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Patent Issued for Medical Devices Containing Oriented Films of Poly-4-Hydroxybutyrate and Copolymers

July 4, 2014



By a News Reporter-Staff News Editor at Health & Medicine Week -- Tepha, Inc. (Lexington, MA) has been issued patent number 8753555, according to news reporting originating out of Alexandria, Virginia, by NewsRx editors (see also Tepha, Inc.).

The patent's inventors are Rizk, Said (Salem, NH); Martin, David P. (Arlington, MA); Ho, Kicherl (Groton, MA); Williams, Simon F. (Sherborn, MA).

This patent was filed on April 11, 2011 and was published online on June 17, 2014.

From the background information supplied by the inventors, news correspondents obtained the following quote: "Poly-4-hydroxybutyrate (P4HB) and copolymers thereof can be produced using transgenic fermentation methods, see, for example, U.S. Pat. No. 6,548,569 to Williams et al., and are produced commercially, for example, by Tepha, Inc. (Cambridge, Mass.). Poly-4-hydroxybutyrate (P4HB, TephaFLEX.RTM. biomaterial) is a strong, pliable thermoplastic polyester that, despite its biosynthetic route, has a relatively simple structure

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"The polymer belongs to a larger class of materials called polyhydroxyalkanoates (PHAs) that are produced by numerous microorganisms (see, for example: Steinbuchel A., et al. Diversity of Bacterial Polyhydroxyalkanoic Acids, FEMS Microbial. Lett. 128:219-228 (1995)). In nature these polyesters are produced as storage granules inside cells, and serve to regulate energy metabolism. They are also of commercial interest because of their thermoplastic properties, and relative ease of production. Several biosynthetic routes are currently known to produce P4HB:

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"This schematic shows some of the known biosynthetic pathways for the production of P4HB. Pathway enzymes are: 1. Succinic semialdehyde dehydrogenase, 2. 4-hydroxybutyrate dehydrogenase, 3. diol oxidoreductase, 4. aldehyde dehydrogenase, 5. Coenzyme A transferase and 6. PHA synthetase.

"Chemical synthesis of P4HB has been attempted, but it has been impossible to produce the polymer with a sufficiently high molecular weight that is necessary for most applications (Hori, Y., et al., Polymer 36:4703-4705 (1995)).

"U.S. Pat. Nos. 6,245,537, 6,623,748 and 7,244,442 describe methods of making PHAs with little to no endotoxin, which is suitable for medical applications. U.S. Pat. Nos. 6,548,569, 6,838,493, 6,867,247, 7,268,205, and 7,179,883 describe use of PHAs to make medical devices. Copolymers of P4HB include 4-hydroxybutyrate copolymerized with 3-hydroxybutyrate or glycolic acid (U.S. patent application No. 20030211131 by Martin and Skraly, U.S. Pat. No. 6,316,262 to Huisman et al., and U.S. Pat. No. 6,323,010 to Skraly et al.). Methods to control molecular weight of PHA polymers have been disclosed by U.S. Pat. No. 5,811,272 to Snell et al.

"PHAs with controlled degradation and degradation in vivo of less than one year are disclosed by U.S. Pat. Nos. 6,548,569, 6,610,764, 6,828,357, 6,867,248, and 6,878,758 to Williams et al. and WO 99/32536 to Martin et al. Applications of P4HB have been reviewed in Williams, S. F., et al., Polyesters, III, 4:91-127 (2002), and by Martin, D. et al. Medical Applications of Poly-4-hydroxybutyrate: A Strong Flexible Absorbable Biomaterial, Biochem. Eng. J. 16:97-105 (2003). Medical devices and applications of P4HB have also been disclosed by WO 00/56376 to Williams et al.

"Several patents including U.S. Pat. Nos. 6,555,123, 6,585,994, and 7,025,980 describe the use of PHAs in tissue repair and engineering.

"In the practice of surgery there currently exists a need for absorbable films with improved performance. These films can be used, for example, to reinforce tissue structures. They may also be used as anti-adhesion membranes, or as components of other devices. A number of other absorbable materials have been used to produce films for use in surgery. For example, films have been made from polylactic acid (PLA) or copolymers containing the different stereoisomers of lactic acid or glycolic acid. SurgiWrap.TM., for example, is a medical film implant made from a copolymer of L-lactide and D,L-lactide, 70:30. These materials do not, however, have ideal properties for many procedures and applications. Films made from PLA, like SurgiWrap.TM., have high modulus values, making them stiff, and preventing these films from contouring to bodily tissues when implanted. The high modulus values of PLA [see Gruber and O'Brien, 2002, in Biopolymers: Polyesters, III (Doi, Y. and Steinbuchel, A., Eds.) vol. 4, pp. 235-250. Weinheim: Wiley-VCH.] result in films of low toughness, and these properties, combined with other PLA properties, limit the ability of the polymer scientist to process PLA into thin films with good handling properties, for example, by solvent casting and melt extrusion.

"U.S. Pat. No. 6,548,569 to Williams et al. discloses an unoriented film of poly-4-hydroxybutyrate produced by compression molding in a batch process, not a continuous process. The film had a tensile strength of 5.27 kgf/mm.sup.2 (7,500 psi), tensile modulus of 6.6 kgf/mm.sup.2 (9,400 psi), and elongation at break of 1,000%.

"It is an object of the present invention to provide methods to produce films of absorbable polymers that have relatively low modulus values, and which are tough and have high strength.

"It is a further object of the present invention to provide continuous processes to produce such films, such as melt processing and solvent casting, as compared to batch processes such as compression molding.

"It is another object of the present invention to provide films which can be used in medical applications, for example, as implants such as devices for anti-adhesion barriers, tissue separation and temporary tissue support, coatings on medical devices, including stent coatings, as well as devices for tissue in-growth particularly where the film has been rendered porous.

"It is therefore an object of the invention to provide continuous processes for polymer film production which yield materials with excellent physical and mechanical properties, and the resulting polymer films."

Supplementing the background information on this patent, NewsRx reporters also obtained the inventors' summary information for this patent: "Continuous processing methods for making absorbable polymeric films with one or more of the following properties: high toughness, low modulus, high tensile strength, and thickness less than 10 mm, more preferably less than 1 mm, and more preferably less than 100 .mu.m, have been developed. In the preferred embodiment, the polymer is a polyhydroxyalkanoate, and in the most preferred embodiment, the polymer comprises 4-hydroxybutyrate. A particularly preferred embodiment is a film of poly-4-hydroxybutyrate or copolymer thereof, wherein the film has a tensile strength greater than 5.5 kgf/mm.sup.2, tensile modulus less than 181 kgf/mm.sup.2, and elongation at break from 10-500%, wherein the film is derived by a continuous process such as melt extrusion or solvent casting, followed by orientation to more than 25% of the film's original length in one or more directions.

"These can be used for a variety of purposes including fabrication of medical devices."

For the URL and additional information on this patent, see: Rizk, Said; Martin, David P.; Ho, Kicherl; Williams, Simon F.. Medical Devices Containing Oriented Films of Poly-4-Hydroxybutyrate and Copolymers. U.S. Patent Number 8753555, filed April 11, 2011, and published online on June 17, 2014. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=8753555.PN.&OS=PN/8753555RS=PN/8753555

Keywords for this news article include: Surgery, Tepha Inc, Legal Issues, Dehydrogenase, Carboxylic Acids, Hydroxybutyrates, Organic Chemicals, 3-Hydroxybutyric Acid, Enzymes and Coenzymes.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC


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Source: Health & Medicine Week


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