CN103952296B - Multi-functional therapeutic treatment substance bluk recombination device - Google Patents

Multi-functional therapeutic treatment substance bluk recombination device Download PDF

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Publication number
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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material
recombiner
therapeutic treatment
treatment substance
multi
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CN201410016186.XA
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Chinese (zh)
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CN103952296A (en
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卢建熙
卢霄
陈雷
王迎军
任力
王臻
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卢建熙
卢霄
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M25/00Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
    • C12M25/14Scaffolds; Matrices
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M21/00Bioreactors or fermenters specially adapted for specific uses
    • C12M21/08Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M33/00Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
    • C12M33/04Means 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

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

Multi-functional therapeutic treatment substance bluk recombination device

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.
CN201410016186.XA 2014-01-14 2014-01-14 Multi-functional therapeutic treatment substance bluk recombination device CN103952296B (en)

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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

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Publication number Priority date Publication date Assignee Title
CN1503683A (en) * 2001-02-28 2004-06-09 克利夫兰临床基金会 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

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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

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1503683A (en) * 2001-02-28 2004-06-09 克利夫兰临床基金会 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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