CN103992381B - Polypeptide, peptide composition and polypeptide biomaterial and its preparation method and application - Google Patents
Polypeptide, peptide composition and polypeptide biomaterial and its preparation method and application Download PDFInfo
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Materials For Medical Uses (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention discloses a kind of polypeptide and peptide composition, and the polypeptide biomaterial based on polypeptide/peptide composition, and their preparation method and purposes, any amino acid sequence that polypeptide is included shown in any amino acid sequence and SEQ ID NO.1 ~ 7 as shown in SEQ ID NO.1 7 have the sequence of at least 60% homology.Peptide composition includes at least two any above sequences.The polypeptide biomaterial is gelatinous, including aforementioned polypeptides or peptide composition and the solvent that can dissolve the polypeptide or peptide composition.Found by atomic force microscope observation, polypeptide biomaterial of the invention forms the netted structure of nanofiber of densification, has the characteristics of hemostasis is fast, easy to use, and security is good, easy large-scale industrial production.
Description
Technical field
The present invention relates to hemostatic material field, especially a kind of polypeptide, peptide composition and polypeptide for field of stopping blooding
Biomaterial, and their preparation method and purposes.
Background technology
Although can obtain blood product, the major reason for being still morbidity and death of losing blood, the later local war of World War II
Data statistics shows that 30%-60%'s falls in battle caused by the reason is that losing blood seriously, and effective hemostasis is that the wounded are improved in wartime situation
The key of survival rate.In addition to wartime, reduction injures and deaths must effectively when hemostasis and operation, natural calamity, accident
Want measure.It is natural in addition to bleeding caused by operation up to 30,000,000 according to middle market conditions report network data, China's operation person-time in 2010
Caused by disaster, accident etc. because of traumatic bleeding and the quantity of Deaths accounts for the 50% of died of wounds.Hand intraoperative hemorrhage is normal
It is often a main problem, many problems of patient can be caused by losing blood, and the possible normal tissue of position bleeding is being not required not
Profit or interference surgeon observe the ability of surgical field of view.When removing blood and control bleeding, it is necessary to postpone operation.Even if
During the operation of minimally-invasive, bleeding may also bring problem.Therefore, in various surgical operations, bleeding is reduced, is shortened
Operating time, has patient's prognosis important influence.
In order to reduce amount of bleeding, complication is reduced, in recent years, the research and application of local hemostatic have obtained rapid hair
Exhibition.Since the 1970s, medical natural macromolecular material and medical synthesis high molecular material are used for the research of hemostat
Make the exploitation of local hemostatic have real leap.The current medicine for being used clinically for hemostasis mainly has five major classes：Fiber
Protein adhesive, collagen hemostatic, chitosan, oxycellulose and oxidized regenerated cellulose, fibrin ferment.
（1）Fibrin Glue：
A large amount of clinical research datas show, are difficult real though Fibrin Glue is widely used in common surgical procedures
Accomplish the loss of blood in fast and effective control surgical procedure, in addition, Fibrin Glue presence may bring human body or animal blood
The shortcomings of property disease in source infects.
（2）Collagen hemostatic：
Research shows that the anastalsis of such material needs the clotting factor in body to participate in, and is having systemic blood coagulation work(
During energy obstacle, then haemostatic effect is not good enough, in addition, collagen-based materials can cause allergic reaction, shows as fever, eosinophils increase
The symptoms such as more, cutaneous anaphylaxis.
（3）Chitosan：
Chitosan has the function of hemostasis, antibacterial, antibiotic property etc., but chitosan anastalsis itself is limited, it is impossible to reaches fast
The perfect condition of short stopping blood.
（4）Oxycellulose and oxidized regenerated cellulose：
The absorbable hemostasia material of gauze-like or cotton shape made of cellulose is oxidation-treated as cellulosic acid,
By the effect of cell or cellulose, activity factor, accelerates Coagulation test, while cellulose can promote platelet adhesion reaction and enhancing
Fibrin net, is conducive to anastalsis.There is also some shortcomings, first it to be reduced in number of platelets for oxycellulose
Its efficient anthemorrhagic performance is kept during with dysfunction；Secondly oxycellulose is absorbed by the body slow, it is possible to create oxygen
Chemical fibre ties up granuloma；Japanese scholars report that oxidized regenerated cellulose can cause peripheral nerve to become due to its powerful acid effect
Property.
（5）Fibrin ferment：
Fibrin ferment can promote fibrinogen to be converted into fibrin, accelerate coagulation process, be stranded suitable for hemostasis by ligation
Difficult thin vessels, capillary and parenchymal viscera bleeding.But fibrin ferment produce and it is inconvenient to use, its antigenicity it is larger
It is limiting factor.
In conclusion above-mentioned hemostatic material there are haemostatic effect it is bad, dependent on the normal coagulation pathway of body, there are dynamic
The shortcomings of material resource communicable disease is dangerous, still needs further research and develop new hemostat in practical applications, make it have
The characteristics of preferable topical hemostatic agent that Silverstein is proposed：Efficient anastalsis；It is easy to use；Good biofacies
Capacitive and security；Can industrialized production.
The content of the invention
In view of the above problems, an object of the present invention be to provide a kind of haemostatic effect it is fast, safely, be suitable for extensive work
The polypeptide of industry production.
The technical solution adopted by the present invention is such：A kind of polypeptide, includes following any one sequence： SEQ ID
Any amino acid sequence shown in amino acid sequence and SEQ ID NO.1 ~ 7 shown in NO.1-7 has at least 60% homology
Sequence.
Synthesis polypeptide of the present invention can be synthesized and produced using Solid phase peptide synthssis mode, include but not limited to Fmoc-SPPS
Mode, BOC-SPPS modes, fragment condensation connection mode.
A kind of method that aforementioned polypeptides are prepared using Fmoc-SPSS modes, is comprised the following steps：Respectively according to SEQ ID
Amino acid sequence shown in NO.1- 7, first amino is connected on solid support resin by fmoc-protected amino acid chain, so
After take off amino protecting group；Then by amino by fmoc-protected second amino acid under the activation of condensing agent with having connected
The amino for being connected on first amino acid of solid phase carrier reacts to form peptide bond；Repeat above-mentioned peptide bond and form reaction, make peptide chain from C-terminal
Grown to N-terminal, until last amino acid accesses；Cutting obtains target polypeptides.This synthetic method is simple and practicable, is produced into
This is low.
The second object of the present invention is, there is provided a kind of peptide composition, includes following at least two sequences： SEQ
Amino acid sequence shown in ID NO.1- 7, have with any amino acid sequence shown in SEQ ID NO.1 ~ 7 it is at least 60% same
The sequence of source property.
The third object of the present invention is, there is provided a kind of gelatinous polypeptide biomaterial, including aforementioned polypeptides or polypeptide
Composition and the solvent of dissolvable aforementioned polypeptides or peptide composition, preferably sterilant solution.
As a preferred embodiment, in aforementioned polypeptides biomaterial, the mass percentage concentration of polypeptide or peptide composition
For >=0.01%, the more preferably mass percentage concentration of polypeptide or peptide composition is in the range of 0.01%-50%.
As a preferred embodiment, aforementioned polypeptides or peptide composition and dissolvable aforementioned polypeptides or peptide composition is molten
Agent is mixed into mass percentage concentration >=0.01%, more preferably after the mixed liquor of 0.01%-50%, agitated mixing or supersound process
Gelatinous polypeptide biomaterial is obtained, wherein, the condition of supersound process is preferably 50-500 W, 5-40 min.
As a preferred embodiment, the solvent that can dissolve aforementioned polypeptides or peptide composition is water, such as deionized water, or
Distilled water or ultra-pure water.
As a preferred embodiment, the present invention can also provide a kind of gelatinous polypeptide biomaterial, including end（Ammonia
Base end or carboxyl terminal）Aforementioned polypeptides after modification or by the peptide composition that the polypeptide after end modified forms with
Can dissolve the solvent of the polypeptide or peptide composition, it is experimentally confirmed that aforementioned polypeptides after end modified, this it is end modified after it is more
The peptide composition of peptide composition can still form gelatinous polypeptide biomaterial together with its solvable solvent, play hemostasis and make
With.
The fourth object of the present invention is, there is provided a kind of preparation method of aforementioned polypeptides biomaterial, by aforementioned polypeptides or
Peptide composition and the solvent of dissolvable aforementioned polypeptides or peptide composition are formulated as mixed liquor, then by mixed liquor be stirred for
Gelatinous or it is sonicated be gel-like biological material.
As a preferred embodiment, the preparation method of aforementioned polypeptides biomaterial, including by polypeptide or peptide composition and
The solvent of aforementioned polypeptides or peptide composition, preferably sterile vehicle are can dissolve, mass percentage concentration >=0.01% is formulated as, into one
Step is preferably the mixed liquor of 0.01%-50%, is slowly stirred until forming gel-like biological material.
As a preferred embodiment, the preparation method of aforementioned polypeptides biomaterial, including by aforementioned polypeptides or polypeptides in combination
It is >=0.01% that thing and the solvent of dissolvable aforementioned polypeptides or peptide composition, which are formulated as mass percentage concentration, more preferably
The mixed liquor of 0.01%-50%, then mixed liquor is sonicated, ultrasound condition is preferably 50-500 W, 5-40 min, Ran Hou
Stood at 4 DEG C, preferably stand 12-24 it is small when after up to gel-like biological material.
The fifth object of the present invention is, there is provided a kind of aforementioned polypeptides, peptide composition and above-mentioned polypeptide biomaterial
Application in haemostatic medicament is prepared.A variety of formulations, example can be made from different auxiliary materials in the polypeptide biomaterial
Such as injection or spray, for hemostasis.
Using atomic force microscope (AFM) to the polypeptide biomaterial of the present invention it has been observed that the polypeptide of the present invention is given birth to
Thing material forms the netted structure of nanofiber of densification.
The present invention provides a kind of polypeptide and peptide composition, and one kind is provided based on this polypeptide or peptide composition
A kind of polypeptide biomaterial is provided based on polypeptide biomaterial, or polypeptide or peptide composition after end modified.This hair
Bright polypeptide biomaterial, can play the biomaterial and is similar to fiber egg in a manner of being applied directly to bleeding part
White effect, achievees the purpose that to make bleeding part quick-acting haemostatic powder.
Compared with existing traditional haemostatic medicament, the beneficial effects of the present invention are：
（1）Hemostasis is fast：
According to the blood platelet blood clotting mechanism in the case of nature, blood clotting at least needs can just start for 90 seconds.With it is wide at present
The characteristics of general chitosan hemostasia products used compare, and polypeptide biomaterial of the invention has shown significant quick-acting haemostatic powder：
Realize within 11 seconds or so that liver stops blooding, bleeding stopping period is about the 5% of gauze pressing haemostatic, and amount of bleeding is about gauze pressing haemostatic
16%.The characteristics of polypeptide biomaterial quick-acting haemostatic powder of the present invention can be that the quality time is won in the rescue of the battlefield wounded and urgent patient,
So as to reduce because bleeding causes complication and reduces the death rate.
（2）It is easy to use：
Polypeptide biomaterial of the present invention is liquid condition, has more preferable plasticity, can enter other solid hemostatic materials
Expect the unapproachable surface of a wound, play the haemostatic effect of the special surface of a wound, really solve the clinical operations such as unknown, the pinprick oozing of blood in blutpunkte
The problem of hemostasis；It may also be fabricated which injection or spray, it is easy to use；Clear, colorless, does not influence while hemostasis in operation
The surgical visual field, significantly improves surgical effect.
（3）It is safe：
As native amino acid molecule by polypeptide obtained by artificial synthesized, there is good biological degradability and compatibility；
The exogenous biological product such as any blood products, collagen is not contained, avoids the danger of animal and plant source communicable disease.
（4）Can large-scale industrial production：
The technology of preparing of polypeptide biomaterial of the present invention is ripe, can realize industrialized production by synthesizing on a large scale.
Brief description of the drawings
Examples of the present invention will be described by way of reference to the accompanying drawings, wherein：
Fig. 1 is the atomic force microscope for the polypeptide biomaterial that embodiment 21 obtains（AFM）Collection of illustrative plates.
Fig. 2 is the atomic force microscope for the polypeptide biomaterial that embodiment 22 obtains（AFM）Collection of illustrative plates.
Fig. 3 is the atomic force microscope for No. 3 samples that embodiment 23 obtains（AFM）Collection of illustrative plates.
Fig. 4 is the control group of embodiment 29 compared with the bleeding stopping period of No. 1 treatment group.
Fig. 5 is the control group of embodiment 29 compared with the bleeding stopping period of No. 2 treatment groups.
Fig. 6 is the control group of embodiment 29 compared with the bleeding stopping period of No. 3 treatment groups.
Fig. 7 is the control group of embodiment 29 compared with the amount of bleeding of No. 1 treatment group.
Fig. 8 is the control group of embodiment 29 compared with the amount of bleeding of No. 2 treatment groups.
Fig. 9 is the control group of embodiment 29 compared with the amount of bleeding of No. 3 treatment groups.
Embodiment
All features disclosed in this specification, or disclosed all methods or during the step of, except mutually exclusive
Feature and/or step beyond, can combine in any way.
This specification（Including any accessory claim, summary and attached drawing）Disclosed in any feature, except non-specifically chatting
State, can be replaced by other alternative features that are equivalent or have similar purpose.I.e., unless specifically stated, each feature
It is an example in a series of equivalent or similar characteristics.
Embodiment 1
A kind of polypeptide, its amino acid sequence is as shown in SEQ ID NO.1.
SEQ ID NO.1：Cys-Arg-Leu-Cys-Gly-Gly-Cys-Arg-Leu-Cys
Embodiment 2
A kind of polypeptide, its amino acid sequence is as shown in SEQ ID NO.2.
SEQ ID NO.2：Cys-Lys-Leu-Pro-Leu-Lys-Val-Gly-Gly-Ile-Arg-Glu-Cys
Embodiment 3
A kind of polypeptide, its amino acid sequence is as shown in SEQ ID NO.3.
SEQ ID NO. 3：Cys-Ile-Lys-Leu-Glu-Ile-Lys-Pro-Leu-Lys-Val-Pro
Embodiment 4
A kind of polypeptide, its amino acid sequence is as shown in SEQ ID NO.4.
SEQ ID NO.4：Pro-Leu-Arg-Leu-Gly-Gly-Pro-Leu-Lys-Val-Pro
Embodiment 5
A kind of polypeptide, its amino acid sequence is as shown in SEQ ID NO.5.
SEQ ID NO.5：Pro-Ser-Ile-Cys-Ile-Lys-Ile-Glu-Ile-Lys-Ile-Glu-Pro
Embodiment 6
A kind of polypeptide, its amino acid sequence is as shown in SEQ ID NO.6.
SEQ ID NO.6：Pro-Pro-Glu-Ile-Val-Glu-Glu-Lys-Glu-Ile-Glu-Glu-Pro
Embodiment 7
A kind of polypeptide, its amino acid sequence is as shown in SEQ ID NO.7.
SEQ ID NO.7：Pro-Glu-Ile-Pro-Glu-Glu-Lys-Glu-Ile-Glu-Glu-Pro
Embodiment 8
A kind of gelatinous polypeptide biomaterial, is made of, the quality of polypeptide the polypeptide and deionized water of SEQ ID NO.1
Percentage concentration is 0.01%.
Embodiment 9
A kind of gelatinous polypeptide biomaterial, is made of, the quality hundred of polypeptide the polypeptide and ultra-pure water of SEQ ID NO.1
It is 50% to divide concentration.
Embodiment 10
A kind of gelatinous polypeptide biomaterial, is made of, the quality hundred of polypeptide the polypeptide and distilled water of SEQ ID NO.3
It is 5.5% to divide concentration.
Embodiment 11
A kind of gelatinous polypeptide biomaterial, is made of, the quality of polypeptide the polypeptide and deionized water of SEQ ID NO.5
Percentage concentration is 11%.
Embodiment 12
A kind of gelatinous polypeptide biomaterial, is made of, the quality of polypeptide the polypeptide and deionized water of SEQ ID NO.6
Percentage concentration is 25.3%.
Embodiment 13
A kind of gelatinous polypeptide biomaterial, is made of, the quality hundred of polypeptide the polypeptide and ultra-pure water of SEQ ID NO.7
It is 42% to divide concentration.
Embodiment 14
A kind of gelatinous polypeptide biomaterial, is made of, the quality of polypeptide the polypeptide and deionized water of SEQ ID NO.2
Percentage concentration is 0.04%.
Embodiment 15
A kind of gelatinous polypeptide biomaterial, is made of, the quality of polypeptide the polypeptide and deionized water of SEQ ID NO.4
Percentage concentration is 1%.
Embodiment 16
A kind of gelatinous polypeptide biomaterial, by the polypeptide of SEQ ID NO.1, the polypeptide of SEQ ID NO.2, SEQ ID
Polypeptide and the deionized water composition of NO.5, the mass percentage concentration of every kind of polypeptide is 1%.
Embodiment 17
A kind of gelatinous polypeptide biomaterial, by the polypeptide of SEQ ID NO.3, SEQ ID NO.6 polypeptide and go from
Sub- water composition, the mass percentage concentration of every kind of polypeptide is 5.5%.
Embodiment 18
A kind of gelatinous polypeptide biomaterial, by the polypeptide and deionized water group of SEQ ID NO.2- SEQ ID NO.7
Into the mass percentage concentration of every kind of polypeptide is 0.6%.
Embodiment 19
A kind of gelatinous polypeptide biomaterial, by the polypeptide of SEQ ID NO.1, the polypeptide of SEQ ID NO.5, SEQ ID
The polypeptide of NO.6, the polypeptide of SEQ ID NO.7 and deionized water composition, the mass percentage concentration of every kind of polypeptide is 2.3%.
Embodiment 20
A kind of gelatinous polypeptide biomaterial, by the polypeptide of SEQ ID NO.2, the polypeptide of SEQ ID NO.3, SEQ ID
The polypeptide of NO.5, the polypeptide of SEQ ID NO.6, the polypeptide of SEQ ID NO.7 and deionized water composition, the quality hundred of every kind of polypeptide
It is 1.33% to divide concentration.
Embodiment 21
A kind of preparation method of gelatinous polypeptide biomaterial, including：
（1）The sterilization treatment of deionized water
In pure water system（Millipore Milli-Q system）In pick up 500 ml deionized waters（18 MΩ）, use
Autoclaving sterilizes, i.e.,：Deionized water is handled 30 minutes at vapour pressure 103.4kPa, 121.3 DEG C of temperature, then
Sterile deionized water is saved backup in 4 DEG C of refrigerator interior sealings；
（2）The preparation of solution
Step is utilized under room temperature, normal pressure in the gnotobasis of super-clean bench（1）The deionized water of sterilization treatment is by SEQ
The polypeptide of ID NO.1 is configured to the solution that mass percentage concentration is 1%；
（3）Plastic
By step（2）Prepared solution ultrasound 20min, ultrasonic power 160W under room temperature, normal pressure, then in normal pressure, 4
DEG C environment in place 12 it is small when, that is, obtain gelatinous polypeptide biomaterial.
Embodiment 22
A kind of preparation method of gelatinous polypeptide biomaterial, including：
（1）The sterilization treatment of deionized water and embodiment 21 are same；
（2）The preparation of solution
Step is utilized under room temperature, normal pressure in the gnotobasis of super-clean bench（1）The deionized water of sterilization treatment is by SEQ
The polypeptide of amino acid sequence shown in ID NO.1-4 is configured to the mixed solution that mass percentage concentration is 0.04%；
（3）Plastic
By step（2）Prepared solution ultrasound 5min, ultrasonic power 500W under room temperature, normal pressure, then in normal pressure, 4
DEG C environment in place 24 it is small when, that is, obtain gelatinous polypeptide biomaterial.
Embodiment 23
A kind of preparation method of gelatinous polypeptide biomaterial, including：
（1）The sterilization treatment of deionized water
In pure water system（Millipore Milli-Q system）In pick up 500 ml deionized waters（18 MΩ）, use
Autoclaving sterilizes, i.e.,：Deionized water is handled 30 minutes at vapour pressure 103.4kPa, 121.3 DEG C of temperature, then
Sterile deionized water is saved backup in 4 DEG C of refrigerator interior sealings；
（2）The preparation of solution
Step is utilized under room temperature, normal pressure in the gnotobasis of super-clean bench（1）The deionized water of sterilization treatment is by polypeptide
Dissolving is mixed into 3 kinds of solution, and No. 1 sample is made of the polypeptide of the amino acid sequence shown in SEQ ID NO.1, the quality hundred of polypeptide
It is 0.1% to divide concentration；No. 2 samples are made of the polypeptide of the amino acid sequence shown in SEQ ID NO.2,4,6, the matter of every kind of polypeptide
It is 0.1% to measure percentage concentration；No. 3 samples are made of the polypeptide of the amino acid sequence shown in SEQ ID NO.1 ~ 7, every kind of polypeptide
Mass percentage concentration is 0.1%.
（3）Plastic
By step（2）Prepared solution ultrasound 20min, ultrasonic power 160W under room temperature, normal pressure, then in normal pressure, 4
DEG C environment in place 12 it is small when, that is, obtain gelatinous polypeptide biomaterial.
Embodiment 24
A kind of preparation method of gelatinous polypeptide biomaterial, including：
（1）The sterilization treatment of deionized water is identical with embodiment 23.
（2）The preparation of solution
Step is utilized under room temperature, normal pressure in the gnotobasis of super-clean bench（1）The deionized water of sterilization treatment is by SEQ
The polypeptide of ID NO.1 ~ 7, which dissolves, is mixed into 3 kinds of sample solutions, and amino acid sequence shown in SEQ ID NO.1 ~ 7 is more in No. 1 sample
Peptide, the mass percentage concentration of every kind of polypeptide is 0.04%；The polypeptide of amino acid sequence shown in SEQ ID NO.1 ~ 7 in No. 2 samples,
The mass percentage concentration of every kind of polypeptide is 0.1%；The polypeptide of amino acid sequence shown in SEQ ID NO.1 ~ 7, every kind of in No. 3 samples
The mass percentage concentration of polypeptide is 0.2%.
（3）Plastic
By step（2）Prepared 1-3 sample solutions ultrasound 5min, ultrasonic power 800W under room temperature, normal pressure, then
When placement 24 is small in normal pressure, 4 DEG C of environment, that is, obtain gelatinous 1-3 polypeptides biomaterial.
The atomic force microscope observation for the polypeptide biomaterial that 25 embodiment 21 of embodiment obtains
Processing：The polypeptide biomaterial that embodiment 21 obtains uniformly is applied to the mica sheet surface newly denuded, smear is complete
Cheng Houyue 30s, unattached thing is removed with 500 μ l deionized water rinsings.Above-mentioned smear is air-dried at room temperature.
AFM scan is carried out to mica sheet in the gas phase, afm image is collected with the logging mode of SPI4000.Use 20 μm
Scanner（400）, Olympus Si-DF20 micro-cantilevers, and spring constant be 12.00N/m pin（Si, radius 10nm, rectangle
Substrate 200.00um）.The free oscillation frequency of cantilever is 127.00kHz.Phase diagram is recorded with the resolution of 512 × 512 pixels.
For the trickle nanostructured of display material, 2 × 2 μm are used to sample2Scope be scanned.
The results are shown in Figure 1 for atomic force microscope (AFM) observation, as seen from Figure 1, the polypeptide biology of embodiment 21
Material forms the netted structure of nanofiber of densification, this structure plays hemostatic function for polypeptide biomaterial and establishes in vivo
The basis of material structure.
The atomic force microscope observation for the polypeptide biomaterial that 26 embodiment 22 of embodiment obtains
Processing：The polypeptide biomaterial that embodiment 22 obtains uniformly is applied to the mica sheet surface newly denuded, smear is complete
Cheng Houyue 30s, unattached thing is removed with 500 μ l deionized water rinsings.Above-mentioned smear is air-dried at room temperature.
AFM scan is carried out to mica sheet in the gas phase, afm image is collected with the logging mode of SPI4000.Swept using 20 μm
Retouch device（400）, Olympus Si-DF20 micro-cantilevers, and spring constant be 12.00N/m pin（Si, radius 10nm, rectangle base
Bottom 200.00um）.The free oscillation frequency of cantilever is 127.00kHz.Phase diagram is recorded with the resolution of 512 × 512 pixels.For
The trickle nanostructured of display material, 2 × 2 μm are used to sample2Scope be scanned.
The results are shown in Figure 2 for atomic force microscope (AFM) observation, as seen from Figure 2, the polypeptide life of embodiment 22
Thing material forms the netted structure of nanofiber of densification, this structure plays hemostatic function for polypeptide biomaterial and establishes in vivo
The basis of material structure.
The atomic force microscope observation for No. 3 samples that 27 embodiment 23 of embodiment obtains
Processing：No. 3 samples that embodiment 23 is obtained uniformly are applied to the mica sheet surface newly denuded respectively, and smear is completed
About 30s afterwards, removes unattached thing with 500 μ l deionized water rinsings respectively.Above-mentioned smear is air-dried at room temperature.
AFM scan is carried out to mica sheet respectively in the gas phase, afm image is collected with the logging mode of SPI4000.Use 20
μm scanner（400）, Olympus Si-DF20 micro-cantilevers, and spring constant be 12.00N/m pin（Si, radius 10nm, square
Shape substrate 200.00um）.The free oscillation frequency of cantilever is 127.00kHz.Phase diagram is remembered with the resolution of 512 × 512 pixels
Record.For the trickle nanostructured of display material, 2 × 2 μm are used to sample2Scope be scanned.This time atomic force microscope
(AFM) the results are shown in Figure 3 for observation,
As seen from Figure 3, No. 3 samples of embodiment 23 form the netted structure of nanofiber of densification, this structure is
Polypeptide biomaterial plays the basis that hemostatic function has established material structure in vivo.
The structure of 28 liver bleeding animal model of embodiment and the therapeutic scheme of polypeptide biomaterial
1st, build
1.1 experiment material
Animal：Female sd inbred rats, average weight 260g or so, reach large bio tech ltd purchased from Chengdu.Standard is raised
The article of material and other and animal contact is handled through autoclaving.
Main agents:75% ethanol, 10% chloraldurate
Equipment:5mL disposable syringes, emgloves, hospital gauze, medical proof fabric, eye scissors, curved tweezer, haemostatic clamp, hand
Art blade etc..
1.2 experimental method
1) 1 mL, 10% chloral hydrate anesthesia rats, are injected intraperitoneally.
2), skin and muscle are cut off along ventrimeson to chest, exposure liver, free liver surrounding ligaments.
3), the right side liver middle period is slightly drawn out with haemostatic clamp, at 0.9 cm, scalpel is being used above right side liver middle period lower edge
Piece does one 1 cm long, the notch of 0.5 cm depths.
2. treatment of the polypeptide biomaterial to liver bleeding animal model
1. 2. material and instrument
The polypeptide biomaterial that embodiment 22 obtains
2.2. experimental method
1) uses the liver bleeding animal model that step 1 is built；
2) rat liver Hemorrhage Model is randomly divided into 2 groups by, and gauze pressing haemostatic group is used after respectively performing the operation（Control
Group）, the polypeptide biomaterial treatment group that is obtained using embodiment 22 after operation（Treatment group）.
3) allows the free bleeding 10s of modeling rat liver notch, is then dried the blood of exudation with hospital gauze.
4) control groups use hospital gauze flicking incision hemostasis immediately, after 20s, observe notch bleeding 20s, if
Occur bleeding in this 20s, then carry out pressing haemostatic 20s again, notch bleeding 20s is then observed, if in this 20s
Occurs bleeding again, then repeatedly aforesaid operations, until hemostasis.Record bleeding stopping period at the same time.
5) the polypeptide biomaterial of 50 μ L is uniformly applied to notch by treatment groups with liquid-transfering gun immediately, and observation notch goes out
Blood situation, if any bleeding, is then dried the blood of outflow with gauze, and timing at the same time, records bleeding stopping period.
6) is weighed with the gauze that electronic balance uses hemostasis, records the amount of bleeding in hemostasis.
Therapeutic effect of the 29 polypeptide biomaterial of embodiment to liver bleeding animal model
1st, liver bleeding animal model is built：
1.1 experiment material
Animal：Female sd inbred rats, average weight 260g or so, reach large bio tech ltd purchased from Chengdu.Standard is raised
The article of material and other and animal contact is handled through autoclaving.
Main agents:75% ethanol, 10% chloraldurate
Equipment:5mL disposable syringes, emgloves, hospital gauze, medical proof fabric, eye scissors, curved tweezer, haemostatic clamp, hand
Art blade etc..
1.2 experimental method
1) 1 mL, 10% chloral hydrate anesthesia rats, are injected intraperitoneally.
2), skin and muscle are cut off along ventrimeson to chest, exposure liver, free liver surrounding ligaments.
3), the right side liver middle period is slightly drawn out with haemostatic clamp, at 0.9 cm, scalpel is being used above right side liver middle period lower edge
Piece does one 1 cm long, the notch of 0.5 cm depths.
2. treatment of the polypeptide biomaterial to liver bleeding animal model
1. 2. material and instrument
Polypeptide biomaterial, the hospital gauze that embodiment 23 obtains；Electronic balance, stopwatch.
2.2. experimental method
1) uses the liver bleeding animal model that step 1 is built；
2) rat liver Hemorrhage Model is randomly divided into 4 groups by, and gauze pressing haemostatic group is used after respectively performing the operation（Control
Group）, No. 1 polypeptide biomaterial being obtained using embodiment 23 after operation be No. 1 treatment group, obtained after operation using embodiment 23
No. 2 polypeptide biomaterials be No. 2 treatment groups, No. 3 polypeptide biomaterials obtained after operation using embodiment 23 are No. 3 processing
Group,.
3) allows the free bleeding 10s of modeling rat liver notch, is then dried the blood of exudation with hospital gauze.
4) control groups use hospital gauze flicking incision hemostasis immediately, after 20s, observe notch bleeding 20s, if
Occur bleeding in this 20s, then carry out pressing haemostatic 20s again, notch bleeding 20s is then observed, if in this 20s
Occur bleeding again, then repeatedly aforesaid operations, until hemostasis, while record bleeding stopping period.
5) .1-3 treatment groups are respectively immediately with liquid-transfering gun by the corresponding polypeptide biomaterial of 50 μ L（1-3 polypeptides
Biomaterial）Notch is uniformly applied to, notch bleeding is observed, if any bleeding, is then dried the blood of outflow with gauze, and together
When timing, record bleeding stopping period.
6) is weighed with the gauze that electronic balance uses hemostasis, records the amount of bleeding in hemostasis.
3. result and analysis
Treatment group is observed using the treatment after the treatment of polypeptide biomaterial and utilizes hospital gauze flicking incision hemostasis
Corresponding control group treatment, as shown in Fig. 4-Fig. 9, wherein, Fig. 4-Fig. 6 is bleeding stopping period situation, and Fig. 7-Fig. 9 is
Blood volume situation.The bleeding stopping period of control group and No. 1 treatment group compares, as shown in figure 4, the amount of bleeding of control group and No. 1 treatment group
Compare, as shown in Figure 7；The bleeding stopping period of control group and No. 2 treatment groups compares, as shown in figure 5, control group and No. 2 treatment groups
Amount of bleeding compares, as shown in Figure 8；The bleeding stopping period of control group and No. 3 treatment groups compares, as shown in fig. 6, at control group and No. 3
Reason group amount of bleeding compares, as shown in Figure 9.
From fig. 6, it can be seen that after liver bleedings are treated using No. 3 specimen materials, bleeding at 11 seconds or so to obtain the final product
To suppression, and still there is the situation of bleeding in control group.In addition, compared with control group, the amount of bleeding of 1-3 treatment groups is significantly few
In control group.
Above it is demonstrated experimentally that the polypeptide biomaterial that the polypeptide of the above, peptide composition are formed, forms fine and close nanometer
Fibrous reticular structure, has the function of to make bleeding part quick-acting haemostatic powder.It is and above-mentioned in addition, applicant is confirmed by many experiments
Amino acid sequence has at least 60% homology（Such as 65%, 70%, 80%）Sequence polypeptide, peptide composition, it may have class
As mechanism.
The invention is not limited in foregoing embodiment.The present invention, which expands to, any in the present specification to be disclosed
New feature or any new combination, and disclose any new method or process the step of or any new combination.
Claims (8)
1. a kind of peptide composition, it is characterised in that the peptide composition is：As the amino acid shown in SEQ ID NO.1~7
Sequence forms.
2. application of the peptide composition as claimed in claim 1 in haemostatic medicament is prepared.
3. a kind of polypeptide biomaterial, it is characterised in that including peptide composition as claimed in claim 1, and can dissolve
The solvent of aforementioned polypeptides composition, the biomaterial are gelatinous.
A kind of 4. polypeptide biomaterial as claimed in claim 3, it is characterised in that the solvent of the dissolvable peptide composition
For water.
5. a kind of polypeptide biomaterial as claimed in claim 4, it is characterised in that the peptide composition and dissolvable polypeptide
The solvent of composition is agitated upon mixing or is ultrasonically treated and obtains gel-like biological material.
A kind of 6. polypeptide biomaterial as claimed in claim 4, it is characterised in that after peptide composition and solvent mixing,
The mass percentage concentration of peptide composition is 0.01%-50%.
It is 7. a kind of such as the preparation method of claim 3-6 any one of them polypeptide biomaterials, it is characterised in that will be such as right
It is required that the solvent of the peptide composition and dissolvable peptide composition described in 1 is formulated as mixed liquor, then mixed liquor is stirred
For gel-like biological material or it is sonicated be gel-like biological material.
It is 8. a kind of such as application of the claim 3-6 any one of them polypeptide biomaterials in haemostatic medicament is prepared.
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