CN110124009A - It is a kind of to contain the pharmaceutical composition and its application that promote repairing of neural injury and regenerated reparation peptide - Google Patents
It is a kind of to contain the pharmaceutical composition and its application that promote repairing of neural injury and regenerated reparation peptide Download PDFInfo
- Publication number
- CN110124009A CN110124009A CN201810135021.2A CN201810135021A CN110124009A CN 110124009 A CN110124009 A CN 110124009A CN 201810135021 A CN201810135021 A CN 201810135021A CN 110124009 A CN110124009 A CN 110124009A
- Authority
- CN
- China
- Prior art keywords
- peptide
- pharmaceutical composition
- reparation
- regenerated
- product
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Peptides Or Proteins (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention discloses a kind of containing the pharmaceutical composition and its application that can promote repairing of neural injury and regenerated reparation peptide.Pharmaceutical composition provided by the invention, the reparation peptide containing 7 amino acid residues composition.Reparation peptide in pharmaceutical composition provided by the invention equally can be in conjunction with FGFR2 compared with product external application recombination FGF2 similar at present, but affinity is higher, molecular weight is smaller, and use chemical synthesis process rather than gene engineering method, therefore under the use condition of equivalent molar concentration, required production cost and use cost is lower, so being the product of the rush neurocyte proliferation of good substitution recombination FGF2.And reparation peptide provided by the invention is with respect to FGF2, because of only 7 amino acid, therefore palliating degradation degree substantially reduces, and the results show disclosed by the invention, the pharmaceutical composition for containing reparation peptide can continuingly act on therapentic part, the reparation of neurotrosis can be remarkably promoted, therefore there is technical advance.
Description
Technical field
The invention belongs to biomedicine field, in particular to it is a kind of containing repair peptide pharmaceutical composition and it making
Regeneration in terms of standby neurotrosis and the application in the product of reparation aspect.
Background technique
Many factors will cause the damage of cell and tissue.Tissue site and its healthy cell nearby survived be not after damage
It is disconnected to be divided and be proliferated, to replace dead cell and repair damaged tissues, this physiological function of organism be known as regenerating and
It repairs.
Under normal circumstances, the reparation of human body Different Organs and power of regeneration are different.Epidermal cell, is made lymphocyte
Haemocyte etc. belongs to the strong cell of regeneration power.And other as vascular endothelial cell, periosteum cell, various body of gland organs cell if
The cell for having stronger regeneration power for belonging to time level-one can also show certain power of regeneration when being damaged.In addition, also
There is regeneration power faint or cell without regeneration power, it is extremely difficult after being damaged if axoneure and gangliocyte regeneration are very weak
Restore original function.
Influence many because being known as of regeneration.In addition to organize and cell itself power of regeneration other than, also there are several types of
Factor: (1) degree and range of tissue damaged's wound.(2) age factor.(3) nutrition condition: sufficient protein, injection Vitamin B_6
It should be able to promote the reparation of damage, reparation on the contrary then that various damages can be delayed with mineral calcium, zinc confession.(4) drug influence: have
A little Drug inhibition inflammation, but be unfavorable for body and eliminate wound infection, moreover it is possible to inhibit granulation tissue growth and collage synthesis, accelerates glue
Original is decomposed；There are also the cell toxicity medicaments in anticarcinogen can also delayed healing.(5) blood supply: after tissue damage, due to local hair
Thin blood vessel is also destroyed or other factors lead to vascular sclerosis etc., can all cause blood supply insufficient and tissue is caused to be sought
Support bad, obstruction healing.(6) innervation: the tissue for losing innervation can lose power of regeneration.
From the above it can be seen that after the tissue of body incurs loss, except can not outside the extraneous such as age objective factor intervened, from
Increase the nutrition supply of damaged part, the new life and mind that it promotes survivaling cell proliferation, promotes capillary using pharmaceutical intervention
Regeneration etc. through cell, can accelerate the reparation of tissue.
Nervous system is the function point analysis system to play a leading role in human body.Each organ of human body, the function of system and various
Physiology course is interknited, is influenced each other, close fit, to realize under the direct or indirect adjusting control of nervous system
With the normal vital movement of maintenance.Meanwhile the nervous system of human body can experience the variation of external environment, receive internal and external environment
Change information constantly carries out rapid and perfect adjustment to internal various functions, human body is made to adapt to the variation of internal external environment.
Nervous system is made of maincenter part and its outer peripheral portion.Hub section point includes brain and spinal cord, is located at cranium
Chamber and intraspinal tube, the two are structurally and functionally being closely connected, and form central nervous system.Outer peripheral portion includes 12 pairs of cranial nerves
With 31 pairs of spinal nerves, they form peripheral neverous system.Peripheral nerve is distributed in whole body, brain and spinal cord and other organs of whole body
Connect, make central nervous system can experience internal and external environment variation (by afferent nerve transmit sensory information) and
Various functions (conveying regulating command by efferent nerve) in vivo is adjusted, to guarantee the complete unified of human body and its fit to environment
It answers.
The central nervous system of human brain and spinal cord composition lacks self-regeneration and repair ability, caused by its damage
Cell death, disorganization and nervous function permanent loss, there is no effective treatment means at present.
Peripheral nerve injury divides open injury and non-open injury.The former generally occurs together in the opening damage of soft tissue
Wound causes the part truncation or full truncation of nerve；The latter concurrently in the non-open injury of the passivity of soft tissue, causes nerve cord
Contusion, compressing or stretching, occur small hemorrhage and oedema, myelin oedema and denaturation in nerve.The result of peripheral nerve injury
It is clinically mainly shown as neural paralysis, sensory disturbance, dyskinesia and muscular atrophy is occurred by the region of the innervation
Deng.
Clinically repairing of neural injury class drug mainly has gangliosides, Cerebrolysin Vial, according to reaching in China at present
La Feng, Oxiracetam, small ox blood (clear) deproteinized and mouse nerve growth factor (mNGF) etc..Gangliosides (GM1) are as mind
Through nutrient drug, it is the natural component part of neuron membrane, brain part amount of blood supply can be increased；Calcium accumulation inside cells are prevented, are dropped
Low cell membrane failure；Glutamic neuron after reduction hypoxic-ischemic, reduces its neurotoxic effect, inhibits ischemic-hypoxic brain injury
Neuron Apoptosis afterwards.Edaravone is the global first mechanism of action listed the not only cerebral protective agent without fibrinolytic but also without anticoagulation,
Improve nervous symptoms, daily life active ability and dysfunction caused by Patients With Acute Cerebral Infarction；But because of its liver renal toxicity, usually only
It is limited for the treatment of acute nerve injury, and to its indication, clinically not as good as mouse nerve growth factor and nerve
It is common to save glycosides rouge.Cerebrolysin Vial stimulates the energetic supersession of neuron, improves cerebrum blood supply, promotes aerobic metabolism, but
There are Product quality and safety risks.Small ox blood (clear) deproteinized is chiefly to facilitate intake and utilization of the cell to glucose and oxygen
With promotion energetic supersession, increase amount of blood supply.Oxiracetam is nootropic agents, and Phosphorylcholine and phosphatidyl ethanolamine is promoted to close
At increasing the synthesis of protein and nucleic acid in brain.But small ox blood (clear) deproteinized and Oxiracetam side effect are more.Mouse mind
It is neuroprotective agent, neurotrophic agents and nerve regeneration agent through growth factor, prevents and treats acute lesion secondary lesion (Ru Naoshui
Swollen, Ca2+ influx, EAA toxicity, free radical damage, dysbolism etc.) and nerve regneration reparation, enhancing endogenous neural is promoted to seek
Supporting property etc.；It can be used for the disease and nervous system development of neuron Incomplete injury caused by all nervous system lesions
Disorder, indication range is relatively wide and side effect very little.In general, clinical common repairing of neural injury class drug is mainly
Mouse nerve growth factor and gangliosides.
Currently, having no the repairing of neural injury drug development success containing small molecule active peptides.
Summary of the invention
In order to overcome the disadvantages and deficiencies of the prior art, mind can be promoted the primary purpose of the present invention is that providing one kind and containing
Through injury repair and the regenerated pharmaceutical composition for repairing peptide.
The pharmaceutical composition provided by the invention contains the reparation peptide of 7 amino acid residues composition, which is to pass through
Phage peptide library (7 peptide library), using the film outer segment of fibroblast growth factor acceptor 2 (FGFR2) as target spot, multi-turns screen simultaneously reflects
It is fixed and acquisition.There is no literature reported on the reparations that the sequences polypeptide can be used for neurotrosis so far.
Another object of the present invention is to provide the applications of aforementioned pharmaceutical compositions.
The purpose of the invention is achieved by the following technical solution:
The present invention provide it is a kind of containing can promote repairing of neural injury and it is regenerated repair peptide pharmaceutical composition, contain
Repair peptide JCH2, sequence GPANVET.
Reparation peptide JCH2 of the present invention can be obtained using chemically synthesized method, molecular weight 686.72Da.
The object of the present invention is to provide the pharmaceutical compositions to prepare the application in repairing of neural injury and regenerated product,
Especially central nervous system injury and peripheral nerve injury caused by preparation brain trauma, headstroke, brain edema and cerebral anoxia etc.
Caused by sensory disturbance, the application in the neural restoration and regenerated product of dyskinesia and dystrophia.
The product is preferably curable product.
The preparation type of the product is preferred but is not limited to solution or dry powder.
The contents of the present invention are the reality on human vascular endothelial HUVEC, chick chorioallantoic membrane and the animal model of rat
It tests.
The present invention has the following advantages and effects with respect to the prior art:
Containing repairing, peptide is and current similar product external application recombinates FGF2 in pharmaceutical composition provided by the present invention
Compared with (155 amino acid, with FGFR2 specific bond), it is suitable promoting cell Proliferation effect, but affinity is higher, molecular weight is smaller,
And use chemical synthesis process rather than gene engineering method, therefore under the use condition of equivalent molar concentration, required production
Cost and use cost are lower, so being the product of the promotion neurotrosis of good substitution recombination FGF2.And recombination FGF2
Storage and transport condition is more harsh in vitro, degradable, causes the accumulation of therapentic part low, it is difficult to continuous action, therefore
Limit and affect in certain degree its using and related dosage form exploitation, and reparation peptide provided by the invention is with respect to FGF2, because
To only have 7 amino acid, therefore palliating degradation degree substantially reduces, and the results show disclosed by the invention, should contain reparation peptide
Pharmaceutical composition can continuingly act on therapentic part, the reparation of neurotrosis can be remarkably promoted, therefore there is technical elder generation
Into property.
Detailed description of the invention
Fig. 1 is the result figure for the affinity that peptide JCH2 and FGF2 and FGFR2 is repaired in the detection of ITC method.
Fig. 2 is that the detection of CCK-8 method repairs peptide JCH2 and FGF2 to the rush cell of human umbilical vein endothelial cell (HUVEC)
The result figure of proliferation function.
Fig. 3 is the result figure repaired peptide JCH2 and chick chorioallantoic membrane medium vessels is promoted to generate.
Fig. 4 is the foundation of rat dorsal root nerve injury model and the schematic diagram of drug therapy.
Fig. 5 is to repair the measurement rat that peptide JCH2 is repaired after dorsal root ganglion damage to withdraw threshold value to mechanical stimulus: vertical
Threshold of the coordinate representation right hand than left hand lift pawl number.It is more to be worth bigger expression lift pawl number, sense more sensitive to mechanical pain stimulation
Feel that functional rehabilitation is better.Label sham is sham-operation group, and PBS is, with PBS solution processing group, JCH2 is using reparation peptide after wound
As a result to be measured group of processing knows the reaction after reparation peptide can improve Damage of Rats to mechanical pain, illustrates to damage dorsal root ganglion
Wound has significant repair.
Fig. 6 is to repair the rat after peptide JCH2 reparation dorsal root ganglion is damaged to test hot pain stimulation recovery: ordinate table
Show threshold of the right hand than the left hand lift pawl time.It is shorter the time required to being worth smaller expression lift pawl, it is more sensitive to hot pain stimulation, feel function
It is better to restore.Label sham is sham-operation group, and PBS is, with PBS solution processing group, JCH2 is using reparation peptide processing after wound
To be measured group, as a result known to repair peptide and can improve reaction after Damage of Rats to hot pain, illustrate to have dorsal root ganglion damage aobvious
The repair of work.
Fig. 7 is after detection dorsal root ganglion crushes, and using repairing after peptide is handled 2 weeks, indirect immunofluorescence detection is neural
The growing state of first aixs cylinder illustrates antibody and fluorescence secondary antibody using marker protein NF200.
Fig. 8 is after detection dorsal root ganglion crushes, and using repairing after peptide is handled 2 weeks, indirect immunofluorescence detection is neural
The growing state of first aixs cylinder illustrates antibody and fluorescence secondary antibody using marker protein Laminin.
Fig. 9 is after detection dorsal root ganglion crushes, and using repairing after peptide is handled 2 weeks, indirect immunofluorescence detection is neural
The growing state of first aixs cylinder illustrates antibody and fluorescence secondary antibody using marker protein CGRP.
Specific embodiment
Present invention will now be described in further detail with reference to the embodiments and the accompanying drawings, but embodiments of the present invention are unlimited
In this.
Experimental method used in the following example is conventional method unless otherwise specified, used in embodiment
Experimental material, reagent etc. unless otherwise specified, be that commercial sources obtain.It should be understood that these embodiments are merely to illustrate this
It invents rather than for limiting the scope of the invention.
Embodiment 1
1, the affinity of peptide JCH2 and FGFR2 are repaired in the detection of ITC method
The affinity detected using isothermal micro-calorimeter (ITC), as a result as shown in Figure 1, repairing peptide JCH2 and FGFR2
Affinity costant K=7.35E8 ± 2.10E8M-1, dissociation constant Kd ≈ 1.37nM, and the affinity costant of FGF2 and FGFR2 is K=
1.62E5±2.50E4M-1, 6.17 μM of dissociation constant Kd ≈.The affinity for repairing peptide JCH2 and FGFR2 as the result is shown is significantly larger than
The affinity of FGF2 and FGFR2, the former is about 4500 times of the latter.(K indicates affinity costant, and Kd indicates dissociation constant, and K is bigger,
Kd is smaller, indicates that affinity is stronger).
2, the detection of CCK-8 method is repaired peptide JCH2 and FGF2 and is proliferated to the rush of human umbilical vein endothelial cell (HUVEC) and makees
With
HUVEC cell is taken, 96 plates is spread after 24 hours hungry after adherent by 4000, every hole cell and JCH2, FGF2 is taken, by 5
× multiplication concentration is handled 24 hours, is handled later using CCK-8 reagent, microplate reader detects each hole OD value.As shown in Fig. 2,
Low concentration group (≤0.16 μM), it is suitable that JCH2, FGF2 promote proliferation activity, and cell Proliferation suppression occur in high concentration group, FGF2 group
The phenomenon that processed, but JCH2 still has rush proliferation activity.As a result it prompts, JCH2 can promote vascular endothelial cell growth, and effect is held
Continuous property is good.
3, the growth of chick chorioallantoic membrane medium vessels can be promoted by repairing peptide JCH2
The fertilized eggs of culture 5 days are taken, head-up shell breaking, exposure chick chorioallantoic membrane, placement silica gel ring, will in center greatly
Each 10 μ L of JCH2 of 25 × multiplication concentration is added dropwise in silica gel ring, and clean filter paper closes opening, and setting up PBS solution processing group is
Blank control.It is further cultured for 3 days, strips chick chorioallantoic membrane later, stereoscopic microscopic observation is taken pictures, and software I mageJ plus is to image
It is analyzed and processed.As shown in figure 3, the capillary in chick chorioallantoic membrane increased significantly, as dosage increases after JCH2 is added
And increase.Illustrate that JCH2 has been obviously promoted the generation of blood vessel.
4, the foundation of rat dorsal root nerve injury model
The model is for detecting the influence that drug restores Peripheral Nerves in Rats sensory function.
Specific method is as shown in figure 4, the segment rat spinal cord C5 to T1 is exposed the method by surgical operation.Use tweezer
Son pressed from both sides under same dynamics on the right side of Dorsal root, make its Dorsal root damage but it is not broken.Later daily at Damage of Rats attachment injection to
Drug is surveyed, is observed continuously 21 days 3 weeks.
5, it repairs peptide JCH2 and repairs reaction of the measurement rat to mechanical stimulus after dorsal root ganglion damage
Mechanical pain irritant test is a kind of classical way for being widely used in and checking the sensory function of neuropathic pain animal.
Specific method: rat is stood on scaoffold, and wherein surface is the wire mesh of wide specification.Von-Frey fiber
(being very accurate calibration metal wire) passes through mesh, exposes the lower surface of fore paw from following insertion.On threshold, animal is fast
Fast ground is thrown away by its claw from fiber.Mechanicalness withdrawal threshold is defined as causing the minimum gauge line of withdrawing reaction to pierce
Swash.Every foot (before left front and right) measures 5 times respectively, the number of record lift pawl.
As shown in figure 5, ordinate indicates threshold of the right hand than left hand lift pawl number.It is more to be worth bigger expression lift pawl number,
More sensitive to mechanical pain stimulation, sensory function restores better.Label sham be sham-operation group, PBS be wound after at PBS solution
Reason group, JCH2 be using repairing to be measured group of peptide processing, as a result known to repair peptide and can improve after Damage of Rats to the anti-of mechanical pain
It answers, illustrating to damage dorsal root ganglion has significant repair.
6, the rat after repairing peptide JCH2 reparation dorsal root ganglion damage is to hot pain stimulation recovery experiment:
Rat is placed in transparent plastic room (18 × 29 × 13cm, 2.2mm are thick).Before testing 20 minutes when be put into and make
Object adapts to environment.Then heat source is placed under the glass plate before the right side or below left front pawl.Pawl recalls automatic activation timer, has
Delay in 0.1 second.It carries out measuring and recording the average paw withdrawal time 3 times with 15 minutes intervals.
As shown in fig. 6, ordinate indicates threshold of the right hand than the left hand lift pawl time.It is got over the time required to being worth smaller expression lift pawl
Short, more sensitive to hot pain stimulation, sensory function restores better.Label sham be sham-operation group, PBS be wound after use PBS solution
Processing group, JCH2 be using repairing to be measured group of peptide processing, as a result known to repair peptide and can improve after Damage of Rats to the anti-of hot pain
It answers, illustrating to damage dorsal root ganglion has significant repair.
7, the growing state of indirect immunofluorescence detection neuron axon
To time point to be measured (2 weeks or 4 weeks), after rat enters deep anaesthesia state, thoracic cavity is opened, exposes heart, gently
Light pruning breaks right auricle of heart, from quasi- apex of the heart position inserting needle to left ventricle.Peristaltic pump is opened, is first perfused with PBS, then with 4%PFA fixer
Perfusion, until rat liver color is peach yellow, body rigidity.
C5-T1 myeloid tissue and Dorsal root are separated with surgical instrument, it is rear in 4%PFA to fix for 24 hours, 4 in 15% sucrose
Night is spent, then 4 spend night in 30% sucrose.Frozen section can be carried out after being embedded with OCT, 15 μm of thickness, only receive the segment C7
Tissue slice carry out next step experiment.
The tissue cryo-sections made are taken, the liquid outside sample is gently wiped with filter paper, enclose group with immunohistochemistry pen
After knitting, with 10% donkey serum, room temperature is closed 1 hour in wet box.Then the confining liquid outside sample is gently wiped with filter paper, is added dropwise
With the diluted primary antibody of 10% donkey serum (1:100), 4 degree of overnight incubations in wet box.Discard primary antibody, PBS solution cleans 3 times, often
Secondary 5min.The liquid outside sample is wiped with filter paper, after the diluted fluorescent marker secondary antibody of 10% donkey serum is added dropwise, is placed in wet box
It is protected from light incubation at room temperature 2h.Secondary antibody is sucked, PBS solution is 3 times light, each 5min.After wiping the liquid outside sample with filter paper, dropwise addition contains
There is the anti-fluorescence quenching of DAPI dye liquor, then with clean coverslip mounting, and is saved in 4 degree of places of being protected from light.Antibody is respectively as follows:
NF200 (is purchased from abcam company, article No. ab40796), and Laminin (is purchased from sigma company, article No. L9393), and CGRP (is purchased from
Sigma company, article No. C8198), it is redyed with fluorescence secondary antibody (being purchased from invitrogen company), fluorescence microscopy is under the microscope
And it takes pictures.
Wherein: NF200 is the marker protein of nerve fibre, the growing state of observable neuron axon；Laminin is week
The marker protein of nerve fibre is enclosed, the case where observable medicine irritation axon growth；CGRP then with the feeling of pain of conducting pain by
Device is related.
Label sham is sham-operation group, and PBS is, with PBS solution processing group, JCH2 is to be measured group after wound.As a result such as Fig. 7
Shown in~9, by experiment detection it is found that repairing the growth that peptide processing group can be obviously promoted nerve synapse, promote impaired Dorsal root mind
The reparation of warp.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
It should be equivalent substitute mode, be included within the scope of the present invention.
Sequence table
<110>Ji'nan University
<120>a kind of to contain the pharmaceutical composition and its application that promote repairing of neural injury and regenerated reparation peptide
<160> 1
<170> SIPOSequenceListing 1.0
<210> 1
<211> 7
<212> PRT
<213>artificial sequence (Artificial Sequence)
<220>
<223>sequence of peptide JCH2 is repaired
<400> 1
Gly Pro Ala Asn Val Glu Thr
1 5
Claims (6)
1. a kind of contain the pharmaceutical composition that can promote repairing of neural injury and regenerated reparation peptide, it is characterised in that the drug
Composition, which contains, repairs peptide JCH2, sequence GPANVET.
2. it is described in claim 1 containing can promote repairing of neural injury and it is regenerated repair peptide pharmaceutical composition preparation mind
Through the application in injury repair and regenerated product.
3. application according to claim 2, it is characterised in that:
Pharmaceutical composition central nervous system injury caused by preparation brain trauma, headstroke, brain edema and cerebral anoxia, and
Application in the neural restoration and regenerated product of sensory disturbance, dyskinesia caused by peripheral nerve injury and dystrophia.
4. application according to claim 2 or 3, it is characterised in that:
The product is curable product.
5. application according to claim 2 or 3, it is characterised in that:
The preparation type of the product is solution or dry powder.
6. application according to claim 4, it is characterised in that:
The preparation type of the product is solution or dry powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810135021.2A CN110124009A (en) | 2018-02-09 | 2018-02-09 | It is a kind of to contain the pharmaceutical composition and its application that promote repairing of neural injury and regenerated reparation peptide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810135021.2A CN110124009A (en) | 2018-02-09 | 2018-02-09 | It is a kind of to contain the pharmaceutical composition and its application that promote repairing of neural injury and regenerated reparation peptide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110124009A true CN110124009A (en) | 2019-08-16 |
Family
ID=67567003
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810135021.2A Pending CN110124009A (en) | 2018-02-09 | 2018-02-09 | It is a kind of to contain the pharmaceutical composition and its application that promote repairing of neural injury and regenerated reparation peptide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110124009A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113651870A (en) * | 2021-07-16 | 2021-11-16 | 暨南大学 | Small molecule modified short peptide for promoting post-traumatic tissue repair and regeneration and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101745098A (en) * | 2010-01-26 | 2010-06-23 | 暨南大学 | Application of nerve polypeptide PACAP38 in the preparation of eye disease curing, injury repair or reproduction drugs |
| CN107427536A (en) * | 2015-04-01 | 2017-12-01 | 桑比欧公司 | For the method and composition for the bioactive compounds for stimulating cellular proliferation and providing FGF2 isotypes |
| CN108503690A (en) * | 2017-02-28 | 2018-09-07 | 暨南大学 | Tissue repair and regenerated reparation peptide and its application after a kind of promotion wound |
| WO2018157773A1 (en) * | 2017-02-28 | 2018-09-07 | 暨南大学 | Repair peptide for use in promoting post-traumatic tissue repair and regeneration, and application thereof |
-
2018
- 2018-02-09 CN CN201810135021.2A patent/CN110124009A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101745098A (en) * | 2010-01-26 | 2010-06-23 | 暨南大学 | Application of nerve polypeptide PACAP38 in the preparation of eye disease curing, injury repair or reproduction drugs |
| CN107427536A (en) * | 2015-04-01 | 2017-12-01 | 桑比欧公司 | For the method and composition for the bioactive compounds for stimulating cellular proliferation and providing FGF2 isotypes |
| CN108503690A (en) * | 2017-02-28 | 2018-09-07 | 暨南大学 | Tissue repair and regenerated reparation peptide and its application after a kind of promotion wound |
| WO2018157773A1 (en) * | 2017-02-28 | 2018-09-07 | 暨南大学 | Repair peptide for use in promoting post-traumatic tissue repair and regeneration, and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| MAYA E. WOODBURY ET AL.: ""Fibroblast growth factor-2 signaling in neurogenesis and neurodegeneration"", 《J NEUROIMMUNE PHARMACOL. 》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113651870A (en) * | 2021-07-16 | 2021-11-16 | 暨南大学 | Small molecule modified short peptide for promoting post-traumatic tissue repair and regeneration and application thereof |
| CN113651870B (en) * | 2021-07-16 | 2023-06-13 | 暨南大学 | Small molecule modified short peptide for promoting tissue repair and regeneration after trauma and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108503690B (en) | Repair peptide for promoting tissue repair and regeneration after trauma and application thereof | |
| Thoenen et al. | Neurotrophic factors and neuronal death | |
| Mo et al. | The repair of the injured adult rat hippocampus with NT-3-chitosan carriers | |
| Varon et al. | Trophic and specifying factors directed to neuronal cells | |
| Jaeger et al. | Transplantation of embryonic occipital cortex to the tectal region of newborn rats: A light microscopic study of organization and connectivity of the transplants | |
| Kasioulis et al. | Inter-dependent apical microtubule and actin dynamics orchestrate centrosome retention and neuronal delamination | |
| Brodkey et al. | The complex nature of interactive neuroregeneration-related molecules | |
| Saris et al. | Periosteum responds to dynamic fluid pressure by proliferating in vitro | |
| Tucker et al. | The use of progenitor cell/biodegradable MMP2–PLGA polymer constructs to enhance cellular integration and retinal repopulation | |
| JP2021518331A (en) | Transient cell reprogramming for cell aging reversal | |
| CN105960411A (en) | Self-assembling peptides, peptidomimetics and peptidic conjugates as building blocks for biofabrication and printing | |
| US11260101B2 (en) | Repair peptide for use in promoting post-traumatic tissue repair and regeneration, and application thereof | |
| Mulligan et al. | Organization of geniculocortical projections in turtles: isoazimuth lamellae in the visual cortex | |
| Frederickson et al. | The fine structure of perinotochordal microfibrils in control and enzyme‐treated chick embryos | |
| Jenke et al. | Transforming growth factor-β1 promotes fibrosis but attenuates calcification of valvular tissue applied as a three-dimensional calcific aortic valve disease model | |
| Schreyer et al. | Growth of corticospinal axons on prosthetic substrates introduced into the spinal cord of neonatal rats | |
| JPH02134327A (en) | Improving method for healing of wound in endo thelium corneae | |
| Mitrousis et al. | Hydrogel-mediated co-transplantation of retinal pigmented epithelium and photoreceptors restores vision in an animal model of advanced retinal degeneration | |
| US20210205372A1 (en) | Method and Composition for Promoting Cell Growth and Tissue Repair | |
| Bernocchi et al. | Premitotic DNA synthesis in the brain of the adult frog (Rana esculenta L.): An autoradiographic 3H‐thymidine study | |
| CN110124009A (en) | It is a kind of to contain the pharmaceutical composition and its application that promote repairing of neural injury and regenerated reparation peptide | |
| EP2528608B1 (en) | Cell homogenate from stem cells derived from growing deer antlers, a method of obtaining it and its use | |
| CA2397610C (en) | In vivo assay for testing the phenotypic stability | |
| Kondo | Microinjection methods for visualization of the vascular architecture of the mouse embryo for light and scanning electron microscopy | |
| Erzurumlu et al. | Target influences on the morphology of trigeminal axons |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190816 |