CN112138003A - Use of 3-n-butyl-isoindolin-1-one in sedative, anticonvulsant and antiepileptic drugs - Google Patents
Use of 3-n-butyl-isoindolin-1-one in sedative, anticonvulsant and antiepileptic drugs Download PDFInfo
- Publication number
- CN112138003A CN112138003A CN201910580960.2A CN201910580960A CN112138003A CN 112138003 A CN112138003 A CN 112138003A CN 201910580960 A CN201910580960 A CN 201910580960A CN 112138003 A CN112138003 A CN 112138003A
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- China
- Prior art keywords
- butyl
- isoindoline
- ketone
- isoindolin
- anticonvulsant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/4035—Isoindoles, e.g. phthalimide
-
- 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
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
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- Neurology (AREA)
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- Anesthesiology (AREA)
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- Pain & Pain Management (AREA)
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- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to application of a compound 3-n-butyl-isoindoline-1-ketone shown in a general formula I in medicines for calming, anticonvulsant and antiepileptic. Pharmacodynamic research facts also show that the 3-n-butyl-isoindoline-1-ketone can obviously reduce autonomous activities, can obviously prolong the latency of the mouse tonic alertness attack, reduce the incidence rate of the tonic convulsion, obviously prolong the death time of the convulsion mouse, reduce the death rate, and have better sedative and antiepileptic effects than butylphthalide. Since 3-n-butyl-isoindolin-1-one is a white powdery solid, suitable for formulation requirements, compared to its oily liquid form like the drug 3-butyl-1-isobenzofuranoneHas larger freedom in preparation, provides more choices for clinical medication and reduces the medication cost.
Description
The technical field is as follows:
the invention belongs to the field of compound medicines, and particularly relates to application of 3-n-butyl-isoindoline-1-ketone and a medicinal composition containing the 3-n-butyl-isoindoline-1-ketone in medicines for sedation, anticonvulsant and antiepileptic.
Background art:
cerebral Infarction (CI), also known as Ischemic Stroke (CIs), is one of three major killers that endanger human life and health, following heart disease and cancer. After cerebral infarction, a patient can have secondary epilepsy, called as 'epilepsy after stroke', and recurrent seizures of epilepsy can further aggravate brain injury and seriously affect the prognosis of the patient with cerebral infarction. But epilepsy treatment is complex and long in course of treatment, so that 70% -80% of all kinds of epileptic seizures can be controlled by the first-line antiepileptic drugs commonly used clinically at present, and the rest intractable epilepsy is treated by surgical operation but is limited by indications, so that new drugs have to be developed and new indications are discovered at the same time
The invention discovers that the 3-n-butyl-isoindoline-1-ketone has good effects of calming, resisting convulsion and resisting epilepsy. When 3-n-butyl-isoindoline-1-ketone is researched to treat cerebral infarction caused by ischemia, 3-n-butyl-isoindoline-1-ketone is unexpectedly found to have a sedative effect, so that 3-n-butyl-isoindoline-1-ketone is inferred to have sedative, anticonvulsant and antiepileptic effects, and pharmacodynamic research facts also show that 3-n-butyl-isoindoline-1-ketone can obviously reduce autonomic activity, can obviously prolong the latent period of tonic alert attacks of mice, reduce the incidence rate of the tonic convulsion, obviously prolong the death time of convulsive mice, reduce the death rate and have better sedative and antiepileptic effects than 3-butyl-1-isobenzofuranone. Since 3-n-butyl-isoindolin-1-one is a white powdery solid, suitable for formulation requirements, it is likely to have a certain therapeutic effect on "post-stroke epilepsy" and refractory epilepsy.
The invention content is as follows:
aiming at the insufficient research that the compound 3-n-butyl-isoindoline-1-ketone shown in the general formula I has the effect of resisting cerebral apoplexy, the invention discovers that the 3-n-butyl-isoindoline-1-ketone has the effects of calming, resisting convulsion and resisting epilepsy, and pharmacodynamic experiments prove that the effects of calming and resisting epilepsy are obviously superior to those of 3-butyl-1-isobenzofuranone, and the compound is probably used for treating 'epilepsy after stroke' and intractable epilepsy.
The above purpose of the invention is realized by the following technical scheme:
the invention particularly relates to application of a medicine or a medicinal composition containing 3-n-butyl-isoindoline-1-ketone for treating 'epilepsy after stroke' and intractable epilepsy.
The research of the invention finds that the 3-n-butyl-isoindoline-1-ketone has better sedative and antiepileptic effects than n-butylphthalide, and the influence of the 3-n-butyl-isoindoline-1-ketone on the autonomous activity of a mouse is observed to find that the compound has good sedative activity. Respectively as follows: (1) the first group was a negative control group (PEG 400); (2) 3-n-butyl-isoindolin-1-one low dose group (L-NBI, 200 mg/kg); (3) 3-n-butyl-isoindolin-1-one (M-NBI, 400 mg/kg); (4) 3-n-butyl-isoindolin-1-one high dose group (H-NBI, 800 mg/kg); (5) group of 3-butyl-1-isobenzofuranones (NBP, 400 mg/kg); (6) diazepam group (DG, 1500 mg/kg). Each group of mice was administered by intraperitoneal injection at 0.2 ml/kg. Before administration, each group of mice is respectively put into an activity box of a GJ-1 photoelectric counter to adapt to administration after 30min, the number of times of 5min autonomous activities of the mice is recorded after 20min and 40min, the obtained data is statistically analyzed by using a sps.13 software, and the significant difference between the groups is compared. L-NBI (P ═ 0.048), M-NBI (P ═ 0.024), and H-NBI (P ═ 0.009) were found to have significant differences compared to the control group. Moreover, the effect of the 3-n-butyl-isoindoline-1-ketone group and the high-dose group is better than that of the 3-butyl-1-isobenzofuranone group.
The results of the invention not only prove that the 3-n-butyl-isoindoline-1-ketone has good effects of sedation, anticonvulsant and antiepileptic, but also have great choice in the field of preparation compared with the oily liquid structure of butylphthalide because the compound is a white powdery solid, thereby providing new possibility for changing the administration mode, being beneficial to reducing the pharmaceutical cost and improving the administration efficiency, and therefore, the 3-n-butyl-isoindoline-1-ketone has wide application prospect.
The present invention relates to pharmaceutical compositions containing as active ingredient a compound of the invention and a pharmaceutically acceptable excipient or adjuvant. Typically, the pharmaceutical compositions of the present invention contain 0.1 to 95% by weight of a compound of the present invention.
Pharmaceutical compositions of the compounds of the present invention may be prepared according to methods well known in the art. For this purpose, the compounds of the invention can, if desired, be combined with one or more solid or liquid pharmaceutical excipients and/or adjuvants and brought into a suitable administration form or dosage form for use as a human or veterinary medicine.
Since the compound of the present invention is in a crystalline form, the compound or a pharmaceutical composition containing the compound can be formulated into a liquid dosage form, a gaseous dosage form, a semisolid dosage form, and a solid dosage form. For example, the liquid dosage form can be true solution, emulsion, suspension, microparticle, colloid, etc.; the gas preparation can be aerosol, spray, powder spray; the semisolid preparation can be oral soft extract, topical paste, cataplasm, etc.; the solid dosage form can be tablet, capsule, dripping pill, powder, suppository, granule, lyophilized powder for injection, etc.
The compounds of the present invention or pharmaceutical compositions containing the compounds may be administered in unit dosage form by enteral or parenteral routes, such as oral, intramuscular, subcutaneous, nasal, oromucosal, dermal, peritoneal, rectal, and the like.
The administration route of the compound or the pharmaceutical composition containing the compound can be injection, including intravenous injection, intramuscular injection, subcutaneous injection, intradermal injection, acupoint injection and the like.
The compound or the medicinal composition containing the compound can be prepared into common preparations, sustained-release and targeted preparations and various particle delivery systems.
In order to prepare the unit dosage form into tablets, various carriers well known in the art can be widely used. Examples of the carrier are, for example, diluents and absorbents such as starch, dextrin, calcium sulfate, lactose, mannitol, sucrose, sodium chloride, glucose, urea, calcium carbonate, kaolin, microcrystalline cellulose, aluminum silicate and the like; wetting agents and binders such as water, glycerin, polyethylene glycol, ethanol, propanol, starch slurry, dextrin, syrup, honey, glucose solution, acacia slurry, gelatin slurry, sodium carboxymethylcellulose, shellac, methyl cellulose, potassium phosphate, polyvinylpyrrolidone and the like; disintegrating agents such as dried starch, alginate, agar powder, brown algae starch, sodium bicarbonate and citric acid, calcium carbonate, polyoxyethylene sorbitol fatty acid ester, sodium dodecylsulfate, methyl cellulose, ethyl cellulose, etc.; disintegration inhibitors such as sucrose, glyceryl tristearate, cacao butter, hydrogenated oil and the like; absorption accelerators such as quaternary ammonium salts, sodium lauryl sulfate and the like; lubricants, for example, talc, silica, corn starch, stearate, boric acid, liquid paraffin, polyethylene glycol, and the like. The tablets may be further formulated into coated tablets, such as sugar-coated tablets, film-coated tablets, enteric-coated tablets, or double-layer and multi-layer tablets.
For example, to form the administration units into pills, various carriers well known in the art are widely used. Examples of the carrier are, for example, diluents and absorbents such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, polyvinylpyrrolidone, kaolin, talc and the like; binders such as acacia, tragacanth, gelatin, ethanol, honey, liquid sugar, rice paste or batter, etc.; disintegrating agents, such as agar powder, dried starch, alginate, sodium dodecylsulfate, methylcellulose, ethylcellulose, etc.
For example, to encapsulate the administration unit, the active ingredient of the compounds of the present invention is mixed with the various carriers described above, and the mixture thus obtained is placed in hard gelatin capsules or soft gelatin capsules. The effective component of the compound can also be prepared into microcapsules, and the microcapsules can be suspended in an aqueous medium to form a suspension, and can also be filled into hard capsules or prepared into injections for application.
For example, the compounds of the present invention may be formulated as injectable preparations, such as solutions, suspensions, emulsions, lyophilized powders, which may be aqueous or non-aqueous, and may contain one or more pharmaceutically acceptable carriers, diluents, binders, lubricants, preservatives, surfactants or dispersants. For example, the diluent may be selected from water, ethanol, polyethylene glycol, 1, 3-propanediol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitol fatty acid ester, etc. In addition, for the preparation of isotonic injection, sodium chloride, glucose or glycerol may be added in an appropriate amount to the preparation for injection, and conventional cosolvents, buffers, pH adjusters and the like may also be added. These adjuvants are commonly used in the art.
In addition, colorants, preservatives, flavors, flavorings, sweeteners or other materials may also be added to the pharmaceutical preparation, if desired.
For the purpose of administration and enhancing the therapeutic effect, the drug or pharmaceutical composition of the present invention can be administered by any known administration method.
The dosage of the pharmaceutical composition of the compound of the present invention to be administered depends on many factors, such as the nature and severity of the disease to be prevented or treated, the sex, age, body weight, character and individual response of the patient or animal, the administration route, the number of administrations and the therapeutic purpose, and thus the therapeutic dosage of the present invention can be widely varied. Generally, the dosage of the pharmaceutical ingredients of the present invention used is well known to those skilled in the art. The prophylactic or therapeutic objectives of the present invention can be accomplished by appropriate adjustment of the actual amount of drug contained in the final formulation of the compound composition of the present invention to achieve the desired therapeutically effective amount.
The total dose required for each treatment can be divided into multiple doses or administered as a single dose. The compounds or compositions of the present invention may be administered alone or in combination with other therapeutic or symptomatic agents and adjusted in dosage.
The present invention will be described in detail with reference to examples, but the present invention is not limited thereto.
Detailed Description
EXAMPLE 13 preparation of n-butyl-isoindolin-1-one tablet
[ prescription ]
Accurately weighing 3-n-butyl-isoindoline-1-ketone with constant weight according to the prescription amount, grinding into powder, and sieving with a 100-mesh sieve for later use. Accurately weighing starch with constant weight, and sieving with 100 mesh sieve. Mixing sieved 3-n-butyl-isoindoline-1-ketone and starch uniformly, adding a proper amount of 50% ethanol, preparing a soft material, granulating through a nylon sieve of 18 meshes, drying at 60-70 ℃, grading through a sieve of 18 meshes, then adding sodium carboxymethyl starch and magnesium stearate, and mixing uniformly. Punching with 8mm diameter die and tabletting.
EXAMPLE 23 preparation of hard capsules of n-butyl-isoindolin-1-one
[ prescription ]
The wet granulation process was the same as in example 1. Accurately weighing 3-n-butyl-isoindoline-1-ketone with constant weight according to the prescription amount, grinding into powder, and sieving with a 100-mesh sieve for later use. Accurately weighing starch with constant weight, and sieving with 100 mesh sieve. Mixing sieved 3-n-butyl-isoindoline-1-ketone and starch uniformly, adding a proper amount of 50% ethanol, preparing a soft material, granulating through a nylon sieve of 18 meshes, drying at 60-70 ℃, grading through a sieve of 18 meshes, detecting the content, and filling into a No. 1 capsule after the content is qualified.
EXAMPLE 33 preparation of Soft capsules of n-butyl-isoindolin-1-one
Mixing 1g of prepared 3-n-butyl-isoindoline-1-ketone, 10g of vegetable oil and 1g of polyglycerol ester, and uniformly mixing in a ball mill to prepare the content of the soft capsule. Using gelatin, glycerin, water and opacifier as capsule material in the ratio of 1 to 0.4 to 0.8 to 0.01, preparing soft capsule by mould pressing method, cold wind solidifying and drying the soft capsule, washing with proper solvent and finally drying to obtain 100 soft capsules.
EXAMPLE 43 preparation of n-butyl-isoindolin-1-one lyophilized powder
Adding 1g of prepared 3-n-butyl-isoindoline-1-ketone into 800ml of water for injection, adding 6g of mannitol after dissolving, supplementing the water for injection to 1000ml after fully dissolving, filtering the solution through a microporous filter membrane after active carbon decarburization, subpackaging the solution in 7ml penicillin bottles, adding 4ml of water for injection into each bottle, plugging, freeze-drying and capping to obtain the compound preparation. The specification is 4 mg/bottle.
EXAMPLE 53 preparation of n-butyl-isoindolin-1-one injection
Adding injection water 900ml into 1g of prepared 3-n-butyl-isoindoline-1-ketone and 9g of sodium chloride, adjusting pH to 6.5-7.2, adding 3g of carbon for injection, stirring, boiling for 15min, filtering the solution with filter paper to remove carbon while the solution is hot, and then finely filtering with a 0.22 mu m microporous filter membrane. Adding water for injection to 1000ml, checking clarity of filtrate, subpackaging in 5ml ampoule bottle after being qualified, sealing by melting, and sterilizing under pressure at 110 deg.C for 30 min.
Example 63 Effect of n-butyl-isoindolin-1-one on the autonomic Activity of mice
(1) Grouping animals
Selecting 20-22g (half each male and female) Kunming mice, putting the mice into a movable box of a GJ-1 type photoelectric counter before an experiment, starting a recorder, recording the number of times of the mice moving in 5min, selecting about 130 times of autonomous movement as normal mice, and then distributing the normal mice to each experiment group according to the number of times of the autonomous movement, wherein the autonomous movement of the mice of each group before the experiment has no obvious difference.
Experiment grouping
Selecting 60 Kunming mice, randomly dividing the Kunming mice into 6 groups, wherein each group comprises 10 mice and is respectively as follows: (1) the first group was a negative control group (PEG 400); (2) 3-n-butyl-isoindolin-1-one low dose group (L-NBI, 200 mg/kg); (3) 3-n-butyl-isoindolin-1-one (M-NBI, 400 mg/kg); (4) 3-n-butyl-isoindolin-1-one high dose group (H-NBI, 800 mg/kg); (5) group of 3-butyl-1-isobenzofuranones (NBP, 400 mg/kg); (6) diazepam group (DG, 1500 mg/kg). Each group of mice was administered by intraperitoneal injection at 0.2 ml/kg. Before administration, each group of mice is respectively put into an activity box of a GJ-1 photoelectric counter to adapt to administration after 30min, the number of times of 5min autonomous activities of the mice is recorded after 20min and 40min, the obtained data is statistically analyzed by using a sps.13 software, and the significant difference between the groups is compared.
Results of the experiment
Effect of 3-n-butyl-isoindolin-1-one on the autonomic Activity of mice (Table-1)
The experimental data were processed with statistical software SPSS17.0 and neurobehavioral differences between groups were examined by one-way analysis of variance (ANOVA), and the results indicated: the 3-n-butyl-isoindoline-1-ketone group can obviously inhibit the spontaneous activity frequency of mice in low, medium and high dose groups, and compared with a control group, L-NBI (P ═ 0.048), M-NBI (P ═ 0.024) and H-NBI (P ═ 0.009) have significant differences. The composition has obvious linear positive correlation on statistical analysis, and the higher the dosage, the more obvious the inhibition of the spontaneous activity of the mice, and the stronger the sedation. Moreover, the effect of the 3-n-butyl-isoindoline-1-ketone group and the high-dose group is better than that of the 3-butyl-1-isobenzofuranone group.
Example 73 Effect of n-butyl-isoindolin-1-one on strychnine-induced epilepsy in mice
(1) Experiment grouping
Selecting 60 healthy Kunming mice with the weight of 20-22g, randomly dividing the mice into 6 groups, wherein each group comprises 10 mice, and the weight is as follows: (1) the first group was a negative control group (PEG 400); (2) 3-n-butyl-isoindolin-1-one low dose group (L-NBI, 200 mg/kg); (3) 3-n-butyl-isoindolin-1-one (M-NBI, 400 mg/kg); (4) 3-n-butyl-isoindolin-1-one high dose group (H-NBI, 800 mg/kg); (5) group of 3-butyl-1-isobenzofuranones (NBP, 400 mg/kg); (6) phenobarbital (PG, 20 g/kg). Each group of mice was administered by intraperitoneal injection at 0.2 ml/kg. After mice are administered by groups for 40min, 2mg/kg of strychnine nitrate is injected into abdominal cavity to cause proficiency, and the incubation period of seizures, the time of death, the incidence rate and the death rate of tonic convulsions are observed and recorded within 2h
(2) Grading standards
The latency, duration, and seizure pattern of epileptiform seizures were observed in each group of rats. Latency refers to the time after intraperitoneal injection of strychnine nitrate until there is a tic response. Duration refers to the time from the onset of the tic response to the cessation of the attack. The seizure behavior was graded by reference to the RACINE grading scale.
Level 0: no response or cessation of tics;
stage I: rhythmic mouth and face twitching;
II stage: nodding or drifting;
grade III: single limb twitching;
stage IV: multi-limb twitching or rigidity;
and V stage: generalized tonic clonic seizures.
Results of the experiment
Effect of 3-n-butyl-isoindolin-1-one on strychnine-induced epilepsy in mice (Table-2)
The experimental data are treated by statistical software SPSS17.0 in an incoming line, and neurobehavioral differences among groups are tested by a one-way ANOVA (ANOVA) method, which shows that compared with a model group, the 3-n-butyl-isoindoline-1-ketone group can obviously prolong the latent period of the tonic alertness attack of mice, the incidence rate of the tonic convulsion is reduced, the death time of the convulsion mice is obviously prolonged, the death rate is reduced, L-NBI (P ═ 0.038), M-NBI (P ═ 0.007), H-NBI (P < 0.001) have obvious statistical differences compared with the model group, and the mice have positive dose correlation, the higher dose has stronger action effect, and the M-NBI has equivalent effect to the 3-butyl-1-isobenzofuranone group, and the difference has no statistical difference (P ═ 0.391).
The results show that the 3-n-butyl-isoindoline-1-ketone has good sedative, anticonvulsant and antiepileptic effects.
Claims (7)
1. Application of 3-n-butyl-isoindoline-1-ketone shown as general formula I in medicines for calming, anticonvulsant and antiepileptic
2. The compound of claim 1, wherein: the 3-n-butyl-isoindoline-1-ketone is (+/-) -3-n-butyl-isoindoline-1-ketone, (+) -3-n-butyl-isoindoline-1-ketone or (-) -3-n-butyl-isoindoline-1-ketone.
3. The use according to claim 1, characterized in that convulsions and epilepsy are caused by various clinical diseases, especially "epilepsy after stroke" caused after cerebral infarction.
4. The use of claim 1, wherein the therapeutically effective amount of the compound is: 0.1-200 mg/kg/day.
5. A pharmaceutical composition for sedation, anticonvulsant and antiepileptic comprising a therapeutically effective amount of 3-n-butyl-isoindolin-1-one of formula I and a pharmaceutically acceptable carrier or excipient,
6. the pharmaceutical composition of claim 5, wherein the pharmaceutical composition comprises a tablet, a capsule, an injection, a granule, a pill, a powder, a sustained release preparation, a controlled release preparation, and various microparticle delivery systems.
7. The pharmaceutical composition according to claim 5, wherein the pharmaceutical composition is used for preparing a medicament for preventing or treating cerebral infarction caused by cerebral ischemia.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4898871A (en) * | 1986-12-02 | 1990-02-06 | Rhone-Poulenc Sante | Pyrrole derivatives and pharmaceutical compositions which contain them as hypnotics and anticonvulsants |
| US4960779A (en) * | 1986-12-02 | 1990-10-02 | Rhone-Poulenc Sante | Pyrrole derivatives, and pharmaceutical compositions which contain them and pharmacological methods of use |
| CN103655555A (en) * | 2012-09-14 | 2014-03-26 | 中山大学 | Application of 3-n-isoindoline-1-ketone in preparation of medicament for preventing and treating cerebral infarction |
-
2019
- 2019-06-27 CN CN201910580960.2A patent/CN112138003A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4898871A (en) * | 1986-12-02 | 1990-02-06 | Rhone-Poulenc Sante | Pyrrole derivatives and pharmaceutical compositions which contain them as hypnotics and anticonvulsants |
| US4960779A (en) * | 1986-12-02 | 1990-10-02 | Rhone-Poulenc Sante | Pyrrole derivatives, and pharmaceutical compositions which contain them and pharmacological methods of use |
| CN103655555A (en) * | 2012-09-14 | 2014-03-26 | 中山大学 | Application of 3-n-isoindoline-1-ketone in preparation of medicament for preventing and treating cerebral infarction |
Non-Patent Citations (1)
| Title |
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| 王晓丽，等: "天然抗脑缺血药物丁苯酞类衍生物的研究进展" * |
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