CN112076202A - Pharmaceutical composition and application thereof in preparation of medicines for preventing and/or treating Alzheimer's disease - Google Patents
Pharmaceutical composition and application thereof in preparation of medicines for preventing and/or treating Alzheimer's disease Download PDFInfo
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- CN112076202A CN112076202A CN202011004391.6A CN202011004391A CN112076202A CN 112076202 A CN112076202 A CN 112076202A CN 202011004391 A CN202011004391 A CN 202011004391A CN 112076202 A CN112076202 A CN 112076202A
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- galactoside
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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Abstract
The invention relates to the technical field of biological pharmacy. The invention provides a pharmaceutical composition and application thereof in preparing a medicament for preventing and/or treating Alzheimer's disease, wherein the pharmaceutical composition contains metformin and cyanidin-3-O-galactoside. The invention takes the metformin and the cyanidin-3-O-galactoside as the composite medicine, and utilizes the rapidly aging mouse SAMP8 to carry out animal experiments, and the experimental results show that the metformin and the cyanidin-3-O-galactoside have the effect of protecting nerve cells and can be prepared into the medicine for resisting the Alzheimer disease. The medicine can obviously improve the frequency of passing through a platform by a mouse and improve the learning and memory ability of the mouse; relieving the anxiety mental status of the mice; preventing the necrosis of neuron cells in cerebral cortex and hippocampus.
Description
Technical Field
The invention relates to the technical field of biological pharmacy, in particular to a pharmaceutical composition and application thereof in preparing a medicament for preventing and/or treating Alzheimer's disease.
Background
Metformin has been used clinically in the last 60 years as a main hypoglycemic agent. Metformin belongs to biguanide hypoglycemic drugs, is mainly used for type 2 diabetes, promotes glucose utilization mediated by insulin by directly acting on the metabolic process of sugar, increases the utilization of peripheral tissues such as brain, blood cells and the like to glucose, inhibits hepatic gluconeogenesis, reduces the glucose intake of intestinal tracts, thereby reducing the blood sugar. The research finds that the metformin is an AMPK activator, activates an AMPK pathway, inhibits autophagy induced by mTOR and has an anti-inflammatory effect. In addition, the metformin also has the effects of resisting aging, resisting oxidation, inhibiting tumors, improving cardiovascular diseases and the like, and has the potential of extremely treating diseases.
Anthocyanin belongs to flavonoid of plant polyphenol, is a secondary metabolite of plant, and is formed by combining anthocyanin with a C6-C3-C6 skeleton structure with glucoside bonds such as glucose, galactose and the like. Anthocyanidin is a water-soluble pigment, and the color of flower, fruit, stem, leaf and root of the plant is related to the anthocyanidin. There are 20 kinds of anthocyanins known in nature, and food-borne anthocyanidins mainly exist in six forms, mostly in the form of glucose esterification. The anthocyanidin is esterified with glucose, galactose, arabinose, xylose, rhamnose and the like to form anthocyanin; and can be subjected to acylation reaction with caffeic acid, p-coumaric acid, sinapic acid, p-hydroxybenzoic acid, ferulic acid, malonic acid, malic acid, succinic acid, acetic acid, etc. to form acylated form anthocyanin. Anthocyanidin contains multiple phenolic hydroxyl groups, has strong antioxidant activity, is used as a free radical scavenger and an antioxidant active substance, and is very unstable, but anthocyanin formed by the series of esterification and acylation structures can well protect anthocyanidin. After ingestion, the anthocyanidin is slowly hydrolyzed under the action of acid or enzyme in a human body to release the anthocyanidin, and the strong antioxidant activity is shown. In addition, cyanidin-3-O-galactoside has higher digestion, absorption and utilization rate due to containing galactoside which is more beneficial to human use.
At present, the value of anthocyanin is not completely developed, and research is mainly focused on the aspects of reducing blood fat, reducing blood sugar, resisting oxidation and the like. The idea of preventing and treating senile dementia by using cyanidin-3-O-galactoside and metformin in combination is not reported.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition and application thereof in preparing a medicament for preventing and/or treating Alzheimer's disease, improving learning and memory ability, relieving anxiety mental conditions, and preventing neuronal necrosis of cerebral cortex and hippocampus.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a pharmaceutical composition which contains metformin and cyanidin-3-O-galactoside.
Preferably, the molar ratio of metformin to cyanidin-3-O-galactoside is 5: 1 to 10.
Preferably, the molar ratio of metformin to cyanidin-3-O-galactoside is 4: 1 to 2.
Preferably, the cyanidin-3-O-galactoside has a purity of 90% or more.
Preferably, the pharmaceutical composition is an oral formulation.
Preferably, the pharmaceutical composition is a capsule, granule, tablet, pill, powder or solution.
Preferably, the pharmaceutical composition further comprises a medically acceptable auxiliary material.
The invention also provides application of the pharmaceutical composition in preparing a medicament for preventing and/or treating Alzheimer's disease.
The invention provides a pharmaceutical composition and application thereof in preparing a medicament for preventing and/or treating Alzheimer's disease, wherein the pharmaceutical composition contains metformin and cyanidin-3-O-galactoside. The invention takes the metformin and the cyanidin-3-O-galactoside as the composite medicine, and utilizes the rapidly aging mouse SAMP8 to carry out animal experiments, and the experimental results show that the metformin and the cyanidin-3-O-galactoside have the effect of protecting nerve cells and can be prepared into the medicine for resisting the Alzheimer disease. The medicine can obviously improve the frequency of passing through a platform by a mouse and improve the learning and memory ability of the mouse; relieving the anxiety mental status of the mice; preventing the necrosis of neuron cells in cerebral cortex and hippocampus.
Drawings
FIG. 1 shows the number of times that the mice pass through the platform in the water maze experiment of different treatment groups;
FIG. 2 shows spontaneous alternation of response rates of Y maze mice in different treatment groups;
FIG. 3 shows the number of faecal particles in open field experimental mice of different treatment groups;
FIG. 4 shows the number of times that the open field experimental mice of different treatment groups entered the central area;
FIG. 5 shows the HE staining results of cerebral cortex and hippocampus of mice in different treatment groups.
Detailed Description
The invention provides a pharmaceutical composition which contains metformin and cyanidin-3-O-galactoside.
In the present invention, the molar ratio of metformin to cyanidin-3-O-galactoside is preferably 5: 1-10, more preferably 4: 1-2, and more preferably 3: 1.
in the present invention, the purity of the cyanidin-3-O-galactoside is preferably 90% or more, and more preferably 95%.
In the present invention, the pharmaceutical composition is preferably an oral formulation.
In the present invention, the pharmaceutical composition is preferably a capsule, granule, tablet, pill, powder or solution.
In the present invention, the pharmaceutical composition preferably further comprises a pharmaceutically acceptable adjuvant.
The invention also provides application of the pharmaceutical composition in preparing a medicament for preventing and/or treating Alzheimer's disease.
The technical solutions provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.
Example 1 experimental design
The subjects selected SAMR1 and SAMP8 mice, SPF grade, male, 4 months of age, body weight 30 g. + -.2 g, of which 10 SAMR1 mice and 50 SAMP8 mice were divided into 5 groups on average. The experiment was started after one week of acclimatization of the experimental animals, each mouse was individually housed and fed freely with light set to 12 hours in the day and 12 hours in the dark, indoor temperature 20 + -2 deg.C and relative humidity 55% + -5%. The daily treatment for each experimental group was as follows:
normal group: SAMR1 mice were in the normal group (No. SAMR1), gavage sterile water;
model group: randomly selecting a group of SAMP8 mice as a model group (with the serial number of SAMP8), and perfusing with sterile water;
donepezil group: randomly selecting a group of SAMP8 mice to be administered with a positive drug of Donepezil (numbered Donepezil), and administering 1mg/kg of Donepezil;
metformin group: a random group of SAMP8 mice was given Metformin (numbered Metformin) at 100mg/kg Metformin (a commercially available drug);
cyanidin-3-O-galactoside group: a random group of SAMP8 mice was dosed with cyanidin-3-O-galactoside (numbered Cy3Gal) at 25mg/kg (cyanidin-3-O-galactoside, 95% pure);
metformin and cyanidin-3-O-galactoside group: the last group of SAMP8 mice was dosed with metformin and cyanidin-3-O-galactoside (numbered Met + Cy3Gal), with 100mg/kg metformin and 25mg/kg (cyanidin-3-O-galactoside, 95% purity);
each group of mice was dosed for 60 days.
Example 2 Water maze experiment
The direction and learning and memory ability of the mice are evaluated through a water maze experiment, and the experiment results of the times of passing through the platform by the mice in the water maze experiment of different treatment groups are shown in figure 1. The experimental result shows that compared with the model group, the metformin and cyanidin-3-O-galactoside group obviously improves the frequency of the mouse crossing the platform and improves the learning and memory ability of the mouse, and is obviously superior to the donepezil group, the metformin group and the cyanidin-3-O-galactoside group.
Example 2Y maze experiment
The spontaneous alternation response rate and the learning and memory ability of the mice are evaluated through the Y maze experiment, and the experiment results of the spontaneous alternation response rate of the mice in the Y maze experiment of different treatment groups are shown in figure 2. The experimental result shows that compared with the model group, the metformin and cyanidin-3-O-galactoside group can obviously improve the spontaneous alternation reaction rate and improve the learning and memory ability of mice, and is obviously superior to the donepezil group, the metformin group and the cyanidin-3-O-galactoside group.
Example 3 open field experiment
The mental condition of anxiety and stress of the mice is evaluated by an open field experiment, the number of defecation grains of the mice in the open field experiment of different treatment groups is shown in figure 3, and the frequency of entering the central area of the mice is shown in figure 4. After the administration of the drugs, the number of defecation particles of mice in a positive drug donepezil group and a metformin and cyanidin-3-O-galactoside group is obviously reduced, and the reduction range of the metformin and cyanidin-3-O-galactoside group is larger; the mice in the group given metformin and cyanidin-3-O-galactoside had significantly increased entry into the central zone, indicating that the mental status of anxiety in the mice was alleviated.
Example 4 pathological observations
The HE stained sections of the brains of the mice of each group were prepared for histopathological observation, and HE staining results of the cerebral cortex and hippocampus of the mice of different treatment groups are shown in fig. 5. Wherein, the neuron cells of the cerebral cortex and the hippocampus of the mice of the SAMP8 group are obviously reduced, the neuron degeneration and necrosis are caused, the intercellular space is enlarged, the vacuole phenomenon of the cells is generated, the cell nucleus is condensed, and the cell level and the number are reduced. The cone cells of the SAMR1 group and the groups for administration of the medicines are clear in level, neat and compact in arrangement, complete in cell structure, clear in nucleolus and uniform in cell staining. The cells in the hippocampal region of SAMP8 mice given with the metformin and cyanidin-3-O-galactoside groups are clear in hierarchy and close in arrangement, particularly the number of the cells in CA1 and CA3 regions is obviously increased compared with that of the SAMP8 group mice, the loss of nerve cells is reduced, the morphological change is the slightest, the cell structure is complete, and the metformin and cyanidin-3-O-galactoside groups have the effects of reducing the cell damage and protecting the nerve cells.
According to the embodiments, the invention provides a pharmaceutical composition and an application thereof in preparing a medicament for preventing and/or treating Alzheimer's disease, wherein the pharmaceutical composition contains metformin and cyanidin-3-O-galactoside. The invention takes the metformin and the cyanidin-3-O-galactoside as the composite medicine, and utilizes the rapidly aging mouse SAMP8 to carry out animal experiments, and the experimental results show that the metformin and the cyanidin-3-O-galactoside have the effect of protecting nerve cells and can be prepared into the medicine for resisting the Alzheimer disease. The medicine can obviously improve the frequency of passing through a platform by a mouse and improve the learning and memory ability of the mouse; relieving the anxiety mental status of the mice; preventing the necrosis of neuron cells in cerebral cortex and hippocampus.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (8)
1. A pharmaceutical composition comprising metformin and cyanidin-3-O-galactoside.
2. The pharmaceutical composition of claim 1, wherein the molar ratio of metformin to cyanidin-3-O-galactoside is 5: 1 to 10.
3. The pharmaceutical composition according to claim 2, wherein the molar ratio of metformin to cyanidin-3-O-galactoside is 4: 1 to 2.
4. A pharmaceutical composition according to any one of claims 1 to 3, wherein the cyanidin-3-O-galactoside is more than 90% pure.
5. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is an oral formulation.
6. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition is a capsule, a granule, a tablet, a pill, a powder, or a solution.
7. The pharmaceutical composition of claim 1, further comprising a pharmaceutically acceptable excipient.
8. Use of a pharmaceutical composition according to any one of claims 1 to 7 in the preparation of a medicament for the prevention and/or treatment of alzheimer's disease.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011004391.6A CN112076202A (en) | 2020-09-22 | 2020-09-22 | Pharmaceutical composition and application thereof in preparation of medicines for preventing and/or treating Alzheimer's disease |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011004391.6A CN112076202A (en) | 2020-09-22 | 2020-09-22 | Pharmaceutical composition and application thereof in preparation of medicines for preventing and/or treating Alzheimer's disease |
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| Publication Number | Publication Date |
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| CN112076202A true CN112076202A (en) | 2020-12-15 |
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| CN202011004391.6A Pending CN112076202A (en) | 2020-09-22 | 2020-09-22 | Pharmaceutical composition and application thereof in preparation of medicines for preventing and/or treating Alzheimer's disease |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101669637A (en) * | 2009-09-18 | 2010-03-17 | 中国人民解放军军事医学科学院卫生学环境医学研究所 | Application of cornflower-3-O-galactoside in preparing foods or medicaments for improving cognitive functions of old people |
| CN104623671A (en) * | 2015-02-09 | 2015-05-20 | 徐云根 | Compound medicine composition containing acetylcholinesterase inhibitor and metformin |
-
2020
- 2020-09-22 CN CN202011004391.6A patent/CN112076202A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101669637A (en) * | 2009-09-18 | 2010-03-17 | 中国人民解放军军事医学科学院卫生学环境医学研究所 | Application of cornflower-3-O-galactoside in preparing foods or medicaments for improving cognitive functions of old people |
| CN104623671A (en) * | 2015-02-09 | 2015-05-20 | 徐云根 | Compound medicine composition containing acetylcholinesterase inhibitor and metformin |
Non-Patent Citations (2)
| Title |
|---|
| HYEON YONG LEE等: "Cognitive-Enhancing Effect of Aronia melanocarpa Extract against Memory Impairment Induced by Scopolamine in Mice", 《EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE》 * |
| 王承展: "二甲双胍通过AMPK-SIRT1-PGC1α信号通路改善SAMP8小鼠的认知功能", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
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