WO2009018764A1 - Matériau hémostatique à base d'amidon modifié résorbable et son procédé de préparation - Google Patents

Matériau hémostatique à base d'amidon modifié résorbable et son procédé de préparation Download PDF

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Publication number
WO2009018764A1
WO2009018764A1 PCT/CN2008/071849 CN2008071849W WO2009018764A1 WO 2009018764 A1 WO2009018764 A1 WO 2009018764A1 CN 2008071849 W CN2008071849 W CN 2008071849W WO 2009018764 A1 WO2009018764 A1 WO 2009018764A1
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modified starch
starch
hemostatic material
etherified
material according
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PCT/CN2008/071849
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English (en)
Chinese (zh)
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Xin Ji
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Xin Ji
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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
    • A61L24/08—Polysaccharides
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L3/00—Compositions of starch, amylose or amylopectin or of their derivatives or degradation products
    • C08L3/04—Starch derivatives, e.g. crosslinked derivatives
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L3/00—Compositions of starch, amylose or amylopectin or of their derivatives or degradation products
    • C08L3/04—Starch derivatives, e.g. crosslinked derivatives
    • C08L3/08—Ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/04—Materials for stopping bleeding
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L2205/00—Polymer mixtures characterised by other features
    • C08L2205/02—Polymer mixtures characterised by other features containing two or more polymers of the same C08L -group

Definitions

  • the invention relates to a modified starch absorbable hemostatic material and a preparation method thereof, in particular to a modified starch hemostatic material which is directly sprayed on a blood wound surface of a human or a mammal for hemostasis and can be absorbed by the human body.
  • the modified starch absorbable hemostatic material is biocompatible and can further be used as one of a surgical anti-adhesion material, a tissue healing material, a surgical sealant, and a wound-free tissue glue.
  • Gelatin sponge is derived from the extract of animal tissues, and its main component is animal collagen. Its hydrophilic and porous structure absorbs moisture from the blood and concentrates the blood to achieve hemostasis.
  • gelatin is a collagen extract derived from animals, containing heterologous proteins, which may cause allergic reactions, and may cause symptoms such as fever in patients.
  • the absorption of gelatin sponge by the human body is slow, generally about 4 weeks, so it will increase. The infection rate of the wound.
  • Collagen sponges are also derived from animal collagen extracts. In addition to concentrating blood by absorbing water from the blood, it is also possible to promote coagulation by activating endogenous coagulation mechanisms.
  • the collagen sponge is derived from animals and is a heterologous protein; and the human body absorbs it slowly, clinically manifested as a complication of the patient's allergic reaction and wound infection, so the clinical use is greatly limited.
  • Oxidized Cel lulose ⁇ Oxidized regenerated cel lulose Oxidized cellulose is one type of cellulose derivative.
  • the hemostasis mechanism concentrates the blood by the characteristic of water absorption of the material and initiates the blood coagulation mechanism.
  • the acidic carboxyl group combines with hemoglobin Fe to produce acidic methemoglobin in the blood, forming a brown rubber block, sealing the end of the capillary and stopping bleeding.
  • Oxidized regenerated cellulose has the same hemostatic mechanism as oxidized cellulose.
  • the oxidized cellulose is artificially synthesized. Normal humans are relatively slow to absorb this type of product due to the lack of enzymes that metabolize cellulose oxide, typically 3 to 6 weeks. It can cause local infection and affect local tissue healing.
  • the experimental results by Nagamatsu suggest that the acidity of oxidized cellulose may cause nerve fiber variability, and the large amount of oxidized cellulose used for peripheral nerves should be avoided.
  • Oxidized cellulose has a strong water absorption. In the bone cavity and the skull, due to the absorption of blood, volume expansion can cause nerve compression symptoms, and clinical application is also limited.
  • Fibrin glue is composed of fibrinogen, thrombin, aprotinin and calcium chloride. Hemostasis is mainly caused by thrombin-activated fibrinogen replication in the third phase of coagulation.
  • the fibrin sealant is a widely used clinical application, and it is a spray device for fibrinogen binding to thrombin. Before use, a nurse needs to dissolve fibrinogen and thrombin separately under the surgery table. It takes about several minutes. When it is difficult to dissolve the product, it needs to be heated in a water bath. After the dissolution, the spray device should be assembled. It takes time and effort, and cannot be used in a timely manner in the case of sudden emergency surgery.
  • fibrin glue is derived from human or animal, it is limited because of its limited source and high cost.
  • fibrin derived from human, bovine or pig is easily caused by foreign body/species protein. Allergic reactions and the occurrence of animal-borne infections.
  • adhesion of fibrin glue to wet tissue wounds is weak, and active bleeding cannot be effectively controlled.
  • the natural biopolysaccharide products currently used for hemostasis are plant polysaccharides and chitosan. They are biocompatible, non-toxic, non-irritating, and are not susceptible to allergic reactions in the body, and they do not cause infections of animal-borne diseases.
  • the chitosan/chitin product is representative of a high-expansion chitosan sponge, which is made from natural marine biological extract chitosan and advanced bioengineering technology. Chitosan has good water absorption, can initiate and accelerate the initiation of its own coagulation mechanism and promote coagulation, so it can be used as a topical hemostatic agent. However, due to the lack of enzymes in the human body that rapidly and efficiently degrade it, it is not yet available for use in surgery. At present, there is no report at home and abroad that it is used as a class III hemostatic material for hemostasis in clinical surgery. Patent Application No. 200480023477. 6 (International Application No.
  • PCT/US2004/019043 provides a hemostatic material formed by depositing microporous polysaccharide microspheres onto chitosan, both of which are hydrophilic and biodegradable. It has similar biocompatibility and hemostatic mechanism, and combines to produce a hemostatic material that is superior to chitosan itself. However, this method cannot be realized in the body or deep in the body cavity because it is subjected to chitosan as a fiber, a puff, a non-woven fabric or the like.
  • MPH Microporous Polysaccharide Hemospheres
  • MK1 produces a fast and powerful blood clot by shrinking the blood. Significantly reduce the time spent on bleeding during surgery. Because it can be catabolized by amylase in the human body, it will be completely decomposed in 7-14 days after surgery, and will not cause complications in the surgical area.
  • Ari staTM absorbable hemostatic material is prepared by reacting starch with epichlorohydrin. The hydroxyl group-containing epichlorohydrin reacts with starch molecules to form ethyl glycerol, which can crosslink starch molecules into a three-dimensional network structure.
  • Ari staTM hemostatic material is arguably one of the most effective hemostatic powders available today, but it still has some problems.
  • this hemostatic material is mainly limited to the skin or soft group. Hemostasis of woven wounds, hemostasis in the deep tissues of the body cavity, especially endoscopic hemostasis (such as gastroscope, colonoscopy and laparoscopy), there is still no effective means;
  • Epichlorohydrin is a colorless oily liquid with irritating odors like ether and chloroform. It is toxic and narcotic, so it is unfavorable to environmental protection and has high production cost.
  • Starch is a kind of dextran, generally insoluble in water, does not absorb water or absorb water at normal temperature, natural starch is in
  • the original starch is processed to treat the molecules to be isomerized, and new chemical and physical properties are obtained, which become modified starch.
  • the starch is classified according to the source, including potato starch, corn starch, etc., and contains amylose and amylopectin, and has a particle size of 1 to 100 Mm and an average diameter of 15 to 30 Mm.
  • the natural raw starch is in the form of powder. Due to the small particles and light particles, it is often floating on the surface of the bleeding blood when sprayed on the bleeding wound surface. In the case of blood, the modified starch self-agglomerates and is not easy to penetrate into the bleeding site, especially for the activity. Bleeding, it is difficult to achieve the purpose of stopping bleeding. Summary of the invention
  • the technical problem to be solved by the invention is to provide a modified starch absorbable hemostatic material, which directly acts on a blood wound, including hemostasis on tissues, organs in the body surface, body and body cavity, rapid hemostasis, absorption for the human body, and Has a sticky plugging effect.
  • a further technical problem to be solved by the present invention is to provide a modified starch absorbable hemostatic material which is also useful as a biocompatible anti-tissue tissue adhesion material, a tissue healing material, a surgical sealant and a wound-free tissue glue.
  • a further technical problem to be solved by the present invention is to achieve the above object by selecting different denaturation methods and processes for starch.
  • the technical solution adopted by the present invention to solve the above technical problems is: a modified starch absorbable hemostatic material, wherein the hemostatic material is etherified modified starch, or combined denaturation of etherification and crosslinking, etherification and esterification Starch, molecular weight is 15,000 ⁇ 2,000,000, particle size is 10 ⁇ 1000Mm, 37 °C, 6.67% starch solution viscosity is 30 ⁇ 557. 9mPa ⁇ s, when the modified starch is saturated with water at room temperature The viscous work is 60 to 100 g ⁇ mm.
  • the modified starch granules preferably have a particle diameter of 30 to 500 Mm, and the starch granules having a particle diameter of 30 to 500 Mm account for not less than 95% of the total starch granules.
  • modified starch granules are further preferably 50 to 250 Mm in particle diameter.
  • the modified starch granules of the above-mentioned particle size range of the present invention have a high penetration rate and an increased water absorption rate when applied to a bleeding wound, and the hemostatic effect is remarkably improved, especially in the case of active bleeding.
  • the modified starch comprises carboxymethyl starch, which is a linear structural polymer, and has the following structural formula:
  • the carboxymethyl starch is an etherified modified starch.
  • the modified starch comprises hydroxyethyl starch and is a linear structural polymer.
  • the hydroxyethyl starch is an etherified modified starch.
  • Both carboxymethyl starch and hydroxyethyl starch are clinically widely used plasma substitutes with good biocompatibility and safety.
  • the hemostatic material of the present invention can be broadened to other plasma substitutes, Known properties make a safe and reliable hemostatic material.
  • the modified starch hemostatic material is a blood cell or a hemostatic powder.
  • the invention provides a preparation method of the modified starch absorbable hemostatic material, wherein the modified starch is made from an etherified modified starch raw material, or a composite modified starch raw material which is etherified and crosslinked, etherified and esterified. After condensing, pelletizing, sieving, the molecular weight is 15,000 ⁇ 2, 000, 000, the particle size is 10 ⁇ 100OMm, 37 °C, 6.67% starch solution viscosity is 30 ⁇ 557. 9mPa ⁇ s The viscosity work when the modified starch is saturated with water at room temperature is 60 ⁇ 100g ⁇ Let.
  • the agglomeration and pelletization are carried out by placing the modified starch raw material in a boiling machine, adding steamed water, and forming the pellet at 40 to 50 °C.
  • the specific process is as follows: The raw material is in an annular fluidized state in the container, and is preheated and mixed by the purified heated air, and the steamed water is atomized and sprayed, so that several particles are accumulated into a pellet containing steamed water. As the hot air continuously dries the material, the water in the pellets evaporates and solidifies. This process is repeated to form ideal, uniform spherical particles.
  • the granules are formed into a film or layer and attached to the fiber fabric.
  • the modified starch of the present invention may have various hemostasis modes, and the powder may be sprayed directly on the blood wound surface, and may be sprayed on the blood wound surface or formed into a film-like or layered product.
  • the fiber fabric as the inner surface of the band-aid, direct compression on the blood-stained surface to stop bleeding.
  • the invention provides a use of the modified starch absorbable hemostatic material for hemostasis of blood wounds of humans, mammals, birds and reptiles.
  • the invention is further applied to the human body surface, the tissues and organs in the body and the blood tissue wounds in the tissues or organs in the body cavity, or used for surgery, trauma first aid, laryngoscope, endoscope, endoscopic hemostasis.
  • the etherified modified starch hemostatic material also includes cationic starch.
  • the etherified, crosslinked composite modified starch hemostatic material comprises cross-linked carboxymethyl starch.
  • the invention further provides a modified starch biocompatible hemostatic material, wherein the hemostatic material is etherified modified starch, or etherified, crosslinked composite modified starch, or compound denaturation of etherification, cross-linking, esterification
  • the hemostatic material is etherified modified starch, or etherified, crosslinked composite modified starch, or compound denaturation of etherification, cross-linking, esterification
  • One or two or more compositions of starch having a molecular weight of 15,000 to 10, 000, 000, granules
  • the particle size is 10 to 1000 Mm
  • the water absorption ratio of the modified starch hemostatic material is 1 to 100 times.
  • the so-called absorbable hemostatic material is a biocompatible hemostatic material that can be absorbed by body tissues.
  • the enzyme in the blood-scarred tissue cells including amylase and carbohydrase, is degraded and converted into a small molecule compound. , such as monosaccharide, absorbed by the body.
  • the absorbable hemostatic material is a kind of biocompatible hemostatic material, which is used in the surgical wounds of human body after being disinfected, and the Chinese Food and Drug Administration classifies it as an I I class medical device.
  • Biocompatibility is generally considered to be a local compatibility between the material and the tissue, ie the material does not cause local tissue reactions.
  • Biocompatible hemostatic material means that the hemostatic material used for blood wounds does not cause local tissue reaction, including non-toxicity, no mucosal irritation, no genotoxicity, no allergic or other immune reaction, no damage to blood cells, etc. .
  • human or other mammals are mainly studied.
  • the modified starch biocompatible hemostatic material preferably has a particle size of 30 to 500 Mffl, and the starch granules having a particle diameter of 30 to 500 Mm account for not less than 95% of the total starch granules. More preferably, it is 50 to 500 Mm.
  • the etherified modified starch comprises at least one of carboxymethyl starch, hydroxyethyl starch, and cationic starch.
  • Carboxymethyl starch and hydroxyethyl starch are clinically widely used plasma substitutes with good biocompatibility and safety.
  • the hemostatic material of the present invention can be broadened to other plasma substitutes to produce a safe and reliable hemostatic material using its generally known properties.
  • Cationic starch in modified starch is used as a hemostatic material. In addition to its water absorption, it is used to attract negatively charged red blood cells to interact with it, thereby accelerating the process of coagulation.
  • the positively charged modified starch adheres tightly to the tissue after contact with the blood, and closes the wound, thereby quickly stopping bleeding.
  • the cationic starch can be used alone as a hemostatic material, or it can be mixed with other modified starches as a hemostatic material.
  • the etherified, crosslinked composite modified starch comprises crosslinked carboxymethyl starch.
  • the modified starch biocompatible hemostatic material may comprise two or more modified starches, according to The requirements for the physical and chemical properties of the hemostatic material may be 99:1 to 1:99 by weight of the two modified starches. These may include: 95: 5, 90: 10, 85: 15, 80: 20, 75: 25, 70: 30, 65: 35, 60: 40, 55: 45, 50: 50.
  • Modified starch biocompatible hemostatic material products including modified starch hemostatic powder, modified starch hemostatic granules, modified starch hemostatic cells, modified starch hemostatic aerosols and aerosols.
  • the modified starch biocompatible hemostatic material is prepared from a modified starch raw material, or an etherified and crosslinked composite modified starch raw material by coagulation, pelletizing and sieving, and has a molecular weight of 15,000 to 10,000,000.
  • the particle size is from 10 to 1000 Mm.
  • the modified starch granules are formed into a film or layer and adhered to the fiber fabric.
  • modified starch absorbable hemostatic material is a hemostatic material for hemostasis of blood wounds in humans, mammals, birds, and reptiles.
  • the modified starch biocompatible hemostatic material of the present invention has an effect of preventing postoperative tissue adhesion and promoting wound tissue healing.
  • the modified starch hemostatic material of the present invention can also be used as Biocompatible anti-adhesion materials after surgery, promote the use of tissue healing materials.
  • the modified starch hemostatic material of the invention is used as a biocompatible surgical sealant and a wound-free tissue glue for treatment in surgery, trauma, first aid, etc. Both are of great significance.
  • Surgical sealant refers to a biological material used to prevent leakage of gas or liquid after surgery in the lungs, liver, brain, gastrointestinal tract, and cardiovascular surgery.
  • the leakage of liquid and gas after surgery is a common complication after surgery, and the modified starch of the present invention is used as a surgical sealant in the tissue around the surgical suture and the retention tube, which can form a mechanical barrier to "plug" the wound, reducing Or prevent leakage of gas or liquid.
  • the sealant is gradually absorbed and absorbed by the body.
  • the method for using the modified starch biocompatible hemostatic material described above is used for human body surface, tissues and organs or tissues or organs in the body cavity, including skin, subcutaneous soft tissue, muscle tissue, bone tissue, brain tissue, nerve tissue, liver, One or more combinations of organ tissues such as kidneys, spleen, or anti-adhesion materials for surgery, tissue healing materials, surgical sealants, and wound-free tissue glue.
  • the modified starch biocompatible hemostatic material according to the present invention is a composite modified starch which is obtained by denaturation of the original starch into etherified starch, or etherification and crosslinking, and the denaturation method includes one or more chemical denaturation, enzyme treatment One of denaturation, one of natural denaturation, or multiple denaturation of one method, or a composite denaturation of at least two methods.
  • the denaturation mechanism of the modified starch is: The starch molecular chain is cut, rearranged or introduced into other chemical groups to change its structure, and the denatured starch has superior performance to the original starch.
  • a modified starch absorbable hemostatic material of the present invention which is used as a hemostatic material, comprises:
  • the modified starch is a modified starch which is denatured to dissolve or swell in water to form a viscous gel or viscous liquid.
  • the mechanism further includes: the modified starch is a modified starch having a hydrophilic group which is denatured.
  • the water-absorbing, water-absorbing and highly viscous modified starch acts on the bleeding wound, it can quickly absorb the moisture in the blood and concentrate the blood. At the same time, the gelled mixture formed with blood and plasma adheres to the bleeding wound, mechanically sealed. Block damaged blood vessels and wounds to achieve hemostasis.
  • the chemical denaturation is at least one chemical denaturation by a chemical reagent, including esterification, etherification, and cross-linking denaturation.
  • the starch By reacting the functional group of the starch glucose unit with a chemical reagent, for example, by carboxylation modification, hydroxylation modification, the starch has a hydrophilic group, and the biogenic or polyfunctional reagent can form an original starch macromolecule.
  • the crosslinked body, or, by grafting, obtains a hydrophilic group of a macromolecule, thereby increasing the water absorption property of the starch and increasing the viscosity.
  • the viscosity of the modified starch is related to the type of the original starch, the degree of substitution, and the functional groups on the cross-linking or grafting.
  • the water absorption of the modified starch and the viscosity after water absorption make the starch-coagulation mixture formed after contact with blood.
  • the composition "has a high viscosity, or the formed clotting mixture acts on the functional groups of the tissue protein to cause the "starch-coagulation mixture” to adhere to the damaged wound tissue to achieve hemostasis and blocking.
  • the modified starch biocompatible hemostatic material of the present invention can be used for hemostasis in surgery or bone tissue damage caused by trauma, particularly hemostasis in the cancellous part of the bone.
  • some patients such as children, the elderly, osteoporosis patients, open thoracic, craniotomy, bleeding in the sternum and skull section is difficult to control, clinically used bone wax (B0NEWAX) on the sternum, skull section, but bone Wax is not easy to absorb, and it is easy to cause complications such as nonunion and infection.
  • the modified starch biocompatible hemostatic material of the invention can replace the bone wax, and utilizes the characteristics of water absorption, good viscosity and good shape to perform hemostasis and mechanical closure and sealing of the fracture or the bone section formed by the operation. After that, it can be quickly metabolized and degraded, avoiding the medical problem of using bone wax to cause complications such as nonunion and infection.
  • the mechanism of action of the present invention as a material for absorbable tissue adhesion prevention can be achieved by reducing local bleeding, exudation, and mechanically isolating wounds or wounds from adjacent tissue organs such as the peritoneum to prevent wound tissue or The purpose of adhesion of organs to other tissues or organs around them.
  • the mechanism of action of the present invention as a material for promoting tissue healing is: by adopting an appropriate operation method and applying an appropriate amount to an organ such as skin, subcutaneous soft tissue, muscle tissue, bone tissue, brain tissue, nerve tissue, liver, kidney, spleen, etc. Damaged tissue can have a role in promoting healing.
  • the wound in a large area burn patient can be used as a "stent" for skin tissue growth to promote the healing of skin tissue; bone growth and crawling can be used as a bone defect caused by trauma, bone tumor resection, etc.
  • the "scaffold” helps the bone tissue to heal and grow; it can be used as a "stent” for brain tissue growth and crawling in the brain tissue caused by brain trauma and brain tumor resection, and help the brain tissue cells to grow.
  • the mechanism of action of the present invention as a biocompatible surgical sealant is that a protective colloid or membrane can be formed on the wound or wound surface to seal blood, tissue fluid, lymph fluid, cerebrospinal fluid, bile, gastric juice caused by surgery, trauma, and the like. , the exudation of intestinal fluid, thereby preventing lymphatic fistula, biliary fistula, pleural effusion, intestinal fistula, cerebrospinal fluid spasm, vasospasm and the like.
  • the mechanism of action of the present invention as a biocompatible wound-free tissue glue is that the damaged nerve tissue, muscle tissue, bone tissue, skin, subcutaneous tissue, organ, etc. can be bonded, repaired, repaired, or It is bonded to his medical materials in tissues, organs and their wounds that need to be repaired.
  • the modified starch hemostatic material of the invention reduces wound bleeding, oozing blood, exudation of tissue fluid and keeping the wound or wound relatively moist or dry during hemostasis, thereby inhibiting bacterial growth and inflammatory reaction, and contributing to local anti-inflammatory of wound , reduce the pain of the patient.
  • a known antibiotic or other anti-inflammatory agent may be added to the material to prepare an anti-inflammatory hemostatic composite material for body surface use and body use.
  • the modified starch material of the present invention may be sterilized after packaging, and the sterilization methods include, but are not limited to, Y-ray irradiation sterilization, ethylene oxide sterilization, and ozone sterilization.
  • U.S. Patent No. 6060461-Microporous Polysaccharide it is also a biocompatible hemostatic material which can be formed by cross-linking of starch with epichlorohydrin and can be absorbed in vivo.
  • the mechanism is: Since the hemostatic material has micropores on the surface or inside, the micropores act as molecular sieves, and the size of the pores can determine that small molecules such as water molecules can enter the interior of the particles, and macromolecules such as red blood cells, platelets, and fibrin. It is then blocked on the surface of the particles to promote coagulation.
  • microporous polysaccharides of this patent are made by a special process and are not disclosed in the patent.
  • ordinary modified starches including cross-linked modified starch, in most cases, this is not the case.
  • Microporous structure In the present invention, it is not necessary to utilize the microporous property of the modified starch as the molecular sieve to achieve the purpose of hemostasis.
  • the present invention has a hydrophilic group by denaturation of the original starch, and directly hydrates with the water molecule, thereby achieving concentration. The effect of blood, promoting blood clotting, rather than the presence or absence of micropores on the surface of the modified starch.
  • the present invention improves the water absorption of the starch and the viscosity after water absorption by selecting or changing the degree of substitution, selecting the ratio of amylopectin to amylose content, and changing the functional group, so that the modified starch forms a starch after contact with blood.
  • a "viscous gel" of the blood mixture that adheres to the tissue and mechanically blocks the blood Tube breaks and wounds which are not mentioned in the microporous polysaccharides of the US6060461 patent, are also a major feature of the present invention over conventional hemostatic materials.
  • modified starch is made into a hemostatic powder, and the hemostatic particles have a microporous structure on the surface of the starch, and the hemostatic effect of the hemostatic material is related to the characteristics of the modified starch from which they are made.
  • the absorbable modified starch of the invention directly acts on the blood wound surface, can be directly sprayed or formed into a film-like external application to the blood wound surface, and immediately stops bleeding, and the water absorption rate is several times that of the existing hemostatic material AristaTM, and the speed of water absorption Also significantly improved.
  • the modified starch of the present invention has greater viscosity and stronger viscosity than the similar products, and can further block the damaged tissue and blood vessels while stopping bleeding, thereby significantly improving the hemostatic effect.
  • the selected carboxymethyl starch and hydroxyethyl starch raw materials are widely used in the medical industry at home and abroad, with high safety and good biocompatibility. Therefore, the products have reliable safety and clinical promotion value.
  • Another advantage of the present invention is that: since the modified starch material of the present invention is easily swelled or dissolved in water, the wound can be washed with a liquid such as physiological saline after the purpose of hemostasis, and the modified starch hemostatic material which is not involved in hemostasis can be easily used. It is washed away by water, sucked away by suction device or wiped off with auxiliary materials to reduce residual in the body, facilitate rapid metabolism and absorption, reduce foreign body reaction and facilitate wound healing.
  • the hemostatic agent When debridement treatment is carried out after war wounds, self-rescue, and emergency treatment, the hemostatic agent can be easily removed, even if a small amount of modified starch hemostatic material remains, it can be absorbed by the body, avoiding the damage caused to the patient and the wounded by tearing gauze and bandage. pain.
  • the modified starch hemostatic material is also stable, not easy to decompose, has a long shelf life, is easy to store, is resistant to high pressure, low pressure, high temperature resistance (up to 60 ° C or higher), low temperature resistance (up to -40 ° C or less), and is not easy to change physical and chemical properties. It can be used as an army, firefighters, ambulances, and homes, especially as a hemostatic material in extreme conditions such as cold, hot areas and deserts, Antarctica, Arctic, high mountains, space, and underwater.
  • Figure 1 is a comparison of the water absorption ratios of 66# and Ari staTM.
  • Figure 2 is a comparison of the water absorption speed of 66# and Ari staTM.
  • Figure 3 is a comparison of the water saturation ratio of 66# and Ari staTM.
  • Figure 4 is a comparison of the viscous work of 66#, 88# and Ari staTM.
  • Figure 5 is a comparison of the viscosity of 66#, 88# and Ari staTM.
  • Figure 6 is a graph showing the hemostatic effect of a rabbit liver hemorrhage positive control group (Ari staTM).
  • Figure 7 is a graph showing the hemostatic effect of the rabbit liver hemorrhage 66# product group.
  • Figure 8 is a graph showing the hemostatic effect of a rabbit liver hepatic negative control group (original starch).
  • Figure 9 is a graph showing the intra-abdominal adhesion of mice in 24 hours.
  • Figure 10 is a graph showing the intraperitoneal degradation of mice in 24 hours.
  • Figure 11 is a graph showing the subcutaneous degradation of the 66# product group in 12 hours.
  • Figure 12 is a graph showing the subcutaneous degradation of the rats in the positive control group (Ari staTM) for 12 hours.
  • Figure 13 is a graph showing the subcutaneous degradation of the negative control group (original starch) in 12 hours.
  • Figure 14 is a graph showing the subcutaneous degradation of the negative control group (original starch) in 24 hours.
  • Figure 15 is a graph showing the adhesion effect of a rat intestinal adhesion control group.
  • Figure 16 is a graph showing the effect of rat intestinal adhesion 66# anti-adhesion.
  • Figure 17 is a graph showing the anti-adhesion effect of rat intestinal adhesion sodium hyaluronate. detailed description
  • a modified starch absorbable hemostatic material comprising carboxymethyl starch, which is obtained by etherification denaturation of original starch (potato starch) into a carboxymethyl starch, and the carboxymethyl starch raw material is placed in a boiling machine at 40 to 50 ° C Next, steamed water was added, and the hemostatic material 66# was prepared by coagulation, pelleting, and sieving (manufacturer Starch Medical Inc. batch number 070717, degree of substitution 2 to 4).
  • the molecular weight of the carboxymethyl starch 66# product is 15,000 ⁇ 2, 000, 000, particle size is 10 ⁇ 1000Mm, wherein the starch granules with a particle size of 30 ⁇ 500Mm account for not less than 95% of the total starch granules, further preferably the particle size is 50 ⁇ 250Mm, 37 °C, 6
  • the viscous work of the modified starch at room temperature is 68. lg ⁇ let.
  • a modified starch absorbable hemostatic material comprising hydroxyethyl starch, which is obtained by etherification and denaturation of raw starch (potato starch) into hydroxyethyl starch, and the hydroxyethyl starch raw material is placed in a boiling machine at 40 to 50 ° C Add steamed water, polymerize, pelletize, and sieve to make hemostatic material 88# (manufacturer Starch Medical Inc. batch number 071122).
  • the hydroxyethyl starch 88# product has a molecular weight of 15,000 to 2,000,000, and a particle size of 10 to 1000 Mm, wherein the starch granules having a particle diameter of 50 to 500 Mm account for not less than 95% of the total starch granules. 2g ⁇ mm ⁇
  • the viscosity of the modified starch is 75. 2g ⁇ mm when the temperature is saturated with water at 30 ° C.
  • the water absorption performance of the invention is measured by a capillary method measuring device, and water is injected into the acid burette so that the zero-scale liquid surface of the acid burette is flush with the lower end of the core funnel filter plate.
  • the filter paper was cut at a radius of 2.25 cm, weighed, placed in a sand core funnel, and completely in contact with the filter plate. Open the piston until the filter paper is completely absorbent. Adjust the acid burette to zero scale, weigh 0. lg powder, spread evenly on the filter paper, put it into the sand core funnel, start from the liquid level, every 20s, 40s, 60s, observe the liquid level drop distance, calculate the sample Water absorption speed and water absorption saturation per unit time.
  • Example 1 The water absorption properties of carboxymethyl starch 66# and Ari staTM (medafor, USA) in Example 1 of the present invention are shown in Table 1.
  • the water absorption ratio refers to the maximum amount of water that can be absorbed by the lg sample.
  • Water absorption ratio (ml/g) water absorption (ml) / sample amount (g).
  • FIG. 1 Please refer to FIG. 1 for the comparison of the water absorption ratio of 66# and AristaTM, and it can be seen from Table 1 that the carboxymethyl starch 66# of the present invention has a significant increase in water absorption ratio relative to Ari staTM, which is about Ari staTM. 3 times; the maximum water absorption rate within 10s of water absorption is nearly 4 times that of Ari staTM.
  • the water absorption saturation ratio refers to the ratio of the water absorption of the sample to its maximum water absorption capacity (ie, the absolute value of the water absorption ratio) for a certain period of time. It can also reflect the water absorption speed of the sample from one side.
  • the test method for the viscous property of the present invention employs a viscous work test using a texture analyzer (physical property tester), manufactured by Stable Micro System, and the product model is TA-XT plus.
  • the test condition is: at room temperature, the speed before the test: 0. 5mm / sec; the test speed: lmm / sec; the speed after the test is 10. Omm / sec; the stress: 100g; the return distance is 5.0 mm; the contact time is 10. Osec; Type: Automatic one 5g.
  • the viscous work index at 75 % saturation is 75. 2g sec, and the viscous work is 75. 2 g ⁇ mm.
  • the 25 % saturation represents the saturation of the sample at a maximum water absorption of 1/4.
  • the 50% saturation represents the saturation of the sample at a maximum water absorption capacity of 1/2.
  • 100% saturation represents the saturation of the sample at maximum water absorption capacity.
  • the viscosity performance test method of the present invention employs a viscometer (brookfi led Dv-2), rotor No. 3; a rotational speed of 60 rpm; a denatured starch solution concentration of 6.67 %, and a temperature of 37 °C.
  • FIG. 5 is a # 66, # 88 compared with FIG Ari sta TM viscosity, it can be seen by Table 3, # 66, # 88 a viscosity substantially greater than Ari sta TM.
  • a biocompatible modified starch for hemostasis comprising cross-linked carboxymethyl starch, which is obtained by etherification and cross-linking of original starch (potato starch) to form cross-linked carboxymethyl starch, cross-linked carboxymethyl starch raw material
  • the mixture was placed in a boiling machine at 40 to 50 ° C, distilled water was added, and the mixture was subjected to polymerization, pelleting, and sieving to prepare a cross-linked carboxymethyl starch hemostatic material 66#+ (manufacturer Starch Medical Inc. batch number 071108).
  • the crosslinked carboxymethyl starch 66#+ product has a molecular weight of 15,000 to 2,000,000 and a particle size of 10 to 1000 Mm, wherein the starch granules having a particle diameter of 50 to 500 Mm are not low in total starch granules. At 95%.
  • the water absorption ratio refers to the maximum amount of water that can be absorbed by the lg sample.
  • Water absorption ratio (ml/g) water absorption (ml) / sample amount (g).
  • both the prepared carboxymethyl starch 66# and the crosslinked carboxymethyl starch 66#+ modified starch have a preferred water absorption ratio.
  • a biocompatible modified starch for hemostasis comprising cationic starch, which is made into a cationic starch by etherification and denaturation of a raw starch, and the cationic starch raw material is placed in a boiling machine at 40 to 50 ° C, and steamed water is added. Polymerization, pelleting, sieving to form a cationic starch hemostatic material.
  • the molecular weight of the cationic starch product is 15, 000 ⁇ 10, 000, 000, particle size is 10 ⁇ 1000Mm, wherein the starch granules with a particle size of 50 ⁇ 500Mm account for not less than 95% of the total starch granules.
  • a modified starch absorbable hemostatic material including carboxymethyl starch, which is obtained by etherification and denaturation of raw starch (potato starch) into a carboxymethyl starch raw material (Shandong Liaocheng Ahua Pharmaceutical Co., Ltd.), which is a raw material of carboxymethyl starch
  • the mixture was placed in a boiling machine at 40 to 50 ° C, steamed water was added, and the mixture was condensed, pelletized, and sieved to prepare a carboxymethyl starch hemostatic material (manufacturer Starch Medical Inc. batch number 080118).
  • the carboxymethyl starch hemostatic material has a molecular weight of 15,000 to 2,000,000 and a particle size of 10 to 1000 Mm.
  • the viscosity is measured by a NH79 rotary viscometer, a No. 3 rotor, and a rotational speed of 60, 37 ° C.
  • the 2% starch solution has a viscosity of about 1800 cps (mPa ⁇ s). Control experiment 1
  • Test method 15 New Zealand white rabbits were randomly divided into 5 groups, which were divided into 66# product group (supplied by American SMI company), positive control group (Ari staTM) (medafor company, USA) and negative control group ( Raw starch - commercially available powder).
  • the New Zealand white rabbits were anesthetized with pentobarbital sodium ear veins (40 mg * kg-; after the fixed position, the hair was removed, disinfected, and the abdominal cavity was opened layer by layer, and the liver was fully exposed. The diameter of each liver surface was made by a puncher. , a wound of 0.3 cm depth, immediately spray the hemostatic material to stop bleeding, pressure For 20 seconds, observe the hemostatic effect of each group of animals.
  • Ari staTM and native starch were administered to the positive control group and the negative control material group, respectively.
  • the test animals were given free access to water and diet after surgery.
  • Each group of the test materials was anesthetized for one hour, one day, two days, three days, and seven days after the operation, and the liver wounds were stained with iodine to observe the degradation of the hemostatic material.
  • the wound tissue of the liver was removed, fixed with 10% formaldehyde, and tissue sections were taken to observe the degradation of the hemostatic material.
  • Observation index and observation time Observe the hemostasis of the drug sprayed on the wound surface, the absorption and degradation of the drug on the liver of the animal, and the recovery of the wound. The observation time was half an hour, one day, two days, three days, seven days after surgery.
  • the positive control group (Ari staTM) stopped bleeding immediately after spraying the hemostatic material; 66# product group stopped bleeding immediately after spraying the hemostatic material; the original starch sprayed the hemostatic material and could not stop bleeding after giving certain pressure. (See Figures 6 to 8)
  • Test method 66# product (supplied by SMI, USA), positive control Ari staTM (medafor, USA) and negative control raw starch were formulated with normal saline to form a solution of 0.1 g/ml. Thirty ICR mice were randomly divided into a product group of 66, a positive control group (Ari staTM) and a negative control group (original starch - commercially available glutinous rice flour). Each intraperitoneal injection of 1 ml of the corresponding solution, 24 hours later open the abdominal cavity, drip iodine, observe color changes and adhesions in the abdominal cavity. Ari staTM and native starch were administered to the positive control group and the negative control material group, respectively.
  • Test drug Name: 66# product (provided by SMI, USA)
  • Test method SD rats were randomly divided into 66# product group, positive control group (Ari S t a TM) (med a f 0 r company, USA) and negative control group (original starch - commercially available glutinous rice flour). Anesthetized with pentobarbital sodium (30 mg/kg), the skin was cut in the back and extremities of the animal, and the test material was sutured. Four rats were anesthetized to open the wound after 12 hours and 24 hours, and the adhesion was observed. The degradation of the hemostatic material was observed by iodine staining and photographed. Ari staTM and native starch were administered to the positive control group and the negative control material group, respectively.
  • Test purpose Observe the degradation of 66# product in vitro.
  • Test method Positive material Ari staTM (medafor, USA), 66# product (supplied by American SMI company) and negative control (original starch - commercially available tantalum powder), each weighing 100 mg into a test tube, adding 37U a -amylase And 240U saccharification enzyme, add physiological saline to 10ml, 37. 5 ° C water bath, respectively, at each time point with glucose kit (Shanghai Fosun Long March Medical Science Co., Ltd., batch number: P070321) test the glucose content in the tube.
  • Test purpose To observe the hemostatic effect of 66# and 88# products under severe trauma, and to test the hemostatic effects of modified physical starches 66# and 88# and Ari staTM with different physical characteristics.
  • Test animals Test dogs.
  • Test method Dogs were randomly divided into control group (gauze press), 66# product group, 88# product group and Ari staTM group. Expose the femoral artery, use a 18-gauge needle to pierce the exposed femoral artery, see arterial blood self-piercing The hole is ejected, allowing it to bleed freely for 2 seconds. The femoral artery injury model was established, and immediately sprayed at the bleeding point with Ali staTM, 66# and 88# of lg, and manually pressed, and the control group was pressed with gauze. Then, the hemostasis was observed at 60 seconds, 90 seconds, 120 seconds, and 180 seconds after the compression, and the bleeding was stopped after the bleeding was stopped by the fistula, and the number of successful hemostasis was recorded.
  • the hemostasis of the femoral artery hemorrhage in the 66# group, 88# group and Ari staTM group was significantly hemostatic compared with the control group.
  • the 66# group and the 88# group had better sealing effect on the femoral artery than the AristaTM group, and the hemostasis time was significantly shortened.
  • the viscous 88# group has an improved sealing effect on the femoral artery through the mouth of the 66# group, and the hemostasis time is shortened.
  • the hemorrhage clamp was used to pinch the corresponding abdominal wall, and the abdominal cavity was closed with a 1-0 silk thread.
  • Intestinal adhesions In the abdominal incision, the abdominal incision was used to cut the abdominal cavity with a bottom-down "U"-shaped incision, and then the abdominal wall flap was lifted up to expose the abdominal cavity, and the end of the cecum and the wound of the abdominal wall were observed.
  • the adhesion situation The degree of intestinal adhesion refers to the Nair grade 5 classification criteria: grade 0, no adhesion at all; grade 1, between the visceral or abdominal wall; grade 2, between the internal organs or between the visceral and abdominal wall; grade 3, more than two adhesions, The viscera does not directly adhere to the abdominal wall; at level 4, the viscera directly adheres to the abdominal wall, regardless of the adhesion zone.
  • Table 7 Results of intestinal adhesion assessment in each group
  • Figure 15 for the adhesion effect of the rat intestinal adhesion control group
  • Figure 16 is the anti-adhesion effect diagram of the rat intestinal adhesion 66#
  • Figure 17 is the anti-adhesion effect diagram of the rat intestinal adhesion sodium hyaluronate. 7 results show that sodium hyaluronate, carboxymethyl starch 66 # can significantly reduce the degree of postoperative intestinal adhesion in rats.
  • Carboxymethyl starch 66# (supplied by SMI, USA), Arista hemostasis (medafor, USA), commercially available bone wax.
  • a sagittal incision with a length of about 4 cm in the center of the head exposes the skull and completely exfoliates the epithelium.
  • Two circular defect holes were drilled on both sides of the midsole of the skull with a 6 mm diameter drill bit. The defect penetrated the whole layer of the parietal bone (the thickness of the parietal bone was basically the same), and did not cross the middle seam.
  • the defect was randomly assigned to cover one of 66#, Arista or bone wax, and the control group did not use any material.
  • periosteum and scalp were sutured with a 4-0 absorbable thread, aseptically wrapped and returned to the cage for 6 weeks.
  • the animal's ear vein was injected with calcein 20 mg/kg (Calcein, Sigma, 2% sodium bicarbonate); 1 day before sacrifice, the other side of the ear was injected with tetracycline 30 mg/kg.
  • Twisted fluorescent line spacing ( ⁇ ⁇ )
  • the sections were dewaxed, dehydrated, and transparent. Using Goldner-Mason-Trichrome and Ponceau staining, the bone-like and mineralized bone areas could be displayed in color, optical microscopy, photographing, and image analysis software to measure the area of each stained part. Defective bone type bone area
  • the indicators of bone healing are shown in Table 8.
  • Blank control group 2.14 ⁇ 0.84 2.02 ⁇ 0.34 12.02 ⁇ 4.32 6.23 ⁇ 2.34 76.21 ⁇ 19.35 66# 1.23 ⁇ 0.45* 3.86 ⁇ 1.19* 35.02 ⁇ 9.85* 28.25 ⁇ 9.35: 43.12 ⁇ 11.87* Arista 1.44 ⁇ 0.23* 3.62 ⁇ 0.98* 28.02 ⁇ 8.57* 32.23 ⁇ 9.30 : 38.34 ⁇ 14.32* bone wax 1.86 ⁇ 0.65 2.87 ⁇ 0.84* 22.02 ⁇ 6.32 16.23 ⁇ 6.86: 58.34 ⁇ 17.64
  • the group was significantly higher than the blank control group; the absent area ratio 66# and Arista group were significantly lower than the blank control group.

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Abstract

La présente invention concerne un matériau hémostatique à base d'amidon modifié résorbable et sa préparation, ledit matériau étant de l'amidon éthérifié ou un mélange d'un ou plusieurs amidons éthérifiés, amidons réticulés. L'amidon modifié a un poids moléculaire de 15 000 à 10 000 000, une taille de particule de 10 à 1 000 µm et un taux d'absorption de l'eau de 1 à 100. Le matériau hémostatique biocompatible peut avoir un effet direct sur la plaie avec du sang, concentrer rapidement le sang pour coaguler ce dernier ; en outre, le mélange en forme de gélatine formé avec le sang est très visqueux, ce qui peut obstruer le tissu lésé et le vaisseau sanguin. Le matériau hémostatique biocompatible est facile à faire gonfler dans l'eau et facile à laver de façon à réduire les résidus ; il est stable, difficile à décomposer et présente une longue durée de conservation et de vie. Le matériau hémostatique biocompatible peut également être utilisé comme un matériau chirurgical résorbable qui ne colle pas, favorisant le matériau de cicatrisation tissulaire, un agent de scellement chirurgical et un adhésif tissulaire sans jonction pour les plaies.
PCT/CN2008/071849 2007-08-09 2008-08-01 Matériau hémostatique à base d'amidon modifié résorbable et son procédé de préparation WO2009018764A1 (fr)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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WO2020167319A1 (fr) * 2019-02-15 2020-08-20 C.R.Bard, Inc. Article d'appareil de biopsie hémostatique
CN110132963A (zh) * 2019-04-26 2019-08-16 安徽省农业科学院烟草研究所 一种快速鉴定糯玉米种质的方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5853749A (en) * 1994-07-30 1998-12-29 Scimat Limited Gel wound dressing
CN1690083A (zh) * 2004-04-23 2005-11-02 郝庆阳 一种复合变性淀粉及其制备方法
CN101121041A (zh) * 2007-08-09 2008-02-13 美国淀粉医疗公司 变性淀粉可吸收性止血材料及其制备方法

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IN192791B (fr) * 1996-06-28 2004-05-22 Johnson & Johnson Medical
US20040265371A1 (en) * 2003-06-25 2004-12-30 Looney Dwayne Lee Hemostatic devices and methods of making same
CN100453122C (zh) * 2006-09-29 2009-01-21 沈晶 一种止血微粒及其制法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5853749A (en) * 1994-07-30 1998-12-29 Scimat Limited Gel wound dressing
CN1690083A (zh) * 2004-04-23 2005-11-02 郝庆阳 一种复合变性淀粉及其制备方法
CN101121041A (zh) * 2007-08-09 2008-02-13 美国淀粉医疗公司 变性淀粉可吸收性止血材料及其制备方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
QIN R.: "The Preparation and Application of Various Modified Starches", GUANGXI CHEMICAL INDUSTRY, vol. 23, no. 1, 1994, pages 23 - 24, 26 - 28, 33 - 34 *
ZHANG C. ET AL.: "The Preparation and Application Development of Chemical Modified Starches (part one)", SHANXI CHEMICAL INDUSTRY, no. 4, 1995, pages 7, 12 - 13 *
ZHANG C. ET AL.: "The Preparation and Application Development of Chemical Modified Starches (part two)", SHANXI CHEMICAL INDUSTRY, no. 2, 1996, pages 1 - 3, 7 - 8 *

Cited By (4)

* Cited by examiner, † Cited by third party
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CN103349791A (zh) * 2013-07-29 2013-10-16 广西信业生物技术有限公司 一种新型微孔医用止血材料及其制备方法
CN103349791B (zh) * 2013-07-29 2014-12-24 广西信业生物技术有限公司 一种新型微孔医用止血材料及其制备方法
CN113667706A (zh) * 2021-10-22 2021-11-19 中国人民解放军军事科学院军事医学研究院 载氨甲环酸交联多孔淀粉及其制备方法
CN113667706B (zh) * 2021-10-22 2022-02-18 中国人民解放军军事科学院军事医学研究院 载氨甲环酸交联多孔淀粉及其制备方法

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