NZ576414A - Bolus in form of plural dosage media connected by flexible material - Google Patents

Abstract

A bolus is formed from plural dosage media bound together with a length of flexible material having a higher disintegration rate than the media.

Description

576414 Received by IPONZ 7 July 2010 PATENTS FORM NO. 5 Fee: $250.00 James & Wells Ref: 130081/47 RD PATENTS ACT 1953 COMPLETE SPECIFICATION After Provisional No: 576414 Dated: 21 April 2009 AN IMPROVED BOLUS We Bomac Research Limited, a New Zealand company having its registered office at Wiri Station Road, Manukau, Auckland, New Zealand hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed to be particularly described in and by the following statement: 576414 Received by IPONZ 7 July 2010 James & Wells 130081/47 RD AN IMPROVED BOLUS TECHNICAL FIELD The present invention relates to an improved bolus. More specifically, the invention relates to an improved bolus and a method of releasing the active from 5 said bolus.

BACKGROUND ART A number of different methods are used by farmers, livestock managers and veterinarians to treat health conditions in livestock such as cows and sheep. For example, a bolus or drench may be used. However, there are problems with 10 current methods of treating animals.

Drench, which is a liquid containing an active agent targeting the health condition of concern, may be used by dosing the animal via a drench gun. To be effective, the drench needs to be delivered to the animal on a frequent basis.

If only a single animal is being treated, applying drench may be not much of a 15 problem. However, it may be an issue if it is a large number of animals which need to be treated, such as a dairy herd.

Thus to treat or prevent a health condition (such as gut parasites) in a dairy herd using drench, the farmer or livestock manager may need to treat several tens or even hundreds of animals on a regular basis. This has obvious time and logistic 20 constraints. For this reason, boluses are commonly used to treat animals.

Essentially, a bolus contains a dissolvable substance which contains an active agent which targets the health condition being treated. The active agent may be, for example, zinc (for treatment of facial eczema), anthelmintics (for treatment of worms and other internal parasites) and/or micro-organisms (to act upon gut flora). 2 576414 Received by IPONZ 7 July 2010 James & Wells 130081/47 RD The bolus is inserted into the rumen of the animal to be treated, and the dissolvable substance slowly erodes. Thus, the active agent is steadily delivered to the animal over a period of time. This maintains a certain level of active agent in the circulatory system of the animal for weeks or even months, which treats or 5 alleviates the condition being treated.

A key advantage of using a bolus as a method of treating health conditions in livestock is that the farmer or livestock manager need only administer the bolus once for delivery over an extended period of time.

It is important that the dissolvable substance in the bolus disintegrates in order for 10 the active agents contained within the boli to circulate through the animal. Normally, the bolus naturally disintegrates through the dissolving action of the rumen fluid of the animal.

However, sometimes the erosion of the bolus can be inconsistent. The bolus may stay in the rumen for longer than intended, due to inadequate breakdown of the 15 bolus constituents.

A side effect of this prolonged breakdown is that the levels of active agent in the circulatory system are lower than is ideal for treating of the targeted health condition. This can allow development of drug resistant internal parasites and micro-organisms, which in turn compromises the efficiency of the active agent 20 treating the targeted health condition.

While boluses may be very effective in delivering a treatment substance to the gut of the animal, the introduction of the bolus to the animal can be difficult to achieve.

Boluses are required to be of sufficiently large volume to deliver the amount of treatment substance required, as well as being densely compacted in order to 25 allow for the slow delivery of the treatment substance. The bolus must also be of a 3 576414 Received by I PONZ 7 July 2010 James & Wells 130081/47 RD sufficient weight so that the bolus can remain within the rumen.

Boluses cannot be readily swallowed by the animal to be treated, in contrast to other methods of treating animals such as tablets and liquid drenching. Furthermore, the bolus needs to be deposited in the bottom of the rumen for it to 5 be effective.

A possible solution to this problem has been the development of a bolus applicator. A bolus applicator is generally comprised of a long tube having at one end a trigger connected to a bolus release, and at the other end, a bolus retainer. In order to insert a bolus into an animal, the tube is inserted down the animal's throat until in 10 position that the bolus can be released and dropped into the animal's rumen.

As can be appreciated, to deliver boluses to animals in such a manner requires considerable skill, particularly when animals are not prone to remaining still during the administration process.

Unfortunately, it is relatively common for animals to be hurt during the 15 administration process, even to such a degree that the animals die as a result. For example, it is relatively common for the bolus to not enter the rumen, but instead be injected accidentally through the back of the animal's oesophagus.

It is obviously desirable if there could be provided a better method of administration of active agents to an animal to be treated.

It is an object of the present invention to address the foregoing problems or at least to provide the public with a useful choice.

All references, including any patents or patent applications cited in this specification are hereby incorporated by reference. No admission is made that any reference constitutes prior art. The discussion of the references states what their 25 authors assert, and the applicants reserve the right to challenge the accuracy and 4 576414 Received by I PONZ 7 July 2010 James & Wells 130081/47 RD pertinency of the cited documents. It will be clearly understood that, although a number of prior art publications are referred to herein, this reference does not constitute an admission that any of these documents form part of the common general knowledge in the art, in New Zealand or in any other country.

Throughout this specification, the word "comprise", or variations thereof such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

Further aspects and advantages of the present invention will become apparent from the ensuing description which is given by way of example only.

DISCLOSURE OF INVENTION According to one aspect of the present invention there is provided a bolus for administration to an animal by deposition into its stomach, the bolus having a 15 construction including: a) a plurality of dosage media, and characterised in that the dosage media is bound together with a binding material which has a disintegration rate greater than that of the dosage media.

According to another aspect of the present invention, there is provided a method of 20 treating an animal, characterised by the step of a) inserting a bolus into the rumen of an animal to be treated, wherein the bolus includes a plurality of dosage media bound together with a binding material.

A bolus should be understood to mean a device intended for the delivery of 576414 Received by I PONZ 7 July 2010 James & Wells 130081/47 RD medicaments or nutritional supplements in the form of dosage media.

The bolus may or may not include a housing for the dosage media. However, in preferred embodiments of the invention, the bolus does not include a housing.

The animal may be any animal which requires treatment of a specific health 5 condition or prevention of a specific health condition from arising.

Preferably, the animal to be treated is a ruminant, such as a cow or sheep, and the bolus is delivered to the rumen of the animal.

Dosage media should be understood to mean a substantially solid medicament or nutritional supplement intended for oral ingestion. For example, the dosage media 10 may be capsules with a gelatin housing.

Preferably, the dosage media is a solid tablet, and shall be referred to as such throughout the remainder of the specification. The tablet may be of any shape. For example, the tablet may be substantially spherical or ovoid. Alternatively, the tablet may be circular only in cross-section, and have an elongate body. Persons 15 skilled in the art will appreciate that the tablet shape will vary according to the requirements of the user.

The constituents of the tablet may vary according to the requirements of the user. For example, as well as containing the active agent to be delivered, the tablet may include plasticizers, emulsifiers, and/or bulking agents such as starch.

The active agent may be any medicament required to treat a specific condition of the animal. In some embodiments of the present invention, the active agent may be a nutrient or combination of nutrients.

For example, the active agent may be an anthelmintic to kill gut parasites such as nematodes or tape worms. Alternatively, the active agent may be an essential 6 576414 Received by I PONZ 7 July 2010 James & Wells 130081/47 RD element, such as zinc or selenium. Other suitable active agents will be readily apparent to a person skilled in the art.

The binding material may be any suitable material which links the tablets together.

For example, the binding material may be string threaded through apertures 5 passing through the centre of each tablet. Alternatively, a biodegradable or biocompatible plastic tie or cable may be used.

Preferably, the binding material is in the form of adhesive tape. The tape may come in various forms and may be paper or cellulose based. For example, the tape may be Sellotape™. Persons skilled in the art will appreciate that the tape is 10 constructed of biocompatible material which will naturally disintegrate within or harmlessly pass through the animal's digestive system.

Preferably, the adhesive tape is applied to the sides of the tablets forming the bolus. However, in some embodiments of the present invention, the adhesive tape be wrapped around the sides and faces of the tablets for a more robust binding.

Adhesive tape is preferred for a binding material as the application of the tape to tablets is relatively easy and inexpensive to automate relative to forming tablets with apertures through which a string must be passed. Reference shall now be made throughout the remainder of the specification to the binding material as being a tape. However, other methods of temporarily binding individual tablets together 20 will be readily apparent to a person skilled in the art.

In use, once the bolus has been inserted into the rumen, the binding material steadily dissolves leaving the tablets to intermittently knock against each other. This accelerates the disintegration of the tablets, assisting in the release of the active agents contained within the tablets to circulate within the circulatory system 25 of the animal being treated. 7 576414 Received by I PONZ 7 July 2010 James & Wells 130081/47 RD In a preferred embodiment of the present invention, the bolus includes four tablets. The inventor has found that four tablets are sufficient for the purpose of treating animals. In this embodiment of the invention, the tablets can be though of as mini-boluses. Collectively, the active agent contained with these mini-boluses equal 5 that contained within a conventional bolus.

This number of mini-boluses is sufficient to allow for an increased disintegration rate of the boluses without unduly accelerating the rate of disintegration. The more mini-boluses which are present in the rumen means that greater more contact, and therefore faster disintegration, between individual mini-boluses is likely to occur.

However, persons skilled in the art will appreciate that certain users may desire a greater number of mini-boluses for precisely this reason, for a greater erosion rate. Obviously, the use of such boluses would be preferably for short-term treatments as such boluses may erode too quickly for long-term treatments.

Mini-boluses may be delivered by a number of means.

In one embodiment of the present invention, a bolus applicator may be used, but with a retention device configured to be able to hold a number of mini-boluses. Thus, when the bolus applicator is within the animal, pulling the trigger would not cause a singular solid length of bolus to extend out as this may result in the bolus inadvertently passing through the oesophagus of the animal.

Instead, a smaller length bolus would emerge and drop out of the retention device before it could reach or be forced into the oesophagus. Thus, pulling the trigger will cause a sequential dropping of small boluses into the animal's stomach.

One aspect of the present invention includes a bolus applicator configured to hold multiple mini-boluses.

In a preferred embodiment of the present invention, at least one end of the bolus is 8 576414 Received by I PONZ 7 July 2010 James & Wells 130081/47 RD essentially rounded so that if there is any contact with the side wall with animal soft tissue, there is less chance of penetration.

In a preferred embodiment of the present invention, the mini-boluses may be attached to each other in such a way that they create a treatment device in the 5 form of a single articulated object.

In this embodiment of the present invention, the tape holds the boluses together. As the tape is flexible, the boluses can move with respect to each other. Thus, on application of the present invention to the animal, the bolus would bend if it meets an obstruction such as the back of the animal's oesophagus.

It is likely that the application of the tape along one side of the mini-boluses could lead to the bolus only being able to flex in one orientation. Therefore, care would be needed when aligning the bolus within the bolus applicator and the bolus applicator relative to the animal.

In some embodiments of the present invention, the adjacent heads and tails of the 15 mini-boluses may be shaped such that the total bolus can articulate sideways as well as in other directions.

In other embodiments, the articulation may be provided by a binding material in the form of a length of flexible material such as a string or cable tie. The string or tie is passed through the interior of the mini-boluses, linking them together.

In preferred embodiments, the string is positioned along the central axis of the mini boluses so that they are aligned to provide the least possible width that may hamper ease of application to the animals.

It should be noted that by having the binding material internal to the boluses, rather than external, a greater degree of flexibility is possible with the bolus being able to 25 articulate in many directions. 9 576414 Received by I PONZ 7 July 2010 James & Wells 130081/47 RD Any number of mini boluses may be used in accordance with the present invention, however the inventor has determined that approximately four mini boluses is the degree of flexibility and size for the required dissolution within the rumen.

It is envisaged that the mini-boluses will be of similar composition to the traditional 5 larger boluses. However, a different surface area to volume ratio may arise as a consequence of having mini-boluses rather than a large bolus. This may mean that alternate coating designs may be used. For example, the coating may have a greater thickness, or less solubility and so forth, than a conventional bolus.

The invention is particularly advantageous, as once dissolved, the lack of a binding 10 material connecting the bolus allows the individual tablets of the bolus to make contact with each other in the rumen. This contact provides an additional method of disintegrating the tablets in the animal's stomach.

Furthermore, the binding material confers a degree of articulation onto the bolus, allowing it to more easily pass through the oesophagus of the animal to be treated.

This reduces the risk of injuring the animal when delivering the bolus to the animal.

BRIEF DESCRIPTION OF DRAWINGS Further aspects of the present invention will become apparent from the following description which is given by way of example only and with reference to the accompanying drawings in which: Figure 1 a side view of one embodiment of the present invention; and Figure 2 a front view of another embodiment of the present invention.

BEST MODES FOR CARRYING OUT THE INVENTION In Figure 1, the bolus (generally indicated by arrow 1) is illustrated in a side view. It 576414 Received by I PONZ 7 July 2010 James & Wells 130081/47 RD can be appreciated that the bolus (1) includes two tablets (2, 3). These tablets (2, 3) are bound together using adhesive tape (4).

When delivered into the rumen of the animal to be treated (not shown), the adhesive tape (4), which disintegrates quickly relative to the tablets (2, 3), allows 5 the tablets (2, 3) to separate from one another in the rumen (not shown). The tablets (2, 3) then are free to make intermittent contact as they circulate about in the rumen (not shown).

This hastens the disintegration rate of the tablets (2, 3), ensuring that the levels of active agent contained within the animal are maintained at a relatively high rate to 10 avoid growth of drug resistant micro-organisms.

Another embodiment of the invention is illustrated in a side view in Figure 2. Here it will be appreciated that the bolus consists of two pairs of two tablets (5, 6) which can be though of as mini-boluses, for a bolus (7) consisting of four tablets (8, 9, 10, 11).

Each tablet (8, 9, 10, 11) has an aperture (12) at its centre through which biodegradable string (13) has been passed.

The string (12) confers a degree of articulation onto the bolus (7). This allows the individual tablets or mini-boluses (8, 9, 10, 11) forming the bolus (7) to move with respect to each other.

If, for example, the bolus (7) contacts the oesophagus of the animal being treated (not shown), the bolus (7) is more able to conform to the oesophagus, reducing the chances of injury to the animal (not shown).

Once inserted into the rumen, the string (13), or whatever binding material has been used, quickly erodes, freeing the tablets (8, 9, 10, 11) to circulate in the 25 rumen. 11 576414 Received by I PONZ 7 July 2010 James & Wells 130081/47 RD Aspects of the present invention have been described by way of example only and it should be appreciated that modifications and additions may be made thereto without departing from the scope thereof. 12

Claims (17)

576414 Received by I PONZ 7 July 2010 James & Weils 130081/47 RD WHAT I CL&SgyH iS:

1. A bolus for administration to a non-human animal by deposition into its stomach, the bolus having a construction including: a) a plurality of dosage media, and characterised in that. the dosage media is bound together with a binding material which has a disintegration rate greater than that of the dosage media, and wherein the binding materia! is a iength of flexible material.

2. A bolus as claimed in claim 1 wherein the binding materia! is in the Form of adhesive tape.

3. A bolus as claimed in clasm 2 wherein the adhesive tape is applied to the sides of the dosage media.

4. A bolus as claimed in claim 1 wherein the dosage media includes an aperture passing through the dosage media.

5. A bolus as claimed in claim 4 wherein the flexible material passes through the aperture of the dosage media.

6. A bolus as claimed in claim 5 wherein the flexible material is biodegradable string,

7. A boSus as claimed in claim 6 wherein the flexible material is a biodegradable cable tie.

8. A bolus as claimed in any one of claims 1 to 7 wherein at least one end of the dosage media is rounded. 13 576414 Received by IPONZ 7 July 2010 James & Wells 130081/47 RD

9. A bolus as claimed in claim 8 wherein the adjacent dosage media is configured with a concave surface complementary to the rounded end of the adjacent dosage media.

10. A boius as claimed sn any one of claims 1 to 19 wherein the dosage media is a tablet.

11. A bolus as daimed in claim 10 wherein the boius includes four tablets,

12. An applicator for delivery of a boius as claimed in any one of claims 1 to 11.

13. A method of treating a non-human animal characterised by the step of a) inserting a boius into the rumen of an animal to be treated, wherein the boius includes a plurality of dosage media bound together with a binding material, and wherein the binding material has a disintegration rate greater than that of the dosage media, and wherein the binding material is a length of flexible material.

14. A method as claimed in claim 13 wherein the animal to be treated Is a ruminant.

15. A bolus for administration to a non-human animal by deposition into its stomach substantially as herein described and with reference to the accompanying drawings.

18. An applicator for delivery of a bolus substantialiy as herein described and with reference to the accompanying drawings. 14 576414 Received by I PONZ 7 July 2010 Jamss a Wells 130081/47 RD

17. A method of treating a non-human animal substantially as herein described and with reference to the accompanying drawings. Bom&c Limited by its authorised agents