WO1981000516A1 - Gel contenant fibrine et antibiotique pour le traitement d'os infectes et son procede de preparation - Google Patents

Gel contenant fibrine et antibiotique pour le traitement d'os infectes et son procede de preparation Download PDF

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Publication number
WO1981000516A1
WO1981000516A1 PCT/EP1980/000083 EP8000083W WO8100516A1 WO 1981000516 A1 WO1981000516 A1 WO 1981000516A1 EP 8000083 W EP8000083 W EP 8000083W WO 8100516 A1 WO8100516 A1 WO 8100516A1
Authority
WO
WIPO (PCT)
Prior art keywords
antibiotic
fibrin
bone
thrombin
gel
Prior art date
Application number
PCT/EP1980/000083
Other languages
German (de)
English (en)
Inventor
A Braun
Original Assignee
Merck Patent Gmbh
A Braun
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 Merck Patent Gmbh, A Braun filed Critical Merck Patent Gmbh
Publication of WO1981000516A1 publication Critical patent/WO1981000516A1/fr

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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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0028—Polypeptides; Proteins; Degradation products thereof
    • A61L26/0042—Fibrin; Fibrinogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
    • 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0031—Hydrogels or hydrocolloids
    • 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
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/225—Fibrin; Fibrinogen
    • 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
    • A61L27/52—Hydrogels or hydrocolloids
    • 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
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00005—The prosthesis being constructed from a particular material
    • A61F2310/00365—Proteins; Polypeptides; Degradation products thereof
    • A61F2310/00377—Fibrin

Definitions

  • Fibrin antibiotic gel for the treatment of infected bone and process for its preparation
  • the invention relates to a fibrin antibiotic gel for the treatment of infected, in particular staphylococcal, infected bone and a method for its production.
  • PMMA polymethyl methacrylate
  • the invention accordingly relates to a fibrin antibiotic gel for the treatment of infected bone with a content of fibrinogen, a thrombin-containing solution enriched with calcium ions and an antibiotic from the group of the aminoglycosides, characterized in that it is an antibiotic tobramycin, gentamycin and / or one of their physiologically acceptable salts.
  • the sulfates are particularly suitable as physiologically acceptable salts. All components of the gel are expediently used in the form of customary commercial preparations.
  • human fibrinogen in the form of a cryoprecipitate containing about 90 mg of thrombinable protein or as a lyophilisate e.g. obtained from human blood from pooled donor plasma.
  • the thrombin-containing solution is expediently prepared by dissolving thrombin (e.g. in the form of a powder) in an aqueous calcium chloride solution.
  • concentration of calcium chloride is preferably about 30 to 50, in particular 40, mmol / l.
  • concentration of thrombin is preferably between about 10 and about 500 NIH units / ml.
  • the antibiotic is expediently used in an amount based on body weight, whereby the maximum daily dose should be observed.
  • concentration of the antibiotic in the gel according to the invention is preferably between about 1 and about 10, in particular between 2 and 5 percent by weight.
  • the gel can be prepared by mixing fibrinogen with an antibiotic (for example, tobramycin sulfate or gentamycin sulfate, each about 5 mg / kg body weight) under sterile conditions and then adding the calcium ion-enriched thrombin-containing solution to polymerize the fibrinogen to fibrin.
  • the gel is preferably produced extracorporeally, ie before it is actually used in the bone cavity.
  • the clotting time depends on the thrombin concentration.
  • the plastic deformability of the resulting clot can be maintained for a period of 1/2 to 1 minute if a thrombin concentration of about 150 NIH units per ml is used.
  • the flow properties of the gel are determined by lower thrombin concentration (10-15 NIH units / ml). Maintained much longer (up to about 3 minutes). Fibrin coagulation is slowed down and the tensile strength of the polymer is increased.
  • the fibrin antibiotic gel with primary cancellous bone plastic not only controls the infection, but also improves the osteogenic potency of the biological implant.
  • Fibrin glue (commercial preparation) is produced from human donor plasma by cold precipitation. For storage, the finished product is deep-frozen and stored at -18 ° C or colder. 1 ml of the solution contains an average of 90 mg of thrombinable protein. The total protein content of the solution is about 10%. In addition to the precipitable fibrinogen, 1 ml of fibrin glue contains 5 - 12% cold-insoluble globulins, a maximum of 5% albumin and about 10 units of factor XIII, as well as traces of plasminogen and coagulation factors of the intrinsic system. The cryopreserved human fibrinogen is thawed at room temperature about 20-30 minutes before its intended use. The viscosity of the preparation decreases with increasing temperature.
  • 3000 NIH units of thrombin dry substance (commercial preparation) are dissolved in 20 ml of an aqueous calcium chloride solution which contains 35 mmol / 1 CaCl 2 .
  • the distal femoral metaphysis was exposed from the side.
  • the corticalis was perforated to a size of 4 x 8 mm with a drill and milling machine and spongy bones were milled out, so that the defect could be filled with approx. 0.5 ml.
  • the marrow was tamped with bone wax for hemostasis.
  • a 4 x 4 x 1 mm collagen fleece was inoculated with 0.05 ml staphylococcal suspension and the bone cavity was contaminated with it. This corresponds to a germ density of 0.5 - 2 x 10 7 colonies.
  • the bone defect was closed in group A with the fibrin-antibiotic gel and in group B with fibrin.
  • group A With good plastic deformability during the polymerization, the distal femoral metaphysis was included in group A. Fill in 0.45 ml fibrin antibiotic gel and compress the fibrin clot over the corticalis window manually for 2 minutes.
  • group B control group
  • 0.1 ml of tobramycin-containing solution was replaced by 0.1 ml of distilled water, so that 0.25 ml of fibrinogen was coagulated by 0.2 ml of thrombin-containing solution.
  • a coagulase-positive, tobramycin-sensitive (MIC ⁇ 0.125 mcg / ml) Staphylococcus aureus isolated from a wound swab from the Orthopedic University Clinic in Heidelberg was used Cultivated 37 ° C, washed off with sterile physiological saline and the bacterial wash-off by turbidity comparison (tube no. 1 of the barium sulfate turbidity series after
  • McFarland to a germ density of approx. 3 x 10 8 germs / ml.
  • the exact number of bacteria (colony-forming units) of the suspension was determined using the plate casting method at the time of application to the animal.
  • a nutrient agar of the following composition was used as the bacterial counting storage (each gram per 1000 ml water):
  • Meat extract 3 Witte Peptone 5, sodium chloride 5, agar 12; pH 7.2.
  • smears from the medullary canal and extra-articular tissue were taken with sterile cotton swabs and each in 0.2% glucose broth and on agar plates (10% mutton blood addition). After an incubation time of 18-24 hours at 37 C, the growth media were checked for growth and incubated for a further 24 hours if there was no turbidity or colony formation. The material was described as sterile if no growth had been shown up to this point. The grown staphylococci were identified by the microscopic preparation, shape and color of the colonies, hemolysis like and detection of the bound coagulase (clumping factor).
  • the pieces of bone taken from the section of the test animals were fixed in 4% neutral, buffered formalin and then carefully decalcified.
  • the decalcifying solution consisted of 200 g of ethylenediaminetetraacetic acid tetrasodium salt, made up to 1000 ml with water and adjusted to pH 7.0-7.2 with citric acid. After decalcification, the samples were embedded in paraffin in the usual way. 3 - 5 u thick layers were stained with hematoxylin-eosin, van Gieson, Di PAS, Giemsa, Ladewig and according to the Weigert's method of presentation of fibrin.
  • the test animals were sacrificed on the 7th postoperative day and the findings were evaluated macroscopically, bacteriologically and histomorphologically. Of the animals in control group B, 15 died of sepsis between the 2nd and 7th day. The decrease in body weight in this group averaged 530 g. In the rabbits (group A) treated with fibrin tobramycin, no animal died from the consequences of an infection. The body weight had only decreased by 136 g on average. I. Macroscopic finding
  • a swab was taken intramedullarily from the surgical area both in the periarticular soft tissue and in the distal femur for bacteriological examination.
  • the smears were sterile in 27 animals and infected in 3 animals. There were found once subcutaneously, once intraosseously and once subcutaneously and intraosseously staphylococci.
  • group B all smears were staphylococcal infected.
  • the test group and control group thus differ with regard to the treatment procedure with an error probability of at most 1%.
  • the local use of Tobra mycin in the fibrin antibiotic gel can be regarded as exceptionally effective according to this statistical statement.
  • the histological examination revealed non-specific inflammation in all animals in the operated area. According to the choice of the pathogen, it was a purulent inflammation, which, however, occurred in different degrees of severity. In group A animals, on average, inflammation was far less severe. An extensive fibrin residue was typically detected in this group. A granulation tissue had already developed around it, which was also permeated with granulocytes and some macrophages. In some cases, newly formed bone trabeculae made of braided bone could be detected. As a rule, the infected area was enclosed by this granulation tissue, the distal epiphyseal joint undamaged, so that one could speak of a localized osteomyelitic process.
  • Example 3 The procedure is analogous to Example 1, but the tobramycin sulfate is replaced by 15 mg of gentamycin sulfate and comparable results are obtained.
  • Example 3 The procedure is analogous to Example 1, but the tobramycin sulfate is replaced by 15 mg of gentamycin sulfate and comparable results are obtained.
  • the application set contains the following individual components:
  • the application set contains the following individual components:

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Transplantation (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Dermatology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Materials Engineering (AREA)
  • Dispersion Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Emergency Medicine (AREA)
  • Biomedical Technology (AREA)
  • Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Materials For Medical Uses (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Un gel a base de fibrine et d'antibiotique pour le traitement d'un os infecte contient du fibrinogene une solution contenant de la thrombine et enrichie en ions calcium ainsi qu'un antibiotique du groupe tobramycine, gentiamycine et/ou un de leurs sels physiologiquement inoffensifs. Le gel peut etre prepare par melange du fibrinogene sous forme d'un lyophilisat ou d'un cryoprecipite avec un antibiotique dans des conditions steriles puis par adjonction d'une solution de thrombine enrichie en ions calcium.
PCT/EP1980/000083 1979-08-31 1980-08-27 Gel contenant fibrine et antibiotique pour le traitement d'os infectes et son procede de preparation WO1981000516A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE2935194 1979-08-31
DE2935194 1979-08-31

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Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2510408A1 (fr) * 1981-07-28 1983-02-04 Immuno Ag Colle pour tissus
US6054122A (en) * 1990-11-27 2000-04-25 The American National Red Cross Supplemented and unsupplemented tissue sealants, methods of their production and use
US6117425A (en) * 1990-11-27 2000-09-12 The American National Red Cross Supplemented and unsupplemented tissue sealants, method of their production and use
US6197325B1 (en) 1990-11-27 2001-03-06 The American National Red Cross Supplemented and unsupplemented tissue sealants, methods of their production and use
WO2001097872A1 (fr) * 2000-06-22 2001-12-27 Austin Sam L Compositions bioadhesives et methodes de preparation et d'utilisation
US6559119B1 (en) 1990-11-27 2003-05-06 Loyola University Of Chicago Method of preparing a tissue sealant-treated biomedical material
US6762336B1 (en) 1998-01-19 2004-07-13 The American National Red Cross Hemostatic sandwich bandage
US6921532B1 (en) 2000-06-22 2005-07-26 Spinal Restoration, Inc. Biological Bioadhesive composition and methods of preparation and use
US7189410B1 (en) 1990-11-27 2007-03-13 The American National Red Cross Supplemented and unsupplemented tissue sealants, methods of their production and use
WO2009014776A1 (fr) * 2007-07-23 2009-01-29 Carnegie Mellon University Procédés et appareil pour fabriquer des matières plastiques à base de plasma et matières bioplastiques produites à partir de celles-ci
US7597687B2 (en) 2004-10-29 2009-10-06 Spinal Restoration, Inc. Injection of fibrin sealant including an anesthetic in spinal applications
US8124075B2 (en) 2004-07-16 2012-02-28 Spinal Restoration, Inc. Enhanced biological autologous tissue adhesive composition and methods of preparation and use
US8206448B2 (en) 2004-10-29 2012-06-26 Spinal Restoration, Inc. Injection of fibrin sealant using reconstituted components in spinal applications
US8403923B2 (en) 2004-10-29 2013-03-26 Spinal Restoration, Inc. Injection of fibrin sealant in the absence of corticosteroids in spinal applications
US8419722B2 (en) 2004-10-29 2013-04-16 Spinal Restoration, Inc. Apparatus and method for injection of fibrin sealant in spinal applications
US8529961B2 (en) 2006-10-17 2013-09-10 Carmell Therapeutics Corporation Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US8529960B2 (en) 2002-03-18 2013-09-10 Carnell Therapeutics Corporation Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US8679528B2 (en) 2002-09-10 2014-03-25 American National Red Cross Hemostatic dressing
US9131929B2 (en) 2007-08-06 2015-09-15 Stb, Ltd. Methods and dressings for sealing internal injuries
WO2022242533A1 (fr) * 2021-05-19 2022-11-24 周晓晨 Composition de gel pour éliminer des fragments de calcul résiduels après la lithotritie

Citations (5)

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Publication number Priority date Publication date Assignee Title
US2385802A (en) * 1942-02-09 1945-10-02 Research Corp Process for the manufacture of plastics
US3723244A (en) * 1971-01-18 1973-03-27 Atomic Energy Commission Fibrous fibrin sheet and method for producing same
DE2511122A1 (de) * 1975-03-14 1976-09-23 Kulzer & Co Gmbh Vorprodukt fuer die zubereitung von knochenzement
DE2651441A1 (de) * 1976-11-11 1978-05-24 Merck Patent Gmbh Antibioticahaltiges mittel und seine verwendung als chirurgisches kunststoffmaterial
DE2852319A1 (de) * 1977-12-05 1979-06-07 Ethicon Inc Absorbierbare haemostatische masse

Patent Citations (5)

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Publication number Priority date Publication date Assignee Title
US2385802A (en) * 1942-02-09 1945-10-02 Research Corp Process for the manufacture of plastics
US3723244A (en) * 1971-01-18 1973-03-27 Atomic Energy Commission Fibrous fibrin sheet and method for producing same
DE2511122A1 (de) * 1975-03-14 1976-09-23 Kulzer & Co Gmbh Vorprodukt fuer die zubereitung von knochenzement
DE2651441A1 (de) * 1976-11-11 1978-05-24 Merck Patent Gmbh Antibioticahaltiges mittel und seine verwendung als chirurgisches kunststoffmaterial
DE2852319A1 (de) * 1977-12-05 1979-06-07 Ethicon Inc Absorbierbare haemostatische masse

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Band 72, Nummer 23, 8. Juni 1970 (Columbus, Ohio, USA) M. POP, "Experimental covering of the dental pulp in the dog with biological substances" siehe Seite 209, Spalte 1, Zusammenfassung 119944n, Stomatologia 1969, 16(5) 397-403(Rom) siehe die Zusammenfassung. *
CHEMICAL ABSTRACTS, Band 80, Nummer 13, 1. April 1974 (Columbus, Ohio, USA) JP, A, 73 80 779, Mihama Hisaharu siehe Seite 114, Spalte 2, Zusammenfassung 67835w, siehe die Zusammenfassung. *
CHEMICAL ABSTRACTS, Band 85, Nummer 24, 13. Dezember 1976 (Columbus, Ohio, USA) I. SUGIE, "The chemical modification of fibrin film as artificial skin", siehe Seite 318, Spalte 1, Zusammenfassung 182381k, Aichi Ika Daigaku Igakukai Zasshi 1976, 4(3) 183-192(Japan) siehe die Zusammenfassung. *

Cited By (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2510408A1 (fr) * 1981-07-28 1983-02-04 Immuno Ag Colle pour tissus
USRE39321E1 (en) * 1990-11-27 2006-10-03 The American National Red Cross Supplemented and unsupplemented tissue sealants, methods of their production and use
US6054122A (en) * 1990-11-27 2000-04-25 The American National Red Cross Supplemented and unsupplemented tissue sealants, methods of their production and use
US6117425A (en) * 1990-11-27 2000-09-12 The American National Red Cross Supplemented and unsupplemented tissue sealants, method of their production and use
US6197325B1 (en) 1990-11-27 2001-03-06 The American National Red Cross Supplemented and unsupplemented tissue sealants, methods of their production and use
US7229959B1 (en) 1990-11-27 2007-06-12 The American National Red Cross Supplemented fibrin matrix delivery systems
US6559119B1 (en) 1990-11-27 2003-05-06 Loyola University Of Chicago Method of preparing a tissue sealant-treated biomedical material
US7208179B1 (en) 1990-11-27 2007-04-24 The American National Red Cross Methods for treating disease and forming a supplemented fibrin matrix
US7189410B1 (en) 1990-11-27 2007-03-13 The American National Red Cross Supplemented and unsupplemented tissue sealants, methods of their production and use
USRE39192E1 (en) * 1990-11-27 2006-07-18 American National Red Cross Supplemented and unsupplemented tissue sealants, methods of their production and use
USRE39298E1 (en) * 1990-11-27 2006-09-19 The American National Red Cross Supplemented and unsupplemented tissue sealants, methods of their production and use
US6762336B1 (en) 1998-01-19 2004-07-13 The American National Red Cross Hemostatic sandwich bandage
US7229633B2 (en) 2000-06-22 2007-06-12 Spinal Restoration, Inc. Biological bioadhesive compositions and methods of preparation and use
AU2001273623B2 (en) * 2000-06-22 2006-06-08 Spinal Restoration, Inc. Bioadhesive compositions and methods of preparation and use
US6921532B1 (en) 2000-06-22 2005-07-26 Spinal Restoration, Inc. Biological Bioadhesive composition and methods of preparation and use
US6468527B2 (en) 2000-06-22 2002-10-22 Sam L. Austin Biological bioadhesive composition and methods of preparation and use
WO2001097872A1 (fr) * 2000-06-22 2001-12-27 Austin Sam L Compositions bioadhesives et methodes de preparation et d'utilisation
US7235255B2 (en) 2000-06-22 2007-06-26 Spinal Restoration, Inc. Biological bioadhesive compositions and methods of preparation and use
US8529960B2 (en) 2002-03-18 2013-09-10 Carnell Therapeutics Corporation Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US8679528B2 (en) 2002-09-10 2014-03-25 American National Red Cross Hemostatic dressing
US8124075B2 (en) 2004-07-16 2012-02-28 Spinal Restoration, Inc. Enhanced biological autologous tissue adhesive composition and methods of preparation and use
US8403923B2 (en) 2004-10-29 2013-03-26 Spinal Restoration, Inc. Injection of fibrin sealant in the absence of corticosteroids in spinal applications
US8206448B2 (en) 2004-10-29 2012-06-26 Spinal Restoration, Inc. Injection of fibrin sealant using reconstituted components in spinal applications
US8419722B2 (en) 2004-10-29 2013-04-16 Spinal Restoration, Inc. Apparatus and method for injection of fibrin sealant in spinal applications
US7597687B2 (en) 2004-10-29 2009-10-06 Spinal Restoration, Inc. Injection of fibrin sealant including an anesthetic in spinal applications
US8986304B2 (en) 2004-10-29 2015-03-24 Bsnc Holding, Llc Injection of fibrin sealant using reconstituted components in spinal applications
US8293530B2 (en) 2006-10-17 2012-10-23 Carnegie Mellon University Method and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US8529961B2 (en) 2006-10-17 2013-09-10 Carmell Therapeutics Corporation Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US8529958B2 (en) 2006-10-17 2013-09-10 Carmell Therapeutics Corporation Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US8911789B2 (en) 2006-10-17 2014-12-16 Carnegie Mellon University Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US9364503B2 (en) 2006-10-17 2016-06-14 Carmell Therapeutics Corporation Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
WO2009014776A1 (fr) * 2007-07-23 2009-01-29 Carnegie Mellon University Procédés et appareil pour fabriquer des matières plastiques à base de plasma et matières bioplastiques produites à partir de celles-ci
US9131929B2 (en) 2007-08-06 2015-09-15 Stb, Ltd. Methods and dressings for sealing internal injuries
WO2022242533A1 (fr) * 2021-05-19 2022-11-24 周晓晨 Composition de gel pour éliminer des fragments de calcul résiduels après la lithotritie

Also Published As

Publication number Publication date
JPS56501129A (fr) 1981-08-13
EP0037814A1 (fr) 1981-10-21

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