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
  • A61L24/0005—Ingredients of undetermined constitution or reaction products thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
  • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
  • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
  • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
  • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• • 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
  • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
  • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
  • A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
  • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
  • A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • 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
  • A61L24/108—Specific proteins or polypeptides not covered by groups A61L24/102 - A61L24/106
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08H—DERIVATIVES OF NATURAL MACROMOLECULAR COMPOUNDS
  • C08H1/00—Macromolecular products derived from proteins
• • 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

Definitions

• Visualization agents include blood compatible chromogenic dyes, where specific visualization agents of interest are those that provide for color contrast with the background tissue, with blue and green being preferred colors, where specific agents include: indocyanine green, methylene blue, FD& C no. 1, FD & C no. 6, eosin, fluorescein, and the like.
• Fluorescence compounds may be used at concentrations visible to the naked eye, e.g., non-toxic fluorescent compounds, fluroescein. Further, fluorescent visualization agents may be used for visualization of fluorescence using a suitable light source or imaging techniques.
• the subject methods can be used to produce enriched protein compositions from cow or sheep milk, where the cow or sheep may be a transgenic animal engineered to produce milk containing a recombinant protein of interest.
• a biological fluid composition may be used immediately upon collection or stored for use at a later time. Any suitable storage means may be employed.
• the storage means may be sterile where the composition is to ultimately be used in a physiological setting, e.g., where it is to be used in a drug delivery vehicle, or as a surgical adhesive.
• One technique of storing the composition is to lyophilize the composition and package the lyophilized product in a sterile packaging for subsequent use, e.g., in a syringe.
• the composition may be stored at a reduced temperature, e.g., from about 4 to -20° C or lower.
• a Michael-type reaction refers to the 1,4 addition reaction of a nucleophile on a conjugate unsaturated system.
• the addition mechanism could be purely polar, or proceed through a radical-like intermediate state(s); Lewis acids or appropriately designed hydrogen bonding species can act as catalysts.
• the term conjugation can refer both to alternation of carbon-carbon, carbon-heteroatom or heteroatom-heteroatom multiple bonds with single bonds, or to the linking of a functional group to a macromolecule, such as a synthetic polymer or a protein.
• Michael-type reactions are discussed in detail in U.S. Pat. No. 6,958,212, which is hereby incorporated by reference for all purposes to the extent it does not contradict what is explicitly disclosed herein.
• the crosslinkers may be used with conventional solvents. And non-conventional solvents may also be used, specifically non-aqueous water soluble biocompatible, non- reactive solvents.
• The may be used for the various types of crosslinkers, including crosslinkers that are liquid or solid at about 10 to about 50° C.
• Conventional approaches to in-situ polymerization have focused on use of aqueous precursors that polymerize with each other at the site of use in the patient.
• Aqueous precursors and aqueous solvents are conventionally regarded as being highly biocompatible. What is not conventionally appreciated, however, is that some organic solvents are also biocompatible. The reduction or elimination of water can improve storage life and stability of crosslinker or other precursors.
• Figure 4 shows Scheme IV using carboxyls wherein an aspartic acid based crosslinker is synthesized.
• Amine groups of aspartic acid 402 are first reacted with succinyl chloride 404 to produce a tetraacid amide derivative 406.
• the acid groups of are then reacted with n-hydroxysuccinimide 106 using DCC 108 as a catalyst to produce product 410 having NHS ester (NHS activated acid groups).
• NHS ester NHS activated acid groups
• many other crosslinkers can be synthesized by choosing different combinations of aminoacids, or diacid chloride/anhydrides can be used to form multifunctional aminoacid derivatives.
• the acid groups of aminoacid derivatives are then activated using n- hydroxysuccinimide groups.
• Figure 5 shows Scheme V wherein hydroxyl amine 502 is reacted with succinic anhydride 102 to form 504 having an amido-ester with terminal carboxylic acid group.
• Nonlimiting examples of organic solvents include; C1-C3 alcohols such as ethanol, 1,2-pro ⁇ ylene glycol, glycerol and isopropanol, 1,4-butane diol, 1,6 hexane diol, n-methyl pyrrolidinone, dimethyl sulfoxide, ethyl lactate, acetone, methyl ethyl ketone, polyethylene glycol and its derivatives.
• Water soluble organic solvents are preferred and n-methyl pyrrolidinone, ethanol, glycerol, propylene glycol and polyethylene glycol 400, methoxy terminated polyethylene glycol are particularly preferred due to their proven safety in human use.
• liquid crosslinkers disclosed in these inventions may also be used to dissolve the low molecular weight crosslinkers.
• the crosslinked materials may be used for tissue engineering applications such as providing matrix for cell growth or coating of vascular grafts.
• dosage of the crosslinking composition will depend upon its intended use. In most surgical application applications 1 to 500 ml total volume of biological fluid (or other precursor fluid) and crosslinker introduced in situ will be sufficient but other volumes may be used as needed; artisans will immediately appreciate that all the ranges and values within the explicitly stated ranges are contemplated.
• Fibrin glues that use a crosslinker instead of thrombin and/or factor XIIF and/or calcium.
• Fibrin glues have a first fibrinogen-containing component that is combined with a second component that has thrombin and/or factor XIII for crosslinking the fibrinogen, usually in the presence of excess calcium ions.
• the fibrinogen portion of fibrin glues have been applied to a tissue repair site either simultaneously or sequentially with a thrombin/calcium ion setting composition. Accordingly, the fibrinogen portion of a fibrin glue, or other fibrinogen-enriched composition, may be applied with a crosslinker or monomer to make a crosslinked fibrin material.
• the fibrinogen component, the crosslinker components, or the entire system is essentially free of water so as to enhance storage, delivery, or reaction; biocompatible solvents may be used as need to solubilized the components.
• BTANHS 200 g was dispersed in 0.8 ml PBS containing 2% Pluronic F 127 (from BASF corporation USA) as a surfactant. Sonication or high speed stirring helps to form the emulsion. 333 mg bovine serum albumin was dissolved in 0.667 ml PBS. 20 microliter BTANHS emulsion in PBS and 20 microliter of albumin solution were mixed in a 1 ml plastic centrifuge tube to form a uniform solution. Addition of 20 microliter triethanol amine to albumin-BTANHS mixture transformed the solution into soft hydrogel in 3 minutes.
• the precipitated dicyclohexylurea is removed by filtration.
• DMF from the filtrate is removed by vacuum distillation.
• the crude product is further purified by column chromatography.
• the product is stored with 0.010 mg of hydroquinone as inhibitor.
• the product is soluble in water.
• Part 2 To a cold (4 0 C) solution of 5 g Hydroxylamine Succinate and 5.1 g n- hydroxysuccinimide in 120 ml dichloromethane, 11.8 g 1, 3-dicyclohexyl carbodiimide in 30 ml of dichloromethane is added under nitrogen atmosphere. The reaction is continued at room temperature for 8 h and urea precipitate is filtered. The filtrate is evaporated the crude compound is recovered. The compound is further purified by flash chromatography.

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• 2007
  • 2007-04-24 AU AU2007243483A patent/AU2007243483B2/en active Active
  • 2007-04-24 WO PCT/US2007/009934 patent/WO2007127198A2/en not_active Ceased
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• 2009
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