CN109125922A - A kind of biology covers the application in terms of nerve stimulator implantation - Google Patents
A kind of biology covers the application in terms of nerve stimulator implantation Download PDFInfo
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- CN109125922A CN109125922A CN201811145176.0A CN201811145176A CN109125922A CN 109125922 A CN109125922 A CN 109125922A CN 201811145176 A CN201811145176 A CN 201811145176A CN 109125922 A CN109125922 A CN 109125922A
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- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/36053—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for vagal stimulation
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- 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
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
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- 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
- A61L27/58—Materials at least partially resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
- A61N1/36062—Spinal stimulation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61N1/00—Electrotherapy; Circuits therefor
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- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
- A61N1/36103—Neuro-rehabilitation; Repair or reorganisation of neural tissue, e.g. after stroke
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- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/372—Arrangements in connection with the implantation of stimulators
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- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/372—Arrangements in connection with the implantation of stimulators
- A61N1/375—Constructional arrangements, e.g. casings
- A61N1/37514—Brain implants
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Abstract
The present invention discloses a kind of biology and covers application in terms of nerve stimulator implantation, which covers the impulse generator for being packed into the embedded nerve stimulators such as spinal stimulator and deep brain stimulator, be implanted to together in the pouch of subcutaneous tissue formation later.The biology set is acellular matrix, has many advantages, such as good biocompatibility, has certain mechanical properties, has biodegradability and antibacterial ability, can reduce the incidence of the complication such as the postoperative pouch infection of embedded nerve stimulator, hemotoncus and ulceration.
Description
Technical field
The present invention relates to Bioabsorbable implanted medical device fields, and in particular to a kind of biology is covered in nerve stimulator
It is implanted into the application of aspect.
Background technique
Embedded nerve stimulator (INS) is to stimulate target nerve with a degree of current impulse, to adjust or restore
The function of brain, nerve or muscle makes a kind of method of remission.Clinically, a variety of neurological diseases or mental disease be still
Lack effective radical cure mode, patient needs for many years even medication throughout one's life, and generates after having a certain proportion of patient's Long-term taking medicine
Serious side reaction, embedded nerve stimulator can be used as the alternative medicine of drug at this time.
The embedded nerve stimulator clinically applied at present mainly has: spinal stimulator, deep brain stimulator, fan are absent-minded
Through stimulator and sacral nerve stimulator etc..
Embedded nerve stimulator is generally made of Implantable Pulse Generator, electrode and conducting wire, and impulse generator is used for
Electric pulse is generated according to the parameter of the program-controlled setting of doctor, electrode is used to electric pulse being transmitted to target nerve, and conducting wire is then pulse
Connection between generator and electrode.The mode that embedded nerve stimulator implants, electrode are to be implanted to specific nerve
Site of action, and its impulse generator is typically implanted subcutaneously, such as the pulse generation of vagus nerve stimulator and deep brain stimulator
Device is implanted to that chest is subcutaneous, subcutaneous near the impulse generator implantation spinal cord of spinal stimulator, the pulse hair of sacral nerve stimulator
It is subcutaneous that raw device is implanted to buttocks.
In recent years, as aging of population and clinical indication expand, receive patient populations' rapid growth of INS treatment,
The annual whole world is more than 1,000,000.But with increasing for implantation amount and increasing for complicated patient with severe symptoms's operation, after INS implantation
The influence of complication is got worse.INS is implanted into infectious-related complication, mainly there is pouch infection, hemotoncus, ulceration, loose electrode placement, electrode
Perforation, conducting wire wear and rupture, interior displacement of equipment body etc., wherein being that INS plants with pouch related complication (infection, hemotoncus, ulceration)
Enter postoperative common complication, incidence causes patient and seriously affect up to 7%, it has also become the difficulty that neurosurgeon faces
Topic.
The principal element for causing pouch related complication to occur has:
(1) device housings are titanium or other alloy materials, it is foreign matter forever for human body, can lead to body and generate row
Reprimand reaction；
(2) some reasons can lead to equipment movement, and if patient is old, thin, skin is relatively thin, pouch is excessive, limb activity etc., and
Equipment is mobile to be easy to cause friction bleeding to allow skin ulceration at hemotoncus, friction；
(3) implantation or replacement of equipment, be easy to cause pouch to infect.
It is clinically directed to the solution of pouch related complication, the mainly product and specification of selection service life length at present
Surgical procedures, but fail to the incidence for being substantially reduced pouch related complication.
The Chinese patent of Publication No. CN 104941065B, is related to a kind of implantable neural electrical stimulator and this is
The protective case of system, but the patent is primarily directed to the problem of electrode cable is broken because of Tensile, it is not related for pouch
What complication occurred mainly causes factor, therefore fails to reduce the incidence of pouch related complication.
And upper biodegradable biology set is covered outside equipment, the hair of pouch related complication will be substantially reduced
Raw rate.
For this purpose, the present invention comes into being.
Summary of the invention
The good biocompatibility that the purpose of the present invention is to provide a kind of for embedded nerve stimulator has certain mechanics
Performance, the acellular matrix biology set with biodegradability, with antibacterial ability, it is intended to it is related to reduce the postoperative pouch of INS
The incidence of complication.
For this purpose, the present invention, which provides a kind of biology, covers application method in terms of nerve stimulator implantation, wherein the biology
Set is made of acellular matrix, for being fitted into the pouch for being implanted to subcutaneous tissue formation after embedded nerve stimulator together,
To have the function that embedded nerve stimulator.
Further, the acellular matrix includes but is not limited to the submucous layer of small intestine of mammal, mucous membrane of urinary bladder
Lower layer, submucous lamina of stomach, one or more combinations of dermal matrix, pericardium, meninx, amnion, internal organs film, peritonaeum.
Further, the acellular matrix is the submucous layer of small intestine of mammal.
Further, embedded nerve stimulator equipment includes but is not limited to spinal stimulator, deep brain stimulator, dorsal column
Stimulator, nervus peripheralis stimulating system, functional point stimulating system, vagus nerve stimulator and sacral nerve stimulator.
Further, the biology set is combined by 2-12 layers of single layer acellular matrix overlapping, complex method packet
One of bonding, suture or a variety of are included, thickness is between 0.1mm-3mm.
Further, the biology set shape includes rectangle, square, circle, trapezoidal, shape of dripping, triangle, ellipse
Shape, irregular shape, the biology set area 4-100cm2, there are micropore, the pore diameter range of the micropore in the surface of the biology set
It is 10-400 μm, pitch of holes is 5-20 mm.
Further, the biology set can be loaded into one or more drugs according to clinical demand, be implanted to subcutaneous tissue
When the pouch of formation, the tissue that the biology set can be sutured in pouch is fixed, for preventing the intracorporal displacement of equipment.
The biocompatibility biology set, be by inactivation of virus, removal immunogenic substances, freeze-drying, punching, suture and
The preparation processes such as sterilizing are made.
The biology set of the good biocompatibility, requires to carry out biological assessment according to GB/T 16886.1, result is nothing
It is pyrogenicity, without hemolytic reaction, without Acute systemic toxicity reaction, cell-cytotoxic reaction no more than 1 grade, without sensitization of skin reaction,
Paradoxical reaction is no different after no intradermal stimulate the reaction, hereditary-less toxicity, muscular grafting and without sub- chronic systemic toxic reaction.
The good biocompatibility biology set, immunogenic substance is extremely low, including residual cell amount no more than 1/
Mirror downward view (400 ×), DNA residual quantity are negative (immunofluorescence assay), lipid no more than 120pg/g, α-Gal antigen
Content is not more than 1%.
The biology set of the good biocompatibility, bacterial endotoxin are not more than 2.15EU/ part.
The biology set for having certain mechanical properties, including tensile strength are not less than 10N, seam not less than 18N, bursting strength
It closes intensity and is not less than 2N not less than 2N, tearing strength.
The biology set of the biodegradability, degradation time in vivo are 8-20 weeks.
The biology set with antibacterial ability, the polypeptide moiety that degradation in vivo generates have antibacterial action.
Biology set suture when being implanted to the pouch of subcutaneous tissue formation, can be fixed on pouch by the biology set
Tissue can prevent the intracorporal displacement of equipment on muscle, fascia and skin.
The biology set can be loaded into one or more drugs according to clinical demand.
Preparation method of the present invention for above-mentioned biology set, comprising:
(1) it pre-processes
It takes the fresh tissue wash for butchering mammal clean, is placed in 0.01% ~ 0.5% acetum and impregnates 10 ~ 120min, go
Raw meat scrapes division using physics and isolates required mucous membrane, is cut into segment, is rinsed at least 3 times using purified water；
(2) inactivation of virus
The mixed aqueous solution for the ethyl alcohol that the Peracetic acid and concentration for the use of concentration being 0.5~1.5% are 15~25%, ultrasound condition
Under, 30 ~ 120min of soaking at room temperature carries out disinfection；It is cleaned by ultrasonic at least 3 times using purified water later；
(3) degreasing
The ethyl alcohol for the use of concentration being 90-100%, under ultrasound condition, soak at room temperature 0.5-12h is cleaned by ultrasonic using purified water later
At least 3 times；
(4) cell is taken off, DNA is removed and removes α-Gal antigen
Using containing 0.01~0.10% trypsase and containing the mixed aqueous solution of 0.01~0.05%EDTA, under ultrasound condition, in 36
15-40min is impregnated under the conditions of ± 2 DEG C, is cleaned by ultrasonic at least 3 times using PBS later；
Using the aqueous solution of the enzyme Han 0.05~10U/ml DNA, under ultrasound condition, 15-40min is impregnated under the conditions of 36 ± 2 DEG C,
Later using PBS drift ultrasonic cleaning at least 3 times；
Using the aqueous solution of the alpha-galactosidase Han 0.05~10U/ml, under ultrasound condition, 15- is impregnated under the conditions of 20-37 DEG C
40min is cleaned by ultrasonic at least 3 times using PBS later；
The NaOH aqueous solution for the use of concentration being 5- 40mM, under ultrasound condition, soak at room temperature 20-60min is super using PBS later
Sound cleaning is until neutral；
(5) it is lyophilized, sterilizes
3~12 layers are superimposed, is fixed on mold, after freeze-drying, is cut into specification needed for clinical use, is packed using PET
Bag is packed, and irradiation sterilization is finally carried out.
Compared with prior art, the present invention have following remarkable advantage and the utility model has the advantages that
A kind of ECM biology set for INS provided by the invention, good biocompatibility have certain mechanical properties, have biology
Degradability has antibacterial ability, is by systems such as inactivation of virus, removal immunogenic substances, freeze-drying, punching, suture and sterilizings
Standby technique is made.When its be packed into INS flutter generator after implant, can obtain it is following the utility model has the advantages that
1. biology set provided by the invention, is acted on by its physical barriers, it can avoid device housings and directly connect with tissue
Touching, it is ensured that implantation equipment will not be repelled by human body, to reduce inflammation and infection generation；
2. biology set provided by the invention, is fixed on pouch surrounding tissue by suture way, avoids and be wrapped in its inside
Equipment is in tissue pouch internal shift, dislocation, to reduce the incidence of pouch hemotoncus and pouch ulceration；
3. biology set provided by the invention, material ECM have promoting healing effect, reduce infection conducive to the reparation of tissue pouch
Rate；
4. biology set provided by the invention, ECM three-dimensional structure tool inducing cell and blood vessel grow into function, grown into new tissue
While itself can gradually degrade, finally equipment periphery formed one layer of collagen film, further avoid human body to implantation
The rejection of equipment；
5. biology set provided by the invention, degradation cycle is 8-20 weeks, and tissue capsule pocket infections are more common in the implantation of INS equipment
Or 1-2 months after replacement, biology set is not yet degradable at this time, is conducive to the taking-up of INS equipment；
6. biology set provided by the invention, the polypeptide moiety of catabolite has anti-microbial property, after can further decreasing implantation
The incidence of inflammation and infection；
7. biology set provided by the invention, according to clinical demand, can be added promoting healing substance or antibiotic during the preparation process,
Promoting healing substance or antibiotic can also be loaded by immersion way before implanting, to further promote Wound healing
With reduction infection rate；
8. biology set provided by the invention, can reduce the risk that INS equipment is corroded and destroys in vivo, guarantee equipment
It works normally.
Detailed description of the invention
Fig. 1 is the pictorial diagram of the according to embodiments of the present invention 3 trees-Osima jacoti, Osima excavata acellular matrixes being prepared.
Fig. 2 is the pictorial diagram of the according to embodiments of the present invention 8 embedded nerve stimulator biology sets being prepared.
Fig. 3 is according to embodiments of the present invention 8 perspective views equipped with embedded nerve stimulator biology set being prepared.
Fig. 4 is according to embodiments of the present invention 8 sectional views equipped with embedded nerve stimulator biology set being prepared.
Fig. 5 is the perspective view of the according to embodiments of the present invention 9 embedded nerve stimulator biology sets being prepared.
Fig. 6 is the sectional view of the according to embodiments of the present invention 9 embedded nerve stimulator biology sets being prepared.
Specific embodiment
Illustrate embodiments of the present invention below by way of specific specific example, those skilled in the art can be by this specification
Other advantages and efficacy of the present invention can be easily understood for disclosed content.The present invention can also pass through in addition different specific realities
The mode of applying is embodied or practiced, the various details in this specification can also based on different viewpoints and application, without departing from
Various modifications or alterations are carried out under spirit of the invention.
Embodiment 1
(1) it pre-processes
It takes the chitterlings tissue wash of fresh slaughtered animals clean, is placed in 0.5% acetum and impregnates 30min, chitterlings and acetic acid
The ratio of solution is 1:5, scrapes mucous layer, muscle layer, placenta percreta, the lymph node that division removes chitterlings jejunum, separation using physics
Submucosa out is cut into segment, is rinsed 3 times using purified water；
(2) it sterilizes
Use the mixed aqueous solution containing 1.0% Peracetic acid and 15% ethyl alcohol, SIS(submucous layer of small intestine) material and mixing water
The ratio of solution is 1:10, and under ultrasound condition, soaking at room temperature 100min carries out disinfection.Later using purified water ultrasonic cleaning 3
Time；
(3) degreasing and de- cell
The ethyl alcohol for the use of concentration being 95%, the ratio of SIS material and ethyl alcohol are 1:10, under ultrasound condition, soak at room temperature 2h.Later
It is cleaned by ultrasonic 3 times using water for injection；
The NaOH aqueous solution for the use of concentration being 25mM, the ratio of SIS material and NaOH solution are 1:20, under ultrasound condition, room temperature
Impregnate 50min.Later using PBS ultrasonic cleaning until neutral；
(4) it is lyophilized, sterilizes
By 4 layers of SIS material be superimposed, be fixed on mold, be freeze-dried, be cut into 4cm × 7cm specification, using PET packaging bag into
Row packaging, finally carries out irradiation sterilization.
Embodiment 2
(1) it pre-processes
It takes the chitterlings tissue wash of fresh slaughtered animals clean, is placed in 0.5% acetum and impregnates 30min, chitterlings and acetic acid
The ratio of solution is 1:5, scrapes mucous layer, muscle layer, placenta percreta, the lymph node that division removes chitterlings jejunum, separation using physics
Submucosa out is cut into segment, is rinsed 3 times using purified water；
(2) it sterilizes
Using the mixed aqueous solution containing 1.0% Peracetic acid and 15% ethyl alcohol, the ratio of SIS material and mixed aqueous solution is 1:
10, under ultrasound condition, soaking at room temperature 100min carries out disinfection.It is cleaned by ultrasonic 3 times using purified water later；
(3) degreasing
The ethyl alcohol for the use of concentration being 95%, the ratio of SIS material and ethyl alcohol are 1:10, under ultrasound condition, soak at room temperature 2h.Later
It is cleaned by ultrasonic 3 times using water for injection；
(4) cell is taken off
Using containing 0.02% trypsase and containing the mixed aqueous solution of 0.02%EDTA, SIS material and trypsase/EDTA solution
Ratio be 1:5, under ultrasound condition, impregnate 30min under the conditions of 37 DEG C.It is cleaned by ultrasonic 3 times using PBS later；
The NaOH aqueous solution for the use of concentration being 25mM, the ratio of SIS material and NaOH solution are 1:20, under ultrasound condition, room temperature
Impregnate 50min.Later using PBS ultrasonic cleaning until neutral；
(5) it is lyophilized, sterilizes
By 4 layers of SIS material be superimposed, be fixed on mold, be freeze-dried, be cut into 4cm × 7cm specification, using PET packaging bag into
Row packaging, finally carries out irradiation sterilization.
Embodiment 3
(1) it pre-processes
It takes the chitterlings tissue wash of fresh slaughtered animals clean, is placed in 0.5% acetum and impregnates 30min, chitterlings and acetic acid
The ratio of solution is 1:5, scrapes mucous layer, muscle layer, placenta percreta, the lymph node that division removes chitterlings jejunum, separation using physics
Submucosa out is cut into segment, is rinsed 3 times using purified water；
(2) inactivation of virus
Using the mixed aqueous solution containing 1.0% Peracetic acid and 15% ethyl alcohol, the ratio of SIS material and mixed aqueous solution is 1:
10, under ultrasound condition, soaking at room temperature 100min is virus inactivated.It is cleaned by ultrasonic 3 times using purified water later；
(3) degreasing
The ethyl alcohol for the use of concentration being 95%, the ratio of SIS material and ethyl alcohol are 1:10, under ultrasound condition, soak at room temperature 2h.Later
It is cleaned by ultrasonic 3 times using water for injection；
(4) cell is taken off, DNA is removed and removes α-Gal antigen
Using containing 0.02% trypsase and containing the mixed aqueous solution of 0.02%EDTA, SIS material and trypsase/EDTA solution
Ratio be 1:5, under ultrasound condition, impregnate 30min under the conditions of 37 DEG C.It is cleaned by ultrasonic 3 times using PBS later；
Using the aqueous solution of the enzyme of DNA containing 5U/ml, the ratio of SIS material and DNA enzymatic solution is 1:5, under ultrasound condition, in 37
20min is impregnated under the conditions of DEG C.Later using PBS drift ultrasonic cleaning 3 times；
Using the aqueous solution of the alpha-galactosidase containing 5U/ml, the ratio of SIS material and alpha-galactoside enzyme solutions is 1:5, is surpassed
Under the conditions of sound, 20min is impregnated under the conditions of 30 DEG C.It is cleaned by ultrasonic 3 times using PBS later；
The NaOH aqueous solution for the use of concentration being 25mM, the ratio of SIS material and NaOH solution are 1:20, under ultrasound condition, room temperature
Impregnate 50min.Later using PBS ultrasonic cleaning until neutral；
(5) it is lyophilized, sterilizes
By 4 layers of SIS material be superimposed, be fixed on mold, be freeze-dried, be cut into 4cm × 7cm specification, using PET packaging bag into
Row packaging, finally carries out irradiation sterilization.
Embodiment 4
The preparation of trees-Osima jacoti, Osima excavata ECM
(1) it pre-processes
It takes the chitterlings tissue wash of fresh slaughtered animals clean, is placed in 0.01% acetum and impregnates 120min, chitterlings and vinegar
The ratio of acid solution is 1:10, scrapes mucous layer, muscle layer, placenta percreta, the lymph node that division removes chitterlings jejunum using physics, point
Submucosa is separated out, segment is cut into, is rinsed 3 times using purified water；
(2) inactivation of virus
Using the mixed aqueous solution containing 0.5% Peracetic acid and 25% ethyl alcohol, the ratio of SIS material and mixed aqueous solution is 1:
15, under ultrasound condition, soaking at room temperature 120min is virus inactivated.It is cleaned by ultrasonic 3 times using purified water later；
(3) degreasing
The ethyl alcohol for the use of concentration being 90%, the ratio of SIS material and ethyl alcohol are 1:15, under ultrasound condition, soak at room temperature 4h.Later
It is cleaned by ultrasonic 3 times using water for injection；
(4) cell is taken off, DNA is removed and removes α-Gal antigen
Using containing 0.05% trypsase and containing the mixed aqueous solution of 0.01%EDTA, SIS material and trypsase/EDTA solution
Ratio be 1:10, under ultrasound condition, impregnate 20min under the conditions of 37 DEG C.It is cleaned by ultrasonic 3 times using PBS later；
Using the aqueous solution of the enzyme of DNA containing 1U/ml, the ratio of SIS material and DNA enzymatic solution is 1:10, under ultrasound condition, in 37
30min is impregnated under the conditions of DEG C.Later using PBS drift ultrasonic cleaning 3 times；
Using the aqueous solution of the alpha-galactosidase containing 1U/ml, the ratio of SIS material and alpha-galactoside enzyme solutions is 1:10, is surpassed
Under the conditions of sound, 30min is impregnated under the conditions of 30 DEG C.It is cleaned by ultrasonic 3 times using PBS later；
The NaOH aqueous solution for the use of concentration being 40mM, the ratio of SIS material and NaOH solution are 1:10, under ultrasound condition, room temperature
Impregnate 30min.Later using PBS ultrasonic cleaning until neutral；
(5) it is lyophilized, sterilizes
By 4 layers of SIS material be superimposed, be fixed on mold, be freeze-dried, be cut into 4cm × 7cm specification, using PET packaging bag into
Row packaging, finally carries out irradiation sterilization.
Embodiment 5
Immunogenic substance detection is carried out to the sample that embodiment 1-4 is prepared.
(1) cell residue quantity measuring method: being fixed, paraffin embedding with 10% neutral formalin, is cut into 0.4 micron thin
Piece, through dimethylbenzene dewaxing, serial dehydration of alcohol, hematoxylin-eosin stains, microscopically observation cell residue situation and matrix
Fibre structure.
(2) DNA content detection method: according to YY/T 0606.25-2014, " animal derived biomaterial DNA residual is measured
Determine method: fluorescence colour " it is detected.
(3) α-Gal antigenic content detection method: after sample is fixed with paraformaldehyde, routine paraffin wax embedded section, piece thickness
3 microns.Immunohistochemical reaction is carried out using the special affinity characteristic of biotin labeling BSI-B4 and α-Gal antigen.Coloration result
Determine: dark brown yellow particle is strong positive (+++), and brown yellow granule is positive (++), and yellow particle is weakly positive (+), not
See and is colored as negative (-).
(4) lipid content detection method: referring to soxhlet extraction methods in " fatty measurement in 5009.6 food of GB/T " into
Row measurement.
Illustrate: Examples 1 and 2 are the absence of DNA and go α-Gal antigen step, and embodiment 1 is with NaOH degreasing
, bigger, Examples 1 and 2 step similar in other patents before being all, for protruding embodiment 3 and 4 is destroyed to structure
Go immunogenicity more excellent.As a result it see the table below:
Embodiment 6
Biology performance, bacterial endotoxin and anti-microbial property detection are carried out to the sample that embodiment 3 is prepared.
(1) biology performance detects
Method: it is tested referring to GB/T16886 series methods
As a result: cell-cytotoxic reaction is 1 grade；Without delayed allergy；Intradermal reaction shows that test specimen and solvent control are flat
The difference scored is less than 1.0；Without pyrogenicity；Without hemolytic reaction；Genetic toxicity test is the results show that salmonella typhimurium returns
Multiple mutation (Ames) test is negative, mouse lymphoma assay is negative, dye-free body distortion property；Without acute systemic
Property toxic reaction；Without sub- chronic generalized toxicity；Muscular grafting 30 days, 60 days, 90 days tissue reactions with negative controls without
Significant difference.
(2) detection of bacterial endotoxin
Method: it is detected referring to correlation technique in GB/T 14233
As a result: less than 2.15EU/ part.
(3) anti-microbial property detects
Sample obtained by embodiment 1 is ground in the hydrochloric acid of 0.01M with grinding rod, until being visible by naked eyes particle, and is adjusted
Its concentration is 100mg/10mL.Pepsin digestion is added, pepsin: sample ratio is 1:10.It is persistently stirred at 25 DEG C
48h, after be cooled to 4 DEG C, the 0.1 M sodium hydroxide that 1/10 volume is added adjusts PH to 7.2-7.4；
Hybrid NC machine tool base plate is prepared, picks them separately a little cultured staphylococcus aureus and Escherichia coli with oese
Bacteria suspension is made in sterile saline 5ml in inclined-plane culture substratess.Take bacteria suspension 1.0ml and the above-mentioned sample through degrading
1ml is added in the culture dish of sterilizing-drying, and addition is cooled to 50 DEG C or so of ordinary nutritional broth agar culture medium, is shaken up,
Spare after sufficiently condensing, 35~37 DEG C of inversions are cultivated 24 hours, observe bacterial growth situation；Increase simultaneously and does not have to antibacterial material
Material and 5 μ g/mL antibacterial peptides of addition compare, and as a result see the table below:
Embodiment 7
Mechanics properties testing is carried out to the sample that embodiment 3 is prepared.
(1) suture strength
Method: with the non-absorbing suture of 3-0 in sample both sides center far from being sutured at edge 2mm, by the suture other end and sample
The other end be separately fixed on tensiometer both ends, stretched with the speed of 20mm/min, until stitch points are torn, record
Maximal force；
As a result: suture strength is in 3N-5N range.
(2) tensile strength
Method: it is 10mm shape that sample is cut to width respectively in both directions；In relative humidity 40%-60%, temperature after cutting
It is tested after being placed 2 hours in 22 ± 2 DEG C of environment of degree.Fixture spacing is 25mm, and sample both ends are fixed on cupping machine
Collet on, the maximal force with the speed tensile of 100mm/min, when record fracture；
As a result: tensile strength is in 30N-35N range.
(3) bursting strength
Method: according to the measurement method of " YY 0500-2004 cardiovascular implant artificial blood vessel " 8.3.3.2 probe rupture strength
9.5mm diameter probe is chosen to be detected；
As a result: bursting strength is in 85N-90N range.
Embodiment 8
Preparation biology set
Be prepared 2, sample of Example 3 carry out capillary processing using low power laser punching instrument, and the aperture of micropore is
It 400 μm, 15 mm of pitch of holes, is cut according to the shape and size of implantation equipment, using Violet 5-0 PDS suture
By 3/4ths tight sutures at 2 laminated edges of sample, pictorial diagram is shown in Fig. 2.
In the schematic perspective view diagram 3 of the present embodiment, encapsulated layer 2 includes two panels encapsulating material, in order to form biology set 3, will be sealed
3/4ths of package material edge unite by a seam, and implantation deep brain stimulator is packed into biology by remaining a quarter opening
In set, the biology set 1 equipped with implantation deep brain stimulator is formed.
Embodiment 9
Preparation biology set
Prepare 1, sample be prepared by embodiment 4, instrument is punched by low power laser, the biology after being sutured is packed into
Row capillary processing, the aperture of micropore are 300 μm, 10 mm of pitch of holes.Selection length is 12.5 cm, and width is the sample of 6.5 cm
Product fold up sample to form clad to form biological set, and the clad folds and laminated in port and level.
Using Violet 5-0 PDS suture by port 2 and 3 and another 4 tight suture of connected side, in the perspective of the embodiment
In figure Fig. 5, implantation deep brain stimulator is packed into biology set by remaining a quarter opening 5, is formed deep equipped with implantation
The biology set 1 of portion's brain stimulator.
Embodiment 10
Prepare drug-loaded biological set
After the completion of embodiment 3(4), it is immersed in biomembrane containing 20 μ g/mld minot ring of concentration
It 24 hours in the solution of element, then completes to implement 1(5).The biology set for being loaded with drug is prepared further according to the mode for implementing 8.
Those skilled in the art can make a variety of variations to the present invention according to the above description.Thus, it is not violating
Under the premise of claim objective of the invention, certain details in embodiment should not constitute limitation of the invention, the present invention
It will be using the range that the appended claims define as protection scope.
Claims (7)
1. a kind of biology covers the application in terms of nerve stimulator implantation, it is characterised in that: the biology set is by acellular matrix
Composition, for being fitted into the pouch for being implanted to subcutaneous tissue formation after embedded nerve stimulator together.
2. biology according to claim 1 covers the application in terms of nerve stimulator implantation, it is characterised in that: described de- thin
Cytoplasmic matrix include but is not limited to the submucous layer of small intestine of mammal, submucous layer of bladder, submucous lamina of stomach, dermal matrix,
One or more combinations of pericardium, meninx, amnion, internal organs film, peritonaeum.
3. biology according to claim 2 covers the application in terms of nerve stimulator implantation, it is characterised in that: described de- thin
Cytoplasmic matrix is the submucous layer of small intestine of mammal.
4. biology according to claim 1 covers the application in terms of nerve stimulator implantation, it is characterised in that: implanted mind
Through stimulator device include but is not limited to spinal stimulator, deep brain stimulator, backstop stimulator, nervus peripheralis stimulating system,
Functionality point stimulating system, vagus nerve stimulator and sacral nerve stimulator.
5. described in any item biologies cover the application in terms of nerve stimulator implantation according to claim 1 ~ 4, it is characterised in that:
The biology set is combined by 2-12 layers of single layer acellular matrix overlapping, and complex method includes one bonded, in suture
Kind is a variety of, and thickness is between 0.1mm-3mm.
6. biology described according to claim 1 ~ any one of 4 covers the application in terms of nerve stimulator implantation, feature exists
In: the biology set shape includes rectangle, square, circle, trapezoidal, shape of dripping, triangle, ellipse, irregular shape, institute
State biology set area 4-100cm2, there is a micropore on the surface of the biology set, and the pore diameter range of the micropore is 10-400 μm,
Pitch of holes is 5-20 mm.
7. described in any item biologies cover the application in terms of nerve stimulator implantation according to claim 1 ~ 4, which is characterized in that
The biology set can be loaded into one or more drugs according to clinical demand, can be with when being implanted to the pouch of subcutaneous tissue formation
The tissue that the biology set is sutured in pouch is fixed, for preventing the intracorporal displacement of equipment.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810923575 | 2018-08-14 | ||
| CN2018109235759 | 2018-08-14 |
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| CN109125922A true CN109125922A (en) | 2019-01-04 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023060823A1 (en) * | 2021-10-11 | 2023-04-20 | 北京博辉瑞进生物科技有限公司 | Biological sleeve for accommodating implantable medical device, preparation method therefor and use thereof |
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| US20160008514A1 (en) * | 2013-03-15 | 2016-01-14 | Lifenet Health | Soft Tissue Pouch and Methods of Use Thereof |
| CN107320777A (en) * | 2017-07-12 | 2017-11-07 | 上海白衣缘生物工程有限公司 | A kind of dura mater biological sticking patch and preparation method thereof |
| US20180071526A1 (en) * | 2016-09-10 | 2018-03-15 | Cook Biotech Incorporated | Electrostimulative graft products, and related methods of use and manufacture |
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|---|---|---|---|---|
| US20110177170A1 (en) * | 2008-09-25 | 2011-07-21 | Bryukhovetskiy Andrey S | implantable neuroendoprosthetic system, a method of production thereof and a method of reconstructive neurosurgical operation |
| US20160008514A1 (en) * | 2013-03-15 | 2016-01-14 | Lifenet Health | Soft Tissue Pouch and Methods of Use Thereof |
| US20180071526A1 (en) * | 2016-09-10 | 2018-03-15 | Cook Biotech Incorporated | Electrostimulative graft products, and related methods of use and manufacture |
| CN107320777A (en) * | 2017-07-12 | 2017-11-07 | 上海白衣缘生物工程有限公司 | A kind of dura mater biological sticking patch and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2023060823A1 (en) * | 2021-10-11 | 2023-04-20 | 北京博辉瑞进生物科技有限公司 | Biological sleeve for accommodating implantable medical device, preparation method therefor and use thereof |
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