CN107530212B - Biological tissue reinforcing material - Google Patents

Abstract

Translated fromChinese

本发明提供一种生物组织加固材料，其能够在不使用作为血液制品的纤维蛋白胶的情况下，更可靠地加固衰弱的组织，同时防止空气渗漏和液体渗漏。本发明提供一种包括层压结构的生物组织加固材料，该层压结构包括：由生物可吸收聚合物制成的纤维结构；和由通过纤维素羟基的醚化产生的醚化纤维素制成的纤维结构。

The present invention provides a biological tissue reinforcement material that can more reliably reinforce weakened tissue while preventing air leakage and fluid leakage without using fibrin glue as a blood product. The present invention provides a biological tissue reinforcement material comprising a laminated structure comprising: a fibrous structure made of a bioabsorbable polymer; and an etherified cellulose produced by etherification of cellulose hydroxyl groups fibrous structure.

Description

Biological tissue reinforcing material

Technical Field

The present invention relates to a biological tissue reinforcement material capable of reinforcing weakened tissue more reliably while preventing air leakage or liquid leakage without using fibrin glue as a blood product.

Background

The most fundamental problem in the field of surgery is the repair of damaged or weakened organs or tissues. For example, bleeding from injured organs is still treated by stopping the bleeding and suturing the wound, even now this is the most common surgical procedure for hemostasis. Furthermore, another important issue in surgical treatment is preventing leakage of liquid or air from weakened or damaged tissue. Particularly in the field of thoracic surgery, it is important to prevent air leakage caused by pneumothorax or after lung cancer resection. In particular, pneumothorax is a difficult disease to treat because of the increased rate of relapse without proper treatment.

Pneumothorax often occurs for the following reasons: air leaks into the chest cavity from the stump or suture site of the lung after resection, the site of the lung after partial resection to remove lung cancer, or the damaged site of lung tissue due to injury; or air leaks into the chest cavity from the tear of a cyst (called a bulla) inverted by some of the alveoli. This leakage has been treated by pleurodesis, in which lung tissue is allowed to adhere to the pleura by means of pharmaceutical or artificial chemical burns. Pleurodesis can prevent pneumothorax recurrence to a certain extent. However, if the lung tissue is not tightly attached to the pleura, the recurrence rate increases. If further surgery is required, the adhesion between the lung tissue and parietal pleura needs to be removed, which prolongs the surgical time or causes bleeding when the adhesion is removed. Therefore, new treatment methods replacing pleurodesis have been investigated.

Furthermore, an important problem in the field of digestive surgery is to prevent leakage of pancreatic juice from the pancreatic stump after a partial pancreatectomy. Pancreatic juice dissolves granulation tissue responsible for wound healing and prevents tissue growth, resulting in difficulty in pancreatic tissue regeneration. Furthermore, it is a concern that leaky digestive vessels of pancreatic juice may cause a life-threatening complication of postoperative bleeding.

For this situation, a combination of fibrin glue and fibrous structures made of bioabsorbable polymers have been used to reinforce lung tissue and seal lung surfaces. Non-patent documents 1 to 4 show that this method can reduce the recurrence rate of pneumothorax more than usual pleurodesis.Non-patent document 5 shows that this method is also used for preventing bleeding after hepatectomy in the field of digestive surgery.

The combined use of fibrin glue and a fibrous structure made of a bioabsorbable polymer is very effective for strengthening weakened tissue. However, air or liquid leakage may occur even in the reinforced area, which may result in the need for further surgery. This is not a high incidence, but leakage can be a risk factor for serious symptoms. Therefore, a reliable reinforcement method is required. In addition, fibrin glue as a blood product may cause unknown viral infections.

Reference list

-non-patent literature

Non-patent document 1: J.Pediatric Surg,42,1225-1230(2007)

Non-patent document 2: interact, Cardiovasc, Thorac, Surg,6,12-15(2007)

Non-patent document 3: the Journal of The Japanese Association for chess Surgery,19 (4); 628-

Non-patent document 4: the Journal of The Japanese Association for The Chest Surgery,22(2),142-

Non-patent document 5: the Japanese Journal of Clinical and Experimental Medicine,84,148(2007)

Disclosure of Invention

Technical problem

An object of the present invention is to provide a biological tissue-reinforcing material capable of reinforcing weakened tissue more reliably while preventing air leakage and liquid leakage without using fibrin glue as a blood product.

-solution of the problem

The present invention is a biological tissue reinforcement material comprising a laminated structure including: a fibrous structure made of a bioabsorbable polymer; and a fibrous structure made of etherified cellulose produced by etherification of cellulose hydroxyl groups.

The present invention is described in detail below.

The present inventors have studied the cause of air leakage or liquid leakage from a biological tissue reinforced with a fibrous structure made of a bioabsorbable polymer in combination with fibrin glue, and found that the cause of leakage is an adhesion region with fibrin glue. Fibrin glue that gels in a short time is very useful as a biogel. However, since the fibrin glue in the form of gel is relatively hard, adhesive failure or interfacial peeling may occur due to impact. Especially in the case of fibrin glue for strengthening lung tissue, adhesive failure or interfacial peeling may occur due to very high pressures on the lung tissue through coughing or sneezing. The gelled fibrin glue, once separated, cannot adhere anymore because of its less adhesive properties. Air or liquid leaks may occur in such separate areas.

The present inventors have further conducted various studies and found that using etherified cellulose produced by etherification of cellulose hydroxyl groups (hereinafter also referred to as "etherified cellulose") instead of fibrin glue allows a weakened tissue to be reinforced more reliably and gives a biological tissue reinforcing material that does not cause air leakage or liquid leakage. Thus, the present invention has been completed.

Etherified cellulose has proven to be a highly safe compound and gels in a short time like fibrin glue to be used as a glue for attaching a fibrous structure made of bioabsorbable polymer to biological tissue. In addition, since the gelled etherified cellulose has a certain degree of adhesion, even if adhesive destruction or interfacial peeling occurs due to high pressure, the etherified cellulose can be adhered again to prevent air leakage or liquid leakage. Further, since the etherified cellulose can be processed into a fiber, a laminated structure preliminarily made by laminating a fibrous structure made of such etherified cellulose on a fibrous structure made of a bioabsorbable polymer can provide a biological tissue reinforcing material which is remarkably easy to use.

The biological tissue reinforcing material of the present invention has a laminated structure including a fibrous structure made of a bioabsorbable polymer and a fibrous structure made of an etherified cellulose.

Fibrous structures made of bioabsorbable polymers are designed to exhibit tissue reinforcement, air leakage prevention, and liquid leakage prevention effects when attached to damaged or weakened organs. The fibrous structure made of etherified cellulose absorbs moisture to gel, and functions as an adhesive to attach the fibrous structure made of bioabsorbable polymer to a biological tissue.

Examples of bioabsorbable polymers include, but are not limited to: synthetic absorbable polymers such as alpha-hydroxy acid polymers (e.g., polyglycolide, polylactide (D, L, DL isomer), glycolide-lactide (D, L, DL isomer) copolymer, glycolide-epsilon-caprolactone copolymer, lactide (D, L, DL isomer) -epsilon-caprolactone copolymer, poly (p-dioxanone), and glycolide-lactide (D, L, DL isomer) -epsilon-caprolactone copolymer); and naturally absorbable polymers such as collagen, gelatin, chitosan or chitin. Any one of these may be used alone, or two or more of these may be used in combination. For example, where synthetic absorbable polymers are used as bioabsorbable materials, naturally absorbable polymers may be used therewith. Particularly preferred are alpha-hydroxy acid polymers which are homopolymers or copolymers of at least one monomer selected from the group consisting of glycolide, lactide, epsilon-caprolactone, p-dioxanone, and trimethylene carbonate due to their high strength. More preferred are polymers of alpha-hydroxy acids as homopolymers or copolymers of glycolide-containing monomers, since the polymers exhibit suitable decomposition behavior.

In the case where polyglycolide (a homopolymer or a copolymer of glycolide) is used as the bioabsorbable material, the preferred lower limit of the weight average molecular weight of the polyglycolide is 30000, and the preferred upper limit thereof is 1000000. Polyglycolide having a weight average molecular weight of less than 30000 is poor in strength and may not impart a sufficient tissue-strengthening effect. Polyglycolide having a weight average molecular weight of more than 1000000 is slowly decomposed in vivo and thus may cause foreign body reaction. A more preferable lower limit of the weight average molecular weight of polyglycolide is 50000, and a more preferable upper limit thereof is 300000.

The fibrous structure made of bioabsorbable polymer may be in any form, and may be in the form of a nonwoven, knitted fabric, woven fabric, gauze, or yarn. Further, these forms may be combined with each other. In particular, a nonwoven is preferred.

In the case where the fibrous structure made of a bioabsorbable polymer is in the form of a nonwoven fabric, the weight per unit area of the nonwoven fabric is not particularly limited, and the preferred lower limitIs 5g/m²And a preferred upper limit is 300g/m². The weight per unit area is less than 5g/m²The nonwoven of (a) has insufficient strength for the biological tissue reinforcement material and may not reinforce weakened tissue. The weight per unit area is more than 300g/m²The nonwoven of (a) may have poor adhesion to the tissue. A more preferable lower limit of the weight per unit area of the nonwoven fabric is 10g/m²And a more preferable upper limit thereof is 100g/m²。

The nonwoven may be made by any method, and examples of the method include conventionally known methods such as electrospinning deposition, melt blowing, needle punching, spun bonding, flash spinning, hydroentangling, air laying (air laying), thermal bonding, resin bonding, or wet processing.

Fibrous structures made from bioabsorbable polymers can be hydrophilized. The fiber structure subjected to the hydrophilization treatment rapidly absorbs moisture such as physiological saline in contact with the structure, and is thus easy to use.

Examples of hydrophilization include, but are not limited to, plasma treatment, glow discharge treatment, corona discharge treatment, ozone treatment, surface graft treatment, ultraviolet irradiation treatment, and the like. In particular, plasma treatment is preferred because it significantly increases water absorption without changing the appearance of the nonwoven.

The thickness of the fibrous structure made of bioabsorbable polymer is not particularly limited, and the preferred lower limit is 5 μm, and the preferred upper limit is 1.0 mm. A fibrous structure made of a bioabsorbable polymer having a thickness of less than 5 μm is poor in strength and may not impart a sufficient tissue reinforcing effect. Fibrous structures made of bioabsorbable polymers with thicknesses greater than 1.0mm may not adequately adhere and secure to tissue. A more preferred lower limit for the thickness of the fibrous structure made of bioabsorbable polymer is 10 μm and a more preferred upper limit thereof is 0.5 mm.

Etherified cellulose is produced by etherification of cellulose hydroxyl groups. Specific examples thereof include hydroxyalkylated celluloses represented by the formula (1), such as hydroxyethylated cellulose (in which the hydroxyl groups of the cellulose are substituted with hydroxyethyl groups), and hydroxypropylated cellulose (in which the hydroxyl groups of the cellulose are substituted with hydroxypropyl groups). In particular, hydroxyethylated cellulose, which has proven to be highly safe, is preferred.

In formula (1), n represents an integer, and R represents hydrogen or-R 'OH, wherein R' represents an alkylene group.

In the case where the etherified cellulose is a hydroxyethylated cellulose, the molar ratio of diethylene glycol groups to ethylene glycol groups (diethylene glycol groups/ethylene glycol groups) in the hydroxyethylated cellulose is preferably 0.1 to 1.0, and the molar ratio of triethylene glycol groups to ethylene glycol groups (triethylene glycol groups/ethylene glycol groups) is preferably 0.1 to 0.5. The etherified cellulose having a molar ratio in such a range imparts excellent initial adhesion when the fibrous structure made of a bioabsorbable polymer is adhered to a biological tissue by the fibrous structure made of the etherified cellulose, and high adhesion is maintained even after the adhesion. Even if adhesion failure or interfacial peeling occurs due to high pressure, the etherified cellulose can be adhered again to prevent air leakage or liquid leakage.

The number of moles of ethylene glycol groups, diethylene glycol groups and triethylene glycol groups can be determined by, for example, NMR or thermal decomposition GC-MS.

In the case where the etherified cellulose is hydroxyethylated cellulose, the average molecular number (Molar Substitution, MS) of the alkylene oxide bound to one anhydroglucose unit is preferably 1.0 at the lower limit, and 4.0 at the upper limit. The etherified cellulose having MS in such a range can be gelled in a short time, has high gel strength, and closely adheres to and fixes tissues. If the MS is less than 1.0, the gelled hydroxyethylated cellulose tends to have a lower viscosity. If the MS is more than 4.0, gelation tends to take a long time. A more preferred lower limit of MS is 1.3, and a more preferred upper limit thereof is 3.0.

In the case where the etherified cellulose is hydroxyethylated cellulose, the average Degree of Substitution (DS) of the alkylene oxide for the hydroxyl groups at the 2, 3 and 6 positions of the anhydroglucose unit is preferably 0.2 at the lower limit and 2.5 at the upper limit. The etherified cellulose having the DS in such a range can be gelled in a short time, has a high gel strength, and closely adheres to and fixes tissues. In addition, strength due to the fiber structure may be imparted, and the fiber may retain moisture therein. If the DS is less than 0.2, gelation may take a long time. If the DS is greater than 2.5, the strength may be reduced because the fiber structure is in a wet state. A more preferred lower limit of DS is 0.3, and a more preferred upper limit thereof is 1.5.

MS and DS can be calculated from the measurement of NMR spectrum of hydroxyethylated cellulose aqueous solution and the quantification of signal intensity of carbon atoms belonging to anhydroglucose ring and substituent carbon atoms in the spectrum (see, for example, JP-H6-41926B).

Specifically, for example, 0.2g of the sample, 30mg of the enzyme (cellulase) and an internal standard material were dissolved in 3ml of heavy water. The resulting solution was subjected to ultrasonic treatment for 4 hours, and its NMR spectrum was measured using an NMR measuring device (for example, JNM-ECX400P manufactured by JEOL) under the conditions of the number of scans of 700, pulse width of 45 °, and observation frequency of 31500 Hz.

Hydroxyethylated cellulose can be prepared, for example, by reaction of ethylene oxide with alkaline cellulose, which is prepared by treating cellulose with an aqueous solution of a base.

Specifically, for example, alkali cellulose is produced from a fibrous structure made of cellulose as a raw material by treating the fibrous structure with an aqueous solution of alkali such as sodium hydroxide. Then, a certain amount of ethylene oxide and a reaction solvent are added to the obtained alkali cellulose to carry out a reaction.

A preferred lower limit of the water absorption rate of the fibrous structure made of etherified cellulose is 200%, and a preferred upper limit thereof is 1000%. The fiber structure made of the etherified cellulose having the water absorption rate in this range can be gelled in a short time, has high gel strength, and closely adheres and fixes the tissue. If the water absorption is less than 200%, gelation may take a long time. If the water absorption is higher than 1000%, the gel strength tends to decrease. A more preferable lower limit of the water absorption rate is 400%, and a more preferable upper limit thereof is 800%.

The water absorption rate herein can be measured by the following method.

Specifically, the initial weight of the sample was measured and placed in a petri dish. Distilled water was slowly added dropwise to the sample. The weight of the sample containing distilled water absorbed to the maximum amount (the sample was in a condition that it could not absorb any more distilled water and excessive water leaked if distilled water was dropped to the sample) was determined as the maximum water absorption weight. The water absorption can be determined from the following equation using the obtained initial weight and maximum water absorption weight.

Water absorption (%) - (maximum water absorption weight-initial weight)/initial weight × 100

A preferred lower limit of the moisture absorption rate of the fibrous structure made of etherified cellulose is 7%, and a preferred upper limit thereof is 50%. The fiber structure made of etherified cellulose having a moisture absorption rate in such a range can be gelled in a short time, has a high gel strength, and closely adheres and fixes tissues. If the moisture absorption rate is less than 7%, gelation may take a long time. If the moisture absorption rate is higher than 50%, the gel strength tends to decrease. A more preferable lower limit of the moisture absorption rate is 10%, and a more preferable upper limit thereof is 35%.

The moisture absorption rate used herein can be measured by the following method.

Specifically, the sample was heated at 105 ℃ for 2 hours. The weight of the resulting sample was determined as absolute dry weight. Next, the absolutely dried sample was left standing at 20 ℃ for 7 hours in an atmosphere of 65% Rh to control the moisture content of the sample. The weight of the sample was determined as the weight after humidity control. Using the obtained absolute dry weight and the humidity-controlled weight, the moisture absorption rate can be calculated from the following equation.

Moisture absorption rate (%) (weight after humidity control-absolute dry weight)/absolute dry weight × 100

The fibrous structure made of etherified cellulose may be in any form, and may be in the form of a nonwoven, knitted fabric, woven fabric, gauze or yarn. Furthermore, fiber structures having this form may be combined with each other. In particular, a nonwoven is preferred.

In the case where the fibrous structure made of etherified cellulose is a nonwoven fabric, the weight per unit area of the nonwoven fabric is not particularly limited, and the preferred lower limit is 20g/m²And a preferred upper limit is 700g/m². If the weight per unit area of the nonwoven is less than 20g/m²The biological tissue reinforcing material cannot be attached to the biological tissue with sufficient adhesive force. If the weight per unit area of the nonwoven is greater than 700g/m²The gelation of the etherified cellulose may take a long time. A more preferable lower limit of the weight per unit area of the nonwoven fabric is 50g/m²And a more preferable upper limit thereof is 500g/m²。

The thickness of the fibrous structure made of etherified cellulose is not particularly limited, and the preferred lower limit is 50 μm and the preferred upper limit is 10 mm. The fibrous structure made of etherified cellulose having a thickness of less than 50 μm may not adhere the biological tissue reinforcing material to the biological tissue with sufficient adhesion. Alternatively, a fibrous structure made of etherified cellulose having a thickness of more than 10mm is not easy to absorb moisture, the texture is impaired, and the handleability is poor. A more preferable lower limit of the thickness of the fibrous structure made of etherified cellulose is 50 μm, and a more preferable upper limit thereof is 5 mm.

It is preferred to integrally combine a fibrous structure made of a bioabsorbable polymer and a fibrous structure made of an etherified cellulose. The integral combination structure exhibits enhanced ease of use.

The method of the integral combination may be any method, and examples of the method include needle punching, water jet punching, air jet entangling, knitting, weaving, or spray spinning (melt blowing, electrospinning).

The phrase "integrally combined" as used herein refers to a state in which two fiber structures laminated to each other can be handled as one structure and are not easily separated.

The biological tissue reinforcing material of the present invention is used to prevent bleeding from damaged or weakened organs or tissues, or to prevent air leakage or liquid leakage in the field of surgical operations. In particular, in the field of thoracic surgery, biological tissue reinforcement materials are advantageously used to prevent air leakage due to pneumothorax or after lung cancer resection.

The biological tissue-reinforcing material of the present invention can be easily attached to an affected part as long as the affected part is provided with a material that is previously immersed in physiological saline. In addition, the biological tissue reinforcing material absorbs blood or liquid from the affected part to exhibit adhesion.

Drawings

Fig. 1 is a diagram schematically showing a pressure test apparatus used in a pressure test performed in the example.

Advantageous effects of the invention

The present invention can provide a biological tissue reinforcing material capable of reinforcing weakened tissue more reliably while preventing air leakage and liquid leakage without using fibrin glue as a blood product.

Detailed Description

The examples described below more particularly illustrate embodiments of the invention. It should be noted that the present invention is not limited to these examples.

Example 1

(1) Preparation of fibrous structures made from hydroxyethylated cellulose

A single knit fabric of 280- μm thickness made of 80-gauge cellulose yarn as a starting material was bleached by hydrogen peroxide bleaching.

Then, 3.55g of the bleached knit fabric was immersed in 140mL of 10% aqueous sodium hydroxide solution at 15 ℃ for 30 minutes to alkalize the cellulose. The alkalized knitted fabric was flattened by applying a load of 2.5 to 3.0 kg.

Next, 12.25g of the resulting knitted fabric made of alkali cellulose was immersed in 50mL of a 0.8mol/L hexane solution of ethylene oxide at 25 ℃ and then reacted at 50 ℃ for 3 hours. The reacted knitted fabric was washed by immersion in 70mL of a mixture of methanol and methyl isobutyl ketone (methanol: methyl isobutyl ketone ═ 35:35) at 25 ℃ for 5 minutes and then neutralized by immersion in 72.6mL of a mixture of methanol, methyl isobutyl ketone and acetic acid (methanol: methyl isobutyl ketone: acetic acid ═ 35:35:2.6) at 25 ℃ for 10 minutes. In addition, the neutralized knitted fabric was immersed in a mixture of 70mL of isopropanol and water (isopropanol: water-63: 7) at 25 ℃ for 3 minutes and 70mL of acetone at 25 ℃ for 5 minutes, and dried at 40 ℃ for 24 hours. In this way, a fibrous structure made of hydroxyethylated cellulose is obtained.

Analysis of the hydroxyethylated cellulose of the resulting fibrous structure using thermal decomposition GC-MS showed a molar ratio of diethylene glycol to ethylene glycol groups (diethylene glycol/ethylene glycol) of 0.20 and a molar ratio of triethylene glycol to ethylene glycol groups (triethylene glycol/ethylene glycol) of 0.21.

(2) Preparation of biological tissue reinforcing material

A150- μ M thick nonwoven made of polyglycolide (NEOVEIL model NV-M015G manufactured by GUNZE LIMITED) was prepared as a fibrous structure made of bioabsorbable polymer.

The biological tissue reinforcement material is obtained in such a manner that: a combination of two kinds of fiber structures made of hydroxyethylated cellulose/a nonwoven made of polyglycolide/a fiber structure made of hydroxyethylated cellulose were laminated in a prescribed order and combined integrally by needle punching.

The obtained biological tissue-reinforcing material was cut into a circular shape having a diameter of 9-mm to obtain a test sample for measurement.

(3) Pressure testing

The pressure test was performed using the pressure test apparatus 1 shown in fig. 1.

A collagen film (produced by nippi.inc.) about 130- μm thick was cut into a circular shape having a diameter of 24-mm, and the cut film was washed with 70% ethanol, and the liquid was wiped off. The cut membrane was placed in a filter holder 2 (Swinnex (registered trademark) 25 produced by Merck Millipore). A hole having a diameter of 3-mm was formed in the center of the collagen membrane placed in thefilter holder 2 with a punch. A 20-ml syringe 3 (TERUMO syringe SS-20ESZ manufactured by term CORPORATION) and a pressure gauge 5 (digital pressure gauge FUSO-8230 manufactured by FUSORIKA co., ltd.) were placed downstream of the filter holder by means of a three-way stopcock 4. The pressure testing device was assembled in this manner.

The purified water was dropped onto one side surface of the test sample where the combination of two fibrous structures made of hydroxyethylated cellulose was combined. The resulting test sample was placed in the center of a collagen membrane disposed in a filter holder such that the combined side surface of the two fibrous structures was in contact with the collagen membrane. After the test sample was allowed to stand for 15 minutes, air was delivered to the test sample by a syringe. The maximum pressure at which peeling of the test sample did not occur was measured using a pressure gauge, and the pressure resistance (initial pressure resistance) was evaluated. After the initial pressure resistance was evaluated, air was delivered through the syringe five times every five minutes, and the maximum air pressure for peeling off the test sample was measured with a pressure gauge each time, and the reproducibility of the pressure resistance was evaluated.

Table 1 shows the results.

Example 2

A fabricated biological tissue-reinforcing material was obtained in the same manner as in example 1, except that a fibrous structure made of hydroxyethylated cellulose was prepared from a 200- μm thick single-knitted fabric made of 160 # cellulose yarn as a starting material, and a combination of three fibrous structures made of hydroxyethylated cellulose/a nonwoven fabric made of polyglycolide/a combination of two fibrous structures made of hydroxyethylated cellulose were laminated in the stated order. The biological tissue augmentation material is subjected to a pressure test. In the pressure test, the resulting test sample was placed in the center of a collagen membrane placed in a filter holder so that the surface of the combined side of three fibrous structures made of hydroxyethylated cellulose was in contact with the collagen membrane.

Table 1 shows the results of the pressure test.

Comparative example 1

The pressure resistance in the case of using a combination of fibrin glue and a fibrous structure made of a bioabsorbable polymer was evaluated by the following method.

A150- μ M thick nonwoven made of polyglycolide (NEOVEIL model NV-M015G manufactured by GUNZE LIMITED) was cut into a circle having a diameter of 9-mm.

A collagen membrane was placed in the filter holder of the pressure testing device prepared in example 1. Then, 20 μ L of fibrin glue liquid a (Beriplast P produced by CSL Behring k.k.) was dropped to the center of the collagen membrane to avoid pores of the collagen membrane and spread in a shape of about 9-mm in diameter. Subsequently, the nonwoven cut into a circle of 9-mm diameter was placed on the diffused liquid A and impregnated with the liquid A. Then, 40. mu.L of liquid A was dropped to the nonwoven, and the nonwoven was sufficiently impregnated with the liquid A. Then, 40. mu.L of liquid B was added dropwise to the nonwoven. After 15 minutes after the end of the dropwise addition of the liquid B, air was sent by a syringe, and the maximum pressure that did not cause peeling of the test sample was measured using a pressure gauge, and the pressure resistance (initial pressure resistance) was evaluated.

After the initial pressure resistance was evaluated, air was sent through the syringe four times every five minutes, and the maximum pressure that did not cause peeling of the test sample was measured each time using a pressure gauge, and the reproducibility of the pressure resistance was evaluated.

Table 1 shows the results.

Comparative example 2

A biological tissue-reinforcing material was obtained in the same manner as in example 1, except that a fibrous structure made of oxidized cellulose (SURGICEL manufactured by Johnson & Johnson k.k.) was used in place of the fibrous structure made of hydroxyethylated cellulose. The biological tissue augmentation material is subjected to a pressure test.

Table 1 shows the results of the pressure test.

TABLE 1

Table 1 shows that the initial pressure resistance was relatively high, up to 34.7mmHg, in the case of using a combination of fibrin glue and a fibrous structure made of bioabsorbable polymer, but a significant decrease in pressure resistance was observed in the test sample (from the second measurement) once separated by pressure. The pressure resistance was not restored to the original level. On the other hand, in the case of using the biological tissue reinforcing materials of examples 1 and 2, the initial pressure resistance was high (59.3mmHg and 52.1 mmHg). Furthermore, once separated by pressure, little decrease in pressure resistance was observed in the test sample (from the second measurement). This is believed to be because the test samples adhered again during the 5 minute interval. In comparative example 2, an example of a fibrous structure made of oxidized cellulose known as an absorbable hemostatic agent was tested. As a result, the initial pressure resistance was as low as 20.7mmHg, and a decrease in pressure resistance was observed from each measurement of the second measurement.

Industrial applicability

The present invention can provide a biological tissue reinforcing material capable of reinforcing weakened tissue more reliably while preventing air leakage and liquid leakage without using fibrin glue as a blood product. The biological tissue reinforcing material of the present invention can also be used for dura mater, oral mucosa, adhesion-preventing materials, and the like.

List of reference symbols

1. Pressure testing device

2. Filter holder

3. Syringe with a needle

4. Three-way cock

5. Pressure gauge

6. Collagen membrane with pores

Claims (11)

Translated fromChinese

1.一种包括层压结构的生物组织加固材料，所述层压结构包括：1. A biological tissue reinforcement material comprising a laminate structure comprising:由生物可吸收聚合物制成的纤维结构；和fibrous structures made of bioabsorbable polymers; and由醚化纤维素制成的纤维结构，所述醚化纤维素通过纤维素羟基的醚化而产生，并且所述由醚化纤维素制成的纤维结构吸收水分而凝胶化，作为粘合剂起作用将所述由生物可吸收聚合物制成的纤维结构附着至生物组织，A fibrous structure made of etherified cellulose, which is produced by etherification of cellulose hydroxyl groups, and which absorbs moisture and gels as a bond agent acts to attach the fibrous structure made of bioabsorbable polymer to biological tissue,其中通过纤维素羟基的醚化而产生的所述醚化纤维素是羟乙基化纤维素，wherein said etherified cellulose produced by etherification of cellulose hydroxyl groups is hydroxyethylated cellulose,其中在羟乙基化纤维素中，二甘醇基与乙二醇基的摩尔比为0.1-1.0，三甘醇基与乙二醇基的摩尔比为0.1-0.5。Wherein, in the hydroxyethylated cellulose, the molar ratio of diethylene glycol group to ethylene glycol group is 0.1-1.0, and the molar ratio of triethylene glycol group to ethylene glycol group is 0.1-0.5.2.根据权利要求1所述的生物组织加固材料，2. The biological tissue reinforcement material according to claim 1,其中由通过纤维素羟基的醚化生成的所述醚化纤维素制成的所述纤维结构是非织造物、机织织物、或纱线的形式。wherein the fibrous structure made of the etherified cellulose produced by etherification of cellulose hydroxyl groups is in the form of a nonwoven, a woven fabric, or a yarn.3.根据权利要求1所述的生物组织加固材料，3. The biological tissue reinforcement material according to claim 1,其中由通过纤维素羟基的醚化生成的所述醚化纤维素制成的所述纤维结构是针织织物或纱布的形式。Wherein the fibrous structure made of the etherified cellulose produced by etherification of cellulose hydroxyl groups is in the form of a knitted fabric or gauze.4.根据权利要求1所述的生物组织加固材料，4. The biological tissue reinforcement material according to claim 1,其中由通过纤维素羟基的醚化生成的所述醚化纤维素制成的所述纤维结构是针织织物的形式。Wherein the fibrous structure made of the etherified cellulose produced by etherification of cellulose hydroxyl groups is in the form of a knitted fabric.5.根据权利要求1或2所述的生物组织加固材料，5. The biological tissue reinforcement material according to claim 1 or 2,其中所述生物可吸收聚合物是α-羟基酸聚合物。wherein the bioabsorbable polymer is an alpha-hydroxy acid polymer.6.根据权利要求5所述的生物组织加固材料，6. The biological tissue reinforcement material according to claim 5,其中所述α-羟基酸聚合物是至少一种选自乙交酯、丙交酯、ε-己内酯、对二氧环己酮、和三亚甲基碳酸酯的单体的均聚物或共聚物。wherein the alpha-hydroxy acid polymer is a homopolymer of at least one monomer selected from the group consisting of glycolide, lactide, ε-caprolactone, p-dioxanone, and trimethylene carbonate or copolymer.7.根据权利要求1或2所述的生物组织加固材料，7. The biological tissue reinforcement material according to claim 1 or 2,其中由所述生物可吸收聚合物制成的所述纤维结构是非织造物、机织织物、或纱线的形式。wherein the fibrous structure made of the bioabsorbable polymer is in the form of a nonwoven, woven fabric, or yarn.8.根据权利要求1或2所述的生物组织加固材料，8. The biological tissue reinforcement material according to claim 1 or 2,其中由所述生物可吸收聚合物制成的所述纤维结构是针织织物或纱布的形式。Wherein the fibrous structure made of the bioabsorbable polymer is in the form of a knitted fabric or gauze.9.根据权利要求1或2所述的生物组织加固材料，9. The biological tissue reinforcement material according to claim 1 or 2,其中由所述生物可吸收聚合物制成的所述纤维结构是非织造物的形式。Wherein the fibrous structure made of the bioabsorbable polymer is in the form of a nonwoven.10.根据权利要求1或2所述的生物组织加固材料，10. The biological tissue reinforcement material according to claim 1 or 2,其中由所述生物可吸收聚合物制成的所述纤维结构和由通过纤维素羟基的醚化生成的所述醚化纤维素制成的所述纤维结构通过针刺、水刺、喷气缠结、针织、编织或喷雾纺丝而结合。wherein the fibrous structure made of the bioabsorbable polymer and the fibrous structure made of the etherified cellulose produced by etherification of cellulose hydroxyl groups are entangled by needle punching, hydroentangling, air jet entanglement , knitting, weaving or spray spinning.11.根据权利要求1或2所述的生物组织加固材料，11. The biological tissue reinforcement material according to claim 1 or 2,其中由所述生物可吸收聚合物制成的所述纤维结构和由通过纤维素羟基的醚化生成的所述醚化纤维素制成的所述纤维结构通过熔喷或静电纺丝而结合。wherein the fibrous structure made of the bioabsorbable polymer and the fibrous structure made of the etherified cellulose produced by etherification of cellulose hydroxyl groups are combined by melt blowing or electrospinning.

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