CN110180018A - A kind of preparation method of calcic alginate/chitosan hemostatic microsphere - Google Patents
A kind of preparation method of calcic alginate/chitosan hemostatic microsphere Download PDFInfo
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- CN110180018A CN110180018A CN201910441782.5A CN201910441782A CN110180018A CN 110180018 A CN110180018 A CN 110180018A CN 201910441782 A CN201910441782 A CN 201910441782A CN 110180018 A CN110180018 A CN 110180018A
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
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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
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Abstract
The present invention provides a kind of preparation method of calcic alginate/chitosan hemostatic microsphere, and preparation method is by emulsification inner gel method, by sodium alginate and insoluble calcium phosphate, such as CaCO3Deng, mixing, water-in-oil emulsion is mutually formed with oily, add the calcium ion in oil-soluble acid release insoluble calcium phosphate, hydrogel microsphere is formed inside drop, then, the surface of hydrogel microsphere is coated on using the covering liquid being made of chitosan and acetic acid, so that calcic alginate produced by the present invention/chitosan hemostatic microsphere stability with higher, stronger anti-Swelling Capacity, good mucus adhesive capacity and tensile property and higher water absorption rate and anthemorrhagic performance, make calcic alginate/chitosan hemostatic microsphere produced by the present invention that there is lesser partial size simultaneously, more regular sphericity and more uniform calcium distribution, it is avoided to form compact outer shell, stop drug release, and then be conducive to accelerate hemostasis.
Description
Technical field
The present invention relates to medical material technical field, in particular to a kind of calcic alginate/chitosan hemostatic microsphere
Preparation method.
Background technique
Alginic acid is a kind of natural marine organism polysaccharide, has nontoxic, high suction by the dressing that raw material is researched and developed of alginate
It is aqueous, inhaled at gelation, high oxygen permeability, good biocompatibility, biodegradable absorbability, hemostatic, promoting healing, macroion
The characteristics such as attached property.Alginic acid is one bonded together to form by α-L- guluronic acid (G) and beta-D-mannuronic acid (M) by 1,4
The random linear block copolymers of kind.Alginic acid has the characteristic of very high gelation and chelated metal ions, the Na with monovalence+、K+、NH4 +Plasma forms the alginate of corresponding solubility, has very strong gelation, with high volence metal ion such as Ca2+、
Mg2+Equal formation corresponding calcium alginate and alginic acid magnesium not soluble in water, can be formed with the sodium ion exchange in blood can coagulate
The sodium alginate of colloidality is covered on wound surface, and the hemostatic composition that the calcium ion after exchanging enters in blood activation blood is right
It is aggregated to form the plugging damaged blood vessel of clot at wound afterwards, to achieve the purpose that hemostasis.
Existing alginate hemostatic microsphere is often prepared with external source emulsion process, and main preparation process is by sodium alginate soln
It is dispersed in divalent calcium ions solution, gelation reaction is gradually internally then occurred by outside.Microballoon during reaction
Surface quickly forms one layer of fine and close gel front, and the calcium ion increased in solution diffuses to the resistance inside microballoon, obtains
Outer close interior thin feature is presented in microballoon usually heterogeneous, structure, and in external source emulsion process, the sodium alginate of high gradient and
Calcium ion concentrates on CaAlg gel bead surface and forms fine and close shell, stops drug release, so that the hemostasis of existing alginate is micro-
The stability and haemostatic effect of ball are poor.
Summary of the invention
In view of this, the present invention is directed to propose a kind of calcic alginate/chitosan hemostatic microsphere preparation method, with solution
The poor problem of the stability and haemostatic effect of certainly existing alginate hemostatic microsphere.
In order to achieve the above objectives, the technical scheme of the present invention is realized as follows:
A kind of preparation method of calcic alginate/chitosan hemostatic microsphere, comprising the following steps:
1) preparation of water phase: being dissolved in deionized water for alginate, then, insoluble calcium phosphate is added, stirring obtains water
Phase；
2) preparation of target oil phase: emulsifier is added into base oil phase, is uniformly mixed, is obtained target oil phase；
3) preparation of calcic seaweed salt microballoon: under the first setting speed of agitator, in Xiang Suoshu target oil phase described in dropwise addition
Water phase stirs the first setting time after the water phase completion of dropwise addition, then, crosslinking agent is added, stirs the second setting time,
Then, it purifies, obtains calcic seaweed salt microballoon；
4) preparation of covering liquid: being dissolved in deionized water for acetic acid, then, chitosan is added, stirring obtains covering liquid；
5) cladding of calcic seaweed salt microballoon: under the second setting speed of agitator, contain described in addition in Xiang Suoshu covering liquid
Calcium seaweed salt microballoon, stirring, then, purification obtains calcic alginate/chitosan hemostatic microsphere.
Optionally, the mass concentration of alginate described in the step 1) is 4%~6%, the insoluble calcium phosphate
Mass concentration is 1.5%~2.5%.
Optionally, alginate described in the step 1) includes sodium alginate, and the insoluble calcium phosphate includes calcium carbonate.
Optionally, base oil described in the step 2) is mutually atoleine, and the emulsifier is span-80；It is described
The volume fraction of span-80 is 3-6%.
Optionally, first speed of agitator is set as 350r/min-550r/min described in the step 3), described first sets
It fixes time as 20-40min, second setting time is 1-1.5h.
Optionally, the volume ratio of water phase described in the step 3) and the target oil phase is 1: 4-1: 7.
Optionally, crosslinking agent described in the step 3) is acetic acid.
Optionally, the volume fraction of acetic acid described in the step 4) is 0.5-1%, and the mass concentration of the chitosan is
0.5-1%.
Optionally, second speed of agitator is set as 200r/min-300r/min described in the step 5), the stirring
Mixing time is 10-30min.
Compared with the existing technology, the preparation method of calcic alginate/chitosan hemostatic microsphere of the present invention has
Following advantage:
1, calcic of the invention alginate/chitosan hemostatic microsphere preparation method, will be extra large by emulsification inner gel method
Mosanom and insoluble calcium phosphate, such as CaCO3Deng mixing mutually forms water-in-oil emulsion with oily, and it is insoluble to add oil-soluble acid release
Calcium ion in property calcium salt, forms hydrogel microsphere, then, using the covering liquid being made of chitosan and acetic acid inside drop
It is coated on the surface of hydrogel microsphere, so that calcic produced by the present invention alginate/chitosan hemostatic microsphere is with higher
Stability, stronger anti-Swelling Capacity, good mucus adhesive capacity and tensile property and higher water absorption rate and hemostatic
Can, while making calcic alginate/chitosan hemostatic microsphere produced by the present invention that there is lesser partial size, more regular ball
Shape degree and the distribution of more uniform calcium, avoid it from forming compact outer shell, stop drug release, and then are conducive to accelerate hemostasis.
2, for the present invention during preparing calcic alginate/chitosan hemostatic microsphere, crosslinking agent is nontoxic acetic acid,
It avoids chemical cross-linking agent and carries out micro-sphere crosslinked generated poisonous effect, while preparation process of the present invention is simple, preparation condition
Mildly, it is advantageously implemented industrialized production.
Specific embodiment
It should be noted that in the absence of conflict, the feature in embodiment and embodiment in the present invention can phase
Mutually combination.
Below in conjunction with embodiment, the present invention will be described in detail.
Embodiment 1
A kind of preparation method of calcic alginate/chitosan hemostatic microsphere, specifically includes the following steps:
1) preparation of water phase: being dissolved in 10ml deionized water for 0.4g sodium alginate, then, 0.15g calcium carbonate, magnetic force is added
4h is stirred, water phase is obtained, at this point, the mass concentration of sodium alginate is 0.4/10 (4%) in water phase, the quality of calcium carbonate in water phase
Concentration is 0.15/10 (1.5%)；
2) preparation of target oil phase: 2ml span-80 is added into 50ml atoleine, is uniformly mixed, is obtained target
Oily phase, at this point, the volume fraction of span-80 is 2/50 (4%) in target oil phase；
3) preparation of calcic seaweed salt microballoon: under the revolving speed of 350r/min, according to the volume of water phase and target oil phase 1: 5
Than, water phase is added dropwise into target oil phase, after water phase completion of dropwise addition, stirs 30min, then, 0.5ml acetic acid is added, stirs 1h,
Then, it is washed, is filtered with 30ml isopropanol, it is dry, obtain calcic seaweed salt microballoon；
4) preparation of covering liquid: being dissolved in 100ml deionized water for 1ml acetic acid, then, 0.5g chitosan is added, sufficiently stirs
It mixes to dissolution, obtains covering liquid, at this point, the volume fraction of acetic acid is 1/100 (1%) in covering liquid, chitosan in covering liquid
Mass concentration is 0.5/100 (0.5%)；
5) under the revolving speed of 250r/min, it is micro- that calcic seaweed salt the cladding of calcic seaweed salt microballoon: is added into covering liquid
Ball stirs 30min, then, filters, dry, obtains calcic alginate/chitosan hemostatic microsphere.
Calcic alginate/chitosan hemostatic microsphere partial size and anthemorrhagic performance of the present embodiment are tested, and
By itself and blank group, that is, the calcic alginate/chitosan hemostatic microsphere nature blood coagulation of the present embodiment is not added, compares.
After tested it is found that calcic alginate/chitosan hemostatic microsphere partial size of the present embodiment is in 25 μm~250 μm models
In enclosing, surface area average grain diameter is 28.093 μm, and volume average particle size is 70.866 μm, and water absorption rate 281.9% is average to stop blooding
Time is 240s, and relative to the average clotting time of blank group 280s, the calcic alginate/chitosan hemostasis of the present embodiment is micro-
The reduced clotting time of ball 40s, illustrates it with good haemostatic effect.
Embodiment 2
A kind of preparation method of calcic alginate/chitosan hemostatic microsphere, specifically includes the following steps:
1) preparation of water phase: being dissolved in 10ml deionized water for 0.4g sodium alginate, then, 0.2g calcium carbonate, magnetic force is added
4h is stirred, water phase is obtained, at this point, the mass concentration of sodium alginate is the quality of calcium carbonate in 0.4/10 (4%) water phase in water phase
Concentration is 0.2/10 (2%)；
2) preparation of target oil phase: 2ml span-80 is added into 50ml atoleine, is uniformly mixed, is obtained target
Oily phase, at this point, the volume fraction of span-80 is 2/50 (4%) in target oil phase；
3) preparation of calcic seaweed salt microballoon: under the revolving speed of 450r/min, according to the volume of water phase and target oil phase 1: 5
Than, water phase is added dropwise into target oil phase, after water phase completion of dropwise addition, stirs 30min, then, 1ml acetic acid is added, stirs 1h, with
Afterwards, it is washed, is filtered with 30ml isopropanol, it is dry, obtain calcic seaweed salt microballoon；
4) preparation of covering liquid: being dissolved in 100ml deionized water for 1ml acetic acid, then, 0.5g chitosan is added, sufficiently stirs
It mixes to dissolution, obtains covering liquid, at this point, the volume fraction of acetic acid is 1/100 (1%) in covering liquid, chitosan in covering liquid
Mass concentration is 0.5/100 (0.5%)；
5) under the revolving speed of 250r/min, it is micro- that calcic seaweed salt the cladding of calcic seaweed salt microballoon: is added into covering liquid
Ball stirs 30min, then, filters, dry, obtains calcic alginate/chitosan hemostatic microsphere.
Calcic alginate/chitosan hemostatic microsphere partial size and anthemorrhagic performance of the present embodiment are tested, and
By itself and blank group, that is, the calcic alginate/chitosan hemostatic microsphere nature blood coagulation of the present embodiment is not added, compares.
After tested it is found that calcic alginate/chitosan hemostatic microsphere partial size of the present embodiment is in 20 μm~150 μm models
In enclosing, surface area average grain diameter is 52.919 μm, and volume average particle size is 66.109 μm, and water absorption rate 329.9% is average to stop
The blood time is 236s, relative to the average clotting time of blank group 280s, the calcic alginate/chitosan hemostasis of the present embodiment
The reduced clotting time of microballoon 44s, illustrates it with good haemostatic effect.
Embodiment 3
A kind of preparation method of calcic alginate/chitosan hemostatic microsphere, specifically includes the following steps:
1) preparation of water phase: being dissolved in 10ml deionized water for 0.4g sodium alginate, then, 0.25g calcium carbonate, magnetic force is added
4h is stirred, water phase is obtained, at this point, the mass concentration of sodium alginate is 0.4/10 (4%) in water phase, the quality of calcium carbonate in water phase
Concentration is 0.25/10 (2.5%)；
2) preparation of target oil phase: 2ml span-80 is added into 50ml atoleine, is uniformly mixed, is obtained target
Oily phase, at this point, the volume fraction of span-80 is 2/50 (4%) in target oil phase；
3) preparation of calcic seaweed salt microballoon: under the revolving speed of 550r/min, according to the volume of water phase and target oil phase 1: 5
Than, water phase is added dropwise into target oil phase, after water phase completion of dropwise addition, stirs 30min, then, 1.5ml acetic acid is added, stirs 1h,
Then, it is washed, is filtered with 30ml isopropanol, it is dry, obtain calcic seaweed salt microballoon；
4) preparation of covering liquid: being dissolved in 100ml deionized water for 1ml acetic acid, then, 0.5g chitosan is added, sufficiently stirs
It mixes to dissolution, obtains covering liquid, at this point, the volume fraction of acetic acid is 1/100 (1%) in covering liquid, chitosan in covering liquid
Mass concentration is 0.5/100 (0.5%)；
5) under the revolving speed of 250r/min, it is micro- that calcic seaweed salt the cladding of calcic seaweed salt microballoon: is added into covering liquid
Ball stirs 30min, then, filters, dry, obtains calcic alginate/chitosan hemostatic microsphere.
Calcic alginate/chitosan hemostatic microsphere partial size and anthemorrhagic performance of the present embodiment are tested, and
By itself and blank group, that is, the calcic alginate/chitosan hemostatic microsphere nature blood coagulation of the present embodiment is not added, compares.
After tested it is found that calcic alginate/chitosan hemostatic microsphere partial size of the present embodiment is in 15 μm~450 μm models
In enclosing, surface area average grain diameter is 24.460 μm, and volume average particle size is 80.638 μm, and water absorption rate 215.8% is average to stop
The blood time is 249s, relative to the average clotting time of blank group 280s, the calcic alginate/chitosan hemostasis of the present embodiment
The reduced clotting time of microballoon 31s, illustrates it with good haemostatic effect.
Embodiment 4
A kind of preparation method of calcic alginate/chitosan hemostatic microsphere, specifically includes the following steps:
1) preparation of water phase: being dissolved in 10ml deionized water for 0.5g sodium alginate, then, 0.15g calcium carbonate, magnetic force is added
4h is stirred, water phase is obtained, at this point, the mass concentration of sodium alginate is 0.5/10 (5%) in water phase, the quality of calcium carbonate in water phase
Concentration is 0.15/10 (1.5%)；
2) preparation of target oil phase: 2ml span-80 is added into 50ml atoleine, is uniformly mixed, is obtained target
Oily phase, at this point, the volume fraction of span-80 is 2/50 (4%) in target oil phase；
3) preparation of calcic seaweed salt microballoon: under the revolving speed of 550r/min, according to the volume of water phase and target oil phase 1: 5
Than, water phase is added dropwise into target oil phase, after water phase completion of dropwise addition, stirs 30min, then, 1ml acetic acid is added, stirs 1h, with
Afterwards, it is washed, is filtered with 30ml isopropanol, it is dry, obtain calcic seaweed salt microballoon；
4) preparation of covering liquid: being dissolved in 100ml deionized water for 1ml acetic acid, then, 0.5g chitosan is added, sufficiently stirs
It mixes to dissolution, obtains covering liquid, at this point, the volume fraction of acetic acid is 1/100 (1%) in covering liquid, chitosan in covering liquid
Mass concentration is 0.5/100 (0.5%)；
5) under the revolving speed of 250r/min, it is micro- that calcic seaweed salt the cladding of calcic seaweed salt microballoon: is added into covering liquid
Ball stirs 30min, then, filters, dry, obtains calcic alginate/chitosan hemostatic microsphere.
Calcic alginate/chitosan hemostatic microsphere partial size and anthemorrhagic performance of the present embodiment are tested, and
By itself and blank group, that is, the calcic alginate/chitosan hemostatic microsphere nature blood coagulation of the present embodiment is not added, compares.
After tested it is found that calcic alginate/chitosan hemostatic microsphere partial size of the present embodiment is in 30 μm~400 μm models
In enclosing, surface area average grain diameter is 49.351 μm, and volume average particle size is 128.205 μm, and water absorption rate 478.1% is average
Bleeding stopping period is 218s, and relative to the average clotting time of blank group 280s, the calcic alginate/chitosan of the present embodiment stops
The reduced clotting time of blood microballoon 62s, illustrates it with good haemostatic effect.
Embodiment 5
A kind of preparation method of calcic alginate/chitosan hemostatic microsphere, specifically includes the following steps:
1) preparation of water phase: being dissolved in 10ml deionized water for 0.5g sodium alginate, then, 0.2g calcium carbonate, magnetic force is added
4h is stirred, water phase is obtained, at this point, the mass concentration of sodium alginate is 0.4/10 (5%) in water phase, the quality of calcium carbonate in water phase
Concentration is 0.2/10 (2%)；
2) preparation of target oil phase: 2ml span-80 is added into 50ml atoleine, is uniformly mixed, is obtained target
Oily phase, at this point, the volume fraction of span-80 is 2/50 (4%) in target oil phase；
3) preparation of calcic seaweed salt microballoon: under the revolving speed of 350r/min, according to the volume of water phase and target oil phase 1: 5
Than, water phase is added dropwise into target oil phase, after water phase completion of dropwise addition, stirs 30min, then, 1.5ml acetic acid is added, stirs 1h,
Then, it is washed, is filtered with 30ml isopropanol, it is dry, obtain calcic seaweed salt microballoon；
4) preparation of covering liquid: being dissolved in 100ml deionized water for 1ml acetic acid, then, 0.5g chitosan is added, sufficiently stirs
It mixes to dissolution, obtains covering liquid；
5) under the revolving speed of 250r/min, it is micro- that calcic seaweed salt the cladding of calcic seaweed salt microballoon: is added into covering liquid
Ball stirs 30min, then, filters, dry, obtains calcic alginate/chitosan hemostatic microsphere.
Calcic alginate/chitosan hemostatic microsphere partial size and anthemorrhagic performance of the present embodiment are tested, and
By itself and blank group, that is, the calcic alginate/chitosan hemostatic microsphere nature blood coagulation of the present embodiment is not added, compares.
After tested it is found that calcic alginate/chitosan hemostatic microsphere partial size of the present embodiment is in 25 μm~550 μm models
In enclosing, surface area average grain diameter is 33.438 μm, and volume average particle size is 106.195 μm, and water absorption rate 196.4% is average
Bleeding stopping period is 254s, and relative to the average clotting time of blank group 280s, the calcic alginate/chitosan of the present embodiment stops
The reduced clotting time of blood microballoon 26s, illustrates it with good haemostatic effect.
Embodiment 6
A kind of preparation method of calcic alginate/chitosan hemostatic microsphere, specifically includes the following steps:
1) preparation of water phase: being dissolved in 10ml deionized water for 0.5g sodium alginate, then, 0.25g calcium carbonate, magnetic force is added
4h is stirred, water phase is obtained, at this point, the mass concentration of sodium alginate is 0.5/10 (5%) in water phase, the quality of calcium carbonate in water phase
Concentration is 0.25/10 (2.5%)；
2) preparation of target oil phase: 2ml span-80 is added into 50ml atoleine, is uniformly mixed, is obtained target
Oily phase, at this point, the volume fraction of span-80 is 2/50 (4%) in target oil phase；
3) preparation of calcic seaweed salt microballoon: under the revolving speed of 450r/min, according to the volume of water phase and target oil phase 1: 5
Than, water phase is added dropwise into target oil phase, after water phase completion of dropwise addition, stirs 30min, then, 0.5ml acetic acid is added, stirs 1h,
Then, it is washed, is filtered with 30ml isopropanol, it is dry, obtain calcic seaweed salt microballoon；
4) preparation of covering liquid: being dissolved in 100ml deionized water for 1ml acetic acid, then, 0.5g chitosan is added, sufficiently stirs
It mixes to dissolution, obtains covering liquid, at this point, the volume fraction of acetic acid is 1/100 (1%) in covering liquid, chitosan in covering liquid
Mass concentration is 0.5/100 (0.5%)；
5) under the revolving speed of 250r/min, it is micro- that calcic seaweed salt the cladding of calcic seaweed salt microballoon: is added into covering liquid
Ball stirs 30min, then, filters, dry, obtains calcic alginate/chitosan hemostatic microsphere.
Calcic alginate/chitosan hemostatic microsphere partial size and anthemorrhagic performance of the present embodiment are tested, and
By itself and blank group, that is, the calcic alginate/chitosan hemostatic microsphere nature blood coagulation of the present embodiment is not added, compares.
After tested it is found that calcic alginate/chitosan hemostatic microsphere partial size of the present embodiment is in 25 μm~350 μm models
In enclosing, surface area average grain diameter is 71.083 μm, and volume average particle size is 97.388 μm, and water absorption rate 195.4% is average to stop
The blood time is 250s, relative to the average clotting time of blank group 280s, the calcic alginate/chitosan hemostasis of the present embodiment
The reduced clotting time of microballoon 30s, illustrates it with good haemostatic effect.
Embodiment 7
A kind of preparation method of calcic alginate/chitosan hemostatic microsphere, specifically includes the following steps:
1) preparation of water phase: being dissolved in 10ml deionized water for 0.6g sodium alginate, then, 0.15g calcium carbonate, magnetic force is added
4h is stirred, water phase is obtained, at this point, the mass concentration of sodium alginate is 0.6/10 (6%) in water phase, the quality of calcium carbonate in water phase
Concentration is 0.15/10 (1.5%)；
2) preparation of target oil phase: 2ml span-80 is added into 50ml atoleine, is uniformly mixed, is obtained target
Oily phase, at this point, the volume fraction of span-80 is 2/50 (4%) in target oil phase；
3) preparation of calcic seaweed salt microballoon: under the revolving speed of 450r/min, according to the volume of water phase and target oil phase 1: 5
Than, water phase is added dropwise into target oil phase, after water phase completion of dropwise addition, stirs 30min, then, 1.5ml acetic acid is added, stirs 1h,
Then, it is washed, is filtered with 30ml isopropanol, it is dry, obtain calcic seaweed salt microballoon；
4) preparation of covering liquid: being dissolved in 100ml deionized water for 1ml acetic acid, then, 0.5g chitosan is added, sufficiently stirs
It mixes to dissolution, obtains covering liquid, at this point, the volume fraction of acetic acid is 1/100 (1%) in covering liquid, chitosan in covering liquid
Mass concentration is 0.5/100 (0.5%)；
5) under the revolving speed of 250r/min, it is micro- that calcic seaweed salt the cladding of calcic seaweed salt microballoon: is added into covering liquid
Ball stirs 30min, then, filters, dry, obtains calcic alginate/chitosan hemostatic microsphere.
Calcic alginate/chitosan hemostatic microsphere partial size and anthemorrhagic performance of the present embodiment are tested, and
By itself and blank group, that is, the calcic alginate/chitosan hemostatic microsphere nature blood coagulation of the present embodiment is not added, compares.
After tested it is found that calcic alginate/chitosan hemostatic microsphere partial size of the present embodiment is in 30 μm~300 μm models
In enclosing, surface area average grain diameter is 89.361 μm, and volume average particle size is 119.584 μm, and water absorption rate 1095.6% is average
Bleeding stopping period is 164s, and relative to the average clotting time of blank group 280s, the calcic alginate/chitosan of the present embodiment stops
The reduced clotting time of blood microballoon 116s, illustrates it with good haemostatic effect.
Embodiment 8
A kind of preparation method of calcic alginate/chitosan hemostatic microsphere, specifically includes the following steps:
1) preparation of water phase: being dissolved in 10ml deionized water for 0.6g sodium alginate, then, 0.2g calcium carbonate, magnetic force is added
4h is stirred, water phase is obtained, at this point, the mass concentration of sodium alginate is 0.6/10 (6%) in water phase, the quality of calcium carbonate in water phase
Concentration is 0.2/10 (2%)；
2) preparation of target oil phase: 2ml span-80 is added into 50ml atoleine, is uniformly mixed, is obtained target
Oily phase, at this point, the volume fraction of span-80 is 2/50 (4%) in target oil phase；
3) preparation of calcic seaweed salt microballoon: under the revolving speed of 550r/min, according to the volume of water phase and target oil phase 1: 5
Than, water phase is added dropwise into target oil phase, after water phase completion of dropwise addition, stirs 30min, then, 0.5ml acetic acid is added, stirs 1h,
Then, it is washed, is filtered with 30ml isopropanol, it is dry, obtain calcic seaweed salt microballoon；
4) preparation of covering liquid: being dissolved in 100ml deionized water for 1ml acetic acid, then, 0.5g chitosan is added, sufficiently stirs
It mixes to dissolution, obtains covering liquid, at this point, the volume fraction of acetic acid is 1/100 (1%) in covering liquid, chitosan in covering liquid
Mass concentration is 0.5/100 (0.5%)；
5) under the revolving speed of 250r/min, it is micro- that calcic seaweed salt the cladding of calcic seaweed salt microballoon: is added into covering liquid
Ball stirs 30min, then, filters, dry, obtains calcic alginate/chitosan hemostatic microsphere.
Calcic alginate/chitosan hemostatic microsphere partial size and anthemorrhagic performance of the present embodiment are tested, and
By itself and blank group, that is, the calcic alginate/chitosan hemostatic microsphere nature blood coagulation of the present embodiment is not added, compares.
After tested it is found that calcic alginate/chitosan hemostatic microsphere partial size of the present embodiment is in 25 μm~400 μm models
In enclosing, surface area average grain diameter is 75.134 μm, and volume average particle size is 104.122 μm, and water absorption rate 332.7% is average
Bleeding stopping period is 230s, and relative to the average clotting time of blank group 280s, the calcic alginate/chitosan of the present embodiment stops
The reduced clotting time of blood microballoon 50s, illustrates it with good haemostatic effect.
Embodiment 9
A kind of preparation method of calcic alginate/chitosan hemostatic microsphere, specifically includes the following steps:
1) preparation of water phase: being dissolved in 10ml deionized water for 0.6g sodium alginate, then, 0.25g calcium carbonate, magnetic force is added
4h is stirred, water phase is obtained, at this point, the mass concentration of sodium alginate is 0.6/10 (6%) in water phase, the quality of calcium carbonate in water phase
Concentration is 0.25/10 (2.5%)；
2) preparation of target oil phase: 2ml span-80 is added into 50ml atoleine, is uniformly mixed, is obtained target
Oily phase, at this point, the volume fraction of span-80 is 2/50 (4%) in target oil phase；
3) preparation of calcic seaweed salt microballoon: under the revolving speed of 350r/min, according to the volume of water phase and target oil phase 1: 5
Than, water phase is added dropwise into target oil phase, after water phase completion of dropwise addition, stirs 30min, then, 1ml acetic acid is added, stirs 1h, with
Afterwards, it is washed, is filtered with 30ml isopropanol, it is dry, obtain calcic seaweed salt microballoon；
4) preparation of covering liquid: being dissolved in 100ml deionized water for 1ml acetic acid, then, 0.5g chitosan is added, sufficiently stirs
It mixes to dissolution, obtains covering liquid, at this point, the volume fraction of acetic acid is 1/100 (1%) in covering liquid, chitosan in covering liquid
Mass concentration is 0.5/100 (0.5%)；
5) under the revolving speed of 250r/min, it is micro- that calcic seaweed salt the cladding of calcic seaweed salt microballoon: is added into covering liquid
Ball stirs 30min, then, filters, dry, obtains calcic alginate/chitosan hemostatic microsphere.
Calcic alginate/chitosan hemostatic microsphere partial size and anthemorrhagic performance of the present embodiment are tested, and
By itself and blank group, that is, the calcic alginate/chitosan hemostatic microsphere nature blood coagulation of the present embodiment is not added, compares.
After tested it is found that calcic alginate/chitosan hemostatic microsphere partial size of the present embodiment is in 35 μm~400 μm models
In enclosing, surface area average grain diameter is 53.585 μm, and volume average particle size is 122.506 μm, and water absorption rate 201.6% is average
Bleeding stopping period is 251s, and relative to the average clotting time of blank group 280s, the calcic alginate/chitosan of the present embodiment stops
The reduced clotting time of blood microballoon 29s, illustrates it with good haemostatic effect.
The above is merely preferred embodiments of the present invention, be not intended to limit the invention, it is all in spirit of the invention and
Within principle, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.
Claims (9)
1. a kind of preparation method of calcic alginate/chitosan hemostatic microsphere, which comprises the following steps:
1) preparation of water phase: being dissolved in deionized water for alginate, then, insoluble calcium phosphate is added, stirring obtains water phase；
2) preparation of target oil phase: emulsifier is added into base oil phase, is uniformly mixed, is obtained target oil phase；
3) preparation of calcic seaweed salt microballoon: under the first setting speed of agitator, being added dropwise the water phase in Xiang Suoshu target oil phase,
After the water phase completion of dropwise addition, the first setting time is stirred, then, crosslinking agent is added, stirs the second setting time, then,
Purification, obtains calcic seaweed salt microballoon；
4) preparation of covering liquid: being dissolved in deionized water for acetic acid, then, chitosan is added, stirring obtains covering liquid；
5) under the second setting speed of agitator, the calcic sea cladding of calcic seaweed salt microballoon: is added in Xiang Suoshu covering liquid
Algae salt microballoon, stirring, then, purification obtains calcic alginate/chitosan hemostatic microsphere.
2. the preparation method of calcic alginate/chitosan hemostatic microsphere according to claim 1, which is characterized in that institute
The mass concentration for stating alginate described in step 1) is 4%~6%, the mass concentration of the insoluble calcium phosphate is 1.5%~
2.5%.
3. the preparation method of calcic alginate/chitosan hemostatic microsphere according to claim 1, which is characterized in that institute
Stating alginate described in step 1) includes sodium alginate, and the insoluble calcium phosphate includes calcium carbonate.
4. the preparation method of calcic alginate/chitosan hemostatic microsphere according to claim 1, which is characterized in that institute
Stating base oil described in step 2) is mutually atoleine, and the emulsifier is span-80；The volume fraction of the span-80 is
3-6%.
5. the preparation method of calcic alginate/chitosan hemostatic microsphere according to claim 1, which is characterized in that institute
It states described in step 3) first and sets speed of agitator as 350r/min-550r/min, first setting time is 20-40min,
Second setting time is 1-1.5h.
6. the preparation method of calcic alginate/chitosan hemostatic microsphere according to claim 1, which is characterized in that institute
The volume ratio for stating water phase described in step 3) and the target oil phase is 1: 4-1: 7.
7. the preparation method of calcic alginate/chitosan hemostatic microsphere according to claim 1, which is characterized in that institute
Stating crosslinking agent described in step 3) is acetic acid.
8. the preparation method of calcic alginate/chitosan hemostatic microsphere according to claim 1, which is characterized in that institute
The volume fraction for stating acetic acid described in step 4) is 0.5-1%, and the mass concentration of the chitosan is 0.5-1%.
9. the preparation method of calcic alginate/chitosan hemostatic microsphere according to claim 1, which is characterized in that institute
It states described in step 5) second and sets speed of agitator as 200r/min-300r/min, the mixing time of the stirring is 10-
30min。
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112999334A (en) * | 2021-03-08 | 2021-06-22 | 中国药科大学 | Insulin heavy microsphere and preparation method and application thereof |
| CN113134108A (en) * | 2021-04-15 | 2021-07-20 | 南开大学 | Cerium-based nano composite material and preparation method and application thereof |
| CN113893384A (en) * | 2021-11-08 | 2022-01-07 | 山东省科学院生物研究所 | Cross-linked chitosan microsphere and application thereof in wound surface hemostasis and repair material |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1374338A (en) * | 2001-03-12 | 2002-10-16 | 中国科学院大连化学物理研究所 | Emulsifying and internal gelifying process of preparing calcium alginate gel beads |
| CN1628861A (en) * | 2003-12-18 | 2005-06-22 | 中国科学院大连化学物理研究所 | Chitosan-calcium alginate gel microsphere soft tissue reinforced material and its preparation method and application |
| US20120220958A1 (en) * | 2003-09-12 | 2012-08-30 | Marine Polymer Technologies, Inc. | Vascular access preservation in hemodialysis patients |
| CN103467771A (en) * | 2013-09-23 | 2013-12-25 | 潍坊美赫曼生物医药科技有限公司 | Preparation method and application of marine organism active hemostasis dressing |
| CN105169459A (en) * | 2015-10-26 | 2015-12-23 | 广东泰宝医疗科技股份有限公司 | Polysaccharide hemostat and preparation method thereof |
| CN109432488A (en) * | 2018-12-14 | 2019-03-08 | 武汉理工大学 | A kind of preparation method of chitosan/gelatin-compounded hemostatic microsphere |
-
2019
- 2019-05-24 CN CN201910441782.5A patent/CN110180018A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1374338A (en) * | 2001-03-12 | 2002-10-16 | 中国科学院大连化学物理研究所 | Emulsifying and internal gelifying process of preparing calcium alginate gel beads |
| US20120220958A1 (en) * | 2003-09-12 | 2012-08-30 | Marine Polymer Technologies, Inc. | Vascular access preservation in hemodialysis patients |
| CN1628861A (en) * | 2003-12-18 | 2005-06-22 | 中国科学院大连化学物理研究所 | Chitosan-calcium alginate gel microsphere soft tissue reinforced material and its preparation method and application |
| CN103467771A (en) * | 2013-09-23 | 2013-12-25 | 潍坊美赫曼生物医药科技有限公司 | Preparation method and application of marine organism active hemostasis dressing |
| CN105169459A (en) * | 2015-10-26 | 2015-12-23 | 广东泰宝医疗科技股份有限公司 | Polysaccharide hemostat and preparation method thereof |
| CN109432488A (en) * | 2018-12-14 | 2019-03-08 | 武汉理工大学 | A kind of preparation method of chitosan/gelatin-compounded hemostatic microsphere |
Non-Patent Citations (6)
| Title |
|---|
| ANT´ONIO J. RIBEIRO ET AL: ""Chitosan-reinforced alginate microspheres obtained through the emulsification/internal gelation technique"", 《EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES》 * |
| FANGNING QU ET AL: ""Effect of acidification on the protection of alginate-encapsulated probiotic based on emulsification/internal gelation"", 《J SCI FOOD AGRIC》 * |
| 何小维: "《医药用碳水化合物》", 31 January 2016 * |
| 侯丹丹等: ""非水相体系中海藻酸钠-壳聚糖微胶囊粒径及强度性能"", 《化工学报》 * |
| 李胜等: ""β-榄香烯海藻酸钙-壳聚糖微囊的制备"", 《中国医药工业杂志》 * |
| 金鑫等: ""海藻酸-壳聚糖微球的制备及其在生物医药领域的应用"", 《国际口腔医学杂志》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112999334A (en) * | 2021-03-08 | 2021-06-22 | 中国药科大学 | Insulin heavy microsphere and preparation method and application thereof |
| CN112999334B (en) * | 2021-03-08 | 2022-06-17 | 中国药科大学 | Insulin heavy microsphere and preparation method and application thereof |
| CN113134108A (en) * | 2021-04-15 | 2021-07-20 | 南开大学 | Cerium-based nano composite material and preparation method and application thereof |
| CN113893384A (en) * | 2021-11-08 | 2022-01-07 | 山东省科学院生物研究所 | Cross-linked chitosan microsphere and application thereof in wound surface hemostasis and repair material |
| CN113893384B (en) * | 2021-11-08 | 2022-06-21 | 山东省科学院生物研究所 | Cross-linked chitosan microsphere and application thereof in wound surface hemostasis and repair material |
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