WO2006102676A1 - Elements de remplissage dermal d’oxyde de polyethylene et dispositifs associes - Google Patents

Elements de remplissage dermal d’oxyde de polyethylene et dispositifs associes Download PDF

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Publication number
WO2006102676A1
WO2006102676A1 PCT/US2006/011201 US2006011201W WO2006102676A1 WO 2006102676 A1 WO2006102676 A1 WO 2006102676A1 US 2006011201 W US2006011201 W US 2006011201W WO 2006102676 A1 WO2006102676 A1 WO 2006102676A1
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WIPO (PCT)
Prior art keywords
polyethylene oxide
dermal filler
composition
injector device
filler gel
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PCT/US2006/011201
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English (en)
Inventor
Edward Perez
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Tissue Engineering Refraction, Inc.
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Application filed by Tissue Engineering Refraction, Inc. filed Critical Tissue Engineering Refraction, Inc.
Publication of WO2006102676A1 publication Critical patent/WO2006102676A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8105—Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers
    • A61K8/8111—Homopolymers or copolymers of aliphatic olefines, e.g. polyethylene, polyisobutene; Compositions of derivatives of such polymers
    • 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
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/91—Injection
    • 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

  • This description relates to the field of injectable implants useful in supplementing soft tissue, particularly skin. More particularly it relates to dermal filler compositions of biocompatible polyethylene oxides that may be introduced, perhaps by injection, into areas of soft tissue often in need of augmentation. Examples include cosmetic enhancement or correction of facial defects due to scarring, aging and the like. This description also relates to kits containing the described polyethylene oxides and to processes of using these compositions.
  • Injectable dermal fillers are used extensively for the augmentation of soft tissue, such as for removing wrinkles, treating dermal scarring due to trauma, acne, surgery and the like, or for augmenting soft tissue of the lips and nasolabial folds.
  • Injectable fillers have several advantages over traditional surgical techniques for implanting filler materials, such as reduced discomfort, ease of administration, and precise control of the augmentation.
  • Desirable injectable materials are biocompatible, non-immunogenic, non-toxic, non-carcinogenic, and non-resorbable. In addition, they should have the ability to conform to a desired shape and not migrate from the implantation site. They should also be inexpensive, easily sterilized, and have a long storage shelf life.
  • injectable fillers for instance, collagen based fillers, hyaluronic acid, synthetic materials such as Silicone or polymethyl methacrylate particles, and autologous materials such as autologous fat (Hotta, Plastic Surgical Nursing 24(1): 14-19, 2004; Ellis et al, Facial Plastic Surgery Clinics of North America 9(3): 405-411, 2001).
  • Polyethylene oxides are non-toxic polymers that used in a variety of products, such as cosmetics, shampoos, drug formulations, and laxatives. Polyethylene oxides are available in sizes ranging in molecular weight from less than 1,000 to as high as 10,000,000, for example from Amerchol (Dow) or Polysciences, Inc. (Warrington, PA). These polymers may be linear, branched, or in some instances crosslinked. Although linear polymers are typically water soluble even at high molecular weights, branching and crosslinking of the polymers may result in decreased water solubility such that substantially insoluble solid or gel materials are formed. Crosslinking of polyethylene oxide polymers by a variety of methods is well known, for example, by methods described in U.S. patents 6,323,287 and 6,537,569, among others.
  • compositions of polyethylene oxide for use as dermal fillers and optionally containing a liquid carrier in which the described polyethylene oxides are substantially insoluble are intended to include aqueous fluids, e.g., water and saline solutions, and includes both imbibed liquids where the selected polyethylene oxides are crosslinked and fluids exterior to polyethylene oxides bodies present in an injectable composition.
  • the liquid carrier may further comprise pharmaceutically acceptable excipients, adjuvants, diluents or stabilizers, or combinations thereof.
  • the liquid carrier comprises saline or neat water.
  • the injectable composition is made up of particles consisting of polyethylene oxide and an aqueous liquid carrier comprising saline or water.
  • the injectable composition is made up of particles consisting of polyethylene oxide and the aqueous carrier consists essentially of saline.
  • the polyethylene oxide compositions have a form that is injectable by an injector, such as injectable through a needle.
  • the form may comprise particles having a particle size and configuration injectable by such injectors.
  • the polyethylene oxide compositions may be substantially non-biodegradable.
  • the polyethylene oxide may be linear or branched and either non-crosslinked or crosslinked. Specifically, the polyethylene oxide may be linear or branched polyethylene oxide that is crosslinked.
  • the crosslinked polyethylene oxide may be in the form of a non-biodegradable hydrogel and in one variation containing such polymer, the composition substantially lacks any organic compound capable of swelling the hydrogel, for example, the composition lacks any organic compound selected from the group consisting of polyethylene glycol having a molecular weight of less than about 10,000, also of less than about 5,000 or less than about 1,000, polyvinyl pyrrolidone, dextran, polyethylene oxide polypropylene oxide copolymer having a molecular weight of less than about 5,000, also of less than about 1,000, polyacrylic acid, polyacrylamide, polyvinyl pyridine, polylysine, polyarginine and oligopeptides.
  • polyethylene glycol having a molecular weight of less than about 10,000, also of less than about 5,000 or less than about 1,000
  • polyvinyl pyrrolidone dextran
  • polyethylene oxide polypropylene oxide copolymer having a molecular weight of less than about 5,000, also of less than
  • the linear or branched polyethylene oxide may be non-crosslinked with a molecular weight in the range of 100,000 to 10,000,000, also 200,000 to 8,000,000, also 400,000 to 8,000,000, or 1,000,000 to 8,000,000.
  • the linear or branched polyethylene oxide may be crosslinked, wherein prior to crosslinking, the polyethylene oxide has a molecular weight in the range of 20,000 to 10,000,000, also 50,000 to 2,000,000, also 500,000 to 2,000,000, also 50,000 to 1,000,000, or 50,000 to 500,000.
  • the crosslinked polyethylene oxide may be in the form of a non-biodegradable hydrogel.
  • the injectable composition may, in addition to including polyethylene oxides, further comprise crosslinked hyaluronic acid, e.g., bodies or particulates consisting essentially of hyaluronic acid having a particle size and configuration that are injectable by an injector, such as injectable through a needle.
  • hyaluronic acid materials similarly are substantially insoluble in the liquid carrier. Where particles are used, such hyaluronic acid particles may be in the same size range as that of the polyethylene oxide particles.
  • the injectable polyethylene oxide or hyaluronic acid particles may be in a size range and configuration that is injectable through a syringe needle, such as having a dimension with a size range of about 10 to 1,000 ⁇ m, also about 20 to 1,000 ⁇ m, also about 50 to 1,000 ⁇ m, or about 100 to 1,000 ⁇ m.
  • the injectable polyethylene oxide or hyaluronic acid bodies, compositions, and particles should be of a size and configuration such that they are injectable through a syringe needle ranging in size from 18 to 33 gauge, also 24 to 31 gauge, or 27 to 30 gauge.
  • dermal filler compositions comprising, consisting essentially of, or consisting of polyethylene oxide and a liquid carrier in which the particles are substantially insoluble.
  • the liquid carrier may be aqueous or non-aqueous. In one instance, the liquid carrier may be aqueous.
  • the aqueous liquid carrier may comprise, consist essentially of, or consist of a saline solution.
  • the liquid carrier may further comprise pharmaceutically acceptable excipients, adjuvants, diluents or stabilizers, or combinations thereof.
  • the liquid carrier may further contain other materials, e.g., antibiotics or local anesthetics, as desired.
  • Suitable local anesthetics include lidocaine (perhaps in the commercial solution known as Xylocaine with or without epinepherine), procaine, benzocaine, tetracaine, chloroprocaine, mepivacane, bupivacaine, etidocaine, prilocaine, etc. and the like.
  • biocompatible liquids such as DMSO, DMF, propylene glycol, glycerol, plant oils, and ethanol may be included in the injectable composition, if so desired.
  • DMSO dimethyl methoxysulfoxide
  • DMF dimethyl methoxysulfoxide
  • the polyethylene oxide polymer may be a linear or branched polyethylene oxide that is crosslinked such that it is in the form of a non-biodegradable hydrogel and the composition containing such polymer may substantially lack any organic compound capable of swelling the hydrogel.
  • the composition may substantially lack an organic compound capable of swelling the hydrogel selected from the group consisting of polyethylene glycol having a molecular weight of less than about 10,000, also of less than about 5,000 or less than about 1,000, polyvinyl pyrrolidone, dextran, polyethylene oxide polypropylene oxide copolymer having a molecular weight of less than about 5,000, also of less than about 1,000, polyacrylic acid, polyacrylamide, polyvinyl pyridine, poly lysine, polyarginine and oligopeptides.
  • the linear or branched polyethylene oxide may be crosslinked, wherein prior to crosslinking, the polyethylene oxide has a molecular weight in the range of 20,000 to 10,000,000, also 50,000 to 2,000,000, also 500,000 to 2,000,000, also 50,000 to 1,000,000, or 50,000 to 500,000.
  • the crosslinked linear or branched polyethylene oxide may be a non-biodegradable hydrogel.
  • the injectable compositions may further comprise particulates comprising, consisting essentially of, or consisting of hyaluronic acid having a particle size and configuration that is injectable through a needle. Those hyaluronic particles may be substantially insoluble in the liquid carrier.
  • the hyaluronic acid particles may be in the same size range as that of the polyethylene oxide particles.
  • the particles may be in a size range and configuration that is injectable through a syringe needle, such as having a dimension with a size range of about 10 to 1,000 ⁇ m, also about 20 to 1,000 ⁇ m, also about 50 to 1,000 ⁇ m, or about 100 to 1,000 ⁇ m.
  • the particles may be of a size and configuration such that they are injectable through a syringe needle ranging from 18 to 33 gauge, also 24 to 31 gauge, or 27 to 30 gauge.
  • the compositions described herein may be sterile.
  • the description includes injectable crosslinked linear or branched polyethylene oxide hydrogel compositions containing imbibed or free liquid carrier in which the hydrogel is substantially insoluble.
  • the hydrogel may be added to the injector device in forms or sizes that functionally allow the user to inject the hydrogel and carrier fluid from the injector device through, e.g., the attached needle.
  • the composition of the injectable material may further include the crosslinked HA described above.
  • the makeup of the carrier fluid may be as described above.
  • the injectable crosslinked linear or branched polyethylene oxide hydrogel compositions may be crosslinked within the injector in a form that is ready for use.
  • kits comprising one or more subcutaneous injectors, such as a syringe and needle, sterile or sterilizable packaging, and a composition as described herein. Methods of making the kits are also described.
  • the kit components such as the syringe, needle and composition may be sterile.
  • the subcutaneous injector or syringe and needle combination may be sized to cooperate with a chosen composition to allow introduction of the composition by flow through the entry component into a treatment site in the human body.
  • the composition may be contained within the injector or syringe ready for use, perhaps with the attachment of an included needle.
  • the composition may be within a container separate from the syringe, such as in a vial.
  • the needle may be in a size range such as 18 to 33 gauge, 24 to 31 gauge, or 27 to 30 gauge.
  • the kit may comprise a composition having particles in a size range of about 50-
  • the kit may comprise one or more of a composition having particles in a size range of about 50 to 400 ⁇ m or about 100 to 300 ⁇ m, a composition having particles in a size range of about 100 to 600 ⁇ m or about 200 to 500 ⁇ m, or a composition having particles in a size range of about 500 to 1,000 ⁇ m or about 700 to 1,000 ⁇ m.
  • the kit may comprise injectable crosslinked linear or branched polyethylene oxide hydrogel compositions containing imbibed or free liquid carrier in which the hydrogel is substantially insoluble.
  • the injectable crosslinked linear or branched polyethylene oxide hydrogel compositions may be added to the injector before the injector is placed in packaging, added to the injector after the injector is removed from kit packaging, or may be crosslinked in the injector either before or after placement in the kit packaging.
  • the kit packaging may be of a type that seals the included components and is capable of maintaining the sterility of the enclosed components until the packaging is opened for use.
  • the description includes methods of treating or augmenting soft tissue, such as methods of treating fine rhytids, wrinkles, periorbital lines, perioral lines, facial folds, scars, nasolabial folds, oral commisures or other conditions requiring augmentation of soft tissue, or to provide tissue enhancement, such as methods of enhancing lips. These methods involve introducing, such as by injecting, the composition into a treatment site in a mammal, such as a human.
  • the methods may involve using an injector, perhaps a syringe, to inject the composition into a treatment site in a mammal.
  • injector perhaps a syringe
  • Variations of the methods include a step of loading a composition from a vial into the injector and injecting the composition, perhaps through a needle, into the treatment site of a mammal.
  • Other variations include introducing a pre-loaded composition into the treatment site.
  • Polyethylene oxides are formed by the polymerization of ethylene oxide with, for example, an alcohol or water initiator. The characteristics of the polymers will depend on their size. When polymerization is initiated by water, linear polyethylene oxides are terminated by hydroxyl groups at the ends. The ends may also be suitably modified, either by modification of the hydroxyl group or by initiation with a suitable alcohol such that the initiation end terminates in other than a hydroxyl group. Polyethylene oxides with one or more reactive termini are available and may be suitably reacted to form branched polyethylene oxides. Further, linear and branched polyethylene oxides may be crosslinked, for example by reacting with a suitable crosslinking agent (e.g.
  • Linear polyethylene oxides tend to be water soluble, even at high molecular weight. Water solubility may be decreased, for instance, by branching and/or crosslinking of the linear polymers. Water insoluble polyethylene oxides may be suitable as dermal filler materials, since they are generally biocompatible, non-immunogenic, non-toxic, non-carcinogenic, and non- resorbable.
  • These polymers may be formulated as injectable particles or bodies that are substantially water insoluble and that have a desired shape that does not substantially migrate from an injection site.
  • Polymers suitable for the compositions include polyethylene oxides that are terminated with non-reactive groups, such as hydroxyl groups, and include linear, branched and crosslinked polyethylene oxides.
  • the described compositions may comprise, consist essentially of, or consist of polyethylene oxide particles, where the particles themselves comprise, consist essentially of, or consist of polyethylene oxide.
  • the terms "comprise”, “consist essentially of or “consist of polyethylene oxide encompass branched or crosslinked polyethylene oxides.
  • particles comprising, consisting essentially of, or consisting of polyethylene oxides include particles or bodies that are primarily made up of polyethylene oxide chains, but the chains may include additional linking groups, such as branching groups and crosslinking groups, or may have non- reactive termini other than hydroxyl groups, such as methoxy, other alkoxy, or similarly non- reactive groups. Often, the branching groups, crosslinking groups, or non-reactive termini are chosen so that the resulting particles are substantially non-biodegradable.
  • the polyethylene oxide particles or bodies may also be suitably reactive, such as having reactive termini, crosslinking groups and the like described above, such that they can be further reacted in situ.
  • suitably sized particles for injection into a treatment site may be mixed with a suitable agent, such as a crosslinking agent, such that upon injection into the treatment site, the particles react further to provide additional structure to the injected material.
  • a suitable agent such as a crosslinking agent
  • the additional structure may be a particle network structure or an increase in the particle size at the injection site relative to the particles injected.
  • Substantially water insoluble particles or bodies comprising polyethylene oxide, whether linear, branched, crosslinked, or non-crosslinked, or combinations thereof, may be formulated for use in the described compositions.
  • Substantially water insoluble particles or bodies are "insoluble in water” in the sense that they maintain a shape in aqueous solution or are not solvated by the water. Particles "insoluble in water” may also be referred to as not substantially soluble in water.
  • the particle or body may comprise a gel-like material, as with hydrogels, or the particle may be of a more rigid material.
  • the particles and bodies are also substantially insoluble in body fluids and, as such, do not dissolve substantially over time at a site of injection, such as in an area of soft tissue.
  • the particles are substantially non-biodegradable.
  • Substantially “nonbiodegradable” particles will not readily break down in the body once injected.
  • Substantially water insoluble, non-biodegradable examples of the described compositions will remain at or in the vicinity of the injection site for extended periods, periods such as: greater than 6 months, also 1 year, also 2 years or longer.
  • the molecular weight may be in the range of 100,000 to 10,000,000, also 200,000 to 8,000,000, also 400,000 to 8,000,000, or 1,000,000 to 8,000,000.
  • the molecular weight of the material prior to crosslinking may be in the range of 20,000 to 10,000,000, also 50,000 to 2,000,000, also 500,000 to 2,000,000, also 50,000 to 1,000,000, or 50,000 to 500,000.
  • the polyethylene oxide polymer is a hydrogel: the crosslinking results in a three dimensional polymer network that swells on absorbing or imbibing water but does not dissolve in water.
  • a crosslinked polyethylene oxide polymer suitable for the injectable composition is one that is substantially non-biodegradable.
  • Solid, semi-solid, gel, or hydrogel materials of polyethylene oxide polymers may be, if desired, comminuted to a selected size by grinding, chopping, microsizing, etc. or other suitable physical process for reducing larger materials to smaller sizes. If a smaller composition is needed for a specific procedure, that material may generally be sized to a suitable size range that is injectable through a selected injector, e.g. a needle using a syringe, to the treatment site. Additionally, for comminuting of hydrogels, the particles may first be lyophilized or frozen while hydrated.
  • the dry particle size is selected to provide the desired particle size upon swelling.
  • the particles may also be formulated in the dry state, or in a liquid, perhaps an aqueous liquid, or as a suspension in a carrier liquid, perhaps an aqueous carrier liquid, or in other suitable forms.
  • the carrier liquid may comprise pharmaceutically acceptable organic liquids, including, but not limited to, DMSO, DMF, propylene glycol, glycerol, and plant oils.
  • Crosslinked polyethylene oxide particles or compositions may be swelled or imbibed with water or saline solutions and formulated in that swelled state to provide an injectable composition.
  • the carrier liquid in the composition may be aqueous in nature but normally need not consist only of water, although it may be so.
  • the carrier liquid may comprise saline or other pharmaceutically acceptable additives, or may be non-aqueous.
  • water soluble organic compounds include polyethylene glycol having a molecular weight of less than about 10,000 (also of less than about 5,000 or less than about 1,000), polyvinyl pyrrolidone, dextran, polyethylene oxide polypropylene oxide copolymer (e.g. Pluronic) having a molecular weight of less than about 5,000 (also of less than about 1,000), polyacrylic acid, polyacrylamide, polyvinyl pyridine, polylysine, polyarginine, and oligopeptides (e.g. polyaspartic acid or polyglutaniic acid).
  • polyethylene glycol having a molecular weight of less than about 10,000 (also of less than about 5,000 or less than about 1,000)
  • polyvinyl pyrrolidone dextran
  • polyethylene oxide polypropylene oxide copolymer e.g. Pluronic
  • polyacrylic acid polyacrylamide
  • polyvinyl pyridine polylysine
  • polyarginine polyarginine
  • compositions in addition to the polyethylene oxide particles or bodies, may also contain hyaluronic acid based materials, which may be polymerized or non-polymerized, and/or crosslinked or non-crosslinked.
  • Hyaluronic acid is a polysaccharide that may be used in gel form as a dermal filler. Commercially available materials include Restylane or Hyaloform.
  • hyaluronic acid gel particles or bodies may be mixed with the polyethylene oxide composition particles or bodies to provide a suitable material for injection.
  • the hyaluronic acid co-composition sometimes provides advantages, such as lubrication of the injected materials for easier injection and providing an implant that potentially better conforms to a desired shape.
  • Hyaluronic acid containing particles may be dry-mixed and then formulated in a carrier liquid suitable for injection, or may be formulated in a liquid separately and the mixtures or suspensions mixed to provide the desired mixture.
  • the sizes of the polyethylene oxide and hyaluronic acid bodies may be in the same size range if so desired, or may be of different size.
  • the individual polymeric particles or bodies utilized in any of the described injectable compositions may comprise, consist essentially of, or consist of polyethylene oxide or of a mixture of polyethylene oxide and one or more other suitable polymers.
  • suitable polymers include, but are not limited to, synthetic polymers such as polyalkylene oxides (e.g. other polyethylene oxides, polypropylene oxides, polyethylene oxide-polypropylene oxide copolymers), polyols, polyacrylics, polymethacrylics, polyacrylamides, polymaleic acid, polyolef ⁇ nic alcohols (e.g. polyvinylalcohol), poly N-vinyl lactams (e.g.
  • polyvinylpyrrolidone polyamino acids (e.g. polylysine), polyoxazolines, and polyvinylamines
  • naturally occurring polymers such as polysaccharides, proteins, proteoglycans, glycosaminoglycans and the like.
  • Suitable naturally occurring polymers include, but are not limited to, hyaluronic acid, dextran, collagen, fibrinogen, elastin, heparin, and albumin.
  • synthetic versions of such naturally occurring polymers such as synthetic collagen, heparin, hyaluronic acid, etc.
  • injectable compositions comprising, consisting essentially of, or consisting of polyethylene oxides in combination with other suitable polymers may be formed in various ways.
  • One procedure entails mixing component polymer particles or bodies such that they are simply physically associated.
  • particles or bodies of one type of polymer may be mixed with bodies of another type of polymer, and the mixture reacted to crosslink the polymer types such that the resulting mixture comprises both polymers.
  • the resulting materials may be comminuted, if desired, to provide a desired size range of polymers comprising, consisting essentially of, or consisting of more than one polymer.
  • compositions described herein may be further modified in situ to provide additional structure to the implanted materials.
  • compositions described herein are combined with a suitable agent or agents prior to injecting into a treatment site, such that the injected material results in structural changes to some or all of the particles.
  • structural changes include, but are not limited to, crosslinking within an injected dermal filler body or to an adjacent filler body.
  • the structural changes may result in a filler body network, or in the formation of larger bodies from smaller ones.
  • Such structural changes may result in reduced migration of injected material from the injection site.
  • the structural change may result in a substantially less biodegradable implant, such that the implanted material remains at the injection site for longer periods of time.
  • An injectable composition comprising, consisting essentially of, or consisting of the polymeric dermal filler components described herein may also comprise agents that will react with the particles to physically link the polymeric materials in situ.
  • agents include crosslinking agents.
  • solid, semi-solid, gel, or hydrogel materials described herein may be comminuted to a selected particle size and combined with suitable agent or agents, such as crosslinking agents, prior to injecting.
  • suitable agent or agents such as crosslinking agents
  • compositions discussed above may be formulated for injection.
  • the hydrogel compositions may vary over a large size range while remaining injectable.
  • Several of the other compositions may be tailored with particle sizes in a desirable range for injection.
  • Suitable particles may range from about 10 to 1,000 ⁇ m, also about 20 to 1,000 ⁇ m, also about 50 to 1,000 ⁇ m, or about 100 to 1,000 ⁇ m.
  • Suitable needle gauges for injection depend on the desired particle size, and are typically 18 or smaller, such as ranging from 18 to 33, also 24 to 31, or 27 to 30 gauge.
  • the desired size range depends to some extent on the intended use, such as whether they will be injected into the superficial dermis, mid dermis or deep dermis.
  • Particles for injection into the superficial dermis such as for treating fine rhytids, periorbital lines and the like may be in a range of about 50 to 400 ⁇ m, also about 100 to 300 ⁇ m.
  • Particles for injection into the mid dermis such as for treating perioral lines, facial folds, shallow scars and the like may be in a range of about 100 to 600 ⁇ m, also about 200 to 500 ⁇ m.
  • Particles for injection into the deep dermis such as for treating nasolabial folds, oral commissures, lip enhancement and the like may be in a range of about 500 to 1,000 ⁇ m, also about 700 to 1,000 ⁇ m.
  • the particles may be placed in a liquid carrier, perhaps an aqueous liquid, such as neat water, a solution comprising saline, which may contain pharmaceutically acceptable excipients, adjuvants, diluents, or stabilizers such as those described, for example, in Gennaro, ed., Remington's The Science and Practice of Pharmacy, 20 th edition, Lippincott Williams &Wilkins.
  • a liquid carrier perhaps an aqueous liquid, such as neat water, a solution comprising saline, which may contain pharmaceutically acceptable excipients, adjuvants, diluents, or stabilizers such as those described, for example, in Gennaro, ed., Remington's The Science and Practice of Pharmacy, 20 th edition, Lippincott Williams &Wilkins.
  • the compositions may also include one or more local anesthetics.
  • Such local anesthetics include, but are not limited to, lidocaine, procaine, prilocaine, mepivicaine, articaine, bupivacaine, benzocaine, chloroprocaine, tetracaine, propoxycaine, and etidocaine.
  • One suitable composition consists essentially of particles consisting of polyethylene oxide in an aqueous saline carrier. Compositions may be suitably sterilized by well known methods, such as electron beam, heat sterilization, or chemical sterilization.
  • kits may comprise at least one injector, such as one or more hypodermic syringe barrel and body and one or more hypodermic needle, and one or more of the injectable compositions described elsewhere herein.
  • the injector, syringe, needle, and composition may be suitably sterilized, variously by chemical sterilants such as ethylene oxide or by radiation sterilization, as by "e-beam" in any packaging or prior to placement in the packaging.
  • the kits may comprise the composition contained within the injector, such as a syringe, or contained in a separate container, such as a vial.
  • the dermal filler composition may be loaded into the injector or into the syringe through a needle, or in a cartridge placed directly into the injector or syringe for injection through the needle.
  • the vial or injector designated to hold the composition may be used as an in situ reactor for a polyethylene oxide hydrogel composition as described above.
  • the vial or injector is loaded with crosslinkable linear or branched polyethylene oxide and irradiated using ionizing radiation in an appropriate amount, to produce a hydrogel. See, for instance, the compositions and irradiation levels noted in U.S. Pat. No. 3,419,006, the entirety of which is incorporated by reference.
  • the kit may comprise one or more needles of a size range of 18 to 33 gauge, also 24 to 31 gauge, or 27 to 30 gauge.
  • the kit may comprise suitable packaging as is commonly used to package medical devices. Of interest is the design utilizing a tray that holds the components and cooperates with a lidding material of, e.g., foil, paper, polymeric materials (such as Tyvek), polymeric films, etc., to maintain the components in a sterile state.
  • a lidding material e.g., foil, paper, polymeric materials (such as Tyvek), polymeric films, etc.
  • Such packaging is well known and is easily opened by the user.
  • Such materials may be selected to be resistant or tolerant to chemical sterilants and sterilizing radiation should the materials be sterilized in the packaging.
  • the packaging may be selected to be tolerant of ionizing radiation if the hydrogel composition is crosslinked in situ.
  • the selected or chosen polyethylene oxide compositions placed in these kits and used as injectable dermal fillers for the augmentation of soft tissue may be selected for specific treatments, such as for treating rhytids, wrinkles, periorbital lines, perioral lines, facial folds, dermal scarring due to trauma, acne, surgery and the like, nasolabial folds, oral commisures, and other conditions, and for enhancing soft tissue such as for lip, chin, and cheek enhancement.
  • the compositions may be used in any mammal, including humans.
  • a method of treating or augmenting soft tissue may include the step of injecting the composition through an injector, such as a needle and syringe combination, into a treatment site.
  • the method may further include loading the composition into a syringe and injecting the composition into the treatment site through a suitable gauge needle.
  • the method may involve injection through a needle having a size range of 18 to 33 gauge, also 24 to 31 gauge, or 27 to 30 gauge.

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  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Medicinal Chemistry (AREA)
  • Transplantation (AREA)
  • Gerontology & Geriatric Medicine (AREA)
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  • Materials For Medical Uses (AREA)
  • Medicinal Preparation (AREA)

Abstract

Cette invention renvoie au domaine des implants injectables utiles pour compléter le tissu mou, en particulier la peau. Plus particulièrement, l’invention renvoie à des compositions de remplissage dermal d’oxydes de polyéthylène biocompatibles, peut-être par injection, dans des zones de tissu mou ayant souvent besoin d’être augmentés. Des exemples incluent l’amélioration ou la correction cosmétique de défauts du visage dus à des cicatrices, au vieillissement et autres du même genre. Cette invention renvoie en outre à des ensembles contenant les oxydes de polyéthylène décrits ci-dessus, et des processus d’utilisation de ces compositions.
PCT/US2006/011201 2005-03-23 2006-03-23 Elements de remplissage dermal d’oxyde de polyethylene et dispositifs associes WO2006102676A1 (fr)

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US60/664,920 2005-03-23

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US8348898B2 (en) 2010-01-19 2013-01-08 Medimop Medical Projects Ltd. Automatic needle for drug pump
US8455459B2 (en) 2007-08-02 2013-06-04 Medicis Pharmaceutical Corporation Method of applying an injectable filler
US8465455B2 (en) 2009-09-15 2013-06-18 Medimop Medical Projects Ltd. Cartridge insertion assembly
USD702834S1 (en) 2011-03-22 2014-04-15 Medimop Medical Projects Ltd. Cartridge for use in injection device
US9011164B2 (en) 2013-04-30 2015-04-21 Medimop Medical Projects Ltd. Clip contact for easy installation of printed circuit board PCB
US9072827B2 (en) 2012-03-26 2015-07-07 Medimop Medical Projects Ltd. Fail safe point protector for needle safety flap
US9173997B2 (en) 2007-10-02 2015-11-03 Medimop Medical Projects Ltd. External drug pump
US9259532B2 (en) 2010-01-19 2016-02-16 Medimop Medical Projects Ltd. Cartridge interface assembly
US9345836B2 (en) 2007-10-02 2016-05-24 Medimop Medical Projects Ltd. Disengagement resistant telescoping assembly and unidirectional method of assembly for such
US9421323B2 (en) 2013-01-03 2016-08-23 Medimop Medical Projects Ltd. Door and doorstop for portable one use drug delivery apparatus
US9452261B2 (en) 2010-05-10 2016-09-27 Medimop Medical Projects Ltd. Low volume accurate injector
US9656019B2 (en) 2007-10-02 2017-05-23 Medimop Medical Projects Ltd. Apparatuses for securing components of a drug delivery system during transport and methods of using same
US9987432B2 (en) 2015-09-22 2018-06-05 West Pharma. Services IL, Ltd. Rotation resistant friction adapter for plunger driver of drug delivery device
US10071196B2 (en) 2012-05-15 2018-09-11 West Pharma. Services IL, Ltd. Method for selectively powering a battery-operated drug-delivery device and device therefor
US10071198B2 (en) 2012-11-02 2018-09-11 West Pharma. Servicees IL, Ltd. Adhesive structure for medical device
US10149943B2 (en) 2015-05-29 2018-12-11 West Pharma. Services IL, Ltd. Linear rotation stabilizer for a telescoping syringe stopper driverdriving assembly
US10293120B2 (en) 2015-04-10 2019-05-21 West Pharma. Services IL, Ltd. Redundant injection device status indication
US10328180B2 (en) 2008-08-04 2019-06-25 Allergan Industrie, S.A.S. Hyaluronic acid-based gels including lidocaine
US10420880B2 (en) 2007-10-02 2019-09-24 West Pharma. Services IL, Ltd. Key for securing components of a drug delivery system during assembly and/or transport and methods of using same
US11167086B2 (en) 2008-09-15 2021-11-09 West Pharma. Services IL, Ltd. Stabilized pen injector
US11311674B2 (en) 2016-01-21 2022-04-26 West Pharma. Services IL, Ltd. Medicament delivery device comprising a visual indicator
US11318254B2 (en) 2015-10-09 2022-05-03 West Pharma. Services IL, Ltd. Injector needle cap remover
US11338090B2 (en) 2016-08-01 2022-05-24 West Pharma. Services IL, Ltd. Anti-rotation cartridge pin
US11364337B2 (en) 2016-01-21 2022-06-21 West Pharma. Services IL, Ltd. Force containment in an automatic injector
US11389597B2 (en) 2016-03-16 2022-07-19 West Pharma. Services IL, Ltd. Staged telescopic screw assembly having different visual indicators
US11547802B2 (en) 2015-10-09 2023-01-10 West Pharma. Services IL, Ltd. Angled syringe patch injector
US11672904B2 (en) 2016-01-21 2023-06-13 West Pharma. Services IL, Ltd. Needle insertion and retraction mechanism
US11730892B2 (en) 2016-08-01 2023-08-22 West Pharma. Services IL, Ltd. Partial door closure prevention spring
US11819673B2 (en) 2016-06-02 2023-11-21 West Pharma. Services, IL, Ltd. Three position needle retraction
US11819666B2 (en) 2017-05-30 2023-11-21 West Pharma. Services IL, Ltd. Modular drive train for wearable injector
US11857767B2 (en) 2017-12-22 2024-01-02 West Pharma. Services IL, Ltd. Injector usable with different dimension cartridges
US11931552B2 (en) 2015-06-04 2024-03-19 West Pharma Services Il, Ltd. Cartridge insertion for drug delivery device
US12097357B2 (en) 2008-09-15 2024-09-24 West Pharma. Services IL, Ltd. Stabilized pen injector

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US8778909B2 (en) 2007-08-02 2014-07-15 Medicis Pharmaceutical Corporation Method of applying an injectable filler
US8455459B2 (en) 2007-08-02 2013-06-04 Medicis Pharmaceutical Corporation Method of applying an injectable filler
US9173997B2 (en) 2007-10-02 2015-11-03 Medimop Medical Projects Ltd. External drug pump
US9345836B2 (en) 2007-10-02 2016-05-24 Medimop Medical Projects Ltd. Disengagement resistant telescoping assembly and unidirectional method of assembly for such
US9782545B2 (en) 2007-10-02 2017-10-10 Medimop Medical Projects Ltd. External drug pump
US10413679B2 (en) 2007-10-02 2019-09-17 West Pharma. Services IL, Ltd. External drug pump
US9861759B2 (en) 2007-10-02 2018-01-09 Medimop Medical Projects Ltd. External drug pump
US10420880B2 (en) 2007-10-02 2019-09-24 West Pharma. Services IL, Ltd. Key for securing components of a drug delivery system during assembly and/or transport and methods of using same
US11504481B2 (en) 2007-10-02 2022-11-22 West Pharma. Services IL, Ltd. Anti-rotation feature for infusion pump cartridge
US11590291B2 (en) 2007-10-02 2023-02-28 West Pharma. Services IL, Ltd. External drug pump
US9656019B2 (en) 2007-10-02 2017-05-23 Medimop Medical Projects Ltd. Apparatuses for securing components of a drug delivery system during transport and methods of using same
US10384017B2 (en) 2007-10-02 2019-08-20 West Pharma. Services IL, Ltd. Anti-rotation feature for infusion pump cartridge
US10391202B2 (en) 2008-08-04 2019-08-27 Allergan Industrie Sas Hyaluronic acid-based gels including lidocaine
US10328180B2 (en) 2008-08-04 2019-06-25 Allergan Industrie, S.A.S. Hyaluronic acid-based gels including lidocaine
US11020512B2 (en) 2008-08-04 2021-06-01 Allergan Industrie, Sas Hyaluronic acid-based gels including lidocaine
US10485896B2 (en) 2008-08-04 2019-11-26 Allergan Industrie Sas Hyaluronic acid-based gels including lidocaine
US11173232B2 (en) 2008-08-04 2021-11-16 Allergan Industrie, Sas Hyaluronic acid-based gels including lidocaine
US11167086B2 (en) 2008-09-15 2021-11-09 West Pharma. Services IL, Ltd. Stabilized pen injector
US12097357B2 (en) 2008-09-15 2024-09-24 West Pharma. Services IL, Ltd. Stabilized pen injector
US8465455B2 (en) 2009-09-15 2013-06-18 Medimop Medical Projects Ltd. Cartridge insertion assembly
US9572926B2 (en) 2009-09-15 2017-02-21 Medimop Medical Projects Ltd. Cartridge insertion assembly
US9149575B2 (en) 2010-01-19 2015-10-06 Medimop Medical Projects Ltd. Needle assembly for drug pump
US8348898B2 (en) 2010-01-19 2013-01-08 Medimop Medical Projects Ltd. Automatic needle for drug pump
US9522234B2 (en) 2010-01-19 2016-12-20 Medimop Medical Projects Ltd. Needle assembly for drug pump
US8915882B2 (en) 2010-01-19 2014-12-23 Medimop Medical Projects Ltd. Needle assembly for drug pump
US9492610B2 (en) 2010-01-19 2016-11-15 MEDIMOP Projects Ltd. Needle assembly for drug pump
US9764092B2 (en) 2010-01-19 2017-09-19 Medimop Medical Projects Ltd. Needle assembly for drug pump
US9259532B2 (en) 2010-01-19 2016-02-16 Medimop Medical Projects Ltd. Cartridge interface assembly
US9452261B2 (en) 2010-05-10 2016-09-27 Medimop Medical Projects Ltd. Low volume accurate injector
USD747799S1 (en) 2011-03-22 2016-01-19 Medimop Medical Projects Ltd. Cartridge
USD702834S1 (en) 2011-03-22 2014-04-15 Medimop Medical Projects Ltd. Cartridge for use in injection device
US9393365B2 (en) 2012-03-26 2016-07-19 Medimop Medical Projects Ltd. Fail safe point protector for needle safety flap
US9072827B2 (en) 2012-03-26 2015-07-07 Medimop Medical Projects Ltd. Fail safe point protector for needle safety flap
US9511190B2 (en) 2012-03-26 2016-12-06 Medimop Medical Projects Ltd. Fail safe point protector for needle safety flap
US10071196B2 (en) 2012-05-15 2018-09-11 West Pharma. Services IL, Ltd. Method for selectively powering a battery-operated drug-delivery device and device therefor
US10071198B2 (en) 2012-11-02 2018-09-11 West Pharma. Servicees IL, Ltd. Adhesive structure for medical device
US9421323B2 (en) 2013-01-03 2016-08-23 Medimop Medical Projects Ltd. Door and doorstop for portable one use drug delivery apparatus
US9166313B2 (en) 2013-04-30 2015-10-20 Medimop Medical Projects Power supply contact for installation of printed circuit board
US9011164B2 (en) 2013-04-30 2015-04-21 Medimop Medical Projects Ltd. Clip contact for easy installation of printed circuit board PCB
US10293120B2 (en) 2015-04-10 2019-05-21 West Pharma. Services IL, Ltd. Redundant injection device status indication
US10149943B2 (en) 2015-05-29 2018-12-11 West Pharma. Services IL, Ltd. Linear rotation stabilizer for a telescoping syringe stopper driverdriving assembly
US11931552B2 (en) 2015-06-04 2024-03-19 West Pharma Services Il, Ltd. Cartridge insertion for drug delivery device
US9987432B2 (en) 2015-09-22 2018-06-05 West Pharma. Services IL, Ltd. Rotation resistant friction adapter for plunger driver of drug delivery device
US11724034B2 (en) 2015-10-09 2023-08-15 West Pharma. Services, IL, Ltd. Injector system
US12036394B2 (en) 2015-10-09 2024-07-16 West Pharma. Services IL, Ltd. Injector needle cap and/or liner remover
US11318254B2 (en) 2015-10-09 2022-05-03 West Pharma. Services IL, Ltd. Injector needle cap remover
US11547802B2 (en) 2015-10-09 2023-01-10 West Pharma. Services IL, Ltd. Angled syringe patch injector
US11759573B2 (en) 2015-10-09 2023-09-19 West Pharma. Services, IL, Ltd. Bent fluid path add on to a prefilled reservoir
US11311674B2 (en) 2016-01-21 2022-04-26 West Pharma. Services IL, Ltd. Medicament delivery device comprising a visual indicator
US11672904B2 (en) 2016-01-21 2023-06-13 West Pharma. Services IL, Ltd. Needle insertion and retraction mechanism
US12005237B2 (en) 2016-01-21 2024-06-11 West Pharma. Services IL, Ltd. Medicament delivery device comprising a visual indicator
US11364337B2 (en) 2016-01-21 2022-06-21 West Pharma. Services IL, Ltd. Force containment in an automatic injector
US11389597B2 (en) 2016-03-16 2022-07-19 West Pharma. Services IL, Ltd. Staged telescopic screw assembly having different visual indicators
US11819673B2 (en) 2016-06-02 2023-11-21 West Pharma. Services, IL, Ltd. Three position needle retraction
US11730892B2 (en) 2016-08-01 2023-08-22 West Pharma. Services IL, Ltd. Partial door closure prevention spring
US11338090B2 (en) 2016-08-01 2022-05-24 West Pharma. Services IL, Ltd. Anti-rotation cartridge pin
US11819666B2 (en) 2017-05-30 2023-11-21 West Pharma. Services IL, Ltd. Modular drive train for wearable injector
US11857767B2 (en) 2017-12-22 2024-01-02 West Pharma. Services IL, Ltd. Injector usable with different dimension cartridges

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