JPH10287570A - Curative promoter for keratopathy - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a curative promoter for keratopathy of high safety that can effectively promote the cure of keratopathy including refractory keratopathy by using a specific amino sugar as an active ingredient. SOLUTION: This curative promoter for keratopathy contains a glycosamine or its derivative or their pharmacologically acceptable salts as an active ingredient. The glycosamine is preferably glucosamine, galactosamine or mannosamine. The glycosamine derivative is preferably N-acylglycosamine, N-sulfated glycosamine derivative and the like. The addition of a substance such as uronic acid to the glycosamine or its derivatives promotes its effects. In addition, this promoter may contain a saccharide chain or its derivative or their salts having a glycosamine bearing a sulfate group or its derivative as a constitution unit.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a corneal disorder healing promoter.

[0002]

2. Description of the Related Art The cornea is composed of five layers: an epithelial cell layer, a Bowman's membrane, a stromal layer, a Descemet's membrane, and an endothelial cell layer. The epithelial cell layer of the cornea may be damaged by corneal herpes, trauma, acid, alkali, or the like, and the epithelial cell layer may be lost.
In such cases, usually, only passive treatments have been performed in which infection and desiccation are prevented and natural healing is expected by protecting from external stimuli. However, in many cases, the corneal disorder is prolonged, and in such cases, treatment with eye drops of fibronectin or a hyaluronate exhibiting an effect of promoting healing of the corneal disorder (Japanese Patent Publication No. 7-23317) has been attempted. Was. However, since fibronectin is unstable, it has been difficult to maintain its effect.

[0003]

For the above reasons, development of a highly safe corneal disorder healing promoter which effectively promotes the cure of corneal disorders including refractory corneal disorders is expected. .

[0004]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventor has found that glycosamine and its derivatives constituting glycosaminoglycans have an effect of promoting healing of corneal disorders. I came to admit. It has also been found that when a substance such as uronic acid is added to glycosamine or a derivative thereof, the effect of promoting corneal disorder healing is enhanced. Furthermore, when a sugar chain having glycosamine having a sulfate group or a monosaccharide that is a derivative thereof as a constituent monosaccharide was applied to corneal dysfunction, a remarkable healing promoting effect on corneal dysfunction was observed. Furthermore, the cell growth / extension promoting activity of glycosamine or a derivative thereof does not decrease even at a high concentration of the substance, and the effective concentration range is wide, so that it depends on the conditions at the time of administration (such as the amount of tear secretion). It was also recognized that the change in activity was small, and the present invention was completed.

That is, a first gist of the present invention is to provide a corneal disorder healing promoter containing glycosamine or a derivative thereof or a pharmacologically acceptable salt thereof as an active ingredient (hereinafter referred to as a corneal disorder healing promoter). 1)
In particular, it is a corneal disorder healing promoter that contains N-acylglycosamine or a derivative thereof as an active ingredient, and promotes cell proliferation and spread of corneal cells. By adding uronic acid or the like as a substance for enhancing the healing promoting effect to this, there is provided a corneal disorder healing promoting agent in which the healing promoting effect of glycosamine or a derivative thereof or a pharmacologically acceptable salt thereof is further enhanced. Is done.

A second gist of the present invention is that a sugar chain having glycosamine having a sulfate group or a derivative thereof as a constituent monosaccharide or a derivative thereof or a pharmacologically acceptable salt thereof is contained as an active ingredient. It is a corneal disorder healing promoter (hereinafter referred to as a corneal disorder healing promoter 2) and includes, for example, glycosamine having a sulfate group or a derivative thereof as a constituent monosaccharide, and uronic acid or galactose as another constituent monosaccharide. A healing promoter for corneal disorders containing, as an active ingredient, keratan sulfate, chondroitin sulfate, dermatan sulfate, heparin or heparan sulfate or a derivative thereof or a pharmacologically acceptable salt thereof.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the corneal disorder healing promoter of the present invention will be described in detail. (1) Corneal disorder healing promoter 1 The corneal disorder healing promoter 1 of the present invention contains glycosamine or a derivative thereof or a pharmacologically acceptable salt thereof as an active ingredient. Further, the composition may contain a substance promoting healing effect such as uronic acid.

[0008] 1. Glycosamine or a derivative thereof Glycosamine or a derivative thereof or a pharmacologically acceptable salt thereof contained in the corneal disorder healing promoter 1 of the present invention is obtained by modifying a functional group such as unmodified glycosamine or an amino group or a hydroxyl group. Glycosamine or a salt thereof, and is not limited as long as glycosamine or a derivative thereof constituting glycosaminoglycan (hereinafter, also referred to as GAG) or a pharmacologically acceptable salt thereof. Glycosamine includes, for example, glucosamine, galactosamine, mannosamine, etc. Among them, glucosamine is particularly preferred. As the form of modification as a derivative, those in which the amino group of glycosamine at the N-position is preferably modified, include N-acylglycosamine,
N-sulfated glycosamine and the like are preferred. As N-acylglycosamine, glycosamine modified with a lower acyl group having 1 to 6 carbon atoms is preferable, and N-acetylglycosamine is particularly preferable. For example, glucosamine which is a preferred form of glycosamine is modified with N-acetylglucosamine (hereinafter referred to as GI
cNAc) is preferred as a glycosamine derivative. Examples of the glycosamine salt include hydrochlorides and sulfates of the above-mentioned substances, and the hydrochloride is particularly preferable.

[0009] 2. Additive of corneal disorder healing promoter 1 The corneal disorder healing promoter 1 of the present invention enhances the corneal disorder healing promoting effect in addition to glycosamine or a derivative thereof or a pharmacologically acceptable salt thereof. Preferably, the substance comprises uronic acid or a derivative thereof or a pharmacologically acceptable salt thereof. As the uronic acid, hexuronic acid is preferable, and examples thereof include hexuronic acid constituting GAG, such as D-glucuronic acid and L-iduronic acid. D-glucuronic acid (hereinafter also referred to as GlcA) is particularly preferable. However, it is not limited to. Examples of the modified form of the uronic acid derivative include sulfated uronic acid and the like, such as 2-O-sulfated hexuronic acid and 3-O-sulfated hexuronic acid. Further, the pharmacologically acceptable salt includes, for example, a sodium salt, a potassium salt, a calcium salt, a barium salt, a magnesium salt and the like, preferably a sodium salt, and most preferably sodium D-glucuronate.

(2) Corneal disorder healing promoter 2 The corneal disorder healing promoter 2 of the present invention is a saccharide having glycosamine having a sulfate group or a derivative thereof (glycosamine or a derivative thereof is as defined above) as a constituent monosaccharide. A chain or a derivative thereof or a pharmacologically acceptable salt thereof is contained as an active ingredient.

1. Sugar Chain Since the sugar chain contained in the corneal disorder healing promoter 2 of the present invention has glycosamine having a sulfate group or a derivative thereof as a constituent monosaccharide, it is clearly distinguished from the sugar chain of hyaluronic acid. As the glycosamine derivative having a sulfate group contained in the sugar chain, N-sulfated glycosamine is preferable. Examples of such a substance include N-sulfated galactosamine and N-sulfated galactosamine.
Sulfated glucosamine and the like. Sugar chains containing these as constituent monosaccharides include, in addition to heparan sulfate and heparin, N-sulfated keratan sulfate obtained by de-N-acetylating keratan sulfate, chondroitin sulfate or dermatan sulfate and then N-sulfated, -Sulfated chondroitin sulfate or N-sulfated dermatan sulfate. As a method for de-N-acetylating the sugar chain, for example, Magn
us H., Johan R., and Ulf L., Anal.Biochem., 119,
236-245 (1982). The de-N-acetylated sugar chain obtained in this manner can be used, for example, in Lynn A. and Arther SP, Carbohydrate Res., 1
45, 267-277 (1986), by N-sulfation by a method applying the method of N-sulfated sugar chains. Of these sugar chains, heparan sulfate is particularly preferred.

Examples of the sugar chain derivative include a sugar chain in which a part of a sulfate group is desulfated, a sugar chain in which a sulfate group is added and persulfated, and a sugar chain in which a specific functional group is modified. However, a sugar chain obtained by desulfating some of the sulfate groups is preferred. Still further, pharmacologically acceptable salts of these sugar chains include, for example, sodium salts, potassium salts, calcium salts, barium salts, magnesium salts and the like,
Among them, a sodium salt is preferable.

The average molecular weight of the sugar chain contained in the corneal disorder healing promoter 2 of the present invention is preferably 10,000 or more, more preferably 20,000 to 40,000, and most preferably 25,000 to 35. , 000.

(3) Additives The above-mentioned corneal disorder healing promoters 1 and 2 of the present invention, in addition to the active ingredient, a substance having the same pharmacological effect as the active ingredient for the purpose of enhancing the pharmacological effect; By coexisting, a pharmaceutical composition can be obtained together with a substance showing the effect of enhancing the efficacy of the active ingredient, or a substance which is usually used pharmaceutically. For example, examples of a substance which exhibits an effect of enhancing its efficacy when coexisting with heparan sulfate include fibroblast growth factor, which is a growth factor, and fibronectin. As other additives, for example, mixed or combined administration of salts, preservatives, antibiotics, anti-inflammatory agents, and growth factors is also possible. As salts, for example, sodium sulfate, sodium chloride, sodium hydrogen phosphate, etc., as preservatives, for example, methyl paraoxybenzoate, propyl paraoxybenzoate, benzalkonium chloride, etc., and as antibiotics, for example, oxytetracycline, etc. Examples of the inflammatory agent include diclofenac and the like. Also,
Since the corneal disorder healing promoters 1 and 2 of the present invention are substances having high stability per se, formulation auxiliaries such as excipients and stabilizers used in producing ordinary pharmaceutical compositions are used. Can be used without any problem.

(4) Dosage Form The above-mentioned corneal disorder healing promoters 1 and 2 of the present invention are used as ophthalmic pharmaceutical preparations as long as they meet the purpose of the present invention.
It is used as a formulation that can be applied externally to the eye. For example, it can be used in the form of eye drops, eye ointments, etc., but preferably as an aqueous solution to which only the active ingredient or a substance for enhancing the effect of promoting the healing of the active ingredient (such as uronic acid described above) is added. An eye drop to be directly instilled or the aqueous solution can be used by being contained in the preparation for the affected area.
The concentration of glycosamine or a derivative thereof or a pharmacologically acceptable salt thereof when used as an aqueous solution is as follows:
The concentration is preferably 0.1 to 50 mg / ml, and when uronic acid or a derivative thereof or a pharmaceutically acceptable salt thereof is further contained, the concentration thereof is preferably 0.1 to 50 mg / ml.
It is 50 mg / ml. When the active ingredient is a sugar chain, its concentration is preferably 0.1 to 10 mg / ml. When used as eye drops, 1 to 10 times a day, 1 to 1 time
Three drops (approximately 0.05-0.2 ml) are used by instillation. A therapeutic contact lens or the like is preferably used as the affected part wearing agent, and a preferred therapeutic contact lens is, for example, a cross-linked hyaluronic acid obtained by crosslinking hyaluronic acid molecules using a cross-linking agent or the like, a cross-linking agent such as dermatan sulfate molecules. It is preferably made of a sustained-release material such as cross-linked dermatan sulfate cross-linked using, and the therapeutic contact lens contains the aqueous solution of the corneal disorder healing promoting agent through the contact lens. It is possible to administer a corneal disorder healing promoter to the affected area. The concentration of glycosamine or a derivative thereof or a pharmacologically acceptable salt thereof when the corneal disorder healing promoter of the present invention is used as an external preparation other than a liquid such as eye drops such as eye ointment is preferably used. Is 0.1 to 50 mg / g, and when it further contains uronic acid or a derivative thereof or a pharmaceutically acceptable salt thereof, the concentration is preferably 0.1 to 15 mg / g. When the active ingredient is a sugar chain, its concentration is preferably 0.1 to 5 mg / g.
When used as an external preparation other than eye drops such as eye ointment, it can be administered in 1 to 3 times a day.

(5) Indications The above-mentioned corneal disorder healing promoters 1 and 2 of the present invention are corneal disorders in mammals including humans, ie, dry eye, Sjogren's syndrome, Stevens Johnson. It is used as a drug that promotes healing of corneal disorders such as syndrome, punctate superficial keratitis (SPK), corneal epithelial erosion, corneal epithelial deficiency, and corneal ulcer, and as a drug administered locally to a disease site. There is no particular limitation on whether these diseases are endogenous diseases or exogenous diseases, and the corneal disorder healing promoters 1 and 2 of the present invention can be used. In addition, the corneal disorder healing promoter of the present invention can be used by adding to an affected part washing solution or the like used at the time of surgery in the art in order to promote early healing of a surgical wound by ophthalmic surgery.

(6) Toxicity The toxicity of glycosamine or a derivative thereof or a pharmacologically acceptable salt thereof, which is an active ingredient of the corneal disorder healing promoter 1 of the present invention, is extremely low. LD ₅₀ due to acute toxicity studies in mice GlcN · HCl, for example glucosamine hydrochloride is 150,000 oral administration
mg / kg or more, subcutaneous or intraperitoneal administration 6,200mg / kg or more, IV at 1,100 mg / kg or more, also, LD ₅₀ due to acute toxicity studies in rats GalN · HCl a hydrochloride salt of the galactosamine, 13 by subcutaneous or intraperitoneal administration
The LD ₅₀ of 5,000 mg / kg or more in the acute toxicity test of the substance in mice was 2,6 mg by subcutaneous or intraperitoneal administration.
It is known that it is 60 mg / kg or more. Since the concentrations of these active ingredients at the time of administration of the corneal disorder healing promoter 1 of the present invention are extremely low as compared with the above toxicity test values, they are the active ingredients of the corneal disorder healing promoter 1 of the present invention. It is clear that glycosamine or a derivative thereof has high safety.

The use of, for example, heparin or a derivative thereof or a pharmacologically acceptable salt thereof as the sugar chain of the active ingredient of the corneal disorder healing promoter 2 of the present invention is also highly safe. For example LD ₅₀ by an acute toxicity test in mice heparin, oral administration 5,000 mg / kg or more,
It is known that the dose is about 2,500 mg / kg or more by subcutaneous or intraperitoneal administration and about 1,000 mg / kg by intravenous injection. Even when heparin is used as an active ingredient of the corneal disorder healing promoter 2 of the present invention, the concentration at the time of application as the drug is extremely low as compared with the above values, and the safety is high. Heparan sulfate has a lower rate of sulfation than heparin, and therefore has a significantly reduced anticoagulant effect of heparin. Therefore, heparan sulfate was used as an active ingredient of the corneal disorder healing promoter 2 of the present invention. In some cases, the safety is even higher. The safety (toxicity and non-inflammatory properties) of heparan sulfate or its derivatives has already been confirmed (Kashima et al., Basic and Clinical, 23 , 6121 (1989); Inoue et al., Basic and Clinical, 23 , 6227 (1
998)). From these facts, it is apparent that heparan sulfate or a derivative thereof, which is a preferable active ingredient of the corneal disorder healing promoter 2 of the present invention, has high safety.

[0019]

EXAMPLES Examples of the present invention will be described below, but the present invention is not limited to these examples.

Test Example 1 Effect of N-acetylglucosamine (GlcNAc) and D-glucuronic acid (GlcA) on the growth of cultured cells derived from corneal epithelial cells 1 × 10 ⁴ rabbit corneal epithelial cells per well in a 96-well multiplate After culturing for 24 hours, the medium was replaced with a medium containing GlcNAc or GlcA at the concentration shown in Table 1, and culturing was continued for another 72 hours. Then, MT
50 μl of T solution (2 mg / ml) was added per well, and 5
After incubation for hours, MTT formazan was dissolved with 2-propanol. The absorbance at 550 nm was measured to determine the cell proliferation activity (Table 1, FIGS. 1 and 2). As a result, Gl
When cNAc was added, a remarkable cell growth promoting activity was observed.

[0021]

[Table 1]

The absorbance at 550 nm (OD) of 8 samples per group
550 nm) ± standard error (SE).

Test Example 2 Effects of Heparan Sulfate, GlcNAc and GlcA on Repair of Corneal Epithelium The effects of heparan sulfate, GlcNAc and GlcA on the repair of rabbit corneal epithelial wounds were examined. SPF grade JW using 8mm inner diameter trepan and micro scissors
The epithelium of the central part of the cornea of 70 female rabbits was peeled off, and 150 μl of the test substance was instilled into the left eye using the right eye as a control. As test substances, sodium heparan sulfate (HS) sodium (derived from bovine kidney: Seikagaku Corporation) 10 mg / ml (GlcNAc, GlcA, and Na ₂ S contained in sodium HS)
O ₄ amounts correspond to about 20 mM each), GlcNAc (Seikagaku Corporation) (4.4, 8.8, 17.6 and 35.
4 concentrations of 2mg / ml (20, 40, 80 and 160m respectively)
M)), and GlcA.Na (Aldrich Chemical Company.
Inc.) (4.6, 9.2, 1
4 concentrations of 8.4 and 36.8 mg / ml (20, 40, respectively)
80 and 160 mM)) in phosphate buffered saline (P
BS). PBS was used as a control. On the first day, the instillation was performed twice every three hours from one hour after the exfoliation, and on the second day, four times every three hours. Day 3
Instillation was carried out twice every hour. One hour after the exfoliation and three hours after the final instillation, the cells were stained with 0.2% sodium fluorescein dissolved in PBS and photographed under a purple light. The photograph taken by this method was analyzed using an image analyzer, and the area of the epithelial defect site was measured. The analysis results 1 hour after the exfoliation and 3 hours after the final instillation were compared, and the re-covered repair area was calculated. Compare the left and right eyes, there is a correspondence composed of the same number
Evaluation was performed by the student's t-test (Table 2, FIG. 3). As a result, a wound healing promoting effect was observed in GlcNAc, and when GlcNAc and GlcA were administered as a mixture,
It was observed that the wound healing promoting effect of GlcNAc was significantly enhanced.

[0024]

[Table 2]

Using 5 to 6 animals per group, the results were shown as the average (%) ± standard error (SE) of the promoting effect. However,
Glc contained in 1% sodium heparan sulfate (HS)
The amounts of NAc, GlcA, and Na ₂ SO ₄ correspond to about 20 mM each.

Test Example 3 Effect of heparan sulfate on repair of corneal epithelium The effect of heparan sulfate on repair of rabbit corneal injury was examined. Using 8mm inner diameter trepan and micro scissors,
The epithelium of the central part of the cornea of 12 SPF-grade JW female rabbits was exfoliated, and 150 μl of the test substance was instilled into the left eye using the right eye as a control. As a test substance, sodium heparan sulfate (HS) (from bovine kidney: Seikagaku Corporation)
A 10 mg / ml solution (dissolved in phosphate buffered saline (PBS)) was used. PBS was used as a control. 1
On the day, the eye was applied four times every three hours from one hour after peeling, and on the second day four times every three hours. On the third day, every 3 hours 2
Instilled. 1 hour after exfoliation and 3 hours after final instillation, PB
Stained with 0.2% sodium fluorescein dissolved in S and photographed under a purple light. The photograph taken by this method was analyzed using an image analyzer, and the area of the epithelial defect site was measured. The analysis results 1 hour after the exfoliation and 3 hours after the final instillation were compared, and the recoated area was calculated. While comparing the left and right eyes, the analysis results were compared, and evaluation was performed by the corresponding student's t-test composed of the same number (Table 3, FIG. 4). As a result, heparan sulfate was observed to have an effect of promoting healing of corneal disorders.

[0027]

[Table 3]

The average value (mm ² ) of the samples of 6 animals per group was used.
± Standard error (SE) is shown.

Test Example 4 Cell Proliferation Action in the Presence of Heparan Sulfate and Fibronectin Changes in the cell growth promotion action of heparan sulfate by fibronectin were examined. Fibronectin solution (30 μg / m
l) Normal rabbit corneal epithelial cells (Lot No. 35: International Reagent) were placed in a 96-well multiplate coated overnight with 50 μl / well and an uncoated 96-well multiplate.
The cells were sowed at a rate of 1 × 10 ⁴ per well, and after 24 hours, the medium was replaced with heparan sulfate (derived from bovine kidney: Seikagaku Corporation).
The medium was replaced with a medium containing 0, 1, 10, 100, or 1,000 μg / ml, and the culture was continued for another 48 hours. Then, [6
- ³ H] - 5 hours labeled thymidine 0.5 pCi / well, cells were lysed in NaOH of 0.5 N, the resulting solution was adsorbed to the glass fiber paper, the said paper at 5% trichloroacetic acid and ethanol Wash, ACS-II (Amersham)
Was added, and the radioactivity was measured with a liquid scintillation counter. The control group was a group without fibronectin-coated or uncoated heparan sulfate, and if the distribution was uniform by the F-test, the student's t-test was used. cochran t-
Statistical processing was performed using a test, and a significant difference test was performed (FIG. 5). As a result, under the uncoated condition of fibronectin, the proliferation of corneal epithelial cells was promoted at a heparan sulfate concentration of 10 μg / ml or more. In addition, under the condition of fibronectin coating, cell proliferation was promoted at a heparan sulfate concentration of 1 μg / ml or more, and the activity was more remarkable than in the uncoated condition.

Formulation Examples (1) Ophthalmic solution To 900 mg of sodium chloride, 26 mg of methyl paraoxybenzoate and 14 mg of propyl paraoxybenzoate, add 80 ml of sterilized purified water, dissolve by heating, return the solution to room temperature, and add 3,000 mg of GlcNAc. In addition, the mixture was dissolved, and sterilized purified water was added to make a total volume of 100 ml. 10 ml of this
Each was dispensed into a container to produce an eye drop. The amount of GlcNAc in the above eye drops was 500 mg, and 500 mg of GlcA was further added to produce eye drops. The eye drops were prepared by changing the GlcNAc of the above eye drops to 100 mg of sodium heparan sulfate. The GlcNAc of the above eye drops was changed to 100 mg of sodium heparan sulfate, and fibronectin 10 μm was further added.
g was added to produce eye drops. GlcNAc in the above eye drops was changed to 100 mg of sodium heparan sulfate, and fibroblast growth factor 10 was further added.
μg was added to produce eye drops.

(2) Ophthalmic ointment Purified lanolin (10 g) and yellow petrolatum (80 g) were combined and melted by heating, and an appropriate amount of liquid paraffin was added to make 100 g. The hot mixture was filtered through a filter paper using a warming funnel, and filtered.
Sterilized at ℃ for 1 hour. After returning the mixture to room temperature, G
3,000 mg of lcNAc and 100 mg of methyl parahydroxybenzoate as a preservative were added and mixed so as to be uniform. An ointment was produced by filling the mixture into containers in an amount of 10 g each. The amount of GlcNAc in the above ointment was 500 mg, and 500 mg of GlcA was further added to produce an ointment. An ointment was prepared by changing the GlcNAc of the above ointment to 100 mg of sodium heparan sulfate. The GlcNAc of the above ointment was changed to 100 mg of sodium heparan sulfate, and 10 μl of fibronectin was further added.
g was added to produce an ointment. GlcNAc in the above ointment was changed to 100 mg of sodium heparan sulfate, and fibroblast growth factor 10
An ointment was prepared by adding μg.

[0032]

EFFECT OF THE INVENTION The agent for promoting corneal disorder healing of the present invention
Healing of corneal disorders including intractable corneal disorders can be effectively and safely promoted.

[Brief description of the drawings]

BRIEF DESCRIPTION OF THE FIGURES FIG. 1. G vs. growth of cultured cells by MTT test.
2 shows the effect of lcNAc.

FIG. 2: G versus cell proliferation by MTT test
2 shows the effect of lcA.

FIG. 3. Heparan sulfate, and GlcNAc and Glc
A shows the corneal disorder healing promoting effect of A.

FIG. 4 shows the effect of heparan sulfate on the repair area.

FIG. 5 shows the effect of fibronectin on the cell growth promoting effect of heparan sulfate.

Claims (13)

[Claims] 1. A corneal disorder healing promoter comprising glycosamine or a derivative thereof or a pharmacologically acceptable salt thereof as an active ingredient. 2. The corneal disorder healing promoter according to claim 1, wherein the glycosamine is selected from glucosamine, galactosamine and mannosamine. 3. The glycosamine is glucosamine,
3. The corneal disorder healing promoter according to claim 2. 4. The corneal disorder healing promoter according to claim 1, wherein the glycosamine derivative is selected from N-acylglycosamine and N-sulfated glycosamine derivatives. 5. The agent for promoting healing of corneal disorders according to claim 4, wherein the glycosamine derivative is N-acylglycosamine. 6. The agent for promoting healing of corneal disorders according to claim 5, wherein the glycosamine derivative is N-acetylglycosamine. 7. A composition comprising, as a healing promoting effect-enhancing substance, uronic acid or a derivative thereof or a pharmacologically acceptable salt thereof, together with glycosamine or a derivative thereof or a pharmacologically acceptable salt thereof. Item 1
7. The agent for promoting healing of corneal disorder according to any one of items 6 to 6. 8. The corneal disorder healing promoter according to claim 7, wherein the uronic acid is glucuronic acid or iduronic acid. 9. A method for treating a corneal disorder, which comprises, as an active ingredient, a sugar chain or a derivative thereof having glycosamine or a derivative thereof having a sulfate group as a constituent monosaccharide, or a pharmacologically acceptable salt thereof. Accelerator. 10. The corneal disorder according to claim 9, wherein the sugar chain having glycosamine having a sulfate group or a derivative thereof as a constituent monosaccharide is a sugar chain having N-sulfated glycosamine as a constituent monosaccharide. Healing accelerator. 11. The agent for promoting healing of corneal disorders according to claim 10, wherein the sugar chain having N-sulfated glycosamine as a constituent monosaccharide is heparan sulfate. 12. A pharmaceutical composition comprising the corneal disorder healing promoter according to any one of claims 1 to 11 as an active ingredient. 13. The pharmaceutical composition according to claim 12, further comprising fibronectin as a substance having an effect of enhancing the efficacy of the corneal disorder healing promoter.