CN111110686A - Application of fructose diphosphate in preparing medicine for treating affective disorder - Google Patents
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- 229930091371 Fructose Natural products 0.000 title claims abstract description 18
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- 239000001177 diphosphate Substances 0.000 title claims abstract description 18
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7024—Esters of saccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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Abstract
The invention provides an application of fructose diphosphate in preparing a medicine for treating affective disorder. The experimental result of the invention shows that the fructose diphosphate can improve the depression state and the anxiety state, can effectively treat the affective disorder, and particularly has obvious treatment effect on epilepsy comorbid affective disorder caused by epilepsy. Therefore, the fructose diphosphate has a very good application prospect in preparing medicines for treating affective disorder, particularly epilepsy comorbid affective disorder.
Description
Technical Field
The invention belongs to the field of pharmacy, and particularly relates to application of fructose diphosphate in preparing a medicine for treating affective disorder, in particular to epilepsy comorbid affective disorder.
Background
Epilepsy refers to a persistent, chronic, benign brain disorder with its neurological, cognitive, psychological and social consequences. Some diseases are easy to coexist with epilepsy in the same individual, and different diseases are difficult to distinguish and mutually affect, so that the epilepsy is commonly encountered. Among them, the common epilepsy comorbidities include cognitive disorders, affective disorders, migraine, schizophrenia, attention deficit hyperactivity disorder, sleep disorders, psychological disorders, mitochondrial encephalomyopathy, and the like. The pathogenesis of epilepsy co-morbidity is currently unclear, presumably as a result of complex factor interactions. The type, number and severity of epilepsy co-morbidities are closely related to the age, sex, age of onset, course, family history, quantity of antiepileptic drugs, seizure control condition and the like of epileptics.
Epilepsy comorbid affective disorder is the most common comorbid disease of epilepsy, which seriously affects the life quality of patients, and related researches are deepened continuously with the increasing attention of scholars at home and abroad. According to survey, the probability of epilepsy patients accompanied with depression is higher than that of normal people, and the probability of epilepsy patients accompanied with depression is also higher than that of normal people. It has been shown that the prevalence of depression in epileptic patients is 21% to 55%, which is higher than that in normal and other chronic patients. Foreign scholars propose that the prevalence rate of epilepsy-induced anxiety is 11% -25%, which is 2.4 times higher than that of normal population.
The investigation of epilepsy co-morbid affective disorder shows that most neurologists mainly treat epileptic diseases, and the diagnosis and treatment rate of epilepsy co-morbid diseases are low. At present, the treatment of epilepsy mainly takes drug therapy as the main treatment, but certain adverse reactions exist when the drugs control the epileptic seizure. Research shows that many drugs for treating epilepsy cannot effectively treat affective disorders, and even can cause anxiety disorder and increase the risk of affective disorder; some drugs that treat affective disorders will lower the threshold for seizures or affect the metabolism of antiepileptic drugs, thereby increasing the risk of seizures.
Therefore, the further research on the relationship between epilepsy and the co-morbidities has very important significance in developing the medicine capable of effectively treating the epilepsy co-morbidities.
Disclosure of Invention
The invention aims to provide a new application of fructose diphosphate in preparing a medicament for treating affective disorders, in particular epilepsy comorbid affective disorders.
The invention provides an application of fructose diphosphate in preparing a medicine for treating affective disorder.
Further, the affective disorder is an epilepsy comorbid affective disorder.
Further, the affective disorder is accompanied by cognitive disorders.
Further, the affective disorder is caused by status epilepticus, acute epilepsy, or chronic epilepsy.
Further, the status epilepticus is induced by pilocarpine and/or edetic acid.
Further, the acute epilepsy is induced by pentaerythriton and/or coriamyrtin.
Further, the chronic epilepsy is induced by pentaerythritonin and/or coriamyrtin.
Further, the medicament is capable of improving a depressive state, and/or improving an anxiety state.
Further, the drug can improve memory.
Fructose diphosphate is FDP.
The experimental result of the invention shows that the fructose diphosphate can improve the cognitive ability and the depressive state and the anxiety state, can effectively treat affective disorder, and particularly has obvious treatment effect on epilepsy comorbid affective disorder caused by epilepsy. Therefore, the fructose diphosphate has a very good application prospect in preparing medicines for treating affective disorder, particularly epilepsy comorbid affective disorder.
Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Detailed Description
The raw materials and equipment used in the invention are known products and are obtained by purchasing commercial products.
Example 1 therapeutic Effect of fructose diphosphate on epilepsy comorbidity cognitive and affective disorders in model epilepsy Holstatus
1. Experimental methods
Adult Wistar rats, weighing about 250g, were from Chengdou laboratory animals, Inc.
Adult rats were injected intraperitoneally with Pilocarpine (Pilo, 30mg/kg) and renolic acid (Kainic acid, 10mg/kg) to induce status epilepticus, and administered diazepam 40 minutes after status epilepticus was terminated, the experimental animals were divided into two groups after termination of status epilepticus, ① FDP group (10) was administered FDP (1g/kg) daily, ② control group (10) was administered an equal amount of physiological saline, and behavioural tests were performed at 2 months, 3 months, and 4 months after termination of status epilepticus, respectively.
The water maze test space memory capacity:
(1) the rat head is put into water towards the wall of the pool and randomly put into one of four quadrants. The time(s) when the animal found the underwater platform was recorded. If this time exceeds 90s, the animal is directed to the platform. The animals were allowed to rest on the platform for 10 s.
(2) The animals were removed and wiped dry. Each animal is trained for 2 times every day, the interval between two times of training is 15-20 min, and training is continuously carried out for 5 days.
(3) The next day after the last acquired training, the platform was removed and the animals were placed in the water from the opposite side of the quadrant of the original platform. The time spent by the animal in the target quadrant (the quadrant where the platform was originally placed) and the number of entries into that quadrant were recorded as an indicator of spatial memory.
Open field testing anxiety status:
(1) the experiment was performed in a quiet environment. And (3) placing the animal in the center of the bottom surface in the box, and simultaneously carrying out 5min shooting and timing. The inner wall and the bottom surface of the square box are cleaned, so that the influence of the information (such as the excrement and urine and the smell of the animal) left by the animal at the last time on the next test result is avoided. Animals were replaced and the experiment continued.
(2) The residence time of the animals in the center compartment per unit time was calculated.
Forced swim test for depression status:
(1) the first day, the rats were placed in a water jar of 20cm diameter, 40cm height, colorless and transparent, and 13cm depth, and the animals were forced to swim in the environment for 15min and then were taken out and dried.
(2) The next day rats were placed in a water jar for 6min and the time of immobility of the last 4min rats was observed.
Fear test contextual memory ability:
(1) the rats are placed in a conditioned fear box on the first day, the plantar electric shock is given after the rats are adapted for 3min, and the rats are taken out 15s after the plantar electric shock.
(2) Keeping the environment in the box unchanged on the next day, putting the rat into the box again for 3min, and recording the time and times of the rat having the catalepsy within 3 min.
2. Results of the experiment
Experiments at 2 months, 3 months and 4 months after the termination of the status epilepticus all find that the memory capacity and emotion of the FDP group are obviously improved compared with those of the normal saline group.
(1) In the water maze experiment, the time spent in the target quadrant in the FDP group was increased compared with the control group, and the difference between the two groups was statistically significant (P < 0.05).
(2) In the open field experiment, the residence time in the central compartment was increased in the FDP group compared to the control group, and the difference between the two groups was statistically significant (P < 0.05).
(3) In forced swim experiments, the final 4min immobility time of the FDP group was reduced compared to the control group, and the difference between the two groups was statistically significant (P < 0.05).
(4) In fear experiments, FDP group showed increased time to catalepsy compared to control group, and the difference between the two groups was statistically significant (P < 0.05).
The experimental animals after the status of the epilepsy persistence of the experiment really show the epilepsy comorbid affective disorder. Compared with a control group, the cognitive ability of the FDP group is obviously improved, and the anxiety state and the depression state are obviously improved, so that the FDP can effectively treat the affective disorder, and particularly has an obvious treatment effect on epilepsy comorbid affective disorder caused by the status epilepticus.
Example 2 therapeutic Effect of fructose diphosphate on epilepsy comorbid cognitive and affective disorders in acute epileptic rats
1. Experimental methods
Adult rats were intraperitoneally injected with 2 drugs of pentaerythrine (50mg/kg) or corilagin (2mg/kg) once a day, respectively, to induce acute seizure models, the test was divided into 4 groups (10 per group), ① and ③ groups were FDP groups, and ② and ④ groups were control groups, wherein ① groups were administered FDP (1g/kg) daily to the tetra-pentan-induced acute seizure models, ② groups were administered an equal amount of physiological saline daily to the tetra-pentan-induced acute seizure models, ③ groups were administered FDP (1g/kg) daily to the corilagin-induced acute seizure models, ④ groups were administered an equal amount of physiological saline daily to the corilagin-induced acute seizure models, water maze, forced swimming, and agoraph tests were performed on days 10 and 20, respectively, and the test methods were the same as in example 1.
2. Results of the experiment
Experiments on the 10 th day and the 20 th day of the administration show that the cognition and the mood of the FDP group are obviously improved compared with those of the normal saline group.
(1) In the water maze experiment, the time spent in the target quadrant in the FDP group was increased compared with the control group, and the difference between the two groups was statistically significant (P < 0.05).
(2) In the open field experiment, the residence time in the central compartment was increased in the FDP group compared to the control group, and the difference between the two groups was statistically significant (P < 0.05).
(3) In forced swim experiments, the final 4min immobility time of the FDP group was reduced compared to the control group, and the difference between the two groups was statistically significant (P < 0.05).
(4) In fear experiments, FDP group showed increased time to catalepsy compared to control group, and the difference between the two groups was statistically significant (P < 0.05).
The acute epilepsy model of the experiment indeed shows that the epilepsy suffers from affective disorder. Compared with a control group, the cognitive ability of the FDP group is obviously improved, and the anxiety state and the depression state are obviously improved, so that the FDP can effectively treat the affective disorder, and particularly has an obvious treatment effect on epilepsy comorbid affective disorder caused by acute epilepsy.
Example 3 therapeutic Effect of fructose diphosphate on epilepsy comorbid cognitive and affective disorders in rats in Chronic epilepsy model
1. Experimental methods
Adult rats were randomly divided into 4 groups (10 per group), ① and ③ groups were FDP groups, and ② and ③ 1 groups were control groups, wherein ① groups were injected daily with FDP (1g/kg), ② groups were injected daily with an equal amount of physiological saline, ③ 0 groups were injected daily with FDP (1g/kg), ④ groups were injected daily with an equal amount of physiological saline, 1 hour later, ① groups were injected with pentaerythrine (30mg/kg), ② groups were injected with pentaerythrine (30mg/kg), ③ groups were injected with coriamyrtin (1.50mg/kg), ④ groups were injected with coriamyrtin (1.50mg/kg), and a chronic seizure model was induced.
2. Results of the experiment
The experiment on the 10 th day and the 20 th day of the administration shows that: the FDP group had significantly improved cognition and mood compared to the saline group.
(1) In the water maze experiment, the time spent in the target quadrant in the FDP group was increased compared with the control group, and the difference between the two groups was statistically significant (P < 0.05).
(2) In the open field experiment, the residence time in the central compartment was increased in the FDP group compared to the control group, and the difference between the two groups was statistically significant (P < 0.05).
(3) In forced swim experiments, the final 4min immobility time of the FDP group was reduced compared to the control group, and the difference between the two groups was statistically significant (P < 0.05).
(4) In fear experiments, FDP group showed increased time to catalepsy compared to control group, and the difference between the two groups was statistically significant (P < 0.05).
The chronic epilepsy experimental animal of the experiment shows that the epilepsy suffers from affective disorder. Compared with a control group, the cognitive ability of the FDP group is obviously improved, and the anxiety state and the depression state are obviously improved, so that the FDP can effectively treat the affective disorder, and particularly has an obvious treatment effect on epilepsy comorbid affective disorder caused by chronic epilepsy.
In conclusion, the invention provides a new application of fructose diphosphate in preparing a medicine for treating affective disorders, in particular epilepsy comorbid affective disorders. The experimental result shows that the fructose diphosphate can improve the cognitive ability and the depression state and the anxiety state, can effectively treat affective disorder and cognitive disorder, and particularly has obvious treatment effect on epilepsy comorbid affective disorder. Therefore, the fructose diphosphate has a very good application prospect in preparing medicines for treating affective disorder, particularly epilepsy comorbid affective disorder.
Claims (9)
1. Use of fructose diphosphate in the preparation of a medicament for the treatment of affective disorders.
2. Use according to claim 1, characterized in that: the affective disorder is an epilepsy comorbid affective disorder.
3. Use according to claim 1, characterized in that: the affective disorder is accompanied by a cognitive disorder.
4. Use according to any one of claims 1 to 3, characterized in that: the affective disorder is caused by status epilepticus, acute epilepsy, or chronic epilepsy.
5. Use according to claim 4, characterized in that: the status epilepticus is induced by pilocarpine and/or hydnocarpic acid.
6. Use according to claim 4, characterized in that: the acute epilepsy is induced by pentaerythritonin and/or coriamyrtin.
7. Use according to claim 4, characterized in that: the chronic epilepsy is induced by pentaerythritonin and/or coriamyrtin.
8. Use according to any one of claims 1 to 3, characterized in that: the medicament can improve depression state, and/or improve anxiety state.
9. Use according to claim 8, characterized in that: the medicine can improve memory.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101590066A (en) * | 2009-06-26 | 2009-12-02 | 连晓媛 | 1, the medical usage of 6-diphosphate fructose in treating epilepsy complication and prevention epilepsy |
| CN106668035A (en) * | 2017-01-24 | 2017-05-17 | 中南大学湘雅三医院 | Antiepileptic pharmaceutical composition |
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| Publication number | Priority date | Publication date | Assignee | Title |
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