EP1000089A1 - Compositions d'adhesif a base de collagene du type i et du type iii - Google Patents

Compositions d'adhesif a base de collagene du type i et du type iii

Info

Publication number
EP1000089A1
EP1000089A1 EP98938008A EP98938008A EP1000089A1 EP 1000089 A1 EP1000089 A1 EP 1000089A1 EP 98938008 A EP98938008 A EP 98938008A EP 98938008 A EP98938008 A EP 98938008A EP 1000089 A1 EP1000089 A1 EP 1000089A1
Authority
EP
European Patent Office
Prior art keywords
composition
collagen
collagen type
monomers
type iii
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.)
Withdrawn
Application number
EP98938008A
Other languages
German (de)
English (en)
Other versions
EP1000089A4 (fr
Inventor
Thomas B. Neff
Kari I. Kivirikko
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.)
ACADEMY OF FINLAND
Fibrogen Inc
Original Assignee
ACADEMY OF FINLAND
Fibrogen Inc
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 ACADEMY OF FINLAND, Fibrogen Inc filed Critical ACADEMY OF FINLAND
Publication of EP1000089A1 publication Critical patent/EP1000089A1/fr
Publication of EP1000089A4 publication Critical patent/EP1000089A4/fr
Withdrawn legal-status Critical Current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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10—Polypeptides; Proteins
    • A61L24/102—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L89/00—Compositions of proteins; Compositions of derivatives thereof
    • C08L89/04—Products derived from waste materials, e.g. horn, hoof or hair
    • C08L89/06—Products derived from waste materials, e.g. horn, hoof or hair derived from leather or skin, e.g. gelatin
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
    • C09J189/00—Adhesives based on proteins; Adhesives based on derivatives thereof
    • C09J189/04—Products derived from waste materials, e.g. horn, hoof or hair
    • C09J189/06—Products derived from waste materials, e.g. horn, hoof or hair derived from leather or skin

Definitions

  • the present invention is directed to polymerized recombinant type I and/or type III collagen based compositions and combinations thereof for medical use as adhesives and sealants and the preparation of such compositions.
  • the recombinant type I and type III collagen compositions are useful as medical adhesives for bonding soft tissues or in a sealant film for a variety of medical uses, including in wound closure devices and tendon wraps for preventing the formation of adhesion following surgical procedures.
  • the polymerized type I and type III collagen composition includes agents which induce wound healing or provide for additional beneficial characteristics desired in a tissue adhesive and sealant.
  • tissue adhesives are derived from human plasma and hence pose potential health risks such as adverse immunogenic reactions and transmission of infectious agents, e.g., Hepatitis B virus. Moreover, the bond strength imparted by such adhesives are relatively weak compared to collagen adhesives (see De Toledo, A. R. et al. Assoc. for Res. in Vision and Ophthalmology, Annual Meeting Abstract, Vol. 31, 317 (1990). Accordingly, there is a need for safe, effective biologically compatible tissue adhesives for biomedical applications. More recently, combination products have been devised for use as a tissue adhesive. For example, Staindl (Ann.
  • Otol (1979) 88:413-418) describes the use of a combination of three separately prepared substances, human fibrinogen cryoprecipitate, thrombin in the presence of calcium ion, and Factor XIII concentrate, to obtain a glue that was applied in skin graft applications, myringoplasty, repair of dural defects, hemeostatis after tonsillectomy, and tracheoplasty.
  • Immuno-AG Vienna, Austria, began producing and commercializing a two-component "fibrin seal" system, wherein one component contains highly concentrated human fibrinogen, Factor XIII, and other human plasma proteins, prepared from pooled blood, and the other component supplies thrombin and calcium ion.
  • Collagen As A Biomaterial. Collagen, the major connective tissue protein in animals, possesses numerous characteristics not seen in synthetic polymers. Characteristics of collagen often cited include good compatibility with living tissue, promotion of cell growth, and absorption and assimilation of implantations (Shimizu, R. et al. Biomat. Med. Dev. Art. Org., 5(1): 49-66 (1977)). Various applications of this material are being tested, for example, as dialysis membranes of artificial kidney (Sterzel, K. H. et al. Ameri. Soc. Artif. Int. Organs 17: 293 (1971)), artificial cornea (Rubin, A. L. et al. Nature 230: 120 (1971) and U.S. Pat. No.
  • Natural collagen fibers are basically insoluble in mature tissues because of covalent intermolecular cross-links that convert collagen into an infinite cross-linked network. Dispersal and solubilization of native collagen can be achieved by treatment with various proteolytic enzymes which disrupt the intermolecular bonds and removes immunogenic non-helical end regions without affecting the basic, rigid triple-helical structure which imparts the desired characteristics of collagen ⁇ see also, U.S. Pat. Nos. 3,934,852; 3,121,049; 3,131,130; 3,314,861; 3,530,037; 3,949,073; 4,233,360 and 4,488,911 for general methods for preparing purified soluble collagen).
  • the prior modified collagen-based adhesives suffer from various deficiencies which include (1) cross-linking/polymerization reactions that generate exothermic heat, (2) long reaction times, and (3) reactions that are inoperative in the presence of oxygen and physiological pH ranges (Lee M. L. et al. Adhesion in Biological Systems, R. S. Manly, ed., Academic Press, New York, 1970, Chap. 17). Moreover, many of the prior modified collagen-based adhesives contain toxic materials, rendering it unsuitable for biomedical use (see, for example, Buonocore, M. G. (1970) and U.S. Pat. No. 3,453,222).
  • collagen-based adhesives also presents immunological concerns as such adhesives have been derived from animal sources and typically bovine sources.
  • studies with respect to the use of such coUagens as injectible devices have reported minor inflammatory responses.
  • potential issues regarding the transmission of disorders to humans related to bovine spongiform encephalopathy (“mad cow disease”) have focused attention, especially in Europe, to limiting bovine sourced materials.
  • a biologically compatible, collagen type III and/or type I product with sealant and adhesive properties can be formed using soluble recombinantly derived collagen type III and/or type I monomers; wherein said monomers are polymerized to form a collagen type III and/or type I composition having adhesive and sealant properties.
  • the collagen is human and derived using recombinant technology.
  • Collagen type III was selected for its unexpectedly superior hemostatic characteristics, as compared to other collagen types.
  • Collagen type I was selected for its structural characetristics.
  • the polymerization reaction may be initiated with an appropriate polymerization initiator such as a chemical oxidant, ultraviolet irradiation, a suitable oxidative enzyme or atmospheric oxygen.
  • the product is comprised preferably of a combination of pure recombinant type I and type III collagen
  • the ratio of pure recombinant collagen type III to pure recombinant type I is about 30% and greater type III collagen to about 70% or less type I collagen. More preferably, the ratio of pure recombinant type III collagen to pure recombinant type I collagen is about 30% to about 50% type III collagen to about 70% to about 50% type I collagen. Most preferably, the ratio of pure recombinant type III collagen to pure recombinant type I collagen is about 30% to about 40% type III collagen to about 70% to about 60% type I collagen.
  • the sealant acts as a hemostatic barrier and reduces the risk of serum, lymph and liquor leakage.
  • collagen type III possesses inherently hemostatic properties, its use in a hemostatic device provides an improvement over known fibrin sealants.
  • Collagen type I also possesses some hemostatic properties.
  • (iii) Wound healing (iii) Wound healing.
  • the sealant promotes the growth of fibroblasts which in combination with efficient hemostasis and adhesion between the wound surfaces provides for an improved healing process.
  • the use of the compositions according to the invention as an anti-adherence/wound healing composition is expected to result in a normal (regenerative) tissue rather than scar tissue, i.e. optimal wound healing. Furthermore, such compositions also reduce the inflammatory response.
  • polymerized collagen type III and/or type I compositions as a safe, effective biological adhesives with appropriate adhesive strength for biomedical applications, particularly involving soft tissues. More specifically, the present invention is directed to compositions useful in sealing punctures and incisions in internal organs, the dermis and large blood vessels.
  • the polymerized materials may assume a number of sizes and shapes consistent with their intended biomedical applications, which include use in ophthalmology, plastic surgery, orthopedics and cardiology.
  • the collagen type III and/or type I composition is further comprised of agents which will confer additional desirable characteristics for a sealant or adhesive.
  • agents which will confer additional desirable characteristics for a sealant or adhesive For example, fibrin, fibrinogen, thrombin, calcium ion, Factor XIII may be included in the composition to better effect the formation of a three-dimensional network of polymerized collagen.
  • the recombinant collagen type III composition incorporates a drug having wound healing capabilities.
  • the drug is connective tissue growth factor and is incorporated in the composition to effect slow-release of the drug to the wound.
  • biologically compatible refers to recombinant collagen type III and/or type I modified in accordance with the present invention (i.e. , a polymerized collagen type III recombinant product) which is incorporated or implanted into or placed adjacent to the biological tissue of a subject and more particularly, does not deteriorate appreciably over time or induce an immune response or deleterious tissue reaction after such incorporation or implantation or placement.
  • pure recombinant collagen type I refers to human collagen type I manufactured by recombinant techniques which is substantially free from other collagen types. The term excludes collagen type I isolated from natural sources.
  • pure recombinant collagen type III refers to human collagen type I manufactured by recombinant techniques which is substantially free from other collagen types. The term excludes collagen type III isolated from natural sources.
  • collagen type I or III will be recombinantly manufactured by culturing a cell which has been transfected with at least one gene encoding the polypeptide comprising collagen type I or III and genes encoding the ⁇ and ⁇ subunits of the post-translational enzyme prolyl 4-hydroxylase and purifying the resultant collagen monomer therefrom.
  • the monomeric soluble collagen type I and III material exhibits a viscous consistency and varying degrees of transparency and clarity.
  • the recombinant collagen type I and III solution may be subsequently subjected to polymerization or cross-linking conditions to produce the polymerized collagen composition of the present invention.
  • Polymerization may be carried out using irradiation, e.g. , UV, gamma, or fluorescent light.
  • UV irradiation may be accomplished in the short wave length range using a standard 254 nm source or using UV laser sources. With a standard 254 nm source, 4-12 watts, polymerization occurs from 10 to 40 minutes, preferably 20 to 30 minutes, at an exposure distance of from 2.5-10 cm, preferably from 2.5 to 5 cm distance. Excess UV exposure will begin to depolymerize the collagen polymers.
  • Polymerization using gamma irradiation can be done using from 0.5 to 2.5 Mrads. Excess Gamma exposure will also depolymerize collage polymers. Polymerization in the presence of oxygen can be done by adding an initiator to the fluid prior to exposure.
  • initiators include sodium persulfate, sodium thiosulfate, ferrous chloride tetrahydrate, sodium bisulfite and oxidative enzymes such as peroxidase or catechol oxidase. When initiators are employed, polymerization occurs in 30 seconds to 5 minutes, usually from 1 to 3 minutes.
  • the polymerizing agent is preferably UV irradiation.
  • the polymerization or cross-linking of the monomeric substituents can be carried out by simply exposing the material to atmospheric oxygen, although the rate of polymerization is appreciably slower than in the case of UV irradiation or chemical agents.
  • difunctional monomeric cross-linking agents may be added to the monomer compositions of this invention to effect polymerization.
  • cross-linking agents are known in the art, for example, to U.S. Pat. No. 3,940,362 (Overhults), which is hereby incorporated by reference herein.
  • compositions of the present invention are comprised of polymerized type I and III collagen wherein said composition is manufactured by a process comprising the steps: (1) production of collagen type I and III monomers by the recombinant methods described above; and (2) polymerization of such monomers.
  • the product is comprised preferably of a combination of pure recombinant type I and type III collagen
  • the ratio of pure recombinant collagen type III to pure recombinant type I is about 30% and greater type III collagen to about 70% or less type I collagen.
  • the ratio of pure recombinant type III collagen to pure recombinant type I collagen is about 30% to about 50% type III collagen to about 70% to about 50% type I collagen. Most preferably, the ratio of pure recombinant type III collagen to pure recombinant type I collagen is about 30% to about 40% type III collagen to about 70% to about 60% type I collagen.
  • compositions of the present invention may be further comprised of other agents which are useful to glueing or sealing tissues.
  • the composition will preferably comprise Factor XIII and/or fibrin/fibrinogen/fibronectin and/or plasminogen.
  • the composition will also include clotting enzyme, i.e. thrombin, especially in combination with bivalent calcium, such as calcium chloride. The concentration of calcium chloride will then vary, e.g.
  • a fibrinolysis inhibitor such as a plasmin inhibitor, e.g. aprotinin, aprilotinin, alpha- 2-antiplasmin, alpha-2-macroglobulin, alpha- 1-antitrypsin, epsilon-aminocaproic add or tranexamic acid, or a plasmin activator inhibitor, e.g. PAI-1 or PAI-2.
  • a plasmin inhibitor such as a plasmin inhibitor, e.g. aprotinin, aprilotinin, alpha- 2-antiplasmin, alpha-2-macroglobulin, alpha- 1-antitrypsin, epsilon-aminocaproic add or tranexamic acid, or a plasmin activator inhibitor, e.g. PAI-1 or PAI-2.
  • the necessary amount of the viscosity enhancing polymer can readily be determined by a person skilled in the art depending on the particular polymer and the intended use form. Thus, if the concentration and/or molecular weight of the viscosity enhancing polymer is too low, the viscosity increase will be insufficient, and a too high concentration and/or molecular weight will inhibit the fibrin polymerization and the adhesion to the tissue.
  • the polymerization of composition of the present invention may be speeded up with a consequential influence on the time until the glue sets.
  • the fibrin of the composition will remain more or less fluid for several minutes after application.
  • a further beneficial effect of increasing the viscosity with a viscosity enhancing polymer in accordance with the invention is therefore the possibility to use lower concentrations of thrombin, which is required in situations where the parts to be sealed require subsequent adaptation even on non-horizontal surfaces.
  • compositions of the present invention may, rather than including a combination of the agents described herein, be a fusion protein wherein the collagen type I and/or type III and, for example, fibrin, are combined to form one molecule.
  • fusion proteins may be manufactured according to the recombinant techniques described herein.
  • the composition of the present invention includes agents useful in wound healing, either by inducing or promoting the formation of tissue, or alternatively, limiting the formation of fibrotic adhesions.
  • agents useful in wound healing include antibiotics, or growth factors, such as connective tissue growth factor, which is described at, for example, U.S. Patent No. 5,408,040 and 5,585,270, said references are incorporated herein by reference.
  • the polymerized collagen type III and/or type I product may be useful to produce mechanical sealants and adhesive systems.
  • Tissue Adhesive Systems Fields of application include among others: ear, nose and throat surgery, general surgery, dentistry, neurosurgery, plastic surgery, thorax and vascular surgery, abdominal surgery, orthopaedics, accident surgery, gynaecology, urology, and opthalmology.
  • the collagen sealants of the present invention have also been used for local application of drugs, such as antibiotics, growth factors and cytostatics.
  • the polymerized collagen products can be made in the form of a sealant film.
  • a collagen based film will be flexible and elastic with the consistency and feel of plastic film, and yet the film should exhibit high biological compatibility.
  • Uses of sealant films include: Prevention of adhesion formation following tendon surgery (i.e. , use as a wrap around tendons), use as a synthetic tympanic membrane, substitute facial tissue and wound dressing component. Additional examples of potential usage of sealant films include: treatment of corneal abrasions, wound closure, coating of catheters and instruments, use as a material to prevent adhesion formation in tissues than tendons (e.g. , peritoneal cavity).
  • sealant and adhesive formulations which can be used as systems specific for delivery of numerous drugs and pharmaceutical compositions, including growth factors, antibiotics, and other biologically beneficial compounds. Such materials can be added to the collagen adhesive or sealant to promote cell migration, cell adhesion, and wound healing.
  • Angioplasty is a diagnostic procedure whereby dye is injected into an artery, preferably the femoral artery, to detect the presence or absence of coronary disease.
  • Angioplasty also known as PCT A, is a therapeutic procedure which involves the inflation of a balloon in an artery, such as the coronary artery, for the purpose of relieving arterial blockages. After puncturing the femoral artery, a balloon-catheter is introduced through the femoral artery and navigated through to the coronary artery blocked by atherosclerosis (plaque).
  • plaque atherosclerosis
  • balloon catheters are commonly used in angioplasty and angiography including over-the-wire catheters which ride over an independent guidewire to the site of the disease; 2) fixed-wire catheters, which combine a balloon catheter with a guidewire into one device; 3) rapid-exchange or single- operator exchange catheters, which are over-the-wire catheters that can be exchanged more conveniently than standard over-the-wire catheters; and 4) perfusion catheters, which allow blood flow during the procedure.
  • a rotational tip catheter removes plaque buildup on arterial walls.
  • These devices utilize a technique called differential cutting. Calcified material is rendered into microscopic particles without damaging the artery due to the elastic nature of the arterial walls.
  • Angioplasty is a more invasive and complicated procedure than angiography, since it requires the insertion of a larger sheath than that used in angiography.
  • the sheath is used as a vehicle for introducing the catheter into the artery.
  • angioplasty also requires the use of blood thinners, such as heparin, to prevent clotting during and after the surgical procedure.
  • the anti-clotting agent prevents the body's natural sealing/clotting mechanism and, thus, sealing punctures requires a significant length of time.
  • an adhesive applicator may optionally be inserted into the sheath and is placed into a position near to or contacting the puncture in the artery.
  • manual or mechanical pressure is applied to the artery to reduce the flow of blood at the puncture site. If possible, excess blood/fluid is removed from the puncture site.
  • recombinant collagen type III and/or type I monomer of the present invention may be applied to the puncture on the external surface of the artery and/or within the puncture track.
  • the monomer then is polymerized and/or cross-linked by the techniques described herein, for example, UV irradiation, such that polymerization takes place within 0 to 300 seconds, preferably 0 to 120 seconds, more preferably 0 to 30 seconds, and even more preferably 3 to 10 seconds.
  • UV irradiation such that polymerization takes place within 0 to 300 seconds, preferably 0 to 120 seconds, more preferably 0 to 30 seconds, and even more preferably 3 to 10 seconds.
  • the surgical adhesive according to the present invention can polymerize almost immediately, the adhesive can polymerize on the surface and/or along the puncture track of the artery without penetrating the interior of the artery. Accordingly, large pieces or particles of material will not enter the circulatory system, thereby substantially reducing risk of embolism. Due to the fast and strong bonding of preferred adhesives of the invention, the patient will need to be immobilized for only a minimal period of time.
  • tissue treatment composition of the present invention may be presented in the same type of preparations as the prior art fibrin sealants.
  • the components may be provided in deep frozen solution form or as lyophilized powders, to be diluted prior to use with appropriate aqueous solutions, e.g. containing aprotinin and calcium ions, respectively.
  • compositions of the present invention comprising pharmaceutical agents, such as an antibiotic, a growth factor, etc, by incorporating said agent into the tissue adhesive so as to be enclosed in the collagen network formed upon application of the tissue adhesive. It will thereby be ensured that the drug is kept at the site of application while being controllably released from the composition, e.g. when used as ocular drops, a wound healing preparation, etc.
  • the pharmaceutically active substance to be released from the present tissue adhesive composition may be the viscosity enhancing polymer in itself or a substance coupled thereto.
  • tissue treatment composition of this invention thus constitutes an advantageous slow-release preparation for proteoglycans such as hyaluronic acid and its salts and derivatives, and considerably increases the bioavailability thereof.
  • compositions of the present invention are not restricted to the adhesive properties, but non-adhesive compositions are also included, especially when the compositions primarily are intended for wound healing.
  • the latter compositions may in particular include non-adhesive proteins such as albumin and/or growth factors.
  • substantially non-adhesive compositions may also be obtained when the polymer part of the composition inhibits the adhesive properties of the protein part.
  • the invention comprises both adhesive and substantially non-adhesive compositions, although it has for simplicity reasons often has been referred to as an "adhesive" in this specification.
  • compositions of the present invention may be applied using a variety of dispensing devices.
  • the surgical adhesive may be applied using the devices set forth in U.S. Pat. Nos. 4,900,303 (Lemelson) and 5,372,585 (Tiesenbrun) while monitoring the application process through an optical viewing system.
  • the composition of the present invention may also be applied by the devices set forth in U.S. Pat. No. 5,129,882 (Weldon et al.). The subject matter of these patents is incorporated herein by reference.
  • the composition according to the present invention may also be applied in conjunction with other sealing means.
  • the adhesive may be applied to puncture sites which have been closed using surgical suture or tape, such as in the sealing of a puncture or incision in internal organs, e.g. , liver, gallbladder, intestines, stomach, kidney, heart, urinary bladder, ureter, lung, esophagus and the like.
  • the adhesive in this instance will provide a complete seal, thereby reducing the risk of body fluid leakage from the organ or vessel, e.g., leakage from liver puncture sites.
  • the surgical adhesive of the present invention may additionally be used in conjunction with other sealing means, such as plugs, and the like. Such techniques are set forth in U.S. Pat. Nos.
  • compositions of this invention can be used to join together two surfaces by applying the particular composition to at least one of said surfaces.
  • the adhesive compositions of this invention can be applied by known means such as with a glass stirring rod, sterile brush or medicine dropper; however, in many situations a pressurized aerosol dispensing package is preferred in which the adhesive composition is in solution with a compatible anhydrous propellant. Aerosol application of the monomers is particularly advantageous for use in hemostasis.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Dermatology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Polymers & Plastics (AREA)
  • Surgery (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Materials For Medical Uses (AREA)
  • Adhesives Or Adhesive Processes (AREA)
  • Compositions Of Macromolecular Compounds (AREA)
  • Polymerisation Methods In General (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

On décrit des compositions à base de collagène polymérisé du type I et/ou du type III destinées à un usage médical en tant qu'adhésif et que matériau d'étanchéité ainsi que la préparation de ces compositions. Avant la polymérisation, les monomères de collagène sont préparés par recombinaison étant donné que les modifications chimiques du collagène ne sont pas nécessaires pour former ces monomères. Des compositions de collagène du type I et/ou du type III sont utiles en tant qu'adhésif utilisé en médecine pour souder des tissus mous ou dans un film d'étanchéité destiné à diverses utilisations en médecine. Dans un autre aspect de cette invention, la composition de collagène polymérisé du type I et/ou du type III comprend des agents qui induisent la cicatrisation ou apporte des caractéristiques intéressantes supplémentaires désirées pour un adhésif destiné à des tissus et un produit assurant l'étanchéité.
EP98938008A 1997-07-28 1998-07-28 Compositions d'adhesif a base de collagene du type i et du type iii Withdrawn EP1000089A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US5387297P 1997-07-28 1997-07-28
US53872P 1997-07-28
PCT/US1998/015382 WO1999005180A1 (fr) 1997-07-28 1998-07-28 Compositions d'adhesif a base de collagene du type i et du type iii

Publications (2)

Publication Number Publication Date
EP1000089A1 true EP1000089A1 (fr) 2000-05-17
EP1000089A4 EP1000089A4 (fr) 2001-08-29

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EP98938008A Withdrawn EP1000089A4 (fr) 1997-07-28 1998-07-28 Compositions d'adhesif a base de collagene du type i et du type iii

Country Status (8)

Country Link
EP (1) EP1000089A4 (fr)
JP (1) JP2001511431A (fr)
CN (1) CN1272118A (fr)
AU (1) AU8662798A (fr)
CA (1) CA2308146A1 (fr)
IL (1) IL134249A0 (fr)
NO (1) NO20000425L (fr)
WO (1) WO1999005180A1 (fr)

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CA2339575A1 (fr) * 1998-08-10 2000-02-24 James W. Polarek Compositions hemostatiques a base de collagene de type i et de type iii, a utiliser en tant que produit de scellement vasculaire et pansement
US6046160A (en) * 1999-07-22 2000-04-04 Deroyal Industries, Inc. Composition and method for enhancing wound healing
WO2012048298A2 (fr) 2010-10-08 2012-04-12 Caridianbct, Inc. Procédés et systèmes de culture et de récolte de cellules dans un système de bioréacteur à fibres creuses avec conditions de régulation
AU2013370223A1 (en) * 2012-12-31 2015-08-06 George David Falus Lyophilized fibrin sealant for high volume hemorrhage
EP3068867B1 (fr) 2013-11-16 2018-04-18 Terumo BCT, Inc. Expansion de cellules dans un bioréacteur
WO2015148704A1 (fr) 2014-03-25 2015-10-01 Terumo Bct, Inc. Remplacement passif de milieu
CN106715676A (zh) 2014-09-26 2017-05-24 泰尔茂比司特公司 按计划供养
WO2017004592A1 (fr) 2015-07-02 2017-01-05 Terumo Bct, Inc. Croissance cellulaire à l'aide de stimuli mécaniques
US11965175B2 (en) 2016-05-25 2024-04-23 Terumo Bct, Inc. Cell expansion
US11104874B2 (en) 2016-06-07 2021-08-31 Terumo Bct, Inc. Coating a bioreactor
US11685883B2 (en) 2016-06-07 2023-06-27 Terumo Bct, Inc. Methods and systems for coating a cell growth surface
EP3576775A4 (fr) * 2017-01-31 2020-11-25 Geniphys, LLC Procédés et compositions pour la préparation de matrices
US11624046B2 (en) 2017-03-31 2023-04-11 Terumo Bct, Inc. Cell expansion
WO2018184028A2 (fr) 2017-03-31 2018-10-04 Terumo Bct, Inc. Expansion cellulaire
CN109529098A (zh) * 2018-12-03 2019-03-29 广州润虹医药科技股份有限公司 一种外科医用粘合剂
JP2024511064A (ja) 2021-03-23 2024-03-12 テルモ ビーシーティー、インコーポレーテッド 細胞捕獲及び増殖
CN116925240A (zh) * 2023-08-09 2023-10-24 山东多美康生物医药有限公司 一种重组胶原蛋白及其表达方法和应用

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IL134249A0 (en) 2001-04-30
JP2001511431A (ja) 2001-08-14
WO1999005180A1 (fr) 1999-02-04
EP1000089A4 (fr) 2001-08-29
CN1272118A (zh) 2000-11-01
NO20000425D0 (no) 2000-01-27
CA2308146A1 (fr) 1999-02-04
AU8662798A (en) 1999-02-16
NO20000425L (no) 2000-03-23

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