JP2604849B2 - Composition for forming intraocular lens - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a method for removing a parenchyma lens while leaving the capsular bag, and then directly injecting into the capsular bag or into a balloon inserted into the capsular bag and curing the capsular bag. In addition, the present invention relates to an injection material for forming an intraocular lens, and more particularly to a composition for forming an intraocular lens which can be cured in a short time by photopolymerization.

(Background Art) As an intraocular lens that replaces the crystalline lens, a liquid material is used.
Some are formed by directly injecting into the lens capsule after the lens parenchyma is extracted, or by injecting into a balloon (thin capsule) inserted into the lens capsule. In addition, as a liquid injection material to be used, for the purpose of preventing the injection material from leaking out of the capsular bag or the balloon through the injection port, a gel-like injection material, or a solidification polymerized in the eye. Etc. have been proposed.

For example, U.S. Pat. No. 4,713,072 discloses the use of a gelled aqueous sodium hyaluronate solution as an injection material into a balloon of a balloon-type intraocular lens. However, when such a gel-like injection material is used, leakage from the inside of the balloon is reduced, but since the viscosity is high, injection using a catheter or the like becomes difficult, and workability is reduced. However, material leakage cannot be completely prevented. In addition, the aqueous solution of sodium hyaluronate has a low refractive index,
There is also a problem that the thickness of the intraocular lens must be increased in order to obtain the same refractive power as the crystalline lens.

JP-A-63-216574 discloses a composition in which two types of organopolysiloxanes having respective groups are blended so that the ratio between the unsaturated aliphatic group and the hydrosilyl group is substantially the same. ing. The injection material having such a composition can be easily injected in a liquid state because the polymerization proceeds and hardens over time, and after injection, solidifies in the eye. It is possible to prevent leakage. However, this composition requires several hours to cure after compounding,
There is a problem that the injection material leaks from the injection port until the composition is hardened, so that an intraocular lens having a desired shape cannot be obtained.

As a countermeasure, a method of shortening the time from injection to curing can be considered by blending in advance and injecting when polymerization has progressed to some extent. However, injection is difficult due to a remarkable increase in viscosity. The problem is inherent.

(Problem to be Solved) The present invention has been made under such circumstances, and a problem to be solved is that, when injected into an eye, it is in a liquid state and is cured in a short time after injection. An object of the present invention is to provide a composition for forming an intraocular lens that can be used.

(Solution) In order to solve this problem, in the present invention, a composition for forming an intraocular lens which is polymerized in the eye to give a target intraocular lens is provided with a photopolymerizable monomer. It was prepared to include a photoinitiator.

When the composition for forming an intraocular lens according to the present invention is directly injected into the lens capsule of the eye, a silicone-based monomer is particularly advantageously selected as the photopolymerizable monomer. When the composition for forming an intraocular lens of the present invention is used as an injectable substance into a balloon housed in a capsular bag, such a monomer is not specified.

(Action / Effect) That is, the composition for forming an intraocular lens according to the present invention comprises:
Since it is liquid and has photocurability, it can be easily injected with low viscosity at the time of injection, and can be cured within several minutes by light irradiation after injection. As a result, the injection material is prevented from leaking from the injection port, and an intraocular lens having a desired shape can be formed.

Further, in the composition for forming an intraocular lens of the present invention, when the photopolymerizable monomer is a silicone-based monomer, biocompatibility can be imparted in terms of toxicity and softness, etc. In addition, the composition for forming an intraocular lens of the present invention can also be used by injecting it into a balloon housed in a capsular bag. Since the injection material does not directly contact the capsular bag, it is not necessary to consider the biocompatibility of the injection material, and the photopolymerizable monomer can be freely selected.

(Specific Configuration) By the way, the photopolymerizable monomer used in the composition of the present invention can be polymerized by irradiation with light under the action of a photoinitiator described later. Some are toxic to However, since the composition of the present invention can also be used as an injection material into a balloon housed in the capsular bag, when using such a balloon body, the monomer is not particularly limited. Absent.

Specifically, balloon bodies (JP-A-63-200755, U.S. Pat. Nos. 4,585,457, 4,693,717, and 47)
Examples of the photopolymerizable monomer that can be used only when injected into a hollow intraocular lens balloon implanted in a capsular bag as shown in the specification of 13072 or the like include the following. Thus, one or more monomers are appropriately selected and used from these monomers. In the following, "... (meth) acrylate" means "... acrylate" or "... methacrylate".

2-ethylhexyl (meth) acrylate, 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, tetrahydrofurfuryl (meth) acrylate, dicyclopentenyl (meth)
Acrylate, dicyclopentenyloxyethyl (meth) acrylate, 1,3-butanediol di (meth) acrylate, 1,4-butanediol di (meth) acrylate, 1,6-hexanediol di (meth) acrylate, diethylene glycol di (Meth) acrylate, triethylene glycol di (meth) acrylate, neopentyl glycol di (meth) acrylate, polyethylene glycol di (meth) acrylate, hydroxypivalic acid ester neopentyl glycol (meth) acrylate, tripropylene glycol di (meth) acrylate Acrylate, 1,3-bis (3 '-(meth) acryloxyethoxy-2'-hydroxypropyl) -5,5-dimethylhydantoin, trimethylolpropane tri (meth) acrylate, pentaerythritol Li (meth) acrylate, dipentaerythritol hexa (meth) acrylate, 2,2-bis - (3-methacryloxy, 2- hydroxypropoxy) propane and the like.

In addition, when directly injecting into the capsular bag without using a balloon body, usable monomers are limited due to safety to ocular tissues, etc., but silicone-based monomers are biocompatible. Is preferable.

The silicone-based monomer that can be used is 1
An organopolysiloxane containing at least one polymerizable group in the molecule, for example, a polymerizable group as shown below.

-CH = CH ₂ -CH = CHCH ₃ −CH ₂ −CH = CH ₂ In the polymer group shown above, R ¹ and R ² are the same or different unsubstituted or substituted monovalent hydrocarbon groups, and R ³ is
A is a hydrogen atom or a methyl group, and a is an integer of 1 to 3. Further, in the polymer group shown above, R is 1
Is a divalent hydrocarbon group, b is 2 or 3, c is an integer of 1 to 3, d and e are each an integer of 0 to 2, and has a relationship of c + d + e = 3. is there.

In such a silicone monomer, the number of repeating units of the organosiloxane is desirably 10 or more and 1000 or less. When the number of units is less than 10, the formed polymer becomes hard, and it is difficult to obtain the softness which is a characteristic of silicone. This is because the ratio of the polymer groups is small and the polymerization rate may be low or the polymer may not polymerize. Then, one or more of such monomers are appropriately selected and used. Needless to say, such a silicone-based monomer can also be used when a balloon body is used.

Next, a photoinitiator used as another essential component of the present invention will be described. In the present invention, a photoinitiator is generally used, including an ultraviolet absorber. However, since the polymerization of the composition of the present invention is carried out in the eye, it is preferable to use a light source that does not contain much light having a wavelength of less than 340 nm for safety with respect to the light to be irradiated, It is desirable that the photoinitiator has a great ability to initiate such light.
One initiator may be used, or two or more initiators may be used in combination for the purpose of improving the initiation ability. The initiator is used in an amount of about 0.01% by weight to 10% by weight, preferably about 10% by weight, based on the total amount of the composition. It is blended at a ratio of about 0.05 to 6% by weight. If the compounding amount is less than 0.01% by weight, the sensitivity is slow, curing takes time, or it may not be cured, and if the compounding amount is more than 10% by weight,
There is a possibility of foaming, and an effect corresponding to the added amount cannot be obtained.

As specific examples of the photoinitiator, acetophenones such as acetophenone, di and trichloroacetophenone, dialkoxyacetophenone, 2,2-dimethoxy-2-phenylacetophenone, 4-dialkylaminoacetophenone, and 2,2-diethoxyacetophenone; Benzophenones such as benzophenone, 4,4'-bis (dimethylamino) benzophenone (Michler's ketone) and 4,4'-bis (diethylamino) benzophenone; benzyl;
Benzoins such as benzoyl and benzoyl alkyl ether; benzyldimethyl ketal; benzoyl zoate; α-acyloxime esters; tetramethylthiuram monosulfide; Azo compounds such as isobutyronitrile; peroxides such as benzoyl peroxide and di-tert-butyl peroxide; benzoyldiethoxyphosphine oxide; trimethylbenzoyldiphenylphosphine oxide; camphorquinone: 5-butylbarbituric acid and the like. I can do it.

The composition of the present invention contains the photopolymerizable monomer and such a photoinitiator, and has a photocurable property. Therefore, the injection material does not leak from the injection port.

In addition, in addition to the photopolymerizable monomer and the photoinitiator, the composition for forming an intraocular lens of the present invention may optionally contain a sensitizer, a hardness adjusting component, a dye, and the like, as necessary. Needless to say,

The sensitizer alone is not activated by the irradiation of ultraviolet light, but is used together with the photoinitiator, so that the sensitizer exerts an effect superior to the case where the photoinitiator is used alone. The amount used is from 0.01 to 0.01% based on the total amount of the composition.
It will be about 10% by weight. This is because even if added in excess of 10% by weight, an effect commensurate with the added amount cannot be expected. Specific examples thereof include amines such as n-butylamine, di-n-butylamine, and triethylamine;
Allylthiourea; s-benzylisothiuronium-p-toluenesulfinate;
Dimethylaminoethyl methacrylate; diethylaminoethyl methacrylate and the like.

The hardness-adjusting component is a component that is blended with the monomer so that the cured intraocular lens has an arbitrary hardness. A component that has good compatibility with the monomer and does not lose transparency even after curing is used. For example, silicone oil, polyethylene glycol and the like are used. The amount used is about 0.01 to 75% by weight based on the total amount of the composition. If it exceeds 75% by weight, it takes a long time to cure, and sometimes it does not cure.

In addition, since the human lens is not strictly transparent and is colored in the elderly, which accounts for the majority of IOL inserters, the color vision of the left and right eyes is matched when only one eye has an IOL inserted. For this purpose, a dye can be added. The dye may be polymerizable or non-polymerizable, and is added at a ratio of about 0.001 to 1% by weight based on the total amount of the composition. If the content is more than 1% by weight, the color is too colored, and the light transmittance is rather lowered. Then, each of these optional components is blended with the blend comprising the photopolymerizable monomer and the photoinitiator to obtain the composition for forming an intraocular lens according to the present invention.

Incidentally, such an intraocular lens forming composition in the capsular bag,
Alternatively, in order to inject into the balloon housed in the capsular bag, according to the same method as in the past, a catheter or the like is used and is performed through a small incision, but since the composition of the present invention is in a liquid state, The injection can be performed very easily.

Then, by performing light irradiation after the injection, the polymerization can be completed in a short time, so that the injection material does not leak from the injection port, and a good intraocular lens can be formed. . In addition, by selecting an appropriate photoinitiator, photopolymerization can be carried out without using much light having a wavelength shorter than 340 nm, which is harmful to the eyes, and therefore, safety is excellent.

(Examples) Hereinafter, some examples of the present invention will be shown to clarify the present invention more specifically. However, the present invention imposes some restrictions by the description of such examples. It goes without saying that you don't have to receive anything.

In addition, in addition to the following examples, the present invention, in addition to the above-described specific description, various changes, corrections, and modifications based on the knowledge of those skilled in the art without departing from the spirit of the present invention. It should be understood that improvements can be made.

The silicone monomer used in this example was
It has a structure as shown below, and is hereinafter referred to as an organosiloxane A, an organosiloxane B, and an organosiloxane C, respectively.

Example 1 An injection material was prepared by mixing 100 parts by weight of an organosiloxane A as a photopolymerizable monomer and 1 part by weight of 2,2-diethoxyacetophenone as a photoinitiator.

This injection material was injected through a catheter into a rabbit eye from which the lens parenchyma had been removed, leaving the capsule in advance. After the injection, use a halogen light (Philips bulb: 15 V, 150 V) with an operating microscope (OMS-70 manufactured by Tokyo Kogaku Kikai Co., Ltd.)
W, the same applies hereafter) from a distance of 17 cm
After a few minutes, the injection material was cured. Thereafter, sutures were performed and the operation was completed.

Three months later, the rabbit eye into which the intraocular lens was inserted was extracted, and the retina was observed. No abnormality was found in the retina. In addition, when the intraocular lens was extracted and observed together with the lens capsule, there was no leakage of the injected material, no wrinkles on the surface of the lens capsule were observed, and the intraocular lens had good optical performance. .

Example 2 75 parts by weight of organosiloxane B as a photopolymerizable monomer, 1 part by weight of 2,2-diethoxyacetophenone as a photoinitiator, and silicone oil as a hardness adjusting component
And 25 parts by weight to prepare an injection material.

Next, this injection material was directly injected into the capsular bag of the rabbit eye in the same manner as in Example 1, and when irradiated with light under the same conditions, the injection material was cured in several minutes. Thereafter, suture was performed, and the operation was completed.

Three months later, when the retina and the capsular bag were observed in the same manner as in Example 1, there were no retinal abnormalities, and no leaking or wrinkling of the injected material was found in the capsular bag, and the intraocular lens had good optical performance. , And having a lower hardness than that of Example 1.

Example 3 An injection material was prepared by mixing 100 parts by weight of organosiloxane C as a photopolymerizable monomer and 0.2 parts by weight of camphorquinone as a photoinitiator.

This injection material was directly injected into the capsular bag of rabbit eyes in the same manner as in Example 1. After the injection, using a UV cut filter (a disk made of polymethyl methacrylate containing 1% by weight of benzophenone having a diameter of 90 mm and a thickness of 1 mm, the same applies hereinafter)
When only the visible light of the halogen light of the operating microscope was continuously irradiated from a distance of 17 cm, the injected material was cured after a few minutes. Thereafter, sutures were performed and the operation was completed.

Three months later, when the retina and the capsular bag were observed in the same manner as in Example 1, there were no retinal abnormalities, and no leaking or wrinkling of the injected material was found in the capsular bag, and the intraocular lens had good optical performance. Had.

Example 4 An injection material was prepared by mixing 100 parts by weight of trimethylolpropane trimethacrylate as a photopolymerizable monomer, 0.1 part by weight of acetopheno as a photoinitiator, and 0.1 part by weight of n-butylamine as a sensitizer.

This injection material was injected through a catheter into a balloon serving as an intraocular lens body previously inserted into a rabbit eye from which the lens capsule had been removed while leaving the capsule. After the injection, light irradiation was performed under the same conditions as in Example 1, and the resin was cured in several minutes. Then, the operation was completed by suturing.

Three months later, the rabbit eye into which the intraocular lens was inserted was excised, and the retina was observed. No retinal abnormalities were observed. When the intraocular lens was excised and observed, leakage of the injected material and the surface of the balloon were observed. No wrinkles were observed, and the intraocular lens had good optical performance.

Example 5 As a photopolymerizable monomer, 70 parts by weight of 2,2-bis- (3-methacryl, 2-hydroxypropoxyphenyl) propane and 30 parts by weight of totiethylene glycol dimethacrylate were used, and camphor was used as a photoinitiator. 3 parts by weight of quinone and 2 parts by weight of 5-butyl barbituric acid were mixed to prepare an injection material.

The obtained injection material was injected into a rabbit eye using a balloon in the same manner as in Example 4. After the injection, irradiation with a Philips Dangsten lamp (24 V, 250 W) was continued from a distance of 17 cm, and after several minutes, the injected material was cured.
Thereafter, suture was performed, and the operation was completed.

Three months later, the rabbit eye into which the intraocular lens was inserted was excised, and the retina was observed. There was no retinal abnormality. When the intraocular lens was excised and observed, leakage of the injection material and wrinkles on the balloon surface were observed. No I was seen and the intraocular lens had good optical performance.

Example 6 The same composition as in Example 4 was injected into a rabbit eye using a balloon in the same manner as in Example 4. After the injection, only the visible light of the halogen light of the surgical microscope was continuously irradiated from a distance of 17 cm using a UV cut filter. As a result, the injected material did not cure even after several tens of minutes. Next, when the UV cut filter was removed and halogen light irradiation was continued, the injected material was cured after several minutes. Thereafter, sutures were performed and the operation was completed.

Three months later, the rabbit eye into which the intraocular lens was inserted was excised, and the retina was observed. There was no retinal abnormality. When the intraocular lens was excised and observed, leakage of the injection material and wrinkling of the balloon surface were observed. No such was seen, and such an intraocular lens had good optical performance.

Comparative Example 1 A gel-like aqueous solution of sodium hyaluronate was used as an injection material.

When the injection material was injected through a catheter into a balloon body as an intraocular lens body previously inserted into a rabbit eye from which the lens capsule was removed, leaving the capsule in advance,
The injection material had a high viscosity and was very difficult to inject.
After the injection, sutures were performed and the operation was completed.

Three months later, the above-mentioned intraocular lens was excised and observed. As a result, it was confirmed that the injection material leaked remarkably and hardly formed a lens.

Comparative Example 2 As a monomer, 2 parts by weight of vinyl polydimethylsiloxane (having a siloxane repeating unit (n) of 560 and three vinylsilane units in the molecular chain) and hydrogenated polydimethylsiloxane [a repeating unit of siloxane] With a number (n) of 190, containing three silicon hydride units in the molecular chain] and 2 parts by weight of the mixture, and then mixing 100 ppm of a platinum nitrate methoxysilane complex as a catalyst in terms of platinum. An injection material was prepared.

This injection material was injected through a catheter into a balloon serving as an intraocular lens body previously inserted into a rabbit eye from which the lens capsule had been removed while leaving the capsule. The injection material cured at 37 ° C. in a few hours.

Next, when the intraocular lens was extracted and observed, there was evidence that the injection material had leaked from the injection port, and wrinkles were recognized on the balloon surface, and satisfactory optical performance could not be obtained.

As is clear from the above results, the composition for forming an intraocular lens according to the present invention has photocurability, so it is easy to inject with low viscosity at the time of injection, and is cured within several minutes using light after injection. As a result, the injected material does not leak from the injection port, and an intraocular lens having a desired shape can be obtained. When a silicone-based monomer is used, it can be directly injected into the lens capsule, while when a balloon body is used, a photopolymerizable monomer can be freely selected. .

In addition, the light source used for polymerization may be a halogen lamp, a tungsten lamp, or the like, which is generally used for eye surgery and does not contain much light having a wavelength of less than 340 nm, which is detrimental to the eyes. Is what it is.

Claims (3)

(57) [Claims] An intraocular lens-forming composition comprising a photopolymerizable monomer and a photoinitiator, which is polymerized in the eye to give a desired intraocular lens. 2. The composition for forming an intraocular lens according to claim 1, wherein the photopolymerizable monomer is a silicone-based monomer and is directly injected into a lens capsule in an eye. 3. The composition for forming an intraocular lens according to claim 1, wherein the composition is injected into a balloon housed in a capsular bag of the eye.