in order to examine the availability of the peptide , phsrn ( seq id no : 1 ), the present inventors examined the effects of the peptide , phsrn ( seq id no : 1 ), on corneal disorder . the details are indicated in the subsequent section on pharmacological tests . the present inventors have found that ophthalmic instillation of the peptide , phsrn ( seq id no : 1 ), provides ( 1 ) a corneal epithelium migration effect in a corneal organ culture system and ( 2 ) an effect of promoting wound healing after corneal epithelial abrasion . it has thereby become clear that the peptide , phsrn ( seq id no : 1 ), is available for the treatment of corneal disorder ( that is , corneal ulcer , corneal epithelial erosion , keratitis , dry eye , and other disorder wherein the cornea is damaged due to various causes and especially corneal epithelial erosion ) and dry eye . though preparation examples of this invention and the results of pharmacological tests shall now be described , the scope of the art of this invention is not limited to the embodiments described below and various modifications are possible without changing the gist of the invention . the scope of the art of this invention covers the scope of equivalents . as formulation 1 , an eye drop , containing 0 . 01 g of ac - pro - his - ser - arg - asn - nh 2 , 0 . 9 g of sodium chloride , and a suitable amount of sterilized purified water in a total amount of 100 ml , was prepared . in the same manner as formulation 1 , eye drops , respectively containing 0 . 00001 g , 0 . 00003 g , 0 . 0001 g , 0 . 0005 g , 0 . 001 g , 0 . 005 g , 0 . 05 g , and 0 . 1 g of ac - pro - his - ser - arg - asn - nh 2 in a total amount of 100 ml , were prepared . as formulation 2 , an eye drop , containing 0 . 1 g of ac - pro - his - ser - arg - asn - nh 2 , 0 . 8 g of sodium chloride , 0 . 1 g of sodium hydrogen phosphate , a suitable amount of sodium dihydrogen phosphate , and a suitable amount of sterilized purified water in a total amount of 100 ml , was prepared . in the same manner as formulation 2 , eye drops , respectively containing 0 . 00001 g , 0 . 00003 g , 0 . 0001 g , 0 . 0005 g , 0 . 001 g , 0 . 005 g , 0 . 05 g , and 0 . 1 g of ac - pro - his - ser - arg - asn - nh 2 in a total amount of 100 ml , were prepared . as formulation 3 , an eye ointment , containing 0 . 05 g of ac - pro - his - ser - arg - asn - nh 2 , 90 g of white petrolatum , and a suitable amount of liquid paraffin in a total amount of 100 g , was prepared . in the same manner as formulation 3 , eye ointments , respectively containing 0 . 00001 g , 0 . 00003 g , 0 . 0001 g , 0 . 0005 g , 0 . 001 g , 0 . 005 g , 0 . 05 g , and 0 . 1 g of ac - pro - his - ser - arg - asn - nh 2 in a total amount of 100 g , were prepared . ac - pro - his - ser - arg - asn - nh 2 was synthesized by a solid phase method . using this compound , ( 1 ) the in vitro corneal epithelium migrating action and ( 2 ) in vivo corneal wound healing promotion action were examined . the detailed data are indicated in the section on pharmacological tests . in comparison to the control groups , migration of corneal epithelial cell layers and quick healing of corneal wounds were exhibited clearly by the groups to which ac - pro - his - ser - arg - asn - nh 2 was added . it was thus proved that ac - pro - his - ser - arg - asn - nh 2 is effective as a treatment agent for corneal disorder . using the cornea of male japanese white rabbits , the effects on corneal epithelium migration were examined using the migrating length of the corneal epithelium in a corneal organ culture system as an index in accordance with the method of nishida et al . ( j . cell . biol ., 97 , pp . 1653 - 1657 ( 1983 )). corneal blocks ( three per group ) were cutout from rabbit corneal tissue . these corneal blocks were incubated for 20 hours under the conditions of 37 ° c . and 5 % co 2 in a culture medium ( medium - 199 ) containing the test compound . after incubation , the corneal blocks were fixed in a mixed solution of ethanol and glacial acetic acid ( volume ratio of 95 : 5 ), embedded in paraffin , and prepared as sections . after deparaffination , the sections were stained with hematoxylin - eosin and the migrating length of the epithelial cell layer was measured under a microscope . as a control , corneal blocks incubated in a culture medium that does not contain the test compound was used . as shown in fig1 , incubation in a medium containing ac - pro - his - ser - arg - asn - nh 2 exhibited significant promotion of the migration of corneal epithelium . using a male japanese white rabbit , a wound of approximately 6 mm in diameter was produced in the cornea by inducing corneal epithelial abrasion in accordance with the method of cintron et al . ( ophthalmic res ., 11 , pp . 90 - 96 ( 1979 )). the wound area was measured using the fluorescein - stained area as an index . the effects of the test compound on corneal wound healing were examined . the eye drops containing the respective concentrations of the test compound were instilled ( 30 μl at a time ) at 0 , 3 , 6 , 9 , 12 , 18 , 24 , 27 , 30 , 33 , 36 , 42 , and 48 hours after inducing corneal epithelial abrasion . in measuring the wound area , fluorescein staining was carried out and a photograph of the cornea was measured . the fluorescein - stained area of the photographed cornea was computed using an image analysis processing system . as a control , a rabbit instilled with the base agent ( pbs ) that does not contain the test compound was used . tables 1 and 2 below show the post - treatment effects of ac - pro - his - ser - arg - asn - nh 2 ( phsrn ( seq id no : 1 )) on a rabbit corneal wound model in the form of healing ratio . as shown in tables 1 and 2 , the instillation of the peptide , phsrn ( seq id no : 1 ), exhibited significant promotion of wound healing . in tables 1 and 2 , the respective values indicate the mean value ± standard deviation ( n = 6 ). statistical analysis was carried out using dunnett &# 39 ; s multiple comparison with respect to pbs with the area of the corneal wound portion immediately after ( 0 hours after ) corneal epithelial abrasion being set to 100 % (* p & lt ; 0 . 05 , ** p & lt ; 0 . 01 ; vs . control ). using the same method as ( 2 ) above , corneal epithelial abrasion was induced in a japanese white rabbit to produce a wound of approximately 8 mm in diameter in the cornea . the wound area was measured using the fluorescein - stained area as an index to examine the effects on corneal wound healing . the eye drops containing the respective concentrations of the test compound were instilled ( 25 μl at a time ) at 0 , 6 , 12 , 18 , 24 , 30 , 36 , 42 , 48 , and 54 hours after induction corneal epithelial abrasion . in measuring the wound area , fluorescein staining was carried out and a photograph of the cornea was measured . the fluorescein - stained area of the photographed cornea was computed using an image analysis processing system . as a control , a rabbit instilled with the base agent ( physiological saline ) that does not contain the test compound was used . tables 3 and 4 below show the post - treatment effects of ac - pro - his - ser - arg - asn - nh 2 ( phsrn ( seq id no : 1 )) on a rabbit corneal wound model in the form of healing ratio . as shown in tables 3 and 4 , the instillation of the peptide , phsrn ( seq id no : 1 ), exhibited significant promotion of wound healing . in tables 3 and 4 , the respective values indicate the mean value ± standard deviation ( n = 6 ). statistical analysis was carried out using dunnett &# 39 ; s multiple comparison with respect to physiological saline with the area of the corneal wound portion immediately after ( 0 hours after ) corneal epithelial abrasion being set to 100 % (* p & lt ; 0 . 05 , ** p & lt ; 0 . 01 ; vs . control ). the above pharmacological tests show that the peptide , phsrn ( seq id no : 1 ), which is the minimum activity expression site of fibronectin , exhibits a wound healing promotion action on corneal epithelim and is available as either or both of a preventive agent and a treatment agent for corneal ulcer , corneal epithelial erosion , keratitis , dry eye , etc ., wherein the cornea is subject to damage due to any of various causes .
an object is to find the minimum activity expression site of fibronectin , clarify the actions of this minimum unit in relation to opthalmological fields , and provide an opthalmological composition having this minimum unit as an effective component . this invention provides an opthalmological composition , in particular , a corneal disorder treatment agent containing the peptide , phsrn ), or ac - pro - his - ser - arg - asn - nh 2 , which is a derivative thereof , or a salt thereof that is allowable as a medical drug as an effective component . the preferred dosage form is an ophthalmic formulation .