WO2010070458A2 - Adhésif à base de polysaccharide - Google Patents

Adhésif à base de polysaccharide Download PDF

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Publication number
WO2010070458A2
WO2010070458A2 PCT/IB2009/008005 IB2009008005W WO2010070458A2 WO 2010070458 A2 WO2010070458 A2 WO 2010070458A2 IB 2009008005 W IB2009008005 W IB 2009008005W WO 2010070458 A2 WO2010070458 A2 WO 2010070458A2
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WO
WIPO (PCT)
Prior art keywords
chitosan
composition
mol
degree
functionalized polysaccharide
Prior art date
Application number
PCT/IB2009/008005
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English (en)
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WO2010070458A3 (fr
Inventor
Aurélie SERRERO
Alain Domard
Laurent David
Stéphane TROMBOTTO
Suzelei Montanari
Yves Bayon
Philippe Gravagna
Original Assignee
Sofradim Production
Centre National De La Recherche Scientifique
Universite Claude Bernard
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.)
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Publication date
Application filed by Sofradim Production, Centre National De La Recherche Scientifique, Universite Claude Bernard filed Critical Sofradim Production
Publication of WO2010070458A2 publication Critical patent/WO2010070458A2/fr
Publication of WO2010070458A3 publication Critical patent/WO2010070458A3/fr

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    • 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
    • A61L24/08—Polysaccharides

Definitions

  • the present disclosure relates to biological adhesives composed of natural polymers intended for surgical or therapeutic use. More particularly, the present disclosure relates to biocompatible and bioresorbable biological adhesives composed of chitosan and a functionalized polysaccharide, such as oxidized starch.
  • the medical field has utilized various techniques in an effort to join or bond body tissue together.
  • Suturing is an accepted technique for rejoining severed tissues and closing wounds by holding the edges of a wound or tissue against one another during the healing process so as to, reduce discomfort, pain, scarring, and the time required for healing.
  • Stapling is another accepted technique for joining tissue that involves the application of staples to the edges of the wound or tissue with the use of a surgical stapler.
  • the present biocompatible and bioresorbable adhesives are intended for surgical and therapeutic uses.
  • the adhesives are composed of a chitosan bonded with a functionalized polysaccharide.
  • a first aspect of the invention is a biological adhesive composition comprising a chitosan bonded to a functionalized polysaccharide.
  • the functionalized polysaccharide is functionalized by oxidative cleavage.
  • the functionalized polysaccharide may be derived from one or more of starch, dextran, agar, cellulose, chitin, alginic acid, and glycosaminoglycans including hyaluronic acid, dermatan sulfate and chondroitin sulfates.
  • the functionalized polysaccharide is starch.
  • the chitosan has a degree of acetylation of about 0% to about
  • the chitosan has a degree of acetylation of about 1% to about 10%.
  • the chitosan has a molecular weight of about 50,000 g/mol to about 550,000 g/mol.
  • the chitosan has a molecular weight of about 450,000 g/mol to about 550,000 g/mol.
  • the chitosan may have a molecular weight of about 50,000 g/mol to about 150,000 g/mol.
  • the functionalized polysaccharide has a degree of oxidation of about 8% to about 30%.
  • the functionalized polysaccharide has a degree of oxidation of about 15%.
  • the composition contains chitosan at a concentration of about 1% to about 7% by weight based on the total weight of the composition.
  • the composition contains chitosan at a concentration of about 2.3% by weight based on the total weight of the composition.
  • the composition contains chitosan at a concentration of about 7% by weight based on the total weight of the composition.
  • chitosan is combined with a functionalized polysaccharide at a mix ratio of at least 1.
  • methods of applying a biological adhesive composition to tissue are also described.
  • Another aspect of the invention is therefore a method of making a biological adhesive composition comprising combining chitosan and functionalized polysaccharide at a mix ratio of at least 1.
  • combining comprises dispensing a first composition comprising chitosan from a first syringe and dispensing a second composition comprising functionalized polysaccharide from a second syringe.
  • combining comprises:
  • the mix ratio is about 5. In embodiments, the mix ratio is from about 5 to about 20. In embodiments, the mix ratio is about 20.
  • the functionalized polysaccharide is functionalized by oxidative cleavage.
  • the functionalized polysaccharide is derived from one or more of starch, dextran, agar, cellulose, chitin, alginic acid, and glycosaminoglycans including hyaluronic acid, dermatan sulfate and chondroitin sulfates.
  • the functionalized polysaccharide is derived from starch.
  • the chitosan has a degree of acetylation of about 0% to about 70%.
  • the chitosan has a degree of acetylation of about 1% to about 10%.
  • the chitosan has a molecular weight of about 100,000 g/mol to about 550,000 g/mol.
  • the chitosan has a molecular weight of about 450,000 g/mol to about 550,000 g/mol.
  • the chitosan has a molecular weight of about 100,000 g/mol to about 150,000 g/mol.
  • kits may be assembled containing the components of the adhesive.
  • kits include an outer package containing a first syringe of a first composition and a second syringe of a second composition.
  • the first composition includes chitosan and the second composition includes a functionalized polysaccharide.
  • kits comprising an outer package containing a first syringe containing a first composition comprising chitosan, and a second syringe containing a second composition comprising a functionalized polysaccharide.
  • Another aspect of the invention is a method comprising applying a biological adhesive composition as described herein to tissue.
  • FIG. 1 is a chart illustrating the influence of the degree of oxidation of starch on the ultimate adhesion strength of chitosan
  • FIG. 2A is a chart illustrating the rheological behavior of a 2.3% (w/w) chitosan solution mixed with native starch;
  • FIG. 2B is a chart illustrating the rheological behavior of a 2.3% (w/w) chitosan solution mixed with oxidized starch having a degree of oxidation of 4%
  • FIG. 2C is a chart illustrating the rheological behavior of a 2.3% (w/w) chitosan solution mixed with oxidized starch having a degree of oxidation of 8%;
  • FIG. 2D is a chart illustrating the rheological behavior of a 2.3% (w/w) chitosan solution mixed with oxidized starch having a degree of oxidation of 15%;
  • FIG. 2E is a chart illustrating the rheological behavior of a 2.3% (w/w) chitosan solution mixed with oxidized starch having a degree of oxidation of 30%;
  • FIG. 3 is a chart illustrating the influence of the mix ratio on the adhesive properties of 1.9% chitosan solution mixed with oxidized starch having a degree of oxidation of 15%;
  • FIG. 4 is a chart illustrating the influence of chitosan concentration on ultimate adhesion strength
  • FIG. 5 is a chart illustrating the influence of the mix ratio on the ultimate adhesion strength of a 1% chitosan solution mixed with oxidized starch having a degree of oxidation of 15%;
  • FIG. 6 is a chart illustrating the influence of the degree of oxidation of starch on the ultimate adhesion strength of LMW chitosan mixed with oxidized starch at a mix ratio of 20;
  • FIG 7 A is a photograph of the histological observation of fibrin glue after 2 weeks
  • FIG. 7B is a photograph of the histological observation of HMW chitosan after 2 weeks
  • FIG. 7C is a photograph of the histological observation of LMW chitosan after 2 weeks.
  • Biological adhesives in accordance with the present disclosure include a chitosan bonded to a functionalized polysaccharide.
  • the adhesive may be obtained by combining starch, modified by a chemical reaction (e.g., oxidative cleavage) to functionalize a pendant portion of the starch with moieties which are capable of forming a covalent bond, in addition to other interactions (e.g., hydrophobic and hydrogen bonding), with the reactive moieties of chitosan.
  • the biological adhesive may be used for therapeutic and surgical uses, such as, bonding tissues together or to an implanted biomaterial or device, cicatrization of surgical or chronic wounds, protection or leak proofing of sutures, inhibition of the formation of post operative adhesions, and release of bioactive agents or medications. Examples of such applications include use for mesh fixation in hernia repair, as a substitute for sutures or staples, and closure of skin flaps.
  • the biological adhesive may also be combined with or used to coat surgical implants, such as two-dimensional meshes, three-dimensional meshes, vascular prostheses, patches, slings, and the like.
  • the adhesive formulation may act as a hemostat and stop bleeding of tissue.
  • the adhesive formulation may also have specific biological properties.
  • the adhesive may degrade rapidly and/or promote cellularization and tissue integration.
  • the adhesive should not delay tissue repair.
  • the adhesive degrades rapidly in order to promote tissue integration, and in some embodiments good adhesion may be presented after a few days without delay of tissue integration.
  • Chitosan is a natural linear co-polymer of N-acetyl D-glucosamine (acetylated unit) and D-glucosamine (non-acetylated unit).
  • Chitosan may be produced by partial or full deacetylation of chitin.
  • Chitin may be extracted from natural sources, e.g., squid pens, exoskeletons of crustaceans such as shrimp shells, or vegetable sources such as mushrooms, e.g. "champignon de Paris.”
  • Chitosan may also be synthetically produced or synthesized by modified microorganisms such as bacteria.
  • chitosan provides viscoelastic properties as well as specific interactions with biological substrates that may not be found in other modified polysaccharides, such as polysaccharides in which the -NH 2 group would be chemically added. Chitosan, then, may provide good viscosity for use as an adhesive and be biologically accepted.
  • the adhesion of chitosan with other polymers includes the association of different kinds of interactions, such as electrostatic interactions, hydrogen bonds, and hydrophobic interactions, to name a few.
  • Chitosan under certain circumstances, is a cationic polymer containing NH 3 groups.
  • the positively charged primary amino groups of chitosan attract anionic groups of other polymers.
  • chitosan and anionic polymers are able to form polyelectrolyte complexes.
  • Polyelectrolyte complex formation may improve the mechanical properties of the polymers and lead to new structures, such as precipitates, films, fibers, and gels.
  • Adhesion of chitosan with other polymers may also be promoted by reinforcing the mechanical properties of the formulation by creating covalent bondings between both the components of the adhesive formulation and with the substrate.
  • Chitosan has NH 2 groups which can react covalently with aldehyde groups.
  • chitosan may be mixed with functionalized polymers having aldehyde groups, such as oxidized polymers.
  • the degree of acetylation (DA), or the percentage of N-acetyl D-glucosamine, in chitosan may be from about 0% to about 70%. In embodiments, the degree of acetylation is from about 0% to about 10%. Low DA's ensure that sufficient amounts Of NH 3 + are available to generate ionic interactions. The degree of acetylation also ensures that the chitosan has the capability, (e.g., free amino groups), to be crosslinked with a functionalized polysaccharide.
  • the chitosan may have a molecular weight from about 10 5 g/mol to about 10 g/mol. In embodiments, chitosan has a high molecular weight (HMW) of about 450,000 g/mol to about 550,000 g/mol. In other embodiments, chitosan has a low molecular weight (LMW) of about 50,000 g/mol to about 150,000 g/mol.
  • HMW high molecular weight
  • LMW low molecular weight
  • a solution of chitosan may be prepared by dissolving chitosan in distilled water with a stoechiometric amount of HCl to ensure the complete protonation of all NH 2 groups.
  • the final solution may contain about 0.5% (w/w) to about 5% (w/w) chitosan.
  • the prepared solution of chitosan may be in a liquid, viscous form and placed in a syringe for immediate or later use.
  • the solution of chitosan may also be directly coated on a support, such as a mesh.
  • the mesh may be prepared by soaking it in the chitosan solution and drying it in an oven or in a laminar flow hood. In embodiments, the process may be repeated several times to ensure a proper coating displaying the required adhesive properties for the selected indication of use, e.g., fixation of extraperitoneal or retroperitoneal meshes, skin flap closure, etc.
  • Polysaccharides of the present disclosure may be of natural origin and may be prepared by using any method known to those skilled in the art to provide pendant portions of a compound with aldehyde functional groups, which are capable of bonding with the reactive chemical groups of chitosan.
  • the polysaccharide may have repeating units of the same saccharide or have different saccharide subunits.
  • the polysaccharide may have a molecular weight of between about 10,000 g/mol and 2,000,000 g/mol.
  • Polysaccharides which may be used according to the present disclosure include, for example, starch, dextran, agar, cellulose, chitin, alginic acid, hyaluronic acid, and other glycosaminoglycans such as dermatan sulfate and chondroitin sulfates; their derivatives and combinations thereof.
  • the polysaccharide is starch.
  • Starch may be prepared by the addition of an oxidizing agent. Contacting starch with an oxidizing agent creates oxidative cleavages along portions of the starch thereby creating pendant aldehyde groups capable of reacting with chitosan.
  • the oxidizing agent may be, for example, iodine, peroxide, periodic acid, hydrogen peroxide, a periodate, a compound containing periodate, sodium periodate, a diisocyanate compound, a halogen, a compound containing halogen, n-bromosuccinimide, a permanganate, a compound containing permanganate, ozone, a compound containing ozone, chromic acid, sulfuryl chloride, a sulfoxide, a selenoxide, an oxidizing enzyme (e.g., oxidase), and combinations thereof.
  • an oxidizing agent e.g., oxidase
  • the oxidizing agent is sodium periodate.
  • Oxidized starch may be used as a crosslinker to improve the mechanical behavior of the adhesive formulation with low toxicity.
  • degree of oxidation (DO), or percentage of aldehydes in the starch is between about 2% and about 65%.
  • an oxidative technique is described by Tardy et al. in U.S. Patent No. 6,165,488, the entire content of which is herein incorporated by reference. Briefly, this technique involves mixing a starch solution with an oxidizing agent, e.g., a 6% w/v starch solution may be mixed with sodium periodate at a final concentration ranging from about 2mM to about 36OmM at room temperature for about two hours. This mixture is then dialyzed against water (membrane porosity of about 6000-8000 g/mol) so as to remove the unreacted sodium periodate and all side products.
  • an oxidizing agent e.g., a 6% w/v starch solution may be mixed with sodium periodate at a final concentration ranging from about 2mM to about 36OmM at room temperature for about two hours. This mixture is then dialyzed against water (membrane porosity of about 6000-8000 g/mol) so as to remove the unreacted sodium periodate and
  • the oxidized starch may be further concentrated by ultrafiltration, by pervaporation, or by any other appropriate technique within the purview of those skilled in the art.
  • the oxidized starch may be stored in solution in a cold room of about +2°C to about +8 0 C.
  • the oxidized starch may be stored in dry form by freeze-drying with or without additives like mono- or di- saccharides or any other known products, which help to keep the oxidative starch reactive.
  • the chitosan solution and oxidized starch may be placed in syringes of different volumes so as to reach a specific ratio of each component.
  • the components, each separately packed in a syringe, are mixed by pushing back and forth, in embodiments up to about 20 times, the contents of one syringe to the other by using a two way connector.
  • the two syringes may be connected to a mixing device.
  • the ratio of each component may be adjusted to provide a desired formulation.
  • Each formulation is characterized by its mix ratio (MR).
  • MR mix ratio
  • the term "mix ratio" means the amount of free amine groups of chitosan over the amount of aldehyde functions of the oxidized starch.
  • the mix ratio may be at least about 1, in embodiments from about 1 to about 40.
  • each component of the adhesive may be diluted with a buffer prior to use for pH adjustment.
  • At least one bioactive agent may be included in the adhesive formulation.
  • the agents may be freely admixed with the components of the adhesive formulation or may be tethered to the components through any variety of chemical bonds.
  • the adhesive can also serve as a vehicle for delivery of the bioactive agent.
  • bioactive agent as used herein, is used in its broadest sense and includes any substance or mixture of substances that have clinical use. Consequently, bioactive agents may or may not have pharmacological activity per se, e.g., a dye, or fragrance.
  • a bioactive agent could be any agent which provides a therapeutic or prophylactic effect, a compound that affects or participates in tissue growth, cell growth, cell differentiation, an anti-adhesive compound, a compound that may be able to invoke a biological action such as an immune response, or could play any other role in one or more biological processes.
  • the bioactive agent may be added to the adhesive in any suitable form of matter, e.g., powders, liquids, gels, and the like.
  • bioactive agents examples include antimicrobials, analgesics, antipyretics, anesthetics, antiepileptics, antihistamines, anti-infiammatories, cardiovascular drugs, diagnostic agents, sympathomimetics, cholinomimetics, antimuscarinics, antispasmodics, hormones, growth factors, muscle relaxants, adrenergic neuron blockers, antineoplastics, immunogenic agents, immunosuppressants, gastrointestinal drugs, diuretics, steroids, lipids, lipopolysaccharides, polysaccharides, platelet activating drugs, clotting factors and enzymes. It is also intended that combinations of bioactive agents may be used.
  • bioactive agents which may be involved include: local anesthetics; non- steroidal antifertility agents; parasympathomimetic agents; psychotherapeutic agents; tranquilizers; decongestants; sedative hypnotics; steroids; sulfonamides; sympathomimetic agents; vaccines; vitamins; antimalarials; anti-migraine agents; anti- parkinson agents such as L-dopa; anti-spasmodics; anticholinergic agents (e.g.
  • oxybutynin antitussives
  • bronchodilators cardiovascular agents such as coronary vasodilators and nitroglycerin
  • alkaloids analgesics
  • narcotics such as codeine, dihydrocodeinone, meperidine, morphine and the like
  • non-narcotics such as salicylates, aspirin, acetaminophen, d-propoxyphene and the like
  • opioid receptor antagonists such as naltrexone and naloxone
  • anti-cancer agents anti-convulsants; anti-emetics
  • antihistamines anti-inflammatory agents such as hormonal agents, hydrocortisone, prednisolone, prednisone, non-hormonal agents, allopurinol, indomethacin, phenylbutazone and the like
  • prostaglandins and cytotoxic drugs chemotherapeutics, estrogens; antibacterials; antibiotics; anti-fungals; anti-
  • lymphokines monokines, chemokines
  • blood clotting factors hemopoietic factors, interleukins (IL-2, IL-3, IL-4, IL-6), interferons (/3-IFN, ( ⁇ -IFN and ⁇ IFN), erythropoietin, nucleases, tumor necrosis factors, colony stimulating factors (e.g., GCSF, GM-CSF, MCSF), insulin, anti-tumor agents and tumor suppressors, blood proteins, fibrin, thrombin, fibrinogen, synthetic thrombin, synthetic fibrin, synthetic fibrinogen, gonadotropins (e.g., FSH, LH, CG, etc.), hormones and hormone analogs (e.g., growth hormone), vaccines (e.g., tumoral, bacterial and viral antigens); somatostatin; antigens; blood coagulation factors; growth factors (e.g., nerve growth factor, insulin-like growth factor); bone morphogenic proteins, TGF
  • Bioactive agents can also be additives, such as fucans, either native or chemically modified glycosaminoglycans, emulsifiers, surfactants, humectants, buffering agents, pH modulators, chelating agents, viscosity agents, and any other product which may enhance tissue repair, limit the risk of sepsis, and modulate mechanical properties of the compounds. It is envisioned that metal ions known for their bioactivity in favor of tissue regeneration may also be used.
  • Adhesion properties of a chitosan and oxidized starch formulation are influenced by different parameters of the chitosan and oxidized starch mixture, including, but not limited to, the degree of oxidation of the starch, the mix ratio of chitosan to starch, the concentration of chitosan, and the molecular weight of chitosan.
  • the degree of oxidation of the starch the degree of oxidation of the starch
  • the mix ratio of chitosan to starch the mix ratio of chitosan to starch
  • concentration of chitosan the concentration of chitosan
  • molecular weight of chitosan molecular weight
  • the degree of oxidation of starch influenced the adhesion strength of the adhesive formulation.
  • adhesion strength was measured for a 2.3% (w/w) HMW chitosan solution with different combinations of starch, including no starch, native starch, and oxidized starch having degrees of oxidation of 4%, 8%, 15%, 30%, and 65%.
  • the mix ratio of the chitosan and oxidized starch formulations was 20.
  • the adhesion strength of fibrin glue was also tested for reference and comparison. The formulation of chitosan alone did not provide any significant adhesion nor did a mix of chitosan and native starch.
  • Oxidized starch did promote adhesion, particularly with a degree of oxidation between about 8% and about 30%. As shown, a degree of oxidation of 15% promoted the best adhesion.
  • FIG. 2A shows the rheological behavior of a 2.3% (w/w) HMW chitosan solution alone and mixed with 1.4% native starch.
  • the dynamic behavior of the formulation was assessed by applying a small oscillatory stress at a frequency, ⁇ , and measuring the resulting strain.
  • the response measured of the material included the storage modulus G' and the loss modulus G".
  • G' represents the elastic response of the material and quantifies the energy stored by the material after the sinusoidal solicitation.
  • G" is related to the viscous response of the material and quantifies the dissipated energy.
  • the behavior of the materials, as shown, is characteristic of viscoelastic fluids. Viscoelastic materials exhibit a storage module greater than the loss module at high frequencies and a storage module less than the loss module at low frequencies.
  • FIG. 2B shows the rheological behavior of a 2.3% (w/w) HMW chitosan solution mixed with oxidized starch having a degree of oxidation of 4% at pH 4 and a mix ratio of 20. The behavior of this formulation was also unchanged compared with sole chitosan.
  • FIG. 2C shows the rheological behavior of a 2.3% (w/w) HMW chitosan solution mixed with oxidized starch having a degree of oxidation of 8% at pH 4 and a mix ratio of 20.
  • the storage and loss modules, G 1 and G" respectively are higher which resulted in a higher viscosity of the system, but still characteristic of a viscoelastic fluid.
  • FIG. 2D shows the theological behavior of a 2.3% (w/w) HMW chitosan solution mixed with oxidized starch having a degree of oxidation of 15% at pH 4 and mix ratio of 20. The plot is different compared with the rheograms illustrated in FIGS. 2A-2C.
  • the storage module, G' is greater than the loss module, G", throughout the entire time of the experiment. Differences, however, between the two modules are slight and decrease with lower frequencies. Thus, the behavior of the material was between the behavior of a solution (which flows) and the behavior of a gel (which is more rigid and does not flow).
  • FIG. 2E shows the rheological behavior of a 2.3% (w/w) HMW chitosan solution mixed with oxidized starch having a degree of oxidation of 30% at pH 4 and a mix ratio of 20.
  • the rheogram is characteristic of a gel with the storage module, G', being greater than the loss module, G", for the whole time of the experiment and with a constant difference between the two modules.
  • FIG. 3 illustrates the adhesion strength of a 1.9% HMW chitosan solution mixed with oxidized starch having a degree of oxidation of 15% at a mix ratio of 1, 20, and 40.
  • the mix ratio affects adhesion. If the mix ratio is too high, i.e., greater than 20, the amount of oxidized starch is not enough to generate sufficient adhesion. On the other hand, if the mix ratio is too low, the amount of oxidized starch is too high and the adhesion is lower because the material is too cohesive due to too much crosslinking. Therefore, an excess of chitosan (MR of at least about 1) is needed to obtain substantial adhesion. As shown, a mix ratio of about 20 produced excellent adhesion properties. In addition, a low amount of cross-linking agent, i.e. a high MR, will limit the toxicity of the adhesive formulation.
  • Chitosan concentration also influences adhesion strength. As shown in FIG. 4, the adhesion strength of high molecular weight chitosan solutions of varying concentrations from 1% to 2.3% were assessed. Concentrations higher than 2.3% were not used because the adhesive becomes too viscous and tough to handle. Lower concentrations were also not used because at a concentration of less than 1% adhesion decreases significantly due to the low cohesion of the material. As shown, excellent adhesion was obtained with a 2.3% chitosan solution.
  • FIG. 5 illustrates the influence of mix ratio on the ultimate adhesion strength of a 1% chitosan solution mixed with oxidized starch having a degree of oxidation of about 15%. As shown, a lower mix ratio provides better adhesion to lower concentration chitosan solutions.
  • the degree of oxidation of starch will influence the adhesion of LMW chitosan as shown in FIG. 6. As shown, a 7% LMW chitosan solution was mixed with oxidized starch having varying degrees of oxidation at a mix ratio of 20. With LMW chitosan, adhesion was optimal with oxidized starch having a degree of oxidation of about 15%. As shown, the adhesion was increased by using LMW chitosan compared to HMW chitosan.
  • the local tolerance of the adhesive was assessed by an in vivo test utilizing subcutaneous implantation into a rat model.
  • HMW chitosan, LMW chitosan, and fibrin glue were implanted by applying 0.5ml of each adhesive on a lcm 2 PARIETEX® mesh in a subcutaneous pocket. Macroscopic and histological observations were carried out after 3 days, 1 week, and 2 weeks.
  • the adhesion strength may be influenced by modifying the degree of deacetylation of chitosan and/or the molar mass of chitosan. Therefore, the above description should not be construed as limiting, but merely as an exemplification of the embodiments. Those skilled in the art will envision other modifications within the scope and spirit of the present disclosure. Such modifications and variations are intended to come within the scope of the following claims.

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  • Health & Medical Sciences (AREA)
  • Surgery (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Un adhésif biocompatible et biorésorbable pour applications chirurgicales et thérapeutiques se compose d'un chitosane lié à un polysaccharide fonctionnalisé.
PCT/IB2009/008005 2008-12-19 2009-12-18 Adhésif à base de polysaccharide WO2010070458A2 (fr)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9877984B2 (en) 2013-12-23 2018-01-30 Massachusetts Institute Of Technology Controllably degradable compositions and methods
US10517988B1 (en) 2018-11-19 2019-12-31 Endomedix, Inc. Methods and compositions for achieving hemostasis and stable blood clot formation
CN111840630A (zh) * 2020-07-21 2020-10-30 华南农业大学 一种抑菌型可吸收医用软组织缝合线及其制备方法与应用
US20210308320A1 (en) * 2020-04-03 2021-10-07 The Trustees Of The University Of Pennsylvania Self-Adhesive Multi-Fiber Materials

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WO2003035122A1 (fr) * 2001-10-24 2003-05-01 Aesculap Ag & Co. Kg Composition contenant un polymere portant des groupes amino et un aldehyde comportant au moins trois groupes aldehyde
WO2007124198A2 (fr) * 2006-04-18 2007-11-01 Endomedix, Inc. Système de biopolymères pour réparer des tissus
US20080075657A1 (en) * 2006-04-18 2008-03-27 Abrahams John M Biopolymer system for tissue sealing

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003035122A1 (fr) * 2001-10-24 2003-05-01 Aesculap Ag & Co. Kg Composition contenant un polymere portant des groupes amino et un aldehyde comportant au moins trois groupes aldehyde
WO2007124198A2 (fr) * 2006-04-18 2007-11-01 Endomedix, Inc. Système de biopolymères pour réparer des tissus
US20080075657A1 (en) * 2006-04-18 2008-03-27 Abrahams John M Biopolymer system for tissue sealing

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9877984B2 (en) 2013-12-23 2018-01-30 Massachusetts Institute Of Technology Controllably degradable compositions and methods
US10736914B2 (en) 2013-12-23 2020-08-11 Massachusetts Institute Of Technology Controllably degradable compositions and methods
US10517988B1 (en) 2018-11-19 2019-12-31 Endomedix, Inc. Methods and compositions for achieving hemostasis and stable blood clot formation
US11033654B2 (en) 2018-11-19 2021-06-15 Endomedix, Inc. Methods and compositions for achieving hemostasis and stable blood clot formation
US20210308320A1 (en) * 2020-04-03 2021-10-07 The Trustees Of The University Of Pennsylvania Self-Adhesive Multi-Fiber Materials
CN111840630A (zh) * 2020-07-21 2020-10-30 华南农业大学 一种抑菌型可吸收医用软组织缝合线及其制备方法与应用

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