CN113730590A - A microcapsule decoction piece for preventing and improving Alzheimer disease and dementia, and its preparation method - Google Patents
A microcapsule decoction piece for preventing and improving Alzheimer disease and dementia, and its preparation method Download PDFInfo
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Abstract
The invention belongs to the technical field of medicine preparation, and particularly relates to a microcapsule decoction piece capable of embedding components for preventing and improving Alzheimer's disease and dementia and a preparation method thereof. The microcapsule decoction pieces are prepared by taking poly-gamma-glutamic acid/chitosan as a carrier and loading a traditional Chinese medicine extract; the traditional Chinese medicine extract comprises the following raw materials: ginseng, salvia miltiorrhiza root, epimedium herb, dried rhizome of turmeric, coffee bean, broccoli bud, acorn and bolete. The gamma-PGA-CS microcapsule decoction pieces prepared by the invention have good slow release effect on the embedded traditional Chinese medicine components; the preparation method is simple, and the cost of raw materials is low; the microcapsule decoction piece provided by the invention has high drug loading, can embed various drugs at the same time, has high bioavailability, and can reduce side effects to the maximum extent to realize the effects of preventing and improving Alzheimer's disease, dementia and the like.
Description
Technical Field
The invention belongs to the technical field of medicine preparation, relates to a novel composite carrier material, and particularly relates to a microcapsule decoction piece capable of embedding components for preventing and improving Alzheimer's disease and dementia and a preparation method thereof.
Background
In the modern life, with the coming of aging age, senile dementia becomes a worldwide burden. Alzheimer's Disease (AD) is not equal to dementia, or it is only one of the branches. AD is a hidden, progressive degenerative disease of the nervous system. Clinically, the overall dementia such as dysmnesia, aphasia, disuse, agnosia, impairment of visual spatial skills, dysfunction in execution, and personality and behavior changes are characterized, and the etiology is unknown. It may be due to the fact that brain cells are difficult to communicate well with each other when there is an excessive accumulation of certain proteins inside and outside the brain cells, resulting in loss of connections between nerve cells, and ultimately in nerve cell death and brain tissue function loss. Alzheimer's disease is not only present in the elderly but also in a small proportion of young people. The current therapeutic efficacy for this disease is low, as the specific etiology is not clear.
Researches find that some traditional Chinese medicines have good effect on preventing the diseases. Like ginseng, it has high medicinal value, and can treat and prevent many diseases, including nervous system diseases, and can help to improve memory; the epimedium also has the effects of calming, resisting depression, protecting heart and cerebral vessels and the like, and has certain prevention effect on the occurrence of Alzheimer disease in the brain diseases; the broccoli buds contain various substances which can help the brain to restore the chemical substance balance, so that the prevention and improvement effects are achieved, and other medicines have the effects of protecting and regulating the nervous system and can generate certain prevention effects. The efficacy value of the traditional Chinese medicines is fully verified, but the utilization rate of the traditional Chinese medicines is low, so that the problem of further improving the biological activity and the utilization rate of the traditional Chinese medicines is urgently needed to be solved.
Disclosure of Invention
In view of the problems in the prior art, the present invention provides a microcapsule decoction piece for embedding components for preventing and improving alzheimer's disease and dementia, which utilizes poly-gamma-glutamic acid and chitosan to enhance biocompatibility with each other so as to be better absorbed by the body.
The invention also provides a preparation method of the microcapsule decoction piece.
In order to achieve the purpose, the invention relates to the following specific technical scheme:
the invention provides a microcapsule decoction piece for embedding components for preventing and improving Alzheimer's disease and dementia, which is prepared by taking poly-gamma-glutamic acid/chitosan as a carrier and loading a traditional Chinese medicine extract;
the traditional Chinese medicine extract is prepared by extracting the following raw materials in percentage by mass: 10% of ginseng, 21% of salvia miltiorrhiza root, 14% of epimedium herb, 17% of dried rhizome of turmeric, 5% of coffee bean, 16% of broccoli bud, 8% of acorn and 9% of boletus.
The invention also provides a preparation method of the microcapsule decoction piece, which comprises the following steps:
(1) mixing the traditional Chinese medicine raw materials according to a certain proportion, grinding the mixture into powder to obtain mixed powder, and dissolving the mixed powder in absolute ethyl alcohol to obtain a solution B;
(2) dissolving chitosan in an acetic acid solution to obtain a mixed solution C, then adding the solution B into the mixed solution C, stirring, and performing ultrasonic treatment to obtain a solution D; adding toluene into the solution D, centrifuging after ultrasonic treatment, and resuspending with ultrapure water to obtain a solution E;
(3) adding water into poly gamma-glutamic acid to prepare a solution F, adding the solution F into the solution E, stirring and ultrasonically treating the solution, and performing rotary evaporation on the obtained solution to obtain a mixed solution G;
(4) and (3) adjusting the pH value of the solution G by using PBS buffer solution, centrifuging after table reaction, washing, freeze-drying into powder, and then entering a tablet press to prepare the microcapsule decoction pieces.
Further, in the step (1), the concentration of the solution B is 0.5-1 mg/mL.
Further, in the step (2), the mass concentration of the mixed solution C is 1-5%; the concentration of the glacial acetic acid solution is 1%; the volume ratio of the toluene to the mixed solution C is 1: 1; the volume ratio of the solution B to the mixed solution C is 2: 1.
Further, in the step (3), the concentration of the solution F is 0.25-1 mg/mL; the volume ratio of the solution E to the solution F is 1: 5-9.
Further, in the steps (2) and (3), the power of the ultrasonic wave is 150-; the centrifugation is 12000r/min and 10 min.
Further, in the step (3), the rotary evaporation is performed by using a rotary evaporator, and the parameters are as follows: the rotary evaporation temperature is set to be 40-60 ℃ under the conditions of 150-175 hPa.
Further, in the step (4), the temperature of the table shaking reaction is 37 ℃, and the reaction is carried out for 2-5h under the condition of 180 r/min; centrifuging for 10min at the rotating speed of 12000 r/min; the pH value is 7-7.4.
The invention utilizes Poly gamma-glutamic acid (Poly-gamma-glutamic acid, (gamma-PGA)) and chitosan to construct the composite drug carrier. The relative molecular weight of the hydrogel which is easy to crosslink and has excellent performance at the later stage is generally between 10 and 100 ten thousand. Compared with other polymer compounds, the polymer compound has the advantages of excellent biocompatibility, low immunogenicity, no toxic or side effect and great advantage as a drug carrier. Chitosan (CS) is a functional oligosaccharide, can reduce cholesterol and improve immunity of organisms, has a structure containing hydroxyl and amino, has high positive charge density, is favorable for cell adhesion, is cheap and easy to obtain, and is nontoxic and tasteless. The chitosan can stabilize the components in the medicine, promote the medicine absorption, delay or control the dissolution speed of the medicine, help the medicine to reach the target organ, resist acid and ulcer and prevent the medicine from stimulating the stomach.
The invention has the beneficial effects that:
1. the poly-gamma-glutamic acid and the chitosan used in the invention are colorless, nontoxic, tasteless and easily degradable microbial fermentation extracts, the carboxyl of the gamma-PGA and the amino of the CS have high coordination coefficient and stable structure, the stability of the medicine in the poly-gamma-PGA is increased, and the poly-gamma-glutamic acid and the chitosan have good slow release effect and biocompatibility, so that the bioavailability of the medicine is higher; the carrier formed by poly-gamma-glutamic acid and chitosan is utilized to play a role together with a plurality of traditional Chinese medicines with the functions of protecting and regulating the nervous system, and has low side effect and quick response.
(2) The gamma-PGA-CS microcapsule decoction pieces prepared by the invention have good slow release effect on the embedded traditional Chinese medicine components; the preparation method is simple and the cost of raw materials is low.
(3) The gamma-PGA-CS microcapsule decoction pieces prepared by the invention have high drug loading capacity, can embed various medicines simultaneously, have high bioavailability, and can reduce side effects to the maximum extent to realize the effects of preventing and improving Alzheimer's disease, dementia and the like.
Drawings
FIG. 1 is a drug loading standard curve.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments, but it should not be construed that the scope of the present invention is limited to the following examples. Various substitutions and alterations can be made by those skilled in the art and by conventional means without departing from the spirit of the method of the invention described above.
Example 1
(1) Mixing the Chinese medicinal materials at a certain ratio, and grinding into powder to obtain mixed powder with a ratio shown in Table 1;
TABLE 1
(2) Because of the insolubility of some traditional Chinese medicines, the mixed powder of the traditional Chinese medicines is dissolved in absolute ethyl alcohol to obtain a traditional Chinese medicine solution with the concentration of 0.5 mg/mL;
(3) dissolving chitosan in 1% acetic acid solution to obtain 2% chitosan solution, adding the Chinese medicinal mixed solution into the chitosan solution, stirring, and performing 150W ultrasound for 10 min;
(4) adding toluene into the solution obtained in the step (3) according to the volume ratio of 1:1 for chemical crosslinking, performing ultrasonic treatment and centrifugation, and performing heavy suspension on ultrapure water to obtain chitosan microspheres wrapping the traditional Chinese medicine;
(5) adding water into poly-gamma-glutamic acid to prepare a poly-gamma-glutamic acid solution with the concentration of 0.75mg/mL, adding the poly-gamma-glutamic acid solution into the solution obtained in the step (4) with the volume ratio of 1:5, stirring and ultrasonically treating the solution for 10min at 150W, and completely evaporating ethanol and toluene in a rotary evaporator;
(6) and (3) adjusting the pH value of the solution obtained in the step (5) to 7.2 by using PBS buffer solution, placing the solution on a shaking table for reaction for 2 hours, centrifuging for 10 minutes, washing, freeze-drying the solution into powder, and then putting the powder into a tablet press to prepare the microcapsule decoction pieces.
Example 2
(1) Mixing the Chinese medicinal materials at a certain ratio and grinding into powder to obtain mixed powder, wherein the ratio is as in example 1;
(2) because of the insolubility of some traditional Chinese medicines, the mixed powder of the traditional Chinese medicines is dissolved in absolute ethyl alcohol to obtain a traditional Chinese medicine solution with the concentration of 0.5 mg/mL;
(3) dissolving chitosan in 1% acetic acid solution to obtain 3% chitosan solution, adding the mixed solution of Chinese medicinal materials into the chitosan acetic acid solution, stirring, and performing 150W ultrasound for 10 min;
(4) adding toluene into the solution obtained in the step (3) according to the volume ratio of 1:1 for chemical crosslinking, performing ultrasonic treatment and centrifugation, and performing heavy suspension on ultrapure water to obtain chitosan microspheres wrapping the traditional Chinese medicine;
(5) adding water into poly-gamma-glutamic acid to prepare a poly-gamma-glutamic acid solution with the concentration of 0.5mg/mL, adding the poly-gamma-glutamic acid solution into the solution obtained in the step (4) according to the volume ratio of 1:6, stirring and ultrasonically treating the solution for 10min at 150W, and completely evaporating ethanol and toluene in a rotary evaporator;
(6) and (3) adjusting the pH value of the solution obtained in the step (5) to 7.2 by using PBS buffer solution, placing the solution on a shaking table for reaction for 2 hours, centrifuging for 10 minutes, washing, freeze-drying the solution into powder, and then putting the powder into a tablet press to prepare the microcapsule decoction pieces.
Example 3
(1) Mixing the Chinese medicinal materials at a certain ratio and grinding into powder to obtain mixed powder, wherein the ratio is as in example 1;
(2) because of the insolubility of some traditional Chinese medicines, the mixed powder of the traditional Chinese medicines is dissolved in absolute ethyl alcohol to obtain a traditional Chinese medicine solution with the concentration of 1 mg/mL;
(3) dissolving chitosan in 1% acetic acid solution to obtain 3% chitosan solution, adding the Chinese medicinal mixed solution into the chitosan solution, stirring, and performing 150W ultrasound for 10 min;
(4) adding toluene into the solution obtained in the step (3) according to the volume ratio of 1:1 for chemical crosslinking, performing ultrasonic treatment and centrifugation, and performing heavy suspension on ultrapure water to obtain chitosan microspheres wrapping the traditional Chinese medicine;
(5) adding water into poly-gamma-glutamic acid to prepare poly-gamma-glutamic acid solution with the concentration of about 0.75mg/mL, adding the poly-gamma-glutamic acid solution into the solution obtained in the step (4) with the volume ratio of 1:7, stirring and ultrasonically treating the solution for 10min at 150W, and completely evaporating the ethanol and the toluene in a rotary evaporator;
(6) and (3) adjusting the pH value of the solution obtained in the step (5) to 7.4 by using PBS buffer solution, placing the solution on a shaking table for reaction for 4 hours, centrifuging for 10min, washing, freeze-drying the solution into powder, and then putting the powder into a tablet press to prepare the microcapsule decoction pieces.
Example 4
(1) Mixing the Chinese medicinal materials at a certain ratio and grinding into powder to obtain mixed powder, wherein the ratio is as in example 1;
(2) because of the insolubility of some traditional Chinese medicines, the mixed powder of the traditional Chinese medicines is dissolved in absolute ethyl alcohol to obtain a traditional Chinese medicine solution with the concentration of 0.75 mg/mL;
(3) dissolving chitosan in 1% acetic acid solution to obtain 4% chitosan solution, adding the Chinese medicinal mixed solution into the chitosan solution, stirring, and performing 150W ultrasound for 10 min;
(4) adding toluene into the solution obtained in the step (3) according to the volume ratio of 1:1 for chemical crosslinking, performing ultrasonic treatment and centrifugation, and performing heavy suspension on ultrapure water to obtain chitosan microspheres wrapping the traditional Chinese medicine;
(5) adding poly-gamma-glutamic acid into water to prepare poly-gamma-glutamic acid solution with the concentration of about 1mg/mL, adding the poly-gamma-glutamic acid solution into the solution obtained in the step (4) with the volume ratio of 1:8, stirring and ultrasonically treating the solution for 10min at 150W, and completely evaporating the ethanol and the toluene in a rotary evaporator;
(6) and (3) adjusting the pH value of the solution obtained in the step (5) to 7.0 by using PBS buffer solution, placing the solution on a shaking table for reaction for 4 hours, centrifuging for 10 minutes, washing, freeze-drying the solution into powder, and then putting the powder into a tablet press to prepare the microcapsule decoction pieces.
Example 5
(1) Mixing the Chinese medicinal materials at a certain ratio and grinding into powder to obtain mixed powder, wherein the ratio is as in example 1;
(2) because of the insolubility of some traditional Chinese medicines, the mixed powder of the traditional Chinese medicines is dissolved in absolute ethyl alcohol to obtain a traditional Chinese medicine solution with the concentration of 1 mg/mL;
(3) dissolving chitosan in 1% acetic acid solution to obtain 5% chitosan solution, adding the Chinese medicinal mixed solution into the chitosan solution, stirring, and performing 150W ultrasound for 10 min;
(4) adding toluene into the solution obtained in the step (3) according to the volume ratio of 1:1 for chemical crosslinking, performing ultrasonic treatment and centrifugation, and performing heavy suspension on ultrapure water to obtain chitosan microspheres wrapping the traditional Chinese medicine;
(5) adding water into poly-gamma-glutamic acid to prepare poly-gamma-glutamic acid solution with the concentration of about 0.25mg/mL, adding the poly-gamma-glutamic acid solution into the solution obtained in the step (4) with the volume ratio of 1:9, stirring and ultrasonically treating the solution for 10min at 150W, and completely evaporating the ethanol and the toluene in a rotary evaporator;
(6) and (3) adjusting the pH value of the solution obtained in the step (5) to 7.2 by using PBS buffer solution, placing the solution on a shaking table for reaction for 2 hours, centrifuging for 10 minutes, washing, freeze-drying the solution into powder, and then putting the powder into a tablet press to prepare the microcapsule decoction pieces.
Comparative example 1
(1) Mixing the Chinese medicinal materials at a certain ratio, and grinding into powder to obtain mixed powder with a ratio shown in Table 1;
(2) because of the insolubility of some traditional Chinese medicines, the mixed powder of the traditional Chinese medicines is dissolved in absolute ethyl alcohol to obtain a traditional Chinese medicine solution with the concentration of 0.5 mg/mL;
(3) dissolving chitosan in 1% acetic acid solution to obtain 2% chitosan solution, adding the Chinese medicinal mixed solution into the chitosan solution, stirring, and performing 150W ultrasound for 10 min;
(4) adding water into poly-gamma-glutamic acid to prepare a poly-gamma-glutamic acid solution with the concentration of 0.75mg/mL, adding the poly-gamma-glutamic acid solution into the solution obtained in the step (3) according to the volume ratio of 1:4, adding toluene with the same volume as that of the chitosan solution for chemical crosslinking, stirring and performing ultrasonic treatment, performing ultrasonic treatment at 150W for 10min, and completely evaporating ethanol and toluene in the obtained solution on a rotary evaporator;
(5) and (3) adjusting the pH value of the solution obtained in the step (5) to 7.2 by using PBS buffer solution, placing the solution on a shaking table for reaction for 2 hours, centrifuging for 10 minutes, washing, freeze-drying the solution into powder, and then putting the powder into a tablet press to prepare the microcapsule decoction pieces.
By way of example of the gels prepared in examples 1 to 5, we carried out the following experiments:
1. drug loading rate determination experiment: (1) determination of the standard curve: dissolving the mixed powder in methanol to obtain solutions with concentration of 0, 0.5, 1, 1.5, 2, and 2.5 μ g/mL, respectively, and measuring OD value at 678 nm.
(2) Detecting the drug loading rate: the microcapsule samples prepared in examples 1 to 5 and comparative example 1 were placed in a test tube, dissolved in methanol, and then measured for OD at 678nm to calculate the drug loading amount. The standard curves and experimental results are shown in fig. 1 and table 2:
TABLE 2 drug loading
It can be seen from the experimental data that the examples all have a relatively high drug loading.
2. Drug release detection experiments: the microcapsule decoction piece samples prepared in examples 1-5 were placed in test tubes, kept at 37 ℃ and then added with 25ml of phosphate buffered saline respectively, and the supernatants at 0, 4, 8, 12 and 24h were collected and the concentration of the herbal ingredients in the solution was measured by UV spectrophotometer at each time interval, and the experimental results are shown in Table 3.
TABLE 3
The experimental data show that the drug slow release effect of the carrier is good, and the effects of drug slow release and drug utilization rate improvement are achieved.
3. BACE-1 inhibition assay: dissolving traditional Chinese medicine powder in DMSO to form a concentration 3 times that in the example by using a FRET-based BACE-1 fluorescence analysis kit, analyzing the inhibitory activity of the traditional Chinese medicine powder on BACE-1, and further detecting the prevention and improvement capacity of the traditional Chinese medicine microcapsule decoction pieces on Alzheimer's disease. The results are shown in Table 4.
TABLE 4
The experimental data show that the microcapsule decoction piece product embedded with the traditional Chinese medicine has obvious inhibition effect on BACE-1, and the result shows that the traditional Chinese medicine decoction piece can have the potential of preventing and improving the Alzheimer disease.
Claims (8)
1. A microcapsule decoction pieces of ingredient for preventing and improving Alzheimer's disease and dementia of embedding, wherein said microcapsule decoction piece is prepared by taking poly gamma-glutamic acid/chitosan as carrier, load Chinese medicinal extract to prepare;
the traditional Chinese medicine extract is prepared by extracting the following raw materials in percentage by mass: 10% of ginseng, 21% of salvia miltiorrhiza root, 14% of epimedium herb, 17% of dried rhizome of turmeric, 5% of coffee bean, 16% of broccoli bud, 8% of acorn and 9% of boletus.
2. A method for preparing the microcapsule decoction pieces as claimed in claim 1, which comprises the steps of:
(1) mixing the traditional Chinese medicine raw materials according to a certain proportion, grinding the mixture into powder to obtain mixed powder, and dissolving the mixed powder in absolute ethyl alcohol to obtain a solution B;
(2) dissolving chitosan in an acetic acid solution to obtain a mixed solution C, then adding the solution B into the mixed solution C, stirring, and performing ultrasonic treatment to obtain a solution D; adding toluene into the solution D, centrifuging after ultrasonic treatment, and resuspending with ultrapure water to obtain a solution E;
(3) adding water into poly gamma-glutamic acid to prepare a solution F, adding the solution F into the solution E, stirring and ultrasonically treating the solution, and performing rotary evaporation on the obtained solution to obtain a mixed solution G;
(4) and (3) adjusting the pH value of the solution G by using PBS buffer solution, centrifuging after table reaction, washing, freeze-drying into powder, and then entering a tablet press to prepare the microcapsule decoction pieces.
3. The method according to claim 2, wherein in the step (1), the concentration of the solution B is 0.5 to 1 mg/mL.
4. The preparation method according to claim 2, wherein in the step (2), the mass concentration of the mixed solution C is 1-5%; the concentration of the glacial acetic acid solution is 1%; the volume ratio of the toluene to the mixed solution C is 1: 1; the volume ratio of the solution B to the mixed solution C is 2: 1.
5. The method according to claim 2, wherein in the step (3), the concentration of the solution F is 0.25 to 1 mg/mL; the volume ratio of the solution E to the solution F is as follows: 1: 5-9.
6. The preparation method according to claim 2, 4 or 5, wherein in the steps (2) and (3), the power of the ultrasound is 150-200W, and the ultrasound lasts for 10 min; the centrifugation is 12000r/min and 10 min.
7. The preparation method according to claim 2 or 5, wherein in the step (3), the rotary evaporation is performed by using a rotary evaporator, and the parameters are as follows: the rotary evaporation temperature is set to be 40-60 ℃ under the conditions of 150-175 hPa.
8. The preparation method according to claim 2, wherein in the step (4), the temperature of the shaking table reaction is 37 ℃ and the reaction is carried out for 2-5h at 180 r/min; centrifuging for 10min at the rotating speed of 12000 r/min; the pH value is 7-7.4.
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| CN102058562A (en) * | 2011-01-26 | 2011-05-18 | 上海应用技术学院 | Method for preparing gamma-polyglutamic acid/chitosan nano capsules |
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