WO2008138202A1 - A chitosan based fiber material, preparing method and application thereof - Google Patents
A chitosan based fiber material, preparing method and application thereof Download PDFInfo
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- WO2008138202A1 WO2008138202A1 PCT/CN2008/000636 CN2008000636W WO2008138202A1 WO 2008138202 A1 WO2008138202 A1 WO 2008138202A1 CN 2008000636 W CN2008000636 W CN 2008000636W WO 2008138202 A1 WO2008138202 A1 WO 2008138202A1
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- chitosan
- water
- fiber
- soluble
- soluble chitosan
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- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F9/00—Artificial filaments or the like of other substances; Manufacture thereof; Apparatus specially adapted for the manufacture of carbon filaments
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/28—Polysaccharides or their derivatives
-
- 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/042—Polysaccharides
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01D1/00—Treatment of filament-forming or like material
- D01D1/02—Preparation of spinning solutions
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01D5/00—Formation of filaments, threads, or the like
- D01D5/06—Wet spinning methods
Definitions
- the invention relates to a medical material, in particular to a water-soluble chitosan-based fiber hemostatic guaiac material, preparation method and application thereof
- Gelatin sponge has been used clinically for many years, but its hydrophilicity is poor, and its hemostatic effect is poor for larger bleeding.
- the hemostatic performance of collagen sponges is better than that of gelatin sponges.
- the raw materials for their production come from bovine tendons and tendons, so there is a risk of transmission of viral diseases from animals.
- Fibrin glue is widely used in clinical hemostasis.
- fibrin glue is a blood product, there is a certain risk of antigenic and viral diseases, and the safety of its application is questioned.
- the above gelatin sponge, collagen sponge and fibrin glue belong to the heterologous animal protein, which have certain immunogenicity and the risk of virus transmission. The same day «Additional wound infection opportunities.
- the hemostasis material produced by using oxidized cellulose as a raw material has been used in various clinical operations for many years, such as neurosurgery, abdominal surgery, cardiovascular surgery, chest surgery, etc.
- This hemostatic material belongs to Johnson & Johnson.
- the company's products are of the highest quality, Surgicel® absorbable hemostatic agents, Surgicel Nu-Knit® absorbable hemostatic agents and Surgicel® Fibrllar absorbable hemostatic agents are Johnson & Johnson's oxidized cellulose hemostatic products, but oxidized cellulose stops bleeding
- the material is effective for the ihtL effect of mild oozing, and for more oozing, the hemostatic effect is still not ideal, and the hemostasis is slow. For more oozing, there is currently no clinical hemostatic material with satisfactory hemostasis effect.
- the material is in the military to stop bleeding, or does not have the function of healing the wound, or the healing function of the wound is not ideal.
- Chitosan is a linear high-polysaccharide compound, which is a male product of chitosan. It is positively charged, non-immunogenic, bio-early, and has many physiological activities, such as wound healing of wounds with 3 ⁇ 4 damage. Hemostasis, analgesic, antibacterial and antibacterial functions.
- the hemostatic function of chitosan is mainly due to the charge interaction between chitosan and red blood cells, which occurs, thus ihi0i.
- due to the insoluble nature of chitosan it is used in applications. In particular, applications in medical materials have been greatly limited.
- Chitosan powder, chitosan membrane, chitosan sponge, chitosan fiber, chitosan nonwoven fabric and fabric prepared by using chitosan as raw material the degradation in vivo is slow, and it takes more than half a year to completely degrade.
- Many research data show that chitosan causes the body's inflammatory reaction in the process of in vivo pottery. Therefore, the ⁇ 1& materials and wound repair materials made of chitosan can only be used in the fine shed.
- a carboxymethyl chitosan fiber and a preparation method and application thereof are disclosed (the chitosan is an alias of chitosan, and thus the carboxymethyl chitosan is also Known as carboxymethyl chitosan).
- the content of this document is hereby incorporated by reference in its entirety.
- the high molecular monomer of the carboxymethyl chitosan fiber has a carboxymethyl substitution degree of 1 to 50%, so that the fiber has high hygroscopic property while maintaining a fibrous structure, that is, maintaining water insolubility.
- the low-substituted carboxymethyl chitosan fiber has a long degradation time in the body and also causes an inflammatory reaction in the body, so it is not suitable for use in the body. Summary of the invention
- the object of the present invention is to provide a water-soluble chitosan-based fibrous material and a process for its preparation and use to overcome the above-mentioned disadvantages of the prior art.
- the iff is a water-soluble chitosan-based fibrous material, wherein the TO/soluble chitosan-based fiber comprises carboxymethyl chitosan fiber, hydroxypropyl chitosan fiber, hydroxyethyl group Chitosan fibers, carboxymethyl hydroxyethyl chitosan fibers or mixtures thereof.
- the water-soluble chitosan-based fiber material according to the present invention may be in the form of fibers, cotton, cotton balls, wadding, non-woven fabric, knitted fabric, woven fabric, woven fabric, or the like.
- a method for preparing a water-soluble chitosan-based fibrous material comprising the following steps:
- the water-insoluble chitosan-based fiber material has a weight percentage concentration of 20 to 50%, a crane 30 to 45% NaOH solution or a KOH solution, wherein the weight ratio of the water-insoluble chitosan-based fiber material to the aqueous solution of the alkali is For 1: (5 ⁇ 40), the crane is 1: (10-25), alkalized at -40 ° C ⁇ room temperature for 2 to 72 hr, i 12 ⁇ 481 ⁇ ; alkalized water-insoluble chitosan
- the base fiber is reacted with a haloacetic acid, or a halogenated ethanol, or a propylene oxide, or a halogenated propanol, or a combination of a haloacetic acid and a halogenated ethanol in a reaction medium for 5 to 36 hr, im 6-24 hr, To form a corresponding water-soluble chitosan-based fiber; wherein the insoluble chitosan-based fiber
- a method for preparing a water-soluble chitosan-based fiber material is Includes the following steps:
- the water-soluble chitosan is dissolved in deionized water, stirred and dissolved, and the viscous gel is leaked, and the filter is filtered to remove trace insoluble matter, and the weight percentage is 2% ⁇ 10%, tfc ⁇ 5% ⁇ 8%.
- the water-soluble chitosan-based spinning solution the spinning liquid is sprayed through a spinneret into a coagulation bath of 30 to 45° , to form a water-soluble chitosan-based fiber which is drawn by a roller, 3 ⁇ 4 ⁇ 3 ⁇ 4 stretch bath, The stretched roller is drawn and stretched, and then stretched by winding to form a water-soluble chitosan-based fiber bundle, the organic marrow 11 is removed, and dried to obtain a dry water-soluble chitosan-based fiber, « ⁇ , » ⁇ , Packaging, sterilizing, obtaining fiber cotton strips, cotton balls or wadding in water-soluble chitosan-based fiber materials; or processing water-soluble chitosan-based fibers into non-woven fabrics, knitted fabrics, woven fabrics , materials in the form of woven fabrics.
- it further relates to the use of a water-soluble chitosan-based fibrous material in the preparation of a drug or medical device that ihl& guaiac or prevents tissue adhesion.
- the invention relates to a medicament or a medical device prepared by using a water-soluble chitosan-based fibrous material in preoperative, intraoperative, postoperative hemostasis, wound healing of a ship, and prevention of tissue adhesion in clinical operations. application.
- the water-soluble chitosan-based fiber material of the invention simultaneously has the functions of stopping bleeding, promoting wound healing and preventing postoperative tissue adhesion; capable of gradually absorbing water and expanding under the physiological pH cake and gradually dissolving the corpus callosum solution, and the local application performance is good, It can better stop the function of hemostasis, guaiac and anti-adhesion; it has no immunogenicity in the body, the P-axis is short in time, and it is compatible with the organism, and the clinical surface is safer. It is suitable for hemostasis in vivo.
- the water-soluble chitosan-based fiber material of the invention is in the form of non-woven fabric, knitted fabric, woven fabric, woven fabric, cotton strip, cotton ball, and cotton floc, all have certain Mechanically moved, the clinical preparation is convenient, the adhesion is firm, and the function can be better utilized to better meet the clinical application.
- the carboxymethyl chitosan may have the following structure:
- ⁇ , -COCH 3 , -CH 2 COONa or -CH 2 COOK is 11, -CH 2 C ⁇ ONa or -CH 2 COOK, wherein the degree of carboxymethyl substitution is greater than 60%.
- the carboxymethyl chitosan fiber is preferably a carboxymethyl shell polymerized thousand or carboxymethyl shell polyene fiber.
- the butyl propyl chitosan may have the following structure:
- R 2 is H or - C3 ⁇ 4CHOHCH 3 , wherein hydroxypropyl » is more than chaotic
- the hydroxyethyl chitosan may have the following structure:
- the carboxymethylethylethylchitosan may have the following structure -
- R, H, -COCH 3 , -C3 ⁇ 4COONa, -CH 2 CO ⁇ K or -CH 2 C3 ⁇ 4OH is -C3 ⁇ 4COONa, -CH 2 CO ⁇ K or -CH 2 CH 2 OH, and its carboxymethyl group
- the sum of hydroxyethyl groups is greater than 60%.
- the water-soluble chitosan-based fibrous material according to the present invention may be composed of, for example, water-soluble carboxymethyl chitosan, light propyl chitosan, hydroxyethyl chitosan, carboxymethyl hydroxyethyl chitosan or a mixture thereof.
- the water-soluble chitosan-based powders of the like are initially produced in accordance with conventional methods. For example, a powder of water-soluble methyl chitosan, hydroxypropyl chitosan, hydroxyethyl chitosan, carboxymethylhydroxyethyl chitosan or a mixture thereof is dissolved in deionized water and stirred under a cake at room temperature.
- the water-soluble chitosan group in the spinning solution may have a concentration by weight of 2% to 10%, preferably a concentration of 5% to 8% by weight.
- the coagulation bath and the stretching bath may be one or two of ethanol or acetone or an aqueous solution having a concentration by weight of more than 90%.
- the temperature of the coagulation bath may be 30 to 45 °C. Difficult sterilization is sterilization or epoxy acetonitrile sterilization.
- the water-soluble chitosan-based fibers obtained as above can be further processed into materials in the form of non-woven fabrics, knitted fabrics, woven fabrics, and woven fabrics according to methods known to those skilled in the art.
- a nonwoven fabric also referred to as a nonwoven fabric, is a sheet, web or batt which is oriented or randomly arranged to be bonded to each other by friction, cohesion or adhesion or a combination of these methods.
- the woven fabric is a fabric which is interwoven by mutually perpendicularly arranging the yarns of the two systems in the transverse direction and the longitudinal direction according to a certain rule.
- Knitted fabric refers to a fabric in which a yarn or a filament is formed into a loop by a knitting needle, and the stitches are sleeved with each other.
- a woven fabric refers to a woven fabric in which a yarn or a cord is knitted.
- the water-soluble chitosan-based fiber material according to the present invention can also be prepared from a water-insoluble chitosan-based fiber comprising: a water-insoluble chitosan-based fiber having a weight percent concentration of 20 ⁇ In a 50% NaOH solution or an aqueous KOH solution, the weight ratio of the water-insoluble chitosan-based fiber to the aqueous solution of the above-mentioned alkali is 1: (5 to 40), and alkalized at -40 ° C to room temperature for 2 to 72 hr; After alkalization, the alkalized water-insoluble chitosan-based fiber is transferred into the reaction medium, and at the room temperature and under the shaking cake, the reagent haloacetic acid or halogenated ethanol or propylene oxide or halopropanol or haloacetic acid is added.
- the molar ratio of the water-insoluble chitosan-based fiber to the base, the haloacetic acid or the haloethanol*f-oxypropane or the halopropanol or the haloacetic acid and the haloethanol is 1: (10 ⁇ 40) : (1.1 ⁇ 15), reaction 5 ⁇ 36 hr ; after the reaction, take out the solid matter, wash the paint with neutral paint, dehydrate, remove excess liquid, and then put it in the P vacuum dryer 205 in the drying, waving to make the residual organic solvent, the finishing, cutting, packing, sterilization.
- the water-insoluble chitosan-based fiber may be chitosan fiber, chitosan fiber nonwoven fabric, chitosan fiber knitted fabric, chitosan fiber woven fabric, chitosan fiber woven fabric.
- the water-insoluble chitosan-based fiber may be chitosan fiber, chitosan fiber nonwoven fabric, chitosan fiber knitted fabric, chitosan fiber woven fabric, chitosan fiber woven fabric.
- the reaction medium may be one or two or three of methanol, ethanol, isopropanol, butanol, acetone, dimethyl sulfoxide, tetrahydrofuran, and dioxane, or an aqueous solution thereof.
- the reaction reagent may be one of haloacetic acid or one of halogenated ethanol or one of glycidyl or halopropanol or one of a combination of haloacetic acid and haloethanol, which is difficult.
- the acetic acid is chloroacetic acid, bromoacetic acid or iodoacetic acid
- the halogenated ethanol is chlorohydrin or bromoethanol
- the halogenated propanol is 1-chloro-2-propanol or 1-bromo-2-propanol.
- the combination of haloacetic acid and haloethanol is chloroacetic acid and chlorohydrin, bromoacetic acid and chlorohydrin, chloroacetic acid and bromoethanol or bromoacetic acid and bromoethanol.
- the washing liquid may be one or two or three of methanol, ethanol, isopropanol, butanol, and acetone, or an aqueous solution having a weight percentage of more than 75% by weight.
- the sterilization of the household can be 6t) Co sterilization or ethylene oxide sterilization.
- the weight percentage of the aqueous solution of the base may be 20 to 50%, and the preferred concentration by weight is 30 to 45%; the weight ratio of the water-insoluble chitosan-based fiber to the aqueous solution of the base may be 1: (5 to 40)
- the weight ratio is 1: (10-25); the alkalization may be -40 ° C to room temperature, the alkalization time is 2 to 72 hr, and the preferred alkalization time is 12 to 48 hr ; 7 insoluble chitosan group
- the molar ratio of fiber to alkali and reaction reagent is 1: (10 ⁇ 40): (1.1 ⁇ 15), the molar ratio is 1: (20-40): (5 ⁇ 12); reaction time can be 5 ⁇ 36 hr, the preferred reaction time is 6 to 24 hr, and the reaction temperature is room temperature.
- the water-insoluble chitosan-based fiber used as a raw material may have a deacetylated glycosyl group in the molecular chemical structure in a molar percentage of the total glycosyl group in the molecule of 0 to 100 ° /. Between The same effect is therefore collectively referred to as water-insoluble chitosan-based fibers.
- the degree of carboxymethyl substitution of the water-soluble carboxymethyl chitosan fiber obtained according to the present invention depends on the number of moles of the reagent side in the reaction, the reaction time, and the carboxymethyl group is mainly present, and some are Ri is in the position.
- the above reaction cakes are selected such that the most frequently found water-soluble carboxymethyl chitosan fibers have a carboxymethyl ⁇ degree of greater than 60%.
- the degree of hydroxypropionation of the hydrothermal 'silver propyl chitosan fiber obtained according to the present invention depends on the number of moles of the reagent side in the reaction, the reaction time, 3 ⁇ 4 ⁇ 4, the hydroxypropyl group is mainly at the health, and also Part of the ffi on the 3 ⁇ 4.
- the reaction cell is selected such that the resulting water-soluble hydroxypropyl chitosan fiber has a hydroxypropylation degree greater than 60%.
- the size of the hydroxyethyl beta of the water-soluble hydroxyethyl chitosan fiber obtained according to the present invention depends on the number of moles of the reaction reagent used in the reaction, the reaction time, and the hydroxyethyl group is mainly on the ⁇ which is present, and Part of it is at R, where it is.
- the above reaction cattle should be selected such that the resulting water-soluble hydroxyethyl chitosan fiber has a hydroxyethyl group generation of more than 60%.
- the degree of substitution of the carboxymethyl group and the hydroxyethyl group of the water-soluble carboxymethyl hydroxyethyl chitosan fiber obtained according to the present invention depends on the number of moles of the reaction reagent surface in the reaction, the reaction time, and the carboxymethyl group.
- the hydroxyethyl group is mainly in the health of the place, and some of it is in the health of the place.
- the above reaction glass is selected such that the carboxymethyl oxime ethyl group of the finally obtained water-soluble carboxymethyl hydroxyethyl chitosan fiber has a deuterium sum of more than 60%.
- the water-soluble chitosan-based fibrous material of the present invention is soft in texture, white in color, and has good water solubility.
- the carboxymethyl shell polymerization powder was produced by Qingdao Boyite Biomaterials Co., Ltd.; and the chitosan fiber, chitosan fiber nonwoven fabric and chitosan fiber knitted fabric were purchased from Shanghai. Donghua University.
- Example 1 Preparation of water-soluble '3 ⁇ 4 ⁇ methyl chitosan fiber nonwoven fabric
- the alkalized chitosan nonwoven fabric was taken out, and 100 g of a 55% acetone aqueous solution was used as a reaction medium in a 3 ⁇ 4 A 500 ml jar, and 85 g of a 50% solution of monochloroacetic acid in ethanol was added as a reaction reagent under shaking of the bovine. The reaction was carried out for 9 hr at room temperature to obtain a carboxymethyl chitosan potassium fiber nonwoven fabric. The carboxymethyl chitosan potassium fiber nonwoven fabric was taken out, washed thoroughly with a 60% aqueous acetone solution as a washing liquid, dehydrated with 3 ⁇ 4 acetone, squeezed or centrifuged to remove excess liquid, and then placed in a washing solution.
- the vacuum drying device containing P 2 0 5 was vacuum dried, and the organic solvent remaining in the dried product was evaporated at 50 Torr to obtain a carboxymethyl chitosan fiber non-woven fabric having a carboxymethyl group of 92%, which was finished and cut. , packaging, 60 Co sterilization, to obtain a water-soluble chitosan-based fiber material.
- the base shell is gathered in the inner fiber.
- the carboxymethyl chitosan fiber was taken out, washed thoroughly with methanol as a wash, neutralized, squeezed or centrifuged to remove excess liquid, and then placed in a vacuum drier containing P 2 0 5 . Vacuum drying, the organic solvent remaining in the dried product at 5 (TC), «A" 96% carboxymethyl chitosan fiber, after finishing, cutting, packaging, epoxy acetonitrile sterilization, A water-soluble chitosan-based fiber material is obtained.
- the water-soluble chitosan-based fibrous material produced by the present invention may be a cotton strip of carboxymethyl chitosan fibers, a cotton ball or a cotton wadding.
- Example 3 Preparation of water-soluble 'with methyl chitosan fiber only cloth
- the residual organic residue I in the dry product is squandered, and the yoke is «90% carboxymethyl chitosan fiber knitted fabric, which is finished, turned, packaged, and epoxidized.
- a water-soluble chitosan-based fiber material is obtained.
- the difficult reaction reagent may be one of haloacetic acid, i.e., one of chloroacetic acid, bromoacetic acid or iodoacetic acid, and the same effect can be obtained.
- Example 4 Preparation of water-soluble propyl chitosan fiber nonwoven fabric
- the alkalized chitosan fiber non-woven fabric was taken out, and a 1000 ml stainless steel reaction bottle with a sealing cap was added, and 150 g of isopropyl alcohol, 25 g of dimethyl sulfoxide and 25 g of dioxane were added as reaction medium, and the mixture was added under shaking. 50 g of propylene oxide was used as a reaction reagent, and the cap was sealed, and the reaction was shaken at room temperature for 24 hr, ⁇ #3 ⁇ 4 propyl chitosan fiber non-woven fabric.
- the hydroxypropyl chitosan nonwoven fabric was taken out, washed thoroughly with 80% aqueous acetone solution as a washing liquid, dehydrated with anhydrous acetone, squeezed or centrifuged to remove excess liquid, and then placed in a suspension.
- a vacuum desiccator there ⁇ 2 0 5 was dried in vacuum at 50 ° C for play to make dried product remaining in the organic solvent, to obtain hydroxypropyl substitution of 86% hydroxypropyl chitosan fiber nonwoven fabric, Li , cutting, packaging, 60 Co sterilization, to obtain water-soluble chitosan-based fiber materials.
- the difficult reaction reagent may be one of propylene oxide or halopropanol, that is, 1 in propylene oxide, 1-chloro-2-propanol or 1-bromo-2-propanol. The same effect can be achieved.
- m 5 Preparation of water-soluble ethyl chitosan fiber nonwoven fabric
- the alkalized chitosan fiber non-woven fabric was taken out, and 1000 g of a sealed stainless steel reaction bottle was placed, and 160 g of acetone, 20 g of dimethyl sulfoxide and 20 g of tetrahydrofuran were added as a reaction medium, and monochloroethanol was added under shaking. 55 g was used as a reaction reagent, and the cap was sealed, and the mixture was shaken at room temperature for 36 hr to obtain a hydroxyethyl chitosan fiber nonwoven fabric.
- the reaction reagent may be one of halogenated ethanol, that is, one of chlorohydrin or bromoethanol, and the same effect can be obtained.
- Example 6 Preparation of water-soluble ' earning methylhydroxyethyl chitosan ruthenium non-woven fabric
- the alkalized chitosan fiber non-woven fabric was taken out, placed in a 1000 ml stainless steel reaction bottle with a sealing cap, and 160 g of acetone, 20 g of dimethyl sulfoxide and 20 g of tetrahydrofuran were added as a reaction medium, and 50% of the vibration was added. 46 g of an ethanol solution of monochloroacetic acid and 30 g of monochloroethanol were used as a reaction reagent, and the cap was sealed, and the mixture was shaken at room temperature for 48 hr to obtain a carboxymethylhydroxyethyl chitosan fiber nonwoven fabric.
- the carboxymethylhydroxyethyl chitosan fiber nonwoven fabric was taken out, washed with 85% acetone aqueous solution as a washing solution to neutrality, dehydrated with acetone, squeezed or centrifuged to remove excess liquid, and then removed. Placed in a vacuum drier containing P 2 0 5 in a vacuum drier, and the organic solvent remaining in the dried product was evaporated at 50 ° C to obtain a carboxymethyl light B with a carboxymethyl group and a hydroxyethyl group substitution of 94%.
- Non-woven fabric of chitosan fiber which is prepared by rinsing, turning, packaging and epoxy oxime to obtain water-soluble chitosan-based fiber
- the spinneret M was sprayed into a coagulation bath of a 95% aqueous solution of ethanol at 40 to 45 ° C to form a carboxymethyl chitosan fiber.
- the fiber is subjected to wire roll drawing, 3 ⁇ 4 ⁇ 95% ethanol aqueous solution stretching bath, drawn by a stretching roll, and then stretched by winding, and the prepared carboxymethyl chitosan fiber bundle is removed, and the dried ghost organic is centrifuged.
- the carboxymethyl chitosan throw, the hydroxypropyl chitosan, the ethyl chitosan, and the water-soluble shell polyfluorene-based material may be used.
- the degree of substitution of carboxymethyl, light propyl or hydroxyethyl groups in the water-soluble chitosan primer is more than 60%, and the same effect can be achieved.
- the weight percentage concentration of the water-soluble chitosan-based material in the household spinning solution may be 2% to 10%, preferably the weight percent concentration It is 5% to 8%.
- the coagulation bath and the stretching bath may be one or two kinds of ethanol or acetone or an aqueous solution having a concentration by weight of more than 90%.
- the coagulation bath of the flank may be 30 to 45 °C.
- Difficult sterilization is 60 Co sterilization or ethylene oxide sterilization. Male 8
- the carboxymethyl chitosan fiber obtained in Example 7 is opened, combed, cut, laid, reinforced, netted, cut, and dried to obtain a methacrylic fiber non-woven fabric, which is cut,
- the package is sterilized by epoxy oxime to obtain a non-woven fabric in a water-soluble chitosan-based fiber material.
- the carboxymethyl chitosan fiber of the oxime may be a hydroxypropyl chitosan fiber or a hydroxyethyl chitosan fiber, and the same effect can be obtained.
- the non-woven fabric in the water-soluble soluble chitosan-based fibrous material is carboxymethyl chitosan fiber nonwoven fabric, hydroxypropyl chitosan fiber nonwoven fabric, and ethyl chitosan fiber nonwoven fabric.
- Rats were used as test animals to make liver tissue defect models, and oxidized regenerated cellulose gauze was evaluated separately.
- oxidized regenerated cellulose gauze control group oxidized regenerated cellulose gauze as material, referred to as oxidized fiber.
- Plain gauze group water-soluble chitosan turning material test group 1 (with carboxymethyl chitosan fiber non-woven fabric as material, referred to as carboxymethyl chitosan fiber non-woven fabric group), 7J soluble shell polymerization
- Sugar-based material test 2 groups hydroxypropyl chitosan fiber nonwoven fabric, referred to as hydroxypropyl chitosan fiber nonwoven fabric group
- water-soluble chitosan 3 ⁇ 4 material test 3 groups with hydroxyethyl
- the chitosan fiber non-woven fabric is a material, abbreviated as a hydroxyethyl chitosan fiber nonwoven fabric group, and 12 rats per group.
- the oxidized cellulose gauze is applied with 3 layers (weight: 61 ⁇ 63mg), and the carboxymethyl chitosan fiber non-woven fabric is applied with 2 layers (weight: 59 ⁇ 61mg).
- Hydroxypropyl chitosan fiber non-woven fabric 2 layers weight: 61 ⁇ 63mg
- hydroxyethyl chitosan fiber non-woven fabric 2 layers weight 60 ⁇ 62mg
- put 10g weight on the material for 20 seconds observe the bleeding condition of the wound for 40 seconds, repeat the steps, observe the bleeding, and record, 3 incision suture ⁇ ! Complex, iodophor disinfection, grouping words, 7 days, 14 to see the wound healing and tissue adhesion of liver tissue defects in animals.
- the test results are shown in Tables 1 and 2.
- the results show that the three water-soluble chitosan-based fiber materials and oxidized regenerated cellulose gauze have significant hemostatic effect, healing effect of wound healing and prevention of postoperative tissue adhesion.
- the three water-soluble chitosan-based fiber materials have better hemostatic, guaiac and prevent postoperative tissue adhesion than oxidized regenerated cellulose gauze, significantly shortening the hemostasis time and shortening the wound healing time. And prevent postoperative interstitial adhesions.
- the non-adhesive hydroxypropyl chitosan fiber material has been hidden, and the material has been used.
- the wound surface of the wound completely non-woven group is about 70-80%.
- the wound of the group is smooth, and the non-adhesive material between the tissues has been adhered.
- the wounds of the non-woven fabrics of the hidden wounds are 70-80% more, the tissue is healed, the wounds are smooth, and there is no adhesion between the tissues.
- the water-soluble chitosan-based fiber material of the present invention can be made into a medicine or a medical device, and is applied to clinical abdominal surgery, thoracic surgery, bone surgery, and women Sputum, microsurgery, burns, plastic surgery, etc., before and during surgery, the water-soluble chitosan-based fiber material is placed in the bleeding site, gently pressed, can effectively fight the army i 4L action, wound healing and prevention of postoperative tissue adhesion.
- the water-soluble chitosan-based fiber material of the present invention has good biocompatibility, does not cause an inflammatory reaction in the body, has a short degradation time in the body, is guaiac and prevents postoperative tissue adhesion, and is suitable for hemostasis and healing in surgical wounds. Create and prevent postoperative tissue adhesion sheds.
- the water-soluble chitosan-based fiber material of the present invention can be used in the preparation of a medicament or a medical device, and can be used for the treatment of hemostasis or wound healing or prevention of postoperative tissue adhesion. medical instruments.
- the reactants and/or the operations used in the above examples are replaced with the generally or specifically described reactants and/or operating conditions of the present invention, and these examples are successfully repeated similarly. While the invention has been described with respect to the embodiments and the specific embodiments of the invention, it is apparent that various changes and modifications may be made without departing from the spirit and scope of the invention.
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Description
一种壳聚糖基纤维材料及其制备方法和应用
本发明涉及一种医用材料, 特别是涉及一种水溶性壳聚糖基纤维止血愈创材 料及其制备方法和应用^ 背景
在临床手术中和手术后控制出血、止血、舰切口愈合,对于缩短手术时间、 手术后并发症是非常必要和重要的。 临床手术操作 ibfii和外伤止血常使用结 扎、 缝合、 电凝等常规止血方法, 但这些止血方法并不总是能有效地控制出血, 特别是在多血管的实质'隱器的手术中, 因此根据临床需要, 已有多种局部 ibfc 材料应用于临床, 这些 i J&材料主 ¾ 明胶海绵、 胶原蛋白海绵、 纤维蛋白胶、 氧化纤维素等产品。 明胶海绵在临床上应用多年, 但其亲水性较差, 对于较大的 出血其止血效果欠佳。 胶原蛋白海绵的止血性能比明胶海绵好, 其生产原料来自 于牛跟腱、 肌腱, 因此存在动物源病毒性疾病传播的危险。 纤维蛋白胶在临床手 术止血中应用较为广泛, 但由于纤维蛋白胶成分属于血液制品, 因此存在着一定 的抗原性和病毒性疾病传播的危险, 其应用的安全性受到一定的质疑。 上述明胶 海绵、 胶原蛋白海绵、 纤维蛋白胶均属于异种动物蛋白, 均有一定的免疫原性和 病毒传播的危险, 同日 «加创面的感染机会。 以氧化纤维素为原料生产的止血材 料应用于各种手术的局部止血已在临床上应用多年,如神经外禾样术、腹部手术、 心血管手术、 胸部手术等, 这种止血材料当属 Johnson&Johnson公司的产品质量 最好, Surgicel®可吸收性止血剂、 Surgicel Nu-Knit®可吸收性止血剂和 Surgicel® Fibrllar可吸收生止血剂都是 Johnson&Johnson公司的氧化纤维素止血产品, 但氧 化纤维素止血材料对于轻度渗血的 ihtL效果 $效子, 而对于较多的渗血情况, 其止 血效果仍不十分理想, 止血速度慢。 对于较多的渗血, 目前临床上还没有一种止 血材料具有较满意的止血效果。 同时上 材料在 军止血功能的同时, 或者 不具^ ¾手术切口愈合的功能, 或者 ί^ί手术创面愈合功能不理想。
壳聚糖是一种线性高^ ^多糖化合物,是甲壳素的脱乙酉雄产物,带正电荷, 无免疫原性, 可生物 早, 具有多种生理活性, 如具有^ ¾损伤创面修复愈合、 止血镇痛、 抗菌抑菌功能。 壳聚糖的止血功能主要源于壳聚糖与红细胞之间电荷 相互作用, 发生 , 从而 ihi0i。 但由于壳聚糖不溶解于水的特性, 使之在应用
方面, 特别是在医用材料方面的应用, 受到了很大的限制。 以壳聚糖为原料制备 的壳聚糖粉、 壳聚糖膜、 壳聚糖海绵、 壳聚糖纤维、 壳聚糖非织布和织物等, 在 体内降解缓慢, 完全降解需要半年以上, 同时许多研究资料表明, 壳聚糖在体内 陶过程中引起机体炎症反应, 因此以壳聚糖为原料制成的 ±1&材料和创伤修复 材料, 只能在戲細面棚。
在专利号为 ZL200410025721.4的中国发明专利中,公开了一种羧甲基甲壳胺 纤维及其制备方法和应用 (此中的甲壳胺是壳聚糖的一个别名, 因而羧甲基甲壳 胺也称为羧甲基壳聚糖)。该文献的内容在此全文并入作为参考。该羧甲基甲壳胺 纤维的高分子单体的羧甲基取代度为 1〜50%, 使得该纤维具有较高的吸湿性能, 同时又保持了纤维状的结构, 即保持了水不溶解性。 然而, 低取代度的羧甲基甲 壳胺纤维在体内的降解时间较长,同时也会引起机体的炎症反应,故不适用体内。 发明内容
本发明的目的是 ¾ί共一种水溶性壳聚糖基纤维材料及其制备方法和应用, 以 克服现有技术的上述缺点。
根据本发明的一个方面, 其 iff共一种水溶性壳聚糖基纤维材料, 其中 TO/ 溶性壳聚糖基纤维包括羧甲基壳聚糖纤维、 羟丙基壳聚糖纤维、 羟乙基壳聚糖纤 维、 羧甲基羟乙基壳聚糖纤维或它们的混合物。 根据本发明的水溶性壳聚糖基纤 维材料可以是纤维、 绵条、 绵球、 绵絮、 非织布、 针织布、 编织布、 机织布等形 式。
根据本发明的另一个方面,其樹共一种水溶性壳聚糖基纤维材料的制备方法, 包括以下步骤:
将水不溶性壳聚糖基纤维材料 重量百分浓度为 20〜50%、鶴 30〜45% 的 NaOH 溶液或 KOH 溶液中, 其中该水不溶性壳聚糖基纤维材料与上述碱 的水溶液的重量比例为 1: (5〜40), 鶴为 1: ( 10-25 ) , 在 -40°C〜室温 牛 下碱化 2〜72 hr, i 12~481ττ; 将经碱化的水不溶性壳聚糖基纤维在反应介质 中与卤代乙酸、 或卤代乙醇、 或环氧丙垸、 或卤代丙醇、 或卤代乙酸与卤代乙醇 的组合反应 5〜36 hr, im 6-24 hr, 以形成相应的水溶性壳聚糖基纤维; 其中 不溶性壳聚糖基纤维材料与碱、 卤代乙酸或卤代乙醇或环氧丙烷或卤代丙 醇或卤代乙酸与鹵代乙醇的组合的用量的摩尔比例为 1: ( 10〜40) : ( 1.1〜15), 优选为 1: (20-40) : (5〜12)。
根据本发明的再一个方面,其 $|共一种水溶性壳聚糖基纤维材料的制备方法,
包括以下步骤:
将水溶性壳聚糖碰末溶解在去离子水中, 搅拌溶解, 成粘稠胶漏夜, 压 滤, 除去微量不溶物,得重量百分浓度为 2%〜10%、 tfc^ 5%〜8%的水溶性壳聚 糖基喷丝液, 喷丝液通过喷丝头喷进 为30〜45°〇的凝固浴中,形成水溶性壳 聚糖基纤维, 该纤维经 辊牵引, ¾Λ¾伸浴, 经拉伸辊牵引拉伸, 再经绕卷 拉伸, 制成水溶性壳聚糖基纤维束, 去除有机髓 11, 干燥, 得干燥的水溶性壳聚 糖基纤维, «理、 »刀、 包装、 灭菌, 制得水溶性壳聚糖基纤维材料中的纤维 绵条、 绵球或绵絮; 或将水溶性壳聚糖基纤«—步加工成非织布、 针织布、 编 织布、 机织布形式的材料。
根据本发明的又一个方面, 其还涉及水溶性壳聚糖基纤维材料在制备 ihl& 愈创或防止组织粘连的药物或医疗器械中的应用。
根据本发明的又一个方面, 其还涉及将水溶性壳聚糖基纤维材料制备的药物 或医疗器械在临床手术的术前、 术中、 术后的止血、 舰创面愈合和防止组织粘 连中的应用。
本发明的水溶性壳聚糖基纤维材料同时具有止血、 促进创面愈合和防止术后 组织粘连的作用;能够在生理 pH餅下逐渐吸水膨胀并逐步溶解形厳体溶液, 局部贴敷性能好, 能更好地雄止血、愈创和防粘连的功能;在体内无免疫原性, P軸军时间短, 与生物体相容†勉子, 临床麵的安全性更好, 适合于体内止血、 愈 仓 |J和防粘连应用;本发明的水溶性壳聚糖基纤维材料为非织布、针织布、编织布、 机织布、绵条、绵球、绵絮的形态, 均具有一定的机械搬, 临床備喿作方便, 粘附牢固, 能更好地发挥其功能, 更好地满足临床应用。 具体实脑式
在根据本发明的水溶性壳聚糖基纤维材料中, 戶/M ^溶性壳聚糖基纤 «自 于羧甲基壳聚糖纤维、 羟丙基壳聚糖纤维、 羟乙基壳聚糖纤维、 羧甲基羟乙基壳 聚糖纤维或它们的混合物。
式中, Η、 -COCH3、 -CH2COONa或 -CH2COOK, 为11、 -CH2C〇ONa或 -CH2COOK, 其中羧甲基取代度大于 60%。该羧甲基壳聚糖纤维优选是羧甲基壳 聚酵千维或羧甲基壳聚藝纤维。
在根据本发明的水溶性壳聚糖基纤维材料中, 戶 ¾轻丙基壳聚糖可以具有以 下结构:
式中, 为^1、 -COCH3或 -C¾CHOHC¾, R2为 H或- C¾CHOHCH3, 其中羟 丙»謹大于亂
在根据本发明的水溶性壳聚糖基纤维材料中, 戶 M羟乙基壳聚糖可以具有以 下结构:
式中, 为11、 -COCH3或 -C¾C¾OH, 为 H或- CH2CH2OH, 并且其羟乙基 取代度大于 60%。
式中, R, H、 -COCH3、 -C¾COONa、 -CH2CO〇K或 -CH2C¾OH, 为 -C¾COONa、 -CH2CO〇K或 -CH2CH2OH, 并且其羧甲基和羟乙基取 ¾ 之和大 于 60%。
根据本发明的水溶性壳聚糖基纤维材料可由诸如水溶性羧甲基壳聚糖、 轻丙 基壳聚糖、 羟乙基壳聚糖、 羧甲基羟乙基壳聚糖或它们的混合物等的水溶性壳聚 糖基粉末起始按照常规方法制造。例如,将水溶 甲基壳聚糖、羟丙基壳聚糖、 羟乙基壳聚糖、 羧甲基羟乙基壳聚糖或它们的混合物的粉末溶解在去离子水中, 在室温餅下搅拌溶解, 静置, mmm , 分别用 200 目、 300 目、 4oo 目、 500目绢布叠加, 于过滤器中压滤, 除去微量不溶物, 滤液真空 牛下脱气, 得透明清澈的胶«液, 即为水溶性壳聚糖基喷丝液。 将该喷丝液通过喷丝头喷 进凝固浴中, 形成水溶性壳聚糖基纤维。 该纤维经受丝辊牵引, 进入拉伸浴, 经 拉伸辊牵引拉伸, 再经绕卷拉伸, 取下制成的水溶性壳聚糖基纤维束, 离心甩干 有机溶剂, 于例如 50〜70°C下干燥, 得干燥的水溶性壳聚糖基纤维, 理、裁 切、 包装、 灭菌, 制得水溶性壳聚糖基纤维材料中的纤维绵条、 绵球或绵絮。
所述的喷丝液中水溶性壳聚糖基的重量百分浓度可以为 2%〜10%,优选的重 量百分浓度为 5%〜8%。 所述的凝固浴和拉伸浴可以是乙醇、 丙酮中的 1种或 2 种或其重量百分浓度大于 90%的含水溶液。 所述的凝固浴的温度可以是 30〜 45°C。 難的灭菌是 灭菌或环氧乙垸灭菌。
如上得到的水溶性壳聚糖基纤维还可按照本领域技术人员已知的方法进一步 加工成非织布、 针织布、 编织布、 机织布形式的材料。
在本发明中, 非织造布又称无紡布, 是定向或随机排列的纤親过摩擦、 抱 合或粘合或者这些方法的组合而相互结^ ^成的薄片、 纤网或絮垫。 机织物是由 相互垂直排列即横向和纵向两系统的纱线在织肚根据一定的规律交织而成的织 物。 针织物是指用织针将纱线或长丝构成线圈, 再把线圈相互串套而成的织物。 编织物是指把纱线或线绳用编织形式编成的织物。
另一方面, 根据本发明的水溶性壳聚糖基纤维材料还可由水不溶性的壳聚糖 基纤维来制备, 该方鲍括:将水不溶性壳聚糖基纤维^ Λ重量百分浓度为 20〜
50%的 NaOH 溶液或 KOH水溶液中, 水不溶性壳聚糖基纤维与上述碱的水溶 液的重量比例为 1 : (5〜40), 在 -40°C〜室温条件下碱化 2〜72 hr; 碱化后将碱 化的水不溶性壳聚糖基纤维转入反应介质中, 在室温和振荡餅下, 加入反应试 剂卤代乙酸或卤代乙醇或环氧丙烷或卤代丙醇或卤代乙酸与 代乙醇的组合, 水 不溶性壳聚糖基纤维与碱、 卤代乙酸或卤代乙醇 *f氧丙烷或卤代丙醇或卤代乙 酸与卤代乙醇的組.合的用量的摩尔比例为 1: (10〜40) : (1.1〜15), 反应 5〜 36 hr; 反应后取出固形物, 用洗漆液洗漆至中性, 脱水, 去除多余液体, 然后将 其放于盛有 P205的真空干燥器中干燥, 挥尽残留的有机溶剂, 经整理、裁切、包 装、 灭菌。
戶;¾的水不溶性壳聚糖纤维非织布、 壳聚糖纤维、 壳聚糖纤维针织布、 壳聚 糖纤维编织布, 均兩尔之为水不溶性壳聚糖基纤维。 在本发明的方法中, 水不溶 性壳聚糖基纤维可以是壳聚糖纤维、 壳聚糖纤维非织布、 壳聚糖纤维针织布、 壳 聚糖纤维编织布、 壳聚糖纤维机织布中的一种。
反应介质可以是甲醇、 乙醇、 异丙醇、 丁醇、 丙酮、 二甲亚砜、 四氢呋喃、 二氧六环中的 1种或 2种或 3种, 或是它们的水溶液。
反应试剂可以是卤代乙酸中的 1种或卤代乙醇中的 1种或环氧丙垸或卤代丙 醇中的 1种或卤代乙酸与卤代乙醇的组合中的 1种, 難的 代乙酸为氯乙酸、 溴乙酸或碘乙酸, 所述的卤代乙醇为氯乙醇或溴乙醇, 所述的卤代丙醇为 1-氯 -2- 丙醇或 1-溴 -2-丙醇, 臓的卤代乙酸与卤代乙醇的组合为氯乙酸与氯乙醇、溴乙 酸与氯乙醇、 氯乙酸与溴乙醇或溴乙酸与溴乙醇。
洗漆液可以是甲醇、 乙醇、 异丙醇、 丁醇、 丙酮中的 1种或 2种或 3种, 或 它们的重量百分浓度大于 75%的水溶液。
戶¾的灭菌可以是 6t)Co灭菌或环氧乙烷灭菌。
碱的水溶液的重量百分浓度可以为 20〜50%, 优选的重量百分浓度为 30〜 45%; 水不溶性壳聚糖基纤维与碱的水溶液的重量比例可以为 1: (5〜40), 优 选的重量比例为 1 : (10-25); 碱化 可以是 -40°C〜室温, 碱化时间是 2〜 72 hr, 优选的碱化时间是 12〜48hr; 7不溶性壳聚糖基纤维与碱、 反应试剂的用 量的摩尔比例为 1 : (10〜40) : (1.1〜15) , 的摩尔比例为 1: (20-40) : (5〜12); 反应时间可以是 5〜36 hr, 优选的反应时间是 6〜24 hr, 反应温度 是室温。
在本发明的方法中, 作为原料使用的水不溶性壳聚糖基纤维, 其分子化学结 构中脱乙酰基糖基占分子中总糖基的摩尔百分数可以在 0〜100°/。之间, 均可达到
同样的效果, 因此统称为水不溶性壳聚糖基纤维。
根据本发明得到的水溶性羧甲基壳聚糖纤维的羧甲基取代度大小取决于反应 中反应试剂侧的摩尔数、 反应时间、 , 而羧甲基主要在 所处的 上, 也有部分在 Ri所处的位置上。上述反应餅的选择应使最 寻到的水溶性羧甲基 壳聚糖纤维的羧甲 β代度大于 60%。
根据本发明得到的水潮'银丙基壳聚糖纤维的羟丙繊代度大小取决于反应 中反应试剂側的摩尔数、反应时间、 ¾¾, 羟丙基主要在 所处的健上, 也 有部分在 ¾所处的 ffi上。 反应纖勺选择应使最终得到的水溶性羟丙基壳 聚糖纤维的羟丙»代度大于 60%。
根据本发明得到的水溶性羟乙基壳聚糖纤维的羟乙 β又代度大小取决于反应 中反应试剂使用的摩尔数、反应时间、 ,其中羟乙基主要在 所处的 β上, 也有部分在 R,所处的位置上。上述反应 牛的选择应使最终得到的水溶性羟乙基 壳聚糖纤维的羟乙 »代度大于 60%。
根据本发明得到的水溶性羧甲基羟乙基壳聚糖纤维的羧甲基、 羟乙基取代度 大小取决于反应中反应试剂麵的摩尔数、 反应时间、 、继, 其中羧甲基、 羟乙 基主要在 所处的健上, 也有部分在 所处的健上。 上述反应纖勺选择 应使最终得到的水溶性羧甲基羟乙基壳聚糖纤维的羧甲握嗨乙基取倾之和大 于 60%。
本发明的水溶性壳聚糖基纤维材料质地柔软, 色泽为白色, 具有良好的水溶 性。
以下将逝实施例更为具体地描述本发明。 在实施这些实施例时, 应清楚地 记住, 根据本发明公开的方法对于本领域技术人员而言毫无疑问地还有其他及不 同的实施方案。 在以上的描述和以下的实施例中, 所有的 都是未经校正的摄 氏度; 而且除非另有说明, 所有的取代度百分数都是以摩尔百分数为基准, 摩尔 百分数定义为在上述相关高 化合物中, 每个糖基平均腿接的羧甲基雜≤丙 基離乙基«甲基与羟乙基之和的摩尔百分数。 而除取代度百分数以外的其它 的百分数都是以重量为基准的百分数。
在以下实施例中,羧甲基壳聚辦内粉末由青岛博益特生物材 Ϋ精限公司生产; 而壳聚糖纤维、 壳聚糖纤维非织布和壳聚糖纤维针织布均购自上海东华大学。
例1: 水溶' ¾^甲基壳聚糖纤维非织布的制备
称取平均重量为 20.5 mg cm2的壳聚糖纤维非织布 12g,置于 500ml的广口试 剂瓶中, 力口入 45%的 KOH 7J溶液 200g, 搅拌使壳聚糖纤维非织布全部^ Λ碱液 中, -20 C下放置 24hr, 碱化, ί赚化壳聚糖纤维非织布。取出该碱化壳聚糖非织 布, ¾A 500ml的广口瓶中, 力口入 55%的丙酮水溶液 180g作为反应介质, 振荡 牛下加入 50%的一氯乙酸的乙醇溶液 85g作为反应试剂, 室温下反应 9 hr, 得 羧甲基壳聚糖钾纤维非织布。取出该羧甲基壳聚糖钾纤维非织布, 用 60%的丙酮 水溶液作为洗涤液充分洗涤至中性, 用¾ 丙酮脱水, 挤压或离心鬼干, 去除多 余液体, 然后将其放于盛有 P205的真空干燥器中真空干燥, 在 50Ό下挥尽干燥 品中残留的有机溶剂, 得羧甲 为 92%的羧甲基壳聚糖纤维非织布, 经整 理、 裁切、 包装、 60Co灭菌, 制得水溶性壳聚糖基纤维材料。
2: 7溶' 甲基壳聚糖纤维的制备
称取长度为 10cm的壳聚糖纤维 5g, 置于 500ml的广口试剂瓶中, 加入 30% 的 NaOH 7溶液 160g, 搅拌使壳聚糖纤维全部^ Λ碱液中, 室温下方 1* 48 hr, 碱化, 得碱化壳聚糖纤维。 取出该碱化壳聚糖纤维, 方 500ml的广口瓶中, 加 入甲醇 160g作为反应介质, 振荡条件下加入 50%的一氯乙酸的甲醇溶液 46g作 为反应试剂, 室温下反应 8hr, 得羧甲基壳聚猶内纤维。 取出该羧甲基壳聚猶内 纤维, 用甲醇作为洗鎌充分洗漆至中性, 挤压或离心鬼干, 去除多余液体, 然 后将其放于盛有 P205的真空干燥器中真空干燥, 在 5(TC下挥尽干燥品中残留的 有机溶剂, «甲«代度为 96%的羧甲基壳聚糖纤维, 经整理、 裁切、 包装、 环氧乙焼灭菌, 制得水溶性壳聚糖基纤维材料。
本发明制得的水溶性壳聚糖基纤维材料可以是羧甲基壳聚糖纤维的绵条、 绵 球或绵絮。 实施例 3: 水溶'隨甲基壳聚糖纤维 只布的制备
称取平均重量为 15.6 mg/cm2的壳聚糖纤维针织布 10g,置于 500ml的广口试 剂瓶中, 加入 40%的 NaOH τ溶液 200g, 搅拌使壳聚糖纤维针织布全部 ¾Λ¾ 液中, 0〜4°C下放置 48 hr,碱化,徵烕化壳聚糖纤维针织布。取出该碱化针织布, 500ml的广口瓶中, 力口入 90%的乙醇水溶液 135g和二甲亚砜 50g作为反应 介质, 振荡 牛下加入 50。/。的一氯乙酸的乙醇溶液 70g作为反应试剂, 室温下反 应 10 hr,得羧甲基壳聚辭内纤维针织布。取出该羧甲基壳聚糖钠针织布, 用 75%
的乙醇水溶液作为洗漆液充分洗涤至中性, 用无水乙醇脱水, 挤压或离心甩干, 去除多余液体, 然后将其放于盛有 P205的真空干燥器中真空干燥, 在 70°C下挥 尽干燥品中残留的有机赚 I」,辯爱甲»«为 90%的羧甲基壳聚糖纤维针织布, 经整理、 翻、 包装、 环氧乙 '烷灭菌, 制得水溶性壳聚糖基纤维材料。
在实施例 1〜实施例 3中, 難的反应试剂可以是卤代乙酸中的 1种, 即氯 乙酸、 溴乙酸或碘乙酸中的 1种, 均可达到同样的效果。 鎌例 4: 水溶服丙基壳聚糖纤维非织布的制备
称取平均重量为 20.5 mg/cm2的壳聚糖纤维非织布 10g,置于 500ml的广口试 齐 1J瓶中, 加入 30%的 NaOH水溶液 200g, 搅拌使壳聚糖纤维非织布全部^ Λ碱 液中, -20°C下方 β 60 hi-, 碱化, ¾化壳聚糖纤维非织布。 取出该碱化的壳聚 糖纤维非织布, M 1000ml的带密封盖的不锈钢反应瓶中, 加入异丙醇 150g、 二甲亚砜 25g和二氧六环 25g作为反应介质, 振荡条件下加入环氧丙垸 45g作为 反应试剂, 密封瓶盖, 室温下振荡反应 24 hr, ί#¾丙基壳聚糖纤维非织布。取出 该羟丙基壳聚糖非织布, 用 80%的丙酮水溶液作为洗涤液充分洗涤至中性, 用无 水丙酮脱水, 挤压或离心甩干, 去除多余液体, 然后将其放于盛有 Ρ205的真空干 燥器中真空干燥, 在 50°C下挥尽干燥品中残留的有机溶剂, 得羟丙基取代度为 86%的羟丙基壳聚糖纤维非织布, 理、 裁切、 包装、 60Co灭菌, 制得水溶性 壳聚糖基纤维材料。
在本实施例中, 難的反应试剂可以是环氧丙烷或卤代丙醇中的 1种, 即环 氧丙烷、 1-氯 -2-丙醇或 1-溴 -2-丙醇中的 1种, 均可达到同样的效果。 m 5: 水溶觀乙基壳聚糖纤维非织布的制备
称取平均重量为 20.5 mg/cm2的壳聚糖纤维非织布 10g,置于 500ml的广口试 剂瓶中, 加入 45%的 KOH水溶液 200g, 搅拌使壳聚糖纤维非织布全部浸入碱液 中, -20°C下方 « 48 hr, 碱化, 槨减化壳聚糖纤维非织布。 取出该碱化的壳聚糖 纤维非织布, 方 j A 1000ml的带密封盖的不锈钢反应瓶中, 加入丙酮 160g、 二甲 亚砜 20g和四氢呋喃 20g作为反应介质, 振荡条件下加入一氯乙醇 55g作为反应 试剂, 密封瓶盖, 室温下振荡反应 36 hr, 得-羟乙基壳聚糖纤维非织布。取出该非 织布, 用 85%的丙酮水溶液作为洗漆液充分洗涤至中性, 用丙酮脱水, 挤压或离 心]!干, 去除多余液体, 然后将其放于盛有 P205的真空干燥器中真空干燥, 在 50°C下挥尽干燥品中残留的有机 ^BJ, 乙 «I®为 91%的羟乙基壳聚糖纤
维非织布, «理、裁切、包装、环氧乙烷灭菌, 制得水溶性壳聚糖基纤维材料。 在本实施例中, 所述的反应试剂可以是卤代乙醇中的 1种, 即氯乙醇或溴乙 醇中的 1种, 均可达到同样的效果。 实施例 6: 水溶'赚甲基羟乙基壳聚糖 隹非织布的制备
称取平均重量为 20.5 mg cm2的壳聚糖纤维非织布 10g,置于 500ml的广口试 剂瓶中, 加入 45%的 KOH水溶液 200g, 搅拌使壳聚糖纤维非织布全部 碱液 中, -20°C下放置 48 hr, 碱化, 得碱化壳聚糖纤维非织布。 取出该碱化的壳聚糖 纤维非织布, 放入 1000ml的带密封盖的不锈钢反应瓶中, 加入丙酮 160g、 二甲 亚砜 20g和四氢呋喃 20g作为反应介质, 振蘋 牛下加入 50%的一氯乙酸的乙醇 溶液 46g与一氯乙醇 30g作为反应试剂, 密封瓶盖, 室温下振荡反应 48 hr, 得羧 甲基羟乙基壳聚糖纤维非织布。取出该羧甲基羟乙基壳聚糖纤维非织布, 用 85% 的丙酮水溶液作洗漆溶液充分洗涤至中性, 用丙酮脱水, 挤压或离心鬼干, 去除 多余液体, 然后将其放于盛有 P205的真空干燥器中真空干燥, 在 50°C下挥尽干 燥品中残留的有机溶剂, 得羧甲基和羟乙基取代度为 94%的羧甲基轻乙基壳聚糖 纤维非织布, 经整理、 翻、 包装、 环氧乙垸灭菌, 制得水溶性壳聚糖基纤维材
实施例 7
称取羧甲基取 f¾S大于 60%的水溶性羧甲基壳聚糖钠粉末 120g,置于 3000ml 的洁净不诱钢容器中, 加入去离子水 2000ml, 在室温条件下搅拌溶解, 静置, 使 羧甲基壳聚 H¾、全部溶解戯占稠胶 «液, 分别用 200目、 300目、 400目、 500 目绢布叠加, 于 5000ml过滤器中压滤, 除去微量不溶物, 滤液真空 牛下脱气, 得透明清澈的羧甲基壳聚糖胶«液, 艮 羧甲基壳聚糖喷丝液。 将喷丝液 M; 喷丝头喷进 95%的乙醇水溶液的 40〜45°C的凝固浴中, 形成羧甲基壳聚糖纤维。 该纤维经受丝辊牵引, ¾Λ 95%的乙醇水溶液拉伸浴, 经拉伸辊牵引拉伸, 再经 绕卷拉伸, 取下制成的羧甲基壳聚糖纤维束, 离心鬼干有机灘 ij, 于 50〜70°C干 燥, 得羧甲基壳聚糖纤维, m, 裁切、 包装、 环氧乙烷灭菌, 制得水溶性壳 聚糖基纤维材料中的羧甲基壳聚糖纤维绵条、 绵球或绵絮。
在实施例 7中, 的羧甲基壳聚辦内可以是羧甲基壳聚糖掷、 羟丙基壳聚 糖、 離乙基壳聚糖, 缀尔为水溶性壳聚糠基材料, 该水溶性壳聚糖翻料中的 羧甲基、轻丙基或羟乙基的取代度均大于 60%, 均可达到同样效果。 戶满的喷丝 液中水溶性壳聚糖基材料的重量百分浓度可以为 2%〜10%,优选的重量百分浓度
为 5%〜8%。 所述的凝固浴和拉伸浴可以是乙醇、 丙酮中的 1种或 2种或其重量 百分浓度大于 90%的含水溶液。脇的凝固浴的 可以是 30〜45°C。難的灭 菌是 60Co灭菌或环氧乙烷灭菌。 雄例 8
实施例 7中得到的羧甲基壳聚糖纤维经开松、 梳理、 切断、 铺网、 加固、 成 网、 切割、 干燥, 得幾甲基壳聚糖纤维非织布, 理、 裁切、 包装、 环氧乙垸 灭菌, 制得水溶性壳聚糖基纤维材料中的非织布。
在实施例 8中, 戶 Μ的羧甲基壳聚糖纤维可以是羟丙基壳聚糖纤维或羟乙基 壳聚糖纤维, 均可达到同样的效果。 所述的水溶性溶性壳聚糖基纤维材料中的非 织布是羧甲基壳聚糖纤维非织布、 羟丙基壳聚糖纤维非织布、 乙基壳聚糖纤 维非织布。 实施例 9
7溶性壳聚糖基纤维材料的止血、愈创和防止术后组织粘连性能的 H验: 以大鼠为试验动物, 制作肝组织缺损模型, 分别评价比较氧化再生纤维素纱布
(Johnson&Johnson公司产品)、实施例 1中制备的水溶十纖甲基壳聚糖纤维非织 布、 实施例 4中制备的水溶性羟丙基壳聚糖纤维非织布、 实施例 5中制备的水溶 性羟乙基壳聚糖纤维非织布对肝组织缺损的 lhlf[L、愈创和防止术后组织粘连作用。 试验前在无菌条件下, 分别将各试验材料剪切成 lcmx lcm的片状, 备用。 选择 体重为 250g±20g的 SD大鼠 60只, 均为雄性, 随机分为阴性对照组(不使用材 料)、氧化再生纤维素纱布对照组(以氧化再生纤维素纱布为材料,简称为氧化纤 维素纱布组)、水溶性壳聚糖翻料 i验 1组 (以羧甲基壳聚糖纤维非织布为材料, 简称为羧甲基壳聚糖纤维非织布组)、 7J溶性壳聚糖基材料试验 2组(以羟丙基壳 聚糖纤维非织布为材料,简称为羟丙基壳聚糖纤维非织布组)、水溶性壳聚糖¾ 料试验 3组(以羟乙基壳聚糖纤维非织布为材料, 简称为羟乙基壳聚糖纤维非织 布组), 每组 12只大鼠。 全部动物均采用戊巴比妥钠腹腔注射麻醉, 剂量为 30mg g。 在各组大鼠腹部正中切长约 3cm的切口, 打开腹腔, 无菌 牛下游离 出肝脏左叶,用手术组织钳于肝脏中偏下部夹取 5mmx5mmx2m i (长 X宽 X厚) 大小的肝组织块, 造成肝组织缺损, 自组织切下计出血时间 5秒钟, 医用棉纱布 吸血, 并立即贴敷相对应的规格为 lcmxlcm的材料。 氧化纤维素纱布贴敷 3层 (重量为 61〜63mg) ,羧甲基壳聚糖纤维非织布贴敷 2层(重量为 59〜61mg),
羟丙基壳聚糖纤维非织布贴敷 2层(重量为 61〜63mg), 羟乙基壳聚糖纤维非织 布贴敷 2层(重量为 60〜62mg), 并分别在贴敷相对应的材料后, 在材料上放置 10g砝码压 20秒钟, 观察创面出血青况 40秒钟, 重^ h述步骤, 观察出血情况, 并记录, 3 中后切口缝合^!复, 碘伏消毒, 分组词养, 分别于 7天、 14 见察 动物肝组织缺损创面愈合和组织粘连情况。
试验结果见表 1和表 2, 结果表明, 三种水溶性壳聚糖基纤维材料和氧化再 生纤维素纱布与阴翻 比较, 均有显著止血效果、 搬创面愈合效果和防止术 后组织粘连效果; 同时从 i验结果还可以看出, 三种水溶性壳聚糖基纤维材料的 止血、 愈创和防止术后组织粘连效果优于氧化再生纤维素纱布, 明显缩短止血时 间, 缩短创面愈合时间, 并防止术后组织间粘连。
表 1.水溶性壳聚糖基纤维材料止血性齢怖验结果 组别 实 ¾¾力物数量(只) 止血时间 (秒) 阴 照组 12 >180
氧化纤维素纱布组 12 80-120
羧甲基壳聚糖纤维非织布组 12 ^0
羟丙基壳聚糖纤维非织布组 12 <30
羟乙基壳聚糖纤维非织布组 12 <30
表 2.组水溶性壳聚糖基纤维材料促进创面愈合和防止术后组织粘连性 ^HiH^ 别
结果
7天的 i验结果 14天的«结果 动物数 i 7天的创面愈合 14天的创面愈合 (只) 情况 (只) 情况 阴翻 -照组 3 创面愈 20%,组织间粘 创面愈合约 40-50%,组 织间粘 ¾ ^重 氧化纤维素纱布组 6 材料基本瞻,形成紫黑色 材料基本贿 ' 创面有 纖,创面愈合约 40-50%, 紫黑色繊, 创面愈合 组织间有粘连 约 80-90%,组织间有粘 连 羧甲基壳聚糖纤维 材料已隨, 材料已軸, 创面完全 非织布组 创面愈合约 70-80%, 組.织 愈合, 创面平整' 组织 间无粘连 间无粘连 羟丙基壳聚糖纤维 材料已隱, 材料已隨, 创面完全 非织布组 创面愈合约 70-80%, 组 愈 创面平整, 组织 间无粘连 间无粘连 材料已隨, 材料已隐 创面完全 非织布组 创面愈 ^勺 70-80%, 组织 愈合, 创面平整, 组织 间无粘连 间无粘连
*阴性对照组实验大鼠术后 24小时内死亡 5只 本发明的水溶性壳聚糖基纤维材料可以制成药物或医疗器械, 并应用于临床 腹腔手术、 胸腔手术、 骨禾 术、 妇禾枰术、 显微外禾粹术、 烧伤禾 术、 整形 外 术等, 于术前、 术中和术后将水溶性壳聚糖基纤维材料放置在出血部位, 轻度按压, 可有效對军 i 4L作用、 创面愈合作用和防止术后组织粘连作用。 特别是本发明的水溶性壳聚糖基纤维材料,生物相容性好,不引起机体炎症反应, 体内降解时间短, 愈创和防止术后组织粘连效果好, 适合在手术创面的止 血、 愈创和防止术后组织粘连棚。
以上实施例表明, 本发明的水溶性壳聚糖基纤维材料, 可以在制备药物或医 疗器械中应用, 制)^用于外禾 术止血或^ ¾创面愈合或防止术后组织粘连的 药物或医疗器械。
用本发明的普遍或具体描述的反应物和 /或操作条件替换上述实施例中使用 的反应物和 /或操作 ^牛,类似成功地重复这些实施例。虽然已相对于制备和具体 的化合物说明了本发明, 但显而易见的是, 在不偏离本发明的精神或范围的情况 下还可对其进行多种改变和改进。
Claims
1、一种水溶性壳聚糖基纤维材料,其中戶 7溶性壳聚糖基纤维包括羧甲基 壳聚糖纤维、 羟丙基壳聚糖纤维、 羟乙基壳聚糖纤维、 羧甲基羟乙基壳聚糖纤维 或它们的混合物。
权
2、如权利要求 1所述的水溶性壳聚糖基纤维材料,其中所述羧甲基壳聚糖具 有以下结构:
式中, 为11、 -COCH3、 -CH2C ONa或 -CH2COOK,书 R2为 H、 -CH2COONa或 -CH2COOK, 其中羧甲基取代度大于 60%。
3、如权利要求 1所述的水溶性壳聚糖基纤维材料,其中所述羟丙基壳聚糖具 有以下结构:
式中, 为¾ -COCH3或 -CH2CHOHCH3, R2为 H或 -C¾CHOHCH3, 其中羟 丙纖倾大于 60%。
式中, 为11、 -COCH3或 -C¾CH2OH, R2为 H或- CH2CH2OH, 并且其羟乙基 取代度大于 60%o 5、如权利要求 1所述的水溶性壳聚糖基纤维材料,其中所述羧甲基羟乙基壳 聚糖具有以下结构:
式中, 为11、 -COC¾、 -C¾COONa、 -C¾COOK或 -C¾C¾OH, 为 H、 -CH2COONa、 -CH2COOK或 -CH2CH2OH, 并且其羧甲 卩羟乙基取 ¾S之和大 于 60%。
6、 如权利要求 1-5之一所述的水溶性壳聚糖基纤维材料, 其为纤维、 绵条、 绵球、 绵絮、 非织布、 针织布、 编织布、 机织布的形式。 7、权利要求 1-6之一戶 M的水溶性壳聚糖基纤维材料的制备方法,其包括以 下步骤:
将水不溶性壳聚糖基纤维材料 靈百分浓度为 20〜50%、鶴 30-45% 的 NaOH水溶液或 KOH水溶液中, 其中该水不溶性壳聚糖基纤维材料与上述碱 的水溶液的重量比例为 1: (5〜40),
l: (10-25), 在 -40 〜室温 牛 下碱化 2〜72 hr, im 12~48hr; 将经碱化的水不溶性壳聚糖基纤维材料在反应 介质中与卤代乙酸、 或卤代乙醇、 或环氧丙垸、 或卤代丙醇、 或卤代乙酸与卤代 乙醇的组合反应 5〜36 hr, im 6〜24 hr, 以形劇 应的水溶性壳聚糖基纤维材 料; 其中所 不溶性壳聚糖基纤维材料与碱、 卤代乙酸或卤代乙醇或环氧丙烷
或卤代丙醇或卤代乙酸与卤代乙醇的组合的用量的摩尔比例为 1: ( 10〜40) (U〜15), t¾ ^为 1: (20—40) : (5〜12)。
8、如权利要求 7戶 M的水溶性壳聚糖基纤维材料的制备方法,其中戶 卤代 乙酸是氯乙酸、 溴乙酸或碘乙酸, 戶 ¾卤代乙醇是氯乙醇或溴乙醇, 戶满卤代丙 醇是 1-氯 -2-丙醇或 1-溴 -2-丙醇,難 代乙酸与卤代乙醇的组合是氯乙酸与氯乙 醇、 溴乙酸与氯乙醇、 氯乙酸与溴乙醇或溴乙酸与溴乙醇。
9、如权利要求 7所述的水溶性壳聚糖基纤维材料的制备方法,其中所述反应 介质为甲醇、 乙醇、 异丙醇、 丁醇、 丙酮、 二甲亚砜、 四氢呋喃、 二 环中的
1种或多种, 或是它们的水溶液。
10、 如权利要求 7戶 ¾的水溶性壳聚糖基纤维材料的制备方法, 其还包括将 所得产品用洗漆液洗涤至中性的步骤。 ιι、如权利要求 10戶; ¾的水溶性壳聚糖基纤维材料的制备方法,其中戶 Μ的 洗漆液可为甲醇、 乙醇、 异丙醇、 丁醇、 丙酮中的 1种或 2种或 3种, 或它们的 重量百分浓度大于 75%的水溶液。 12、 如权利要求 7戶 Μ的水溶性壳聚糖基纤维材料的制备方法, 其进一步包 括灭菌的步骤。
13、如权利要求 12戶 ¾的水溶性壳聚糖基纤维材料的制备方法,其中戶 灭 菌是 6QC。灭菌或环氧乙垸灭菌。
14、如权利要求 7-13之一腿的水溶性壳聚糖基纤维材料的制备方法,其中 i¾7 不溶性壳聚糖基纤维是为以下形式中的一种: 壳聚糖纤维、 壳聚糖纤维非 织布、 壳聚糖纤维针织布、 壳聚糖纤维编织布、 壳聚糖纤维机织布! 腿白勺水不 溶性壳聚糖基纤维的分子化学结构中的脱乙酰基糖基占分子中总糖基的摩尔百分 数可为 0〜100%。
15、 权利要求 1-6之一戶 ¾的水溶性壳聚糖基纤维材料的制备方法, 其包括
以下步骤:
将水溶性壳聚糖基粉末溶角 ½去离子水中,得重量百分浓度为 2%〜10%、优 选 5%〜8%的水溶性壳聚糖基喷丝液,喷丝液通过喷丝头喷进温度为 30〜45 的 凝固浴中, 形成水溶性壳聚糖基纤维, 该纤维经 辊牵引, 进入拉伸浴, 经拉 伸辊牵引拉伸, 再经绕卷拉伸, 制成水溶性壳聚糖基纤维束, 去除有机溶剂, 干 燥, 得干燥的水溶性壳聚糖基纤维。
16、如权利要求 15戶¾的水溶性壳聚糖基纤维材料的制备方法,其进一步包 括以下步骤: 整理、 裁切、 包装和灭菌。
17、如权利要求 15戶 ¾的水溶性壳聚糖基纤维材料的制备方法,其进一步包 括将碰干燥的水溶性壳聚糖基纤腿一步加工成纤维绵条、 绵球或绵絮、 非织 布、 针织布、 编织布、 机织布形式的材料。 18、如权利要求 15所述的水溶性壳聚糖基纤维材料的制备方法,其中所 ¾ΤΚ 溶性壳聚糖基粉末可为羧甲基壳聚糖、 羟丙基壳聚糖、 羟乙基壳聚糖、 羧甲基羟 乙基壳聚糖或它们的混合物的粉末, 其中的羧甲基、 羟丙基 乙基的取代度均 大于 60%。
19、如权利要求 15戶 Μ的水溶性壳聚糖基纤维材料的制备方法,其中戶 ¾凝 固浴和拉伸浴可以是乙醇、丙酮中的 1种或 2种或其重量百分浓度大于 90%的含 水溶液
20、如权利要求 16所述的水溶性壳聚糖基纤维材料的制备方法,其中所述灭 菌是 60Co灭菌或环氧乙烷灭菌。
21、 权利要求 1-6之一腿的水溶性壳聚糖基纤维材料在制备止血、 愈创或 防止组织粘连的药物或医疗器械中的应用 22、权利要求 20所述的应用,其中 药物或医疗器械是在临床手术的术前、 术中、 术后用于止血、 «创面愈合和防止组织粘连。
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WO2024123259A1 (en) * | 2022-12-05 | 2024-06-13 | Fikrettin Sahin | New polymer-based hemostatic formulations provided with anti microbial, anti-viral and anti-inflammatory properties and production method thereof |
Also Published As
Publication number | Publication date |
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US20100305489A1 (en) | 2010-12-02 |
EP2156849B1 (en) | 2017-10-25 |
CN101049513A (zh) | 2007-10-10 |
CN101049513B (zh) | 2010-05-19 |
EP2156849A4 (en) | 2010-08-18 |
EP2156849A1 (en) | 2010-02-24 |
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