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EP-3590547-B1 - COMPOSITION FOR TREATING FIBROCARTILAGE TISSUE DAMAGE

EP3590547B1EP 3590547 B1EP3590547 B1EP 3590547B1EP-3590547-B1

Inventors

  • KONDO, EIJI
  • IWASAKI, NORIMASA
  • ONODERA, TOMOHIRO
  • KIM, WOOYOUNG
  • KAWAGUCHI, YASUYUKI

Dates

Publication Date
20260506
Application Date
20180301

Claims (15)

  1. A composition for use in treating a meniscus injury, wherein the composition is to be applied to an injured part of the meniscus comprising an injury caused in an avascular area of the meniscus of a target, has fluidity or is flaky or powdery when applied to the injured part of the meniscus, comprises a monovalent metal salt of alginic acid, and is free of cells.
  2. The composition for use in treating a meniscus injury according to claim 1, wherein the monovalent metal salt of alginic acid is a low endotoxin monovalent metal salt of alginic acid.
  3. The composition for use in treating a meniscus injury according to claim 1 or 2, wherein (i) the timing of applying the composition to the injured part of the meniscus comprising an injury caused in an avascular area of the meniscus is the timing of bringing the composition into contact with the injured meniscus comprising an avascular area of the meniscus; and/or (ii) the composition having fluidity is used so as to be at least partially cured after the application to the injured part of the meniscus comprising an injury caused in an avascular area of the meniscus.
  4. The composition for use in treating a meniscus injury according to any one of claims 1 to 3, wherein (i) the composition having fluidity is cured by bringing a crosslinking agent into contact with at least a part of the surface of the composition; and/or (ii) the apparent viscosity of the composition having fluidity is 100 mPa·s to 30000 mPa·s as measured as average apparent viscosity value with a cone-plate viscometer under a condition of a 2% aqueous solution at 20 o C for 0.5 to 2.5 min; and/or (iii) the weight-average molecular weight (absolute molecular weight) of the monovalent metal salt of alginic acid is 30,000 or more as measured by a GPC-MALS method; and/or (iv) the concentration of the monovalent metal salt of alginic acid in the composition having fluidity is 0.1 w/w% to 5 w/w%.
  5. The composition for use in treating a meniscus injury according to claim 3 or 4, wherein (i) the composition having fluidity does not contain the crosslinking agent in an amount that allows curing of the composition upon making contact with the injured part of the meniscus comprising an injury caused in an avascular area of the meniscus of the target; and/or (ii) the composition having fluidity is brought into contact with the crosslinking agent for curing the composition, after application of the composition to the injured part of the meniscus comprising an injury caused in an avascular area of the meniscus of the target.
  6. The composition for use in treating a meniscus injury according to any one of claims 1 to 5, wherein the composition having fluidity has fluidity that allows injection with a 21G needle after leaving the composition to stand at 20 °C for an hour.
  7. The composition for use in treating a meniscus injury according to any one of claims 4 to 6, wherein the crosslinking agent is a divalent or higher valent metal ion compound.
  8. The composition for use in treating a meniscus injury according to any one of claims 1 to 7, wherein the meniscus injury is at least one condition or disease selected from a meniscus injury, a traumatic meniscus injury, a degenerative meniscus, a discoid meniscus, and/or a sports injury.
  9. The composition for use in treating a meniscus injury according to any one of claims 1 to 8, wherein the injured meniscus comprising an injury caused in an avascular area of the meniscus is a sutured injured meniscus comprising an injury caused in an avascular area of the meniscus
  10. The composition for use in treating a meniscus injury according to any one of claims 1 to 9, wherein the composition is applied to the injured part of the meniscus comprising an injury caused in an avascular area of the meniscus in combination with suturing.
  11. The composition for use in treating a meniscus injury according to any one of claims 1 to 10, wherein the composition is in a dry state or a solution state before being applied to the injured part of the meniscus comprising an injury caused in an avascular area of the meniscus, preferably the composition in a dry state is a lyophilizate.
  12. The composition for use in treating a meniscus injury according to any one of claims 1 to 11, which is used for treating an injured part of the meniscus comprising an injury caused in an avascular area of the meniscus, the method comprising the steps of: (a) enabling visual recognition of the injured part of the meniscus comprising an injury caused in an avascular area of the meniscus through an incision or with an arthroscope or an endoscope; (b) if necessary, removing an unnecessary tissue from the injured part of the meniscus comprising an injury caused in an avascular area of the meniscus and the peripheral part thereof; (c) if necessary, suturing the injured part of the meniscus comprising an injury caused in an avascular area of the meniscus; (d) applying the composition containing the monovalent metal salt of alginic acid to the injured part of the meniscus comprising an injury caused in an avascular area of the meniscus; (e) if necessary, adding a crosslinking agent to the surface of the applied composition, and leaving the resultant for a predetermined period of time to bring the composition into contact with the crosslinking agent; (f) if necessary, washing the site where the crosslinking agent had been added; and (g) if necessary, closing the incision or the opening resulting from insertion of the arthroscope, the endoscope or other instrument.
  13. The composition for use in treating a meniscus injury according to any one of claims 1 to 12, wherein the composition is free of growth factors.
  14. A kit for use in treating an injured part of a meniscus comprising an injury caused in an avascular area of the meniscus, said kit comprising at least the composition according to any one of claims 1 to 13.
  15. A low endotoxin monovalent metal salt of alginic acid for use in treating a meniscus injury, wherein the low endotoxin monovalent metal salt is applied to an injured part of the meniscus comprising an injury caused in an avascular area of the meniscus of a target and is not used in combination with cells.

Description

TECHNICAL FIELD The present invention relates to a composition for use in treating an injury in a avascular area of a meniscus. The present invention also relates to a kit for use in treating an injury in an avascular area of a meniscus. BACKGROUND ART In the knee joint, or the wrist joint , there is tissue referred to as the meniscus or the articular disc that is arranged to make up for the space between the opposing articular cartilage surfaces. In particular, the meniscus in the knee joint is a fibrocartilage between the femur and the tibia, which is mainly a fibrous tissue. The meniscus serves as a cushion for dispersing the load of the body weight applied on the joint, stabilizes the position of the joint, smoothens the joint movement between the femur and the tibia, and protects the articular cartilage. A normal meniscus is a white and evenly translucent fibrocartilage. The meniscus mostly consists of a fibrous extracellular matrix with a mixture of small amounts of cartilage-like cells and fibrocartilage-like cells, thereby maintaining its physiological functions. While the biochemical structure of the meniscus resembles that of an articular cartilage, they greatly differ in terms of the component ratio and the component at the molecular level. In a normal meniscus in an adult knee, the moisture content accounts for 70% or more of the wet weight. The main component other than moisture is collagen, which accounts for 60-90% of the dry weight, and is slightly higher than its component ratio in the articular cartilage. 90% of the collagen is type I collagen. Meanwhile, the amount of proteoglycan is very small as compared to the articular cartilage, which is about 1/10 the proteoglycan content of the articular cartilage and only 1% of the wet weight. The meniscus differs from the articular cartilage also in terms of component in that dermatan sulfate is present as a mucopolysaccharide side chain of a proteoglycan monomer (Non-patent document 1). The menisci are either a lateral meniscus or a medial meniscus. A normal meniscus in an adult knee contains blood vessels generally only in the peripheral 10-30% of the meniscus, where nutrition is received through blood circulation. Most of other parts are nourished by the joint fluid. Since the inner circumference, an area other than the peripheral part, is an avascular area with no blood vessel, it has little self-repairing capacity. In particular, when a major meniscus injury is caused, the injured part is known to be non-healing. Moreover, since the menisci of middle-aged persons are usually degenerated, repair becomes more difficult. The meniscus injuries may range in form, for example, including a horizontal tear, a vertical tear, a transverse tear, a bucket-handle tear, and a flap tear. As a method for treating such an injury, meniscus resection or meniscus suturing is often employed. While meniscus resection and suturing are generally employed methods of treatment, the chance of regeneration is limited to the vascular area in the outer circumference of the meniscus, while the self-repairing capacity is poor as described above and thus regeneration hardly takes place in the avascular area in the inner circumference of the meniscus. Furthermore, the regeneration capacity is considered to be low for a meniscus injury of an aged person since the meniscus healing capacity is generally low and the meniscus is often associated with degeneration, and thus suturing is rarely employed. In cases of a meniscus injury that developed osteoarthritis or in cases associated with locking, meniscectomy is applied since retear is highly likely to be caused even when suturing is performed. Furthermore, a torn meniscus is sometimes associated with degeneration, in which case the regeneration capacity is considered to be further low. Since the part of the meniscus will be completely lost after the resection, the cartilage in the knee joint at that site makes direct contact, where a cartilage degeneration progresses with the following 10-20 years and often leads to an articular cartilage injury. Meanwhile, the meniscus is said to be relatively regenerative in the vascular area if suturing is employed but the regenerated part is often inferior to a normal meniscus in terms of the mechanical properties, and there are many non-suturable cases, for example, in old cases or depending on the form of the tear. Moreover, even if the injured part in the avascular area of the meniscus is physically joined by suturing, the gap cannot be filled by regeneration and thus the surrounding meniscus is further injured if a load is continuously applied thereto. Accordingly, suturing is rarely employed for a tear in the avascular area. In addition, aging and overuse of the joint may cause cartilage degeneration, and the wear of the joint surface at the early stage of osteoarthritis may progress to a cartilage defect over a wide area. Therefore, since the articular menisci lack sufficient self-repa