CN1275655C - Artificial peripheral nerve containing substance for promoting peripheral nerve regeneration - Google Patents
Artificial peripheral nerve containing substance for promoting peripheral nerve regeneration Download PDFInfo
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- CN1275655C CN1275655C CNB2004100094293A CN200410009429A CN1275655C CN 1275655 C CN1275655 C CN 1275655C CN B2004100094293 A CNB2004100094293 A CN B2004100094293A CN 200410009429 A CN200410009429 A CN 200410009429A CN 1275655 C CN1275655 C CN 1275655C
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Abstract
The present invention relates to an artificial peripheral nerve containing substances for promoting peripheral nerve regeneration, wherein active cells or factors or the extracts of traditional Chinese medicines are added in absorptive artificial nerve canals for promoting the regeneration of peripheral nerves. Through the verification of animal research, the artificial peripheral nerve can effectively treat the defects of the peripheral nerves and can replace autologous skin nerve transplantation.
Description
Technical field:
The present invention relates to a kind of artificial peripheral nerve for the treatment of peripheral nerve defection, be specifically related to contain the artificial peripheral nerve that promotes the peripheral nerve regeneration material.
Background technology:
Peripheral nerve injury is sickness rate and hinders the high wound of back disability rate.For repairing damaged method behind the peripheral nerve injury, the at present employing from the body Lateral Cutaneous Nerve Graft more.This method must cut on the one hand, sacrifice the sensory nerve from body, causes the sensory disturbance in the certain zone of limbs, and the tegumentary nerve donor that the while human body can Gong be taked is extremely limited.And when the body Lateral Cutaneous Nerve Graft, the tegumentary nerve donor of implantation is the nerve of one section degeneration, can only as with nerve fiber in a organized way affinity organize bridge, can not promote neuranagenesis effectively.
Therefore, develop the artificial peripheral nerve that is used for the peripheral nerve defection reparation is necessary very much.
At present, big quantity research concentrates on the artificial pipe bridge both at home and abroad, thirsts for substituting from the body tegumentary nerve with biomaterial.The artificial pipe bridge of early stage report mostly is the silica gel tube material, owing to silica gel tube can not absorb, and can only be as a kind of experimental model of observing the peripheral nerve growth pattern.So it is more that chitosan and chitin pipe bridge class etc. can attract biomaterial to be paid close attention to.But because the former degraded and absorbed poor-performing and surrounding tissue inflammatory reaction are obvious, residual in latter's manufacturing process to the organism harmful substance, can't use.
Though the report of some artificial neurons is arranged in the prior art, has been mostly to add the artificial neuron sleeve pipe of vertical property fiber.Be the artificial neuron sleeve pipe that adds vertical property collagen fiber as patents such as Chinese patents 97199928.7,99807035.1,00810000.4,02113103.1.Because the peripheral nerve fiber has the regenerated characteristics of selectivity, therefore too much vertical property fiber might hinder sensory fiber and the motor fiber selectivity far-end schwann cell band of growing on the contrary, and vertically collagen fiber occupy the space of neuranagenesis, are unfavorable for peripheral nerve regeneration.Therefore do not repair after being suitable for peripheral nerve injury.
Chinese patent 99123745.5,02129367.8 discloses and has made the composition of the neural material of repairing, but does not see that specifically being used for conduct repairs perineural artificial neuron material.
Chinese patent 02114482.6 discloses the nerve repair material with equidirectional microtubule type architectural characteristic, and characteristics are to make different external forms as required, as column type, and rectangle etc.But the outer surface of this material of explanation is a full-closed structure in the patent document, so this kind material in fact more is applicable to repair of spinal cord injury.Because airtight fully, be unfavorable for peripheral nerve regeneration on the contrary.
In fact, still not having up to now a kind of feasible material and method can be as the neural transplantation donor beyond the autologous nerve.Chinese patent 01134542.X and 011363314.2 is to be the biological tube of the promotion neuranagenesis made of primary raw material with chitosan or sodium alginate, its advantage is the absorption cycle that has excellent biological compatibility and can control, test shows that this sleeve pipe can effectively substitute traditional epineurial neurorrhaphy and the bundle film is sewed up, but its purposes mainly is the Therapeutic Method that a kind of peripheral nerve injury that is used for N/D is repaired, be used for substituting original epineurial neurorrhaphy and the stitching of bundle film, and different with the artificial neuron that is used for the treatment of neurologic defect.
In addition, all there is not the active substance that effectively promotes neuranagenesis in the artificial neuron material of prior art.
Peripheral nerve is to be the particular tissues of major function structure by the aixs cylinder of neurocyte and dendron, does not wherein contain neurocyte, has only a kind of neural Interstitial cell-Schwann cell.Another characteristics are, behind the peripheral nerve injury, degeneration appears in the fiber of far-end, and after surgical repair will rupture damaged bridge grafting nerves, nerve fiber can be again reaches effector from the near-end far-end of growing into, and then recovers original function.The characteristics above-mentioned according to peripheral nerve tissue, the key element that satisfies the neural transplantation donor is: 1) but bridge joint has the two damaged nervus lateralis broken ends of fractured bone; 2) good nervous tissue's compatibility is arranged; 3) cell changes that promotes and induce the nerve fiber growth is arranged.
Summary of the invention:
The objective of the invention is to develop a kind of artificial peripheral nerve for the treatment of peripheral nerve defection, this artificial neuron should be able to satisfy the requirement of neural transplantation donor, can substitute from the body Lateral Cutaneous Nerve Graft wholly or in part.
Technical scheme of the present invention is: add the competent cell or the factor when making the adsorbable artificial neurocele, prepare and contain the adsorbable artificial peripheral nerve that promotes the peripheral nerve regeneration material.
Described artificial neural canal is made by seaweeds, chitin analog derivative raw material, can use the chitin analog derivative that is certain deacetylation or is " amino ionizing ".
Described promotion peripheral nerve regeneration material comprises the competent cell or the factor of the conventional promotion peripheral nerve regeneration that uses of those skilled in the art, also comprises having the active Chinese medicine extraction material of the peripheral nerve regeneration of promotion etc.
The above-mentioned competent cell or the factor are preferably used nerve growth factor (NGF), marrow stromal cell, basic fibroblast growth factor (bFGF) etc.;
Above-mentioned Chinese medicine comprises one or more in Radix Hedysari, Herba Epimedii, Pheretima, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Flos Carthami, Semen Persicae, the Radix Paeoniae Rubra; In preferred use Radix Hedysari, Herba Epimedii, Pheretima, the Radix Angelicae Sinensis one or more; Extract with the Radix Hedysari single medicinal material also has satisfied effect.
Through experiment confirm, the artificial neuron of the interpolation active substance of the present invention's development can promote neuranagenesis effectively, and has excellent biological compatibility and controlled absorption cycle.
The specific embodiment:
Embodiment 1 adds the artificial perineural preparation of marrow stromal cell and the experimentation of repairing the animal peripheral nerve defection
1. the technology path of the preparation pipe bridge of adsorbable artificial marine organisms pipe bridge preparation is: and Sargassum and chitin derivativ → solution preparation → hollow extrudes → and coagulating bath solidifies → hollow circular tube drawing-off → molecular structure regulation and control and physics and biochemical modification → post-treatment and sterilization treatment → artificial bio-membrane's pipe bridge.
Previous experiments has been observed pipe bridge and be 4-12 week mutually when the intravital absorption of rat, bridged donor as neural transplantation, need to retain the phase in the body for more time, neural in growth course, the growth delay in 2 weeks is arranged when initial, later on approximately with every day 1mm speed grow to far-end, so the neurologic defect of bridge joint is longer, it is also of a specified duration more to keep the required time of structure in vivo, as the neurologic defect of bridge joint 5cm, estimates need keep 8 weeks of structure in vivo at least; As neurologic defect is 10cm, then needs for 16 weeks at least.Therefore, further investigate from the thickness and the absorption cycle of tube wall, to prepare the pipe bridge that is applicable to different defect length.Meanwhile, also need repeat in the animal body and external Study on biocompatibility to every batch of new pipe bridge sample.
2. the separation and Extraction of marrow stromal cell, In vitro culture and the research that lapses to thereof
The separation of marrow stromal cell: bone marrow aspiration blood drawing, sorting marrow stromal cell, people and Os Mus marrow → Ficoll routine sub-elect mononuclear cell → washing and remove non-adherent cell, and adherent cell is marrow stromal cell → In vitro culture.
Experiment in vitro: set up by marrow stromal cell directional induction neurocyte standardization cultivating system
The marrow stromal cell of cultivating is carried out behind the labelling and its co-cultivation of Schwann cell, observe it and can be divided into Schwann cell (a kind of Interstitial cell that peripheral nerve is unique).
Experiment in the body: the marrow stromal cell of In vitro culture is carried out making up with pipe bridge behind the labelling, place neurologic defect portion, observe lapsing to of interior time-to-live of its body, activity change and attribute.
Identify: identify with the SABC method whether marrow stromal cell is divided into neural stem cell, neuronal cell, Schwann cell in the above experiment in vivo and vitro, used monoclonal antibody is respectively nestin, NSE, S-100; With the antibody of various neurotrophic factors, utilize ELISA whether to identify in atomization to comprise NGF, CNTF, BDNF, NF-3, GDNF etc. by the secretory nerve trophic factors; Simultaneously the nervous tissue's cell that induces being carried out neuropotential measures.
3. artificial perineural preparation
On the marine organism material support, the two is together added changes in the wall type bioreactor then with the marrow stromal cell suspension inoculation of the people of In vitro culture and Mus, makes that cell and material are uniform to be combined, the structure artificial neuron.
4. repair the experimentation of animal peripheral nerve defection with artificial peripheral nerve
Experiment will divide two parts to carry out, and the experimental stage that lapses in observing artificial perineural histocompatibility and marrow stromal cell body, the sciatic nerve of employing toy rat is repaired the laboratory observation of neurologic defect; After the toy experimental result confirms its effectiveness, enter the damaged reparation experiment of the long section of median nerve of primates monkey,
(1) rat sciatic nerve defect repair experiment
Experiment grouping and method: select 24 healthy male SD rats (330-400g) for use, be divided into A, B, C3 group at random, adopt chlore-ammonia ketone (2ml/kg, lumbar injection) anesthesia.Aseptic condition exposes the bilateral sciatic nerve down, the A group: left side (A0) be 10mm and 15mm place cut-out sciatic nerve above the sciatic nerve crotch, and original position is sewed up with 8-0 nylon wire 3 pin adventitias respectively.Right side (A1) is 10mm and 15mm place cut-out sciatic nerve above the sciatic nerve crotch, remove neural free section as the neurologic defect model, adopt long 9mm, the chitin sleeve pipe bridge joint neurologic defect of internal diameter 1.5mm, 2mm is inserted at two ends respectively, and 8-0 nylon wire 2 pins are fixed.B group: left side B 0 is 10mm and 20mm place cut-out sciatic nerve above the sciatic nerve crotch, and original position is sewed up with 8-0 nylon wire 3 pin adventitias respectively.Right side B 1 is 10mm and 20mm place cut-out sciatic nerve above the sciatic nerve crotch, remove neural free section as the neurologic defect model, adopt long 14mm, the chitin sleeve pipe bridge joint neurologic defect of internal diameter 1.5mm, 2mm is inserted at two ends respectively, and 8-0 nylon wire 2 pins are fixed.The C group: left side C0 is 8mm and 23mm place cut-out sciatic nerve above the sciatic nerve crotch, and original position is sewed up with 8-0 nylon wire 3 pin adventitias respectively.Right side C1 is 8mm and 23mm place cut-out sciatic nerve above the sciatic nerve crotch, remove neural free section as the neurologic defect model, adopt long 19mm, the chitin sleeve pipe bridge joint neurologic defect of internal diameter 1.5mm, 2mm is inserted at two ends respectively, and 8-0 nylon wire 2 pins are fixed.
Draw materials: 12 weeks of postoperative at room temperature, with the method anesthetized rat fixing after, free bilateral sciatic nerve, stimulating electrode is placed on the distance end of graft or anastomosis earlier, recording electrode places the gastrocnemius stage casing, reference electrode places muscle on every side.Parameter is selected: the wide 0.1ms of square wave stimulus wave, 1 hertz, constant current stimulus intensity 5-8mA.Record muscle compound action potential and motor conduction velocity.
After electric physiology result detects, nerve is left and taken histological specimen, each group is gone into flesh point place with the proximal end 2mm of nerve suture place to the shin peroneal nerve and is left and taken, formalin fixed 30 minutes, cannula portion and transplanting portion stay and do immunohistochemical staining and adopt GFAP, s100, GAP43, MAP dyeing rip cutting and cross section, stage casing to observe respectively, and far-end 2mm place begins to leave and take the 2mm specimen and carries out cross section osmic acid dyeing counting comparison.
Statistical disposition as a result: unit visual field myelinated nerve fiber counting and electrophysiologic study result adopt spss10.0 to carry out one factor analysis of variance, compare between organizing.
Finding under 40 times of fibrescope after the nerve injury, with interior damaged, can observing newborn fiber continuity and exist, and the new vessels sex-linkage of climing shape is arranged for 10mm.Osmic acid dyeing is visible far-end new life's nerve fiber and myelin also.It is damaged with interior rat sciatic nerve that histology's presentation of results, this kind biological tube can bridge joint have a 10mm; The generation of neuromuscular compound action potential shows: nerve had been grown damaged section after 12 weeks, and the far-end target organ of having grown into, the nerve conduction function begins to recover, prove this sleeve pipe effectively bridge joint 10mm with interior rat sciatic nerve damaged (6-8 of diameter nerve doubly), pass through the statistical analysis histological stain simultaneously and electric physiology results suggest is damaged for 5mm and 10mm, the index result of function of nervous system also shows that the repairing effect of this kind artificial neuron and font neural transplantation are similar, can substitute nerve autograft.
Embodiment 2 adds the artificial perineural preparation of nerve growth factor (NGF) and the experimentation of repairing the animal peripheral nerve defection
Used NGF is Wuhan Haite Bio-pharmaceutical Co., Ltd's product (authentication code: traditional Chinese medicines examination word s20020117); 4500U/ props up, and adopts the 1000u/cm artificial neuron.
Wherein artificial perineural preparation method is to contain the biogel of NGF except that the active substance that adds, with embodiment 1.
Embodiment 3 adds the artificial perineural preparation of Chinese medicine compound active ingredient and makes up artificial peripheral nerve research jointly with the marine organisms sleeve pipe
1. effective components of Chinese medicinal is extracted
Crude drug: Radix Hedysari, Herba Epimedii, Pheretima.Radix Hedysari is available from Gansu, original producton location, and all the other medical materials are purchased in Beijing pharmacy of Tongrentang.Drug dose is than being 10 parts of (weight portion) Radix Hedysari, 5 parts of Herba Epimedii, 3 parts of Pheretimas
Equipment: Rotary Evaporators (containing vacuum pump), electric heating decoction vessel, condensing tube, glass apparatus such as eggplant-shape bottle.
Extraction step:
1) takes by weighing every kind of medicine by prescription, wherein, Radix Hedysari is cut the segment of hand hay cutter into about 2cm, roll the back weighing.
2) medicine is placed in the round-bottomed flask, decocting three times, each is with 10 times of dose, and 8 times, 6 times of water add, first pass decocted two hours, respectively fried in shallow oil one hour for twice the back, and every time fried liquid is filtered in the container, and fried liquid is dewatered by revolving the steaming instrument, be the liquid that contains crude drug amount 2g/ml with the distillation aqueous fusion then, go to freezing preservation in the aseptic bottle.
2. Chinese medicine compound is extracted cell toxicity test
With the traditional Chinese medicine compound extract of the present invention 0.22 μ m strainer filtering of purifying, cultivate (Gibco BRL, the U.S.) doubling dilution with the PRMI1640 that contains 15% hyclone, split in 24 orifice plates.The SP2/0 cell of exponential phase, the adjustment cell concentration is 106/ml, adds 10ul respectively in 24 orifice plates of the Radix Hedysari culture fluid that contains doubling dilution, 37 ℃ of cultivations.Every day the observation of cell upgrowth situation.
Observe that the result shows the compound recipe Radix Hedysari extract at 1: 16000 after 3 days, 1: 32000 o'clock (being that NGF acts on dosage effectively) all has the effect that promotes hypertrophy and differentiation to Schwann cell.Explanation can promote the hypertrophy of Schwann cell.Drug safety.
3. artificial marine organisms pipe bridge preparation and performance optimization
The biological property of material (reaching histocompatibility when absorbing in the animal body mutually) research; The material and the Schwann cell compatibility and be suppressed to the fibroblast growth The Characteristic Study: specific as follows, aseptic operation takes out sciatic nerve, shred, carrying out external Schwann cell with culture fluid in culture dish cultivates, pad is freeed the thing material membrane in the culture dish, and contrast is set, divide different times to observe Schwann cell and fibroblastic form, activity and density with means such as inverted microscope, light microscopic section, histology and immunohistochemical staining, scanning electron microscopies, carry out the unit are counting, and observe the internal structure and the functional activity of Schwann cell.
4. will induce the nervous tissue's cell suspension that differentiates or stem cell and traditional Chinese medicine compound extract to be seeded on the marine organism material support that this problem develops, then the two together being added changes in the wall type bioreactor, make that cell and material are uniform to be combined, make up the neuranagenesis chamber, carry out the rat sciatic nerve repairing test.
1. laboratory animal is divided into two groups greatly at random, and first group is further divided into A group: get the capable adventitia suture in situ of rat left side lower limb sciatic nerve; B group: get the right capable sleeve pipe of the lower limb sciatic nerve little gap original position socket of rat.Second group is further divided into the C group: get the capable adventitia Rotate 180 of rat left side lower limb sciatic nerve degree and sew up; D group: get the right little gap of the capable sleeve pipe of the lower limb sciatic nerve distally broken ends of fractured bone Rotate 180 degree socket of rat.Other gets a group rat as normal neural contrast.2. experimental technique: the SD rat with 2.5% pentobarbital sodium (50mg/kg) intraperitoneal injection of anesthesia after, enter by the vastus lateralis gap and to expose the bilateral sciatic nerve, the sharp property in 1.0cm place cut-out sciatic nerve carries out respective handling according to each group then below ischial tuberosity.3. test each treated animal bone marrow aspiration in advance in advance, separate marrow stromal cell and hemopoietic tissue stem cell and train into nervous tissue's cell for a certain area, nervous tissue's cell of experimental group individuality is used for biological tissue's pipe bridge preparation, and all the other are respectively organized nervous tissue's cell and are used for the external activity laboratory observation; 4. distinguish first, second, third and fourth week after surgery, get rat at random, the back row operating microscope observation down of drawing materials, myelinated nerve fiber counting under the light microscopic from first group and second group at every turn, electrophysiological examination and functional check (sciatic nerve function index) are observed by osmic acid dyeing Histological section.
Above embodiment 2 and 3 experimental result show:
1. the artificial peripheral nerve that adds Chinese medicine compound and NGF all has the effect that promotes peripheral nerve regeneration.
2. traditional Chinese medicine compound extract whole body of the present invention administration has protective effect to spinal neuron.Confirm aspect the said preparation Its Mechanisms: it has the propagation of the Schwann cell that plays a significant role in the promotion neuranagenesis process, the function of differentiation.The cell of proof differentiation simultaneously is a new outgrowth cell behind the drug effect.Therefore, can think that traditional Chinese medicine compound extract of the present invention plays a part sure to perineural reparation.Its mechanism of action may be for after the nerve injury around, give full play to its expand neural periphery and internal blood vessel, improve injured nerve microcirculation, improve arteriolar blood flow, and energy raise immunity, improve the activity of macrophage, promote nucleic acid, protein anabolism, accelerate the removing of injured nerve degeneration necrosis material, increase supply the neuranagenesis material, promote the recovery of axoplasmic flow, and then prevent neuronic degeneration necrosis and promote its early recovery.
The neuranagenesis pipe, adopt medical chitosan and the compound basic fibroblast growth factor of sodium alginate material (bFGF) and/or nerve growth factor (NGF) to make, good biocompatibility, body is had no adverse reaction, effect with guiding nerve fiber regeneration is used for the clinical practice that spinal cord and peripheral nerve injury patient regenerate and rebuild.
Attached: artificial peripheral nerve technical standard
1. specification:
Internal diameter: 1.5mm, 2mm, 3mm, 4mm, 5mm, 8mm, 10mm.
Length: 3cm, 4cm, 5cm, 6cm, 7cm, 8cm, 9cm, 10cm, 15cm, 20cm.
Internal diameter and length should meet compliance marker ± 10%, and pipe thickness is answered≤2mm.
2. specification requirement
2.1 physical property
Outward appearance should be white in color or faint yellow tubulose, should clean no visible foreign substance pollution; Tensile strength should be not less than 0.5Mpa; Elongation at break should be not less than 25%.
2.2 chemical requirement
Acid-base value: the difference of test liquid and blank liquid pH value is not more than 1.5; Total metals should be not more than 10 μ g/g; Arsenic content should be not more than 1 μ g/g;
Be positive in conjunction with the cell growth factor discrimination test;
Being used for its biodegradation period of belled pipe bridge should be greater than 12 week, be used to repair neurologic defect neuranagenesis pipe biodegradation period should be greater than 24 weeks.
2.3 biological requirement
Should meet aseptic, apyrogeneity requirement;
Cytotoxicity should be not more than 1 grade;
Should there be acute general toxicity effect, no Intradermal stimulation, no sensitization;
Implant inflammatory cell half a year and react the requirement that should meet GB/T16886.6-1997;
Hereditary-less toxicity (comprising AMES test, micronucleus test and chromosomal aberration test).
3. test method
3.1 physical test
Outward appearance: the normal or professional's direct observation of correcting defects of vision of vision;
Specification: employing standard or special measuring tool are measured;
Intensity: after earlier exsiccant sample being soaked 30 minutes in phosphate buffer (PBS) before the test, adopt material pull-test machine to measure, the result should meet the requirements.
3.2 chemical test
The acid-base value test: test liquid is pressed sample 0.2g and is added the 1ml distilled water, soaks 24 hours under 37 ℃ of conditions, and put and be chilled to room temperature preparation, serve as contrast liquid to criticize water together.Test liquid is undertaken by 5.4 methods among the GB/T14233.1-1998;
Content of beary metal test: undertaken by the method for stipulating in two appendix VIII of Pharmacopoeia of People's Republic of China version in 2000 H heavy metal inspection technique;
Arsenic content: undertaken by the method for stipulating in two appendix VIII of Pharmacopoeia of People's Republic of China version in 2000 J arsenic inspection technique;
Neuranagenesis pipe jointing cell growth factor discrimination test: the section of neuranagenesis pipe is fixed on the microscope slide, adopting anti--bFGF antibody and anti-NGF antibodies to carry out immunohistochemical staining should be positive, adopt the negative contrast of neuranagenesis pipe of acellular somatomedin, reaction should be negative.
Neuranagenesis pipe biodegradation test: the sample (W1) of weighing placed contain 10mg/ml lysozyme phosphate buffer (PH=7.4), placed 7 days at 37 ℃, change the lysozyme buffer during this time 2 times, weighed (W2) after with purified rinse water, drying, constant weight in the 7th day, by formula (1) calculates degradation rate.
Degradation rate=[(W1-W2)/W1] * 100%
3.3 biologic test
The preparation of experimental liquid: sample thief is pressed 0.2g and is added the 1ml normal saline, soaks 24 hours under 37 ℃ of conditions, puts to be chilled to filter that room temperature adopts 0.2 micron to filter the back standby, serving as contrast liquid with batch normal saline;
Sterility test and pyrogen testing: undertaken by the method for stipulating among the GB/T14233.2-1993;
Cell toxicity test, whole body acute toxicity test, Implantation Test and genetic toxicity test: undertaken by the method for stipulating among the GB16886.5-1997;
Intradermal stimulates and sensitization test (STT): undertaken by the method for stipulating among the GB16886.10-2000.
Claims (9)
1. artificial peripheral nerve of being made by the chitin analog derivative, feature are to contain to promote the peripheral nerve regeneration material.
2. the described artificial peripheral nerve of claim 1, described chitin analog derivative is deacetylation or is amino Ionized chitin analog derivative.
3. claim 1 or 2 described artificial peripheral nerves, described promotion peripheral nerve regeneration material are the competent cell or the factors that promotes peripheral nerve regeneration.
4. the described artificial peripheral nerve of claim 3, the competent cell of described promotion peripheral nerve regeneration or the factor are NGF.
5. the described artificial peripheral nerve of claim 3, the competent cell of described promotion peripheral nerve regeneration or the factor are marrow stromal cells.
6. claim 1 or 2 described artificial peripheral nerves, described promotion peripheral nerve regeneration material is a Chinese medicine extract.
7. the described artificial peripheral nerve of claim 6, described Chinese medicine is one or more in Radix Hedysari, Herba Epimedii, Pheretima, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Flos Carthami, Semen Persicae, the Radix Paeoniae Rubra.
8. the described artificial peripheral nerve of claim 6, described Chinese medicine is Radix Hedysari, Herba Epimedii, Pheretima and Radix Angelicae Sinensis.
9. the described artificial peripheral nerve of claim 6, described Chinese medicine is Radix Hedysari.
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