CN106667999A - Pharmaceutical composition for treating Alzheimer's syndrome and application thereof - Google Patents

Abstract

The invention belongs to a pharmaceutical composition for treating Alzheimer's syndrome and its application; the pharmaceutical composition is prepared from the following raw materials: glycoside pinone, geraniol, and piperonal; It has the advantages of obvious effect, stable quality control, low cost, natural and non-toxic, and suitable for long-term use.

Description

Pharmaceutical composition for treating Alzheimer's syndrome and its application

technical field

The invention belongs to the technical field of medicine, and in particular relates to a pharmaceutical composition for treating Alzheimer's syndrome and its application.

Background technique

Alzheimer's syndrome is a persistent high-level neurological activity disorder, that is, in the state of no disturbance of consciousness, obstacles in memory, thinking, analysis and judgment, visuospatial recognition, emotion, etc.

The main treatment principles include: ① Use brain metabolism activators (coenzyme Q ₁₀ , citicoline) and brain circulation promoters (hydroergot alkaloids, flunarizine) to activate brain metabolism and 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) can improve neurological symptoms by increasing the function of the acetylcholine system; neuropeptides can improve the cognition and memory of the elderly, and reduce symptoms of depression and weakness; ③ For symptomatic treatment, thioridazine, fluphenazine, fluperbutanol, etc. are often used to control the impatience and excessive behavior of patients with Alzheimer's syndrome; Ritalin and cloxacyl are commonly used to improve the depression symptoms of patients with Alzheimer's syndrome; Diazepam is commonly used to improve anxiety symptoms in patients with Alzheimer's syndrome.

Contents of the invention

The purpose of the present invention is to overcome the defects in the prior art, and provide a stable quality control, safe, effective, natural and non-toxic pharmaceutical composition for treating Alzheimer's syndrome and its application.

The purpose of the present invention is achieved in this way: the pharmaceutical composition is prepared from the following raw materials: glucoside, geraniol, and piperonal.

A pharmaceutical composition for treating Alzheimer's syndrome. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 10-100 parts of pinocinone, 10-100 parts of geraniol, 7 parts of piperonal ~100 copies.

A pharmaceutical composition for treating Alzheimer's syndrome. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 10-80 parts of pinocinone, 10-80 parts of geraniol, 7 parts of piperonal ~80 servings.

A pharmaceutical composition for treating Alzheimer's syndrome. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 10-50 parts of pinocinone, 10-50 parts of geraniol, 7 parts of piperonal ~50 copies.

A pharmaceutical composition for treating Alzheimer's syndrome, which comprises the following raw materials prepared in parts by weight: 20 parts of pinocinone, 15 parts of geraniol, and 7 parts of piperonal.

The present invention provides the application of the above pharmaceutical composition in preparing the pharmaceutical composition for treating Alzheimer's syndrome.

The glycosides pinocinone, geraniol, and piperonal described in the present invention can be obtained directly 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, 20-30 mg/time, 3 times/day; children, 10-15 mg/kg·time, 3 times/day Days, can achieve the effect of treating clinical symptoms of Alzheimer's syndrome; 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 glycoside pine new ketone described in the present invention has a molecular formula of C ₁₅ H ₂₂ O ₃ , a molecular weight of 250.00, and a molecular structural formula of:

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

Piperonal, the molecular formula is C ₈ H ₆ O ₃ , and the molecular weight is 150.13. The molecular structural formula is:

According to the research, the compound composed of pinexinone, geraniol, and piperonal can effectively inhibit the morphological changes of nerve tissue in rats with Alzheimer's syndrome, and improve the cognition and learning of rats with Alzheimer's syndrome. And memory ability, significantly reduce the symptoms of Alzheimer's syndrome, the treatment effect is better than ergometrine, citicoline, calcium hyperpantothenate, amantadine, lecithin.

Prove that the present invention can effectively improve the cognition, learning, memory ability of Alzheimer's syndrome rats by rat platform test, rat dark avoidance test, the therapeutic effect is better than ergometrine, citicoline, high Calcium pantothenate, amantadine, lecithin.

Observation by light microscope reveals that the present invention can significantly inhibit the arrangement disorder of three layers of pyramidal cells, swelling of pyramidal cells, infiltration of inflammatory cells, proliferation of astroglial cells, partial pyramidal cell The cell body becomes smaller or triangular, the apical dendrites are elongated, the nucleus is condensed and ruptured, the cytoplasm is eosinophilic, the matrix is loose with microvacuole formation, and there is erythrocyte exudation around blood vessels and other morphological changes.

The invention has the advantages of obvious effect on treating Alzheimer's syndrome, stable quality control, low cost, natural and non-toxic, and suitable for long-term administration.

Description of drawings

Fig. 1 is the graph of the influence of the present invention on the morphology of cortical pyramidal cells in CA1 region of hippocampus of Alzheimer's syndrome rats (light microscope 0.8K×).

detailed description

The present invention is a pharmaceutical composition for treating Alzheimer's syndrome and its application. The pharmaceutical composition is prepared from the following raw materials: pinocinone, geraniol, and piperonal.

A pharmaceutical composition for treating Alzheimer's syndrome. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 10-100 parts of pinocinone, 10-100 parts of geraniol, 7 parts of piperonal ~100 copies.

A pharmaceutical composition for treating Alzheimer's syndrome. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 10-80 parts of pinocinone, 10-80 parts of geraniol, 7 parts of piperonal ~80 servings.

A pharmaceutical composition for treating Alzheimer's syndrome. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 10-50 parts of pinocinone, 10-50 parts of geraniol, 7 parts of piperonal ~50 copies.

A pharmaceutical composition for treating Alzheimer's syndrome, which comprises the following raw materials prepared in parts by weight: 20 parts of pinocinone, 15 parts of geraniol, and 7 parts of piperonal.

The present invention provides the application of the above pharmaceutical composition in preparing the pharmaceutical composition for treating Alzheimer's syndrome.

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 Alzheimer's syndrome, which comprises the following raw materials prepared in parts by weight: 9 parts of pinocinone, 102 parts of geraniol, and 6 parts of piperonal.

Embodiment two

A pharmaceutical composition for treating Alzheimer's syndrome, which comprises the following raw materials prepared in parts by weight: 103 parts of pinocinone, 9.5 parts of geraniol, and 101 parts of piperonal.

Embodiment three

A pharmaceutical composition for treating Alzheimer's syndrome, which comprises the following raw materials prepared in parts by weight: 9 parts of pinocinone, 12 parts of geraniol, and 102 parts of piperonal.

Embodiment Four

A pharmaceutical composition for treating Alzheimer's syndrome, which comprises the following raw materials prepared in parts by weight: 10 parts of pinocinone, 10 parts of geraniol, and 7 parts of piperonal.

Embodiment five

A pharmaceutical composition for treating Alzheimer's syndrome, which comprises the following raw materials prepared in parts by weight: 100 parts of pinocinone, 100 parts of geraniol, and 100 parts of piperonal.

Embodiment six

A pharmaceutical composition for treating Alzheimer's syndrome, which comprises the following raw materials prepared in parts by weight: 55 parts of pinocinone, 55 parts of geraniol, and 53.5 parts of piperonal.

Embodiment seven

A pharmaceutical composition for treating Alzheimer's syndrome. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 45 parts of pinocinone, 80 parts of geraniol, and 80 parts of piperonal.

Embodiment Eight

A pharmaceutical composition for treating Alzheimer's syndrome, which comprises the following raw materials prepared in parts by weight: 80 parts of pinocinone, 45 parts of geraniol, and 43.5 parts of piperonal.

Embodiment nine

A pharmaceutical composition for treating Alzheimer's syndrome. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 50 parts of pinocinone, 30 parts of geraniol, and 50 parts of piperonal.

Embodiment ten

A pharmaceutical composition for treating Alzheimer's syndrome. The pharmaceutical composition comprises the following raw materials prepared in parts by weight: 30 parts of pinocinone, 50 parts of geraniol, and 28.5 parts of piperonal.

Embodiment Eleven

A pharmaceutical composition for treating Alzheimer's syndrome, which comprises the following raw materials prepared in parts by weight: 20 parts of pinocinone, 15 parts of geraniol, and 7 parts of piperonal.

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 glycoside pinone, geraniol, and piperonal, such as water solvent, powder and mixture; when the water solvent needs to be prepared, the medicine is weighed according to the following weight: glycoside Pinoxinone 20mg, geraniol 30mg, piperonal 15mg, mix, dissolve in triple 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 pinocinone, 30 g of geraniol, and 15 g of piperonal, mixed and subpackaged. When the mixture needs to be prepared, the medicines are weighed according to the following weights: 20 g of pinoxinone, 30 g of geraniol, and 15 g of piperonal, mixed, subpackaged, and filled into capsules.

Experimental example 1

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

1. Raw materials: glycoside pinone, geraniol, and piperonal were purchased from Shanghai Kexing Trading Co., Ltd.; hydrogenated ergot alkaloids were purchased from Shanghai Huatai Pharmaceutical Co., Ltd.; citicoline was purchased from Suzhou Tianma Fine Chemicals Co., Ltd.; high pantothenate calcium was purchased from Shanghai Jialun Biotechnology Co., Ltd.; amantadine was purchased from Shijiazhuang Sanhe Pharmaceutical Co., Ltd.; lecithin was purchased from Guangzhou Bangli Biotechnology 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 consecutive weeks; (2) Alzheimer's syndrome Syndrome model group: 20 rat models of Alzheimer's syndrome prepared by 2VO method; (3) low-dose group of the present invention: 20 rats of Alzheimer's syndrome, gavage with the solution of the present invention on an empty stomach every morning, Concentration of gavage 5mg/kg, gavage volume is 10ml/kg administration, continuous gavage for 8 weeks; (4) middle dose group of the present invention: 20 Alzheimer's syndrome model rats, use the present invention on an empty stomach every morning Solution gavage, gavage concentration 10mg/kg, gavage capacity is 10ml/kg administration, continuous gavage for 8 weeks; (5) high dose group of the present invention: 20 Alzheimer's syndrome model rats, every morning Gavage with solution of the present invention on an empty stomach, gavage concentration 20mg/kg, gavage capacity is 10ml/kg administration, continuous gavage for 8 weeks; (6) hydroergot alkaloid group: 20 Alzheimer's syndrome model rats , gavage with hydrogenated ergot alkaloid solution on an empty stomach every morning, with a concentration of 2.0mg/kg, and a volume of 10ml/kg, for continuous gavage for 8 weeks; (7) citicoline group: Alzheimer's type 20 syndrome model rats were gavaged with citicoline solution on an empty stomach every morning, with a gavage concentration of 1.0 mg/kg and a gavage volume of 10ml/kg, for 8 weeks of continuous gavage; (8) high pantothenic acid Calcium group: 20 Alzheimer's syndrome model rats were gavaged with a high-pantothenate calcium solution every morning on an empty stomach, with a gavage concentration of 2 mg/kg, and a gavage volume of 10 ml/kg for administration, and continuous gavage for 8 weeks; ( 9) Amantadine group: 20 Alzheimer's syndrome model rats were fed with amantadine solution on an empty stomach every morning, with a concentration of 0.5 mg/kg and a volume of 10 ml/kg for administration. Stomach for 8 weeks; (10) Lecithin group: 20 Alzheimer's syndrome model rats were administered intragastrically with lecithin solution on an empty stomach every morning, with a concentration of 0.2mg/kg and a volume of 10ml/kg. , Continuous gavage for 8 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 influence of the present invention on the rat platform test: the test results show that the present invention can obviously improve the incubation period of the rat platform test, reduce the number of mistakes, and has significant dose dependence; Calcium pantothenate, amantadine, lecithin control group, there is a significant difference (P <0.05). (See Table 1 for the results)

Table 1 The present invention can be to the influence of platform jumping test of Alzheimer's syndrome rat

Note: compared with the Alzheimer's syndrome model group, *P<0.05; compared with the high-dose group of the present invention, #<0.05.

7.2 The influence of the present invention on the dark avoidance test of rats with Alzheimer's syndrome: the test results show that the present invention can significantly improve the latent period of the dark avoidance test of rats with Alzheimer's syndrome, reduce the number of errors, and have a significant dose-dependent Compared with the control group of hydrogenated ergot alkaloid, citicoline, calcium pantothenate, amantadine and lecithin, there was a significant difference (P<0.05). (See Table 2 for the results)

Table 2 The influence of the present invention on the dark avoidance test of Alzheimer's syndrome rats

Note: compared with the Alzheimer's syndrome model group, *P<0.05; compared with the high-dose group of the present invention, #<0.05.

Experimental example 2

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

1. Raw materials: glycoside pine new ketone, geraniol, piperonal All the above raw materials were 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 three-distilled water on an empty stomach every morning, with a volume of 10ml/kg, for 8 consecutive weeks; (2) Aerhai Murray's syndrome model group: 20 rat models of Alzheimer's syndrome prepared by 2VO method; (3) taking the present invention group: 20 Alzheimer's syndrome model rats, filled with the solution of the present invention on an empty stomach every morning Stomach, gavage concentration 10mg/kg, gavage volume 10ml/kg administration, 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 CA1 region of the hippocampus of rats with Alzheimer's syndrome (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 Alzheimer's syndrome model group 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, and there are nuclear pyknosis and rupture. Out, individual small blood vessel proliferation can be seen. The high dose of the present invention can obviously inhibit the morphological changes of hippocampal CA1 pyramidal cells, and the cell morphology is basically normal, and a typical three-layer cell arrangement can be seen. The normal control group shown in Figure 1 is 1; the Alzheimer's syndrome model group is 2; the group taking the present invention 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 the treatment of Alzheimer's syndrome, characterized in that: the pharmaceutical composition is formulated from the following raw materials: glucoside, geraniol, and piperonal. 2. The pharmaceutical composition for treating Alzheimer's syndrome according to claim 1, characterized in that: the pharmaceutical composition comprises the following raw materials formulated in parts by weight: 10 to 100 parts of pine new ketone, geraniol 10-100 parts, piperonal 7-100 parts. 3. The pharmaceutical composition for treating Alzheimer's syndrome according to claim 1, characterized in that: the pharmaceutical composition comprises the following raw materials prepared according to parts by weight: 10-80 parts of pine new ketone, Geranol 10-80 parts, piperonal 7-80 parts. 4. The pharmaceutical composition for treating Alzheimer's syndrome according to claim 1, characterized in that: the pharmaceutical composition comprises the following raw materials prepared according to parts by weight: 10-50 parts of pine new ketone, geraniol 10-50 parts, piperonal 7-50 parts. 5. The pharmaceutical composition for treating Alzheimer's syndrome according to claim 1, characterized in that: the pharmaceutical composition comprises the following raw materials formulated in parts by weight: 20 parts of pine pine new ketone, Alcohol 15 parts, piperonal 7 parts. 6. The application of the pharmaceutical composition as claimed in claims 1-5 in the preparation of a pharmaceutical composition for the treatment of Alzheimer's syndrome.