It is said that patients who are receiving dialysis treatment for renal failure caused by deterioration or loss of kidney function are now about 220,000 in Japan, and about 95% of the aforementioned patients are receiving hemodialysis treatment using an extracorporeal blood circulation system, and remaining 5% of the patients are receiving peritoneal dialysis. In the case of medical treatment by hemodialysis, generally, the patient needs to remove waste products from exteriorized blood about 3 times a week spending almost 4 hours for 1 cure in the specialty hospital, and therefore, time constraints to the patient is strong. On the other hand, in the peritoneal dialysis, a catheter is embedded in the abdomen of the patient in advance, and a hypertonic dialysis fluid is introduced and stored through the aforementioned catheter in the inside of the abdominal cavity surrounded by the peritoneal membrane which covers internal organs such as the stomach and the intestine; this generates a difference in osmotic pressure between the stored dialysis fluid and the body fluid, and through the use of this osmotic pressure difference, excess water and waste products in the body are transferred to the peritoneal dialysis fluid in the abdominal cavity from the peritoneal capillary vessel. Therefore, since the medical treatment by peritoneal dialysis does not require a device for blood exteriorization as compared with hemodialysis, the burden on patients is low from the viewpoint of the “quality of life”.
However, the patient who is receiving peritoneal dialysis treatment may develop encapsulating peritoneal sclerosis (EPS), peritoneal sclerosis, or peritoneal fibrosis and the like which are known as a general term of disorder of peritoneal membrane thickening. Cause of the peritoneal membrane thickening has not been clarified to date, however, for example, on the basis of assumption that neoangiogenesis may be involved in the peritoneal membrane thickening from the fact that abnormalities of blood vessel and increased number of blood vessel are observed in the thickened peritoneal tissue, and that vascular endothelial growth factor (VEGF) is present in high concentration in the intra-abdominal fluid of patients who is receiving peritoneal dialysis treatment, a study on the inhibition of peritoneal membrane thickening by administrating TNP-470 that is an agent for inhibiting vascular endothelial growth factor (VEGF) which is a growth factor having an action to facilitate neoangiogenesis has been reported in Non-Patent Literature 1. According to this study, by the administration of TNP-470, inhibition of neoangiogenesis and suppression of myofibroblastic cell proliferation have been reported.
In addition, in Non-Patent Literature 2, it has been reported to the effect that the expression of molecular chaperon Hsp47 specific for collagen is a cause of the peritoneal membrane thickening, and type I and type III collagen are produced when the Hsp47 is expressed in mesothelial cell and actin-positive cell. Furthermore, as an invention for inhibiting the peritoneal membrane thickening in relation to this report, there is Patent Literature 1. Patent Literature 1 describes that after the peritoneal membrane thickening is produced in rat by inoculating chlorhexidine gluconate in the abdominal cavity in advance, an oligonucleotide is administered as a substance of inhibiting Hsp47 in the abdominal cavity.
In addition, as a technology focused on the relationship between the above-described abnormal production of collagen and neoangiogenesis, for example, an invention on suppressing production of collagen as shown in Patent Literature 2 is included. In the invention of the aforementioned Patent Literature 2, in addition to inhibiting the peritoneal membrane thickening by administration of a medical drug which inhibits vascular endothelial growth factor (VEGF) by the reason that neoangiogenesis maybe involved in the peritoneal membrane thickening as shown in the above-described Non-Patent Literature 1, based on the report describing that the collagen synthesis in extracellular skeleton such as basal membrane plays an important role in neoangiogenesis (Maragoudakis, E., Sarmonika, M., and Panoutsacopoulous, M., J. Pharmacol. Exp. Ther., 244:729, 1988; Ingber, D. E., Madri, J. A., and Folkman, J., Endocrinology, 199:1768, 1986), it was confirmed that a glycoprotein complex derived from Basidiomycete belonging to Trametes versicolor inhibited specifically the synthesis of Hsp47 in the tissue cell of pathological condition. According to this invention, it has been described to the effect that the glycoprotein complex inhibits not only fibrosis and hardening of organ and tissue, but the above-described metastasis of cancer can also be suppressed since it has been clarified that the stroma which is constituted by type I collagen and fibronectin as a basic skeleton plays a role of guide in leading a released cancer cell to invasion into adjacent vascular channel in cancer metastasis.
Furthermore, in Non-Patent Literature 3, it has been reported that the chlorhexidine-induced peritoneal lesion is remitted by administration of ganciclovir which is an antiviral drug, describing to the effect that after the peritoneal membrane thickening is produced in mouse by administrating chlorhexidine in the abdominal cavity previousely, and the peritoneal membrane thickening is alleviated when the ganciclovir is infused into the abdominal cavity in 2 weeks.