CN107158452A - A kind of bone surface of a wound hemostatic composition and its preparation method and application - Google Patents
A kind of bone surface of a wound hemostatic composition and its preparation method and application Download PDFInfo
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- CN107158452A CN107158452A CN201710309890.8A CN201710309890A CN107158452A CN 107158452 A CN107158452 A CN 107158452A CN 201710309890 A CN201710309890 A CN 201710309890A CN 107158452 A CN107158452 A CN 107158452A
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- wound
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- hemostatic composition
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- wound hemostatic
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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
- A61L24/0015—Medicaments; Biocides
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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
-
- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/08—Polysaccharides
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
- A61L2300/406—Antibiotics
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/418—Agents promoting blood coagulation, blood-clotting agents, embolising agents
Abstract
The invention discloses a kind of bone surface of a wound hemostatic composition and its preparation method and application, it is made up of solvent substrate, thickener, excipient and ion salt, the solvent substrate is polyhydroxy-alcohol, the ion salt is the one or more in inorganic calcium salt and inorganic molysite.Hemostatic composition bone good adhesion of the present invention, plasticity are good, mechanical can clog bone surface of a wound crack and blood sinus, moreover it is possible to accelerate nature coagulation process, haemostatic effect is good；It is degradable in human body or animal body, can by Absorption And Metabolism, good biocompatibility, it is non-stimulated to body, have no toxic side effect, it is safe, do not influence wound healing, Clinical practice is convenient, has good application prospect in terms of the bone surface of a wound hemostasis of human or animal.
Description
Technical field
The present invention relates to a kind of bone surface of a wound hemostatic composition and its preparation method and application, and in particular to a kind of plasticity
By force, bone surface of a wound hemostatic composition that adhesiveness is good, absorbable, do not influence wound healing and its preparation method and application, belongs to bone
Hemostatic technique field.
Background technology
Clinically, cancellous bone structure is loose, blood fortune is abundant, and surface of a wound bleeding is generally oozing of blood, cancellous bone surface of a wound haemophilia or
It is difficult to thoroughly hemostasis, is because bone wound tissue is loosely organized, blood fortune is abundant forms densely covered blood sinus, blood vessels in tissue shrinkage
Difference, platelet aggregation, blood clot is difficult to adhere to the bone surface of a wound.Bone surface of a wound bleeding is difficult to voluntarily stop blooding by vessel retraction, in art also
It is difficult to by conventional method hemostasis such as coagulation, clamp, hemostatic gauze, gelfoam fillings.The conventional bone wax of clinic carries out cancellous bone wound
Stop blooding in face.The main component of bone wax is beeswax, sesame oil etc., and bone wax is the mixture of sterilized beeswax and vaseline, with good
Good softening performance, energy plastotype after softening is rubbed with hand rubbing, nontoxic.The action principle of bone wax is that marrow portion hair is blocked with physical method
Thin angiorrhea, stops blooding during available for various first-aid patients bone oozings of blood.Clinical conventional bone wax is exactly based between closing bone at present
Bleeding path, principle of this machinery filling of control bone injury bleeding stopped blooding, and its anastalsis is quick, effective, but its
Poor biocompatibility and it is difficult to be degraded by body, absorbs, group will be on the one hand reduced as in foreign matter longer-term persistence body after
The anti-infection ability knitted, the risk increase for occurring postoperative infection；On the other hand the also reparation of the hindering bone surface of a wound, forms foreign matter meat
Bud is swollen to cause the symptoms such as local pain, sepage.Domestic and foreign scholars are in terms of artificial synthesized high polymer material, biological agent
The research work of bone wax substitute products, such as collagenous fibres, gelfoam, oxycellulose, PLA and polysaccharide etc. are carried out.
Zoopery and clinical practice show：Although these material biocompatibilities preferably, with degradability, most of is powder
Shape, glue, it is poor with surface of a wound adhesion, it is not easy to operate in art, easily washed away by blood flow.In addition, this family macromolecule substitute materials is also
There are expensive starting materials, physical behavior and be difficult the still unsolved practical problem such as modification, material safety, therefore, not yet can at present
It is transformed into being suitable for the ideal material of bone surface of a wound hemostasis, still needs to further further investigation and improve.At present, there are some passes
Disclosed in the patent of such product, it is as follows：
The patent of application number 201210067344.5 discloses a kind of bone degradable, alternative in human body or animal body
Wax, the bone surface of a wound hemostasis for not changing doctor's use habit and the material for promoting bone tissue healing, the material include oligosaccharide, poly
The mixture of sugar or oligosaccharide and polysaccharide, excipient is one kind or many in the one or more in polyhydroxy-alcohol, vegetable oil
Kind, the one or more in emulsifying agent.The material carbohydrate matrix content is big, hydrophilic carbohydrate and polyhydroxy-alcohol with it is hydrophobic
The paste stability of vegetable oil composition is not good enough, there is the shorter term of validity, less stable, water imbibition if commercialized product is developed into
Relatively low defect.Also, the product preparation process is needed after being cooled down under the conditions of being immediately placed in 0-4 DEG C after being blended under vacuum
It is made.Hemostatic material disclosed in the patent is the more excellent a kind of bone styptic of performance in current degradation material, but the hemostasis
The preparation technology of agent is complex, and high temperature preparation had both been related in technique, vacuum reaction is further related to, and further relates to sub-cooled, and parent
The paste stability that aqueous and hydrophobic medium is constituted is not good enough, the phase is imitated if commercialized product is developed into shorter.Simultaneously, it is considered to produce
Batch production difficulty is larger, and production cost is higher, is probably difficult to batch production, it is impossible to preferably solves bone wax market and deposits at present
The problem of.
The patent of application number 200410040076.3 discloses the adsorbable bone hemostasis in a kind of surgery or bone surgery
Agent, its material includes chitosan or modification of chitosan and other materials, and chitosan is material relatively conventional in hemostatic material, its
Hemostasis principle mainly uses the positive charge of itself institute's band, can accelerate blood coagulation, enrichment blood platelet so as to reach haemostatic effect,
Besides this material is that biomaterial is degradable absorbable.But chitosan class material belongs to animal derived material, has to human body
Certain potential hazard.The clay formed by main component of chitosan is used as bone styptic, its water imbibition, adhesion, biology
Other performances such as compatibility are not reported.The intracutaneous stimulation of general chitosan class material is higher, handles bad then with larger
Biostimulation.Besides the material be heated, irradiate it is perishable, sterilizing, storage and transport be required for particular design so that material
Cost can be greatly increased.
The patent of application number 200910076033.3 discloses a kind of degradable bone lacuna inside haemostatic material and its preparation
Method, including sodium alginate, medical starch and inorganic particulate, the adhesion of Sodium Alginate Hydrogel Films are poor.The material water imbibition,
Other performances such as adhesion, biocompatibility, plasticity, haemostatic effect, degradation characteristic are not reported.
The patent of application number 201410780581.5 discloses a kind of chitosan hemostatic gauze and preparation method thereof, the hemostasis
Gauze contains chitosan, sodium alginate, sodium carboxymethylcellulose, HES, saualane, traditional Chinese medicine ingredients, water, using electrostatic
Spin processes are woven into fiber.In the invention, chitosan is animal derived material first, there is certain potential hazard to human body.With
Chitosan be the gauze of main component formation as the hemostatic material of the bone surface of a wound, its water imbibition, adhesion, biocompatibility etc. its
He is not reported performance.The intracutaneous stimulation of general chitosan class material is higher, handles bad then with larger biostimulation,
Besides the hemostatic material of gauze form is typically difficult firm in the adhesion of the bleeding bone surface of a wound.Besides the material is heated, it is easy to irradiate
Rotten, sterilizing, storage and transport are required for particular design, so that material cost can be greatly increased.
The patent of application number 200510117740.4 discloses polymer nanofiber that is a kind of biodegradable and absorbing
Membrane material and its production and use, the product is nano fibrous membrane, contains gelatin, hyaluronic acid, chitosan, collagen egg
In vain, one kind in heparin, PGA, polyvinylpyrrolidone, polyvinyl alcohol, cellulose family, starch Polymer material
Or it is a variety of, calcium carbonate, potassium chromate, phosphoric acid hydrogen this etc. inorganic strengthening agent composition.The invention is used as bone surface of a wound blood sinus during hemostatic material；
Secondly, plasticity is poor, can not otherness filling and smearing for the bone surface of a wound of different shapes；In addition, many compositions in the invention
Such as gelatin, chitosan, collagen are animal derived material, there is potential source biomolecule harm；Finally, in the invention many macromolecules into
Point, when stopping blooding for the bone surface of a wound, degradation time is longer, hindering bone organization healing.
Disclose and prepared using the polymer such as polymer such as polyoxyethylene, polyoxypropylene, PLA in many reports in addition
Bone styptic, such material is the high molecular polymer with certain molecular weight, though the absorption that can degrade, degradation speed is slow, drop
The solution cycle is long, hinders knitting；In addition, water imbibition is poor, it is impossible to preferably absorb blood, adhesion and plasticity compared with
Difference, clinical manipulation is inconvenient.
Preferable bone hemostatic material should have the following advantages that：1. soft texture, plasticity are strong, and splitting for the surface of a wound can be filled rapidly
Gap and blood sinus；2. there is bone adhesiveness, can firmly stick the surface of a wound, not fallen off in certain time；3. good biocompatibility, nontoxic
Side effect, tissue reaction are small；4. it can gradually degrade, be absorbed by body tissue after the completion of anastalsis, not influence wound healing.From
The understanding of prior art is seen above, and preferable bone hemostatic material appearance can be met, it is necessary to further grind there is presently no good
Study carefully and improve.
The content of the invention
The deficiency existed for existing bone hemostatic material, the invention provides a kind of bone surface of a wound hemostatic composition, the hemostasis
Composition bone good adhesion, plasticity are good, mechanical can clog bone surface of a wound crack and blood sinus, moreover it is possible to accelerate nature coagulation process,
Haemostatic effect is good.Composition is degradable in human body or animal body, can be good biocompatibility, stingless to body by Absorption And Metabolism
Swash, have no toxic side effect, it is safe, do not influence wound healing.
Present invention also offers the preparation method of above-mentioned bone surface of a wound hemostatic composition, this method prepares simple, it is easy to implement,
Cost is low, and products obtained therefrom has preferable hardness, toughness and viscosity, shaping can apply wipe, haemostatic effect it is good, it is nontoxic secondary to make
It is small with, tissue reaction, wound healing is not influenceed, Clinical practice is convenient.
Present invention also offers above-mentioned bone surface of a wound hemostatic composition answering in human or animal's bone surface of a wound hemostatic article is prepared
With the product can be used for the hemostasis of all bone surface of a wound bleedings of human or animal in operation technique.
Further, the bone surface of a wound hemostatic composition that the present invention is provided, by solvent substrate, thickener, excipient and ion
Salt is constituted, and the solvent substrate is polyhydroxy-alcohol, and the ion salt is the one or more in inorganic calcium salt and inorganic molysite.
In above-mentioned bone surface of a wound hemostatic composition, the solvent substrate is polyhydroxy-alcohol, and the effect of the solvent substrate is for increasing
Thick dose and excipient one basic environment of offer, but it is preferable compared with strong, plasticity powder or liquid is formed a kind of adhesion
Paste or jelly.In addition, the change of solvent substrate content can cause the property such as plasticity, adhesion, water absorption character and degradation time
The change of energy.The polyhydroxy-alcohol is one kind or two in glycerine, PEG-4000, polyethylene glycol -300 and propane diols
Plant, preferably one or both of glycerine and PEG-4000.
In above-mentioned bone surface of a wound hemostatic composition, weight percentage of the solvent substrate in bone surface of a wound hemostatic composition is
30%~80%, preferably 50-70%.
In above-mentioned bone surface of a wound hemostatic composition, the effect of the thickener is the adhesion and plasticity for improving composition,
The thickener is one in sodium carboxymethylcellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, carragheen and carbomer
Plant or two kinds.When thickener selects special viscosity, products obtained therefrom performance is more excellent.Sodium carboxymethylcellulose is divided into by viscosity：
Superelevation stick sodium carboxymethylcellulose, high glutinous sodium carboxymethylcellulose, in stick sodium carboxymethylcellulose, low glutinous carboxymethyl cellulose
Sodium, the height of the present invention preferably medical grade stick sodium carboxymethylcellulose, in stick sodium carboxymethylcellulose or low glutinous carboxymethyl cellulose
Sodium.Hydroxypropyl methyl cellulose preferentially from the hydroxypropyl methyl cellulose that nominal viscosity is 6~15000cps, is more preferably selected
50~1500cps hydroxypropyl methyl cellulose.Hydroxyethyl cellulose is preferentially 250-400cps, 1500- from nominal viscosity
2500cps, 3500-5500cps or 4500-6500cps hydroxyethyl cellulose, are 1500- more preferably from nominal viscosity
One kind in 2500cps and 3500-5500cps hydroxyethyl cellulose；Carragheen preferentially selects medical rank.Carbomer is preferential
From carbomer 910, carbomer 934, Acritamer 940 or Carbopol 941, more preferably from carbomer 934 and Acritamer 940
One kind.The nominal viscosity is the viscosity measured using rotation viscometer.
In above-mentioned bone surface of a wound hemostatic composition, weight percentage of the thickener in bone surface of a wound hemostatic composition is
0.5%~10%, preferably 5-7%.
In above-mentioned bone surface of a wound hemostatic composition, the effect of the excipient is the plasticity, adhesion and the suction that improve product
Aqueous, excipient is in sodium carboxymethyl starch, farina, soluble starch, sodium alginate, dextrin and dextrin derivative
It is one or more.
In above-mentioned bone surface of a wound hemostatic composition, weight percentage of the excipient in bone surface of a wound hemostatic composition is 10%
~55%, preferably 20-45%.
In above-mentioned bone surface of a wound hemostatic composition, the ion salt functions as coagulant, accelerates and auxiliary hemostasis.From
Alite is inorganic calcium salt, inorganic molysite, or is inorganic calcium salt and the mixture of inorganic molysite.The inorganic calcium salt is sulfuric acid
Calcium, calcium chloride, calcium nitrate, the inorganic molysite are iron chloride, ferric nitrate, ferric sulfate, and the ion salt can be inorganic from these
Selected in calcium salt and inorganic molysite, for example, can select the one or more in inorganic calcium salt, inorganic molysite can be selected
In one or more, one kind can respectively be selected with inorganic calcium salt and inorganic molysite, can respectively select a variety of with inorganic calcium salt and inorganic molysite,
Can select a kind of selection of inorganic molysite a variety of with inorganic calcium salt, can also inorganic molysite select a kind of inorganic calcium salt selection a variety of.
In above-mentioned bone surface of a wound hemostatic composition, weight percentage of the ion salt in bone surface of a wound hemostatic composition is
0.05%~5%, preferably 1-3%.
The preparation method of bone surface of a wound hemostatic composition of the present invention comprises the following steps：
A. solvent substrate and thickener are mixed, stirred at 20 DEG C~75 DEG C, until sticky solvent substrate is formed, it is molten
It is swollen to stay overnight；
B. excipient is slowly added under stirring, blending or kneading conditions and is swelled complete sticky solvent substrate
In, continue to stir, be blended or mediate after adding, until forming homogeneous lotion or jelly；
C. ion salt is slowly added in lotion or jelly in stirring, blending or under mediating, continues stirring, blending after adding
Or mediate, until forming homogeneous lotion or jelly, as bone surface of a wound hemostatic composition.
Bone surface of a wound hemostatic composition of the present invention is a kind of homogeneous sticky lotion or jelly, and it has excellent smearing simultaneously
Operability, plasticity, adhesiveness and excellent Specificity of Bloodsucking, absorbable and degradable, do not interfere with wound healing, nontoxic to body yet
Gubernaculum swashs, and the formulations such as paste or liniment can be made.In actual use, in order to suitable for different surface of a wound shapes, position,
Different shapes can be made in the homogeneous lotion or jelly, for example, the homogeneous lotion can be directly placed into closing paste box
In, it is vacuum-sealed in aluminium foil bag, normal temperature is preserved after sterilizing.It can also be made of different moulds sheet, column or its
His shape, then with being vacuum-sealed in after film paper wrapper in aluminium foil bag, normal temperature is preserved after sterilizing.Can also be by it loaded on various
In medical operation instrument, such as medical applicator, flexible pipe for medical purpose, injector for medical purpose in, be then vacuum-sealed in aluminium foil bag,
Normal temperature is preserved after sterilizing.But no matter which kind of shape the lotion or jelly are made, are stored in which kind of container, are respectively provided with and well may be used
Plasticity.
In above-mentioned steps a, it is warming up to 20 DEG C~75 DEG C and continues to stir, until forming sticky solvent substrate.About need
30min or so.
In above-mentioned steps b and c, mixed stirring, blending or by way of mediating, these operations can be with stirring
Mix in container, emulsifying mixer, blender or the kneader of device and complete.
In above-mentioned steps b, the time for forming homogeneous lotion is about 1-2h；In step c, the time for forming homogeneous lotion is about
0.5-1h。
Bone surface of a wound hemostatic composition of the present invention has good random-shaping feature, can be according to the characteristics of the bone surface of a wound by clinic
Doctor is moulding on demand, can smear, can clog, therefore can be used for the hemostasis of various bone surface of a wound bleedings, and clinical application effect is good.Base
In this, present invention also offers application of the above-mentioned bone surface of a wound hemostatic composition in human or animal's bone surface of a wound hemostatic article is prepared.
Wherein, the bone surface of a wound can be the surface of a wound that bone wound that a variety of causes is caused is formed.
The invention has the advantages that：
1st, this composition has good random-shaping feature, can on demand be moulded by clinician according to the characteristics of the bone surface of a wound
Shape, can smear, can clog, while said composition has good bone adhesiveness, can be securely by its distinctive adhesion strength
The bone surface of a wound is adhered to, the bleeding part (blood sinus and crack) of the bone surface of a wound can be clogged, good haemostatic effect is played.In addition, the group
Compound has higher water absorption character, and liquid-absorbent is not less than 30 times, after contacting blood, can absorb what the bone surface of a wound oozed out
Blood platelet, red blood cell, blood coagulating protein in moisture, concentrate blood in blood, aggregation blood, accelerate nature coagulation process, from
And improve bone surface of a wound haemostatic effect.
2nd, present composition pH is neutrality, and indices control is strict, solvent substrate, thickener and the figuration used
Agent is degradable in human body or animal body, and metabolism can be absorbed by organisms after degraded, noresidue in human body or in animal body, to machine
Body is stimulated without any, is had no toxic side effect, safe, good biocompatibility, it is to avoid user's foreign body reaction and tissue inflammation
Etc. the appearance of complication, wound healing is not influenceed.
3rd, present composition preparation method is simple, easy to use, with preferable hardness, toughness and viscosity, shaping
It can smear, degradable absorbable, haemostatic effect is good, and Clinical practice is convenient, has in terms of the bone surface of a wound hemostasis of human or animal very well
Application prospect.
4th, composition of the invention addition growth factor, calcium phosphate, hydroxyapatite, calcium carbonate, calcium sulfate, bioactivity
It can be developed to the bone styptic for promoting knitting after the material of glass and other promotion bone uptakes；The composition of the present invention
Addition antibiotic or other have treatment sexual function medicine after can be developed to as with anti-infective or other treatment effectiveness bone
Styptic.
Embodiment
The present invention is described in further detail with reference to specific implementation example.
Embodiment 1
Bone surface of a wound hemostatic composition formula of the present invention is as shown in table 1 below：
The formula table of 1. embodiment of table 1
The bone surface of a wound hemostatic composition preparation method is as follows：
1. weigh glycerine by formula table, the height of medical grade sticks and obtains homogeneous under sodium carboxymethylcellulose, stirring condition
Solution.The solution is slowly heated up, 30min is stirred at a temperature of 30 DEG C, uniform solution is changed into sticky solvent substrate, was swelled
Night.
2. weighing sodium carboxymethyl starch by formula table, it is slowly added to be swelled in complete sticky solvent substrate, side is added
Side strong stirring, until forming homogeneous lotion, about 2h；
3. weighing calcium sulfate by formula table, it is slowly added into above-mentioned lotion, continues to stir, until homogeneous lotion is formed,
About 1h.
4. the lotion that step 3 is obtained is fitted into closing paste box, it is vacuum-sealed in aluminium foil bag, normal temperature is protected after sterilizing
Deposit；Or sheet and column is made using tablet press machine, and then with being vacuum-sealed in after film paper wrapper in aluminium foil bag, normal temperature after sterilizing
Preserve；Or loaded in injector for medical purpose, be vacuum-sealed in aluminium foil bag, normal temperature is preserved after sterilizing；Or loaded on in gel device, very
Sky is sealed in aluminium foil bag, and normal temperature is preserved after sterilizing.
Embodiment 2
Bone surface of a wound hemostatic composition formula of the present invention is as shown in table 2 below：
The formula table of 2. embodiment of table 2
The bone surface of a wound hemostatic composition preparation method is as follows：
1. it is fine to weigh the hydroxypropyl methyl that glycerine, PEG-4000, nominal viscosity are 50~1500cps by formula table
The uniform solution obtained under the hydroxyethyl cellulose that the plain and nominal viscosity of dimension is 1500-2500cps, stirring condition.To the solution
Slow heating, stirs 30min at a temperature of 75 DEG C, uniform solution is changed into sticky solvent substrate, be swelled overnight.
2. obtained sticky solvent substrate is put into kneader, kneader stirring is started, alginic acid is weighed by formula table
Sodium, dextrin, both is mixed, and is then slowly added in kneader, is mediated when adding until forming homogeneous lotion, about
1h；
3. weighing calcium chloride, ferric sulfate by formula table, it is slowly added into successively in above-mentioned lotion, continues to mediate, until shape
Into homogeneous lotion, about 0.5h.
4. the lotion that step 3 is obtained is fitted into closing paste box, it is vacuum-sealed in aluminium foil bag, normal temperature is protected after sterilizing
Deposit；Or sheet and column is made using tablet press machine, and then with being vacuum-sealed in after film paper wrapper in aluminium foil bag, normal temperature after sterilizing
Preserve；Or loaded in injector for medical purpose, be vacuum-sealed in aluminium foil bag, normal temperature is preserved after sterilizing；Or loaded on in gel device, very
Sky is sealed in aluminium foil bag, and normal temperature is preserved after sterilizing.
Embodiment 3
Bone surface of a wound hemostatic composition formula of the present invention is as shown in table 3 below：
The formula table of 3. embodiment of table 3
The bone surface of a wound hemostatic composition preparation method is as follows：
1. propane diols, polyethylene glycol -300, medical rank carragheen, nominal viscosity are weighed for 250-400cps by formula table
Hydroxyethyl cellulose and hydroxypropyl methyl cellulose that nominal viscosity is 4000~9000cps, what is obtained under stirring condition is equal
One solution.The solution is slowly heated up, 30min is stirred at a temperature of 50 DEG C, uniform solution is changed into sticky solvent substrate, is swelled
Overnight.
2. obtained sticky solvent substrate is put into kneader, kneader stirring is started, potato is weighed by formula table
Starch, sodium carboxymethyl starch, both is mixed, and is then slowly added in kneader, is mediated when adding, until forming equal
One lotion, about 1h；
3. weighing ferric nitrate by formula table, it is slowly added into above-mentioned lotion, continues to mediate, until homogeneous lotion is formed,
About 0.5h.
4. the lotion that step 3 is obtained is fitted into closing paste box, it is vacuum-sealed in aluminium foil bag, normal temperature is protected after sterilizing
Deposit；Or sheet and column is made using tablet press machine, and then with being vacuum-sealed in after film paper wrapper in aluminium foil bag, normal temperature after sterilizing
Preserve；Or loaded in injector for medical purpose, be vacuum-sealed in aluminium foil bag, normal temperature is preserved after sterilizing；Or loaded on in gel device, very
Sky is sealed in aluminium foil bag, and normal temperature is preserved after sterilizing.
Embodiment 4
Bone surface of a wound hemostatic composition formula of the present invention is as shown in table 4 below：
The formula table of 4. embodiment of table 4
The bone surface of a wound hemostatic composition preparation method is as follows：
1. weighing PEG-4000 and carbomer 934 by formula table, it is put into emulsifying mixer, fully stirs at room temperature
Mix, until forming sticky solvent substrate, be swelled overnight.
2. obtained sticky solvent substrate is put into kneader, kneader stirring is started, solubility is weighed by formula table
Starch, sodium carboxymethyl starch and dextrin, this three is mixed, is then slowly added in kneader, is mediated when adding, until
Form homogeneous lotion, about 1.5h；
3. weighing calcium nitrate by formula table, it is slowly added into above-mentioned lotion, continues to mediate, until homogeneous lotion is formed,
About 0.5h.
4. the lotion that step 3 is obtained is fitted into closing paste box, it is vacuum-sealed in aluminium foil bag, normal temperature is protected after sterilizing
Deposit；Or sheet and column is made using tablet press machine, and then with being vacuum-sealed in after film paper wrapper in aluminium foil bag, normal temperature after sterilizing
Preserve；Or loaded in injector for medical purpose, be vacuum-sealed in aluminium foil bag, normal temperature is preserved after sterilizing；Or loaded on in gel device, very
Sky is sealed in aluminium foil bag, and normal temperature is preserved after sterilizing.
Embodiment 5
Bone surface of a wound hemostatic composition formula of the present invention is as shown in table 5 below：
The formula table of 5. embodiment of table 5
The bone surface of a wound hemostatic composition preparation method is as follows：
1. weighing the hydroxyethyl cellulose that propane diols, propane diols and nominal viscosity are 4500-6500cps by formula table, stir
The uniform solution obtained under the conditions of mixing.The solution is slowly heated up, 30min is stirred at a temperature of 40 DEG C, is changed into uniform solution
Sticky solvent substrate, is swelled overnight.
2. obtained sticky solvent substrate is put into kneader, kneader stirring is started, dextrin is weighed by formula table, slowly
Slowly it is added in kneader, is mediated when adding, until forms homogeneous lotion, about 1.5h；
3rd, iron chloride is weighed by formula table, be slowly added into above-mentioned lotion, continue to mediate, until homogeneous lotion is formed,
About 0.5h.
4. the lotion that step 3 is obtained is fitted into closing paste box, it is vacuum-sealed in aluminium foil bag, normal temperature is protected after sterilizing
Deposit；Or sheet and column is made using tablet press machine, and then with being vacuum-sealed in after film paper wrapper in aluminium foil bag, normal temperature after sterilizing
Preserve；Or loaded in injector for medical purpose, be vacuum-sealed in aluminium foil bag, normal temperature is preserved after sterilizing；Or loaded on in gel device, very
Sky is sealed in aluminium foil bag, and normal temperature is preserved after sterilizing.
Embodiment 6
Bone surface of a wound hemostatic composition formula of the present invention is as shown in table 6 below：
The formula table of 6. embodiment of table 6
The bone surface of a wound hemostatic composition preparation method is as follows：
1. weighing glycerine, carbomer 934, the low glutinous sodium carboxymethylcellulose of medical grade and nominal viscosity by formula table is
The uniform solution obtained under 3500-5500cps hydroxyethyl cellulose, stirring condition.30min is stirred at room temperature, is made homogeneous molten
Liquid is changed into sticky solvent substrate, is swelled overnight.
2. obtained sticky solvent substrate is put into kneader, start kneader stirring, by formula table weigh dextrin and
Sodium carboxymethyl starch, both is mixed, and is then slowly added in kneader, is mediated when adding, until forming homogeneous cream
Body, about 1h；
3. weighing iron chloride by formula table, it is slowly added into above-mentioned lotion, continues to mediate, until homogeneous lotion is formed,
About 1h.
4. the lotion that step 3 is obtained is fitted into closing paste box, it is vacuum-sealed in aluminium foil bag, normal temperature is protected after sterilizing
Deposit；Or sheet and column is made using tablet press machine, and then with being vacuum-sealed in after film paper wrapper in aluminium foil bag, normal temperature after sterilizing
Preserve；Or loaded in injector for medical purpose, be vacuum-sealed in aluminium foil bag, normal temperature is preserved after sterilizing；Or loaded on in gel device, very
Sky is sealed in aluminium foil bag, and normal temperature is preserved after sterilizing.
Embodiment 7
Bone surface of a wound hemostatic composition formula of the present invention is as shown in table 7 below：
The formula table of 7. embodiment of table 7
The bone surface of a wound hemostatic composition preparation method is as follows：
1. weigh the hydroxypropyl methyl cellulose and carbomer that glycerine, nominal viscosity are 10000-15000 by formula table
910, the uniform solution obtained under stirring condition.The solution is slowly heated up, 30min is stirred at a temperature of 30 DEG C, is made homogeneous molten
Liquid is changed into sticky solvent substrate, is swelled overnight.
2. weighing sodium carboxymethyl starch, farina and dextrin by formula table, it is slowly added into successively under strong stirring
To being swelled in complete sticky solvent substrate, stir while adding, until forming homogeneous lotion, about 2h；
3. weighing iron chloride, calcium chloride by formula table, it is slowly added into above-mentioned lotion, continues to stir, until forms equal
One lotion, about 1h.
4. the lotion that step 3 is obtained is fitted into closing paste box, it is vacuum-sealed in aluminium foil bag, normal temperature is protected after sterilizing
Deposit；Or sheet and column is made using tablet press machine, and then with being vacuum-sealed in after film paper wrapper in aluminium foil bag, normal temperature after sterilizing
Preserve；Or loaded in injector for medical purpose, be vacuum-sealed in aluminium foil bag, normal temperature is preserved after sterilizing；Or loaded on in gel device, very
Sky is sealed in aluminium foil bag, and normal temperature is preserved after sterilizing.
Comparative example 1
It is formulated as (%w/w)：Solvent substrate：Glycerine 35%, mannitol 30%, thickener：PVP 5.5%, xanthans
1.5%, excipient：Soluble starch 26%, ion salt：Calcium dihydrogen phosphate 2%.
According to the method for embodiment 2, glycerine, mannitol, PVP, xanthans are mixed, what is obtained under stirring condition is homogeneous
Solution.The solution is slowly heated up, 30min is stirred at a temperature of 75 DEG C, uniform solution is changed into sticky solvent substrate, was swelled
Night.Obtained sticky solvent substrate is put into kneader, kneader stirring is started, soluble starch is slowly added to, side is added
Side is mediated up to well mixed, is then slowly added into calcium dihydrogen phosphate, continues to mediate, until being well mixed.By gained mixture
It is fitted into closing paste box, is vacuum-sealed in aluminium foil bag, normal temperature is preserved after sterilizing；Or processing slabbing, column or other shapes
Shape, with being vacuum-sealed in after film paper wrapper in aluminium foil bag, normal temperature is preserved after sterilizing.
Comparative example 2
It is formulated as (%w/w)：Maltose 10%, carboxymethyl cellulose 20%, hydroxypropul starch 15%, chitosan 10%,
Gelatin 10%, glycerine 30%, tween 5%.
Glycerine and tween are mixed, 40 DEG C are warming up to, sealing stirring 1h, then add maltose, carboxymethyl cellulose,
Hydroxypropul starch, chitosan and gelatin, 4-5h is stirred under vacuum at 60 DEG C.Gained mixture is fitted into closing paste box, very
Sky is sealed in aluminium foil bag, and normal temperature is preserved after sterilizing；Or with being vacuum-sealed in after film paper wrapper in aluminium plastic bag, normal temperature after sterilizing
Preserve.
The premium properties such as the validity of product of the present invention, stability, security, biocompatibility, hemostatic can by with
Lower experiment enters line justification to advantage of the present invention.
Verify example 1：Validity and stability test
According to YY/T 0681.1-2009《Aseptic medical equipment packaging test method part 1：Accelerated aging test refers to
South》Specified in method, we have carried out accelerated aging test to the sample after sterilizing, the property of the sample after observation accelerated ageing
Whether can stablize, whether performance is good, to evaluate the stability of sample.Accelerated aging test evaluation index mainly has：
1. acid-base value：Sample after sterilizing is put in 60 DEG C of climatic chambers, respectively at being taken out after 0 month, 3 months, is pressed
Certain proportion is mixed with purified water, is stirred, the acid-base value of gained after extraction 24h；
2. smear operability：Sample after sterilizing is put in 60 DEG C of climatic chambers, is taken respectively at after 0 month, 3 months
Go out, sample is applied in hand held on the model being immersed in water in advance, see whether easily to smear uniform, whether sample can
Firmly stick on model；
3. plasticity：Sample after sterilizing is put in 60 DEG C of climatic chambers, respectively at being taken out after 0 month, 3 months, is used
Any kneading of hand is moulding, evaluates the complexity in moulding process, whether good observes moulding rear state；
4. water imbibition：Sample after sterilizing is put in 60 DEG C of climatic chambers, respectively at being taken out after 0 month, 3 months, is soaked
Steep in enough water, after sample is completely dispersed uniformly, isolate moisture, the moisture for calculating sample absorption is many of example weight
Few times.
5. intensity：Sample after sterilizing is put in 60 DEG C of climatic chambers, respectively at after 0 month, 3 months take out, according to
Professional standard BS757:1975 regulations, using the Bloom systems of Texture instrument, the intensity that test sample has, the production of this Index Influence
The smearing operability of product, plasticity, are also the stable major parameter of properties of sample.
Above-described embodiment and comparative example product are subjected to accelerated aging test respectively, as a result as shown in table 8 below and 9：
It is 0 month properties of sample table before the accelerated aging test of table 8.
It can be seen from the results above that the properties of sample that inventive formulation and technique are prepared is excellent, it can appoint as needed
Meaning is moulding, easily smeared during the hemostasis of the bone surface of a wound, and sticks firmly, because with excellent liquid-absorbent, haemostatic effect is good
It is good, it is especially suitable for the clinical manipulation of clinician.
9. accelerated aging test of table properties of sample table after 3 months
It can be seen from the results above that after degradation, properties of sample is stable, still possesses clinician and carry out bone wound
Requirement when face is stopped blooding.Provided by standard, 60 DEG C of accelerated ageings 3 months, equivalent to the time that room temperature deposits about two years, this experiment
As a result show, the sample obtained by present invention process formula not only produces easily realization in batches, meets clinical operation requirement, and
And the still requirement of function admirable in 24 months terms of validity of general commercialized product is met, with than larger practical significance.
Verify example 2：Security and biocompatibility test
To ensure security when being used for clinical, the evaluation of biocompatibility has been carried out to sample.Evaluation method is as follows：
1. cell toxicity test
It is prepared by 1.1 test liquids：
Sample is taken to be extracted in cell culture medium containing serum, extracting condition is 37 ± 1 DEG C, 24 ± 2h.
It is prepared by 1.2 cell suspensions
It will cultivate and cell culture fluid added after the eugonic cells of 48h~72h are digested with digestive juice, suction pipe piping and druming is mixed
Counted under the microscope with blood counting chamber after even, cell density is calculated as follows：
C=104×n/4
In formula：
C---- cell densities, unit is every milliliter (an individual/mL)；
The big lattice inner cell sum of N---- tallies corner four, unit is individual.
According to actual measurement cell density, the cell suspension that the appropriate cell culture fluid of addition is configured to test requirements document density is standby.
1.3 by prepare 1 × 104/ mL cell suspension inoculations are in 96 well culture plates, if blank control, negative control, sun
Property control and test sample group, every group sets at least 6 holes, per hole be inoculated with 100 μ L cell suspensions.Put CO2gas incubator and (contain body
The carbon dioxide of fraction 5%) after 37 DEG C of culture 24h, discard original fluid.Blank control group adds fresh cells culture
Liquid, negative control group adds negative controls leaching liquor, and positive controls add positive control solution or positive reference substance extraction
Liquid, test sample group adds test specimen leaching liquor, per the μ L of hole 100, puts carbon dioxide gas incubator and continues to cultivate 72h.
In changing the 72h after nutrient solution, micro- Microscopic observation cellular morphology is put.It is 5g/L that 20 μ L mass concentrations are added per hole
Tetrazolium salting liquid, continue to discard liquid in hole after cultivating 4h, add 150 μ L DMSO, put and 10min is shaken on oscillator, in enzyme
Absorbance is determined under mark instrument 570nm and 630nm wavelength, relative appreciation rate (RGR) is calculated as follows.
RGR=A/A0× 100%
In formula：
RGR---- is with respect to appreciation rate, %；
A---- test samples group (negative, positive group) absorbance；
A0--- blank control group absorbance.
Judged according to RGR accordings to the form below grade scale.The reaction of negative control group should be not more than 1 grade, and positive controls are at least
For 3 order reactions.Closed such as negative control group when positive controls react invalid to test again.
Cell-cytotoxic reaction hierarchical table
| Rank | With respect to appreciation rate/% |
| 0 | ≥100 |
| 1 | 80~99 |
| 2 | 50~79 |
| 3 | 30~49 |
| 4 | 0~29 |
Result judgement：In the case where negative control and positive control produce anticipation reaction, analysis judges test sample cell
Toxic reaction degree.
2. intradermal reaction
It is prepared by 2.1 test liquids：
Sample is taken to be extracted in cell culture medium containing serum, extracting condition is 37 ± 1 DEG C, 24 ± 2h.
2.2 test procedure
Preceding 4~the 18h of experiment, thoroughly removes back part of animal backbone both sides hair, in case injection leaching liquor.
5 every rabbit backbone side are selected the leaching liquor that intracutaneous injection 0.2mL is prepared with polar solvent.Equally at every
Rear five intracutaneous injections 0.2mL polar solvent comparison liquids of rabbit backbone the same side.In the backbone opposite side injection of every rabbit
Leaching liquor and non-polar solven control group prepared by non-polar solven, operating procedure is ibid.
At once and in the situation of each injection site of 24h, 48h and 72h observed and recorded after injection.Points-scoring system according to the form below
Carry out tissue reaction's scoring, and log.
3. hemolytic test
Sample is taken to be extracted under 37 ± 1 DEG C, 72 ± 2h, extraction medium is physiological saline, it is right using physiological saline as feminine gender
According to sterile purified water is positive control.Respectively plus dilution after new fresh rabbit blood, supernatant is taken, with ultraviolet specrophotometer in 545nm
Under wavelength, respective OD value (OD) value is determined.Hemolysis rate is calculated as follows：
Hemolysis rate (%)=(Dt-Dnc)/(Dpc-Dnc)
In formula, DtFor test sample absorbance；DncFor negative control absorbance；DpcFor positive control absorbance.
The hemolysis rate of test sample is to meet regulation within 5%.
4. pyrogen testing
Sample is taken to be extracted in cell culture medium containing serum, extracting condition is 37 ± 1 DEG C, 72 ± 2h, obtains need testing solution.
Take applicable rabbit 3 to determine after its normal body temperature within 15 minutes, prescribed dose is slowly injected simultaneously from ear vein
About 38 DEG C of need testing solution is warmed to, then its body temperature was measured 1 time by preceding method every 30 minutes, surveyed 6 times altogether, with 6 body temperature
Middle highest once subtracts normal body temperature, is the rise temperature of the rabbit body temperature.
In 3 rabbit, body temperature rise is below 0.6 DEG C, and 3 rabbit body temperature rise summations are less than 1.3 DEG C.Judge
The pyrogen test of test sample meets regulation.
5. acute systemic toxicity
Sample is taken to be extracted in cell culture medium containing serum, extracting condition is 37 ± 1 DEG C, 72 ± 2h, obtains test liquid.From strong
The mouse that it is qualified that health is quarantined, every group 5, be 50ml/kg to sample dosage through tail vein/intraperitoneal injection test liquid.Observed after injection
The body weight increase situation and general shape of mouse immediate reaction, and 4h, 24h after to sample, 48h, 72h observations and record each group animal
State, toxicity performance and dead animal number.Body weight rises appreciably, and no dead, general behavior inspection and analyses without exception, non-toxic anti-
Should be as qualified.
6. bone Implantation Test
As former state, bone is implanted into 1 week, 4 weeks, 12 weeks test specimen, and histological observation should be good.According to GB/T 16886.6-
Bone method for implantation as defined in 1997 is by the sample preparation after sterilizing into a diameter of 2cm, and long 6cm cylinder is inserted rabbit femoral and got out
Bone cavity in.
Above-described embodiment and comparative example product carry out security and biocompatibility test, experimental result such as table 10 below respectively
It is shown：
The security of table 10. and evaluation of its biocompatibility result
By the biological assessment experiment repeated, every time strict operation, end product shows that present invention process formula is obtained
Secure sample it is non-stimulated, and performance is stable, can be used safely in clinical practice.
Verify example 3：Hemostasis trial
From healthy adult regular grade NZw, male and female are not limited, 2.5~3.0Kg of body weight.Raising temperature：20~26
℃；Relative humidity：40~70%；Illumination：15~20Lx；Feed complete granular rabbit feed, free water.
1. ilium stops blooding
Autogenous Cancellous Bone Graft area is larger, and bone hole network structure is enriched, and aperture is larger, is organism skeletal bones surface of a wound bleeding
Most positions, the haemostatic effect for observing bone hemostatic composition at this position is more representative.
Experimental animal 5 is taken, with 2% yellow Jackets through ear vein injecting anesthetic, lose hair or feathers preserved skin, the sterilization of art area is completed
Aseptic operation hole towel, does the outer lateral incision of bilateral crista iliaca, peels off periosteum, spill ilium outside plate, utilize diameter 2.5mm bone drill respectively
The deep surface of a wound of about 4mm is got out, after surface of a wound bleeding, smearing hemostasis, observation hemostasis effect are carried out using the sample of the embodiment of the present invention 2
Really.On wound surface smearing after inventive samples, inventive samples energy secure adhesion is on the bone surface of a wound, around without oozing of blood, and sample is smeared
Finish rear oozing of blood to be pinned, hemostasis is rapid.The another surface bone parts for biting ilium outside plate about 1mm thickness broken using bone forceps, appear ilium
The bone surface diameter about 1cm surface of a wound, superficial hemorrhages are rapid and amount of bleeding is larger, smeared using the sample of the embodiment of the present invention 7
Hemostasis, observes haemostatic effect.Because bone surface of a wound area is larger, slightly oozing of blood, then add sample after one layer of inventive samples is smeared
After applying amount, no oozing of blood.The bleeding stopping period at two positions is not less than 5min.Whole process is easy to operate, smears simple, hemostasis
Work well.
Experimental animal 3 is taken, the deep surface of a wound of about 4mm is got out on ilium outside plate according to method same above, the surface of a wound goes out
Smearing hemostasis is carried out after blood with the sample of comparative example 1, haemostatic effect is observed.On wound surface smearing after the sample of comparative example 1, sample can not
Adhere to the oozing of blood bone surface of a wound, hemostasis not yet in effect.Meanwhile, ilium outside plate about 1mm thickness is bitten broken using bone forceps using same method
Surface bone parts, appear ilium surface, carry out smearing hemostasis with the sample of comparative example 1, observe haemostatic effect.On wound surface smearing
After the sample of comparative example 1, sample can not adhere to the oozing of blood oozing of blood bone surface of a wound, hemostasis not yet in effect.
2. skull stops blooding
Skull position because with higher intracranial pressure, if skull position have a Cranial defect and during bleeding, typically because pressure is too big
The difficult hemostasis of the larger more rapid comparison of amount of bleeding.
Experimental animal 5 is taken, with 2% yellow Jackets through ear vein injecting anesthetic, lose hair or feathers preserved skin, the sterilization of art area is completed
Aseptic operation hole towel, wardrobe portion center is about 3cm otch, peels off periosteum, spills head parietal bone, will be pushed up using bone drill and rongeur
Elevator opens the surface of a wound of irregular shape, after surface of a wound bleeding, carries out smearing hemostasis using the sample of the embodiment of the present invention 4, observation stops
Blood effect.On wound surface smearing after inventive samples, inventive samples energy secure adhesion is on the bone surface of a wound, after sample is immersed by blood
Become red by white, the micro oozing of blood of surrounding has no the increase of oozing of blood amount in five minutes, sample hemostasis is rapid.For irregular bone
The surface of a wound, this composition is equally easy to operate, and haemostatic effect is good.
Experimental animal 3 is taken, the surface of a wound of irregular shape is outputed at parietal bone using same method, comparative example 1 is utilized
Sample carry out smearing hemostasis, observe haemostatic effect.On wound surface smearing after the sample of comparative example 1, sample can not adhere to bone wound
Face, hemostasis not yet in effect.
Verify example 4：Degrading experiment
From healthy adult regular grade NZw, male and female are not limited, 2.5~3.0Kg of body weight.Raising temperature：20~26
℃；Relative humidity：40~70%；Illumination：15~20Lx；Feed complete granular rabbit feed, free water.
Experimental animal 24 is taken, is divided into 4 groups, with 2% yellow Jackets through ear vein injecting anesthetic, lose hair or feathers preserved skin, art area
Sterilization, completes aseptic operation hole towel, and the otch at femur peels off periosteum, appears femur, is intermittently bored with the slow-speed of revolution on bone
Hole, bit diameter is 2mm, with the abundant lavation of physiological saline during operation, in case local organization is overheated.Every femur gets out 3 holes,
Every group is respectively implanted in the sample of embodiment 3,6,7 and comparative example 2 in group in the left thigh bone hole of new zealand rabbit, and right thigh bone hole is empty
In vain.It is postoperative to randomly select 2 animals respectively respectively at 1 week, 4 weeks, 12 weeks and put to death, art area is appeared in the same manner, observation is new
The western left leg implant site healing state of blue rabbit and sample carryover situation, and made comparisons with the right leg of same rabbit.Intercept femur
Implant part, removes musculature, is soaked and fixed with formalin solution, send pathological observation.
Observed in experiment, embodiment 3,6,7 has been disappeared in bone hole at 1 week, and embodiment 3,6,7 is implanted into after 4 weeks
Bone hole and right thigh bone scab growing state without larger difference, it is most of to have masked bone hole, left and right leg indifference, poroma after 12 weeks
Bone hole is all covered, knitting is good., it is apparent that sample naked eyes are hidden after 4 weeks at bone hole during the sample of comparative example 21 week
It is about visible, there is about a quarter to 1/2nd part to be covered by poroma at bone hole, but the right thigh bone scab of same rabbit will
Bone hole is largely covered.The implant site of comparative example 2 is visible by naked eyes sample after 12 weeks, and poroma largely covers bone hole, same
The right thigh bone scab of rabbit all covers bone hole.
Claims (10)
1. a kind of bone surface of a wound hemostatic composition, it is characterized in that：It is made up of solvent substrate, thickener, excipient and ion salt, it is described
Solvent substrate is polyhydroxy-alcohol, and the ion salt is the one or more in inorganic calcium salt and inorganic molysite.
2. bone surface of a wound hemostatic composition according to claim 1, it is characterized in that：The solvent substrate is glycerine, poly- second
One in one or both of glycol -400, polyethylene glycol -300 and propane diols, preferably glycerine and PEG-4000
Plant or two kinds；The inorganic calcium salt is calcium sulfate, calcium chloride, calcium nitrate, and the inorganic molysite is iron chloride, ferric nitrate, sulfuric acid
Iron, one or more of the ion salt in above-mentioned inorganic calcium salt, or one kind or many in above-mentioned inorganic molysite
Kind, or the one or more in above-mentioned inorganic calcium salt and inorganic molysite.
3. bone surface of a wound hemostatic composition according to claim 1, it is characterized in that：The thickener is carboxymethyl cellulose
It is one or two kinds of in sodium, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, carragheen and carbomer；The excipient is carboxylic first
One or more in base sodium starch, farina, soluble starch, sodium alginate, dextrin and dextrin derivative.
4. bone surface of a wound hemostatic composition according to claim 3, it is characterized in that：The sodium carboxymethylcellulose is medical grade
Height stick sodium carboxymethylcellulose, in stick sodium carboxymethylcellulose or low glutinous sodium carboxymethylcellulose；The hydroxypropyl methyl is fine
Dimension element is the hydroxypropyl methyl cellulose that nominal viscosity is 6~15000cps, and preferably nominal viscosity is 50~1500cps hydroxyl
Propyl methocel；The hydroxyethyl cellulose is that nominal viscosity is 250-400 cps, 1500-2500 cps, 3500-
5500 cps or 4500-6500cps hydroxyethyl cellulose, preferably nominal viscosity is 1500-2500 cps or 3500-5500
Cps hydroxyethyl cellulose；The carragheen is medical rank carragheen；The carbomer be carbomer 910, carbomer 934,
Acritamer 940 or Carbopol 941, preferably carbomer 934 or Acritamer 940.
5. the bone surface of a wound hemostatic composition according to any one of claim 1-4, it is characterized in that：Solvent substrate is in the bone surface of a wound
Weight percentage in hemostatic composition is 30%~80%；Weight percent of the thickener in bone surface of a wound hemostatic composition contains
Measure as 0.5%~10%；Weight percentage of the excipient in bone surface of a wound hemostatic composition is 10%~55%；Ion salt is created in bone
Weight percentage in the hemostatic composition of face is 0.05%~5%.
6. bone surface of a wound hemostatic composition according to claim 5, it is characterized in that：Solvent substrate is in bone surface of a wound hemostatic composition
In weight percentage be 50-70%；Weight percentage of the thickener in bone surface of a wound hemostatic composition is 5-7%；Figuration
Weight percentage of the agent in bone surface of a wound hemostatic composition is 20-45%；Weight of the ion salt in bone surface of a wound hemostatic composition
Percentage composition is 1-3%.
7. a kind of preparation method of bone surface of a wound hemostatic composition, it is characterized in that comprising the following steps：
A. solvent substrate and thickener are mixed, stirred at 20 DEG C~75 DEG C, until forming sticky solvent substrate, was swelled
Night；
B. excipient is slowly added into stirring, blending or under mediating and be swelled in complete sticky solvent substrate, after adding
Continue to stir, be blended or mediate, until forming homogeneous lotion or jelly；
C. ion salt is slowly added in lotion or jelly in stirring, blending or under mediating, continues to stir after adding, is blended or pinches
Close, until forming homogeneous lotion or jelly, as bone surface of a wound hemostatic composition.
8. preparation method according to claim 7, it is characterized in that：Also include by bone surface of a wound hemostatic composition be made sheet,
The step of column or other shapes；Or also including the step of bone surface of a wound hemostatic composition is made into paste or liniment.
9. the bone surface of a wound hemostatic composition any one of claim 1-6 is in human or animal's bone surface of a wound hemostatic article is prepared
Application.
10. application according to claim 9, it is characterized in that：The bone wound institute shape that the bone surface of a wound causes for a variety of causes
Into the surface of a wound.
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| CN201710309890.8A Active CN107158452B (en) | 2017-05-05 | 2017-05-05 | Bone wound hemostatic composition and preparation method and application thereof |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107715167A (en) * | 2017-09-19 | 2018-02-23 | 中国人民武装警察部队后勤学院 | Chitosan-based hemostatic paste and preparation method as bone wax substitute |
| CN110464869A (en) * | 2019-07-29 | 2019-11-19 | 亳州市新健康科技有限公司 | A kind of preparation method and applications from thickening bone surface of a wound hemostasis gel |
| CN111068101A (en) * | 2019-12-16 | 2020-04-28 | 天新福（北京）医疗器材股份有限公司 | Material for preparing absorbable biological repair bone wax, method and application |
| CN111317858A (en) * | 2018-12-17 | 2020-06-23 | 北京化工大学 | Degradable and absorbable bone hemostatic material and preparation method thereof |
| CN111317857A (en) * | 2018-12-17 | 2020-06-23 | 北京化工大学 | Degradable and absorbable bone hemostatic material containing chitosan and preparation method thereof |
| CN111921002A (en) * | 2020-08-06 | 2020-11-13 | 湖北联结生物材料有限公司 | Antibacterial osteogenesis-promoting absorbable bone wax and preparation method thereof |
| CN114470307A (en) * | 2022-04-06 | 2022-05-13 | 天新福（北京）医疗器材股份有限公司 | Degradable hemostatic plugging adhesive and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101444635A (en) * | 2009-01-05 | 2009-06-03 | 北京化工大学 | Degradable bone lacuna inside haemostatic material and preparation method thereof |
| CN101524543A (en) * | 2008-03-07 | 2009-09-09 | 大连永兴生物医药孵化器有限公司 | Hemostatic gel film agent |
| CN102727930A (en) * | 2011-04-01 | 2012-10-17 | 广州奥托沙医药科技有限公司 | Medical absorbable skeletal wound hemostatic material and preparation method thereof |
| WO2014165253A1 (en) * | 2013-03-12 | 2014-10-09 | Nbip, Llc | Compositions and methods for preventing infection of a wound and for advancing the healing process |
| CN104857552A (en) * | 2015-05-18 | 2015-08-26 | 赵明 | Hemostasis patch and preparation method thereof |
| CN105749360A (en) * | 2016-03-28 | 2016-07-13 | 山东赛克赛斯药业科技有限公司 | Cornea protecting composition as well as preparation method and application thereof |
-
2017
- 2017-05-05 CN CN201710309890.8A patent/CN107158452B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101524543A (en) * | 2008-03-07 | 2009-09-09 | 大连永兴生物医药孵化器有限公司 | Hemostatic gel film agent |
| CN101444635A (en) * | 2009-01-05 | 2009-06-03 | 北京化工大学 | Degradable bone lacuna inside haemostatic material and preparation method thereof |
| CN102727930A (en) * | 2011-04-01 | 2012-10-17 | 广州奥托沙医药科技有限公司 | Medical absorbable skeletal wound hemostatic material and preparation method thereof |
| WO2014165253A1 (en) * | 2013-03-12 | 2014-10-09 | Nbip, Llc | Compositions and methods for preventing infection of a wound and for advancing the healing process |
| CN104857552A (en) * | 2015-05-18 | 2015-08-26 | 赵明 | Hemostasis patch and preparation method thereof |
| CN105749360A (en) * | 2016-03-28 | 2016-07-13 | 山东赛克赛斯药业科技有限公司 | Cornea protecting composition as well as preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 谢大福: "硫酸铁粉外用止血", 《辽宁畜牧兽医》 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107715167A (en) * | 2017-09-19 | 2018-02-23 | 中国人民武装警察部队后勤学院 | Chitosan-based hemostatic paste and preparation method as bone wax substitute |
| CN111317858A (en) * | 2018-12-17 | 2020-06-23 | 北京化工大学 | Degradable and absorbable bone hemostatic material and preparation method thereof |
| CN111317857A (en) * | 2018-12-17 | 2020-06-23 | 北京化工大学 | Degradable and absorbable bone hemostatic material containing chitosan and preparation method thereof |
| CN110464869A (en) * | 2019-07-29 | 2019-11-19 | 亳州市新健康科技有限公司 | A kind of preparation method and applications from thickening bone surface of a wound hemostasis gel |
| CN110464869B (en) * | 2019-07-29 | 2021-11-19 | 亳州市新健康科技有限公司 | Preparation method and application of self-thickening bone wound hemostasis gel |
| CN111068101A (en) * | 2019-12-16 | 2020-04-28 | 天新福（北京）医疗器材股份有限公司 | Material for preparing absorbable biological repair bone wax, method and application |
| CN111068101B (en) * | 2019-12-16 | 2021-10-26 | 天新福（北京）医疗器材股份有限公司 | Material for preparing absorbable biological repair bone wax, method and application |
| CN111921002A (en) * | 2020-08-06 | 2020-11-13 | 湖北联结生物材料有限公司 | Antibacterial osteogenesis-promoting absorbable bone wax and preparation method thereof |
| CN114470307A (en) * | 2022-04-06 | 2022-05-13 | 天新福（北京）医疗器材股份有限公司 | Degradable hemostatic plugging adhesive and preparation method thereof |
| CN114470307B (en) * | 2022-04-06 | 2022-06-24 | 天新福（北京）医疗器材股份有限公司 | Degradable hemostatic plugging adhesive and preparation method thereof |
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