EP1022986A2

EP1022986A2 - Dispenser for an adhesive tissue sealant

Info

Publication number: EP1022986A2
Application number: EP98953887A
Authority: EP
Inventors: David F. Wirt
Original assignee: Minnesota Mining and Manufacturing Co
Current assignee: 3M Co
Priority date: 1997-10-22
Filing date: 1998-10-22
Publication date: 2000-08-02
Also published as: AU1114599A; JP2001520086A; WO1999020328A2; WO1999020328A3

Abstract

A dispenser in which a dry powder (one component of a two-part adhesive tissue sealant) is stored in a container (e.g., a carpule) having a septum at one end, an open end opposite the septum, and a movable plug. The powder is retained at the septum end of the container by the movable plug, which is displaced and pushed back as the solvent used for reconstituting the powder is introduced (e.g., through the septum). The second part of the tissue sealant is contained within a second container, also with a movable plug. After the first part is reconstituted, a manifold is fitted which pierces both septums and allows the contents to be dispensed. A dual syringe body supports the containers, and has pistons that enter the open ends to advance the movable plugs.

Description

DISPENSER FOR AN ADHESIVE TISSUE SEALANT

Technical Field The invention relates generally to the dispensing of adhesive tissue sealants and other liquid preparations, including those requiring mixing immediately prior to use.

Background of the Invention A variety of techniques have been used to bond or seal living tissue. For example, different types of tissues have been mechanically bound or sealed with a number of procedures, materials and methods including sutures, staples, tapes and bandages. In some applications, these materials are made of absorbable materials which are intended to bond and/or seal tissue as it heals and then to be absorbed over a period of time.

A recent addition to the techniques which can e used is application of an absorbable adhesive sealant composition to bond and/or seal tissue. The adhesive composition is readily formed from a two component mixture which includes a first part of a crosslinking agent and a second part of a protein, preferably a serum protein such as albumin. When the two parts of the mixture are combined, the mixture is initially liquid. The combined mixture then cures a vivo on the surface of tissue to give a substantive composition which securely bonds to the tissue. A more complete discussion can be found in coassigned U.S. Patent No. 5,583,114, "ADHESIVE SEALANT COMPOSITION", to Barrows et al.

Among the limitations on the widespread use of this material are that the first part when rehydrated has a limited shelf life and must be dissolved relatively shortly before use, and that the two parts must be kept strictly separate until dispensed onto the tissue because the reaction time to the forming of the finished sealant is quite fast. These limitations increase the complexity for appropriate dispensing by the medical practitioner to form an effective adhesive tissue sealant on the tissue surface.

A known approach for dispensing two-part tissue sealants is to supply the user with a kit consisting of two syringes, vials containing the components, a syringe body for receiving and supporting both syringes, and a manifold for connecting the two syringes to a common nozzle. The user fills the syringes by piercing the septums on the vials and withdrawing solution into the barrel of the syringe. If a component is in powder form within a vial, the user first injects a solvent and then withdraws the reconstituted solution. The needles on the syringes are removed, the syringe barrels and plungers are supported in a syringe body, and the syringe nozzles are received in a manifold.

Another approach is disclosed in U.S. Patent No. 4,735,616 to Eibl. Dry powder is stored within both barrels of a dual barrel syringe. In each instance, the powder is stored on one side of a sliding plug, and solvent is stored on the other side. When the user presses down on the syringe plunger, the plugs slide along the barrels to positions at which the barrels each have a bulge that provides a bypass for the solvent to reach the powder.

In these prior art dispensers, the manifold passages connecting the two syringes to the common nozzle are typically narrow conduits of circular cross section. E.g., U.S. Patent No. 4,631,05 to Redl. Carpules have been used in some syringes, e.g., U.S. Patent No. 3,767,085 to

Cannon shows a dual carpule syringe for mixing compositions used in dentistry.

Summary of the Invention The present invention provides an improved dispenser suitable, e.g., for quickly and easily setting up and dispensing two-part sealants or other two-part compositions requiring separation of the components until just prior to application on the tissue surface.

In a first aspect, the invention features a dispenser in which a dry powder (one component of a two-part adhesive tissue sealant) is stored in a container (e.g., a carpule) having a septum at one end, an open end opposite the septum, and a movable plug. The powder is retained at the septum end of the container by the movable plug, which is displaced and pushed back as the solvent used for reconstituting the powder is introduced (e.g., through the septum). The second part of the tissue sealant is contained within a second container, also with a movable plug. After the first part is reconstituted, a manifold is fitted which pierces both septums and allows the contents to be dispensed. A dual syringe body supports the containers, and has pistons that enter the open ends to advance the movable plugs.

Preferred implementations of the first aspect may include one or more of the following features. The first component may be a dry powder of a water-compatible or water- soluble crosslinking agent.

The aqueous solution for dissolving the powder may be introduced through the first septum (e.g., either via the piercer or via a second injection through the septum by a syringe). The movable plug may be positioned in a position in which the space between the plug and the septum is substantially the minimum necessary to contain the dry powder, thereby reducing the amount of air in that space and consequently the amount of pressure rise associated with injecting liquid through the septum. The movable plug can move away from the septum as liquid is injected to reduce any pressure rise. The second component stored in the second carpule may be a solution.

The second component may be a protein dissolved in an aqueous buffer and capable of reacting with the solution of the first component to provide the adhesive tissue sealant.

In a second aspect, the invention features an improved manifold for a two-part dispenser. Two containers (e.g., carpules), each having a septum at one end, an open end opposite the septum, and a movable plug, are supported in a dual syringe body, which has pistons configured to enter the open ends of the containers to advance the movable plugs. A manifold has cavities that receive the septum ends of the containers, and a disk supporting a piercer (e.g., hollow needle) is mounted in the base of each cavity so that the septum of a container is pierced when it is installed in a cavity. Each disk is supported a distance above the base of a cavity to form a plenum defined by the disk and adjacent walls of the base of the cavity. Liquid exiting a container travels through the lumen of the piercer, then into the adjacent plenum, and then out of the plenum along a conduit extending to the nozzle. This arrangement of disks each supporting a piercer and forming a plenum provides an effective, relatively low-cost way of constructing a manifold for connecting carpule piercers to a common nozzle. Preferred implementations of the second aspect may include one or more of the following features.

Each disk may be sealed to the surrounding wall of the cavity (e.g., by an elastomeric sealing member on the disk) so that the adjacent plenum is defined by the disk and the base of the cavity.

The conduit and piercer lumen may each communicate with the plenum at laterally spaced apart locations so that flow from the piercer lumen to the conduit changes direction from a generally longitudinal flow path through the piercer lumen, to a generally lateral direction in the plenum, and then to a generally longitudinal flow path in the conduit.

The disk may be supported from the base of the cavity by standoffs.

The first container may contain a quantity of the first component in the form of a dry powder so that the first component must be dissolved prior to use by introduction of an aqueous solvent. The second container may contain a quantity of protein in an aqueous buffer that is capable of reacting with a dissolved first component to provide an adhesive tissue sealant.

In a third aspect, the invention features a method for dispensing a component stored in a dispenser in dry powder form and reconstituted by introduction of a solvent. A carpule is provided with a septum at one end, an open end opposite the septum end, and a movable plug disposed therebetween. The dry powder is stored between the septum and the movable plug. Solvent is introduced into the interior of the container by piercing the septum with a syringe and injecting the solvent into the carpule. The carpule is installed in a syringe body and manifold, the latter providing a flow path from the piercer to an outlet nozzle.

Preferred implementations of the third aspect may include one or more of the following features.

Installing the carpule in the syringe body and manifold may occur before or after the solvent is injected through the septum. The first movable plug may be positioned in a position in which the space between the plug and the septum is substantially the minimum necessary to contain the dry powder, thereby reducing the amount of air in that space and reducing the pressure increase within the carpule when the solvent is introduced by piercing the first septum. The movable plug can move away from the septum as liquid is injected to reduce any pressure rise.

The dispenser may comprise a second carpule comprising a second septum at one end, an open end opposite the second septum and a second movable plug disposed therein, the second carpule containing a second component, and the syringe body and manifold may be sized and configured to accept the first and second carpule.

The second component may be a protein in an aqueous buffer and capable of reacting with the first component to provide an adhesive tissue sealant.

The dry powder of the first component may be water-compatible or water- soluble crosslinking agent capable of reacting with the second component to provide the adhesive tissue sealant.

The invention provides a significantly simpler and easier to use dispenser, one particularly well suited to handling adhesive tissue sealants. It is also simple and relatively inexpensive to manufacture. It delivers excellent performance, and is particularly good at mixing solutions reconstituted from dry powder. Other features and advantages of the invention will be apparent from the following description and drawings, and from the claims.

Installing the carpule in the syringe body and manifold may occur before or after the solvent is injected through the septum.

The first movable plug may be positioned in a position in which the space between the plug and the septum is substantially the minimum necessary to contain the dry powder, thereby reducing the amount of air in that space and reducing the pressure increase within the carpule when the solvent is introduced by piercing the first septum. The movable plug can move away from the septum as liquid is injected to reduce any pressure rise. The dispenser may comprise a second carpule comprising a second septum at one end, an open end opposite the second septum, and a second movable plug disposed therein, the second carpule containing a second component, and the syringe body and manifold may be sized and configured to accept the first and second carpule. The second component may be a protein in an aqueous buffer and capable of reacting with the first component to provide an adhesive tissue sealant.

The dry powder of the first component may be a water-compatible or water- soluble crosslinking agent capable of reacting with the second component to provide the adhesive tissue sealant. The invention provides a significantly simpler and easier to use dispenser, one particularly well suited to handling adhesive tissue sealants. It is also simple and relatively inexpensive to manufacture. It delivers excellent performance, and is particularly good at mixing solutions reconstituted from dry powder.

Other features and advantages of the invention will be apparent from the following description and drawings, and from the claims.

Brief Description of the Drawings

Figs. 1A, IB, 1C and ID are side views of elements of a preferred embodiment of the invention; Fig. 2 is a side view of the base of the dual syringe body;

Fig. 3 is a bottom view of the base of Fig. 2;

Fig. 4 is a cross-sectional view taken along section lines 4-4 in Fig. 3;

Fig. 5 is a cross-sectional view taken along section lines 5-5 in Fig. 3;

Fig. 6 is a perspective view of the dual piston; Fig. 7 is a side view of the dual piston of Fig. 6;

Fig. 8 is a side view of the manifold;

Fig. 9 is a bottom view of the manifold of Fig. 9; and

Fig. 10 is a cross-sectional view taken along section lines 10-10 in Fig. 9. Detailed Description Referring now to Figs. 1A-1D, side views of the elements of a dispenser kit 20 according to the present invention are illustrated. The dispenser kit 20 includes a first carpule 22, a second carpule 24, a dual syringe body 26 adapted to receive and support the first and second carpules, a syringe 28, and a manifold (nozzle body) 30. First carpule 22 has a first septum 32 at one end of first carpule body 34, the other end of the first carpule body being an open end 36. There is a first movable plug 38 disposed within the first carpule 22 so that a quantity of a first component 40 is contained between the first septum 32 and the first movable plug. In preferred embodiments, first component 40 is a quantity of dry powder of a water-compatible or water-soluble multi-functional crosslinking agent. Conveniently, the first carpule body 32 has a ridge 42 near open end 36 to facilitate the retaining of the first carpule within dual syringe 26.

First movable plug 38 is positioned so that the space between the plug and the septum is substantially the minimum necessary to contain the dry powder, thereby reducing the amount of air in the space between the plug and septum. Reducing the amount of air entrapped with the powder has the benefit that when solvent is injected into the carpule to dissolve the powder there is less rise in pressure within the carpule, as the plug is able to move away from the septum to reduce any pressure rise. Elevated pressure is undesirable in that it could lead to difficulty when the solvent is injected into the carpule and when the carpule is later pierced on insertion in the manifold 30. An elevated pressure could result, once piercing occurs, in immediate flow of the first component into the manifold and nozzle.

Second carpule 24 has a second septum 44 at one end of second carpule body 46, the other end of the second carpule body being an open end 48. There is a second movable plug 50 disposed within the second carpule 24 so that a quantity of a second component 52 is contained between the second septum 44 and the second movable plug. In preferred embodiments, second component 52 is a quantity of protein in an aqueous buffer. Conveniently, the second carpule body 46 has a ridge 56 near open end 48 to facilitate the retaining of the second carpule within dual syringe 26. Dual syringe body 26 includes a base 57 having two cylinders 58 and 60 adapted to receive and support the first and second carpules 22 and 24. Dual piston 62 is provided, adapted to enter the open ends 36 and 48 of the carpules 22 and 24 so as to contact and advance the first and second movable plugs 38 and 50. A flange 64 is provided to allow the practitioner to grip the dual syringe body 26 during injection in the conventional manner for syringes. A pair of latches 66 (only one being visible in this view) are provided to attach dual syringe body 26 to manifold 30.

Syringe 28 is conveniently of conventional type, having a body 68, a nozzle or needle 70 at one end, and a piston 72 at the other end. A protective cap 74 is provided to preserve the needle 70 in a sterile condition until the kit is to be used. The needle 70 is adapted to pierce the first septum 32 for injecting the aqueous solvent 76 contained within syringe 28 into the first carpule 22. In a preferred embodiment, solvent 76 is pyrogen free sterile water for dissolving the dry powder of a water-compatible or water-soluble multi-functional crosslinking agent. Manifold 30 is adapted to fit over and pierce the first and second septums 32 and 44 after the first component 40 has been mixed with the solvent 76. Manifold 30 has a dual nozzle 78, which in the preferred embodiment keeps the first and second components 40 and 52 complete separate until just after the moment of dispensing. A pair of receptacles 80 (only one being visible in this view) are provided to attach dual syringe body 26 to manifold 30 by receiving latches 66. Optionally, the kit 20 may include a static mixer and/or dispensing tip which is adapted to be fitted onto nozzle 78.

Referring now to Fig. 2, a side view of the base 57 of the dual syringe body 26 is illustrated in isolation. It will be noted that the latches 66 each have a projection 82 which allows them to interact with the receptacles 80 as discussed above. Referring now to Fig. 3, a bottom view of the base 57 of Fig. 2 is illustrated. In this view it can be seen that cylinders 58 and 60 have internal through bores 84 and 86 respectively which are sized to receive first and second carpules 22 and 24 (shown in Figs. 1 A-1D). It can also be seen that projecting inwards from the walls of each of the cylinders 58 and 60 are four tapered ledges 88 which interact with ridges 42 and 56 of first and second carpules 22 and 24 respectively to retain the carpules within the bores 84 and 86.

Referring now to Fig. 4, a cross-sectional view of base 57 taken along section lines 4-4 in Fig. 3 is illustrated. In this view it can be seen that projecting inwards from the walls of each of the cylinders 58 and 60 are four tapered retainers 90 which interact with and retain dual piston 62 within the bores 84 and 86. This will be discussed in more particularity below. In Fig. 5, a cross-section view of base 57 taken along section lines 5-5 in Fig. 3 is illustrated so that the features of the base can be more readily seen. Referring now to Figs. 6 and 7, views of dual piston 62 are illustrated. A pair of push rods 92 and 94 extend from a thumb plate 96. Each of the push rods 92 and 94 has a circumferential ridge 97 and 98 adapted to interact with the tapered retainers 90 discussed in connection with Figs. 4 and 5 to retain dual piston 62 within bores 84 and 86. The free ends 100 and 102 are intended to contact movable plugs 38 and 50 (seen in Figs. 1 A- ID) to advance them and pressurize the fluid in carpules 22 and 24 when pressure is exerted by the hand of the practitioner on the thumb plate 96.

Referring now to Fig. 8, a side view of the manifold 30 is illustrated in isolation. The manifold 30 includes barrels 104 and 106 which are sized and shaped to enclose the ends of the of carpules 22 and 24 having septums 32 and 44 when the carpules have been inserted into the base 57 and the manifold has been attached to the base by interlocking latches 66 with receptacles 80.

Referring now to Fig. 9, a bottom view of manifold 30 of Fig. 8 is illustrated. In this view it can be seen that nozzle 78 includes openings 108 and 110 to allow the components in carpules 22 and 24 to be dispensed as separate solutions. A further nozzle element (not shown) could be installed over nozzle 78 to contain and promote mixing of the two streams of liquid emerging from openings 108, 110.

Referring now to Fig. 10, a cross-sectional view taken along section lines 10-10 in Fig. 9 is illustrated. It can now be seen that barrels 104 and 106 have cylindrical, hollow interiors (or cavities) 112 and 114 respectively to receive the carpules 22 and 24. A pair of piercers 116 and 118 are provided to pierce the septums 32 and 44 when the manifold 30 is mounted on the base 57. The piercers are conveniently mounted on mounting disks 120 and 122, the edges of which form a seal with the walls of cylinders 104 and 106. This may be conveniently accomplished by solvent bonding, by ultrasonic welding, or by having an elastomeric member (e.g., an o-ring within a groove) along the edge of the mounting disks 120 and 122 which contact the walls 104 and 106 and hold the mounting disks 120 and 122 in place by friction fit. Access is available for the contents of carpules 22 and 24 through the hollow central bore of each of the piercers into plenums 124 and 126 and on into passageways (or conduits) 128 and 130 to openings 108 and 110. Several standoffs 132 are conveniently molded into the base of cavities 112 and 114 to position the mounting disks 120 and 122 in the right location to provide for plenums 124 and 126.

The dispenser kit is easily sterilized. The carpules can be sterile filled, and the assembled kit undergoes a terminal sterilization (e.g., with ethylene oxide gas).

Other embodiments of the invention are within the scope of the following claims. E.g., in some aspects of the invention, materials other than an adhesive tissue sealant may be dispensed, the solvent for dissolving the dry powder could be nonaqueous, and the solvent (whether aqueous or nonaqueous) could be introduced into the carpule by means other than a syringe piercing the septum (e.g., the solvent could be drawn into the carpule by moving the syringe plunger outwardly to create a vacuum). More than two barrels and carpules (e.g., three) could be fitted to a syringe body and manifold. Individual pistons could be used instead of the dual piston 62.

Claims

WHAT IS CLAIMED IS:

1. A dispenser for simultaneously dispensing first and second components of an adhesive tissue sealant, wherein at least the first component is stored in the dispenser as dry powder that is dissolved prior to use by introduction of a solvent, the dispenser comprising the combination of:

(a) a first container comprising a first septum at one end, an open end opposite the first septum, and a first movable plug disposed therein, the first container containing a quantity of the first component in the form of a dry powder stored between the first septum and the first movable plug;

(b) a second container comprising a second septum at one end, an open end opposite the second septum, and a second movable plug disposed therein the second container containing a quantity of the second component;

(c) a dual syringe body sized and configured to receive and support the first and second containers, and having pistons sized and configured to enter the open ends of the containers to advance the first and second movable plugs; and

(d) a manifold sized and configured to fit over and pierce the first and second septums and to convey the first and second components via first and second flow paths to a nozzle from which the first and second components are dispensed to combine to form the adhesive tissue sealant.

2. The dispenser of claim 1 wherein, prior to use, the first movable plug is positioned in a position in which the space between the plug and the septum is substantially the minimum necessary to contain the dry powder, thereby reducing the amount of air in that space.

3. The dispenser of claim 1 wherein the nozzle is sized and configured so that the first and second component are kept separated until dispensed from the nozzle.

4. The dispenser of clam 1 wherein the second component stored in the second container comprises a liquid.

5. The dispenser of claim 4 wherein the second component is a protein in an aqueous buffer and is capable of reacting with a solution of the first component to provide the adhesive tissue sealant.

6. The dispenser of claim 5 wherein the dry powder forming the first component is a water-compatible or water-soluble crosslinking agent.

7 The dispenser of claim 1 in combination with means for introducing the liquid solvent through the first septum into the first container by means other than the piercer.

8. The dispenser of claim 1 in combination with a syringe sized and configured to inject a liquid solvent into the first container through the first septum.

9. The dispenser of claim 8 wherein the syringe is preloaded with the liquid solvent.

10. The container of claim 1 wherein the first and second containers are carpules.

11. The dispenser of claim 1 wherein the pistons are connected to form a dual piston,.

12. the elements of claim 8 combined as a kit.

13. A dispenser for simultaneously dispensing first and second components of a two-part composition, the dispenser comprising the combination of:

(a) a first container comprising a first septum at one end, an open end opposite the first septum, and a first movable plug disposed therein, the first container containing a quantity of the first component;

(b) a second container comprising a second septum at one end, an open end opposite the second septum, and a second movable plug disposed therein, the second container containing a quantity of the second component;

(d) a manifold sized and configured to fit over the first and second septums, the manifold having first and second cavities into which the first and second containers are received;

(e) first and second piercers mounted in the manifold for piercing the first and second septums, each piercer extending through and being supported by a disk that is supported adjacent the base of a cavity, each disk being supported a distance above the base of cavity to form first and second plenums, each defined by a disk and adjacent walls of the cavity, the first and second piercers conveying the first and second components to the first and second plenums;

(f) first and second conduits in the manifold for conveying the first and second components from the first and second plenums to a nozzle from which the first and second components are dispensed to combine to form the adhesive tissue sealant.

14. The dispenser of claim 13 wherein each disk is sealed to the surrounding wall of the cavity.

15. The dispenser of claim 14 wherein the seal between the disk and the surrounding wall is provided by an elastomeric seal member on the disk.

16. The dispenser of claim 14 wherein the wall of the cavity is cylindrical and the periphery of the disk is circular.

17. The dispenser of claim 14 wherein one of the first and second conduits and one of the first and second piercers communicate with the corresponding plenum at laterally spaced apart locations so that flow from the piercer lumen to the conduit changes direction from a generally longitudinal flow path through the piercer lumen, to a generally lateral direction in the plenum, and then to a generally longitudinal flow path in the conduit.

18. The dispenser of claim 14 wherein each disk is supported from the base of the cavity by standoffs.

19. The dispenser of claim 13 wherein the first container contains a quantity of the first component in the form of a dry powder so that the first component must be dissolved prior to use by introduction of an aqueous solvent and wherein the second component is a protein in an aqueous buffer and the first component is capable of reacting with the second component to provide an adhesive tissue sealant.

20. The dispenser of claim 13 wherein the first and second containers are carpules.

21. A method for dispensing a first component stored in the dispenser as dry powder that is dissolved prior to use by introduction of a solvent, the method comprising: (a) providing a first carpule comprising a first septum at one end, an open end opposite the first septum, and a first movable plug disposed therein, the first carpule containing the dry powder stored between the first septum and the first movable plug; (b) introducing the solvent into the first carpule to dissolve the dry powder to form a solution of the first component by piercing the first septum with a syringe and injecting the solvent into the first carpule;

(c) installing the first carpule in a syringe body, the syringe body having a piston adapted to enter the open end of the carpule to contact and advance the first movable plug; and

(d) providing a nozzle body sized and configured to fit over and pierce the first septum and to convey the solution of the first component via a flow path to a nozzle from which the first component is dispensed.

22. The method of claim 21 wherein step (b) is performed after step (c).

23. The method of claim 21 wherein, prior to use, the first movable plug is positioned in a position in which the space between the plug and the septum is substantially the minimum necessary to contain the dry powder, thereby reducing the amount of air in that space and reducing the pressure increase within the carpule when the solvent is introduced by piercing the first septum.

24. The method of claim 21 further comprising the step of providing a second carpule comprising a second septum at one en, an open end opposite the second septum, and a second movable plug disposed therein, the second carpule containing a second component, and wherein the syringe body and nozzle body are sized and configured to accept the first and second carpule.

25. The method of claim 24 wherein the second component is a protein in an aqueous buffer and is capable of reacting with the first component to provide an adhesive tissue sealant.

26. The method of claim 25 wherein the dry powder of the first component comprises a water-compatible or water-soluble crosslinking agent capable of reacting with the second component to provide the adhesive tissue sealant.

27. The kit of claim 12 wherein first and second containers are sterile filled and the kit is terminally sterilized.

28. The dispenser of claim 13 wherein first and second containers are sterile filled and the dispenser is terminally sterilized.