CN113143985A - Application of liposome of radix Tripterygii Wilfordii extract in preparing medicine for preventing and treating behavior cognitive disorder induced by lipopolysaccharide by nasal administration - Google Patents
Application of liposome of radix Tripterygii Wilfordii extract in preparing medicine for preventing and treating behavior cognitive disorder induced by lipopolysaccharide by nasal administration Download PDFInfo
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Abstract
An application of liposome containing radix Tripterygii Wilfordii extract in preparing medicine for preventing and treating behavior cognitive disorder induced by lipopolysaccharide by nasal administration; the radix Tripterygii Wilfordii extract is tripterygium glycosides, triptolide or tripterine; the invention can obviously inhibit the reaction of the cranial nerve inflammation and relieve the behavior cognitive disorder induced by lipopolysaccharide, is an innovation of medicaments for preventing and treating diseases related to the cognitive disorder and has great social and economic benefits.
Description
Technical Field
The invention relates to the field of medicines, in particular to application of a tripterygium wilfordii extract component liposome in preparing a medicine for preventing and treating behavior cognitive disorder induced by lipopolysaccharide by nasal administration.
Background
When a brain generates an inflammatory reaction, the brain is difficult to be accurately regulated and controlled by self due to a complex internal structure, symptoms such as headache, dizziness, ear pain and the like are often caused by reaction disorder, the drugs can be relieved, and a central nervous system disease can be caused by long-term chronic inflammation, so that behavior cognitive impairment such as learning and memory function reduction, limb discordance and the like is caused, and the symptoms are common in many diseases, such as Alzheimer Disease (AD), Parkinson Disease (PD) and the like. In recent years, a great deal of research shows that neuroinflammation is an important reason for the occurrence of cognitive impairment of various brain diseases, when infection and inflammation occur, the expression increasing level of relevant inflammation indexes such as TNF-alpha, IL-1 beta and the like in the cortex and the hippocampus of the brain is consistent with the severity of the inflammatory infection, so that the neuroinflammation degree can be judged, and the learning and memory ability of the water maze for detecting the spatial position sense and the directional sense can reflect the cognitive degree.
A fat-soluble component mixture tripterygium glycosides (also called total tripterygium glycosides) extracted from the root of the peeled tripterygium wilfordii is prepared into tablets as a natural non-steroidal immunosuppressant, the physiological activity of the tripterygium wilfordii is synergistically generated by a plurality of components (diterpene lactone, alkaloid, triterpene and the like), and the tripterygium wilfordii is widely applied to clinical treatment of various inflammation-related diseases, such as rheumatoid arthritis, glomerulonephritis, nephrotic syndrome, lupus erythematosus, xerophthalmia, various skin diseases and the like. Triptolide, a representative component of diterpenoid compounds in tripterygium glycosides, is considered to have the most efficacy at present but has the strongest toxicity, and has become one of the hot research medicines which are sought at home and abroad. Research shows that triptolide has obvious inhibiting effect on vascular permeability increase, inflammatory factor generation and release, fibrous hyperplasia in the later stage of inflammation and the like in the inflammatory process. Tripterine is a natural product with various biological activities, and modern researches show that: it has strong antioxidation, anti-cancer angiogenesis, and anti-rheumatoid effects. However, no report is available at present in the medicines for treating behavior cognitive impairment induced by lipopolysaccharide by nasal administration of tripterygium wilfordii extract component liposome.
Disclosure of Invention
In view of the above situation, in order to overcome the defects of the prior art, the invention aims to provide the application of the tripterygium wilfordii extract liposome in preparing the medicine for preventing and treating the behavior cognitive disorder induced by lipopolysaccharide by nasal administration, which can effectively solve the problem of preparing the medicine for treating the behavior cognitive disorder induced by lipopolysaccharide by nasal administration of the tripterygium wilfordii extract liposome.
In order to achieve the purpose, the invention adopts the technical scheme that the application of the lipidosome of the tripterygium wilfordii extract component in preparing the medicine for preventing and treating the behavior cognitive disorder induced by lipopolysaccharide by nasal administration.
The radix Tripterygii Wilfordii extract is tripterygium glycosides, triptolide or tripterine.
The preparation method of the tripterygium wilfordii extract liposome comprises the following steps:
(1) weighing the following components in parts by weight: ultrasonically dissolving 40 parts of soybean lecithin, 10 parts of cholesterol and 1 part of tripterygium wilfordii extract by using an organic solvent dichloromethane for 5-10min, and rotationally evaporating at 20rpm for 20min in a constant-temperature water bath at 40 ℃ for 20min to obtain a uniform lipoid film;
(2) drying the lipoid film for 4 hours in vacuum, adding 25000 parts by weight of phosphate buffer PBS (phosphate buffered saline) in volume ratio, stirring for 4 hours at normal temperature, placing the mixture in 100w ultrasound for 5 minutes, then sequentially passing the mixture through 200nm and 100nm filter membranes by using a manual squeezer, carrying out secondary ultrafiltration by using a 50000MWCO ultrafiltration tube, and taking supernatant, namely the tripterygium wilfordii extract component liposome;
the weight to volume ratio is solid in g and liquid in ml.
The invention can obviously inhibit the reaction of the cranial nerve inflammation and relieve the behavior cognitive disorder induced by lipopolysaccharide, is an innovation of medicaments for preventing and treating diseases related to the cognitive disorder and has great social and economic benefits.
Drawings
FIG. 1 is a diagram of the walking trajectory of the Morris water maze space exploration experiment of each group of mice in the experiment of the present invention;
wherein A is a normal group, B is a sham group, C is a model group, D is a triptolide liposome low-dose group, E is a triptolide liposome medium-dose group, and F is a triptolide liposome high-dose group.
Detailed Description
The following detailed description of the embodiments of the invention is provided in connection with the accompanying drawings and the detailed description.
Example 1
In the specific implementation of the invention, the liposome of the tripterygium wilfordii extract component is as follows:
(1) weighing 40 parts by weight of soybean lecithin, 10 parts by weight of cholesterol and 1 part by weight of tripterygium glycosides, ultrasonically dissolving the mixture for 5 to 10min by using an organic solvent dichloromethane, and rotationally evaporating the mixture for 20min at 20rpm in a constant-temperature water bath at 40 ℃ under reduced pressure to obtain a uniform lipoid film;
(2) drying the lipoid film for 4 hours in vacuum, adding 25000 parts by weight of phosphate buffer solution PBS (phosphate buffered saline) in volume ratio, stirring for 4 hours at normal temperature, placing the mixture in 100w ultrasound for 5 minutes, then sequentially passing the mixture through 200nm and 100nm filter membranes by using a manual squeezer, carrying out secondary ultrafiltration by adopting a 50000MWCO ultrafiltration tube, and then taking supernatant, namely the tripterygium glycosides lipidosome;
the weight volume ratio is that solid is measured by g, and liquid is measured by l.
Example 2
In the specific implementation of the invention, the liposome of the tripterygium wilfordii extraction component is as follows:
(1) weighing 40 parts by weight of soybean lecithin, 10 parts by weight of cholesterol and 1 part by weight of triptolide, ultrasonically dissolving the mixture for 5 to 10min by using an organic solvent dichloromethane, and rotationally evaporating the mixture for 20min at 20rpm in a constant-temperature water bath at 40 ℃ under reduced pressure to obtain a uniform lipoid film;
(2) drying the lipoid film for 4 hours in vacuum, adding 25000 parts of phosphate buffer PBS (phosphate buffered saline) in a weight-volume ratio (same as the above), stirring for 4 hours at normal temperature, placing the mixture in a 100w ultrasonic wave for 5 minutes, then sequentially passing the mixture through 200nm and 100nm filter membranes by using a manual squeezer, performing secondary ultrafiltration by using a 50000MWCO ultrafiltration tube, and taking supernatant, namely the triptolide liposome.
Example 3
In the specific implementation of the invention, the liposome of the tripterygium wilfordii extraction component is as follows:
(1) weighing 40 parts by weight of soybean lecithin, 10 parts by weight of cholesterol and 1 part by weight of tripterine, ultrasonically dissolving the soybean lecithin, the cholesterol and the tripterine for 5-10min by using an organic solvent dichloromethane, and rotationally evaporating the soybean lecithin, the cholesterol and the tripterine for 20min at 20rpm in a constant-temperature water bath at 40 ℃ to obtain a uniform lipoid film;
(2) drying the lipoid film for 4 hours in vacuum, adding 25000 parts of phosphate buffer PBS (phosphate buffer solution) in a weight-volume ratio (same as the above), stirring for 4 hours at normal temperature, placing the mixture in 100w ultrasound for 5 minutes, then sequentially passing the mixture through 200nm and 100nm filter membranes by using a manual squeezer, performing secondary ultrafiltration by using a 50000MWCO ultrafiltration tube, and taking supernatant, namely the tripterine liposome.
The method is stable and reliable, the obtained thunder god vine extract component liposome is used for preparing the medicine for preventing and treating the behavior cognitive disorder induced by the lipopolysaccharide by nasal administration, the problem of medication of the medicine for treating the behavior cognitive disorder induced by the lipopolysaccharide by nasal administration is effectively solved, and the experiment fully proves that the experiment data is as follows by taking the example 1 as an example:
first, experimental material and animal
Lipopolysaccharides (LPS) were purchased from Sigma company; dimethyl sulfoxide (DMSO) was purchased from shanghai mclin biochemistry technologies, ltd; cholesterol was purchased from beijing carbofuran technologies ltd; triptolide was purchased from west ampere Hao Xuan. C57BL/6J mouse, male, SPF grade, 18-22 g, purchased Zhengzhou city Huizhen district Huaxing experimental animal farm, production license number: SC xk (yu) 20190002.
Second, experimental method (taking triptolide liposome as an example, namely example 1)
1. Preparation of triptolide liposome
Respectively weighing 40 parts by weight of soybean lecithin, 10 parts by weight of cholesterol and 1 part by weight of triptolide, ultrasonically dissolving the soybean lecithin, 10 parts by weight of cholesterol and 1 part by weight of triptolide in an organic solvent dichloromethane for 5-10min, rotationally evaporating the dissolved substances for 20min at 20r/min in a constant-temperature water bath at 40 ℃ under reduced pressure to form a uniform lipoid film, and drying the lipoid film for 4h in vacuum; adding 25 parts by weight of phosphate buffer PBS (phosphate buffered saline) in volume ratio, stirring at normal temperature for 4h, performing ultrasonic treatment at 100w for 5min, sequentially passing through 200nm and 100nm filter membranes by using a manual squeezer, performing secondary ultrafiltration by using a 50000MWCO ultrafiltration tube, and obtaining the triptolide liposome.
Observing the form of the liposome by using a transmission electron microscope, and measuring the average particle size of the liposome by using a particle size analyzer; measuring the content of the drug by using a high performance liquid chromatography, and calculating the encapsulation efficiency, wherein the formula is as follows: c inclusion ═ amount of drug C encapsulated/total amount of drug C added × 100%. Storing the prepared triptolide liposome in a refrigerator at 4 ℃, sampling at 3d, 7d and 14d, observing whether the triptolide liposome is clear and transparent, and detecting the particle size and distribution condition of the triptolide liposome.
2. Molding: bilateral hippocampal CA1 region brain stereotaxic injection of LPS
Fixing The prone position of a mouse anesthetized by isofradane on a Brain stereotaxic apparatus, selecting a bilateral hippocampal CA1 area of The mouse as an injection area according to The theory of The mouse Brain, positioning The injection area 2.2mm behind bregma (Y), releasing 2mm of a left middle line and a right middle line (X), vertically drilling a small hole in a dental drill, vertically inserting a microinjector, injecting LPS after leaving a needle for 5min, leaving The needle for 5min after injection, and slowly withdrawing The needle. End up
Then, an absorbable suture line is used for aseptic suture, then, erythromycin ointment is used for smearing wounds for sealing, infection is prevented, meanwhile, an infrared physiotherapy lamp is used for irradiating for 3-5 hours to relieve pain, and the body temperature is kept constant.
3. Group administration
A: normal group (or normal control group), B: sham group (same volume of saline injection), C: a model group; d: triptolide liposome low dose group (64 μ g/kg, i.e. the amount of triptolide in triptolide liposome determined according to the weight of the mouse), E: triptolide liposome medium dose group (96 μ g/kg), F: triptolide liposome high dose groups (128 μ g/kg), 10 each group, using 10 μ L pipette to absorb 10 μ L of drug solution, holding the mice in supine position, carefully and slowly dropping on the left nostril, after breathing and inhaling, putting down free movement and dosing the next mouse, after the left dosing of all mice is finished, dosing on the right side, 20 μ L/time, twice a day, namely 40 μ L/day, and continuously dosing for 21 d.
4. Detection of the water maze: and (3) administering the drug at 15d for water maze training, taking the first 5d as a training period, putting the mouse into the water maze for free swimming for 1min from 4 different quadrants, recording the escape latency time, removing the platform at 6d, putting the mouse into the water maze from the opposite side of the platform, and recording the time occupied in the platform area and the times of passing through the platform.
5. Measurement of mRNA expression amount extracted after homogenization of hippocampus and cortex of mouse
5.1 extraction of Total RNAs: firstly, killing a mouse after anesthesia, taking out a complete brain, placing the complete brain on an ice box, cutting the left brain and the right brain, and separating a hippocampus and a cortex mark liquid nitrogen for freezing and storing for later use; secondly, taking a proper amount of cortex or hippocampus in an enzyme-free centrifuge tube, adding Trizol, and fully grinding and homogenizing; thirdly, adding 200uL of chloroform solution, covering the sample tube cover tightly, shaking for 15 seconds with force, and standing for 10-15min at room temperature; centrifugation in a refrigerated centrifuge at 12000rpm for 10min, carefully removing the three layered lysis mixture with the RNA in the supernatant, carefully aspirating and transferring to a clean EP tube (taking care not to aspirate the middle white floc); adding 500uL isopropanol, mixing, standing at room temperature for 10min, centrifuging at 4 ℃ at 12000rpm for 10min to obtain white precipitate of visible gel attached to the bottom of the EP tube, and collecting RNA; sixthly, discarding the supernatant, adding 1mL of 75% ethanol, shaking and uniformly mixing, washing the precipitate, centrifuging at 4 ℃ and 5000rpm for 5min, discarding the supernatant, and drying the RNA precipitate. And seventhly, adding a proper amount of DEPC water, dissolving the precipitate, and detecting the concentration and the purity of the RNA.
5.2 reverse transcription of RNA, using Biyuntian reverse transcription kit, according to the instructions.
5.3 quantitative analysis of mRNA, detection using appodibiosystems kit:
the relative expression level of the target mRNA/GAPDHmRNA was used as the relative content of the target mRNA in each group.
6. Statistical analysis
Data were processed using GraphPad Prism 6.0 statistical software and the results were analyzed using mean ± standard deviation (mean ± SD) for the data, with P <0.05 being statistically significant.
Third, experimental results
1. Behavioral water maze test, as shown in table 1-table 2;
note: in comparison with the normal group,*P<0.05，***P<0.001，****P<0.0001. for each of the models, compared to the model set,#P<0.05，##P<0.01，###P<0.001，####P<0.0001。
TABLE 1 escape latency table for 5 days before mice in each group
TABLE 2 comparison of spatial exploration Capacity of groups of mice
2. The relative amounts of inflammation-associated target mRNA in the cortex and hippocampus of each group of mice are shown in tables 3-6.
Note: compared with the normal control group, the composition has the advantages that,*P<0.05，***P<0.001，****P<0.0001. for each of the models, compared to the model set,#P<0.05，##P<0.01，###P<0.001，####P<0.0001。
TABLE 3 relative TNF-. alpha.mRNA levels in hippocampus and cortex of groups of mice
TABLE 4 relative IL-1. beta. mRNA content in hippocampus and cortex of mice in each group
TABLE 5 relative IL-6mRNA content in hippocampus and cortex of mice in each group
TABLE 6 relative content of COX-2mRNA in hippocampus and cortex of each group of mice
The experiments of the invention in examples 2-3 according to the above experimental method all achieve the same or similar results, which are not listed here.
Third, conclusion
The stereotactic injection of lipopolysaccharide in brain is a common model causing behavior cognitive disorder, the expression level of inflammation related indexes such as TNF-alpha, IL-1 beta and the like in cerebral cortex and hippocampus can reflect the degree of inflammation, and the learning and memory ability of water maze detection space position sense and direction sense can reflect the cognitive degree. In the experimental result, compared with a control group, the expression level of inflammation related indexes of the model group is obviously increased, and the escape latency period of 5 days before the water maze is not shortened, which indicates that the modeling is successful. Compared with a model group, the levels of relevant inflammation indexes of the triptolide liposome groups with different dosages are obviously reduced, and the triptolide liposome groups show dose dependence, which shows that the triptolide liposome can obviously inhibit the reaction of the cerebral neuritis, relieve the behavior cognition disorder induced by lipopolysaccharide, have certain protection effect on nerve cells, obviously shorten the escape latency 5 days before the water maze, increase the times of platform crossing, combine the structure advantages of the liposome and the nasal administration route, have the application prospect of developing the medicaments for the behavior cognition disorder related diseases caused by the cerebral neuritis, are innovations on the medicaments for preventing and treating the cognition disorder, develop a new way for treating the cognition disorder, and have huge social and economic benefits.
Sequence listing 1
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Application of thunder god vine extract liposome in preparation of medicine for preventing and treating behavior cognitive disorder induced by lipopolysaccharide by nasal administration
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Claims (3)
1. An application of liposome containing radix Tripterygii Wilfordii extract in preparing medicine for preventing and treating behavior cognitive disorder induced by lipopolysaccharide by nasal administration is provided.
2. The use of the liposome of extracted tripterygium wilfordii of claim 1 in the preparation of a medicament for nasal administration for the prevention and treatment of lipopolysaccharide-induced behavioral cognitive impairment, wherein the extracted tripterygium wilfordii component is tripterygium wilfordii polyglycoside, triptolide, or tripterine.
3. The method for preparing the liposome of the extracted components of thunder god vine according to claim 1, characterized by comprising the following steps:
(1) weighing the following components in parts by weight: ultrasonically dissolving 40 parts of soybean lecithin, 10 parts of cholesterol and 1 part of tripterygium wilfordii extract by using an organic solvent dichloromethane for 5-10min, and performing rotary reduced pressure evaporation for 20min at 20rpm in a constant-temperature water bath at 40 ℃ to obtain a uniform lipoid film;
(2) drying the lipoid film for 4 hours in vacuum, adding 25000 parts by weight of phosphate buffer PBS (phosphate buffered saline) in volume ratio, stirring for 4 hours at normal temperature, placing the mixture in 100w ultrasound for 5 minutes, then sequentially passing the mixture through 200nm and 100nm filter membranes by using a manual squeezer, carrying out secondary ultrafiltration by using a 50000MWCO ultrafiltration tube, and taking supernatant, namely the tripterygium wilfordii extract component liposome;
the weight to volume ratio is solid in g and liquid in ml.
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| CN115154422A (en) * | 2022-07-28 | 2022-10-11 | 四川大学 | CD44 targeting and ROS responding nano micelle medicine composition, preparation method and application |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101239040A (en) * | 2008-03-11 | 2008-08-13 | 中国药科大学 | Celastrol liposome and preparation thereof |
| CN103462898A (en) * | 2013-08-06 | 2013-12-25 | 南京中医药大学 | Breast cancer treatment triptolide liposome preparation and preparation method thereof |
| CN105125493A (en) * | 2015-09-11 | 2015-12-09 | 华侨大学 | Preparation method for triptolide nano-liposome |
| CN105816428A (en) * | 2016-04-29 | 2016-08-03 | 福建省医学科学研究院 | Triptolide nano-liposome and preparation method thereof |
| CN107149593A (en) * | 2017-04-11 | 2017-09-12 | 中国人民解放军第三医院八临床部 | Celastrol flexible lipidosome, gel and preparation method thereof |
| CN107899022A (en) * | 2017-12-07 | 2018-04-13 | 深圳市老年医学研究所 | A kind of stealth Brain targeting triptolide nano liposomes and preparation method |
| CN108186574A (en) * | 2018-03-01 | 2018-06-22 | 燕山大学 | A kind of triptolide liposome of platinum-gold nano ball shell cladding and preparation method thereof |
-
2021
- 2021-01-25 CN CN202110096110.2A patent/CN113143985A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101239040A (en) * | 2008-03-11 | 2008-08-13 | 中国药科大学 | Celastrol liposome and preparation thereof |
| CN103462898A (en) * | 2013-08-06 | 2013-12-25 | 南京中医药大学 | Breast cancer treatment triptolide liposome preparation and preparation method thereof |
| CN105125493A (en) * | 2015-09-11 | 2015-12-09 | 华侨大学 | Preparation method for triptolide nano-liposome |
| CN105816428A (en) * | 2016-04-29 | 2016-08-03 | 福建省医学科学研究院 | Triptolide nano-liposome and preparation method thereof |
| CN107149593A (en) * | 2017-04-11 | 2017-09-12 | 中国人民解放军第三医院八临床部 | Celastrol flexible lipidosome, gel and preparation method thereof |
| CN107899022A (en) * | 2017-12-07 | 2018-04-13 | 深圳市老年医学研究所 | A kind of stealth Brain targeting triptolide nano liposomes and preparation method |
| CN108186574A (en) * | 2018-03-01 | 2018-06-22 | 燕山大学 | A kind of triptolide liposome of platinum-gold nano ball shell cladding and preparation method thereof |
Non-Patent Citations (7)
| Title |
|---|
| 国家药典委员会: "《中华人民共和国药典临床用药须知 中药饮片卷》", 30 September 2017, 中国医药科技出版社 * |
| 李红茹 等: "雷公藤复杂提取物脂质体的制备及稳定性研究", 《中国中药杂志》 * |
| 林宁: "《生物药剂学与药物动力学》", 30 June 2017, 中国医药科技出版社 * |
| 潘卫三: "《工业药剂学》", 31 August 2015, 中国医药科技出版社 * |
| 郭毅 等: "雷公藤多苷类脂质体贴剂透皮机制及抗炎作用评价", 《西北药学杂志》 * |
| 阙慧卿 等: "雷公藤内酯醇纳米脂质体温敏凝胶的制备与鼻腔黏膜渗透性考察", 《中草药》 * |
| 马永兴 等: "《衰老、痴呆与预防医学新进展》", 30 June 2016, 科学技术出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115154422A (en) * | 2022-07-28 | 2022-10-11 | 四川大学 | CD44 targeting and ROS responding nano micelle medicine composition, preparation method and application |
| CN115154422B (en) * | 2022-07-28 | 2023-07-07 | 四川大学 | CD44 targeting and ROS response nano micelle pharmaceutical composition, and preparation method and application thereof |
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