JPH01265967A - Photo-hardening resin composition for medical treatment - Google Patents

Abstract

PURPOSE:To obtain a film to cover an affected part by spreading a composition of mixing a prepolymer including two ethylenic unsaturated double bonds, a monomer which can be copolymerized with the prepolymer, when necessary, a photo-polymerization initiator, and a photo-sensitizer, when necessary, and then irradiating the composition with the light. CONSTITUTION:Polypropylene glycol and methacrylic acid are dehydrated to obtain a prepolymer. Glycidyl methacrylate as a monomer, benzylmethyl ketal and anthraquinone as a photo-polymerization initiator, and dimethylamino ethylmethacrylate as a photo-sensitizer are mixed to the prepolymer, the resul tant mixture is spread to the affected part where the back side skin of a rabbit is removed, and the affected part is irradiated with a ultraviolet ray to form a film. In such a way, the affected part can be protected and the recovery is promoted. Furthermore, said composition can be made into a film at any time by irradiating with the light.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a photocurable medical resin composition, which exhibits particularly high sensitivity to light sources in both visible and ultraviolet light regions. , relates to a photocurable medical resin composition with excellent physical properties.

[Prior Art] Conventionally, as a photocurable medical resin composition, a dental photocurable resin is known (Japanese Patent Application Laid-Open No. 62-61908). Surgical adhesives are also known as flexible medical resin compositions (Japanese Unexamined Patent Publication No. 148666/1983).

[Problems to be Solved by the Invention] However, the photocurable resins conventionally used in dentistry etc. have extremely high hardness, and although they are effective as composite resins for filling and hard resins for veneers, they cannot be used in flexible in-vivo tissues. When applied to humans, there are problems such as the inability to follow the movements of living organisms. Furthermore, although surgical adhesives are flexible medical resin compositions, they harden quickly, so they are not effective for detailed work that requires a long time.

[Means for Solving the Problems] In view of the above-mentioned problems, the present inventors developed a photocurable material that can follow the movements of a living body and that can be used without curing until it is irradiated with actinic rays. As a result of intensive studies to find a medical resin composition, the present invention was arrived at.

That is, the present invention comprises a photopolymerizable prepolymer (A) having molecules fftlo00 or more containing two ethylenically unsaturated double bonds, a monomer (B) copolymerizable with component A if necessary, and a photopolymerization initiator. and, if necessary, a photosensitizer (C
), and a photopolymerizable prepolymer (A) containing two ethylenically unsaturated double bonds and having a molecular weight of 1000 or more,
A photocurable product characterized by containing as main components a monomer (B) copolymerizable with component A if necessary, a photopolymerization initiator, a photosensitizer (C) if necessary, and a physiologically active drug (D). It is a medical resin compound.

In the present invention, a photocombinable prepolymer containing 100 or more molecules containing two ethylenically unsaturated double bonds (
As A), (meth)acrylate (hereinafter referred to as acrylate or methacrylate) containing polyethers and/or polyesters can be used.

Examples of polyethers include adducts of alkylene oxides and compounds having two active hydrogens (for example, low-molecular polyols, phenols, amine compounds, etc.) and polyoxytetramethylene glycol.

Examples of divalent low-molecular polyols include ethylene glycol, propylene glycol, and! , 3- or l.

4-butylene gelicol, neopentyl glycol, hydrogenated bisphenol A1 hydrogenated bisphenol F1 polyoxytetramethylene glycol, polyester diol,
Terminal silanol polysiloxane compounds and phenolic compounds include bisphenols (bisphenol A5).
Bisphenol F1, bisphenol S, etc.), amine compounds include aliphatic mono- or polyamines having two active hydrogens, aromatic mono- or polyamines, and alkanolamines. Among these, preferred are low molecular weight polyols.

Examples of alkylene oxides include alkylene oxides having 2 to 4 carbon atoms, such as ethylene oxide (hereinafter abbreviated as Eo), propylene oxide (hereinafter abbreviated as P○), butylene oxide (1,2-, 1,3-, 2゜3- and 1.
4-butylene oxide) and mixtures thereof. Among these, preferred are E○ and PO.

When used in combination, a random copolymer, a block copolymer, or a mixture of both may be used. Preferably it is a random copolymer. By increasing the E○ content in polyethers, the hydrophilicity of the resulting photocurable medical resin increases, and the effect of absorbing body fluids etc. can be obtained. When body fluid absorbency is required, EO is added to the total weight of component A and component B.
The content is usually 30% or more, preferably 50% or more.

Examples of the polyesters include condensed polyester diols (e.g., ethylene adipate, diethylene adipate, butylene adipate, etc.), lactone-based polyester diols (e.g., polyols obtained by ring-opening polymerization of ε-caprolactone), and polycarbonate diols.

Among these, preferred are lactone polyester diols.

(meth)acrylate synthesis methods include dehydration reaction of polyether diol and/or polyester diol with (meth)acrylic acid, polyether diol and/or polyester diol and alkyl (meth)
Transesterification reaction with acrylates, converting polyether diols and/or polyester diols and (meth)acrylates into polyisocyanates (e.g. tolylene diisocyanate, diphenylmethane diisocyanate,
Examples include a synthesis method in which a urethane reaction is performed via a urethane (P-phenylene diisocyanate, fluorine-containing diisocyanate, etc.), and a method in which a polyoxyalkylene (meth)acrylate is reacted with a polyisocyanate.

As component A, (meth)furyl ether [C11□=C(R)-COO- is C112
=C(R)-CH2- (R:I or methyl group) can also be used.

The molecular weight of component A is 1000 or more, preferably 20
00-6000. If it is less than 1,000, the flexibility of the resulting photocurable medical resin will be extremely reduced, causing practical problems such as being unable to follow the movements of the living body.

As the monomer (B) that can be copolymerized with component A, there are examples of monomers (B) that can be copolymerized with component A, such as "rUV-E B Curing Handbook (Genryoku Fuku)" published by Kobunshi Kankokai and "UV-
Monofunctional and polyfunctional monomers described in "EB Curing Technology" may be mentioned. Among these, preferred are monofunctional monomers (e.g. alkyl (meth)acrylates,
polyalkylene glycol (meth)acrylate, alkoxypolyalkylene glycol (meth)acrylate, etc.), monofunctional monomers having reactive groups (e.g. alkyl (meth)acrylates having epoxy groups, carboxylic acid groups, phosphate groups, cyano groups, etc.) acrylate, polyalkylene glycol (meth)acrylate).

The blending amount of component A and component B is the total of A and B ff1ffi
Component A is usually 30 to 100%, preferably 40%
~80%. If component A is less than 30%, the material lacks flexibility and cannot follow the movements of the living body.

The photopolymerization initiator and, if necessary, the photosensitizer (C) may be anything that can initiate the polymerization of the photopolymerization component upon irradiation with actinic rays. The active light preferably has a wavelength that effectively activates the photopolymerization initiator and, if necessary, the photosensitizer (C), and practically, light in the ultraviolet to visible range is desirable.

Photopolymerization initiators that meet these conditions include benzoin alkyl ethers (benzoin methyl ether, benzoin ethyl ether, benzoin isobutyl ether, benzoin isopropyl ether, etc.) and thioxanthone (2-chlorothioxanthone, 2,4- Dimethylthioxanthone, 2,4-diethylthioxanthone, 2
, 4-diisopropylthioxanthone, isopropylthioxanthone, etc.), ketals (benzyl dimethyl ketal, benzyl diethyl ketal, benzyl di(2-
methoxyethyl) ketal, etc.), anthraquinones (
anthraquinone, 1-chloroanthraquinone, 2-chloroanthraquinone, 1,2-benzoanthraquinone, etc.), benzophenone (benzophenone, 3,3ξcymethyl-4-methoxybenzophenone, 3.3', 4
．． Examples include 4ξtet(t-butylperoxycarbonyl)benzophenone, benzoylbenzoic acid, methyl benzoylbenzoate, etc.), benzyl type (benzyl, methyl benzoyl formate, etc.), acetophenone type, phenyl ketone type, etc. Among these, preferred are benzoin alkyl ether, thioxanthone, ketal, and anthraquinone, and particularly preferred are benzoin isopropyl ether, 2-chlorothioxanthone, 2,4-dimethylthioxanthone, 2,
4-diethylthioxanthone, benzyl dimethyl ketal. These can be used alone or in combination of two or more. The amount of the photopolymerization initiator is usually 0.0 per 1iffi of the medical resin composition of the present invention.
It is 1 to 10%, preferably 0.1 to 5%.

As a photosensitizer, aromatic amine type (ethyl P-dimethylaminobenzoate, isoamyl P-dimethylaminobenzoate, methyl P-dimethylaminobenzoate/2-n-butoxyethyl-4-(dimethylamino)benzoate ,
2-dimethylaminoethylbenzoate, etc.), aliphatic amines (triethanolamine, dimethylaminoethanol, dimethylaminoethyl methacrylate, primary,
(secondary and tertiary alkylamines, etc.), urea-based, sulfur compound-based, nitrile-based, phosphorus compound-based, etc. Among these, aromatic amines and aliphatic amines are preferred. A photosensitizer is not used alone but in combination with a photopolymerization initiator. The combined amount of the photopolymerization initiator and photosensitizer is usually 0.01 to 10%, preferably 0.1 to 5%, based on the weight of the medical resin composition of the present invention. If it is less than 0.01%, curing will be poor, and if it exceeds 10%, there will be a problem of poor storage stability.

The physiologically active drug (D) may be an oil-soluble drug, a water-soluble drug, or a powder, and may include, but is not particularly limited to, bactericides, local narcotics, antihistamines, anti-inflammatory analgesics, antibiotics, and astringents. , vitamins, antifungal agents, peripheral nerve paralyzing agents, blood circulation promoters, hormones, herbal medicine extracts/tinctures, herbal medicine powders, antihypertensive agents, and antianginal agents, etc., depending on the purpose of use. Incidentally, specific examples of the above-mentioned drugs include, but are not limited to, the drugs described in JP-A-61-172817. The blending amount of the physiologically active drug (D) is usually o, oot based on the weight of the medical resin composition of the present invention.
-20%, preferably 0.05-5%.

The medical resin composition of the present invention may optionally contain fillers (for example, inorganic powders such as lime powder, alumina powder, glass powder, kaolin, talc, calcium carbonate, barium aluminosilicate glass, titanium oxide, and colloidal silica). : Acrylic resin powder such as polymethyl acrylate, polymethacrylate, etc. Organic-inorganic composite filler, etc.)
can be blended. Said no 83! It is preferable that the bulk filler is treated with a coupling agent capable of damaging both the filler and components (A) and (B) before blending. In addition, the medical resin composition of the present invention may optionally contain stabilizers (for example, quaternary ammonium chloride, diethylhydroxyamine, cyclic amide, nitrile compound, substituted urea, benzothiazole, hydroquinone, hydroquinone) for the purpose of improving storage stability. methyl ether, lactic acid, oxalic acid, benzoic acid, etc.). The blending amount of fillers and stabilizers is usually 0 to 20%, preferably 0 to 5%, based on the weight of the medical resin composition of the present invention.

The active energy rays used for curing the medical resin composition of the present invention may be visible rays, ultraviolet rays, or active energy rays containing both visible rays and ultraviolet rays within its spectrum. Examples of light sources that can be used in the composition of the present invention include carbon arcs, mercury lamps, xenon lamps, metal halide lamps, fluorescent lamps, tungsten lamps, and argon ion lasers.

Since the medical resin composition of the present invention initiates polymerization by visible light or ultraviolet light, it can be stored for a long period of time by filling it into a container such as an ampoule that blocks these active energy rays.

When using the medical resin composition of the present invention, examples of application methods include a method using a brush, tweezers, a special spatula, and a method using a spray using Freon or nitrogen gas.

Direct adhesion method in which adhesive is applied directly to the affected area; Dacron, oxidized cellulose, collagen,
Examples include a coating adhesion method in which a piece of cloth or cotton-like material such as chitin, polyurethane, polyester, or PVA or a piece of biological tissue such as vein, fascia, or muscle is applied to the affected area and the present medical resin composition is applied. . In addition, the medical resin composition of the present invention can be used as a coating material for arterial calendars, as a protective treatment for burns, labial wounds, etc., as a sealing material, and as a material for cerebrospinal fluid leakage, etc., by utilizing its flexibility and bondability with living tissues. Apply to the affected area or catheter as a sealing substance.

It can be used by methods such as injection using a tube or the like.

[Examples] The present invention will be further explained below with reference to Examples and Comparative Examples, but the present invention is not limited thereto. Example,
The raw materials used in the comparative example are as follows.

Prepolymer A.

Polyether diol (EO/PO random copolymer, average molecular weight 4,000, oxyethylene content 80%) dehydrated under reduced pressure and MDI were mixed at an OH/NCO ratio of 1/2.
The reaction was carried out at a temperature of 1/280° C. for 5 hours to obtain an NGO-terminated urethane prepolymer. This prepolymer and HEA
were blended so that the OH/NCO ratio was 1/H: and further reacted at 80°C for 5 hours to obtain prepolymer A having double bonds at both ends.

Prepolymer A2 Polypropylene glycol dehydrated under reduced pressure (average molecular fi
t3,000) and methacrylic acid were heated to reflux in a benzene solvent using benzenesulfonic acid as a catalyst to perform a dehydration reaction. Prepolymer A2 was obtained by removing the solvent under reduced pressure and removing unreacted substances by a flow separation operation.

Prepolymer A3 Polyoxytetramethylene glycol dehydrated under reduced pressure (
The average molecular weight i3,000) and methacrylic acid were subjected to a dehydration reaction according to the above method to obtain prepolymer A3.

Hydrophilic urethane prepolymer C3 TDI and polyether diol (Eo/PO random copolymer, average molecular weight 3,000. Oxyethylene containing f
NGO-terminated hydrophilic urethane prepolymer 〇, obtained by reacting with f180%).

Examples 1 to 5, Comparative Examples 1 to 3 Both Examples and Comparative Examples were medical resin compositions formulated according to Table 1.

Test Example-1 Photocuring experiments were conducted for Examples 1 to 5 and Comparative Examples 1 to 2. The above test sample 18 was placed on a hydrous collagen film to a thickness of 1 mm, and ultraviolet light was irradiated from 5 mm above to measure the curing time and flexibility of the polymer.

In addition, in Comparative Example 3, 1 g of sample was placed on a hydrous collagen film at a thickness of 1 opening and cured. The results are shown in Table-2.

Table-2 curing time Time until tack runs out.

Workability Can you do detailed work?

O: Good workability ×: Poor workability A needle penetration test (load: 300 g) was performed on the flexible cured resin material of the polymer to evaluate it.

O: Soft and the needle penetrates sufficiently.

×: Hard and difficult to penetrate with needle.

Test Example 2 A simulated wound was created by cutting the hair on the rabbit's back skin and removing the epidermis to a size of I x 1 cm to expose the endothelial layer. The photocurable medical resin composition obtained in Example 4 was coated on the affected area after sterilization, and by irradiating it with ultraviolet light, the affected area could be covered with a film of medical resin. With this product, the affected area was well protected and the wound area healed well.

Test Example-3 After cutting the nerve of an adult dog and bringing both ends together, Example-1
A small amount of the photocurable medical resin composition obtained in step 1 was applied and visible light was irradiated. It cured in 3 seconds and the bonding was good.

[Effects of the Invention] The photocurable medical resin composition of the present invention is flexible and can follow the movements of a living body, and also does not cause a curing reaction until it is irradiated with actinic rays, so it can be used to cure fine particles. Coupling of microvessels and fixation of nerves (coupling) that require work
It is effective for such things.

The photocurable medical resin composition containing the physiologically active drug of the present invention further promotes the healing effect of the drug by protecting the affected area with the resin. Also, because of its good workability, it can be applied to small parts and curved parts.

Conventionally, ultrafine sutures and hydrophilic urethane prepolymers have been used to join blood vessels, but it is extremely difficult to join microvessels with Since it is a hardened type, it was not effective for detailed work. Regarding nerves, although sutures can be used for thick nerves, thin nerves are simply joined using a blood coagulation reaction using a laser scalpel. Therefore, the bonding was insufficient. In order to solve these problems, the photocurable medical resin composition of the present invention satisfies all of the requirements for curing speed, workability, bondability with biological tissues, and flexibility that can follow the movements of living organisms. It is something.

In view of the above points, the photocurable medical resin composition of the present invention can shorten surgical time, prevent bleeding, prevent leakage of enzymes from the digestive organs, etc., avoid stenosis accidents of the smallest blood vessels, strengthen nerve junctions, and suturing. Significant improvements in medical technology can be seen, including temporary fixation prior to treatment and reliability through the combined use of sutures and adhesives.

In addition to the above-mentioned surgical joining techniques, it has the effect of imparting high confidence and high performance to all aspects of medical care, such as protecting against thoughts and promoting healing through a delivery system for physiologically active drugs to the affected area.

Claims (1)

[Claims] 1. Molecular weight 1 containing two ethylenically unsaturated double bonds
000 or more photopolymerizable prepolymer (A), optionally a monomer copolymerizable with component A (B), a photopolymerization initiator, and optionally a photosensitizer (C). A photocurable medical resin composition. 2. Molecular weight 1 containing two ethylenically unsaturated double bonds
000 or more photopolymerizable prepolymer (A), optionally a monomer copolymerizable with component A (B), a photopolymerization initiator and optionally a photosensitizer (C), a physiologically active drug (D) A photocurable medical resin composition comprising as a main component.