WO2011120281A1 - Use of l-oxiracetam in manufacture of medicaments for preventing or treating cognitive dysfunction - Google Patents

Abstract

The present invention provides the use of L-oxiracetam in the manufacture of the medicaments for preventing or treating cognitive dysfunction. L-oxiracetam with the purity of more greater than 99.3% is used in the present invention, which effectively excludes toxic hazards caused by the inactive ingredients in the medicaments. Meanwhile L-oxiracetam in the medicaments of the present invention is used as single active ingredient, which makes the medicaments quality much easier to control.

Description

 Application of L-Oxacetam in the preparation of drugs for preventing or treating cognitive dysfunction Technical field

 The invention relates to the medical use of L-Oxacetam, in particular to the application of L-Oxacetam in the preparation of a medicament for preventing or treating cognitive dysfunction.

Background technique

 L-Oxacetam ((S)- 4-hydroxy-2-oxo-1-pyrrolidineacetamide) is Oxiracetam (Oxiracetam CAS) The left-handed body of 62613-82-5 is a white microcrystalline powder with a melting point of 135-136 ° C and an optical rotation of -36.0 ° (C=1.00 in water). The solubility of L-Oxacetam is significantly better than that of the mixed spin. Oxiracetam is a synthetic hydroxyaminobutyric acid (GABOB) cyclic derivative that promotes ATP in the brain, promotes acetylcholine synthesis and enhances the conduction of nerve excitation, and improves the retrograde forgetfulness caused by hypoxia. Can enhance memory and improve learning ability. Because of the unsatisfactory effect of oxiracetam in the treatment of mental retardation in the clinic, it is mainly due to the ineffective or even antagonistic right-handed oxiracetam in the active ingredient. L-Olaxiracee has not been reported as a drug alone.

 It is clear to the industry that age is the most important factor affecting the incidence of cognitive dysfunction. With the increase of age, the incidence of cognitive dysfunction increases rapidly. Cognitive dysfunction has become an important disease affecting the health and quality of life of middle-aged and elderly people. The manifestations of cognitive dysfunction include not only memory impairment, aphasia, agnosia, misuse and visual spatial disorder, but also anxiety, depression and agitation. Emotional behavioral disorders such as impulsiveness, which are medically defined as having cognitive dysfunction diseases when patients exhibit at least the above three symptoms at the same time. These emotional and behavioral disorders are also causes of disability of the patients, bringing to society and families. heavy burden.

At present, the treatment of cognitive dysfunction drugs, for the hypothesis of different causes, clinically proposed a variety of drug treatment methods, such as huperzine A, donepezil, rivastigmine, galantamine, memantine, nimodipine, Ergots, pyrrolidines, aspirin, ibuprofen, statins, etc. However, some of the drugs used in clinical use have limited efficacy due to their toxic side effects, so it is necessary to develop new drugs for the treatment of cognitive dysfunction.

 CN 101367757A discloses a (S)- A process for the preparation of 4-hydroxy-2-oxo-1-pyrrolidineacetamide. It uses (S)-4-halo-3-hydroxybutyrate as a raw material to react with a polar solvent and basic conditions to obtain L-Oxacetam, wherein the reaction under alkaline conditions is through the reaction process. The alkali is added in portions, and the chloroform is added dropwise to control the pH of the reaction. The crude product is subjected to cation exchange resin to obtain an acidic aqueous solution of the product, and then neutralized with an anion exchange resin. The neutralized liquid is concentrated to obtain a crude product, and the crude product is recrystallized by ethanol. L-Oxacetam was prepared by one time by crystallizing once with a methanol/acetone mixed solvent or by recrystallization of isopropyl alcohol once.

technical problem

The object of the present invention is to provide a use of L-Oxacetam in the field of pharmacy, in particular to provide a use of L-Oxacetam in the preparation of a medicament for preventing or treating cognitive dysfunction.

Technical solution

The present invention specifically relates to the use of L-Oxacetam as a medicament for the preparation of a medicament for preventing or treating memory dysfunction; as a preparation for the preparation of a medicament for preventing or treating linguistic disability; as an application for preparing a medicament for preventing or treating visual dysfunction; Use in the prevention or treatment of drugs for attention disorders; as an application in the preparation of drugs for the prevention or treatment of reasoning and abstract thinking abilities.

The use of L-Oxacetam in the preparation of a medicament for preventing or treating cognitive dysfunction, in particular, a pharmaceutical composition comprising L-Oxacetam as an active ingredient, and the dosage form may be an oral preparation such as a tablet or a pill. , powder, granules, capsules, etc.; injections such as powder for injection, lyophilized powder for injection, etc., the above dosage forms can be prepared according to conventional methods.

 The above dosage forms are preferably oral capsules, tablets and injections.

 The above oral preparation is administered at a dose of 5 to 30 mg/kg/day, more preferably 10 to 20 mg/kg/day.

 The invention provides a drug for preventing or treating cognitive dysfunction containing levorotaxtam The purity of the L-Oxacetam starting material used is preferably 99.3% or more (optical purity) in terms of weight percent.

Beneficial effect

In order to further verify the medicinal effects of the present invention, the inventors conducted the following tests.

 (1) Pharmacokinetics and Absolute Bioavailability of L-Oxacetam in Animals

 Based on the comparison with the pharmacokinetics of the mixed-race oxiracetam, the dose of the intragastric and intravenous administration of Beagle dogs was determined to be 50 mg. /kg.

 Take 6 adult Beagle dogs, half male and half female, weighing 10.0±0.5kg. Randomly divided into three groups, each group of 2, male and female. The dose of 50mg was administered to the Beagle dogs by the Latin square three-crossover experiment (see Table 1 below). /kg. Samples with a purity of 99.3% (optically pure) of L-Oxacetam were used and each route of administration was separated by one week. The rats were administered by intragastric administration for 12 hours after fasting, and continued to be fasted for 3 hours after administration. Take blank blood before administration, 0.083, 0.25, 0.5, 0.75 after intragastric administration, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 12.0, 24.0 hours; 0.083, 0.25, 0.5, 0.75 after intravenous administration 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 12.0, 24.0 hours, 1 mL of blood was taken from the forelimb vein in heparinized tubes, and plasma was taken by centrifugation. The plasma concentration of the drug was determined by LC-MS-MS. . The results are shown in Table 2-7 below.

 Table 1 Three-cycle three-crossover Latin square experimental design Beagle dog grouping situation

 Note: ORT is oxiracetam; s-ORT is levorotatory oxiracetam

 The plasma drug concentrations in dogs after intravenous injection and gavage 50 mg/kg oxiracetam and levoracetamer are shown in Table 2-4.

 Table 2 Plasma concentration in Beagle dogs after intravenous administration of 50 mg/kg oxiracetam (μg/mL)

 ND: less than 0.5μg/mL

 Table 3 Plasma concentration (μg/mL) in Beagle dogs after 50 mg/kg L-Oxacetam

 ND: less than 0.5μg/mL

 Table 4 Plasma concentration (μg/mL) in Beagle dogs after intravenous injection of 50 mg/kg L-Oxacetam

 ND: less than 0.5μg/mL

 Table 5 Pharmacokinetic parameters of Beagle dogs after perfusion of 50 mg/kg levoracetam

 Table 6 Pharmacokinetic parameters of Beagle dogs after 50 mg/kg L-Oxacetam

 Table 7 Pharmacokinetic parameters of Beagle dogs after intravenous injection of 50 mg/kg L-Oxacetam

It can be seen that after Beagle dogs were given 50 mg/kg of oxiracetam, the AUC _0-∞ was 165.04 ± 24.02 h, the clearance rate was 0.31 ± 0.04 L/h/kg, and the peak time and peak concentration were 1.25. ± 0.27 h, 39.67 ± 7.55 μg/mL; after administration of 50 mg/kg L _- Oxacetam by intragastric administration, AUC _0-∞ was 160.97 ± 27.86 h, and the peak time and peak concentration were 1.21 ± 0.53 h, respectively. 41.28 ± 11.29 μg/mL; the absolute bioavailability of AUC _0-∞ was 242.72 ± 37.75 h after intravenous administration was 65.76 ± 9.12%, see Figure 1 and Figure 2 for details.

 It is concluded that L-Oxacetam retains the pharmacokinetic parameters of the original oxiracetam.

 (2) Study on the effect of levorotatory oxiracetam on animal learning ability

 Part I: Effect of scopolamine-induced learning and memory in mice with mild dementia

 1. Materials and methods

Scopolamine (Cat. No. 84785-1G) was purchased from Fluka; L-Olaxiracene (batch number: 20071024), Olaracetam (batch number: 20071101) Provided by Chongqing Dongze Pharmaceutical Technology Development Co., Ltd. It is prepared with physiological saline and is used now.

 The Morris water maze was purchased from the Institute of Materia Medica, Chinese Academy of Medical Sciences (diameter: 120 cm; height: 40 cm).

The experimental animals were ICR mice, male, weighing 19-22 g, purchased from Vitallihua Experimental Animal Co., Ltd. Animals were randomly divided into 6 groups: blank control group, 0.8 mg scopolamine model group, 30 mg The left oxiracetam group, the 60 mg levoracetam group, the 30 mg oxiracetam group, and the 60 mg oxiracetam group, 12 rats in each group.

Mode of administration: Intravenous injection of normal saline, oxiracetam or levoracetamone 1 hour before the experiment, intraperitoneal injection of scopolamine half an hour before the experiment. Dosing once a day until the end of the experiment.

 Morris Water Labyrinth Experiment: The Morris Water Labyrinth consists of a metal cylindrical pool and automatic display, recording device, and a safety island (platform). The pool is divided into 4 quadrants (East, South, West, and North) and the platform is placed in the center of one of the quadrants. Water temperature is maintained at 24 ± 2 oC, the water surface is higher than the platform 1.0 Cm. Each mouse received 2 training sessions per day, starting with two different water inlet points, and two training intervals of 15 minutes, recording the incubation period (the time to find the platform). If the mouse does not find the platform within 120 seconds, the incubation period is calculated in 120 seconds. The mice stayed on the platform for 10 seconds, regardless of whether the platform was found within 120 seconds. The mice were placed on the platform for 10 seconds before the start of the first experiment. After the last day of training, the experiment was carried out, and the platform was removed. The mice were free to swim for 120 seconds to find the platform. The recorded indicators included: swimming speed of the mouse, % of the quadrant staying time of the platform, time of crossing the platform for the first time, and number of times of crossing the platform.

 Statistical method: the result is mean ± SEM said. Two-way ANOVA with repeated measures was used to study the effects of treatment and time on each group and use Dunnett's Test compares the differences between the two groups. Animal weight and exploration experiments were compared by one-way ANOVA with post hoc LSD. p< 0.05 is considered to have a significant difference.

 2. Experimental results

 (1) Animal weight:

 ICR The mice were randomly divided into groups. The body weight of each group was about 20 g, and there was no significant difference between the groups (p>0.05). See Figure 3 for details.

 (2), Morris Water Maze:

 Two-way analysis of variance for repeated measures showed that days of training [F = 12.47, p < 0.01] and treatment factors [F = 22.72, p <0.01] has a significant impact on latency. At the same time, the number of days × treatment interaction factors also have a significant impact on the incubation period [F = 1.94, p<0.05]. After four days of training, the latency of the platform found in the blank control group decreased from (85.2±7.2) seconds to (29.2±4.5) seconds; the latency of the model group decreased from (117.5±2.0) seconds to (100.0±6.4) seconds. There was a significant difference between the two groups (p<0.01, two Way ANOVA, see Figure 4A). 60mg levoracetam and 60mg Oxiracetam can reduce the latency of scopolamine-injured mice, and there is a significant difference compared with the model group (p<0.05, two way) ANOVA, see Figures 4B and C). The improvement effect of the other groups was not obvious.

After the training phase is over, a platform exploration experiment is conducted. The residence time of the blank control mice in the quadrant of the platform (32.3 ± 3.4 seconds) was significantly longer than that of the model group (23.6 ± 2.5 seconds), with significant differences (p < 0.05, see Figure 5B). At the same time, the number of times the blank group animals crossed the platform position and the time of the first crossing the platform position in 120 seconds were also significantly different from the model group (p<0.05, see Figures 5C and D). L-Oxacetam and oxiracetam can improve the above three indicators to varying degrees, but there is no significant difference compared with the model group. There was no significant change in the swimming speed of the mice between the groups (see Figures 4D and 5A).

 Part II: Effect of scopolamine-induced learning and memory in mice with severe dementia

 1. Materials and methods

Scopolamine (Cat. No. 84785-1G) was purchased from Fluka; Left Olasacetam (batch number: 20071024) and Olaracetam (batch number: 20071101) were provided by Chongqing Dongze Pharmaceutical Technology Development Co., Ltd. It is prepared with physiological saline and is used now. The Morris water maze experimental device was purchased from the Institute of Materia Medica, Chinese Academy of Medical Sciences (diameter: 120 cm; height: 40 cm). The experimental animals were ICR mice, male, weighing 24~26g during the experiment, purchased from Vitallihua Experimental Animal Co., Ltd. Animals were randomly divided into 6 groups: blank control group, 0.8 mg scopolamine model group, 30 mg The left-handed oxiracetam group, the 60 mg left-handed oxiracetam group, the 30 mg oxiracetam group, and the 60 mg oxiracetam group, 12 rats in each group.

Mode of administration: The water maze test was started on the third day after continuous intraperitoneal injection of scopolamine in mice. One hour before the experiment, intraperitoneal injection of normal saline, levorotatory or oxiracetam; intraperitoneal injection of scopolamine half an hour before the experiment. Dosing once a day until the end of the experiment.

 Morris Water Labyrinth Experiment: The Morris Water Labyrinth consists of a metal cylindrical pool and automatic display, recording device, and a safety island (platform). The pool is divided into 4 quadrants (East, South, West, and North) and the platform is placed in the center of one of the quadrants. Water temperature is maintained at 24 ± 2 oC, the water surface is higher than the platform 1.0 Cm. Each mouse received 2 training sessions per day, starting with two different water inlet points, and two training intervals of 15 minutes, recording the incubation period (the time to find the platform). If the mouse does not find the platform within 120 seconds, the incubation period is calculated in 120 seconds. The mice stayed on the platform for 10 seconds, regardless of whether the platform was found within 120 seconds. The mice were placed on the platform for 10 seconds before the start of the first experiment. After the last day of training, the experiment was carried out, and the platform was removed. The mice were free to swim for 120 seconds to find the platform. The recorded indicators included: swimming speed of the mouse, % of the quadrant staying time of the platform, time of crossing the platform for the first time, and number of times of crossing the platform.

 Statistical method: the result is mean ± SEM said. Two-way ANOVA with repeated measures was used to study the effects of treatment and time on each group and use Dunnett's Test compares the differences between the two groups. Animal weight and exploration experiments were compared by one-way ANOVA with post hoc LSD. P< 0.05 is considered to have a significant difference.

 2. Experimental results

 (1), weight when grouping

 ICR The mice were randomized and each group weighed approximately 25 g. There was no significant difference between the groups (p>0.05). See Figure 6 for details.

 (2), Morris water maze

 Two-way analysis of variance for repeated measures showed that days of training [F = 15.41, p < 0.01] and treatment factors [F = 20.87, p <0.01] has a significant impact on latency. However, the number of days × treatment interaction factors had no significant effect on latency (F = 0.81, p>0.05]. After four days of training, the latency of the platform found in the blank control group decreased from (67.7±9.0) seconds to (40.2±7.3) seconds; the latency of the model group decreased from (118.0±1.2) seconds to (92.9±8.4) seconds. There was a significant difference between the two groups (p<0.01, two Way ANOVA, see Figure 7A). 60 mg of left oxiracetam can reduce the latency of scopolamine-injured mice, which is significantly different from the model group (p<0.05, two way) ANOVA, see Figure 7C). The improvement of the remaining groups was not significant (see Figure 7E).

After the training phase is over, a platform exploration experiment is conducted. In the blank control group, the number of times the blank group of animals crossed the platform position and the time of the first crossing of the platform position were significantly different from the model group in 120 seconds (p<0.05, see Figure 8D); There was no significant difference in the dwell time of the quadrant in the platform (see Figure 8B); there was no significant difference in swimming speed and number of crossing platforms (see Figures 8A, 8C). L-Oxacetam and oxiracetam can improve the above three indicators to varying degrees, but there is no significant difference compared with the model group. Scopolamine was administered two days prior to the water maze experiment, causing the swimming speed of the model group mice to be significantly higher than the blank control group (see Figure 7B and Figure 8A). Administration of L-Oxacetam and Oxiracetam reduced the swimming speed of the mice to varying degrees (see Figure 7D, Figure 7F and Figure 8A). Based on the above experimental results, the following conclusions can be drawn:

 60mg/kg L-Oxacetam can significantly improve the learning and memory ability of scopolamine-induced severe dementia mice, and has different characteristics compared with oxiracetam:

Although oxiracetam is effective, it can directly resist the damage of scopolamine. The latency of the first two days of the learning period is significantly improved compared with the model group, but it does not show protection as the damage increases. In particular, when scopolamine was given two days in advance, resulting in heavier injury, the administration of oxiracetam did not significantly improve the learning and memory ability of the mice.

With the increase of administration time, L-Oxacetam gradually showed the improvement of learning and memory ability of dementia mice. Even after administration of scopolamine two days in advance, L-Oxacetam can still significantly improve the spatial memory capacity of mice after heavier injury.

 (3) Protective effect of L-oxiracetam on cognitive dysfunction induced by chronic cerebral ischemia in rats

 Materials and Methods

L-Olaxitaxan (batch number: 20071024) and Olaracetam (batch number: 20071101) were provided by Chongqing Dongze Pharmaceutical Technology Development Co., Ltd. It is prepared with physiological saline and is used now.

The experimental animals used 40 SD rats, male, weighing 190-220 g, purchased from Chongqing Southwest Hospital. Animals were randomly divided into 4 groups: sham operation group, cerebral ischemia group, left-handed oxiracetam treatment group and oxiracetam treatment group. Ten rats in each group were treated with 100 mg/kg in the L-oxiracetam treatment group and 200 mg/kg in the oxiracetam-treated group once daily for 37 days from the day of surgery.

The rat model of cerebral ischemia was used to permanently occlude bilateral carotid arteries. The rats in the cerebral ischemia group and the two treatment groups were anesthetized with sodium pentobarbital 40 mg/kg, and the suture line 4 was used to separate and ligature the bilateral two-way neck. The common arteries cut the artery between the distant and proximal ligation points and suture the wound. The sham operation group was used to separate the bilateral common carotid arteries for immediate suturing. Pay attention to animal insulation during surgery.

 Morris The water maze experimental device was purchased from the Institute of Materia Medica, Chinese Academy of Medical Sciences (diameter: 120 cm; height: 40 cm).

 Experimental result

The escape latency of the L-Oxacetam administration group was significantly shorter than that of the model group and was significantly better than that of the mixed rotation. In addition, L-Oxacetam significantly increased the swimming time of the target in the target [(35.23±7.03) seconds vs (20.18±5.26) seconds, P<0.01】, the reference group mixed race oxiracetam was 31.23±5.03 seconds, which was slightly worse than the left-handed body. It indicated that L-Oxacetam can significantly improve the cognitive impairment caused by cerebral ischemia in rats, and its effect is better than that of oxiracetam.

Based on the above results, the inventors can demonstrate the results of the above-mentioned experimental animal experiments: aphasia, agnosia, disuse, attention disorder, in the treatment of cognitive dysfunction, with levorotaxtam as the main active ingredient, Reasoning and abstract thinking ability disorders and visual disorders have significant effects.

 (4) Toxicological test

The toxicity of L-oxiracetam and oxiracetam was compared under GLP conditions. The dose was 5g/kg, 10 animals per group, weighing 18.3±1.5g, male and female, 0.5% CMC solution. Oral administration after preparation. The results showed that the animals in the two groups had normal activities and no obvious toxicity. There was no significant difference in toxicity between the two groups after 14 days of continuous observation. It shows that L-Oxacetam does not increase the drug effect while increasing toxicity.

 The beneficial effects of the invention are:

 1 The invention directly adopts L-Oxacetam to prepare a medicament for preventing or treating cognitive dysfunction, thereby effectively reducing the dosage of the patient and improving the therapeutic effect.

 2 The invention uses the L-Oxacetam raw material with a purity greater than 99.3%, which effectively eliminates the hidden danger of the drug toxicity caused by the presence of the ineffective component in the drug, and makes the drug safer.

 3 In the drug of the present invention, L-Oxacetam is a single active ingredient, which makes the quality of the drug easier to control, and the curative effect is more clear.

DRAWINGS

 DRAWINGS

Figure 1: The drug time curve after oral administration of L-oxiracetam, oxiracetam and intravenous oxiracetam in each dog. It is the pharmacokinetics and absolute bioavailability study of L-Oxacetam in animals. Test, gavage for each dog 50 Mg/kg oxiracetam, and intravenous and intragastric 50 mg/kg Plasma concentration-time data of dogs after L-Oxacetam, in which CK-sox is L-Oxacetam and CK-hox is mixed oxiracetam.

 figure 2 : The average drug-time curve after oral administration of levoracetam, oxiracetam and intravenous levoracetam for dogs, in the study of pharmacokinetics and absolute bioavailability in L-Oxacetam For the Begale dog 50 Mg/kg oxiracetam, and intravenous and intragastric 50 mg/kg The mean plasma concentration-time data in plasma after L-Oxacetam, in which CK-sox is L-Oxacetam and CK-hox is mixed oxiracetam.

Figure 3 is a graph showing the weight of mice grouped during mild modeling, which is an indicator of the uniformity of animal grouping in the study of the effect of L-Oxacetam on animal cognitive ability, in which CK-sox is L-Oxazidine, CK-hox is a mixed oxiracetam.

Figure 4: The effect of each group on the incubation period and swimming speed in the water maze training stage in the mild dementia model. It is the two key observations in the study of the effect of levo-oxiracetam on animal cognitive ability. Among them, CK-sox is left-handed oxiracetam and CK-hox is mixed-race oxiracetam.

Figure 5: The effect of each group on the platform exploration after the water maze training stage, is an observation index of the spatial recognition ability in the study of the effect of L-Oxacetam on animal cognitive ability, in which CK-sox is L-Olaxitan and CK-hox are mixed oxiracetam.

Figure 6 is a graph showing the weight of mice divided into groups during heavy modeling, wherein CK-sox is L-Oxacetam and CK-hox is mixed oxiracetam.

Figure 7: The effect of each group on the incubation period and swimming speed in the water maze training stage in the severe dementia model. It is the two main observation indicators in the study of the effect of levo-oxiracetam on animal cognitive ability, among which CK -sox is a left-handed oxiracetam and CK-hox is a mixed-race oxiracetam.

Figure 8: The effect of each group on the platform exploration after the water maze training phase of the severe dementia model. It is an important index in the study of the effect of L-oxiracetam on animal cognitive ability, in which CK-sox is left-handed. Oxiracetam and CK-hox are mixed oxiracetam.

BEST MODE FOR CARRYING OUT THE INVENTION

 detailed description

 Several embodiments of the present invention will be described below, but the content of the present invention is not limited thereto.

 Example 1:

 The prescription consists of:

 (a) L-Oxacetam (purity of 99.5%) 200mg/granule

 (b) Lactose 80mg / grain

 (c) Microcrystalline cellulose 70mg/granule

Taking 1000 tablets of levorotatory oxiracetam capsule as an example, the specific preparation method is as follows: firstly, the original auxiliary material is passed through an 80 mesh sieve, and the prescribed amount of L-Oxacetam, lactose and microcrystalline cellulose are uniformly mixed, directly Fill the capsules.

 Example 2:

 The prescription consists of:

 (a) L-Oxacetam (purity 99.6%) 200mg/tablet

 (b) Starch 34mg/tablet

 (c) Microcrystalline cellulose 60 mg/tablet

 (d) Talc powder 6mg/tablet

 (e) 2% hydroxypropyl methylcellulose (K4M model)

Taking 1000 tablets of levorotatory oxiracetam tablets as an example, the specific preparation method is as follows: firstly, the original auxiliary materials are passed through an 80 mesh sieve, and the prescribed amount of levorotatory oxiracetam, starch, and microcrystalline cellulose are uniformly mixed. 2% HPMC aqueous solution is made of soft material, granulated, dried, and granulated. The prescribed amount of talc powder is added to the granules, uniformly mixed, and tableted.

 Example 3:

 The prescription consists of:

 (a) L-Oxacetam (purity of 99.3%) 200mg/granule

 (b) Lactose 80.8mg / grain

 (c) sodium carboxymethyl starch 72mg/granule

 (d) talc powder 7.2mg / grain

 (e) 10% polyvinylpyrrolidone

Take 1000 tablets of levorotatory oxiracetam capsule as an example. The specific preparation method is as follows: firstly, the original auxiliary material is passed through an 80 mesh sieve, and the prescribed amount of left oxiracetam, lactose and sodium carboxymethyl starch is uniformly mixed. Add 10% PVP ethanol solution to make soft materials, granulate, dry, and granulate. Add the prescribed amount of talc powder to the granules, mix well and fill the capsules.

 Example 4:

Taking L-Oxacetam injection as an example, the specific preparation method is: weighing left-handed oxiracetam (purity of 98%) 50g, glucose 150g, 500ml of water for injection dissolved in a rare tank, the temperature is controlled at 50 ～60 ° C, stir until completely dissolved, the solution is cooled to 25 ° C, decolorized by adding activated carbon to the above prepared solution, and then the activated carbon is removed by filtration, and the phosphate solution is added to the solution. The H value was adjusted to 4.0, and water for injection was added to 5000 ml, potted, and sterilized at 105 ° C for 30 minutes to obtain a left-handed oxiracetam injection.

Embodiments of the invention

Industrial applicability

Sequence table free content

Claims (12)

 The use of L-Oxacetam in the preparation of a medicament for preventing or treating cognitive dysfunction. Use of L-Oxacetam in the preparation of a medicament for preventing or treating memory dysfunction; or use of L-Oxacetam in the preparation of a medicament for preventing or treating linguistic disability; or L-Oxacetam in the preparation of a preventive or therapeutic visual space Uses in disorders drugs; or the use of levorotaxtam in the preparation of drugs for the prevention or treatment of attention disorders; or the use of levorotaxtam in the preparation of drugs for the prevention or treatment of reasoning and abstract thinking disorders. The use according to claim 1 or 2, wherein the drug containing L-Oxacetam is an oral preparation or an injection. The use according to claim 3, wherein the oral preparation is an oral capsule or tablet administered at a dose of 5 to 30 mg/kg/day. The use according to claim 4, wherein the dose is 10 to 20 mg/kg/day. The use according to claim 4 or 5, characterized in that the raw material of the left-handed oxiracetam is 99.3% or more by weight. The use according to claim 1 or 2, characterized in that the raw material of the left-handed oxiracetam is 99.3% or more by weight. The use according to claim 3, characterized in that the raw material of the L-Oxacetam used has a purity of 99.3% or more by weight. A medicament for preventing or treating a cognitive dysfunction comprising the active ingredient L-Oxacetam and a pharmaceutically acceptable adjuvant. The medicament according to claim 9, wherein the drug is an oral preparation or an injection. The medicament according to claim 10, wherein the pharmaceutical oral preparation is an oral capsule or tablet. The medicament according to any one of claims 9 to 11, wherein the purity of the L-Oxacetam raw material used in the drug is More than 99.3% by weight.

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