CN108187128A - A kind of absorbable hemostasis bone wax and preparation method thereof - Google Patents
A kind of absorbable hemostasis bone wax and preparation method thereof Download PDFInfo
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- CN108187128A CN108187128A CN201810123352.4A CN201810123352A CN108187128A CN 108187128 A CN108187128 A CN 108187128A CN 201810123352 A CN201810123352 A CN 201810123352A CN 108187128 A CN108187128 A CN 108187128A
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- gelatin
- bone wax
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- hemostasis
- absorbable
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/0047—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L24/0073—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix
- A61L24/0094—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix containing macromolecular fillers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0042—Materials resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
Abstract
The present invention provides a kind of absorbable hemostasis bone wax and preparation method thereof, and the hemostasis bone wax is made of gelatin and poloxamer, and wherein the mass ratio of gelatin and poloxamer is 1:1~9:1.Hemostasis bone wax provided by the invention has degradability, excellent physics plugging effect and anthemorrhagic performance.In addition, the preparation method of present invention hemostasis bone wax is by being carried out cross-linked gelatin after being fully swollen, carrying out mechanical crushing, freeze-drying and separating twice, then swell in Poloxamer solution again, freeze-drying again obtains.The preparation method of the present invention is simple for process, the hemostasis bone wax of preparation has suitable volume sweell(ing) rate and saturated water absorption, and the degradation time for the bone wax that stops blooding is 8 weeks ~ 50 weeks, and burst pressure is not less than 60mmHg, with good plugging effect, orthopaedics hemostasis field can be widely applied to.
Description
Technical field
The present invention relates to hemostatic material technical fields, relate more specifically to a kind of absorbable hemostasis bone wax and its preparation side
Method.
Background technology
Bone wax is a kind of material that marrow portion capillary oozing of blood is blocked by physical method, can effectively block cancellous bone
Bleeding, hemostasis during available for various first-aid patients bone oozings of blood.The specific mechanism of action of bone wax is：One side bone wax is stopping blooding
There is very high absorption to liquid in the process, by the moisture in absorbing blood rapidly in the bleeding surface of a wound to promote blood platelet
Concentration, so as to enhance hematoblastic aggegation speed and agglutinability；On the other hand, it is gluey that water-setting is formed after bone wax water suction, it can
It blocks in wound surface, increases the effect of hemostasis.In addition, after bone wax water swelling, peripheral vessels, which can be formed, has centainly
The contention effect of pressure further promotes hemostasis.
Clinically present used bone wax, is mostly 70% beeswax and the mixture of 30% vaseline, has good soft
Change performance, energy plastotype, nontoxic after rubbing softening with hand rubbing, but can not be degraded and absorb by body.Since beeswax and vaseline mix
Bone wax material prepared by object is unable to organism absorption, leaves the probability that can increase infection as foreign matter in vivo.Simultaneously as molecule
Gap is too small, and bone tissue can not be by bone wax material, and the growth of meeting hindering bone is postoperative to will appear the problem of wound does not recover for a long time,
It needs to carry out postoperative debridement when necessary.Treatment time is not only extended in this way, also increases the pain of patient.
Therefore develop that a kind of haemostatic effect is good and the bone wax material of degradable absorption, while bone wax is made to disclosure satisfy that clinic
The mechanical property requirements used have great importance and are worth.
Invention content
The purpose of the present invention is being directed to bone wax non-degradable absorption in the prior art, leave and be unfavorable for wound healing in vivo
The defects of, a kind of absorbable hemostasis bone wax is provided.The present invention is by using the phase transition temperature of poloxamer and dropping for gelatin
Not only there is excellent physics to block, clog performance and haemostatic effect, but also can give birth to completely for Xie Xing, the bone wax product being prepared
Object degradation absorbs, while product has excellent mechanical performance.
In order to solve the above technical problems, the technical solution adopted in the present invention is：
A kind of absorbable hemostasis bone wax, prepares the matter that material includes gelatin and poloxamer, wherein gelatin and poloxamer
The ratio between amount is 1:1~9:1.Preferably, the mass ratio of gelatin and poloxamer is 7:3.
Preferably, the hydrophilic lipophilic balance of the poloxamer（HLB）It is 20 ~ 29.
Preferably, the poloxamer is PLURONICS F87, Pluronic/Lutrol F 108, one kind in poloxamer188 or several
Kind, it is further preferred that the poloxamer is poloxamer188.
Effective plugging material when bone wax is for cancellous bone bleeding, mixture of the traditional material for paraffin and beeswax, body
Interior non-degradable, therefore the growth of newborn bony structures can be limited.The hemostasis bone wax of the present invention is by using biodegradable suction
The gelatin of receipts and can the poloxamer of phase transition temperature be made, there is excellent physics to block, filling performance and haemostatic effect, and
Fully biodegradable absorbs, and without limitation on the growth of newborn bony structures, while product has excellent mechanical performance.
The present invention also provides a kind of preparation methods for the bone wax that stops blooding, and include the following steps：
S1. aqueous gelatin solution is prepared；
S2. crosslinking agent is added in institute's gelatin water solution, carries out crosslinking Treatment；
S3. the gelatin after crosslinking Treatment is placed in water and is fully swollen；
S4. the gelatin after being swollen in step S3 is divided into fritter, is then ground into micron-sized gelatin particle；
S5. the gelatin particle is subjected to cryogenic freezing, is freeze-dried after complete freezing, obtains dry gelatin；
S6. the gelatin after freeze-drying is subjected to separating twice；
S7. the gelatin after separating twice step S6 obtained, which is placed in Poloxamer solution, to be fully swollen；
S8. the gelatin in Poloxamer solution after swelling of step S7 is freeze-dried.
The present invention is adequately water-swellable by the way that the gelatin after crosslinking Treatment is carried out, and then carries out mechanical crushing, freezing is done
It after dry, separating twice, then places it in Poloxamer solution and is fully swollen so that poloxamer and gelatin carry out fully
Fusion, be finally freeze-dried again, obtain hemostasis bone wax.The volume sweell(ing) behavior of bone wax depends on gelatin crosslinking Treatment
There is hydrophilic radical can adjust for the degree of swelling of the degree of cross linking and infiltration in water and Poloxamer solution, wherein poloxamer
The swelling ratio of the hemostasis bone wax of preparation so that the hemostasis bone wax that this method is prepared not only has good water absorbing properties and object
Reason blocks, filling performance, and osteorrhagia can be carried out to block and stop blooding well.
Preferably, the mass concentration of aqueous gelatin solution described in step S1 is 5% ~ 50%, and aqueous gelatin solution heating is completely molten
The temperature of solution is 40 DEG C ~ 80 DEG C.
Preferably, the dosage of crosslinking agent is the 4% ~ 20% of gelatin quality in step S2.It is further preferred that the crosslinking agent
It is added in during whisking gelatin solution.
Preferably, it is crushed described in step S4 using water phase materials crusher.
Preferably, gelatin is ground into 0.1 μm ~ 2 μm of particle in step S6.
It is highly preferred that the crushing speed used in step S6 is 30000r/min, grinding time 1min.
Preferably, the mass concentration of Poloxamer solution is 10% ~ 50% in the S6, and the poloxamer is poloxamer
407。
In order to obtain the bone wax that evenly preferably stops blooding with filling performance, the preparation method further includes：
S9. freeze-drying prods step S8 obtained carry out third time crushing.It can make the microscopic particles of hemostasis bone wax more in this way
Small, texture is finer and smoother, and the plasticity and closure filling performance for the bone wax that stops blooding are also more preferable.
Preferably, the preparation method is further included carries out irradiation sterilization to obtained hemostasis bone wax, you can obtains to apply
In the hemostasia products on the surface of a wound.
The bone wax that preparation method of the present invention obtains can be applied directly to the enterprising whereabouts blood of the surface of a wound of bleeding, can also add
Enter after a small amount of water is mixed and use, the bone wax that stops blooding in this way has good flexibility, can carry out moulding, can play as needed
Preferably filling and plugging effect.
Preferably, in order to reduce the residual quantity of crosslinking agent in the hemostasis bone wax, the safety of hemostasis bone wax, this hair are improved
It is bright to use the crosslinking agent water-soluble carbodiimide for being not involved in reaction（EDC）, and will be handed over by particular step in preparation method
Join agent to remove, the hemostasis bone wax product crosslinking agent residual quantity finally obtained can be stingless to organizing in 100ppm hereinafter, safety is good
Swash.
Specifically, above-mentioned preparation process further includes following steps：
（1）Crosslinking agent described in step S2 is water-soluble carbodiimide（EDC）, the quality of EDC is the 4% ~ 20% of gelatin quality,
EDC is added in whisking gelatin solution processes, and the mixing speed of gelatin solution is 100r/min ~ 5000r/min, preferably
The addition speed of 1000r/min, EDC are 0.1mL/s ~ 10mL/s, preferably 2mL/s；
（2）After step s4, gelatin is placed in progress ultrasound-centrifuge cycle in pure water by way of centrifugal deposition, preferably
Centrifugal rotational speed is 10000r/min ~ 20000r/min, 5 ~ 10min of time of single spin, it is highly preferred that the centrifugal rotational speed
For 15000r/min, supersonic frequency is 25KHz ~ 130KHz, and the time of single sonication is 5min ~ 30min.
It is conventional that glutaraldehyde etc. is selected to be crosslinked it for the gelatin materials of low swelling, but it is crosslinked the post-crosslinking of end
Agent component can be present in finished product, gradually be discharged in the subsequent degradation process of gelatin materials, bring irritation influence or potential
Carcinogenicity risk.Gelatin materials are effectively crosslinked by the present invention using the crosslinking agent for being not involved in reaction, pass through centrifugation after crosslinking
The modes such as deposition separation, purified water dialysis, which purify crosslinking agent, to be removed, and effectively avoids the residual and toxicity of pungent.
A kind of hemostatic article, the absorbable hemostatic bone wax prepared including the above method.
Hemostasis bone wax anti-burst pressure prepared by the present invention is not less than 60mmHg, volume sweell(ing) rate adjustable extent for 50% ~
500%, the adjustable extent of saturated water absorption is 100% ~ 2000%, and the adjustable extent of degradation time is 8 weeks ~ 50 weeks, can be made only
Blood works well, the hemostatic article of good mechanical performance and degradable absorption.
Compared with prior art, the beneficial effects of the invention are as follows：
The present invention provides a kind of absorbable hemostasis bone wax and preparation method thereof, and hemostasis bone wax is by gelatin and poloxamer group
Into having the function of that degradability and excellent physical block and anthemorrhagic performance.It is provided by the invention hemostasis bone wax preparation method be
By the way that cross-linked gelatin is carried out after being fully swollen, mechanical crushing, freeze-drying and separating twice are carried out, then swells in pool Lip river again
In husky nurse solution, freeze-drying again obtains.The preparation method of the present invention is simple for process, and the hemostasis bone wax of preparation has suitably
Volume sweell(ing) rate and saturated water absorption, the degradation time of bone wax is 8 weeks ~ 50 weeks, and burst pressure is not less than 60mmHg, has good
Good plugging effect can be widely applied to orthopaedics hemostasis field.
Description of the drawings
Fig. 1 is the picture of the absorbable hemostatic bone wax of the present invention.
Fig. 2 is the absorbable hemostatic bone wax of the present invention and the mixed picture of a small amount of water.
Fig. 3 is result of the leaching liquor culture cell of the absorbable hemostatic bone wax of embodiment 1 after 24 hours.
Fig. 4 is result of the leaching liquor culture cell of the absorbable hemostatic bone wax of embodiment 1 after 72 hours.
Specific embodiment
The present invention is further illustrated With reference to embodiment, but embodiment the present invention is not done it is any
The restriction of form.
Embodiment 1
A kind of absorbable hemostasis bone wax, the wherein mass ratio of gelatin and poloxamer are 7:3, the hemostasis bone wax includes as follows
Preparation process：
S1. 40g gelatin is taken to be placed in beaker, 60g water is added in, is placed in 50 DEG C of baking ovens and treats that gelatin is completely dissolved, be prepared into quality
A concentration of 40% aqueous gelatin solution；
S2. water-soluble carbodiimide（EDC）1.6g is dissolved in 10ml purified waters（EDC mass is the 4% of gelatin quality）, institute
Crosslinking agent is added in gelatin water solution while stirring, carries out crosslinking Treatment, wherein the speed of the stirring is 1000r/min,
The addition speed 2mL/s of crosslinking agent；
S3. the gelatin after crosslinking Treatment is placed in water and is fully swollen；
S4. the gelatin after being swollen in step S3 is divided into fritter, is then ground into micron order with water phase materials crusher
Gelatin particle, gelatin is placed in pure water by way of centrifugal deposition and carries out the processing of ultrasound-centrifuge cycle, centrifugal rotational speed
15000r/min, single spin time 5min, ultrasonic frequency are 25KHz, and the time of single sonication is 5min, and cycle is secondary
Number is 3 times；
S5. the gelatin particle is subjected to cryogenic freezing, is freeze-dried after complete freezing, obtains dry gelatin；
S6. the gelatin after freeze-drying is subjected to separating twice, crushing speed is 30000r/min, grinding time 1min；
S7. the gelatin after separating twice step S6 obtained is placed in poloxamer188 solution and is fully swollen, and moors Lip river
The mass concentration of husky 407 solution of nurse is 25%；
S8. the gelatin after step S7 is swollen is freeze-dried, and is crushed again after freeze-drying, filling in auxiliary instrument,
It irradiates spare, obtains absorbable hemostasis bone wax, as shown in Figure 1.
Hemostasis bone wax obtained can be applied directly to the enterprising whereabouts blood of the surface of a wound of bleeding, can also add in a small amount of water and carry out
It is used after mixing, as shown in Figure 2.In this way hemostasis bone wax it is soft and can carry out as needed it is moulding, can play preferably filling and
Plugging effect.
Embodiment 2
A kind of absorbable hemostasis bone wax, the wherein mass ratio of gelatin and poloxamer are 9:1, the hemostasis bone wax includes as follows
Preparation process：
S1. 20g gelatin is taken to be placed in beaker, 80g water is added in, is placed in 80 DEG C of baking ovens and treats that gelatin is completely dissolved, be prepared into quality
A concentration of 20% aqueous gelatin solution；
S2. water-soluble carbodiimide（EDC）2g is dissolved in 10ml purified waters（EDC mass is the 10% of gelatin quality）, institute
Crosslinking agent is added in gelatin water solution while stirring, carries out crosslinking Treatment, wherein the speed of the stirring is 1000r/min,
The addition speed 2mL/s of crosslinking agent；
S3. the gelatin after crosslinking Treatment is placed in water and is fully swollen；
S4. by step S3 be swollen after gelatin be divided into fritter, be subsequently placed in water phase materials crusher be ground into it is micro-
Gelatin by way of centrifugal deposition is placed in pure water and carries out ultrasound-centrifuge cycle processing by the gelatin particle of meter level, and centrifugation turns
Fast 15000r/min, single spin time 5min, ultrasonic frequency are 100KHz, and the time of single sonication is 10min, is followed
Ring number 3 times；
S5. the gelatin particle is subjected to cryogenic freezing, is freeze-dried after complete freezing, obtains dry gelatin；
S6. the gelatin after freeze-drying is subjected to separating twice, crushing speed is 30000r/min, grinding time 1min；
S7. the gelatin after separating twice step S6 obtained is placed in poloxamer188 solution and is fully swollen, and moors Lip river
The mass concentration of husky 407 solution of nurse is 10%；
S8. the gelatin after step S7 is swollen is freeze-dried, and is crushed again after freeze-drying, filling in auxiliary instrument,
It irradiates spare.
Embodiment 3
A kind of absorbable hemostasis bone wax, the wherein mass ratio of gelatin and poloxamer are 1:1, the hemostasis bone wax includes as follows
Preparation process：
S1. 5g gelatin is taken to be placed in beaker, 95g water is added in, is placed in 40 DEG C of baking ovens and treats that gelatin is completely dissolved, be prepared into quality
A concentration of 5% aqueous gelatin solution；
S2. water-soluble carbodiimide（EDC）0.5g is dissolved in 10ml purified waters（EDC mass is the 10% of gelatin quality）,
Crosslinking agent is added in institute's gelatin water solution while stirring, carries out crosslinking Treatment, wherein the speed of the stirring is 1000r/
Min, the addition speed 2mL/s of crosslinking agent；
S3. the gelatin after crosslinking Treatment is placed in water and is fully swollen；
S4. fritter is divided into after gelatin materials complete swelling after being swollen in step S3, is placed in water phase materials crusher,
Gelatin after crushing is the gelatin particle of micron-sized saturation swelling, by way of centrifugal deposition by gelatin be placed in pure water into
Row ultrasound-centrifuge cycle processing, centrifugal rotational speed 15000r/min, single spin time 10min, ultrasonic frequency is 75KHz, single
The time of secondary supersound process be 10min, cycle-index 3 times；
S5. the gelatin particle is subjected to cryogenic freezing, is freeze-dried after complete freezing, obtains dry gelatin；
S6. the gelatin after freeze-drying is subjected to separating twice, crushing speed is 30000r/min, grinding time 1min；
S7. the gelatin after separating twice step S6 obtained is placed in poloxamer188 solution and is fully swollen, and moors Lip river
The mass concentration of husky 407 solution of nurse is 50%；
S8. the gelatin after step S7 is swollen is freeze-dried, and is crushed again after freeze-drying, filling in auxiliary instrument,
It irradiates spare.
Performance detection
（1）Specific surface area detects
Specific surface area detection method be：Using multiple spot BET method, product to be measured is specifically taken to be put into the sample cell of analytical instrument
In, wherein, analytical instrument is quick full-automatic specific surface area and Porosimetry, model U.S. health tower NOVA 4200e.
Low temperature（Liquid nitrogen bath）Under the conditions of, a certain amount of Adsorbate Gas is passed through into sample cell（N2）, according to gas volume before and after absorption
Variation determine the sample to adsorption molecule（N2）Adsorbance；With reference to standard GB/T/T24533-2009-gas
BET principles are adsorbed to measure the specific surface area of solid matter.
The calculation of specific surface area is：It is put into the sample in gaseous environment, material surface（Extra-granular and inside
The surface area in gap）Physical absorption will occur at low temperature.When absorption reaches balance, the adsorbed gas of equilibrium adsorptive pressure is measured
The scale of construction calculates sample mono layer adsorption amount, so as to calculate the specific surface area of sample according to BET equations.Wherein, BET
Equation is：
In formula：
P --- adsorbate divides, unit Pa；
P0--- adsorbent saturated vapor pressure, unit Pa；
V --- the practical adsorbance of sample, unit cm3；
Vm--- individual layer saturated extent of adsorption, unit cm3；
C --- with the relevant constant of sample adsorption capacity.
It is tested with the gelatin particle after separating twice in embodiment 1-3, test result is as shown in table 1.
（2）The detection of volume sweell(ing) rate
The test method of volume selects fluid-discharge therapy, after hemostasis bone wax material is infiltrated on graduated cylinder, reads liquid level raising numerical value.Volume
Swelling ratio computational methods are：Volume V after saturation swelling1With initial volume V0Difference account for initial volume V0Percentage.Detection
It the results are shown in Table 1.
（3）The detection of quality swelling ratio
The test method of quality swelling ratio selects weight method, after hemostasis bone wax material complete wetting, removes, removes and do not absorbed
Excessive moisture, weigh.Quality swelling ratio computational methods are：Mass M after saturation swelling1With initial mass M0Difference account for just
Beginning mass M0Percentage.Testing result is shown in Table 1.
（4）Resistance to compression explosion bulge test
External resistance to compression explosion bulge test experimental method：Using pressure test method, specifically preparing the thickness with multi-pore structure is
The acrylic plectane of 1cm, plectane closed can be fixed on pressure tester port, and pressure tester is the Ya Ke there are plectane interface
Power box, the opposite connection pressure-detecting device and device for exerting of plectane interface, after closed acrylic box connects plectane, in circle
Plate aperture position smears the hemostasis bone wax material of the present invention, and material will fill up entire hole, and plectane direction is downward, is filled in box
Water presses and detects leakage numerical value.
External resistance to compression explosion bulge test is carried out to the hemostasis bone wax that embodiment 1 ~ 3 obtains, experimental result is as shown in table 1.
The performance parameter test result of the hemostasis bone wax of table 1
| Embodiment | The BET specific surface area of gelatin particle | The volume sweell(ing) rate of bone wax | The quality swelling ratio of bone wax | The external resistance to compression explosion bulge test value of bone wax |
| 1 | 30 m2/g | 296% | 530% | 60.23±11.74 mmHg |
| 2 | 40 m2/g | 396% | 1260% | 80.35±20.61 mmHg |
| 3 | 70 m2/g | 512% | 1800% | 85.95±15.23 mmHg |
（5）Cellulotoxic experiment
Culture cell is contacted by leaching liquor, using L929 as experimental cell, cell proliferation observation is evaluated prepared by embodiment 1
Bone wax to the toxic effect of cell in vitro.
The detailed process of experiment is as follows：Use complete medium（+ 10% fetal calf serum of DMEM culture mediums（FBS）+ 1% is dual anti-（It is green
The mixed liquor of mycin and streptomysin））According to the ratio extraction hemostasis bone wax material of 0.1g/mL, 100% leaching liquor is obtained, with 100%
Leaching liquor is diluted, and obtains 75% leaching liquor and 25% leaching liquor.
Experimental group：Using complete medium（+ 10% fetal calf serum of DMEM culture mediums（FBS）+ 1% is dual anti-（Penicillin and strepto-
The mixed liquor of element））, leaching liquor is added, adds in cell suspension, carries out cell culture.
Control group：Using complete medium（+ 10% fetal calf serum of DMEM culture mediums（FBS）+ 1% is dual anti-（Penicillin and strepto-
The mixed liquor of element））Cell suspension is added in, carries out cell culture.Leaching liquor is not added in control group, remaining cell culture condition with
Experimental group is identical.
Blank group：Using complete medium（+ 10% fetal calf serum of DMEM culture mediums（FBS）+ 1% is dual anti-（Penicillin and strepto-
The mixed liquor of element））, leaching liquor and cell suspension are not added in blank group, are positioned over and experimental group and control group in same time
In identical environment, reference during measuring absorbance value as experimental group and control group.
The preparation of leaching liquor is carried out using the hemostasis bone wax of embodiment 1, extraction temperature is (37 ± 1) DEG C, and extraction time is
(24 ± 2) h obtains the leaching liquor of 100%, 75%, 25% concentration gradient.Then L929 cells are resuspended using complete medium, be made
A concentration of 4 × 104The cell suspension of a cell/mL.Using 96 hole plates as culture plate, wherein experimental group and control group is are cultivating
Above-mentioned cell suspension is added in plate, 100 μ L are added in per hole；Complete culture of the blank group to add in 100 μ L per hole in culture plate
Base is added without cell suspension.
The culture plate of experimental group, control group and blank group is placed in preculture 24 hours in incubator（At 37 DEG C, 5%CO2
Under the conditions of）.Then the leaching liquor of above-mentioned concentration gradient is added in into experimental group, 100 μ L are added in per hole, control group and blank group are not
Add leaching liquor, each culture plate is placed in incubator cultivates 24 hours, 72 hours later（At 37 DEG C, 5%CO2Under the conditions of）.Then
The culture solution in hole is carefully sucked out, then the CCK-8 mixed liquors of 100 μ L are added in into every hole（By+10 μ L of complete medium of 90 μ L
CCK-8 be mixed）, then culture plate is placed in incubator and is incubated 2 hours.Then it is measured at 450nm with microplate reader
Absorbance.
Fig. 3, Fig. 4 are in cellulotoxic experiment, and the absorbance value after blank group is individually subtracted in experimental group, control group（OD values）.
As can be seen that being approached with the cell proliferation rate after leaching liquor culture with control group from figure, therefore, hemostasis bone wax of the invention tool
There is good safety, have no toxic side effect to cell growth.
（6）Block validity experiment
Prove that it blocks validity by external resistance to compression explosion bulge test experiment, specific experiment method is：Preparing has concrete dynamic modulus knot
The thickness of structure is the acrylic plectane of 1cm, and plectane closed can be fixed on pressure tester port, and pressure tester is there are plectanes
The acrylic box of interface, the opposite connection pressure-detecting device and device for exerting of plectane interface, closed acrylic box connection
After plectane, this material is smeared in plectane aperture position, material will fill up entire hole, and plectane direction is downward, and water is filled in box,
It presses and detects leakage numerical value.
（7）Validity of stopping blooding experiment
After experimental dog is anaesthetized, using normal sterile surgical procedure, dog hind leg skin is cut, manufactures bone defect bleeding.Experimental group
Stopped blooding using the hemostasis bone wax of embodiment 1, control group is without hemostasis.As a result experimental group can effectively stop in 20 seconds
Blood, and without oozing phenomenon, haemostatic effect is notable.Control group bleed site continuous bleeding.
Claims (10)
1. a kind of absorbable hemostasis bone wax, which is characterized in that the material for preparing of the hemostasis bone wax includes gelatin and pool Lip river sand
The mass ratio of nurse, wherein gelatin and poloxamer is 1:1~9:1.
2. absorbable hemostasis bone wax according to claim 1, which is characterized in that the poloxamer for PLURONICS F87,
One or more of Pluronic/Lutrol F 108, poloxamer188.
3. the preparation method of absorbable hemostasis bone wax described in claims 1 or 2, which is characterized in that include the following steps：
S1. aqueous gelatin solution is prepared；
S2. crosslinking agent is added in institute's gelatin water solution, carries out crosslinking Treatment；
S3. the gelatin after crosslinking Treatment is placed in water and is fully swollen；
S4. the gelatin after being swollen in step S3 is divided into fritter, is then ground into micron-sized gelatin particle；
S5. the gelatin particle is subjected to cryogenic freezing, is freeze-dried after complete freezing, obtains dry gelatin；
S6. the gelatin after freeze-drying is subjected to separating twice；
S7. the gelatin after separating twice step S6 obtained, which is placed in Poloxamer solution, to be fully swollen；
S8. the gelatin in Poloxamer solution after swelling of step S7 is freeze-dried.
4. the preparation method of absorbable hemostasis bone wax according to claim 3, which is characterized in that crosslinking agent in step S2
Dosage is the 4% ~ 20% of gelatin quality.
5. the preparation method of absorbable hemostasis bone wax according to claim 3, which is characterized in that by gelatin in step S6
It is ground into 0.1 μm ~ 2 μm of particle.
6. the preparation method of absorbable hemostasis bone wax according to claim 3, which is characterized in that poloxamer in the S6
The mass concentration of solution is 10% ~ 50%, and the poloxamer is poloxamer188.
7. the preparation method of absorbable hemostasis bone wax according to claim 3, which is characterized in that the method further includes
Following steps：S9. freeze-drying prods step S8 obtained carry out third time crushing.
8. the preparation method of absorbable hemostasis bone wax according to claim 3, which is characterized in that the preparation method is also wrapped
It includes and irradiation sterilization is carried out to obtained hemostasis bone wax.
9. according to the preparation method of any one of claim 3 to the 8 absorbable hemostasis bone wax, which is characterized in that further include：
Crosslinking agent described in step S2 is water-soluble carbodiimide, and the quality of the water-soluble carbodiimide is the 4% of gelatin quality
~ 20%, water-soluble carbodiimide adds in whisking gelatin solution processes, and the mixing speed of gelatin solution is 100r/min
~ 5000r/min, the addition speed of water-soluble carbodiimide is 0.1mL/s ~ 10mL/s；It, will between step S4 and step S5
Obtained gelatin particle, which is placed in pure water, carries out ultrasound-centrifuge cycle processing, and crosslinking agent is removed.
10. a kind of hemostatic article, which is characterized in that including hemostasis bone wax absorbable described in claims 1 or 2 or including by
The absorbable hemostatic bone wax that the preparation method of any one of claim 3 to the 9 absorbable hemostasis bone wax obtains.
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| CN109200332A (en) * | 2018-11-26 | 2019-01-15 | 广州新诚生物科技有限公司 | A kind of biodegradable hemostasis bone wax and preparation method thereof |
| CN109453419A (en) * | 2018-11-26 | 2019-03-12 | 广州新诚生物科技有限公司 | Absorbable hemostasis bone wax of one kind and preparation method thereof |
| CN109893677A (en) * | 2019-03-01 | 2019-06-18 | 广州锐澄医疗技术有限公司 | A kind of absorbable bone wax and preparation method thereof |
| CN109908397A (en) * | 2019-03-01 | 2019-06-21 | 广州锐澄医疗技术有限公司 | A kind of absorbable hemostatic bone wax and preparation method thereof |
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| CN109172858A (en) * | 2018-11-23 | 2019-01-11 | 广州新诚生物科技有限公司 | Absorbable hemostasis bone wax of one kind and preparation method thereof |
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| CN109893677A (en) * | 2019-03-01 | 2019-06-18 | 广州锐澄医疗技术有限公司 | A kind of absorbable bone wax and preparation method thereof |
| CN109908397A (en) * | 2019-03-01 | 2019-06-21 | 广州锐澄医疗技术有限公司 | A kind of absorbable hemostatic bone wax and preparation method thereof |
| CN115887741A (en) * | 2022-11-10 | 2023-04-04 | 东莞博捷生物科技有限公司 | Absorbable bone wax and preparation method thereof |
| CN115887741B (en) * | 2022-11-10 | 2024-03-19 | 东莞博捷生物科技有限公司 | Absorbable bone wax and preparation method thereof |
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