Title of Invention	A DEVICE FOR DISPENSING A POLYMERIZABLE OR CROSS-LINKABLE MONOMER
Abstract	ABSTRACT OF THE DISCLOSURE A method of joining together in vivo living tissue surfaces includes (a) holding together at least two tissue surfaces to form abutted tissue surfaces, (b) applying across said abutted tissue surfaces an excessive amount of an adhesive composition comprising at least one monomer that forms a medically acceptable polymer with an applicator having a porous applicator tip; and (c) maintaining said tissue surfaces in contact in vivo until said composition polymerizes to form a thick film of polymerized composition on said abutted tissue surface.

Title of Invention

A DEVICE FOR DISPENSING A POLYMERIZABLE OR CROSS-LINKABLE MONOMER

Abstract

ABSTRACT OF THE DISCLOSURE A method of joining together in vivo living tissue surfaces includes (a) holding together at least two tissue surfaces to form abutted tissue surfaces, (b) applying across said abutted tissue surfaces an excessive amount of an adhesive composition comprising at least one monomer that forms a medically acceptable polymer with an applicator having a porous applicator tip; and (c) maintaining said tissue surfaces in contact in vivo until said composition polymerizes to form a thick film of polymerized composition on said abutted tissue surface.

Full Text	This invention relates to monomer and polymer compositions useful to form biomedical adhesives and sealants, and methods of applying them. More particularly, this invention relates to methods of applying monomer and polymer compositions and their use for medical, surgical and other in vivo applications. 2. Description of Related Art Products in primary use for wound closure are surgical sutures and staples. Sutures are recognized to provide adequate wound support. However, sutures cause additional trauma to the wound site (by reason of the need for the needle and suture to pass through tissue and the need to anesthetize the wound area via needle application) and are time-consuming to place, and, at skin level, can cause unattractive wound closure marks. Surgical staples have been developed to speed wound apposition and provide improved cosmetic results. However, surgical staples also impose additional wound trauma and require the use of ancillary and often expensive devices for positioning and applying the staples. Both sutures and staples are especially problematic in pediatric cases where the patient may have a strong fear response and refuse tc cooperate with their placement, and in geriatric pases where the skin tissue is weaker and prone to tearing. Alternatively, adhesives have been proposed as wound closure devices. One group of such adhesives is the monomeric forms of alpha-cyanoacrylates. Reference is made, for example, to U.S. Patents Nos. 5,328,687 to Leung et al; 3,527,841 to Wicker et al.; 3,722,599 to Robertson et al.; 3,995,641 to Kronenthal et al.; and 3,940,362 to Overhults, which disclose alpha-cyanoacrylates that are useful as surgical adhesives. All SUMMARY OF THE INVENTION The present invention provides a process for application of a surgical adhesive composition in a bridge structure that provides an unexpectedly improved bond strength over conventional application techniques of the polymerized composition on the wound or incision site, which increases the effectiveness of monomers and polymers in in vivo applications. The surgical adhesive forms a flexible and strong bond over wounds and incisions. Moreover, the method of applying a surgical adhesive to a wound or incision provides a strong and flexible biocompatible bond. The present invention is also directed to methods of applying a monomeric composition with a porous applicator tip and with an applicator tip having a non-uniform distribution of initiator or rate modifier. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS One embodiment of the present invention provides a wound closure monomer composition, comprising: A) at least one monomer, which forms a medically acceptable wound closure polymer: B) at least one plasticizing agent; and C) at least one acidic stabilizing agent. In other embodiments, the present invention is directed to methods of using the above-described monomers, copolymers and polymers made therefrom for biomedical purposes.. See U.S. Patent Serial No. 0B/6Q9,921, incorporated in its entirety herein by reference. In one such embodiment, the edges of a wound or incision are held together and an excessive amount of the above-described surgical adhesive composition is applied to the already pinched or abutted opposing wound edges, preferably utilizing more than one application stroke. This process forms a bridge over the abutted opposing wound edges that is flexible and possesses high tensile strength. The excessive amount of adhesive placed on the The present invention provides a process for application of a surgical adhesive composition in a bridge structure that provides an unexpectedly improved bond strength over conventional application techniques of the polymerized composition on the wound or incision site, which increases the effectiveness of monomers and polymers in in vivo applications. The surgical adhesive forms a flexible and strong bond over wounds and incisions. Moreover, the method of applying a surgical adhesive to a wound or incision provides a strong and flexible biocompatible bond. The present invention is also directed to methods of applying a monomelic composition with a porous applicator tip and with an applicator tip having a non-uni-form distribution of initiator or rate modifier. Accordingly the present invention provides a device for dispensing a polymerizable or cross-linkable monomer material composition, comprising: an applicator having a porous applicator tip, wherein said applicator tip has an anisotropic distribution of a polymerization or cross-linking initiator or rate modifier disposed thereon, and containing a polymerizable or cross-linkable monomer material composition. WE CLAIM: 1. A device for dispensing a polymerizable or cross-linkable monomer material composition, comprising: an applicator having a porous applicator tip, wherein said applicator tip has an anisotropic distribution of a polymerization or cross-linking initiator or rate modifier disposed thereon, and containing a polymerizable or cross-linkable monomer material composition. 2. A device as claimed in claim 1, wherein said anisotropic distribution forms a concentration gradient of said polymerization or cross-linking initiator or rate modifier in said applicator tip. 3. A device as claimed in claim 1, wherein said applicator tip comprises a first end and a second end, said second end located downstream in a fluid flow direction from said first end, and a concentration of said polymerization or cross-linking initiator ror rate modifier in said applicator tip is greater at said second end than at said first end. 4. A device as claimed in claim 1, wherein said applicator tip comprises a first end and a second end, said second end located downstream in a fluid flow direction from said first end, and a concentration of said polymerization or cross-linking initiator or rate modifier in said applicator tip is greater at said first end than at said second end. 5. A device as claimed in claim 1, wherein said applicator tip has an average pore size of l μm to 500 urn. 6. A device as claimed in claim 1, wherein said applicator tip has an average pore size of 20 to 140 μm and said monomer material composition has a viscosity of 7 to 250 cPs at 25°C. 7. A device as claimed in claim 1, wherein said applicator tip has an average pore size of about 20 urn and said monomer material composition has a viscosity of about 7 cPs at 25°C. 8. A device as claimed in claim 1, wherein said applicator tip has an average pore size of about 140 fim and said monomer material composition has a viscosity of about 250 cPs at 25°C. 9. A device as claimed in claim 1, wherein said applicator tip has a porosity defined by the open volume of the pores of the applicator tip divided by the total volume of the applicator tip, of less than or equal to 80 percent. 10. A device as claimed in claim 1, wherein said polymerization or cross- linking initiator or rate modifier is a polymerization or cross-linking initiator or rate modifier for said monomer material composition. i 11A device as claimed in claim 1, wherein said applicator tip is integral with said applicator. 12. A device as claimed in claim 1. wherein said applicator is selected from the group consisting of a syringe, a flexible cylinder, a tube, a pipette and an eyedropper. 13 A device as claimed in claim 1, wherein said monomer is at least one monomer located in said applicator in a non-contacting relationship with said porous applicator tip prior to dispensing said monomer. 14.A device as claimed in claim 1, wherein said applicator contains an adhesive composition, comprised of at least one monomer that forms a medically acceptable polymer; at least one plasticizing agent present in the composition in an amount of from 0.5 wt% to 16wt% of the composition; and at least one acidic stabilizing agent having a pKa ionization constant of from 0 to 7. 15A device as claimed in claim 1, wherein said monomer material comprises a 1,1-disubstituted ethylene monomer. 16.A device as claimed in claim 1, wherein said monomer material comprises an a-cyanoacrylate monomer. 17.A device as claimed in claim 1, wherein said monomer material comprises at least one member selected from butyl a-cyanoacrylate monomer and octyl a-cyanoacrylate monomer. 18.Manufacture of the device of claim 1 which comprises: (a) holding together at least two in vivo living tissue surfaces to form abutted tissue surfaces, (b) applying across said abutted tissues surfaces, with said applicator having a porous applicator tip, an excess amount of an adhesive composition that is uniformly distributed comprising at least one monomer that forms a medically acceptable polymer; and fc) maintaining said abutted surfaces in contact until said composition polymerizes to form a thick film of medically acceptable polymerized composition on said abutted tissue surfaces. 19,Manufacture as claimed in claim 18, wherein said method comprises more than one application of said adhesive composition across said abutted tissue surfaces. 20.Manufacture as claimed in claim 19. wherein said method comprises allowing said adhesive composition applied across said abutted tissue surfaces to at least partially polymerize prior to subsequent coatings or applications of said adhesive composition. 21.A device for dispensing a polymerizable or cross-linkable monomer material composition substantially as herein described and exemplified.

Full Text

This invention relates to monomer and polymer compositions useful to form biomedical adhesives and sealants, and methods of applying them. More particularly, this invention relates to methods of applying monomer and polymer compositions and their use for medical, surgical and other in vivo applications. 2. Description of Related Art
Products in primary use for wound closure are surgical sutures and staples. Sutures are recognized to provide adequate wound support. However, sutures cause additional trauma to the wound site (by reason of the need for the needle and suture to pass through tissue and the need to anesthetize the wound area via needle application) and are time-consuming to place, and, at skin level, can cause unattractive wound closure marks. Surgical staples have been developed to speed wound apposition and provide improved cosmetic results. However, surgical staples also impose additional wound trauma and require the use of ancillary and often expensive devices for positioning and applying the staples. Both sutures and staples are especially problematic in pediatric cases where the patient may have a strong fear response and refuse tc cooperate with their placement, and in geriatric pases where the skin tissue is weaker and prone to tearing.
Alternatively, adhesives have been proposed as wound closure devices. One group of such adhesives is the monomeric forms of alpha-cyanoacrylates.
Reference is made, for example, to U.S. Patents Nos. 5,328,687 to Leung et al; 3,527,841 to Wicker et al.; 3,722,599 to Robertson et al.; 3,995,641 to Kronenthal et al.; and 3,940,362 to Overhults, which disclose alpha-cyanoacrylates that are useful as surgical adhesives. All

SUMMARY OF THE INVENTION The present invention provides a process for application of a surgical adhesive composition in a bridge structure that provides an unexpectedly improved bond strength over conventional application techniques of the polymerized composition on the wound or incision site, which increases the effectiveness of monomers and polymers in in vivo applications. The surgical adhesive forms a flexible and strong bond over wounds and incisions. Moreover, the method of applying a surgical adhesive to a wound or incision provides a strong and flexible biocompatible bond. The present invention is also directed to methods of applying a monomeric composition with a porous applicator tip and with an applicator tip having a non-uniform distribution of initiator or rate modifier.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS One embodiment of the present invention provides a wound closure monomer composition, comprising:
A) at least one monomer, which forms a medically acceptable wound closure polymer:
B) at least one plasticizing agent; and
C) at least one acidic stabilizing agent.
In other embodiments, the present invention is directed to methods of using the above-described monomers, copolymers and polymers made therefrom for biomedical purposes.. See U.S. Patent Serial No. 0B/6Q9,921, incorporated in its entirety herein by reference.
In one such embodiment, the edges of a wound or incision are held together and an excessive amount of the above-described surgical adhesive composition is applied to the already pinched or abutted opposing wound edges, preferably utilizing more than one application stroke. This process forms a bridge over the abutted opposing wound edges that is flexible and possesses high tensile strength. The excessive amount of adhesive placed on the

The present invention provides a process for application of a surgical adhesive composition in a bridge structure that provides an unexpectedly improved bond strength over conventional application techniques of the polymerized composition on the wound or incision site, which increases the effectiveness of monomers and polymers in in vivo applications. The surgical adhesive forms a flexible and strong bond over wounds and incisions. Moreover, the method of applying a surgical adhesive to a wound or incision provides a strong and flexible biocompatible bond. The present invention is also directed to methods of applying a monomelic composition with a porous applicator tip and with an applicator tip having a non-uni-form distribution of initiator or rate modifier.
Accordingly the present invention provides a device for dispensing a polymerizable or cross-linkable monomer material composition, comprising: an applicator having a porous applicator tip, wherein said applicator tip has an anisotropic distribution of a polymerization or cross-linking initiator or rate modifier disposed thereon, and containing a polymerizable or cross-linkable monomer material composition.

WE CLAIM:
1. A device for dispensing a polymerizable or cross-linkable monomer material composition, comprising:
an applicator having a porous applicator tip, wherein said applicator tip has an anisotropic distribution of a polymerization or cross-linking initiator or rate modifier disposed thereon, and containing a polymerizable or cross-linkable monomer material composition.
2. A device as claimed in claim 1, wherein said anisotropic distribution forms a concentration gradient of said polymerization or cross-linking initiator or rate modifier in said applicator tip.
3. A device as claimed in claim 1, wherein said applicator tip comprises a first end and a second end, said second end located downstream in a fluid flow direction from said first end, and a concentration of said polymerization or cross-linking initiator ror rate modifier in said applicator tip is greater at said second end than at said first end.
4. A device as claimed in claim 1, wherein said applicator tip comprises a first end and a second end, said second end located downstream in a fluid flow direction from said first end, and a concentration of said polymerization or cross-linking initiator or rate modifier in said applicator tip is greater at said first end than at said second end.

5. A device as claimed in claim 1, wherein said applicator tip has an average pore size of l μm to 500 urn.
6. A device as claimed in claim 1, wherein said applicator tip has an average pore size of 20 to 140 μm and said monomer material composition has a viscosity of 7 to 250 cPs at 25°C.
7. A device as claimed in claim 1, wherein said applicator tip has an average pore size of about 20 urn and said monomer material composition has a viscosity of about 7 cPs at 25°C.
8. A device as claimed in claim 1, wherein said applicator tip has an average pore size of about 140 fim and said monomer material composition has a viscosity of about 250 cPs at 25°C.
9. A device as claimed in claim 1, wherein said applicator tip has a porosity defined by the open volume of the pores of the applicator tip divided by the total volume of the applicator tip, of less than or equal to 80 percent.
10. A device as claimed in claim 1, wherein said polymerization or cross-
linking initiator or rate modifier is a polymerization or cross-linking
initiator or rate modifier for said monomer material composition.
i

11A device as claimed in claim 1, wherein said applicator tip is integral with said applicator.
12. A device as claimed in claim 1. wherein said applicator is selected from the group consisting of a syringe, a flexible cylinder, a tube, a pipette and an eyedropper.
13 A device as claimed in claim 1, wherein said monomer is at least one monomer located in said applicator in a non-contacting relationship with said porous applicator tip prior to dispensing said monomer.
14.A device as claimed in claim 1, wherein said applicator contains an adhesive composition, comprised of at least one monomer that forms a medically acceptable polymer; at least one plasticizing agent present in the composition in an amount of from 0.5 wt% to 16wt% of the composition; and at least one acidic stabilizing agent having a pKa ionization constant of from 0 to 7.
15A device as claimed in claim 1, wherein said monomer material comprises a 1,1-disubstituted ethylene monomer.
16.A device as claimed in claim 1, wherein said monomer material comprises an a-cyanoacrylate monomer.

17.A device as claimed in claim 1, wherein said monomer material comprises at least one member selected from butyl a-cyanoacrylate monomer and octyl a-cyanoacrylate monomer.
18.Manufacture of the device of claim 1 which comprises:
(a) holding together at least two in vivo living tissue surfaces to form abutted tissue surfaces,
(b) applying across said abutted tissues surfaces, with said applicator having a porous applicator tip, an excess amount of an adhesive composition that is uniformly distributed comprising at least one monomer that forms a medically acceptable polymer; and
fc) maintaining said abutted surfaces in contact until said composition polymerizes to form a thick film of medically acceptable polymerized composition on said abutted tissue surfaces.
19,Manufacture as claimed in claim 18, wherein said method comprises more than one application of said adhesive composition across said abutted tissue surfaces.
20.Manufacture as claimed in claim 19. wherein said method comprises allowing said adhesive composition applied across said abutted tissue surfaces to at least partially polymerize prior to subsequent coatings or applications of said adhesive composition.

21.A device for dispensing a polymerizable or cross-linkable monomer material composition substantially as herein described and exemplified.

Documents:

1941-mas-1998 abstract.pdf

1941-mas-1998 claims.pdf

1941-mas-1998 correspondence-others.pdf

1941-mas-1998 description(complete).pdf

1941-mas-1998 form-26.pdf

1941-mas-1998 form-4.pdf

1941-mas-1998 form-6.pdf

1941-mas-1998 petition.pdf

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Patent Number

187812

Indian Patent Application Number

1941/MAS/1998

PG Journal Number

30/2009

Publication Date

24-Jul-2009

Grant Date

10-Jan-2003

Date of Filing

28-Aug-1998

Name of Patentee

M/S. CLOSURE MEDICAL CORPORATION

Applicant Address

5250 GREENS DAIRY ROAD, RALEIGH, NORTH CAROLINA 27616

Inventors:

#	Inventor's Name	Inventor's Address
1	JEFFREY G. CLARK	908, BENNINGTON DRIVE, RELEIGH, NORTH COROLINA 27617,
2	JEFFREY C LEUNG	813 BERWYN WAY, RALEIGH, NORTH CAROLINA 27615,

PCT International Classification Number

A61J 3/08

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	08/920,876	1997-08-29	U.S.A.