CN103952296B - Multi-functional therapeutic treatment substance bluk recombination device - Google Patents
Multi-functional therapeutic treatment substance bluk recombination device Download PDFInfo
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- CN103952296B CN103952296B CN201410016186.XA CN201410016186A CN103952296B CN 103952296 B CN103952296 B CN 103952296B CN 201410016186 A CN201410016186 A CN 201410016186A CN 103952296 B CN103952296 B CN 103952296B
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
- C12M25/14—Scaffolds; Matrices
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M21/00—Bioreactors or fermenters specially adapted for specific uses
- C12M21/08—Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
- C12M33/04—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus by injection or suction, e.g. using pipettes, syringes, needles
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Abstract
The present invention relates to a kind of multi-functional therapeutic treatment substance recombiners, referred to as " recombiner ".The recombiner is made of device for storing liquid, article-storage device and attachment device three parts.The therapeutic treatments substance such as histocyte, biological agent and drug is combined among porous biomaterial by the recombiner application filter method, and reaching therapeutic substance can be simple and quick with uniform high-efficiency compound, improves biological effect or/and curative effect of medication.The clutch can make cell attach to material internal structure surface in recombination process, the cell loss as caused by bleeding and flushing when being effectively prevented from complex application.The clutch can also be used as cell culture apparatus, make cell portion's proliferation and differentiation in the porous material.The recombiner can control the form and size of storing bin, makes the material it is suitable for different shape and specification, can also load the material of heterogeneity and dosage form.A possibility that therapeutic treatment substance can be made to carry out in enclosed sterile environment with Material cladding process, can avoid chemistry and biological pollution, the product after reaching compound can be immediately used for clinic.The recombiner can be used for the domains such as biology, pharmacy, medicine and animal doctor.
Description
Technical field
The present invention relates to a kind of application filtration methods to be combined to multiporous biological for substances such as histocyte, biological agent and drugs
Device among material not only can be suitably used for the material of heterogeneity, form and size, but also simple and quick with uniform high-efficiency can will
Therapeutic treatment substance is combined to inside porous material, and can clinical use at once.The device can be applied to biology, pharmacy, medicine
With the fields such as animal doctor.
Background technique
With the development of life, material and mechanical subject, there is new technical field, i.e. bioengineered tissue, it
Application cell biology and engineering principles study biosubstitute, are used for the repair and reconstruction of injury tissue function.It will train in vitro
The mescenchymal stem cell supported and expanded, is adsorbed in bio-compatible and degradable stock support, and then position is repaired in implantation.In material
Expect that cell continues to multiply differentiation and secretion matrix in gradually degradation process, reaches repair tissue and Reconstruction of The Function.And this process
The influence factor of middle most critical is cell adhesion in the effect of timbering material.
Cell adhesion is in such a way that " receptor and ligand " combines, and electrostatic interaction and van der Waals interaction are negligible
Disregard.The receptor of cell adhesion mainly has integrin, immunoglobulin, selectin and cadherins.And cell and outer matrix are glutinous
Attached major receptors are integrin, are typically located at the contact zone of dispersion, referred to as talin.Stick tightness and depends on adhesion
The service life of spot and the set of adhesion strength.The service life of talin and the influence factor of intensity have that medium to stick size (several hundred to receive
Rice is to 1 micron), rigid substrate, the solidification of cytoskeleton and pre- and low angle stretch.The static models of cell inoculation are divided
Analysis show that cell adhesion depends on material property and inoculation flow velocity, ligand sizes, coefficient of elasticity, internal structure and the Bi Biao of material
Area can influence, and hydrodynamic shear and the low angle stretching of cell liquid can influence, and the solidification of cytoskeleton and pre- open can influence.Mesh
The inoculation method of preceding seed cell has static method and dynamic method, and static inocalation method mainly uses sessile drop method, immersion method and microinjection
Deng they are that cell suspension is made to enter internal stent by osmosis, easy to operate；But inoculation time is longer and efficiency compared with
It is low, it can only often be seeded in the surface of three-dimensional rack, it is difficult to realize that cell is uniformly distributed in timbering material.Dynamic inocalation method master
Have centrifugation inocalation method, negative-pressure adsorption method, succusion and bioreactor inoculation etc., not only increase the inoculation efficiency of cell and
And improve the spatial distribution of cell in the bracket.But dynamic inocalation method needs expensive instrument and equipment, and technology is wanted
It asks higher, limits their application to a certain extent.
Syringe negative-pressure adsorbs inoculating cell, and there are many reports, and effect is affirmed.But no matter material is put into note
Emitter takes out negative pressure, or negative pressure is taken out out of container that deposit material with syringe, since the negative pressure that syringe generates is limited, on
The method of stating is limited only to small dimension material.In addition, density lower material will appear material floats when being inoculated with, cell is seriously affected
Rate of vaccination.Patent CN202610234 introduces a kind of negative pressure cell inoculation device, including negative pressure generator, inoculation storehouse and tee tube.
The device can connect different vaccination storehouse as needed, and can be inoculated with multiple brackets simultaneously, but still unresolved various shapes and material
The problems such as material floating.Patent CN101735984 is introduced using bacterium syringe as inoculating tool, and timbering material is put from syringe rear portion
Enter, the cell suspension being then inoculated with needed for sucking.Reserve a certain amount of air in syringe, closed injection device mouth pumpback syringe,
The negative pressure of formation makes cell suspension penetrate into porous material, realizes that initial stage of the seed cell in timbering material is uniformly distributed inoculation.
Patent CN202530084 describes-kind it is used for the centrifuge tube of cell inoculation, that is, reduced diameter is to the cylinder of bottom
Shape tube body can be connected to the top cap at the top of the tube body with opening, and removably be socketed in the bottom cap of tube bottom, and have and accommodate
The space of the bracket of inoculating cell.Different specifications can be made as needed and adapt to actual needs.
Multi-functional therapeutic treatment substance bluk recombination device
Summary of the invention
The present invention relates to a kind of multi-functional therapeutic treatment substance recombiners, referred to as " recombiner ".The recombiner is filled by liquid storage
Set 1 (containing containing liquid chamber 4 and propeller 10), article-storage device 2 (containing storing bin 14, dual-pushing type propeller 19,23 and sealing cover 18) and
Attachment device 3 (containing connecting tube 27 and triple valve 8) three parts composition (Fig. 1).The recombiner can be widely used for biology, pharmacy, doctor
It learns and the fields such as animal doctor.
The purpose of the present invention is the therapeutic treatments substance such as histocyte, biological agent and drug is compound for application filter method
To among porous biomaterial, reaching therapeutic substance can be simple and quick with uniform high-efficiency compound, improves biological effect or/and medicine
Object curative effect.
It, can be effectively it is another object of the present invention to make cell that can attach to material internal structure surface in recombination process
Avoid cell-composite body when applying since bleeding and flushing cause cell loss.
It is another object of the present invention to using recombiner as cell culture apparatus, making cell, portion is proliferated in the porous material
And differentiation.
It is another object of the present invention to the form and size by adjusting recombiner storing bin 14, reaches and be suitable for not similar shape
The timbering material of shape and specification can also load the material of heterogeneity and dosage form.
It, can it is another object of the present invention to carry out therapeutic treatment substance in enclosed sterile environment with Material cladding process
Be effectively prevented from chemistry and biological pollution, enable it is compound after the completion of product be immediately used for clinic.
The making material of the recombiner can be metal (such as stainless steel, titanium alloy, aluminium alloy, copper, gold, silver and tantalum), have
Machine material (such as PEEK, PM MA, PETG and PCTG) and inorganic material (glass, aluminium oxide and zirconia ceramics etc.), can also be
Two or more composite material.
The device for storing liquid 1 of the recombiner has a cast containing liquid chamber 4, and the cross section Guan Cang can be garden, ellipse, square and rectangular etc. shapes
Shape.The open ports 5 of storehouse upper end outward flanging, orlop are to close micro- vertebra shape cecum 6, and center has through hole 7 to be connected with triple valve 8.
Inside has channel 9 to communicate with storing bin 14 under storehouse.Storehouse inner piston type propeller 10 has push rod 11 to connect silica piston 12 and push handle
13, the long outlet pipe storehouse of push rod 11,12 size of silica piston matches with storehouse internal diameter, to guarantee the tightness in storehouse (Fig. 2).
2 form of article-storage device and size and device for storing liquid 1 of the recombiner are similar, and difference is with outer spiral shell at 14 bottom of storing bin
The open ports of line 15 are provided with internal screw thread 16 and unscrew the sealing cover 18 of piece 17.Storehouse inner piston type propeller is dual-pushing type (center
With it is nestable).Nestable propeller 19 is that implantation material fixinig plate 21 and push handle 22 are connected by round tube push rod 20, and fixinig plate 21 is netted knot
Structure is fixed with push rod 20 at vertical, and effect is fixation implant.Center propeller 23 passes through from the center of nestable propeller 19,
Push rod 24 connects silica piston 25 and push handle 26 (Fig. 2 and Fig. 3).
The attachment device 3 of the recombiner can be there are two types of mode, and one kind has side opening to be directly connected to 9 between two storehouse lower sections, another-
Kind is to pass through 8 indirect communication 28 (Fig. 3) of pipeline 27 and/or triple valve.
The operating process of recombiner of the present invention is (Fig. 4)：
1. implantation material is aseptically loaded into storing bin 14, sealing-plug 18 is tightened, sealing is confirmed the validity；
2. therapeutic treatment substance is injected containing liquid chamber 4 by triple valve 8 by application syringe, make the height on its 10 top of propeller
Position, is then turned off triple valve 8；
3. pushing away the propeller 10 of containing liquid chamber 4 while fixed nestable propeller 19 slowly, liquid is made to enter storage by implantation material
Object storehouse 14 and jack-up center propeller 23；
4. slowly pushing center propeller 23, so that liquid is passed through implantation material once again and enter containing liquid chamber 4, past and repeated multiple times energy
Reach high composite effect；
5. after liquid is pushed into containing liquid chamber 4, opening the sealing cover 18 of storing bin 14, it is spare to take out implantation material.
Detailed description of the invention
Fig. 1 is the overall schematic of recombiner of the present invention.
Fig. 2 is that the device for storing liquid of recombiner of the present invention and article-storage device structure are intended to.
Fig. 3 is that the attachment device structure of recombiner of the present invention is intended to.
Fig. 4 is the operational flowchart of recombiner of the present invention.
Fig. 5 is to treat bone defect clinical effectiveness x radiograph using complex.
Specific embodiment
Embodiment 1：With answering PETG material to prepare recombiner of the present invention.Device for storing liquid 1 isGarden pipe
Containing liquid chamber 4, thickness of pipe wall 2mm, the open ports 5 of silo roof flanging 5mm, orlop are to close micro- vertebra shape 6, and center hasPerforation
Hole 7 is connected with triple valve 8, there is inside under storehouseHole 9 and 14 intercommunication of storing bin.There is piston-type propeller 10 in storehouse,
" ten " the font push rod 11 of 120mm long connects silica piston 12With push handle 13.2 form of article-storage device and ruler
It is very little similar with device for storing liquid 1, but orlop is the open ports with external screw thread 15, is provided with internal screw thread 16 and unscrews piece 17 (22 × 10
× 4mm) sealing cover 18Storehouse inner piston type propeller is dual-pushing type.Nestable propeller 19 is pushed away by round tube
Bar 20Connect implantation material fixinig plate 21With push handle 22, fixinig plate 21 is reticular structure, and is pushed away
Handle 22 is at vertical fixed.Center propeller 23 has 120mm round tube push rod 24Connect silica piston 25With push handle 26, center push rod 20 is longer than nestable push rod 24, both grows storing bin 14.(Fig. 2 b).
There is side opening to be directly connected to 9 (Fig. 3 b) between two storehouse lower sections.
Embodiment 2：Recombiner of the present invention is prepared using stainless steel material.Device for storing liquid 1 isGarden
Pipe containing liquid chamber 4, thickness of pipe wall 2mm, the open ports 5 of silo roof flanging 5mm, orlop center hasThrough hole 7 and triple valve 8
It is connected.Storehouse inner piston type propeller 10 is by push rod 11Connect silica piston 12With push handle
13.Article-storage device 2 hasRound tube storing bin 14, the open ports of silo roof flanging 5mm；Orlop is band external screw thread
Open ports 15, be provided with and internal screw thread 16 and unscrew the sealing cover 18 of piece 17 (30 × 10 × 4mm)It is living in storehouse
Plunger type propeller is dual-pushing type.Nestable propeller 19 is that have tubular type push rod 20Connect implantation material fixinig plate 21With push handle 22, fixinig plate 21 is reticular structure, with push rod 20 at vertical fixed.Center propeller 23 has 120mm
Cylinder push rod 24Connect silica piston 25 With push handle 26.Center push rod 23 from
Nestable 20 center of push rod passes through (Fig. 2 a).Two storehouses pass through 8 indirect communication 28 (Fig. 3 a) of pipeline 27 and triple valve.
Embodiment 3：It is stem cell enriched multiple with β-ICP bioceramic particle that recombiner described in Application Example 2 carries out marrow
It closes.First aseptically by 10g β-ICP bioceramic particleAfter being loaded into storing bin 14,18 He of sealing cover is tightened
Check confirmation (Fig. 4 a).The 50ml autologous bone marrow liquid for doing elementization is injected into containing liquid chamber 4 with syringe, makes 10 top of propeller in storehouse
A high position is closed triple valve 8 (Fig. 4 b).It is slowly advanced the propeller 10 of containing liquid chamber 4 while fixed nestable propeller 19, makes liquid
Body enters storing bin 14 by implantation material and jacks up center propeller 23 (Fig. 4 c).Being slowly advanced center propeller 23 makes liquid again
It spends logical implantation material and enters containing liquid chamber 4, it is past and repeatedly tens of secondary, it improves combined efficiency (Fig. 4 d).After liquid is pushed into containing liquid chamber, beat
Storing bin sealing cover is opened, it is spare (Fig. 4 e) to take out implantation material.
Embodiment 4：Marrow prepared by Application Example 3 is stem cell enriched to be controlled with β-ICP bioceramic particle composites
Treat bone nonunion case.Male patient 29 years old because caused by traffic accident right shin middle and lower sections open fracture then occur with segmental defect
The infection of various bacteria is controlled through antibiotic treatment infection.But bone defect is not proved effective every year using a variety of methods treatment 2,
And there is bone nonunion.Soft tissue removing is carried out in bone defect portion, compound prepared by 3 method of embodiment is implanted into, using outer solid
Determine frame to fix.Clinical and x mating plate follow-up discovery has bon e formation March, and bone defect is cured entirely after 1 year, removes external fixing rack, Huan Zheneng
Autonomous (Fig. 5).
Claims (9)
1. a kind of multi-functional therapeutic treatment substance bluk recombination device, which is characterized in that by device for storing liquid, article-storage device and attachment device
Three parts composition；
The device for storing liquid is cast containing liquid chamber, and storehouse upper end is the open ports of outward flanging, and orlop is closing cecum, and center is passed through
Through-hole is connected with triple valve；Inside has channel to communicate with the storing bin of article-storage device under storehouse；Storehouse inner piston type propeller is by push rod
Connection silica piston and push handle, silica piston size match with storehouse internal diameter, to guarantee the tightness in storehouse；
The storing bin bottom of the article-storage device is to be provided with internal screw thread with externally threaded open ports and unscrew the sealing cover of piece；Storehouse
Inner piston type propeller is dual-pushing type, and the dual-pushing type storehouse inner piston type propeller is center propeller and nestable propeller, institute
It states nestable propeller and implantation material fixed network shape stator and push handle is connected by cast push rod；The center propeller is from nestable propeller
The heart passes through, and connects silica piston by push rod and push handle, silica piston size match with storehouse internal diameter；Center push rod is longer than nestable push away
Bar both grows storing bin.
2. a kind of multi-functional therapeutic treatment substance bluk recombination device according to claim 1, which is characterized in that the recombiner
Histocyte, biological agent and drug are combined among porous biomaterial using filter method, reaching therapeutic substance can letter
It is single quickly and uniform high-efficiency ground compound, raising biological effect or/and curative effect of medication.
3. a kind of multi-functional therapeutic treatment substance bluk recombination device according to claim 1, which is characterized in that the recombiner
Cell can be made to attach to material internal structure surface in recombination process, due to bleeding and punching when being effectively prevented from complex application
Cell loss caused by washing.
4. a kind of multi-functional therapeutic treatment substance bluk recombination device according to claim 1, which is characterized in that the recombiner
As cell culture apparatus, cell portion's proliferation and differentiation in the porous material can be made.
5. a kind of multi-functional therapeutic treatment substance bluk recombination device according to claim 1, which is characterized in that the recombiner
The form and size that can control storing bin reach the timbering material suitable for different shape and specification, and load heterogeneity and
The material of dosage form.
6. a kind of multi-functional therapeutic treatment substance bluk recombination device according to claim 1, which is characterized in that the recombiner
Therapeutic treatment substance can be made to carry out in enclosed sterile environment with Material cladding process, can avoid the possibility of chemistry and biological pollution
Property, enable it is compound after product be immediately used for clinic.
7. a kind of multi-functional therapeutic treatment substance bluk recombination device according to claim 1, which is characterized in that the recombiner
The material of production is metal, organic material and the above two or two or more composite material of inorganic material.
8. a kind of multi-functional therapeutic treatment substance bluk recombination device according to any one of claims 1 to 7, which is characterized in that
For the attachment device of the recombiner there are two types of mode, one kind is that containing liquid chamber is directly connected to storing bin by lower section side opening, another
Kind is to pass through pipeline and/or triple valve indirect communication.
9. a kind of multi-functional therapeutic treatment substance bluk recombination device according to any one of claims 1 to 7, which is characterized in that
Histocyte, biological agent and drug can be combined in porous material to simple and quick and uniform high-efficiency by the recombiner, and
Can clinical application at once, which can be used for biology, pharmacy, medicine and veterinary applications.
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| CN201410016186.XA CN103952296B (en) | 2014-01-14 | 2014-01-14 | Multi-functional therapeutic treatment substance bluk recombination device |
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| CN201410016186.XA CN103952296B (en) | 2014-01-14 | 2014-01-14 | Multi-functional therapeutic treatment substance bluk recombination device |
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| CN104789450B (en) * | 2015-05-19 | 2017-01-11 | 山东大学 | Connecting device for fermented container and extracellular fermented product researching container |
| CN108379663B (en) * | 2018-04-24 | 2023-05-26 | 中国人民解放军第四军医大学 | Device and method for trapping and enriching cells in porous regular body scaffold material |
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|---|---|---|---|---|
| CN1503683A (en) * | 2001-02-28 | 2004-06-09 | �ٴ����� | Composite bone marrow graft matrial with method and kit |
| CN101332135A (en) * | 2007-06-27 | 2008-12-31 | 德普伊产品公司 | Osteogenic prostheses, related appliance and method |
| CN201453418U (en) * | 2009-09-07 | 2010-05-12 | 中国人民解放军第三军医大学第一附属医院 | Bone marrow concentrator |
| CN101735984A (en) * | 2008-11-27 | 2010-06-16 | 四川大学 | Simple and convenient method for inoculating cell for scaffold material of tissue engineering |
| CN102408988A (en) * | 2011-12-02 | 2012-04-11 | 中国人民解放军第二军医大学 | Smooth muscle cell planter for tissue-engineered blood vessels |
| CN103156703A (en) * | 2011-12-13 | 2013-06-19 | 西安瑞捷生物科技有限公司 | Human tissue repairing material constructing device |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6530896B1 (en) * | 1996-05-13 | 2003-03-11 | James B. Elliott | Apparatus and method for introducing an implant |
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2014
- 2014-01-14 CN CN201410016186.XA patent/CN103952296B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1503683A (en) * | 2001-02-28 | 2004-06-09 | �ٴ����� | Composite bone marrow graft matrial with method and kit |
| CN101332135A (en) * | 2007-06-27 | 2008-12-31 | 德普伊产品公司 | Osteogenic prostheses, related appliance and method |
| CN101735984A (en) * | 2008-11-27 | 2010-06-16 | 四川大学 | Simple and convenient method for inoculating cell for scaffold material of tissue engineering |
| CN201453418U (en) * | 2009-09-07 | 2010-05-12 | 中国人民解放军第三军医大学第一附属医院 | Bone marrow concentrator |
| CN102408988A (en) * | 2011-12-02 | 2012-04-11 | 中国人民解放军第二军医大学 | Smooth muscle cell planter for tissue-engineered blood vessels |
| CN103156703A (en) * | 2011-12-13 | 2013-06-19 | 西安瑞捷生物科技有限公司 | Human tissue repairing material constructing device |
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Effective date of registration: 20190325 Address after: Room 402, Building 9, 188 Xinjunhuan Road, Minhang District, Shanghai, 20114 Patentee after: Shanghai Bio-lu Biomaterials Company Limited Address before: 201112 No. 20, Lane 1659, Puchi Road, Minhang District, Shanghai Co-patentee before: Lu Xiao Patentee before: Lu Jianxi |
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Effective date of registration: 20190327 Address after: Room 402, Building 9, 188 Xinjunhuan Road, Minhang District, Shanghai, 20114 Patentee after: Shanghai Bio-lu Biomaterials Company Limited Address before: 201112 No. 20, Lane 1659, Puchi Road, Minhang District, Shanghai Co-patentee before: Lu Xiao Patentee before: Lu Jianxi |