CN114681659B - Composite styptic powder and preparation method and application thereof - Google Patents
Composite styptic powder and preparation method and application thereof Download PDFInfo
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Classifications
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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
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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
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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
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
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- Health & Medical Sciences (AREA)
- Surgery (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Materials Engineering (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention provides composite hemostatic powder and a preparation method and application thereof. The composite hemostatic powder comprises hemostatic particles derived from a fibrous material comprising a hydrophilic fibrous material; and the hemostatic particles have a tissue repair portion and a hemostatic portion, the fibrous material of the tissue repair portion and the fibrous material of the hemostatic portion being different. The composite hemostatic powder has good hemostatic effect, good fluidity and convenient use, can promote tissue repair, prevent wound surface adhesion and solve the problem of single function of the existing hemostatic powder material.
Description
Technical Field
The invention relates to the technical field of biomedical materials, in particular to composite hemostatic powder and a preparation method and application thereof.
Background
Biomedical materials are high and new technical materials developed in the last three decades, and hemostatic materials gradually attract attention of the medical field along with the increase of accidents such as traffic accidents, serious burns and scalds, and serious disasters. With the rapid development of modern science and technology, the research on the hemostatic materials has made a very rapid progress, various novel hemostatic materials are continuously appeared, and the performance is greatly improved. Currently, the commonly used topical hemostatic materials include fibrin glue, thrombin powder, gelatin sponge, collagen sponge, chitosan sponge, oxidized cellulose, microfibril collagen, alginic acid fiber, zeolite, cyanoacrylate, phyto-polysaccharide powder, and the like. Biomedical hemostatic materials with excellent hemostatic effect, convenient use, good biocompatibility and controllable degradation rate have become the main objects of attention and research of people.
The forms of the commonly used hemostatic materials include various forms, such as powder, e.g. freeze-dried thrombin powder, plant polysaccharide powder, zeolite powder, and microfibril collagen powder; of the solution type, such as cyanoacrylate, chitosan solutions; is liquid, but forms gel or colloid on wound surface, such as fibrin glue, glutaraldehyde-albumin Bioglue; film-shaped, such as chitosan film, polylactic acid film; and sponges such as collagen sponge, gelatin sponge, microfibrillar collagen sponge, fibrin patch, and the like. Hemostatic materials of various forms have their own advantages and their own advantages for use, and are selected primarily according to the type of wound and the clinical treatment modality.
In the prior art, a powdery hemostatic material is mainly polysaccharide microspheres or starch granules, and the surface of the material is microporous by technologies such as an ultrasonic method, a wet-heat method, a microwave method, a mechanical method or enzyme perforation, so that the specific surface area and the hydrophilic performance of the material are improved, the material plays a role of a molecular sieve on the surface of a wound, the concentration of a blood coagulation factor is improved by adsorbing water in blood, and the generation of a blood coagulation mechanism is accelerated, so that the hemostatic effect is realized. The existing hemostatic powder generally only has a single hemostatic function, however, in clinical use, as the hemostatic material is not taken out, the wound and peripheral tissues are easily stimulated in the degradation process, so that the problem of wound adhesion or poor healing after operation easily occurs.
At present, hemostatic powder materials with multiple functions are compounded, for example, patent ZL200910016401.5 discloses a microporous polysaccharide hemostatic powder compounded by starch polysaccharide and carboxymethyl chitosan, and patent CN106421878a discloses an antibacterial carboxylated starch-polylysine hemostatic powder, in both patents, because a cross-linking agent is needed in the preparation process of the hemostatic powder, the biocompatibility and safety of the product are affected finally because the cross-linking agent is usually difficult to remove or possible degradation products have potential toxicity.
Disclosure of Invention
Problems to be solved by the invention
In view of the technical problems in the prior art, for example: the invention provides a compound hemostatic powder, which is prepared by mixing a raw material, a matrix and a matrix, wherein the matrix is prepared from a porous material and a porous material. The composite hemostatic powder solves the problem of single function of the existing hemostatic powder, does not contain toxic and harmful substances, can achieve hemostasis, and has excellent functions of promoting tissue repair and preventing adhesion.
Furthermore, the invention also provides a preparation method of the composite hemostatic powder, the preparation method can tightly combine the hemostatic part and the tissue repair part, the layering is not easy to occur, no toxic or harmful substances are introduced in the preparation process, and the safety and the biocompatibility of the product are good. In addition, the preparation method has the advantages of simple steps, good operability, greatly shortened powder preparation time, low generated heat, capability of preventing the material from thermal degradation, high product yield and suitability for mass production.
Means for solving the problems
The invention provides composite hemostatic powder, wherein the composite hemostatic powder comprises hemostatic particles with the particle size of not more than 500 mu m, wherein,
the hemostatic particles are derived from a fibrous material comprising a hydrophilic fibrous material; and is
The hemostatic particles have a tissue repair portion and a hemostatic portion, the fibrous material of the tissue repair portion and the fibrous material of the hemostatic portion being different.
Further, the tap density of the composite hemostatic powder is not less than 0.6g/cm 3 Preferably 0.6 to 0.9g/cm 3 (ii) a And/or the angle of repose of the composite hemostatic powder is 1-10 degrees, preferably 2-8 degrees.
Further, the fiber materials on the surface and/or inside of the hemostatic particles are fused into a whole, and the surface and/or inside of the hemostatic particles do not have the fiber silk shape; and/or the hemostatic particles are prepared by laminating fiber layers made of fiber materials, then carrying out humidification treatment and compression molding, and then crushing.
Further, the content of the hemostatic particles with the particle size of less than 75 μm is 5-35 percent, preferably 5-15 percent, based on the total mass of the composite hemostatic powder; the content of the hemostatic particles with the particle size of 100-250 μm is not less than 40 percent, and preferably 60-80 percent.
Further, the fiber material of the tissue repair part comprises one or more of chitosan or derivative fiber thereof, alginic acid or derivative fiber thereof and silk fiber; the fiber material of the hemostatic part comprises cellulose or derivative fiber thereof; preferably, the hemostatic particles further comprise a bioactive material.
The invention also provides a preparation method of the composite hemostatic powder, which comprises the following steps:
preparing a tissue repair layer and a hemostasis layer by using a fiber material;
after the tissue repair layer and the hemostasis layer are laminated, humidifying the tissue repair layer and the hemostasis layer by using a solution, and then performing compression molding to obtain a composite fiber membrane, wherein the thickness of the composite fiber membrane is less than 500 mu m;
and crushing and screening the composite fiber membrane to obtain the composite hemostatic powder.
Furthermore, in the humidification treatment, the humidification amount accounts for 10-60%, preferably 20-50% of the total mass of the tissue repair layer and the hemostatic layer;
more preferably, the solution used for the humidification treatment is water or an aqueous solution containing a bioactive material; preferably, the bioactive material comprises one or a combination of two or more of a viscous polysaccharide, collagen, and a growth factor.
Further, the tissue repair layer or the hemostatic layer is not less than 1 layer respectively, and the single-layer gram weight ratio of the tissue repair layer or the hemostatic layer is 2-30 g/m 2 The fiber web of (1).
Further, the composite fiber film is obtained by rolling, hydraulic pressure or vertical pressing, and/or the density of the composite fiber film is not less than 1g/cm 3 。
The invention also provides a hemostatic product which comprises the composite hemostatic powder or the composite hemostatic powder prepared by the preparation method.
ADVANTAGEOUS EFFECTS OF INVENTION
The composite hemostatic powder has good hemostatic effect, good fluidity and convenient use, has the functions of promoting wound repair and preventing adhesion, and solves the problem of single function of the existing hemostatic powder material.
Furthermore, the preparation method of the composite hemostatic powder can ensure that the hemostatic part and the tissue repair part in the hemostatic particles are tightly combined, layering or peeling is not easy to occur, toxic and harmful substances are not introduced in the preparation process, and the safety and the biocompatibility of the product are good. In addition, the preparation method has the advantages of simple steps, good operability, greatly shortened powder preparation time, low generated heat, capability of preventing the material from thermal degradation, high product yield and suitability for mass production.
Drawings
Fig. 1 shows a schematic structure diagram of a hemostatic particle in the composite hemostatic powder of the present invention.
Detailed Description
The present invention will be described in detail below. The technical features described below are explained based on typical embodiments and specific examples of the present invention, but the present invention is not limited to these embodiments and specific examples. It should be noted that:
in the present specification, the numerical range represented by "numerical value a to numerical value B" means a range including an end point numerical value A, B.
In the present specification, "plurality" of "plural", and the like means a numerical value of 2 or more unless otherwise specified.
In the present specification, the term "substantially", "substantially" or "essentially" means that the error is less than 5%, or less than 3% or less than 1% compared to the relevant perfect or theoretical standard.
In the present specification, "%" denotes mass% unless otherwise specified.
In the present specification, the meaning of "may" includes both the meaning of performing a certain process and the meaning of not performing a certain process.
In this specification, "optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event occurs and instances where it does not.
Reference in the specification to "some specific/preferred embodiments," "other specific/preferred embodiments," "embodiments," and so forth, means that a particular element (e.g., feature, structure, property, and/or characteristic) described in connection with the embodiment is included in at least one embodiment described herein, and may or may not be present in other embodiments. In addition, it is to be understood that the described elements may be combined in any suitable manner in the various embodiments.
<First aspect>
The first aspect of the present invention provides a composite hemostatic powder comprising hemostatic particles having a particle diameter of not more than 500 μm, wherein,
the hemostatic particles are derived from a fibrous material comprising a hydrophilic fibrous material; and is
The hemostatic particles have a tissue repair portion and a hemostatic portion, the fibrous material of the tissue repair portion and the fibrous material of the hemostatic portion being different.
The composite hemostatic powder is multifunctional absorbable composite hemostatic powder, and has the advantages of proper particle size, good fluidity and good hemostatic effect. The composite hemostatic powder does not contain toxic and harmful substances, can achieve intraoperative hemostasis, and has excellent postoperative tissue or wound repair promoting and anti-adhesion effects.
As shown in fig. 1, the composite styptic powder of the present invention includes styptic particles. As can be seen in fig. 1, the hemostatic particles have a tissue repair portion and a hemostatic portion. In this case, the hydrophilic fibrous material on the surface and/or inside the hemostatic particles of the present invention has been fused together, i.e., there is no longer a boundary between fibers, and the fiber profile of the individual fibers disappears. Specifically, in the present invention, the composite hemostatic powder may include a plurality of hemostatic particles. The surface of the hemostatic particles of the present invention is smoother than the surface of prior art hemostatic particles, with only some of the hemostatic particles having an irregular structure due to cutting, grinding, etc.
Specifically, in the present invention, the composite hemostatic powder of the present invention may include a plurality of hemostatic particles, the composite hemostatic powder may be formed by stacking a plurality of hemostatic particles, and pores may be formed between the hemostatic particles and the hemostatic particles.
The particle size of the hemostatic particles is not more than 500 μm, specifically, the particle size of the hemostatic particles can be 50 μm to 500 μm, can be 100 μm to 450 μm, can be 150 μm to 400 μm, can be 200 μm to 350 μm, can be 250 μm to 300 μm, and the like; the proper particle size distribution is beneficial to hemostasis and can ensure that the product has high yield.
Specifically, in the present invention, the content of the hemostatic particles having a particle diameter of 75 μm or less is 5 to 35% based on the total mass of the composite hemostatic powder, for example: 8%, 10%, 12%, 15%, 18%, 20%, 22%, 25%, 18%, 30%, etc., preferably 5 to 15%. When the content of the hemostatic particles with the particle size of less than 75 microns is less than 5 percent, the proportion of the particles with the particle size of 400-500 microns is increased, and the tube is easily blocked when an auxiliary device is used; when the content of the hemostatic particles having a particle size of 75 μm or less is more than 35%, the hemostatic effect is poor.
Further, the content of the hemostatic particles with the particle size of 100-250 μm is not less than 40% by mass of the composite hemostatic powder, such as: 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, etc., preferably 60% to 80%. When the content of the hemostatic powder hemostatic particles having a particle size of 100 μm to 250 μm is less than 40%, the content of the hemostatic particles having a particle size of 75 μm or less is too large, for example, more than 35%, resulting in poor hemostatic effect.
In some specific embodiments, the gram weight ratio of the fibrous raw material of the tissue repair part and the fibrous raw material of the hemostatic part is not particularly limited, and may be set as needed. Specifically, the grammage ratio of the fiber material of the tissue repair portion and the fiber material of the hemostatic portion may be 1:9 to 9:1.
Further, in the present invention, the hemostatic particles are derived from a fibrous material, preferably a hydrophilic fibrous material. Specifically, the hemostatic particles of the present invention can be prepared by laminating fiber layers made of fiber materials, performing humidification treatment and compression molding, and pulverizing.
In some specific embodiments, the present invention may be achieved by preparing a tissue repair layer and a hemostatic layer from a fibrous material; after the tissue repair layer and the hemostasis layer are laminated, humidifying the tissue repair layer and the hemostasis layer by using a solution, and then pressing and forming to obtain a composite fiber membrane; and then the particles are crushed to prepare the hemostatic particles.
Specifically, the humidifying treatment is to humidify the fiber material by 10 to 60%, preferably 20 to 50%, and more preferably 30 to 50% of the mass of the fiber material; for example: 15%, 21%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, etc.; when the humidifying amount of the fiber material is 10-60% of the total mass of the tissue repair layer and the hemostatic layer, the hemostatic particles without the form of the fiber yarn can be prepared. When the humidification quantity is too low, the compression molding is not uniform, and the density is not uniform; when the amount of humidification is too high, molding is not good at the time of pressing, crushing is easy, and the density is hardly increased.
Further, the tap density of the composite hemostatic powder is not less than 0.6g/cm 3 Preferably 0.6 to 1.0g/cm 2 (ii) a For example: the tap density of the composite hemostatic powder can be 0.65g/cm 3 、0.7g/cm 3 、0.75g/cm 3 、0.8g/cm 3 、0.85g/cm 3 、0.95g/cm 3 、1g/cm 3 、1.05g/cm 3 And the like. The absorbable hemostatic powder has high tap density and good hemostatic effect.
In some specific embodiments, the angle of repose of the composite hemostatic powder is 1 to 10 °; preferably 2 to 8 °, more preferably 2 to 5 °, for example: 3 °,4 °,6 °, 7 °, 9 °, etc. The absorbable hemostatic powder has proper fluidity, is convenient for doctors to use powder spraying equipment in clinic, is beneficial to uniformly spray on wound surfaces, and has a quick hemostatic effect.
In some specific embodiments, the hemostatic particles of the present invention further comprise a bioactive material. The biological active material is used for further promoting the adhesion prevention and healing of the wound surface. Preferably, the bioactive material comprises one or a combination of two or more of a viscous polysaccharide, collagen, growth factor, and the like, and specifically, the viscous polysaccharide may be hyaluronic acid and derivatives thereof.
Further, in the present invention, the fiber material of the tissue repair part is derived from one or a combination of two or more of chitosan or a derivative fiber thereof, alginic acid or a derivative fiber thereof, and silk fiber.
As the chitosan or its derivative, there are included, but not limited to, substituted chitosan (e.g., carboxymethyl chitosan (also called carboxymethyl cellulose, CMC), hydroxypropyl chitosan (HPCS)), chitosan salts (e.g., chitosan hydrochloride, chitosan quaternary ammonium salt, chitosan lactate, chitosan glutamate, etc.), chitosan sulfate, chitosan oligosaccharide, hyaluronic acid-like chitosan, etc., and copolymers of the above chitosan as a grafting raw material, etc.
For alginic acid or derivatives thereof, it may be an alginate, such as sodium alginate, potassium alginate, and the like.
The present invention is not particularly limited to the fiber material of the hemostatic section, as long as it can produce the hemostatic particles of the present invention, and for example, oxidized regenerated fibers or non-oxidized regenerated fibers may be used. The oxidation mode of the oxidized regenerated fiber is not particularly limited in the present invention, and may be any oxidation mode commonly used in the art, for example: can be prepared by an oxidation method disclosed in a patent CN 106421875B. The source of the oxidized regenerated fiber is not particularly limited in the present invention, and may be obtained by oxidizing natural and common fibers.
Specifically, the fibrous material of the hemostatic section is derived from cellulose or a derivative fiber thereof. Cellulose and cellulose derivative fibers may be cellulose fibers, carboxyl cellulose fibers, oxidized regenerated cellulose fibers, or the like. For oxidized regenerated cellulose fibers, they can be prepared by the method of ZL 201611004985.0.
The fiber material provided by the invention also has good biocompatibility and can be quickly degraded and absorbed by organisms.
<Second partyNoodle>
A second aspect of the present invention provides a method for preparing the composite hemostatic powder according to the first aspect of the present invention, which comprises the steps of:
preparing a tissue repair layer and a hemostasis layer by using a fiber material;
after the tissue repair layer and the hemostasis layer are laminated, humidifying by using a solution, and then performing compression molding to obtain a composite fiber membrane, wherein the thickness of the composite fiber membrane is less than 500 mu m;
and (3) pulverizing and screening the composite fiber membrane to obtain the composite hemostatic powder.
The preparation method of the absorbable hemostatic powder has the advantages of simple steps, good operability, greatly shortened powder preparation time, low generated heat, high yield of the obtained final product, controllable particle size range and suitability for mass production.
In some specific embodiments, the tissue repair layer and the hemostatic layer of the present invention may be prepared by a non-woven process or an electrospinning technology, and preferably, both the tissue repair layer and the hemostatic layer are prepared by a non-woven process, so that after the tissue repair layer and the hemostatic layer are laminated, since fibers between the non-woven fiber layers are easily lapped and wound, two fiber films can be tightly combined and are not easily layered, and in the finally prepared hemostatic particles, the hemostatic part and the tissue repair part are tightly combined and are not easily layered or peeled. In particular, the non-woven process comprises opening, and/or carding, and/or lapping, and/or cutting the fibrous raw material, thereby obtaining the tissue repair layer or the hemostatic layer.
In some specific embodiments, when the fiber is spun by a non-woven process, a fiber net is formed, and the tissue repair layer or the hemostatic layer is not less than 1 layer, such as 2 layers, 5 layers, 10 layers, 15 layers, 20 layers, 30 layers and the like; multiple layers of fiber webs are stacked together to form a tissue repair or hemostatic layer. The web of the present invention may have a grammage in the range of 2 to 30g/m 3 E.g. 5g/m 3 、10g/m 3 、12g/m 3 、15g/m 3 、18g/m 3 、20g/m 3 、22g/m 3 、25g/m 3 、28g/m 3 And the like.
Further, after the tissue repair layer and the hemostatic layer are laminated, a solution is used for humidification. The mode of humidification treatment is not particularly limited, and may be any one of the modes of humidification treatment commonly used in the art. Such as spraying, dipping, showering, etc. In order to make the humidification treatment more uniform and not affect the subsequent process, the invention can use an atomizer and the like to humidify the fibers.
In some specific embodiments, the solution used for the humidification treatment is water or an aqueous solution containing a bioactive material; preferably, the bioactive material includes one or a combination of two or more of viscous polysaccharide, collagen, growth factor, and the like, and the adhesion prevention, healing, and the like of the wound surface can be further promoted by using the bioactive material, and specifically, the viscous polysaccharide may be hyaluronic acid and derivatives thereof. When the solution used is an aqueous solution containing a bioactive material, the hemostatic particles can be made to contain the bioactive material.
Specifically, in the humidification treatment, the amount of humidification is 10 to 60%, preferably 20 to 50%, based on the total mass of the tissue repair layer and the hemostatic layer, for example: 15%, 21%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, etc. The inventor finds that when the humidification amount accounts for 10-60% of the total mass of the tissue repair layer and the hemostasis layer, the subsequent compaction is facilitated, and the density of the compacted material is not lower than 1g/cm 3 . When the amount of humidification is too low, the press molding is not uniform and the density is not uniform, and when the amount of humidification is too high, the press molding is not good and the crushing is easy and the density is hardly increased.
The present invention is also not particularly limited to the press-molding method, and may be a method commonly used in the art. In the present invention, the wet fiber layer is preferably subjected to press forming by means of rolling, hydraulic pressure, or vertical pressure, thereby obtaining a composite fiber film. The density of the composite fiber membrane can be enabled to be not less than 1g/cm through compression molding 3 For example: 1.1g/cm 3 、1.2g/cm 3 、1.3g/cm 3 、1.4g/cm 3 、1.5g/cm 3 、1.6g/cm 3 、1.8g/cm 3 、2g/cm 3 、2.1g/cm 3 、2.4g/cm 3 、2.5g/cm 3 、2.8g/cm 3 、3g/cm 3 、3.2g/cm 3 And so on. The composite fiber membrane has tight connection among fibers, does not have fiber outlines, and is tightly attached to the tissue repair layer and the hemostasis layer, so that the tissue repair layer and the hemostasis layer are not easy to separate.
In some specific embodiments, the pressure for the press forming is 300 to 700kg, for example: 350kg, 400kg, 450kg, 500kg, 550kg, 600kg, 650kg, etc.; the press-forming time is 2 to 60min, preferably 10 to 50min, for example: 5min, 10min, 15min, 20min, 25min, 30min, 35min, 40min, 45min, 50min, 55min, etc. When the pressure and time are within the range of the present application, a density of not less than 1g/cm can be more easily obtained 3 And the connection between the fibers is tight, and the composite fiber membrane has no fiber contour.
Generally, the water content of the composite fiber membrane after press forming has been reduced to 10 to 30% by mass of the formed body. If the content of the composite fiber membrane is still higher than 30%, the composite fiber membrane may be subjected to a drying treatment. And further reducing the water content of the composite fiber membrane to 10-30% of the mass of the composite fiber membrane through drying treatment. The drying method is not particularly limited, and may be any drying method commonly used in the art, for example, drying at elevated temperature.
Further, the composite fiber membrane is pulverized and sieved, so that the fiber material is obtained. The present invention is not particularly limited to the powder-making process, and may be some powder-making processes commonly used in the art, for example: milling, ball milling, shearing, etc.
And screening the product obtained after the powder preparation to obtain a plurality of hemostatic particles with the particle size of not more than 500 mu m, namely the fiber material.
<Third aspect of the invention>
In a third aspect, the invention provides a hemostatic product, which comprises the composite hemostatic powder according to the first aspect of the invention, or the composite hemostatic powder prepared by the preparation method according to the second aspect of the invention.
In particular, the hemostatic article of the present invention may be a hemostatic occlusive article. The hemostatic preparation can be used for hemostasis during tissue bleeding and filling repair of tissue defects, and/or parenchymal organ bleeding hemostasis and plugging repair. Under the condition of hemostasis and restoration when applied to lacuna bleeding, the hemostatic gauze can be applied to the bleeding of the lacuna and other parts by means of auxiliary matching instruments, or doctors can combine the hemostatic gauze with other commercially available products according to experience, such as hemostatic sponges, hemostatic gauze and other products, so that a better hemostatic effect is achieved.
In addition, the hemostatic product of the invention forms gel with better adhesive capacity on the surface of the wound due to good adhesive property of the hemostatic particles, and realizes compression hemostasis by good physical occlusion. Meanwhile, the problem of wound surface adhesion or poor healing can not occur after the operation.
Examples
Embodiments of the present invention will be described in detail below with reference to examples, but it will be understood by those skilled in the art that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention. The examples, in which specific conditions are not specified, were carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are conventional products which are commercially available, and are not indicated by manufacturers.
Alginic acid fiber, qingdao Bangte fiber, inc.; chitosan fiber, shandong Yida fiber, inc.; oxidized regenerated cellulose fibers, spontaneously developed by the company (prepared according to the method of patent No. ZL201611004985.0, not described in detail here)
Example 1
Firstly, oxidized regenerated cellulose is adopted to prepare a plurality of oxidized regenerated cellulose layers through non-woven, and the gram weight of each layer is 10g/m 2 As a haemostatic layer. Then, carboxymethyl chitosan fiber and sodium alginate fiber are adopted, wherein the mass ratio of the carboxymethyl chitosan fiber to the sodium alginate fiber is 1:1, by notSpinning to prepare a plurality of layers containing carboxymethyl chitosan fiber and sodium alginate fiber, wherein the gram weight of each layer is 15g/m 2 As a tissue repair layer. Then, 2 hemostatic layers and 2 tissue repair layers were laminated together, and humidification treatment was performed by ultrasonic atomization so that the amount of humidification reached 25%. Then tabletting with 500kg of pressure for 30min to obtain 350 μm thick tablet with 2g/cm density 3 The sheet of (1). Then, the powder is milled by a ball mill for 60min at the rotating speed of 350 r/min, and the powder is sieved by a sieving machine with a 500-micron sieve, so that the composite hemostatic powder with the particle size of less than 500 microns is obtained.
Example 2
Firstly, adopting oxidized regenerated cellulose to prepare a plurality of oxidized regenerated cellulose layers by non-woven, wherein the gram weight of each layer is 15g/m 2 As a haemostatic layer. Then preparing a plurality of carboxymethyl chitosan fiber layers by adopting carboxymethyl chitosan fibers through non-woven, wherein the gram weight of each layer is 10g/m 2 As a tissue repair layer. Then, 4 hemostatic layers and 2 tissue repair layers are laminated together, and the humidification amount is 50% through ultrasonic atomization humidification treatment. Then tabletting with 500kg of pressure for 30min to obtain 400 μm thick tablet with 1.5g/cm density 3 The sheet of (1). Then, the powder is prepared by a shearing machine, the shearing speed is 3000 r/min, the time is 10min, meanwhile, the shearing machine is provided with a 500-micron screen, the screening process is automatically completed in the shearing process, and the composite hemostatic powder with the particle size less than 500 microns is obtained.
Example 3
Firstly, oxidized regenerated cellulose is adopted to prepare a plurality of oxidized regenerated cellulose layers through non-woven, and the gram weight of each layer is 20g/m 2 As a haemostatic layer. Then adopting sodium alginate fiber to prepare a plurality of sodium alginate fiber layers through non-woven, wherein the gram weight of each layer is 20g/m 2 As a tissue repair layer. Then 5 hemostatic layers and 2 tissue repair layers were laminated together and humidified to 10% by ultrasonic atomization. Then tabletting with 700kg of pressure for 30min to obtain 450 μm thick tablet with 3g/cm density 3 The sheet of (2). Then milling the mixture by a mill for 60min,the rotating speed is 350 r/min, and the powder is sieved by a 500-micron screen after being prepared into powder, so as to obtain the composite hemostatic powder with the particle size of less than 500 microns.
Example 4
Adopting oxidized regenerated cellulose, preparing multiple layers of oxidized regenerated cellulose by non-woven, wherein the gram weight of each layer is 10g/m 2 As a haemostatic layer. Then, the silk fiber is adopted to prepare a plurality of layers of silk fiber layers through non-woven, and the gram weight of each layer is 5g/m 2 As a tissue repair layer. Then 5 hemostatic layers and 5 tissue repair layers were laminated together and humidified by ultrasonic atomization to achieve 60% humidification. Then tabletting under 300kg for 30min to obtain a tablet with a thickness of 480 μm and a density of 2g/cm 3 The sheet of (1). Then, the powder is milled by a ball mill for 60min at the rotating speed of 350 r/min and sieved by a sieving machine with a 500-micron screen, and the composite hemostatic powder with the particle size of less than 500 microns is obtained.
Comparative example 1
Adopting oxidized regenerated cellulose, preparing multiple layers of oxidized regenerated cellulose by non-woven, wherein the gram weight of each layer is 10g/m 2 As a haemostatic layer. Then 4 hemostatic layers were laminated together and humidified to 25% by ultrasonic atomization. Then tabletting with 500kg of pressure for 30min to obtain a thickness of 300 μm and a density of 1.5g/cm 3 The sheet of (1). Then, the powder is milled by a ball mill and sieved by a sieving machine with a 500 mu m sieve to obtain the composite hemostatic powder with the particle size of less than 500 mu m.
Comparative example 2
Firstly, oxidized regenerated cellulose is adopted to prepare a plurality of oxidized regenerated cellulose layers through non-woven, and the gram weight of each layer is 10g/m 2 As a haemostatic layer. Then, carboxymethyl chitosan fiber and sodium alginate fiber are adopted, wherein the mass ratio of the carboxymethyl chitosan fiber to the sodium alginate fiber is 1:1, preparing a plurality of layers containing carboxymethyl chitosan fiber and sodium alginate fiber by non-woven, wherein the gram weight of each layer is 15g/m 2 As a tissue repair layer. Then 2 hemostatic layers and 2 tissue repair layers were laminated together. Then tabletting under 500kg of pressure while pressingAfter 30min, the thickness of the obtained product is 350 microns, and the density of the obtained product is 2g/cm 3 The sheet of (1). Then, the powder is milled by a ball mill for 60min at the rotating speed of 350 r/min and sieved by a sieving machine with a 500-micron screen, and the composite hemostatic powder with the particle size of less than 500 microns is obtained.
Comparative example 3
Firstly, oxidized regenerated cellulose is adopted to prepare a plurality of oxidized regenerated cellulose layers through non-woven, and the gram weight of each layer is 10g/m 2 As a hemostatic layer. Then, carboxymethyl chitosan fiber and sodium alginate fiber are adopted, wherein the mass ratio of the carboxymethyl chitosan fiber to the sodium alginate fiber is 1:1, preparing a plurality of layers containing carboxymethyl chitosan fiber and sodium alginate fiber by non-woven, wherein the gram weight of each layer is 15g/m 2 As a tissue repair layer. Then, 2 hemostatic layers and 2 tissue repair layers were laminated together, and the amount of humidification was 70% by ultrasonic atomization humidification. Then tabletting with 500kg of pressure for 30min to obtain a tablet with a thickness of 350 μm and a density of 2g/cm 3 The sheet of (1). Then, the powder is milled by a ball mill for 60min at the rotating speed of 350 r/min and sieved by a sieving machine with a 500-micron screen, and the composite hemostatic powder with the particle size of less than 500 microns is obtained.
Performance test
1. Particle size distribution
The test method comprises the following steps: the particle size distribution detection method comprises measuring the particle size and particle size distribution of 0932 in four parts of the 2015 edition according to manual sieving method, weighing the sample, placing into a medicine sieve with specified number (a closed receiving container is arranged below the sieve), and covering on the sieve. The sieve was shaken in a horizontal direction for at least 3 minutes with occasional taps in the vertical direction. The sieved particles and powder were weighed and the ratio (%) was calculated, wherein the mesh number of the selected mesh was 32 mesh (355 μm), 60 mesh (250 μm), 150 mesh (100 μm) and 200 mesh (75 μm), respectively, and the specific results are shown in table 1 below.
2. Tap density
The test method comprises the following steps: the detection is carried out according to the general method for measuring the tap density of the GB/T21354-2008 powder product, and the specific results are shown in the following table 1.
3. Angle of repose
The test method comprises the following steps: the angle of repose was determined according to the method used in the measurement of the angle of repose of the surfactant powders and granules in GB/T11986-1989, and the specific results are shown in Table 1 below.
4. Hemostatic effectiveness test
The test method comprises the following steps: cutting off the rabbit hair at the belly by adopting a rabbit liver bleeding model, opening the belly at the center of a standard, dissociating and exposing the liver; forming a 10X 2mm wound on the same part of the liver; the wound surface was cleaned with gauze, the wound surface was covered with the same weight of hemostatic product and covered with gelatin sponge, pressed, the sponge removed and the wound was observed for bleeding. The hemostasis time was recorded and the effectiveness of hemostasis was evaluated, with the specific results shown in table 1 below.
TABLE 1
As can be seen from Table 1, the composite hemostatic powders of examples 1 to 4 of the present invention have a suitable particle size distribution, in which the content of particles having particle sizes of 75 μm or less is 5 to 35% by mass and the content of particles having particle sizes of 100 μm to 250 μm is not less than 40% by mass; the tap density is 0.6g/cm 3 The angle of repose is 1-10 degrees, and the fluidity is good; the composite hemostatic powder has short hemostatic time and good hemostatic effect.
Comparative example 2, in which no humidification treatment was performed, the content of particles having a particle size of 75 μm or less was more than 35%, resulting in a content of particles having a particle size of 100 μm to 250 μm of less than 40% by mass, and the hemostatic powder product prepared therefrom had low tap density, poor flowability, excessively long hemostatic time, and poor hemostatic effect.
In comparative example 3, excessive humidification leads to poor tabletting effect and low sheet density, the tap density of the prepared particles is low, and the content of particles smaller than 75 μm is excessive, thus leading to long hemostasis time and poor hemostasis effect.
5. Accelerated aging test (Material stability)
The samples were placed in an oven and accelerated aged at 60 ℃ for 0 month, 1 month, 2 months, 3 months and 6 months, respectively, and then sampled to test the fluidity of the samples, and the results are shown in table 2 below.
TABLE 2
The results of the above tests show that the product of the invention has a low angle of repose, which is maintained after 1-6 months of accelerated aging. The smaller the angle of repose, the better the fluidity of the product, so the test results show that the hemostatic powder product of the invention has good fluidity and higher stability. Because if the product is unstable, the hemostatic particles will break or disintegrate during storage or aging, resulting in a product with an increased angle of repose and reduced product flowability.
6. Tissue repair/adhesion prevention experiment
In the hemostasis experiment, the oxidized cellulose hemostasis powder (control group) only having the hemostasis effect in the comparative example 1 and the composite hemostasis powder (experimental group) in the embodiment 2 of the invention are respectively adopted for hemostasis, after the hemostasis is finished, the wound surface is closed, after 14 days of operation, the dissection is carried out, and the adhesion and the repair condition of the wound surface are observed by naked eyes. The result shows that the hemostatic powder of the control group and the experimental group is completely degraded, but the wound surface of the control group is not completely healed, obvious wound surfaces still exist, and a little adhesion exists, while the wound surface of the experimental group is completely healed, the color of a repair area is normal, and no adhesion phenomenon exists.
It should be noted that, although the technical solutions of the present invention are described by specific examples, those skilled in the art can understand that the present invention should not be limited thereto.
While embodiments of the present invention have been described above, the above description is illustrative, not exhaustive, and not limited to the disclosed embodiments. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The terminology used herein was chosen in order to best explain the principles of the embodiments, the practical application, or technical improvements to the market, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.
Claims (13)
1. A composite hemostatic powder, characterized in that it comprises hemostatic particles having a particle size of not more than 500 μm, wherein,
the hemostatic particles are derived from a fibrous material comprising a hydrophilic fibrous material; and is
The hemostatic particles are provided with a tissue repair part and a hemostatic part, the tissue repair part and the hemostatic part are combined, the tissue repair part is positioned on one side of the hemostatic part, and the fiber material of the tissue repair part is different from that of the hemostatic part;
the tap density of the composite hemostatic powder is not less than 0.6g/cm 3 (ii) a The repose angle of the composite hemostatic powder is 1-10 degrees;
the fiber materials on the surface of the hemostatic particles are fused into a whole, and the surface of the hemostatic particles does not have a fiber silk form;
based on the total mass of the composite hemostatic powder, the content of hemostatic particles with the particle size of less than 75 μm is 5-35%; the content of the hemostatic particles with the particle size of 100-250 mu m is not less than 40 percent.
2. The composite hemostatic powder according to claim 1, wherein the tap density of the composite hemostatic powder is 0.6 to 0.9g/cm 3 (ii) a And/or the angle of repose of the composite hemostatic powder is 2-8 degrees.
3. The composite hemostatic powder according to claim 1 or 2, wherein the fibrous materials inside the hemostatic particles are fused together, and the inside of the hemostatic particles do not have a fibrous filament morphology; and/or the hemostatic particles are prepared by laminating fiber layers made of fiber materials, then carrying out humidification treatment and compression molding, and then crushing.
4. The composite hemostatic powder according to claim 1 or 2, wherein the content of hemostatic particles having a particle diameter of 75 μm or less is 5% to 15% based on the total mass of the composite hemostatic powder; the content of the hemostatic particles with the particle size of 100-250 mu m is 60-80 percent.
5. The composite hemostatic powder according to claim 1 or 2, wherein the fibrous material of the tissue repair part comprises one or a combination of two or more of chitosan or derivative fiber thereof, alginic acid or derivative fiber thereof, and silk fiber; the fiber material of the hemostasis part comprises cellulose or derivative fibers thereof.
6. The composite hemostatic powder of claim 5, further comprising a bioactive material comprising one or a combination of two or more of a viscous polysaccharide, collagen, and a growth factor.
7. A preparation method for preparing the composite hemostatic powder as defined in any one of claims 1 to 6, comprising the steps of:
preparing a tissue repair layer and a hemostasis layer by using a fiber material;
after the tissue repair layer and the hemostasis layer are laminated, humidifying the tissue repair layer and the hemostasis layer by using a solution, and then performing compression molding to obtain a composite fiber membrane, wherein the thickness of the composite fiber membrane is less than 500 mu m;
crushing and screening the composite fiber membrane to obtain composite hemostatic powder;
in the humidification treatment, the humidification amount accounts for 10-60% of the total mass of the tissue repair layer and the hemostasis layer.
8. The method for preparing a composite hemostatic powder according to claim 7, wherein the humidifying amount is 20 to 50% of the total mass of the tissue repair layer and the hemostatic layer.
9. The method for preparing composite hemostatic powder according to claim 8, wherein the solution used in the humidification treatment is water or an aqueous solution containing a bioactive material, and the bioactive material comprises one or a combination of two or more of viscous polysaccharide, collagen, and growth factor.
10. The method for preparing composite hemostatic powder according to any one of claims 7 to 9, wherein the tissue repair layer or the hemostatic layer is not less than 1 layer, and the gram weight ratio of the single layer of the tissue repair layer or the hemostatic layer is 2 to 30g/m 2 The fiber web of (1).
11. The method for preparing composite hemostatic powder according to any one of claims 7 to 9, characterized in that the composite fiber membrane is obtained by rolling or hydraulic pressure, and/or the density of the composite fiber membrane is not less than 1g/cm 3 。
12. The method for preparing a composite hemostatic powder according to any one of claims 7 to 9, characterized in that the composite fiber membrane is obtained by means of vertical pressing.
13. A hemostatic article comprising the composite hemostatic powder according to any one of claims 1 to 6 or the composite hemostatic powder produced by the production method according to any one of claims 7 to 12.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011623462.0A CN114681659B (en) | 2020-12-31 | 2020-12-31 | Composite styptic powder and preparation method and application thereof |
| PCT/CN2021/084597 WO2022141884A1 (en) | 2020-12-31 | 2021-03-31 | Absorbable hemostatic powder, preparation method therefor and application thereof |
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| US20040265371A1 (en) * | 2003-06-25 | 2004-12-30 | Looney Dwayne Lee | Hemostatic devices and methods of making same |
| FR2989281B1 (en) * | 2012-04-13 | 2014-04-25 | Brothier Lab | POWDER FORMING DRESSING AND CORRESPONDING ABSORBENT MATERIAL |
| ES2950114T3 (en) * | 2015-11-06 | 2023-10-05 | Ethicon Inc | Compacted hemostatic cellulosic aggregates |
| KR102656226B1 (en) * | 2016-12-09 | 2024-04-09 | 한국생산기술연구원 | Hemostatic material comprising calcium carboxymethyl cellulose powder and water-soluble chitosan compound powder and process for preparing the same |
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