CN108210818B - Pharmaceutical composition for preventing and treating neurodegenerative diseases and preparation method and application thereof - Google Patents
Pharmaceutical composition for preventing and treating neurodegenerative diseases and preparation method and application thereof Download PDFInfo
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- CN108210818B CN108210818B CN201810338226.0A CN201810338226A CN108210818B CN 108210818 B CN108210818 B CN 108210818B CN 201810338226 A CN201810338226 A CN 201810338226A CN 108210818 B CN108210818 B CN 108210818B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/232—Angelica
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
- A61K36/725—Ziziphus, e.g. jujube
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9062—Alpinia, e.g. red ginger or galangal
Abstract
The invention belongs to the technical field of traditional Chinese medicines, and particularly provides a pharmaceutical composition for preventing and treating neurodegenerative diseases, which comprises 1-30 parts by weight of ginseng, 1-50 parts by weight of angelica and 1-50 parts by weight of fructus alpiniae oxyphyllae. The invention also provides a preparation method and specific application of the pharmaceutical composition. The drug combination of the invention is proved by pharmacodynamic experiments that the drug combination can test relevant objective indexes of rat dementia models, vascular rat dementia models, rat pia mater microcirculation models and the like, and has better treatment effect on degenerative changes of the central nervous system.
Description
Technical Field
The invention relates to a pharmaceutical composition for preventing and treating neurodegenerative diseases, a preparation method and application thereof, in particular to a pharmaceutical composition for treating and relieving senile dementia, vascular dementia or mild cognitive impairment, a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicines.
Background
Vascular Dementia (VD) is a chronic, acquired, progressive cognitive dysfunction syndrome caused by different types of cerebrovascular lesions, with impairment of learning and memory functions as the main symptoms, which may be accompanied by motor, speech, visual space and personality disorders. According to epidemiological investigation, the incidence rate of dementia in the elderly of over 65 years old in China reaches 3.9%, wherein VD accounts for 68.5%. With the aging process of the world population, the morbidity of VD is remarkably increased, and the VD becomes a common disease and an intractable disease for middle-aged and elderly people. The existing research shows that chronic cerebral hypoperfusion injury is one of the main causes of VD, and accumulation of oxygen free radicals and lipid peroxidation products caused by cerebral hypoperfusion injury can cause oxidative stress injury, cell energy failure and apoptosis of neurons, and finally cause VD.
Vascular dementia is the name of modern medicine, and belongs to the categories of traditional Chinese medicine amnesia, coma, dementia, mania and the like. The understanding of the symptoms and pathogenesis of this disease is seen in medical books of doctors of all ages. For example, Ling Shu, big Huo Lun: "what is the leading qi of a person who is forgotten? … … deficient upper qi and excessive lower qi, … … deficiency can cause the nutrient and defensive qi to stay below the body, and the body is forgotten when the body is not too long; ling Shu, Jing Mai (Ling Shu, Jing Mai): "the human beings, first become essence, essence and brain marrow are born"; ling Shu Jing, Hai Lun (treatise on the Lai of Lai): "brain is the sea of marrow"; lingshu Tiannian (Lingshu): sixty years old, failure of heart qi … …, seventy years old, spleen qi deficiency, dry skin. Eighty years old, lung qi failing to nourish the body, so it is good at wrong; su Wen & Wu zang Sheng: all marrow belonging to the brain; su Wen & Mai Yao Jing Wei Lun (plain questions & pulse essentials treatise on essence) states that the headaches and the house of essence and Ming dynasties. Deep head inclination and mental will also be lost; the theory of Su Wen and Ting tiao Jing (plain questions & menstruation regulating treatise) says that the theory that blood is in the lower part and qi is in the upper part and disorder is easy to forget; treatise on febrile diseases: "this time with disease and blood, so it is happy and forgotten"; the medical mind states that kidney governs intelligence and deficiency governs intelligence deficiency; the Jingyue complete book: "or gradually to dementia by stasis, or by hemiplegia, or by anxiety, or by panic"; the treatise on blood syndrome: for heart blood stasis, it is unclear that amnesia … … is turbid and obstructed with blood. Blood stasis in the case of sudden amnesia due to blood loss; danxi Heart method: amnesia, short spirit, and phlegm; the records of Western medicine of Zhongzhao: phlegm-fire invading the heart and brain and causing brain obstruction and coma; 'doctor Lin correction': the spiritual thought and the memory in the brain, … … high years without memory, the marrow of the brain gradually empties.
From the above theory, it can be seen that the occurrence of "dementia" is closely related to the strength of the body constitution, the age, the climatic conditions, the living environment, etc. Many doctors believe that the disease is caused by deficiency of viscera, deficiency of yin essence, failure of filling in brain, insufficiency of marrow and sea, and the addition of toxic factors such as phlegm, turbidity and blood stasis, etc., which cause deficiency, phlegm and blood stasis to be combined together, damage brain collaterals and cause mental loss, and then the disease develops into dementia. The discussion in the "blood syndrome treatise" has clearly pointed out that the dementia caused by blood stasis obstructing the orifices is mainly vascular dementia clinically, and the occurrence of the disease is mainly related to cerebrovascular disease, or caused by cerebral infarction or cerebral hemorrhage, or caused by chronic cerebral ischemia.
Patent CN 1518995A provides an anti-senile dementia drug, a preparation method and application thereof. The traditional Chinese medicine prescription and compatibility: 1-40 parts of white paeony root, 1-40 parts of ginseng, 1-40 parts of angelica, 1-20 parts of liquorice, 1-10 parts of pinellia ternate, 1-40 parts of poria cocos, 1-10 parts of calamus, 1-40 parts of radix curcumae, 1-20 parts of rhizoma arisaematis, 1-10 parts of radix bupleuri, 1-10 parts of jujube kernel and 1-20 parts of medicated leaven, active ingredients are extracted by water boiling, and the Chinese medicinal composition is prepared into various dosage forms, has an effective protection effect on nerve cell injury, is beneficial to enhancing memory and can obviously improve senile dementia. But the problems of complex prescription, complex preparation process and the like still exist.
Therefore, a safe and effective medicament with low cost and simple process for preventing and treating neurodegenerative diseases is urgently needed.
Disclosure of Invention
In order to solve the technical problems, the invention provides a novel pharmaceutical composition capable of preventing and treating the degenerative disease of the central nervous system, a preparation method and application thereof.
The preparation is prepared from the following raw materials in parts by weight: 1-30 parts of ginseng, 1-50 parts of angelica and 1-50 parts of fructus alpiniae oxyphyllae.
Further, the preparation is prepared from the following raw materials in parts by weight: 5-20 parts of ginseng, 10-30 parts of angelica sinensis and 10-30 parts of fructus alpiniae oxyphyllae.
Further, the preparation is prepared from the following raw materials in parts by weight: 3 parts of ginseng, 5 parts of angelica and 1 part of sharpleaf galangal fruit;
or, it is a preparation prepared from the following raw materials in parts by weight: 1 part of ginseng, 5 parts of angelica and 3 parts of sharpleaf galangal fruit.
Further, the pharmaceutical composition also comprises the following raw materials: semen Ziziphi Spinosae.
Further, the preparation is prepared from the following raw materials in parts by weight: 1 part of ginseng, 1 part of angelica, 1 part of sharpleaf galangal fruit and 1 part of spina date seed.
Furthermore, the traditional Chinese medicine composition is a preparation prepared by taking medicinal powder of raw material medicines, water or organic solvent extract of the raw material medicines as active ingredients and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
Further, the preparation is tablets, capsules, granules, oral liquid, powder and powder.
The invention also provides a method for preparing the pharmaceutical composition, which comprises the following steps:
1) weighing the raw materials according to the weight ratio;
2) the medicine powder of the raw material medicines is added with pharmaceutically acceptable auxiliary materials or auxiliary components to prepare the preparation.
The invention also provides application of the composition in preparing a medicament for preventing and treating neurodegenerative diseases.
Wherein the neurodegenerative disease is vascular dementia, senile dementia or cognitive disorder.
In order to make the above dosage forms possible, pharmaceutically acceptable excipients, such as: fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, bases, and the like. The filler comprises: starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose, etc.; the disintegrating agent comprises: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, crospolyvinylpyrrolidone, low-substituted hydroxypropylcellulose, croscarmellose sodium, etc.; the lubricant comprises: magnesium stearate, sodium lauryl sulfate, talc, silica, and the like; the suspending agent comprises: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose, and the like; the adhesive comprises starch slurry, polyvinylpyrrolidone, hydroxypropyl methylcellulose, etc.; the sweetener comprises: saccharin sodium, aspartame, sucrose, sodium cyclamate, glycyrrhetinic acid, and the like; the flavoring agent comprises: sweeteners and various essences; the preservative comprises: parabens, benzoic acid, sodium benzoate, sorbic acid and its salts, benzalkonium bromide, chloroacetidine acetate, eucalyptus oil, etc.; the matrix comprises: PEG6000, PEG4000, insect wax, etc.
The experimental result proves that the pharmaceutical composition has different degrees of treatment effects on memory dysfunction and vascular dementia, the dosage of the angelica is increased and the dosages of the ginseng and the fructus alpiniae oxyphyllae are reduced on the premise of the same administration dosage, the treatment effect is more excellent compared with that of an equal-ratio dosage formula, the synergistic interaction effect is more obvious, the total usage amount of the raw material medicines is saved, and the optimal proportioning range of the pharmaceutical composition is obtained through repeated pharmaceutical test screening.
Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Detailed Description
The technical solution of the present invention is further described in detail with reference to the following specific examples, but the scope of the present invention is not limited to the following.
Example 1 preparation of a pharmaceutical composition of the invention
1. Prescription: 30g of ginseng, 50g of angelica and 10g of sharpleaf galangal fruit
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and tabletting to obtain tablets.
Example 2 preparation of a pharmaceutical composition of the invention
1. Prescription: 10g of ginseng, 50g of angelica and 30g of fructus alpiniae oxyphyllae
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and tabletting to obtain tablets.
Example 3 preparation of a pharmaceutical composition of the invention
1. Prescription: 10g of ginseng, 30g of angelica and 50g of fructus alpiniae oxyphyllae
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and tabletting to obtain tablets.
Example 4 preparation of a pharmaceutical composition of the invention
1. Prescription: 50g of ginseng, 50g of angelica and 50g of sharpleaf galangal fruit
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and tabletting to obtain tablets.
Example 5 preparation of a pharmaceutical composition of the invention
1. Prescription: 50g of ginseng, 50g of angelica, 50g of sharpleaf galangal fruit and 50g of spina date seed
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and tabletting to obtain tablets.
Example 6 preparation of a pharmaceutical composition of the invention
1. Prescription: 1g of ginseng, 1g of angelica and 1g of sharpleaf galangal fruit
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and tabletting to obtain tablets.
Example 7 preparation of a pharmaceutical composition of the invention
1. Prescription: 30g of ginseng, 50g of angelica and 50g of fructus alpiniae oxyphyllae
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and tabletting to obtain tablets.
Example 8 preparation of a pharmaceutical composition of the invention
1. Prescription: ginseng 5g, Chinese angelica root 10g, bitter cardamon 10g
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and tabletting to obtain tablets.
Example 9 preparation of a pharmaceutical composition of the invention
1. Prescription: 20g of ginseng, 30g of angelica and 30g of sharpleaf galangal fruit
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and tabletting to obtain tablets.
Example 10 preparation of a pharmaceutical composition of the invention
1. Prescription: ginseng 5g, Chinese angelica root 10g, bitter cardamon 10g
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and tabletting to obtain tablets.
Example 11 preparation of a pharmaceutical composition of the invention
1. Prescription: ginseng 5g, Chinese angelica root 5g, bitter cardamon 10g
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and tabletting to obtain tablets.
EXAMPLE 12 preparation of a pharmaceutical composition of the invention
1. Prescription: ginseng 10g, Chinese angelica root 5g, bitter cardamon 10g
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and tabletting to obtain tablets.
Example 13 preparation of a pharmaceutical composition of the invention
1. Prescription: 15g of ginseng, 5g of angelica and 10g of sharpleaf galangal fruit
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and tabletting to obtain tablets.
EXAMPLE 14 preparation of a pharmaceutical composition of the invention
1. Prescription: 10g of ginseng, 5g of angelica, 15g of sharpleaf galangal fruit
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and tabletting to obtain tablets.
Example 15 preparation of a pharmaceutical composition of the invention
1. Prescription: ginseng 3g, Chinese angelica root 5g, bitter cardamon 1g
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and filling the granules into capsules to obtain capsules.
EXAMPLE 16 preparation of a pharmaceutical composition of the invention
1. Prescription: 1g of ginseng, 5g of angelica and 3g of sharpleaf galangal fruit
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding auxiliary materials of starch for granulation, magnesium stearate, dextrin and microcrystalline cellulose, uniformly preparing granules, and filling the granules into capsules to obtain capsules.
EXAMPLE 17 preparation of a pharmaceutical composition of the invention
1. Prescription: ginseng 3g, Chinese angelica root 5g, bitter cardamon 1g
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding conventional auxiliary materials, and preparing into granules.
EXAMPLE 18 preparation of a pharmaceutical composition of the invention
1. Prescription: 1g of ginseng, 5g of angelica and 3g of sharpleaf galangal fruit
2. The preparation method comprises the following steps: taking the raw materials according to the prescription amount, adding conventional auxiliary materials and preparing the oral liquid.
The advantageous effects of the present invention are described below by way of test examples.
Test example 1 test of the drug of the present invention against pseudodementia mouse caused by scopolamine
1 materials of the experiment
1.1 Experimental animals
Male mice of Kunming species, weighing 20 ± 2g, were provided by WUDUDUDO animal experiments, Inc., animal license number: SCXK (Chuan) 2015-030, raised at room temperature 22-26 ℃ and ingested with free water.
1.2 drugs and reagents
Donepezil hydrochloride tablets, national drug standard H20070181, 10 mg/tablet, manufactured by drug industry Co., Ltd. Scopolamine hydrobromide solution, manufactured by Shanghai Hefeng pharmacy Co., Ltd. ACHE kit, Nanjing, to build bioengineering institute. Fructus alpiniae oxyphyllae and spina date seeds are purchased from a traditional Chinese medicine room in a subsidiary hospital of Chengdu traditional Chinese medicine university, and are prepared according to equal dosage proportion by a ginseng group, a angelica group, a fructus alpiniae oxyphyllae group (ginseng: angelica sinensis ═ 1:1), a fructus alpiniae oxyphyllae group (fructus alpiniae oxyphyllae: ginseng ═ 1:1), a ginseng group, an angelica group, a fructus alpiniae oxyphyllae group (ginseng: angelica sinensis: fructus alpiniae oxyphyllae ═ 1:1), a ginseng group, an angelica group, fructus alpiniae oxyphyllae group and spina date seeds (ginseng: angelica sinensis: fructus alpiniae oxyphyllae: spina ═ 1:1: 1).
1.3 main experimental instruments:
refrigerated centrifuge, Thermo Fisher corporation, usa; precision electronic balance, Sartorius, germany; DT-200 diving tower tester (and test box), Gengtai Union technologies, Inc.; BA-200 automatic dark-avoiding tester (and test box), Chengtai Union science and technology Limited.
2 method of experiment
2.1 grouping and processing
Mice were randomly divided into a normal control group, a model control group, a positive control group (donepezil hydrochloride tablets), a test group a (ginseng and angelica group), a test group B (angelica and sharpleaf galangal fruit group), a test group C (sharpleaf galangal fruit and ginseng group), a test group D (ginseng and angelica and sharpleaf galangal fruit), and a test group E (ginseng and angelica and sharpleaf galangal fruit and spina date seed) according to body weight. Decocting the above materials with water by conventional method, concentrating to obtain medicinal liquid with crude drug content of 0.6g/ml, and administering to animals of each group according to dosage of 0.2ml/10g body weight/day ig. 50min after administration on day 14 of each group of mice in the darkness-avoiding and diving platform experimental groups, except for a blank control group, each group of mice is subjected to 2mg/kg body weight (0.1ml/10g body weight) of scopolamine hydrobromide solution 10min before darkness-avoiding training and diving platform training, so that a memory acquisition obstacle model of the mice is caused. The blank control group was gavaged with equal amount of distilled water. Animals of each group of mice were sacrificed after the behavioral test was completed, whole brains were picked and blood traces were washed with ice-cold physiological saline, cerebral cortex and hippocampus tissues were separated at low temperature, sufficiently ground in a homogenizing tube to make 10% brain tissue homogenate, centrifuged to take supernatant, and stored in a refrigerator at-20 ℃ for later use. Taking 10% brain tissue homogenate to be detected, preparing a reagent according to the requirements of the kit, and detecting AchE activity and ChAT activity by a colorimetric method.
2.2 mouse learning and memory Capacity test
2.2.1 dodging method
(1) Dark avoidance training: after the mice in the darkness-avoiding test group are subjected to gastric lavage administration or distilled water 50min on the 14 th day of the experiment, except a blank control group, the mice in other groups are subjected to intraperitoneal injection of scopolamine hydrobromide liquid (3mg/kg) for molding to prepare a memory acquired disorder model, 10min after molding, the animals are placed in a darkness-avoiding box in a light room with the back facing to an opening to adapt to 3min, 36V alternating current is applied, the time is immediately timed, and the latency and the error times of the animals within 5min are recorded.
(2) Dark avoidance testing: and (3) after the mice in the darkness-avoiding group are subjected to gastric gavage administration or distilled water for 60min on the 15 th day of the experiment (after 24 hours of darkness-avoiding training), the mice are placed in a darkness-avoiding box bright room, meanwhile, 36V alternating current is conducted, time is counted, and the latency and the error times of each animal within 5min are recorded.
2.2.2 diving platform method
(1) And (3) diving platform training: after the mice in the test group are subjected to intragastric administration or distilled water administration on the 14 th day of the experiment for 50min, a mouse memory obtaining obstacle model is manufactured by the same method as a dark avoidance experiment, after 10min, the mice in each group are placed on a diving platform to adapt for 3min, then 32V alternating current is applied, the time is immediately counted, and the incubation period and the error times of the animals in 5min are recorded.
(2) And (3) jump table testing: and (3) after the mice in the diving platform group are subjected to gastric lavage administration or distilled water 60min on the 15 th day of the experiment (after 24 hours of diving platform training), the mice are placed on the diving platform in the same way, 32V alternating current is supplied, time is counted, and the latency and the error times of the animals within 5min are recorded.
3. Results
3.1 influence on mouse memory acquired disorder caused by scopolamine evasion latency and error frequency (evasion method)
Compared with the blank group, the escape latency of the model group mice is obviously shortened, and the error frequency is obviously increased. After drug treatment, compared with a model control group, the donepezil hydrochloride group, the test C group, the test D group and the test E group can obviously prolong the latency period of the mice (p is less than 0.05) and reduce the error frequency of the mice within 5min (p is less than 0.05), and the results are shown in table 1.
TABLE 1 influence on the escape latency and number of errors in scopolamine-induced acquired memory impairment mice (avoidance method)
Note: p <0.05 compared to model group; p <0.01.
3.2 influence on mouse memory acquired disorder caused by scopolamine escape latency and error frequency (diving platform method)
Compared with the blank group, the escape latency of the model group mice is obviously shortened, and the error frequency is obviously increased. After drug treatment, compared with a model control group, the donepezil hydrochloride group, the test D group and the test E group can obviously prolong the latency period of the mice (p is less than 0.05), reduce the error frequency of the mice within 5min (p is less than 0.05), and have no obvious change in the test A group, the test B group and the test C group. The results are shown in Table 2.
TABLE 2 influence of the escape latency and the number of errors in scopolamine-induced acquired memory impairment mice (diving platform method)
Note: p <0.05 compared to model group; p <0.01.
3.3 Effect on AchE and ChAT Activity in memory acquisition disorder mouse brain tissue
Compared with the blank group, the AchE activity in the brain tissue of the mouse in the model group is obviously increased, and the ChAT activity is obviously reduced. After treatment, the activity of Ach E of donepezil hydrochloride group, experiment D group and experiment E group is obviously reduced (p is less than 0.05), the activity of ChAT is obviously improved (p is less than 0.05), and the experiment A group, the experiment B group and the experiment C group have no obvious change. The results are shown in Table 3.
TABLE 3 Effect on AchE and ChAT Activity in the brain of mice model for memory impairment
Note: in comparison with the set of models,*P<0.05；**P<0.01.
the above experimental results show that: under the condition of the same administration dosage, the compatibility of the ginseng, the angelica and the fructus alpiniae oxyphyllae and the compatibility of the ginseng, the angelica, the fructus alpiniae oxyphyllae and the spina date seeds can effectively improve the learning and memory capacity of a mouse with pseudodementia caused by scopolamine, reduce the ACHE activity of brain tissues and improve the ChAT activity, so that the learning and memory capacity of the mouse with dementia can be effectively improved, the cognition and judgment capacity of the mouse with dementia can be enhanced, and the mouse with dementia can be used for treating senile dementia; the compatibility of ginseng and angelica, angelica and sharpleaf galangal fruit, and the compatibility of sharpleaf galangal fruit and ginseng can not improve the learning and memory ability of a mouse with pseudodementia caused by scopolamine, reduce the ACHE activity of brain tissues and increase the ChAT activity, and basically has no treatment effect on the mouse with dementia.
Test example 2 test of the pharmaceutical composition of the present invention against vascular dementia model
1 materials of the experiment
1.1 Experimental animals:
SPF male SD rat, 250-280g, was provided by Woods great laboratory animals GmbH, animal license number: SCXK (Chuan) 2015-030, raised at room temperature 22-26 ℃ and ingested with free water.
1.2 drugs and reagents:
himalayan (dihydroergotoxine mesylate tablets), specification: 1 mg/tablet, national drug standard H31021182, Shanghai drug-mail pharmaceutical factory Co., Ltd; MDA, MAO kit, Nanjing to build bioengineering institute. The ginseng, angelica and fructus alpiniae oxyphyllae group (ginseng: angelica: fructus alpiniae oxyphyllae 1:1:1), the ginseng, angelica, fructus alpiniae oxyphyllae + spina date seed group (ginseng: angelica: fructus alpiniae oxyphyllae: spina date seed: 1:1:1) are all mixed according to equal dosage ratio and purchased from traditional Chinese medicine houses in subsidiary hospitals of Chengdu traditional Chinese medicine university.
2 method of experiment
2.1 model preparation
Permanently ligating bilateral common carotid arteries of rats by adopting a 2-VO method, separating the bilateral common carotid arteries of a blank group without ligation, injecting 10 ten thousand units of penicillin sodium into each rat per im after operation for resisting infection for 3 days, performing attention to water supplement during operation, performing attention to heat preservation after operation, and freely feeding the rats after one month after the operation for grouped administration.
2.2 grouping and administration
60 model rats SD are divided into a normal control group, a model control group, a positive control group (donepezil hydrochloride tablets), an experiment A group (ginseng, angelica and fructus alpiniae oxyphyllae group) and an experiment B group (ginseng, angelica, fructus alpiniae oxyphyllae and spina date seed group) according to weight layering at random, all the groups of medicines are decocted with water according to a conventional method and concentrated into liquid medicine with the crude drug content of 0.6g/ml for later use, all the groups of animals are subjected to gastric lavage administration according to 1ml/100g of weight per day, the model control group and the blank control group are subjected to equal amount of distilled water, administration is carried out for 15 days continuously, a water maze behaviouristic test is started after administration on the 11 th day of the experiment, a positioning navigation experiment is carried out on the first 4 days, and a space search experiment is carried.
2.3 Morris Water maze test rat learning and memory ability
The MT-200 water maze pool is divided into 4 quadrants in an average way, the platform is positioned in the center of the SW quadrant, the water surface is 1.5cm higher than the platform, milk is added into the water until the water is opaque, the rat enters the water towards the pool wall at the middle position of the SW quadrant every day, the experimental time is 120s, the rat sails in a fixed position in the first 4 days, the latency, the platform residence time and the platform residence distance are automatically recorded by an instrument, the number of times of passing the platform is counted as 120s, if the rat does not find the platform in 120s, all the rats are stopped on the platform for 10s after the experiment to enhance the memory; and 5 days in total, the platform is removed on the fifth day of the experiment, a space search experiment is carried out for 120s, the latency period of the space search experiment is manually recorded, and the number of times the space search experiment passes through the platform, the retention time of the platform and the retention distance of the platform are automatically recorded by an instrument. The results are shown in Table 4.
2.4 rat Hippocampus, determination of serum MDA content, MAO Activity
And (3) killing the rat after the behavioral test is finished, freezing and storing hippocampal tissues for later use, taking blood and separating serum, and detecting the hippocampal, serum MDA content and MAO activity of the rat according to the kit. The results are shown in tables 5 and 6.
3 results of the experiment
3.1 Effect of drugs on spatial search Capacity in mice
Compared with the model control group, each treatment group can shorten the escape latency of rats to different degrees and increase the platform passing times, the platform residence time and the platform residence distance of the rats within 120s, and the results are shown in table 4.
TABLE 4 influence on spatial learning and memory ability of VD model rats
Note: p <0.05 compared to model group; p <0.01.
3.2 Effect on rat Hippocampus tissue, serum MDA content, MAO Activity
Compared with a model control group, the positive control group can obviously reduce the MDA content and the MAO activity of rat hippocampal tissues (p is less than 0.05); the MDA content of the hippocampal tissues of rats in the experiment A group and the experiment B group has a descending trend, wherein the MAO descending trend of the experiment B group is obvious (p is less than 0.05), and the statistical significance is realized. The results are shown in Table 5.
TABLE 5 Effect on rat Hippocampus tissue MDA content, MAO Activity
Note: p <0.05 compared to model group.
Compared with a model control group, the positive control group can obviously reduce the MDA content and the MAO activity of the serum of the rat (p is less than 0.05); experiment A and B groups of rats have a descending trend of MDA content and MAO activity in hippocampal serum. The results are shown in tables 5 and 6.
TABLE 6 Effect on rat serum MDA content, MAO Activity
Note: p <0.05 compared to model group; p <0.01.
The above experimental results show that: under the condition of the same administration dosage, the compatibility of the ginseng, the angelica and the fructus alpiniae oxyphyllae and the compatibility of the ginseng, the angelica, the fructus alpiniae oxyphyllae and the spina date seed have different degrees of influence on MDA and MAO activities in hippocampal tissues and serum of rats, so that the effect of improving the learning and memory capacity of the rats with the model of the vascular dementia to a certain extent is proved, and the pharmaceutical composition can be used for treating the vascular dementia.
Test example 3 test of drug against vascular dementia model at different dose ratios
1 materials of the experiment
1.1 Experimental animals:
SPF male SD rat, 250-280g, was provided by Woods great laboratory animals GmbH, animal license number: SCXK (Chuan) 2015-030, raised at room temperature 22-26 ℃ and ingested with free water.
1.2 drugs and reagents:
himalayan (dihydroergotoxine mesylate tablets), specification: 1 mg/tablet, national drug standard H31021182, Shanghai drug-mail pharmaceutical factory Co., Ltd; MDA, MAO kit, Nanjing to build bioengineering institute. Experiment group a (ginseng: angelica sinensis: sharpleaf galangal fruit ═ 10:5:1 group), experiment group B (ginseng: angelica sinensis: sharpleaf galangal fruit ═ 5:3:1 group), experiment group C (ginseng: angelica sinensis: sharpleaf galangal fruit ═ 1:1:1 group), experiment group D (ginseng: angelica sinensis: sharpleaf galangal fruit ═ 1:3:5 group), experiment group E (ginseng: angelica sinensis: sharpleaf galangal fruit ═ 1:5:10 group), experiment group F (ginseng: angelica sinensis: sharpleaf galangal fruit ═ 1:5:3 group), experiment group G (ginseng: angelica sinensis: sharpleaf galangal fruit ═ 3:5:1 group), and purchased from traditional Chinese medicine houses belonging to hospitals of traditional Chinese medicine universities.
2 method of experiment
2.1 model preparation
Permanently ligating bilateral common carotid arteries of rats by adopting a 2-VO method, separating the bilateral common carotid arteries of a blank group without ligation, injecting 10 ten thousand units of penicillin sodium into each rat per im after operation for resisting infection for 3 days, performing attention to water supplement during operation, performing attention to heat preservation after operation, and freely feeding the rats after one month after the operation for grouped administration.
2.2 grouping and administration
60 model rats SD are divided into a normal control group, a model control group, a positive control group (donepezil hydrochloride tablet), an experiment A group (ginseng: angelica sinensis: sharpleaf galangal fruit-10: 5:1 group), an experiment B group (ginseng: angelica sinensis: sharpleaf galangal fruit-5: 3:1 group), an experiment C group (ginseng: angelica sinensis: sharpleaf galangal fruit-1: 1:1 group), an experiment D group (ginseng: angelica sinensis: sharpleaf galangal fruit-1: 3:5 group), an experiment E group (ginseng: angelica sinensis: sharpleaf galangal fruit-1: 5:10 group), an experiment F group (ginseng: angelica sinensis: sharpleaf galangal fruit-1: 5:3 group) and an experiment G group (ginseng: angelica sinensis: sharpleaf galangal fruit-3: 5:1 group) according to weight layers, the medicines are decocted by a conventional method, concentrated into liquid medicine containing crude medicines of 0.6G/ml, and the animals of each group are administrated by a filling stomach of 1ml/100G day, and (3) feeding distilled water with the same amount to the model control group and the blank control group, continuously feeding the distilled water for 15 days, starting to perform the water maze behavioural test after the 11 th day of the test, performing the positioning navigation test in the first 4 days, and performing the space search test by going to the platform in the 5 th day.
2.3 Morris Water maze test rat learning and memory ability
The same as in test example 2. The results are shown in Table 7.
2.4 rat Hippocampus, determination of serum MDA content, MAO Activity
The same as in test example 2. The results are shown in tables 8 and 9.
3 results of the experiment
3.1 Effect of drugs on spatial search Capacity in mice
Compared with a model control group, each drug treatment group can shorten the escape latency of rats and increase the platform passing times, platform residence time and platform residence distance of the rats within 120s, wherein a positive control group, an experiment C group, an experiment D group, an experiment F group and an experiment G group have statistical significance (p is less than 0.05), an experiment A group, an experiment B group and an experiment E group have no statistical significance, and the results are shown in a table 7.
The experimental results show that the escape latency of the rat can be effectively shortened and the platform passing times, the platform residence time and the platform residence distance of the rat in 120s can be increased under the proportion of the experimental group C, the experimental group D, the experimental group F and the experimental group G, while the escape latency of the rat cannot be shortened under the proportion of the experimental group A, the experimental group B and the experimental group E, and the platform passing times, the platform residence time and the platform residence distance of the rat in 120s cannot be increased.
TABLE 7 Effect on spatial learning and memory of VD model rats
Note: p <0.05 compared to model group; p <0.01.
3.2 Effect on rat Hippocampus tissue, serum MDA content, MAO Activity
Compared with a model control group, the positive control group can obviously reduce the MDA content and the MAO activity (p is less than 0.05) of rat hippocampal tissues, and each drug treatment group has the effect of reducing the MDA content and the MAO activity of the rat hippocampal tissues, wherein the positive control group, the experiment C group and the experiment D group have the most obvious effect (p is less than 0.05) in the experiment F combined experiment G group and have statistical significance, while the experiment A group, the experiment B group and the experiment E group have no statistical significance, and the results are shown in a table 8.
TABLE 8 Effect on rat Hippocampus tissue MDA content, MAO Activity
Note: p <0.05 compared to model group.
Compared with a model control group, the positive control group can obviously reduce the MDA content and the MAO activity of the serum of the rat (p is less than 0.05), each drug treatment group has the effect of reducing the MDA content and the MAO activity of the serum of the rat, wherein the positive control group, the experiment D group and the experiment F combined experiment G group are most obvious (p is less than 0.05) and have statistical significance, and the results are shown in a table 9.
TABLE 9 Effect on rat serum MDA content, MAO Activity
Note: p <0.05 compared to model group; p <0.01.
The above experiments show that: under the condition of the same administration dosage, the formula of the ginseng, the angelica sinensis and the fructus alpiniae oxyphyllae has different degrees of treatment effects on vascular dementia within the range of 1-3: 1-5: 1-3 of the ratio of the ginseng, the angelica sinensis and the fructus alpiniae oxyphyllae, preferably, the ratio of the ginseng, the angelica sinensis and the fructus alpiniae oxyphyllae is 1-3: 5: 1-3 of the ratio of the ginseng, the angelica sinensis and the fructus alpiniae oxyphyllae is further preferably 3:5:1 or 1:5:3 of the ratio of.
From the results, the pharmaceutical composition has a good treatment effect on relieving senile dementia, vascular dementia or mild cognitive impairment, is simple in components, low in cost, simple in preparation process, more suitable for large-scale factory production, and has a wide market application prospect.
Claims (10)
1. A pharmaceutical composition for preventing and treating neurodegenerative diseases, which is characterized in that: the preparation is prepared from the following raw material medicines in parts by weight: 1-3 parts of ginseng, 1-5 parts of angelica and 1-5 parts of fructus alpiniae oxyphyllae.
2. The pharmaceutical composition of claim 1, wherein: the preparation is prepared from the following raw material medicines in parts by weight: 1-3 parts of ginseng, 1-5 parts of angelica and 1-3 parts of fructus alpiniae oxyphyllae.
3. The pharmaceutical composition of claim 1, wherein: the preparation is prepared from the following raw materials in parts by weight: 1-3 parts of ginseng, 5 parts of angelica and 1-3 parts of fructus alpiniae oxyphyllae.
4. The pharmaceutical composition of claim 1, wherein: the preparation is prepared from the following raw material medicines in parts by weight:
3 parts of ginseng, 5 parts of angelica and 1 part of sharpleaf galangal fruit;
or, the preparation is prepared from the following raw material medicines in parts by weight: 1 part of ginseng, 5 parts of angelica and 3 parts of fructus alpiniae oxyphyllae;
or, the preparation is prepared from the following raw material medicines in parts by weight: 1 part of ginseng, 3 parts of angelica and 5 parts of sharpleaf galangal fruit;
or, the preparation is prepared from the following raw material medicines in parts by weight: 1 part of ginseng, 1 part of angelica and 1 part of sharpleaf galangal fruit.
5. A pharmaceutical composition for preventing and treating neurodegenerative diseases, which is characterized in that: the preparation is prepared from the following raw material medicines in parts by weight:
1 part of ginseng, 1 part of angelica, 1 part of sharpleaf galangal fruit and 1 part of spina date seed.
6. The pharmaceutical composition according to any one of claims 1 to 5, wherein: the preparation is prepared by taking medicinal powder of raw material medicines, water or organic solvent extract of the raw material medicines as active ingredients and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
7. The pharmaceutical composition of claim 6, wherein: the preparation can be tablet, capsule, granule, oral liquid, or powder.
8. A process for preparing a pharmaceutical composition according to any one of claims 1 to 7, characterized in that: it comprises the following steps:
1) weighing the raw materials in a weight ratio;
2) the medicine powder of the raw material medicines is added with pharmaceutically acceptable auxiliary materials or auxiliary components to prepare the preparation.
9. Use of the composition of any one of claims 1 to 5 for the preparation of a medicament for the prevention and treatment of neurodegenerative diseases.
10. Use according to claim 9, characterized in that: the neurodegenerative disease is vascular dementia, senile dementia or cognitive disorder.
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| TW201313137A (en) * | 2011-09-30 | 2013-04-01 | Chuan Xi Biochemistry Technology Co Ltd | Natural intelligence-helpful brain-healthcare beverage |
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