JP6193067B2 - Surgical hemostatic material substrate and surgical hemostatic material - Google Patents

Description

  The present invention relates to a surgical hemostatic base material and a surgical hemostatic material.

  In surgical operations on organs (respiratory and digestive organs, etc.), internal organs (heart, etc.), mucous membranes and blood vessels (arteries, etc.), etc. For this purpose, a medical material or a medical adhesive is used.

  As a medical material (hemostatic material) for the purpose of hemostasis, starch-derived hemostatic material (Arista AH; manufactured by Izumi Kogaku Medical Trading Co., Ltd.), oxidized cellulose hemostatic material (surge cell: manufactured by Johnson & Johnson), gelatin Sponge hemostatic material (Zelfoam; manufactured by Pfizer), collagen sheet hemostatic material (Instat; manufactured by Johnson & Johnson), collagen sheet hemostatic material containing fibrin (Takocomb; manufactured by CSL Bering Co., Ltd.), etc. Is commercially available. However, these hemostatic materials have low adhesiveness with tissue and sometimes cannot close the bleeding site, and in particular, in the case of severe bleeding, a sufficient hemostatic effect is often not obtained.

As a hemostatic material with enhanced adhesion, soluble methylcellulose (carboxymethylcellulose) fibers and alginic acid powder (see Patent Document 1) have been proposed. As for carboxymethylcellulose, there are also proposed those that are fibrous or cotton-like (see Patent Document 2) or contain fibrin in order to enhance the hemostasis / adhesion effect (see Patent Document 3). However, since both are soluble, it is insufficient for reinforcing the damaged part.
Moreover, in order to leave a soluble hemostatic material positively on a wound surface, the hemostatic material which provided the fixing sheet | seat which can be peeled on the soluble hemostatic material is also proposed (refer patent document 4). However, in this case as well, after removing the fixing sheet, the hemostatic material portion melts and the strength is significantly reduced, so that the damaged portion cannot be sufficiently reinforced.

Examples of medical adhesives include an adhesive composed of gelatin and resorcin gel and a formaldehyde solution (GRF Glue; manufactured by Nippon BX I), an adhesive composed of an albumin solution and a glutaraldehyde solution (Bio Glue). Century Medical Co., Ltd.), fibrin glue (Beriplast P; manufactured by CSL Behring Co., Ltd.), a cyanoacrylate adhesive (Aron Alpha A “Sankyo” manufactured by Daiichi Sankyo Co., Ltd.) A urethane adhesive composition (see Patent Document 5 or 6) is known.
These medical adhesives have a strong adhesive force and a high hemostatic effect because they adhere to the hemostatic site. However, when used in a hemostatic site where the surgical field is narrow, there is a problem that the adhesive adheres to the tissue around the bleeding site until the adhesive is cured.

JP 2000-186048 A JP-A-10-77571 JP-A-11-322615 Japanese Patent Laid-Open No. 9-294765 JP-A-1-227762 International Publication No. 03/051952

An object of the present invention is to provide a surgical hemostatic material base material that can cover a damaged part and obtain a surgical hemostatic material having a high hemostatic effect.
Another object of the present invention is to provide a surgical hemostatic material that can cover a damaged part and has a high hemostatic effect.

The inventors of the present invention have arrived at the present invention as a result of intensive studies to solve the above problems.
That is, the present invention is a surgical hemostatic material substrate made of a urethane film , wherein the urethane film has a thickness of 10 to 5,000 μm, and the elongation rate of the urethane film at the time of water absorption and swelling according to JIS K6251-2004 is 100. ˜4,000%, 100% modulus at the time of the following water absorption swelling according to JIS K6251-2004 is 9.8 × 10 ^{−3 to} 4.9 N / mm ² , and the following water absorption is 1.1 to 10 Ri, urethane film below urethane resin forming composition cured der Ru surgical hemostatic material substrates (a); surgical hemostatic comprised the surgical hemostatic material substrates and medical adhesive (B) It is a material.
During water absorption swelling: When immersed in physiological saline at 25 ° C. for 3 hours.
Water absorption: Ratio of weight after immersion when immersed in physiological saline at 25 ° C. for 3 hours {weight after immersion / weight before immersion}.
Urethane resin-forming composition (A): a composition containing a urethane prepolymer (U) which is a reaction product of a polyisocyanate component (E) and a polyol component (F) having a hydrophilic polyol (F1) as an essential component. The isocyanate group content in (A) is 1.2 to 8% by weight based on the weight of (A), and the content of oxyethylene groups in (F) is A composition that is 45-77% by weight based on the weight of oxyalkylene groups

  The surgical hemostatic material using the surgical hemostatic material base material of the present invention can prevent adhesion between the medical adhesive and the surrounding tissue by covering the damaged part, is difficult to peel off, and has a high hemostatic effect Play.

It is a schematic diagram of a suture model blood vessel for performing a pulse pressure load test of a surgical hemostatic material. It is the apparatus connection schematic of a pulse pressure load test. It is a schematic diagram of the test piece of an adhesiveness test.

In the present invention, the surgical hemostatic material is used for surgical operations of organs (respiratory and digestive organs, etc.), internal organs (heart, etc.), mucous membranes and blood vessels (arteries, etc.) In this case, the material is affixed to the surgical site for the purpose of hemostasis when bleeding does not stop even after surgical procedures such as suturing and anastomosis.
In the present invention, the surgical hemostatic material base material is a base material for the surgical hemostatic material, and the surgical hemostatic material base material is a surgical hemostatic material by applying a medical adhesive to the surgical hemostatic material base material. . In addition, the surgical site to which the medical adhesive is applied can be covered.

The surgical hemostatic material substrate of the present invention is a surgical hemostatic material substrate made of a urethane film, and the elongation rate at the time of the following water absorption swelling according to JIS K6251-2004 of the urethane film is 100 to 4,000%, A surgical hemostatic base material having a 100% modulus at the time of the following water absorption swelling according to JIS K6251-2004 of 9.8 × 10 ^{−3 to} 4.9 N / mm ² and the water absorption rate of 1.1 to 10 below. .
During water absorption swelling: When immersed in physiological saline at 25 ° C. for 3 hours.
Water absorption: Ratio of weight after immersion when immersed in physiological saline at 25 ° C. for 3 hours {weight after immersion / weight before immersion}.

Due to the high stretchability of the urethane film (surgical hemostatic material base material), it is possible to follow the movement of tissues such as blood vessels. For this reason, stress concentration does not occur on the adhesion surface with the tissue, and separation becomes difficult.
The elongation percentage of the urethane film is preferably 110 to 3,900%, more preferably 120 to 3,800% from the viewpoint of the hemostatic effect and the difficulty of peeling.
The elongation percentage of the urethane film is a value obtained by preparing a tensile test piece dumbbell No. 3 according to JIS K6251 and performing measurement according to “tensile test” (25 ° C., humidity 65%).
The elongation rate of the urethane film can be adjusted by changing the water absorption rate of the urethane film. As the water absorption increases, the elongation increases. The water absorption can be adjusted by the sum of the urethane group concentration and the urea group concentration, and the water absorption increases as the sum of the urethane group concentration and the urea group concentration decreases.
Moreover, when a urethane film is a urethane film which consists of urethane resin (X-1) which is the hardened | cured material of the urethane resin (X) or urethane resin-forming composition (A) mentioned later, the oxy in polyol (F) It can be adjusted by changing the ethylene group content or by changing the total urethane group concentration and urea group concentration in the resin. The elongation rate increases as the content of oxyethylene groups in (F) is higher and / or the sum of the urethane group concentration and urea group concentration (isocyanate group content) in the resin is lower.

The 100% modulus at the time of water absorption swelling of the urethane film is preferably 4.9 × 10 ^{−2 to} 3.9 N / mm ² , more preferably 0.16 to 1 from the viewpoint of hemostatic effect and difficulty of peeling. 0.0 N / mm ² .
The 100% modulus at the time of water absorption swelling of the urethane film can be adjusted by changing the water absorption rate of the urethane film. As the water absorption increases, the 100% modulus increases.
Moreover, when a urethane film is a urethane film which consists of urethane resin (X-1) which is the hardened | cured material of the urethane resin (X) or urethane resin-forming composition (A) mentioned later, in a polyol component (F) It can be adjusted by changing the content of oxyethylene groups or changing the total of urethane group concentration and urea group concentration in the resin. The higher the content of oxyethylene groups in (F) and / or the lower the total urethane group concentration and urea group concentration (isocyanate group content) in the urethane resin, the higher the 100% modulus.

The water absorption rate of the urethane film is preferably from 1.2 to 8.0, more preferably from 1.3 to 7.0, and still more preferably from the viewpoint of hemostatic effect and difficulty of peeling. 3 to 5.0.
The water absorption rate of the urethane film is measured by the following measurement method. It can be adjusted by changing the hydrophilicity of the urethane film. If hydrophilicity becomes high, a water absorption will become large.
Moreover, when a urethane film is a urethane film which consists of urethane resin (X-1) which is the hardened | cured material of the urethane resin (X) or urethane resin-forming composition (A) mentioned later, the oxy in polyol (F) It can be adjusted by changing the ethylene group content or by changing the total urethane group concentration and urea group concentration in the resin. The higher the content of oxyethylene groups in (F) and / or the lower the total of the urethane group concentration and urea group concentration (isocyanate group content) in the resin, the higher the water absorption rate.

<Measurement of water absorption rate>
1.00 g of a measurement sample was immersed in 100 mL of 0.9 wt% physiological saline in a 100 mL beaker without stirring for 3 hours, taken out, and the water adhering to the surface was removed lightly. x1) is measured. The water absorption is calculated by applying the measured weight to the following formula.
Water absorption rate = (x1) /1.00

Although the thickness of the urethane film depends on the size of the film, it is preferably 1 to 5,000 μm, more preferably 5 to 4,000 μm, particularly preferably from the viewpoint of difficulty of peeling and a hemostatic effect. Is 10 to 3,000 μm.
When the urethane film is a cured product of the urethane resin-forming composition (A) described later, the thickness of the urethane film is determined from the viewpoint of difficulty in peeling, the viewpoint of the hemostatic effect, and the amount of bubbles generated during the creation of the cured product. From the viewpoint, it is preferably 1 to 5,000 μm, more preferably 5 to 4,000 μm, and particularly preferably 10 to 3,000 μm.

The shape of the urethane film is not particularly limited as long as it can have a size covering the affected part, and examples thereof include a rectangle, a square, a circle, and an ellipse.
The size of the urethane film is also appropriately selected depending on the size of the affected area and operability. For example, when the shape of the urethane film is rectangular, the length of the long side is preferably 0.1 to 100 cm, more preferably 0.2 to 90 cm, and particularly preferably 0.5 to 80 cm. Moreover, it is preferable that the length of a short side is 0.1-50 cm, More preferably, it is 0.2-40 cm, Most preferably, it is 0.5-30 cm. When the shape of the urethane film is square, the length of one side is preferably 0.1 to 100 cm, more preferably 0.2 to 90 cm, and particularly preferably 0.5 to 80 cm. When the shape of the urethane film is circular, the diameter is preferably a circle having a diameter of 0.1 to 100 cm, more preferably 0.2 to 90 cm, and particularly preferably 0.5 to 80 cm. When the urethane film has an elliptical shape, the major axis is preferably 0.1 to 100 cm, more preferably 0.2 to 90 cm, and particularly preferably 0.5 to 80 cm. The length of the minor axis is preferably 0.1 to 50 cm, more preferably 0.2 to 40 cm, and particularly preferably 0.5 to 30 cm.

The urethane film is obtained by processing a urethane resin into a sheet or film, and may satisfy the above-described elongation, 100% modulus, and water absorption. A conventional urethane film can be used and is not particularly limited. What processed resin (X) into the sheet form or the film form is contained.
Urethane resin (X): A urethane resin that is a reaction product of the polyisocyanate component (E) and the polyol component (F) having the hydrophilic polyol (F1) as an essential component.

  In the urethane resin (X), as the polyisocyanate component (E), a known polyisocyanate can be used without limitation, and includes a fluorine-containing polyisocyanate (E1) and a polyisocyanate (E2) containing no fluorine atom.

As the fluorine-containing polyisocyanate (E1), known {Japanese Patent Laid-Open No. 62-148666 (Patent Document 7), Japanese Patent Laid-Open No. 62-290465 (Patent Document 8), Japanese Patent Laid-Open No. 01-227762 (Patent Document 9), Fluorine-containing polyisocyanate described in JP-A-2003-552828 (Patent Document 10) or JP-A-2005-31935 (Patent Document 11) can be used, and includes the following (E11) to (E13).
(E11) Fluorine-containing aliphatic diisocyanate having 3 to 24 carbon atoms represented by OCN-Rf-NCO (Rf represents a perfluoroalkylene group having 1 to 22 carbon atoms) and OCN-CH ₂ -Rf-CH ₂ -NCO (Rf represents a perfluoroalkylene group having 1 to 20 carbon atoms) and the like, specifically, those represented by OCN-Rf-NCO {difluoromethylene diisocyanate, Perfluorodimethylene diisocyanate, perfluorotrimethylene diisocyanate, perfluorooctylene diisocyanate, perfluoroeicosylene diisocyanate, etc.}; represented by OCN—CH ₂ —Rf—CH ₂ —NCO {Bis (isocyanatomethyl) difluoro Methane, bis (isocyanatomethyl) perfluoroethane Bis (isocyanatomethyl) perfluoropropane, bis (isocyanatomethyl) perfluorobutane, bis (isocyanatomethyl) perfluoropentane, bis (isocyanatomethyl) perfluorohexane and bis (isocyanatomethyl) perfluoroeco Sun etc.}.
(E12) Fluorine-containing alicyclic diisocyanate having 8 to 21 carbon atoms, diisocyanatoperfluorocyclohexane, bis (isocyanatomethyl) perfluorocyclohexane, bis (isocyanatomethyl) perfluorodimethylcyclohexane, bis (isocyanatoperfluorocyclohexyl) ) Perfluoropropane and bis (isocyanatomethylperfluorocyclohexyl) perfluoropropane.
(E13) Fluorine-containing poly (3- to 6-valent) isocyanates having 9 to 72 carbon atoms (E11) and (E12) nurate bodies, diisocyanate adduct bodies, tris (isocyanatotetrafluorocyclohexyl) methane, and the like.

(E1) may be one kind or a mixture of two or more kinds.
The fluorine-containing polyisocyanate (E1) is preferably a fluorine-containing aliphatic polyisocyanate (E11) from the viewpoint of safety such as mutagenicity, and more preferably represented by OCN—CH ₂ —Rf—CH ₂ —NCO. Fluorinated aliphatic polyisocyanate represented by the formula: OCN-Rf-NCO, particularly preferably difluoromethylene diisocyanate, perfluorodimethylene diisocyanate, perfluorotrimethylene diisocyanate, perfluorooctylene diol Isocyanates, perfluoroeicosylene diisocyanate, bis (isocyanatomethyl) perfluoropropane, bis (isocyanatomethyl) perfluorobutane, bis (isocyanatomethyl) perfluoropentane and bis (iso Anatomechiru) is perfluorohexane.

Further, from the viewpoint of water absorption of the urethane film and the availability of isocyanate, the proportion (% by weight) of fluorine atoms in the fluorine-containing polyisocyanate (E1) is 35 based on the weight of (E1). -70 is preferable, More preferably, it is 38-70, Most preferably, it is 40-56.
Within this range, the water absorption of the urethane film made of the urethane resin (X) obtained using (E1) is good.

  In the urethane resin (X), the urethane resin composition (A), and the urethane prepolymer (U), the polyisocyanate component (E) is water-absorbing, easy to produce the urethane film, elongation rate of the urethane film, safety and From the viewpoint of the hemostatic effect, a polyisocyanate component (E ′) containing a fluorine-containing polyisocyanate (E1) as an essential component is preferable.

As polyisocyanate (E2) which does not contain a fluorine atom, the polyisocyanate which does not contain a fluorine atom of publicly known {described in Patent Documents 7 to 11, etc.} is included.
In addition, the polyisocyanate (E2) which does not contain a fluorine atom may be used alone or in combination of two or more.
Among polyisocyanates (E2) not containing fluorine atoms, aromatic polyisocyanates not containing fluorine atoms {1,3- or 1,4-phenylene diisocyanate (PDI), 2,4 from the viewpoint of flexibility of the urethane film -Or 2,6-tolylene diisocyanate (TDI), 2,4'- or 4,4'-diphenylmethane diisocyanate (MDI) and crude MDI, etc.} are preferred, and MDI and TDI are more preferred.

  From the viewpoint of the flexibility of the urethane film, the total of the urethane group concentration and the urea group concentration in the urethane resin (X) is preferably 2.8 to 27.8% by weight, and more preferably 3.4 to 22.0% by weight. %, Particularly preferably 4.2 to 16.6% by weight. In addition, a urethane group density | concentration is computed from the preparation amount of a polyisocyanate component (E) and a polyol component (F).

In the urethane resin (X), the polyol component (F) contains the hydrophilic polyol (F1) as an essential component.
The hydrophilic polyol (F1) contains an oxyethylene group, and the content of the oxyethylene group is 30 to 100% by weight based on the weight of (F1). Polyols can be used and include (F11) below.

(F11) Polyether polyol containing an oxyethylene group Ethylene oxide (hereinafter abbreviated as EO) adduct to a compound having at least two active hydrogens, or EO and an alkylene oxide having 3 to 8 carbon atoms (1, Co-addition with 2-propylene oxide (hereinafter abbreviated as PO), 1,3-propylene oxide, 1,2-, 1,3-, 2,3- or 1,4-butylene oxide and styrene oxide Examples include the body. In the case of a co-adduct, the addition form may be random, block, or a combination thereof, but is preferably random from the viewpoint of water absorption of the urethane film.
Moreover, as a C3-C8 alkylene oxide, PO is preferable from a water absorptive viewpoint of a urethane film.
Examples of the compound having at least two active hydrogens include water, diol (such as ethylene glycol and 1,2-propylene glycol), dicarboxylic acid (such as maleic acid and succinic acid), and tri- and tetravalent polycarboxylic acid (trimerit Acid and pyromellitic acid), monoamines (such as methylamine and ethylamine), polyamines (such as ethylenediamine and propylenediamine), and polythiols (such as ethanedithiol).
Preferred examples of (F11) include EO adducts to diols (EO adducts to ethylene glycol, EO adducts to propylene glycol, etc.), EO to diols, and alkylene oxides having 3 to 8 carbon atoms. (E.g., random or block coadducts of EO and PO with ethylene glycol, and random or block coadducts of EO and butylene oxide with ethylene glycol), and the like.
(F11) is preferably an EO adduct to a diol and a co-adduct of EO and PO to a diol, particularly preferably a co-addition of EO and PO to a diol, from the viewpoint of water absorption of a urethane film. Is the body.
(F11) may be a single type or a mixture of two or more types.

The content (% by weight) of the oxyethylene group in the hydrophilic polyol (F1) is preferably 30 to 100, more preferably 40 to 95, based on the weight of (F1), from the viewpoint of water absorption of the urethane film. Next, it is more preferably 50 to 90.
The hydroxyl group equivalent (number average molecular weight per hydroxyl group) of (F1) is preferably from 50 to 5,000, more preferably from 100 to 5,000, from the viewpoint of easy preparation of a urethane film and water absorption of the urethane film. 4,000, particularly preferably 200 to 3,000.
The hydroxyl group equivalent is determined by measuring the hydroxyl value based on JIS K1557-1: 2007 and applying it to the following formula.
Hydroxyl group equivalent = 1,000 × 56.1 / value of hydroxyl value

The number average molecular weight (Mn) of the hydrophilic polyol (F1) is preferably 600 to 10,000 from the viewpoint of easy preparation of a urethane film.
In the present invention, the number average molecular weight (Mn) is measured by gel permeation chromatography (GPC) by preparing a calibration curve using polyethylene glycol as a standard substance.

As the polyol component (F), the hydrophilic polyol (F1) is essential, but other polyol (F2) having low hydrophilicity may be included. (F2) is not particularly limited, and includes known ones other than (F1) {Patent Documents 7 to 11 etc.].
Among (F2), from the viewpoint of water absorption of the urethane film, an EO adduct to polypropylene glycol (EO content of less than 5 to 30% by weight) is preferable, and an EO adduct to polypropylene glycol (EO) is more preferable. Content of 15 to 30% by weight).
The polyether polyol (F2) may be a single type or a mixture of two or more types.
The number average molecular weight (hydroxyl group equivalent) per hydroxyl group and the preferred range of Mn in (F2) are the same as in (F1).

When using other polyol (F2) having low hydrophilicity, the content (% by weight) of the hydrophilic polyol (F1) is based on the weight of the polyol component (F) from the viewpoint of water absorption of the urethane film. 30-99 are preferable, More preferably, it is 50-98, Most preferably, it is 70-95.
When the polyol (F2) having low hydrophilicity is used, the content (% by weight) of the polyol (F2) is 1 to 70 based on the weight of the polyol component (F) from the viewpoint of water absorption of the urethane film. More preferably, it is 2-50, Most preferably, it is 5-30.

In the urethane resin (X), the content (% by weight) of the oxyethylene group in the polyol component (F) is based on the weight of the oxyalkylene group in (F) from the viewpoint of water absorption of the urethane film. 30 to 79, more preferably 40 to 78, and particularly preferably 45 to 77.
By adjusting the content (% by weight) of the oxyethylene group in the polyol component (F) within this range, an appropriate water absorption rate is obtained, and the elongation rate and the value of 100% modulus are preferable.

  In the urethane resin (X), the average hydroxyl group equivalent of the entire polyol component (F) is preferably from 50 to 5,000, more preferably from 100 to 5,000, from the viewpoint of water absorption of the urethane film and ease of production. 4,000, particularly preferably 200 to 3,000, most preferably 500 to 2,000.

  When using other polyol (F2) having low hydrophilicity, the content of oxyethylene group is based on the weight of the oxyalkylene group as the other polyol (F2) having low hydrophilicity from the viewpoint of water absorption of the urethane film. Polyether polyols less than 30% by weight are preferred, more preferably polyethers containing oxypropylene groups and the content of oxyethylene groups being less than 30% by weight based on the total weight of oxyethylene groups and oxypropylene groups A polyol is preferred, and polypropylene glycol is particularly preferred.

The urethane resin (X) can contain other components described below (described in Patent Documents 7 to 11) as necessary.
Other components include physiologically active drugs (central nervous system drugs, allergy drugs, cardiovascular drugs, respiratory system drugs, gastrointestinal drugs, hormone drugs, metabolic drugs, antineoplastic agents, antibiotics Preparations and chemotherapeutic agents), fillers (carbon black, bengara, calcium silicate, sodium silicate, titanium oxide, acrylic resin powders and various ceramic powders, etc.), and plasticizers (dibutyl phthalate (DBP), phthalates) Acid dioctyl (DOP), tricresyl phosphate (TCP), tributoxyethyl phosphate, and various other esters).
When other components are included, the content thereof is appropriately determined depending on the application.

  The urethane resin (X) may further contain a phenolic hydroxyl group-containing radical scavenger (PRS) known in the art {described in Patent Documents 7 to 11}. When a phenolic hydroxyl group-containing radical scavenger (PRS) is contained, it is preferable because degradation and degradation with time of the prepared urethane film can be suppressed and deterioration of physical properties (strength, hemostasis, etc.) can be prevented.

  Among the phenolic hydroxyl group-containing radical scavengers (PRS), bisphenolic hydroxyl group-containing radical scavengers and polymer-type phenolic hydroxyl group-containing radical scavengers are preferred, and more preferably, from the viewpoint of suppressing degradation over time of the urethane film. Tetrakis- [methylene-3- (3 ′, 5′-di-t-butyl-4′-hydroxyphenyl) propionate] methane, 1,1,3-tris (2-methyl-4-hydroxy-5-t-) Butylphenyl) butane, 1,3,5-trimethyl-2,4,6-tris (3,5-di-tert-butyl-4-hydroxybenzyl) benzene, 1,3,5-tris (3 ′, 5 '-Di-t-butyl-4'-hydroxybenzyl) -sec-triazine-2,4,6- (1H, 3H, 5H) trione and 1,6-hexane All - bis [3- (3,5-di -t- butyl-4-hydroxyphenyl) propionate].

  The content (% by weight) of the phenolic hydroxyl group-containing radical scavenger (PRS) in the urethane resin (X) is preferably from 0.01 to 3, more preferably from 0.1 to 3, based on the weight of the urethane resin (X). It is 02 to 1, particularly preferably 0.05 to 0.5. Within this range, deterioration of the urethane film over time can be suppressed.

As a urethane film, the urethane film which consists of urethane resin (X-1) which is a hardened | cured material of the following urethane resin-forming composition (A) from a viewpoint of the adhesive force between medical adhesives (B) further. preferable.
Urethane resin-forming composition (A): a composition containing a urethane prepolymer (U) which is a reaction product of a polyisocyanate component (E) and a polyol component (F) having a hydrophilic polyol (F1) as an essential component. object.

The urethane prepolymer (U) is obtained by reacting the polyisocyanate component (E) and the polyol component (F) (prepolymer reaction).
From the viewpoint of easy handling of (U), the use ratio of the polyisocyanate component (E) to the polyol component (F) is the equivalent ratio (NCO) of the isocyanate group of (E) and the hydroxyl group of (F). Group / OH group) is preferably used in a ratio of 1.5 to 3, more preferably 1.8 to 2.3, and particularly preferably 1.9 to 2.1. It is.

  The isocyanate group content (% by weight) in the urethane resin-forming composition (A) (weight ratio of isocyanate group in the total weight of (A)) is preferably 1 to 10, more preferably 1.2 to 8. Especially preferably, it is 1.5-6. Within this range, the water absorption of the urethane film is further improved.

  The isocyanate group content in the urethane resin-forming composition (A) is determined by a method in which an excess di-n-butylamine solution is added to the sample and reacted, and unreacted di-n-butylamine is back titrated with a hydrochloric acid standard solution. For example, it is measured according to JIS K7301-1995, 6.3 isocyanate group content.

  The content (% by weight) of the oxyethylene group in the urethane prepolymer (U) is preferably 20 to 70, more preferably 25 to 65, based on the weight of (U), from the viewpoint of water absorption of the urethane film. Especially preferably, it is 30-60.

  The number average molecular weight (Mn) of the urethane prepolymer (U) is preferably from 500 to 30,000, more preferably from 800 to 20,000, and particularly preferably from 1,000 to 950, from the viewpoint of easy preparation of the urethane film. 10,000, most preferably 1,200 to 8,000.

In the urethane resin-forming composition (A), in addition to the urethane prepolymer (U), a phenolic hydroxyl group-containing radical scavenger (PRS) and the other components described above can be included as necessary.
The phenolic hydroxyl group-containing radical scavenger (PRS) may be added to the urethane prepolymer (U), or added in advance to the polyisocyanate component (E) and / or the polyol component (F) before the urethane prepolymer. (U) may be obtained.
In addition, other components may be mixed in advance with the polyisocyanate component (E), the polyol component (F) and / or the phenolic hydroxyl group-containing radical scavenger (PRS) to carry out the prepolymer reaction. The urethane prepolymer (U) and / or the phenolic hydroxyl group-containing radical scavenger (PRS) may be mixed.

As urethane resin-forming composition (A), medical adhesive (B) {especially (B11)} is difficult to be peeled off at interface, hardly deteriorated, high in safety, high in hemostatic effect and difficult to peel off. From the viewpoint, a cured product of the following urethane resin-forming composition (A1) is preferable.
Urethane resin forming composition (A1): The reaction of the polyisocyanate component to the fluorine-containing polyisocyanate (E1) as an essential component (E '), and the polyol component to hydrophilic polyol (F1) as an essential component (F) The composition containing the urethane prepolymer (U1) which is a thing.

In the urethane resin-forming composition (A1), the polyisocyanate component (E ′) contains the fluorine-containing polyisocyanate (E1) as an essential component.
The content (% by weight) of (E1) in the polyisocyanate component (E ′) is preferably from 80 to 100, more preferably from 90 to 100, and particularly preferably from 95 to 100, from the viewpoint of the elongation percentage of the urethane film. 100.
The content (% by weight) of (E2) in the polyisocyanate component (E ′) is preferably 0 to 20 based on the weight of the polyisocyanate component (E ′) from the viewpoint of the elongation percentage of the urethane film, Preferably it is 0-10, Most preferably, it is 0-5.

The content (% by weight) of fluorine atoms contained in the polyisocyanate component (E ′) is 28 to 85 on the basis of the weight of (E ′) from the viewpoint of water absorption of the urethane film and availability of isocyanate. More preferably, it is 35-70, Most preferably, it is 40-56.
When (E ′) is used in this range for the urethane composition (A1), the water absorption of the urethane film is good.

As a method for producing the urethane prepolymers (U) and (U1), a conventionally known method {International Publication WO 03/051952 Pamphlet (the disclosure of US Patent Application No. 10 / 499,331 is incorporated into this application by reference)} For example, a method of reacting the polyisocyanate component (E) {or (E ′)} and the polyol component (F) at 50 to 100 ° C. for 1 to 10 hours may be mentioned. In this case, the method of adding the polyisocyanate component (E) and the polyol component (F) may be a method of adding from the beginning or a method of gradually dropping.
Since the polyisocyanate component (E) is extremely easy to react with moisture, it is necessary to remove moisture in the reaction apparatus and raw materials as much as possible. In particular, the polyol component (F) that easily contains moisture is preferably subjected to dehydration treatment. As the dehydration treatment, a method of dehydrating for 0.5 to 10 hours at 50 to 150 ° C. and 0.001 hPa to atmospheric pressure while supplying an inert gas (nitrogen gas or the like) as necessary can be applied.
As a mixing method of the polyisocyanate component (E) and the polyol component (F), (1) a method of mixing at once, (2) a method of gradually dropping (F) into (E), (3) (E ) And (F) gradually dropping, (4) (E) and a part of (F) are mixed and reacted, and then the remaining (F) is dropped or mixed at once. Either is acceptable. Of these, the method (1) and the method (2) are preferable, and the method (1) is more preferable, from the viewpoint of simplicity of the reaction operation.
The reaction may be performed in the presence of a catalyst (an organic metal compound such as dibutyltin oxide or dibutyltin dilaurate, or an organic acid metal salt such as zirconium acetate).

  As a method for producing a urethane film by curing the urethane resin-forming composition (A), the urethane resin-forming composition (A) spread in a single layer on a plate is moisture-cured with moisture in the air. The method of obtaining a urethane film (single-layer moisture curing method), applying a urethane resin-forming composition (A) on a urethane film produced by a single-layer moisture curing method, and further curing the moisture repeatedly. A method of repeatedly producing a urethane film (multilayer moisture curing method), a method of dissolving a urethane resin-forming composition (A) in an organic solvent, and then pouring it into a mold to cure moisture (organic solvent curing method), and on a plate There is a method (water curing method) in which water, physiological saline or an infusion solution is directly brought into contact with the urethane resin-forming composition (A) spread on the surface of the urethane resin-forming composition (A).

When the urethane resin-forming composition (A) is cured by a single layer moisture curing method, a multilayer moisture curing method or a water curing method, as a plate used for spreading the urethane resin-forming composition (A), Any material can be used as long as the cured urethane film can be peeled off. For example, glass, silicone resin (methylsilicone resin, vinylmethylsilicone resin, phenylmethylsilicone resin, fluorosilicone resin, etc.), fluorine resin (polytetrafluoroethylene, ethylene) -Tetrafluoroethylene copolymer, perfluoroalkoxyalkane, polyvinylidene fluoride, etc.), polypropylene, polyethylene, stainless steel, polyamide, polyvinyl chloride, polystyrene, polyvinyl acetate, ABS resin, AS resin, acrylic resin, polyacetal, polycar Sulfonates, modified polyphenylene ether, polybutylene terephthalate, polyethylene terephthalate, glass fiber reinforced polyethylene terephthalate, and cyclic polyolefins, and the like.
The surface of the plate to which the urethane resin-forming composition (A) is applied may be a smooth surface, but may be a rough surface from the viewpoint of preventing repellency of the urethane resin-forming composition (A). Moreover, in (iii) mentioned later, when a urethane film has a dent, you may have the unevenness | corrugation which can form a dent.

  When the urethane resin-forming composition (A) is cured by the multilayer moisture curing method, if the final thickness of the urethane film is within the range of 1 to 5,000 μm, the thickness per one time and the number of laminations are limited. No.

  When the urethane resin-forming composition (A) is cured by a single layer moisture curing method or a multilayer moisture curing method, the temperature is preferably −10 to 75 ° C., more preferably −5 to 5 ° C., from the viewpoint of reducing the amount of bubble foaming. 50 ° C., particularly preferably 0 to 40 ° C. Further, from the viewpoint of reducing the amount of foamed bubbles, the humidity is preferably 1 to 95% RH, more preferably 2 to 80% RH, and particularly preferably 3 to 60% RH.

  When the urethane resin-forming composition (A) is cured by a single layer moisture curing method, a multilayer moisture curing method, or an organic solvent curing method, the urethane resin (X-1) that is a cured product can be peeled from the plate, but more In order to make it peel easily, water, physiological saline, or an infusion solution may be made to water-swell into urethane resin (X-1), and may be made to peel.

  When the urethane resin-forming composition (A) is cured by the organic solvent curing method, the solvent used dissolves the urethane resin-forming composition (A) and does not react with the urethane resin-forming composition (A). Any one may be used, and examples thereof include acetone, diethyl ether, dimethylformamide, dimethyl sulfoxide, acetonitrile, hexane, ethyl acetate, methyl acetate, tetrahydrofuran, cyclohexane, toluene, benzene and xylene.

When the urethane resin-forming composition (A) is cured by the organic solvent curing method, the material of the mold for forming the film may be anything as long as it can peel the urethane resin (X-1) that is a cured product. For example, glass, silicone resin (methylsilicone resin, vinylmethylsilicone resin, phenylmethylsilicone resin, fluorosilicone resin, etc.), fluororesin (polytetrafluoroethylene, ethylene-tetrafluoroethylene copolymer, perfluoroalkoxyalkane and Polyvinylidene fluoride, etc.), polypropylene, polyethylene, stainless steel, polyamide, polyvinyl chloride, polystyrene, polyvinyl acetate, ABS resin, AS resin, acrylic resin, polyacetal, polycarbonate, modified polyphenylene ether, polybutylene tele Tallates, polyethylene terephthalate, glass fiber reinforced polyethylene terephthalate, and cyclic polyolefins, and the like.
The surface of the film-forming mold may be a smooth surface, but may be a rough surface from the viewpoint of preventing repellency of the urethane composition. Moreover, in (iii) mentioned later, when (A) has a dent, you may have an unevenness | corrugation which can form a dent.

  In the present invention, the medical adhesive (B) can be used for surgical procedures such as suturing and anastomosis in surgical operations in organs (respiratory and digestive organs, etc.), internal organs (heart etc.), mucous membranes and blood vessels (arteries etc.) This adhesive is used for the purpose of hemostasis when bleeding does not stop even if it is carried out, and includes a urethane adhesive composition (B1) and / or a cyanoacrylate adhesive (B2).

As the urethane adhesive composition (B1), known liquid medical adhesives can be used, and are not particularly limited, but examples thereof include urethane adhesives described in Patent Documents 7 to 11 and the like. Specifically, the following urethane adhesive composition (B1) can be used.
Urethane adhesive composition (B1): an adhesive containing a urethane prepolymer (P) which is a reaction product of a polyisocyanate component (E) and a polyol component (F) having a hydrophilic polyol (F1) as an essential component. Composition.
In the urethane adhesive composition (B1), preferable conditions for the polyisocyanate component (E), the hydrophilic polyol (F1), the polyol component (F) and the urethane prepolymer (P) are the above-mentioned urethane resin-forming composition ( The same as the polyisocyanate component (E), hydrophilic polyol (F1) and urethane prepolymer (U) of A). Moreover, what is preferable as a phenolic hydroxyl group containing radical scavenger which can be contained in (B1) and another component is the same as that of the case of a urethane resin-forming composition (A) as above-mentioned.

(B1) is preferably the following urethane adhesive composition (B11) from the viewpoint of safety and resistance to peeling from the surgical hemostatic material substrate (urethane film), resistance to deterioration, and safety.
Urethane adhesive composition (B11): a reaction product of a polyisocyanate component (E ′) having a fluorine-containing polyisocyanate (E1) as an essential component and a polyol component (F) having a hydrophilic polyol (F1) as an essential component An adhesive composition containing a urethane prepolymer (P1).

Isocyanate group content (% by weight) in urethane adhesive composition (B11) {weight ratio of isocyanate group in the total weight of (B11)} is the reactivity of urethane adhesive composition (B11) and (B11) From the viewpoint of adhesive strength, 1 to 10 is preferable, 1.2 to 8 is more preferable, and 1.5 to 6 is particularly preferable.
The content (% by weight) of (E1) in the polyisocyanate component (E ′) is preferably 80 to 100 from the viewpoint of the reactivity of the urethane adhesive composition (B11) and the adhesive strength of (B11). Preferably it is 90-100, Most preferably, it is 95-100.
The proportion (% by weight) of fluorine atoms in the fluorine-containing polyisocyanate (E1) is the weight of (E1) from the viewpoint of the adhesive strength of the urethane adhesive composition (B11) and the availability of isocyanate. As a standard, 35-70 are preferable, More preferably, it is 38-70, Most preferably, it is 40-56.
The content (% by weight) of (E2) in the polyisocyanate component (E ′) is determined from the viewpoint of the reactivity of the urethane adhesive composition (B11) and the adhesive strength of (B11). 0 to 20 is preferable, more preferably 0 to 10, particularly preferably 0 to 5, based on the weight of the above.
The content (% by weight) of fluorine atoms contained in the polyisocyanate component (E ′) is (E ′) from the viewpoint of the reactivity of the urethane adhesive composition (B11), the curing time, and the availability of isocyanate. 28-85 are preferable on the basis of weight, More preferably, it is 35-70, Most preferably, it is 40-56.

The content (% by weight) of the oxyethylene group in the hydrophilic polyol (F1) is preferably 30 to 100 based on the weight of (F1) from the viewpoint of the adhesive strength of the urethane adhesive composition (B11). More preferably, it is 40-95, and still more preferably 50-90.
The hydroxyl group equivalent (number average molecular weight per hydroxyl group) of (F1) is preferably 50 to 5,000, more preferably 100 to 4,000, from the viewpoint of the adhesive strength of the medical adhesive (B). Particularly preferred is 200 to 3,000.
The content (% by weight) of the oxyethylene group in the urethane prepolymer (P1) is preferably 20 to 70 based on the weight of (P1) from the viewpoint of the adhesive strength of the urethane adhesive composition (B11). More preferably, it is 25-65, Most preferably, it is 30-60.

When other polyol (F2) having low hydrophilicity is used, the content (% by weight) of the hydrophilic polyol (F1) is determined from the viewpoint of the reactivity (curing speed) of the urethane adhesive composition (B11). 30-99 are preferable based on the weight of a component (F), More preferably, it is 50-98, Most preferably, it is 80-95.
When the polyol (F2) having low hydrophilicity is used, the content (% by weight) of (F2) is determined from the polyol component (F) from the viewpoint of the reactivity (curing speed) of the urethane adhesive composition (B11). Based on weight, 1-70 are preferable, More preferably, it is 2-50, Most preferably, it is 5-20.
When other polyol (F2) having low hydrophilicity is used, the content (% by weight) of oxyethylene groups in the entire polyol component (F) is the reactivity (curing speed) of the urethane adhesive composition (B11). From a viewpoint, based on the weight of the oxyalkylene group in (F), 30-79 are preferable, More preferably, it is 40-78, Most preferably, it is 45-77.
The average hydroxyl group equivalent of the entire polyol component (F) is preferably 50 to 5,000, more preferably 100 to 4,000, and particularly preferably 200, from the viewpoint of the adhesive strength of the urethane adhesive composition (B11). ˜3,000, most preferably 500˜2,000.

  The number average molecular weight (Mn) of the urethane prepolymer (P1) is preferably 500 to 30,000, more preferably 800 to 20,000, and particularly preferably from the viewpoint of the adhesive strength of the urethane adhesive composition (B11). 1,000 to 10,000, most preferably 1,200 to 8,000.

  In the urethane adhesive composition (B11), it is preferable as the fluorine-containing polyisocyanate (E1), polyisocyanate component (E ′), hydrophilic polyol (F1), polyol component (F) and urethane prepolymer (P1) other than those described above. The conditions are the same as those of the fluorine-containing polyisocyanate (E1), polyisocyanate component (E ′), hydrophilic polyol (F1) and urethane prepolymer (U1) of the urethane resin-forming composition (A1). Moreover, what is preferable as a phenolic hydroxyl group containing radical scavenger which can be contained in (B11) and another component is the same as that of the case of a urethane resin-forming composition (A1) as above-mentioned.

  As the cyanoacrylate adhesive (B2), a known cyanoacrylate adhesive composition can be used, and is not particularly limited. For example, the cyanoacrylate adhesive described in JP-A-2007-61658 or JP-A-6-145606 is used. Examples thereof include compositions.

  The viscosity at 25 ° C. of the medical adhesive (B) is preferably 1,000 to 5,000,000 mPa · s, more preferably 3,000 to 1,000,000 mPa · s, and particularly preferably 5,000 to 5,000. 500,000 mPa · s. By being in this range, it can be easily applied to a urethane film, and can be applied to the affected part, which is an adherend, in a thin and appropriate thickness.

  The thickness of the medical adhesive (B) is preferably 1 to 5,000 μm, more preferably 5 to 4,000 μm, and particularly preferably 10 to 3,000 μm from the viewpoint of the amount of bubbles generated.

The surgical hemostatic material of the present invention is a surgical hemostatic material composed of a surgical hemostatic material substrate and a medical adhesive (B). From the viewpoint of preventing inadvertent adhesion to living tissue other than the hemostatic target site, the surface that contacts the affected area of the surgical hemostatic material has (B), and the urethane that does not contact the affected area of the surgical hemostatic material Those having a film are preferred. Specifically, the following (i) to (iii) are included.
(I) It consists of a surgical hemostatic material base material and (B), and has (B) on a part of one side or all of one side of the surgical hemostatic material base material.
(Ii) A surgical hemostatic base material, comprising (B) and an intermediate layer (Y), and having (Y) between the surgical hemostatic base material and (B).
(Iii) A surgical hemostatic material base material and (B), having a dent on a part of one side of the surgical hemostatic material base material, and having (B) in this dent.

In (i), as having (B) on a part of one side of the surgical hemostatic material base material, (B) is a fixed shape (circular, elliptical, triangular) on one side of the surgical hemostatic material base material. , Quadrangular and polygonal etc.) or indeterminate, and one or two or more locations on one side of the surgical hemostatic material base material applied at random or at regular intervals. When it is a part, the ratio (%) of the area which apply | coats (B) in the single side | surface of the surgical hemostatic base material (Area which applied (B) / the area of the single side | surface of a surgical hemostatic base material x100) Is preferably 10 to 100, more preferably 40 to 100.
Here, the surgical hemostatic material substrate may be composed of one layer of surgical hemostatic material substrate, or may be a laminate of two or more layers. When the surgical hemostat base material is a laminate of two or more layers, the thickness of the surgical hemostatic base material laminate is preferably in the above range.

In (ii), the intermediate layer (Y) can be used without any particular limitation, and may specifically include an antibacterial agent, blood coagulation factor, cell growth factor, fiber, and the like.
The antibacterial agent suppresses bacterial growth in the affected area, and examples include amphotericin B, gentamicin, penicillin, and streptomycin.
A blood coagulation factor is a drug for promoting the blood coagulation system, and includes fibrin and thrombin.
Cell growth factor is for healing promotion, fibroblast growth factor, transforming growth factor, epithelial cell growth factor, hepatocyte growth factor, platelet-derived growth factor, insulin-like growth factor, vascular endothelial growth factor , Nerve growth factor, stem cell factor, leukemia inhibitory factor, bone morphogenetic factor, heparin-binding epidermal growth factor, neurotrophic factor, connective tissue growth factor, angiopoietin, cytokine, interleukin, adrenamodulin and natriuretic peptide Peptides are included. Among these, epithelial cell growth factor, fibroblast growth factor, transforming growth factor, insulin-like growth factor and bone morphogenetic factor are preferable from the viewpoint of wide range of applicable cells and high cell proliferation. These include epidermal growth factor, fibroblast growth factor, transforming growth factor and insulin-like growth factor.
The fiber is for increasing the strength of the surgical hemostatic material, and may be a mesh, non-woven fabric or woven fabric. Examples of these materials include polyester, expanded PTFE, oxidized cellulose, polyglycolic acid, glycolic acid-lactic acid. Examples include polyester and polypropylene.

In (iii), the depth of the dent is preferably 1 to 5,000 μm, more preferably 5 to 4,000 μm, and particularly preferably 10 to 3,000 μm, from the viewpoint of the amount of bubbles generated and the hemostatic effect.
When cut in a vertical direction with respect to a dent surface, examples of the cross-sectional shape of the dent include a V shape, a square shape, and an arc shape. However, from the viewpoint of the curability of (B), it may be a square shape. preferable.
The planar view shape of the dent can be used without any particular limitation, and examples thereof include an indeterminate shape, a fixed shape (rectangle, square, circle, ellipse, etc.).
When the dent is rectangular in plan view, the size of the dent is appropriately selected depending on the size of the affected part, but from the viewpoint of operability, the length of the long side is preferably 2 to 100 cm, and more preferably 3 to 3 cm. 90 cm, particularly preferably 4 to 80 cm. The length of the short side is appropriately selected depending on the size of the affected part, but is preferably 0.5 to 50 cm, more preferably 1 to 40 cm, and particularly preferably 1.5 to 30 cm from the viewpoint of operability.
The dent may have the long side or the short side the same as the long side or the short side of the surgical hemostatic material base so that one side is opened or the entire circumference is closed. May be.
When the dent is elliptical, the length of the major axis is appropriately selected depending on the size of the affected part, but is preferably 0.5 to 50 cm, more preferably 1 to 40 cm, and particularly preferably from the viewpoint of operability. 1.5-30 cm.
From the viewpoint of operability, the opening area of the dent is preferably 1 to 90%, more preferably 3 to 85%, particularly preferably relative to the total area of the dent surface of the surgical hemostatic material substrate. Is 5-80.
From the viewpoint of durability and operability of the surgical hemostatic material substrate, the thickness from the bottom of the dent portion to the opposite surface of the surgical hemostatic material substrate is preferably 1 to 5,000 μm, more preferably 5 to 5 μm. It is 4,000 μm, particularly preferably 10 to 3,000 μm.
The number of the dents may be at least one, but 1 to 10 is preferable from the viewpoint of operability.

  As the surgical hemostatic material of the present invention, among the above (i) to (iii), (i) is preferable from the viewpoint of preventing hemostasis and interfacial peeling, and more preferably, one side of the surgical hemostatic material substrate. All have (B).

  As the surgical hemostatic material of the present invention, the surgical hemostatic material base material is a urethane film made of a urethane resin (X-1) obtained by curing the urethane resin-forming composition (A), and the medical adhesive (B). Is preferably a urethane adhesive composition (B11), more preferably a surgical hemostatic base material is a urethane film comprising a urethane resin obtained by curing the urethane resin-forming composition (A1), and a medical adhesive. (B) is a urethane adhesive composition (B11).

The surgical hemostatic material of the present invention is provided with a protective film on the application surface of the medical adhesive (B) (surface in contact with the affected area) in order to prevent moisture intrusion and inadvertent adhesion to the adhesive during distribution and use. It may be provided in preparation. The material for the protective film may be any material that can be peeled, and examples thereof include silicone resins and fluororesins. Examples of the silicone resin include MQ (methyl silicone resin), VMQ (vinyl methyl silicone resin), PMQ (phenyl methyl silicone resin), FVMQ (fluorosilicone resin), and nitrile silicone resin. Examples of the fluororesin include synthetic resins obtained by polymerizing olefins containing fluorine. Specifically, PTFE (polytetrafluoroethylene), ETFE (ethylene-tetrafluoroethylene copolymer), PFA (perfluorocarbon). Examples include alkoxyalkanes (copolymers of tetrafluoroethylene (C ₂ F ₄ ) and perfluoroalkoxyethylene) and PVDF (polyvinylidene fluoride).

  In the distribution of the surgical hemostatic material of the present invention, the surgical hemostatic material substrate and the medical adhesive (B) are provided separately, and the surgical hemostatic material substrate is coated with (B) before use. The surgical hemostat of the present invention may be used.

When providing a surgical hemostat base material alone, it may be left as it is, but measures may be taken to prevent the base materials from sticking together. For example, a method of covering with a peelable sheet, a method of providing by impregnating with water, physiological saline or infusion, a method of providing by providing powder on the surface of a substrate (urethane film), and the like can be mentioned.
Examples of the peelable sheet material include paper, dust-free paper, non-woven fabric, silicone rubber, and polytetrafluoroethylene.
The powder to be adhered to the substrate surface may be a highly safe substance, and examples thereof include monosaccharide, disaccharide, oligosaccharide, polysaccharide and amino acid powders.

  As an application method when using the surgical hemostatic material of the present invention and joining a suture part or an anastomosis part in surgery, there is a method of directly attaching the surgical hemostatic material of the present invention to the hemostatic part. Further, for the purpose of improving the adhesion between the hemostatic part and the surgical hemostatic material, the hemostatic part to which the surgical hemostatic material is attached may be compressed using a hand, gauze, forceps or the like.

  When the surgical hemostatic material base material is supplied alone, after applying the medical adhesive (B) to the surgical hemostatic material base material, the method is applied to the hemostatic part, and the medical adhesive is applied to the hemostatic part. After applying (B), a method of applying a surgical hemostatic base material from above is mentioned.

The surgical hemostatic material of the present invention is used for surgical operations in organs (respiratory organs, digestive organs, etc.), internal organs (hearts, etc.), mucous membranes and blood vessels (arteries, etc.), and is susceptible to leakage of blood and body fluid It exerts a significant hemostatic effect in blood vessels such as arteries, respiratory organs and digestive organs. In addition, the surgical hemostatic material of the present invention has a high elongation rate and a low 100% modulus, and is a surgical hemostatic material that does not adhere and peel even to pulsatile tissues such as blood vessels. Can prevent leakage of blood or cerebrospinal fluid, and re-leakage hardly occurs. In addition, it can be applied regardless of whether blood anticoagulant such as heparin is administered, and can be hemostatic in a short time. Therefore, it can be used for heart and aorta surgery performed by administering blood anticoagulant. it can. In addition, since eruptive bleeding can be stopped in a short time, it is particularly suitable for surgical operations on blood vessels.
In addition to the above, it can also be used as a hemostatic material such as skin.

  A blood anticoagulant such as heparin is always administered in a heart or aorta surgery using a heart-lung machine. While this blood anticoagulant is acting, the bleeding blood does not clot, so a large amount of bleeding during surgery can be a fatal obstacle for the patient. However, even in such a case, the surgical hemostatic material of the present invention can be applied regardless of whether or not a blood anticoagulant is administered, and can be hemostatic in a short time.

  Since the surgical hemostatic material base material constituting the surgical hemostatic material of the present invention has high airtightness and pressure resistance, it is also suitable for treatment of air leakage in the respiratory region.

  The surgical hemostatic material of the present invention can also be used for surgery on animals other than humans (pets and livestock).

  Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples. In addition, a part shows a weight part and% shows weight%.

<Production Example 1>
The autoclave was charged with 15.5 parts of ethylene glycol and 3.8 parts of potassium hydroxide, purged with nitrogen (oxygen concentration in the gas phase part: 450 ppm), and vacuum dehydrated at 120 ° C. for 60 minutes.
Subsequently, a mixture of 784.5 parts of EO and 200 parts of PO was injected at 100 to 130 ° C. in about 10 hours, and then the reaction was continued at 130 ° C. for 3 hours to obtain a liquid crude polyether.
1,000 parts of this liquid crude polyether was put into an autoclave, nitrogen substitution (oxygen concentration in the gas phase part 450 ppm) was performed, 30 parts of ion-exchanged water was added, and then synthetic magnesium silicate (sodium content 0.2 %) Was substituted with nitrogen again, and then stirred at 90 ° C. for 45 minutes at a stirring speed of 300 rpm. Subsequently, filtration was performed under nitrogen using a glass filter (GF-75: manufactured by Toyo Roshi) to obtain an EO / PO random co-adduct (f1). This (f1) had a number average molecular weight of 4,000 and an oxyethylene group content of 80%.

<Production Example 2>
The autoclave was charged with 362 parts of prolene glycol and 3.8 parts of potassium hydroxide, purged with nitrogen (oxygen concentration in the gas phase part 450 ppm), and vacuum dehydrated at 120 ° C. for 60 minutes.
Then, 632 parts of PO632 was injected at about 100 to 130 ° C. for about 10 hours, and then the reaction was continued at 130 ° C. until the volatile content was 0.1% or less, to obtain a liquid crude polyether.
This liquid crude polyether was treated with synthetic magnesium silicate in the same manner as in Production Example 1 to obtain a PO adduct (f2). The number average molecular weight of this (f2) was 210, and the content of oxyethylene groups was 0%.

<Production Example 3>
The autoclave was charged with 141.8 parts of prolene glycol and 3.8 parts of potassium hydroxide, and after nitrogen substitution (oxygen concentration in the gas phase part 450 ppm), vacuum dehydration was performed at 120 ° C. for 60 minutes.
Next, a mixture of 781 parts of EO and 193 parts of PO was injected at 100 to 130 ° C. in about 10 hours, and then the reaction was continued at 130 ° C. until the volatile content was 0.1% or less to obtain a liquid crude polyether.
This liquid crude polyether was treated with synthetic magnesium silicate in the same manner as in Production Example 1 to obtain a PO adduct (f3). The number average molecular weight of this (f3) was 600, and the content of oxyethylene groups was 72%.

<Production Example 4>
Using a mixture of 90 parts of the EO / PO random co-adduct (f1) obtained in Production Example 1 and 10 parts of the PO adduct (f2) obtained in Production Example 2 as a polyol component (F), 100 After dehydration under reduced pressure at 2 ° C. for 2 hours, the mixture was cooled to 50 ° C., and 0.5 parts of tetrakis- [methylene-3- (3 ′, 5′-di-t] was added as a phenolic hydroxyl group-containing radical scavenger (PRS). -Butyl-4'-hydroxyphenyl) propionate] methane (Irganox 1010, manufactured by BASF) was added and stirred uniformly for 30 minutes. After further cooling to 40 ° C., bis (isocyanatomethyl) perfluorobutane {OCN—CH ₂ — (CF ₂ ) ₄ —CH ₂ —NCO} which is a fluorine-containing polyisocyanate (E1) as the polyisocyanate component (E) After adding 45.6 parts (NCO group / OH group ratio = 2/1) and stirring uniformly, the temperature was raised to 80 ° C and reacted at 80 ° C for 6 hours to obtain a urethane prepolymer (U1). . The isocyanate group content of (U1) was 4.0%. The content of oxyethylene groups in (F) is 72%, the content of oxyethylene groups in (U) is 49%, and the fluorine content in (E) is 49%.
Moreover, this urethane prepolymer (U1) was also used as a urethane prepolymer (P1).

<Production Example 5>
As a polyol component (F), a mixture of 90 parts of the EO / PO random co-adduct (f1) obtained in Production Example 1 and 10 parts of the PO adduct (f2) obtained in Production Example 2, and a polyisocyanate component (E) A urethane prepolymer (U2) was obtained in the same manner as in Production Example 4 except that 25.4 parts of 2,4-tolylene diisocyanate (TDI) (NCO group / OH group ratio = 2/1) was used. The isocyanate group content of (U2) was 4.8%. In addition, the oxyethylene group content in (F) is 72%, the oxyethylene group content in (U) is 57%, and the fluorine content in (E) is 0%.

<Production Example 6>
As the polyol component (F), a mixture of 70 parts of the EO / PO random coadduct (f1) obtained in Production Example 1 and 30 parts of the PO adduct (f2) obtained in Production Example 2, a fluorine-containing isocyanate component (E) A urethane prepolymer (U3) was obtained in the same manner as in Production Example 4, except that 100 parts of bis (isocyanatomethyl) perfluorobutane (NCO group / OH group ratio = 2/1) was used. The isocyanate group content of (U3) was 6.7%. The oxyethylene group content in the polyol component (F) is 56%, the oxyethylene group content in (U) is 28%, and the fluorine content in (E) is 49%.
Moreover, this urethane prepolymer (U3) was also used as a urethane prepolymer (P3).

<Production Example 7>
90 parts of the EO / PO random co-adduct (f3) obtained in Production Example 3 as the polyol component (F) and 123 parts of bis (isocyanatomethyl) perfluorobutane (NCO group / OH group) as the fluorine-containing isocyanate component (E) A urethane prepolymer (U4) was obtained in the same manner as in Production Example 4 except that the ratio = 2/1) was used. The isocyanate group content of (U4) was 7.4%. In addition, the oxyethylene group content in (F) is 65%, the oxyethylene group content in (U) is 29%, and the fluorine content in (E) is 49%.

<Production Example 8>
As a polyol component (F), a mixture of 95 parts of the EO / PO random co-adduct (f1) obtained in Production Example 1 and 5 parts of the PO adduct (f2) obtained in Production Example 2, a fluorine-containing isocyanate component (E) A urethane prepolymer (U5) was obtained in the same manner as in Production Example 4 except that 29.7 parts of bis (isocyanatomethyl) perfluorobutane (NCO group / OH group ratio = 2/1) was used. The isocyanate group content of (U5) was 3.0%. In addition, the oxyethylene group content in (F) is 76%, the oxyethylene group content in (U) is 59%, and the fluorine content in (E) is 49%.

<Production Example 9>
Urethane prepolymer in the same manner as in Production Example 4, except that 65.6 parts of bis (isocyanatomethyl) perfluorobutane (NCO group / OH group ratio = 3/1) is used as the fluorine-containing polyisocyanate component (E). (U6) was obtained. The isocyanate group content of (U6) was 5.3%. In addition, the oxyethylene group content in (F) is 72%, the oxyethylene group content in (U) is 43%, and the fluorine content in (E) is 49%.

<Production Example 10>
As the polyol component (F), 100 parts of the EO / PO random co-adduct (f1) obtained in Production Example 1, and as the fluorine-containing isocyanate component (E), 15.6 parts (NCO group) bis (isocyanatomethyl) perfluorobutane A urethane prepolymer (U7) was obtained in the same manner as in Production Example 4 except that / OH group ratio = 2/1) was used. The isocyanate group content of (U7) was 1.8%. In addition, the content of oxyethylene groups in (F) is 80%, the content of oxyethylene groups in (U) is 69%, and the fluorine content in (E) is 49%. (U7) was also used as the urethane prepolymer (P7).

<Production Example 11>
As a polyol component (F), a mixture of 50 parts of the EO / PO random co-adduct (f1) obtained in Production Example 1 and 50 parts of the PO adduct (f2) obtained in Production Example 2, a fluorine-containing isocyanate component (E) A urethane prepolymer (U8) was obtained in the same manner as in Production Example 4 except that 156.4 parts of bis (isocyanatomethyl) perfluorobutane (NCO group / OH group ratio = 2/1) was used. The isocyanate group content of (U8) was 8.2%. In addition, the oxyethylene group content in (F) is 40%, the oxyethylene group content in (U) is 16%, and the fluorine content in (E) is 49%.

<Production Example 12>
As polyol component (F), a mixture of 99.5 parts of EO / PO random co-adduct (f1) obtained in Production Example 1 and 0.5 part of PO adduct (F2) obtained in Production Example 2, fluorine-containing isocyanate The urethane prepolymer (U9) was prepared in the same manner as in Production Example 4 except that 25.5 parts of bis (isocyanatomethyl) perfluorobutane (NCO group / OH group ratio = 3/1) was used as the component (E). Obtained. The isocyanate group content of (U9) was 2.7%. In addition, the oxyethylene group content in (F) is 79.6%, the oxyethylene group content in (U) is 63.4%, and the fluorine content in (E) is 49%. Moreover, this urethane prepolymer (U9) was also used as a urethane prepolymer (P9).

<Example 1>
After extending 1.0 g of the urethane prepolymer (U1) obtained in Production Example 4 to a thickness of 150 μm on a glass plate, and allowing it to stand for 48 hours in an environment of 5 ° C. and 25% RH and moisture-curing, from the glass plate It peeled and the urethane film (C1) was obtained. The thickness of this urethane film was 150 μm. This urethane film (C1) was used as a surgical hemostatic base material (1).

<Example 2>
19.8 g of the urethane prepolymer (U2) obtained in Production Example 5 was dissolved in 79.2 g of acetone and poured into a 3 cm × 11 cm glass frame. After leaving still at 25 degreeC and 60% RH environment for 48 hours, and vaporizing acetone and carrying out moisture hardening, it peeled from the glass plate and obtained the urethane film (C2). The thickness of (C2) was 5,000 μm. This urethane film (C2) was used as a surgical hemostatic base material (2).

<Example 3>
1.0 g of the urethane prepolymer (U3) obtained in Production Example 6 was stretched to a thickness of 50 μm on a glass plate, and allowed to stand for 48 hours in an environment of 10 ° C. and 30% RH for moisture curing. This operation was further repeated 9 times, and then peeled from the glass plate to obtain a urethane film (C3). The thickness of (C3) was 500 μm. This urethane film (C3) was used as a surgical hemostatic base material (3).

<Example 4>
After extending 1.0 g of the urethane prepolymer (U4) obtained in Production Example 7 to a thickness of 10 μm on a glass plate, it was quickly immersed in 0.9 wt% physiological saline (25 ° C.) and moisture-cured. . After curing, the film was peeled off from the glass plate, and then dried in a dryer heated to 50 ° C. to obtain a urethane film (C4). The thickness of this (C4) was 10 μm. This urethane film (C4) was used as a surgical hemostatic base material (4).

<Example 5>
1.0 g of the urethane prepolymer (U5) obtained in Production Example 8 was stretched to a thickness of 50 μm on a glass plate, and allowed to stand for 48 hours in an environment of 2 ° C. and 20% RH for moisture curing. After repeating this operation once more, it peeled from the glass plate and obtained the urethane film (C5). The thickness of (C5) was 100 μm. This urethane film (C5) was used as a surgical hemostatic base material (5).

<Example 6>
3.85 g of the urethane prepolymer (U6) obtained in Production Example 9 was dissolved in 15.4 g of acetone and poured into a 3 cm × 11 cm glass frame. After leaving still at 30 degreeC and 60% RH environment for 48 hours, acetone volatilization and moisture hardening, it peeled from the glass plate and obtained the urethane film (C6). The thickness of (C6) was 1,000 μm. This urethane film (C6) was used as a surgical hemostat base material (6).

<Comparative Example 1>
23.7 g of the urethane prepolymer (U7) obtained in Production Example 10 was dissolved in 94.6 g of acetone and poured into a 3 cm × 11 cm glass frame. After leaving still at 25 degreeC and 60% RH environment for 48 hours, acetone volatilization and moisture hardening, it peeled from the glass plate and obtained the urethane film (C'1). This (C′1) had a thickness of 6,000 μm. This urethane film (C′1) was used as a surgical hemostatic base material (1 ′).

<Comparative example 2>
A polyester artificial blood vessel (Zelweve, manufactured by Nippon Lifeline) was used as a surgical hemostatic base material (2 ′) for comparison.

<Comparative Example 3>
0.003 g of the urethane prepolymer (U8) obtained in Production Example 11 was dissolved in 13.8 g of acetone and poured into a 3 cm × 11 cm glass frame. After leaving still at 25 degreeC and 60% RH environment for 48 hours, acetone volatilization and moisture hardening were carried out, it peeled from the glass plate and obtained the urethane film (C'3). The thickness of (C′3) was 1 μm. This urethane film (C′3) was used as a surgical hemostatic base material (3 ′).

<Comparative Example 4>
20.2 g of the urethane prepolymer (U3) obtained in Production Example 6 was dissolved in 80.8 g of acetone and poured into a 3 cm × 11 cm glass frame. The mixture was allowed to stand for 48 hours in an environment of 25 ° C. and 60% RH, volatilized with acetone and moisture cured, and then peeled from the glass plate to obtain a urethane film (C′4). The thickness of (C′4) was 5,500 μm. This urethane film (C′4) was used as a surgical hemostatic base material (4 ′).

<Comparative Example 5>
20.2 g of the urethane prepolymer (U9) obtained in Production Example 12 was dissolved in 80.8 g of acetone and poured into a 3 cm × 11 cm glass frame. After leaving still at 25 degreeC and 60% RH environment for 48 hours, acetone volatilization and moisture hardening, it peeled from the glass plate and obtained the urethane film (C'5). The thickness of (C′5) was 5,500 μm. This urethane film (C′5) was used as a surgical hemostatic base material (5 ′).

<Evaluation 1: Elongation>
<Preparation of test piece>
The surgical hemostatic base materials (1) to (6) and (1 ′) to (5 ′) were soaked in 0.9% by weight physiological saline for 3 hours and then swollen. A test piece was produced by punching out using a dumbbell-shaped No. 3 mold.
<Measurement>
The test piece was installed in a tensile tester by fixing with both-end clamps, and pulled until cut. A length obtained by applying a load until cutting was divided by a distance between marked lines before applying the load, and a value multiplied by 100 was calculated as an elongation rate. The tensile tester used was Autograph AGS-500D manufactured by Shimadzu Corporation, and the tensile speed was 300 mm / min.

<Evaluation 2: 100% modulus>
The test piece of Evaluation 1 was fixed with the both-side gripping tool and installed in a tensile tester and pulled. The tension when the distance between the marked lines was doubled was measured, and the value divided by the cross-sectional area before applying the load was calculated as the elongation. The tensile tester used was Autograph AGS-500D manufactured by Shimadzu Corporation, and the tensile speed was 300 mm / min.

<Evaluation 3: Water absorption>
Surgical hemostatic base materials (1) to (6) and (1 ′) to (5 ′) were cut to 1.00 g. This was submerged in 100 mL of 0.9 wt% physiological saline in a 100 mL beaker for 3 hours, lightly removed from the surface, and the weight (x1) was measured again. The water absorption was calculated by applying the measured weight to the following formula.
Water absorption rate = (x1) /1.00

  From the results in Table 1, the surgical hemostat base materials (1) to (6) of Examples 1 to 6 absorbed water and exhibited stretchability. On the other hand, since the surgical hemostatic base material (1 ') obtained in Comparative Example 1 absorbed water and changed to a gel, the elongation and 100% modulus could not be measured. The surgical hemostatic base material (2 ') of Comparative Example 2 was not able to be measured because it absorbs water but does not stretch (exceeds the measurement limit). In addition, the surgical hemostatic material substrate (3 ') of Comparative Example 3 had a lower water absorption rate than Examples 1 to 6, and did not exhibit stretchability. Further, the surgical hemostatic base material (4 ') of Comparative Example 4 had a high water absorption rate but a low elongation rate. Further, the surgical hemostatic base material (5 ') of Comparative Example 5 had a moderate elongation, but had a too high water absorption rate and an extremely low 100% modulus.

<Example 7>
The surgical hemostat base material (1) obtained in Example 1 was cut into a size of 1.0 cm × 7.0 cm, and the urethane prepolymer obtained in Production Example 4 was used as a medical adhesive (B) on one side. Surgical hemostatic material (S1) was obtained by spreading polymer (P1) with a thickness of 100 μm.

<Example 8>
In Example 7, using “surgical hemostatic material substrate (2)” instead of “surgical hemostatic material substrate (1)”, the thickness of the medical adhesive (B) was changed to “100 μm”. A surgical hemostatic material (S2) was obtained in the same manner except that the thickness was 10 μm.

<Example 9>
In Example 7, using “surgical hemostatic material substrate (3)” instead of “surgical hemostatic material substrate (1)”, the thickness of the medical adhesive (B) was changed to “100 μm”. A surgical hemostatic material (S3) was obtained in the same manner except that the thickness was 500 μm.

<Example 10>
In Example 7, using “surgical hemostatic material substrate (4)” instead of “surgical hemostatic material substrate (1)”, the thickness of the medical adhesive (B) was changed to “100 μm”. A surgical hemostatic material (S4) was obtained in the same manner except that the thickness was set to “5,000 μm”.

<Example 11>
A surgical hemostatic material (S5) was obtained in the same manner as in Example 7, except that “surgical hemostatic material substrate (5)” was used instead of “surgical hemostatic material substrate (1)”.

<Example 12>
In Example 7, using “surgical hemostatic material substrate (6)” instead of “surgical hemostatic material substrate (1)”, “urethane prepolymer (P1)” as the medical adhesive (B) Instead of using “cyanoacrylate adhesive (Aron Alpha A“ Sankyo ”, Daiichi Sankyo Co., Ltd.)”, a surgical hemostatic material (S6) was obtained.

<Comparative Example 6>
In Example 7, using “surgical hemostatic material substrate (1 ′)” instead of “surgical hemostatic material substrate (1)”, “urethane prepolymer (P1) as a medical adhesive (B)” Surgical hemostatic material (S′1) was obtained in the same manner except that “urethane prepolymer (P7)” was used instead of “.

<Comparative Example 7>
In Example 7, a surgical hemostatic material (S′2) was obtained in the same manner except that “surgical hemostatic material substrate (2 ′)” was used instead of “surgical hemostatic material substrate (1)”. It was.

<Comparative Example 8>
The surgical hemostat base material (3 ′) obtained in Comparative Example 3 was cut into a size of 1.0 cm × 7.0 cm, and fibrinogen of fibrin glue (Beriplast P combination set, manufactured by CSL Bering Co., Ltd.) on one side. A surgical hemostatic material (S′3) was obtained by spraying a mixed solution of the solution and aprotinin solution to a thickness of 2,000 μm.

<Comparative Example 9>
In Example 7, using “surgical hemostatic material substrate (4 ′)” instead of “surgical hemostatic material substrate (1)”, “urethane prepolymer (P1) as a medical adhesive (B)” Surgical hemostatic material (S′4) was obtained in the same manner except that “urethane prepolymer (P3)” was used instead of “.

<Comparative Example 10>
In Example 7, using “surgical hemostatic material substrate (5 ′)” instead of “surgical hemostatic material substrate (1)”, “urethane prepolymer (P1) as the medical adhesive (B)” Surgical hemostatic material (S′5) was obtained in the same manner except that “urethane prepolymer (P9)” was used instead of “.

<Evaluation 4: Pulse pressure load test>
<Production of suture model blood vessel>
A 10-mm incision was made in the porcine blood vessel (pig thoracoabdominal aorta with peripheral fat removed and intercostal artery ligated), and sutured at 2 mm intervals with 3-0 suture (product name: Proleen, manufactured by Johnson & Johnson Co., Ltd.) As a result, a suture model blood vessel was prepared.
<Hemostasis determination>
Both ends of this suture model blood vessel were connected to a pressure load test device (manufactured by Anhiko Co., Ltd.) line (see FIG. 1 for the suture model blood vessel, and FIG. 2 for the device connection outline of the pressure load test device) and heparinized. Horse blood was filled. The downstream side of the pressure load testing device line was blocked, and a pulse pressure of 120/60 mmHg (16,000 Pa / 8,000 Pa) was applied at a cycle of 1 second, and it was confirmed that there was bleeding from the sutured part. Once the blood in the suture model blood vessel was removed, the blood adhering to and around the sutured part was wiped off.
The surgical hemostatic materials of Examples 7 to 12 and Comparative Examples 6 to 10 cut to 1 cm × 2 cm were affixed to the sutured portion, 0.9% by weight physiological saline was applied, and the entire surgical hemostatic material was applied from above with fingers. Press for 3 minutes to cure.
Again, heparinized horse blood is filled into the suture model blood vessel, the downstream side of the pressure load test device line is blocked, and a pulse pressure of 120/60 mmHg (16,000 Pa / 8,000 Pa) is obtained in a cycle of 1 second. It was over. After applying the pulse pressure, it was observed for 5 minutes. The results are shown in Table 2.

<Evaluation 5: Adhesion test>
<Preparation of test piece>
A strong double-sided tape (Nystack super strong type, manufactured by Nichiban Co., Ltd.) was cut into a size of 1 cm × 4 cm, and both surfaces thereof were covered with a collagen film (collagen casing, manufactured by Nippi Co., Ltd.) to form an adherend.
After bonding the adherend to both ends of the surgical hemostats of Examples 7 to 12 and Comparative Examples 6 to 10 cut to 1.0 cm × 7.0 cm so as to overlap 1.0 cm × 1.0 cm in the horizontal direction. 0.9% by weight physiological saline was applied to adhere the surgical hemostatic material and the adherend for 5 minutes. This was immersed in 0.9% by weight physiological saline for 3 hours to swell and absorb water to obtain a test piece (see FIG. 3 for the appearance of the test piece).
<Measurement>
Next, in an environment of 25 ± 5 ° C and humidity of 65 ± 5RH%, continuously pull both ends of the test piece in the opposite direction (the direction in which the sheet extends) and measure the number of pulls until the test piece peels off. The adhesiveness was evaluated. Three test pieces were prepared for each surgical hemostatic material, and the measured value was the average value.
The tensile testing machine used imada Co., Ltd. measurement stand MX-500N. The continuous cycle mode was set, and the pulling distance was set to 25 mm and the pulling speed was set to 300 mm / min. Further, the part to be fixed with the gripping tool was an end 1 cm portion where the adherend was not bonded and an end 1 cm portion where the other adherend was not bonded, and was fixed so as not to loosen.

From the results in Table 2, it can be seen that the surgical hemostatic material (Examples 7 to 12) of the present invention and the surgical hemostatic material of Comparative Example 7 were able to stop bleeding at the incision of the porcine blood vessel. Moreover, the surgical hemostats of Comparative Examples 6 and 8 to 10 were unable to stop bleeding at the incision of the porcine blood vessel.
Moreover, it can be seen from the results in Table 2 that the surgical hemostatic material (Examples 7 to 12) of the present invention was higher in adhesiveness and difficult to peel off than Comparative Examples 7 to 10. In particular, when the surgical hemostatic materials of Examples 7 and 9 to 12 were used, it was found that the hemostatic effect was extremely high in the adhesion test, even when the number of tensions was 18 or more. Note that Comparative Example 6 could not be measured because it absorbed water and changed to a gel.
Therefore, it can be seen that the surgical hemostatic material (Examples 7 to 12) of the present invention is excellent in flexibility at the time of water absorption swelling, does not come into close contact with a moving place, and has a high hemostatic effect.

The surgical hemostatic material of the present invention has a high elongation rate and a low 100% modulus, and provides a surgical hemostatic material that does not adhere and peel even to pulsatile tissues such as blood vessels. Can prevent leakage of blood or cerebrospinal fluid, making re-leakage less likely to occur.
In addition, the surgical hemostatic material substrate of the present invention can be applied regardless of the presence or absence of administration of a blood anticoagulant such as heparin, and can stop hemostasis in a short time. It can also be used for aortic surgery.

DESCRIPTION OF SYMBOLS 1 Porcine blood vessel 2 Suture part 3 Hose band 4 Tube connector 5 Rubber stopper with a hole that can be inserted into the tube connector 6 Compressor 7 Low pressure regulator 8 High pressure regulator 9 Tank 10 Timer 11 Solenoid valve 12 Throttle valve 13 Manometer 14 Compliance tank 15 Horse blood 16 Pressure load test equipment line (upstream side)
17 Pressure load test device body 18 Blood inlet 19 Sutured blood vessel model 20 in FIG. 1 Roller clamp 21 Pressure load test device line (downstream side)
22 Adherent 23 Surgical hemostatic material

Claims (7)

A surgical hemostatic material substrate made of a urethane film , wherein the urethane film has a thickness of 10 to 5,000 μm, and the urethane film has an elongation percentage of 100 to 4,000% at the time of water absorption and swelling according to JIS K6251-2004. , and the a below water 100% modulus at swelling 9.8 × 10 ^-3 ~4.9N / mm ² according to JIS K6251-2004, Ri following water absorption 1.1 to 10 der, the urethane film below urethane resin forming composition cured der Ru surgical hemostatic material substrates (a).
When water absorption swells: When immersed in physiological saline at 25 ° C. for 3 hours
Water absorption: ratio of weight after immersion to weight before immersion when immersed in physiological saline at 25 ° C. for 3 hours {weight after immersion / weight before immersion}
Urethane resin-forming composition (A): a composition containing a urethane prepolymer (U) which is a reaction product of a polyisocyanate component (E) and a polyol component (F) having a hydrophilic polyol (F1) as an essential component. The isocyanate group content in (A) is 1.2 to 8% by weight based on the weight of (A), and the content of oxyethylene groups in (F) is A composition that is 45-77% by weight based on the weight of oxyalkylene groups The surgical hemostatic material substrate according to claim 1, wherein the polyisocyanate component (E) is a polyisocyanate component (E ') containing a fluorine-containing polyisocyanate (E1) as an essential component. The surgical hemostatic base material according to claim 1 or 2, wherein the content of oxyethylene groups in the urethane prepolymer (U) is 25 to 65% by weight based on the weight of (U). The equivalent ratio of the isocyanate group in the polyisocyanate component (E) and the hydroxyl group in the polyol component (F) (NCO group / OH group) is 1.5 to 3, 4. The surgical hemostatic material base material as described in 1. Surgical hemostat consisting of surgical hemostatic material substrates and medical adhesive according to any one of claims 1~ 4 (B). The surgical hemostatic material according to claim 5 , wherein the medical adhesive (B) is a urethane adhesive composition (B1) and / or a cyanoacrylate adhesive composition (B2). The surgical hemostatic material according to claim 5 or 6 , wherein the medical adhesive (B) is the following urethane adhesive composition (B11).
Urethane adhesive composition (B11): a reaction product of a polyisocyanate component (E ′) having a fluorine-containing polyisocyanate (E1) as an essential component and a polyol component (F) having a hydrophilic polyol (F1) as an essential component Adhesive composition containing urethane prepolymer (P1)

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