CN107260686A - A kind of complex microsphere of double-layer circular spherical structure - Google Patents
A kind of complex microsphere of double-layer circular spherical structure Download PDFInfo
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- CN107260686A CN107260686A CN201710663241.8A CN201710663241A CN107260686A CN 107260686 A CN107260686 A CN 107260686A CN 201710663241 A CN201710663241 A CN 201710663241A CN 107260686 A CN107260686 A CN 107260686A
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- complex microsphere
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
- A61L2300/622—Microcapsules
Abstract
The invention discloses a kind of complex microsphere of double-layer circular spherical structure, it is made up of the concentric spheroid layer of outer layer and internal layer two.The small ball of outer layer that outer layer is mainly mainly distributed on 1 μm 3 μm by large number of grain size is constituted, and internal layer is mainly made up of diameter dimension interior layer spheroid cavity not of uniform size.The beneficial effects of the invention are as follows double-layer circular spherical structure complex microsphere, interface binding power is strong, adds the mechanical strength properties of micro-sphere material, meanwhile, double-layer circular spherical structure is conducive to decomposition in vivo to digest, and discharges the load medicine of complex microsphere internal layer.The mode of appearance of microballoon is also very good, and surface is smooth.The transmission of medicine and bioactive molecule is mainly used in, the microcarrier of Porcine HGF in osseous tissue renovating material and cell engineering can be also used in.
Description
Technical field
It is a kind of apply in bioengineering and field of medicaments specifically the present invention relates to a kind of Biofunctional materials
A kind of complex microsphere of double-layer circular spherical structure, belongs to materialogy field.
Background technology
After traditional approach intake medicine, most drug composition is released rapidly, causes people's vivo medicine concentration rapid
Rise, reach reduces rapidly after peak value, and violent fluctuation, which often causes, produces unacceptable side effect in peak value, then again
Cause therapeutic effect insufficient because the concentration of drug in blood serum is too low.In order to ensure internal necessary drug concentration, it can only adopt
With regular medicine taking or injection for several times on the one, and arranged on dosage and administration time interval.Nonetheless body
Interior blood concentration is still within fluctuation status.Oral administration is the approach of most universal and extensive release medicine, and it not only takes
With convenient, safety, it is often more important that, for those must even lifelong drug administration for a long time patient, such as diabetic,
It is orally most preferable and most easy received mode.But it is low also all to there is drug effectiveness, security in the administration of this traditional approach,
The low problem of patient's submissiveness, therefore, the research for drug delivery system is extremely more urgent.
Double-deck microballoon is with the particularity of its structure, the polytropy of performance, the popularity applied, in medicine, biomedical work
There is highly important effect in journey field.On the one hand it can pass through outer layer protection medicine as oral drugs carrier, into after people
Thing is not destroyed by hydrochloric acid in gastric juice etc., on the other hand, additionally it is possible to the contained medicine of slow release internal layer in enteron aisle, keeps blood concentration.
Therefore, a kind of drug bearing microsphere of double-decker for oral use is developed, is extremely necessary and with extensively using valency
Value.
The content of the invention
The technical problems to be solved by the invention are to provide a kind of double-deck drug bearing microsphere for oral use, above-mentioned in order to solve
Problem, the technical scheme is that：A kind of complex microsphere of double-layer circular spherical structure, is made up of outer layer and internal layer two parts.Its
It is characterised by：The complex microsphere is divided into outer layer and the concentric spheroid layer of internal layer two.The grain size of complex microsphere being capable of root
Produced according to demand, distribution is mainly selected between 200 μm -800 μm, but can also expand this particle size range to 0.1mm-
Between 1.5mm, that is, select 100 μm of particle size ranges between -200 μm, or 0.8mm-1.5mm, simply relatively difficult, output
Rate is low.The radius of sphericity size of internal layer is outer layer radius of sphericity size, that is, complex microsphere radius size 3/5-2/3 it
Between.That is outer layer spheroid has certain thickness, and can enter in human body has a digestion process, possesses in certain time
Inside play a part of protecting internal layer effect.Complex microsphere surface is shallow except surface of the diameter dimension between 15 μm -35 μm is distributed with
Outside pit, the surfacing of complex microsphere, this is conducive to oral smooth and internal flowing.The outer layer of complex microsphere is main
The small ball of outer layer for being mainly distributed on 1 μm -3 μm by large number of grain size is constituted, also close bag inside the small ball of outer layer
The grain size wrap up in, being sporadicly distributed is mainly distributed on 10 μm -30 μm of the big ball of outer layer.Between between outer layer roundlet ball
Gap between gap, and the small ball of outer layer and the big ball of outer layer, is all filled with the network-like outer layer of the fine and close space multistory of quality
Network bracket, is bonded together tightly to each other between outer layer network bracket and the big ball of outer layer and the small ball of outer layer.It is this double
Layer ball structure is the intensity for being conducive to improving two-layer compound microballoon, can easily decompose digestion in vivo again, and release is compound micro-
The load medicine of ball internal layer.The spherome surface of complex microsphere internal layer has one layer of fine and close top layer, make complex microsphere outer layer and internal layer it
Between have an obvious ectonexine line of demarcation.Internal layer is mainly made up of diameter dimension interior layer spheroid cavity not of uniform size, internal layer
It has been covered with internal layer small holes on spherical hollow space, has made internal layer formation alveolar shape, but there are the numerous holes being mutually communicated again between alveolar
Hole identical space structure.It is the fine and close inner stent of quality between each interior layer spheroid cavity.
As the preferred embodiment of above-mentioned technical proposal, the component of the complex microsphere is by chitosan or chitin modified spreads out
Biology, adds PLA or polylactic acid modified derivative, adds inorganic mineral or metal powder or metal oxide powder, then add
Upper contained medicine powder, more than three kinds component compositions.For example：By chitosan CS, polylactic acid PLA, hydroxyapatite HA；Or it is bright
Glue, poly lactic-co-glycolic acid PLGA, calcium silicates；Or chitosan CS, polylactic acid PLA, tricalcium silicate；Or chitosan CS, PLA
PLA, three components of silica composition, along with contained medicine powder.
As the preferred embodiment of above-mentioned technical proposal, the molecular weight of the PLA of one of the component of the complex microsphere >=
80000, molecular weight >=80,000 of polylactic acid modified derivative；The chitosan of one of the component of the complex microsphere is chitin modified
Derivative, requires the property being not dissolved in the water of pH neutral；The inorganic mineral of one of the component of the complex microsphere,
Or metal powder or metal oxide powder, along with contained medicine powder, all it is machined to nano level powder.
Compared with prior art, the present invention can be applied to the transmission of medicine and bioactive molecule, can also be used in life
The microcarrier of Porcine HGF in the osseous tissue renovating material and cell engineering of thing engineering.The present invention has following beneficial effect
Really.
（1）Double-layer circular spherical structure complex microsphere, interface binding power is strong, adds the mechanical strength properties of micro-sphere material.
（2）Double-layer circular spherical structure is conducive to decomposition in vivo to digest, and discharges the load medicine of complex microsphere internal layer.
（3）The microballoon mode of appearance of the present invention is very good, microballoon of the particle size range in 0.1mm ~ 1.5mm.
Brief description of the drawings
Fig. 1 is the photo in kind of complex microsphere of the present invention.
Fig. 2 is the electron micrograph of complex microsphere of the present invention, amplifies 300 times.
Fig. 3 is the electron micrograph of exposure inside complex microsphere of the present invention, amplifies 300 times.
Fig. 4 is the electron micrograph of the internal layer layer structure of complex microsphere of the present invention, amplifies 1500 times.
Fig. 5 is the electron micrograph of the internal layer layer structure of complex microsphere of the present invention, amplifies 1000 times.
Fig. 6 is the electron micrograph of the layer structure of complex microsphere of the present invention, amplifies 3000 times.
In figure：1. complex microsphere；2. outer layer；3. ectonexine line of demarcation；4. internal layer；5. in layer spheroid cavity；6. internal layer branch
Frame；7. internal layer small holes；8. the big ball of outer layer；9. the small ball of outer layer；10. outer layer network bracket；11. surface pit.
Embodiment
Further the present invention is illustrated with reference to the accompanying drawings and examples.
Referring to figs. 1 to Fig. 6, a kind of complex microsphere of double-layer circular spherical structure is made up of outer layer 2 and the two parts of internal layer 4, and it is special
Levy and be：1 point of the complex microsphere is outer layer 2 and the concentric spheroid layer of internal layer 4 two, and the grain size of complex microsphere 1 can
As needed, selected in the interval between 0.1mm-1.5mm.The radius size of the spheroid of internal layer 4 is the spheroid of outer layer 2, that is,
Between the 3/5-2/3 of the radius size of complex microsphere 1.The surface of complex microsphere 1 except be distributed with diameter dimension 15 μm -35 μm it
Between surface pit 11 outside, the surfacing of complex microsphere 1 can say smoother.The outer layer 2 of complex microsphere 1 is main
The small ball 9 of outer layer for being mainly distributed on 1 μm -3 μm by large number of grain size is constituted, and the small inside of ball 9 of outer layer is also close
The grain size be wrapped in, being sporadicly distributed is mainly distributed on 10 μm -30 μm of the big ball 8 of outer layer.Between outer layer roundlet ball 9
Gap between gap, and the small ball 9 of outer layer and the big ball 8 of outer layer, is all filled with the close space multistory of quality network-like
Outer layer network bracket 10.One is bonded in tightly to each other between outer layer network bracket 10 and the big ball 8 of outer layer and the small ball 9 of outer layer
Rise.The spherome surface of the internal layer 4 of complex microsphere 1 has one layer of fine and close top layer, makes have one between the outer layer 2 of complex microsphere 1 and internal layer 4
Individual obvious ectonexine line of demarcation 3.Internal layer 4 is mainly made up of diameter dimension interior layer spheroid cavity 5 not of uniform size.Internal layer is spherical
It has been covered with internal layer small holes 7 on cavity 5, has made the formation alveolar shape of internal layer 4, but there are the numerous holes being mutually communicated again between alveolar
Identical space structure.It is the fine and close inner stent 6 of quality between each interior layer spheroid cavity 5.
Optimization, the component of the complex microsphere 1 adds PLA or poly- breast by chitosan or chitin modified derivative
Sour modification derivant, adds inorganic mineral or metal powder or metal oxide powder, along with contained medicine powder, three kinds with
Upper component composition.For example：By chitosan, PLA, hydroxyapatite；Or gelatin, poly lactic-co-glycolic acid, calcium silicates；Or shell
Glycan, PLA, tricalcium silicate；Chitosan, PLA, silica, along with contained medicine powder.
Optimization, molecular weight >=80,000 of the PLA of one of component of the complex microsphere 1, polylactic acid modified derivative
Molecular weight >=80,000；The chitosan or chitin modified derivative of one of the component of the complex microsphere 1, are required insoluble
Property in the water of pH neutral；The inorganic mineral or metal powder or metal oxygen of one of the component of the complex microsphere 1
Compound powder, along with contained medicine powder, is all machined to nano level powder.
Claims (3)
1. a kind of complex microsphere of double-layer circular spherical structure, by outer layer（2）And internal layer（4）Two parts are constituted, it is characterised in that：It is described
Complex microsphere（1）It is divided into outer layer（2）And internal layer（4）Two concentric sphere volume layers, complex microsphere（1）Grain size 100 μm-
Between 1.5mm, internal layer（4）The radius size of spheroid is outer layer（2）Spheroid, i.e. complex microsphere（1）Radius size 3/5-2/3
Between；Complex microsphere（1）Remove and surface pit of the diameter dimension between 15 μm -35 μm is distributed with surface（11）Outside, it is combined
Microballoon（1）Surfacing；Complex microsphere（1）Outer layer（2）Mainly 1 μm -3 is mainly distributed on by large number of grain size
μm the small ball of outer layer（9）Composition, the small ball of outer layer（9）Inside goes back that tight, the grain size that is sporadicly distributed mainly divides
Outer layer big ball of the cloth at 10 μm -30 μm（8）；In outer layer roundlet ball（9）Between gap, and the small ball of outer layer（9）With outer layer
Big ball（8）Between gap, be all filled with the network-like outer layer network bracket of the fine and close space multistory of quality（10）, outer layer net
Network support（10）With the big ball of outer layer（8）With the small ball of outer layer（9）Between be bonded together tightly to each other；Complex microsphere（1）
Internal layer（4）Spherome surface have one layer of fine and close top layer, make complex microsphere（1）Outer layer（2）And internal layer（4）Between have one it is bright
Aobvious ectonexine line of demarcation（3）；Internal layer（4）Mainly by diameter dimension interior layer spheroid cavity not of uniform size（5）Constitute, internal layer ball
Shape cavity（5）On be covered with internal layer small holes（7）；Each interior layer spheroid cavity（5）Between be the fine and close inner stent of quality
（6）.
2. a kind of complex microsphere of double-layer circular spherical structure according to claim 1, it is characterised in that：The complex microsphere
（1）Component by chitosan or chitin modified derivative, add PLA or polylactic acid modified derivative, add inorganic mineral
Matter or metal powder or metal oxide powder, along with contained medicine powder, more than three kinds component compositions.
3. a kind of complex microsphere of double-layer circular spherical structure according to claim 2, it is characterised in that：The complex microsphere
（1）One of component PLA molecular weight >=80,000, molecular weight >=80,000 of polylactic acid modified derivative；The complex microsphere
（1）One of component chitosan or chitin modified derivative, require the property being not dissolved in the water of pH neutral；Institute
State complex microsphere（1）One of component inorganic mineral or metal powder or metal oxide powder, along with contained medicine
Powder, is all machined to nano level powder.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710663241.8A CN107260686A (en) | 2017-08-05 | 2017-08-05 | A kind of complex microsphere of double-layer circular spherical structure |
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| CN201710663241.8A CN107260686A (en) | 2017-08-05 | 2017-08-05 | A kind of complex microsphere of double-layer circular spherical structure |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109364288A (en) * | 2018-11-26 | 2019-02-22 | 温州生物材料与工程研究所 | Hole-hole composite micro-nano structure polysaccharide microsphere is in the purposes for preparing bleeding-stopping dressing |
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| US20040180091A1 (en) * | 2003-03-13 | 2004-09-16 | Chang-Yi Lin | Carbonated hydroxyapatite-based microspherical composites for biomedical uses |
| CN101590388A (en) * | 2009-06-18 | 2009-12-02 | 重庆文理学院 | A kind of preparation method of nano hydroxyapatite/polylactic acid composite microspheres |
| CN101658497A (en) * | 2009-09-16 | 2010-03-03 | 清华大学 | Dual drug-loading composite microsphere and preparation method thereof |
| CN102489231A (en) * | 2011-12-26 | 2012-06-13 | 重庆科技学院 | Preparation method of hydroxy apatite / polylactic acid / chitosan composite microballoon |
| CN106511315A (en) * | 2016-12-27 | 2017-03-22 | 苏州科技大学 | Degradable polymer core-shell microsphere loaded with protein drugs |
-
2017
- 2017-08-05 CN CN201710663241.8A patent/CN107260686A/en not_active Withdrawn
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040180091A1 (en) * | 2003-03-13 | 2004-09-16 | Chang-Yi Lin | Carbonated hydroxyapatite-based microspherical composites for biomedical uses |
| CN101590388A (en) * | 2009-06-18 | 2009-12-02 | 重庆文理学院 | A kind of preparation method of nano hydroxyapatite/polylactic acid composite microspheres |
| CN101658497A (en) * | 2009-09-16 | 2010-03-03 | 清华大学 | Dual drug-loading composite microsphere and preparation method thereof |
| CN102489231A (en) * | 2011-12-26 | 2012-06-13 | 重庆科技学院 | Preparation method of hydroxy apatite / polylactic acid / chitosan composite microballoon |
| CN106511315A (en) * | 2016-12-27 | 2017-03-22 | 苏州科技大学 | Degradable polymer core-shell microsphere loaded with protein drugs |
Non-Patent Citations (1)
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109364288A (en) * | 2018-11-26 | 2019-02-22 | 温州生物材料与工程研究所 | Hole-hole composite micro-nano structure polysaccharide microsphere is in the purposes for preparing bleeding-stopping dressing |
| CN109364288B (en) * | 2018-11-26 | 2021-04-02 | 温州生物材料与工程研究所 | Application of hole-hole composite micro-nano structure polysaccharide microspheres in preparation of hemostatic dressing |
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Application publication date: 20171020 |