CN110339180A - A kind of anti-inflammatory targeted delivery systems and preparation method thereof - Google Patents
A kind of anti-inflammatory targeted delivery systems and preparation method thereof Download PDFInfo
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- CN110339180A CN110339180A CN201910740365.0A CN201910740365A CN110339180A CN 110339180 A CN110339180 A CN 110339180A CN 201910740365 A CN201910740365 A CN 201910740365A CN 110339180 A CN110339180 A CN 110339180A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5063—Compounds of unknown constitution, e.g. material from plants or animals
- A61K9/5068—Cell membranes or bacterial membranes enclosing drugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Abstract
The invention discloses a kind of anti-inflammatory targeted delivery systems and preparation method thereof.Anti-inflammatory targeted delivery systems of the invention include platelet-derived vesica and the anti-inflammatory drug for being loaded in platelet-derived vesica or being attached to platelet-derived vesicle surface, and the blood platelet after platelet-derived vesica is activated by ultracentrifugation obtains.Anti-inflammatory targeted delivery systems of the invention are prepared by blood platelet, do not include any artificial synthesized macromolecule or other materials, and biological safety is high.Platelet-derived vesica can be obtained by activated blood platelet one-step method, and separating technology is simple, and operating procedure is simple, and from a wealth of sources.Furthermore, blood platelet has inherent affinity to inflammation part, including atherosclerotic plaque, and the targeted delivery systems property of can choose in blood platelet source combine various kinds of cell type, relevant endothelial cell is formed such as macrophage and to atherosclerotic plaque, thus anti-inflammatory drug can be delivered to inflammation part using this targeted delivery systems.
Description
Technical field
The present invention relates to a kind of anti-inflammatory targeted delivery systems and preparation method thereof, belong to pharmaceutical carrier preparation technical field.
Background technique
The main reason for cardiovascular disease (Cardiovascular disease, CVD) is still the death rate and disease incidence.
Atherosclerosis (Atherosclerosis, AS) is the pathologic basis of cardiovascular disease, is a kind of chronic inflammation disease,
It is characterized in that local immunity response function obstacle.There are still dispute and X factors for the pathogenesis of atherosclerosis.Facing
In bed practice, the traditional treatment of atherosclerosis disease includes the drug or percutaneous coronary for reducing cholesterol and blood coagulation
The surgical operations such as interventional therapy.However, there are adverse reactions for these therapeutic treatments, and it is concentrated mainly on and alleviates symptom rather than subtract
Few potential atherosclerosis, therefore, it is necessary to develop more effective antiatherosclerosis strategy.
It has recently been demonstrated that inflammation plays an important role in atherosclerosis.Vascular inflammation has been found and artery
The acceleration of atherosis complication is closely related.For example, the downstream biomarker of pro-inflammatory signals access, is such as tied containing pyrin
The signaling pathway protein matter 3 (NLRP3) in structure domain, high-sensitive C-reactive protein and interleukin-1 ' beta ' (IL-1 β) and cardiovascular risk
Increase it is closely related, it is unrelated with cholesterol levels.2017, Canakinumab was that mankind's anti-il-i-beta monoclonal antibody can neutralize
IL-1 signal beta has shown that lower cardiovascular (CV) event in clinical test, has started anti-inflammatory treatment atherosclerosis
New era.In spite of prospect, but still need to improve curative effect, while reducing side effect.Carrying out treatment for inflammation is still one big
Challenge, it is still necessary to further develop the targeted delivery systems for adjusting atherosclerosis local inflammation microenvironment.
Have the report of multiple anti-inflammatory targeted delivery systems for animal model, such as Thijs J.Beldman at present
People uses hyaluronic acid as anti-inflammatory targeted delivery systems, and atherosclerosis correlation is inquired by using the sodium hyaluronate grain of rice
Inflammation, improve atherosclerosis.Diana Dehaini et al. erythrocyte membrane and platelet membrane packet PLGA are as anti-
Scorching targeted delivery systems.It can be seen that most of anti-inflammatory targeted delivery systems use synthetic material at present, or need to carry out
Chemical modification, technique is relative complex, and the biochemical reaction and catabolite participated in vivo is often not clear enough, these are all
Clinic conversion facing challenges.Therefore, larger to the potential risk of human health.Therefore, it using chemical substance modification or will form
When the anti-inflammatory targeted system closed is used for human body, the safety used is the largest problem.
In addition, the defect of the method for existing platelet membrane packet PLGA includes that extraction separating step is cumbersome, needs to extract, divide
From macromolecule PLGA nano grain surface is modified after platelet membrane again, complex steps are complicated, with high costs, limit its into
The clinical application of one step.
Summary of the invention
In order to solve the above technical problems, the present invention provides a kind of anti-inflammatory targeted delivery systems, it is prepared by blood platelet,
Not comprising any artificial synthesized macromolecule or other materials, biological safety is high.Platelet-derived vesica can be small by activation blood
Plate one-step method obtains, and separating technology is simple, and operating procedure is simple, and from a wealth of sources.In addition, blood platelet has inflammation part
Inherent affinity, including atherosclerotic plaque, and the targeted delivery systems property of can choose in blood platelet source combine
Various kinds of cell type forms relevant endothelial cell such as macrophage and to atherosclerotic plaque, thus utilizes this targeting
Anti-inflammatory drug can be delivered to inflammation part by delivery system.
The first purpose of the invention is to provide a kind of anti-inflammatory targeted delivery systems, the anti-inflammatory targeted delivery systems packet
It includes platelet-derived vesica and is loaded in the platelet-derived vesica or is attached to the platelet-derived vesica table
The anti-inflammatory drug in face, the blood platelet after the platelet-derived vesica is activated by ultracentrifugation obtain.
Further, the partial size of the platelet-derived vesica is 100-10000nm.
Further, the anti-inflammatory drug is hydrophily or hydrophobic small molecule anti-inflammatory drug.In some cases,
Small molecule compound is active small molecular drug.
Further, the anti-inflammatory drug is MCC950, auranofin, in TAK-242, bromoxone, curcumin
One or more kinds of combinations.
Further, the blood platelet is from the self or consistent donor of blood group.
A second object of the present invention is to provide the preparation methods of the anti-inflammatory targeted delivery systems, including walk as follows
It is rapid:
(1) it disperses the blood sample containing blood platelet in the buffer containing platelet aggregation inhibitor, in 50-
150g is centrifuged to supernatant and clarifies, and removes red blood cell and leucocyte, obtains the supernatant for containing only blood platelet；
(2) anti-inflammatory drug is uniformly mixed with the blood platelet that step (1) obtains, then carries out platelet activation；
(3) blood platelet after step (2) activation is centrifuged 15-25min in 600-1000g, collects supernatant；
(4) supernatant for collecting step (3) carries out ultracentrifugation at least 2 500g revolving speeds, collects precipitating, obtains institute
The anti-inflammatory drug targeted delivery systems stated.
Further, further include the steps that purifying blood platelet after step (1): step (1) be collected upper
Clear liquid is centrifuged in 600-1000g, collects pellet platelets, and the buffer washing containing the anticoagulant inhibitor of blood platelet is added, and is washed
It is centrifuged after washing in 600-1000g, collects precipitating, be platelet purification.When in use, it is resuspended using buffer.
Further, the platelet activation passes through addition platelet activation inducer activation.
Further, the platelet activation inducer includes fibrin ferment, collagen, thrombospondin, ADP, blood
One of bolt element A2 or more than one combinations.
Further, in step (4), the ultracentrifugal time is at least 30min.
Further, one or more platelet suppressant drugs are provided in Xiang Suoshu sample, in the platelet suppressant drug
At least one is prostaglandin H 1.
Further, in step (3), the anti-inflammatory drug and platelet purification are mixed according to 1:1 ratio is higher than
It closes.
Further, in step (1), the buffer is PBS buffer solution.
The beneficial effects of the present invention are:
Anti-inflammatory targeted delivery systems of the invention, are prepared by blood platelet.Since blood platelet is from organism, because
This blood platelet is can to take part in intracorporal metabolism with complete biodegradable, without toxic side effect, thus derives from blood platelet
Platelet-derived vesica also there is good biocompatibility.The platelet-derived vesica obtained does not include any artificial synthesized
Macromolecule or other materials, using anti-inflammatory targeted delivery systems of the invention without using heterologous or polylactic acid glycolic acid
(PLGA) etc. for synthetic materials substance as anti-inflammatory targeted delivery vector, biological safety is high.In addition, present invention process is simple
Single, without extracting platelet membrane, platelet-derived vesica is very easy to obtain, and blood platelet can derive from patient itself or source
In the consistent donor of blood group, platelet-derived vesica can be obtained by activated blood platelet one-step method, and separating technology is simple, operation
Step is simple.In addition, blood platelet has inherent affinity to inflammation part, the cardiovascular disease such as including atherosclerotic plaque
Disease, and the targeted delivery systems property of can choose in blood platelet source combine inflammation activation cell type, as macrophage is thin
Born of the same parents and relevant endothelial cell is formed to atherosclerotic plaque, thus can be by anti-inflammatory drug using this targeted delivery systems
It is delivered to inflammation part.
Detailed description of the invention
Fig. 1 is the microscope inspection figure of platelet-derived vesica of the invention；
Fig. 2 is the grain size distribution of platelet-derived vesica of the invention；
Fig. 3 is the change of size figure of platelet-derived vesica of the invention in different solutions；
Fig. 4 is the electrophoretic analysis figure of platelet-derived vesica of the invention, blood platelet；
Fig. 5 is the Western Blot result figure of platelet-derived vesica of the invention, blood platelet；
Fig. 6 is the inflammatory factor figure of platelet-derived vesica of the invention, secretion of platelet；
Fig. 7 is that platelet-derived vesica of the invention targets macrophage figure；
Fig. 8 is that platelet-derived vesica of the invention targets endothelial cell figure；
Fig. 9 is that small animal imaging figure is targeted in platelet-derived vesica body of the invention；
Figure 10 is that histotomy of the invention is total to focused view；
Figure 11 is anti-inflammatory composition MCC950 UV absorption figure of the invention；
Figure 12 is anti-inflammatory composition MCC950 elution profiles of the invention；
Figure 13 is that anti-inflammatory composition of the invention expresses figure to macrophage IL-1 β；
Figure 14 is that anti-inflammatory composition Human Umbilical Vein Endothelial Cells IL-1 β of the invention expresses figure；
Figure 15 is anti-inflammatory composition of the invention to macrophage NLRP3 expression figure；
Figure 16 is anti-inflammatory composition Human Umbilical Vein Endothelial Cells NLRP3 expression figure of the invention；
Figure 17 is the HE colored graph that anti-inflammatory composition of the invention bends that Patch size is influenced on mouse aorta；
Figure 18 is anti-inflammatory composition of the invention to arch of aorta patch IL-1 β immunohistochemical staining figure；
Figure 19 is anti-inflammatory composition of the invention to arch of aorta patch Mac3 immunohistochemical staining figure；
Figure 20 is that anti-inflammatory composition of the invention expresses figure to blood inflammatory factor.
Specific embodiment
The present invention will be further explained below with reference to the attached drawings and specific examples, so that those skilled in the art can be with
It more fully understands the present invention and can be practiced, but illustrated embodiment is not as a limitation of the invention.
The C57BL/6 mouse and ApoE-KO mouse of 6-8 week old are purchased from this experimental animal Co., Ltd of Changzhou Cavan.Mouse
Operating method is instructed to be handled according to Chinese Academy of Sciences's biochemistry and the cell management of laboratory animal committee, institute (IACUC).
Mouse macrophage RAW264.7, endothelial cell HUVECs are purchased from American Type Culture collection (abbreviation
ATCC).RAW264.7 and HUVECs is in the streptomysin added with 10% fetal calf serum, 100U/ml penicillin and 100U/ml
Dulbecco improves preservation in Eagle culture medium.Using the cell of the third generation or forth generation secondary culture for of the invention each
Embodiment.
Embodiment 1: the extraction of blood platelet
Blood is taken out from C57BL/6 mouse orbit, is stored in the PBS containing 5mM EDTA and 1 μM of PGE1.100g from
15 minutes removal red blood cells of the heart repeat step until supernatant is clarified, and collection supernatant is simultaneously centrifuged 20 minutes with 800g；It will centrifugation
Sediment stores at room temperature, to further use after suspending again.
Embodiment 2: the extraction of platelet-derived vesica
After pellet platelets object is suspended again, the fibrin ferment of 2U/mL is added, is activated 30 minutes in 37 DEG C, then with 800g
Centrifugation 20 minutes collects supernatant and carries out the platelet-derived vesica of ultracentrifugation acquisition, dense with the rate of 2 500g (2 hours)
Shorten particle into, as platelet-derived vesica.
Embodiment 3: the qualitative analysis of platelet-derived vesica
The characterization that platelet-derived vesica is detected by transmission electron microscope (TEM), as a result as shown in Figure 1, diameter about 100-
150nm.The partial size of partial size and platelet-derived vesica in different solutions at any time is measured by dynamic light scattering (DLS) to become
Change, as a result such as Fig. 2, shown in Fig. 3, is stored at 4 DEG C in various buffers at least 4 days.In no platelet aggregation inhibitor
In the case where PGE1, the size of PVs does not have significant variation, shows the high stability of PVs.Extract blood platelet and platelet-derived capsule
After steeping albumen, protein analysis, knot are carried out to blood platelet and platelet-derived vesicle protein matter using PAGE gel electrophoresis
Fruit as shown in figure 4, can show that platelet-derived vesica contains the partially protein from blood platelet, however, losing height as a result,
The cytoplasmic protein matter of molecular weight, such as actin and myosin.
Western Blot detection technique is utilized later, and blood platelet and blood are separated by electrophoresis using 10% PAGE gel
Platelet derives vesicle protein, in transferring film to bifluoride resin film (pvdf membrane) after, carry out the incubation of primary antibody secondary antibody.Then it uses
600 hypersensitive Multifunctional imaging instrument of AMERSHAM IMAGER carries out development analysis to the content of CD41.As a result as shown in figure 5,
The presence of CD41 further demonstrates platelet-derived vesica actually from blood platelet.
Whether proinflammatory cytokine is discharged upon activation to measure platelet-derived vesica, is tried by Enzyme-linked Immunosorbent Assay
Test IL-1 β and the IL-6 expression in the supernatant of detection thrombin activation.As a result as shown in fig. 6, platelet-derived vesica regardless of
Proinflammatory factor is secreted, shows that platelet-derived vesica when as anti-inflammatory targeted delivery vector, does not generate side effect to body, as
The pharmaceutical carrier of inflammation treatment has good development prospect.
Embodiment 4: the targeting analysis of platelet-derived vesica
(1) targeting is analyzed
Blood platelet is dyed with DiD first, is collected after activated and obtains the platelet-derived vesica of DiD label.By macrophage
Cell oxidation LDL processing is allowed to be converted into foam cells, then by foam cells and the blood platelet or blood platelet with DiD label
Derivative vesica PVs is incubated for.As a result as shown in fig. 7, being observed by fluorescence imaging, compared with non-activated macrophage, blood is small
The derivative vesica PVs of plate shows higher affinity to foam cells.The blood platelet or platelet-derived vesica PVs of DiD label
It is incubated for altogether with through LPS processing Human umbilical vein endothelial cells, as a result as shown in figure 8, likewise, platelet-derived vesica targeted activation
Endothelial cell afterwards.In short, these results have strong parent in the main component for showing targeted delivery systems and atherosclerosis
And power, it can be used for drug targeting and be delivered to atherosclerotic plaque inflammatory microenvironment.
(2) targeting analysis in vivo
The platelet-derived vesica PVs that free DiD or DiD is marked, is injected intravenously into ApoE-KO mouse.Injection
6 hours afterwards, mouse is implemented to be euthanized.Heart and aorta are cut off for being imaged in vitro.As a result as shown in figure 9, what DiD was marked
Significant accumulation of the platelet-derived vesica in the rat aorta atherosclerotic lesion in ApoE-KO mouse.On the contrary, in free dye
Expect to detect seldom signal in the ApoE-KO mouse of processing.In addition, not showing PVs in aorta in wild-type mice
Accumulation, shows that targeting ability is caused by the macrophage as PVs and activation or the affinity between endothelium.In confocal fluorescent
The slice of atherosclerotic lesion is further checked under microscope, the results are shown in Figure 10.With free DiD processing or wild type
Mouse is compared, and the enrichment of platelet-derived vesica further demonstrates the target of platelet-derived vesica in atherosclerotic plaque
To ability.
Embodiment 5: the preparation of anti-inflammatory composition
Anti-inflammatory drug MCC950 is mixed with platelet purification and carries out total incubation 24 hours, 800g, which is centrifuged to obtain for 20 minutes, to sink
Starch, sediment are the blood platelet that MCC950 is loaded, and sediment is resuspended again, the fibrin ferment of 2U/mL is added, and are activated in 37 DEG C
30 minutes, then with 800g centrifugation 20 minutes, collect supernatant and carry out the platelet-derived of ultracentrifugation acquisition MCC950 loading
Vesica is condensed into particle with the rate of 100,000rpm (2 hours), as anti-inflammatory targeted delivery systems.
Embodiment 6: the qualitative analysis of anti-inflammatory composition
Using the ultraviolet absorption peak of UV absorption instrument measurement anti-inflammatory composition, as a result as shown in figure 11, MCC950 is absorbing
Characteristic absorption peak in spectrum shows that anti-inflammatory drug MCC950 is loaded successfully on platelet-derived vesica.
Load and release profiles using high performance liquid chromatography (HPLC) measurement MCC950, as a result as shown in figure 12, drug
Percentage load is about 15.3%, and slow release is presented in the release profiles of drug.
Embodiment 7: the antiphlogistic effects analysis of anti-inflammatory composition
(1) mitigate the therapeutic effect of inflammation in vitro
After macrophage and endothelial cell bed board culture, when cell is uniformly grown to 60%, original fluid is discarded, addition contains
The new culture solution of 100ng/mL LPS is separately added into same dose of anti-inflammatory drug MCC950, targeted delivery systems again after 1 hour
Platelet-derived vesica PVs, anti-inflammatory composition MCC950-PVs.Cell supernatant is collected after 24 hours detects inflammation using ELISA
The expression of sex factor IL-1 β.Cell protein is similarly extracted after 24 hours, is detected using Western Blot detection technique
The expression of NLRP3.As a result respectively as shown in figures 13-16, the macrophage and interior handled with LPS can be seen that by Figure 13-16
The a large amount of IL-1 β of skin cell secretion, and up-regulation NLRP3 expression.Opposite, it is significantly inhibited after anti-inflammatory agent or anti-inflammatory composition processing
IL-1 β and NLRP3 expression illustrate that anti-inflammatory composition of the invention has good antiphlogistic effects.
(2) mitigate the therapeutic effect of inflammation in vivo
ApoE-KO mouse high lipid food is fed 12 weeks, and the mouse that another normal diet is fed makees untreated control.It is high in fat
The mouse of forage feed receives 9 venoclysis PBS, anti-inflammatory drug MCC950 or anti-inflammatory composition MCC950- in 21 days
PVs, the MCC950 dosage of infusion application is 5mg/kg every time.All mouse were implemented to be euthanized in 24 hours after final infusion.Solution
Mouse aorta bow is taken, Quantitative Histology analysis has been carried out to the patch in the mouse aorta bow through various treatments.Artery
The cross section of atherosclerotic plaque carries out immunostaining with h and E (H&E), and to IL-1 β, Mac3 (macrophage).
As a result as in figs. 17-19, histological examination confirms that there are biggish patches in high lipid food nursing mouse untreated group.?
In treatment group, it has been found that receive the mouse intimal thickening and high cholesterol group and pure medicine of anti-inflammatory composition MCC950-PVs treatment
Significant reduction is compared in object treatment, and patch significantly reduces, and lesion also significantly reduces.It is worth noting that, anti-inflammatory composition
The therapeutic effect of MCC950-PVs is more preferable, it may be possible to higher due to having by targeted delivery systems targeted delivery in plaque site
MCC950 concentration.
The expression of inflammatory factor IL-1 β, IL-6 and TNF-α in peripheral blood are tested by ELISA.As a result such as Figure 20 institute
Show, the expression of proinflammatory cytokine is raised in IUGR high-fat diet group, on the contrary, in anti-inflammatory drug MCC950 or anti-inflammatory composition
In MCC950-PVs processing group, the significant decline of the secretion of proinflammatory factor.These are the result shows that anti-inflammatory composition of the invention also delays
Systemic inflammatory is solved.
Embodiment described above is only to absolutely prove preferred embodiment that is of the invention and being lifted, protection model of the invention
It encloses without being limited thereto.Those skilled in the art's made equivalent substitute or transformation on the basis of the present invention, in the present invention
Protection scope within.Protection scope of the present invention is subject to claims.
Claims (10)
1. a kind of anti-inflammatory targeted delivery systems, which is characterized in that the anti-inflammatory targeted delivery systems include platelet-derived capsule
Steep and be loaded in the platelet-derived vesica or be attached to the anti-inflammatory drug of the platelet-derived vesicle surface, institute
Blood platelet after the platelet-derived vesica stated is activated by ultracentrifugation obtains.
2. a kind of anti-inflammatory targeted delivery systems according to claim 1, which is characterized in that the platelet-derived vesica
Partial size be 100-10000nm.
3. a kind of anti-inflammatory targeted delivery systems according to claim 1, which is characterized in that the anti-inflammatory drug is hydrophilic
Property or hydrophobic small molecule anti-inflammatory drug.
4. a kind of anti-inflammatory targeted delivery systems according to claim 3, which is characterized in that the anti-inflammatory drug is
One of MCC950, auranofin, TAK-242, bromoxone, curcumin or more than one combinations.
5. a kind of preparation method of the described in any item anti-inflammatory targeted delivery systems of claim 1-4, which is characterized in that including such as
Lower step:
(1) disperse the blood sample containing blood platelet in the buffer containing platelet aggregation inhibitor, 50-150g from
The heart to supernatant is clarified, and red blood cell and leucocyte are removed, and obtains the supernatant for containing only blood platelet；
(2) anti-inflammatory drug is uniformly mixed with the blood platelet that step (1) obtains, then carries out platelet activation；
(3) blood platelet after step (2) activation is centrifuged 15-25min in 600-1000g, collects supernatant；
(4) supernatant for collecting step (3) carries out ultracentrifugation at least 2 500g revolving speeds, collects precipitating, obtains described
Anti-inflammatory drug targeted delivery systems.
6. according to the method described in claim 5, it is characterized in that, the platelet activation passes through addition in step (2)
The activation of platelet activation inducer.
7. according to the method described in claim 6, it is characterized in that, the platelet activation inducer includes fibrin ferment, glue
One of original, thrombospondin, ADP, thromboxane A2 or more than one combinations.
8. according to the method described in claim 5, it is characterized in that, the ultracentrifugal time is at least in step (4)
30min。
9. according to the method described in claim 5, it is characterized in that, before at least one of described platelet aggregation inhibitor is
Column parathyrine H1.
10. according to the method described in claim 5, it is characterized in that, in step (3), the anti-inflammatory drug and purifying blood
Platelet is mixed according to 1:1 ratio is higher than.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111110874A (en) * | 2019-11-14 | 2020-05-08 | 中国药科大学 | Radionuclide-labeled platelet membrane vesicle and preparation method and application thereof |
| CN111184684A (en) * | 2020-02-08 | 2020-05-22 | 苏州大学 | Erythrocyte gel delivery system and preparation method and application thereof |
| WO2021027425A1 (en) * | 2019-08-12 | 2021-02-18 | 苏州大学 | Anti-inflammatory targeted delivery system and preparation method therefor |
| CN112891317A (en) * | 2021-02-05 | 2021-06-04 | 东南大学 | Preparation method of platelet drug delivery system |
| WO2021126832A1 (en) * | 2019-12-16 | 2021-06-24 | North Carolina State University | Compositions and methods for delivering therapeutic antibodies using platelet-derived microparticles |
| WO2021154992A1 (en) * | 2020-01-28 | 2021-08-05 | Orgenesis Inc. | Process and system for acellular therapy |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10363226B2 (en) * | 2015-08-12 | 2019-07-30 | North Carolina State University | Platelet membrane-coated drug delivery system |
| EP3254684B1 (en) * | 2016-06-08 | 2019-10-23 | Lysatpharma GmbH | Human platelet lysate or fraction enriched in human platelet-derived extracellular vesicles, for use in medicine |
| EP3612193A4 (en) * | 2017-04-20 | 2020-12-30 | North Carolina State University | Platelet vesicle-engineered cells and extracellular vesicles for targeted tissue repair |
| CN108619114B (en) * | 2018-05-02 | 2020-08-11 | 东南大学 | Dexamethasone-loaded macrophage-derived microvesicle and preparation method and application thereof |
| CN110339180B (en) * | 2019-08-12 | 2020-10-09 | 苏州大学 | Anti-inflammatory targeted delivery system and preparation method thereof |
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2019
- 2019-08-12 CN CN201910740365.0A patent/CN110339180B/en active Active
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021027425A1 (en) * | 2019-08-12 | 2021-02-18 | 苏州大学 | Anti-inflammatory targeted delivery system and preparation method therefor |
| CN111110874A (en) * | 2019-11-14 | 2020-05-08 | 中国药科大学 | Radionuclide-labeled platelet membrane vesicle and preparation method and application thereof |
| WO2021126832A1 (en) * | 2019-12-16 | 2021-06-24 | North Carolina State University | Compositions and methods for delivering therapeutic antibodies using platelet-derived microparticles |
| WO2021154992A1 (en) * | 2020-01-28 | 2021-08-05 | Orgenesis Inc. | Process and system for acellular therapy |
| CN111184684A (en) * | 2020-02-08 | 2020-05-22 | 苏州大学 | Erythrocyte gel delivery system and preparation method and application thereof |
| CN111184684B (en) * | 2020-02-08 | 2022-08-30 | 苏州大学 | Erythrocyte gel delivery system and preparation method and application thereof |
| CN112891317A (en) * | 2021-02-05 | 2021-06-04 | 东南大学 | Preparation method of platelet drug delivery system |
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| CN110339180B (en) | 2020-10-09 |
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