JPH0613453B2 - Anterior chamber injection for anterior segment surgery - Google Patents

Description

TECHNICAL FIELD The present invention relates to an anterior chamber injection for anterior segment surgery.

[Conventional technology]

In recent years, by performing an operation by injecting a viscoelastic hyaluronate preparation into the anterior chamber during anterior segment surgery, such as cataract surgery, glaucoma surgery, corneal transplant, artificial intraocular lens transplant, etc. It is generally used because it can prevent damage to the tissue surface, can safely and reliably perform procedures such as suturing, and can prevent adhesions after surgery.

However, currently hyaluronate is relatively expensive because it is mainly extracted from chicken crown, vitreous body, etc., and high-purity hyaluronate that is preferably used is the protein contained in the raw material. It is more expensive because it is difficult to remove.

In addition, when used as an anterior chamber injection for anterior segment surgery, the inside of the anterior segment is washed to remove hyaluronate after surgery, but hyaluronate that is not completely removed is anterior segment. However, it has a drawback that it often remains in the inside of the body, which often causes an increase in intraocular pressure after surgery.

Further, hyaluronic acid has a drawback that the sterilization treatment is difficult because the viscosity is reduced by heating.

On the other hand, chitin is contained in crustaceans such as shrimp and crabs, insects such as grasshoppers and beetles, and is widely distributed in nature, and purification is not so difficult, so high purity products are commercially available at relatively low prices. However, it cannot be used for anterior segment surgery because it is insoluble in water.

[Problems to be solved by the invention]

An object of the present invention is to provide an inexpensive anterior chamber injection for anterior segment surgery.

[Means for solving problems]

That is, the present invention relates to an anterior chamber injection for anterior segment surgery, which contains chitin carboxymethylated to be water-soluble.

Carboxymethylated chitin (hereinafter referred to as CM chitin) is obtained by using chitin as alkali chitin and reacting it with a monohalogenoacetic acid salt.

The degree of carboxymethyl substitution of CM chitin can be changed by changing the amount of monohalogenoacetate salt relative to chitin, but if the degree of substitution is too small, it will not dissolve in water, and if it is too large, the viscoelasticity of the aqueous solution will disappear. It is preferably in the range of 1.0 to 2.5 per saccharide residue.

The molecular weight of CM chitin depends on the molecular weight of the raw material chitin, but if the molecular weight is too small, the viscosity will decrease, so CM
The molecular weight of chitin is preferably 200,000 or more. The viscosity is preferably in the range of about 10,000 to 150,000 centistokes, and more preferably about 80,000 to 120,000 centistokes.

For physiological isotonicity, there is no significant difference in viscosity, whether it is isotonic with a non-electrolyte or isotonic with an electrolyte.
You can choose freely. Examples of the tonicity agent of the electrolyte include
Examples of the non-electrolyte tonicity agent include glycerin, ethylene glycol, glucose, mannose, sorbitose, and the like. In addition, a bactericide or the like may be added if necessary.

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to the examples.

〔Example〕

(Example 1) Powdered chitin (manufactured by Shin Nippon Chemical Co., Ltd., trade name Chitin-SS) was dispersed in 200 ml of 42% aqueous sodium hydroxide solution, and kept at room temperature under reduced pressure (20 mmHg) for 5 hours to allow alkali to permeate the chitin. . Then, after cooling with ice, 500 g of ice was gradually added and well stirred to obtain an alkaline chitin solution.

Add sodium monochloroacetate to this alkaline chitin solution.
What melt | dissolved 210 g in 240 g of water was dripped at 5 degreeC or less over 30 minutes, and after that, it was made to react at 5 degreeC or less for 5 hours, and normal temperature for 18 hours. The reaction product was neutralized with acetic acid, poured into ethanol to precipitate, and further washed with a solution of ethanol: water = 2: 1 and dried. After drying, reprecipitation purification was performed with ethanol as a 1.5% aqueous solution.

The obtained sodium salt of carboxymethyl chitin (hereinafter C
M chitin Na) as an aqueous solution, and the amount of sodium is measured by atomic absorption spectrometry to obtain monosaccharide residue 1
Carboxymethyl substitution degree per piece (hereinafter simply “substitution degree”)
Called. ) Was calculated, the degree of substitution was 2.12.

(Examples 2 to 3) In order to obtain CM chitin Na having different substitution degrees, the substitution degree of CM chitin Na was the same as in Example 1 except that the amounts of sodium monochloroacetate were changed to 57.4 g and 34.0 g, respectively. It was measured. The measurement result is the same as the measurement result of the first embodiment.
Shown in the table.

(Example 4) CM chitin Na obtained in Example 1 (hereinafter referred to as CM-1)
The CM chitin Na (hereinafter referred to as CM-3) obtained in Example 3 was dissolved in physiological saline, and the viscosity and osmotic pressure at various concentrations were measured. Also, as a comparison, sodium hyaluronate (trade name HA manufactured by QP Fine Chemyl Co., Ltd.
-S, hereinafter referred to as HA-S) in physiological saline,
Viscosity and osmolality at various concentrations were measured. The results are shown in Table 2. In the following, cst represents centistokes.

From this table, to obtain the same viscosity, CM with a high degree of substitution
Although it is necessary that the concentration of chitin Na is slightly higher than that of HA-S, CM chitin Na having a small degree of substitution may have a concentration almost equal to that of HA-S.

(Example 5) In order to confirm the self-degradability of the residue after the intraocular lavage after surgery, the time-dependent change in viscosity at a low concentration was measured. That is, C
M-1 was used as a 0.1% solution, and 0.05% HA-S was used for comparison and stored at 40 ° C., and the change in viscosity was observed. First result
Shown in the figure.

It can be seen that CM-1 has higher self-degradability than HA-S.

(Example 6) In order to confirm the safety of residues after intraocular lavage after surgery, a 0.1% aqueous solution of CM-1 and HA-S for comparison were compared.
The "test" of the "proliferation inhibition test of cultured cells" of the intraocular lens approval criteria (May 10, 1985, Yakuhin No. 489), using an extract as a 0.05% aqueous solution that has been sterilized by filtration with a 0.45μ Millipore filter. Method ”was used to measure the cell culture inhibition rate. The results were as follows.

0.1% CM-1 (stored at 40 ° C for 2 weeks) 10.8% 0.05% HA-S (stored at 40 ° C for 2 weeks) 13.3% The safety of the formulation remaining after washing after surgery is similar to or better than that of sodium hyaluronate The nature is high.

(Example 7) In order to investigate the decrease in viscosity due to heat sterilization, CM-1 and HA-S as a comparative example were dry heat sterilized at 170 ° C for 20 minutes in a dry state, and the viscosity of an aqueous solution before and after the sterilization treatment was measured. .
The results are shown in Table 3.

HA-S had a large decrease in viscosity, whereas CM chitin did not show a decrease in viscosity.

(Effects of the Invention) The CM chitin of the present invention is (1) an extremely inexpensive anterior chamber injection for anterior segment surgery.

(2) The tonicity agent can be freely selected. That is, since there is no difference in viscosity between the use of an electrolytic tonicity agent and the use of a non-electrolyte tonicity agent, both can be used.

(3) Since it decomposes faster than sodium hyaluronate, it is possible to minimize the increase in intraocular pressure after surgery.

(4) The safety of the formulation remaining after washing after surgery is the same as or higher than that of sodium hyaluronate.

(5) The viscosity does not decrease even after dry heat sterilization at 170 ° C for 20 minutes.

Such effects are recognized, and it is very effective as an anterior chamber injection for anterior segment surgery.

[Brief description of drawings]

FIG. 1 is a graph showing changes with time in viscosity of an aqueous sodium hyaluronate solution and an aqueous carboxymethylated chitin solution.

Claims (2)

[Claims] 1. An anterior chamber injection for anterior segment surgery, which contains carboxymethylated chitin. 2. The degree of carboxymethyl substitution of carboxymethylated chitin is 1.0 to 1 per monosaccharide residue.
The anterior chamber injection for anterior segment surgery according to claim 1, which is 2.5.