[go: up one dir, main page]

WO2009132298A1 - Implant à élution de médicament pour administration de médicament locale et régionale - Google Patents

Implant à élution de médicament pour administration de médicament locale et régionale Download PDF

Info

Publication number
WO2009132298A1
WO2009132298A1 PCT/US2009/041704 US2009041704W WO2009132298A1 WO 2009132298 A1 WO2009132298 A1 WO 2009132298A1 US 2009041704 W US2009041704 W US 2009041704W WO 2009132298 A1 WO2009132298 A1 WO 2009132298A1
Authority
WO
WIPO (PCT)
Prior art keywords
drug
sis
sealed
packet
collagenous material
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2009/041704
Other languages
English (en)
Inventor
Xin Wu
Joseph Wood
Meet Patel
Vincent Wu
Dhanya Rangaraj
Henry Chang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Device Evolutions LLC
Original Assignee
Device Evolutions LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Device Evolutions LLC filed Critical Device Evolutions LLC
Publication of WO2009132298A1 publication Critical patent/WO2009132298A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/44—Medicaments
    • 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
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/40—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing ingredients of undetermined constitution or reaction products thereof, e.g. plant or animal extracts
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3629—Intestinal tissue, e.g. small intestinal submucosa
    • 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
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/402—Anaestetics, analgesics, e.g. lidocaine
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602—Type of release, e.g. controlled, sustained, slow

Definitions

  • the invention relates to the field of medical devices, and more specifically, to drug-eluting implants.
  • drugs are administered to patients systemically.
  • drugs are taken orally or injected intravenously or intramuscularly, and exert their effects on the entire body or a substantial portion of it.
  • Systemic modes of delivery are appropriate to treat many conditions, particularly those conditions that are themselves systemic. However, many conditions affect only a particular area or region of the body, and systemic treatment may not be indicated, or may carry with it unwanted side effects.
  • a drug may need to be administered systemically at a much higher dose than would have been necessary had it been administered locally.
  • a drug may be administered systemically in a higher dose for several reasons.
  • the drug may be administered in a higher dose anticipating that only some of the administered drug will reach the bloodstream or the affected area. This is the case, for example, with many orally administered drugs.
  • a drug may be administered in greater quantity because of the pharmacokinetics involved. Most drugs exert their effects over a defined period of time as the body gradually metabolizes and excretes them.
  • NSAIDs nonsteroidal anti-inflammatory drugs
  • NSAIDs are often used. Although some NSAIDs are administered intravenously, under many circumstances, they are taken orally. Unfortunately, NSAIDs generally carry risks of gastrointestinal bleeding, risks that may be amplified by the relatively large doses in which they are administered orally.
  • narcotic opiates and opioids which exert their pain relief effects primarily through the central nervous system, are often used.
  • Common opiates and opioids include morphine, diamorphine, Fentanyl, codeine, propoxyphene, hydrocodone, and oxycodone.
  • Opiates and opioids are extremely effective in pain control; however, they carry with them side effects including cognitive impairment, nausea, and constipation, as well as a risk of addiction.
  • analgesic bupivacaine is often injected at or around the incision site, sometimes in combination with epinephrine, which acts to constrict blood vessels, reduce blood flow, and thus, increase the effective life of the bupivacaine on site by inhibiting the process by which the drug is washed out and metabolized.
  • U.S. Patent No. 7,119,062 discloses the use of an aqueous dispersion of purified collagen and an anesthetic, such as bupivacaine, that may be injected into or near the incision site. This approach may prolong the application of bupivacaine, but it can be difficult to pinpoint exactly where the drug is released, and the dispersion is not necessarily bioresorbable.
  • the implant comprises a collagenous material in the form of a sealed packet, the sealed packet defining an internal space.
  • a drug is disposed in the internal space of the sealed packet and is arranged within the sealed packet so as to diffuse out of it over a period of time after the drug-eluting implant is implanted.
  • the collagenous material of natural origin may be small intestine submucosa (SIS).
  • Another aspect of the invention relates to a method of making a drug-eluting implant.
  • the method comprises forming a partial packet using a collagenous material, filling the partial packet with a drug, and sealing any open edges of the partial packet under defined conditions of temperature and pressure to form a sealed packet.
  • forming the partial packet may comprise folding a generally rectangular piece of the collagenous material and sealing at least two edges of the folded collagenous material using defined conditions of temperature and pressure.
  • the defined conditions of temperature and pressure may be conditions of temperature and pressure sufficient to bond the collagenous material to itself.
  • a further aspect of the invention relates to a method for treating a wound.
  • the method comprises inserting a sealed packet into the wound or an area proximate to the wound.
  • the sealed packet includes a collagenous material defining an internal space, and a drug disposed in the internal space of the sealed packet.
  • the drug is arranged within the sealed packet so as to diffuse out of it over a period of time.
  • the method may further comprise closing the wound.
  • FIG. 1 is a perspective view of an implant according to an embodiment of the invention
  • FIG. 2 is a schematic illustration of an apparatus used to test the diffusion rates of drug across a membrane
  • FIG. 3 is a graph of the bupivacaine concentration over time when diffusing across different types of small intestine submucosa (SIS) membranes in the apparatus of FIG. 2; and
  • SIS small intestine submucosa
  • FIG. 4 is a graph of diffusion rate over time corresponding to the bupivacaine concentration data of FIG. 3.
  • Embodiments of the invention are directed to drug-eluting implants for sustained local and regional delivery of drugs.
  • the drug-eluting implants may be used to dispense many kinds of drugs to a local or regional area of the body over a relatively long duration; for example, they may be particularly useful in delivering analgesics or other drugs to the site of a surgical incision for hours or days after a surgical procedure.
  • the drug-eluting implants are comprised of a collagenous material in the form of a sealed packet.
  • the collagenous material may be a collagenous material of natural origin.
  • the phrase "of natural origin” should be construed to include both unmodified materials and materials that have been modified to sterilize them, to increase biological or mechanical stability, or to increase shelf life.
  • a therapeutic amount of a drug is within the sealed packet and is arranged to diffuse out of the sealed packet over time to deliver the drug when the implant is in use.
  • the collagenous material of natural origin comprises small intestine submucosa (SIS).
  • SIS small intestine submucosa
  • the origin, processes of preparation and manufacture, and characteristics of SIS are well-described in the literature, including in U.S. Patent No. 6,666,892, in the references cited by that patent, and in Hiles, et al., "A New Biomaterial Derived From Small Intestine Submucosa and Developed Into a Wound Matrix Device" MedS cape: Wounds 14(4): 150-166, 2002, all of which are incorporated by reference herein in their entirety.
  • SIS As a biomaterial of natural origin, broadly speaking, SIS contains collagen as well as various bioactive protein-carbohydrate complexes, and growth factors; therefore, in addition to acting as a diffusion barrier and controlling the rate of diffusion of a drug enclosed by it, SIS encourages wound healing and tissue remodeling, and is bioresorbable. Thus, for applications in which wound healing is desired, the performance of SIS may be superior to that of pure collagen matrices, which may not, and generally do not, contain wound healing agents and growth factors.
  • drug refers to any biologically active compound.
  • a wide range of drugs may be used in drug-eluting implants according to embodiments of the invention.
  • An exemplary, but not exclusive or exhaustive, list of drugs includes wound healing factors like immunomodulators (e.g., platelet derived growth factor (PDGF), interleukins, macrophage chemoattractant protein- 1 (MCP-I), lactoferrin, thymorin beta 4, and T cell immune response cDNA 7 (TIRC 7)), neuropeptides (e.g., substance P, and neuropeptide Y), growth factors (e.g., vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), nerve growth factor (NGF), connective tissue growth factor (CTGF), hepatocyte growth factor (HGF), and human epidermal growth factor (hEGF)), and other wound healing factors (e.g., homeobox genes, and treptossinil); anti-infective agents (e.g., homeo
  • drugs that are chemical compounds may be present in the implant in the form of a pharmaceutically and/or physiologically acceptable salt, such as the hydrochloride salt, the bromide salt, the acetate salt, or the citrate salt.
  • a pharmaceutically and/or physiologically acceptable salt such as the hydrochloride salt, the bromide salt, the acetate salt, or the citrate salt.
  • Drugs in the form of nonaqueous particulates or powders may, in some embodiments, be pressed into pellets, tablets, or another similar solid, unitary form to aid in loading the drug into the implant or, potentially, to alter its diffusion or delivery rate.
  • FIG. 1 is a perspective view of one embodiment of a drug-eluting implant according to an embodiment of the invention, generally indicated at 10.
  • the outer layer 12 of the implant comprises a single-thickness layer of SIS, and in the illustrated embodiment, one edge 14 is folded over itself and the other three edges 16, 18, 20 are sealed to define a sealed packet with an interior space (not shown in FIG. 1).
  • a sheet of SIS material is cut to an appropriate size and then folded over to define the folded edge 14.
  • edges 16, 18 are then sealed together, the implant 10 is filled with the desired drug through the open edge, and then the open edge is itself sealed. Following the sealing, or at any point during the process, the edges 14, 16, 18, 20 may be trimmed or otherwise modified to meet dimensional or other requirements.
  • the manufacture and filling of the implant 10 are performed under sterile conditions, although for some purposes, sterility may not be necessary.
  • a generally rectangular implant 10 is shown in FIG. 1; however, a sheet of SIS may be folded in substantially any way in order to form an implant. For example, a rectangular sheet of SIS may be folded on the diagonal so as to have a final triangular shape with two sealed edges.
  • it may be advantageous in some embodiments to make one edge of the implant 10 with a fold in other embodiments, it may be desirable or useful to make an implant from two separate sheets of SIS, one placed on top of another, with all of the resulting edges sealed.
  • the edges of the SIS material may be sealed during the process of making the implant 10 in any number of ways.
  • One particularly advantageous method of sealing the edges of the implant 10 is by application of heat and pressure to form a bond between the two SIS surfaces. For example, temperature and pressure conditions of 230°C and 4700 psi for 3 minutes have been found to create an adequate bond between layers of SIS.
  • the layers of SIS may be bonded by a biocompatible glue to form the implant 10.
  • a biocompatible glue may provide an acceptable bond between SIS layers in some embodiments.
  • the implant 10 may be made to any size that is desired or required for a particular application.
  • the implant 10 may be generally rectangular in shape, about 2 cm x 2 cm or less in length and width, and have a capacity of about 200 mg of bupivacaine.
  • the desired in situ rate of diffusion/dispensation of drug from the implant 10 may vary according to the nature of the drug, the nature of the procedure, and the nature of the patient.
  • a final in situ diffusion/dispensation rate of bupivacaine of approximately 2.5 mg/hr may be acceptable for at least some patients and at least some procedures.
  • a drug-eluting implant 10 would be able to supply drug to the surrounding area for approximately 72-80 hours. That 72-80 hour period for drug delivery may be particularly advantageous for an analgesic such as bupivacaine because it would reduce the patient's pain levels during the first few days after surgery, when the patient would typically experience the greatest levels of pain.
  • the SIS can be modified to increase its porosity, or a form of SIS with larger pores can be used.
  • the time frame over which drug is dispensed by the implant 10 may vary with the embodiment, the nature of the drug, the location in which the implant 10 is placed within the body, and with local physiological conditions in that location, among other factors. In order to deliver drug over a shorter delivery time frame, one could, for example, either reduce the amount of drug present in the implant or alter the properties of the SIS to increase the diffusion/drug delivery rate, as appropriate considering the nature of the drug.
  • implants according to embodiments of the present invention are constructed and adapted such that diffusion is at least initially the primary means by which drug leaves the implant and enters the surrounding region. This is in contrast to implants and materials in which the matrix encapsulating the drug degrades to release it.
  • the body's natural collagenases may begin to break down the SIS and, especially during long-duration drug delivery, and that degradation may increase the rate at which drug is being delivered.
  • an implant according to embodiments of the invention may be briefly soaked in saline, so that it does not need to be hydrated by body tissue.
  • implants contained only one drug.
  • an implant according to embodiments of the invention may contain more than one drug, so long as the two or more drugs are chemically and physiologically compatible.
  • drugs are primarily dispensed from the implant by diffusion, it is advantageous if the two or more drugs have diffusion rates and characteristics that are compatible.
  • more than one drug is to be delivered, more than one implant may be used, each implant containing a different drug.
  • implants according to embodiments of the invention may contain any number of compartments, each filled with one or more drugs.
  • bupivacaine-eluting implant As was described above, a number of drugs may be used. Unless otherwise noted, the SIS used in the examples was obtained from Cook Biotech Inc. (West Lafayette, Indiana, United States), and the bupivacaine, in the form of bupivacaine hydrochloride, was obtained from Sigma- Aldrich, Inc. (St. Louis, Missouri, United States).
  • Example 1 Diffusion rates of Bupivacaine Across SIS Membrane Examples of four different types of SIS were obtained from Cook Biotech,
  • each type of SIS was individually placed in the diffusion apparatus 50 schematically shown in FIG. 2.
  • the SIS 53 acts as part of a watertight junction 56 between two fluid reservoirs 52, 54, so that the only communication between those reservoirs 52, 54 is by diffusion through the SIS.
  • One reservoir 54 was filled with a 1 mM solution of bupivacaine in phosphate buffered saline; the other reservoir 52 was filled with phosphate buffered saline.
  • the bupivacaine concentration in both chambers was determined and recorded over the course of 45 hours using UV spectroscopy.
  • the apparatus 50 was maintained at room temperature.
  • Each reservoir 52, 54 included ports 58 through which fluid could be withdrawn to check concentration.
  • two apparatuses 50 were mounted side-by-side, such that multiple tests could be performed simultaneously.
  • FIGS. 3 and 4 are, respectively, a graph of bupivacaine concentration versus time for all four types of SIS, and a graph of diffusion rate versus time for all four types of SIS.
  • the results demonstrate that SIS can contain bupivacaine and allow it to diffuse out over time.
  • the diffusion rate of bupivacaine through single layer SIS was approximately 0.25 mg/hr under the conditions of the test.
  • this test did not simulate convective effects, enzymatic effects, or caloric effects, all of which may increase the diffusion rate in vivo.
  • a piece of SIS about 5 cm x 3 cm was cut and folded in half as shown in FIG. 1. Two edges of the folded SIS sheet were sealed under the temperature and pressure conditions given above in Example 2 to form a pocket with an approximately 0.5 - 0.75 cm wide sealed edges. The resulting pocket was filled with 200 mg bupivacaine hydrochloride powder and sealed. The edges of the sealed packet were trimmed so that the edges were all uniformly approximately 2 mm wide and the resulting implant had a size of about 2 cm x 2 cm.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Botany (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Materials Engineering (AREA)
  • Urology & Nephrology (AREA)
  • Medicinal Preparation (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L’invention concerne des implants à élution de médicament et des procédés pour leur fabrication et utilisation. Les implants comprennent des matières collagènes d’origine naturelle sous la forme de paquets étanches, dans lesquels un médicament est agencé pour se diffuser hors de l’implant sur une période de temps après l’implantation. La matière collagène peut être une sous-muqueuse de l’intestin grêle (SIS). Le médicament peut, dans certains modes de réalisation, être un analgésique tel que la bupivacaïne. Le paquet étanche peut être formé en appliquant des conditions définies de chaleur et de pression à la matière collagène pour lier ses bords. Les procédés d’utilisation des implants comprennent le placement de l’implant à l’intérieur de ou à proximité d’une plaie avant la fermeture de la plaie pour fournir une analgésie, anesthésie localisée ou encourager la cicatrisation de la plaie.
PCT/US2009/041704 2008-04-25 2009-04-24 Implant à élution de médicament pour administration de médicament locale et régionale Ceased WO2009132298A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US4784808P 2008-04-25 2008-04-25
US61/047,848 2008-04-25

Publications (1)

Publication Number Publication Date
WO2009132298A1 true WO2009132298A1 (fr) 2009-10-29

Family

ID=41217162

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2009/041704 Ceased WO2009132298A1 (fr) 2008-04-25 2009-04-24 Implant à élution de médicament pour administration de médicament locale et régionale

Country Status (1)

Country Link
WO (1) WO2009132298A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6666892B2 (en) * 1996-08-23 2003-12-23 Cook Biotech Incorporated Multi-formed collagenous biomaterial medical device
US6916483B2 (en) * 2002-07-22 2005-07-12 Biodynamics, Llc Bioabsorbable plugs containing drugs

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6666892B2 (en) * 1996-08-23 2003-12-23 Cook Biotech Incorporated Multi-formed collagenous biomaterial medical device
US6916483B2 (en) * 2002-07-22 2005-07-12 Biodynamics, Llc Bioabsorbable plugs containing drugs

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BROWN-ETRIS, MARIE ET AL., A NEW BIOMATERIAL DERIVED FROM SMALL INTESTINE SUBMUCOSA AND DEVELOPED INTO A WOUND MATRIX DEVICE, MEDSCAPE: WOUNDS, vol. 14, no. 4, 2002, pages 150 - 166, Retrieved from the Internet <URL:http://www.medscape.com/viewarticle/437577> *
LEE, C.H. ET AL.: "Biomedical applications of collagen", INTERNATIONAL J. PHARMACEUTICS, vol. 221, 2001, pages 1 - 22 *
RATNER, B.D.: "Reducing capsular thickness and enhancing angiogenesis around implant drug release systems", J. CONTROLLED RELEASE, vol. 78, 2002, pages 211 - 218 *

Similar Documents

Publication Publication Date Title
US10952961B2 (en) Implants and constructs including hollow fibers
CN103140226B (zh) 用于治疗脊髓损伤的制剂
US5919473A (en) Methods and devices for delivering opioid analgesics to wounds via a subdermal implant
US8709468B2 (en) Closed cell culture system
US5980927A (en) Method and apparatus for administering analgesics, and method for making same device
JP4599498B2 (ja) 非ポリマー持続性解離供給システム
KR100783837B1 (ko) 흉터 조직 형성을 감소시키기 위한 조성물 및 방법
EP2144640B1 (fr) Réduction de l&#39;infection associée aux dispositifs médicaux
CN105848693A (zh) 用于抑制糖尿病患者的异物反应的方法和系统
BRPI0406172B1 (pt) dispositivo de entrega de agente ativo minimamente invasiva de biomaterial
CN102006893A (zh) 粘膜组织敷料及其使用方法
CN111278478A (zh) 用于锚固植入式医疗装置的套件
EP1802282A1 (fr) Particules de proteines biocompatibles, dispositifs a particules et methodes associees
EP3979947A1 (fr) Procédés, dispositifs et compositions pour une administration locale
JP2011156355A (ja) 薬物溶出医療デバイスの差示的装填
CN101528283A (zh) 给内耳和其他组织递送治疗剂和/或其他药剂的设备和方法
CN104000652B (zh) 一种可吸收防粘连释药袋膜
WO2009132298A1 (fr) Implant à élution de médicament pour administration de médicament locale et régionale
WO2025258414A1 (fr) Matériau d&#39;échafaudage pour plaie destiné à supprimer une cicatrice d&#39;un tissu biologique
JP2025185685A (ja) 生体組織の瘢痕化を抑制するための創傷用足場材
CN116583310A (zh) 外科手术系统和使用方法
JP2025185432A (ja) 生体組織の瘢痕化を抑制するための創傷用足場材
US20230173764A1 (en) Surgical system and methods of use
Baker In vitro elution of analgesic medications from an absorbable gelatin sponge
HK40020691A (en) Bioerodible drug delivery devices

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09734352

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 09734352

Country of ref document: EP

Kind code of ref document: A1