CN107519485A - Non- full closed bovine serum albumin(BSA) hydroxyapatite nano particle preparation technology - Google Patents
Non- full closed bovine serum albumin(BSA) hydroxyapatite nano particle preparation technology Download PDFInfo
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- CN107519485A CN107519485A CN201710995112.9A CN201710995112A CN107519485A CN 107519485 A CN107519485 A CN 107519485A CN 201710995112 A CN201710995112 A CN 201710995112A CN 107519485 A CN107519485 A CN 107519485A
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- bsa
- serum albumin
- bovine serum
- nano particle
- hydroxyapatite nano
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/38—Albumins
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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
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5115—Inorganic compounds
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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
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
-
- 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
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5192—Processes
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Optics & Photonics (AREA)
- Nanotechnology (AREA)
- Physics & Mathematics (AREA)
- Inorganic Chemistry (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract
Present invention relates to non-full closed bovine serum albumin(BSA) hydroxyapatite nano particle preparation technology, comprise the following steps:Step 1:By bovine serum albumin(BSA) hydroxyapatite nano particle is dry, to air-dry into powder standby;Step 2:Bovine serum albumin(BSA) hydroxyapatite nano particle powder is uniformly dispersed, it is laid in smooth bright and clean and enough surface strength plane, another smooth bright and clean and enough hardness surface is pressed on bovine serum albumin(BSA) hydroxyapatite nano particle powder again and pressurizeed, adjust moulding pressure, then macromolecule polymer solution is added dropwise around bovine serum albumin(BSA) hydroxyapatite nano particle powder dropwise, wetting, keeps under normal temperature being vented to volatilization and finishes.
Description
Technical field
Present invention relates to non-full closed bovine serum albumin(BSA)-hydroxyapatite nano particle preparation technology.
Background technology
Drug sustained release system is an important research direction of pharmaceutical field, its advanced subject as pharmaceutical preparation subject
By the extensive concern of pharmaceutical industry.Hydroxyapatite is a kind of porous inorganic material, because it has excellent biofacies
Capacitive and the high-affinity with protein molecule, have been widely used for albumen sustained-release drug carrier.A variety of sides are used in recent years
The hydroxyapatite nano particle of method synthesis has the advantages that solubility is higher, surface energy is larger, bioactivity is good.With hydroxyl phosphorus
Lime stone nano-particle is carrier, and stripped serum albumin has simultaneously investigated the factor for influenceing its absorption, while have studied hydroxy-apatite
The release rule in vitro of stone nano-particle-bovine serum albumin(BSA) compound system, so as to for hydroxyapatite nano particle as egg
White slow releasing carrier of medication provides theoretical foundation.
Synthesize the hydroxyapatite particle of nano-scale and it is characterized, have studied bovine serum albumin(BSA) as pattern
Albumen explores the factor for influenceing its absorption while determines hydroxyapatite and receive to the adsorbance of hydroxyapatite nano particle
The vitro release of rice corpuscles-bovine serum albumin(BSA) compound.Test result indicates that:Hydroxyapatite nano particle being capable of conduct
The carrier of protide slow releasing pharmaceutical.
Research finds that the release behavior of medicine can be by microballoon outer surface, the parent of modified high molecular polymer covering layer
Hydrophobicity and thickness control.Hydrophilic and hydrophobic such as PEG-PLA is different and different because of the two molecular weight, therefore can be by using
The release behavior of PEG-PLA clads control medicine with different molecular weight.
But the release behavior of polymer covering layer control medicine is by polymer concentration, molecular weight, coating thickness etc.
The influence of many factors, therefore, in laboratory needing to find a kind of can quickly adjust releasing for polymer covering layer control medicine
The method for putting speed, in favor of studying under different pharmaceutical rate of release, embed the property of the nano polylactic acid particle of taxol.
The content of the invention
In view of this, in order to solve the above problems, the present invention provides a kind of non-full closed bovine serum albumin(BSA)-hydroxy-apatite
Stone nano-particle preparation technology.
Non- full closed bovine serum albumin(BSA)-hydroxyapatite nano particle preparation technology, comprises the following steps:
Step 1:By bovine serum albumin(BSA)-hydroxyapatite nano particle is dry, to air-dry into powder standby;
Step 2:Bovine serum albumin(BSA)-hydroxyapatite nano particle powder is uniformly dispersed, is laid in smooth bright and clean and surface
In the enough planes of intensity, then another smooth bright and clean and enough hardness surface is pressed in bovine serum albumin(BSA)-hydroxy-apatite
Pressurizeed in stone nanoparticle powder, adjust moulding pressure, then dropwise in bovine serum albumin(BSA)-hydroxyapatite nano
It is added dropwise macromolecule polymer solution around particle powder, wetting keeps under normal temperature being vented to volatilization and finished.
Further, in step 2, after the volatilization of first time macromolecule polymer solution, repeat that polyphosphazene polymer is added dropwise
Polymer solution is to being covered to complete.
Further, planar pressing surfaces are made from diamond, ceramics or glass, but hard alloy can not be used to make.
Further, planar pressing surfaces Mohs' hardness is more than 6.0.
High molecular polymer clad is fine and close and surface porosity, when the speed of its release internal drug is wrapped up with it
Use the concentration of solution(Molecular weight)It is relevant with integument thickness.In order to obtain the integument of different rate of release, conventional art
Need to adjust solution molecule amount or repeatedly be repeatedly carried out wrapping up.Often obtain once the integument of different rate of release, it is necessary to
Carry out the once complete technique from drug-carried fine particle to outer layer covers.It is and undesirable(Rate of release)Experiment product can only
Abandon, lose time and medicine.And the additive of solution is poisonous when wrapping up(Chloroform), bag is adjusted using multiple parcel
The technique of covering layer thickness, it is dangerous to experimenter., only need to be in step after technique using the pressurized control rate of release of the application
Moulding pressure size is adjusted in rapid 2, you can quick regulation integument rate of release.When the parcel for needing to configure different rate of release
During layer, it is only necessary to make bovine serum albumin(BSA)-hydroxyapatite nano particle powder in a collection of step 4, then in step 2
It is unified only to wrap up a macromolecule polymer solution using different moulding pressures(Now solution is only using once)It can make
Go out the integument of different rate of release.
After the nano polylactic acid particle of high molecular polymer cladding embedding taxol, the polylactic acid nano of taxol is embedded
Particle structure is spherical, and it combines closely from each other after pressurization, and surface is overlapping from each other, overlapping degree and plus
Pressure pressure is substantially linear.After infiltration is in macromolecule polymer solution, the underlapped surface of microballoon superscribes high score
Sub- polymeric layer, overlapping surface are not wrapped up.After air-drying, form surface and be uneven, it is local to wrap up high molecular polymer
Layer, the local microballoon for not wrapping up high polymer layer.The drug releasing rate and high polymer layer solution point of the microballoon
Son amount and microsphere surface parcel degree are relevant.When constant of high polymer layer solution molecule amount, drug releasing rate only with
Moulding pressure(Microsphere surface is in pressurization, overlapping degree from each other)It is relevant.Therefore by the technical program, in laboratory
The rate of release of high molecular polymer clad control medicine can quickly be adjusted so that research is in different pharmaceutical rate of release
Under, embed the property of the nano polylactic acid particle of taxol.
Brief description of the drawings
Fig. 1 is the structural representation of the present invention.
Embodiment
1. hydroxyapatite nano particle synthesizes
Hydroxyapatite nano particle presses document(Narasaraju T S B , Phebe D E. Some physico-
chemi-cal aspect s of hydroxylapatite[J] . Journal of Materi-al Science ,
1996 , 31 (1) : 1-21.)Synthesized in aqueous phase.The p H values of Ca (NO3) 2 and N H4 H2 PO4 solution are used
Ammoniacal liquor is adjusted to more than 10, then 2 kinds of solution are mixed according to calcium phosphorus metering ratio for 1. 67, and reaction terminates through centrifuging, sinking
Form sediment, it is 7 to be washed with deionized to p H values, then is washed with n-butanol, is deposited in 80 DEG C of drying, and in 500 DEG C of calcium
Change 5 h.
2. protein adsorption
Precision weighs 20mg hydroxyapatite nano particles and is placed in 5ml protein solutions, and 1 h is stirred at room temperature.After centrifugation,
With the content of protein solution in spectrophotometry supernatant, so as to determine protein adsorption quantity.
By bovine serum albumin(BSA)-hydroxyapatite nano particle powder air-dry after be uniformly dispersed, be laid in it is smooth bright and clean and
In the enough planes of surface strength, then another smooth bright and clean and enough hardness surface is pressed in bovine serum albumin(BSA)-hydroxyl
Pressurizeed on phosphorite nano particle powder, adjust moulding pressure, then dropwise in bovine serum albumin(BSA)-hydroxyapatite
It is added dropwise macromolecule polymer solution around nanoparticle powder, wetting keeps under normal temperature being vented to solution evaporation and finished.
Such as Fig. 1, kernel 1 is bovine serum albumin(BSA)-hydroxyapatite nano particle, PEG and PLA-PEG integuments 2 because
Squeezed tight from each other during parcel, so as to cause deep mixed breach 21 on the surface of integument 2.And single nanometer cow's serum
Albumin-some parts of hydroxyapatite nano particle surface are enclosed with PEG and PLA-PEG clads 2, some parts 22 are not wrapped
Wrap up in PEG and PLA-PEG clads 2.
Claims (4)
1. non-full closed bovine serum albumin(BSA)-hydroxyapatite nano particle preparation technology, comprises the following steps:
Step 1:By bovine serum albumin(BSA)-hydroxyapatite nano particle is dry, to air-dry into powder standby;
Step 2:Bovine serum albumin(BSA)-hydroxyapatite nano particle powder is uniformly dispersed, is laid in smooth bright and clean and surface
In the enough planes of intensity, then another smooth bright and clean and enough hardness surface is pressed in bovine serum albumin(BSA)-hydroxy-apatite
Pressurizeed in stone nanoparticle powder, adjust moulding pressure, then dropwise in bovine serum albumin(BSA)-hydroxyapatite nano
It is added dropwise macromolecule polymer solution around particle powder, wetting keeps under normal temperature being vented to volatilization and finished.
2. non-full closed bovine serum albumin(BSA)-hydroxyapatite nano particle preparation technology as claimed in claim 1, its feature
For:In step 2, after the volatilization of first time macromolecule polymer solution, repeat to be added dropwise macromolecule polymer solution to cladding
Complete.
3. non-full closed bovine serum albumin(BSA)-hydroxyapatite nano particle preparation technology as claimed in claim 2, its feature
For:Planar pressing surfaces are made from diamond, ceramics or glass, but hard alloy can not be used to make.
4. non-full closed bovine serum albumin(BSA)-hydroxyapatite nano particle preparation technology as claimed in claim 3, its feature
For:Planar pressing surfaces Mohs' hardness is more than 6.0.
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CN201710995112.9A CN107519485A (en) | 2017-10-23 | 2017-10-23 | Non- full closed bovine serum albumin(BSA) hydroxyapatite nano particle preparation technology |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110772485A (en) * | 2019-11-18 | 2020-02-11 | 上海交通大学 | Bovine serum albumin/hydroxyapatite composite nano drug-loaded particle as well as preparation method and application thereof |
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2017
- 2017-10-23 CN CN201710995112.9A patent/CN107519485A/en not_active Withdrawn
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110772485A (en) * | 2019-11-18 | 2020-02-11 | 上海交通大学 | Bovine serum albumin/hydroxyapatite composite nano drug-loaded particle as well as preparation method and application thereof |
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Application publication date: 20171229 |