WO2000009037A1

WO2000009037A1 - Material delivery devices and methods

Info

Publication number: WO2000009037A1
Application number: PCT/NZ1999/000126
Authority: WO
Inventors: Craig Robert Bunt; Michael John Rathbone
Original assignee: DEC RESEARCH
Current assignee: DEC RESEARCH
Priority date: 1998-08-14
Filing date: 1999-08-11
Publication date: 2000-02-24
Anticipated expiration: 2001-02-14
Also published as: AU5453199A; GB2361711A; GB0103901D0; NZ331391A

Abstract

Dispensing apparatus for a formulation including an active agent reliant upon expulsion of the formulation from a carrier reliant upon electrolysis gases generated in a way that allows such expulsion with an appropriate degree of control. Options include reliance upon a preference by electrolysis gases to travel along electrodes in the formulation over undirected travel through the formulation itself.

Description

MATERIAL DELIVERY DEVICES AND METHODS

TECHNICAL BACKGROUND

The present invention relates to dispensing apparatus for dispensing an agent or its precursor(s), methods of use thereof and related means, methods and applications. BACKGROUND ART

There are many instances where it is desired to activate or allow the activation of the release of an active agent or its precursor(s) whether as a single dose, a continuous dose or as a pulsile dose. Instances include microprocessor control active delivery of agents as might be used to release a medicament into a body cavity such as, for example, disclosed in PCT/NZ98/00011.

Many forms of such active delivery device (in addition to microprocessor or other logic means capable of empowering the release) utilise a reservoir or barrel having a membrane or piston that separates the formulation of the active agent or its precursor(s) from a gas generating arrangement, eg; a hydrogel and its electrodes. Such constructions are expensive to manufacture and have the prospect of occasional failure in the case of a piston arrangement owing to jamming. DISCLOSURE OF THE INVENTION The present invention is directed to providing dispensing apparatus which lends itself to an easier manufacturing procedure (as will be described hereinafter in more detail) and therefore it is an object of the present invention to provide such apparatus and related means, methods and procedures.

In a first aspect the present invention consists in dispensing apparatus for dispensing an agent or its precursor(s), said apparatus comprising or including a formulation (complex or simple) of the agent or its precursor(s), the formulation having an electrolyte character, a pair of electrodes disposed and enabled or enablable by electrolysis of at least part of the formulation to generate at least one gas, and housing means with at least one outlet (whether closed or not) housing at least part (preferably all) of said formulation and at least part of at least one (preferably both) of said electrodes, wherein enablement of the electrodes by the provision of an electric potential thereto generates by electrolysis gas(es) which

(a) if the formulation is of an appropriate viscosity or is appropriately conduited or has the electrodes appropriately positioned, issues from the formula and has the effect of opening said outlet which in the absence of the pressure of such gas(es) would remain closed and thus confine the formulation from its environs or in said housing means, and/or

(b) if the formulation is plug like in character [or is of a kind where the interface of the gas generating electrode(s) to the formulation offers to the gas(es) so generated at such electrode(s) less resistance to gas travel than the formulation itself] (for example, of a consistency less conducive to gas passage there-through, such as might be the case with a suitably viscous liquid, a suitable gel, a suitable solid, or the like, irrespective of orientation of the apparatus) migrates along at least one electrode away from said outlet so as to gas pressurise a movement of the formulation at least towards said outlet. Preferably in the scenario (b) the formulation whilst having an electrolyte character is in the form of a gel or solid but one in which preferably said agent or its precursor (for example, a bio-precursor) does not provide the majority or any of the electrolyte character of the formulation. In other forms however it may.

In the case of option (b) the outlet may include a disruptible seal or closure capable of being opened by movement of the formulation and/or gas pressure.

Preferably in option (b) the formulation is expressed at least partly out of said outlet.

In the case of option (a) the outlet is closed by a rupturible seal. In option (a) the formula is preferably liquid or, if solid or a gel, is conduited or provided with electrodes such that gas pressure directly (rather than the formula) ruptures the seal. In another aspect the present invention consists in dispensing apparatus for dispensing an agent or its precursor(s), said apparatus comprising or including a formulation (complex or simple) of the agent or its precursor(s), the formulation having an electrolyte character, a pair of electrodes disposed and enabled or enablable to generate at least one gas by electrolysis of at least part of the formulation, means enabling and/or to enable the pair of electrodes by the provision of an electric potential across the electrodes, and housing means with at least one outlet (whether closed or not) housing at least part (preferably all) of said formulation and at least part of at least one (preferably both) of said electrodes, wherein enablement of the electrodes by the provision of an electric potential thereto generates by electrolysis gas(es), and wherein the formulation is of a kind where the interface of the gas generating electrode(s) to the formulation offers to the gas(es) so generated at such electrode(s) less resistance to gas travel than the formulation itself] and wherein at least a substantial amount of any gas(es) generated at the gas generating electrode(s) migrates along said at least one electrode away from said outlet so as to gas pressurise a movement of the formulation at least towards said outlet.

Preferably the formulation whilst having an electrolyte character is in the form of a gel or solid but one in which preferably said agent or its precursor (for example, a bio-precursor) does not provide the majority or any of the electrolyte character of the formulation. In other forms however it may.

The outlet may include a disruptible seal or closure capable of being opened by movement of the formulation and/or gas pressure. Preferably the formulation is expressed at least partly out of said outlet.

In still another aspect the present invention consists in dispensing apparatus for dispensing an agent or its precursor(s), said apparatus comprising or including a formulation (complex or simple) of the agent or its precursor(s), the formulation having an electrolyte character, a pair of electrodes disposed and enabled or enablable to generate at least one gas by electrolysis of at least part of the formulation, means enabling and/or to enable the pair of electrodes by the provision of an electric potential across the electrodes, and housing means with at least one outlet (whether closed or not) housing at least part (preferably all) of said formulation and at least part of at least one (preferably both) of said electrodes, wherein enablement of the electrodes by the provision of an electric potential thereto generates by electrolysis gas(es), and wherein the formulation is of a consistency less conducive to gas passage therethrough than a low viscosity liquid (such as might be the case with a suitably viscous liquid, a suitable gel, a suitable solid, or the like, irrespective of orientation of the apparatus) whereby any electrode generated gas(es) migrates along such electrode away from said outlet so as to gas pressurise a movement of the formulation at least towards said outlet. Preferably the formulation whilst having an electrolyte character is in the form of a gel or solid but one in which preferably said agent or its precursor (for example, a bio-precursor) does not provide the majority or any of the electrolyte character of the formulation. In other forms however it may.

The outlet may include a disruptible seal or closure capable of being opened by movement of the formulation and/or gas pressure.

Preferably the formulation is expressed at least partly out of said outlet.

In still a further aspect the invention consists in dispensing apparatus for dispensing an agent or its precursor(s), said apparatus comprising or including a formulation (complex or simple) of the agent or its precursor(s), the formulation having an electrolyte character, a pair of electrodes disposed and enabled or enablable to generate at least one gas by electrolysis of at least part of the formulation, means enabling and/or to enable the pair of electrodes by the provision of an electric potential across the electrodes, and housing means with at least one outlet (whether closed or not) housing at least part (preferably all) of said formulation and at least part of at least one (preferably both) of said electrodes, wherein enablement of the electrodes by the provision of an electric potential thereto generates by electrolysis gas(es) which issues (or issue) from the formulation and has the effect of opening said outlet which in the absence of the pressure of such gas(es) would remain closed and thus confine the formulation in said housing means.

Preferably the arrangement is an option (A), (E) or (F) as disclosed hereafter by reference to Figure 1.

Preferably the outlet is closed by a rupturible seal. In still another aspect the invention is a dispensing device for a formulation containing an active material in solution or suspension and an electrolytic media of electrolytes or polyvalent polymers which preferably (although not essentially) have a standard reduction potential more positive than the standard reduction potential of the active material and which can at least in part be expressed from a delivery reservoir under the action of at least one gas generated on the provision of an electric potential across electrodes in contact with said formulation.

Preferably the formulation may be liquid, gel or solid.

♦ Options Include: (A) Gas and water tight chambers for the location of the formulation are sealed from the external environment by a gas and water tight cover or plug. (B) Electrodes of sufficient length to maintain contact with a liquid formulation regardless of orientation. (C) Electrodes of sufficient length to maintain contact with a gel or solid formulation until completion of the desired partial or full expulsion of the formulation. (D) The delivery reservoir is such that upon partial expulsion of the formulation (eg; gel or solid) gas is able escape around the formulation thereby terminating the active expulsion of the formulation.

In other aspects the present invention consists in dispensing apparatus substantially as hereinbefore described when used to deliver the formulation into an environment whether it be a body of a mammal or not.

In still a further aspect the present invention consists in a method of delivery of an agent or its precursor(s) which comprises disposing dispensing apparatus in accordance with the present invention in a position from which the agent or its precursor(s) can be effectively released and thereafter allowing the dispensing apparatus to dispense the formulation.

Preferably said dispensing is under the control of a timer and/or microprocessor. Preferably by movement of the formulation there is a total or partial expulsion. Such movement(s) may be such as to provide instant, continuous or pulsile release.

Preferably said device includes its own logic and power circuits for the electrodes. The invention consists in the foregoing and also envisages constructions of which the following gives examples. DETAILED DESCRIPTION OF THE INVENTION

Preferred forms of the present invention will now be described with reference to Figure 1 in which; (A), (B), (C), (D), (E) and (F) show different kinds of delivery device each having a pair of electrodes within the formulation to be delivered and each having the provision of power (eg; from a battery) to such electrodes under the control of a microprocessor, timer or the like.

Figure 1. Examples of various device configurations. (A) Liquid filled, upon activation seal ruptures or is expelled allowing liquid to pour out.

(B) Gel filled, upon activation the Gel migrates forward along the electrodes and is expelled from the chamber.

(C) Gel filled, upon activation the Gel migrates forward along the electrodes and is partially expelled (related to the length of the electrodes) from the chamber. (D) Gel filled, upon activation the Gel migrates forward along the electrodes and is partially expelled (once the linear portion of the gel fills the tapered portion of the chamber gas may escape) from the chamber.

(E) Gel filled, upon activation seal ruptures yet the gel remains in the chamber as gas passes through channels from behind the gel to rupture or expel the seal.

(F) Gel filled, upon activation the Gel migrates forward along the electrodes yet the gel remains in the chamber (once the linear portion of the gel reaches the tapered portion of the chamber it is physically hindered) from the chamber.

Figure 1 in each instance (A) to (F) shows a barrel or reservoir having an outlet in each case at the upper end. Preferably in each case the formulation is protected within the barrel by a rupturible seal 1 which in the case of (A) maintains the liquid formulation 2 within the barrel 3 around the electrodes 4. The option (A) is that which has been hitherto defined as option (a) on page 2 hereof in the sense that gas issuing at one or other of the electrodes will pressurise the sealed chamber and ultimately rupture the seal 1 thereby allowing delivery of the liquid formulation from the outlet initially sealed by seal 1.

Preferred forms of the present invention however are as disclosed by reference to (B), (C), (D), (E) and (F) where a gel or solid (or indeed even a heavily viscous liquid) is depicted having a capability in each instance of being expressed progressively (where continuously or in a pulsile manner) from the respective barrel upon generation of a gas about at least one of the electrodes which will migrate along the electrode in preference to general migration through the formulation to thereby achieve a pressurisation having the net effect as if the gas issues solely at the zone 5.

As can be seen the length of the electrodes depicted in option (B) will mean that substantially all of the formulation 6 is expressed from the barrel.

The option as depicted as (C) however with its shorter electrodes will cease gas production much earlier and thus will not fully eject actively the material 7 from the barrel. In each case however it can be seen that movement of the material 6 or 7 initially under the pressure of gas being generated will have the effect of rupturing an optional seal 1.

The option shown in (D) shows how the delivery reservoir or barrel need not be a true barrel, ie; it can be divergent. The divergent form shown as (D) has the effect, despite the longer electrodes shown for (D), of allowing gas migration around the formulation (if it is shape retaining) after a certain stage of movement of the formulation out of the optionally sealed opening.

Option (E) and (F) show options where gas may issue above and below the formulation to first rupture seal 1 and to release gas above the formulation 6 prior to thereafter having some of the gas produced providing a net force urging formulation to the outlet.

Persons skilled in the art will appreciate how the broad procedure can be employed without a true barrel if the material has the characteristics to move as a plug under the action of gas generated by the electrolysis procedure. In some forms of the present invention the outlet may be such that the plug does not simply emerge but rather extrudes (eg; as in option (F)). Therefore there is no mandatory requirement for the outlet to be axially aligned with the axis of a barrel. Persons skilled in the art will appreciate how the empowerment of the electrodes could be by any of their means mentioned in the aforementioned PCT Application No. PCT/NZ98/00011 or related prior art.

♦ Formulation examples

1. Electrolyte solution, e.g. NaCl 5%w/v. 2. Polyionic polymer solution, e.g. Na dextran sulphate 10%w/v.

3. Gelled electrolyte that maintains its physical shape once expelled into an environment below the gelling point of the gel, e.g. agarose 3.5%w/v and NaCl 5%w/v.

4. Gelled polyionic polymer that maintains its physical shape once expelled into an environment below the gelling point of the gel, e.g. agarose 3.5%w/v and

Na dextran sulphate 10%w/v. 5. Gelled electrolyte that dissolves when in contact with water, e.g. glycerin 70%w/w and gelatin 14%w/w and NaCl 5%w/v.

♦ Examples when such a device would be used. 1. Timed delivery of a therapeutic agent to the rumen of a ruminant animal, e.g. anthelmintics (of which ivomectin is an example) and antibiotics (of which monensin is an example).

2. Timed delivery of a therapeutic agent to the vagina of an animal for the control of oestrus, eg; oestrogens (of which oestradiol 17β is an example) and prostaglandins (of which cloprostenol is an example).

3. Timed delivery of an anticorrosive agent to an aquatic environment such as an air conditioning system.

4. Timed delivery of an antimicrobial agent to an aquatic environment such as an air conditioning system.

♦ Examples of such devices and characteristics of operation

Device formulation Configuration Voltage Disrupt Expulsion of (V) seal contents

(mins) (mins)

Gelled formulations

10 ml agarose 3.5%"/„, NaCl 5%^w/ B >5 >60 10 ml agarose 3.5%"/„, NaCl 5%"/„ B <5 <60 10 ml agarose 3.5%"/ , NaCl 5%"7„ C <5 content partially expel until gel matrix clear of electrodes

10 ml agarose 3.5%"7_V, NaCl 5%"7„ <5 content not expelled, gas by-passed gel mass 10 ml agarose 3.5%^w/„, NaCl 5%^w/„ <5 content not expelled, gas passed through gel orifice

1 ml agarose 3.5%"/,, NaCl 5%"/, <5 content not expelled, gel mass retained by reduced oπfice at outlet

10 ml gelatin 10% "V. <5 contents did not expel, gas passed through gel matrix

1 ml agarose 3.5% ^w/„ NaCl 5%"/, 12 =0.5 <5

Liquid formulations

10 ml 5% "7„ NaCl <5 content expelled when reservoir orientated appropπately

1 ml 5%"/ NaCl <0.5 content expelled when reservoir orientated appropnately

1 ml 5% "A NaCl 12 <0.5 content expelled when reservoir orientated appropriately

Claims

CLAIMS:

1. Dispensing apparatus for dispensing an agent or its precursor(s), said apparatus comprising or including a formulation (complex or simple) of the agent or its precursor(s), the formulation having an electrolyte character, a pair of electrodes disposed and enabled or enablable by electrolysis of at least part of the formulation to generate at least one gas, and housing means with at least one outlet (whether closed or not) housing at least part of said formulation and at least part of at least one of said electrodes, wherein enablement of the electrodes by the provision of an electric potential thereto generates by electrolysis gas(es) which

(b) if the formulation is plug like in character or is of a kind where the interface of the gas generating electrode(s) to the formulation offers to the gas(es) so generated at such electrode(s) less resistance to gas travel than the formulation itself, migrates along at least one electrode away from said outlet so as to gas pressurise a movement of the formulation at least towards said outlet."

2. Apparatus as claimed in claim 1 wherein an enablement of the electrodes by the provision of an electric potential thereto generates electrolysis gas(es) which will have the effect of scenario (a).

3. Apparatus as claimed in claim 1 wherein an enablement of the electrodes by the provision of an electric potential thereto generates electrolysis gas(es) which will have the effect of scenario (b).

4. Apparatus as claimed in claim 3 wherein the formulation, whilst having an electrolyte character, is in the form of a gel or solid.

5. Apparatus as claimed in claim 4 wherein said formulation does not have the agent or its precursor(s) providing the electrolyte character of the formulation.

6. Apparatus as claimed in any one of claims 1 to 5 wherein the outlet includes a disruptible seal or closure capable of being opened by movement of the formulation and/or gas pressure.

7. Apparatus as claimed in any one of claims 1 to 6 wherein the formulation is expressed at least partly out of said outlet by the gas pressure in use.

8. Apparatus as claimed in any one of the preceding claims wherein the outlet is closed by a rupturible seal.

9. Apparatus as claimed in claim 8 wherein the formulation is a liquid, a solid or a gel and is conduited or provided with electrodes such that gas pressure directly rather than the formulation itself ruptures the seal.

10. Dispensing apparatus for dispensing an agent or its precursor(s), said apparatus comprising or including a formulation (complex or simple) of the agent or its precursor(s), the formulation having an electrolyte character, a pair of electrodes disposed and enabled or enablable to generate at least one gas by electrolysis of at least part of the formulation, means enabling and/or to enable the pair of electrodes by the provision of an electric potential across the electrodes, and housing means with at least one outlet (whether closed or not) housing at least part of said formulation and at least part of at least one of said electrodes, wherein enablement of the electrodes by the provision of an electric potential thereto generates by electrolysis gas(es), and wherein the formulation is of a kind where the interface of the gas generating electrode(s) to the formulation offers to the gas(es) so generated at such electrode(s) less resistance to gas travel than the formulation itself, and wherein at least a substantial amount of any gas(es) generated at the gas generating electrode(s) migrates along said at least one electrode away from said outlet so as to gas pressurise a movement of the formulation at least towards said outlet.

1 1. Dispensing apparatus for dispensing an agent or its precursor(s), said apparatus comprising or including a formulation (complex or simple) of the agent or its precursor(s), the formulation having an electrolyte character, a pair of electrodes disposed and enabled or enablable to generate at least one gas by electrolysis of at least part of the formulation, means enabling and/or to enable the pair of electrodes by the provision of an electric potential across the electrodes, and housing means with at least one outlet (whether closed or not) housing at least part (preferably all) of said formulation and at least part of at least one (preferably both) of said electrodes, wherein enablement of the electrodes by the provision of an electric potential thereto generates by electrolysis gas(es), and wherein the formulation is of a consistency less conducive to gas passage therethrough than a low viscosity liquid (such as might be the case with a suitably viscous liquid, a suitable gel, a suitable solid, or the like, irrespective of orientation of the apparatus) whereby any electrode generated gas(es) migrates along such electrode away from said outlet so as to gas pressurise a movement of the formulation at least towards said outlet.

12. Dispensing apparatus for dispensing an agent or its precursor(s), said apparatus comprising or including a formulation (complex or simple) of the agent or its precursor(s), the formulation having an electrolyte character, a pair of electrodes disposed and enabled or enablable to generate at least one gas by electrolysis of at least part of the formulation, means enabling and/or to enable the pair of electrodes by the provision of an electric potential across the electrodes, and housing means with at least one outlet (whether closed or not) housing at least part (preferably all) of said formulation and at least part of at least one (preferably both) of said electrodes, wherein enablement of the electrodes by the provision of an electric potential thereto generates by electrolysis gas(es) which issues (or issue) from the formulation and has the effect of opening said outlet which in the absence of the pressure of such gas(es) would remain closed and thus confine the formulation in said housing means.

13. Apparatus of any one of the preceding claims wherein the arrangement is an option (A), (B), (C), (D), (E) or (F) as disclosed hereafter by reference to Figure 1.

14. Dispensing device for a formulation containing an active material in solution or suspension and an electrolytic media of electrolytes or polyvalent polymers which have a standard reduction potential more positive than the standard reduction potential of the active material and which can at least in part be expressed from a delivery reservoir under the action of at least one gas generated on the provision of an electric potential across electrodes in contact with said formulation.

15. A method of delivery of an agent or its precursor(s) which comprises disposing dispensing apparatus in accordance with any one of the preceding claims in a position from which the agent or its precursor(s) can be effectively released and thereafter allowing the dispensing apparatus to dispense the formulation.

16. A method of claim 15 wherein said dispensing is under the control of a timer and/or microprocessor.

17. A method of claim 16 wherein by movement of the formulation there is a total or partial expulsion.

18. A method of claim 17 wherein such movement(s) may be such as to provide instant, continuous or pulsile release.

19. Apparatus or the use of apparatus substantially as hereinbefore described with reference to the accompanying drawings.