Prosthesis (i.e. – artificial body members) – parts thereof – or ai – Implantable prosthesis – Hollow or tubular part or organ
Reexamination Certificate
1999-05-20
2001-06-05
Isabella, David J. (Department: 2164)
Prosthesis (i.e., artificial body members), parts thereof, or ai
Implantable prosthesis
Hollow or tubular part or organ
Reexamination Certificate
active
06241774
ABSTRACT:
TECHNICAL FIELD
The present invention relates to an artificial esophagus.
BACKGROUND ART
Although materials of biological origin as well as artificial materials composed of polymer materials and so forth are used as an artificial esophagus for esophagus reconstruction following excision of the esophagus due to esophageal cancer and so forth, an artificial esophagus (Japanese Patent Provisional Publication No. 2-109569) has been reported in which a collagen coating layer is formed on the outer surface of a silicone tube for use as an artificial esophagus that promotes regeneration of esophageal epithelium at the portion where the esophagus is missing to regenerate a new esophagus without any artificial material remaining following esophagus reconstruction. However, since the collagen coating layer in this artificial esophagus swells and softens as a result of coming in contact with humor, suturing is difficult, thereby requiring sophisticated technique by the surgeon. In the case of suturing by a surgeon not having sophisticated technique, there is the risk of hemorrhage and leakage of air from the sutured site, and in the case of applying as a mediastinal esophagus, the postoperative process is not very good and there is the risk of causing death of the patient in which the artificial esophagus is applied.
DISCLOSURE OF INVENTION
With this in mind, there has been a need for the development of an artificial esophagus that is able to maintain for a desired duration the characteristic effect of collagen of promoting regeneration of esophageal epithelium at the portion where the esophagus is missing to regenerate a new esophagus, is degraded and absorbed by the body together with generation of new esophagus without leaving a foreign object in the body, has physical properties (strength) that do not require the surgeon who performs suturing to have a sophisticated technique, prevents hemorrhage and leakage of air from the sutured site, and allows a stent to be easily removed following esophagus reconstruction.
As a result of earnest research to solve the above problems, the inventor of the present invention found that an artificial esophagus having a fine fibrous collagen layer has excellent effects, thereby leading to completion of the present invention.
The present invention is characterized by being an artificial esophagus having a fine fibrous collagen layer on the outer surface of a tube. In addition, the present invention is characterized by being a method for producing said artificial esophagus that includes a step wherein a fine fibrous collagen layer is formed on the outer surface of a tube followed by performing crosslinking treatment.
The artificial esophagus of the present invention is an artificial esophagus having a non-woven fabric-like collagen layer wherein fine fibers composed of collagen molecules are overlapped in multiple layers on the outside of a tube that fulfills the role of a lumen retaining core member. The thickness of this fine fibrous collagen layer is preferably about 2-10 mm, and particularly preferably about 5 mm. In addition, the tube serving as the lumen retaining core member uses a tube composed of, for example, medical silicone sheet (thickness: preferably about 0.5-5 mm, and particularly preferably 1-2 mm). Since the artificial esophagus of the present invention is sutured to the body with a tube serving as a lumen retaining core member, the inner diameter of the tube used is preferably about 15-30 mm, and particularly preferably 20 mm, or can be different depending on the particular case. The length of the tube used can also be different depending on the particular case. Although the artificial esophagus of the present invention has strength that allows suturing to be performed easily even with this artificial esophagus alone, in cases when even higher levels of strength are required, it may also have a collagen membrane layer on at least one side (outside) of the fine fibrous collagen layer. This collagen membrane differs from the fine fibrous collagen layer in that it is a collagen membrane having an amorphous structure in which collagen molecules are dispersed in the form of monomers and oligomers. The collagen which is the raw material of the fine fibrous collagen layer of the artificial esophagus of the present invention may be various types of conventional collagen, and preferably neutral solubilized collagen, acidic solubilized collagen, alkaline solubilized collagen or enzyme solubilized collagen. Alkaline solubilized collagen and enzyme solubilized collagen are the result of treating insoluble collagen with base or enzyme, respectively (examples of which include pepsin, trypsin, chymotrypsin, papain and pronase). As a result of this treatment, the strongly antigenic telopeptide portion of the collagen molecules is removed resulting in decreased antigenicity. Consequently, these types of collagen can be used particularly preferably. There are no particular restrictions on the origin of these collagens, and collagens can typically be used that are obtained by extraction and purification from the skin, bone, cartilage, tendon or organs of animals such as cows, pigs, rabbits, sheep and kangaroos.
In preparing the artificial esophagus of the present invention using the above-mentioned collagen as a raw material, a fine fibrous collagen layer is formed on the outer surface of a tube used as a lumen retaining core member of the artificial esophagus, for example, a tube composed of medical silicone sheet as described above.
The fine fibrous collagen layer can be formed on the outer surface of the tube preferably by the method described below. To begin with, an approximately 1 N hydrochloric acid solution (about pH 3) of extracted and purified collagen as described above (preferably about 0.5-3 wt % and particularly preferably about 1 wt %) is prepared, and the above tube (a rod-shaped core member, for example, a rod of made of Teflon, may be used) is immersed in the collagen hydrochloric acid solution (the lumen of said tube is sealed by inserting a rod-shaped object). By using such a method, a collagen hydrochloric acid solution layer is formed at a uniform thickness on the outer surface of the tube. The thickness of the collagen hydrochloric acid solution layer is preferably about 20-100 mm, and particularly preferably about 50 mm. This is then frozen preferably at about −15° C. to 0° C., and particularly preferably about 0° C., for preferably about 6-24 hours, and particularly preferably about 12 hours. As a result of this freezing, fine fragments of ice are formed between the collagen molecules dispersed in the hydrochloric acid solution, and this causes the collagen hydrochloric acid solution to separate into layers. Fine fibers are then formed as a result of the collagen molecules rearranging. Next, the silicone tube having the above frozen collagen hydrochloric acid solution layer on its outer surface is freeze-dried in a vacuum preferably at about −15° C. to 0° C., and particularly preferably about 0° C., for preferably about 12-48 hours, and particularly preferably about 24 hours. As a result of this freeze-drying, in addition to the fine ice fragments between the collagen molecules vaporizing, the collagen hydrochloric acid solution layer becomes a non-woven fabric-like collagen layer in which fine fibers composed of collagen molecules are overlapped in multiple layers. Moreover, the tube having on its outer surface this fine fibrous collagen layer is uniformly compressed using a pressing apparatus. In the artificial esophagus of the present invention, the thickness of the fine fibrous collagen layer after compression is preferably about 2-10 mm, and particularly preferably about 5 mm. Thus, the compression ratio, which is the ratio of the thickness of the collagen layer after compression to the thickness before compression, is preferably about 0.05-0.3, and particularly preferably about 0.1.
Next, the tube on which is formed on its outer surface the above fine fibrous collagen layer is subjected to crosslinking treatme
Buchanan Robert L.
Conlin David G.
Edwards & Angell LLP
Isabella David J.
Shimizu Yasuhiko
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