CN101514225A - Self-polymerization polypeptide and preparation method and application thereof - Google Patents

Self-polymerization polypeptide and preparation method and application thereof Download PDF

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CN101514225A
CN101514225A CNA2008102317097A CN200810231709A CN101514225A CN 101514225 A CN101514225 A CN 101514225A CN A2008102317097 A CNA2008102317097 A CN A2008102317097A CN 200810231709 A CN200810231709 A CN 200810231709A CN 101514225 A CN101514225 A CN 101514225A
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amino acid
val
polypeptide
hemostasis
synthetic polypeptide
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CN101514225B (en
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王亚宏
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XI'AN LANJING BIO-TECH Co Ltd
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XI'AN LANJING BIO-TECH Co Ltd
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Abstract

The invention discloses a synthetic polypeptide, the amino acid sequence of the synthetic polypeptide meets the following general formula: Ac-X0-(X1-X2-X3-X4)n-NH2, wherein Ac is an acetylized N-terminal; X0 is an L-amino acid, and the type of the amino acid is Ala, Val or Gly; X1, X2, X3 and X4 are all L-amino acids or D-amino acids, X1 is a positive charge amino acid Arg, Lys or His, X3 is a negative charge amino acid Asp or Glu, and X2 and X4 are amino acids Ala, Val or Gly without charge; X1-X2-X3-X4 is a repeated sequence; and n is repeated times of amino acid arrangement in the sequence, and is equal to 2, 3 and 4. The polypeptide has the characteristics of forming a nano fiber screen through self-assembly, and can form a gel-like fiber screen in the particle environment in vitro or in vivo for hemostasis or wound nursing.

Description

Self-polymerization polypeptide and its production and application
Technical field
The present invention relates to the application of peptide-based gel fiber aspect hemostasis and promotion wound healing of a kind of self-polymerization polypeptide and formation thereof, belong to biotechnology polypeptide and medical material field.
Background technology
Any surgical procedures relates to hemorrhage and hemostasis bar none.Operation technique or wound, hemorrhage, the oozing of blood of the particularly big surface of a wound is difficult to control sometimes, and not only can cause blood loss to increase, but also can increase operating difficulty, even threat to life, and good hemostasis prerequisite and guarantee that to be operation safety carry out.Hemostatic drug can be by shrinking arteriole and capillary vessel, or strengthen platelet function, or quicken, strengthen the blood coagulation process, or suppress the clot dissolution process and produce anastalsis.
Hemostatic technique has been developed into the technical system of the numerous and complicated under the modern surgery condition by simple apparatus hemostasis measure of past.
At present, the hemostasis method of using always in the surgical operation comprises following a few each side:
1, operation technique hemostasis measure: the hemostasis measure of promptly in surgical procedure, taking, as methods such as ligation, stitching, electricity coagulate, tamp, these measures require operation implementers that the bleed scope, time, final result etc. of control of part are had deep understanding, deal with improperly then can bring out infection, secondary hemorrhage etc. problem.
2, intervention property hemostasis measure: intervention property hemostatic treatment is meant under scope, ultrasonic, CT or X line monitor and will treat in conduit, entry needle, air bag or other related equipments importing internal organs of usefulness, and give localized pulverization or injection haemostatic medicament, xanthan gum, chemical glue etc. carry out embolotherapy, or import chemical factors such as high-frequency current, laser, microwave, reach the purpose of treatment hemorrhagic focus.It is simple to operate, wound is little, recovery is fast.
3, physics and chemistry hemostasis measure: as coagulate by electricity, laser, microwave, heat reaches hemostasis.
4, external application hemostatic drug: mostly be the local hemostasis purposes.Mechanism mostly is hemostatic agent and forms thin film in the wound, the gluing surface of a wound and stopping blooding.As fibrin gel, microfilament fiber collagen hemostatic agent, SURGICEL and oxidized regenerated cellulose, the agent of collagen absorbable hemostasia, chemical glue, gelfoam, zymoplasm, Shi Bizhi, Chinese herbal medicine for external use preparation etc.
5, controlled hypotension: use the narcology method and reduce patient's blood pressure, to reduce in the art and postoperative hemorrhage.
Domestic clinical hemostatic drug commonly used has kind more than 20 approximately at present, according to the different links of its clotting mechanism, is divided into four big classes.
The one, clot-promoting factor active drug: by influencing some thrombin, promote or recover coagulation process and stop blooding.Represent medicine that hemocoagulase, Desmopressin, vitamin K1, vitamin K3, methylnaphthohydroquinone, glycine quadrol etc. are arranged.
The 2nd, reduce the capillary permeability medicine: can strengthen the resistibility of capillary vessel, reduce the permeability of capillary vessel, promote impaired blood capillary pipe end to shrink and stop blooding to damage.Represent medicine that carbazochrome, Carbazochrome Sodium Sulfonate are arranged.
The 3rd, Fibrinogen and antifibrinolytics:, proplasmin can not be activated, thereby suppress fibrinous dissolving by suppressing the incitant of plasminogen.Represent medicine that hexosamine, Aminomethylbenzoic Acid, tranexamic acid, Trypsin inhibitor,Trasylol etc. are arranged.
The 4th, external application hemostatic drug: No. 8, blood stanching agent, gelfoam, SURGICEL, Aldocellulose, berbamine, Yunnan white powder, the styptic powder that can absorb the surface of a wound, hemostasis and anti-inflammation subsides etc. are arranged.
The operative technique that these hemostasis methods and medicine etc. are had relatively high expectations, bleeding stopping period is longer, in various degree have bad reaction or a complication, as: some powder formulation medicines can not flow to wound location and bring into play its hemostatic function; The medicine that some is liquid, as cyanoacrylate adhesive, competence exertion drug effect under the exsiccant environment; Some medicines can cause immune response, cause contiguous necrocytosis, and human body is caused extra pressure, prolong or the obstruction rehabilitation; The preservation period of some drugs is short, and needs special store method; Many showing is difficult to act on the uncontrollable internal milieu of manpower with hemostatic agent.The artificial hemostasis by compression method of tradition, hemostasis required time and bed braking time are longer, are prone to complication such as oozing of blood, hemotoncus and vagus reflex simultaneously.In addition,, just must adopt extra nursing, guarantee the blood supply of wound, avoid the damage or the death of its hetero-organization if swelling agent is used in treatment.This point is particularly important when using expanded foam.Because the shelf time is short, many hemostatic agents must just be ready to before use.Surgical instruments as cauter, pliers and clip, must be used under controlled situation by the professional, and above-mentioned a lot of pharmaceutical cpd complexity perhaps contain the macromolecular material of difficult degradation, and biocompatibility is poor, has toxicity etc.
Scientist finds that part of polypeptide has the self-assembly phenomenon, can form the laminated structure of nano-scale fiber, as the international monopoly WO2005/014615 A2 that on February 17th, 2005 announced, announces the wound healing function of this self-assembly polypeptide; Patent CN200710048975.1 has announced the burn treatment effect of RADA16-1 peptide.
In the long term studies process, the contriver has found a kind of single component polypeptide self-assembly compound that mass-producing is used that is suitable for unexpectedly, utilizes its performance that can form nanofiber can improve or improve hemostasis or wound care.
Summary of the invention
One of purpose of the present invention provides the novel polypeptide of a class, and such polypeptide has can be self-assembled under ionic environment and is the nano-scale fiber lamella, to reach the purpose of quick-acting haemostatic powder.
Another purpose of the present invention provides the application of above-mentioned synthetic polypeptide aspect haemostatic medicament and wound care.
The present invention thes contents are as follows:
A kind of synthetic polypeptide, its aminoacid sequence satisfy following general formula (I):
Ac-X 0-(X 1-X 2-X 3-X 4) n-NH 2 (I)
Wherein, Ac is the acetylize N-terminal;
X 0Be L-amino acid, the amino acid type is: Ala, Val or Gly;
X 1, X 2, X 3And X 4Complete is L type amino acid or D type amino acid, wherein, and X 1Be positively charged amino acid Arg, Lys or His, X 3Be electronegative amino acid Asp or Glu, X 2And X 4Be neutral amino acid Ala, Val or Gly;
X 1-X 2-X 3-X 4Be tumor-necrosis factor glycoproteins, n is the amino acid whose multiplicity that is arranged in the sequence, n=2~4.
Peptide molecule design replacement data in conjunction with the simulation of computer free energy and β-lamella, the contriver has found to reach the hematostatic purpose, the peptide sequence that is self-assembled into to the nano-scale fiber barrier has following characteristics: as shown in Figure 1, arrange between the amino acid and form by hydrophilic-hydrophobic amino acid tumor-necrosis factor glycoproteins, pattern of rows and columns is:-+-+-+-+, interaction by water-wet side and hydrophobic side between the peptide molecule, form β-lamella, be stacked, tumor-necrosis factor glycoproteins is pressed 2-5 time, can form stable self-assembled structures, between the hydrophilic and hydrophobic amino acid be uncharged amino acid at interval, satisfy that can to form the aperture in the moistening in vivo ionic environment of the polypeptide solution of this structure sequence be 50-200nm reticulated structure (nanofiber barrier), thereby reach the hematostatic purpose.
The synthetic polypeptide of the present invention can adopt the synthetic and production of solid-phase polypeptide synthesis mode, includes but not limited to the Fmoc-SPPS mode, BOC-SPPS mode, fragment condensation mode of connection.
Adopt Fmoc-protection or BOC-protection solid-phase polypeptide synthetic technology (Solid phage peptidesynthesis; SPPS) polypeptide of synthetic above-mentioned general formula; resin adopts Fmoc-Rink-MBHA-resin; after hexahydropyridine/dimethyl formamide solution with 20% removes the FMOC protecting group; adopt Peptide synthesizer or manual polypeptide synthesis mode; hold the described all sequences polypeptide of substep coupling invention general formula by the N end to C; connect amino acid Fmoc-amino acid successively; catalyzer (HBTU; HOBT) adopt 1.5-4 doubly to the resin mol ratio; whether Kaise tests per step connection complete; monitor; finish until sequence; after in the end an amino acid Fmoc-removes protection; the solution that adds diacetyl oxide/DCM carries out the acetylize sealing; become polypeptide resin; with standard TFA cutting mixture [95% trifluoroacetic acid (TFA): 0.4% thioanisole (thioanisole): 0.4%1; 2-3-mercaptoethanol (EDT): 0.2% water] cut 2-3 hour; cutting liquid filters; precipitating is come out in the importing ice ether, centrifugal 3-4 time, becomes the crude product polypeptide; utilize the preparation scale liquid chromatography, freeze-drying becomes the polypeptide powder of 98% above purity grade behind the purifying.
Take by weighing the polypeptide powder, being made into mass volume ratio with distilled water or deionized water is the 0.5%-10% polypeptide solution, is used for hemostasis or wound care, also can directly be used for hemostasis or wound care with the polypeptide powder.
Polypeptide powder or polypeptid solution are running into blood or under the particle environment, and oneself very fast assembling becomes gelled fibre (fiber barrier), and outward appearance forms clear gel, as fine and close gauze, and performance hemostasis merit and wound care function.
Its useful effect of polypeptide of the present invention is: have the advantages that self-assembly forms the nano-scale fiber barrier, can form the gel fiber barrier that polypeptide is formed in external or body under the particle environment, be used for hemostasis or wound care.Polypeptide of the present invention also can with other drug and pharmaceutical composition, auxiliary material, vehicle etc. are combined into different medicament forms, be used to stop blooding and the extensive use of wound care, itself belongs to peptide material, is easy to be degraded, hemostatic mechanism has a extensive future with medicine was different in the past.
Figure of description
Fig. 1 forms the synoptic diagram of fiber gel for the synthetic polypeptide of the present invention;
Fig. 2 self-assembly polypeptide synthesizes the MS collection of illustrative plates;
Fig. 3 self-assembly peptide purification HPLC collection of illustrative plates;
The 1% solution self-assembly of Fig. 4 polypeptide forms gel AFM picture;
Fig. 5 nanofiber forms schematic diagram.
Embodiment
Can form the replaceable amino acid of polypeptide general formula such as the following table of self-assembly:
General formula: Ac-X0-(X1-X2-X3-X4) n-NH 2
Figure A20081023170900081
By the following examples invention is done further and set forth; embodiment further explains of the present invention; be not limited to this embodiment, the serializing compound that meets the amino acid Substitution Rules that other are unlisted, preparation and application also belong to protection scope of the present invention.
Embodiment:
X0 is Val, and X1 is Arg, and X2 is Val, and X3 is Asp, and X4 is Val, and when sequence repeated 2 times (n=2), sequence was as follows:
Ac-Val-Arg-Val-Asp-Val-Arg-Val-Asp-Val-NH 2
The self-assembly polypeptide is synthetic: take by weighing Fmoc-Rink-MBHA-resin resin 10g (substitution degree d=0.87); after hexahydropyridine with 20%/dimethyl formamide solution 200ml removes the FMOC protecting group; adopt Peptide synthesizer or manual polypeptide synthesis mode; hold the described sequences polypeptide of substep coupling invention general formula by the N end to C; connect amino acid; Fmoc-amino acid; catalyzer (HBTU; HOBT) the resin mol ratio is adopted 2 times of amounts; do catalysis with DIEA; activation is 5 minutes in DMF; add the polypeptide reactor and carry out the amino acid coupling; whether Kaise tests per step connection complete; monitor; constantly repeat above step; finish until sequence is synthetic; after in the end an amino acid Fmoc-removed protection, the solution that adds diacetyl oxide/DCM carried out acetylize sealing 30 minutes, becomes polypeptide resin; cut mixture 100ml[95% trifluoroacetic acid (TFA) with standard TFA: 0.4% thioanisole (thioanisole): 0.4%1; 2-3-mercaptoethanol (EDT): 0.2% water] cutting 2.5 hours, cutting liquid filters, and filtrate is poured in the ice ether precipitating into and is come out; centrifugal 3-4 time; become the crude product polypeptide, utilize the preparation scale liquid chromatography, purification condition is: A phase 0.1%TFA+H 2O, B phase 0.1%TFA+ acetonitrile with C18 preparative column 40 * 250mm, adopts B phase 10-60% line style wash-out, behind the collection main peak, concentrates the polypeptide powder 4.2g that the back freeze-drying becomes 98% above purity grade.(mass spectrometric detection 1097.52, theoretical value MS is 1097.5)
Fig. 2 is the synthetic MS collection of illustrative plates of self-assembly polypeptide; Fig. 3 is a self-assembly peptide purification HPLC collection of illustrative plates; The 1% solution self-assembly of Fig. 4 polypeptide forms gel AFM picture; Fig. 5 nanofiber forms schematic diagram.As can be seen, the synthetic polypeptide that obtains is Ac-Val-Arg-Val-Asp-Val-Arg-Val-Asp-Val-NH 2
Obviously, can synthesize following sequences polypeptide by above-mentioned same program:
X0 is Val, and X1 is Arg, and X2 is Val, and X3 is Asp, and X4 is Val, and when sequence repeated 2 times (n=2), sequence was as follows:
Ac-Val-Arg-Val-Asp-Val-Arg-Val-Asp-Val-NH 2
X0 is Val, and X1 is Arg, and X2 is Val, and X3 is Asp, and X4 is Val, and when sequence repeated 3 times (n=3), sequence was as follows:
Ac-Val-Arg-Val-Asp-Val-Arg-Val-Asp-Val-Arg-Val-Asp-Val-NH 2
X0 is Val, and X1 is Arg, and X2 is Val, and X3 is Asp, and X4 is Val, and when sequence repeated 4 times (n=4), sequence was as follows:
Ac-Val-Arg-Val-Asp-Val-Arg-Val-Asp-Val-Arg-Val-Asp-Val-Arg-Val-Asp-Val-NH 2
X0 is Ala, and X1 is Lys, and X2 is Ala, and X3 is Glu, and X4 is Ala, and when sequence repeated 3 times (n=3), sequence was as follows:
Ac-Ala-Lys-Ala-Glu-Ala-Lys-Ala-Glu-Ala-Lys-Ala-Glu-Ala-NH 2
The technician of the industry also can be easy to synthetic new sequence according to the invention, meets the amino acid of replacing tabulation and replaces all sequences that produces, all at protection domain of the present invention.
Polypeptide compound experiment material and abbreviation expression:
Fmoc-SPPS: utilize FMOC-protective amino acid assembling synthetic solid-phase polypeptide synthetic (Solid phagepeptide synthesis, SPPS) method
BOC-SPPS: utilize BOC-protective amino acid assembling synthetic solid-phase polypeptide synthetic (Solid phagepeptide synthesis, SPPS) method
The Fmoc-:9-fluorenylmethyloxycarbonyl
BOC-: tertbutyloxycarbonyl
Fmoc-Rink-MBHA-resin: amino peptide synthetic resins, available from Xi'an wound scape biotechnology company
DCM: methyl chloride
DMF: dimethyl formamide
TFA: trifluoroacetic acid
Thioanisole: thioanisole
EDT:1, the 2-3-mercaptoethanol
HBTU:O-(Benzotriazol-1-yl)-N,N,N’,N’-tetramethyl uronium hexafluorophosphate
HOBT:1-hydroxybenzene a pair of horses going side by side triazole
DIEA:N, N-di-isopropyl diethylamine
Fmoc-amino acid (purity is more than 98.5%, available from Chengdu Kai Tai company) is as follows:
Fmoc-Ala-OH (Fmoc-L-Ala)
Fmoc-Arg (Pbf)-OH (Fmoc-arginine)
Fmoc-Asp (OtBu)-OH (Fmoc-aspartic acid)
Fmoc-Glu (OtBu)-OH (Fmoc-L-glutamic acid)
Fmoc-Gly-OH (Fmoc-glycine)
Fmoc-His (Trt)-OH (Fmoc-Histidine)
Fmoc-Lys (Boc)-OH (Fmoc-Methionin)
Fmoc-Val-OH (Fmoc-Xie Ansuan)
The hemostasis experiment
(sequence is: Ac-Val-Arg-Val-Asp-Val-Arg-Val-Asp-Val-NH to take by weighing polypeptide powder 200mg 2), or be made into quality volume (wt/V) than for the 1%-3% polypeptide solution with deionized water, be used for the experiment of hemostasis or wound care.
Polypeptide powder rat tails cuts off the hemostasis experiment
Rat is adopted in experiment, and body weight 270 ± 30g is available from Shanghai Communications University, Xi'an Experimental Animal Center.Anaesthetize with rat vetanarcol 50mg/kg ip, it is fixing to lie on the back, rat tails is sterilized with thimerosal, afterbody is cut off with sharp blade at the most advanced and sophisticated 5cm of afterbody place, be sprinkled upon rapidly on the afterbody section immediately the following pad of residual afterbody section one gauze of weighing in advance, and with quantitative above-mentioned synthetic polypeptides freeze-dry powder end, write down the bleeding time (staunch blood time fully) simultaneously, with the weight of weighting method weighing gauze, calculate blood loss.Experimental technique sees reference for details: Kathy L.Ryan, et al.Efficacy of FDA-approved hemostatic drugs to improvesurvival and reduce bleeding in rat models of uncontrolled hemorrhage.Resuscitation2006,70:133-144 (the rat haemostatic medicament of FDA approval recovers the survival model); 2. Stephen W.Rothwell et al.Addition of a propyl gallate-based procoagulant to a fibrin bandageimproves hemostatic performance in a seine arterial bleeding model.ThromvosisResearch 2003,108:335-340 (vein hemostasis model).
Table 1 polypeptide powder foot couple rat tails cuts off hemorrhage anastalsis
Experiment material Blood loss (g) Bleeding stopping period (second)
Common gauze 2.37±1.11 330±15
The hemostasis gelatin 1.89±0.20 210±12
The polypeptide powder 0.08±0.03 15±3
Table 1 as seen, polypeptide hemostasis powder is compared with the common gauze and the gelatin control group that stops blooding, the anastalsis of generation is rapid-action, haemostatic effect is definite, can significantly reduce the afterbody blood loss, obviously shortens the bleeding time.Can be used for the hemorrhage hemostasis of tiny blood vessels clinically, and the hemostasis of some traumatic hemorrhage and wound care.
Polypeptide 1% hydrogel is to rabbit ear skin incision hemostasis experiment
Laboratory animal selects White Rabbit, and body weight 2.7 ± 0.3kg is available from Shanghai Communications University, Xi'an Experimental Animal Center.With vetanarcol 45mg/kg ip anesthesia, it is fixing to lie on the back, and trachea cannula is shaved hair with the rabbit auris dextra, uses iodine disinfection, cuts the otch of a 1.5CM with scalpel at the rabbit ear, makes it hemorrhage.1% the polypeptide hydrogel that will configure immediately is coated on the otch, and covers with the gauze of weighing in advance, record bleeding stopping period and the time of stopping blood fully, the hemorrhage blood loss of usefulness weighting method weighing rabbit ear otch.
Table 2 polypeptide 1% hydrogel is to the anastalsis of rabbit ear skin incision
Hemostatic material Blood loss (g) Bleeding stopping period (second)
Common gauze 1.85±1.22 115.11±10.36
Yunnan white powder 0.75±0.31 43.43±8.22
Polypeptide 1% hydrogel 0.32±0.28 17.03±2.25
The result shows (seeing Table 2), polypeptide 1% hydrogel and the common gauze of control group, and Yunnan white powder etc. are compared, and the anastalsis onset is faster, haemostatic effect is definite, can significantly reduce the hemorrhage blood loss of rabbit ear skin incision, obviously shortens the bleeding time.Can be used for the hemostasis of skin surface wound hemorrhage clinically, the hemorrhage quick-acting haemostatic powder of especially various skin injuries.
The hemostasis polypeptide is to the hemostasis experiment of rabbit femoral vein angiorrbagia
White Rabbit is selected in experiment for use, and body weight 2.7 ± 0.3kg is available from Shanghai Communications University, Xi'an Experimental Animal Center.With vetanarcol 45mg/kg ip anesthesia, it is fixing to lie on the back, trachea cannula, rabbit right side inguinal region is shaved hair, use iodine disinfection, cut off skin, separate subcutis, expose femoral vein, vein is cut off fully, it is bled, immediately quantitative chitosan porous microsphere is sprinkling upon on the surface of a wound, and covers with the gauze of weighing in advance, the balance of a 50g counterweight is placed in the below, the record bleeding stopping period is with the blood loss of weighting method weighing rabbit femoral vein angiorrbagia.It is the same that experimental technique sees reference for details.
Table 3 hemostasis polypeptide is to the hemostasis experiment of rabbit femoral vein angiorrbagia
Hemostatic material Blood loss (g) Bleeding stopping period (second)
Common gauze 35.21±4.01 620±50
The chitosan gauze 32.35±5.10 550±43
2% peptide-based gel 6.35±3.36 25±3
Experimental result shows (seeing Table 3), 2% self-assembly peptide-based gel is rapid-action with the anastalsis that control group (common gauze and chitosan gauze) is compared generation, haemostatic effect is definite, can significantly reduce rabbit femoral vein angiorrbagia blood loss, obviously shorten the bleeding time.Can be used for the hemorrhage hemostasis of vein blood vessel clinically.
The hemostasis that the hemostasis polypeptide is bled to rabbit femoral artery blood vessel
White Rabbit is selected in experiment for use, and body weight 2.7 ± 0.3kg is available from Shanghai Communications University, Xi'an Experimental Animal Center.With vetanarcol 45mg/kg ip anesthesia, it is fixing to lie on the back, trachea cannula, rabbit right side inguinal region is shaved hair, use iodine disinfection, cut off skin, separate subcutis, separate one section artery, the about 3.4cm of length, clamp with bulldog clamp respectively at two ends, cuts the slotted eye of a 2 * 3mm on femoral artery with the carefulness of ophthalmology iris scissors, take out the bilateral bulldog clamp, it is bled.3% peptide-based gel for preparing immediately is coated on the surface of a wound, and covers with the gauze of weighing in advance, and places a 100g counterweight, and the record bleeding stopping period is with the blood loss of weighting method weighing rabbit femoral artery angiorrbagia.
The anastalsis that table 4 hemostasis polypeptide is bled to rabbit femoral artery blood vessel
Hemostatic material Blood loss (g) Bleeding time (min)
Common gauze 55.45±7.76 33.12±8.56
The chitosan-containing gauze 46.64±7.43 28.26±5.23
3% peptide-based gel 4.21±2.24 0.50±0.25
Experimental result shows (seeing Table 4), and 3% peptide-based gel compares with control group that the anastalsis of generation is rapid-action, haemostatic effect is definite, can significantly reduce the blood loss that rabbit femoral artery blood vessel is bled, and obviously shortens the bleeding time.The quick-acting haemostatic powder that can be used for the profuse bleeding that great vessels hemorrhage hemostasis, especially war wound, various urgent wound cause clinically.

Claims (7)

1, a kind of synthetic polypeptide, its aminoacid sequence satisfies following general formula (I):
Ac-X 0-(X 1-X 2-X 3-X 4) n-NH 2(I)
Wherein, Ac is the acetylize N-terminal;
X 0Be L-amino acid, the amino acid type is: Ala, Val or Gly;
X 1, X 2, X 3And X 4Complete is L type amino acid or D type amino acid, wherein, and X 1Be positively charged amino acid Arg, Lys or His, X 3Be electronegative amino acid Asp or Glu, X 2And X 4Be neutral amino acid Ala, Val or Gly;
X 1-X 2-X 3-X 4Be tumor-necrosis factor glycoproteins, n is the amino acid whose multiplicity that is arranged in the sequence, n=2~4.
2, according to the described synthetic polypeptide of claim 1, it is characterized in that: X 0Be Ala or Val.
3, according to the described synthetic polypeptide of claim 1, it is characterized in that: X 1, X 2, X 3, X 4Be L type amino acid.
4, according to one of any described synthetic polypeptide of claim 1 to 3, it is characterized in that: X 1Be Arg or Lys.
5, according to one of any described synthetic polypeptide of claim 1 to 3, it is characterized in that: n is 2 or 3.
6, according to one of any described synthetic polypeptide of claim 1 to 3, it is characterized in that: X 0With X 4Be same amino acid.
7, the application of the described synthetic polypeptide of claim 1 aspect hemostasis and wound care.
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