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WO2002017816A1 - Procedes et compositions permettant une augmentation tissulaire - Google Patents

Procedes et compositions permettant une augmentation tissulaire Download PDF

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Publication number
WO2002017816A1
WO2002017816A1 PCT/US2001/027142 US0127142W WO0217816A1 WO 2002017816 A1 WO2002017816 A1 WO 2002017816A1 US 0127142 W US0127142 W US 0127142W WO 0217816 A1 WO0217816 A1 WO 0217816A1
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composition
pvp
compositions
ptfe
phase
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PCT/US2001/027142
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English (en)
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Wallace K. Dyer
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Dyer Wallace K
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Priority to AU2001288585A priority Critical patent/AU2001288585A1/en
Publication of WO2002017816A1 publication Critical patent/WO2002017816A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/06—Flowable or injectable implant compositions

Definitions

  • TECHNICAL FIELD This application relates to novel biphasic and single phase compositions for soft tissue volume replacement, and methods of use of such compositions.
  • the present invention relates to methods for use of such compositions as material in plastic and reconstructive surgery.
  • injectable implant material can be designed to be tolerated by the host and to mimic the tissue it is designed to replace or augment. Even the well-tolerated implant, however, still acts as a foreign body after placement.
  • a layer of host proteins rapidly adsorbs onto the hydrophobic implant surface of most polymers and attempts to degrade the polymer. The denatured proteins elicit an acute inflammatory response from the patient, attracting neutrophils, macrophages, and f ⁇ broblasts. Collagen is then deposited over the matrix on the implant, laying the groundwork for subsequent cellular adhesion.
  • the degree of chronic inflammation that persists depends upon the specific qualities of the implant, as well as the local tissue environment. Implant materials that undergo enzymatic degradation, nonspecific hydrolysis, or stress fragmentation will release breakdown products into the local environment.
  • Local macrophages will generally engulf those particles that are 60 microns or smaller and may transport them to regional lymph nodes. Submicrometer-sized particles are the most easily transported and may remain intracellularly indefinitely. Particles ranging from 20 to 60 microns approach the size of a macrophage and may cause the death of the cell when engulfed. The dead cell then releases its intracellular enzymes, such as cytokines, which then attract more phagocytes.
  • Bovine collagen and its use as an injectable implant was first developed by Collagen Corporation in 1975 and called ZYDERMTM.
  • Bovine collagen is not desirable in facial plastic and reconstructive surgery because most users of ZYPLASTTM, another bovine collagen product, describe a clinical effect of merely three to four months, while ZYDERMTM 's results were even more short lived.
  • FIBRELTM FIBRELTM
  • FIBRELTM consists of plasma mixed with porcine-derived gelatin and e-aminocaproic acid (e-ACA)
  • e-ACA e-aminocaproic acid
  • the plasma serves as a source of fibrin and clotting factors
  • the gelatin defines the site of the reaction
  • the e-ACA limits fibrinolysis.
  • the tissue reaction that occurs upon injection leads to f ⁇ brinogen deposition, followed by fibrinolysis and collagen formation.
  • a disadvantage of FIBRELTM is that "touchups" are frequently required.
  • ZYDERMTM, ZYPLASTTM, and FIBRELTM are poorly suited for soft tissue augmentation because they rapidly biodegrade, and therefore, their effect is only transitory.
  • Hylaform/Biomatrix and Q-med Uppsala developed derivatives of hyaluronic acid to be used as injectable soft tissue builders. These products are currently being evaluated by the FDA.
  • Hylaform's HYLAN BTM gel product is an insoluble derivative produced by treating hyaluronic acid with vinyl sulfone.
  • Q-Med Uppsala's RESTYLANETM product also consists of hyaluronic acid but is cross-linked and processed into a 2% gel.
  • Hyaluronic acid is a polysaccharide that plays an integral role in stabilizing the extracellular matrix, as well as lubricating, hydrating, and increasing its viscoelastic properties. Because hyaluronic acid is not species-specific, it does not elicit a humoral or cell-mediated immune response in the patient. The use of hyaluronic acid as an injectable filler results in greater than 33% improvement at 18 weeks.
  • DERMALOGENTM homologous collagen dispersion
  • DERMALOGEN is a suspension of processed dermis obtained from AATB-accredited tissue banks. A mechanical process homogenizes the decellularized dermis to produce a suspension of mostly type I collagen, with trace amounts of types III and IN collagen, elastin, fibronectin, chondroitin sulfate, and other proteoglycans.
  • ALLODERMTM is an acellular sheet of meshed dermal proteins prepared from cadaver skin. Surgeons use this material for soft tissue augmentation in a variety of situations. An advantage of this material is that its effect is somewhat long term, lasting greater than one year. A distinct disadvantage is that use of this material requires an incision. Trials of long term efficacy will soon conclude for an injectable form of this material developed by the manufacturer.
  • the injectable form consists of micronized ALLODERMTM particles ranging in size from 60 to 600 microns and is injected into a deep dermal level with a 26 gauge needle.
  • Isolagen Technologies attempts to enhance production of collagen with its ISOLAGENTM product, by directly introducing cultured autologous fibroblasts. After a skin biopsy, autologous f ⁇ broblasts are isolated and expanded in vitro. A suspension of these fibroblasts is injected into the dermis and has been shown to provide persistent soft tissue augmentation. West and Alster treated eleven patients with ISOLAGENTM and noted persistent correction in the nasolabial folds six months after the injection. In addition, Watson et al. found that injected fibroblasts seemed to be incorporated into the dermis and lead to new collagen production. Subjective improvement of the treated areas increased over a six month followup, however, widespread use of this product will depend on more long term results. Injectable Synthetic Material
  • ARTEPLASTTM a product developed by Rofil Medical International BN.
  • ARTEPLASTTM is an injectable material composed of microspheres of polymethylmethylacrylate (PMMA) suspended in a gelatin solution. Following implantation, the gelatin is resorbed and replaced by native collagen.
  • PMMA polymethylmethylacrylate
  • ARTECOLLTM is a product, currently available in Europe and Canada, that the FDA is considering for use in the United States.
  • ARTECOLLTM consists of smooth 30 to 40 micron PMMA spheres, suspended in bovine collagen from a closed pharmaceutical herd at a concentration of 25% PMMA, 75% collagen, by weight with 0.3% lidocaine. Because ARTECOLLTM contains bovine collagen, skin testing for allergy to bovine collagen is recommended. Although the PMMA beads averaged 30 to 40 microns in size, and are thus theoretically subject to phagocytosis by macrophages, no phagocytosis of PMMA spheres was detected.
  • Silicone injection into facial soft tissues became popular during the 1960's and 1970's, due to Dow Coming's introduction of medical grade silicone (MDX 4-4011). Silicone appears to be tolerated when in small amounts in the face and can be injected interdermally or subcutaneously. Microdroplets of silicone are dispersed within dermal tissues and are individually surrounded by foreign body reactions. Fibrosis around these droplets localizes the material, but a low grade inflammatory process remains.
  • a distinct drawback of injectable liquid silicone is that particles may migrate if the silicone is used in large quantities. Silicone particles have been found in the liver, brain, lungs, and kidneys. Injection of small quantities of medical silicone, less than two milliliters, is successful and safe for the treatment of hemifacial atrophy and other tissue deficiencies of the face. However, liquid silicone used in large doses can provoke serious general complications due to the migration of the particles.
  • TEFLONTM Another injectable synthetic material is TEFLONTM, produced by Dupont.
  • TEFLONTM is inappropriate for usage in the face because migration of small particles of TEFLONTM paste and solid TEFLON have been reported.
  • BioplastiqueTM Uroplasty BV designed BIOPLASTIQUETM a biphasic material, consisting of solid silicone particles, ranging from 100 to 400 microns in size, suspended in a polyvinylpyrridolone ((C 6 H 9 NO) n ) carrier (PVP).
  • PVP polyvinylpyrridolone
  • Bioplastique elicits a low-grade inflammatory response upon injection. In a rabbit model, the liydrogel carrier is reabsorbed by the body within 96 hours and renally eliminated in an intact form.
  • the hydrogel carrier is replaced by fibrin and inflammatory cells. Fibroblasts are recruited into the area by 14 days and begin to replace the fibrin bed with a collagen matrix. The collagen encapsulates and localizes the silicone, and animal studies have not shown any evidence of foreign body migration. Deposition of collagen progresses, replacing the organic component of the material in a ratio slightly greater than 1:1. Connective tissue cells develop and replace about 30% of the matrix with host collagen fibrils. At day 382 after injection, fibrosis was complete, and each individual BIOPLASTIQUETM microimplant particle appeared to be encased in its own fibrous capsule.
  • BIOPLASTIQUETM is very stable. Neither histologic examination of the regional lymph nodes at the base of the rabbit ears or cross-sections of the ear below the injected area showed microimplant particles in any of the rabbits under study.
  • BIOPLASTIQUETM The gel phase of the biphasic BIOPLASTIQUETM is PNP, a member of the plasdone family.
  • the gel is scavenged by the reticuloendothelial system and excreted unchanged by the kidneys within a matter of days.
  • the PNP used in BIOPLASTIQUE has a molecular weight between 15,000 and 30,000 Da and has an appearance and consistency similar to that of honey.
  • the plasdones have been used as vehicles and extenders for a variety of medications without negative effects for nearly fifty years.
  • BIOPLASTIQUETM is generally implanted through a blunt,
  • BIOPLASTIQUETM should only be used deep under the skin and never in the skin. BIOPLASTIQUETM currently does not have FDA approval, but the manufacturer is evaluating an identical product, Macroplastique, for urethral incontinence under an FDA investigational drug exemption.
  • BIOPLASTIQUETM has the distinct disadvantage of using silicone as the solid substrate.
  • the solid phase of BIOPLASTIQUETM is fully polymerized and vulcanized methyl methylpolysiloxane [(CH 2 ) -SiO]. Questions exist about the long-term safety of silicone materials.
  • the present invention generally relates to methods and compositions comprising inert injectable materials for soft tissue volume replacement, and particularly to compositions having multiple components, and more particularly to compositions comprising a biphasic injectable material, comprising a solid polymer particle phase and a gel phase.
  • a preferred embodiment of the present invention comprises Gore-Tex (e- PTFE, an expanded, fibrillated form of polytetrafluoroethelene (PTFE)) as the solid polymer particle phase.
  • the hydrogel carrier phase of a preferred embodiment comprises polyvinylpyrrolidone (PNP), a member of a family of polymers that have been used pharmaceutically for nearly fifty years.
  • solid polymer particles made from materials including but not limited to, PDS II (polydioxanone, a monofilament), ⁇ UROLO ⁇ (a long chain aliphatic polymer Nylon 6 or Nylon 6,6) ETHILON (a long chain aliphatic polymer Nylon 6 and Nylon 6,6), PROLENE (Polypropylene, isotactic crystalline stereoisomer of polypropylene, a synthetic linear polyolefin.), NICRYL (copolymer made from 90% glycolide and 10% L-lactide), silk, MO ⁇ ACRYL (poly e- caprolactone.), polylactide, polyglycolide, poly lactide-co-glycolide, MEDPOR (biocompatible (micronized) polyethylene), BIOGLASS (bioactive glass particulate), ⁇ ONABO ⁇ E, ⁇ ONABO ⁇ E-CM, and BIOPOL (polyhydroxyvalerate).
  • PDS II polydioxanone, a
  • inert polymers have all been approved for medical use and are used in suture and implant materials. These polymers provide a solid phase for at least more than three days. Such polymers may remain solid within the body for a long time or may be resorbed by the body in a few weeks.
  • solid polymer comprises both long-lasting polymers and polymers that are resorbed by the body.
  • compositions of multiple materials for use in tissue augmentation provides compositions of a biphasic injectable material for use in soft tissue augmentation, such as subcutaneous placement.
  • Another embodiment of the present invention also provides methods of use of compositions, which comprise single phase compositions such as PNP which are useful for effacing fine rhytids, such as crows feet, depressed acne scars, perioral rhytids, stretch marks and furrows.
  • Such compositions are particularly useful in methods of intradermal augmentation.
  • the compositions of the present invention can be used for tissue augmentation at any site in the body where tissue bulking or augmentation is needed, whether for functional or aesthetic purposes.
  • a particularly preferred method comprises using the compositions of the present invention for urological conditions.
  • tissue augmentation and compositions that are permanent or that may be resorbed by the body, resistant to infection, resistant to extrusion and non-antigenic.
  • Another object of the present invention is to provide compositions comprising particles of a size that are large enough to prevent ingestion by macrophages and to prevent migration to distant sites after implantation.
  • Still another object of the present invention is to provide methods for tissue augmentation and compositions that are useful in soft tissue augmentation that is mechanically stable with respect to the surrounding tissues.
  • Yet another object of this invention is to provide a method for treating stress incontinence through functional augmentation.
  • the present invention is directed to methods of tissue augmentation and novel compositions of injectable material suitable for soft tissue replacement that are permanent or semi-permanent, biocompatible, moldable, mechanically stable, and have the consistency of the tissues that are replaced.
  • tissue ingrowth occurs when implant surfaces are textured or patterned, and the ingrowth prevents host-prosthesis interface micro- motion, resulting in a more intimate mechanical bond between the mammalian host and the inert implant.
  • studies by Taylor and Gibbons, Whalen, Beisang, and Ersek, and others demonstrate that the use of textured surfaces results in a thinner, less reactive encapsulation than smooth-surfaced implants in the same animal at the same time.
  • Implant infection can occur either by direct inoculation (e.g., placement of an implant through a contaminated area) or hematogenously.
  • implant pores provide a potential space for infection to develop if these spaces are not occupied by host tissues.
  • Merritt et al. showed that porous implants are more susceptible to early infection, but less susceptible to late infection, when compared to solid implants.
  • Scalfani et al. showed that the presence of soft tissue ingrowth into porous implants has a protective effect against experimentally-induced infections.
  • the present invention comprises methods of use of compositions comprising multiple materials, such as solid particles and a carrier.
  • a most preferred solid particle comprises micronized particles of e- PTFE ("Gore-Tex").
  • Other materials that are suitable for use in the present invention include, but are not limited to, PDS II (polydioxanone, a monofilament), NUROLON (a long chain aliphatic polymer Nylon 6 or Nylon 6,6) ETHILON (a long chain aliphatic polymer Nylon 6 and Nylon 6,6), PROLENE (Polypropylene, isotactic crystalline stereoisomer of polypropylene, a synthetic linear polyolefin.), VICRYL (copolymer made from 90% glycolide and 10% L-lactide), silk, MONACRYL (poly e- caprolactone.), polylactide, polyglycolide, poly lactide-co-glycolide, MEDPOR (biocompatible (micronized) polyethylene), BIO
  • Carriers that are suitable for use in the present invention include, but are not limited to, PNP, silicone oil, saline, gelatin, collagen, autologous fat, hyaluronic acid, autologous plasma and other physiological carriers.
  • Preferred embodiments of the present invention comprise compositions comprising solid particles of Gore-Tex of an injectable size.
  • This material is nontoxic, physically stable, and chemically biocompatible.
  • Gore-Tex is manufactured as an expanded, fibrillated form of polytetrafluoroethelene (PTFE).
  • PTFE polytetrafluoroethelene
  • Compositions comprising Gore-Tex provide a much more stable implant than other materials used in relatively large implants. Such textured microparticles in the compositions of the present invention lead to a more lasting implant result.
  • a combined composition may comprise Gore-Tex, fat, and collagen.
  • the carrier material may be PNP, water, saline, or other solutions that are capable of being injected and act as a carrier for the solid particles. Any of the known materials for tissue augmentation may be used in combinations of the present invention, though most preferable combinations comprise these materials and Gore-Tex.
  • Sheets of Gore-Tex material have been used in tissue augmentation. Pores between the PTFE fibrils in Gore-Tex average about twenty-two microns in size and allow limited soft tissue ingrowth. Gore- Tex evokes a mild chronic inflammatory response and is rapidly surrounded by a thin fibrous capsule. At present, sheets of Gore-Tex have been used in subcutaneous volume augmentation on the chin, malar area, nasal dorsum, nasolabial folds, and lips. e-PTFE is a suitable implant for soft tissue augmentation of the face because of its soft, natural feel and high biocompatibility.
  • e-PTFE implants in mobile facial areas make removal possible and provide easy sterilization, they are also unstable due to the limited implant surface for tissue ingrowth which results in inflammation and extrusion.
  • Advantages of the present invention comprising Gore-Tex particles are that limited fibrous tissue ingrowth into the surface of the material provides early stabilization, while allowing for removal if necessary. Gore-Tex is inert and does not change shape or reabsorb with time. Additionally, Gore-Tex is not carcinogenic, rarely allergenic, and causes only minimal tissue reaction. After implantation, fibrous encapsulation inhibits breakdown of the particles. The size of the particles prevents the material from being phagocytosed, and thus, it does not serve as an antigen.
  • compositions comprising particles greater than one hundred microns in size with a textured surface. Such compositions are interspersed in a host-generated fibrotic tissue matrix within a few weeks.
  • Compositions of the present invention comprise particles having a size range of approximately 60 microns to approximately one millimeter are useful in methods for soft tissue augmentation. For other methods, differently sized particles are contemplated by the present invention.
  • compositions of injectable material suitable for tissue replacement that are biocompatible, moldable, mechanically stable, and have a consistency similar to the tissue that it replaces.
  • Such compositions may be used in methods of tissue augmentation known to those in the surgical arts.
  • the biphasic compositions are injected into tissue sites, and most preferably, are used in subcutaneous injection methods. Additional preferable methods include methods of injection of the compositions of the present invention in tissue sites such as those in the urethra or other urological sites. Other preferable sites include tissue sites such as the vocal cords.
  • PNP polyvinylpyrrolidone
  • tissue augmentation material includes polyvinylpyrrolidone (PNP) as a tissue augmentation material.
  • PNP is a water-soluble polyamide that possesses unusual complexing and colloidal properties and is physiologically inert. It does not act as a skin or eye irritant or as a skin-sensitizer.
  • PNP is well tolerated by intraperitoneal, intramuscular, and intravenous routes, as well as parenteral uses such as usage for plasma volume expansion. No cancer effect for PVP has been demonstrated by any route.
  • PVP is a biocompatible gel vehicle that is freely transported through the body and is excreted unchanged by the kidneys.
  • This gel has the trade name Au24k and consists of macromolecules from the plasdone family, having the empirical formula (CHCH 2 ) 2 N(CH 2 ) 3 -CO. Polymers of this family have been used as binders, extenders, and vehicles for a variety of medications for nearly fifty years. In fact, over 4,000 papers have been published on the use of PVP in pharmacy and medicine since 1940.
  • PVP is available commercially in many molecular weight ranges and is polymerized to have an average molecular weight in a particular solution.
  • PVP is available in solutions of an average molecular weight of 10,000 daltons, 40,000 daltons and 360,000 daltons.
  • PVP is also defined by its viscosity measurement, or K value. K values range from approximately less than 12 to 100.
  • a preferred PVP composition of the present invention has a range of K values of less than 12 to 50, more preferably less than 12 to 20, and most preferable is a composition of K17.
  • PVP is commercially available from GAF Chemical Corp., Wayne, NJ, USA, and from BASF Aktiengesellschaft, Germany.
  • the gel polymer may be diluted with deionized water to produce the desired osmotic gradient, is sterilized, and placed in cartridges for injection.
  • An inflammatory reaction due to the reabsorption of the PVP occurs a few days after implantation, and the PVP undergoes a prompt replacement by host fibrin or protocollagen within 96 hours.
  • this fibrin substitution is completed, fibroblasts appear within the matrix and begin fabricating host collagen by the sixth day; by the sixth week, this fibrosis is complete. The result is stable and final after approximately three months.
  • a preferred composition of the present invention comprises solid substrate particles of Gore-Tex (e-PTFE) ranging in size from one hundred to two hundred microns mixed with PVP hydrogel.
  • the composition has all of the desirable characteristics of an injectable soft tissue implant.
  • the small Gore-Tex particles, having a textured surface form an inert biocompatible polymer that can be mixed, at a range 5:95 to 95:5, more preferably 20:80, most preferably 40 to 60, by weight, with a biocompatible solution of water and organic polymer gel.
  • Utilizing the hydrogel carrier PNP not only promotes ingrowth, but also provides a barrier to bacterial invasion of the textured e-PTFE surface.
  • Preferred methods include injection of such biphasic compositions, more preferably, the compositions are injected subcutaneously. Other injection sites such as intramuscular and intradermal are included in the methods of the present invention. Preferred methods include tissue bulking methods, particularly for urological conditions. For example, the compositions of the present invention are injected into the walls of the urethra to aid in the treatment of incontinence. Other methods of tissue bulking are also contemplated by the present invention, such as for vocal cord augmentation or repair.
  • compositions comprising carriers such as PNP or known physiological carriers in combination with materials, including but limited to, collagen, bovine or human, other particles made from materials such as PDS II (polydioxanone, a monofilament), ⁇ UROLO ⁇ (a long chain aliphatic polymer Nylon 6 or Nylon 6,6) ETHILON (a long chain aliphatic polymer Nylon 6 and Nylon 6,6), PROLENE (Polypropylene, isotactic crystalline stereoisomer of polypropylene, a synthetic linear polyolef ⁇ n.), NICRYL (copolymer made from 90% glycolide and 10% L-lactide), silk, MONACRYL (poly e-caprolactone.), polylactide, polyglycolide, poly lactide-co-glycolide , MEDPOR (biocompatible (micronized) polyethylene), BIOGLASS (bioactive glass particulate), NONABONE, NONABONE-CM, and
  • the present invention further utilizes methods and compositions for tissue augmentation that comprise injection of PVP for tissue augmentation, preferably intradermal injection, particularly for fine rhytids, such as crows feet, depressed acne scars and perioral rhytids.
  • PVP undergoes a prompt replacement by host fibrin or protocollagen within 96 hours. As this fibrin substitution is completed, fibroblasts appear within the matrix and begin fabricating host collagen by the sixth day; by the sixth week, this fibrosis is complete. The result is stable and final after about three months.
  • Preferred methods of the present invention comprise use of PVP as an intradermal injection material to generate deposition of host collagen to efface fine rhytids such as crows feet, depressed acne scars and perioral rhytids.
  • the preparation of the intradermal sites to be injected are cleansed initially with a germicidal soap such as Hibiclens®.
  • a germicidal soap such as Hibiclens®.
  • the patient is then marked in the upright position with a fine surgical marking pen and those areas marked are lightly swabbed with alcohol prior to injection with the patient in the supine position.
  • Diffuse overhead light is the best illumination when injecting the face.
  • a bright light directed onto the face does not allow shadows to be cast which further identify the lines, depressions, scars, etc. that are outlined in ink.
  • the serial puncture technique is utilized: the thumb is placed one centimeter behind the index finger as both digits of the left hand (if one is right-handed) straddle and raise the affected area.
  • the needle is repeatedly inserted (at an oblique angle) into the skin between the thumb and finger at intervals of several millimeters along the course of the wrinkle, depression or area to be augmented.
  • This Example is directed to intradermal use, primarily.
  • the injectable techniques illustrated herein can also be adapted to subcutaneous, intramuscular, periurethral or other deeper injection sites with a biphasic augmentation material for functional or cosmetic applications.
  • Common cosmetic applications include intramuscular lip augmentation and subcutaneous augmentation of the nasolabial creases.
  • Special blunt 20-gauge cannulas measuring about 4 inches in length are attached to a leveraged "gun" that receives syringe cartridges. This gun allows very precise injection of the material in small, evenly spaced quantities of the biphasic augmentation material.
  • First the area to be treated is outlined with a pen, and the estimated volume is recorded. This area is then injected with lidocaine with epinephrine to provide anesthesia and to minimize bleeding.
  • the blunt cannula is then introduced to the subcutaneous tissue.
  • Subcutaneous cosmetic augmentation of the nasolabial creases and reconstructive augmentation of iatrogenic or traumatic lipodystrophy (dents due to subcutaneous fat loss) are performed in a similar fashion.
  • the entire area is injected with Xylocaine 1% with epinephrine 1:100,000, providing the local block needed as well as hemostasis.
  • a remote puncture is then performed with a 18-gauge sharp needle on each side of the area for augmentation, peripheral to the outlined area, so that 1 to 2cm of "no-man's land” isolates the puncture sites from the area of planned implantation. Pretunneling is done in various planes.
  • microparticles are then implanted from the same remote puncture site by means of the injection gun. Injection is done only on withdrawal, mimicking the path and technique of the pocar and injecting only to the midline.
  • the cannula is kept in constant motion, and trigger pressure is gently maintained on withdrawal such that a 0.1 -cc volume injection is 30cm in length.
  • These methods allow precise and even placement of the solid phase microparticles at the intended plane and prevent deposition near the puncture site, which could impede healing of the dermis and result in palpable elevations. Such techniques also provide a maximum host- prosthesis interface and a minimum of beading or coalescing of these particles.
  • the pressure is released in the gun and the cannula quickly withdrawn. Digital pressure is applied to the midline while the puncture site and "no man's land" are rinsed with local anesthesia to further prevent extrusion.
  • Functional augmentation with the biphasic injectable may be utilized in treatment of stress incontinence.
  • the patient In the case of females, the patient is placed in the lithotomy position. The vulva and vagina are cleansed and the patient is draped as for a cystoscopic procedure. The urethra is calibrated with a bougie for evidence of strictures. Cystoscopy and urethroscopy are performed.
  • a 20 gauge needle, approximately 4 inches long, is attached to a Lewy syringe that has been loaded with biphasic augmentation material, inserted at the urethral meatus and advanced periurethrally toward the bladder neck. At this point several cubic centimeters of the paste are injected. The injection is continued as the needle is withdrawn.
  • the procedure is performed at approximately 3, 6 and 9 o'clock positions around the urethra.
  • the needle can be guided along the narrow septum between the urethra and vagina with an examining finger in the vagina.
  • Approximately 10 to 15 ml. of paste are injected.
  • the urethra is inspected with a panendoscope during the injections to be certain that the needle has not perforated the bladder or urethra.
  • resistance develops to the movement of the panendoscope in the urethra, hi male patients, the external genitalia and the perineum are carefully cleansed and draped.
  • the urethra is calibrated to be certain that strictures are not present.
  • Urethrograms are obtained when necessary.
  • the bladder and urethra are inspected with careful attention to the prostatic and membranous urethra.
  • the panendoscope is left in the urethra as a 17 gauge needle is inserted into the perineum and advanced toward the apex of the prostate. By gentle to and fro motion one can observe the tip of the needle advancing toward the region of the external sphincter. Care is taken to avoid penetration of the urethral lumen, which would provide an escape for the biphasic augmentation material.
  • the Lewy syringe is attached and the injections are started.
  • the needle is advanced, withdrawn or moved to a new position when appropriate to try to produce complete closure or narrowing of the membranous urethra.
  • the injection can be monitored through the panendoscope and the blebs produced by the injections are visualized clearly. Generally, 15cc of the paste are injected.
  • An alternate method is to enter the lumen of the urethra several centimeters away from the area to be injected. The needle is advance through the lumen and the urethral wall is penetrated a few millimeters from the area to be injected. The needle tip is advanced within the urethral wall and the paste is injected.
  • Boss WK Marko O. Isolagen. In: Klein AW, ed., Tissue Augmentation in Clinical Practice; Procedures and Techniques, New York: Marcel Dekker; 1998:335-347

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  • Materials For Medical Uses (AREA)

Abstract

L'invention concerne des procédés et des compositions destinées au remplacement de la masse tissulaire. Les compositions décrites comprennent une combinaison de matières comprenant de préférence une phase de particules polymères solides, et une phase gel, et peut également comprendre des compositions monophasées. Les formes de réalisation préférées comprennent plus particulièrement une phase de particules polymères solides produites à partir de matériaux suivants ; Gore-Tex (e-PTFE micronisé), PDS II (polydioxanone, un monofilament), NUROLON (un nylon 6 ou nylon 6,6 polymère aliphatique à longue chaîne), ETHILON (Nylon 6 et Nylon 6,6 polymère aliphatique à longue chaîne), PROLENE (polypropylène, stéréoisomère cristallin isotactique de polypropylène, une polyoléfine linéaire synthétique), VICRYL (copolymère composée de 90 % de glycolide de 10 % de L-lactide), soie, MONACRYL (poly ε-caprolactone), polylactide, polyglycolide, polylactide-co-glycolide, et BIOPOL (polyhydroxyvalérate), MEDPOR (polyéthylène biocompatible (micronisé)), BIOGLASS (particules de verre bioactif), NOVABONE et NOVABONE-CM, et la phase gel comprend du polyvinylpyrrolidone (PVP). Les compositions monophasées préférées comprennent du PVP. Les procédés décrits consistent à injecter ces compositions afin d'augmenter la masse tissulaire.
PCT/US2001/027142 2000-08-30 2001-08-30 Procedes et compositions permettant une augmentation tissulaire WO2002017816A1 (fr)

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AU2001288585A AU2001288585A1 (en) 2000-08-30 2001-08-30 Methods and compositions for tissue augmentation

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US22908500P 2000-08-30 2000-08-30
US60/229,085 2000-08-30
US22998900P 2000-09-05 2000-09-05
US60/229,989 2000-09-05
US24163600P 2000-10-19 2000-10-19
US60/241,636 2000-10-19

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1610674A4 (fr) * 2003-03-13 2008-05-21 Cheryl M Burgess Procedes pour administrer une matiere a un patient afin d'obtenir une amelioration dermique
CN111110918A (zh) * 2019-09-26 2020-05-08 中新棠国业(苏州)医疗科技有限公司 一种高强度植入级骨材料的制备方法

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US4946377A (en) * 1989-11-06 1990-08-07 W. L. Gore & Associates, Inc. Tissue repair device
US5098779A (en) * 1990-06-25 1992-03-24 W. L. Gore & Associates, Inc. Carvable implant material
US5158573A (en) * 1989-06-09 1992-10-27 American Medical Systems, Inc. Injectable polymeric bodies
US5368859A (en) * 1989-07-24 1994-11-29 Atrix Laboratories, Inc. Biodegradable system for regenerating the periodontium

Patent Citations (4)

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Publication number Priority date Publication date Assignee Title
US5158573A (en) * 1989-06-09 1992-10-27 American Medical Systems, Inc. Injectable polymeric bodies
US5368859A (en) * 1989-07-24 1994-11-29 Atrix Laboratories, Inc. Biodegradable system for regenerating the periodontium
US4946377A (en) * 1989-11-06 1990-08-07 W. L. Gore & Associates, Inc. Tissue repair device
US5098779A (en) * 1990-06-25 1992-03-24 W. L. Gore & Associates, Inc. Carvable implant material

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1610674A4 (fr) * 2003-03-13 2008-05-21 Cheryl M Burgess Procedes pour administrer une matiere a un patient afin d'obtenir une amelioration dermique
US7637900B2 (en) 2003-03-13 2009-12-29 Cheryl Burgess Methods of administering a material into a patient for dermal enhancement
US8038665B2 (en) 2003-03-13 2011-10-18 Burgess Cheryl M Methods of administering a material into a patient for dermal enhancement
CN111110918A (zh) * 2019-09-26 2020-05-08 中新棠国业(苏州)医疗科技有限公司 一种高强度植入级骨材料的制备方法
WO2021057234A1 (fr) * 2019-09-26 2021-04-01 中新棠国业(苏州)医疗科技有限公司 Procédé de préparation d'une substance osseuse de qualité pour l'implantation et de grande résistance

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