USRE42377E1 - Composition for creating vascular occlusions - Google Patents

Composition for creating vascular occlusions Download PDF

Info

Publication number
USRE42377E1
USRE42377E1 US11/827,668 US82766807A USRE42377E US RE42377 E1 USRE42377 E1 US RE42377E1 US 82766807 A US82766807 A US 82766807A US RE42377 E USRE42377 E US RE42377E
Authority
US
United States
Prior art keywords
cyanoacrylate
composition
ppm
methoxyphenol
hydroquinone
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.)
Expired - Lifetime
Application number
US11/827,668
Inventor
Robert E. Krall
Charles W. Kerber
Kimberly Knox
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.)
Stryker European Operations Holdings LLC
Original Assignee
Stryker NV Operations Ltd
Stryker Corp
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 Stryker NV Operations Ltd, Stryker Corp filed Critical Stryker NV Operations Ltd
Priority to US11/827,668 priority Critical patent/USRE42377E1/en
Assigned to STRYKER NV OPERATIONS LIMITED, STRYKER CORPORATION reassignment STRYKER NV OPERATIONS LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BOSTON SCIENTIFIC CORPORATION
Assigned to STRYKER CORPORATION, STRYKER NV OPERATIONS LIMITED reassignment STRYKER CORPORATION CORRECTIVE ASSIGNMENT TO CORRECT THE THE STATE/COUNTRY IN RECEIVING PARTY DATA FOR STRYKER NV OPERATIONS LIMITED FROM ISRAEL TO IRELAND. PREVIOUSLY RECORDED ON REEL 025853 FRAME 0773. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Assignors: BOSTON SCIENTIFIC CORPORATION
Application granted granted Critical
Publication of USRE42377E1 publication Critical patent/USRE42377E1/en
Assigned to STRYKER MEDTECH LIMITED reassignment STRYKER MEDTECH LIMITED NUNC PRO TUNC ASSIGNMENT (SEE DOCUMENT FOR DETAILS). Assignors: STRYKER NV OPERATIONS LIMITED
Assigned to STRYKER EUROPEAN HOLDINGS I, LLC reassignment STRYKER EUROPEAN HOLDINGS I, LLC NUNC PRO TUNC ASSIGNMENT (SEE DOCUMENT FOR DETAILS). Assignors: STRYKER MEDTECH LIMITED
Assigned to STRYKER MEDTECH LIMITED reassignment STRYKER MEDTECH LIMITED CORRECTIVE ASSIGNMENT TO CORRECT THE INCORRECT SERIAL # 09/905,670 AND 07/092,079 PREVIOUSLY RECORDED AT REEL: 037153 FRAME: 0034. ASSIGNOR(S) HEREBY CONFIRMS THE NUNC PRO TUNC ASSIGNMENT. Assignors: STRYKER NV OPERATIONS LIMITED
Assigned to STRYKER EUROPEAN HOLDINGS I, LLC reassignment STRYKER EUROPEAN HOLDINGS I, LLC CORRECTIVE ASSIGNMENT TO CORRECT THE INCORRECT LISTED SERIAL NOS. 09/905,670 AND 07/092,079 PREVIOUSLY RECORDED AT REEL: 037153 FRAME: 0241. ASSIGNOR(S) HEREBY CONFIRMS THE NUNC PRO TUNC ASSIGNMENT EFFECTIVE DATE 9/29/2014. Assignors: STRYKER MEDTECH LIMITED
Anticipated expiration legal-status Critical
Assigned to STRYKER EUROPEAN OPERATIONS HOLDINGS LLC reassignment STRYKER EUROPEAN OPERATIONS HOLDINGS LLC CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: STRYKER EUROPEAN HOLDINGS III, LLC
Assigned to STRYKER EUROPEAN HOLDINGS III, LLC reassignment STRYKER EUROPEAN HOLDINGS III, LLC NUNC PRO TUNC ASSIGNMENT (SEE DOCUMENT FOR DETAILS). Assignors: STRYKER EUROPEAN HOLDINGS I, LLC
Expired - Lifetime 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
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/242—Gold; Compounds thereof
    • 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
    • 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
    • C09J4/00—Adhesives based on organic non-macromolecular compounds having at least one polymerisable carbon-to-carbon unsaturated bond ; adhesives, based on monomers of macromolecular compounds of groups C09J183/00 - C09J183/16
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/36—Materials or treatment for tissue regeneration for embolization or occlusion, e.g. vaso-occlusive compositions or devices

Definitions

  • This invention relates to a composition used to treat arteriovenous malformations (“AVMs”) and other vascular abnormalities.
  • the composition includes a cyanoacrylate liquid monomer and gold in a prepolymerized polymer of cyanoacrylate.
  • the composition is placed into the body lumen via standard catheter procedures or directly percutaneously.
  • AVMs and vascular tumors are exceedingly difficult to treat. These growths may occur all over the body, but are especially difficult to treat when in the brain or brain stem.
  • the composition of the invention is especially useful in treating neurological AVMs, but may also be used to treat tumors anywhere in the body.
  • Cyanoacrylate adhesives have been used surgically but are limited in their usefulness by cytotoxicity and heat generation. The brain is unusually sensitive to cytotoxicity and heat.
  • the invention provides a composition that may be placed in a body lumen including veins and arteries by super selective catheterization or direct puncture using standard tools of the interventional angiographer.
  • the composition of the invention has been successfully tested in simulated models of the AVMs and tumors under fluoroscopy and in systems that closely resembles the neurological condition of the human body. Further studies have been done in the pig rete.
  • the rete is a body of fine arteries that allows the blood to flow into the pig brain which closely resembles normal human AVMs.
  • the composition is a cyanoacrylate which involves mixing two separate containers of the material immediately prior to administration of the material into the AVM by catheter.
  • the composition may contain seven ingredients which are divided into two parts prior to mixture and use. It furnishes properties that are useful for closing neurological AVMs.
  • the product can also be used to close any growth resembling an AVM in any part of the body. Because of the sensitive nature of the tissues in the brain, the general sensitivity of the product must be controlled. In less sensitive areas, the product will work equally as well.
  • Part I consists of a cyanoacrylate liquid monomer containing pure phosphoric acid (250 ppm) hydroquinone (100 ppm) and P-methoxyphenol (1200 ppm). This composition is stable and unchanging we believe for over two years.
  • the container in which Part I is stored requires cleaning and preparation before such stability can be achieved.
  • the liquid monomer of choice for this usage is 2-hexyl cyanoacrylate.
  • Part II consists of pure powdered gold (5 ⁇ 3 microns), a small amount of prepolymerized polymer of the same cyanoacrylate and ethyl myristate. Any of the large chain fatty acid esters will work to replace ethyl myristate so long as they are liquids.
  • the pre-polymerized polymers of cyanoacrylate are unstable and change their structures and properties even in the solid state.
  • the change is exponential and therefore the polymer must be used within a limited amount of time before deterioration occurs.
  • the polymer is prepared by addition of part 1 to a rapidly stirring weak bicarbonate-water solution. The addition must be added drop-wise to avoid unpolymerized masses from forming.
  • the solid polymer is washed thoroughly with pure water to remove any traces of bicarbonate, then washed thoroughly with pure methanol to remove the water. Methanol dries rapidly and when the polymer is further dried at a high reduced pressure for 16–18 hours, it is considered dry.
  • the polymer must be used in the next step within 24 hours to obtain consistent results in the final product. This mixture must be sterilized within 72 hours from the time of preparation.
  • Part II is sterilized with ethylene oxide gas with the stopper held in an open position.
  • Ethylene oxide is an alkylating agent and after sterilization the prepolymerized polymer is stable. Hence, the stability and sterilization of part 2 are carried out simultaneously.
  • the sterilized samples of Part II are capped in a clean room under sterile handling conditions.
  • the pre-polymerized polymer can be stabled by treatment with any of the strong alkylating agents, like ethylene oxide, ketene, etc.
  • composition of matter has good cohesion as well as adequate adhesion to function well for AVMs and other similar uses within the vascular tree.
  • the cohesion keeps the material together during the time required for it to polymerize.
  • the adhesion makes it stick to the artery walls.
  • the polymerized device will cause a modest but desirable inflammatory response in the treated tissues.
  • Part I 2-Hexyl Cyanoacrylate 999,550 ppm Hydroquinone 100 ppm p-Methoxyphenol 100 ppm Pure Phosphoric Acid 250 ppm
  • Part II (M2) Pure Gold 1.0000 g Pure Ethyl Myristate 0.5000 g FMS* 0.0200 g *FMS is a specially prepared polymer of 2-hexyl cyanoacrylate and must be used within 24 hours of preparation or will change and be unusable. Further, it must be sterilized within 72 hours.
  • This cyanoacrylate homolog was chosen because it biodegrades very slowly in blood or any living tissue.
  • the secondary alcohol will biodegrade several thousand times slower than its primary derivative. This very slow degradation rate also lowers greatly the histotoxicity.
  • Tantalum, platinum and gold are all radiopaque. Gold was best for us because it could be suspended colloidally in the mixture. One gram of gold is used per device.
  • Subbicates are useful for fastening the polymers of the cyanoacrylates. They also will stabilize the pre-formed polymers of the cyanoacrylates so that they may be used as thickeners.
  • ethyl myristate an esterified, biocompatible fatty acid because of the convenience of purification and analysis and because is works well to give the formulation the desirable properties.
  • FMS is the polymer of 2-hexyl cyanoacrylate formed in a weak, aqueous sodium bicarbonate solutions.
  • the polymer differs in structure and size depending on how it is formed. This polymer will remain stable until M2 can be formulated. The polymer must be formed and dried completely before use. The final formulation of M2 must occur within 24 hours because the ethyl myristate stabilized FMS until sterilization can be performed. After sterilization the product is stable for several years.
  • M1 and M2 are mixed immediately before use.
  • the mixture should be used within 4 hours after mixing. If there is a delay, the syringe should be turned over several times a minute to resuspend the gold which will be settled.

Abstract

A composition including 2-hexyl cyanoacrylate and gold is useful in treating arteriovenous malformations (AVMs) and other body lumens to be blocked.

Description

This application claims the benefit of U.S. Provisional Application No. 60/058,510, filed on Sep. 11, 1997.
More than one reissue application has been filed for the reissue of U.S. Pat. No. 6,037,366. This reissue Application is a continuation of U.S. application Ser. No. 10/873,413, filed Jun. 22, 2004, now abandoned, which in turn is a continuation of U.S. application Ser. No. 09/823,775, filed Mar. 30, 2001, now reissue RE39,150, which is a reissue of application Ser. No. 09/151,621, filed Sep. 11, 1998, now U.S. Pat. No. 6,037,366, which claims the benefit of U.S. Provisional Application No. 60/058,510, filed Sep. 11, 1997. Reissue application Ser. Nos. 11/827,668 (present application), 10/873,413 (abandoned) and 09/823,775 (RE39,150) are all reissue applications of U.S. Pat. No. 6,037,366.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a composition used to treat arteriovenous malformations (“AVMs”) and other vascular abnormalities. The composition includes a cyanoacrylate liquid monomer and gold in a prepolymerized polymer of cyanoacrylate. The composition is placed into the body lumen via standard catheter procedures or directly percutaneously.
2. Description of the Related Art
AVMs and vascular tumors, especially those of the brain, are exceedingly difficult to treat. These growths may occur all over the body, but are especially difficult to treat when in the brain or brain stem. The composition of the invention is especially useful in treating neurological AVMs, but may also be used to treat tumors anywhere in the body.
Cyanoacrylate adhesives have been used surgically but are limited in their usefulness by cytotoxicity and heat generation. The brain is unusually sensitive to cytotoxicity and heat.
The art described in this section is not intended to constitute an admission that any patent, publication or other information referred to herein is “prior art” with respect to this invention, unless specifically designated as such. In addition, this section should not be construed to mean that a search has been made or that no other pertinent information as defined in 37 C.F.R. § 1.56(a) exists.
SUMMARY OF THE INVENTION
The invention provides a composition that may be placed in a body lumen including veins and arteries by super selective catheterization or direct puncture using standard tools of the interventional angiographer. The composition of the invention has been successfully tested in simulated models of the AVMs and tumors under fluoroscopy and in systems that closely resembles the neurological condition of the human body. Further studies have been done in the pig rete. The rete is a body of fine arteries that allows the blood to flow into the pig brain which closely resembles normal human AVMs.
The composition is a cyanoacrylate which involves mixing two separate containers of the material immediately prior to administration of the material into the AVM by catheter. The composition may contain seven ingredients which are divided into two parts prior to mixture and use. It furnishes properties that are useful for closing neurological AVMs. The product can also be used to close any growth resembling an AVM in any part of the body. Because of the sensitive nature of the tissues in the brain, the general sensitivity of the product must be controlled. In less sensitive areas, the product will work equally as well.
Part I consists of a cyanoacrylate liquid monomer containing pure phosphoric acid (250 ppm) hydroquinone (100 ppm) and P-methoxyphenol (1200 ppm). This composition is stable and unchanging we believe for over two years. The container in which Part I is stored requires cleaning and preparation before such stability can be achieved. The liquid monomer of choice for this usage is 2-hexyl cyanoacrylate.
Part II consists of pure powdered gold (5±3 microns), a small amount of prepolymerized polymer of the same cyanoacrylate and ethyl myristate. Any of the large chain fatty acid esters will work to replace ethyl myristate so long as they are liquids.
The pre-polymerized polymers of cyanoacrylate are unstable and change their structures and properties even in the solid state. The change is exponential and therefore the polymer must be used within a limited amount of time before deterioration occurs.
The polymer is prepared by addition of part 1 to a rapidly stirring weak bicarbonate-water solution. The addition must be added drop-wise to avoid unpolymerized masses from forming. The solid polymer is washed thoroughly with pure water to remove any traces of bicarbonate, then washed thoroughly with pure methanol to remove the water. Methanol dries rapidly and when the polymer is further dried at a high reduced pressure for 16–18 hours, it is considered dry. The polymer must be used in the next step within 24 hours to obtain consistent results in the final product. This mixture must be sterilized within 72 hours from the time of preparation.
Part II is sterilized with ethylene oxide gas with the stopper held in an open position. Ethylene oxide is an alkylating agent and after sterilization the prepolymerized polymer is stable. Hence, the stability and sterilization of part 2 are carried out simultaneously. The sterilized samples of Part II are capped in a clean room under sterile handling conditions.
The pre-polymerized polymer can be stabled by treatment with any of the strong alkylating agents, like ethylene oxide, ketene, etc.
This composition of matter has good cohesion as well as adequate adhesion to function well for AVMs and other similar uses within the vascular tree. The cohesion keeps the material together during the time required for it to polymerize. The adhesion makes it stick to the artery walls.
The polymerized device will cause a modest but desirable inflammatory response in the treated tissues.
A Formulation for Arteriovenous Malformations and Tumors
It is desirable to prepare a formulation for the intravascular occlusion of AVMs and Tumors that will have the following properties:
    • The product has a very slow rate of biodegradation.
    • Both liquid and solid forms should have excellent cohesion.
    • The delivered product should have medium adhesion
    • The delivered product must be radiopaque.
    • The solid polymer should be soft and pliable.
    • The delivered product must have a very low or negligible histotoxicity.
    • The deposited product must have no long term negative properties such as carcinogenicity, teratogenicity, systemic toxicity or other unpredictable biological and medical effects.
    • The products must be sterile.
    • The delivered product must have good flow characteristics for selective catheterization.
    • The product must be stable on storage for an extended period of time.
    • The formulation should be made from pure products and be reproducible for simple manufacturing procedures.
      The product formulation is:
Part I (M1)
2-Hexyl Cyanoacrylate 999,550 ppm
Hydroquinone 100 ppm
p-Methoxyphenol 100 ppm
Pure Phosphoric Acid 250 ppm
Part II (M2)
Pure Gold 1.0000 g
Pure Ethyl Myristate 0.5000 g
FMS* 0.0200 g
*FMS is a specially prepared polymer of 2-hexyl cyanoacrylate and must be used within 24 hours of preparation or will change and be unusable. Further, it must be sterilized within 72 hours.
Each item of this formulation is critical to the proper performance of the product.
2-Hexyl Cyanoacrylate
This cyanoacrylate homolog was chosen because it biodegrades very slowly in blood or any living tissue. The secondary alcohol will biodegrade several thousand times slower than its primary derivative. This very slow degradation rate also lowers greatly the histotoxicity.
Hydroquinone
When the amount of hydroquinone is reduced by half (50 ppm) the product shows low shelf life stability. Large amounts over 100 ppm do not seem to effect the product stability. This inhibitor lowers the effect of the high energy free radicals that may appear in the cyanoacrylate.
p-Methoxyphenol
The slow polymerization of cyanoacrylates even under refrigeration is caused by low energy free radicals. When 100 ppm of p-methoxyphenol is present this slow polymerization is prevented and long term stability is achieved. Less p-methoxyphenol (50 ppm) will not protect the product.
Sulfur Dioxide
The faintest trace of sulfur dioxide is present in the product. One part per million can be seen and less is present. However, this very faint trace adds to the stability of Neuracryl* ml in the ampule.
Gold
Tantalum, platinum and gold are all radiopaque. Gold was best for us because it could be suspended colloidally in the mixture. One gram of gold is used per device.
Ethyl Myristate
Subbicates, fatty acid esters and other plasticizers, are useful for fastening the polymers of the cyanoacrylates. they also will stabilize the pre-formed polymers of the cyanoacrylates so that they may be used as thickeners. We have chosen ethyl myristate, an esterified, biocompatible fatty acid because of the convenience of purification and analysis and because is works well to give the formulation the desirable properties.
FMS
FMS is the polymer of 2-hexyl cyanoacrylate formed in a weak, aqueous sodium bicarbonate solutions. The polymer differs in structure and size depending on how it is formed. This polymer will remain stable until M2 can be formulated. The polymer must be formed and dried completely before use. The final formulation of M2 must occur within 24 hours because the ethyl myristate stabilized FMS until sterilization can be performed. After sterilization the product is stable for several years.
Neuracryl M
M1 and M2 are mixed immediately before use. The mixture should be used within 4 hours after mixing. If there is a delay, the syringe should be turned over several times a minute to resuspend the gold which will be settled.

Claims (16)

1. A composition for creating therapeutic vascular occlusions in an animal comprising a mixture of:
(a) Part 1 comprised of 2-hexyl cyanoacrylate, hydroquinone, p-methoxyphenol and phosphoric acid; and
(b) Part 2 comprising gold metal powder, ethyl myristate and a sterilized polymer of 2-hexylcyanoacrylate in weak aqueous bicarbonate solution.
2. The composition of claim 1 wherein Part 1 comprises about 100 PPM hydroquinone, 100 PPM p-methoxyphenol, 250 PPM phosphoric acid and the remainder 2-hexyl cyanoacrylate.
3. The composition of claim 2 wherein Part 2 comprises about 65 percent by weight gold, about 30 percent by weight ethyl myristate and the remainder said sterilized polymer of 2-hexylcyanoacrylate in weak aqueous bicarbonate solution.
4. The composition of claim 1 wherein Part 2 includes sulfur dioxide as a stabilizer.
5. A method for creating therapeutic vascular occlusions in an animal needing therapeutic vascular occlusion comprising the steps of:
(a) Mixing together Part 1 comprised of 2-hexyl cyanoacrylate, hydroquinone, p-methoxyphenol and phosphoric acid with Part 2 comprising gold metal powder, ethyl myristate and a sterilized polymer of 2-hexylcyanoacrylate in weak aqueous bicarbonate solution; and
(b) injecting the mixture into a vascular site needing occlusion with the gold metal powder suspended in the mixture.
6. A composition for creating therapeutic vascular occlusions in an animal comprising a mixture of:
(a) Part 1 comprising a cyanoacrylate liquid monomer, hydroquinone, p-methoxyphenol and phosphoric acid; and
(b) Part 2 comprising a radiopaque metal powder selected from the group consisting of gold, tantalum and platinum, a large chain fatty acid ester in liquid form and stabilized polymer of cyanoacrylate, wherein the cyanoacrylate is the same as the cyanoacrylate of Part 1.
7. The composition of claim 6, wherein the cyanoacrylate is 2-hexyl cyanoacrylate.
8. The composition of claim 6, wherein the vascular occlusion is created in an arteriovenous malformation (AVM).
9. The composition of claim 6, wherein the fatty acid ester is ethyl myristate.
10. The composition of claim 6, wherein Part 1 comprises 999,550 ppm 2-hexyl cyanoacrylate, 100 ppm hydroquinone, 100 ppm p-methoxyphenol and 250 ppm pure phosphoric acid.
11. The composition of claim 6, wherein Part 1 consists of a cyanoacrylate liquid monomer containing 250 ppm pure phosphoric acid, 100 ppm hydroquinone and 1200 ppm p-methoxyphenol.
12. A method for creating therapeutic vascular occlusions in an animal needing therapeutic vascular occlusion comprising the steps of:
(a) mixing together Part 1 comprised of cyanoacrylate liquid monomer, hydroquinone, p-methoxyphenol and phosphoric acid with Part 2 comprising a radiopaque metal powder selected from the group consisting of gold, tantalum and platinum, a large chain fatty acid ester in liquid form and a stabilized polymer of cyanoacrylate, wherein the cyanoacrylate is the same as the cyanoacrylate of part 1; and
(b) administering the mixture into a vascular site needing occlusion.
13. The method of claim 12, wherein the cyanoacrylate is 2-hexyl cyanoacrylate.
14. The method of claim 12, wherein the fatty acid ester is ethyl myristate.
15. The method of claim 12, wherein the vascular occlusion is created in an arteriovenous malformation (AVM).
16. The method of claim 12, wherein the administering is by catheter or by percutaneous methods.
US11/827,668 1997-09-11 2007-07-12 Composition for creating vascular occlusions Expired - Lifetime USRE42377E1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US11/827,668 USRE42377E1 (en) 1997-09-11 2007-07-12 Composition for creating vascular occlusions

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US5851097P 1997-09-11 1997-09-11
US09/151,621 US6037366A (en) 1997-09-11 1998-09-11 Composition for creating vascular occlusions
US09/823,775 USRE39150E1 (en) 1997-09-11 2001-03-30 Composition for creating vascular occlusions
US87341304A 2004-06-22 2004-06-22
US11/827,668 USRE42377E1 (en) 1997-09-11 2007-07-12 Composition for creating vascular occlusions

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US09/151,621 Reissue US6037366A (en) 1997-09-11 1998-09-11 Composition for creating vascular occlusions

Publications (1)

Publication Number Publication Date
USRE42377E1 true USRE42377E1 (en) 2011-05-17

Family

ID=26737696

Family Applications (3)

Application Number Title Priority Date Filing Date
US09/151,621 Ceased US6037366A (en) 1997-09-11 1998-09-11 Composition for creating vascular occlusions
US09/823,775 Expired - Lifetime USRE39150E1 (en) 1997-09-11 2001-03-30 Composition for creating vascular occlusions
US11/827,668 Expired - Lifetime USRE42377E1 (en) 1997-09-11 2007-07-12 Composition for creating vascular occlusions

Family Applications Before (2)

Application Number Title Priority Date Filing Date
US09/151,621 Ceased US6037366A (en) 1997-09-11 1998-09-11 Composition for creating vascular occlusions
US09/823,775 Expired - Lifetime USRE39150E1 (en) 1997-09-11 2001-03-30 Composition for creating vascular occlusions

Country Status (1)

Country Link
US (3) US6037366A (en)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6538026B1 (en) * 1997-09-11 2003-03-25 Provasis Therapeutics, Inc. Compositions useful for remodeling body spaces
US6476069B2 (en) * 1997-09-11 2002-11-05 Provasis Therapeutics Inc. Compositions for creating embolic agents and uses thereof
US6037366A (en) 1997-09-11 2000-03-14 Prohold Medical Technologies, Inc. Composition for creating vascular occlusions
US6476070B2 (en) * 1997-09-11 2002-11-05 Provasis Therapeutics Inc. Compositions useful for remodeling body spaces
US6652883B2 (en) 2000-03-13 2003-11-25 Biocure, Inc. Tissue bulking and coating compositions
DE60130544T2 (en) 2000-03-13 2008-06-26 Biocure, Inc. EMBOLIC COMPOSITIONS
US7687053B2 (en) * 2001-08-20 2010-03-30 Boston Scientific Scimed, Inc. Embolic compositions with non-cyanoacrylate rheology modifying agents
US7060023B2 (en) 2001-09-25 2006-06-13 The Foundry Inc. Pericardium reinforcing devices and methods of using them
US6695769B2 (en) 2001-09-25 2004-02-24 The Foundry, Inc. Passive ventricular support devices and methods of using them
US7341716B2 (en) * 2002-04-12 2008-03-11 Boston Scientific Scimed, Inc. Occlusive composition
DE10235602B4 (en) * 2002-08-02 2010-01-14 Universität Duisburg-Essen Metal cluster nanocompounds for the treatment of tumor diseases
HUP0203719A2 (en) * 2002-10-31 2007-09-28 Stepan Dr Gudak Polyuretan composition for fillin blood vessels and method of aplication of it
US7471784B2 (en) * 2004-07-29 2008-12-30 International Business Machines Corporation Dialed number service routing in a telephone network by reference to a database
US20060083762A1 (en) * 2004-10-13 2006-04-20 Gaelle Brun Uses of compositions comprising electrophilic monomers and micro-particles or nanoparticles
EP1647262B2 (en) * 2004-10-13 2012-02-08 L'Oréal Anhydrous cosmetic composition comprising electrophilic monomers and acid, and use for cosmetic treatment of hair
BRPI0504500A (en) * 2004-10-13 2006-05-23 Oreal use of a composition, cosmetic composition, process of treatment of keratin materials and kit
US20060085924A1 (en) * 2004-10-13 2006-04-27 Gaelle Brun Coloring composition comprising at least one pigment and at least one electrophilic cyanoacrylate monomer
US20070078207A1 (en) * 2005-09-30 2007-04-05 Jonn Jerry Y Stabilizer cyanoacrylate formulations
US20080241249A1 (en) * 2007-03-30 2008-10-02 Closure Medical Corporation Cyanoacrylate composite
KR20100106966A (en) * 2007-11-12 2010-10-04 밸러 메디컬, 인코포레이티드 Single vial formulation for medical grade cyanoacrylate
US20090137981A1 (en) * 2007-11-26 2009-05-28 Valor Medical Methods of treating a blood vessel
US9232805B2 (en) 2010-06-29 2016-01-12 Biocure, Inc. In-situ forming hydrogel wound dressings containing antimicrobial agents
CN104363922B (en) 2012-06-14 2017-06-30 微仙美国有限公司 Polymer therapeutic combination
AU2013331439B2 (en) 2012-10-15 2016-05-12 Microvention, Inc. Polymeric treatment compositions
US10111904B2 (en) 2013-01-09 2018-10-30 Berlock Aps Micron-sized gold, kit comprising said gold and its use as a non-toxic immune suppressor
US20160346423A1 (en) * 2014-01-07 2016-12-01 Covidien Lp Cyanoacrylate compositions including non-agglomerating radiopaque nanoparticles
US10368874B2 (en) 2016-08-26 2019-08-06 Microvention, Inc. Embolic compositions
JP7362598B2 (en) 2017-10-09 2023-10-17 マイクロベンション インコーポレイテッド radioactive liquid embolic material

Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4359454A (en) 1980-12-16 1982-11-16 World Health Organization Method and composition containing MCA for female sterilization
US4713235A (en) 1981-05-26 1987-12-15 Crx Medical, Inc. Radiopaque cyanoacrylates
US4740534A (en) 1985-08-30 1988-04-26 Sanyo Chemical Industries, Ltd. Surgical adhesive
US5328687A (en) 1993-03-31 1994-07-12 Tri-Point Medical L.P. Biocompatible monomer and polymer compositions
EP0664104A2 (en) 1994-01-24 1995-07-26 Micro Therapeutics, Inc. Balloon catheter for occluding aneurysms or branch vessels
US5525334A (en) 1994-06-03 1996-06-11 Japan As Represented By Director General Of Agency Of Industrial Science And Technology Method for vascular embolization
US5624685A (en) 1991-10-16 1997-04-29 Terumo Kabushiki Kaisha High polymer gel and vascular lesion embolizing material comprising the same
US5695480A (en) 1996-07-29 1997-12-09 Micro Therapeutics, Inc. Embolizing compositions
US5702361A (en) 1996-01-31 1997-12-30 Micro Therapeutics, Inc. Method for embolizing blood vessels
US5759194A (en) 1993-09-28 1998-06-02 Hemodynamics, Inc. Vascular patch applicator
WO1999042535A1 (en) 1998-02-18 1999-08-26 Closure Medical Corporation Cyanoacrylate compositions with terminal vinyl group in the alcohol part
US5981621A (en) 1996-02-29 1999-11-09 Closure Medical Corporation Monomeric compositions effective as wound closure devices
US6037366A (en) 1997-09-11 2000-03-14 Prohold Medical Technologies, Inc. Composition for creating vascular occlusions
WO2000044287A1 (en) 1999-01-29 2000-08-03 Prohold Medical Technologies, Inc. Cyanoacrylates comprising inhibitors and an opacifying agent as adhesives
US6143352A (en) 1994-06-28 2000-11-07 Closure Medical Corporation pH-modified biocompatible monomer and polymer compositions
US20020018752A1 (en) 2000-05-23 2002-02-14 Krall Robert E. Polymerizable compositions and methods of use
US6476070B2 (en) 1997-09-11 2002-11-05 Provasis Therapeutics Inc. Compositions useful for remodeling body spaces
US20030194389A1 (en) 2002-04-12 2003-10-16 Porter Stephen C. Occlusive composition

Patent Citations (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4359454A (en) 1980-12-16 1982-11-16 World Health Organization Method and composition containing MCA for female sterilization
US4713235A (en) 1981-05-26 1987-12-15 Crx Medical, Inc. Radiopaque cyanoacrylates
US4740534A (en) 1985-08-30 1988-04-26 Sanyo Chemical Industries, Ltd. Surgical adhesive
US5624685A (en) 1991-10-16 1997-04-29 Terumo Kabushiki Kaisha High polymer gel and vascular lesion embolizing material comprising the same
US5328687A (en) 1993-03-31 1994-07-12 Tri-Point Medical L.P. Biocompatible monomer and polymer compositions
US5759194A (en) 1993-09-28 1998-06-02 Hemodynamics, Inc. Vascular patch applicator
EP0664104A2 (en) 1994-01-24 1995-07-26 Micro Therapeutics, Inc. Balloon catheter for occluding aneurysms or branch vessels
US5795331A (en) 1994-01-24 1998-08-18 Micro Therapeutics, Inc. Balloon catheter for occluding aneurysms of branch vessels
US5525334A (en) 1994-06-03 1996-06-11 Japan As Represented By Director General Of Agency Of Industrial Science And Technology Method for vascular embolization
US6143352A (en) 1994-06-28 2000-11-07 Closure Medical Corporation pH-modified biocompatible monomer and polymer compositions
US5702361A (en) 1996-01-31 1997-12-30 Micro Therapeutics, Inc. Method for embolizing blood vessels
US5981621A (en) 1996-02-29 1999-11-09 Closure Medical Corporation Monomeric compositions effective as wound closure devices
US5695480A (en) 1996-07-29 1997-12-09 Micro Therapeutics, Inc. Embolizing compositions
US6037366A (en) 1997-09-11 2000-03-14 Prohold Medical Technologies, Inc. Composition for creating vascular occlusions
US6476070B2 (en) 1997-09-11 2002-11-05 Provasis Therapeutics Inc. Compositions useful for remodeling body spaces
US6476069B2 (en) 1997-09-11 2002-11-05 Provasis Therapeutics Inc. Compositions for creating embolic agents and uses thereof
USRE39150E1 (en) * 1997-09-11 2006-06-27 Prohold Technologies, Inc. Composition for creating vascular occlusions
WO1999042535A1 (en) 1998-02-18 1999-08-26 Closure Medical Corporation Cyanoacrylate compositions with terminal vinyl group in the alcohol part
US6174919B1 (en) 1998-02-18 2001-01-16 Closure Medical Corporation Cyanoacrylate compositions with vinyl terminated ester groups
WO2000044287A1 (en) 1999-01-29 2000-08-03 Prohold Medical Technologies, Inc. Cyanoacrylates comprising inhibitors and an opacifying agent as adhesives
US20020018752A1 (en) 2000-05-23 2002-02-14 Krall Robert E. Polymerizable compositions and methods of use
US20030194389A1 (en) 2002-04-12 2003-10-16 Porter Stephen C. Occlusive composition

Non-Patent Citations (22)

* Cited by examiner, † Cited by third party
Title
Almen, et al., "Basic Methdos of Investigative Neuroradiology" Chapter 6 in Radiocontrast Agents M. Sovak ed., Springer-Verlag Press, pp. 341-366 (1984).
Barr, John D., "Temporary and Permanent Occlusion of Cerebral Arteries," Neurovascular Surgery 11(1):27-38 (2000).
Berthelsen, et al., "Embolization of Cerebral Arteriovenous Malformations With Bucrylate," Acta Radiologica 31:13-21 (1990).
Freeny, et al., "Transcatheter Therapy of Genitourinary Abnormalities Using Isobutyl 2-Cyanoacrylate(Bucrylate)," AJR 133:647-656 (1979).
Gobin, et al., "Treatment of Brain Arteriovenous Malformations by Embolization and Radiosurgery," J. Neurosurg 85:19-28 (1996).
Halbach, et al., "Preoperative Balloon Occlusion of Arteriovenous Malformations," Neurosurgery 22(2):301-308 (1988).
Kerber, et al., "Liquid Acrylic Adhesive Agents in Interventional Neuroradiology," Neuroendovascular Surgery 11(1):85-99 (2000).
Lefkowitz, et al.,"Balloon-Assisted Guglielmi Detachable Coiling of Wide-Necked Aneurysms: Part II-Clinical Results," Neurosurgery 45(3):531-538 (1999).
Levy, Dr. David I., "Embolization of Wide-Necked Anterior Communication Artery Aneurysm: Technical Note," Neurosurgery 41(4):979-982 (1997).
Malek, et al., "Balloon-Assist Technique for Endovascular Coil Embolization of Geometrically Difficult Intracranial Aneurysms," Neurosurgery 46(6):1397-1407 (2000).
Mathis, et al., "Hydrophilic Coatings Diminish Adhesion of Glue to Catheter: an in Vitro Simulation of NBCA Embolization," AJNR 18(9)1087-1091 (1997).
Mericle, Robert A., M.D., "Temporary Balloon Protection as an Adjunct TI Endosaccular Coiling of Wide-Necked Cerebral Aneurysms," Neurosurgery 41(4): 1992-1998 (1997).
Moret, et al., "The 'Remodeling Technique' in the Treatment of Wide Neck Intracranial Aneurysms," Interventional Neuroradiology 3:21-35 (1997).
Pelz, et al., "Preoperative Embolization of Brain AVMS With Isobutyl-2 Cyanoacrylate," AJNR 9:757-764 (1988).
Rao, et al., "Dissolution of Isobutyl-2 Cyanoacrylate on Long Term Follow Up," AJNR 10:135-141 (1989).
Spiegel, et al., "Adjusting the Polymerization Time of Isobutyl-2 Cyanoacrylate," AJNR 7:109-112 (1986).
The Merck Index, Merck & Co., Inc., Whitehouse Station, NJ, 1996, 12th ed., p. 647, item No. 3849.
Tseng et al., "Modified Ethoxyethyl Cyanoacrylate for Therapeutic Embolization of Arteriovenous Malformation," Journal of Biomedical Materials Research 24:65-77 (1990).
Vinuela, et al., "Angiographic Follow-Up of Large Cerebral AVMS Incompletely Embolized With Isobutyl 2-Cyanoacrylate," AJNR 7:919-925 (1986).
Vinuela, et al., "Dominant-Hemisphere Arteriovenous Malformations: Therapeutic Embolization With Isobutyl-2 Cyanoacrylate," AJNR 4:959-966 (1983).
Vinuela, et al., "Progressive Thrombosis of Brain Arteriovenous Malformations After Embolizations With Isobutyl 2-Cyanoacrylate,"AJNR 4:1233-1238 (1983).
Woodward, "Physiological and Biochemical Evaluation of Implanted Polymers," Annals of the New York Academy of Sciences 146:225-250 (1968).

Also Published As

Publication number Publication date
USRE39150E1 (en) 2006-06-27
US6037366A (en) 2000-03-14

Similar Documents

Publication Publication Date Title
USRE42377E1 (en) Composition for creating vascular occlusions
EP1154723B1 (en) Cyanoacrylates comprising inhibitors and an opacifying agent
CA2410387C (en) Polymerizable compositions and methods of use
DE60305906T2 (en) OCCLUSION COMPOSITION COMPRISING A POLY (2-CYANOACRYLATE) MONOMER
Liau et al. Treatment of iatrogenic femoral artery pseudoaneurysm with percutaneous thrombin injection
JP5438878B2 (en) Methods to prevent the formation of endoleaks associated with endovascular repair of celiac aortic aneurysms
DE60222680T2 (en) EMBOLIC COMPOSITION WITH NON CYANOACRYLATE RHEOLOGY MODIFIERS
Gershony et al. Novel vascular sealing device for closure of percutaneous vascular access sites
Hill et al. Coronary arterial aneurysm formation after balloon angioplasty
JP2002539856A (en) Method of treating internal leakage during endovascular repair of abdominal aortic aneurysm
US6476070B2 (en) Compositions useful for remodeling body spaces
US20030228273A1 (en) Novel high viscosity embolizing compositions comprising prepolymers
JPH11510173A (en) Cellulose diacetate compositions for vascular embolization
EP0592903A2 (en) Use of ancrod for the preparation of drugs for the treatment of restenosis
COARD et al. Isobutyl‐2‐cyanoacrylate pulmonary emboli associated with occlusive embolotherapy of cerebral arteriovenous malformations
JPH0517369A (en) Thromboembolic agent
Kardaras et al. Septic endarteritis following percutaneous transluminal coronary angioplasty
White Jr Interventional radiology: overview
Rifón et al. Fibrinolysis after coronary bypass surgery in relation to thrombosis and bleeding
Jømrgensen et al. Segmentally enclosed thrombolysis eliminates intraarterial thrombin activity produced by percutaneous transluminal angioplasty
CS225634B1 (en) Copolimer of polyvinylacetate-polyvinylalcohol for the terapeutic embolization of the vessel bed

Legal Events

Date Code Title Description
FEPP Fee payment procedure

Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

AS Assignment

Owner name: STRYKER CORPORATION, MICHIGAN

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:BOSTON SCIENTIFIC CORPORATION;REEL/FRAME:025853/0773

Effective date: 20110103

Owner name: STRYKER NV OPERATIONS LIMITED, ISRAEL

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:BOSTON SCIENTIFIC CORPORATION;REEL/FRAME:025853/0773

Effective date: 20110103

AS Assignment

Owner name: STRYKER NV OPERATIONS LIMITED, IRELAND

Free format text: CORRECTIVE ASSIGNMENT TO CORRECT THE THE STATE/COUNTRY IN RECEIVING PARTY DATA FOR STRYKER NV OPERATIONS LIMITED FROM ISRAEL TO IRELAND. PREVIOUSLY RECORDED ON REEL 025853 FRAME 0773. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT;ASSIGNOR:BOSTON SCIENTIFIC CORPORATION;REEL/FRAME:025948/0123

Effective date: 20110103

Owner name: STRYKER CORPORATION, MICHIGAN

Free format text: CORRECTIVE ASSIGNMENT TO CORRECT THE THE STATE/COUNTRY IN RECEIVING PARTY DATA FOR STRYKER NV OPERATIONS LIMITED FROM ISRAEL TO IRELAND. PREVIOUSLY RECORDED ON REEL 025853 FRAME 0773. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT;ASSIGNOR:BOSTON SCIENTIFIC CORPORATION;REEL/FRAME:025948/0123

Effective date: 20110103

AS Assignment

Owner name: STRYKER MEDTECH LIMITED, MALTA

Free format text: NUNC PRO TUNC ASSIGNMENT;ASSIGNOR:STRYKER NV OPERATIONS LIMITED;REEL/FRAME:037153/0034

Effective date: 20151013

Owner name: STRYKER EUROPEAN HOLDINGS I, LLC, MICHIGAN

Free format text: NUNC PRO TUNC ASSIGNMENT;ASSIGNOR:STRYKER MEDTECH LIMITED;REEL/FRAME:037153/0241

Effective date: 20151013

AS Assignment

Owner name: STRYKER EUROPEAN HOLDINGS I, LLC, MICHIGAN

Free format text: CORRECTIVE ASSIGNMENT TO CORRECT THE INCORRECT LISTED SERIAL NOS. 09/905,670 AND 07/092,079 PREVIOUSLY RECORDED AT REEL: 037153 FRAME: 0241. ASSIGNOR(S) HEREBY CONFIRMS THE NUNC PRO TUNC ASSIGNMENT EFFECTIVE DATE 9/29/2014;ASSIGNOR:STRYKER MEDTECH LIMITED;REEL/FRAME:038043/0011

Effective date: 20151013

Owner name: STRYKER MEDTECH LIMITED, MALTA

Free format text: CORRECTIVE ASSIGNMENT TO CORRECT THE INCORRECT SERIAL # 09/905,670 AND 07/092,079 PREVIOUSLY RECORDED AT REEL: 037153 FRAME: 0034. ASSIGNOR(S) HEREBY CONFIRMS THE NUNC PRO TUNC ASSIGNMENT;ASSIGNOR:STRYKER NV OPERATIONS LIMITED;REEL/FRAME:038039/0001

Effective date: 20151013

AS Assignment

Owner name: STRYKER EUROPEAN OPERATIONS HOLDINGS LLC, MICHIGAN

Free format text: CHANGE OF NAME;ASSIGNOR:STRYKER EUROPEAN HOLDINGS III, LLC;REEL/FRAME:052860/0716

Effective date: 20190226

Owner name: STRYKER EUROPEAN HOLDINGS III, LLC, DELAWARE

Free format text: NUNC PRO TUNC ASSIGNMENT;ASSIGNOR:STRYKER EUROPEAN HOLDINGS I, LLC;REEL/FRAME:052861/0001

Effective date: 20200519