JP2011523878A - Block polymer membrane for reducing scar tissue - Google Patents

Abstract

  Disclosed is a resorbable polymer micromembrane that can be pre-cut and shaped by the user. This micromembrane is constructed from a resorbable polymer and is designed to reduce adhesions and be absorbed by the body relatively slowly over time. The membrane can be formed to have a very thin thickness, for example between about 0.010 mm and about 0.030 mm, while maintaining sufficient strength. This membrane can be extruded from a polylactide polymer with relatively high viscosity properties, can be stored in a sterile package, and can be pre-molded with relatively high reproducibility during transplantation surgery .

Description

1. FIELD OF THE INVENTION This invention relates generally to medical implants, and more specifically to resorbable membranes and methods of use and methods of use as medical implants.

CROSS REFERENCE TO RELATED APPLICATIONS This application is filed on June 8, 2008, and is entitled US Provisional Application No. 61 / 059,795 (Attorney Docket No. MB8110PR) entitled “Block Polymer Membrane for Reduction of Scar Tissue”. No. 12 / 199,760 filed Aug. 27, 2008 and entitled “Resorbable Barrier Micromembrane for Reduction of Scar Tissue During Treatment” No. MB8039P), filed March 10, 2003, entitled “Resorbable Barrier Micromembrane for Reduction of Scar Tissue During Treatment”, US Application No. 10 / 385,399 No. (Attorney Docket No. MA9496CON), ie current US Pat. No. 6,673,362, the contents of each and all of which are expressly incorporated herein by reference. The

  No. 10 / 631,980 filed on Jul. 31, 2003 (Attorney Docket No. MA9604P), U.S. Application No. 11 / 203,660 filed on Aug. 12, 2005. (Attorney Docket No. MB9828P), US Application No. 10 / 019,797 (Attorney Docket No. MB9962P) filed on July 26, 2002, US provisional application filed on August 27, 2007 No. 60 / 966,782 (Attorney Docket No. MB8039PR) and US Provisional Application No. 60 / 966,861 (Attorney Docket No. MB8039PR2) filed on August 29, 2007. The above-mentioned applications are assigned to the same assignee, the entire contents of each and all of which are expressly incorporated herein by reference.

2. 2. Description of Related Art A major clinical problem with surgical repair or inflammatory diseases is adhesions that occur during the early stages of the healing process after surgery or disease. Adhesion is a condition that involves the formation of an abnormal tissue bond caused by the formation of fibrous scar tissue. These bonds can, for example, impair bodily function, cause infertility, can block other parts of the intestine and gastrointestinal tract (eg, intestinal obstruction), and systemic imperfections. Pleasures, such as pelvic pain, can occur. This condition can be life threatening in some cases. The most common forms of adhesions occur as a result of surgical interventions, but adhesions can occur in other processes such as pelvic inflammatory disease, Khron's disease, peritonitis, mechanical injury, radiation therapy, and the presence of foreign bodies Or it may occur as a result of an event.

  Various attempts have been made to prevent adhesions, particularly postoperative adhesions. For example, changes in surgical techniques such as peritoneal lavage, heparinized solution, use of procoagulant, use of microscope or laparoscopic surgical techniques, removal of talc from surgical gloves, use of smaller sutures, and serosal surface All attempts have been made to use physical barriers (membranes, gels or solutions) aimed at minimizing juxtaposition. Unfortunately, these methods have had limited success. In addition, various forms of barrier materials such as membranes and viscous intraperitoneal solutions designed to limit tissue apposition have also had limited success. These barrier materials can include cellulose barriers, polytetrafluoroethylene materials, and dextran solutions.

  US Pat. No. 5,795,584 to Tokahura et al. Discloses an anti-adhesion or scar tissue reducing film or membrane, and US Pat. No. 6,136,333 to Cohn et al. Is similar. The structure is disclosed. In Tokafra et al., A bioabsorbable polymer is copolymerized with a suitable carbonate, which then becomes a nonporous monolayer adhesion barrier such as a thin film. In Korn et al., Polymeric hydrogels to prevent or reduce adhesions are formed without crosslinking by using urethane chemistry. Both of these patents included that relatively complex chemical formulas and / or chemical reactions resulted in specific structures used as surgical adhesion barriers. There is a continuing need for improved membranes.

  This invention can be used in various surgical contexts, for example during tissue healing, to reduce scarring, for example to suppress, delay or prevent tissue adhesion and be absorbed or dissolved after an appropriate time An improved resorbable micromembrane is provided. The membrane can be formed to have a very thin thickness, for example from about 0.010 mm to about 0.300 mm, while maintaining sufficient strength.

  The present invention is an improved resorbable micromembrane that can be easily and reliably formed and positioned on, around, or in close proximity to anatomical structures containing hard or soft tissue I will provide a. This membrane can be used in a variety of surgical situations, for example to delay or prevent tissue adhesion and reduce scarring. In addition, the copolymers of the present invention may facilitate the provision of relatively simple chemical reactions and / or formulations and / or improve or make more controllable mechanical strength and / or other, eg One or more of accelerating or allowing more control over degradation of the parent poly (ester) may be provided.

  According to one exemplary implementation of the present invention, a resorbable micromembrane comprising a substantially uniform composition of a diblock copolymer can be provided. The diblock copolymer may comprise, consist essentially of, or consist of one or more polylactides and / or polyglycolides (eg PLA, PGA or PLGA) A block and a second block that may comprise or consist essentially of one or more polyethylene glycols (eg, PEG). The first block designated as PLA / PGA block may comprise hydrophobic and biodegradable PLA / PGA blocks, and the second block designated as PEG block may comprise hydrophilic PEG blocks. Good.

  According to another aspect of the invention, there is provided a resorbable micromembrane comprising, consisting essentially of, or consisting of a substantially uniform composition of a triblock copolymer. The triblock copolymer may comprise polylactide and / or polyglycolide (eg PLA, PGA or PLGA), may consist essentially of or consist of a first block and one or more polyethylenes A second block that may comprise or consist essentially of a glycol (eg PEG) and may comprise polylactide and / or polyglycolide (eg PLA, PGA or PLGA), And a third block that may consist essentially of or consist of. The first and third blocks, each denoted as PLA / PGA block, may preferably include one or more hydrophobic and biodegradable PLA / PGA blocks, and are denoted as PEG blocks. The two blocks may preferably comprise one or more hydrophilic PEG blocks.

  When the first block and the third block are the same or share one or more common characteristics, both the first and third blocks may be denoted as “A” blocks The second block may be referred to as a “B” block.

  The first PLA / PGA block and the second PEG block may together form a PLA / PGA-PEG (ie, AB) copolymer, and by adding a third PLA / PGA block, PLA / PGA-PEG-PLA / PGA (ie ABA) copolymers may be formed. These PLA / PGA-PEG (and / or PLA / PGA-PEG-PLA / PGA) copolymer membranes can be formed, for example by extrusion, with, for example, initial relatively high viscosity properties. The initial high viscosity characteristics may help ensure that the film is formed, for example, by reducing the occurrence of film breakage or tearing during the extrusion process. After processing and sterilization, the viscosity or clay properties of the polymer comprising the membrane may generally be low. In order to increase the strength of PLA / PGA-PEG (and / or PLA / PGA-PEG-PLA / PGA) copolymer materials during manufacturing processes such as extrusion, other viscosity properties (eg relatively high viscosity properties) It can be used according to other aspects of the invention. In a modified embodiment, the initial viscosity characteristics need not be relatively high. The extrusion manufacturing process may impart a biased molecular orientation to the film.

  According to another feature of the invention, the membrane has a first substantially smooth surface and a second substantially smooth surface, is nonporous, and has a first substantially smooth surface. When measured between the surface and the second substantially smooth surface, the thickness is from about 0.01 mm to about 0.300 mm. The membrane can have a varying cross-sectional thickness. For example, the membrane can include at least one relatively thick portion that can form at least a portion of the edge of the membrane. In other embodiments, the membrane may be uniform in thickness.

  Although apparatus and methods have been described or described herein to provide grammatical fluidity with functional descriptions, unless otherwise indicated, the claims are “means” or “ It should not be construed as limited in any way by the structure of "steps", but gives the full meaning and equivalents of the definition provided by the claims under legal doctrine. It is done.

  Any feature or combination of features described herein is provided that the features contained in any such combination as apparent from the context, the specification and the knowledge of those skilled in the art do not conflict with each other. Are included within the scope of this invention. In addition, any feature or combination of features may be specifically excluded from any embodiment of the invention. For purposes of summarizing the invention, certain aspects, advantages and novel features of the invention are described. Of course, it should be understood that not all such aspects, advantages or features may be implemented in a particular implementation of the invention. Further advantages and aspects of the present invention are apparent in the following detailed description and claims.

FIG. 2 elucidates the composition and properties of an exemplary embodiment according to the present invention. FIG. 2 elucidates the composition and properties of an exemplary embodiment according to the present invention. FIG. 2 elucidates the composition and properties of an exemplary embodiment according to the present invention. FIG. 2 elucidates the composition and properties of an exemplary embodiment according to the present invention. FIG. 2 elucidates the composition and properties of an exemplary embodiment according to the present invention. FIG. 2 elucidates the composition and properties of an exemplary embodiment according to the present invention.

  Reference will now be made in detail to the presently preferred embodiments of the invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same or similar reference numbers are used in the drawings and the description to refer to the same or like parts. The drawings are simplified and do not follow a uniform scale. With reference to the disclosure herein, for the sake of convenience and clarity only, top, bottom, left, right, top, bottom, cover, top, bottom, directly below, back and front, etc. Directional terms are used with reference to the accompanying drawings. Terms referring to such directions should not be construed as limiting the scope of the invention in any way.

  While the disclosure herein refers to particular illustrated examples, it is to be understood that these examples are presented by way of example and not limitation. This disclosure describes exemplary embodiments, but all variations of the embodiments so that the following detailed description may be within the spirit and scope of the invention as defined by the appended claims. It is intended to be construed as including examples, alternatives, and equivalents.

  The barrier membranes of this invention may be constructed from a variety of biodegradable materials such as resorbable polymers. According to one embodiment, non-limiting polymers that may be used to form the barrier films of the present invention may include diblock copolymers. As practiced herein, the diblock copolymer may comprise or consist essentially of polylactide and / or polyglycolide (eg, PLA, PGA or PLGA). A first block and a second block that may comprise, consist essentially of, or consist of polyethylene glycol (eg, PEG) may be included. The first block, designated PLA / PGA block, may include one or more hydrophobic and biodegradable PLA / PGA blocks, and the second block, designated PEG block, is a hydrophilic PEG block. Can be included. The first PLA / PGA block may be referred to as an “A” block, and the second PEG block may be referred to as a “B” block. The first PLA / PGA block and the second PEG block may together form a PLA / PGA-PEG (ie, AB or AB) diblock copolymer.

  Other non-limiting block polymers that may be used to form the barrier films of this invention include triblock copolymers or star block copolymers. As practiced herein, the triblock copolymer comprises a first block that may comprise or consist of polylactide and / or polyglycolide (eg, PLA, PGA or PLGA) and polyethylene. A second block that may or may comprise glycol (eg PEG) and may or may comprise polylactide and / or polyglycolide (eg PLA, PGA or PLGA) A good third block. The first block designated as PLA / PGA block may comprise hydrophobic and biodegradable PLA / PGA blocks, and the second block designated as PEG block may comprise hydrophilic PEG blocks; A third block, labeled PLA / PGA block, can include hydrophobic and biodegradable PLA / PGA blocks. When the first PLA / PGA block and the third PLA / PGA block are the same or share one or more common characteristics, the first and third PLA / PGA blocks each have “A The second PEG block may be referred to as the “B” block. The first PLA / PGA block, the second PEG block, and the third PLA / PGA block together form a PLA / PGA-PEG-PLA / PGA (ie ABA or ABA) triblock copolymer. May be.

  Alternatively, the combination block copolymer may be characterized as a PEG-PLA / PGA-PEG (ie BAB or BAB) triblock copolymer.

  In other implementations, the combination block copolymer comprises PEG blocks (ie, B blocks) formed, coupled to, or disposed between, three or more PLA / PGA blocks (ie, A blocks), for example It may be a 4 addition (ie, 4 or more blocks) block copolymer. Alternatively, a 4-addition block copolymer is formed with, or joined to, or between PLA / PGA blocks (ie, A blocks) formed with three or more PEG blocks (ie, B blocks). For example.

  A 4-addition block copolymer has one or more symmetrical and star-shaped shapes and combines (eg, connected) three or more PLA / PGA blocks (ie, A blocks) that are numbers that may include, for example, 4. PEG blocks (ie, B blocks) with regions (eg, arms, branches or dots) may be included. In the preferred embodiment, the number of regions is equal to the number of PLA / PGA blocks. Alternatively, a 4-addition block copolymer has one or more symmetric and star shapes and combines (eg, connected to or comprises) three or more PEG blocks (ie, B blocks). It may contain PLA / PGA blocks (ie A blocks) with regions (eg arms, branches or points). The number of regions may be equal to the number of PEG blocks, as in the previous example, and in certain examples may include 4.

  This combination block copolymer film can be formed with an initial relatively high viscosity characteristic by extrusion. The initial high viscosity characteristics may help ensure that the film is formed, for example, by reducing the occurrence of breakage or tearing during the extrusion process. After processing and sterilization, the viscosity properties of the membrane may generally be low. According to other aspects of the invention, other relatively high viscosity properties can be used, for example, to increase the strength of the material. The extrusion process can advantageously provide efficient production of the membrane. In addition, membranes produced by such extrusion techniques can be free of solvent adsorption on the membrane and can also be given a molecular bias, including, for example, a predetermined molecular bias. . The membrane may be produced using single screw extrusion or twin screw extrusion.

  The composition of the combination block copolymer can be extruded to form the membrane of this invention. In certain examples, the PLA / PGA-PEG block copolymer takes the form of one or more of the following polymers: 1. poly (L-lactide-co-PEG); 2. poly (L-lactide-co-DL-lactide-co-PEG) and Poly (L-lactide-co-glycolide-co-PEG). The PLA / PGA-PEG-PLA / PGA block copolymer takes the following form: 4. 4. poly (L-lactide-co-PEG-co-L-lactide); 5. poly (L-lactide-co-PEG-co-L-lactide-co-DL-lactide), 6. poly (L-lactide-co-PEG-co-L-lactide-co-glycolide), Poly (L-lactide-co-DL-lactide-co-PEG-co-L-lactide-co-DL-lactide), 8. 8. poly (L-lactide-co-DL-lactide-co-PEG-co-L-lactide-co-glycolide), 9. poly (L-lactide-co-glycolide-co-PEG-co-L-lactide-co-glycolide), and Other forms from the above combinations and / or substitutions for star block and / or 4-addition block copolymers (optionally with any one or more other products disclosed or referenced herein) Can be manufactured or obtained. For example, such products may be manufactured or obtained from Boehringer Ingelheim KG, Germany, for extrusion into the membranes of the present invention, but are not limited thereto.

  The following are exemplary chemical structures as well as construction and scientific name conventions used herein.

  Scheme B shows the incorporation of polyethylene glycol (PEG) units into the block copolymer with PLGA again by the action of a catalyst. PEG has low systemic toxicity and is currently used in various medical drugs and pharmaceuticals.

  The resulting block copolymer can be schematically represented as follows:

  Commercially obtained PLGA: PEG block copolymers include RESOMER® PEG products from Boehringer Ingelheim.

  One preferred (but non-exclusive) product is the Resomer® PEG sample MB type LRP d70 55, where LR represents the resomer acronym LR (A-block) and P is PEG (B- 70 represents the molar ratio within the A-block, the first 5 represents the weight percent of PEG, and the second 5 represents the molecular weight of PEG divided by 1000.

  Typical and non-limiting examples of PLA / PGA-PEG (and / or PLA / PGA-PEG-PLA / PGA) copolymers are as follows: In the case of a controlled release mechanism (CR), the polymer typically comprises about 5% to about 15% PEG. In the case of medical devices (MD), the polymer typically contains less than about 5% PEG. In the case of controlled release, the A block may comprise, for example, D, L-lactide-co-glycolide (RG). In the case of a medical device, the A block may include, for example, L-lactide (L), L-lactide-co-D, L-lactide (LR), or L-lactide-co-glycolide (LG).

  1-6 illustrate the composition and properties of contemplated examples according to the present invention. The membrane of the present invention can have at least one substantially smooth surface. Preferably, the membrane of the present invention has two (opposing) substantially smooth surfaces. When measured between opposing faces, the thickness of the membrane of this invention can be from about 0.01 mm to about 0.3 mm, more preferably from about 0.01 mm to about 0.1 mm. In a preferred embodiment, the thickness of the membrane of this invention is from about 0.015 mm to about 0.025 mm. In another preferred embodiment, the thickness of the membrane of this invention is about 0.02 mm. Preferred micromembranes of the present invention may include one or more substantially uniform compositions and molecular orientation in the biased membrane as a result of, for example, extrusion.

  As used herein, the term “nonporous” refers to a material that is generally waterproof and, according to a preferred embodiment, not fluid permeable. However, in a variant embodiment of the invention, the micropores (which are fluid permeable but not cell permeable) reduce the smoothness of the surface of the resorbable micromembrane, eg to cause tissue scarring. It may be present in the micromembrane of the present invention so as not to substantially interfere. In a substantially modified embodiment for a particular application, pores that are cell permeable but not vascular permeable may be made and used.

  As currently practiced, many of the thinner film thicknesses can be well profiled without heating to the glass transition temperature. As currently practiced, reabsorption of resorbable membranes can be between approximately 2-24 months. In one embodiment, the membrane of the present invention is, for example, about 10-20 weeks, or about 20-30 weeks, or according to other implementations, from the first implantation of the membrane into the mammalian body up to about 18 months. Or may be capable of being resorbed (ie, absorbed by the mammalian body) within a period of up to about 24 months. The resorbable membrane can be resorbed within a period of approximately one year to the point where there is no substantial strength in the patient's body. Complete resorption of the resorbable membrane may occur substantially after a total period of 1.5-2 years from the time of initial implantation. In other embodiments, the most acute membrane may comprise a plastic material or metal material that is totally or somewhat non-resorbable.

  Micromembrane is used for surgical repair of orbital fundus fractures, surgical repair of nasal septum and perforated tympanic membrane, protective covering material to facilitate bone formation, surgical repair of urethral anatomy and urethral stricture As a temporary cover for ruptured prenatal ruptured umbilical hernia during repair of bone marrow, prevention of bone fusion during craniolysis and complete forearm fracture surgery, relief of soft tissue fibrosis or bone growth For guided tissue regeneration between the sac and gingival margin, tympanic membrane repair, dural cover and nerve repair, cardiovascular repair, hernia repair, tendon anastomosis, temporary connecting spacer, wound dressing, scar cover, and gastric wall rupture As a cover, it may be used in a number of surgical applications including. The micromembrane of the present invention is particularly suitable for preventing abnormal fibrous connectivity of tissues after surgery that can lead to abnormal scarring and / or interfere with normal physiological functions. Can be. In some cases, such scarring may force follow-up surgery, corrective surgery or other surgery and / or may interfere with those surgery.

  The very thin structure of these membranes is believed to substantially accelerate the rate of absorption of the membrane compared to the rate of absorption of the same material and increased thickness of membrane implants. However, too fast reabsorption of membranes into the body can sometimes lead to an undesirable drop in local pH levels and thus generate / enhance eg local inflammation, discomfort and / or foreign antibody response It is believed that. Furthermore, the resulting non-uniform (eg, cracked, broken, roughened, or delaminated) surfaces of micromembranes that are too fast to decompose can be interstitial, for example, before fully healing. It can undesirably cause tissue disruption, possibly leading to tissue irritation and / or scarring and also the risk of tissue adhesion, thus ruining the purpose of the membrane. In other examples, according to aspects of the invention, the absorption rate can be changed temporally and / or spatially by changing the material of the membrane or part of the membrane, or can be adapted to the contours of the human body Different (eg, faster) reabsorption may be sought in one or more areas of a patient and / or at one or more points in one or more surgical procedures.

  The micromembrane according to one aspect of the invention may be provided by the manufacturer in a rectangular shape with each side being, for example, a few centimeters before packaging and sterilization, or other specific shape, configuration and size. Can be cut and formed. In alternative embodiments, various known compositions and copolymers, for example consisting of polylactide, can affect the physical properties of the micromembrane. The micromembrane of the present invention may be flexible enough to fit on and / or around the anatomy, but in an increased thickness configuration, Heating may be necessary. In alternative embodiments, for example, thicknesses above 0.25 mm may be somewhat stiff and brittle and may be softened by forming with other polymers, copolymers and / or other monomers such as epsilon-caprolactone The polylactide may be realized, for example, to form a micromembrane.

  Further, according to another aspect of the invention, the micromembrane comprises a chemotactic substance that affects cell migration, an inhibitory substance that affects cell migration, a mitogenic growth factor that affects cell proliferation, and cell differentiation. There may be provided a substance for cell control, such as at least one of the growth factors affecting the cell. Such materials may be disposed on or impregnated on the membrane, but may be coated on one or more sides of the membrane. In addition, the substance may be contained in or on individual units on the membrane, which can be effective to facilitate selective release of the substance when the membrane is inserted into a patient. Other configurations for accommodating different anatomical structures may be formed. For example, the configuration may be designed to fit around the base portion, for example formed in a conical structure, with the protrusion extending through the center of the membrane. Suture perforations may be formed in the outer periphery of the membrane and may also include cell and vascular permeable pores.

  In general, any detail, feature, or combination thereof described or referenced herein (in whole or in part in terms of structure or steps) is considered to be any of the documents referred to herein. May be combined (in whole or in part, in terms of structure or steps) with any detail, feature or combination thereof described or referenced in US Application No. 11 / 203,660 and US Provisional Application No. 60 / 966,861 and / or US Application No. 10 / 019,797 (details included in any such combination) Or any combination that the person skilled in the art would consider possible or possible to modify as long as the features do not contradict each other In place, in structure or step, in whole or in part), including. Each of these patent applications is expressly incorporated herein by reference.

  According to one implementation of the invention, the pre-formed micromembrane can be pre-formed and encapsulated in a sterile package for subsequent use by the surgeon. Since one purpose of the micromembrane of the present invention may be to reduce sharp edges and surfaces, membrane pre-formation may be relatively less in some cases to reduce chafing, tissue disruption and inflammation. Though small, it is believed to help facilitate rounding the edges. That is, the surface of the micromembrane and any sharp edges can degrade very slightly over time in response to the membrane being exposed to atmospheric moisture, thereby creating a more rounded edge. It is believed that an edge can be formed. This is considered a very minor effect. Furthermore, any initial heating to the glass temperature of the pre-cut membrane just prior to implantation can conceivably round any sharp edges. Furthermore, the very small membranes of the present invention may be particularly susceptible to these phenomena, at least theoretically, and are likely to be more susceptible to tearing or damage due to handling, and therefore, Pre-formation is probably beneficial for maintaining its integrity.

  According to one aspect of the invention, a surgical prosthesis (eg, a resorbable scar tissue-reducing micromembrane system) is provided with an adhesion-resistant region (eg, biodegradable) as described herein. Region, biodegradable side, membrane and / or micromembrane) and any tissue ingrowth region (eg, another membrane, bridge membrane, biodegradable region and / or biodegradable side or mesh) May be further provided.

  Surgical prostheses (eg, biodegradable surgical prostheses) are used to repair soft tissue defects such as soft tissue defects caused by incisional and other hernias and soft tissue defects caused by tumor extraction surgery Can be built. Surgical prostheses may also be used in cancer surgeries such as those involving sarcomas of the limbs where the goal is to save the limbs. Other applications of the surgical prosthesis of this invention include laparoscopic or standard hernia repair in the heel area, umbilical hernia repair, paracolostomy hernia repair, femoral hernia repair, lower back Hernia repair, as well as other abdominal wall defects, chest wall defects and diaphragmatic hernia and defect repair may be included.

  According to one aspect of the invention, the tissue ingrowth region and the adhesion resistant region may differ in both (A) surface appearance and (B) surface function. For example, a tissue ingrowth region can be constructed with at least one of surface topography (appearance) and surface composition (function), all of which are strong, lifetime or lack, and / or Or, for example, it can facilitate a substantial fibroblast response in the host tissue to the anti-adhesion region. On the other hand, the adhesion resistant region can be constructed with at least one of surface topography and surface composition, both of which are biodegradable surgical implants and An anti-adhesion effect with the host tissue can be facilitated.

A. Surface topography (appearance):
The tissue ingrowth region can be formed to have an open, non-smooth and / or featured surface comprising regularly or irregularly dispersed pores and / or pores, for example. In further embodiments, the tissue ingrowth region can additionally or alternatively be formed to have a non-uniform (eg, cracked, broken, roughened, or peeled) surface. This aspect, like the above aspect, can cause tissue disruption (eg, potential tissue inflammation and / or scarring) between the host tissue and the tissue ingrowth region.

  Over time, relative to the tissue ingrowth region, the patient's fibrous tissue and collagen tissue can be substantially completely larger than the tissue ingrowth region, growing on the tissue ingrowth region, Paste the tissue ingrowth area onto the tissue. In one implementation, the tissue ingrowth region comprises a plurality of small holes or apertures that are visible to the naked eye, through which the host tissue can grow or over the plurality of small holes or apertures, Can achieve substantial fixation.

  As an example, the pores may be formed in the tissue ingrowth region by drilling or other manner of machining, or using laser energy. The non-smooth surface may be formed, for example, by attriting the tissue ingrowth region with a relatively rough surface (eg, having a surface such as 40 grit or preferably higher grit abrasive paper) or alternatively In particular, a non-smooth surface is created by bringing the tissue ingrowth region to its softening or melting temperature and imprinting it with a template (a surface like abrasive paper to use the same example) May be. Imprinting may be performed, for example, during or after the initial forming process.

  On the other hand, the adhesion resistant region can be formed to have a closed, continuous, smooth and / or non-porous surface. In an illustrative example, at least a portion of the adhesion resistant region is smooth and does not have a ridge, stoma or vascular permeable pore, so that the tissue ingrowth region and the host tissue Reduce the occurrence of adhesions between.

  In a molding example, one side of the press may be formed to produce any of the tissue ingrowth area surfaces described above, while the other side of the press is the adhesion resistant described above. It may be formed to generate a region plane. Additional features (eg, roughening or forming apertures) may be added thereafter, for example to further define the surface of the tissue ingrowth region. In an extrusion embodiment, one side of the output orifice may be formed to create a tissue ingrowth region (eg, may be ridged) (subsequent processing may be performed with transverse ribs). The surface may be further defined, such as by adding / features and / or small holes), the other side of the orifice may be formed to produce an adhesion-resistant biodegradable region surface. In one example, the adhesion resistant region is extruded to have a smooth surface, and in another example, the adhesion resistant region is further processed (eg, smoothed) after extrusion.

B. Surface composition (function):
As currently practiced, the tissue ingrowth region comprises a first material and the adhesion resistant region comprises a second material that is different from the first material. In alternative embodiments, the tissue ingrowth region and the adhesion resistant region may comprise the same or substantially the same material. In other examples, the tissue ingrowth region and the adhesion resistant region may comprise different materials, eg, caused by an additive introduced into at least one of the tissue ingrowth region and the adhesion resistant region.

  According to an implementation of the invention, the adhesion resistant area is constructed to minimize the occurrence of adhesions of host tissue (eg, internal organs) to the surgical prosthesis. In an alternative embodiment, the adhesion resistant area and tissue ingrowth area of the surgical prosthesis may functionally be formed from the same material or a relatively non-diffusing material, such as the surgical resistant area It may be used in conjunction with an anti-inflammatory gel applied on the adhesion resistant area during implantation of the dental prosthesis. According to other broad embodiments, the adhesion resistant region and the tissue ingrowth region can be any of the materials or materials disclosed herein (including embodiments in which the two regions share the same layer of material). The adhesion resistant region may be used in conjunction with an anti-inflammatory gel applied on the adhesion resistant region, for example during implantation of a surgical prosthesis. May be.

  The tissue ingrowth region can be formed of a material similar to and / or different from that described above, and its strength, life span or lack, and / or substantial fibroblasts in, for example, host tissue Facilitates direct post-operative cell colonization by inducing a reaction. In the example shown, the tissue ingrowth region is constructed to be substantially incorporated into the host tissue and / or to substantially increase the structural integrity of the surgical prosthesis. After implantation of the surgical prosthesis, body tissue (eg, subcutaneous tissue and / or outer fascia) begins to incorporate the body tissue itself into the tissue ingrowth region. Although not wishing to be limited by theory, it is believed that the body is positioned to deliver fibrous tissue upon sensing the presence of the tissue ingrowth region of the present invention, which fibrous tissue Growing in, around, and / or through the tissue ingrowth region, and at least partially entangled with the tissue ingrowth region. In this way, the surgical prosthesis can be securely attached to the host body tissue.

  With respect to different materials, according to one aspect of the invention, the tissue ingrowth region has one or more characteristics that differ from the characteristics of the biodegradable (eg, resorbable) polymer composition of the adhesion resistant area. Degradable (eg, resorbable) polymer compositions can be provided. The different characteristics affect (1a) the biodegradation time or rate affected by the additive, (1b) the biodegradation time or rate affected by the polymer structure / composition, and (2) the strength or structural integrity. The polymer composition to affect, and (3) the ability to facilitate a fibroblast reaction may be included.

  In accordance with the method of the present invention, the surgical prosthesis can be used, for example, to facilitate hernia repair in the abdominal region of the body. An implanted surgical prosthesis can be provided having an adhesion resistant region disposed on one side of the surgical prosthesis and a tissue ingrowth region disposed on the second side of the surgical prosthesis. The abdominal wall may include muscles that are surrounded by outer and inner fascia and held in place. An inner layer called the peritoneum can cover the inside of the inner fascia. The peritoneum is a softer, bendable layer of tissue that forms a sac-like housing for the intestines and other internal organs. A layer of skin and a layer of subcutaneous fat cover the outer fascia.

  Surgical repair of soft tissue defects (eg, hernia) can be performed by closing substantially all soft tissue defects using, for example, conventional techniques or advanced laparoscopic methods. According to one implementation, an incision can be made through the skin and subcutaneous fat, and then the skin and fat can be stripped, followed by any protruding internal organs (not shown) Positioned inside. In certain implementations, an incision can be made in the peritoneum, followed by insertion of the surgical prosthesis into the hernia opening such that the surgical prosthesis is centered on the hernia opening. One or both of the tissue ingrowth region and the adhesion resistant region may be attached, for example, by stitching to the same layer of the abdominal wall, eg, the relatively strong outer fascia. Alternatively, the adhesion resistant region may be attached to another site such as the medial fascia and / or peritoneum. The tissue ingrowth region can be surgically attached to the outer fascia, whereas the adhesion resistant region can be, for example, thermal bonding, suturing, and / or other application protocols disclosed herein or their Substantial equivalents can be used to attach to the tissue ingrowth region and / or optionally to the outer fascia. Those skilled in the art will recognize that other methods of sizing / modifying / orienting / attaching the surgical prosthesis of this invention may be implemented according to the context of the particular surgical procedure.

  The size of a surgical prosthesis is generally determined by the size of the defect. The use of a surgical prosthesis in an untensioned closure may be associated with less pain and less post-operative fluid accumulation. Exemplary sutures may be implemented to at least partially secure the surgical prosthesis to the abdominal wall structure. The suture can be implemented so that no lateral tension is applied to the outer fascia and / or muscle. When collapsed, the skin and fat may return to their normal position with the skin and fat incision edges held together using suitable means such as subsurface sutures.

  In alternative embodiments of the present invention, one or both of the tissue ingrowth region and the adhesion resistant region of the surgical prosthesis can be heat bonded (or in alternative embodiments, such as by suturing, etc. Can be attached in a manner). Thermal bonding is accomplished, for example, by bipolar electrocautery, ultrasonic welding, or similar seals between the tissue ingrowth and adhesion resistant regions and / or directly to the surrounding tissue. May be. Such a device can be used to heat the surgical prosthesis at least above the glass transition temperature, preferably above the softening point temperature, at various locations, such as at the edge and / or along the way. . The material is heated, for example with adjacent tissue, so that the two components are joined at the interface. Thermal bonding may also be used initially to, for example, keep the tissue ingrowth region in an adhesion resistant region. Since the tissue ingrowth region performs more load bearing functions, some exemplary embodiments may exclude thermal bonding as the only means to keep this region in the host tissue. In other embodiments, the technique of thermally joining the surgical prosthesis to the surgical prosthesis itself or body tissue may be combined with another attachment method to improve adhesion. For example, a surgical prosthesis may be temporarily affixed to an appropriate location using two or more points of thermal bonding using an electrocautery device and then (or in other embodiments, an alternative In addition, sutures, staples or glue can be added to hold the surgical prosthesis in place.

  The tissue ingrowth region and the adhesion resistant region may be arranged to form two or more layers or substantially one layer, or the regions are both formed as a single, integral piece. May belong to another layer. For example, the tissue ingrowth region and the opposing adhesion resistant region may be arranged in two layers, with one region located on the other region and on the opposite side of the other region.

  In one example, the tissue ingrowth region and the adhesion resistant region may be combined on a single side of a surgical prosthesis, for example, substantially in one layer, and these regions may be Adjacent to each other on one side of the object. As a slightly deviating example, a surgical prosthesis having a tissue ingrowth region on at least one side (preferably both sides) may be manufactured using any of the techniques described herein. Well, then, the adhesion resistant region may smooth, fill or otherwise treat the area of the tissue ingrowth region with a suitable material or technique disclosed herein (eg, a liquid or flowable polymer composition). May be formed, for example, on one side, thereby having adhesion-resistant properties relative to the properties of the tissue ingrowth region Form an adhesion resistant area.

  Similarly, patches of adhesion resistant areas may be sized and applied directly to at least one of the tissue ingrowth area and surrounding host tissue at the time of implantation (eg, a bipolar electrocautery device, etc. Or may be ultrasonically welded or similarly applied). In alternative embodiments, the application may be accomplished using, for example, a press or an adhesive bond or suture. In a further embodiment, at least some of the application may be performed during manufacture of the surgical prosthesis prior to packaging. Patches of adhesion resistant areas are alternatively listed in the area of tissue ingrowth area (eg non-peripheral or central area), eg in the non-peripheral or central area of the adhesion-resistant area (eg listed in this paragraph) Technique), so that the surgeon can apply the adhesion resistant dorsal degradable implant to the tissue ingrowth area while the adhesion resistant area (and / or tissue ingrowth at the time of implantation). Area) can be arranged. For example, the tissue ingrowth region may substantially surround the adhesion resistant region on one side of the surgical prosthesis, and only the tissue ingrowth region may be formed on the other side of the surgical prosthesis. In such an implementation, the adhesion resistant region of the surgical prosthesis can be sized and shaped to substantially cover any opening created by the soft tissue defect, and the tissue ingrowth region is Facilitates surgical attachment and incorporation into host tissue on at least one side, preferably both sides, of the surgical prosthesis.

  In an alternative embodiment, the tissue ingrowth region and / or the adhesion resistant region on a given surface of the surgical prosthesis each have any size or shape suitable to fit a particular soft tissue defect. You may do it. For example, any tissue in-growth region and / or adhesion-resistant region on a given surface of a surgical prosthesis may have an oval, rectangular shape, and various complex or other shapes. Well, for each such implementation, the proportions and / or dimensions of the two regions relative to each other may be essentially the same or different.

  In general, various techniques may be utilized to create a surgical prosthesis typically having one or two layers that define a tissue ingrowth region and an adhesion resistant region. Useful techniques include solvent evaporation methods, phase separation methods, interface methods, extrusion molding methods, molding methods, injection molding methods, hot pressing methods and the like known to those skilled in the art. The tissue ingrowth region and the adhesion resistant region may comprise two separate layers or may be integrally formed together as one layer.

  The tissue ingrowth region and the adhesion resistant region may be formed or joined together, partially or substantially entirely. Coupling can be accomplished by stitching or mechanical methods such as using metal clips such as hemostatic clips, or other methods such as chemical bonding or thermal bonding.

  The above embodiments are provided as examples, and the present invention is not limited to these examples. In light of the above description, to the extent that they are not mutually exclusive, those skilled in the art will recognize a number of variations and modifications to the disclosed embodiments. Furthermore, other combinations, omissions, substitutions, and modifications will be apparent to those skilled in the art in view of the disclosure herein. As repeated above, any feature or combination of features described and referenced herein is included in any such combination as will be apparent from the context, the specification, and the knowledge of one of ordinary skill in the art. Are included within the scope of the present invention, provided that the features are consistent with each other. For example, any implants and implant components, subcomponents or applications, and any details or features or other features thereof, including method steps and techniques, may be combined in whole or in part, in any combination or replacement. It may be used with other structures and processes described or referenced in the specification. Accordingly, the invention is not intended to be limited by the disclosed embodiments, but is defined by reference to the appended claims.

Claims (34)

  Resorbable scar tissue reduction to reduce or prevent the formation of post-operative scar tissue between the post-surgical site and the adjacent surrounding tissue following in vivo surgery on the healing post-operative site A micromembrane system, wherein the system has a pre-implantation configuration defined as a configuration of the system immediately before the system is formed between the post-operative site and the adjacent surrounding tissue; The system comprises a substantially planar membrane comprising a resorbable polymer substrate having a first substantially smooth side and a second substantially smooth side, wherein the resorbable polymer group A substantially planar membrane of material comprises a single layer of resorbable polymer substrate between the first substantially smooth side and the second substantially smooth side. A single layer comprising the resorbable polymer substrate comprises (a) At least one hydrophobic block with one or more of a cutide and glycolide, and (b) at least one hydrophilic block with polyethylene glycol, further comprising triblock copolymers and star block copolymers A resorbable scar tissue reducing micromembrane system comprising one or more of the forms. The single layer of resorbable polymer substrate has a substantially uniform composition;
The thickness of the single layer of the resorbable polymer substrate is about 10 microns to about when measured between the first substantially smooth side and the second substantially smooth side. Between 300 microns,
The single layer of the resorbable polymer substrate is non-porous,
A single layer of the resorbable polymer substrate is formed over a relatively long period of time sufficient to reduce or eliminate any formation of scar tissue between the post-operative site and the adjacent surrounding tissue. The resorbable scar tissue-reducing micromembrane system of claim 1, wherein the surface is adapted to maintain a smooth barrier between a post-operative site during healing and the adjacent surrounding tissue.   Resorbable scar tissue reduction to reduce or prevent the formation of post-operative scar tissue between the post-surgical site and the adjacent surrounding tissue following in vivo surgery on the healing post-operative site A micromembrane system, wherein the system has a pre-implantation configuration defined as a configuration of the system immediately before the system is formed between the post-operative site and the adjacent surrounding tissue; The system comprises a substantially planar membrane comprising a resorbable polymer substrate having a first substantially smooth side and a second substantially smooth side, wherein the resorbable polymer group A substantially planar membrane of material comprises a single layer of resorbable polymer substrate between the first substantially smooth side and the second substantially smooth side. A single layer comprising the resorbable polymer substrate comprises (a) 4 additions comprising at least one hydrophobic block with one or more of a cutide, glycolide or a mixture of lactide and glycolide, and (b) at least one hydrophilic block with polyethylene glycol A resorbable scar tissue-reducing micromembrane system comprising a block copolymer form. The single layer of resorbable polymer substrate has a substantially uniform composition;
The thickness of the single layer of the resorbable polymer substrate is about 10 microns to about when measured between the first substantially smooth side and the second substantially smooth side. Between 300 microns,
The single layer of the resorbable polymer substrate is non-porous,
The resorbable scar tissue-reducing micromembrane system of claim 3, wherein the substantially planar layer of resorbable polymer substrate is disposed within a package.   The single layer of resorbable polymer substrate comprises (i) a first hydrophobic block comprising one or more of lactide, glycolide or a mixture of lactide and glycolide; and (ii) polyethylene glycol A resorbable scar tissue reducing micromembrane system according to claim 3 comprising a plurality of second hydrophilic blocks comprising:   6. The resorbable scar tissue-reducing micromembrane system of claim 5, wherein the single layer of resorbable polymer substrate comprises a star block copolymer.   The single layer of the resorbable polymer substrate comprises (i) a first hydrophobic PLA / PGA block and (ii) three or more second hydrophilic PEG blocks. The resorbable scar tissue-reducing micromembrane system of claim 3, comprising a block copolymer.   The single layer of resorbable polymer substrate comprises (i) a first hydrophobic block comprising at least one polyethylene glycol, and (ii) each of lactide, glycolide or a mixture of lactide and glycolide A resorbable scar tissue-reducing micromembrane system according to claim 3, comprising a plurality of second hydrophilic blocks comprising one or more of the following.   9. The resorbable scar tissue-reducing micromembrane system of claim 8, wherein the single layer of resorbable polymer substrate comprises a star block copolymer.   The single layer of resorbable polymer substrate comprises a star having (i) at least a first hydrophobic PEG block and (ii) three or more second hydrophilic PLA / PGA blocks. The resorbable scar tissue-reducing micromembrane system of claim 3, comprising a mold block copolymer.   The single layer comprising the resorbable polymer substrate comprises a first hydrophobic block comprising one or more of lactide, glycolide or a mixture of lactide and glycolide, and a first layer comprising at least one polyethylene glycol. A triblock or 4-addition block copolymer comprising two hydrophobic blocks and a third hydrophobic block comprising one or more of lactide, glycolide, a mixture of lactide and glycolide, and polyethylene glycol, The resorbable scar tissue micromembrane system of claim 3.   The resorbable scar tissue-reducing micromembrane system of claim 3, wherein the maximum thickness is about 100 microns.   The resorbable scar tissue-reducing micromembrane system of claim 3, wherein the maximum thickness is about 200 microns.   4. The resorbable scar tissue-reducing micromembrane system of claim 3, wherein the single layer of resorbable polymer substrate is not fluid permeable.   A single layer of the resorbable polymer substrate is a chemotactic substance that affects cell migration, an inhibitor that affects cell migration, a mitogenic growth factor that affects cell proliferation, and an influence on cell differentiation. The resorbable scar tissue-reducing micromembrane system according to claim 3, comprising at least one of a growth factor that affects vascularization and a factor that promotes angiogenesis.   The resorbable scar tissue-reducing micromembrane system of claim 3, wherein the resorbable scar tissue-reducing micromembrane system is encapsulated in sterile packaging. 4. The reclaim of claim 3, wherein the single layer of resorbable polymer substrate comprises a plurality of holes disposed along an edge of the single layer of resorbable polymer substrate. Absorbable scar tissue-reducing micromembrane system.   4. The single layer of resorbable polymer substrate does not comprise any holes substantially away from the edge of the single layer of resorbable polymer substrate. A resorbable scar tissue-reducing micromembrane system as described in 1.   4. The resorbable scar tissue-reducing micromembrane system of claim 3, wherein the edge extends around a single layer of the resorbable polymer substrate.   The resorbable scar tissue-reducing micro of claim 3, wherein a slit is formed on the outer periphery of the single layer of the resorbable polymer substrate so that the edge extends along the slit. Membrane system. The single layer of resorbable polymer substrate further comprises a plurality of holes disposed away from the edge;
Each of the holes near the outer periphery has a first diameter;
Each of the holes near the center has a second diameter;
The resorbable scar tissue-reducing micromembrane system according to claim 3, wherein the first diameter is greater than the second diameter.   The resorbable scar tissue-reducing micro of claim 3, wherein a slit is formed on the outer periphery of the single layer of the resorbable polymer substrate so that the edge extends along the slit. Membrane system.   4. The resorbable scar tissue reducing micromembrane system of claim 3, wherein the single layer of resorbable polymer substrate comprises a slit disposed in the nonporous substrate.   A single layer of the resorbable polymer substrate is cut into a size and shape suitable to fit snugly and anatomically on the anatomical structure. 4. The resorbable scar tissue-reducing micromembrane system of claim 3, wherein the resorbable scar tissue-reducing micromembrane system is reduced or prevented from forming between the tissue and surrounding tissue and encapsulated in sterile packaging.   The resorbable body of claim 3, wherein the single layer of resorbable polymer substrate is cut with a tab that folds over and around the anatomical structure. Scar tissue reduction micromembrane system.   4. The resorbable scar tissue-reducing micromembrane system of claim 3, wherein the single layer of resorbable polymer substrate comprises at least one notch disposed in the nonporous substrate.   4. The resorbable scar tissue-reducing micromembrane system of claim 3, wherein the single layer of resorbable polymer substrate comprises a plurality of notches disposed in the nonporous substrate.   The resorbable scar tissue-reducing micromembrane system of claim 3, wherein the single layer of resorbable polymer substrate is cut into a non-rectangular and non-circular shape and encapsulated in sterile packaging.   4. The resorbable scar tissue reducing micromembrane system of claim 3, further comprising another membrane that has a maximum thickness of less than 2000 microns and is permeable.   4. The resorbable scar tissue-reducing micromembrane system of claim 3, wherein the another membrane is a bridge membrane.   4. The resorbable scar tissue-reducing micromembrane system of claim 3, wherein the another membrane is fluid permeable.   4. The resorbable scar tissue-reducing micromembrane system of claim 3, wherein the other membrane is cell permeable.   4. The resorbable scar tissue-reducing micromembrane system of claim 3, wherein the other membrane is vascular permeable.   4. The resorbable scar tissue-reducing micromembrane system of claim 3, wherein the another membrane comprises a thickness between 500 microns and 2000 microns.