A kind of starch base micropore hemostatic material with anti-microbial property and its preparation method and application
Technical field
The invention belongs to tissue damage to repair field of medical materials, and in particular to a kind of shallow lake with anti-microbial property
Powder base micropore hemostatic material and its preparation method and application.
Background technology
Bleeding is blood flow to tissue space from blood vessel or heart, in body cavity or a kind of external phenomenon, is fighting
Strive, be relatively conventional in traffic accident, natural calamity, first aid and surgical operation.Bleeding often along with infection,
Even entail dangers to therefore prepares a kind of new rapid hemostatic material of superior performance, gesture to the life security of people
It must go.
After the completion of hemostasis, the material that surface of a wound surface is remained covers, and is exposed to for a long time in air, this space-time
Bacterium in gas can be deposited at material surface, the remaining material of such wound just into the carrier of bacterial reproduction,
The risk of surface of a wound inflammation and infection will be greatly increased;Situation about inherently having been infected plus bleeding wound, develop
A kind of anthemorrhagic performance and the starch-based material of anti-microbial property of having both has very big actual application value.
Traditional hemostatic fashion is tied, pressed, dressing etc., and main hemostatic material has bandage, tourniquet
Deng although the survival rate of the wounded can be improved, haemostatic effect is not all good enough, and using inconvenience, having to neglect
Depending on the defects of.
Recently as the further research to hemostatic mechanism, hemostatic material has also obtained development at full speed.Mesh
The preceding hemostatic material for having the blood surface of a wound for surgery and wound mainly includes:
Porous zeolite is a kind of particulate mineral matter derived from slag, by silicon, aluminium, sodium and magnesium elements
Composition.With special pore passage structure and larger specific surface area, adsorption capacity is stronger, can quickly absorb blood
Moisture in liquid, assemble blood platelet and clotting factor, slow down blood flow and form thrombus, reach the work of rapid blood coagulation
With.But zeolite releases substantial amounts of heat, easy burn wound, causes inflammatory reaction during use,
And zeolite can not degrade in vivo.
Fibrin Glue is a kind of soluble component in blood, mainly including fibrinogen, fibrin ferment and
Calcium chloride.Fibrin Glue has good hemostasis, bond properties and histocompatbility, can be to a certain extent
Effectively stopped blooding, but repressive hemostasis can not be carried out, thus it is bad for big surface of a wound Bleeding.
The production technology of Fibrin Glue is complex, and from animal and human body, therefore price is costly, adds
The probability of big communicable disease.
Natural polymer of the chitosan as unique positively charged in nature, have hemostasis, promote wound healing,
The effects such as antibacterial, anticancer, lipid-loweringing, enhancing be immune are a kind of biocompatibilities compared with good material.Chitosan
Hemostatic mechanism essentially consists in it and carries certain positive charge, can be connected with red blood cell negatively charged in blood
Come, form network structure to catch more red blood cells, form thrombus, reach blood coagulation;And cause blood platelet
Activation, promote platelet adhesion reaction to be gathered in chitosan surface.In addition, Chitosan-phospholipid complex to bacterium,
The microorganisms such as yeast, fungi have good inhibiting effect.But the haemostatic effect of chitosan in itself is limited, need
The anthemorrhagic performance of material is improved by other compound styptics.
Oxycellulose and oxidized regenerated cellulose are a kind of materials being modified by natural plant fibre, tool
Have good biocompatibility, degradability and it is nontoxic the features such as, by the water absorbing properties of material and itself take
Iron ion in the carboxyl and hemoglobin of band combines to form blob of viscose, and sealing blood vessels end is stopped blooding.But its
Sour environment that is loosely organized, and itself carrying, causes the denaturation of nerve fibre in human body.
Starch type polysaccharide hemostatic material derives from converted starch, starch as a kind of natural macromolecular material,
Wide material sources, it is cheap, there is good biocompatibility, degradable, nontoxic, safe to use, side
Just, extensive concern is obtained in biomedicine field.The AristaTM AH developed such as C.R.Bard companies of the U.S.
(production of reason Medafor companies) spherex, the moisture in blood can be quickly absorbed, accelerate pachyemia,
Increase the concentration of visible component in blood, slow down blood flow.Viscosity of material increase after water suction, can be to oppressing blood
Pipe, sealing blood vessels end, and then quick-acting haemostatic powder.It is big to parenchymal viscera but its water absorption rate is low
Bleeding control effect is bad.In addition, needed in material synthesis processes by and epichlorohydrin cross-linked, to environment not
Profit, along with expensive, it can not clinically obtain extensive use.It will be further appreciated that AristaTM
AH spherex can not be killed or suppressed growth of microorganism, prevention or infection control for bleeding part
Then it is at a complete loss as to what to do.
In summary, preferable hemostatic material should possess:Quickly and efficiently control multiple location bleeding, potent
Antibacterial ability, fast degradation, good biocompatibility and wound adhesive capacity, low cost and conveniently make
Performance.At present, the report of the material of summary performance is had no.
The content of the invention
The purpose of the present invention is to overcome the weak point of existing hemostatic material, there is provided a kind of good biocompatibility,
Starch base hemostatic material that degradation property is good, anti-microbial property is good, water absorption rate is higher and preparation method thereof.
The first aspect of the present invention, there is provided a kind of starch base micropore hemostatic material, the starch microporous, and
Load amino cation.
In another preference, the starch base micropore hemostatic material has controllable microcellular structure.
In another preference, the microporous or microcellular structure are formed by enzyme hydrolysis.
In another preference, the pore size of the starch base micropore hemostatic material is 0.1-6 μm.
In another preference, the starch base micropore hemostatic material has following one or more performances:
Water absorption rate is 100%-800%;
Can be degradable in vivo in 4h-10d;
Sterilizing rate reaches 50%-100%;
Bleeding stopping period is 20s-4min;
It is sticky big;And/or
Good biocompatibility.
The second aspect of the present invention, there is provided a kind of preparation method of starch base micropore hemostatic material, including it is following
Step:
(1) preparation of micropore starch
Starch and enzyme are added in phosphate buffer, stirred under conditions of being 4-8 at 40-80 DEG C and pH,
Enzyme digestion reaction is carried out, after 3-16 hours, separation is filtered, is dried to obtain micropore starch;Wherein,
Described starch and the mass ratio of enzyme are 1:(0.01-0.3);
The mass volume ratio of described starch and the total amount of enzyme and phosphate buffer is 100g:
(150-1000)mL;
(2) cationization of micropore starch
Micropore starch, cation modifier, catalyst and water made from step (1) are mixed according to certain ratio
Conjunction stirs evenly, and persistently stirring insulation carries out reacting 4-30 hours at 30-80 DEG C, with the mixed liquor of water-isopropanol
Obtained cationic micropore starch is dried after centrifuge washing, wherein,
Described micropore starch, cation modifier, the ratio of catalyst and water are 1:(0.1~1.0):
(0~0.08):(0~10.0);
The volume ratio of described water-isopropanol is 1:(0.01~1.0).
In another preference, the speed stirred described in step (1) is 200-500r/min.
In another preference, the time dried described in step (1) is 12-24 hours.
In another preference, the speed stirred described in step (2) is 200-500r/min.
In another preference, the rotating speed centrifuged described in step (2) is 3000-6000r/min.
In another preference, the time dried described in step (2) is 12-24 hours.
In another preference, in step (1), described starch be from potato, sweet potato, cassava, corn,
At least one of food-grade starches refined in wheat, mung bean;And/or the enzyme be beta amylase, α-
In amylase, glucoamylase, isoamylase, carbohydrase, debranching enzyme, general Shandong indigo plant enzyme, phosphorylase
At least one.
In another preference, in step (2), described cation modifier is nitrogenous cation modifier.
In another preference, described nitrogenous cation modifier is the chloro- 2- Hydroxyproyl Trimethyls chlorinations of 3-
Ammonium, DTAC, 2,3- epoxypropyltrimethylchloride chlorides, methylene dimethylamine hydrochloric acid
At least one of salt, hydroxymethyl dimethylamine hydrochloride.
In another preference, in step (2), described catalyst is sodium hydroxide, potassium hydroxide, hydrogen-oxygen
Change at least one of calcium.
In another preference, in step (1), the phosphate buffer is the disodium hydrogen phosphate aqueous solution, phosphorus
At least one of acid dihydride sodium water solution, aqueous dibasic potassium phosphate solution and potassium dihydrogen phosphate aqueous solution, it is described
The mass percent concentration of phosphate buffer is 5-40%.
The third aspect of the present invention, there is provided the application of the starch base micropore hemostatic material of first aspect present invention,
For preparing for bleeding in surgical operation or hemostatic material or bleed-control material for traumatism and bleeding.Institute
Surgical operation is stated to be selected from the group:Department of general surgery, liver and gall surgical department, gastrointestinal surgery, uropoiesis anal intestine, cardiothoracic surgery,
Orthopaedics, vascular surgery, Oncological Surgery, gynemetrics, neurosurgery, Department of B urn, plastic surgery, emergency department,
The department of stomatology, ear-nose-throat department, Minimally Invasive Surgery.
The fourth aspect of the present invention, there is provided the application of the starch base micropore hemostatic material of first aspect present invention,
For prepare for internal parenchymal viscera bleed profusely or the bleeding control of moving part or difficult puncture site
Prepared material.
The fifth aspect of the present invention, there is provided the application of the starch base micropore hemostatic material of first aspect present invention,
It is used to preventing and preventing the medical material infected bleeding part for preparing.
The starch base micropore hemostatic material of the present invention, forms micropore in the presence of enzymolysis, leads on this basis
Etherification reaction load amino cation is crossed, forms electropositive micropore starch.After modified, its water absorption rate and
Viscosity increases substantially, and can quickly absorb the moisture in blood, assembles the visible component in blood, quick shape
Into thrombus, and wound can be tightly adhered to, reach hemostasis purpose.In addition, the adsorbable blood of positive charge carried
In electronegative red blood cell and blood platelet, cause hematoblastic aggregation and activation, activate chemical hemostatic mechanism,
And then strengthen haemostatic effect.In addition, absorbing the amination Starch formation hydrogel structure after body fluid, organizing
Between form barrier, isolation, suppress tissue adhesion, tissue adhesion can be prevented.
The starch base micropore hemostatic material of the present invention, entrained positive charge are inhaled by electrostatic force and hydrogen bond action
Attached cell membrane is in electronegative bacterial body, blocks nutrition supply passage, causes bacterial growth suppressed and dead;
Its hydrophobic alkyl can also act on the hydrophilic group of bacterium simultaneously, change the permeability of film, and lysis then occurs and makees
With, destroy eucaryotic cell structure, cause the dissolving and death of cell.At the same time, the cationic nitrogenous of preparation forms sediment
Powder base micropore hemostatic material is acted on normal cytotoxic evil, has good histocompatbility.
After the starch base micropore hemostatic material of the present invention enters in vivo, in the effect of lysozyme and other biological enzyme
Under it is degradable into monose, be absorbed by organisms using or excreted through organism metabolism, removed in vivo thorough.
The starch base micropore hemostatic material of the present invention, there is provided a kind of quick-acting haemostatic powder, good biocompatibility, drop
Solution excellent performance, anti-microbial property are good, the higher material of water absorption rate.
It should be understood that within the scope of the present invention, above-mentioned each technical characteristic of the invention and below (such as implementation
Example) in specifically describe each technical characteristic between can be combined with each other, so as to form new or preferable skill
Art scheme.As space is limited, no longer tire out one by one herein and state.
Brief description of the drawings
Fig. 1 is starch base micropore hemostatic material sample drawing.
Fig. 2 is micropore starch and loads the microstructure of the starch base micropore hemostatic material of amino:(a) 5000 times
The micropore starch of the lower unsupported amino through enzymolysis, the micropore of the unsupported amino through enzymolysis forms sediment under 1500 times of (b)
Powder, loads the micropore starch of amino under 5000 times of (c), the micropore starch of amino is loaded under 1800 times of (d).
Fig. 3 is the water absorption rate figure of starch base micropore hemostatic material:(a) micropore starch of unsupported amino, (b) are negative
Carry the micropore starch of amino.
Fig. 4 is the auricular vein hemostasis model figure of the micropore starch of unsupported amino.
Fig. 5 is the auricular vein hemostasis model figure of the micropore starch of load amino.
Fig. 6 is the fungistatic effect figure of starch base micropore hemostatic material, and (a) blank control, (b) loads ammonia
The micropore starch of base, the micropore starch of (c) unsupported amino.
Embodiment
Present inventor has been surprisingly found that starch base micropore starch through amino by in-depth study extensively
After change, not only stopping blooding rapidly and efficiently, good biocompatibility good with surface of a wound adhesiveness, degraded is fast in vivo, and
And there is anti-microbial property, the bacterium infection problem of bleeding part can be efficiently solved.On this basis, complete
The present invention.
Starch base micropore hemostatic material
The starch base micropore hemostatic material of the present invention, is amidized starch base micropore hemostatic material, the shallow lake
Powder microporous, and load amino cation.The alternatively referred to as micropore starch of amination or load amino.
The starch base micropore hemostatic material has controllable microcellular structure.
The pore size of the starch base micropore hemostatic material is 0.1-6 μm.
The water absorption rate of the starch base micropore hemostatic material is 100%-800%;Can be complete in vivo in 4h-10d
Degraded;Sterilizing rate reaches 50%-100%;Bleeding stopping period is 20s-4min;It is sticky big;And good biocompatibility.
The starch base micropore hemostatic material has controllable microcellular structure.
The microcellular structure is formed by enzyme hydrolysis.
The preparation method of starch base micropore hemostatic material
The preparation method of the starch base micropore hemostatic material of the present invention, comprises the following steps:
(1) preparation of micropore starch
Starch and enzyme are added in phosphate buffer, stirred under conditions of being 4-8 at 40-80 DEG C and pH,
Enzyme digestion reaction is carried out, after 3-16 hours, separation is filtered, is dried to obtain micropore starch;Wherein,
Described starch and the mass ratio of enzyme are 1:(0.01-0.3);
The mass volume ratio of described starch and the total amount of enzyme and phosphate buffer is 100g:
(150-1000)mL;
(2) cationization of micropore starch
Micropore starch, cation modifier, catalyst and water made from step (1) are mixed according to certain ratio
Conjunction stirs evenly, and persistently stirring insulation carries out reacting 4-30 hours at 30-80 DEG C, with the mixed liquor of water-isopropanol
Obtained cationic micropore starch is dried after centrifuge washing, wherein,
Described micropore starch, cation modifier, the ratio of catalyst and water are 1:(0.1~1.0):
(0~0.08):(0~10.0);
The volume ratio of described water-isopropanol is 1:(0.01~1.0).
In another preference, the speed stirred described in step (1) is 200-500r/min.
In another preference, the time dried described in step (1) is 12-24 hours.
In another preference, the speed stirred described in step (2) is 200-500r/min.
In another preference, the rotating speed centrifuged described in step (2) is 3000-6000r/min.
In another preference, the time dried described in step (2) is 12-24 hours.
In another preference, in step (1), described starch be from potato, sweet potato, cassava, corn,
At least one of food-grade starches refined in wheat, mung bean;And/or the enzyme be beta amylase, α-
In amylase, glucoamylase, isoamylase, carbohydrase, debranching enzyme, general Shandong indigo plant enzyme, phosphorylase
At least one.
In another preference, in step (2), described cation modifier is nitrogenous cation modifier.
In another preference, described nitrogenous cation modifier is the chloro- 2- Hydroxyproyl Trimethyls chlorinations of 3-
Ammonium, DTAC, 2,3- epoxypropyltrimethylchloride chlorides, methylene dimethylamine hydrochloric acid
At least one of salt, hydroxymethyl dimethylamine hydrochloride.
In another preference, in step (2), described catalyst is sodium hydroxide, potassium hydroxide, hydrogen-oxygen
Change at least one of calcium.
In another preference, in step (1), the phosphate buffer is the disodium hydrogen phosphate aqueous solution, phosphorus
At least one of acid dihydride sodium water solution, aqueous dibasic potassium phosphate solution and potassium dihydrogen phosphate aqueous solution, it is described
The mass percent concentration of phosphate buffer is 5-40%.
In the preferred embodiment of the present invention, the preparation method of starch base micropore hemostatic material, including it is following
Step:
(1) preparation of micropore starch
Starch and enzyme are added in phosphate buffer, under conditions of 40-80 DEG C and pH are 4-8 with
200-500r/min speed stirring, carries out enzyme digestion reaction, after 3-16 hours, filters separation, dries 12-24
Hour obtains micropore starch;Wherein,
Described starch and the mass ratio of enzyme are 1:(0.01-0.3);
The mass volume ratio of described starch and the total amount of enzyme and phosphate buffer is 100g:
(150-1000)mL;
(2) cationization of micropore starch
Micropore starch, cation modifier, catalyst and water made from step (1) are mixed according to certain ratio
Conjunction stirs evenly, and continues to carry out reacting 4-30 hours with 200-500r/min speed stirring insulation at 30-80 DEG C,
Dry 12-24 hours are made after being washed with the mixed liquor of water-isopropanol with 3000-6000r/min centrifugation
Cationic micropore starch, wherein,
Described micropore starch, cation modifier, the ratio of catalyst and water are 1:(0.1~1.0):
(0~0.08):(0~10.0);
The volume ratio of described water-isopropanol is 1:(0.01~1.0).
The application of starch base micropore hemostatic material
The starch base micropore hemostatic material of the present invention can be used for such as department of general surgery, liver and gall surgical department, gastrointestinal surgery, secrete
Urinate anal intestine, cardiothoracic surgery, orthopaedics, vascular surgery, Oncological Surgery, gynemetrics, neurosurgery, Department of B urn,
Bleeding stops in a variety of surgical operations such as plastic surgery, emergency department, the department of stomatology, ear-nose-throat department, Minimally Invasive Surgery
Blood or bleeding control, it may also be used for hemostasis or the bleeding control of various traumatism and bleedings.
The present invention starch base micropore hemostatic material can be used for internal parenchymal viscera bleed profusely or activity
The bleeding control of position or difficult puncture site.
The starch base micropore hemostatic material of the present invention can be used for preventing and prevent bleeding part to infect.
The starch base micropore hemostatic material of the present invention can be used alone or is used in combination with carrier material.
The present invention is advantageous in that
(1) starch base micropore hemostatic material of the invention, possesses the alveolate texture containing multiple ducts,
Specific surface area is big;Surface is rich in hydroxyl, and after amino is loaded, material possesses superpower water absorbing capacity, from
And reach the purpose of quick-acting haemostatic powder.
(2) starch base micropore hemostatic material of the invention, after amino is loaded, viscosity improves, can be tightly
Wound is adhered to, reaches hemostasis purpose.
(3) starch base micropore hemostatic material of the invention, positive charge, adsorbable blood are carried after loading amino
Red blood cell and blood platelet in liquid, blood platelet is activated, trigger chemism hemostatic mechanism, reach hemostasis purpose.
(4) starch base micropore hemostatic material of the invention, positive charge is carried after loading amino, it is adsorbable thin
Thalline, cause bacterial death, have the function that antibacterial, prevent wound infection, can be provided simultaneously with stopping blooding and resist
The effect of bacterium.
(5) starch base micropore hemostatic material of the invention, can fast degradation in vivo.Starch in vivo may be used
Degraded by various digestion enzyme effects, and the microcellular structure of material increases its specific surface area, increase and body fluid
Contact area, the degraded of accelerated material;Material after amination, water solubility improve, and further speed up material
Expect the speed of degraded.
(6) starch base micropore hemostatic material of the invention, good biocompatibility, battalion of the starch as human body
Form point, safe and non-toxic, its catabolite can also store as the glycogen of human body, therefore biocompatibility
It is good, adverse reaction will not be caused.
(7) starch base micropore hemostatic material of the invention, prepare simply and cost is low, the source of starch is wide
It is general, belong to renewable resource, it is cheap.
(8) starch base micropore hemostatic material of the invention, has a wide range of application, can not only be applied to people's body surface
The bleeding at the positions such as skin, in-vivo tissue, can be used for internal parenchymal viscera bleed profusely or moving part,
Or the bleeding of difficult puncture site.
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are only used for
The bright present invention rather than limitation the scope of the present invention.The experiment side of unreceipted actual conditions in the following example
Method, generally according to normal condition, or according to the condition proposed by manufacturer.Unless otherwise indicated, otherwise
Percentage and number are calculated by weight.
Embodiment 1
(a) preparation of micropore starch
By 100g cornstarch and 3g carbohydrase, the phosphate disodium hydrogen phosphate for being added to 300mL pH=6 is water-soluble
In liquid cushioning liquid, stir, enzyme digestion reaction 8h, vacuum filtration washing are carried out at 45 DEG C, and freezing
20h is dried in dry machine, obtains Microporous Maize Starch.
(b) cationization of micropore starch
10g Microporous Maize Starchs are dissolved in 45g water, add 0.25g potassium hydroxide and 3.0g methylene two
Methylamine hydrochloride, stir, react 20h at 50 DEG C, carrying out centrifugation with the mixed liquor of water-isopropanol washes
Wash, be put into freeze dryer and dry 20h, obtain amidized Microporous Maize Starch.Sample morphology is as shown in Figure 1.
Embodiment 2~5
Embodiment 2~5 repeats the experimental procedure of embodiment 1, and difference is part Experiment condition, specifically
As shown in table 1-2.
The preparation of the micropore starch of table 1
The cationization of the micropore starch of table 2
Observe the micropore starch of the unsupported amino that step (a) obtains in embodiment 1 respectively using ESEM
Micropore starch after the load amino that (see Fig. 2 (a) and 2 (b)) and step (b) obtain is (see Fig. 2 (c)
With 2 (d)).As seen from the figure, the particle diameter of the micropore starch of unsupported amino is about 10~20 μm,
Channel diameter is about 1~4 μm, and after amino modified, micropore remains in that completely.
The micropore starch of load amino prepared by embodiment 2-5, particle diameter is about 9~30 μm, and duct is straight
Footpath is about 0.5~5 μm.
Embodiment 6
Choose the amidized jade that the Microporous Maize Starch and step (b) that step (a) obtains in embodiment 1 obtain
Rice micropore starch, water absorption rate test is carried out to it.
A certain amount of sample (W0) is weighed, is laid in the funnel containing filter paper, is drawn with dropper certain
The human body simulation body fluid of amount, squeeze and drip in sample surfaces, stop when the first drop of liquid is under dripping, weigh
The quality (W1) of record now, the calculation formula of water absorption rate (A%) are as follows:A%=[(W1-W0)/W0)]
× 100%, as a result see Fig. 3.
As a result show that the micropore starch water absorption rate after load amino significantly improves.
Embodiment 7
Choose the amidized jade that the Microporous Maize Starch and step (b) that step (a) obtains in embodiment 1 obtain
Rice micropore starch, biological assessment is carried out to its anthemorrhagic performance by zoopery.
Zoopery:New zealand white rabbit, average 3kg, cleaning grade (Shanghai Univ. of Traditional Chinese Medicine experimental animal
Center provides).
Experimental method:New zealand white rabbit 3 is taken only to be placed on operating table, by the way that concentration is injected intraperitoneally as 0.3%
Nembutal sodium solution, after Animal Anesthesia, the rabbit hair on ear face is shaved off, with scalpel on ear vein side
Edge does cross section wound, after wound is bled, wipes surface blood away with gauze, sample is spilt in wound,
Slightly pressed with gauze, observe and record hemostasis.
The vein stanch model of the micropore starch of unsupported amino and the micropore starch of load amino is respectively such as Fig. 4
Shown in Fig. 5.
As a result show that the micropore starch auricular vein haemostatic effect for loading amino is substantially more preferable.With unsupported amino
Micropore starch compare, through load amino micropore starch processing after wound can stop blooding completely;And
In the case of identical amount of bleeding, after the micropore starch processing for loading amino, wound hemostasis is faster.
Embodiment 8
Choose the amidized jade that the Microporous Maize Starch and step (b) that step (a) obtains in embodiment 1 obtain
Rice micropore starch, bacteriostatic experiment is carried out to it.
Sample is dispersed in concentration as 10 according to 10mg/mL concentration6The nutrient solution of cfu/mL Escherichia coli
In, co-culture 24h.After culture terminates, bacterium solution is diluted to 10 successively with physiological saline5cfu/mL、104
cfu/mL、103Cfu/mL, 10 are recorded as respectively-1、10-2、10-3.Finally the dilute of each gradient is drawn successively
The μ l of liquid 10 are released, is coated in the flat board containing nutrient broth, as a result sees Fig. 6.
As a result show that the micropore starch fungistatic effect after load amino significantly improves.
The micropore starch of the load amino prepared to embodiment 2~5 carries out water absorption rate, auricular vein haemostatic effect
Test with fungistatic effect shows:Loading the significant effect of the micropore starch after amino improves.
Unless otherwise defined, all specialties used in text and scientific words and one skilled in the art institute are ripe
The meaning known is identical.
All it is incorporated as referring in this application in all documents that the present invention refers to, just as each document
It is individually recited as with reference to such.In addition, it is to be understood that after the above-mentioned instruction content of the present invention has been read,
Those skilled in the art can make various changes or modifications to the present invention, and these equivalent form of values equally fall within this Shen
Please appended claims limited range.