CN114288352A - Pharmaceutical composition for treating vascular dementia and application thereof - Google Patents
Pharmaceutical composition for treating vascular dementia and application thereof Download PDFInfo
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- CN114288352A CN114288352A CN202210030843.0A CN202210030843A CN114288352A CN 114288352 A CN114288352 A CN 114288352A CN 202210030843 A CN202210030843 A CN 202210030843A CN 114288352 A CN114288352 A CN 114288352A
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Abstract
The invention is applicable to the technical field of medicines, and provides a pharmaceutical composition for treating vascular dementia and related diseases, which comprises 1-6 parts of stilbene glucoside, 0.2-4 parts of catalpol, 0.5-4 parts of sodium danshensu, 3-8 parts of senkyunolide I, 3-8 parts of rhizoma acori graminei volatile oil and 0.2-5 parts of tenuifolin. The pharmaceutical composition provided by the invention is simple in formula, economical and practical, complementary and reasonable in compatibility, and can effectively treat vascular dementia. Moreover, the components are all derived from natural products, and the health-care tea has no adverse reaction and toxic or side effect after long-term use, and is worthy of popularization and application. The invention also provides a preparation method of the pharmaceutical composition, which is characterized in that the components with the formula amount are uniformly mixed and are mixed with pharmaceutically acceptable auxiliary materials to prepare the pharmaceutical composition.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a pharmaceutical composition for treating vascular dementia and application thereof.
Background
Vascular dementia (VaD) is a dementia syndrome with cerebrovascular lesions as the main cause, belongs to a more serious group in vascular cognitive impairment, and is the most common dementia type after alzheimer disease, the prevalence rate of the dementia is 1.26-2.40% in people over 60 years old, and accounts for 12-20% of all dementia diseases. Cerebrovascular lesions cause cerebral ischemia hypoxia and hypoperfusion, followed by local neuronal necrosis in the brain, ultimately leading to cognitive dysfunction. Vascular dementia is characterized mainly by cognitive impairment, psychobehavioral symptoms and decreased living ability, and has evidence of cerebrovascular disease. With the aging of the population in China and the increase of the number of hypertension patients, the reduction of the incidence and disability rate of vascular dementia becomes an important task at present.
At present, the cholinesterase inhibitor represented by galantamine is mainly used for treating vascular dementia in western medicine, but actually, the cholinesterase inhibitor has a slight improvement effect on mild-to-moderate senile dementia and has no obvious benefit on the vascular dementia, and the medicine can also increase adverse reactions in a dose-dependent manner, particularly gastrointestinal tract, nerve and cardiovascular risks by 2-5 times, and further cause more harm to patients. Therefore, the exploration of the treatment effect of the active components of the traditional Chinese medicine on the vascular dementia has important significance on the national health of China at the present stage. In view of this, the present invention is proposed.
Disclosure of Invention
The purpose of the invention is as follows: in order to solve the problems, the invention aims to provide a pharmaceutical composition for treating vascular dementia and application thereof.
The invention aims to solve the problems of insufficient medicine, poor curative effect and more adverse reactions in the existing effective treatment of vascular dementia, and provides a pharmaceutical composition prepared by mixing stilbene glycoside, catalpol, sodium danshensu, senkyunolide I, rhizoma acori graminei volatile oil and tenuifolin.
The technical scheme is as follows: the purpose of the invention is realized by the following scheme:
in a first aspect, the invention provides a pharmaceutical composition for treating vascular dementia, which comprises stilbene glycoside, catalpol, sodium danshensu, senkyunolide I, rhizoma acori graminei volatile oil and tenuifolin.
Furthermore, the medicine composition comprises 1-6 parts of stilbene glycoside, 0.2-4 parts of catalpol, 0.5-4 parts of sodium danshensu, 3-8 parts of senkyunolide I, 3-8 parts of rhizoma acori graminei volatile oil and 0.2-5 parts of tenuifolin.
Furthermore, the medicine composition comprises 2-4 parts of stilbene glycoside, 0.5-2 parts of catalpol, 1-3 parts of sodium danshensu, 4-6 parts of senkyunolide I, 5-7 parts of rhizoma acori graminei volatile oil and 1-3 parts of tenuifolin.
Furthermore, the medicine composition comprises 3 parts of stilbene glycoside, 1 part of catalpol, 2 parts of danshensu sodium, 5 parts of senkyunolide I, 6 parts of rhizoma acori graminei volatile oil and 2 parts of tenuifolin.
The invention provides a pharmaceutical preparation containing the traditional Chinese medicine composition, which consists of the traditional Chinese medicine composition and pharmaceutically acceptable auxiliary materials. The pharmaceutical preparation is preferably an oral preparation selected from tablets, capsules, sustained-release tablets, pills, granules, dispersible tablets and powders, preferably tablets.
Preferably, the composition further comprises pharmaceutically acceptable pharmaceutical excipients, including one or more of starch, magnesium stearate and talcum powder.
In addition, the invention also provides application of the pharmaceutical composition or the medicament in preparing a product for treating encephalopathy.
Further, the encephalopathy is vascular dementia.
Through the technical scheme, the following beneficial effects can be obtained.
The pharmaceutical composition provided by the invention comprises stilbene glycoside, catalpol, sodium danshensu, senkyunolide I, rhizoma acori graminei volatile oil and tenuifolin. The pharmaceutical composition provided by the invention has simple component formula, reasonable compatibility, mutual assistance, economy and practicability, and the clinical curative effect is superior to that of the conventional western medicine or Chinese traditional medicine. In addition, the main components are natural extracts, adverse reactions and toxic and side effects are avoided after long-term use, and the Chinese medicinal composition is worthy of popularization and application.
Stilbene glucoside is an important active ingredient of radix Polygoni Multiflori Preparata, and is also an index ingredient of radix Polygoni Multiflori Preparata in Chinese pharmacopoeia. Modern researches show that the traditional Chinese medicine composition has positive effects on oxidation resistance, memory improvement, free radical elimination, blood fat reduction, atherosclerosis resistance, liver protection, tumor resistance, nerve protection and the like. Catalpol is an important active ingredient of prepared rehmannia root, and researches show that catalpol can improve depression state by resisting oxidative stress. The danshensu is derived from a traditional Chinese medicine salvia miltiorrhiza capable of promoting blood circulation to remove blood stasis, is commonly used for treating myocardial ischemic diseases clinically, has a protective effect on vascular diseases, but is prepared into sodium salt due to instability, so that the effect is unchanged, but the stability is better. Ligustrazine is considered as the active substance basis of the ligusticum wallichii, but the content of the ligustrazine is less than 0.10 mu g/g, so the activity of the ligusticum wallichii is derived from other components. Later period, it is found that the gafeng substance mainly comprises organic acid component (such as ferulic acid) and phenyl peptides, and senkyunolide I is one of phenyl peptide active components, and its content can reach 0.5% of medicinal materials. Modern researches show that the senkyunolide I can realize the protection effect on cerebral ischemia by up-regulating p-Erk1/2 and Nrf2/HO-1 channels, relieve the apoptosis of neurons by inhibiting the expression of caspase-3 and simultaneously relieve the inflammatory response of the neurons, and the effects have positive significance on the treatment of vascular encephalopathy. The volatile oil is a key component of the rhizoma acori graminei of the resuscitation inducing medicine, has excellent distribution characteristics in brain, particularly contains alpha-asarone and beta-asarone, can reduce the formation of inflammatory factors TNF-alpha and IL-1 beta by inhibiting the activation of NF-kB, thereby relieving inflammatory injury, and has important significance for treating vascular dementia due to anti-inflammation. The tenuifolin is the main active ingredient of traditional Chinese medicine polygala tenuifolia, and can improve cognitive disorder after cerebral apoplexy by inhibiting beta-amyloid (Abeta) aggregation in brain, relieving neurotoxicity generated by Abeta, reducing tau protein abnormal phosphorylation, eliminating neuroinflammation and inhibiting the release of proinflammatory cytokines. The effective combination of the traditional Chinese medicines has clinical treatment basis and accords with the compatibility principle of the traditional Chinese medicine.
The medicine provided by the invention is prepared from the medicine composition provided by the invention, has definite active ingredients, and can quickly and effectively treat vascular dementia.
The invention provides the preparation method of the pharmaceutical composition, the components are uniformly mixed according to the formula amount and are mixed with pharmaceutically acceptable auxiliary materials to prepare the pharmaceutical preparation, and the preparation method is simple, convenient to operate and suitable for mass production.
The vascular dementia belongs to the categories of forgetfulness, dementia and the like in traditional Chinese medicine, the occurrence of the vascular dementia is usually caused by old physical weakness, exogenous diseases, emotional emotions or chronic diseases, the disease is located in the brain, the deficiency of kidney essence is taken as the basis, phlegm stagnation and blood stasis are taken as the targets, and the treatment mainly includes kidney tonifying, essence replenishing, blood circulation promoting, blood stasis removing, phlegm reducing and resuscitation inducing. However, the quality control of the drug effect material basis is difficult in the traditional Chinese medicine, and clear and stable evidence is lacked in the medicine compatibility mechanism, so that the problems restrict the further development of new traditional Chinese medicine. The component traditional Chinese medicine is a breakthrough of traditional Chinese medicine innovation, not only accords with the compatibility theory of traditional Chinese medicine, but also has more definite clinical indications, material basis and action mechanism, and has better advantages in the aspects of medicine quality control and industrialized popularization. Stilbene glucoside and catalpol are respectively active ingredients of the kidney-tonifying essence-replenishing medicine on radix Polygoni Multiflori Preparata and radix rehmanniae Preparata; salvianic acid A sodium and senkyunolide I are respectively active ingredients of blood-activating and stasis-resolving medicines for salvia miltiorrhiza and ligusticum wallichii, and the volatile oil of rhizoma acori graminei and the tenuifolin are derived from phlegm-resolving and resuscitation-inducing medicines for rhizoma acori graminei and polygala tenuifolia, so the combination of the above medicines has the functions of tonifying kidney, activating blood and resolving phlegm.
Drawings
FIG. 1 the results of the test of the pharmaceutical composition of example 2 on the Morris water maze of rats with vascular dementia
In comparison with the normal group,##p<0.01; comparison with model group<0.05，**p<0.01。
FIG. 2 example 2 Effect of pharmaceutical composition on Neisseria score in Hippocampus tissue of rats with vascular dementia
In comparison with the normal group,##p<0.01; comparison with model group<0.05，**p<0.01。
FIG. 3 Effect of the pharmaceutical composition of example 2 on oxidative stress of Hippocampus tissues of rats with vascular dementia
In comparison with the normal group,##p<0.01; comparison with model group<0.05，**p<0.01。
FIG. 4 Effect of example 2 pharmaceutical composition on vascular dementia in rat T-ChE
Comparison with model group<0.05，**p<0.01。
FIG. 5 Effect of the pharmaceutical composition of example 2 on vascular dementia rat Hippocampus inflammatory factor levels
In comparison with the normal group,##p<0.01; comparison with model group<0.05，**p<0.01。
FIG. 6 Effect of example 2 pharmaceutical compositions on vascular dementia in rat hippocampal tissue VEGF and VEGFR2 expression
In comparison with the normal group,#p<0.05; comparison with model group<0.05，**p<0.01。
Detailed Description
The foregoing aspects of the present invention are described in further detail below by way of examples, but it should not be construed that the scope of the above-described subject matter of the present invention is limited to the following examples, and that all the technologies implemented based on the above-described aspects of the present invention are within the scope of the present invention.
The present invention provides a pharmaceutical composition comprising: stilbene glycoside, catalpol, sodium danshensu, senkyunolide I, rhizoma acori graminei volatile oil and tenuifolin.
Example 1
The component sources are as follows.
The preparation method of the stilbene glucoside in the polygonum multiflorum comprises the following steps: adding 12 times of water into coarse powder (20 meshes) of the polygonum multiflorum, soaking for 24h, percolating at the flow rate of 10mL/min per kilogram of the medicinal material, introducing the percolate into a macroporous resin column, eluting with 25% ethanol with the volume 5 times of that of the resin, recovering the solvent from the eluent, drying, introducing into a silica gel column by a dry method, and eluting with ethyl acetate-methanol-water (200:4: 3). Recovering solvent and drying to obtain the product. The yield of stilbene glucoside is 97.83%.
The preparation method of the rhizoma acori graminei volatile oil comprises the following steps: placing rhizoma Acori Graminei powder (20 mesh) and 500 times volume of distilled water in 1000mL electric heating jacket, extracting by steam distillation for 4h, extracting the obtained essential oil with diethyl ether, dehydrating with anhydrous sodium sulfate, and recovering diethyl ether.
Catalpol standard product is purchased from China institute for testing and testing food and drug (lot number 0808-9803); the danshensu sodium standard substance is purchased from China institute for food and drug testing (batch No. 110855-; senkyunolide I reference, purchased from Doudo Cromar Biotech Co., Ltd. (batch No. 140827); polygala tenuifolia saponins were purchased from Dowmattest Biotech limited (batch No. 20100913).
Example 2
A preparation method of a pharmaceutical composition for treating vascular dementia comprises the following steps: weighing 3 parts of stilbene glycoside, 1 part of catalpol, 2 parts of sodium danshensu, 5 parts of senkyunolide I, 6 parts of rhizoma acori graminei volatile oil and 2 parts of tenuifolin. Mixing with 1.5 parts of starch, sieving, drying, adding 0.1 part of magnesium stearate and 0.1 part of talcum powder, and tabletting.
Example 3
A preparation method of a pharmaceutical composition for treating vascular dementia comprises the following steps: weighing 4 parts of stilbene glycoside, 2 parts of catalpol, 3 parts of salvianic acid A sodium, 6 parts of senkyunolide I, 7 parts of rhizoma acori graminei volatile oil and 3 parts of tenuifolin. Mixing with 1.9 parts of starch, sieving, drying, adding 0.12 part of magnesium stearate and 0.12 part of talcum powder, and encapsulating.
Example 4
A preparation method of a pharmaceutical composition for treating vascular dementia comprises the following steps: weighing 6 parts of stilbene glycoside, 4 parts of catalpol, 4 parts of sodium danshensu, 8 parts of senkyunolide I, 8 parts of rhizoma acori graminei volatile oil and 5 parts of tenuifolin. Mixing with 2.6 parts of starch, sieving, drying, adding 0.18 part of magnesium stearate and 0.18 part of talcum powder, and making into granule.
EXAMPLE 5 pharmacodynamic test related to the functional indications of pharmaceutical compositions
In order to examine the functions and indications of the pharmaceutical composition provided by the present invention, pharmacodynamic tests were conducted using the pharmaceutical composition preparation prepared in example 2.
1. Experimental Material
1.1 Experimental animals: clean grade SD rats, male, body weight 200 ± 20g, provided by the hangzhou medical college, production license number: SCXK (Zhe) 2019 plus 0002, which is bred in Nanjing university of traditional Chinese medicine animal center. Free intake and drinking of water, experiments were performed 3 days after acclimation in the experimental environment.
1.2 preparation of Experimental drugs
Kidney tonifying and marrow filling group: stilbene glucoside and catalpol provided in example 1 were combined at a ratio of 3:1, and sodium carboxymethylcellulose (CMC-Na) was used to prepare 38.0mg/mL, and the mixture was gavaged at 10mL/kg, i.e. the administration dose was 0.38 g/kg.
Group for promoting blood circulation and removing blood stasis: the sodium danshensu and the senkyunolide I provided in the example 1 are combined in a ratio of 2:5, CMC-Na is used for preparing 38.0mg/mL, and the mixture is intragastrically administered according to 10mL/kg, namely the administration dosage is 0.38 g/kg.
Phlegm-resolving and resuscitation-inducing group: the acorus gramineus volatile oil and tenuifolin provided in the embodiment 1 are combined in a ratio of 3:1, CMC-Na is used for preparing 38.0mg/mL, and the mixture is intragastrically administered according to 10mL/kg, namely the administration dosage is 0.38 g/kg.
Combination low dose group: example 2 the drug was prepared with CMC-Na to 20.7mg/mL, i.e., the drug concentration was 19.0mg/mL, and the gavage was performed at 10mL/kg, i.e., the dose was 0.19 g/kg.
Combination high dose group: example 2 the drug was prepared with CMC-Na to 41.4mg/mL, i.e., 38.0mg/mL, and gavage at 10mL/kg, i.e., 0.38 g/kg.
Galantamine hydrobromide tablet (5 mg/tablet), jinhuakang enbei biopharmaceutical ltd, zhejiang. Each tablet is dissolved in 16.7mL CMC-Na solution, and the solution is irrigated by 10mL/kg, namely the administration dose is 3 mg/kg.
2. Experimental methods
2.1 method of vascular dementia modeling
10% chloral hydrate (10mL/kg) is injected into abdominal cavity, after anesthesia, an incision with a length of about 1cm is made in the middle of the neck, one side of common carotid artery is exposed, and after ligation of two ends, the blood vessel is cut off. The false operation group is only separated and not ligated, the tissue is sutured layer by layer after the operation is finished, and the common carotid artery on the other side is ligated by the same method after 3 days.
2.2 methods of treatment
After modeling, rats were divided into 7 groups, namely a model group, a galantamine group, a kidney-tonifying and marrow-filling group, a blood circulation-promoting and stasis-removing group, a phlegm-resolving and resuscitation-inducing group, a combined low-dose group and a combined high-dose group, 12 rats in each group were subjected to intragastric administration for 1 time every day for 30 consecutive days, and the sham operation group and the model group were administered with physiological saline of the same volume. After 30 days, the following criteria were examined.
2.3 index detection
2.3.1 Morris Water maze experiment
The Morris water maze experiment was performed according to the previous study method. The experiment consisted of a stainless steel circular basin with a diameter of 100cm and a depth of 50cm and a platform. Firstly, injecting clear water into a pool, then adding a little ink to turn the water black, and controlling the water temperature to be (22 +/-2) DEG C. The pool was divided into 2 zones. The distance between the platform and the platform is less than 50cm, namely a near platform area, and the distance between the platform and the platform is more than 50cm, namely a far platform area. The training time is set to 70s at ordinary times as the maximum latency of escaping to the platform, and if the training time exceeds 70s, the rat is directly pulled to the platform. During the experiment, the rat is randomly placed in any quadrant, the time for searching the platform is taken as a latency period, the track traveled by the platform is taken as a total path, and the total path, the latency period, the path of the near station area, the path of the far station area and the path ratio of the near station area to the far station area of the rat are recorded.
2.3.2 Niss score
Taking 3 rats from each group for Niger staining examination, specifically taking brains from decapitation, placing in 4% paraformaldehyde solution for fixation, embedding in paraffin, slicing, staining with toluidine blue, observing the number of Niger corpuscles in the hippocampal region under a microscope after mounting, and carrying out Niger scoring according to the number.
2.3.3 Biochemical and inflammatory indices
Taking 6 rats per group, rapidly taking brain, separating hippocampal tissue, adding ice-cold normal saline, homogenizing 10% brain tissue with high speed disperser, centrifuging, and collecting supernatant. According to the steps of a reagent specification, an enzyme-labeling instrument is adopted to detect the contents of the superoxide dismutase (SOD), the glutathione peroxidase (GSH-Px), the Malondialdehyde (MDA) and the acetylcholinesterase (T-ChE) in the homogenate of the hippocampal tissues. In addition, ELISA method is adopted to detect the content of three inflammatory factors of IL-1 beta, IL-6 and TNF-alpha in the brain homogenate.
2.3.4 expression of VEGF and VEGFR2
Brain tissue of 3 rats in each group was collected, hippocampus tissue was isolated, and total protein was extracted and quantified by BCA method. Loading 20 μ g of sample per well, performing SDS-PAGE electrophoresis, membrane transfer and blocking, incubating the primary antibody overnight at 4 ℃, washing the membrane for three times by TBST, incubating the secondary antibody at room temperature, washing the membrane for three times again, performing color development imaging, and performing gray scale and area calculation by using ImageJ. Expression of VEGF and VEGFR2 was respectively expressed as a percentage of GAPDH, and the relative expression of each was obtained.
2.3.5 statistical methods
Experimental data on
Expressed, Graphpad prism is adopted8.0 software for data analysis, p<0.05 was statistically different.
3. Results of the experiment
3.1Morris Water maze test results
Compared with the normal group, the rats in the model group are obviously increased in total swimming distance, latency and distance station zone track distance, and are obviously reduced in distance station zone track distance and distance station zone distance ratio (P <0.01), so that the rats in the model group are prompted to have reduced learning function. After galantamine, a kidney-tonifying and marrow-filling group, a blood circulation-promoting and blood stasis-removing group and a phlegm-reducing and resuscitation-inducing group are treated in combination with low-dose and high-dose treatment, the track path of a far station area is obviously shortened and the path ratio of a near station area to a far station area is obviously increased (compared with a model group, P is less than 0.05 and 0.01), and the improvement of learning and memory of rats with vascular dementia by various medicaments is better. In addition, the galantamine group, the kidney tonifying and marrow filling group and the combined low dose and high dose can shorten the total swimming path and the incubation period (compared with the model group, P is less than 0.05 and 0.01), while the galantamine and the two combined treatment groups can increase the track path of a near-station area (compared with the model group, P is less than 0.05), which indicates that in the combined treatment, although the kidney tonifying and marrow filling group is relatively more important in improving the learning and memory of the vascular dementia rats, the effect of the combined treatment group is still better, and the compatibility advantages of the combined application of the kidney tonifying and marrow filling, the blood circulation promoting and the blood stasis removing and the phlegm reducing and resuscitation are reflected. The galanthamine group has basically similar effects with the combined high-dose group in the indexes. The results are detailed in table 1 and figure 1.
TABLE 1 EXAMPLE 2 results of the pharmaceutical composition on the Morris water maze test of vascular dementia rats
In comparison with the normal group,##p<0.01; in comparison with the set of models,*p<0.05，**p<0.01。
3.2 Nicol score results
A significant decrease in hippocampal tissue niemann score (P <0.01) was seen in the model rats compared to the normal group, suggesting that the model rats had experienced a decrease in neuronal number and a decrease in function. Compared with the model group, the galantamine, the kidney tonifying and marrow filling group, the blood circulation promoting and blood stasis removing group, the combined low dose group and the high dose group can obviously improve the Nie score (P <0.05,0.01), and the improvement degree of the combined high dose group is better than that of other groups, including the galantamine group. The obvious compatibility advantage of the combined application of the three treatment methods on the protection of the neurons is reflected. The results are shown in table 2 and fig. 2.
Table 2 example 2 effect of pharmaceutical composition on niemann's score in hippocampal tissue of rats with vascular dementia
In comparison with the normal group,##p<0.01; in comparison with the set of models,*p<0.05，**p<0.01。
3.3 results of oxidative stress test
As shown in table 3 and fig. 3, the model group showed significant decrease in hippocampal SOD, GSH-Px and significant increase in MDA (P <0.01) compared to the normal group, suggesting that the vascular dementia model rats had already developed oxidative stress. Compared with the model group, the kidney tonifying and marrow filling group, the blood circulation promoting and blood stasis removing group and the combined low and high dose group can see the remarkable increase of SOD and GSH-Px and the remarkable decrease of MDA (P is less than 0.05 and 0.01), wherein the effect of the combined high dose group is most remarkable. The galanthamine group does not have the improvement of the indexes (P is more than 0.05), and the improvement of the vascular dementia and the antioxidation are not obviously related.
TABLE 3 example 2 Effect of pharmaceutical compositions on oxidative stress of Hippocampus tissues in rats with vascular dementia
In comparison with the normal group,##p<0.01; in comparison with the set of models,*p<0.05，**p<0.01。
3.4 Hippocampus tissue T-ChE assay results
As shown in Table 4 and FIG. 4, although no significant change in T-ChE was observed in the model group (P >0.05 compared to the normal group), the kidney-tonifying and marrow-replenishing group, the phlegm-resolving and resuscitation-inducing group, and the combination high-dose group all significantly reduced the formation of T-ChE (P <0.05), while the galantamine group was more effective (P <0.01), it was confirmed that the anti-vascular dementia effect of galantamine and the inhibition of T-ChE are closely related, and the pharmaceutical composition could improve the dementia symptoms by increasing the acetylcholine content through the inhibition of T-ChE.
TABLE 4 example 2 Effect of pharmaceutical compositions on vascular dementia in rat T-ChE
In comparison with the set of models,*p<0.05，**p<0.01。
3.5 Hippocampus inflammatory factor assay results
As shown in Table 5 and FIG. 5, significant increases in IL-1 β, IL-6 and TNF- α were seen in the model group compared to the normal group (P <0.01), suggesting that inflammatory lesions had occurred in the hippocampal tissues of the model rats. The positive drug galantamine treatment did not show significant reduction in the above three inflammatory factors (P >0.05), suggesting that anti-inflammation may not be one of the mechanisms of the drug in improving vascular dementia. The phlegm-reducing and resuscitation-inducing group and the combined treatment group can obviously reduce the levels of the three inflammatory factors, and particularly the combined high-dose group has the best effect (P is less than 0.05 and 0.01), so that the phlegm-reducing and resuscitation-inducing group is mainly anti-inflammatory, and the kidney-tonifying and marrow-replenishing group and the blood circulation-promoting and blood stasis-removing group are not obviously improved, but are combined with the phlegm-reducing and resuscitation-inducing group, so that the anti-inflammatory activity of the latter can be further improved.
TABLE 5 EXAMPLE 2 Effect of pharmaceutical compositions on vascular dementia rat Hippocampus tissue inflammatory factor levels
In comparison with the normal group,##p<0.01; in comparison with the set of models,*p<0.05，**p<0.01
3.6 Hippocampus tissue VEGF and VEGFR2 expression results
As shown in table 6 and fig. 6, compared with the normal group, the expression of VEGF and VEGFR2 in the hippocampal tissues of the model group was significantly increased (P <0.05), suggesting that angiogenesis could be induced after vascular dementia modeling, which is consistent with the literature report. The galanthamine group does not show the increase of the expression content of the two proteins (P >0.05), but the combination of tonifying kidney and filling marrow, the combination of activating blood and dissolving stasis, and the combination of the low-dose group and the high-dose group can both obviously increase the expression of VEGFR2, especially the combination of the high-dose group has the best effect (P <0.05,0.01), and the combination of activating blood and dissolving stasis and the combination of the high-dose group can also increase the VEGF level (P < 0.05). The results suggest that the promotion of angiogenesis may be one of the key mechanisms of the pharmaceutical composition for resisting vascular dementia, wherein the combined application effect of the three treatment methods is the best, and the compatibility advantages of the three treatment methods are reflected, which is a mechanism that the western medicine galanthamine does not have.
TABLE 6 example 2 Effect of pharmaceutical compositions on vascular dementia rat hippocampal tissue VEGF and VEGFR2 expression
In comparison with the normal group,#p<0.05; in comparison with the set of models,*p<0.05，**p<0.01
4. conclusion of the experiment
The medicine composition can obviously shorten the total swimming distance, the incubation period and the far station area track distance in the vascular dementia rat Morris water maze test, and increase the near station area track distance and the near/far station area track distance ratio. The combination also significantly increased the niemann score in the pathology test and the improvement was better in the high dose group than in the galantamine group. In further mechanism research, the protection of the drug combination on the nerve function of the rat with vascular dementia is found to be related to relieving oxidative stress, inhibiting acetylcholine ester, inhibiting the formation of inflammatory factors such as IL-1 beta, IL-6 and TNF-alpha and promoting angiogenesis. These results suggest that the combination has the characteristics of multi-link combined regulation and control in protecting the neuron function, improving the learning and memory ability and maintaining the neuron morphology.
In addition, in the further compatibility mechanism research, the effects of resisting oxidative stress and promoting angiogenesis of the composition are mainly from a kidney-tonifying and marrow-filling group and a blood circulation-promoting and blood stasis-removing group, the inflammation inhibition effect is mainly from a phlegm-reducing and resuscitation-inducing group, and the kidney-tonifying and marrow-filling group and the phlegm-reducing and resuscitation-inducing group can also inhibit acetylcholinesterase.
Claims (10)
1. A pharmaceutical composition for treating vascular dementia is characterized by comprising stilbene glycoside, catalpol, sodium danshensu, senkyunolide I, rhizoma acori graminei volatile oil and tenuifolin.
2. The pharmaceutical composition for treating vascular dementia according to claim 1, which is prepared from the following raw materials in parts by weight: 1-6 parts of stilbene glucoside, 0.2-4 parts of catalpol, 0.5-4 parts of sodium danshensu, 3-8 parts of senkyunolide I, 3-8 parts of rhizoma acori graminei volatile oil and 0.2-5 parts of tenuifolin.
3. The pharmaceutical composition for treating vascular dementia according to claim 2, which is prepared from the following raw materials in parts by weight: 2-4 parts of stilbene glucoside, 0.5-2 parts of catalpol, 1-3 parts of sodium danshensu, 4-6 parts of senkyunolide I, 5-7 parts of rhizoma acori graminei volatile oil and 1-3 parts of tenuifolin.
4. The pharmaceutical composition for treating vascular dementia according to claim 3, which is prepared from the following raw materials in parts by weight: 3 parts of stilbene glucoside, 1 part of catalpol, 2 parts of sodium danshensu, 5 parts of senkyunolide I, 6 parts of rhizoma acori graminei volatile oil and 2 parts of tenuifolin.
5. The pharmaceutical composition for treating vascular dementia according to any one of claims 1 to 4, wherein the pharmaceutical composition is prepared into a pharmaceutical preparation by adding a pharmaceutical excipient.
6. The pharmaceutical composition for treating vascular dementia according to claim 5, wherein the dosage form of the pharmaceutical preparation is an oral preparation.
7. The pharmaceutical composition for treating vascular dementia according to claim 6, wherein the oral preparation is in a dosage form selected from one of tablets, capsules, sustained-release tablets, pills, granules, dispersible tablets and powders.
8. The pharmaceutical composition for treating vascular dementia according to claim 7, wherein the oral preparation is in the form of tablets.
9. The pharmaceutical composition for treating vascular dementia according to claim 5, wherein the pharmaceutical excipients are one or more of starch, magnesium stearate and talcum powder.
10. The use of the pharmaceutical composition for treating vascular dementia according to claim 1 in the preparation of a product for treating vascular dementia.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101385815A (en) * | 2007-09-14 | 2009-03-18 | 尹克华 | Traditional Chinese medicine for treating dementia after stroke |
| CN112220870A (en) * | 2019-12-30 | 2021-01-15 | 首都医科大学宣武医院 | Pharmaceutical composition for treating Alzheimer disease |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101385815A (en) * | 2007-09-14 | 2009-03-18 | 尹克华 | Traditional Chinese medicine for treating dementia after stroke |
| CN112220870A (en) * | 2019-12-30 | 2021-01-15 | 首都医科大学宣武医院 | Pharmaceutical composition for treating Alzheimer disease |
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| 何瑾瑜等: "李巧兰治疗血管性痴呆经验介绍", 《江西中医药》 * |
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Application publication date: 20220408 |