-acetyl-N' -caffeoylbutanediamine on the voluntary locomotor activity test of mice
Note that: # indicates that the pre-dosing model group was compared to the normal control group, # P<0.05, ## P<0.01, ### P<0.001the method comprises the steps of carrying out a first treatment on the surface of the * Indicating that the comparison after the last administration with the corresponding pre-administration, * P<0.05， ** P<0.01， *** P<0.001。
as can be seen from Table 1 and FIG. 1, the number of independent activities of mice in the insomnia group caused by PCPA is significantly increased compared with that of the normal control group (190+ -30.85) before administrationp<0.001). After the last administration, compared with the prior administration, the number of the independent activities of the mice in the normal control group and the model group is not obviously changed, and the number of the independent activities of the mice in each dosage group of positive medicine and N-acetyl-N' -caffeoyl butanediamine is obviously reducedp<0.001) The N-acetyl-N' -caffeoylbutanediamine has obvious improving effect on insomnia, anxiety or depression.
Weight of body
The body weight of each group of mice was recorded before molding, after molding, on the 3 rd day of administration, on the 7 th day of administration, and changes in body weight of the mice were observed (see Table 2).
TABLE 2 influence of N-acetyl-N' -caffeoylbutanediamine on mouse body weight
Note that: compared with the method before the molding process, # P<0.05， ## P<0.01， ### P<0.001；note that: in comparison with the set of models, * P<0.05， ** P< 0.01， *** P<0.01。
the result shows that the weight of the normal control group mice is gradually increased along with the experiment after the molding and before the moldingp<0.01) The body weight of the model mice is basically unchanged, and the model mice have no statistical difference. On day 3 of dosing, the mice weight (26.50 + -3.39 g) was significantly reduced compared to the normal control group (31.71+ -2.27 g) by the model groupp<0.001) The method comprises the steps of carrying out a first treatment on the surface of the Compared with the model group, the weight of mice in each dosage group of positive medicine and N-acetyl-N' -caffeoylbutanediamine is obviously increasedp<0.001). On day 7 of dosing, the model group mice had a somewhat lower body weight (29.95±4.07 g) but not statistically significant, compared to the normal control group (32.45 ±1.34 g); compared with the model group, the weight of mice in each dosage group of positive medicine and N-acetyl-N' -caffeoyl butanediamine is obviously increasedp<0.05）。
Sleep time determination by specular reflection experiment
Mice sleep latency and sleep time were recorded 1h after day 7 dosing by intraperitoneal injection of pentobarbital sodium suspension (50 mg/kg) into each group. Recording sleep latency from the end of intraperitoneal injection to the disappearance of the mouse eversion and reflection for more than 1 min; the recovery from the fall asleep to the flip-flop of the mice was noted as sleep time. (the results are shown in Table 3, FIG. 2 and FIG. 3)
TABLE 3 influence of N-acetyl-N' -caffeoylbutanediamine on sleep latency and sleep time in mice
Note that: in comparison with the normal control group, # P<0.01, ## P<0.01, ### P<0.001the method comprises the steps of carrying out a first treatment on the surface of the In comparison with the set of models, * P< 0.05， ** P<0.01， *** P<0.001。
the results showed that the mice in the model group had significantly increased sleep latency (332.67.+ -. 62.76 s) compared to the normal control group (229.00.+ -. 13.70 s) in terms of sleep latency index levelp<0.001) The model of insomnia of the mice caused by PCPA is successful, so that the mice have the phenomena of difficulty in falling asleep, anxiety or depression. Compared with the model group, the sleeping latency of mice in each dosage group of positive medicine and N-acetyl-N' -caffeoyl butanediamine is obviously shortenedp<0.05) The positive medicines melatonin and N-acetyl-N' -caffeoyl butanediamine can regulate the sleep latency of mice, and have an improving effect on insomnia, anxiety or depression of the mice caused by PCPA. Compared with the normal control group (15.29+/-7.60 min), the model group mice have obviously shortened sleep time (7.38+/-3.81 min) in terms of sleep time index levelp＜0.05) The result shows that the model of insomnia of the mice caused by PCPA is successful, so that the sleeping time of the mice is shortened. Compared with the model group, the sleeping time of the mice in the group with high and medium doses of the positive drug and the N-acetyl-N' -caffeoyl butanediamine is obviously prolongedp＜0.01) The positive medicines melatonin and N-acetyl-N' -caffeoyl butanediamine are shown to increase the sleeping time of mice, and have an improving effect on insomnia, anxiety or depression of the mice caused by PCPA.
By combining the experimental results, after the mice are insomnia, the mice have the phenomena of continuous activities, eating, sleep reduction and the like in the daytime, so that the number of times of autonomous activities is increasedp<0.001) Prolonged sleep latencyp<0.001) The sleeping time is shortenedp<0.05) The rate of weight gain in mice decreased. The N-acetyl-N' -caffeoyl butanediamine can reduce the number of autonomous activities of insomnia mice in different doses, shorten sleep latency, increase sleep time and improve the weight increase rate reduction of the insomnia mice caused by PCPA. The above data demonstrate that N-acetyl-N' -caffeoylbutanediamine has a significant sedative hypnotic effect.
4. Neurotransmitter level determination
After 7 days of administration, the mice were sacrificed by cervical dislocation, the brains were taken out by breaking the ends on an ice table, and the brains were uniformly ground by a tissue homogenizer, and 10% brain tissue homogenate was prepared by adding physiological saline. Centrifuging at 4deg.C for 15 min at 3000r/min, collecting supernatant, and detecting monoamine neurotransmitter 5-HT, 5-HIAA level (results shown in Table 4 and figures 4 and 5) and amino acid neurotransmitter level Glu and GABA level (results shown in Table 5 and figures 6, 7 and 8) in supernatant by ELISA method.
TABLE 4 influence of N-acetyl-N' -caffeoylbutanediamine on mouse monoamine neurotransmitters
Note that: in comparison with the normal control group, # P<0.05， ## P<0.01， ### P<0.001the method comprises the steps of carrying out a first treatment on the surface of the In comparison with the set of models, ** P< 0.01， *** P<0.001。
table 4 and FIG. 5 show that the 5-HT (238.66 + -34.66 ng/g) content in the brain tissue of mice in the model group is significantly reduced compared with the normal control group (322.96 + -28.00 ng/g)p< 0.001), indicating that the PCPA induced insomnia, anxiety or depression mouse model was successful. Compared with the model group, the 5-HT content in the brain tissue of the mice in the positive drug group and the high and medium dose groups of N-acetyl-N' -caffeoyl butanediamine is obviously increasedp< 0.01) and has a positive correlation with a dose, i.e. the larger the dose administered, the higher the 5-HT content. Compared with the normal control group (34.37+/-3.71 ng/g), the 5-HIAA (29.66 +/-1.74 ng/g) content in the brain tissue of the mice in the model group is obviously reducedp< 0.001), indicating that the PCPA induced insomnia, anxiety or depression mouse model was successful. Compared with the model group, the content of 5-HIAA (37.15+/-1.56 ng/g) in the brain tissue of the mice in the positive drug group is obviously increasedp< 0.001). The content of 5-HIAA in the brain tissue of the mice in the high and low dose groups of N-acetyl-N' -caffeoyl butanediamine is obviously increasedp< 0.05). To sum up, brain tissue after insomnia, anxiety or depression in miceThe content of 5-HT and 5-HIAA is reducedp< 0.05). The high dose groups of N-acetyl-N '-caffeoylbutanediamine were able to significantly increase the levels of 5-HT and 5-HIAA, suggesting that N-acetyl-N' -caffeoylbutanediamine may improve insomnia, anxiety or depression symptoms directly by increasing the levels of 5-HT and 5-HIAA in brain tissue of insomnia mice.
TABLE 5 influence of N-acetyl-N' -caffeoylbutanediamine on mouse amino acid neurotransmitters
Note that: in comparison with the normal control group, # P<0.05， ## P<0.01， ### P<0.001the method comprises the steps of carrying out a first treatment on the surface of the In comparison with the set of models, ** P< 0.01， *** P<0.001。
table 5 and fig. 6, fig. 7 and fig. 8. Compared with the normal control group (8.47+/-2.31 nmol/L), the GABA (5.94+/-0.83 nmol/L) content in the brain tissue of the mice in the model group is obviously reducedp< 0.01), indicating a decrease in GABA content in brain tissue of mice suffering from insomnia, anxiety or depression caused by PCPA. Compared with the model group, the GABA (6.89+/-1.11 nmol/L) content in the brain tissue of the mice in the positive drug group is increased, but has no statistical significance. GABA content in brain tissue of mice of each dosage group of N-acetyl-N' -caffeoyl butanediamine is obviously increasedp< 0.01). Glu (65.56+ -4.33. Mu. Mol/gprot) content in brain tissue of mice in model group was significantly increased compared to normal control group (60.31 + -1.93. Mu. Mol/gprot)p< 0.05), indicating an increase in Glu content in brain tissue of insomnia mice caused by PCPA. Compared with the model group, the Glu (53.52 +/-7.23 mu mol/gprot) content in the brain tissue of the mice in the positive drug group is obviously reducedp< 0.001). The Glu content in the brain tissue of the mice can be reduced to different degrees by different dosage groups of N-acetyl-N' -caffeoylbutanediamine, wherein the low dosage and the medium dosage have obvious differencep< 0.05). Glu/GABA values (10.79.+ -. 1.96) were evident in the brain tissue of mice in the model group compared to the normal control group (8.00.+ -. 1.94)Greatly enlarged%p< 0.01). Compared with the model group, the Glu/GABA values in the brain tissue of mice in the groups with different doses of positive medicine and N-acetyl-N' -caffeoyl butanediamine are obviously reducedp< 0.05). In conclusion, after insomnia, anxiety or depression in mice, GABA content in brain tissue is reduced (p < 0.01), glu content and Glu/GABA value are increased (p < 0.05). Each dose group of N-acetyl-N' -caffeoylbutanediamine can increase the GABA content in brain tissue of insomnia, anxiety or depression mice, and reduce Glu content and Glu/GABA value. It is speculated that N-acetyl-N' -caffeoylbutanediamine may improve insomnia, anxiety or depression symptoms by decreasing Glu content, increasing GABA content, decreasing Glu/GABA values.
Examples
An injection for preventing and treating insomnia, anxiety and depression, wherein the single application dose of N-acetyl-N' -caffeoylbutanediamine is 1mg/kg.
Examples
An oral tablet for preventing and treating insomnia, anxiety and depression, wherein the single application dose of N-acetyl-N' -caffeoylbutanediamine is 10mg/kg.
Examples
A topical patch for preventing and treating insomnia, anxiety and depression, wherein the single application dose of N-acetyl-N' -caffeoylbutanediamine is 100mg/kg.
Examples
An oral granule for preventing and treating insomnia, anxiety and depression, wherein the single application dose of N-acetyl-N' -caffeoylbutanediamine is 10mg/kg.
In the present specification, each embodiment is described in a progressive manner, and each embodiment is mainly described in a different point from other embodiments, and identical and similar parts between the embodiments are all enough to refer to each other.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (3)
- The use of N-acetyl-N '-caffeoylbutanediamine in the preparation of a formulation for the treatment of insomnia, characterized in that the structure of said N-acetyl-N' -caffeoylbutanediamine is:。
- 2. the use according to claim 1, wherein the formulation is any one of a powder, a tablet, a capsule, a emulsion, a pill and a granule.
- 3. The use according to claim 1, wherein the formulation is in the form of an oral dosage form or an injectable solution.
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| JPS60152454A (en) * | 1984-01-18 | 1985-08-10 | Terumo Corp | Amide derivative and 5-lipoxigenase inhibitor containing said derivative as active component |
| CN104277081A (en) * | 2013-07-05 | 2015-01-14 | 中国科学院大连化学物理研究所 | Hydroxy cinnamic acid amine compounds and preparation and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JPS60152454A (en) * | 1984-01-18 | 1985-08-10 | Terumo Corp | Amide derivative and 5-lipoxigenase inhibitor containing said derivative as active component |
| CN104277081A (en) * | 2013-07-05 | 2015-01-14 | 中国科学院大连化学物理研究所 | Hydroxy cinnamic acid amine compounds and preparation and application thereof |
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