CN101224311B - Preparing method of compound collagen hemostatic material - Google Patents
Preparing method of compound collagen hemostatic material Download PDFInfo
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- CN101224311B CN101224311B CN2008100573845A CN200810057384A CN101224311B CN 101224311 B CN101224311 B CN 101224311B CN 2008100573845 A CN2008100573845 A CN 2008100573845A CN 200810057384 A CN200810057384 A CN 200810057384A CN 101224311 B CN101224311 B CN 101224311B
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Abstract
A preparing method of complex collagen hemostatic material belongs to the field of medical biomaterials. Hemostatic time is the standard for evaluating the quality of hemostatic materials; therefore, increasing the hemostatic properties of collagen material is still the key point of research and development. The invention firstly uses aldehydes to do chemical modification to soluble collagen, thus making into modified collagen web, and as the water affinity of the collagen is improved, the hemostatic property is improved. Furthermore, Chinese herbal medicine that can catalyze soluble fibrin in plasma into dissoluble fibrin is chosen to prepare into solution; the wed of the modified collagen is immerged in the medical solution completely. Owning to the molecular bond of modified collagen and the herbal, the diffusion and permeability, drug molecules can enter the three-screw structure of the collagen, thus forming the complex collagen hemostatic material. The material has obvious improvement on the basis of modification in both normal coagulation and abnormal coagulation, and the hemostatic time is 45 seconds to 60 seconds, and the material is superior to medical collagen hemostatic materials in board and to similar medical collagen hemostatic materials in Japan.
Description
Technical field
The present invention modifies collagen, and modifies back collagen and make composite with Chinese herbal medicine again, shortens the bleeding stopping period of composite, is suitable for the hemostatic material category in biomaterial for medical purpose field.
Background technology
Hemorrhage many risks and harm of bringing for surgical operation and human lives, seek desirable effectively hemorrhage is the focus of studying both at home and abroad always.After Afghanistan, the war in Iraq and anti-terrorism are worldwide launched, US military is developed quick hemostasis agent, (bleeding stopping period is 30s), the quality of hemorrhage is evaluation criterion with the bleeding stopping period both at home and abroad at present, this performance to hemostatic material proposes higher requirement again.Along with improving constantly of Medical Technology level, hemostatic material and method have had very great development.In recent years, many hemorrhages have been developed both at home and abroad, commonly used have a gelfoam, Fibrin Glue, oxidized cellulose, thrombins etc. are with traditional hemostatic material and method such as gauze, ligation etc. are compared, and haemostatic effect is obviously good, but speed also is not very fast, and they also exist certain shortcoming or side effect respectively: gelatin may increase the infection rate of wound, the wound of Wu Raning especially, and its attached viscous force difference more easily comes off, as be used for viscus hemostasis and need sutured, in addition because its anastalsis must rely on the thrombin participation of body, so with disturbances of blood coagulation the time, its haemostatic effect is often undesirable; Fibrin Glue is a blood products, the danger of propagating haematogenous infectious disease such as hepatitis or AIDS is arranged, and in use should not directly inject in the blood vessel, and is in case thrombosis or produce anaphylaxis, not good to tremulous pulse, the anastalsis hemorrhage than large vein in addition; The acidity of oxidized cellulose may cause the nerve fiber degeneration, and it has very strong water absorption, if will influence its anastalsis after making moist; Though thrombin can obviously promote hematoblastic attached, the gathering of killing, price is expensive; Then there is not above-mentioned defective in another effective hemorrhage-collagen hemostasis agent, and compares with above-mentioned all persons, and its bleeding stopping period is short, and effective, the little and less expensive of side effect is a kind of ideal hemorrhage.
Summary of the invention
At present its average bleeding stopping period of the domestic medical collagen that generally uses as 90s about, compare with the bleeding stopping period of external hemorrhage (US military hemorrhage bleeding stopping period is 30s) and to remain in very big gap, therefore the research of domestic quick hemostasis agent becomes hot subject again.
The complexity of the multiformity of collagen protein existence and haemostatic effect research thereof, the anthemorrhagic performance of collagen remains major subjects.The collagen hemostatic material of present domestic use is substantially through modifying, in addition, because the hemostasis of collagen depends on normal clotting mechanism, so for accepting anticoagulant therapy or having for the patient of coagulation disorders its haemostatic effect often undesirable.Given this, the present invention is on the basis that collagen extracts, and collagen and other haemostatic medicament carried out the anthemorrhagic performance that composite methods strengthens and improve collagen after plan adopted cryochemistry to modify and will modify.
The invention provides the preparation of step 1) collagen web:
The cow split leather is become graywall, and adding mass percentage concentration is the liming agent Ca (OH) of 2-4%
2, and 10 times of water to the graywall quality carry out liming, and behind the room temperature reaction 24-48h, fully washing; The reuse mass percentage concentration is the deliming agent NH of 4-8%
4Cl or (NH
4)
2SO
4, and 5 times of water to graywall carry out deliming, and behind the room temperature reaction 4-10h, fully washing; Broken; With mass percentage concentration is that 3 ‰ pepsin carries out enzyme hydrolysis 48-72h; Centrifugal, rotating speed is 10000-20000rpm; Regulate pH value to 7 with NaOH, adopting mass percentage concentration is that 4% NaCl saltouts, and room temperature leaves standstill more than the 24h; Secondary centrifuging, rotating speed are 10000-20000rpm; With the acetic acid of 0.5mol/L, carry out the acid dissolving, the collagen web is made in lyophilization below 10 ℃;
Step 2) collagen is modified:
Obtain solution: the preparation mass percent concentration is 2～4% formaldehyde, and one of acetaldehyde and glutaraldehyde solution are 7～9 with hydrochloric acid and sodium hydrate regulator solution pH value, the sodium phosphate of cofabrication pH=8 or dibastic sodium phosphate buffer;
Modify: the collagen web is soaked in the aldehyde solution of above-mentioned preparation, range of reaction temperature is 25～35 ℃, and soak time is 48～96h; Rinsing: wash with phosphate solution; Place alcoholic solution to go out except that antibacterial; Lyophilization below 10 ℃ obtains modifying collagem membrane;
The preparation of step 3) collagen composite materials:
The configuration quality percent concentration is 2～4% soluble fiber albumen in the blood plasma can be catalyzed into the proteic Chinese herbal medicine solution of insoluble fiber, regulate pH5～7, collagem membrane after modifying is immersed in the drug solution, reaction temperature is 23～30 ℃, soak time is 6～24h, place freezer dryer freezing below 10 ℃, drying obtains compound collagen hemostatic material.
Anthemorrhagic performance improves explanation:
Collagen has the effect that promotes platelet blood coagulation and blood plasma caking, compares with other hemorrhage commonly used, and the gross hemostasis rate height, effective, the little and less expensive of side effect is a kind of very ideal hemostatic material; But at present the collagen that uses of China is substantially through modifying, with external modified to compare bleeding stopping period long, so the present invention is necessary natural collagen is carried out chemical modification, and compound with Chinese herbal medicine, to improve the collagen composite materials anthemorrhagic performance.
The modification of collagen:
Collagen is the same with other protein, also be to be rearranged by aminoacid, and aminoacid belongs to ampholyte, promptly in a part, has both contained the amino (NH of alkalescence
2), contain tart carboxyl again (COOH).
The active amino of collagen can react with the carbonyl in the aldehyde:
As can be seen, dressing agent aldehyde has played removal effect to a certain degree to active amino hydrophobic on the collagen side chain, and hydrophilic pendant carboxylic group quantity does not change, relative number but increases to some extent, this makes the hydrophilicity of collagen be enhanced, thereby has improved the collagen composite materials anthemorrhagic performance.
It is compound to modify back collagen and Chinese herbal medicine:
Vegetable Chinese herbal medicine is with hemostasis and improve the effect of clotting mechanism, and this medicine is relatively cheap, no side effects.Its hemostatic mechanism is: lead to the release of platelet aggregation and composition thereof, comprise the release of gland nucleotide and calcium, change soluble Fibrinogen in the blood plasma into insoluble fibrin piece, thereby reach local hemostatic effect.When collagem membrane fully floods in vegetable Chinese herbal medicine solution, because intermolecular active force and diffusion, osmosis make drug molecule enter into the space of collagen triple-helix structure, so in hemostasis, can produce the effect of cooperative reinforcing, thereby further strengthen the anthemorrhagic performance of collagen.
Benefit of the present invention: the present invention extracts high-purity collagen from the leather by-product, on this basis its anthemorrhagic performance is carried out applied basic research, adopt collagen extraction → chemical modification → to have and independently develop the composite collagen hemorrhage with the compound process route of vegetable Chinese herbal medicine.The protein modification technology now has been applied to improve the function and the anthemorrhagic performance of collagen protein biomaterial.Collagen is carried out quantitatively controlled chemical modification, develop hemostatic material of new generation.On the basis of improving the bio-medical material scientific and technological content, enlarged China's biomaterial for medical purpose market share, for China people's life health quality is given security.
Description of drawings
Fig. 1 aldehydes is modified the infared spectrum of collagen
The infared spectrum of Fig. 2 composite collagen
Fig. 3 collagen composite materials sketch map
Wherein represent tropocollagen molecule;
Show collagen web structure; Zero expression medical herbs molecule
The specific embodiment
Amido modified for the collagen side chain, aldehyde is comparatively to be suitable for and the extraordinary dressing agent of effect.It is dressing agent that the present invention selects formaldehyde, Biformyl, glutaraldehyde respectively for use, the amino of collagen is modified, the collagen after the modification again with the compound hemostatic material of making of Chinese herbal medicine, this compound hemostatic material bleeding stopping period shortens greatly.Cryodesiccated temperature is below 10 ℃.
Example 1: pentanedial decoration collagen Chinese herbal medicine is compound
The preparation of step 1) collagen web:
The cow split leather is become graywall, take by weighing 10g, fragmentation.The adding mass percentage concentration is 2% liming agent Ca (OH)
2, water 100ml, liming, behind room temperature reaction 24h, fully washing, the reuse mass percentage concentration is 4% deliming agent NH
4Cl, water 50ml carries out deliming, room temperature reaction 6h; Fully washing; Rub; With the pepsin hydrolysis 48h of mass percentage concentration 3 ‰, centrifugal, rotating speed is 10000rpm; Regulate pH value to 7 with NaOH, adopting mass percentage concentration is that 4% NaCl saltouts, and leaves standstill 24h; Secondary centrifuging, rotating speed are 10000rpm; Acetic acid 200ml with 0.5mol/L carries out the acid dissolving, and the collagen web is made in lyophilization.
Step 2) collagen is modified:
The preparation mass percent concentration is 2% glutaraldehyde solution, is 7 with hydrochloric acid and sodium hydrate regulator solution pH value, and the collagen web is soaked in the above-mentioned glutaraldehyde solution, and reaction temperature is 25 ℃, soaks 48h; The sodium phosphate buffer rinsing of cofabrication pH=8; Place alcoholic solution to go out except that antibacterial; Lyophilization then obtains modifying the collagen web.
Glutaraldehyde belongs to dialdehyde, and being has three C atoms to link to each other between two carbonyls, and its chemical molecular formula is:
These three carbon atoms have produced neighbouring group effect, make carbonyl have very big activity, basically being equivalent to two single aldehyde is playing a role simultaneously, lysine and hydroxylysine in the main and collagen of glutaraldehyde react, but owing to the diffusion of glutaraldehyde molecule the time, permeate at pH=7, thus with the contacting and react comparatively abundant, complete of tropocollagen molecule; And on the other hand, the amino isoreactivity group that reacts with aldehyde radical can take place to dissociate preferably under alkali condition, helps reacting with glutaraldehyde, reaches to remove amino effect.
As shown in Figure 1, collagem membrane is at 3386cm
-1Near a strong and wide absworption peak is arranged, this peak is corresponding to the stretching vibration characteristic absorption peak of N-H key in the amido link in the collagen protein; At 1700～1300cm
-1Between three absworption peaks appear respectively, they are the amide I band 1656cm in the protein
-1, C=O key stretching vibration peak, amide II are with 1542cm
-1, N-H mixing peak and amide III crooked and the C-N stretching vibration are with 1387cm
-1, C-N key stretching vibration peak, these are absworption peaks of feature among the proteinic IR.
Contrast collagem membrane and pentanedial decoration collagem membrane, as can be seen: after the aldehyde modification, at 3386cm
-1The peak of position moves to the shortwave direction, and this is mainly relevant with NH key and H key in the collagen protein.After aldehyde inserts collagen helix inside, destroyed the hydrogen bond between the spiral to a certain extent, but C=O in the while amide band and the hydrone that is generated have formed more hydrogen bond again, so the peak moves to the shortwave direction; In addition, three amide bands modifying in the collagen of back have weakened, and this shows that the infiltration of aldehyde makes that the vibration of amido link has been subjected to containment in the collagen, and promptly modification reaction occurs in the position of amido link; But these three peaks still exist, and illustrate through the collagen behind the pentanedial decoration degeneration does not all take place.Glutaraldehyde is modified former anthemorrhagic performance the best to modification effect the best of collagen at this moment.Modification rate 80%.
The preparation of step 3) collagen composite materials:
The configuration quality percent concentration is 2% the Chinese herbal medicine (XB030020109 of Beijing pharmaceutical factory of traditional Chinese medicine, composition is: inorganic elements P, the Ca etc. of C44.9%, H6.4%, N0.8% and trace) solution, regulate pH to 5, collagem membrane after modifying is immersed in the drug solution, reaction temperature is 23 ℃, soak 6h, lyophilization obtains collagen composite materials.
As seen from Figure 2, collagen is through after compound with medicine, the peak of its N-H stretching vibration peak and three amide bands is all corresponding the appearance in the collection of illustrative plates of composite collagen, and the N-H peak has taken place to move to the long wave direction, show that this recombination process has destroyed the hydrogen bond between the collagen helix to a certain extent, cause its intermolecular force that variation has taken place, the medical herbs molecule has entered in the modification collagen web as shown in Figure 3, and in the molecule formation physical bond of collagen, so in hemostasis, can produce the cooperative reinforcing effect of collagen and medical herbs, thereby further strengthen the anthemorrhagic performance of collagen.The bleeding stopping period of collagen composite materials is 51S.
Example 2: pentanedial decoration collagen Chinese herbal medicine is compound
The preparation of step 1) collagen web:
The cow split leather is become graywall, take by weighing 10g, fragmentation.The adding mass percentage concentration is 3% liming agent Ca (OH)
2, water 100ml, liming, behind room temperature reaction 36h, fully washing, the reuse mass percentage concentration is 6% deliming agent NH
4Cl, water 50ml carries out deliming, room temperature reaction 6h; Fully washing; Rub; With the pepsin hydrolysis 60h of mass percentage concentration 3 ‰, centrifugal, rotating speed is 15000rpm; Regulate pH value to 7 with NaOH, adopting mass percentage concentration is that 4% NaCl saltouts, and leaves standstill 24h; Secondary centrifuging, rotating speed are 15000rpm; Acetic acid 200ml with 0.5mol/L carries out the acid dissolving, and the collagen web is made in lyophilization.
Step 2) collagen is modified:
The preparation mass percent concentration is 2% glutaraldehyde solution, is 7 with hydrochloric acid and sodium hydrate regulator solution pH value, and the collagen web is soaked in the above-mentioned glutaraldehyde solution, and reaction temperature is 25 ℃, soaks 96h; The dibastic sodium phosphate buffer rinsing of cofabrication pH=8; Place alcoholic solution to go out except that antibacterial; Lyophilization then obtains modifying the collagen web, and the modification rate is 85%.
The preparation of step 3) collagen composite materials:
The configuration quality percent concentration is 2% Chinese herbal medicine solution, regulates pH to 5, and the collagem membrane after modifying is immersed in the drug solution, and reaction temperature is 28 ℃, soaks 12h, and lyophilization obtains collagen composite materials.
As seen from Figure 2, collagen through with medicine recombination time lengthening after, the peak of its N-H stretching vibration peak and three amide bands is all corresponding the appearance in the collection of illustrative plates of composite collagen, and to the long wave direction moving ratio 1 having taken place, moves obviously at the N-H peak, recombination process is at the hydrogen bond that has destroyed between the collagen helix, cause its intermolecular force that variation has taken place, the medical herbs molecule has entered in the modification collagen web as shown in Figure 3, and it is more complete to form physical bond in the molecule of collagen, thereby has further strengthened the anthemorrhagic performance of collagen.The bleeding stopping period of collagen composite materials is 45S.
Example 3: it is compound that Biformyl is modified the collagen Chinese herbal medicine
The preparation of step 1) collagen web:
The cow split leather is become graywall, take by weighing 10g, fragmentation.The adding mass percentage concentration is 3% liming agent Ca (OH)
2, water 100ml, liming, behind room temperature reaction 48h, fully washing, the reuse mass percentage concentration is 8% deliming agent (NH
4)
2SO
4, water 50ml carries out deliming, room temperature reaction 10h; Fully washing; Rub; With the pepsin hydrolysis 72h of mass percentage concentration 3 ‰, centrifugal, rotating speed is 20000rpm; Regulate pH value to 7 with NaOH, adopting mass percentage concentration is that 4% NaCl saltouts, and leaves standstill 24h; Secondary centrifuging, rotating speed are 20000rpm; Acetic acid 200ml with 0.5mol/L carries out the acid dissolving, and the collagen web is made in lyophilization.
Step 2) collagen is modified:
The preparation mass percent concentration is 3% glyoxal solution, is 8 with hydrochloric acid and sodium hydrate regulator solution pH value, and the collagen web is soaked in the above-mentioned glutaraldehyde solution, and reaction temperature is 32 ℃, soaks 96h; The sodium phosphate buffer rinsing of cofabrication pH=8; Place alcoholic solution to go out except that antibacterial; Lyophilization then obtains modifying the collagen web.
Biformyl is different with glutaraldehyde, and it also belongs to dialdehyde, and is that the simplest dialdehyde, molecular formula are C
2H
2O
2, chemical molecular formula is:
3 C have promptly been lacked.Main and the arginic guanidine radicals of Biformyl
React, but product is not very stable; Relevant in addition studies show that: in the guanidine radicals reaction, arginic clearance is about 83%, and being lost in more than 20% of lysine shows that guanidine radicals reaction specificity is not strong, so Biformyl can also react with the epsilon-amino in a small amount of lysine.When Biformyl concentration is 3%, reaches and remove amino effect.
As shown in Figure 1, collagem membrane is at 3386cm
-1Near a strong and wide absworption peak is arranged, this peak is corresponding to the stretching vibration characteristic absorption peak of N-H key in the amido link in the collagen protein; At 1700～1300cm
-1Between three absworption peaks appear respectively, they are the amide I band 1656cm in the protein
-1, C=O key stretching vibration peak, amide II are with 1542cm
-1, N-H mixing peak and amide III crooked and the C-N stretching vibration are with 1387cm
-1, C-N key stretching vibration peak, these are absworption peaks of feature among the proteinic IR.As can be seen: after the aldehyde modification, at 3386cm
-1The peak of position moves to the shortwave direction, and this is mainly relevant with NH key and H key in the collagen protein.After aldehyde inserts collagen helix inside, destroyed the hydrogen bond between the spiral to a certain extent, but C=O in the while amide band and the hydrone that is generated have formed more hydrogen bond again, so the peak moves to the shortwave direction; In addition, three amide bands modifying in the collagen of back have weakened, and this shows that the infiltration of aldehyde makes that the vibration of amido link has been subjected to containment in the collagen, and promptly modification reaction occurs in the position of amido link; But these three peaks still exist, and illustrate through the collagen after the Biformyl modification degeneration does not all take place.This moment Biformyl and glutaraldehyde to specific strength a little less than, the modification rate is 75%.
The preparation of step 3) collagen composite materials:
The configuration quality percent concentration is 3% Chinese herbal medicine solution, regulates pH to 6, and the collagem membrane after modifying is immersed in the drug solution, and reaction temperature is 30 ℃, soaks 9h, and lyophilization obtains collagen composite materials.
As seen from Figure 2, collagen is through after compound with medicine, the peak of its N-H stretching vibration peak and three amide bands is all corresponding the appearance in the collection of illustrative plates of composite collagen, and the N-H peak has taken place to move to the long wave direction, show that this recombination process has destroyed the hydrogen bond between the collagen helix to a certain extent, cause its intermolecular force that variation has taken place, the medical herbs molecule has entered in the modification collagen web as shown in Figure 3, and in the molecule formation physical bond of collagen, so in hemostasis, can produce the cooperative reinforcing effect of collagen and medical herbs, thereby further strengthen the anthemorrhagic performance of collagen.The bleeding stopping period of collagen composite materials is 57S.
Example 4: it is compound that formaldehyde is modified the collagen Chinese herbal medicine
The preparation of step 1) collagen web:
The cow split leather is become graywall, take by weighing 10g, fragmentation.The adding mass percentage concentration is 4% liming agent Ca (OH)
2, water 100ml, liming, behind room temperature reaction 48h, fully washing, the reuse mass percentage concentration is 8% deliming agent (NH
4)
2SO
4, water 50ml carries out deliming, room temperature reaction 10h; Fully washing; Rub; With the pepsin hydrolysis 72h of mass percentage concentration 3 ‰, centrifugal, rotating speed is 20000rpm; Regulate pH value to 7 with NaOH, adopting mass percentage concentration is that 4% NaCl saltouts, and leaves standstill 24h; Secondary centrifuging, rotating speed are 20000rpm; Acetic acid 200ml with 0.5mol/L carries out the acid dissolving, and the collagen web is made in lyophilization.
Step 2) collagen is modified:
The preparation mass percent concentration is 4% formalin, is 9 with hydrochloric acid and sodium hydrate regulator solution pH value, and the collagen web is soaked in the formalin, and reaction temperature is 35 ℃, soaks 96h; The sodium phosphate buffer rinsing of cofabrication pH=8; Place the alcoholic solution sterilization treatment; Lyophilization then obtains modifying the collagen web.
. formaldehyde is the simplest single aldehyde, and its molecule is less, only contains a carbonyl, and molecular formula is HCHO, and chemical molecular formula is:
Formaldehyde molecule is less, more often than not can be earlier and the epsilon-amino of the lysine generation imine intermediate that reacts in the collagen protein, and then with tyrosine reaction forms intermolecular cross-linking
[52Thereby, form stable, firm network.Help to strengthen the collagen water absorbing properties.As shown in Figure 1, collagem membrane is at 3386cm
-1Near a strong and wide absworption peak is arranged, this peak is corresponding to the stretching vibration characteristic absorption peak of N-H key in the amido link in the collagen protein; At 1700～1300cm
-1Between three absworption peaks appear respectively, they are the amide I band 1656cm in the protein
-1, C=O key stretching vibration peak, amide II are with 1542cm
-1, N-H mixing peak and amide III crooked and the C-N stretching vibration are with 1387cm
-1, C-N key stretching vibration peak, these are absworption peaks of feature among the proteinic IR.As can be seen: after the aldehyde modification, at 3386cm
-1The peak of position moves to the shortwave direction, and NH key and H key relevant this moment of formaldehyde and Biformyl contrast mobile less in this main and collagen protein.After aldehyde inserts collagen helix inside, destroyed the hydrogen bond between the spiral to a certain extent, but C=O in the while amide band and the hydrone that is generated have formed more hydrogen bond again, so the peak moves to the shortwave direction; In addition, three amide bands modifying in the collagen of back have weakened, and this shows that the infiltration of aldehyde makes that the vibration of amido link has been subjected to containment in the collagen, and promptly modification reaction occurs in the position of amido link; But these three peaks still exist, and illustrate through the collagen after the formaldehyde modification degeneration does not all take place.This moment formaldehyde and Biformyl to specific strength a little less than, the modification rate is 70%.
The preparation of step 3) collagen composite materials:
The configuration quality percent concentration is 4% Chinese herbal medicine solution, regulates pH to 7, and the collagem membrane after modifying is immersed in the drug solution, and reaction temperature is 30 ℃, soaks 24h, and lyophilization obtains collagen composite materials.
As seen from Figure 2, collagen is through after compound with medicine, the peak of its N-H stretching vibration peak and three amide bands is all corresponding the appearance in the collection of illustrative plates of composite collagen, and the N-H peak has taken place to move to the long wave direction, show that this recombination process has destroyed the hydrogen bond between the collagen helix to a certain extent, cause its intermolecular force that variation has taken place, the medical herbs molecule has entered in the modification collagen web as shown in Figure 3, and in the molecule formation physical bond of collagen, so in hemostasis, can produce the cooperative reinforcing effect of collagen and medical herbs, thereby further strengthen the anthemorrhagic performance of collagen.The bleeding stopping period of collagen composite materials is 60S.
Claims (1)
1. the preparation method of a compound collagen hemostatic material is characterized in that, may further comprise the steps:
The preparation of step 1) collagen web:
The cow split leather is become graywall, and adding mass percentage concentration is the liming agent Ca (OH) of 2-4%
2, and 10 times of water to the graywall quality carry out liming, and behind the room temperature reaction 24-48h, fully washing; The reuse mass percentage concentration is the deliming agent NH of 4-8%
4Cl or (NH
4)
2SO
4, and 5 times of water to graywall carry out deliming, and behind the room temperature reaction 4-10h, fully washing; Broken; With mass percentage concentration is that 3 ‰ pepsin carries out enzyme hydrolysis 48-72h; Centrifugal, rotating speed is 10000-20000rpm; Regulate pH value to 7 with NaOH, adopting mass percentage concentration is that 4% NaCl saltouts, and room temperature leaves standstill more than the 24h; Secondary centrifuging, rotating speed are 10000-20000rpm; With the acetic acid of 0.5mol/L, carry out the acid dissolving, the collagen web is made in lyophilization below 10 ℃;
Step 2) collagen is modified:
Obtain solution: the preparation mass percent concentration is 2～4% formaldehyde, and one of acetaldehyde and glutaraldehyde solution are 7～9 with hydrochloric acid and sodium hydrate regulator solution pH value, the sodium phosphate of cofabrication pH=8 or dibastic sodium phosphate buffer;
Modify: the collagen web is soaked in the aldehyde solution of above-mentioned preparation, range of reaction temperature is 25～35 ℃, and soak time is 48～96h; Rinsing: wash with phosphate solution; Place alcoholic solution to go out except that antibacterial; Lyophilization below 10 ℃ obtains modifying collagem membrane;
The preparation of step 3) collagen composite materials:
The configuration quality percent concentration is 2～4% soluble fiber albumen in the blood plasma can be catalyzed into the proteic Chinese herbal medicine solution of insoluble fiber, regulate pH5～7, collagem membrane after modifying is immersed in the drug solution, reaction temperature is 23～30 ℃, soak time is 6～24h, place freezer dryer freezing below 10 ℃, drying obtains compound collagen hemostatic material; This Chinese herbal medicine is the XB030020109 of Beijing pharmaceutical factory of traditional Chinese medicine, and composition comprises inorganic elements P, the Ca of C44.9%, H6.4%, N0.8% and trace.
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| CN103030831B (en) * | 2012-12-26 | 2014-06-25 | 上海欣吉特生物科技有限公司 | Hemostatic or anticoagulant collagen material |
| CN104667336B (en) * | 2013-03-28 | 2017-01-25 | 北京桀亚莱福生物技术有限责任公司 | Human body biological dressing for covering burn wound surfaces and applications of dressing |
| GB201508020D0 (en) * | 2015-05-11 | 2015-06-24 | Haemostatix Ltd | Haemostatic material |
| CN107349456B (en) * | 2017-08-02 | 2020-06-23 | 武汉轻工大学 | Preparation method of collagen sponge with pore size self-adaptive adjusting capacity and collagen sponge |
| CN107929796A (en) * | 2017-12-11 | 2018-04-20 | 河南亚都实业有限公司 | Biological hemostatic film |
| CN107982573A (en) * | 2017-12-11 | 2018-05-04 | 河南亚都实业有限公司 | A kind of preparation method of the internal styptic sponge of absorbable and degradable |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1259388A (en) * | 1999-12-02 | 2000-07-12 | 石全贵 | Gauze containing traditional Chinese compound medicine |
| CN1406628A (en) * | 2001-09-10 | 2003-04-02 | 武继民 | Hemostatics powder and preparation thereof |
| JP4050369B2 (en) * | 1997-12-23 | 2008-02-20 | 株式会社日立製作所 | Reciprocating compressor |
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2008
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4050369B2 (en) * | 1997-12-23 | 2008-02-20 | 株式会社日立製作所 | Reciprocating compressor |
| CN1259388A (en) * | 1999-12-02 | 2000-07-12 | 石全贵 | Gauze containing traditional Chinese compound medicine |
| CN1406628A (en) * | 2001-09-10 | 2003-04-02 | 武继民 | Hemostatics powder and preparation thereof |
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