AU7242400A - A system for applying a fibrin sealant - Google Patents

Description

AUSTRALIA

Patents Act COMPLETE SPECIFICATION

(ORIGINAL)

Class Int. Class Application Number: Lodged: Complete Specification Lodged: Accepted: Published: Priority Related Art: 0 0 0 Name of Applicant: Bristol-Myers Squibb Company Actual Inventor(s): Niels-Erik Holm, Allan Garbasch, John E Fairbrother, Frank Castellana Address for Service: PHILLIPS ORMONDE FITZPATRICK Patent and Trade Mark Attorneys 367 Collins Street Melbourne 3000 AUSTRALIA Invention Title: A SYSTEM FOR APPLYING A FIBRIN SEALANT Our Ref: 633693 POF Code: 232049/232049 The following statement is a full description of this invention, including the best method of performing it known to applicant(s): 1 6006q 2 A SYSTEM FOR APPLYING A FIBRIN SEALANT This application is a divisional application of Australian Patent Application No.

14118/97 the entire contents of which are herein incorporated by reference.

Technical Field The present invention relates to a system for co-applying one or more components of a fibrin sealant with a gas to form a spray.

Background Art US-PS No. 4,359,049 to Redl discloses a double barrel syringe for applying a tissue adhesive such as fibrin glue or fibrin sealant to a human or animal in need thereof. The fibrin sealant described comprises predominantly two major components, a fibrinogen-containing component and a thrombin-containing component, each in liquid form upon use. Essentially, the thrombin and fibrinogen, when mixed, provide that the peptide chains of the fibrinogen are cleaved and conditions are provided so that the resulting fibrin polymerises into a clot which is useful for sealing fluid and air leaks, in haemostasis and to connect tissue. To avoid premature clot formation double-barrelled applicators 20 are employed which, of course, keep the two components separate until application to a patient is required. The'049 patent discloses that pistons within the two cartridges, each containing one component, can be commonly actuated to dispense fluid simultaneously from each.

o 25 Other prior art patents describe various mixing heads for mixing two or more components used in these and other surgical sealants. For example, go o• V:RhonavSpecfficatironstIVB of 14118.doc US-PS No. 5,116,315 assigned to Hemaldics describes a head where the liquid conducts leading from the component cartridge enter a mixing chamber fashioned so as to provide a swirling of the components before they exit a common exit channel. Adequate mixing of the components is desired so as to form a uniform fibrin sealant. Inefficient mixing results in the coadministration of fibrinogen and thrombin which may only result in a small yield of actual sealant. A difficulty with fibrin sealant applicators can be the premature formation of the clot within the cvice, especially those devices where the components are mixed within a mixing head and/or those devices wherein the components exit through a common channel.

After the first spray of sealant is complete, a clot may block the exit channels rendering the applicator useless and greatly reducing the surgeon's flexibility in carrying out the sealant part of the surgical procedure.

US-PS No. 4,631,055 to Immuno includes a gas conveying channel for blowing a gas through the needle or mixing head during discharge of the components. However, an even, uniform distribution of the materials over the anatomical area of interest is still not achieved. Indeed, a significant "amount of the components are wasted.

EP-PS No. 592,242 to Edwardson et al. discloses the first completely autologous fibrin sealant. It provides for the coadministration of a fibrin monomer solution with a buffer solution conducive to polymerisation of the fibrin monomer prepared in less than 30 minutes from a single source of blood (preferably that of the patient to receive the sealant). This breakthrough technology provides a fixed amount of fibrin monomer solution from a sample of about 140 to 160 ml of blood. Uniform and efficient mixing is even more important in order to benefit from this safe, efficient, autologous sealant product and therefore new devices and methods for applying two or more components to form a surgical sealant would be useful addition to the art.

PCT Application W096/17618 discloses a device and a method of applying components of a fibrin sealant. The device comprises a source of a gas and a reservoir for each component wherein the gas source and component reservoirs can be actuated by common means. Each of the reservoirs and gas source are separately in fluid communication with a spray head having a center aperture at its outlet end and annular apertures, arranged concentric with and radially outward from the center aperture whereby the gas and each of said components are discharged through separate apertures. Preferably, the gas is discharged through the center aperture and the fibrin sealant forming components are discharged separately through each of the annular apertures.

The discussion of the background to the invention herein is included to explain the context of the invention. This is not to be taken as an admission that any of the material referred to was published, known or part of the common general knowledge in Australia as at the priority date of any of the claims.

:i Brief Description of the Invention S 20 In accordance with the present invention there is provided a system for applying a fibrin sealant to a site in need thereof comprising: a spray pen adapted to be held and actuated in one hand and comprising at one end a spray head from which one or more components of said sealant and a gas are dispensable and separate channel means for transferring said one or more components and gas to said spray from a second end of said pen; tubing means providing fluid communication between said second end of said spray pen and a source of said one or more components and gas; and an expelling means remote from said spray pen comprising a source of said gas and sources of said one or more components and controllable means for 30 transferring said gas and one or more components from said expelling means, through said tubing means, through said spray pen and out of said spray head.

In a preferred embodiment of the present invention, the flow rates of the one or more components and gas are selected such that the one or more components VARhona\SpefficajonsDIVB of 141iB.doc preferably liquid, are drawn or sucked into the gas being expelled from the spray head as they exit outlets of their respective channel means.

In this manner the one or more components are mixed outside the spray head before they are sucked into the gas jet since the component exiting the farthest from the gas outlet sucked across the outlet nearer to the gas outlet. The components are further mixed in the gas jet and the mixture and gas form a spray. In addition, the outlets of the channel means, are preferably relatively small with the result that a relatively small amount of the components is exposed to the surroundings when the expelling is stopped. Furthermore, the clogging tendency in the outlets is substantially eliminated since there is no mixing of components in the nozzle head. Also the amount of the components remaining in said outlets after the application procedure is almost negligible.

The latter factor is of vital importance in connection with a mixture of an autologous fibrin monomer solution and a buffer solution where the amount of fibrin monomer solution is relatively limited and accordingly must be utilized to an optimum.

When the components are discharged at mutually differing volume flows, it is S* 20 according to the invention particularly advantageous to discharge the component with the lowest volume flow through the outlet of the channel means accommodated farthest away from the gas jet. In this manner it is ensured that the component being discharged with the lowest volume flow is mixed with the component being discharged with the highest volume flow before said 25 components enter the gas jet in the mixed stage.

The expelling of the components through the spray head may according to the invention be carried out by means of an expelling means, which is activated by means of an electronic control unit, and the expelling of the gas may be carried 30 out by means of a pump also activated by means of the electronic control unit, said electronic unit in turn being activated by means of a signaller controlled by the user handling the spray pen. As a result, the expelling of the components and the gas can be carried out in a homogenous manner at substantially constant volume flows.

V:RhonaSpecificatioinsDIVB of 14118.doc 6 In connection with a method using syringes with their respective expelling piston as containers for the components, the interruption of the expelling means through the control unit may according to the invention imply that the control unit activates said expelling means to retract the pistons of the syringes a short distance with the result that the components are retracted a short distance from the outlets of the spray head. As a result, the risk of the two components coming into contact with one another and consequently the risk of a clogging of the outlets of the channel means have been considerably reduced.

The invention relates furthermore to a device for applying a mixture of two liquid components kept in their respective containers, where said components are fed to a spray pen through their respective liquid-transferring means, said spray pen head comprising a separate outlet channel for each component as well as a separate outlet channel for a gas fed through a gas-transferring means from a gas source, and where said device comprises an expelling means simultaneously activating the containers containing their respective component.

The device according to the invention is characterised in that the component outlets and the gas outlet in the spray head are aligned along a substantially rectilinear line, the gas outlet being accommodated at one end of the line of 20 outlets. Such a spray head is relatively easy to manufacture by way of any convenient means, injection moulding, and furthermore it ensures an efficient, good mixture of the components.

t l V:VftnSpedflcationsMVB of 14118.doc 7 According to the invention the spray head may be supported by an elongated handle, and the component and gas-transferring means may be substantially resilient tubings which extend from said handle to a remote accommodation of the expelling means with the containers and the gas source, respectively. The resulting handling is relatively easy and can be carried out without interference by the presence of the expelling means and the gas source.

Furthermore, the handle may according to the invention be associated with a push-button for actuation of the expelling means and the feeding of gas through a differential pressure-adjusting device. As a result, the component source containers, the pistons in the syringe cartridges, can be actuated to supply the gas and components without the presence of electricity adjacent the spray head and the associated handle.

When the containers used for the components are syringes with their respective piston for expelling the component in question, the expelling means may according to the invention comprise a holder for the securing of the syringes, and an electrically driven elevator means for a simultaneous actuation of the :i pistons of the syringes with the result that a particularly accurate and constant S.o 20 volume flow set in advance is obtained through each outlet in the spray head upon such actuation.

Finally, it is according to the invention particularly preferred that the expelling means and the gas source in form of a gas pump are combined as a separate unit together with an electrically driven control unit, said control unit being adapted to control the expelling means and the gas pump at a signal from the user of the spray pen.

Brief Description of the Drawings The invention is explained in greater detail below with reference to the accompanying drawing, in which Fig. 1 shows a device according to the invention, V:%Rhona\SpedficatIonSDIVB of 14118.doc 8 Fig. 2 is a front view of a nozzle head used in the device, and Fig. 3 the same taken along the lines 1-1 in Fig. 2.

Fig. 4 shows another view of a device according to the invention.

Description of the Preferred Embodiments The device shown in Fig. 1 comprises a spray head 1 secured at the end of a handle designated the general reference numeral 2. This handle comprises a tubular body 3 connected through a transition portion 4 to the spray head 1, said tubular body 3, said transition portion 4, and said spray head 1, respectively, having a circular cross section. However, any convenient handle or means to hold or accommodate the spray head could be employed.

As illustrated in particular in Figs. 2 and 3, the spray head is preferably conically shaped with three through channels 5, 6 and 7, where two channels serve as :I outlet channels for two different components while the third channel serves as outlet channel for a gas. Of course, additional channels and outlets can be e*.

utilized as required by the particular material or product to be applied. The outlet channels 5, 6 and 7 are formed by any convenient means, by the spray head being molded in a suitable plastic material, such as polystyrene material, SAN. The outlet channels extend from their respective opening at the broadest end of the spray head 5 adjacent the handle 2, said openings being placed at the corners of an isosceles triangle, cf. the dotted lines of Fig. 2. At the corners of the isosceles triangle, each channel is of a diameter of approximately 1.2 mm, and preferably after a short distance with a substantially constant diameter each channel narrows down so as to be of the desired diameter at the opposite end. This is done to accommodate using fluid transfer tubing which may be larger in diameter than the desired outlet size. Any convenient diameter outlets can be utilized, but outlets having diameters of .3 to mm and preferably .3 mm are preferred. At this end of the channels, the outlets are aligned along a rectilinear line with a center distance of V:\Rhona\SpedficationsDIVB of 14118.ldoc 9 approximately 0.5 mm. The outlets have been designated the reference numerals 8, 9 and 10, respectively, in Fig. 2.

The above short distance of a substantially constant inner diameter of the outlet channels 5, 6 and 7 in the spray head serves to receive the end of fluid transfer tubes 11, 12 and 13 respectively, which in turn are provided for the feeding of said components and said gas. These fluid transfer tubes 11, 12 and 13 extend axially through the handle 2 and forwards to a coupling plate 14, which is arranged and associated with an expelling means for the components and designated the general reference numeral 15, as well as a gas pump 16. The tubings 11-15 can be surrounded by a resilient protecting jacket 17. At the end of the handle 2 opposite the spray head 1, the protecting jacket 17 with the tubings 11-12 can be preferably retained in the handle 2 by means of a cap 18 inserted thereon. The cap 18 is provided with a central, through opening and co-operates with the protecting jacket 17 and is retained in said handle 2 by way of friction.

As mentioned above, the device according to this invention comprises a spray applicator or "pen" which is remote from, but in fluid communication with, the .i 20 sources of liquid components and/or gas. In areas such as the application of fibrin sealants this provides a greatly improved tool for the surgeon. This is because the prior art fibrin sealant applicators all include the sources of components in the hand-held applicator. As discussed previously, prior art fibrin sealant applicators are typically double-barrel syringes attached to a Ypiece or mixing lead. This is generally an awkward instrument for the surgeon to control and even when the surgeon uses both hands, a less than desirable application is achieved. One embodiment of the device of this invention is set forth in Figure 4.

30 The present spray applicator comprises a spray head with outlets and separate fluid transfer tubes for each component providing fluid communication between the outlets and the sources of components to be applied. Preferably, the spray pen has a handle which can be an elongated "pen" accommodating the spray head at one end with the fluid transfer tubes extending therethrough, exiting the of 14118.doc opposite end and continuing to said sources of components. The sources of components at the remote location, which can be in any convenient containers, syringe cartridges, are preferably part of an expelling means which dispenses or expels these components from the sources through the fluid transfer tubes and out of the outlets of the spray head, as desired by the operator or surgeon. This can be accomplished by any convenient means such as valves in the spray head or handle of the applicator or preferably by providing an actuating means which sends a signal to the supply unit upon actuation by the operator or surgeon. The actuating means can be a foot pedal or a button in the applicator as are known in the device art. In a preferred embodiment the actuating means is a resilient bladder positioned in the applicator and connected via a pressurized line to a signal means, such that upon depression of the resilient bladder by the fingertip or hand of the surgeon the signal means detects a difference in pressure and signals the supply unit to V:\Rho\Spedfit8ns\DIVB of 14118.doc supply the components.

The gas used to co-apply the components can be also supplied from, and controlled by, the expellingness in a preferred embodiment or, can be supplied and/or controlled separately from the liquid components.

Returning to Figure 1 in further describing the preferred expelling means, at the coupling plate 14, the fluid transfer tubes 11, 12 are inserted in their respective through bore (not shown), at the opposite end of which the tubings are adapted to be connected with their respective syringe 19 (or other convenient component source container) for their respective component. The drawing shows only one syringe 19 communicating with the tubing 11. The coupling plate 14 is adapted such that both the tubings 11 and 12 and the syringes, such as the syringe 19, can be easily removed.

Beyond the latter coupling plate 14 for receiving the syringes 19, the expelling means 15 comprises an elevator means 20 for expelling the 15 contents of the syringes oO•. As illustrated in Fig. 1, the third tubing 13 serves to feed the gas and is _.connected to the gas pump 16 through an outlet nozzle 21 and a luer coupling 22. The luer coupling 22 implies furthermore that the above tubing can be easily coupled to and removed from said coupling plate 14.

A filter means is provided within the outlet nozzle 21.

As illustrated in Fig. 1, a fourth tubing 23 is furthermore accommodated inside the protecting jacket 17. The said fourth tubing 23 is at one end associated with a diagrammatically shown push-button 24 inside the handle 2, while the opposite end thereof is detachably connected to a control unit 25 in a manner not described in greater detail, said control unit being associated with the expelling means 15. When the push-button is pressed down, the tubing 23 with said push-button 24 and the control unit is adapted to transfer the resulting pressure difference inside the tubing 23 as a signal to the control unit 25. As a result, the control unit initiates through the diagrammatically shown tubings 26, 27 the necessary activation of the elevator means 20 of the expelling means 15 and the air pump 16, respectively. The tubing 23 is detachably coupled to the control unit in a manner not described in greater detail by means known to those skilled in the art.

The described device is mainly intended for application of a mixture of two or more components in, fibrin monomer and a buffer fluid with a pH of 10, respectively, as set forth in the aforementioned WO 96/17638 and EP 592,242. These two components are received in their respective syringe, such as the syringe 19, said syringes being dimensioned such relative to one another that the desired mixing ratio is established by a simultaneous activation of the pistons of the syringes by means of the elevator means 20. The mixing ratio of the pH 10-buffer to fibrin monomer is preferably 1 to 7, and usually a 5 ml syringe is used for receiving fibrin monomer and a 1 ml syringe for the pH 10-buffer. The tubings 11-13 are aclol.

cording to a preferred embodiment shaped by way of co-extrusion, the inner layer of the tubings being made of polyurethane which is inert to the fluids in question, and the outer layer of said tubings being made of polyurethane or PVC. The tubings are formed with an inner diameter of 0.3 mm with the result that a length of 2 m only allows approximately 0.3 ml of fluid to be received in each tubing, a total of .6 ml of fluids.

When the expelling means 15 and the air pump 16 are activated by the ~push-button 24 being pressed down, the two components are expelled S"from their respective outlet in the spray head 1 while the gas is simultaneously being expelled through the associated outlet in the spray head.

The gas is expelled through the outlet at one end of the row of outlets, while the component to be fed in the lowest amount, viz. the pH-buffer, is expelled through the outlet 9 provided at the opposite end. The other component, fibrin monomer, is expelled through the outlet 8 in the middle of the row of outlets. These components can be expelled at any convenient rate but low flow rates have been found to be advantageous. Accordingly, the pH 10 buffer can be expelled at flow rates between .0040 and .0100 ml/sec and the fibrin solution between .028 and .070 ml/secs preferably at the aforementioned 1:7 ratio. Most preferably, the fibrin monomer and pH 10-buffer to be mixed are expelled at a volume flow of approximately 0.04 ml/sec and 0.0057 ml/sec, respectively.

Air is used as gas in the preferred embodiment, said air being sucked in from the surroundings and subsequently carried from the pump 16 through a filter to the spray head 1. Alternatively, any source of desired gas can be employed. The speed of the air molecules must be relatively high at the same time as the amount of air used must be kept at a minimum. An outlet diameter of 0.3 mm has the effect that the volume flow of the air is approximately 1.25 I/min. during the expellihg procedure, lower volume flow being preferred.

When the air and the two components flow out of their respective outlets, the fluids are sucked into the flow of air and are substantially atomized.

The mixing of the two fluid components has been at least partially accomplished when said components are sucked into the flow of air. A lowering of the respective discharge speeds is carried out by an adjustment of the diameters of the outlets and their mutually distance in such a manner that both are as small as possible. In this manner it is possible to operate with relatively long tubings, i.e. the distance between the spray head 1 and the coupling plate 14 can be relatively long, such as for instance 2 m. The low 14 discharge speeds render it possible to apply the liquid mixture in thin uniform layers with the result that a layer of a higher total thickness may be provided by laying more layers on top of each other.

The expelling of the components from the respective syringes is as mentioned carried out inside the expelling means 15 which forms a combined unit together with the control unit 25. Both the expelling means 15 and the control unit 25 are electrically driven. This unit may be placed relatively far away from the site where the mixture is to be applied, and it can be adapted for reuse, whereas the spray head with the handle 2 and tubings 11, 12, and 13 may be adapted to be disposable. The control unit 25 can be such that an interruption of the application procedure before the syringes 19 are empty can have the effect that the elevator means 20 retracts the pistons in the syringes 19 a short distance in such a manner that the fluids in question are sucked a short distance away from the outlets in the 15 spray head 1. In this manner it is avoided that an interruption of the apply- .:ing procedure involves a post-expelling caused by pressures accumulated in the walls of the tubings, and especially in optionally present air bubbles in the syringe containing fibrin I. The preferred retraction volume is approxii mately 0.04 ml, which corresponds to the expelling for 1 sec.

The described device renders it possible to apply a fluid mixture in a thickon hess of approximately 170 pm, which implies that an amount of 5 ml fibrin "and a corresponding amount of pH 10-buffer can cover an area of 300 Scm 2 In connection with a length of tubing of approximately 2 m, the total amount of lost fluid in said tubings is, as mentioned, approximately 0.3 ml, whereby the amount of not used components after the complete expelling from the syringe is relatively low.

The invention has been described with reference to a preferred embodiment of a device for dispensing a mixutre of fibrin monomer and a pH 10-buffer. The mixing ratios used must ensure that the mixture is relatively neutral, and preferably said neutral state has already been achieved in the air before the application site has been reached. During the production procedure, the fibrin monomer in question has been admixed a coagulation-stopping agent with a pH-value of 4.6. The restoration of fibrin monomer to the neutral state implies that the coagulation process starts again.

The device in question can also be used for other components beyond fibrin 1 and pH 10-buffer, where the mixing ratios and the volume flows must be adapted to these components. For example, fibrinogen-containing components and components containing thrombin or a thrombin-like enzyme can also be applied using the instant device and method.

Throughout the description and the claims of the specification the word "comprise" and variations of the word, such as "comprising" or "comprises" is not intended to exclude other additives, components, integers or steps.

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Claims (4)

1. A system for applying a fibrin sealant to a site in need thereof comprising: a spray pen adapted to be held and actuated in one hand and comprising at one end a spray head from which one or more components of said sealant and a gas are dispensable and separate channel means for transferring said one or more components and gas to said spray from a second end of said pen; tubing means providing fluid communication between said second end of said spray pen and a source of said one or more components and gas; and an expelling means remote from said spray pen comprising a source of said gas and sources of said one or more components and controllable means for transferring said gas and one or more components from said expelling means, through said tubing means, through said spray pen and out of said spray head.

2. The system of claim 1 wherein said components are a fibrin monomer solution and a component which when mixed with said solution will cause said fibrin monomer to polymerize. o. 20

3. The system of claim 1 wherein said components are a fibrinogen- 0containing composition and a composition containing thrombin or a thrombin- S .i like enzyme.

4. The system of any one of claims 1 to 3 wherein a control means for SS 25 controlling the flow of said gas and components is located on said spray pen and is capable of communicating with said expelling means via signal means. DATED: 19 December 2000 PHILLIPS ORMONDE FITZPATRICK Attorneys for: BRISTOL-MYERS SQUIBB COMPANY V:RhonASpedficansDrVB of 14118.doc