Prosthesis (i.e. – artificial body members) – parts thereof – or ai – Implantable prosthesis – Hair or skin
Reexamination Certificate
1999-11-30
2002-05-07
McDermott, Corrine (Department: 3738)
Prosthesis (i.e., artificial body members), parts thereof, or ai
Implantable prosthesis
Hair or skin
C623S015110
Reexamination Certificate
active
06383220
ABSTRACT:
Priority is hereby claimed to EP 98204031.3 filed Nov. 30, 1998 and EP 98204203.8 filed Dec. 11, 1998.
The invention relates to artificial skin which is suitable for wound covering, and which can be used externally on various types of wounds.
Human skin forms a barrier against adverse external influences such as infections. If part of the skin is damaged, as for example in the case of a burn, complications usually arise. These complications are due to the protective function of the skin being lost, as a result of which microbial invasion may occur, and to a substantial loss of moisture that may take place at the place of the wound.
Many studies have been carried out in order to provide an artificial skin which is able to take over all, or a large part of the functions of natural skin during the period that the wound is not covered by an epidermis and dermis. To this end, the artificial skin preferably comprises autologous cells provided on a scaffold. Alternatively, the artificial skin itself may serve as carrier material for cultured autologous keratinocytes and/or fibroblasts, which have a favorable influence on the recovery of the epidermis and/or dermis. Either way, it is desired that an artificial skin, or that a scaffold material comprised by the artificial skin, has suitable properties to serve as carrier for said cells.
An artificial skin of this type must, however, satisfy various requirements. On the one hand, it should provide a barrier, so that the wound is closed to bacteria and the like, and so that substantial moisture loss is avoided. On the other hand, it must be possible for adequate water vapor transport to take place through the artificial skin. During this transport, nutrients from the underlying tissue may reach the recovering skin in sufficient quantity. Another important requirement is that the artificial skin adheres to the underlying wound bed immediately after its application to the wound. Furthermore, a permanent adhesion must be formed as a result of ingrowth of tissue.
In U.S. Pat. No. 5,147,401, an artificial skin is disclosed, of which the outer surface (the surface facing away from a wound to which the skin is to be applied) is virtually closed. This is achieved, in one embodiment, by providing a bi-layer system comprising an upper layer, which is dense and non-porous, on top of a lower layer, which is porous. In a different embodiment, this is achieved by providing a single-layer system of a segmented material, so that one of the sides of the skin is virtually closed, and the other side is fairly open.
It has now been found that when the outer surface of the artificial skin is virtually closed, a poor adherence of the skin to a wound may be observed. Under certain conditions, the artificial skin shows more or less a ‘curling-up effect’, in that the edges of the skin are forced away from the wound, leading to a poor adherence.
Of course, when the adherence of the artificial skin to the wound is unsatisfactory, the protection of the wound by the artificial skin is equally unsatisfactory. It is therefore an object of the present invention to provide an artificial skin which shows an improved adherence.
Surprisingly, the desired improved adherence may be obtained by the provision of an artificial skin comprising an upper and a lower side, both of which are porous. Thus, the invention relates to an artificial skin based on a copolymer of a polyalkylene glycol and an aromatic polyester, which skin has a thickness between 50 and 2000 &mgr;m, and which skin has an upper and a lower side, both having a macroporosity between 10% and 95%.
An artificial skin according to the invention adheres very well to a wound when applied thereto. Under many circumstances, adherence is achieved in a period of a few minutes after application. The so-called ‘curling-up effect’ that has been observed with the prior art artificial skins has not been found to occur with the present skin. Furthermore, the artificial skin of the invention provides a highly suitable carrier for autologous cells, thus enabling tissue repair.
An artificial skin according to the invention is based on a specific copolymer, which is biodegradable. Advantageously, the biodegradability (the rate of degradation under certain conditions) may be controlled, depending on the envisaged site of application of the artificial skin.
The specific copolymer on which the present skin is based, is a copolymer of a polyalkylene glycol and an aromatic polyester. In a preferred embodiment, an artificial skin according to the invention is a single-layer system composed of the specific copolymer.
Preferably, the copolymer comprises 40-80 wt. %, more preferably 50-70 wt. % of the polyalkylene glycol, and 60-20 wt. %, more preferably 50-30 wt. % of the aromatic polyester. A preferred type of copolymers according to the invention is formed by the group of block copolymers.
Preferably, the polyalkylene glycol has a weight average molecular weight of from 150 to 4000, more preferably of 200 to 1500. The aromatic polyester preferably has a weight average molecular weight of from 200 to 5000, more preferably of from 250 to 4000. The weight average molecular weight of the copolymer preferably lies between 20,000 and 200,000, more preferably between 50,000 and 120,000. The weight average molecular weight may suitably be determined by gel permeation chromatography (GPC). This technique, which is known per se, may for instance be performed using tetrahydrofuran as a solvent and polystyrene as external standard.
In a preferred embodiment, the polyalkylene glycol component has units of the formula —OLO—CO—Q—CO—, wherein 0 represents oxygen, C represents carbon, L is a divalent organic radical remaining after removal of terminal hydroxyl groups from a poly(oxyalkylene)glycol, and Q is a divalent organic radical.
Preferred polyalkylene glycols are chosen from the group of polyethylene glycol, polypropylene glycol, and polybutylene glycol and copolymers thereof, such as poloxamers. A highly preferred polyalkylene glycol is polyethylene glycol.
The terms alkylene and polyalkylene generally refer to any isomeric structure, i.e. propylene comprises both 1,2-propylene and 1,3-propylene, butylene comprises 1,2-butylene, 1,3-butylene, 2,3-butylene, 1,2-isobutylene, 1,3-isobutylene and 1,4-isobutylene (tetramethylene) and similarly for higher alkylene homologues. The polyalkylene glycol component is preferably terminated with a dicarboxylic acid residue —CO—Q—CO—, if necessary to provide a coupling to the polyester component. Group Q may be an aromatic group having the same definition as R, or may be an aliphatic group such as ethylene, propylene, butylene and the like.
The polyester component preferably has units —O—E—O—CO—R—CO—, wherein 0 represents oxygen, C represents carbon, E is a substituted or unsubstituted alkylene or oxydialkylene radical having from 2 to 8 carbon atoms, and R is a substituted or unsubstituted divalent aromatic radical.
In a preferred embodiment, the polyester is chosen from the group of polyethylene terephthalate, polypropylene terephthalate, and polybutylene terephthalate. A highly preferred polyester is polybutylene terephthalate.
The preparation of the copolymer will now be explained by way of example a polyethylene glycol/polybutylene terephthalate copolymer. Based on this description, the skilled person will be able to prepare any desired copolymer within the above described class. An alternative manner for preparing polyalkylene glycou/polyester copolymers is disclosed in U.S. Pat. No. 3,908,201.
A polyethylene glycol/polybutylene terephthalate copolymer may be synthesized from a mixture of dimethyl terephthalate, butanediol (in excess), polyethylene glycol, an antioxidant and a catalyst. The mixture is placed in a reaction vessel and heated to about 180° C., and methanol is distilled as transesterification proceeds. During the transesterification, the ester bond with methyl is replaced with an ester bond with butylene. In this step the polyethyene glycol substantially does not react. After transesterific
Ponec M.
Riesle J. U.
van Blitterswijk C. A.
van Dorp Annette G. M.
Banner & Witcoff , Ltd.
Barrett Thomas
IsoTis N.V.
McDermott Corrine
LandOfFree
Artificial skin does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Artificial skin, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Artificial skin will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2842912