CN105194712A - Hemostatic material and preparation method thereof - Google Patents
Hemostatic material and preparation method thereof Download PDFInfo
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- CN105194712A CN105194712A CN201410233783.8A CN201410233783A CN105194712A CN 105194712 A CN105194712 A CN 105194712A CN 201410233783 A CN201410233783 A CN 201410233783A CN 105194712 A CN105194712 A CN 105194712A
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Abstract
The invention relates to a hemostatic material and a preparation method thereof. Raw materials containing 0.1-10 parts by weight of carboxymethyl cellulose and 90-99.9 parts by weight of starch and water are mixed to form a uniform mixture and the mixture is subjected to freeze drying. The preparation method comprises taking carboxymethyl cellulose and starch according to a certain ratio, mixing the materials and water to obtain a uniform mixture, and carrying out freeze drying to obtain a spongy product, or carrying out freeze drying and then carrying out crushing to obtain a powdery product. The hemostatic material has good haemostasis effects, high bio-safety, simple preparation processes, no use of a chemical cross-linking agent, environmental friendliness, a low production cost and a good application prospect.
Description
Technical field
The present invention relates to a kind of hemostatic material and preparation method thereof, the plant available polysaccharide hemostatic material be specifically composited by carboxymethyl cellulose and modified starch.
Background technology
Along with the fast development of medical skill and the continuous expansion of range of operation, clinician is exploring how effectively to reduce operative hemorrhage always, shortens operating time.In recent years, the research and development of Medical absorbable hemostatic material has caused the great attention of various countries' medical circle.The more general hemostatic material of current clinical practice has gelfoam and Gelatin fleece, alginate, collagen protein, Chitosan-phospholipid complex, cellulose and oxidized regenerated cellulose, starch and zeolite etc.
Wherein, starch has nature wide material sources, low-cost feature, after making hemostatic material, can moisture in absorbing blood, and the type composition that has in blood is gathered together shutoff wound, increases the concentration of local thrombin simultaneously, accelerate intrinsic coagulation.But rate of water absorption and the saturated water absorption of starch itself are not high enough, and after water suction, viscosity is poor, can not to the tissue of breakage, the effective viscosity shutoff of vascularization, and easily washed away by blood flow, haemostatic effect is not ideal enough.
In order to improve the haemostatic effect of starch, current most starches class hemostatic material all adopts and first carries out degeneration improvement to native starch, re-uses crosslinked method to improve the performance of material.Such as, the safe styptic powder of current most widely used Ali Si (US Patent No. 6060461), react obtained a kind of polysaccharide microporous particles by micropore starch and chloropropylene oxide emulsification and cross linked, as the representational starch based hemostatic material of most up to now, in surgical hemostasis and war, all play good effect.
For another example, the compound micropore polysaccharide styptic powder " instantaneous " (Chinese patent CN101584876B) that Sai Kesaisi company produces, that starch and carboxymethyl chitosan compound are made micropore polysaccharide hemostatic material through epoxychloropropane or formaldehyde crosslinking, network structure after being cross-linked by enhancing starch, improve the intensity of its gel, strengthen haemostatic effect.
In addition, Chinese patent CN100453122C, Chinese patent CN102139123A and the hemostasia products disclosed in Chinese patent CN102406956B also use and first carry out degeneration improvement to native starch, re-use the method for chemical crosslinking to obtain the better product of anthemorrhagic performance.
The something in common of the preparation method of above-mentioned starch based hemostatic material is the step all containing chemical crosslinking, this is because stable not to this body structure of starch granules, and adopt the hands section of degeneration improvement, such as common microporous, the grain structure of meeting destruction ative starch to a certain degree, make some physical properties, as gelatinization point, freeze-thaw stability, viscosity stability, anti-shear ability, granule robustness etc., all lower than ative starch, the basis of degeneration is cross-linked it, not only can strengthen its absorption property, and the stability of starch granules structure can be improved, strengthen its granule intensity (Cui great Peng. micropore starch, the preparation of crosslinking microporous starch and crosslinking microporous starch microsphere and applied research [D] thereof. Lanzhou University 2010).But, Chemical Crosslinking Methods will inevitably bring the problem of safety, namely inevasiblely in the product to introduce as toxic chemical cross-linking agent such as chloropropylene oxide, formaldehyde, epoxychloropropane, the potential hazard to human body can be caused, and easily cause environmental pollution in industrial processes.When being applied to commercial production, in order to reduce the murder by poisoning that cross-linking agent brings, also needing to introduce complicated purification step, turn increasing technology difficulty and production cost.
Therefore, if it is better without the need to chemical crosslinking, safety to develop one, and the novel hemostatic material of haemostatic effect excellence, a new way will be opened up for hemostasis Material Field.
Summary of the invention
The object of the invention is the defect in order to overcome existing starch based hemostatic material, there is provided a kind of without the need to chemical crosslinking and the novel hemostatic material of haemostatic effect excellence, the plant available class hemostatic material be specifically composited by carboxymethyl cellulose and starch, additionally provides the method not using cross-linking step to prepare this hemostatic material.
Composite plant Absorbable hemostatic material of the present invention, by the raw material containing 0.1 ~ 10 weight portion carboxymethyl cellulose and 90 ~ 99.9 weight portion native starches or modified starch, in water after mixing, lyophilization obtains; Preferably, the weight portion of carboxymethyl cellulose and the weight ratio of native starch or modified starch are (0.5:99.5) ~ (1:99); More preferably, the weight portion of carboxymethyl cellulose and the weight ratio of native starch or modified starch are 0.5:99.5.
Above-mentioned raw materials by by mass fraction be 0.1% ~ 10% carboxymethyl cellulose and mass fraction be 90% ~ 99.9% native starch or modified starch form.
In above-mentioned composite plant Absorbable hemostatic material, the mass fraction content of carboxymethyl cellulose is preferably 0.1% ~ 1%, is preferably 0.5 ~ 1%, is more preferably 0.5%.
The viscosity of the carboxymethyl cellulose that the present invention uses is 1200 ~ 20000mpa.s, and be preferably 1200 ~ 15000mpa.s, more preferably viscosity is 10000 ~ 15000mpa.s, and further preferred viscosities is 15000mpa.s.
The defects such as native starch is also called ative starch, derives from plant, and as Semen Tritici aestivi, Semen Maydis, Rhizoma Solani tuber osi, Maninot esculenta crantz. etc., it is poor that native starch exists gel stability, and viscosity is unstable.Modified starch, namely adopts the modes such as physics, chemistry or enzyme process native starch to be processed to the novel starch obtained, and can increase some of starch functional or introduce some new characteristics, make it be more suitable for the application requirement of some special occasions.Physical modification refers to and makes starch microstructure and physicochemical property that certain change occur by physical methods such as heating, extruding, radiation, and obtaining the starch denaturalization technology of required specified properties, gained modified starch has gelatinized starch, ultrasound wave modified starch, very fine starch, particulate form starch dissolvable in cold water etc.Chemical modification is by the process of ative starch by chemical reagent, makes the change of its recurring structure and reaches the object changing its character, as Oxytarch, acidified starch, esterification starch, etherification starch etc.Enzyme denaturation refer to by enzyme be used for change the characteristics such as the granule of starch, chain length distribution and gelatinizing character, to reach the degeneration technology meeting commercial Application and require, as micropore starch, resistant starch and slowly digestible starch etc. (Cui great Peng. the preparation of micropore starch, crosslinking microporous starch and crosslinking microporous starch microsphere and applied research [D] thereof. Lanzhou University 2010, P1 ~ 12).
In view of modified starch is than the superiority of ative starch, the present invention preferably uses modified starch.The modified starch that the present invention uses be selected from many micropore starch, gelatinized starch, carboxymethyl starch one or more.
Starch gelatinization is that starch is constantly stirring the homogeneous suspension of formation in water, and heating makes granule reversibly imbibition, when being heated to a certain temperature, granule expands suddenly, and crystal structure disappears, and finally becomes the paste of thickness, though stop stirring, the phenomenon also can not sunk very soon.The temperature occurred needed for gelatinizing is called gelatinization point.Starch granules after gelatinizing is called gelatinized starch (being also called alphalise starch).The essence of gelatinizing is that hydrone enters in starch grain, and the hydrogen bond rupture between crystalline phase and the starch molecule of amorphous phase, destroys the associated state between starch molecule, is dispersed in water and becomes hydrophilic colloid solution.Industrial main use cylinder drying and squeezing and pressing method produce gelatinized starch.(Zhang Yanping, " modified starch Manufacture and application ", Chemical Industry Press, 2007, P43, P73) carboxymethyl starch take starch as a kind of anionic natural polyelectrolytes ether that raw material reacts with monoxone in the basic conditions, color is white or micro-band yellow, in Powdered, slightly saline taste, its gelatinization point is lower than ative starch, cold water solubles, be insoluble to most of organic solvent, pharmaceutically using mainly as efficient, powerful, slow-releasing medicated disintegrating agent.The preparation method of carboxymethyl starch known be at present divided into hydrophily method, organic solvent method, semidry method or dry method Four types (the beautiful Gui of tribute. the preparation of modified carboxy methyl starch functional material and performance study [D] thereof. Wuhan University of Technology, 2011, P3 ~ 5).Many micropore starch (having another name called micropore starch, porous-starch), as a kind of novel modified starch, the starch being formed a kind of hollow structure by native starch after physics, chemistry and biological method process, its surface be covered with differ in size, the depth is different, the aperture of skewness, goed deep into center by the surface of starch granules, its porosity can reach 50% of starch granules volume.Many micropore starch have large specific surface area and specific pore volume relative to ative starch, lower grain density and bulk density, better absorbability, and Chang Zuowei organic adsorbent and embedded material are applied to biomedicine field.
The present invention finds according to contrast test, adopts compound hemostatic material prepared by many micropore starch and carboxymethyl cellulose, and haemostatic effect time large to amount of bleeding is better than other starch gained composites, and therefore, the present invention can preferably use many micropore starch.
The preparation method of many micropore starch mainly contains physical method (ultrasound wave, spraying), mechanical means (machinery installation) and biochemical method (alcohol degeneration, acid hydrolysis, enzyme hydrolysis), such as supercritical ultrasonics technology, wet heat treatment method, microwave method, Mechanical Method or enzyme process (Cui great Peng. the preparation of micropore starch, crosslinking microporous starch and crosslinking microporous starch microsphere and applied research [D] thereof. Lanzhou University 2010, P18 ~ 23).
In a specific embodiment of the present invention, many micropore starch prepared by choice for use enzyme process: get native starch and amylase, namely enzyme digestion reaction obtains many micropore starch in buffer.
Many micropore starch prepared by so-called enzyme process, namely amylase is adopted to carry out modification to native starch, wherein, in diastatic selection, generally believe at present except beta amylase, the saccharifying enzyme of separate sources, α-amylase, debranching enzyme have the ability of degraded ative starch.Therefore, when enzyme process of the present invention prepares many micropore starch, enzyme used is any amylase except beta amylase.
In a specific embodiment of the present invention, comparatively conventional α-amylase is selected to prepare many micropore starch, its operating procedure is as follows: get native starch He α ?amylase, react after 10 ~ 20 hours at 40 ~ 50 DEG C in acetate buffer, many micropore starch.
Wherein ， α ?amylase: native starch=(0.6 ~ 1.2): 100w/w, such as α ?amylase: native starch=1:100w/w.The pH value of buffer is 4.0 ~ 5.0, and such as pH value is 4.5.
Wherein, buffer be Ning Meng Suan ?sodium hydrogen phosphate buffer, acetate buffer, Gou Yuan Suan ?sodium hydrogen phosphate buffer, Cu Suan ?sodium-acetate buffer or Cu Suan ?ammonium acetate buffer, preferably, use acetate buffer.
Wherein, as long as buffer consumption guarantees reactant to be effectively uniformly dispersed, the condition of applicable enzyme digestion reaction is reached.Too much can increase the wastewater flow rate of production, equipment needed thereby also wants corresponding increase, and consumption is crossed and not easily operated at least, and the ratio that therefore the present invention preferably uses is starch: buffer=(1:40) ~ (1:400) g/ml, such as, starch: buffer=1:50g/ml.
Wherein, reaction temperature is 43 ~ 47 DEG C, and such as reaction temperature is 45 DEG C ± 0.5 DEG C.
Wherein, the response time is 13 ~ 17 hours, and the such as response time is 15 ± 0.5 hours.
Wherein, described native starch be cereal starch, potato starch, bean starch one or more, be preferably potato starch, be more preferably potato starch.
Present invention also offers the method preparing above-mentioned hemostatic material, comprise the following steps: get carboxymethyl cellulose and modified starch by proportioning, add water mix homogeneously, and lyophilization obtains foam product, or powdery product is pulverized to obtain in lyophilization.
Wherein, carboxymethyl cellulose and modified starch gross mass: quality=(1:1) ~ (1:20) of water.
Preferably, when preparing foam product, carboxymethyl cellulose and modified starch gross mass: quality=(1:5) ~ (1:10) of water.
Preferably, when preparing powdery product, carboxymethyl cellulose and modified starch gross mass: the quality of water is (1:2) ~ (1:3).
In preparation method of the present invention, adopt lyophilization, high temperature can be avoided the destruction of product, the condition conveniently freeze-dry process of lyophilizing.
The product obtained according to preparation method of the present invention can be spongiform or pulverous, and wherein, the physical form of foam product can be the shape of mating with wound arbitrarily.
Comprehensive prior art and result of study of the present invention known, all adopt the mode of chemical crosslinking in current starch based hemostatic material, improve the anthemorrhagic performance of starch based hemostatic material; But, the present invention is not when using crosslinked completely, only by selection nanocomposite constituents kind and proportioning thereof, physical mixed is used to add cryodesiccated simple preparation method, just can obtain that a kind of and commercially available classic products haemostatic effect is similar to, even more excellent novel hemostatic material, while having ensured excellent haemostatic effect, effectively prevent the potential safety issue that chemical cross-linking agent exists in hemostatic material use procedure, medical safe is higher.
The preparation method of hemostatic material of the present invention, only needs simple mixing and frozen dried, compares chemical crosslinking operation more easy, and without the need to using chemical cross-linking agent in production process, avoid the health hazard of cross-linking agent to operator, safer, environmental protection.
Obviously, according to foregoing of the present invention, according to ordinary technical knowledge and the customary means of this area, not departing under the present invention's above-mentioned basic fundamental thought prerequisite, the amendment of other various ways, replacement or change can also be made.
Below by way of detailed description of the invention, foregoing of the present invention is described in further detail again.But this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following example.All technology realized based on foregoing of the present invention all belong to scope of the present invention.
Detailed description of the invention
The each kind of starch used in the present invention and carboxymethylcellulomaterials materials, all obtaining by buying commercially available prod, also can refer to prior art and preparing.In order to avoid the test error that the difference of different batches commercially available prod is brought, the present invention adopts the many micropore starch of self-control to carry out subsequent experimental.
Embodiment 1: the preparation of many micropore starch
Prepare many micropore starch with reference to existing document, concrete operations are as follows:
Potato starch is selected to be raw material, many micropore starch are made: get 10g potato starch with enzyme perforation method, add the sodium-acetate buffer 500ml of PH4.0 ~ 5.0,0.6 ~ 1.2g α ?amylase, at 40 ~ 50 DEG C, stirring reaction 10 ~ 20 hours, reacting liquid filtering, with the washing of 1000ml purified water, filters, 3 times repeatedly, make many micropore starch.
Embodiment 2: the preparation of many micropore starch
Prepare many micropore starch with reference to existing document, concrete operations are as follows:
Potato starch is selected to be raw material, many micropore starch are made: get 10g potato starch with enzyme perforation method, add the sodium-acetate buffer 500ml of PH4.5,1g α ?amylase, at 45 DEG C, stirring reaction 15 hours, reacting liquid filtering, with the washing of 1000ml purified water, filters, 3 times repeatedly, make many micropore starch.
Embodiment 3: the preparation of hemostatic material of the present invention
In the many micropore starch obtained according to embodiment 2, adding viscosity is the carboxymethyl cellulose of 15000mpa.s, the mass ratio of carboxymethyl cellulose and many micropore starch is made to be 0.5:99.5, again according to carboxymethyl cellulose and many micropore starch gross mass: purified water quality is that the ratio of 1:3 adds purified water, mix homogeneously, inserts in mould, freezer dryer Zhong ?less than 50 DEG C lyophilizing 48 hours, pulverize, cross 200 mesh sieves, obtain pulverous composite plant Absorbable hemostatic material.
Embodiment 4: the preparation of hemostatic material of the present invention
In the many micropore starch obtained according to embodiment 2, adding viscosity is the carboxymethyl cellulose of 15000mpa.s, the mass ratio of carboxymethyl cellulose and many micropore starch is made to be 0.5:99.5, again according to carboxymethyl cellulose and starch gross mass: purified water quality is that the ratio of 1:10 adds purified water, mix homogeneously, insert in mould, freezer dryer Zhong ?less than 50 DEG C lyophilizing 48 hours, obtain spongiform composite plant Absorbable hemostatic material.
Embodiment 5: the preparation of hemostatic material of the present invention
Potato starch is selected to be raw material, adding viscosity is the carboxymethyl cellulose of 15000mpa.s, the mass ratio of carboxymethyl cellulose and starch is made to be 0.5:99.5, then according to carboxymethyl cellulose and starch gross mass: purified water quality is that the ratio of 1:3 adds purified water, mix homogeneously, be heated to gelatinizing in a water bath, insert in mould, freezer dryer Zhong ?less than 50 DEG C lyophilizing 48 hours, pulverize, cross 200 mesh sieves, obtain pulverous composite plant Absorbable hemostatic material.
Embodiment 6: the preparation of hemostatic material of the present invention
Potato starch is selected to be raw material, adding viscosity is the carboxymethyl cellulose of 15000mpa.s, the mass ratio of carboxymethyl cellulose and starch is made to be 0.5:99.5, again according to carboxymethyl cellulose and starch gross mass: purified water quality is that the ratio of 1:10 adds purified water, mix homogeneously, is heated to gelatinizing in a water bath, inserts in mould, freezer dryer Zhong ?less than 50 DEG C lyophilizing 48 hours, obtain spongiform composite plant Absorbable hemostatic material.
Embodiment 7: the preparation of hemostatic material of the present invention
Potato starch is selected to be raw material, carboxymethyl starch is made through carboxy methylation, adding viscosity is the carboxymethyl cellulose of 15000mpa.s, makes the mass ratio of carboxymethyl cellulose and carboxymethyl starch be 0.5:99.5, then according to carboxymethyl cellulose and starch gross mass: purified water quality is that the ratio of 1:3 adds purified water, mix homogeneously, insert in mould, freezer dryer Zhong ?less than 50 DEG C lyophilizing 48 hours, pulverize, cross 200 mesh sieves, obtain pulverous composite plant Absorbable hemostatic material.
Embodiment 8: the preparation of hemostatic material of the present invention
Potato starch is selected to be raw material, carboxymethyl starch is made through carboxy methylation, adding viscosity is the carboxymethyl cellulose of 15000mpa.s, make the mass ratio of carboxymethyl cellulose and carboxymethyl starch be 0.5:99.5 again according to carboxymethyl cellulose and starch gross mass: purified water quality is that the ratio of 1:10 adds purified water, mix homogeneously, insert in mould, freezer dryer Zhong ?less than 50 DEG C lyophilizing 48 hours, obtain spongiform composite plant Absorbable hemostatic material.
Beneficial effect of the present invention is illustrated below by way of experimental example.
Experimental example 1
Experiment material: the many micropore starch prepared according to embodiment 2, the composite plant polysaccharide hemostatic material prepared respectively according to embodiment 3, embodiment 5, embodiment 7, the safe styptic powder of commercially available Ali Si (Arista), Sai Kesaisi styptic powder (instantaneous), Starch Company (Perclot), carboxymethyl cellulose hemostatic gauze (safe thin silk fabric)
1, saturated water absorption and rate of water absorption detect
Capillary tube method is adopted to measure saturated water absorption and the rate of water absorption of hemostatic material: water filling in acid buret, makes acid buret zero graduation liquid level concordant with sand core funnel filter plate lower end.Filter paper is cut into sand core funnel internal diameter size, weighs, put into sand core funnel, contact completely with filter plate.Open piston, absorb water completely to filter paper.Adjustment acid buret is to zero graduation, and take 0.1g powder, filter paper evenly spreads out, put into sand core funnel, timing when declining from liquid level also observes liquid level dropping distance, calculation sample rate of water absorption and saturated water absorption.Rate of water absorption and saturated water absorption have a direct impact anthemorrhagic performance.
(1) the composite plant polysaccharide hemostatic material to choose in embodiment 2 obtained pure many micropore starch, preparing according to embodiment 3, embodiment 5, embodiment 7 respectively, the safe styptic powder of Ali Si, Sai Kesaisi styptic powder, Starch Company, carboxymethyl cellulose hemostatic gauze be totally 7 groups of samples, rate of water absorption when measuring 1 minute respectively and water suction saturated after saturated water absorption, and record.
Water absorption (ml)/sample size (g) during 1 minute water absorption rate=1 minute
Water absorption (ml)/sample size (g) during saturated water absorption=absorb water saturated
Perusal when liquid level define when within 30 seconds, interval is unchanged sample reach water suction saturated
The rate of water absorption of the different hemostatic material of table 1. and saturated water absorption measurement result
Data in upper table show, the rate of water absorption of the composite plant hemostatic material finally obtained according to embodiment 3 and saturated water absorption, although lower than pure many micropore starch, be obviously better than other commercially available prod.
The hemostatic material rate of water absorption that embodiment 5, embodiment 7 obtain and lower slightly than embodiment 3 of saturated water absorption, suitable with Sai Kesaisi styptic powder, still safe far above Ali Si; And the hemostatic gauze that pure carboxymethyl cellulose is made (safe thin silk fabric) is that rate of water absorption or saturated water absorption are all obviously poor.
(2) composite plant hemostatic material rate of water absorption and the saturated water absorption of different carboxymethyl cellulose level is measured, and record.
The rate of water absorption of the composite plant hemostatic material of the different carboxymethyl cellulose level of table 2. and saturated water absorption measurement result (high viscosity: 15000mpa.s; Low viscosity: 1200mpa.s, lower same)
Data in upper table show, when viscosity is identical, along with the increase of carboxymethyl cellulose level, the rate of water absorption of compound hemostatic material and saturated water absorption decline, when carboxymethyl cellulose level reaches 10%, the water absorbing properties of compound hemostatic material is obviously deteriorated; When content is identical, it is less to add the impact of high viscosity carboxymethyl cellulose on composite water absorbing properties.
2, viscosimetric analysis
Viscosimetric analysis adopt NDJ ?5S viscometer, test condition: No. 1 rotor, 60 revs/min, 17 DEG C.
The compound hemostatic material sample preparation obtained when adding the carboxymethyl cellulose of different content with viscosity is become the solution of 2%, measure its viscosity respectively.The viscosity of the gel that the viscosity of this solution can be formed after the water suction of indirect reaction hemostatic material, and viscosity has a direct impact anthemorrhagic performance.
Table 3. adds the viscosity measurements of the compound hemostatic material of different carboxymethyl cellulose
Data in upper table show, when viscosity is identical, along with the increase of carboxymethyl cellulose level, the viscosity of compound hemostatic material solution obviously promotes; When content is identical, it is larger to add the impact of high viscosity carboxymethyl cellulose on composite emulsion viscosities.
3, viscosity merit measures
Viscosity merit measure adopt StableMicroSystem company TA ?XT Texture instrument, test condition: room temperature, test before speed 0.5mm/sec, test speed 1mm/sec, speed 10.0mm/sec, stress 100g after test, reply distance 5.0mm, time of contact 10.0sec, burst types Zi Dong ?5g.
In the process measuring viscosity merit, can be subject to the bonding force of sample to it when probe does return movement, therefore probe wants complete ablation experiment sample to do work, and during this, institute's work is exactly viscosity merit.Viscosity merit can react the bond strength of hemostatic material and detecting head surface, and the indirect reaction adhesion property of hemostatic material and tissue, this performance has a direct impact anthemorrhagic performance.
Table 4. adds the viscosity merit measurement result of the compound hemostatic material of different carboxymethyl cellulose
Data in upper table show, when viscosity is identical, along with the increase of carboxymethyl cellulose level, the viscosity merit of compound hemostatic material has obvious lifting; When content is identical, it is larger to add the impact of high viscosity carboxymethyl cellulose on viscosity merit.
Brief summary:
More than comprehensive analysis 3 tests, namely the addition of carboxymethyl cellulose and the carboxymethyl cellulose of different viscosities are on the impact of the technical specification such as rate of water absorption, saturated water absorption, viscosity, viscosity merit of compound hemostatic material, can find out:
(1) in 1200 ~ 15000mpa.s range of viscosities, the viscosity of carboxymethyl cellulose is higher, and the various performances of gained hemostatic material are better, can preferably use viscosity to be the carboxymethyl cellulose of 10000 ~ 15000mpa.s in the present invention.
(2) addition of carboxymethyl cellulose is larger, the water absorbing properties of gained hemostatic material decreases, but affect the important performance of hemostatic material anthemorrhagic performance---the also corresponding increase of viscosity and viscosity merit, therefore, in order to ensure the balance between water absorbing properties and viscosity, viscosity merit, the present invention preferably add mass fraction be 0.5 ~ 1% carboxymethyl cellulose prepare hemostatic material.
4, zoopery detects
Object: by observing, evaluating combined plant available hemostatic material is to the haemostatic effect of new zealand white rabbit Hemorrhage Model
Animal divides into groups:
Experimental group 1 (compound hemostatic material prepared according to embodiment 3), experimental group 2 (the pure many micropore starch prepared according to embodiment 2), experimental group 3 (compound hemostatic material prepared according to embodiment 5), experimental group 4 (compound hemostatic material prepared according to embodiment 7), positive controls 1 (carboxymethyl cellulose medical hemostatic gauze), positive controls 2 (the safe styptic powder group of Ali Si), positive controls 3 (Sai Kesaisi styptic powder).
Choose new zealand white rabbit 16, be divided into 8 groups at random, often organize use 2, on same rabbit, respectively experimental group 1 and experimental group 2, experimental group 1 are carried out comparative study, totally 8 control experiments with positive control 3, experimental group 4 with positive control 3 with positive control 3, experimental group 3 with positive control 2, experimental group 1 with positive control 1, experimental group 1 with experimental group 4, experimental group 1 with experimental group 3, experimental group 1.Such as, left ear, left outside leaf liver, buttocks left muscles experiment No. 1 sample on same rabbit, auris dextra, right middle lobe liver, buttocks right muscles experiment No. 2 samples, 2 rabbits calculate average bleeding stopping period.
Animal Anesthesia: after every new zealand white rabbit is weighed, by the dosage of 30mg/kg body weight, the pentobarbital sodium of 3% slowly injected the auricular vein of the left ear of rabbit, observe animal muscular tension, breathe the change with corneal reflex, anesthesia afterwards dorsal position is fixed on rabbit operating-table.
Build Hemorrhage Model:
(1) rabbit ear edge venous hemorrhage model
After rabbit ear edge position epilation mode being lost hair or feathers (need aseptic operation to operate, animal needs sterilization, drape), with the knife blade otch that transverse cuts 0.5cm is long gently at the auricular vein place of auris dextra, scratch the hemorrhage wound surface of vascularization.
(2) rabbit liver Hemorrhage Model
The method depilation that hair shaved by rabbit abdominal part shaver (needs aseptic operation to operate, animal needs sterilization, drape), successively open abdomen after row median incision and expose liver, be inserted in prefabricated metal mould circle at left outside leaf surface, excise projection with knife blade, cause 0.5cm
2the bleeding wound surface of otch (dark 2 ~ 3mm).
(3) rabbit buttocks muscles Hemorrhage Model
The method depilation (need aseptic operation to operate, animal needs sterilization, drape) of hair shaved by rabbit shaver, cuts skin, uses blade cuts biceps femoris muscle bundle respectively, make the hemorrhage wound surface of otch of the dark 5mm of long 1cm outside the left and right buttocks of rabbit.
(4) rabbit femoral artery Hemorrhage Model
The method depilation (need aseptic operation to operate, animal needs sterilization, drape) of hair shaved by rabbit shaver, and anatomical isolation side femoral artery, No. 8 syringe needle puncture tremulous pulsies, tremulous pulse spray blood, after 2 seconds, imposes hemostatic material.A rabbit can only be cooked the femoral artery Hemorrhage Model of side.
Observe haemostatic effect:
To the Hemorrhage Model of different group, use different hemostatic materials, observe and record bleeding stopping period, the time is shorter, and stop blooding rapider, haemostatic effect is better.By the Clinical practice experience of hemostatic material, for ensureing haemostatic effect, the various hemostatic material of all excessive use in bleeding part.The results are shown in following table:
The bleeding stopping period measurement result of the different hemostatic material of table 5.
Brief summary:
(1) data in upper table show, the bleeding stopping period of experimental group 1 is obviously short than the bleeding stopping period of experimental group 2, although illustrate that the water absorbing properties of pure many micropore starch that the compound hemostatic material of the present invention of the carboxymethyl cellulose being compounded with 0.5% is prepared than same method is poor, but bleeding stopping period obviously shortens, actual haemostatic effect is higher, illustrates that the compound of starch and carboxymethyl cellulose creates good collaborative anastalsis.
(2) bleeding stopping period of experimental group 1 is obviously short than the bleeding stopping period of positive controls 1 and positive controls 2, illustrate that the anthemorrhagic performance of compound hemostatic material of the present invention is obviously better than the safe styptic powder of commercially available Ali Si and carboxymethyl cellulose medical hemostatic gauze, particularly run into the situation that amount of bleeding is larger, the difference of anthemorrhagic performance shows especially outstanding.
(3) haemostatic effect of comprehensive various aspects, the bleeding stopping period of experimental group 1, experimental group 3, experimental group 4 and the bleeding stopping period no significant difference of positive controls 3 (Sai Kesaisi styptic powder), but, compared with the production technology of Sai Kesaisi compound hemostatic powder, the present invention does not use chemical cross-linking agent to be cross-linked, remain without toxic chemical cross-linking agent, physical method has only been used to mix and cryodesiccated simple production technique, safety is better, can also reach equal haemostatic effect simultaneously.
(4) experimental group 1 is compared with experimental group 3, experimental group 4, at the situation lower hemostasia time no significant difference that amount of bleeding is less; But during amount of bleeding comparatively large (as femoral artery is hemorrhage), experimental group 1 shows better haemostatic effect than experimental group 3 and experimental group 4, the technical scheme of optimization experiment group 1.
In sum, the compound hemostatic material that the present invention only utilizes physical method all kinds of starch hemostatic material and carboxymethyl cellulose hemostatic material to be prepared, although do not carry out crosslinking Treatment to starch based material, but still the bleeding stopping period of different parts wound surface can be shortened significantly, there is good haemostatic effect, and with adopt the commercially available classical hemostatic material effect of chemical crosslinking process suitable, for clinical application provide safer, effectively select.
Claims (16)
1. a hemostatic material, is characterized in that: it is by the raw material containing 0.1 ~ 10 weight portion carboxymethyl cellulose and 90 ~ 99.9 weight starch, and in water after mixing, lyophilization obtains.
2. hemostatic material according to claim 1, is characterized in that: described raw material is that the carboxymethyl cellulose of 0.1% ~ 10% and the starch of 90% ~ 99.9% form by mass fraction.
3. hemostatic material according to claim 1 and 2, is characterized in that: described starch is native starch or modified starch; Preferably, described modified starch is one or more in many micropore starch, gelatinized starch, carboxymethyl starch, is more preferably many micropore starch.
4. hemostatic material according to claim 3, is characterized in that: described many micropore starch are prepared by supercritical ultrasonics technology, wet heat treatment method, microwave method, Mechanical Method or enzyme process; Preferably, described many micropore starch are prepared by enzyme process, and step is as follows: get native starch and amylase, and in buffer, namely enzyme digestion reaction obtains many micropore starch.
5. hemostatic material according to claim 4, is characterized in that: described amylase is any amylase beyond beta amylase;
Described amylase be preferably α ?amylase.
6. hemostatic material according to claim 5, it is characterized in that: α ?amylase: native starch=(0.6 ~ 1.2): 100w/w, preferably ， α ?amylase: native starch=1:100w/w.
7. hemostatic material according to claim 4, is characterized in that: described buffer be Ning Meng Suan ?sodium hydrogen phosphate buffer, acetate buffer, Gou Yuan Suan ?sodium hydrogen phosphate buffer, Cu Suan ?sodium-acetate buffer or Cu Suan ?ammonium acetate buffer; Described buffer is preferably acetate buffer.
8. hemostatic material according to claim 7, is characterized in that: the pH value of described buffer is 4.0 ~ 5.0, and preferably, described pH value is 4.5.
9. the hemostatic material according to claim 4 ~ 8 any one, is characterized in that: native starch: buffer=(1:40) ~ (1:400) g/ml, preferably, and native starch: buffer=1:50g/ml.
10. hemostatic material according to claim 4, is characterized in that: reaction temperature is 40 ~ 50 DEG C, and preferably, reaction temperature is 43 ~ 47 DEG C, and more preferably, reaction temperature is 45 DEG C ± 0.5 DEG C.
11. hemostatic materials according to claim 4, is characterized in that: the response time is 10 ~ 20 hours, and preferably, the response time is 13 ~ 17 hours, and more preferably, the response time is 15 ± 0.5 hours.
12. hemostatic materials according to claim 1 ~ 11 any one, is characterized in that: described native starch be cereal starch, potato starch, bean starch one or more, be preferably potato starch, be more preferably potato starch.
13. hemostatic materials according to claim 2, is characterized in that: the mass fraction of described carboxymethyl cellulose is 0.1% ~ 1%, are preferably 0.5 ~ 1%, are more preferably 0.5%.
14. hemostatic materials according to claim 1,2 or 13, it is characterized in that: described carboxymethyl cellulose viscosity is 1200 ~ 20000mpa.s, be preferably 1200 ~ 15000mpa.s, be more preferably 10000 ~ 15000mpa.s, more preferably 15000mpa.s.
15. 1 kinds of methods preparing hemostatic material described in claim 1 ~ 14 any one, it is characterized in that: comprise the following steps: get carboxymethyl cellulose and modified starch by proportioning, add water mix homogeneously, and lyophilization obtains foam product, or powdery product is pulverized to obtain in lyophilization.
16. preparation methoies according to claim 15, is characterized in that: carboxymethyl cellulose and modified starch gross mass: quality=(1:1) ~ (1:20) of water; Preferably,
When preparing foam product, carboxymethyl cellulose and modified starch gross mass: quality=(1:5) ~ (1:10) of water; When preparing powdery product, carboxymethyl cellulose and modified starch gross mass: the quality of water is (1:2) ~ (1:3).
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| CN109125792A (en) * | 2018-07-16 | 2019-01-04 | 广西民族大学 | A kind of cassava porous-starch hemostatic material and its preparation method and application |
| CN109125795A (en) * | 2018-10-18 | 2019-01-04 | 赛克赛斯生物科技股份有限公司 | A kind of polysaccharide hemostatic composition and the preparation method and application thereof |
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| CN113423369A (en) * | 2019-02-15 | 2021-09-21 | 巴德股份有限公司 | Hemostatic biopsy tract product |
| CN113423369B (en) * | 2019-02-15 | 2023-08-18 | 巴德股份有限公司 | Hemostatic biopsy channel product |
| CN110038153A (en) * | 2019-03-27 | 2019-07-23 | 广东医科大学 | A kind of medical hemostatic bibre material and preparation method thereof |
| CN112773928A (en) * | 2021-01-05 | 2021-05-11 | 珠海原妙医学科技股份有限公司 | Starch-based fluffy particles and preparation method and application thereof |
| CN112773928B (en) * | 2021-01-05 | 2021-09-21 | 珠海原妙医学科技股份有限公司 | Starch-based fluffy particles and preparation method and application thereof |
| TWI804954B (en) * | 2021-01-05 | 2023-06-11 | 大陸商珠海原妙醫學科技股份有限公司 | Starch-based fluffy granules, preparation method and application thereof |
| CN112999407A (en) * | 2021-03-25 | 2021-06-22 | 杭州维力医疗器械有限公司 | Degradable hemostatic sponge, preparation method and application thereof, and degradable drug-loaded hemostatic sponge |
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