WO1999047087A1 - Procede de reduction des allergenes proteiques dans les produits en latex - Google Patents

Procede de reduction des allergenes proteiques dans les produits en latex Download PDF

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Publication number
WO1999047087A1
WO1999047087A1 PCT/US1999/005773 US9905773W WO9947087A1 WO 1999047087 A1 WO1999047087 A1 WO 1999047087A1 US 9905773 W US9905773 W US 9905773W WO 9947087 A1 WO9947087 A1 WO 9947087A1
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WO
WIPO (PCT)
Prior art keywords
latex
aldehyde
sap
product
proteins
Prior art date
Application number
PCT/US1999/005773
Other languages
English (en)
Other versions
WO1999047087A9 (fr
Inventor
George W. Weinert
Original Assignee
Risk Management Associates Ltd.
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 Risk Management Associates Ltd. filed Critical Risk Management Associates Ltd.
Priority to US09/646,415 priority Critical patent/US6740719B1/en
Priority to AU31881/99A priority patent/AU3188199A/en
Publication of WO1999047087A1 publication Critical patent/WO1999047087A1/fr
Publication of WO1999047087A9 publication Critical patent/WO1999047087A9/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
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A61L29/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/04—Macromolecular materials
    • A61L29/044—Proteins; Polypeptides; Degradation products thereof
    • A61L29/048—Other specific proteins or polypeptides not covered by A61L29/045 - A61L29/047
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/043—Proteins; Polypeptides; Degradation products thereof
    • A61L31/047—Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08C—TREATMENT OR CHEMICAL MODIFICATION OF RUBBERS
    • C08C1/00—Treatment of rubber latex
    • C08C1/02—Chemical or physical treatment of rubber latex before or during concentration
    • C08C1/04—Purifying; Deproteinising
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action

Definitions

  • This invention relates to a process for reducing protein allergy caused by latex products, such as latex gloves and latex-containing devices used by the medical profession, which are made from the latex sap of the Hevea brasilisensis tree.
  • cell mediated allergic response is a true allergic response, with reaction restricted to the area of contact between the glove and the skin when the glove is made from the sap of the Hevea brasilisensis tree.
  • the reaction may include swelling and blistering and, after washing of the hands upon removal of the gloves, it takes from about 24 to 48 hours for the person's skin to return to normal.
  • This allergy is caused by several water soluble proteins in latex sap.
  • Systemic latex allergy the most serious of the latex- related diseases, is characterized by allergic rhinitis - asthma - and can escalate to anaphylaxis and death.
  • This allergy is caused by several water soluble proteins in the latex sap from the Hevea brasilisensis tree present in products made from such sap, which proteins are dispersed in the air and are breathed in by people.
  • Methods of measurement of airborne concentrations of latex antigen as well as latex antigen concentrations in products, such as gloves, in amount as low as 1 nanogram per cubic meter (ng/M 3 ) are known.
  • ng/M 3 nanogram per cubic meter
  • U.S. Patent No. 5,580,942 acknowledges the severe allergic reactions in hypersensitive people caused by the proteins present in the natural rubber latex obtained from Hevea brasilisensis trees.
  • the patentee has a simple solution to the problem, namely, avoiding use of the latex from the Hevea brasilisensis in making latex products.
  • the patentee uses latex extracted from the Parthenium argontatum (guayule) plant or the Ficus elastica plant, which plants have a different protein profile, whereby the proteins from the sap of these plants do not cause allergic reactions in hypersensitive humans.
  • Electrophoretic profiles of NAL reveals major proteins at 46, 29 and 14kDa, and minor bands at 90, 55, 40, 36, 24, 20 and 18kDa.
  • Hevein (4kDa) and hevamine (29kDa) are two proteins in latex sera which have been cloned and sequenced
  • rubber particles contain the tightly bound proteins prenyltransferase (38kDa) and rubber elongation factor (14.5kDa) which have also been sequenced (Dennis et al . , Biol . Chem . , 1989, 264, 18618- 26; Light et al., J. Biol . Chem . ,1989 264, 18589-97).
  • Ammonification of latex alters the proteins. Storage of latex in ammonia alters the electrophoretic profiles of proteins such that SDS-PAGE profile changes from distinct bands to a smear of polypeptides with an increase in high molecular weight material (Breezhold et al . , Arch . Surg. , 1992, 127, 1354-1357). Many, but not all, of the changes that occur are due to hydrolysis of the proteins. Since NAL serum proteins migrate primarily below 46kDa, the appearance of high molecular weight polypeptides suggests that ammonification (and/or other compounding ingredients) induce a type of polymerization of the latex proteins that produces the larger polypeptides. This process may contribute to the allergenicity of the latex proteins.
  • ammonification also extracts some of the rubber bound proteins (primarily rubber elongation factor) making them soluble proteins and thus potential allergens (Hasma, J. Na t . Rubb . Res . , 1992, 7 (2) , 102-112) .
  • Latex proteins are drawn to the surface of the latex during drying. The surface proteins can be collected directly from the surface by dry swabbing (Dalrymple et al .
  • U.S. Patent No. 5,610,212 acknowledges that products made of natural rubber, such as rubber gloves, produce allergic reactions in some people, which reactions are attributed to the proteins present in natural rubber.
  • the patent also discusses prior deproteinizing processes for latex which have been used to get around the problem caused by natural rubber.
  • the patent discloses a process for markedly improving the stabilization of deproteinized natural rubber latex which has been treated with a protease and a surfactant, by addition thereto of a specific surfactant or an oligomer or polymer.
  • U.S. Patent No. 5,622,998 discusses various known processes for depolymerizating natural rubber and discloses a process for forming a liquid depolymerized natural rubber which produces no immediate allergy.
  • the patentee dissolves a deproteinized natural rubber into an organic solvent to a concentration of about 1 to 30 percent by weight and then carries out air oxidation of the resulting solution in the presence of a metallic catalyst.
  • the process of the invention comprises reacting proteins in the sap of the Hevea brasilisensis plant and other rubber plants, which sap is used in the known processes for the manufacture of latex products, such as latex gloves or other latex-containing products, automobile tires and medical devices which are intended to come into contact with people or will be exposed to people, such as patients, doctors, nurses, laboratory technicians and others, with an aldehyde, such as a mono-aldehyde, such as formaldehyde, or a dialdehyde, such as glutaraldehyde or semialdehydes or any chemical containing an aldehyde group, to cross-link such proteins.
  • an aldehyde such as a mono-aldehyde, such as formaldehyde
  • a dialdehyde such as glutaraldehyde or semialdehydes or any chemical containing an aldehyde group
  • the cross-linked proteins no longer have the capability to cause an allergic reaction to persons coming into contact with the latex products made by the process of the invention.
  • the cross- linking reaction between the proteins in the latex sap and the aldehyde can take place in the solution used to prepare the final product, or after the final latex product has been formed, or during various intermediate steps of the known processes for forming the latex products.
  • the invention comprises a process for significantly reducing and/or eliminating the allergy caused to certain people who come into contact with latex products made from the latex sap of the Hevea brasilisensis plant or any latex producing plant due to the presence of proteins from the latex sap.
  • Processes for making such latex products are well known. Applicant has found that he can significantly decrease and/or even eliminate the presence of these proteins in the sap which causes the allergic reactions by reacting such proteins with an aldehyde, such as formaldehyde, or preferably with a dialdehyde, most preferably, glutaraldehyde . Such reaction can take place in the latex solution used in a step of the known process of making the latex product.
  • Such aldehyde and preferably glutaraldehyde, is added to and stirred in the latex solution in an amount sufficient to react with the proteins in the latex solution and to cross-link substantially all of the proteins into polymers.
  • the reaction between the proteins in the sap of the latex and the aldehyde can take place during other steps in the known processes for making the latex products, as long as the proteins in the latex come into contact with and react with the aldehyde and are cross-linked to form a polymer.
  • Such reaction can also take place after the latex product, such as the rubber glove, is formed.
  • the reaction of the proteins in the latex which are on the surfaces of the latex product are reacted with the aldehyde, such as by the coating of the surface with the aldehyde, or by the immersion of the product in the aldehyde, for a period of time sufficient to completely react and cross-link the proteins with the aldehyde.
  • the use of an aldehyde and, particularly, glutaraldehyde, to obtain the significant reduction of protein allergies caused by latex products made from the sap of the Hevea brasil isensis tree is contrary to what one would be expected to use.
  • Glutaraldehyde is one of two high-level disinfectant chemicals currently approved by the FDA for disinfecting endoscopes, bronchoscopes, cystoscopes, ultrasonic transducers and other devices not amenable to disinfection by heat, steam, radiation or other means.
  • Glutaraldehyde presents a health hazard to persons working with it, such as red burning eyes, sore throat, nasal discharge and red itchy skin.
  • Glutaraldehyde is also a skin sensitizer and has been known to aggravate asthma.
  • Applicant has found that by reacting two known health hazards to humans, namely, the proteins in the latex sap of the Hevea brasilisensis tree and glutaraldehyde, the proteins cross-linked with the glutaraldehyde form a reaction product which eliminates the protein allergy of the latex product.
  • the latex with reduced allergans that is produced by the method of the invention will result in significantly increased safety for latex allergic persons who use or are exposed to the following types of latex containing products: Emergency Equipment
  • Blood pressure cuffs stethoscopes, disposable gloves, oral and nasal airways, endotracheal tubes, tourniquets, intravenous tubing, syringes and electrode pads
  • the radio-immunosorbant assay (RAST) is often used as a sensitive technique which employs radio-isotope labelled anti- IgE to measure specific IgE antibody in patient sera.
  • the latex RAST (Pharmacia) is used to determine if specific IgE to the latex proteins is present and is semi-quantitative in determining the amount of IgE present.
  • the assay is used primarily as a diagnostic test for latex allergy.
  • the RAST assay employed below is performed as a competition assay (RAST inhibition) to quantitate the amount of allergen in a latex extract.
  • RAST inhibition a competition assay (RAST inhibition) to quantitate the amount of allergen in a latex extract.
  • soluble allergens in latex extracts compete for binding to latex specific IgE in pooled sera from latex allergic individuals.
  • IgE soluble allergens react with the IgE
  • the amount of inhibition reflects the level of soluble allergens in the extract.
  • the RAST inhibition assay is a very sensitive method to quantitate latex allergens.
  • Ammoniated latex (C.N.L from the General Latex and Chemical Corporation, Billerica, MA) was treated with glutaraldehyde and formaldehyde to effectively cross-link the natural rubber proteins. 20 cc of a 20 % glutaraldehyde solution (Sigma
  • the glutaraldehyde-latex solution was coated on a glass plate and allowed to air dry (23 degrees C for 30 minutes) .
  • a control of the untreated latex was applied to another glass plate in a similar fashion and allowed to air dry (23 degrees C for 30 minutes) .
  • the plates were incubated at 130 degrees C for 30 minutes .
  • the formed films were sent to the MAYO clinic to determine the concentration antigen by the RAST inhibition test, a test specific to measure the antigenic proteins .
  • the control sample contained 409,140 nanograms per gram of antigenic protein
  • the glutaraldehyde treated latex sample contained 42,672 nanograms per gram of antigenic protein.
  • Ammoniated latex (C.N.L. from the General Latex Corporation, Billerica, MA) was treated with formaldehyde and glutaraldehyde as confirmation of earlier experimental tests demonstrating the crosslinking of the natural rubber proteins previously discussed.
  • samples of the latex were treated with, citronellal
  • the formed films were sent to the MAYO Clinic to determine the concentration of antigen by the RAST inhibition test, a test specific to measure antigenic proteins.
  • This control sample contained 9370 nanograms per gram of antigenic protein.
  • 400 microliters of formaldehyde were added to 20 milliliters of latex.
  • the sample contained 2249 nanograms per gram of antigenic protein. This was a 76 percent reduction as compared to the control sample .
  • citronellal were added to 20 milliliters of latex, and the sample contained 4515 nanograms per gram of antigenic protein. This was a 52 percent reduction as compared to the control sample .
  • Example 3 Example 3 .
  • a typical manufacturing sequence for a dipped product such as a glove or a condom involves sequential steps of:
  • the product is then stripped from the form or mandrill and packaged.
  • Some products, such as surgical gloves, may also be sterilized, usually by radiation.
  • the method of the invention can be performed at different steps of the manufacturing process.
  • the aldehyde solution can be mixed with the latex dipping solution. Generally the aldehyde is added to the latex solution with mixing to promote uniformity. The aldehyde can also be in line blended with the latex solution to maintain a consistent depth of the dipping solution.
  • some glove manufactures spray water on the vulcanized glove to wash away water- soluble surface protein or pass the gloves on the mandrills through a series of leaching tanks.
  • the aldehyde can be added to the washing or leaching solutions or could be sprayed directly onto the finished product to cross-link the surface proteins .

Abstract

L'invention concerne un processus permettant de réduire l'antigénie de la sève et de produits à base de sève dérivée de la plante Hevea brasilisensis et d'autres plantes à caoutchouc. Le procédé consiste à mettre la sève ou un produit en caoutchouc latex en contact avec un mono ou dialdéhyde, un semialdéhyde ou tout autre produit chimique contenant un groupe aldéhyde pour réticuler des protéines antigènes dans la sève ou le produit en latex. Les protéines réticulées ne sont dès lors plus en mesure de provoquer une réaction allergique chez les personnes qui vont être en contact avec les produits en latex obtenus par ce procédé. La réaction de réticulation entre les protéines de la sève latex et de l'aldéhyde peut avoir lieu dans la solution utilisée pour préparer le produit final ou après la formation du produit en latex final ou encore pendant les étapes intermédiaires de la formation des produits en latex.
PCT/US1999/005773 1998-03-18 1999-03-17 Procede de reduction des allergenes proteiques dans les produits en latex WO1999047087A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US09/646,415 US6740719B1 (en) 1998-03-18 1999-03-17 Process for reducing protein allergens in latex products
AU31881/99A AU3188199A (en) 1998-03-18 1999-03-17 Process for reducing protein allergens in latex products

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US7838898P 1998-03-18 1998-03-18
US60/078,388 1998-03-18

Publications (2)

Publication Number Publication Date
WO1999047087A1 true WO1999047087A1 (fr) 1999-09-23
WO1999047087A9 WO1999047087A9 (fr) 2000-10-12

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AU (1) AU3188199A (fr)
WO (1) WO1999047087A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113717298A (zh) * 2020-05-26 2021-11-30 中胶永生东南亚乳胶制品股份有限公司 一种低蛋白天然浓缩胶乳的制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5691446A (en) * 1995-08-25 1997-11-25 Dove; Jeffrey S. Methods for reducing allergenicity of natural rubber latex articles and articles so produced
US5741885A (en) * 1995-08-25 1998-04-21 Baxter International Inc. Methods for reducing allergenicity of natural rubber latex articles

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5691446A (en) * 1995-08-25 1997-11-25 Dove; Jeffrey S. Methods for reducing allergenicity of natural rubber latex articles and articles so produced
US5741885A (en) * 1995-08-25 1998-04-21 Baxter International Inc. Methods for reducing allergenicity of natural rubber latex articles

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113717298A (zh) * 2020-05-26 2021-11-30 中胶永生东南亚乳胶制品股份有限公司 一种低蛋白天然浓缩胶乳的制备方法

Also Published As

Publication number Publication date
AU3188199A (en) 1999-10-11
WO1999047087A9 (fr) 2000-10-12

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