CN107019684A - Treat pharmaceutical composition and its application of craniocerebral injury caused by mental disorder - Google Patents

Abstract

The invention belongs to a pharmaceutical composition for treating mental disorders caused by craniocerebral injury and its application; the pharmaceutical composition is prepared from the following raw materials: nicotinyl benzyl ester, bisabolol, and isoborneol; it has stable quality control and safety It has the advantages of being effective, natural and non-toxic, stable in effect, low in cost and suitable for long-term use.

Description

Pharmaceutical composition and application thereof for treating mental disorder caused by craniocerebral injury

technical field

The invention belongs to the technical field of medicine, and in particular relates to a pharmaceutical composition for treating mental disorders caused by craniocerebral injury and its application.

Background technique

Trauma to the brain due to various reasons is more common in daily life, 40% of traumatic brain injuries are caused by car accidents, 30% are caused by sports injuries, 20% are caused by falls, and 10% are caused by assaults . In sports, sports such as boxing, football, ice hockey, skiing, and mountaineering are likely to cause traumatic brain injuries.

Mental disorders caused by craniocerebral injuries refer to mental abnormalities that occur when the cranial brain is directly or indirectly affected by external forces, causing brain organic or functional disorders. Due to the direct or indirect effect of external force on the brain, brain tissue ischemia and hypoxia, causing organic or functional mental disorders of the brain, and disorders of cognition, will, behavior, language, and thinking activities of patients.

The clinical manifestations of mental disorders caused by craniocerebral injury include acute mental disorders and chronic mental disorders. Acute mental disorders mainly include concussion and delirium, and chronic mental disorders mainly include epilepsy, concussion syndrome, personality changes, and cognitive dysfunction. Among them, cognitive dysfunction has a serious impact on the later life of patients.

At present, the main treatment principles for mental disorders caused by craniocerebral injury include: ① Use brain metabolism activators (coenzyme Q10, citicoline) and cerebral circulation accelerators (hydroergot alkaloids, flunarizine) to activate brain metabolism, Indirectly inhibit the development of dementia. Cerebral metabolism activators mainly promote glucose absorption and metabolism, secondary expansion of cerebral blood vessels, and improve nutrient metabolism, while cerebral circulation enhancers are drugs that directly expand cerebral blood vessels; ② drugs for the treatment of neurotransmission block, such as amantadine Promote the release of dopamine and inhibit its reuptake; high calcium pantothenate can promote the absorption and metabolism of glucose in the brain, increase the concentration of serotonin in brain tissue and cerebral blood flow, and significantly improve neurological symptoms; prodrugs of acetylcholine (lecithin, chloride Choline) and cholinesterase inhibitors (physostigmine, tetrahydroaminopyridine) improve neurological symptoms by increasing the function of the acetylcholine system; neuropeptides can improve the cognition and memory of the elderly, and reduce depression and weakness symptoms;③ For symptomatic treatment, thioridazine, fluphenazine, flurbutanol, etc. are often used to control the impatience and excessive behavior of patients with mental disorders caused by craniocerebral injury; Ritalin and cloxacyl are commonly used to improve depression in patients with mental disorders caused by craniocerebral injury Symptoms; Diazepam is commonly used to improve anxiety symptoms in patients with mental disorders caused by craniocerebral injury.

However, these treatments did not have the desired effect clinically. Therefore, finding effective drugs for the treatment of cognitive dysfunction caused by mental disorders caused by craniocerebral injury is of great significance for the rehabilitation and prognosis of patients with craniocerebral injury.

Contents of the invention

The purpose of the present invention is to overcome the defects in the prior art and provide a pharmaceutical composition with stable quality control, safe and effective, natural and non-toxic, stable effect, low cost and suitable for long-term use for the treatment of mental disorders caused by craniocerebral injury and its application.

The object of the present invention is achieved in the following way: the pharmaceutical composition is prepared from the following raw materials: nicotinyl benzyl ester, bisabolol and isoborneol.

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury, which comprises the following raw materials formulated in parts by weight: 10-100 parts of nicotinyl benzyl ester, 10-100 parts of bisabolol, isoborneol 7 to 100 copies.

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury, the pharmaceutical composition comprises the following raw materials formulated in parts by weight: 10-80 parts of nicotinyl benzyl ester, 10-80 parts of bisabolol, isoborneol 7 to 80 copies.

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury, the pharmaceutical composition is prepared by preparing the following raw materials in parts by weight: 10-50 parts of nicotinyl benzyl ester, 10-50 parts of bisabolol, isoborneol 7 to 50 copies.

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury, the pharmaceutical composition is prepared by preparing the following raw materials in parts by weight: 20 parts of nicotinyl benzyl ester, 15 parts of bisabolol, and 7 parts of isoborneol.

The present invention provides the application of the above pharmaceutical composition in the preparation of the pharmaceutical composition for treating mental disorder caused by craniocerebral injury.

The nicotinyl benzyl ester, bisabolol and isoborneol described in the present invention can be directly obtained from the market, or can be obtained through plant extraction. In the present invention, the above raw materials are pulverized and sieved according to parts by weight, mixed, packed into capsules or pressed into tablets; or mixed with pharmaceutically acceptable carriers or diluents, then packed into capsules or pressed into tablets.

The present invention also provides the method of taking the pharmaceutical composition, the dosage is based on the composition: adults, 2-3 mg/time, 3 times/day; children, 1-1.5 mg/kg/time, 3 times / day, can achieve the effect of treating clinical symptoms of mental disorders caused by craniocerebral injury. In particular, pregnant women and other special groups should follow the doctor's advice when taking it, and no special adverse reactions have been found so far. The treatment described in the present invention means the treatment after the onset, not the intervention before the onset.

The nicotinic benzyl ester described in the present invention has a molecular formula of C ₉ H ₁₂ O, a molecular weight of 136.19, and a molecular structural formula of:

Bisabolol has a molecular formula of C ₁₅ H ₂₆ O and a molecular weight of 222.37. The molecular structural formula is:

Isoborneol has a molecular formula of C ₁₀ H ₁₈ O and a molecular weight of 154.25. The molecular structural formula is:

According to the research, the compound composed of nicotinic acid benzyl ester, bisabolol and isoborneol can effectively inhibit the morphological changes of nerve tissue in rats with mental disorders caused by craniocerebral injury, and improve the cognition of rats with mental disorders caused by craniocerebral injury. , learning and memory ability, significantly reducing the symptoms of mental disorders caused by craniocerebral injury, and the therapeutic effect is better than that of ergometrine, citicoline, calcium hyperpantothenate, amantadine, and lecithin.

Through the rat platform test and the rat dark avoidance test, it is proved that the present invention can effectively improve the cognition, learning and memory abilities of rats with mental disorders caused by craniocerebral injury, and the therapeutic effect is better than that of ergometrine, citicoline, Calcium hyperpantothenate, amantadine, lecithin.

Through light microscope observation, it is found that the present invention can significantly inhibit the disorder of pyramidal cell arrangement, swelling of pyramidal cells, inflammatory cell infiltration, astrocyte hyperplasia, partial pyramidal The cell body becomes smaller or triangular, the apical dendrites elongate, nuclear pyknosis and rupture, cytoplasmic eosinophilia, matrix loosening with microvacuole formation, erythrocyte exudation around blood vessels and other morphological changes.

The invention has the advantages of obvious effect on treating mental disorder caused by craniocerebral injury, stable quality control, low cost, natural and non-toxic, and suitable for long-term administration.

Description of drawings

Fig. 1 is a schematic diagram of the influence of the present invention on the morphology of cortical pyramidal cells in the CA1 region of the hippocampus of rats with mental disorders caused by craniocerebral injury (light microscope 0.8K×).

detailed description

The present invention is a pharmaceutical composition for treating mental disorder caused by craniocerebral injury and its application. The pharmaceutical composition is formulated from the following raw materials: nicotinyl benzyl ester, bisabolol and isoborneol.

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury, which comprises the following raw materials formulated in parts by weight: 10-100 parts of nicotinyl benzyl ester, 10-100 parts of bisabolol, isoborneol 7 to 100 copies.

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury, the pharmaceutical composition comprises the following raw materials formulated in parts by weight: 10-80 parts of nicotinyl benzyl ester, 10-80 parts of bisabolol, isoborneol 7 to 80 copies.

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury, the pharmaceutical composition is prepared by preparing the following raw materials in parts by weight: 10-50 parts of nicotinyl benzyl ester, 10-50 parts of bisabolol, isoborneol 7 to 50 copies.

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury, the pharmaceutical composition is prepared by preparing the following raw materials in parts by weight: 20 parts of nicotinyl benzyl ester, 15 parts of bisabolol, and 7 parts of isoborneol.

The present invention provides the application of the above pharmaceutical composition in the preparation of the pharmaceutical composition for treating mental disorder caused by craniocerebral injury.

In order to explain the present invention more clearly, it is further described in conjunction with specific embodiments. Concrete embodiment is as follows:

Embodiment one

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 9 parts of nicotinyl benzyl ester, 9 parts of bisabolol, and 101 parts of isoborneol.

Embodiment two

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury, the pharmaceutical composition comprises the following raw materials formulated in parts by weight: 102 parts of nicotinyl benzyl ester, 8 parts of bisabolol, and 6 parts of isoborneol.

Embodiment three

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 8.5 parts of nicotinyl benzyl ester, 102 parts of bisabolol, and 6.5 parts of isoborneol.

Embodiment Four

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury, which comprises the following raw materials formulated in parts by weight: 10 parts of nicotinyl benzyl ester, 10 parts of bisabolol, and 7 parts of isoborneol.

Embodiment five

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 100 parts of nicotinyl benzyl ester, 100 parts of bisabolol, and 100 parts of isoborneol.

Embodiment six

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 55 parts of nicotinyl benzyl ester, 55 parts of bisabolol, and 53.5 parts of isoborneol.

Embodiment seven

A pharmaceutical composition for treating mental disorder caused by craniocerebral injury, the pharmaceutical composition is prepared by preparing the following raw materials in parts by weight: 80 parts of nicotinyl benzyl ester, 80 parts of bisabolol, and 80 parts of isoborneol.

Embodiment eight

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury. The pharmaceutical composition comprises the following raw materials formulated in parts by weight: 45 parts of nicotinyl benzyl ester, 45 parts of bisabolol, and 43.5 parts of isoborneol.

Embodiment nine

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 50 parts of nicotinyl benzyl ester, 50 parts of bisabolol, and 50 parts of isoborneol.

Embodiment ten

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 30 parts of nicotinyl benzyl ester, 30 parts of bisabolol, and 28.5 parts of isoborneol.

Embodiment Eleven

A pharmaceutical composition for treating mental disorders caused by craniocerebral injury. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 20 parts of nicotinyl benzyl ester, 15 parts of bisabolol, and 7 parts of isoborneol.

The above-mentioned embodiments are only examples for clearly illustrating the present invention, rather than limiting the implementation. For those skilled in the art, other changes or changes in different forms can be made on the basis of the above description. It is not necessary and impossible to exhaustively list all the implementation modes here, and the obvious changes or changes derived therefrom are still within the scope of protection of the claims of the present invention.

The present invention can be prepared into various forms of medicaments through nicotinic benzyl ester, bisabolol and isoborneol, such as water solvent, powder and mixture; when it is necessary to prepare water solvent, take the medicine according to the following weight: tobacco Benzyl ester 20mg, bisabolol 30mg, isoborneol 15mg, dissolve in three distilled water, and pack it separately. When the powder needs to be prepared, the medicines are weighed according to the following weights: 20 g of nicotinyl benzyl ester, 30 g of bisabolol, and 15 g of isoborneol, mixed and packed separately. When the mixture needs to be prepared, the medicines are weighed according to the following weights: 20 g of nicotinyl benzyl ester, 30 g of bisabolol, 15 g of isoborneol, sub-packaged, and filled into capsules.

Experimental example one

Detect the impact of the present invention on rat platform jumping and dark test;

1. Raw materials: nicotine benzyl ester, bisabolol, and isoborneol. The above-mentioned raw materials were all purchased by Beijing Cloud Science and Technology Co., Ltd.; hydrogenated ergot alkaloids were purchased by Shanghai Huatai Pharmaceutical Co., Ltd.

2. Instruments: The rat jumping platform recording system was purchased by Huaibei Zhenghua Biological Instrument Equipment Co., Ltd., and the rat dark avoidance instrument was purchased by Huaibei Zhenghua Biological Instrument Equipment Co., Ltd.

3. Animals: Sprague-Dawley (SD) rats, 6 weeks old, male, 180-220 g, clean grade provided by the Experimental Animal Center of Henan Province.

4. Experimental grouping: (1) Blank control group: 20 healthy SD rats, fed with triple distilled water on an empty stomach every morning, with a volume of 10ml/kg, for 8 weeks; (2) caused by craniocerebral injury Mental disorder model group: 20 healthy SD rats, using 200g weight 1m glass tube to vertically hit the rat's parietal and occipital area once; (3) Low dose of the present invention group: 20 mental disorder model rats caused by craniocerebral injury , gavage with the solution of the present invention on an empty stomach every morning, gavage concentration 5mg/kg, gavage capacity is 10ml/kg administration, continuous gavage for 8 weeks; (4) group of the present invention in dose: brain injury caused by mental disorder 20 model rats were gavaged with the solution of the present invention on an empty stomach every morning, and the gavage concentration was 10 mg/kg, and the gavage capacity was 10 ml/kg for administration, and the gavage was continued for 8 weeks; (5) high dose of the present invention group: craniocerebral 20 mental disorder model rats caused by injury, were gavaged with the solution of the present invention on an empty stomach every morning, with a gavage concentration of 20 mg/kg, and a gavage capacity of 10 ml/kg for administration, and continuous gavage for 8 weeks; (6) hydroergot alkaloids Group: 20 mental disorder model rats caused by craniocerebral injury were administered intragastrically with hydrogenated ergot alkaloid solution on an empty stomach every morning at a concentration of 2.0 mg/kg and a volume of 10ml/kg for 8 consecutive weeks.

5. Experimental content: Rat jumping platform test, rat dark avoidance test.

6. Statistical method: All data are expressed as mean ± standard deviation express. Differences between groups were compared using ANOVA and Newman-Student multiple comparisons; t-test analysis was completed by SPSS 13.0 statistical software, and bilateral P<0.05 was considered significant.

7. Results

7.1 The present invention is to the influence of rat platform test: test result shows, the present invention can obviously improve rat platform test incubation period, reduce the number of mistakes, and has significant dose dependence; With hydroergot alkaloid, there is obvious difference (P＜ 0.05). (See Table 1 for the results)

Table 1 The present invention can be to the impact of platform jumping test on rats with mental disorders caused by craniocerebral injury

Note: Compared with the mental disorder model group caused by craniocerebral injury, *P<0.05; compared with the high dose of the present invention group, #<0.05.

7.2 The influence of the present invention on the dark avoidance test of rats with mental disorders caused by craniocerebral injury: the test results show that the present invention can significantly improve the latency of the dark avoidance test of rats with mental disorders caused by craniocerebral injury, reduce the number of errors, and have significant Dose-dependent; and hydroergot alkaloids (P <0.05). (See Table 2 for the results)

Table 2 The influence of the present invention on avoiding the dark test of mental disorder rats caused by craniocerebral injury

Note: Compared with the mental disorder model group caused by craniocerebral injury, *P<0.05; compared with the high dose of the present invention group, #<0.05.

Experimental example two

Detect the influence of the present invention on the morphology of pyramidal cells in the CA1 area of rat hippocampus.

1. Raw materials: nicotine benzyl ester, bisabolol, and isoborneol. The above raw materials were all purchased by Beijing Cloud Science and Technology Co., Ltd.

2. Instrument: TS1000 Nikon microscope.

3. Animals: SD rats, 6 weeks old, male, 180-220 g, clean grade, provided by the Experimental Animal Center of Henan Province.

4. Experimental grouping: Grouping: (1) Normal control group: 20 healthy SD rats, fed with triple distilled water on an empty stomach every morning, with a volume of 10ml/kg, for 8 consecutive weeks; (2) Craniocerebral rats Injury-induced mental disorder model group: 20 healthy SD rats, using a 200g weight 1m glass tube to vertically impact the parietal and occipital part of the rat once; (3) taking the present invention group: craniocerebral injury-induced mental disorder model rats 20 rats were gavaged with the solution of the present invention on an empty stomach every morning, with a gavage concentration of 10 mg/kg, and a gavage capacity of 10 ml/kg for administration, and continuous gavage for 8 weeks.

5. Experimental content: Morphological observation under light microscope.

6. Results: the influence of the present invention on the morphology of cortical pyramidal cells in the hippocampus CA1 area of rats with mental disorders caused by craniocerebral injury (light microscope 0.8K×). As shown in Figure 1, the three layers of pyramidal cells in the hippocampal CA1 area of the rats in the mental disorder model group caused by craniocerebral injury were arranged in disorder; some pyramidal cells were swollen, with inflammatory cell infiltration and astrogliosis; some pyramidal cells The cell body becomes smaller or triangular in shape, the apical dendrites are elongated, with nuclear pyknosis and rupture, and the cytoplasm is uniformly eosinophilic; some pyramidal cells have light nuclei, loose matrix and microvacuole formation; red blood cells around blood vessels Exudation, individual small blood vessel proliferation can be seen. The invention can obviously inhibit the morphological change of hippocampal CA1 pyramidal cells, and the cell shape is basically normal, and a typical three-layer cell arrangement can be seen. The blank control group shown in Figure 1 is 1; the mental disorder model group caused by craniocerebral injury is 2; the invention group is 3.

The form and characteristics of the pharmaceutically acceptable carrier or diluent described in the present invention are determined by the amount of active ingredient to be mixed with it, the route of administration, the process in vivo (including absorption, distribution, metabolism, excretion) and other known determined by the variable. These carriers must be "acceptable" in the sense that they should be compatible with the other ingredients of the formulation, not interfere with the efficacy of the formulation and not be deleterious to the recipients of the formulation. For example, the pharmaceutical carrier used can be solid or liquid. Examples of solid carriers are lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, stearic acid, polyethylene glycol, polyvinylpyrrolidone, collagen hydrolyzate, and the like. Examples of liquid carriers are phosphate buffered saline, syrups, emulsions, wetting agents, sterile solutions and the like. Similarly, the carrier or diluent may include time delay materials well known in the art, such as glyceryl monostearate or glyceryl distearate alone or with a wax. A wide range of drug forms are available. Thus, if a solid carrier is used, the preparation may be in the form of tablets, placed in powder or granules in hard gelatin capsules, troches or lozenges. The amount of solid carrier will vary widely but will preferably be from about 50 mg to about 1 g. When a liquid carrier is used, the preparation can be in the form of syrup, emulsion, soft gelatin capsule.

Claims (6)

1. A pharmaceutical composition for treating mental disorders caused by craniocerebral injury, characterized in that: the pharmaceutical composition is prepared from the following raw materials: nicotinyl benzyl ester, bisabolol, and isoborneol. 2. The pharmaceutical composition for treating mental disorders caused by craniocerebral injury according to claim 1, characterized in that: the pharmaceutical composition comprises the following raw materials formulated in parts by weight: 10-100 parts of nicotinyl benzyl ester, red 10-100 parts of bisabolol, 7-100 parts of isoborneol. 3. The pharmaceutical composition for treating mental disorders caused by craniocerebral injury according to claim 1, characterized in that: the pharmaceutical composition comprises the following raw materials formulated in parts by weight: 10-80 parts of nicotinyl benzyl ester, red 10-80 parts of bisabolol, 7-80 parts of isoborneol. 4. The pharmaceutical composition for treating mental disorders caused by craniocerebral injury according to claim 1, characterized in that: the pharmaceutical composition comprises the following raw materials formulated in parts by weight: 10-50 parts of nicotinyl benzyl ester, red 10-50 parts of bisabolol, 7-50 parts of isoborneol. 5. The pharmaceutical composition for treating mental disorders caused by craniocerebral injury according to claim 1, characterized in that: the pharmaceutical composition comprises the following raw materials formulated in parts by weight: 20 parts of nicotinic benzyl ester, birrha 15 parts of alcohol, 7 parts of isoborneol. 6. The application of the pharmaceutical composition as claimed in claims 1-5 in the preparation of a pharmaceutical composition for the treatment of mental disorders caused by craniocerebral injury.