Nano preparation for improving cognitive impairment as well as preparation method and application of nano preparation

Abstract

The invention provides a nano preparation for improving cognitive impairment and a preparation method and application thereof, and belongs to the technical field of biological medicine. The nano preparation provided by the invention takes beta-cyclodextrin as a capsule material, and takes an active component and vegetable oil as core materials; the active ingredients comprise the following components: a rice bran extract, vitamin C, a radix angelicae extract, a red date extract and a Chinese yam extract. According to the nano preparation disclosed by the invention, the rice bran extract, the vitamin C, the radix angelicae extract, the red date extract and the Chinese yam extract are matched, so that cognitive impairment can be improved from multiple angles. Besides, the beta-cyclodextrin inclusion compound is prepared by taking beta-cyclodextrin as a capsule material and taking the active component and vegetable oil as core materials, so that the active component can be slowly released, the effects of sustained release and continuous effect of the active component within a period of time can be achieved, and the cognitive impairment can be improved for a long time.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and in particular relates to a nano preparation for improving cognitive impairment, and a preparation method and application thereof. Background Art

[0002] Cognitive impairment refers to the impairment of one or more of the cognitive functions such as memory, language, visual space, execution, calculation, and understanding and judgment, which affects the individual's daily or social abilities and can be diagnosed as dementia. The basis of cognition is the normal function of the cerebral cortex. Any factor that causes abnormalities in the function and structure of the cerebral cortex can lead to cognitive impairment. Due to the complexity of brain functions and the interrelationship of different types of cognitive impairment, that is, cognitive problems in one aspect can cause cognitive abnormalities in another or multiple aspects. Therefore, cognitive impairment is one of the most difficult problems in the diagnosis and treatment of brain diseases. At present, the treatment methods for cognitive impairment include symptomatic treatment with different neuroprotectants targeting the causes and pathogenesis of cognitive impairment, restoring and maintaining the normal levels of neurotransmitters or performing surgical treatment. There is still a lack of effective therapeutic drugs for cognitive impairment in clinical practice. Summary of the invention

[0003] The purpose of the present invention is to provide a nano preparation for improving cognitive impairment and a preparation method and application thereof. The nano preparation of the present invention can effectively improve cognitive impairment and provide a new solution for the treatment of cognitive impairment.

[0004] The invention provides a nano preparation for improving cognitive impairment, which uses beta-cyclodextrin as a capsule material and uses active ingredients and vegetable oil as core materials; the active ingredients include the following components in parts by weight: 2 to 6 parts of rice bran extract, 0.3 to 0.5 parts of vitamin C, 0.2 to 0.4 parts of angelica dahurica extract, 0.01 to 0.04 parts of red date extract and 0.01 to 0.04 parts of yam extract; the ratio of the mass of the rice bran extract to the volume of the vegetable oil is 0.1 to 1 g / 1 mL.

[0005] Preferably, the mass ratio of the β-cyclodextrin to the active ingredient is (1-30):1.

[0006] Preferably, the particle size of the nano preparation is ≤500 nm.

[0007] Preferably, the vegetable oil includes one or more of corn oil, soybean oil and rapeseed oil.

[0008] The present invention also provides a method for preparing the nanoformulation described in the above scheme, comprising the following steps:

[0009] The rice bran extract and the vegetable oil are first mixed to obtain a mixed liquid; the vitamin C, the angelica dahurica extract, the red date extract and the yam extract are secondly mixed to obtain a mixed material; the mixed liquid, the mixed material and a saturated aqueous solution of beta-cyclodextrin are thirdly mixed and subjected to high-pressure homogenization to obtain an inclusion compound; the inclusion compound is sequentially filtered, washed and dried to obtain a nano preparation.

[0010] Preferably, the pressure of the high-pressure homogenization is 25 to 35 MPa; the temperature of the high-pressure homogenization is 20 to 30° C.; the number of high-pressure homogenization is 4 to 6 times, and the time of each high-pressure homogenization is 10 to 15 minutes.

[0011] Preferably, after the high-pressure homogenization, the material after the high-pressure homogenization is ultrasonically treated; the temperature of the ultrasonic treatment is 20 to 30° C.; the time of the ultrasonic treatment is 60 to 120 minutes; and the power of the ultrasonic treatment is 400 to 800W.

[0012] The present invention also provides the use of the nano preparation described in the above scheme or the nano preparation prepared by the preparation method in the preparation of drugs for improving cognitive impairment.

[0013] The present invention also provides a drug for improving cognitive impairment, which comprises an active ingredient and a pharmaceutically acceptable excipient; the active ingredient comprises the nanoformulation described in the above scheme or the nanoformulation prepared by the preparation method.

[0014] Preferably, the dosage form of the drug includes an oral preparation.

[0015] The present invention provides a nano preparation for improving cognitive impairment, with β-cyclodextrin as capsule material, and active ingredients and vegetable oil as core materials; the active ingredients include the following components: rice bran extract, vitamin C, angelica dahurica extract, red date extract and yam extract. In the present invention, the main active ingredient of the rice bran extract is ferulic acid, and the main active ingredient of the angelica dahurica extract is kumaric acid; the rice bran extract and angelica dahurica extract can inhibit the fibrillation of β-amyloid protein and remove β-amyloid protein, and promote the proliferation of nerve cells; the vitamin C has an antioxidant effect and helps to improve cognitive impairment; the main active ingredient of the red date extract is red date polysaccharide; the red date extract can delay the development of brain atrophy and improve memory; the main active ingredient of the yam extract is yam polysaccharide, which has the function of inhibiting the generation and aggregation of brain amyloid protein (Aβ), promoting its removal activity, and thus repairing nerve atrophy and degeneration. The present invention combines rice bran extract, vitamin C, angelica dahurica extract, red date extract and yam extract, and can improve cognitive impairment from multiple angles. In addition, the present invention uses β-cyclodextrin as the capsule material and the active ingredient and vegetable oil as the core material to prepare a β-cyclodextrin inclusion complex, which can slowly release the active ingredient, achieve the effect of sustained release and continuous effectiveness of the active ingredient over a period of time, and can achieve long-term improvement of cognitive impairment. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is the result of Y-maze behavioral testing of rats' spatial learning and memory abilities. DETAILED DESCRIPTION

[0017] The invention provides a nano preparation for improving cognitive impairment, which uses beta-cyclodextrin as a capsule material and uses active ingredients and vegetable oil as core materials; the active ingredients include the following components in parts by weight: 2 to 6 parts of rice bran extract, 0.3 to 0.5 parts of vitamin C, 0.2 to 0.4 parts of angelica dahurica extract, 0.01 to 0.04 parts of red date extract and 0.01 to 0.04 parts of yam extract; the ratio of the mass of the rice bran extract to the volume of the vegetable oil is 0.1 to 1 g / 1 mL.

[0018] In the present invention, the active ingredient is preferably composed of the following components in parts by mass: 2-6 parts of rice bran extract, 0.3-0.5 parts of vitamin C, 0.2-0.4 parts of angelica dahurica extract, 0.01-0.04 parts of red date extract and 0.01-0.04 parts of yam extract.

[0019] In the present invention, the active ingredient includes 2 to 6 parts of rice bran extract, preferably 3 to 5 parts, and more preferably 4 parts by mass. In the present invention, the rice bran extract has the effect of anti-inflammatory and blocking CGRP or its receptor. In the present invention, the main active ingredient of the rice bran extract is ferulic acid, and the mass content of ferulic acid in the rice bran extract is preferably ≥98%; in the present invention, the rice bran extract is preferably derived from conventional commercial products or prepared by the following method: mixing rice bran and ethanol for leaching; performing solid-liquid separation on the leaching product, collecting the liquid component, and obtaining an leaching solution; purifying the leaching solution by anion exchange resin; and then eluting the substance adsorbed by the anion exchange resin with an aqueous solution containing electrolytes to obtain an eluent; the anion exchange resin is pre-adsorbed with hydroxide ions; the aqueous solution containing electrolytes preferably includes a NaCl aqueous solution; the preparation method of the rice bran extract is preferably referred to JP2011140443A. Alternatively, the rice bran extract is prepared by the following method: defatted rice bran and a natural deep eutectic solvent (NADES) are mixed, ultrasonic extraction is performed to obtain an ultrasonic extract, and the ultrasonic extract is sequentially concentrated and freeze-dried to obtain the rice bran extract; the NADES consists of water, choline chloride and D-glucose; the volume concentration of water in the NADES is 50%; the mass ratio of choline chloride to D-glucose is 1:1; the ratio of the mass of the defatted rice bran to the volume of the NADES is 1g:20mL; the power of the ultrasonic extraction is 50W; the temperature of the ultrasonic extraction is 50°C; the duty cycle of the ultrasonic extraction is 50%; and the time of the ultrasonic extraction is 16min.

[0020] In the present invention, the active ingredient includes 0.3 to 0.5 parts of vitamin C, preferably 0.4 parts, by mass; the vitamin C has the function of relaxing cerebral blood vessels. In the present invention, the vitamin C is from conventional commercial sources.

[0021] In the present invention, the active ingredient includes 0.2-0.4 parts of Angelica dahurica extract, preferably 0.3 parts, by mass; the main active ingredient of the Angelica dahurica extract is komaric acid, and the Angelica dahurica extract functions to increase the content of the inflammatory mediator 5-hydroxytryptamine (5-HT). In the present invention, the preparation method of the Angelica dahurica extract preferably includes the following steps: mixing Angelica dahurica powder and methanol, extracting to obtain an extract, and successively performing reduced pressure concentration and freeze drying on the extract to obtain the Angelica dahurica extract; the extraction temperature is 60°C; the extraction time is 36h; the ratio of the mass of the Angelica dahurica powder to the volume of methanol is preferably 1g: (6-10)mL, more preferably 1g: 8mL.

[0022] In the present invention, the active ingredient includes 0.01-0.04 parts of red date extract, preferably 0.02-0.03 parts, by mass; the main active ingredient of the red date extract is red date polysaccharide; the red date extract can delay the development of brain atrophy and improve memory. In the present invention, the red date extract is preferably prepared by the following method: mixing red date powder and water, performing microwave-assisted extraction to obtain an extract; separating the extract from solid and liquid, and collecting the extract; decompressing and concentrating the extract, vacuum freeze-drying to obtain a red date extract; separating the extract from solid and liquid to obtain an extract; the mass ratio of the red date powder to water is preferably 1:30; the power of the microwave-assisted extraction is preferably 400W; the temperature of the microwave-assisted extraction is preferably 75°C; the time of the microwave-assisted extraction is preferably 60min.

[0023] In the present invention, the active ingredients include 0.01 to 0.04 parts of yam extract, preferably 0.02 to 0.03 parts by mass; the main active ingredient of the yam extract is yam polysaccharide, which has the function of inhibiting the generation and aggregation of brain amyloid protein (Aβ) and promoting its scavenging activity, thereby repairing nerve atrophy and degeneration; the yam extract is preferably prepared by the following method: mixing fresh yam pulp and water for extraction to obtain an extract; centrifuging the extract, collecting the supernatant and precipitate; concentrating the supernatant under reduced pressure to obtain a fluid extract with a Baume degree of 20; precipitating the fluid extract with alcohol to obtain an alcohol precipitate; centrifuging the alcohol precipitate, collecting the sediment, and re-dissolving the sediment with water to obtain an aqueous solution; centrifuging the aqueous solution, collecting the supernatant, and vacuum freeze-drying the supernatant to obtain a yam extract. In the present invention, the fresh yam pulp is preferably prepared by the following method: peeling, washing, crushing, beating and grinding the fresh yam in sequence to obtain the fresh yam pulp; the crushing is preferably carried out by a crusher; the beating is preferably carried out by a pulverizer; the grinding is preferably carried out by a colloid mill. In the present invention, the extraction temperature is preferably 55°C; the extraction time is preferably 1 to 5h. In the present invention, the temperature of the reduced pressure concentration is preferably 60°C. In the present invention, the reagent used for the alcohol precipitation is preferably an ethanol aqueous solution with a volume concentration of 95%; the volume ratio of the ethanol aqueous solution of the fluid extract is preferably 1: (2 to 20).

[0024] In the present invention, the active ingredient is preferably pulverized by a nano-scale ultrafine pulverizer before use; the particle size of the active ingredient is preferably ≤50nm, more preferably 2-25nm.

[0025] In the present invention, the mass ratio of the β-cyclodextrin to the active ingredient is preferably (1-30):1, more preferably (1-10):1, and most preferably (2-5):1.

[0026] In the present invention, the particle size of the nano preparation is preferably ≤500 nm, more preferably ≤200 nm, and most preferably ≤100 nm.

[0027] In the present invention, the vegetable oil preferably includes one or more of corn oil, soybean oil and rapeseed oil, and more preferably corn oil.

[0028] The present invention also provides a method for preparing the nano preparation described in the above scheme, comprising the following steps: first mixing the rice bran extract and the vegetable oil to obtain a mixed liquid; second mixing the vitamin C, the angelica dahurica extract, the red date extract and the yam extract to obtain a mixed material; third mixing the mixed liquid, the mixed material and a saturated aqueous solution of β-cyclodextrin, and performing high-pressure homogenization to obtain an inclusion compound; and sequentially filtering, washing and drying the inclusion compound to obtain the nano preparation.

[0029] The present invention first mixes the rice bran extract and the vegetable oil to obtain a mixed solution. The present invention has no special restrictions on the parameters of the first mixing, which is subject to uniform mixing.

[0030] The present invention secondly mixes the vitamin C, angelica dahurica extract, red date extract and yam extract to obtain a mixture. The present invention has no special restrictions on the parameters of the second mixing, which is subject to uniform mixing.

[0031] After obtaining the mixed liquid and the mixed material, the present invention thirdly mixes the mixed liquid, the mixed material and a saturated aqueous solution of beta-cyclodextrin, and performs high-pressure homogenization to obtain an inclusion compound.

[0032] In the present invention, the saturated aqueous solution of β-cyclodextrin is preferably prepared by the following method: at 60° C., a saturated solution of β-cyclodextrin with a mass fraction of 15% is prepared by using distilled water.

[0033] In the present invention, the pressure of the high-pressure homogenization is preferably 25-35 MPa; the temperature of the high-pressure homogenization is preferably 20-30°C; the number of high-pressure homogenization is preferably 4-6 times, and the time of each high-pressure homogenization is preferably 10-15 minutes. In the present invention, the homogenization treatment of high-pressure homogenization can promote inclusion, increase the inclusion rate, and reduce the particle size of the inclusion compound.

[0034] After the high-pressure homogenization, the present invention preferably further comprises ultrasonicating the material after the high-pressure homogenization; the temperature of the ultrasonication is preferably 20-30°C, more preferably 25°C; the time of the ultrasonication is preferably 60-120min, more preferably 80-100min; the power of the ultrasonication is preferably 400-800W, more preferably 500-600W; the frequency of the ultrasonication is preferably 1-10KHz, more preferably 1KHz.

[0035] After obtaining the inclusion compound, the present invention sequentially performs suction filtration, washing and drying on the inclusion compound to obtain the nano preparation.

[0036] In the present invention, the reagent used for washing includes water. In the present invention, the drying includes freeze drying.

[0037] The present invention also provides the use of the nano preparation described in the above scheme or the nano preparation prepared by the preparation method in the preparation of drugs for improving cognitive impairment.

[0038] In the present invention, the cognitive disorder preferably includes Alzheimer's disease, Parkinson's disease, frontotemporal dementia, Lewy body dementia or corticobasal degeneration.

[0039] The present invention also provides a drug for improving cognitive impairment, which comprises an active ingredient and a pharmaceutically acceptable excipient; the active ingredient comprises the nanoformulation described in the above scheme or the nanoformulation prepared by the preparation method.

[0040] In the present invention, the dosage form of the drug preferably includes an oral preparation.

[0041] In the present invention, the pharmaceutically acceptable excipient is any known compound or combination of known compounds known to those skilled in the art that can be used to prepare a pharmaceutical composition. In the specific implementation of the present invention, the pharmaceutically acceptable excipient preferably includes citric acid.

[0042] The present invention also provides a method for improving cognitive impairment, comprising the following steps: administering a therapeutically effective amount of the nanoformulation or drug described in the above scheme to the subject; the therapeutically effective amount is any amount of the dosage required to produce the desired effect when administered to the subject.

[0043] In order to further illustrate the present invention, a nanoformulation for improving cognitive impairment provided by the present invention, a preparation method thereof and an application thereof are described in detail below in conjunction with the accompanying drawings and examples, but they should not be construed as limiting the scope of protection of the present invention.

[0044] The ferulic acid content in the rice bran extract in the embodiment of the present invention is 98% by mass, is food grade, and is purchased from Shaanxi Snort Biotechnology Co., Ltd.

[0045] The angelica dahurica extract in the embodiment of the present invention is prepared by the following preparation method: 2 kg of angelica dahurica powder and 16 L of methanol are mixed, and extracted at 60° C. for 36 hours to obtain an extract; the extract is centrifuged to obtain an extract solution, and the extract solution is pressurized and concentrated and freeze-dried in sequence to obtain the angelica dahurica extract.

[0046] The vitamin C in the embodiments of the present invention is food grade and was purchased from Xi'an Musen Bioengineering Co., Ltd.

[0047] The red date extract in the embodiment of the present invention is prepared by the following preparation method: 1 kg of red date powder and 30 kg of water are mixed, and microwave-assisted extraction is performed at 400 W and 75° C. for 60 min to obtain an extract; the extract is centrifuged to obtain an extract solution, and the extract solution is pressurized and concentrated and vacuum freeze-dried in sequence to obtain a red date extract.

[0048] The yam extract in the embodiment of the present invention is prepared by the following preparation method: peeling fresh yam, washing with tap water, crushing with a crusher, beating with a pulverizer, and grinding with a colloid mill to prepare fresh yam pulp; pumping the fresh yam pulp into an extraction tank, adding water, heating to 55° C., stirring and extracting for 5 hours; centrifuging the water extract, concentrating the supernatant at 60° C. under reduced pressure to prepare a fluid extract with a Baume degree of 20; using ethanol aqueous solution with a volume concentration of 95% of 2 times the volume of the fluid extract for alcohol precipitation; centrifuging the alcohol precipitation, adding 10 times the weight of water to the sediment, stirring and dissolving it to prepare an aqueous solution; centrifuging the aqueous solution, and vacuum freeze-drying the supernatant.

[0049] The above components are pulverized by a nano-scale ultra-fine pulverizer before use, and the particle size is 5 to 25 nm.

[0050] Example 1

[0051] 1. Formula: active ingredients, water and corn oil; wherein, 500 g of β-cyclodextrin and 200 mL of corn oil; the active ingredients are composed of the following components: 200 g of rice bran extract, 30 g of vitamin C, 20 g of angelica dahurica extract, 1 g of red date extract and 1 g of yam extract.

[0052] 2. Preparation method:

[0053] 1) mixing rice bran extract and vegetable oil to obtain a mixed solution;

[0054] 2) mixing the vitamin C, angelica dahurica extract, red date extract and yam extract uniformly to obtain a mixture;

[0055] 3) At 60° C., a saturated solution of β-cyclodextrin with a mass fraction of 15% was prepared using distilled water.

[0056] 4) After the mixed solution, the mixed material and the saturated aqueous solution of β-cyclodextrin are stirred and mixed uniformly, high pressure homogenization is performed under the conditions of a homogenization pressure of 30 MPa, 5 homogenization times, each time for 10 min, and a temperature of 25° C. to obtain an inclusion compound;

[0057] 5) The inclusion compound is filtered, washed with water and freeze-dried in sequence to obtain a nano preparation.

[0058] The diameter of the nanoparticles was measured by Malvern particle size analyzer and the distribution was 184.09-465.12 nm. The inclusion rate was 78.12%.

[0059] Example 2

[0060] After high pressure homogenization in step 4) of Example 1, the high pressure homogenized material was subjected to ultrasound, and the ultrasound conditions were: ultrasound temperature 25° C., time 90 min, power 800 W and frequency 1 KHz. The rest was the same as Example 1.

[0061] The diameter of the nanoparticles was measured by Malvern particle size analyzer and the distribution was 74.96-289.33 nm. The inclusion rate was 85.34%.

[0062] Example 3

[0063] 1. Formula: active ingredient, β-cyclodextrin and corn oil; wherein, β-cyclodextrin 1500g, corn oil 600mL; the active ingredient is composed of the following components: rice bran extract 600g, vitamin C 50g, angelica dahurica extract 40g, red date extract 4g and yam extract 4g.

[0064] 2. The preparation method is the same as that in Example 1.

[0065] The particle size of the nanoparticles was measured by a particle size analyzer, and the results showed that the particle size of the nanoparticles ranged from 214.73 to 488.64 nm, and the inclusion rate was 75.26%.

[0066] Comparative Example 1

[0067] 1. Formulation: Same as Example 1.

[0068] 2. Preparation method: Replace high pressure homogenization with ultrasound; the power of ultrasound is 1KW, the temperature is 25°C, the frequency is 1KHz, and the time is 10min.

[0069] The particle size of the nanoparticles was measured by a particle size analyzer, and the results showed that the particle size of the nanoparticles ranged from 603.65 to 827.36 nm, and the inclusion rate was 66.98%.

[0070] Comparative Example 2

[0071] 1. The red date extract was omitted from the formula, and the rest was the same as in Example 1.

[0072] 2. Preparation method: same as Example 1.

[0073] Comparative Example 3

[0074] 1. The Chinese yam extract was omitted from the formula, and the rest was the same as in Example 1.

[0075] 2. Preparation method: same as Example 1.

[0076] Test Example 2

[0077] In order to evaluate the effect of the nanoformulations prepared in Examples 1 to 3 and Comparative Examples 1 to 3 on improving cognitive impairment, an Alzheimer's disease mouse model was constructed, and the experimental process was as follows:

[0078] 1) Modeling

[0079] 90 SPF SD male rats, 10-12 weeks old, weighing 200-250 g, were selected. After the rats were adaptively fed for 7 days, 10 rats were randomly selected as the blank group, and the remaining 80 rats were intraperitoneally injected with 100 mg / kg D-galactose once a day for 42 consecutive days. On the 14th day, the rats were anesthetized by intraperitoneal injection of 4% sodium pentobarbital, and Aβ was injected intracranially into the hippocampus using a brain stereotaxic instrument. 25-35 After the operation, rats in each group were given 2×10 6 / m L sodium penicillin powder on the wound surface, suture the wound, and then inject 80,000 units of sodium penicillin every day for 3 consecutive days. The rats with successful modeling were randomly divided into a model group, a positive drug group (1.4 mg / kg of donepezil) and an embodiment 1 group (6 mg / kg of the nanoformulation prepared in embodiment 1), an embodiment 2 group (6 mg / kg of the nanoformulation prepared in embodiment 2), an embodiment 3 group (6 mg / kg of the nanoformulation prepared in embodiment 3), a comparative example 1 group (6 mg / kg of the nanoformulation prepared in comparative example 1), a comparative example 2 group (6 mg / kg of the nanoformulation prepared in comparative example 2) and a comparative example 3 group (6 mg / kg of the nanoformulation prepared in comparative example 3), 10 in each group. Each drug group was gavaged after intraperitoneal injection of D-galactose on the 21st day, and the blank group and the model group were gavaged with an equal volume of normal saline, a dose of 10 mL / kg, once a day, for 21 consecutive days.

[0080] 2) Y-maze behavioral test of rats' spatial learning and memory ability

[0081] The Y-maze is a radial maze with three equal arms of 40 cm in length and an angle of 120°. The three arms are marked A, B, and C. The rat is placed at the end of the arm, and the camera system is used to observe and record the movement trajectory of the rat between the arms during the 8-minute free exploration of the maze. The rat entering the three arms in sequence will be regarded as one alternation (correct alternation). If the order of entry is A, B, A, it will not be regarded as an alternation. The spontaneous alternation accuracy rate is calculated to evaluate the spatial learning and memory ability of the rat. The calculation formula for the spontaneous alternation accuracy rate is as follows:

[0082] The accuracy rate of spontaneous alternation = [number of correct alternations / (total number of entries into the three arms - 2)] × 100%.

[0083] Results Figure 1 ,Depend on Figure 1 It can be seen that compared with the blank group, the correct rate of spontaneous alternation of rats in the model group was reduced (P<0.01), indicating that the brain cognitive function of rats in the model group was decreased; compared with the model group, the correct rate of spontaneous alternation of rats in the positive control group and Examples 1 to 3 was increased.

[0084] 3) ELISA detection of serum IL-1β, IL-6, and TNF-α levels After the rats in each group were anesthetized with sodium pentobarbital, blood was collected from the abdominal aorta and centrifuged at 3000 r / min for 15 min. The upper serum was taken and the serum inflammatory factors IL-1β, IL-6, and TNF-α levels were detected according to the instructions of the relevant kits. The measurement results are shown in Table 1.

[0085] Table 1 Results of biochemical index determination in rats

[0086]

[0087] Note: * indicates significant difference compared with the model group, P < 0.05.

[0088] As can be seen from Table 1, compared with the blank group, the levels of serum IL-6, IL-1β, and TNF-α in the model rats were increased; compared with the model group, the levels of serum IL-6, IL-1β, and TNF-α in the positive control group and Example 1 rats were significantly reduced, and the levels of serum IL-1β and TNF-α in the comparative example 2 and comparative example 3 rats were reduced. It can be seen that the treatment effect of Example 1 group is better than that of comparative example 2 and comparative example 3 groups, and the difference is statistically significant (P<0.05).

[0089] Clinical Case 1

[0090] 160 patients with Alzheimer's disease were selected as the research subjects. After clinical examination, the selected patients all met the diagnostic criteria for AD in the "Guidelines for the Diagnosis and Treatment of Alzheimer's Disease in China (2020 Edition)". The patients mainly showed cognitive impairment, memory impairment, recent amnesia, reduced living ability, and language disorders, aged 40 to 80 years old. The selected patients were randomly divided into 4 groups, namely, Example 1 Group, Comparative Example 2 Group, Comparative Example 3 Group and Control Group, with 40 patients in each group.

[0091] Treatment method: conventional western medicine treatment was given, and rivastigmine tablets (Wanquan Wante Pharmaceutical Jiangsu Co., Ltd.) were taken orally. The initial treatment dose was 1.5 mg, twice a day, for 4 consecutive weeks; the dose was increased to 3.0 mg orally twice a day for those who could tolerate it, divided into morning and evening, for 4 weeks. During the treatment period, the dose was adjusted according to the patient's tolerance. If the tolerance was good, the dose could be increased to 6.0 mg orally twice a day. The efficacy was evaluated after 12 consecutive weeks of treatment. The patients in Example 1, Comparative Example 2 and Comparative Example 3 groups took the nanoformulations prepared in Example 1, Comparative Example 2 and Comparative Example 3 on the basis of conventional western medicine treatment, 3 times a day, 10 g each time, taken with water, once in the morning, noon and evening, and the course of treatment was 15 days. The control group was only given conventional western medicine treatment.

[0092] The efficacy evaluation standard adopts the scoring method of "Traditional Chinese Medicine Clinical Diagnosis and Efficacy Evaluation Standard for Alzheimer's Disease (Trial)", and evaluates the patient's memory, recognition, comprehension, language, action, dining, defecation, and self-care ability in 8 items, each item is scored from 0 to 10 points, with a full score of 80 points.

[0093] Basic control: score > 64 points; marked effect: score increase > 16 points; effective: score increase > 9 points; ineffective: score increase < 8 points or score decrease, no change in main symptoms or even worsening.

[0094] Total effective rate = (basic control + marked effect + effective) / total number of cases × 100%.

[0095] The results are shown in Table 2.

[0096] Table 2 Comparison of clinical efficacy in patients with Alzheimer's disease

[0097] Group Number of cases Basic Control / Example Significantly effective / case Valid / Example Invalid / Example Total effective rate / % Control group 40 3 3 22 12 70％ Example 1 Group 40 6 7 20 7 82.5％ Comparative Example 1 40 4 5 21 10 75％ Comparative Example 2 40 4 5 22 9 77.5％

[0098] The results showed that after relevant treatment, the total effective rate of patients in Example 1 group was higher than that in the other three groups. It can be seen that the clinical treatment effect of Example 1 group was ideal compared with the other three groups, and the difference was statistically significant (P<0.05).

[0099] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A nanoparticle preparation for improving cognitive impairment, characterized in that: β-cyclodextrin is used as the capsule material, and active ingredients and vegetable oil are used as the core material; The active ingredients include the following components in parts by weight: 2 to 6 parts of rice bran extract, 0.3 to 0.5 parts of vitamin C, 0.2 to 0.4 parts of angelica dahurica extract, 0.01 to 0.04 parts of red date extract and 0.01 to 0.04 parts of yam extract; The ratio of the mass of the rice bran extract to the volume of the vegetable oil is 0.1-1 g / 1 mL.

2. The nanoformulation according to claim 1, characterized in that The mass ratio of the β-cyclodextrin to the active ingredient is (1-30):

1.

3. The nanoformulation according to claim 1, characterized in that The particle size of the nano preparation is ≤500nm.

4. The nanoformulation according to claim 1 or 3, characterized in that: The vegetable oil includes one or more of corn oil, soybean oil and rapeseed oil.

5. The method for preparing the nanoformulation according to any one of claims 1 to 4, characterized in that: The following steps are involved: The rice bran extract and the vegetable oil are first mixed to obtain a mixed solution; The vitamin C, angelica dahurica extract, red date extract and yam extract are mixed for the second time to obtain a mixture; The mixed solution, the mixed material and the saturated aqueous solution of β-cyclodextrin are mixed for the third time, and high pressure homogenized to obtain an inclusion compound; The inclusion compound is filtered, washed and dried in sequence to obtain a nano preparation.

6. The preparation method according to claim 5, characterized in that: The pressure of the high-pressure homogenization is 25-35 MPa; the temperature of the high-pressure homogenization is 20-30° C.; the number of high-pressure homogenization is 4-6 times, and the time of each high-pressure homogenization is 10-15 minutes.

7. The preparation method according to claim 5 or 6, characterized in that: After the high-pressure homogenization, the material after the high-pressure homogenization is ultrasonically processed; the temperature of the ultrasonic process is 20 to 30° C.; the time of the ultrasonic process is 60 to 120 minutes; the power of the ultrasonic process is 400 to 800 W; and the frequency of the ultrasonic process is 1 to 10 KHz.

8. Use of the nanoformulation according to any one of claims 1 to 4 or the nanoformulation prepared by the preparation method according to any one of claims 5 to 7 in the preparation of a drug for improving cognitive impairment.

9. A drug for improving cognitive impairment, characterized in that: The drug comprises an active ingredient and a pharmaceutically acceptable excipient; the active ingredient comprises the nanoformulation described in any one of claims 1 to 4 or the nanoformulation prepared by the preparation method described in any one of claims 5 to 7.

10. The drug according to claim 9, characterized in that The dosage form of the drug includes oral preparations.

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