Composition for treating senile dementia as well as preparation method and application thereof

Abstract

The invention provides a composition for treating senile dementia as well as a preparation method and application thereof, and belongs to the technical field of medicines. The composition for treating senile dementia is composed of the acer truncatum seed oil and the acer truncatum leaf extract, the acer truncatum seed oil and the acer truncatum leaf extract are combined to achieve a synergistic effect, and remarkable anti-oxidation, anti-aging and nerve repairing functions are achieved. The invention further optimizes the preparation methods of the acer truncatum seed oil and the acer truncatum leaf extract, and provides a preparation method and application of the composition based on the acer truncatum seed oil and the acer truncatum leaf extract, and the composition is remarkable in senile dementia treatment effect, high in safety and free of side effects.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medicine, and particularly relates to a composition for treating senile dementia and a preparation method and application thereof. BACKGROUND

[0002] Senile dementia, medically known as Alzheimer's disease (AD), is a degenerative disease of the central nervous system. Its main features include progressive cognitive dysfunction and behavioral impairment, and clinical manifestations include memory loss, aphasia, apraxia, agnosia, visual-spatial ability impairment, abstract thinking and calculation impairment, personality and behavior changes, etc. With the aggravation of population aging, the incidence of senile dementia is increasing year by year, which has brought a heavy burden to society and family.

[0003] Currently, the treatment means for senile dementia are relatively limited. The commonly used drugs in clinical practice mainly include acetylcholinesterase inhibitors (such as donepezil, rivastigmine, etc.), N-methyl-D-aspartate (NMDA) receptor antagonists (such as memantine), etc. These drugs can improve the symptoms of patients to a certain extent and delay the progression of the disease, but they cannot fundamentally cure senile dementia and have many adverse reactions. For example, acetylcholinesterase inhibitors may cause adverse reactions of the gastrointestinal tract and cardiovascular system such as nausea, vomiting, diarrhea, and bradycardia; NMDA receptor antagonists may cause dizziness, headache, drowsiness, fatigue, and other discomfort symptoms. In addition, there are some other types of drugs, such as non-steroidal anti-inflammatory drugs, estrogen, oxygen free radical scavenging drugs, neuroprotective agents, and A beta protein related drugs, which also have problems such as uncertain efficacy and large side effects.

[0004] Acorn maple is a tree species of Aceraceae Aceraceae. Current research reports that acorn maple seed oil is rich in nervonic acid, which is an important substance that can repair damaged nerve fibers and promote the regeneration of nerve cells, and has potential effects on improving nerve function. The acorn maple leaf extract contains flavonoids, polyphenols and other active ingredients, which have various biological activities such as antioxidant, anti-inflammatory and free radical scavenging, and can reduce the inflammatory response of nerves and protect nerve cells from damage. Although some patents or research reports give related reports on acorn maple seed oil and acorn maple leaf extract, there is no report on the use of the two in combination for the treatment of senile dementia. SUMMARY

[0005] In order to solve the problems in the prior art, the purpose of the present application is to provide a composition for treating senile dementia and a preparation method thereof. Acorn maple seed oil and acorn maple leaf extract have a synergistic effect, and the combination of the two can exert significant antioxidant, anti-aging and nerve repair functions.

[0006] The application also aims to provide the use of the composition in the preparation of anti-oxidation, anti-aging drugs, nerve repair drugs or drugs for treating senile dementia.

[0007] In order to achieve the above-mentioned application purposes, the application provides the following technical solutions.

[0008] The application provides a composition for treating senile dementia, which is prepared from 1-10 parts of Pterocarya stenoptera seed oil and 1-5 parts of Pterocarya stenoptera leaf extract by mass fraction.

[0009] Preferably, the extraction method of the Pterocarya stenoptera seed oil comprises the following steps: mixing Pterocarya stenoptera seed powder with water, adding a composite enzyme for enzymolysis; mixing the slurry after the enzymolysis with an ethanol solution, and performing ultrasonic extraction; and performing rotary evaporation on the extracted liquid obtained after the ultrasonic extraction to obtain the Pterocarya stenoptera seed oil; the composite enzyme is composed of cellulase, pectinase and lipase at an enzyme activity ratio of 1:2:1.

[0010] Preferably, the solid-liquid ratio of the Pterocarya stenoptera seed powder and water is 1:(2-10) g / mL; the addition amount of the composite enzyme is 2000-50000 U / g in terms of the mass of the Pterocarya stenoptera seed powder; the enzymolysis temperature is 40-50 DEG C, the time is 2-4 h, and the pH is 4-6.

[0011] Preferably, the ethanol solution is a 70-85% ethanol solution; the volume ratio of the slurry and the ethanol solution is 1:(1-3); the ultrasonic extraction temperature is 30-40 DEG C, and the time is 20-30 min.

[0012] Preferably, the rotary evaporation temperature is 30-40 DEG C, the rotation speed is 100-200 rmp, and the pressure is 0.1-0.5 atm.

[0013] Preferably, the preparation method of the Pterocarya stenoptera leaf extract comprises the following steps: drying and crushing Pterocarya stenoptera leaves, adding an ethanol solution, magnetically stirring and leaching to obtain leaching liquid A and residue A; adding an ethanol solution to the residue A, performing ultrasonic extraction, and performing suction filtration after the ultrasonic extraction to obtain filtrate B and residue B; adding an ethanol solution to the residue B, performing water bath heating and refluxing, performing suction filtration after the refluxing to obtain filtrate C and residue C; adding water to the residue C, leaching in a boiling water bath, and performing reduced-pressure filtration and concentration on the leaching liquid to obtain product D; and mixing the leaching liquid A, the filtrate B, the filtrate C and the product D to obtain the Pterocarya stenoptera leaf extract.

[0014] Preferably, the ethanol solution is a 70-80% ethanol solution.

[0015] Preferably, the magnetic stirring leaching time is 20-40 min; the ultrasonic extraction time is 20-40 min, and the temperature is 45-55 DEG C; the water bath heating reflux time is 1-2 h, and the water bath temperature is 60-70 DEG C; the leaching time in boiling water bath is 1-2 h.

[0016] The application further provides a preparation method of the composition, which comprises uniformly mixing the Acer truncatum Bunge seed oil and the Acer truncatum Bunge leaf extract to obtain the composition.

[0017] The application further provides application of the composition in any one of the following: (1) preparation of an antioxidant and anti-aging drug; (2) preparation of a nerve repair drug; and (3) preparation of a drug for treating senile dementia.

[0018] Compared with the prior art, the technical scheme of the application has the following beneficial effects:

[0019] The application provides a composition for treating senile dementia, which is prepared by compounding Acer truncatum Bunge seed oil and Acer truncatum Bunge leaf extract. The Acer truncatum Bunge seed oil and the Acer truncatum Bunge leaf extract have a synergistic effect on each other, and the combination of the two has a synergistic effect. The application verifies the effect by using APP / PS1 mice. The APP / PS1 double transgenic mice (AD) can express a fusion of mutant human presenilin (DeltaE9) and human-mouse amyloid precursor protein (APPswe). The results show that the combination of the Acer truncatum Bunge seed oil and the Acer truncatum Bunge leaf extract can significantly improve the neuron damage of the APP / PS1 mice, improve the behavior cognitive level of the APP / PS1 mice, and play a significant role in antioxidant, anti-aging and nerve repair. DETAILED DESCRIPTION

[0020] The application provides a composition for treating senile dementia, which is prepared by compounding Acer truncatum Bunge seed oil and Acer truncatum Bunge leaf extract. The Acer truncatum Bunge seed oil and the Acer truncatum Bunge leaf extract have a synergistic effect on each other, and the combination of the two has a synergistic effect. The application verifies the effect by using APP / PS1 mice. The APP / PS1 double transgenic mice (AD) can express a fusion of mutant human presenilin (DeltaE9) and human-mouse amyloid precursor protein (APPswe). The results show that the combination of the Acer truncatum Bunge seed oil and the Acer truncatum Bunge leaf extract can significantly improve the neuron damage of the APP / PS1 mice, improve the behavior cognitive level of the APP / PS1 mice, and play a significant role in antioxidant, anti-aging and nerve repair.

[0021] The extraction method of the Acer truncatum Bunge seed oil comprises the following steps: mixing Acer truncatum Bunge seed powder with water, adding a composite enzyme for enzymolysis; mixing the enzymolysis slurry with an ethanol solution, and performing ultrasonic extraction; and performing rotary evaporation on the extracted solution obtained after ultrasonic extraction to obtain the Acer truncatum Bunge seed oil; and the composite enzyme is composed of cellulase, pectinase and lipase at an enzyme activity ratio of 1:2:1.

[0022] The application preferably screens the Acer truncatum seeds to remove impurities. Then, the Acer truncatum seeds are ground into powder by using a high-speed grinder, and the particle size of the powder is preferably 50-100 mesh. The Acer truncatum seeds are crushed to increase the surface area, which is helpful for the subsequent enzymatic hydrolysis process.

[0023] The application mixes the Acer truncatum seed powder with water, preferably deionized water, and the solid-liquid ratio of the Acer truncatum seed powder to water is 1:(2-10) g / mL, preferably 1:3 g / mL, 1:4 g / mL, 1:5 g / mL, 1:6 g / mL, 1:7 g / mL, 1:8 g / mL or 1:9 g / mL.

[0024] The application adds a compound enzyme to the mixture of the Acer truncatum seed powder and water for enzymatic hydrolysis. The addition amount of the compound enzyme is 2000-50000 U / g, preferably 5000-20000 U / g, based on the mass of the Acer truncatum seed powder. The enzymatic hydrolysis temperature is 40-50 DEG C, preferably 42-48 DEG C or 44-46 DEG C, the time is 2-4 h, preferably 3 h, and the pH is 4-6, preferably 4.5, 5 or 5.5.

[0025] The application mixes the slurry after enzymatic hydrolysis with an ethanol solution, and the ethanol solution is a 70-85% ethanol solution, preferably a 75-80% ethanol solution. The volume ratio of the slurry to the ethanol solution is 1:(1-3), preferably 1:2.

[0026] The application performs ultrasonic extraction on the mixed solution, and the ultrasonic extraction temperature is 30-40 DEG C, preferably 32-38 DEG C or 34-36 DEG C, and the time is 20-30 min, preferably 22-28 min or 25-26 min.

[0027] The application performs rotary evaporation on the extract obtained after ultrasonic extraction, and the rotary evaporation temperature is 30-40 DEG C, preferably 34-38 DEG C or 32-35 DEG C, the rotation speed is 100-200 rmp, preferably 150 rmp, and the pressure is 0.1-0.5 atm, preferably 0.2-0.4 atm. The application removes the solvent (without alcohol taste) by rotary evaporation to obtain Acer truncatum seed oil.

[0028] The application releases the effective components in the Acer truncatum seeds by biological enzyme catalysis, and realizes an efficient, low-temperature and low-loss extraction process by combining ultrasonic and low-temperature separation technologies, so as to maximize the retention of active ingredients in the Acer truncatum seed oil and improve the pharmacological efficacy of the Acer truncatum seed oil.

[0029] The preparation method of the Acer truncatum Bunge leaf extract comprises the following steps: drying and crushing the Acer truncatum Bunge leaves, adding an ethanol solution, magnetically stirring and leaching, to obtain leaching liquid A and residue A; adding an ethanol solution to the residue A, performing ultrasonic extraction, performing suction filtration after the ultrasonic extraction is completed, to obtain filtrate B and residue B; adding an ethanol solution to the residue B, performing water bath heating and refluxing, performing suction filtration after the refluxing is completed, to obtain filtrate C and residue C; adding water to the residue C, performing leaching in a boiling water bath, performing reduced pressure filtration and concentration on the leaching liquid, to obtain product D; and mixing the leaching liquid A, the filtrate B, the filtrate C and the product D, to obtain the Acer truncatum Bunge leaf extract.

[0030] Preferably, the fresh Acer truncatum Bunge leaves are rinsed with clean water to remove impurities, and then dried and low-temperature (40-50 DEG C) dried until the moisture content is less than or equal to 4%. Then, a high-speed pulverizer is used to grind the Acer truncatum Bunge leaves into powder, and the particle size of the powder is preferably 20-50 mesh. The Acer truncatum Bunge leaves are crushed to increase the surface area, which is helpful for the subsequent extraction process.

[0031] The crushed Acer truncatum Bunge leaves are leached by magnetic stirring to obtain leaching liquid A and residue A, and the leaching liquid A is rich in compounds such as catechins, chlorogenic acids, flavonoids and amino acids. The ethanol solution is 70-80% ethanol solution, and the solid-liquid ratio of the Acer truncatum Bunge leaves to the ethanol solution is preferably 1:(80-120) g / mL, and more preferably 1:100 g / mL. The magnetic stirring leaching is preferably performed at room temperature (20-25 DEG C), and the time of the magnetic stirring leaching is 20-40 min, preferably 30 min. The magnetic stirring leaching is preferably repeated twice, the filtrate is collected, and the filtrates of the two times are combined to obtain the leaching liquid A and the residue A.

[0032] The residue A is ultrasonically extracted to obtain filtrate B and residue B. The ethanol solution is 70-80% ethanol solution, preferably 75% ethanol solution, and the solid-liquid ratio of the residue A to the ethanol solution is preferably 1:(80-120) g / mL, and more preferably 1:100 g / mL. The ultrasonic extraction is performed for 20-40 min, preferably 30 min, and the temperature is 45-55 DEG C, preferably 50 DEG C. As an optional embodiment, the ultrasonic power is 300-600 W, and the frequency is 20-40 kHz. The ultrasonic extraction is preferably repeated twice, suction filtration is performed after the ultrasonic extraction is completed, and the filtrates of the two times are combined to obtain the leaching liquid B and the residue B.

[0033] The present application carries out water bath heating reflux on the filter residue B to obtain filtrate C and filter residue C, the ethanol solution is 70-80% ethanol solution, preferably 75% ethanol solution, and the material-liquid ratio of the filter residue B and the ethanol solution is preferably 1:(80-120) g / mL, more preferably 1:100 g / mL. The water bath heating reflux time of the present application is 1-2 h, the water bath temperature is 60-70 DEG C, preferably 65 DEG C; the water bath heating reflux of the present application is preferably repeated twice, and after the reflux is completed, suction filtration is carried out, and the filtrates of two times are combined to obtain the extraction liquid C and the filter residue C.

[0034] The present application adds water to the filter residue C and extracts in a boiling water bath, the material-liquid ratio of the filter residue C and water is 1:(60-100) g / mL, more preferably 1:(80-90) g / mL; the extraction time in the boiling water bath is 1-2 h, more preferably 20 min each time. The extraction of the present application is preferably repeated twice, and immediately after the extraction is completed, hot filtration is carried out under reduced pressure, and the residue is preferably washed with hot distilled water for 2-3 times. The present application carries out reduced pressure filtration and concentration on the extraction liquid to obtain product D. The filtration is preferably vacuum suction filtration, and the concentration is preferably rotary evaporation concentration, the rotary evaporation temperature is 30-40 DEG C, preferably 34-38 DEG C or 32-35 DEG C, the rotation speed is 100-200 rmp, preferably 150 rmp, and the pressure is 0.1-0.5 atm, preferably 0.2-0.4 atm.

[0035] The present application mixes the extraction liquid A, the filtrate B, the filtrate C and the product D to obtain the extract of Acer truncatum Bunge leaves. The present application improves the content of the pharmacologically active ingredients in the extract of Acer truncatum Bunge leaves through multi-step extraction, and the obtained extract of Acer truncatum Bunge leaves is rich in epicatechin, epigallocatechin, gallocatechin gallate, chlorogenic acid, quercetin, kaempferol, isorhamnetin and free amino acid. The obtained extract of Acer truncatum Bunge leaves is combined with Acer truncatum Bunge seed oil, and the two have synergistic effect, so as to play a significant role in antioxidant, anti-aging and nerve repair.

[0036] The present application also provides a preparation method of the above-mentioned composition, uniformly mixing the Acer truncatum Bunge seed oil and the extract of Acer truncatum Bunge leaves to obtain the composition.

[0037] The present application also provides application of the above-mentioned composition in any one of the following: (1) preparation of an antioxidant and anti-aging drug; (2) preparation of a nerve repair drug; (3) preparation of a drug for treating senile dementia. The present application finds that the Acer truncatum Bunge seed oil and the extract of Acer truncatum Bunge leaves have synergistic effect on each other, and the two have synergistic effect when combined, can significantly improve the neuron damage of APP / PS1 mice, improve the behavior cognitive level of APP / PS1 mice, and play a significant role in antioxidant, anti-aging and nerve repair.

[0038] The technical solutions in the present application will be clearly and completely described below in combination with the embodiments in the present application. Apparently, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all the other embodiments obtained by a person of ordinary skill in the art without creative effort shall fall within the protection scope of the present application.

[0039] In the following examples, all the conventional methods are used unless otherwise specified.

[0040] In the following examples, all the materials and reagents used are commercially available unless otherwise specified.

[0041] Example 1

[0042] A composition for treating Alzheimer's disease, which is composed of: 1 part of Acer truncatum Bunge seed oil and 1 part of Acer truncatum Bunge leaf extract.

[0043] The extraction method of Acer truncatum Bunge seed oil is as follows: the Acer truncatum Bunge seeds are screened to remove impurities, and a high-speed pulverizer is used to grind the Acer truncatum Bunge seeds into powder with a particle size of 100 meshes. The Acer truncatum Bunge seed powder is mixed with water at a solid-liquid ratio of 1:10 g / mL, and a composite enzyme (50000 U / g of Acer truncatum Bunge seed powder, composed of cellulase, pectinase and lipase at an enzyme activity ratio of 1:2:1) is added for enzymolysis at a temperature of 50℃ for 2 h and a pH of 4. The slurry after enzymolysis is mixed with 70% ethanol solution at a volume ratio of 1:3, and ultrasonic extraction is performed at a temperature of 40℃ for 20 min. The extract obtained after ultrasonic extraction is subjected to rotary evaporation at a temperature of 40℃, a rotation speed of 100 rmp and a pressure of 0.1 atm, and the solvent is removed by rotary evaporation to obtain Acer truncatum Bunge seed oil.

[0044] The preparation method of Acer truncatum Bunge leaf extract is as follows:

[0045] Fresh Acer truncatum Bunge leaves are selected, rinsed with clean water to remove impurities, and then dried at a low temperature of 50℃ until the water content is ≤4%. A high-speed pulverizer is used to grind the Acer truncatum Bunge leaves into powder with a particle size of 50 meshes. The Acer truncatum Bunge leaf powder is mixed with 80% ethanol solution at a solid-liquid ratio of 1:120 g / mL, and 20 min of magnetic stirring at 25℃ is performed for extraction to obtain extraction liquid A and residue A;

[0046] The residue A is added with 80% ethanol solution at a solid-liquid ratio of 1:120 g / mL, and ultrasonic extraction (power of 600 W and frequency of 20 kHz) is performed at a temperature of 55℃ for 20 min. After the ultrasonic extraction, suction filtration is performed to obtain filtrate B and residue B;

[0047] The residue B is added with 80% ethanol solution according to the solid-liquid ratio of 1:120 g / mL, heated in a water bath to reflux, the time is 2h, the water bath temperature is 60℃, after reflux, the filter is obtained by suction filtration, and the residue C is obtained by suction filtration;

[0048] The residue C is added with water according to the solid-liquid ratio of 1:100 g / mL, and is immersed in a boiling water bath for 2h, and is shaken every 20 min, the immersion liquid is suction filtered, and the filtrate is rotary evaporated, the rotary evaporation temperature is 40℃, the rotary evaporation speed is 100rmp, the pressure is 0.1atm, the solvent is removed by rotary evaporation, and the product D is concentrated to obtain;

[0049] The immersion liquid A, the filtrate B, the filtrate C and the product D are mixed to obtain the extract of the leaves of Acer truncatum bunge.

[0050] The preparation method of the composition for treating senile dementia is as follows: the oil of Acer truncatum bunge seed and the extract of the leaves of Acer truncatum bunge are uniformly mixed according to the proportion.

[0051] Example 2

[0052] A composition for treating senile dementia, which is composed of 10 parts of the oil of Acer truncatum bunge seed and 5 parts of the extract of the leaves of Acer truncatum bunge.

[0053] The extraction method of the oil of Acer truncatum bunge seed is as follows: the Acer truncatum bunge seed is screened to remove impurities, and is ground into powder by using a high-speed grinder, and the particle size is 50 mesh. The Acer truncatum bunge seed powder is mixed with water according to the solid-liquid ratio of 1:2 g / mL, and is subjected to enzymatic hydrolysis by adding a composite enzyme (2000 U / g of the Acer truncatum bunge seed powder, cellulase, pectinase and lipase are composed according to the enzyme activity ratio of 1:2:1), the enzymatic hydrolysis temperature is 40℃, the time is 4h, and the pH is 6; the slurry after enzymatic hydrolysis is mixed with 85% ethanol solution according to the volume ratio of 1:1, and is subjected to ultrasonic extraction, the ultrasonic extraction temperature is 30℃, the time is 30 min; the extraction liquid obtained after ultrasonic extraction is subjected to rotary evaporation, the rotary evaporation temperature is 30℃, the rotary evaporation speed is 200rmp, the pressure is 0.5atm, and the solvent is removed by rotary evaporation to obtain the oil of Acer truncatum bunge seed.

[0054] The preparation method of the extract of the leaves of Acer truncatum bunge is as follows:

[0055] The fresh leaves of Acer truncatum bunge are selected, rinsed with clean water to remove impurities, and then dried at low temperature of 40℃ until the water content is ≤4%. The leaves of Acer truncatum bunge are ground into powder by using a high-speed grinder, and the particle size is 20 mesh. The leaf powder of Acer truncatum bunge is mixed with 70% ethanol solution according to the solid-liquid ratio of 1:80 g / mL, and is subjected to immersion for 40 min under magnetic stirring at 20℃ to obtain the immersion liquid A and the residue A;

[0056] The residue A is added with 70% ethanol solution according to the solid-liquid ratio of 1:80 g / mL, and is subjected to ultrasonic extraction (the power is 600W, the frequency is 20kHz) for 40 min at 45℃, and then is suction filtered after ultrasonic extraction to obtain the filtrate B and the residue B.

[0057] The filter residue B is added to a 70% ethanol solution according to a material-liquid ratio of 1:80 g / mL, heated in a water bath to reflux, the time is 1 h, the water bath temperature is 70℃, after the reflux is completed, the filter residue C is obtained by suction filtration, and the filter residue C is obtained by suction filtration;

[0058] The filter residue C is added to water according to a material-liquid ratio of 1:60 g / mL, and immersed in a boiling water bath for 1 h, and shaken every 20 min, the immersion liquid is suction filtered, and the filter residue is concentrated to obtain the product D by rotary evaporation of the filter liquid, the rotary evaporation temperature is 30℃, the rotation speed is 200 rmp, and the pressure is 0.5 atm;

[0059] The immersion liquid A, the filter liquid B, the filter liquid C and the product D are mixed to obtain the extract of the leaves of Pterocarya stenoptera C. DC.

[0060] The preparation method of the composition for treating senile dementia is as follows: the Pterocarya stenoptera C. DC. seed oil and the Pterocarya stenoptera C. DC. leaf extract are uniformly mixed according to the proportion.

[0061] Example 3

[0062] A composition for treating senile dementia, which is composed of 5 parts of Pterocarya stenoptera C. DC. seed oil and 2 parts of Pterocarya stenoptera C. DC. leaf extract.

[0063] The extraction method of the Pterocarya stenoptera C. DC. seed oil is as follows: the Pterocarya stenoptera C. DC. seeds are screened to remove impurities, and a high-speed pulverizer is used to grind the Pterocarya stenoptera C. DC. seeds into powder with a particle size of 80 mesh. The Pterocarya stenoptera C. DC. seed powder is mixed with water according to a material-liquid ratio of 1:5 g / mL, and a composite enzyme (10000 U / g Pterocarya stenoptera C. DC. seed powder, cellulase, pectinase and lipase according to an enzyme activity ratio of 1:2:1) is added for enzymolysis, the enzymolysis temperature is 45℃, the time is 3 h, and the pH is 5; the slurry after enzymolysis is mixed with a 75% ethanol solution according to a volume ratio of 1:2, ultrasonic extraction is performed, the ultrasonic extraction temperature is 35℃, the time is 25 min; the extraction liquid obtained after ultrasonic extraction is subjected to rotary evaporation, the rotary evaporation temperature is 35℃, the rotation speed is 200 rmp, the pressure is 0.2 atm, and the solvent is removed by rotary evaporation to obtain the Pterocarya stenoptera C. DC. seed oil.

[0064] The preparation method of the Pterocarya stenoptera C. DC. leaf extract is as follows:

[0065] Fresh Pterocarya stenoptera C. DC. leaves are selected, rinsed with clean water to remove impurities, and then dried at a low temperature of 45℃ until the water content is ≤4%. A high-speed pulverizer is used to grind the Pterocarya stenoptera C. DC. leaves into powder with a particle size of 20 mesh. The Pterocarya stenoptera C. DC. leaf powder is mixed with a 75% ethanol solution according to a material-liquid ratio of 1:100 g / mL, and the immersion liquid A and the filter residue A are obtained by immersion for 30 min of magnetic stirring at 20℃.

[0066] The filter residue A is added with 75% ethanol solution according to the solid-liquid ratio of 1:100 g / mL, and ultrasonic extraction (power of 600 W, frequency of 20 kHz) is performed for 30 min at a temperature of 50°C, and then suction filtration is performed after ultrasonic extraction to obtain filter liquor B and filter residue B;

[0067] The filter residue B is added with 70% ethanol solution according to the solid-liquid ratio of 1:100 g / mL, and reflux extraction is performed in a water bath at a temperature of 65°C for 1 h, and then suction filtration is performed after reflux extraction to obtain filter liquor C and filter residue C;

[0068] The filter residue C is added with water according to the solid-liquid ratio of 1:80 g / mL, and extraction is performed in a boiling water bath for 1 h with shaking every 20 min, and then suction filtration is performed on the extraction liquid, and then rotary evaporation is performed on the filter liquor at a temperature of 35°C, a rotation speed of 200 rmp and a pressure of 0.2 atm to remove the solvent, and then concentration is performed to obtain product D;

[0069] The extraction liquid A, the filter liquor B, the filter liquor C and the product D are mixed to obtain a maple leaf extract.

[0070] A preparation method of a composition for treating senile dementia: uniformly mix maple seed oil and maple leaf extract according to a proportioning relationship.

[0071] Example 4

[0072] A composition for treating senile dementia, which is composed of 5 parts of maple seed oil and 2 parts of maple leaf extract.

[0073] A preparation method of maple seed oil: same as example 3.

[0074] A preparation method of maple leaf extract:

[0075] Fresh maple leaves are selected, rinsed with clean water to remove impurities, and then dried at a low temperature of 45°C until the water content is ≤4%. The maple leaves are ground into powder with a particle size of 20 mesh using a high-speed grinder. The maple leaf powder is mixed with 75% ethanol solution according to the solid-liquid ratio of 1:100 g / mL, and then magnetic stirring extraction is performed at 20°C for 30 min to obtain extraction liquid. The filter residue is mixed with 75% ethanol solution again according to the solid-liquid ratio of 1:100 g / mL, and then magnetic stirring extraction is performed at 20°C for 30 min. The two extraction liquids are combined as extraction liquid A, and the remaining filter residue is A;

[0076] The filter residue A is mixed with 75% ethanol solution according to the solid-liquid ratio of 1:100 g / mL, and ultrasonic extraction (power of 600 W, frequency of 20 kHz) is performed for 30 min at a temperature of 50°C. After ultrasonic extraction, suction filtration is performed to obtain a suction filtrate. The filter residue is mixed with 75% ethanol solution again according to the solid-liquid ratio of 1:100 g / mL, and ultrasonic extraction (power of 600 W, frequency of 20 kHz) is performed for 30 min at a temperature of 50°C. After ultrasonic extraction, suction filtration is performed. The two suction filtrates are combined to obtain filter liquid B, and the remaining residue is filter residue B;

[0077] The filter residue B is mixed with 70% ethanol solution according to the solid-liquid ratio of 1:100 g / mL, and reflux extraction is performed in a water bath at a water bath temperature of 65°C for 1 h. After reflux extraction, suction filtration is performed to obtain a suction filtrate. The filter residue is mixed with 75% ethanol solution again according to the solid-liquid ratio of 1:100 g / mL, and reflux extraction is performed in a water bath at a water bath temperature of 65°C for 1 h. After reflux extraction, suction filtration is performed. The two suction filtrates are combined to obtain filter liquid C, and the remaining residue is filter residue C;

[0078] The filter residue C is mixed with water according to the solid-liquid ratio of 1:80 g / mL, and extraction is performed in a boiling water bath for 1 h. The extraction liquid is suction filtered to obtain a suction filtrate. The filter residue is mixed with water again according to the solid-liquid ratio of 1:80 g / mL, and extraction is performed in a boiling water bath for 1 h. The extraction liquid is suction filtered. The two suction filtrates are combined and subjected to rotary evaporation at a temperature of 35°C, a rotation speed of 200 rmp, and a pressure of 0.2 atm. The solvent is removed by rotary evaporation to obtain product D.

[0079] The extraction liquid A, the filter liquid B, the filter liquid C, and the product D are mixed to obtain a maple leaf extract.

[0080] A preparation method of a composition for treating senile dementia: uniformly mix maple seed oil and maple leaf extract according to a ratio.

[0081] Comparative Example 1

[0082] A nerve repair composition is prepared according to the following formula (parts by weight) by a method including the following steps:

[0083] The curcuma powder 1 part, the maple seed oil 45.5 parts, the flavin adenine dinucleotide 1 part, the a-tocopherol 0.5 part, and the vitamin B6 0.5 part are uniformly mixed and stirred to obtain the nerve repair composition.

[0084] The preparation method of the turmeric powder comprises the following steps: adding dry turmeric root powder into ethanol with a volume fraction of 95%, and performing ultrasonic extraction for 60 min to obtain an ethanol extract; performing vacuum concentration on the ethanol extract at 50 DEG C and 0.1 MPa to obtain a concentrated solution; and performing freeze drying on the concentrated solution at -40 DEG C to obtain the turmeric powder; the prepared turmeric powder contains 5wt% of curcuminoids, the content of C1 curcumin in the curcuminoids is 60wt%, the content of C2 demethoxycurcumin is 17wt%, the content of C3 bisdemethoxycurcumin is 1.5wt%, and the balance is other curcuminoids.

[0085] Comparative Example 2

[0086] A kind of acer truncatum bunge seed oil, the extraction method of acer truncatum bunge seed oil: same as example 3.

[0087] Comparative Example 3

[0088] A kind of acer truncatum bunge leaf extract, the extraction method of acer truncatum bunge leaf extract: same as example 4.

[0089] Comparative Example 4

[0090] The difference from example 4 is only that:

[0091] The preparation method of acer truncatum bunge leaf extract (only magnetic stirring extraction is performed):

[0092] Fresh acer truncatum bunge leaves are selected, rinsed with clean water to remove impurities, and then drained and dried at low temperature of 45 DEG C until the moisture content is less than or equal to 4%. A high-speed grinder is used to grind the acer truncatum bunge leaves into powder with a particle size of 20 mesh. The acer truncatum bunge leaf powder is mixed with 75% ethanol solution according to a solid-liquid ratio of 1:100 g / mL, and then extracted by magnetic stirring at 20 DEG C for 30 min to obtain an extract. The filter residue is mixed with 75% ethanol solution again according to a solid-liquid ratio of 1:100 g / mL, and then extracted by magnetic stirring at 20 DEG C for 30 min. The extract obtained in the first extraction and the extract obtained in the second extraction are combined to obtain the acer truncatum bunge leaf extract.

[0093] Comparative Example 5

[0094] The difference from example 4 is only that:

[0095] The preparation method of acer truncatum bunge leaf extract (ultrasonic extraction and boiling water bath extraction steps are abandoned):

[0096] Fresh Acer truncatum Bunge leaves were selected and rinsed with clean water to remove impurities, and then dried at low temperature of 45°C until the moisture content was less than or equal to 4%. The leaves were ground into powder with a particle size of 20 mesh using a high-speed grinder. The leaf powder was mixed with 75% ethanol solution at a solid-liquid ratio of 1:100 g / mL, and then extracted by magnetic stirring at 20°C for 30 min to obtain an extraction solution. The residue was mixed with 75% ethanol solution at a solid-liquid ratio of 1:100 g / mL, and then extracted by magnetic stirring at 20°C for 30 min. The two extraction solutions were combined as extraction solution A, and the remaining residue was residue A.

[0097] The residue A was mixed with 70% ethanol solution at a solid-liquid ratio of 1:100 g / mL, and then extracted by heating in a water bath at a temperature of 65°C for 1 h. After the extraction, the residue was filtered to obtain a filtered solution. The residue was mixed with 75% ethanol solution at a solid-liquid ratio of 1:100 g / mL, and then extracted by heating in a water bath at a temperature of 65°C for 1 h. After the extraction, the residue was filtered to obtain a filtered solution. The two filtered solutions were combined as filtered solution B, and the remaining residue was residue B.

[0098] The extraction solution A and the filtered solution B were mixed to obtain an Acer truncatum Bunge leaf extract.

[0099] Comparative Example 6

[0100] The difference from Example 4 is only that:

[0101] Preparation method of Acer truncatum Bunge leaf extract (boiling water bath extraction step is omitted):

[0102] Fresh Acer truncatum Bunge leaves were selected and rinsed with clean water to remove impurities, and then dried at low temperature of 45°C until the moisture content was less than or equal to 4%. The leaves were ground into powder with a particle size of 20 mesh using a high-speed grinder. The leaf powder was mixed with 75% ethanol solution at a solid-liquid ratio of 1:100 g / mL, and then extracted by magnetic stirring at 20°C for 30 min to obtain an extraction solution. The residue was mixed with 75% ethanol solution at a solid-liquid ratio of 1:100 g / mL, and then extracted by magnetic stirring at 20°C for 30 min. The two extraction solutions were combined as extraction solution A, and the remaining residue was residue A.

[0103] The residue A was mixed with 75% ethanol solution at a solid-liquid ratio of 1:100 g / mL, and then extracted by ultrasonic treatment (power of 600 W, frequency of 20 kHz) at a temperature of 50°C for 30 min. After the ultrasonic treatment, the residue was filtered to obtain a filtered solution. The residue was mixed with 75% ethanol solution at a solid-liquid ratio of 1:100 g / mL, and then extracted by ultrasonic treatment (power of 600 W, frequency of 20 kHz) at a temperature of 50°C for 30 min. After the ultrasonic treatment, the residue was filtered to obtain a filtered solution. The two filtered solutions were combined as filtered solution B, and the remaining residue was residue B.

[0104] Filter residue B was added to a 70% ethanol solution at a ratio of 1:100 g / mL, and heated under reflux in a water bath for 1 hour at a temperature of 65°C. After reflux, the mixture was filtered to obtain filtrate. Filter residue B was then mixed with a 75% ethanol solution at a ratio of 1:100 g / mL, and heated under reflux in a water bath for 1 hour at a temperature of 65°C. After reflux, the mixture was filtered. The two filtrates were combined to obtain filtrate C, and the remainder was filter residue C.

[0105] Extract A, filtrate B, and filtrate C were mixed to obtain the Acer truncatum leaf extract.

[0106] Comparative Example 7

[0107] The only difference from Example 4 is that:

[0108] Extraction method of Acer truncatum seed oil: Acer truncatum seeds are screened to remove impurities and ground into powder using a high-speed pulverizer to a particle size of 80 mesh. The Acer truncatum seed powder is mixed with water at a material-to-liquid ratio of 1:5 g / mL and soaked in a water bath at 45℃ for 3 hours. Then, it is mixed with 75% ethanol solution at a volume ratio of 1:2 and subjected to ultrasonic extraction at 35℃ for 25 minutes. The extract obtained after ultrasonic extraction is subjected to rotary evaporation at 35℃, a rotation speed of 200 rpm, and a pressure of 0.2 atm to remove the solvent, thus obtaining Acer truncatum seed oil.

[0109] Comparative Example 8

[0110] A composition for treating Alzheimer's disease, comprising the following components: 5 parts nervonic acid and 2 parts Acer truncatum leaf extract.

[0111] Preparation method of Acer truncatum leaf extract: same as in Example 4.

[0112] Test case

[0113] Female APP / PS1 mice aged 24 weeks were selected. The mice were housed with 3 mice per cage under the following environmental conditions: room temperature 22±2℃, relative humidity 55±5%, and a 12-hour light / 12-hour dark cycle.

[0114] After two weeks of adaptive feeding, the mice were randomly divided into 11 groups of 10 each: a control group, a low-dose Example 4 group, a high-dose Example 4 group, a Comparative Example 1 group, a Comparative Example 2 group, a Comparative Example 3 group, a Comparative Example 4 group, a Comparative Example 5 group, a Comparative Example 6 group, a Comparative Example 7 group, and a Comparative Example 8 group. The control group was subjected to 2 mL of normal saline by gavage daily, the low-dose Example 4 group was subjected to the Example 4 composition by gavage (50 mg / kg / d) daily, the high-dose Example 4 group received the Example 4 composition by gavage (100 mg / kg / d) daily, and the Comparative Examples 1-8 groups were subjected to the corresponding composition by gavage (100 mg / kg / d) daily. A total of 6 weeks of gavage treatment was performed for subsequent experiments.

[0115] 1. Water maze experiment

[0116] The water maze experiment is mainly used to detect the spatial learning and memory ability of mice. One day before the experiment, the mice were placed in the water maze experiment room to adapt to the environment. The experiment was divided into two stages. The first stage was called the positioning cruise experiment, which was performed continuously for 5 days. First, the appropriate amount of water was injected into the maze, and the water temperature was controlled at 22±2℃. Four water entry points were selected to divide the maze into four quadrants, and different markers were pasted on each quadrant. The platform was placed in the III quadrant and located 1 cm below the water surface. The platform position remained unchanged during the experiment. Titanium dioxide was added to the water and stirred evenly to make the platform invisible. The midpoint of the pool wall of the four quadrants was used as the water entry point, and the mouse was placed in the water with its face facing the pool wall. The time taken by the mouse to find the platform in 60s was recorded as the escape latency. If the platform was not found within 60s, the mouse was guided to the platform position and stayed for 10s, and the escape latency was recorded as 60s. The second stage was the spatial exploration experiment. On the 6th day of the experiment, the platform was removed, and the mouse was placed in the water on the opposite side of the original platform. The number of times the mouse crossed the platform, the platform quadrant residence time, the movement distance, and the movement speed were recorded within 60s using water maze software, and the results are shown in the following table.

[0117] Table 1 Water maze experiment results of mice in each group

[0118]

[0119] The results show that the number of times the mice in the low-dose Example 4 group and the high-dose Example 4 group crossed the platform was significantly higher than that of the control group, and the effect was better than that of the Comparative Examples 1-8. Among the Comparative Examples 1-8, the effects of the Comparative Example 1 group and the Comparative Examples 7-8 were not significantly different, but the effects were lower than those of the low-dose Example 4 group. The platform quadrant residence time of the mice in the low-dose Example 4 group and the high-dose Example 4 group was significantly lower than that of the control group, and the effect was better than that of the Comparative Examples 1-8. Among the Comparative Examples 1-8, the effects of the Comparative Example 1 group and the Comparative Examples 7-8 were not significantly different, but the effects were lower than those of the low-dose Example 4 group. There was no significant difference in the movement distance and movement speed of the mice in each group.

[0120] 2. Open field test

[0121] The open field test is mainly used to detect the mood-related behavior of mice, such as activity level, anxiety behavior and exploration behavior. The open field test equipment is composed of a white opaque box with a size of 45cmx45cmx45cm and a behavior analysis software. Before the experiment, the mice are placed in the experimental environment for 1h in advance. Then, the corresponding parameters are set in the behavior analysis software, each mouse is placed in the box with its back against the side wall of the box, and is allowed to freely explore for 10min. The total walking distance of the mouse, the activity time in the center area, the frequency of entering the center area, the distance of movement in the center area and the number of standing behaviors of the mouse are recorded, and the results are shown in the following table.

[0122] Table 2: Open field test results of mice in each group

[0123]

[0124] The results show that the total walking distance of mice in each group is not significantly different, but the activity time in the center area, the frequency of entering the center area, the distance of movement in the center area and the number of standing behaviors of mice in the low-dose group of Example 4 and the high-dose group of Example 4 are significantly higher than those in the control group, and the effect is better than that in the groups of Comparative Examples 1-8.

[0125] The above results show that the acer truncatum seed oil and the acer truncatum leaf extract provided by the present application have a synergistic effect on each other, can significantly improve the behavior cognitive level of APP / PS1 mice, and suggest that the combination of the two has a synergistic effect, which can improve the neuron damage of APP / PS1 mice, play a significant antioxidant, anti-aging and nerve repair function, and improve the behavior cognitive level of APP / PS1 mice, and has the effect of treating senile dementia.

[0126] The above only describes the preferred embodiments of the present application, and it should be pointed out that for ordinary skilled persons in the art, without departing from the principles of the present application, a number of improvements and refinements can be made, and these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. A composition for treating Alzheimer's disease, characterized in that, The composition comprises 1-10 parts by mass of Acer truncatum Bunge seed oil and 1-5 parts by mass of Acer truncatum Bunge leaf extract.

2. The composition of claim 1, wherein, The extraction method of the Acer truncatum Bunge seed oil comprises the following steps: mixing Acer truncatum Bunge seed powder with water, adding a composite enzyme for enzymolysis; mixing the enzymolysis slurry with an ethanol solution, and performing ultrasonic extraction; and performing rotary evaporation on the obtained extraction liquid after ultrasonic extraction to obtain Acer truncatum Bunge seed oil; the composite enzyme is composed of cellulase, pectinase and lipase in a ratio of 1:2:1 in terms of enzyme activity.

3. The composition of claim 2, wherein, The solid-liquid ratio of the Acer truncatum Bunge seed powder to water is 1:(2-10) g / mL; the amount of the composite enzyme added is 2000-50000 U / g in terms of the mass of the Acer truncatum Bunge seed powder; the enzymolysis temperature is 40-50 DEG C, the time is 2-4 h, and the pH is 4-6.

4. The composition of claim 2, wherein, The ethanol solution is an ethanol solution of 70-85%; the volume ratio of the slurry to the ethanol solution is 1:(1-3); the ultrasonic extraction temperature is 30-40 DEG C, and the time is 20-30 min.

5. The composition of claim 2, wherein, The rotary evaporation temperature is 30-40 DEG C, the rotation speed is 100-200 rmp, and the pressure is 0.1-0.5 atm.

6. The composition of claim 1, wherein, The preparation method of the Acer truncatum Bunge leaf extract comprises the following steps: drying and crushing Acer truncatum Bunge leaves, adding an ethanol solution, performing magnetic stirring and leaching to obtain leaching liquid A and residue A; adding an ethanol solution to the residue A, performing ultrasonic extraction, and performing suction filtration after the ultrasonic extraction to obtain filtrate B and residue B; adding an ethanol solution to the residue B, performing water bath heating and reflux, performing suction filtration after the reflux to obtain filtrate C and residue C; adding water to the residue C, performing leaching in a boiling water bath, performing reduced-pressure filtration and concentration on the leaching liquid to obtain product D; and mixing the leaching liquid A, the filtrate B, the filtrate C and the product D to obtain the Acer truncatum Bunge leaf extract.

7. The composition of claim 6, wherein, The ethanol solution is an ethanol solution of 70-80%.

8. The composition of claim 6, wherein, The magnetic stirring and leaching time is 20-40 min; the ultrasonic extraction time is 20-40 min, and the temperature is 45-55 DEG C; the water bath heating and reflux time is 1-2 h, and the water bath temperature is 60-70 DEG C; and the leaching time in the boiling water bath is 1-2 h.

9. Process for the preparation of a composition according to any one of claims 1 to 8, characterized in that, The Acer truncatum Bunge seed oil and the Acer truncatum Bunge leaf extract are uniformly mixed to obtain the composition.

10. The composition according to any one of claims 1-8 is used in any one of the following: (1) preparation of an antioxidant and anti-aging drug; (2) preparation of a nerve repair drug; and (3) preparation of a drug for treating senile dementia.

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