JPS63220866A - Vitreous body humor - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a vitreous replacement fluid, and more particularly to a vitreous replacement fluid that can be used as a substitute for or as a supplement to the vitreous humor of the eyeball.

The vitreous replacement fluid of the present invention can be used in the extraction of the crystalline lens in the treatment of cataracts, the insertion of artificial lenses after the extraction of the crystalline lens, and other ocular surgical operations.

[Technical background and explanation of conventional technology]

The space between the crystalline lens, ciliary body, and mesentery of the eyeball is filled with a completely transparent, water-rich, soft, semi-liquid vitreous body. The vitreous body is thin and transparent.

It is composed of various connective tissue cells and vitreous humor, which contains mucoids, urea, glucose, and various inorganic salts in addition to small amounts of protein.

(Kyoritsu Shuppan Co., Ltd., Chemistry Dictionary J Vol. 4, "Vitreous Body") Opacification may occur in the vitreous body of the eye, and treatments such as vitreous aspiration and intravitreal injection of anterior aqueous humor may be necessary to treat this. Surgical operations on the eyeballs ("Vitreous opacification", p. 970 of the Medical Dictionary, published by Nanzando) are performed, and in order to treat cataracts that cause clouding of the crystalline lens of the eye, the cloudy lens is removed from Surgical surgery to remove the crystalline lens (Nanzando Medical Dictionary, No. 1670 W, "Cataract"), surgical surgery to insert an artificial lens after removing the crystalline lens, and lens cleavage to create a path for light through the opacity of the crystalline lens. Surgical operations on the eyeballs of the law (published by Nanzando, Medical Dictionary, No. 1100m)
The lens cutting method) is being performed.

Recently, when performing surgery on the eyeball, a highly viscous solution that does not cause inflammation or immunological rejection is injected into the eyeball to prevent tissue damage and undesirable adhesions after surgery (viscosurgery). ) is being attempted.

On the other hand, chitin is a polysaccharide obtained from the shells of crustaceans such as shrimp and crabs. Chitosan is a deacetylated polyadhesive of chitin.

It has been proposed to coat wounds with a lyophilized solution of chitosan to promote the recovery of tissue destroyed by the wound. (Patent Application No. 59-261807) The present inventors have been conducting research on chitin and chitosan for many years, but
In this research, it was found that chitin and chitosan are easily compatible with living organisms, and that no trouble occurs when they come into contact with living tissue, and that 〇-carboxyalkyl chitin has a high viscosity and does not come in contact with living tissue. It was also discovered that a solution can be formed that does not cause troubles such as rejection reactions, and the present invention was achieved based on these findings.

[Object of the invention and summary of the invention]

An object of the present invention is to provide a vitreous replacement fluid that can be injected into the eyeball. Specifically, it is transparent, does not cause trouble due to contact with living bodies, and can be used in eyeball treatment and surgery. The objective is to provide a vitreous replacement fluid that can be used.

The present invention is a vitreous humor collection fluid containing 0-carboxyalkyl chitin as an active ingredient, which is dissolved in a physiologically harmless solvent.

As the 0-carboxyalkyl chitin in the vitreous fluid of the present invention, a substance represented by the above general formula (T) can be used, and as the 0-carboxyalkyl chitin, 0-carboxymethyl chitin can be used. is possible,
Further, the degree of substitution by carboxyalkyl in 0-carboxyalkyl chitin is 0.5 or more (preferably 0.6
~0.9) can be used, and physiologically harmless solvents such as physiological saline or phosphate buffered physiological saline solution (pH: 7.4) can be used.

[Detailed description of the invention]

The 0-carboxyalkyl chitin in the vitreous fluid of the present invention is produced by chemically modifying the hydroxyl group of the carbon atom at the 6-position of chitin obtained from the shells of crustaceans such as shrimp and crabs with haloalkylcarboxylic acids or salts thereof. In the chemical modification, the degree of substitution of chitin by haloalkylcarboxylic acid is preferably 0.5 or more, more preferably 0.6 to 0.9.

It is preferable to use a haloalkylcarboxylic acid having 2 to 10 carbon atoms, and it is more preferable to use a halomethylcarboxylic acid such as monochloroacetic acid.

The vitreous fluid of the present invention is made by dissolving 〇-carboxyalkyl chitin in a physiologically harmless solvent. Components contained in body fluids can also be added, thereby making the vitreous replacement fluid physiologically compatible.

Any solvent can be used to dissolve 0-carboxyalkyl chitin as long as it is not physiologically harmful and can form a transparent solution, but physiological saline or Preferably, a phosphate 51WF physiological saline solution (pH near, 4) is used.

O-carboxyalkyl chitin can be dissolved in a physiologically harmless solvent at any concentration that is not physiologically harmful, but is preferably dissolved at a concentration of 1 to 5%.

The vitreous replacement fluid of the present invention can be injected into the eyeball during eye surgery, thereby preventing tissue damage within the eyeball, and can also prevent the occurrence of adhesions after surgery. separation of tissues can be ensured.

For example, it is suitable for use in cataract surgery, surgery for removing the crystalline lens, surgery for inserting an artificial lens into the eyeball, or surgery for drilling into the cloudy part of the crystalline lens.

The vitreous replacement fluid of the present invention can be injected into the eyeball in the treatment of eye diseases. For example, in the treatment of vitreous opacity, when the vitreous fluid of the present invention is injected into the eyeball, the vitreous opacity disappears and recovery of visual acuity is promoted. When the vitreous fluid of the invention is injected into the eyeball, it can promote the disappearance of bleeding and promote the recovery of visual acuity. Therefore, it can be used for the treatment of systemic diseases accompanied by vitreous hemorrhage, such as vitreous hemorrhage, kidney disease, or third stage spirochete.

EXAMPLES Below, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples.

Example 1 (Preparation of chitin) Pulverized product of red snow crab shell 10 and 9 in 5% hydrochloric acid + 00
After stirring for 5 hours at room temperature, the supernatant liquid was separated and removed, and the solid residue was washed with water.

Add this solid to a 5% aqueous sodium hydroxide solution +007! After heating to 90°C for 2.5 hours with stirring, the supernatant was removed, the residual solid was washed with water, and the
Drying at 5°C gave chitin 2.3 to 9.

(Preparation of 0-lupoxymethyl chitin) 10 g of chitin was mixed with 42% (v/v) containing 0.2% sodium dodecyl sulfate.
v) The mixture was added to 200 ml of aqueous sodium hydroxide solution and stirred at room temperature under reduced pressure all day and night.

The residue was filtered using glass filter paper and a small amount of 42% (v/
v) Washed with aqueous sodium hydroxide solution.

It was transferred to a beaker, 150 g of crushed ice was added, and the mixture was thoroughly mixed in an ice water bath until it became a highly viscous alkaline chitin. Then, 25% (w/w) sodium hydroxide water solution was added and mixed well to adjust the final concentration of sodium hydroxide to 4% (v/v). Monochloroacetic acid 1 while cooling in an ice water bath.
7. Gradually add 69 dissolved in 18 liters of water to 30
After being left for 24 hours at room temperature.

Then, 20-acetic anhydride was added while cooling with water. After neutralization, dialysis was performed against ion-exchanged water for 4 days, and the dialysate was concentrated using a rotary evaporator and freeze-dried in vacuum to obtain 0-carboxymethyl chitin of ++ and ag. The degree of substitution of the carboxymethyl group in this 0-carboxymethyl chitin was 0.9.

(tMi of 0-carboxymethyl chitin solution!!) 9 g of 0-carboxymethyl chitin obtained above was added to 20
mmol of Na HPO and 150 +u+ol of NaC
A 1.5% solution was obtained by dissolving it in a phosphate buffered physiological saline solution of pH 77.4 containing 1 to give a concentration of 600%.

This physiological saline solution had a viscosity of 51,200 centivoices, was clear, and did not contain pyrogens.

When the viscous, transparent, pyrogen-free 0-carboxymethyl chitin solution prepared in this way was injected into the anterior chamber of the rabbit eye, it remained transparent and showed minimal inflammatory reactions. It was demonstrated that it is useful as a vitreous substitute.

Example 2 (Preparation of 0-carboxyethyl chitin) Chitin log was converted to 42% (V/
V) The mixture was added to 200 ml of aqueous sodium hydroxide solution and stirred for one day at room temperature under reduced pressure.

Filter using glass filter paper and remove the residue with a small amount of 42% (V/
V) Washed with an aqueous sodium hydroxide solution.

It was transferred to a beaker, 150 g of crushed ice was added, and the mixture was thoroughly mixed in an ice water bath until it became a highly viscous alkaline chitin. Then, 280% of a 25% (V/V) aqueous sodium hydroxide solution was added and mixed well, so that the final concentration of sodium hydroxide was adjusted to 14% (1/1). While cooling this solution in an ice water bath, a solution of 20.29 .beta.-chloropropionic acid dissolved in 21.degree. of water was gradually added, and the mixture was left to stand for 30 minutes, and then left to stand at room temperature for 24 hours.

Then, while cooling with water, 2 (1 mjl) of acetic anhydride was added. After neutralization, dialysis was performed against ion-exchanged water for 4 days.
The dialysate was concentrated using a rotary evaporator and freeze-dried in vacuum to obtain 11.3 JF of 0-carboxyethyl chitin. The degree of substitution of the carboxyethyl group in this 0-carboxyethyl chitin was 0.89.

(Preparation of 0-carboxyethyl chitin solution) 0-carboxyethyl chitin 9I obtained above was added to 20 mmo
pH: 7.4 phosphate-buffered saline containing 1 Na HPO and 150 mmol NaCl
A 1.5% solution was obtained by dissolving the solution to a concentration of 0 d.

The viscosity of this physiological saline solution was 4,300 centipoise, clear and pyrogen-free.

When the viscous, transparent, pyrogen-free 0-carboxyethyl chitin solution prepared in this way was injected into the anterior chamber of the rabbit eye, it remained transparent and showed minimal inflammatory reactions. It was demonstrated that it is useful as a vitreous substitute.

〔Effect of the invention〕

According to the present invention, in the 0-carboxyalkyl chitin solution, the carboxyalkyl group of 0-carboxyalkyl chitin is mainly substituted at C at the 6-position, but the degree of substitution is 0.
．． 5 or more and 1-5% (by weight) in buffered physiological saline solution
It is isotropic, transparent, viscous, and contains no pyrogenic substances, making it useful in surgical operations in the field of ophthalmology.

Further, according to the present invention, the viscous solution is made by dissolving 0-carboxyalkyl chitin in a buffered physiological saline solution at a concentration of 1 to 5% (by weight), and is made to maintain a transparent state in the eyeball. Therefore, a material useful as a vitreous substitute can be obtained.

6 to 1 good chemistry 17/L Sue

Claims (5)

[Claims] (1) General formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ In formula (I), R is -(CH_2)_n・COO
H, (n is a positive integer of 1 or more) or -H. A vitreous replacement fluid comprising O-carboxyalkyl chitin having the repeating unit shown in the following as an active ingredient, the O-carboxyalkyl chitin being dissolved in a physiologically harmless solvent. (2) The vitreous replacement fluid according to claim 1, wherein in the O-carboxyalkyl chitin, n in R in formula (I) is 1 to 9. (3) The vitreous replacement fluid according to claim 1 or 2, wherein the O-carboxyalkyl chitin is O-carboxymethyl chitin. (4) O-carboxyalkyl chitin, -(CH_2)_nCOOH/-H in R of formula (I) is 6/4
The vitreous replacement fluid according to any one of claims 1 to 3, characterized in that the vitreous replacement fluid has a molecular weight of 9/1 to 9/1. (5) The method according to any one of claims 1 to 4, wherein the physiologically harmless solvent is a phosphate buffered physiological saline solution (pH: 7.4). Vitreous fluid replacement.