DESCRIPTION
ADHESIVE COMPOSITION FOR SOFT TISSUES, ADHESIVE COMPOSITION
FOR WOUND DRESSING OR WOUND DRESSING COMPOSITION
5 Technical Field
[OOOl]
The present invention relates to an adhesive composition
for soft tissues, an adhesive composition for wound dressing
or a wound dressing composition.
10 Background Art
[0002]
As soft tissue adhesives, adhesives for wound dressing
or wound dressings, various compositions, e.g., compositions
containing cyanoacrylate and compositions using materials
15 derived from organisms, such as compositions containing
fibrin and compositions containing albumin, have been studied
in the past (see, for example, patent literature 1 and patent
literature 2).
[ 0 0 0 3 ]
20 The compositions containing cyanoacrylate are excellent
in view of high adhesive strength, but they have poor
biocompatibility, and there is a serious problem that
formaldehyde generated by hydrolysis of cured products of the
compositions exhibits high toxicity to organisms and inhibits
healing. Particularly in parts that come into direct contact
with central nervous system, blood vessels, etc., these
compositions cannot be used. Moreover, since the curing time
is extremely short, they are sometimes difficult to use.
5 [0004]
The compositions containing materials derived from
organisms are excellent in that the biocompatibility is high
and healing is rarely inhibited, but they have low adhesive
strength. Further, when the composition containing fibrin is
10 used as an adhesive or the like, there is a side view that
fibrin glue contained in the composition becomes a culture
medium for bacteria, so that there is the risk of infection
after operation or treatment and there is a fear of
harmfulness.
15 [0005]
When an adhesive is used for a wound of the skin or a
soft tissue, or when a wound dressing is used for a wound, it
is a usual way that the components are mixed in advance in a
container or the like to prepare a composition and then the
20 composition is applied to the surface of the soft tissue, the
wound dressing part or the like, taking into consideration of
workability, prevention of infection, etc. However, the
state of the composition after mixing sometimes has influence
on the workability during the application of the composition,
that is, for example, if the viscosity of the composition is
too high, the composition is hard to apply, or if the
viscosity is too low, the composition runs out of the
necessary area. Moreover, if properties, such as elasticity
5 and tensile elongation, of a film obtained by polymerization
and solidification of the adhesive or the wound dressing are
not proper, there sometimes occurs a problem that the film
peels off from the skin after application because the skin or
the soft tissue is a flexible adherend.
10 [0006]
Since acrylic adhesives using an initiator containing an
organoboron compound have low toxicity and low harmfulness
and have high adhesive strength, development of them to
dental applications has been promoted (see, for example,
15 patent literature 3). However, if other medical applications,
such as surgical applications, soft tissue adhesion
applications and wound dressing applications, are intended,
further improvement in handling stability or workability of
the composition between mixing of the components and
20 application to the application area has been sometimes
required.
Citation List
Patent Literature
[0007]
Patent literature 1: Japanese Patent Laid-Open
Publication No. 061658/2007
Patent literature 2: Japanese Patent Laid-Open
Publication No. 051121/2006
5 Patent literature 3: Japanese Patent Laid-Open
Publication No. 110913/1997
Summary of Invention
Technical Problem
[0008]
10 It is an object of the present invention to provide a
composition which not only has low toxicity, low harmfulness
and high adhesive strength but also is excellent in
workability during application and is capable of forming a
film having properties that are preferable for an adhesive
15 for soft tissues, an adhesive for wound dressing or a wound
dressing.
Solution to Problem
[0009]
In order to solve the above problems, the present
20 inventors have earnestly studied compositions which are
preferable as adhesives for soft tissues, adhesives for wound
dressing or wound dressings. As a result, they have found
that the above problems can be solved by a specific adhesive
composition or wound dressing composition comprising a
monomer, a polymer and a specific polymerization initiator
composition, preferably the adhesive composition or wound
dressing composition having a viscosity of a specific range
after mixing of components including these components, and
5 they have accomplished the present invention. The adhesive
composition for soft tissues, the adhesive composition for
wound dressing or the wound dressing composition of the
present invention means a composition of materials, with
which wounds made in soft tissues, such as skins, muscles,
10 internal organs and blood vessels of organisms, by operations,
accidents, etc., i.e., disconnected tissues, are surfacecovered
to carry out adhesion of skins of the wounds or
temporary dressing of the wounds.
[OOlO]
15 That is to say, an adhesive composition for soft tissues,
an adhesive composition for wound dressing or a wound
dressing composition of the present invention comprises a
monomer (A), polymer particles (B) having a weight-average
molecular weight of 210,000 or more and 1,500,000 or less and
20 a volume mean particle diameter of 1.0 p or more and 90 p
or less, and a polymerization initiator composition (C)
containing an organoboron compound. The polymer (B)
preferably has a weight-average molecular weight of 250,000
or more and 1,400,000 or less.
[OOll]
The polymer particles (B) preferably include at least
one type selected from
polymer particles (Bl) having a weight-average molecular
5 weight of 1,000,000 or more and 1,400,000 or less and a
volume mean particle diameter of 1.0 p or more and 90 p or
less,
polymer particles (B2) having a weight-average molecular
weight of 750,000 or more and less than 1,000,000 and a
10 volume mean particle diameter of more than 30 p and 90 p or
less,
polymer particles (B3) having a weight-average molecular
weight of 250,000 or more and 950,000 or less and a volume
mean particle diameter of 1.0 p or more and 30 p or less,
15 polymer particles (B4) having a weight-average molecular
weight of 350,000 or more and 700,000 or less and a volume
mean particle diameter of more than 30 p and 90 p or less,
and
polymer particles (B5) having a weight-average molecular
20 weight of more than 950,000 and less than 1,000,000 and a
volume mean particle diameter of 30 p.
[0012]
The adhesive composition or the wound dressing
composition preferably has a viscosity of 0.4 to 75,000 cp
within 30 seconds after mixing of the components (A), (B) and
(C)
[0013]
A film, which is obtained from the above adhesive
5 composition or wound dressing composition, is given 24 hours
after the preparation of the composition and has a thickness
of not less than 0.1 pm, a length of not less than 25 mm and
a width of not less than 2 mm, preferably has a flexural
modulus, as measured under the conditions of a test rate of 2
10 mm/min, of not more than 750 MPa and a tensile elongation, as
measured under the conditions of a test rate of 1 mm/min, of
not less than 5%.
[0014]
The adhesive composition or the wound dressing
15 composition may further comprise, for example, a
polymerization inhibitor (D), an ultraviolet light absorber,
and a plasticizer.
[0015]
In a preferred embodiment, the content of the
20 polymerization inhibitor (D) in the composition is in the
range of 10 to 5000 ppm based on the monomer (A).
[0016]
The polymerization inhibitor (D) is preferably at least
one substance selected from hydroquinone, dibutylhydroquinone,
hydroquinone monomethyl ether, 2,6-di-tert-butylphenol, 2,6-
di-tert-butyl-p-cresol, catechol, pyrogallol, benzoquinone,
2-hydroxybenzoquinone, p-methoxyphenol, t-butylcatechol,
butylated hydroxyanisole, butylated hydroxytoluene and t-
5 butylhydroquinone.
[0017]
The adhesive composition or the wound dressing
composition may further comprise at least one substance
selected from:
10 anti-infectious agents, antibiotics, antibacterial
agents, anti-virus agents, analgesics, compositions of
analgesics, anorectic drugs, antihelmintic drugs,
antiarthritic agents, antiasthmatic drugs, anticonvulsants,
antidepressants, antidiuretics, antidiarrheal agents,
15 antihistamine drugs, anti-inflammatory drugs, antimigraine
drugs, antiemetic agents, antineoplastic drugs,
antiparkinsonian agents, antipruritic drugs, antipsychotics,
antipyretic drugs, antispasmodic drugs, anticholinergic
agents, sympathomimetic agents, cardiovascular drugs,
20 antiarrhythmic drugs, antihypertensive drugs, diuretics,
vasodilators, immunosuppressant drugs, muscle-relaxant drugs,
parasympatholytic drugs, stimulants, sedative drugs,
tranquilizers, cholinergic agents, chemotherapeutic drugs,
radio pharmaceuticals, bone inductive drugs, heparin
neutralizer agents of static bladder, procoagulants,
hemostatic agents, xanthine derivatives, hormones, proteins
of natural origin or proteins synthesized by genetic
engineering, polysaccharides, glycoproteins, lipoproteins,
oligonucleotides, antibody, antigen, vasopressin, vasopressin
analogs, epinephrine, selectin, clot promoting toxicants,
plasminogen activating factor inhibitors, platelet activators,
synthetic peptides having hemostatic action, and
perfumes, such as orange oil, grapefruit oil, lemon oil,
lime oil, clove oil, wintergreen oil, peppermint oil,
peppermint spirit, banana distillate, cucumber distillate,
honey distillate, rose water, menthol, anethole, alkyl
salicylate, benzaldehyde, monosodium glutamate, ethylvanillin,
thymol and vanillin.
[0018]
The kit of the present invention used as an adhesive for
soft tissues, an adhesive for wound dressing or a wound
dressing has members in which the components of the monomer
(A), the polymer particles (B) and the polymerization
initiator composition (C) containing an organoboron compound,
which are contained in the adhesive composition or the wound
dressing composition, are encased in two or more divided
groups in an optional combination.
[0019]
The above kit preferably has constitution in which the
monomer (A), the polymer particles (B) and the polymerization
initiator composition (C) are each independently encased, and
the monomer (A) is first mixed with the polymerization
initiator composition (C) containing an organoboron compound
and subsequently mixed with the polymer particles (B).
[0020]
When the above kit contains the polymerization inhibitor
(D), the kit has members in which the components of the
monomer (A), the polymer particles (B), the polymerization
initiator composition (C) containing an organoboron compound
and the polymerization inhibitor (D), which are contained in
the adhesive composition for soft tissues, the adhesive
composition for wound dressing or the wound dressing
composition, are encased in two or more divided groups in an
optional combination.
[0021]
The kit containing the polymerization inhibitor (D)
preferably has constitution in which a mixture of the monomer
(A) and the polymerization inhibitor (D), the polymer
particles (B) and the polymerization initiator composition
(C) are each independently encased, and the mixture of the
monomer (A) and the polymerization inhibitor (D) is first
mixed with the polymerization initiator composition (C)
containing an organoboron compound and subsequently mixed
with the polymer particles (B) .
[0022]
In the kit, a jig that is used for applying a
5 composition obtained by mixing adhesive components or wound
dressing components containing the components (A), (B) and
(C) and the components added when needed may be further
included.
100231
10 The jig is, for example, a brush, a fiber ball, a cloth,
a sponge ball or a piece of sponge.
[0024]
In the above kit, an aqueous solution for adhesion
pretreatment containing 1 to 15% by weight of citric acid and
15 1 to 5% by weight of iron(II1) chloride may be further
contained.
Advantageous Effects of Invention
[0025]
The adhesive composition for soft tissues, the adhesive
20 composition for wound dressing or the wound dressing
composition of the present invention not only has low
toxicity, low harmfulness and high adhesive strength but also
is excellent in workability during application and is capable
of forming a film having properties that are preferable for
an adhesive for soft tissues, an adhesive for wound dressing
or a wound dressing. When the composition is applied to a
wound, the wound can be strongly bonded with the adhesive.
Especially when the composition of the invention is applied
5 to a wound of the outer skin, the wound of the outer skin can
be joined with the adhesive, and after healing, the adhesive
can be naturally separated from the outer skin.
Brief Description of Drawings
[00261
10 [Fig. 11 Fig. 1 is a schematic view showing a process
for preparing a sample film used in the examples of the
present invention.
[Fig. 21 Fig. 2 is a schematic view showing a process
for preparing an evaluation sample for evaluating adhesive
15 strength with YMP skin.
Description of Embodiments
[0027]
In the adhesive composition for soft tissues, the
adhesive composition for wound dressing or the wound dressing
20 composition of the present invention, a monomer (A) is
contained. As the monomer (A), any monomer can be used
without specific restriction as long as it can be polymerized
by the later-described polymerization initiator composition
(C). As the monomer (A), any of a monofunctional monomer and
a polyfunctional monomer can be used depending upon the use
purpose.
[0028]
Examples of the monomers (A) include methacrylates,
5 acrylates and other vinyl compounds.
[0029]
Of such monomers (A), acrylates and methacrylates are
preferable from the viewpoint of relatively low irritation of
the human body. In particular, methacrylates are more
10 preferable. Hereinafter, (meth)acrylates may be used to
refer to acrylates and methacrylates.
[0030]
Of the monomers (A), monomers having an acidic group are
preferable from the viewpoint of excellent adhesion
15 properties.
[ 0 0 3 1 ]
Therefore, use of a combination of a (meth)acrylate
(having no acidic group) and a monomer having an acidic group
I
I as the monomer (A) is also a preferred embodiment.
20 [0032]
Examples of monofunctional (meth)acrylates (having no
acidic group) include:
alkyl (meth)acrylates, such as methyl (meth)acrylate,
ethyl (meth) acrylate, propyl (meth) acrylate, butyl
(meth)acrylate, hexyl (meth)acrylate, 2-ethylhexyl
(meth) acrylate, dodecyl (meth) acrylate, lauryl (meth) acrylate,
cyclohexyl (meth)acrylate, benzyl (meth)acrylate and
isobornyl (meth)acrylate;
5 hydroxyalkyl esters of (meth)acrylic acid, such as 2-
hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate,
3-hydroxypropyl (meth)a crylate, 4-hydroxybutyl (meth)a crylate,
5-hydroxypentyl (meth)acrylate, 6-hydroxyhexyl (meth)acrylate,
1,2-dihydroxypropyl mono(meth)acrylate, 1,3-dihydroxypropyl
10 mono (meth)a crylate and erythritol mono (meth)a crylate;
polyalkylene glycol mono(meth)acrylates, such as
diethylene glycol mono(meth)acrylate, triethylene glycol
mono(meth)acrylate, polyethylene glycol mono(meth)acrylate
and polypropylene glycol mono(meth)acrylate;
15 (po1y)alkylene glycol monoalkyl ether (meth)acrylates,
such as ethylene glycol monomethyl ether (meth)acrylate,
ethylene glycol monoethyl ether (meth)acrylate, diethylene
glycol monomethyl ether (meth)acrylate, triethylene glycol
monomethyl ether (meth)acrylate, polyethylene glycol
20 monomethyl ether (meth)acrylate and polypropylene glycol
monoalkyl ether (meth) acrylate;
fluoroalkyl esters of (meth)acrylic acid, such as
perfluorooctyl (meth)acrylate and hexafluorobutyl
silane compounds having a (meth)acryloxyalkyl group,
such as y- (meth) acryloxypropyltrimethoxysilane and y-
(meth)acryloxypropyltri(trimethylsiloxy)silane; and
(meth)acrylates having a heterocyclic ring, such as
5 tetrahydrofurfuryl (meth)acrylate.
Examples of the polyfunctional (meth)acrylates (having
no acidic group) include:
poly(meth)acrylates of alkanepolyols, such as ethylene
10 glycol di (meth)a crylate, propylene glycol di (meth)a crylate,
butylene glycol di(meth)acrylate, neopentyl glycol
di(meth)acrylate, hexylene glycol di(meth)acrylate,
trimethylolpropane tri(meth)acrylate and pentaerythritol
tetra (meth) acrylate;
15 polyoxyalkane polyol poly(meth)acrylates, such as
diethylene glycol di(meth)acrylate, triethylene glycol
di (meth) acrylate, polyethylene glycol di (meth) acrylate,
dipropylene glycol di(meth)acrylate, polypropylene glycol
di (meth)a crylate, dibutylene glycol di (meth)a crylate and
, 20 dipentaerythritol hexa(meth)acrylate;
alicyclic or aromatic di(meth)acrylates represented by
the following formula (1) :
[0034]
wherein R is a hydrogen atom or a methyl group, m and n
are numbers of 0 to 10 which may be the same or different,
5 and R' is any one of the following:
[0037]
alicyclic or aromatic epoxy di(meth)acrylates
represented by the following formula (2):
CH2 II
H H H H H H H H H
C-C-0-CI
II
R O H P H H Y H
5 wherein R is a hydrogen atom or a methyl group, n is a
number of 0 to 10, and R' is any one of the following:
and
polyfunctional (meth)acrylates having a urethane bond in
a molecule, which are represented by the following formula
(3) :
5 [0042]
1 wherein R is a hydrogen atom or a methyl group, and R* is
I I 10 any one of the following:
[0045]
[0046]
Of these (meth)acrylates, preferred monofunctional
(meth)acrylates include:
5 alkyl (meth)acrylates, such as methyl (meth)acrylate and
ethyl (meth) acrylate;
hydroxyalkyl esters of (meth)acrylic acid, such as 2-
hydroxyethyl (meth)acrylate, 1,3-dihydroxypropyl
mono(meth)acrylate and erythritol mono(meth)acrylate; and
10 polyethylene glycol mono(meth)acrylates, such as
triethylene glycol monomethyl ether (meth)acrylate and
triethylene glycol mono(meth)acrylate.
[0047]
Preferred polyfunctional (meth)acrylates include:
15 di(meth)acrylates having an ethylene glycol chain in a
molecule, such as triethylene glycol di(meth)acrylate and
polyethylene glycol di(meth)acrylate;
compounds represented by the following formula (1)-a:
[0048]
wherein R is a hydrogen atom or a methyl group, and m
and n are numbers of 0 to 10 which may be the same or
different;
compounds represented by the following formula (2)-a:
[0050]
CH2 II
H H H
I l l
H H H
I l l CH2
C-C-0-C-C-C-0
II
I II I l l +r-0-c-C-C-0-C-C
R 0 H 0 H CH3
I l l II I
I
H O H O R
I
wherein R is a hydrogen atom or a methyl group;
and
compounds represented by the following formula (3)-a:
[0052]
wherein R is a hydrogen atom or a methyl group.
[0054]
These (meth)acrylates can be used singly or in
15 combination of two or more kinds.
Examples of the monomers having an acidic group include:
monomers having a carboxylic acid group or its anhydride
group, such as (meth)acrylic acid and its anhydride, 1,4-
20 di(meth)acryloxyethylpyromellitic acid, 6-
(meth)acryloxyethylnaphthalene-1,2,6-tricarboxylic acid, N(
meth)acryloyl-p-aminobenzoic acid, N-(meth)acryloyl-oaminobenzoic
acid, N-(meth)acryloyl-m-aminobenzoic acid, N-
(meth)acryloyl-5-aminosalicylic acid, N-(meth)acryloyl-4-
aminosalicylic acid, 4-(meth)acryloxyethyltrimellitic acid
5 and its anhydride, 4-(meth)acryloxybutyltrimellitic acid and
its anhydride, 4-(meth)acryloxyhexyltrimellitic acid and its
anhydride, 4-(meth)acryloxydecyltrimellitic acid and its
anhydride, 2-(meth)acryloyloxybenzoic acid, 3-
(meth)acryloyloxybenzoic acid, 4-(meth)acryloyloxybenzoic
10 acid, P- (meth)a cryloyloxyethyl hydrogensuccinate, PI
(meth)acryloyloxyethyl hydrogenmaleate, PI
(meth)acryloyloxyethyl hydrogenphthalate, 11-
(meth)acryloyloxy-1,l-undecanedicarboxylic acid, and pvinylbenzoic
acid;
I 15 monomers having a phosphoric acid group, such as (2-
I
(meth) acryloxyethyl) phosphoric acid, (2-
(meth)acryloxyethylphenyl)phosphoric acid and 10-
(meth)acryloxydecylphosphoric acid; and
monomers having a sulfonic acid group, such as p-
20 styrenesulfonic acid and 2-acrylamido-2-methylpropanesulfonic
acid.
Of these monomers having an acidic group, 4-
methacryloxyethyltrimellitic acid and its anhydride are
preferable.
[0057]
These monomers having an acidic group can be used singly
or in combination of two or more kinds. By the use of these
5 monomers having an acidic group, the adhesive composition for
soft tissues, the adhesive composition for wound dressing or
the wound dressing composition of the present invention tends
to have more improved adhesion properties.
[0058]
10 The monomer having an acidic group is preferably
contained in an amount of 1 to 20 parts by weight, more
preferably 1 to 10 parts by weight, still more preferably 1
to 8 parts by weight, based on 100 parts by weight of the
total amount of the (meth)acrylate (having no acidic group)
15 and the monomer having an acidic group. If the amount
thereof is out of the above range, an evil influence is
sometimes exerted on the adhesive strength or the
biocompatibility.
[0059]
20 The amount of the monomer (A) is preferably in the range
of 25.9 to 77.7 parts by weight, more preferably 25.9 to 73.0
parts by weight, still more preferably 30.6 to 63.6 parts by
weight, based on 100 parts by weight of the total amount of
the monomer (A), the later-described polymer particles (B)
and the later-described polymerization initiator composition
( C )
[0060]
If the amount of the monomer (A) is less than the lower
5 limit of the above range, the viscosity is increased, and
application tends to be difficult. If the amount of the
monomer (A) exceeds the upper limit of the above range, the
adhesive strength is poor, and there is a possibility that
the mixture runs out of the desired area to obstruct the
10 treatment.
[0061]
In the adhesive composition for soft tissues, the
adhesive composition for wound dressing or the wound dressing
composition of the present invention, polymer particles (B)
15 are further contained. The polymer particles (B) have a
weight-average molecular weight of 210,000 or more and
1,500,000 or less, preferably 250,000 or more and 1,400,000
or less. The polymer particles (B) have a volume mean
particle diameter of 1.0 pn or more and 90 pn or less.
20 [0062]
The polymer particles (B) preferably include at least
one type selected from the following (Bl) to (B5) :
(Bl) polymer particles having a weight-average molecular
weight of 1,000,000 or more and 1,400,000 or less and a
volume mean particle diameter of 1.0 p or more and 90 p or
less,
(B2) polymer particles having a weight-average molecular
weight of 750,000 or more and less than 1,000,000 and a
5 volume mean particle diameter of more than 30 p and 90 p or
less,
(B3) polymer particles having a weight-average molecular
weight of 250,000 or more and 950,000 or less and a volume
mean particle diameter of 1.0 p or more and 30 p or less,
10 (B4) polymer particles (B4) having a weight-average
molecular weight of 350,000 or more and 700,000 or less and a
volume mean particle diameter of more than 30 p and 90 p or
less, and
(B5) polymer particles (B5) having a weight-average
I
I 15 molecular weight of more than 950,000 and less than 1,000,000
!
and a volume mean particle diameter of 30 p.
By using such polymer particles (B), the dispersibility
of the polymer particles (B) is excellent in mixing of the
polymer particles (B) with the monomer (A) and the
20 polymerization initiator composition (C) in a container; in
addition, extrusion properties of the resultant mixture from
the container are excellent; furthermore, application
properties of the mixture are excellent and the mixture is
applied without spreading to outside of the affected part.
The volume mean particle diameter of the polymer
particles is measured by dispersing the polymer particles in
a dispersion medium (for example, special grade reagent
5 methanol (refractive index: 1.33, available from Wako Pure
Chemical Industries, Ltd.)) by an ultrasonic homogenizer and
carrying out the measurement by the laser
diffraction/scattering method (for example, by the use of
Microtrac MT3300EXII (manufactured by Microtrac Inc.)
10 particle size distribution meter).
[0064]
The polymer particles (Bl) preferably have a weightaverage
molecular weight of 1,000,000 or more and 1,370,000
or less, more preferably 1,000,000 or more and 1,350,000 or
15 less.
[0065]
The polymer particles (B2) preferably have a weightaverage
molecular weight of 780,000 or more and less than
1,000,000, more preferably 800,000 or more and less than
20 1,000,000.
[0066]
The polymer particles (B3) preferably have a weightaverage
molecular weight of 250,000 or more and 940,000 or
less, more preferably 250,000 or more and 930,000 or less.
[0067]
The polymer particles (B4) preferably have a weightaverage
molecular weight of 350,000 or more and 690,000 or
less, more preferably 350,000 or more and 680,000 or less.
[0068]
When the weight-average molecular weight of the polymer
particles is within such a range, the dispersibility of the
polymer particles (B) tends to be more excellent in mixing of
the polymer particles (B) with the monomer (A) and the
polymerization initiator composition (C) in a container; in
addition, the extrusion properties of the resultant mixture
from the container tend to be excellent; furthermore, the
application properties of the mixture tend to be more
excellent and the mixture is applied without spreading to
outside of the affected part. When the weight-average
molecular weight of the polymer particles (B) is excessively
low, for example, less than 250,000, the application
properties tend to be degraded.
[0069]
The polymer particles (Bl) preferably have a volume mean
particle diameter of 1.5 p or more and 75 p or less, more
preferably 2.0 pn or more and 65 pm or less, still more
preferably 2.0 p or more and 50 p or less, particularly
preferably 2.0 p or more and 40 p or less.
The polymer particles (B2) preferably have a volume mean
particle diameter of more than 30 pm and 80 p or less, more
preferably more than 30 p and 70 pm or less, still more
5 preferably more than 30 p and 60 pn or less, particularly
preferably 30 p or more and 50 p or less.
[0071]
The polymer particles (B3) preferably have a volume mean
particle diameter of 1.5 p or more and 30 p or less, more
10 preferably 2.0 p or more and 30 p or less.
[0072]
The polymer particles (B4) preferably have a volume mean
particle diameter of more than 30 p and 85 pm or less, more
preferably more than 30 p and 80 pn or less, still more
15 preferably more than 30 p and 70 p or less, particularly
preferably 30 p or more and 50 p or less.
[0073]
When the volume mean.particle diameter of the polymer
particles is within such a range, the dispersibility of the
20 polymer particles (B) tends to be more excellent in mixing of
the polymer particles (B) with the monomer (A) and the
polymerization initiator composition (C) in a container; in
addition, the extrusion properties of the resultant mixture
from the container tend to be excellent; furthermore, the
application properties of the mixture tend to be more
excellent and the mixture is applied without spreading to
outside of the affected part. When the volume mean particle
diameter of the polymer particles (B) is excessively small,
5 for example, less than 1 p, the dispersibility tends to be
degraded.
[0074]
The specific surface area of the polymer particles (Bl)
is generally 0.056 m2/g or more and 10 m2/g or less,
10 preferably 0.067 m2/g or more and 6.7 m2/g or less, more
preferably 0.077 m2/g or more and 5.0 m2/g or less, still more
preferably 0.10 m2/g or more and 5.0 m2/g or less.
[0075]
The specific surface area of the polymer particles (B2)
15 is generally 0.056 m2/g or more and 0.17 m2/g or less,
preferably 0.063 m2/g or more and 0.17 m2/g or less, more
preferably 0.070 m2/g or more and 0.17 m2/g or less, still
more preferably 0.083 m2/g or more and 0.17 m2/g or less.
[0076]
20 The specific surface area of the polymer particles (B3)
is generally 0.17 m2/g or more and 10 m2/g or less, preferably
0.17 m2/g or more and 6.7 m2/g or less, more preferably 0.17
m2/g or more and 5.0 m2/g or less.
[0077]
The specific surface area of the polymer particles (B4)
is generally 0.056 m2/g or more and 0.17 m2/g or less,
preferably 0.059 m2/g or more and 0.17 m2/g or less, more
preferably 0.063 m2/g or more and 0.17 m2/g or less, still
5 more preferably 0.070 m2/g or more and 0.17 m2/g or less.
[0078]
The specific surface area of the polymer particles (B5)
is generally 0.17 m2/g.
[0079]
10 When the specific surface area of the polymer particles
is within such a range, the dispersibility of the polymer
particles (B) tends to be more excellent in mixing of the
polymer particles (B) with the monomer (A) and the
polymerization initiator composition (C) in a container; in
15 addition, the extrusion properties of the resultant mixture
from the container tend to be excellent; furthermore, the
application properties of the mixture tend to be more
excellent and the mixture is applied without spreading to
outside of the affected part. The specific surface area is a
20 value determined by nitrogen gas adsorption (BET method) at
I the liquid nitrogen temperature (77 K) .
[0080]
Examples of polymers forming the polymer particles (B)
include methacrylate polymers, acrylate polymers, styrenebased
elastomers, vinyl chloride-based elastomers, olefinbased
elastomers, polyester-based elastomers, polyamide-based
elastomers, urethane-based elastomers, an ethylene/vinyl
acetate copolymer and a silicon polymer. These polymers can
5 be used singly or in combination of two or more kinds.
[0081]
Of these polymers, preferable are methacrylate polymers
and acrylate polymers from the viewpoint of homogeneity in
the mixing process. The methacrylate polymers and the
10 acrylate polymers are sometimes generically referred to as
"(meth)acrylate polymers" hereinafter.
[0082]
Examples of the (meth)acrylate polymers include:
uncrosslinked polymers, such as polymethyl
15 (meth) acrylate, polyethyl (meth) acrylate, a methyl
(meth)acrylate/ethyl (meth)acrylate copolymer, a methyl
(meth)acrylate/butyl (meth)acrylate copolymer and a methyl
(meth)acrylate/styrene copolymer: and
crosslinked polymers, such as a methyl
20 (meth) acrylate/ethylene glycol di (meth) acrylate copolymer, a
methyl (meth)acrylate/triethylene glycol di(meth)acrylate
copolymer and a copolymer of methyl (meth)acrylate and a
butadiene-based monomer.
[0083]
When the rubbers, such as natural rubbers and synthetic
rubbers, and the elastomers, such as thermoplastic elastomers,
among the above polymers are used by mixing them with the
(meth)acrylate polymer, they function as flexibilizers and
5 can enhance flexibility of the composition. Examples of the
synthetic rubbers include EPT (ethylene/propylene/terpolymer) .
Examples of the thermoplastic elastomers include styrenebased
elastomers, vinyl chloride-based elastomers, olefinbased
elastomers, polyester-based elastomers, polyamide-based
10 elastomers, urethane-based elastomers, an ethylene/vinyl
acetate copolymer and a silicon polymer.
[0084]
The molecular weight of the above elastomer is usually
in the range of 1,000 to 1,000,000, preferably 2,000 to
15 500,000. The glass transition point (Tg) of the elastomer is
I
I usually not higher than 20°c, preferably not higher than OOc.
[0085]
In the (meth)acrylate polymers, organic or inorganic
composites in which metal oxides or metal salts are coated
20 with above-mentioned uncrosslinked polymers or crosslinked
polymers are further included.
[0086]
The above molecular weight is a molecular weight in
terms of standard polymethyl methacrylate, as determined by
gel permeation chromatography (GPC).
[0087]
The amount of the polymer particles (B) is preferably in
the range of 17.5 to 72.5 parts by weight, more preferably
5 22.5 to 72.5 parts by weight, still more preferably 32.5 to
67.5 parts by weight, based on 100 parts by weight of the
total amount of the monomer (A), the polymer particles (B)
and the polymerization initiator composition (C).
[0088]
If the amount of the polymer particles (B) is less than
the lower limit of the above range, progress of
polymerization becomes difficult, adhesion effect is poor,
and besides, there is a possibility that the mixture runs out
of the desired area to obstruct the treatment. If the amount
15 of the polymer particles (B) exceeds the upper limit of the
above range, mixing with the monomer (A) becomes difficult.
Further, because of rapid increase of viscosity, extrusion of
the mixture from the container tends to become difficult.
Furthermore, polymerization proceeds to immediately form a
20 polymerization cured product in some cases, so that the
composition tends to be not excellent in operability as an
adhesive or a wound dressing.
The adhesive composition for soft tissues, the adhesive
composition for wound dressing or the wound dressing
composition of the present invention is characterized by
using the later-described organoboron compound (cl) as the
polymerization initiator composition (C) contained, and when
5 the organoboron compound is added to a composition containing
a monomer, polymerization reaction begins slowly in a
relatively early stage and proceeds. This greatly differs
from a case of using a peroxide as a polymerization initiator
where a relatively long time is required for the beginning of
10 polymerization even if the polymerization initiator is added,
and if the polymerization reaction once begins, the reaction
proceeds rapidly and is completed in a relatively short time.
In order to prepare a composition that is preferably used for
wounds, soft tissues, etc., therefore, it is important to use
15 such polymer particles (B) of the present invention in such
an amount as described above based on the monomer (A). By
the use of such polymer particles (B), not only can
workability be ensured over a long time but also fluidity and
application properties that are preferable in use for wounds,
20 soft tissues, etc. can be ensured.
[0090]
The polymerization initiator composition (C) contained
in the adhesive composition for soft tissues, the adhesive
composition for wound dressing or the wound dressing
SF-2524
0
composition of the present invention contains an oragnoboron
compound (cl) as an essential component, and can contain an
aprotic solvent (c2) and an alcohol (c3), when needed. Since
the polymerization initiator composition (C) containing the
5 organoboron compound (cl) is contained in the composition of
the present invention, a residue of the monomer (A) tends to
be smaller when the whole composition is cured after
application of the composition to a wound, a soft tissue or
the like, as compared with a composition using a peroxide as
10 a polymerization initiator. Further, a part of it penetrates
into the epithelium and begins to undergo polymerization.
Hence, the composition of the present invention is favorably
used for organisms.
[0091]
15 Examples of the organoboron compounds (cl) include
trialkylboron, alkoxyalkylboron, dialkylborane and partially
oxidized trialkylboron.
[0092]
Examples of the trialkylborons include trialkylborons
20 having an alkyl group of 2 to 8 carbon atoms, such as
triethylboron, tripropylboron, triisopropylboron,
tributylboron, tri-sec-butylboron, triisobutylboron,
tripentylboron, trihexylboron, triheptylboron, trioctylboron,
tricyclopentylboron and tricyclohexylboron. The alkyl group
may be any of a straight-chain alkyl group, a branched alkyl
group and a cycloalkyl group, and three alkyl groups
contained in the trialkylboron may be the same or different.
[0093]
5 The alkoxyalkylboron is, for example,
monoalkoxydialkylboron or dialkoxymonoalkylboron.
Specifically, the alkoxyalkylboron is, for example,
monoalkoxydialkylboron such as butoxybutylboron. The alkyl
group of the alkoxyalkylboron may be the same as or different
10 from the alkyl part of the alkoxy group.
[0094]
Examples of the dialkylboranes include
dicyclohexylborane and diisoamylborane. Two alkyl groups of
the dialkylborane may be the same or different. Two alkyl
15 groups contained in the dialkylborane may be bonded to form a
monocyclic structure or a bicyclo structure. Examples of
such compounds include 9-borabicyclo[3.3.1]nonane.
[0095]
The partially oxidized trialkylboron is a partially
20 oxidized product of the above trialkylboron. As the
partially oxidized trialkylboron, partially oxidized
tributylboron is preferable. As the partially oxidized
trialkylboron, partially oxidized trialkylboron obtained by
the addition of oxygen in an amount of preferably 0.3 to 0.9
mol, more preferably 0.4 to 0.6 mol, based on 1 mol of the
trialkylboron can be used.
[0096]
Of the above organoboron compounds, tributylboron or
5 partially oxidized tributylboron is preferable, and partially
oxidized tributylboron is more preferable. When
tributylboron or partially oxidized tributylboron is used as
the organoboron compound (cl), not only is the operability of
the composition improved but also the composition tends to
10 have proper reactivity to organisms having moisture content.
When tributylboron or partially oxidized tributylboron is
used as the organoboron compound (cl), further, the reaction
is initiated and proceeds even in a place of high moisture
content such as an organism, so that the monomer rarely
15 remains on the interface between the adhesive or the wound
dressing and an organism. Hence, the injurious properties to
the organism are extremely little. Such organoboron
compounds (cl) can be used singly or in combination of two or
more kinds.
20 [0097]
In the polymerization initiator composition (C), an
aprotic solvent (c2) may be contained. Since the aprotic
solvent is contained in the polymerization initiator
composition (C) as above and the organoboron compound is
diluted, exothermic properties of the organoboron compound
(cl) having ignition properties become gentler to suppress
ignition properties, and hence, handling of the composition
during transportation, storage and mixing is facilitated. In
5 the case where an extremely large amount of an adhesive or a
wound dressing is used, rapid generation of heat can be
inhibited because of proper lowering of the exothermic
properties, and consequently, damage of an organism that is
in contact with the adhesive or the wound dressing of the
10 present invention tends to be decreased. The boiling point
of the aprotic solvent (c2) at 1 atm is usually in the range
of 3 0 " ~to 150°c, preferably 50°c to 120"~.I f the boiling
point is lower than the lower limit of the above range, the
aprotic solvent is evaporated or scattered from the
15 polymerization initiator composition during transportation or
storage, and the ignition property suppressing effect of the
organoboron compound (cl) tends to be lowered. If the
boiling point exceeds the upper limit of the above range, a
residue of the aprotic solvent in a cured product formed from
20 the adhesive composition or the wound dressing composition of
the present invention is increased, and consequently, the
adhesion performance of the composition tends to be lowered.
[0098]
As the aprotic solvent (c2), a solvent that is
unreactive to the organoboron compound (cl) and is capable of
forming a homogeneous solution is preferable.
[0099]
Examples of the aprotic solvents (c2) include:
5 hydrocarbons, such as pentane, hexane, cyclohexane,
heptane, benzene and toluene;
halogenated hydrocarbons, such as fluorobenzene, 1,ldichloroethane,
1,2-dichloroethane and so-called flons;
ethers, such as diethyl ether, diisopropyl ether,
10 ethylene glycol dimethyl ether and tetrahydrofuran;
ketones, such as acetone, methyl ethyl ketone and
diethyl ketone; and
esters, such as methyl acetate, ethyl acetate and
isopropyl acetate.
15 [OlOO]
Of these, saturated aliphatic hydrocarbons, such as
pentane, hexane and heptane, ethers and esters are preferable,
and hexane, diisopropyl ether and ethyl acetate are more
preferable.
20 [OlOl]
These aprotic solvents (c2) can be used singly or in
combination of two or more kinds.
[OlOZ]
The content of the aprotic solvent (c2) in the
polymerization initiator composition (C) is preferably in the
range of 30 to 80 parts by weight based on 100 parts by
weight of the organoboron compound (cl).
[0103]
If the content of the aprotic solvent (c2) is less than
the lower limit of the above range, satisfactory dilution
effect is not obtained, and the effect to suppress generation
of heat or ignition tends to be insufficient. On the other
hand, if the content of the aprotic solvent (c2) exceeds the
10 upper limit of the above range, polymerization initiation
ability of the polymerization initiator composition (C) tends
to become lower than needed.
[0104]
In the polymerization initiator composition (C), an
15 alcohol (c3) may be further contained in addition to the
aprotic solvent (c2). By adding a small amount of the
alcohol (c3) to the polymerization initiator composition (C),
the reaction by the oragnoboron compound (cl) is made still
gentler without lowering the polymerization activity, and
20 even if the composition is brought into contact with paper or
the like in air, burning or ignition tends to be suppressed.
[ 0 10 5 ]
Examples of the alcohols (c3) include methanol, ethanol,
n-propanol and its isomers, n-butanol and its isomers, npentanol
and its isomers, n-hexanol and its isomers, and nheptanol
and its isomers.
[0106]
Of these alcohols (c3), alcohols of 4 or less carbon
5 atoms, namely, methanol, ethanol, n-propanol and its isomers,
and n-butanol and its isomers are preferable, and ethanol and
n-propanol are more preferable.
[0107]
These alcohols (c3) can be used singly or in combination
10 of two or more kinds.
[0108]
The content of the alcohol (c3) in the polymerization
initiator composition (C) is preferably in the range of 0.2
to 5 parts by weight, more preferably 0.3 to 4.5 parts by
15 weight, still more preferably 0.5 to 4 parts by weight, based
on 100 parts by weight of the organoboron compound (cl).
[0109]
If the content of the alcohol (c3) is less than the
lower limit of the above range, satisfactory dilution effect
20 is not obtained, and the effect to suppress generation of
heat or ignition tends to be insufficient. On the other hand,
if the content of the alcohol (c3) exceeds the upper limit of
the above range, polymerization initiation ability of the
1 polymerization initiator composition (C) tends to become
lower than needed.
[OllO]
When the alcohol (c3) and the aprotic solvent (c2) are
used in combination, the content of the aprotic solvent (c2)
5 in the polymerization initiator composition (C) is preferably
in the range of 5 to 40 parts by weight, more preferably 10
to 30 parts by weight, still more preferably 10 to 25 parts
by weight, based on 100 parts by weight of the organoboron
compound (cl) .
10 [Olll]
If the content of the aprotic solvent (c2) is less than
the lower limit of the above range based on 100 parts by
weight of the organoboron compound (cl), the effect to
suppress generation of heat or ignition tends to be
15 insufficient. On the other hand, if the content of the
aprotic solvent (c2) exceeds the upper limit of the above
range based on 100 parts by weight of the organoboron
compound (cl), polymerization initiation ability of the
polymerization initiator composition (C) tends to be lowered.
20 [0112]
The amount of the polymerization initiator composition
( C ) is preferably in the range of 1.7 to 4.9 parts by weight,
more preferably 1.7 to 4.6 parts by weight, still more
preferably 2.0 to 4.0 parts by weight, based on 100 parts by
weight of the total amount of the monomer (A), the polymer
particles (B) and the polymerization initiator composition
(C).
[0113]
If the amount of the polymerization initiator
composition (C) is less than the lower limit of the above
range, progress of polymerization is difficult, and the
adhesion effect tends to become poor. If the amount of the
polymerization initiator composition (C) exceeds the upper
10 limit of the above range, there is a possibility of lowering
viscosity because of dilution or a possibility of exerting
evil influence on safety. Moreover, it is presumed that
rapid polymerization proceeds to form a polymerization cured
product immediately, and therefore, the composition tends to
15 be not excellent in operability as an adhesive or a wound
dressing.
[0114]
In the adhesive composition or the wound dressing
composition, other components may be further contained when
20 needed, as long as they do not exert evil influence on the
performance of the composition.
[ 0 11 5 ]
As one of the other components, a polymerization
inhibitor (D) can be mentioned. Examples of the

inhibitor (D) in an amount of 10 to 5000 ppm based on the
monomer (A). By preparing such a composition, for example,
when an adhesive is applied to an adherend, such as the
affected part (affected part that is not dried because of
5 exudate from the incised part) in the surgical operation, a
wound or a soft tissue, the composition becomes more
excellent in ensuring application properties and a proper
curing time and can be more stably handled as an adhesive or
a dressing than before. Moreover, the composition is
10 excellent in workability.
[0120]
Although the amount of the polymerization inhibitor (D)
is as described above, the polymerization inhibitor (D) is
more preferably added in an amount of 50 to 1000 ppm, still
15 more preferably 50 to 500 ppm, based on the monomer (A). By
preparing such a composition, for example, the composition
can be not only handled stably during application but also
tends to be cured efficiently after application. If the
content of the polymerization inhibitor (D) is less than the
20 lower limit of the above range, curing takes place
immediately after mixing of the monomer (A), the polymer (B)
and the polymerization initiator composition (C), and hence,
application tends to become difficult. On the other hand, if
the content of the polymerization inhibitor (D) exceeds the
methoxycarbonylethyl)phenyl)-5-chlorobenzotriazoleI 2-(3'-
tert-butyl-2'-hydroxy-5'-(2-
methoxycarbonylethyl)phenyl)benzotriazole, 2-(3'-tert-butyl-
2'-hydroxy-5'-(2-octyloxycarbonylethyl)phenyl)benzotriazoleI
2- (3 ' -tert-butyl-5' - [2- (2-ethylhexyloxy)c arbonylethyl]- 2 -
hydroxyphenyl)benzotriazole, 2-(3'-dodecyl-2'-hydroxy-5'-
methylphenyl)benzotriazole, a mixture of 2-(3'-tert-butyl-2'-
hydroxy-5'-(2-isooctyloxycarbonylethyl)phenyl)benzotriazole
and 2,2'-methylene-bis [4- (1, 1, 3, 3-tetramethylbutyl) -6-
benzotriazol-2-ylphenol], an ester interchange reaction
product of 2-[3'-tert-butyl-5'-(2-methoxycarbonylethy1)-2'-
hydroxyphenyl]benzotriazole with polyethylene glycol 300, and
[R-CH2CH2-COOCH2]3 ]2 - (wherein R is 3 ' -tert-butyl-4 ' -hydroxy-
15 benzophenone compounds, such as 2,4-
dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2-
hydroxy-4-octoxybenzophenone, 2-hydroxy-4-
decyloxybenzophenone, 2-hydroxy-4-dodecyloxybenzophenone, 2-
hydroxy-4-benzyloxybenzophenone, 2,2',4,4'-
20 tetrahydroxybenzophenone, and 2,2'-dihydroxy-4,4'-
dimethoxybenzophenone;
4-tert-butylphenyl salicylate, phenyl salicylate,
octylphenyl salicylate, dibenzoylresorcinol, bis(4-tertbutylbenzoyl)
resorcinol, benzoylresorcinol, 2,4-di-tertbutylphenyl
3,5-di-tert-butyl-4-hydroxybenzoate, hexadecyl
3,5-di-tert-butyl-4-hydroxybenzoate, octadecyl 3,5-di-tertand
phenyl 3,5-di-tert-butyl-4-hydroxybenzoate;
5 hindered amine compounds, such as bis(2,2,6,6-
tetramethylpiperidyl) sebacate, bis (2,2,6,6-
tetramethylpiperidyl) succinate, bis (1,2,2,6,6-
pentamethylpiperidyl) sebacate, bis (1,2,2,6,6-
pentamethylpiperidyl) n-butyl-3,5-di-tert-butyl-4-
10 hydroxybenzylmalonate, a condensation product of 1-
hydroxyethyl-2,2,6,6-tetramethyl-4-hydroxypiperidine and
succinic acid, a condensation product of N,N1-bis(2,2,6,6-
tetramethyl-4-piperidy1)hexamethylenediamine and 4-tert-
15 tetramethyl-4-piperidyl) nitrilotriacetate, tetrakis (2,2,6,6-
tetramethyl-4-piperidyl) -1 , 2 , 3 , 4-butanetetraoate, 1 , 1' - (1 2-
ethanediyl)bis(3,3,5,5-tetramethylpiperazinone), 4-benzoyl-
2,2,6,6-tetramethylpiperidine, 4-stearyloxy-2,2,6,6-
tetramethylpiperidine, bis(l,2,2,6,6-pentamethyl-4-
20 piperidyl)-2-n-butyl-2-(2-hydroxy-3,5-di-tertbutylbenzyl)
malonate, 3-n-octyl-7,7,9,9-tetramethyl-1,3,8-
triazaspiro [4.5] decane-2 , 4-dione, bis (1-octyloxy-2,2, 6, 6-
tetramethylpiperidyl)sebacate, bis(1-octyloxy-2,2,6,6-
tetramethylpiperidyl)succinate, a condensation product of
and 4-morpholino-2,6-dichloro-1,3,5-triazine a condensation
product of 2-ch1oro-4,6-di-(4-n-buty1amino-2,2,6,6-
tetramethylpiperidyl)-1,3,5-triazine and 1,2-bis(3-
5 aminopropylamino)ethane, a condensation product of 2-chloro-
4,6-di- (4-n-butylamino-1, 2, 2 , 6, 6-pentamethylpiperidyl) -1, 3, 5-
triazine and 1,2-bis(3-aminopropylamino)ethane, 8-acetyl-3-
dodecy1-7,7,9,9-tetramethy1-1,3,8-triazaspiro[4.5]decane-2,4-
dione, 3-dodecyl-1-(2,2,6,6-tetramethyl-4-
10 piperidy1)pyrrolidine-2,5-dione, and 3-dodecyl-1-(1,2,2,6,6-
pentamethyl-4-piperidy1)pyrrolidine-22-dione;
oxalamide compounds, such as 4,4'-dioctyloxyoxanilide,
diethoxyoxanilide, 2,2'-dimethoxyoxanilide, 2,4'-
15 dimethoxyoxanilide, 4,4'-dimethoxyoxanilide, 2,2'-dioctyloxybutyloxanilide,
2-ethoxy-2'-ethyloxanilide, N,N1-bis(3-
dimethylaminopropyl)oxalamide, 2-ethoxy-5-tert-butyl-2'-
ethyloxanilide, and a mixture of 2-ethoxy-5-tert-butyl-2'-
20 ethyloxanilide and 2-ethoxy-2'-ethyl-5,4'-di-tertbutyloxanilide;
2- (2-hydroxyphenyl) -1 , 3, 5-triazine compounds, such as
2,4,6-tris (2-hydroxy-4-octyloxyphenyl)- 13 5 - t r a n e 2- (2-
hydroxy-4-octy1oxypheny1)-4,6-bis(2,4-dimethy1pheny1)-1,3,5-
triazine, 2- (2,4-dihydroxyphenyl)- 4 ,6 -bis (2Jdimethylphenyl)
-1, 3, 5-triazine, 2,4-bis (2-hydroxy-4-
5 triazine, 2-(2-hydroxy-4-dodecyloxyphenyl)-4,6-bis(2,4-
triazine, 2-[2-hydroxy-4-(2-hydroxy-3-
octyloxypropyloxy) phenyl] -4,6-bis (2,4-dimethylphenyl) -1 , 3 , 5-
10 triazine, and 2-[4-dodecyl/tridecyloxy-(2-hydroxypropy1)oxy-
2-hydroxyphenyl]- 4,6-bis (2,4-dimethylphenyl)- 1,3 ,5 -triazine;
and
phosphite compounds or phosphonite compounds, such as
triphenyl phosphite, diphenylalkyl phosphite, phenyldialkyl
15 phosphite, tris(nonylphenylphosphite), trilauryl phosphite,
trioctadecyl phosphite, distearyl pentaerythrytyl diphosphite,
tris(2,4-di-tert-butylphenyl)phosphite, diisodecyl
pentaerythrityl diphosphite, bis(2,4-di-tertbutylpheny1)
pentaerythrityl diphosphite, bis(2,6-di-tert-
20 butyl-4-methylpheny1)pentaerythrityl diphosphite,
bisisodecyloxypentaerythrityl diphosphite, bis(2,4-di-tertbutyl-
6-methylpheny1)pentaerythrityl diphosphite, bis(2,4,6-
tri-tert-butylpheny1)pentaerythrityl diphosphite, tristearyl
sorbityl triphosphite, tetrakis(2,4-di-tert-butylpheny1)-
4,4'-biphenylene diphosphonite, 6-isoocty1oxy-2,4,8,10-tetratert-
butyl-12H-dibenzo[d.g]-1,3,2-dioxaphosphocine, 6-fluoro-
2,4,8,10-tetra-tert-butyl-12-methyldibenzo [d, g] -1, 3, 2-
dioxaphosphocine, bis(2,4-di-tert-butyl-6-methylpheny1)methyl
5 phosphite, and bis(2,4-di-tert-butyl-6-methylpheny1)ethyl
phosphite.
[0122]
As the ultraviolet light absorber, a benzotriazole
compound is preferable.
10 [0123]
When the ultraviolet light absorber is added, the amount
thereof is preferably in the range of 10 to 1,000 ppm, more
preferably 100 to 800 ppm, based on the monomer (A). By
adding the ultraviolet light absorber as above, coloring of a
15 liquid containing a monomer is suppressed, and storage
stability of the monomer itself tends to be enhanced.
[0124]
As one of the other components, a plasticizer can be
further mentioned.
20 [0125]
Examples of the plasticizers include hydroxycarboxylic
acid esters, such as citrate esters, isocitrate esters,
tartrate esters, malate esters, lactate esters, glycerate
esters and glycolate esters; trimethyl trimellitate esters,
diethylene glycol dibenzoate esters, diethyl malonate esters,
triethyl o-acetylcitrate esters, benzyl butyl phthalate
esters, dipropylene glycol dibenzoate esters, diethyl adipate
esters, tributyl o-acetylcitrate esters, dimethyl sebacate
5 esters, and alkylene glycol diesters.
[0126]
Although the amount of the plasticizer is properly
selected according to the type of the material, the
plasticizer is used so that it may be usually contained in an
10 amount of 0 to 30% by weight, preferably 0 to 20% by weight,
more preferably 0 to 10% by weight, in the whole adhesive
composition or wound dressing composition.
[0127]
As one of the other components, a preservative can be
15 further mentioned.
[0128]
Examples of the preservatives include:
methylparaben, methylparaben sodium, ethylparaben,
propylparaben, propylparaben sodium, butylparaben;
20 cresol, chlorocresol;
resorcinol, 4-n-hexylresorcinol, 3a14,7,7a-tetrahydro-2-
( (trichloromethyl) thio) -lH-isoindole-1,3 (2H) dione;
benzalkonium chloride, benzalkonium sodium chloride,
benzethonium chloride;
benzoic acid, benzyl alcohol, cetylpyridinium chloride,
chlorobutanol, dehydroacetic acid, o-phenylphenol, phenol,
phenylethyl alcohol, potassium benzoate, potassium sorbate,
sodium benzoate, sodium dehydroacetate, sodium propionate,
5 sorbic acid, thimerosal, thymol;
phenylmercuric compounds, such as phenylmercuric borate,
phenylmercuric nitrate and phenylmercuric acetate; and
formaldehyde.
[0129]
10 As examples of the other components, there can be
further mentioned anti-infectious agents, antibiotics,
antibacterial agents, anti-virus agents, analgesics,
compositions of analgesics, anorectic drugs, antihelmintic
drugs, antiarthritic agents, antiasthmatic drugs,
15 anticonvulsants, antidepressants, antidiuretics,
antidiarrheal agents, antihistamine drugs, anti-inflammatory
drugs, antimigraine drugs, antiemetic agents, antineoplastic
drugs, antiparkinsonian agents, antipruritic drugs,
antipsychotics, antipyretic drugs, antispasmodic drugs,
20 anticholinergic agents, sympathomimetic agents,
cardiovascular drugs, antiarrhythmic drugs, antihypertensive
drugs, diuretics, vasodilators, immunosuppressant drugs,
muscle-relaxant drugs, parasympatholytic drugs, stimulants,
sedative drugs, tranquilizers, cholinergic agents,
chemotherapeutic drugs, radio pharmaceuticals, bone inductive
drugs, heparin neutralizer agents of static bladder,
procoagulants, hemostatic agents, xanthine derivatives,
hormones, proteins of natural origin or proteins synthesized
5 by genetic engineering, polysaccharides, glycoproteins,
lipoproteins, oligonucleotides, antibody, antigen,
vasopressin, vasopressin analogs, epinephrine, selectin, clot
promoting toxicants, plasminogen activating factor inhibitors,
platelet activators, and synthetic peptides having hemostatic
10 action. Since these components are contained, the
composition of the present invention can be used for the drug
delivery system or the purpose of regenerative medicine.
[0130]
In the adhesive composition or the wound dressing
15 composition, angiogeneric factor, basic fibloblast growth
factor, epidermal growth factor, etc. may be contained as the
above proteins for the purpose of accelerating tissue
reparation.
[0131]
20 Examples of the antibacterial agents include:
element iodine, solid polyvinylpyrrolidone iodine,
polyvinylpyrrolidone iodine;
phenol compounds, such as tribromophenol,
trichlorophenol, tetrachlorophenol, nitrophenol, 3-methyl-4-
chlorophenol, 3,5-dimethyl-4-chlorophenol, phenoxyethanol,
dichlorophene, o-phenylphenol, m-phenylphenol, p-phenylphenol,
2-benzyl-4-chlorophenol, 2,4-dichloro-3,5-dimethylphenol, 4-
chlorothymol, chlorophene, triclosan, fenticlor, phenol, 2-
5 methylphenol, 3-methylphenol, 4-methylphenol, 4-ethylphenol,
2,4-dimethylphenol, 2,5-dimethylphenol, 3,4-dimethylphenol,
2,6-dimethylphenol, 4-n-proylphenol, 4-n-butylphenol, 4-naminophenol,
4-tert-amylphenol, 4-n-hexylphenol, 4-nheptylphenol,
monoalkylhalophenol, polyalkylhalophenol,
10 aromatic halophenol, and ammonium salts, alkali metal salts
and alkaline earth metal salts of these substances;
silver nitrate, hexachlorophene, merbromin,
tetracycline.HC1, tetracycline hydrate and erythromycin.
[0132]
15 As examples of the other components, there can be
further mentioned perfumes, such as orange oil, grapefruit
oil, lemon oil, lime oil, clove oil, wintergreen oil,
peppermint oil, peppermint spirit, banana distillate,
cucumber distillate, honey distillate, rose water, menthol,
20 anethole, alkyl salicylate, benzaldehyde, monosodium
glutamate, ethylvanillin, thymol and vanillin.
[0133]
Furthermore, an inorganic filler, an organic filler, an
organic composite filler, a filler colorant, etc. may be
contained as the other components.
LO1341
Examples of the inorganic fillers include:
metal oxide powders, such as zirconium oxide, bismuth
5 oxide, titanium oxide, zinc oxide and aluminum oxide
particles;
metal salt powders, such as bismuth carbonate, zirconium
phosphate and barium sulfate;
glass fillers, such as silica glass, aluminum-containing
10 glass, barium-containing glass, strontium-containing glass
and zirconium silicate glass;
fillers having silver sustained-release property; and
fillers having fluorine sustained-release property.
[0135]
15 From the viewpoint of formation of strong bonding
between an inorganic filler and the monomer (A) after curing,
it is preferable to use an inorganic filler having been
subjected to surface treatment such as silane treatment or
polymer coating.
20 [0136]
These inorganic fillers can be used singly or in
combination of two or more kinds.
[0137]
As examples of the other components, X-ray contrast
media, such as barium sulfate and zirconium oxide, can be
further mentioned. In the present invention, zirconium oxide
is preferable as the X-ray contrast medium.
LO1381
5 The adhesive composition for soft tissues, the adhesive
composition for wound dressing or the wound dressing
composition of the present invention preferably has a
viscosity of 0.4 to 75,000 cp within 30 seconds after mixing
of the components (A), (B) and (C) and the components to be
10 contained when needed (from mixing until when 30 seconds have
elapsed).
[0139]
When the viscosity is in the above range, the
composition is easily applied as an adhesive or a wound
15 dressing.
[0140]
From the viewpoints of operability and fluidity, the
viscosity is more preferably in the range of 0.4 to 10,000 cp,
still more preferably 1 to 10,000 cp.
20 [0141]
The adhesive composition or the wound dressing
composition of the present invention preferably has a
viscosity of 10 to 1,000,000 cp, more preferably 20 to
1,000,000 cp, still more preferably 30 to 800,000 cp, at 60
seconds after mixing of the components (A), (B) and (C) and
the components to be contained when needed.
101421
When the viscosity is in the above range, the
5 composition can be easily extruded from a container as an
adhesive or a wound dressing, and has excellent operability
such as ease of application.
[0143]
The composition of the present invention is excellent in
10 operability as an adhesive or a wound dressing, namely,
application properties such as fluidity. Even if the
composition of the present invention is compared with a
composition using a peroxide as an initiator component, the
operator tends to be able to ensure a longer time than the
15 time necessary for the mixing operation, and also from this
viewpoint, the composition of the present invention is
excellent in operability.
[0144]
A film, which is obtained from the adhesive composition
20 or the wound dressing composition of the present invention,
is given 24 hours after the preparation of the composition
and has a thickness of not less than 1 pn (preferably not
more than 1 cm), a length of not less than 25 mrn and a width
of not less than 2 mm, preferably has a flexural modulus, as
measured under the conditions of a test rate of 2 mm/min, of
not more than 750 MPa, more preferably not more than 740 MPa,
still more preferably not more than 730 MPa. A film, which
is obtained from the composition, is given 24 hours after the
5 preparation of the composition and has a thickness of not
less than 1 p (preferably not more than 1 cm), a length of
not less than 25 mrn and a width of not less than 2 mm, may
preferably have a flexural modulus, as measured under the
conditions of a test rate of 2 mm/min, of not more than 750
10 MPa, more preferably not more than 600 MPa, still more
preferably not more than 550 MPa.
[0145]
The flexural modulus of the above film may be preferably
not less than 100 MPa, more preferably not less than 150 MPa,
15 still more preferably not less than 200 MPa.
[0146]
A film, which is obtained from the adhesive composition
or the wound dressing composition of the present invention,
is given 24 hours after the preparation of the composition
20 and has a thickness of not less than 1 p (preferably not
more than 1 cm), a length of not less than 25 mm and a width
of not less than 2 rnrn, preferably has a tensile elongation,
as measured under the conditions of a test rate of 1 mm/min,
of not less than 5%, more preferably not less than 15%, still
more preferably not less than 25%.
[0147]
The tensile elongation may be preferably not less than
5%, more preferably not less than 7%, still more preferably
5 not less than 9%. The tensile elongation may be preferably
not less than 30%, more preferably not less than 40%, still
more preferably not less than 50%.
[0148]
A cured product obtained from the adhesive composition
10 or the wound dressing composition of the present invention
provides a coating film having properties excellent for soft
tissues or the skin and also excellent in adhesion to the
skin on the bending portions such as a joint.
[0149]
15 In the present invention, the monomer (A), the polymer
particles (B), the polymerization initiator composition (C)
and the components to be contained when needed are previously
mixed to prepare an adhesive composition or a wound dressing
composition, and the composition can be used by applying it
20 to a wound (affected part in the surgical operation, wound to
be dressed), a soft tissue or the like.
[0150]
When these components are mixed, the order of mixing is
not specifically restricted, but it is preferable that the
monomer (A) is first mixed with the polymerization initiator
composition (C) and subsequently mixed with the polymer
particles (B), from the viewpoint that the components can be
homogeneously and stably mixed.
5 [0151]
When the adhesive composition or the wound dressing
composition of the present invention contains the
polymerization inhibitor (D), it is preferable that a mixture
of the monomer (A) and the polymerization inhibitor (D) is
10 first mixed with the polymerization initiator composition (C)
and subsequently mixed with the polymer particles (B), from
the viewpoint that the resultant composition is more
excellent in stability.
[0152]
15 Prior to or during curing of the adhesive composition or
the wound dressing composition of the present invention, the
composition may be irradiated with electromagnetic waves,
such as visible light, ionizing radiation (e.g., y-rays) or
i electron rays, to perform sterilization. Irradiation with
20 visible light is sometimes desirable because the visible
light does not greatly change the curing conditions.
Sterilization may be carried out by treatment with gas such
as ethylene oxide (EO) or hydrogen peroxide, dry heat, steam,
filtration, liquid, autoclave sterilization, or the like.
Prior to application of the adhesive composition or the
wound dressing composition of the present invention to a
wound, a soft tissue or the like, the surface of the wound,
5 the soft tissue or the like may be disinfected with a
disinfectant such as alcohol.
[0154]
Prior to application of the adhesive composition or the
wound dressing composition of the present invention to a
10 wound, a soft tissue or the like, pretreatment may be further
carried out for the purpose of improving adhesion properties.
A treatment liquid for the pretreatment is, for example, an
aqueous solution containing 1 to 15% by weight of citric acid
and 1 to 5% by weight of iron(II1) chloride.
15 [0155]
When the adhesive composition or the wound dressing
composition of the present invention is applied to a wound,
the composition is polymerized and cured to form a film, and
therefore, the composition can be used for bonding the wound
20 or covering the surface of the wounded area (that is, after
the wound edges are put together, the adhesive is applied to
the surface of the wounded area, and it adheres to the
surface and is cured). For the purpose of fixing or
protecting the edge or the whole of the cured film or
maintaining or increasing the adhesive force, covering
articles, such as film, sheet, paper, plaster, bondage and
gauze, may be used during or after application of the
composition to a wound, a soft tissue surface or the like.
5 These covering articles may have adhesiveness, or may have
tackiness.
[0156]
The adhesive composition or the wound dressing
composition can be applied to a wound during or after
10 application of an alginate dressing material, a hydrogel or a
hydropolymer to the wound.
[0157]
If there is a fear that the form or the performance of
the adhesive composition or the wound dressing composition of
15 the present invention varies because of preservation or
storage of a long time, thereby impairing the effect of the
present invention, it is possible that the components
comprising the monomer (A), the polymer particles (B), the
polymerization initiator composition (C) and the components
20 to be contained when needed, such as the polymerization
inhibitor (D), are stored in the form of a kit which is used
as an adhesive for soft tissues, an adhesive for wound
dressing or a wound dressing and has two or more members in
which the above components are encased independently or in
groups divided in an optional combination, and prior to use,
the components are mixed to form the adhesive composition or
the wound dressing composition. The members for encasing the
components therein are, for example, sealable resin
5 containers having gas barrier properties or glass syringes in
order to prevent evaporation or scattering of the monomer (A)
and the polymerization initiator composition (C) . The
members for encasing the polymer particles (B) therein are,
for example, resin containers having good sealing properties
10 or glass containers in order to prevent moisture absorption.
As for the quantity to be encased in a container, there is a
case where the quantity that is used up one time is encased
or a case where the quantity that is used plural times is
encased.
15 [0158]
Examples of manners to store the components include a
manner in which the components are divided into three groups
consisting of a mixture of the component (A) and the
components to be contained when needed, a mixture of the
20 component (B) and the components to be contained when needed,
and a mixture of the component (C) and the components to be
contained when needed, followed by storing them; a manner in
which the components are divided into two groups consisting
of a mixture of the component (A), the component (B) and the
components to be contained when needed, and the component (C),
followed by storing them; a manner in which the components
are divided into two groups consisting of a mixture of the
component (A) and the component (B), and a mixture of the
5 component (C) and the components to be contained when needed,
followed by storing them; a manner in which the components
are divided into two groups consisting of a mixture of the
component (A), the component (B) and a part of the components
to be contained when needed, and a mixture of the component
10 (C) and a residue of the components to be contained when
needed, followed by storing them; a manner in which the
components are divided into two groups consisting of a
mixture of the component (A) and the components to be
contained when needed, and a mixture of the component (B) and
15 the component ( C ) , followed by storing them; a manner in
which the components are divided into two groups consisting
of the component (A), and a mixture of the component (B), the
component (C) and the components to be contained when needed,
followed by storing them; and a manner in which the
20 components are divided into two groups consisting of a
mixture of the component (A) and a part of the components to
be contained when needed, and a mixture of the component (B),
the component (C) and a residue of the components to be
contained when needed, followed by storing them.
When the polymerization inhibitor (D) is contained,
examples of manners to store the components include a manner
in which the components are divided into three groups
5 consisting of a mixture of the component (A) and the
components to be contained when needed, a mixture of the
component (B) and the components to be contained when needed,
and a mixture of the component (C) and the components to be
contained when needed, followed by storing them; a manner in
10 which the components are divided into two groups consisting
of a mixture of the component (A), the component (B), the
component (D) and the components to be contained when needed,
and the component (C), followed by storing them; a manner in
which the components are divided into two groups consisting
15 of a mixture of the component (A), the component (B) and the
component (D), and a mixture of the component (C) and the
components to be contained when needed, followed by storing
them; a manner in which the components are divided into two
groups consisting of a mixture of the component (A), the
20 component (B), the component (D) and a part of the components
to be contained when needed, and a mixture of the component
(C) and a residue of the components to be contained when
needed, followed by storing them; a manner in which the
components are divided into two groups consisting of a
mixture of the component (A), the component (D) and the
components to be contained when needed, and a mixture of the
component (B) and the component (C), followed by storing
them; a manner in which the components are divided into two
5 groups consisting of a mixture of the component (A) and the
component (D), and a mixture of the component (B), the
component (C) and the components to be contained when needed,
followed by storing them; and a manner in which the
components are divided into two groups consisting of a
10 mixture of the component (A), the component (D) and a part of
the components to be contained when needed, and a mixture of
the component (B), the component (C) and a residue of the
components to be contained when needed, followed by storing
them.
15 [0160]
When a mixture of a monomer having an acidic group and a
monomer having no acidic group is used as the monomer (A),
the components may be stored in such a manner that the
monomer having an acidic group is not in contact with the
20 polymerization initiator composition, in addition to the
above manners. Examples of such manners include a manner in
which the components are divided into two groups consisting
of a mixture of the monomer having an acidic group, the
component (B) and the components to be contained when needed,
and a mixture of the monomer having no acidic group and the
component (C), followed by storing them; a manner in which
the components are divided into two groups consisting of a
mixture of the monomer having an acidic group and the
5 component (B), and a mixture of the monomer having no acidic
group, the component (C) and the components to be contained
when needed, followed by storing them; a manner in which the
components are divided into two groups consisting of a
mixture of the monomer having an acidic group and the
10 components to be contained when needed, and a mixture of the
monomer having no acidic group, the component (B) and the
component (C), followed by storing them; and a manner in
which the components are divided into two groups consisting
of the monomer having an acidic group, and a mixture of the
15 monomer having no acidic group, the component (B), the
component (C) and the components to be contained when needed,
followed by storing them.
[0161]
The components divided into two groups are placed in
20 separate members, e.g., containers such as syringes, and the
members are encased in a kit that is used as an adhesive for
soft tissues, an adhesive for wound dressing or a wound
dressing, and the kit can be provided as an article.
[0162]
The constitution of the kit is not specifically
restricted as long as there is no fear that the form or the
performance is changed by the storage to impair the effect of
the present invention, but the kit preferably has
5 constitution in which the monomer (A), the polymer particles
(B) and the polymerization initiator composition (C) are each
independently encased, and the monomer (A) is first mixed
with the polymerization initiator composition (C) containing
an organoboron compound and subsequently mixed with the
10 polymer particles (B). By virtue of such constitution, an
adhesive composition or a wound dressing composition having
more stable performance tends to be obtained.
101631
Examples of such kits include:
15 a kit having members (e. g., containers, syringes) in
which the monomer (A), the polymer particles (B) and the
polymerization initiator composition (C) are each
independently encased and having a member (e.g., mixing
container, mixing dish) for taking out the encased components
20 from the members and mixing them; and
a kit having one container which has three or more
chambers separated by partitions, in said chambers the
monomer (A), the polymer particles (B) and the polymerization
initiator composition (C) being each independently encased,
and having a stirring unit for mixing the monomer (A) and the
polymerization initiator composition (C) with the polymer
particles (B), said components (A) and (C) having passed
through a bypass formed in a syringe owing to rapture of the
5 partitions or shifting of the partitions.
[0164]
When the kit contains the polymerization inhibitor (D),
the kit preferably has constitution in which a mixture
containing the monomer (A) and the polymerization inhibitor
10 (D), the polymer particles (B) and the polymerization
initiator composition (C) are each independently encased, and
the mixture containing the monomer (A) and the polymerization
inhibitor (D) is first mixed with the polymerization
initiator composition (C) containing an organoboron compound
15 and subsequently mixed with the polymer particles (B). By
virtue of such constitution, an adhesive for soft tissues, an
adhesive for wound dressing or a wound dressing having more
stable performance tends to be obtained.
[0165]
20 Examples of such kits include:
a kit having members (e.g., containers, syringes) in
which a mixture containing the monomer (A) and the
polymerization inhibitor (D), the polymer particles (B) and
the polymerization initiator composition (C) are each
independently encased and having a member (e.g., mixing
container, mixing dish) for taking out the encased components
from the members and mixing them; and
a kit having one container which has three or more
5 chambers separated by partitions, in said chambers a mixture
containing the monomer (A) and the polymerization inhibitor
(D), the polymer particles (B) and the polymerization
initiator composition (C) being each independently encased,
and having a stirring unit for mixing the mixture containing
10 the monomer (A) and the polymerization inhibitor (D) and the
polymerization initiator composition (C) with the polymer
particles (B) , said mixture and said component (C) having
passed through a bypass formed in a syringe owing to rapture
of the partitions or shifting of the partitions.
1 5 [0166]
The kit having one container wherein the components are
encased in the separated three or more chambers requires less
labor as compared with a means wherein the composition of the
present invention is divided, placed in two or more members,
typically containers, and mixed immediately before use.
Moreover, this kit uses no mixing container or the like and
can be economically used by taking a necessary amount of the
composition out of the container and bringing it into contact
with a jig such as sponge.
It is also possible that a jig that is used for applying
the adhesive composition or the wound dressing composition to
a wound, a soft tissue or the like is allowed to contain a
5 part or the whole of the polymerization initiator composition
(C) in advance, and, immediately prior to use, the jig is
brought into contact with the monomer (A) or a mixture
containing the monomer (A) and the polymerization inhibitor
(D), the polymer particles (B) and the components to be
10 contained when needed to prepare the adhesive composition or
the wound dressing composition of the present invention in
situ, followed by applying it to a wound, a soft tissue or
the like.
[0168]
15 Examples of the jigs for applying the composition to a
wound, a soft tissue or the like include a brush, a fiber
ball, a cloth, a sponge ball and a piece of sponge.
[0169]
In the kit, the aforesaid disinfectant liquid such as
20 alcohol, the aforesaid pretreatment liquid for improving
adhesion properties, the aforesaid covering article, etc. may
be included.
[0170]
When the components of the composition are stored in the
kit, they may be subjected to sterilization treatment with
electromagnetic waves such as visible light preferably under
the conditions that the components are not modified (e.g.,
monomer is not cured).
5 [0171]
The adhesive composition for soft tissues, the adhesive
composition for wound dressing or the wound dressing
composition of the present invention can be used for, for
example, adhesion of organism tissues, such as closure,
10 protection or obstruction of wounds, fixing (adhesion) of
soft tissue graft, hemostasis, vascular anastomosis, vascular
obstruction, bronchial anastomosis, bronchial obstruction and
ophthalmologic operations.
[0172]
15 By directly applying the composition of the present
invention to a wound formed in the outer skin of an organism
such as skin or mucous membrane, the opening of the wound can
be easily closed. Moreover, the composition of the present
invention can be used also for fixing a graft to the skin
20 transplantation area in the skin transplantation.
[0173]
When the composition of the present invention is used as
a wound dressing, the adhesive is not applied to the wound
surface usually, but the adhesive is applied to the surface
of the wounded area after the wound edges are put together,
and it adheres to the surface and is cured. In the case of a
wound having no incised surface, such as scratch, crush wound
or contused wound, the composition may be directly applied to
5 the affected part in order to dress the wound.
EXAMPLES
[0174]
The present invention is further described in detail
with reference to the following examples, but it should be
10 construed that the present invention is in no way limited to
those examples.
[0175]
Examples 1 to 29, Comparative Examples 1 to 26
In the following examples and comparative examples, a
15 monomer (A), polymer particles (B) and a polymerization
initiator composition (C) described in the following
"Reagents" were used to prepare compositions in accordance
with blending ratios described in the following Tables 2 to 7.
The compositions were evaluated by the later-described
20 evaluation method.
[0176]
Reagents
In the examples, the following compounds and composition
were used as the monomer (A), the polymer particles (B) and
the polymerization initiator composition (C).
[0177]
Monomer (A): 4-META/MMA, methyl methacrylate solution of
4-methacryloxyethyltrimellitic anhydride (weight ratio: about
5 5%)
Polymer particles (B): molecular weights and properties
of the polymethyl methacrylate (PMMA) particles (1) to (13)
are set forth in the following Table 1.
[0178]
10 Table 1
PMMA
(1)
PMMA
(2)
PMMA
(3)
PMMA
(4)
PMMA
(5)
PMMA
- ( 6 )
PMMA
- (7)
PMMA
- (8)
; PMMA
(9
. PMMA
(10)
PMMA
(11)
PMMA
(12)
RMMA
(13)
Volume mean
particle diameter
8.2 pm
8.2 pm
24.6 pm
24.6 pm
37.5 p
40.1 pm
19.7 pm
4.6 pm
6-8 pm
0.4 p
102.7 pm
109.1 p
; 99.0 p
Weight-average
molecular weight
1,270,000
260,000
1,220,000
290,000
987,000
359,000
843,000
1,127,000
1,024,000
414,000
64,000
600,000
50,000
Specific
surface area
0.87 m2/g
0.87 m2/g
0.40 m2/g
0.40 m2/g
0.15 m2/g
0.18 m2/g
0.33 m2/g
1.29 m2/g
1.38 m2/g
12.49 m2/g
0.058 m2/g
0.060 m2/g
0.055 m2/g
The volume mean particle diameter of PMMA (refractive
index: 1.49) particles was measured by the use of Microtrac
MT3300EXII (particle size distribution meter manufactured by
5 Microtrac Inc.) in the following manner. As a dispersion
medium, special grade reagent methanol (refractive index:
1.33, available from Wako Pure Chemical Industries, Ltd.) was
used. The PMMA particles were dispersed in the dispersion
medium by an ultrasonic homogenizer integrated in the
10 apparatus for 5 minutes (output: 25 W), and the measurement
was carried out under the concentration conditions of the
proper range of the apparatus Loading Index at a circulation
rate of 50% (100%: 65 ml/sec).
[0180]
15 The specific surface area was determined by nitrogen gas
adsorption (BET method) at the liquid nitrogen temperature
(77 K) using Autosorb 3 (manufactured by Quantachrome
Instruments).
20 Polymerization initiator composition (C): TBB A type,
namely, partially oxidized tributylboron: 80 parts by weight,
hexane: 19 parts by weight, ethanol: 1 part by weight
Evaluation of dispersibility
In a 5 ml latex-free luer lock syringe (manufactured by
0 SF-2524
HENKE SASS WOLF) having a plastic cap (manufactured by Osaka
Chemical Co., Ltd.) at the luer part, the polymer particles
(B) were weighed in accordance with a blending ratio
described in Examples 1 to 29 and Comparative Examples 1 to
5 26 of the following Table 1. Subsequently, in this syringe,
the monomer (A) and the polymerization initiator composition
( C ) , which had been mixed together in a 10 ml glass sample
tube in accordance with a blending ratio described in the
above-described Examples and Comparative examples, were
10 injected, and the syringe was vigorously shaken with hand at
25°C for 20 seconds to stir and mix the contents. The state
of the mixture in the syringe was confirmed by visual
observation after 5 seconds elapsed from the start of shaking
and after 20 seconds elapsed from the start of shaking (at
15 the end of the mixing). A case where a powder of the polymer
particles (B) was not detected after 5 seconds elapsed from
the start of shaking was evaluated to be 4; a case where a
powder of the polymer particles (B) was not detected after 20
I seconds elapsed from the start of shaking was evaluated to be
I 20 3; a case where a powder of the polymer particles (B) was
slightly detected after 20 seconds elapsed from the start of
shaking was evaluated to be 2; and a case where a powder of
the polymer particles (B) was detected in a large amount
after 20 seconds elapsed from the start of shaking was
evaluated to be 1. In the cases where the dispersibility was
evaluated to be 1, evaluations in terms of extrusion
properties and application properties and measurement of
viscosity were not performed and oblique lines were drawn in
5 the Tables describing the results. The evaluation results
are set forth in the following Tables 2 to 7.
[0182]
Evaluation of extrusion properties and application
properties
10 In a 5 ml syringe (manufactured by HENKE SASS WOLF)
having a plastic cap (manufactured by Osaka Chemical Co.,
Ltd.) at the luer part, the polymer particles (B) were
weighed in accordance with a blending ratio described in
Examples 1 to 29 and Comparative Examples 1 to 26 of the
15 following Tables 2 to 7. Subsequently, in this syringe, the
monomer (A) and the polymerization initiator composition ( C ) ,
which had been mixed together in a sample tube in accordance
with a blending ratio described in the above-described
Examples and Comparative Examples, were injected, and the
20 syringe was vigorously shaken with hand at 25'~ for 20
seconds to mix the contents. Thereafter, the cap of the
syringe was removed, a nozzle having an opening of a width of
1 cm and a thickness of 0.5 mm was fitted, and 1 ml of the
obtained adhesive composition (dressing composition) was
applied by 4 cm onto a polyethylene sheet. Extrusion
properties from the syringe were evaluated as follows. A
case where extrusion could be easily carried out was
evaluated to be 3; a case where extrusion could be carried
5 out by applying a pressure with both hands was evaluated to
be 2; and a case where extrusion was impossible, a case where
the polymer particles (B) having been mixed were separated
from the mixture of the monomer (A) and the polymerization
initiator composition (C) and the liquid portion was first
10 extruded nonuniformly, and a case where uniform dispersion
was achieved but the polymer particles (B) were separated
from the liquid portion after application were evaluated to
be 1. The evaluation results are set forth in Tables 2 to 7.
Evaluation of application properties was performed by
15 observing the degree of spreading of the applied composition
(the width of the applied composition). A case where the
width of the applied composition was 1 to 1.2 cm was
evaluated to be 5; a case where the width of the applied
composition was 1.2 cm to 1.4 cm was evaluated to be 4; a
20 case where the width of the applied composition was 1.4 cm to
1.6 cm was evaluated to be 3; a case where the width of the
applied composition was 1.6 cm to 1.8 cm was evaluated to be
2; a case where the width of the applied composition was 1.8
cm to 3 cm was evaluated to be 1; and a case where the width
of the applied composition was 3 cm or more was evaluated to
be 0. In the cases where the extrusion properties were
evaluated to be 1, evaluations in terms of application
properties and measurement of viscosity were not performed
5 and oblique lines were drawn in the Tables describing the
results. The evaluation results are set forth in Tables 2 to
7.
[0183]
Evaluation of viscosity
10 In a 5 ml latex-free luer lock syringe (manufactured by
HENKE SASS WOLF) having a plastic cap (manufactured by Osaka
Chemical Co., Ltd.) at the luer part, the polymer particles
(B) were weighed in accordance with a blending ratio
described in Examples 1 to 29 and Comparative Examples 1 to
15 26 of the following Table 1. Subsequently, in this syringe,
the monomer (A) and the polymerization initiator composition
(C), which had been mixed together in a 10 ml glass sample
tube in accordance with a blending ratio described in the
above-described Examples and Comparative Examples, were
20 injected, and the syringe was vigorously shaken with hand at
2 5 " ~fo r 20 seconds to stir and mix the contents. Thereafter,
the cap of the syringe was removed, the adhesive composition
(dressing composition) obtained from the syringe was extruded.
The viscosity of the adhesive composition (dressing
composition) after 60 seconds from preparation was measured
at 35'~ by the use of a rheometer (manufactured by HAAKE,
RS600). The viscosity at the time of preparation was not
less than 0.4 cp, and it was confirmed that the viscosity
5 increased with time. The evaluation results are set forth in
the following Tables 2 to 7.
[0184]
It was confirmed that in the case of the adhesive
composition or the wound dressing composition containing the
10 components (A), (B) and (C) and having a viscosity of less
than 0.4 cp after 30 seconds, the width of the applied
composition was too large, and in the case of the composition
having a viscosity of more than 75000 cp after 30 seconds,
application using a syringe was impossible.
15 [0185]
Overall evaluation
Regarding evaluations in terms of dispersibility,
extrusion properties from container (extrusion properties),
and spreading of applied composition (application properties),
20 a case where the point of application properties was 4 or
more was evaluated to be AA; a case where the point of
application properties was 2 or 3 was evaluated to be A; a
case where the point of application properties was 1 was
evaluated to be B; and a case where the point of application
properties was 0 and a case where application was impossible
were evaluated to be C. The evaluation results are set forth
in Tables 2 to 7.
[0186]
5 Preparation of polymerized and solidified film
In a 5 ml latex-free luer lock syringe (manufactured by
HENKE SASS WOLF) having a plastic cap (manufactured by Osaka
Chemical Co., Ltd.) at the luer part, the polymer particles
(B) were weighed in accordance with a blending ratio
10 described in Examples 1 to 29 and Comparative examples 1 to
26 of the following Tables 2 to 7. Subsequently, in this
syringe, the monomer (A) and the polymerization initiator
composition (C), which had been mixed together in a sample
tube in accordance with a blending ratio described in the
15 above-described Examples and Comparative examples, were
injected, and the syringe was vigorously shaken with hand at
2 5 " ~fo r 20 seconds to mix the contents. After that, the
resulting adhesive composition (dressing composition) was
immediately filled in a frame to prepare a sample film in
20 accordance with the following procedure, as illustrated in
Fig. 1 as an example. On a glass plate, a sheet of PE
Lumirror (trade mark) and a fluororesin frame having a
thickness of 0.5 mm (internal size of frame: 25 mrn (length) x
2 mm (width)) were superposed in this order. In this frame,
the adhesive composition (dressing composition) prepared was
filled. The filling work was carefully carried out so that
bubbles should not be formed. After the filling was
completed, a sheet of PE Lumirror (trade mark) and a glass
5 plate were further superposed thereon in this order, and the
four corners of the outermost two glass plates were fixed
with clips. Thereafter, they were allowed to stand for 24
hours at 25'~ (room temperature), and then the film was taken
out of the frame. When the resulting film had irregularities
10 on the surfaces, the surfaces were abraded with a waterproof
abrasive paper #600 to remove irregularities, whereby a
sample film was prepared. The resulting sample film had a
size of a length of 25 mm, a width of 2 mm and a thickness of
0.5 mm.
15 [0187]
Flexural modulus (test rate: 2 mm/min) and tensile
elongation (test rate: 1 mm/min) of the sample film were
determined by an Autograph (EZ-S manufactured by Shimadzu
Corporation). The values of the flexural modulus and the
20 tensile elongation of the film are each a mean of values
measured on four sample film strips. As a result, it was
confirmed that the compositions of Examples had sufficiently
high flexural modulus and tensile elongation as an adhesive
for soft tissues, an adhesive for wound dressing and a wound
dressing composition.
[0188]
Evaluation of adhesive strength using YMP skin
A test was carried out based on ASTM F2255-05 using YMP
5 skin (available from Charles River Laboratories Japan, Inc.) .
That is to say, as illustrated in Fig. 2, YMP skin having a
thickness of 2 to 3 mm, from which a fat layer had been
removed, was cut into a size of 25 mm (width) x 20 mm
(length), and both surfaces of the skin were wiped with paper.
10 Then, the width (25 mm) of the skin was set to the edges of
an acrylic plate having a size of 25 mm (width) x 80 mm
(length), and the dermis side of the skin was bonded to the
plate with Aron Alpha (trade mark, available from TOAGOSEI
CO., LTD.) in such a manner that the outer skin was on the
15 upper side. Thereafter, to the skin (outer skin) of an area
having a length of not less than 10 mm from the edge of the
acrylic plate in the longitudinal direction and to the side
surface of the skin, Teflon Grease was applied to define an
"adhesive application surface (25 mm (width) x 10 mm
20 (length))", whereby an adherend was formed. This adherend
was wrapped up in gauze having been soaked with a
physiological saline solution, then placed in a closed
container and kept warm at 37'~ for 30 minutes. Thereafter,
in a 5 ml latex-free luer lock syringe (manufactured by HENKE
SASS WOLF) having a plastic cap (manufactured by Osaka
Chemical Co., Ltd.) at the luer part, the polymer particles
(B) were weighed in accordance with a blending ratio
described in Examples 1 to 29 and Comparative Examples 1 to
5 26 of the following Tables 2 to 7. Subsequently, in this
syringe, the monomer (A) and the polymerization initiator
composition (C), which had been mixed together in a sample
tube in accordance with a blending ratio described in the
above-described Examples and Comparative Examples, were
10 injected, and the syringe was vigorously shaken with hand at
25OC for 20 seconds to mix the contents. Thereafter, in the
manner illustrated as an example in Fig. 2, the resulting
adhesive composition (dressing composition) was immediately
applied to the adhesive application surface (25 mm x 10 mm).
15 Two of such samples were prepared, and these were laid one
upon the other in such a manner that the adhesive applied
surfaces faced each other, and allowed to stand still for 1
hour under a load of 140 g. Thereafter, the resulting sample
was wrapped up in gauze having been soaked with a
20 physiological saline solution, placed in a container and then
allowed to stand still at 3 7 ' ~ for 24 hours to prepare an
adhesive strength evaluation sample.
[0189]
The evaluation sample was subjected to tensile test
using an Autograph (EZ-S manufactured by Shimadzu
Corporation) at a test rate of 5 mm/min. A mean of values
measured on four test strips was determined as adhesive
strength. As a result, it was confirmed that the
5 compositions of Examples had sufficiently high adhesion as an
adhesive for soft tissues, an adhesive for wound dressing and
a wound dressing composition.
[0190]
Table 2
r
Ex. 1
Ex. 2
Ex. 3
Ex. 4
Ex. 5
Ex. 6
Ex. 7
Ex. 8
Ex. 9
Ex. 10
Adhesive composition or wound dressing composition
(part(s) by weight)
Monomer (A): 560 mg (37.6)
.Polymer (B): PMMA (1) 893 mg (60.0)
Polymerization initiator composition (C): 35 rng (2.4)
Monomer (A): 560 mg (47.1)
Polymer (B): PMMA (1) 595 mg (50.0)
Polymerization initiator composition (C): 35 mg (2.9)
Monomer (A): 560 mg (51.8)
Polymer (B): PMMA (1) 487 mg (45.0)
Polymerization initiator composition (C): 35 mg (3.2)
Monomer (A): 560 rng (65.9)
Polymer (B): PMMA (I) 255 mg (30.0)
Polymerization initiator composition (C): 35 mg (4.1)
Monomer (A): 560 mg (32.9)
Polymer (B): PMMA (2) 11 05 mg (65.0)
Polymerization initiator composition (C): 35 mg (2.1)
Monomer (A): 560 rng (42.4)
Polymer (B): PMMA (2) 727 mg (55.0)
Polymerization initiator composition (C): 35 mg (2.6)
Monomer (A): 560 mg (51.8)
Polymer (B): PMMA (2) 487 rng (45.0)
Polymerization initiator composition (C): 35 mg (3.2)
Monomer (A): 560 mg (65.9)
Polymer (B): PMMA (2) 255 mg (30.0)
Polymerization initiator composition (C): 35 mg (4.1)
Monomer (A): 560 mg (37.6)
Polymer (6): PMMA (3) 893 mg (60.0)
Polymerization initiator composition (C): 35 mg (2.4)
Monomer (A): 560 mg (42.4)
Polymer (B): PMMA (3) 727 mg (55.0)
Polymerization initiator composition (C): 35 mg (2.6)
Dispersibility
4
4
4
4
4
4
4
4
4
4
Application
properties
5
4
3
1
5
4
3
1
5
4
Extrusion properties
3
3
3
3
2
3
3
3
3
3
Viscosity
(cp)
1850
2830
707
6.2
Overall
evaluation
AA
AA
A
B
AA
AA
A
B
AA
AA
[0191]
Table 3
Ex. 11
-
Ex. 12
Ex. 13
Ex. 14
Ex. 15
Ex. 16
Ex. 17
Ex. 18
Ex. 19
Ex. 20
Adhesive composition or wound dressing composition
(part(s) by weight)
Monomer (A): 560 mg (47.1)
Polymer (B): PMMA (3) 595 mg (50.0)
Polymerization initiator composition (C): 35 mg (2.9)
~ G o m e(rA ): 560 mg (56.5)
Polymer (B): PMMA (3) 397 mg (40.0)
Polymerization initiator composition (C): 35 mg (3.5)
Monomer (A): 560 mg (32.9)
Polymer (B): PMMA (4) 1105 mg (65.0)
Polymerization initiator composition (C): 35 mg (2.1)
Monomer (A): 560 mg (37.6)
Polymer (B): PMMA (4) 893 mg (60.0)
Polymerization initiator composition (C): 35 mg (2.4)
Monomer (A): 560 mg (28.2)
Polymer (B): PMMA (5) 1388 mg (70.0)
Polymerization initiator composition (C): 35 rng (1.8)
Monomer (A): 560 mg (65.9)
Polymer (B): PMMA (5) 255 mg (30.0)
Polymerization initiator composition (C): 35 mg (4.1)
Monomer (A): 560 mg (32.9)
Polymer (B): PMMA (6) 11 05 mg (65.0)
Polymerization initiator composition (C): 35 mg (2.1)
Monomer (A): 560 mg (37.6)
Polymer (B): PMMA (6) 893 mg (60.0)
Polymerization initiator composition (C): 35 mg (2.4)
Monomer (A): 560 mg (32.9)
Polymer (B): PMMA (7) 11 05 mg (65.0)
Polymerization initiator composition (C): 35 mg (2.1)
Monomer (A): 560 mg (37.6)
Polymer (B): PMMA (7) 893 mg (60.0)
Polymerization initiator composition (C): 35 mg (2.4)
Dispersibility
4
--
Extrusion
properties
3
Application
properties
3
4
4
4
4
4
4
4
4
4
3.7 B
B
B
A
B
B
B
AA
AA
Viscosity
(cp)
---
3
3
3
2
3
2
3
3
3
Overall
evaluation
A
1
1
1
3
1
1
1
5
4
[0192]
Table 4
Ex. 21
Ex. 22
Ex. 23
Ex. 24
Ex. 25
Ex. 26
Ex. 27
Ex. 28
Ex. 29
Adhesive composition or wound dressing composition
(part(s) by weight)
Monomer (A): 560 mg (51.8)
Polymer (B): PMMA (7) 487 mg (45.0)
Polymerization initiator composition (C): 35 mg (3.2)
Monomer (A): 560 mg (37.6)
Polymer (B): PMMA (8) 893 mg (60.0)
Polymerization initiator composition (C): 35 mg (2.4)
Monomer (A): 560 mg (61.2)
Polymer (B): PMMA (8) 320 mg (35.0)
Polymerization initiator composition (C): 35 mg (3.8)
Monomer (A): 560 mg (70.6)
Polymer (B): PMMA (8) 198 mg (25.0)
Polymerization initiator composition (C): 35 mg (4.4)
Monomer (A): 560 mg (75.3)
Polymer (B): PMMA (8) 149 mg (20.0)
Polymerization initiator composition (C): 35 mg (4.7)
Monomer (A): 560 mg (37.6)
Polymer (B): PMMA (9) 893 mg (60.0)
Polymerization initiator composition (C): 35 mg (2.4)
Monomer (A): 560 mg (51.8)
Polymer (B): PMMA (9) 487 mg (45.0)
Polymerization initiator composition (C): 35 mg (3.2)
Monomer (A): 560 mg (61.2)
Polymer (B): PMMA (9) 320 mg (35.0)
Polymerization initiator composition (C): 35 mg (3.8)
Monomer (A): 560 mg (75.3)
Polymer (B): PMMA (9) 149 mg (20.0)
Polymerization initiator composition (C): 35 mg (4.7)
Dispersibility
4
--
4
4
4
4
3
4
4
4
Extrusion
properties
3
--
2
3
3
3
3
3
3
3
Application
properties
1
5
4
3
1
5
4
2
1
Viscosity
(cp)
Overall
evaluation
B
AA
AA
A
B
AA
AA
A
B
[0193]
Table 5
Ex.
Ex.
EX'
Ex'
EX'
Ex.
'Omp.
Ex'
'Omp.
Ex.
'Omp.
Ex'
Ex' lo
Adhesive composition or wound dressing composition Dispersibility Extrusion Application Viscosity Overall
(part@) by weight) properties properties (cp) evaluation
Monomer (A): 560 mg (32.9
' ~ o l ~ m(eB)r: PMMA (1) 110 : mg (65.0 3 1 C
Polymerization initiator composition (43:5 m g (2.1)
Monomer (A): 560 mg (70.6
Polymer (B): PMMA (1) 198)mg (25.0 C
Polymerization initiator composition (k): 35 mg (4.4)
Monomer (A): 560 mg (28.2
Polymer (B): PMMA (2) 138; mg (70.0 C
Polymerization initiator composition (C;: 35 mg (1.8)
Monomer (A): 560 mg (70.6
Polymer (B): PMMA (2) 198)mg (25.0
Polymerization initiator composition (A): 35 mg (4.4)
Monomer (A): 560 mg (32.9
Polymer (B): PMMA (3) 11 0: mg (65.0
Polymerization initiator composition (43:5 m g (2.1)
Monomer (A): 560 mg (61.2
polymer (8): PMMA (3) 320)mg (35.0
Polymerization initiator composition (L): 35 mg (3.8)
Monomer (A): 560 mg (28.2
:polymer (B): PMMA (4) 138; mg (70.0
Polymerization initiator composition (C: 35 mg (1.8)
Monomer (A): 560 mg (42.4
:polymer (B): PMMA (4) 727)mg (55.0
Polymerization initiator composition (k): 35 mg (2.6)
Monomer (A): 560 mg (23.5
Polymer (B): PMMA (5) 178: rng (75.0
Polymerization initiator composition (C)): 35 mg (1.5)
Monomer (A): 560 mg (70.6
Polymer (B): PMMA (5) 198)mg (25.0
Polymerization initiator composition (k): 35 mg (4.4)
4
3
4
3
1
3
1 C
0
4
1
4
C
3
C
0
0
C
C
C
. .
3 0 C
[0194]
Table 6
Ex'
- EX' l2
Ex'
'Omp.
Ex' l4
'Omp'
, Ex l5
'Omp.
Ex
'Omp.
Ex. l7
Camp'
EX' l8
'Omp'
Ex'
Camp'
Ex. 20
Adhesive composition or wound dressing composition
(part(s) by weight)
Monomer (A): 560 mg (28.2
Polymer (B): PMMA (6) 138; mg (70.0
Polymerization initiator composition (C: 35 mg (1.8)
Monomer (A): 560 mg (42.4
Polymer (B): PMMA (6) 727)mg (55.0
Polymerization initiator composition (A): 35 mg (2.6)
Monomer (A): 560 mg (28.2
Polymer (B): PMMA (7) 138; mg (70.0
Polymerization initiator composition (C)): 35 mg (1.8)
Monomer (A): 560 mg (56.5
Polymer (B): PMMA (7) 397)mg (40.0
Polymerization initiator composition (A): 35 mg (3.5)
Monomer (A): 560 mg (32.9
Polymer (B): PMMA (8) 11 0: mg (65.0
Polymerization initiator composition (43:5 r ng (2.1)
Monomer (A): 560 mg (80.0
Polymer (B): PMMA (8) 105)mg (1 5.0
Polymerization initiator composition (L): 35 mg (5.0)
Monomer (A): 560 mg (32.9
Polymer (B): PMMA (9) 110: mg (65.0
Polymerization initiator composition (C)): 35 mg (2.1)
Monomer (A): 560 mg (80.0
Polymer (B): PMMA (9) 105)mg (15.0
Polymerization initiator composition (L): 35 mg (5.0)
Monomer (A): 560 mg (47.1
Polymer (B): PMMA (10) 59: mg (50.0
Polymerization initiator composition (C;: 35 mg (2.9)
Monomer (A): 560 mg (56.5
Polymer (B): PMMA (1 0) 39: mg (40.0
Polymerization initiator composition (C: 35 mg (3.5)
Dispersibility
4
4
Extrusion Application viscosity Overall
properties properties (cp) evaluation
1
3
1 C
4
3
4
3
4
0 C
1 C
1 C
J
3 0 C
1 C
3 0 C
1 C
3 0 C
[0195]
Table 7
Ex 21
'Omp'
Ex. 22
'Omp.
Ex' 23
'Omp'
Ex. 24
Camp'
Ex' 25
Camp
Ex' 26
Dispersibility
4
4
3
4
3
4
Adhesive composition or wound dressing composition
(part(s) by weight)
Monomer (A): 560 mg (37.6
Polymer (B): PMMA (11) 89; mg (60.0
Polymerization initiator composition (C)): 35 mg (2.4)
Monomer (A): 560 mg (56.5
Polymer (B): PMMA (11) 39: mg (40.0
Polymerization initiator composition (C)): 35 mg (3.5)
Monomer (A): 560 mg (37.6
Polymer (B): PMMA (12) 89; mg (60.0
Polymerization initiator composition (Cj: 35 mg (2.4)
Monomer (A): 560 mg (61.2
Polymer (B): PMMA (12) 32; mg (35.0
Polymerization initiator composition (C;: 35 mg (3.8)
Monomer (A): 560 mg (37.6
Polymer (B): PMMA (13) 89; mg (60.0
Polymerization initiator composition (C;: 35 mg (2.4)
Monomer (A): 560 mg (56.5
Polymer (B): PMMA (13) 39: mg (40.0
polymerization initiator composition (C;: 35 mg (3.5)
Extrusion
properties
3
Application
properties
I
1 C
1 C
Viscosity
(cp)
3
Overall
evaluation
C
1 C
C
C
1
1
3 1
Reference Signs List
11: glass plate, 12: Lumirror (trade mark), 13:
fluororesin frame (the central white part indicates a space
5 of 25 mm (length) x 2 mm (width), and this part is filled
with the adhesive composition or the wound dressing
composition.), 21: Teflon Grease applied part, 22: YMP skin
(outer skin: upper side), 23: acrylic plate

An adhesive composition, an adhesive composition for
5 wound dressing or a wound dressing composition, comprising a
monomer (A), polymer particles (B) having a weight-average
molecular weight of 210,000 or more and 1,500,000 or less and
a volume mean particle diameter of 1.0 pm or more and 90 pm
or less, and a polymerization initiator composition (C)
10 containing an organoboron compound.
[Claim 21
The adhesive composition, the adhesive composition for
wound dressing or the wound dressing composition as claimed
in claim 1, wherein the polymer particles (B) include at
15 least one type selected from
polymer particles (Bl) having a weight-average molecular
weight of 1,000,000 or more and 1,400,000 or less and a
volume mean particle diameter of 1.0 pm or more and 90 pm or
less,
20 polymer particles (B2) having a weight-average molecular
weight of 750,000 or more and less than 1,000,000 and a
volume mean particle diameter of more than 30 p and 90 p or
less,
polymer particles (B3) having a weight-average molecular
weight of 250,000 or more and 950,000 or less and a volume
mean particle diameter of 1.0 p or more and 30 p or less,
polymer particles (B4) having a weight-average molecular
weight of 350,000 or more and 700,000 or less and a volume
5 mean particle diameter of more than 30 p and 90 p or less,
and
polymer particles (B5) having a weight-average molecular
weight of more than 950,000 and less than 1,000,000 and a
volume mean particle diameter of 30 p .
10 [Claim 33
The adhesive composition for soft tissues, the adhesive
composition for wound dressing or the wound dressing
composition as claimed in claim 1, having a viscosity of 0.4
to 75,000 cp within 30 seconds after mixing of the components
15 (A), (B) and (C) .
[Claim 41
The adhesive composition for soft tissues, the adhesive
composition for wound dressing or the wound dressing
composition as claimed in claim 1, wherein a film, which is
20 obtained from said adhesive composition or wound dressing
composition, is given 24 hours after the preparation of the
composition and has a thickness of not less than 0.1 p , a
length of not less than 25 mm and a width of not less than 2
mrn, has a flexural modulus, as measured under the conditions
of a test rate of 2 mm/min, of not more than 750 MPa and a
tensile elongation, as measured under the conditions of a
test rate of 1 mm/min, of not less than 5%.
[Claim 51
5 The adhesive composition for soft tissues, the adhesive
composition for wound dressing or the wound dressing
composition as claimed in claim 1, which further comprises a
polymerization inhibitor (D) .
[Claim 61
10 The adhesive composition for soft tissues, the adhesive
composition for wound dressing or the wound dressing
composition as claimed in claim 5, wherein the content of the
polymerization inhibitor (D) is in the range of 10 to 5000
ppm based on the monomer (A), the content of the monomer (A)
15 is in the range of 5 to 98.95 parts by weight, the content of
the polymer particles (B) is in the range of 1 to 75 parts by
weight, and the content of the polymerization initiator
composition (C) containing an organoboron compound is in the
range of 0.05 to 20 parts by weight, with the proviso that
20 the total amount of the components (A), (B) and ( C ) is 100
parts by weight.
[Claim 71
The adhesive composition for soft tissues, the adhesive
composition for wound dressing or the wound dressing
composition as claimed in claim 5, wherein the polymerization
inhibitor (D) is at least one substance selected from
hydroquinone, dibutylhydroquinone, hydroquinone monomethyl
ether, 2,6-di-tert-butylphenol, 2,6-di-tert-butyl-p-cresol,
5 catechol, pyrogallol, benzoquinone, 2-hydroxybenzoquinone, pmethoxyphenol,
t-butylcatechol, butylated hydroxyanisole,
butylated hydroxytoluene and t-butylhydroquinone.
[Claim 81
The adhesive composition for soft tissues, the adhesive
10 composition for wound dressing or the wound dressing
composition as claimed in claim 1, which further comprises a
plasticizer.
[Claim 91
An adhesive kit for soft tissues, an adhesive kit for
15 wound dressing or a wound dressing kit, having members in
which the components of the monomer (A), the polymer
particles (B) and the polymerization initiator composition
(C) containing an organoboron compound, which are contained
in the adhesive composition for soft tissues, the adhesive
20 composition for wound dressing or the wound dressing
composition as claimed in claim 1, are encased in two or more
divided groups in an optional combination.
[Claim 101
The adhesive kit for soft tissues, the adhesive kit for
wound dressing or the wound dressing kit as claimed in claim
9, which has constitution in which the monomer (A), the
polymer particles (B) and the polymerization initiator
composition (C) are each independently encased, and the
5 monomer (A) is first mixed with the polymerization initiator
composition (C) containing an organoboron compound and
subsequently mixed with the polymer particles (B).
[Claim 111
An adhesive kit for soft tissues, an adhesive kit for
10 wound dressing or a wound dressing kit, having members in
which the components of the monomer (A), the polymer
particles (B), the polymerization initiator composition (C)
containing an organoboron compound and the polymerization
inhibitor (D), which are contained in the adhesive
15 composition for soft tissues, the adhesive composition for
wound dressing or the wound dressing composition as claimed
in claim 5, are encased in two or more divided groups in an
optional combination.
[Claim 121
i 20 The adhesive kit for soft tissues, the adhesive kit for
I
I wound dressing or the wound dressing kit as claimed in claim
11, which has constitution in which a mixture of the monomer
(A) and the polymerization inhibitor (D), the polymer
particles (B) and the polymerization initiator composition
98
Orrry:Th+ v I F\; ,* tkL
(C) are each independently encased, and the mixture of the
monomer (A) and the polymerization inhibitor (D) is first
mixed with the polymerization initiator composition (C)
containing an organoboron compound and subsequently mixed
5 with the polymer particles (B).
[Claim 131
The adhesive kit for soft tissues, the adhesive kit for
wound dressing or the wound dressing kit as claimed in claim
9 or 11, which includes a jig that is used for applying a
10 composition obtained by mixing adhesive components or wound
dressing components containing the components (A), (B) and
(C), or a composition obtained by mixing adhesive components
or wound dressing components containing the components (A),
(B) , (C) and (Dl -
15 [Claim 141
The adhesive kit for soft tissues, the adhesive kit for
wound dressing or the wound dressing kit as claimed in claim
13, wherein the jig is at least one jig selected from a brush,
a fiber ball, a cloth, a sponge ball and a piece of sponge.
20 [Claim 151
The adhesive kit for soft tissues, the adhesive kit for
wound dressing or the wound dressing kit as claimed in claim
9 or 11, which further contains an aqueous solution for
adhesion pretreatment containing 1 to 15% by weight of citric
99
; ,1G ,*,
acid and 1 to 5% by weight of iron(II1)
Dated this 1611 2120.1 3 ~i"i" NEHA RTVASTAVA
OF REMFRY & SAGAR
ATTORNEY FOR THE APPLICANT