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 PDF

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Publication number
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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China
Prior art keywords
bsa
serum albumin
bovine serum
nano particle
hydroxyapatite nano
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CN201710995112.9A
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Chinese (zh)
Inventor
顾炎
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Xishan District Donggang Xiaoming Electronic Product Management Department
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Xishan District Donggang Xiaoming Electronic Product Management Department
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Priority to CN201710995112.9A priority Critical patent/CN107519485A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/38Albumins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules 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
    • A61K9/51Nanocapsules; Nanoparticles
    • A61K9/5107Excipients; Inactive ingredients
    • A61K9/5115Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules 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
    • A61K9/51Nanocapsules; Nanoparticles
    • A61K9/5107Excipients; Inactive ingredients
    • A61K9/513Organic macromolecular compounds; Dendrimers
    • A61K9/5146Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules 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
    • A61K9/51Nanocapsules; Nanoparticles
    • A61K9/5192Processes

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • 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)
  • Medicinal Preparation (AREA)

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

Non- full closed bovine serum albumin(BSA)-hydroxyapatite nano particle preparation technology
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.
CN201710995112.9A 2017-10-23 2017-10-23 Non- full closed bovine serum albumin(BSA) hydroxyapatite nano particle preparation technology Withdrawn CN107519485A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
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

Cited By (1)

* Cited by examiner, † Cited by third party
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