WO2007022563A1

WO2007022563A1 - Package with bitter taste aversive agent for infant deterrant

Info

Publication number: WO2007022563A1
Application number: PCT/AU2006/001190
Authority: WO
Inventors: Graham Scott; Stephen Shield
Original assignee: Graham Scott; Stephen Shield
Priority date: 2005-08-24
Filing date: 2006-08-21
Publication date: 2007-03-01

Abstract

A taste aversive container or packaging for substantially deterring an infant or toddler from accessing contents of the container, the container including a structure for storing a medicant or other potentially injurious agent, wherein the structure comprises a polymeric or other type of non water soluble matrix having an effective amount of between abo 0.005% and 2.0% w/v of a bitter taste aversive composition such as benzoic benzylamine amide, denatonium benzoat alkaloids, amino acids, trichloro anisole, methyl anthranilate and quinine. Upon exposing a surface of the structure t sufficient moisture such as salvia, the bitter taste aversive composition is released from the matrix. The aversive composition may contain micro-particles having a' bitter taste aversive agent which burst on contact with salvia. Also disclosed is a multi-layered packaging film including a first inert film layer with a bitter taste aversive coating and a second degradable outer film applied to the coating.

Description

IMPROVED AVERSIVE SAFETY INTERVENTION FOR INFANT DETERRANT

FIELD OF INVENTION The present invention relates to primary safety intervention means to deter infants from instinctive behaviour in relation to general items including, but not limited to packaging of pharmaceuticals, household chemicals, detergents, eucalyptus oil, and other potentially injurious agents. The present invention particularly relates to primary deterrent safety intervention for packaging, which acts as an infant/toddler deterrent to substantially limit handling and/or ingestion of items by infants, such as, but not limited to, pharmaceuticals, chemicals and other hazardous items.

BACKGROUND OF THE INVENTION Each year world wide many thousands of children are poisoned by ingesting either pharmaceuticals or other non-pharmaceutical chemicals, and other hazardous material, which are present for domestic use. This problem is ubiquitous, and has both a geographic and temporal constancy.

In an article by Agran et al (2003) titled "Rates of pediatric injuries by 3-month injuries for children 0 to 3 years of age" in the journal Pediatrics, 111, e683- e692, the scope of childhood poisoning within California, USA is demonstrated. Their study examined a range of common childhood injuries. Agran et al (2003) argued convincingly that the usual age groupings used to study childhood injury are much too broad. Consequently, previous studies using the traditional age groupings (1-4, 5-9, and 10-14 years) were unable to demonstrate the relationship between the child's stage of development and the risk for a variety of injury causes, including the risk for injury via poisoning. These authors stated that: ".single year of age rates for children younger that 4 years may not reflect the variations in risk as a result of rapid developmental changes,"

Three monthly intervals were used, and the categorisation took into account physical, motor, behavioural and cognitive developmental milestones of children 0 to 3 years, which is the age group most commonly poisoned. In fact in California, USA poisoning by medication was the leading specific cause of injury for all age groups from 18 to 35 months, and exceeded poisoning by all other substances. Age-related differences were detected within each major cause of injury, including poisoning. Beginning at 9-11 months, the rate of childhood poisoning progressively rose to a peak at 21- 23 months, and then steeply declined to a low at 42-47 months. The rate of poisoning for "other substances" was consistently lower that the fate of poisoning by medications for all age groups (excepting only 3-5 months- a non ambulatory stage). The rate of poisoning for other substances peaked at 12-20 months. These results are presented graphically in Figures 1-3 below. Poisoning by medication therefore remains a leading cause of injury for youfltg children. Designs for more effective interventions have been called for by these authors.

Agran et al (2003) concluded that:

"differences ha rates by narrow age groups for young children can be related to developmental achievements, which place the child at risk for specific causes of injury Children aged 15 to 17 months had the highest overall injury rate before 15 years. This coincides with developmental achievements such as independent mobility, exploratory behaviours and hand-to mouth activity. The child is able to access hazards but has not yet developed cognitive hazard awareness and avoidance skills"

In early childhood development, exploratory behaviour includes placing articles into the oral cavity. This type of behaviour is typically observed in infants and toddlers because oral sensory and taste receptors are for more developed at an early age compared to early manual dexterity skills, tactile sensory receptors, and olfactory receptors, The natural compulsion driving infants to explore objects by insertion into their oral cavity, places them ia a. high risk group for poisoning.

Therefore it can be seen that there is a particularly substantial problem in young children accessing products due to exploratory behaviours. There is also a substantial cost to be paid due to the results of their exploratory behaviour.

Based on annual cost estimates for child pharmaceutical poisoning alone a substantial investment is warranted in targeted prevention methods. On .the basis of a costing model developed by Watson and Ozanne-Smith (1997), the average lifetime costs for poisoning, for each level of severity, per injured person, Victoria, Australia "Cost of Injury" report (1993/1994) are estimated to be: Deaths $629,970

Hospital Admissions $18,215

Non-Hospital poisoning $1,224

The above figures relate to health costs associated with single event poisonings. Apart from the associated morbidity, these figures demonstrate a substantial health insurance cost to be met by the taxpayer. If these figures can be brought down by preventative measures, then insurance premiums can be at least in part reduced.

From Australian child pharmaceutical poisoning data (see Figure 4 below), the age distribution of child poisoning appears to be remarkably stable. The age distribution is 'normal' with a mean at age of two years. The vast majority of poisoning cases occur for a child between the age of eighteen months to ihirty- six months. Overall it has been estimated that the cost of pharmaceutical poisonings alone in 1995/1996 for Victoria, Australia was about $41 million.

For the eleven-year period between 19S7 and 1998, 5,619 hospital admissions were made to public hospitals in Victoria, Australia for children under the age of five. Of these, 3,052 poisonings were listed according to an identified location of which the overwhelming majority of incidents (97%) occurred in homes.

In Germany it was estimated that annually there are 10,000 childhood poisonings with symptoms, of which 500 are life threatening, and 20-40 of which are fatal. About 68% of life threatening poisonings are associated with medications. Annually within the European Union (EU) it might be expected that around 2700 life-threatening poisonings occur, with 1800 being from medicines. Of the pharmaceutical agents responsible for poisoning, paracetamol; psychotropics, particularly benzodiazepines; cough, cold and flu medications and antihistamines are generally found to be the most frequently ingested agents.

Referring to Figure 4, around 93% of all poisoning admissions in Australia in 1997 occurred for children aged less than 48 months of age. Child age therefore is found to have the strongest correlation with poisoning and is linked to behaviours and to the child's size (a hepato-toxic dose of paracetamol, 140 mg/kg, would require ingestion of only four 50Qmg tablets in a two year old girl of average weight).

Clearly a peak incidence occurs at around two years of age. This pattern is found throughout the world, and has been reported for more than 40 years.

Infants and toddlers are compelled to explore orally as their oral sensory and taste receptors are far more advanced at this age than are either their tactile sensory receptors,, or manual dexterity. Hence they learn from oral sensations and from taste. Also at this period, teething is prominent with the eruption of deciduous molars. Placing objects in the mouth serves two functions (i) primarily to explore their environment and (ϋ) secondarily to relieve irritation from erupting teeth. The following characteristics of children poisoned are:

•Around two years of age (18-36 months);

•Inquisitive;

•Mobile;

•Use oral exploration (i.e. immediately place object on their mouth to explore them);

•Teething (first and second deciduous molars); and

•Poorly developed manual dexterity. An infant/toddler also uses role modelling to leam. That is if "daddy" or "mummy" use scissors- the infant/toddler wants to use scissors; if "daddy" or "mummy" use keys - the infant/toddler wants to use keys. It is understood that the super-ego (that part of a person's psyche which dictates to that person that they should refrain from certain activities) is not developed in an infant. Consequently while an infant may not touch Items when the parents are present, because he/she has learnt that they will be disciplined by parents/caregivers, in the absence of parents an infant/child cannot resist touching "forbidden" items such as keys, power cords, and medicines.

Consequently, when left alone the child will opportunistically explore his/her environment, and sample objects orally, as this is the primary sense for two year olds. If unattended_* infants/toddlers will place whatever they can in their mouths.

A common chain of events leading to child poisoning arises typically when an infant/toddler is at the exploring stage. At this stage it can be said that an infant/toddler is not driven to explore by purposeful behaviours such as thirst or urges otherwise associated with adult-centric behaviours. If a container/packaging containing a hazardous material such as a medicament or other potentially injurious agent is/was currently in use on a bench by a family member such as a parent, an infant may be urged by instinctive behaviour to investigate the container and/or its contents. Infants/toddlers have . poorly developed superego- that part of the psyche which limits an adult's propensity to succumb to urges. By two years of age the child has learned not to touch

"forbidden" items because they will be disciplined by the care givers. However, when left alone, the child is not able to resist exploring "forbidden" itefns, and will purposefully target them for exploration,

A container of medicament or chemical may or may not have a functional child resistant feature. Although caking of medication may be one factor that contributes, caking is only an issue with liquid medications'. In fact many children access medications and other harmful agents in packaging -, both bottles and blister packs- which have intact and operational child resistant features, and without any caking. The parent is unaware of any risk and may be distracted, for example, by household chores or answering the telephone. In essence the infant/toddler: (i) is left alone;

(ii) is curious;

(iii) wants/needs to explore; and the parent or family member is distracted.

Before the introduction of child resistant packaging, various interventions were tried. Often poisoning occurs for medications or poisons in use, which were not properly stored after use. For many, the situation of use was when either or both parents and children were ill. Interventions, which have been tried, include:

•education of parents;

•introduction of bench top storage containers; and introducing aversive tasting agents directly into potentially injurious agents e.g. dishwashing detergent.

There has been very limited success with any of the above-mentioned prior art measures to address the problem of infant deterrent, and the lack of success of the measures has been documented time and again (Mclntyre et al 1976 'How effective is safety packaging clinical toxicology 9 page 419 to 4253- Educational measures failed because the target group was constantly changing, and because children most often accessed substances in use. In practice it is tedious to store substances safely; and to be successful the intervention requires a degree of compliance by the parents. In many instances parents can become complacent with such routine. This is the reason that storage in cupboards or even bench top containers has failed to produce a major reduction in the problem of infant poisoning. For this reason aversive agents have been placed directly within poisons or other potentially injurious agents, using a classical conditioning paradigm based on a single trial learning response. The problem with this form of intervention however is that while it may reduce the amount of substance that the child consequently ingests, it does not prevent, in the first instance, the child from accessing the agent. A further problem is that the agent needs to be diffused through the contents of the packaging - for example detergent, and so is more expensive and also potentially also harmful to the child. A further problem with aversive agents is that bodies such as the

American Association of Poison Control Centers (sic) advise against placing these agents directly into medications, and so this avenue is not available to medicines.

Since the start of the 1970's increasing efforts have been made to address problems associated with childhood/infant death caused by drug poisoning resulting from active and/or passive opening of drug packaging. To help address the problem of drug poisoning by such means, parents of infants generally place items such as drugs out of reach. Indeed therapeutic goods regulations recommend pharmaceutical suppliers to place information on packaging to both describe the harmful effects of drugs (consumer medicine, information) and the need to place on such packaging labelling such as 'Keep out of reach of children', hi some instances trlalling of warning stickers such as 'Mr. Yuck' have had no effect on ingestion incidents (in the same way that warning labels on cigarette packets do not deter smokers), and there are concerns that such labelling may even attract children rather than act as a deterrent It is also understood that since infants and toddlers explore their world in an oral sensory manner, general items of potential harm if swallowed or placed in the mouth need to be placed out of reach. Packaged articles however often inadvertently end up within reach of children whose general curiosity urges them to explore packaging and contents therein.

The introduction of child resistant packaging has reduced the incidence of childhood poisoning, but as the data (Figures 1-4) clearly demonstrate, the problem still persists. The introduction of child resistant packaging has consistently been shown to be successful, and reducing the incidence, of childhood poisoning by 40%. In the USA, poison prevention packaging was : associated with a 65% decline in overall ingestions packaged m child resistant containers whereas ingestion of prescription drugs declined by only 36%. Substantial numbers of cases continue to occur with medicaments that require packaging in a child resistant container. There are also a wide range of medicaments associated with child poisoning that are not required by regulatory standards (within Australia- or other similar US legislative body such as the FDA) to be dispensed in a child resistant container but which are relatively commonly implicated in childhood emergency department presentations and/or produce severe poisoning episodes. Nonetheless, further gains are needed since the commonest cause is that children defeat the child resistant feature of the packaging which is intact. The method that children or infants/toddlers defeat child resistant packaging is irrelevant, because however they defeat it, the vast majority will place the packaging into their mouths as part of their initial exploratory activities once they have access to the packaging.

Within Australia and the USA, a standard for testing child resistant packaging has been established. Over the last standard, the testing age was increased to be older thaw 48 months, This age group was selected because it was considered that they would have the best chance of opening the packaging. It was assumed, albeit incorrectly, that the progression of childhood development is linear.

Children progress through developmental stages, and after a child progresses through such a stage the behaviours they exhibit change radically. Therefore it would appear that the set of childhood poisonings reflects not a homogenous set of children but two heterogeneous groups, being older children who have increased manual dexterity, and younger children, far less manually dexterous that still explore the world orally because they have primarily developed oral tactile sensation.

While it is true that these older children have better manual dexterity, the standard ignores important differences in which the children approach, explore and access the packaging. Older children, like adults, use their hands to explore objects. A core issue is mat two year olds explore objects by placing the object in the mouth. This oral behaviour is very different from that displayed by four year olds, or adults. A peripheral issue is that the propensity to place objects in the mouth is further increased with teething of the second deciduous molar at around two years of age. At that stage the child actively seeks an object to bite on to ease their unpleasant symptoms. Consequently it is argued that choosing a panel of children ages over 48 months, which represents only 7% of the total poisoned, is inappropriate. The age group selection represents the tail of the normally distributed age groups- see Figure 1- and consequently is not a representative sample of the children being poisoned. This conclusion was seen in Australia and aligns with the work completed by Agran et al in California, USA. This finding is reflected in the published literature where a group of older children have been labelled "hard core refractory even to safety packaging". Younger children who comprise the bulk of poisoning cases explore their environment orally, by placing objects in their mouth. This propensity is exacerbated when they are teething. It is therefore possible to target that behaviour to implement a primary prevention strategy.

Currently the safety packaging industry, consumer groups, agencies and standards are all universally oriented towards a particular type of solution, namely providing physical barriers to limit a child's access to substances contained within the packaging. New solutions are almost inevitably variations upon this recurrent theme, and consequently entirely new approaches have not been forthcoming. Despite the passage of 35 years since the introduction of child safety packaging, and the concerted effort by consumer groups, industry and government, there have been no further new steps taken which have produced any further major gams in the reduction of childhood poisonings.

These groups appear to be locked exclusively in the thought pattern of using mechanical contrivances to limit children's access, The issue of ease of opening the packaging for seniors continues to be a major problem for all packaging that depends upon mechanical contrivances. To date, while significant efforts have been expended on limiting a toddler/infant's access, to items stored in packaging by various mechanical contrivances, better and more effective primary prevention means are still required to substantially avoid a situation where an infant/toddler will want to place a package into their mouth. No method has addressed the primary question as to the infant/toddler wanting to place the packaging into their mouth, or wanting to continue to explore the packaging and contents once they have access to the packaging.

Blister packs are a widely accepted child resistant packaging means from which tablets and other potentially injurious agents can be and dispensed. They are an example of non-recloseable child resistant packaging. Child resistant blister packages presently on the market generally work on a "difficult to open" blister principal. That is to say, that the child resistant feature is dependent on making it difficult for the child to open the blister pack. However, in order to keep children out of the package, packaging design makes it so difficult to open the package as to make it objectionable to adults.

Injury prevention literature discusses prevention activities that could intervene at any point in the childhood poisoning scenario. Consequently the concept of primary, secondary and tertiary prevention was introduced. Ozanne-Smith and Williams¹ (1995) discussed Haddon's matrix (Table 1) for injury prevention, and which is reproduced below. The occurrence of injury results as a chain, of events, and the matrix provides a conceptual framework for understandϊog that chain of events. The temporal (time) phases are associated with primary (pre- eveϊ-t)_» secondary (event) and tertiary (post-event) injury prevention. It is useful to consider the matrix in terms of a familiar example- a motor vehicle "accident". Table one: Haddons's Matrix

Factors

Pre-

I Event

Phases Event

Post- Event

Source: Ozanne-Smith and Williams

In that case a primary prevention (pre-event) might be some sort of action to make the car safer, such as adding ABS braking system, in order to decrease the likelihood that the driver would lose control and skid the vehicle resulting in a collision, A secondary prevention measure would be to include seatbelts and/or airbags, so that when a collision occurs, the injury to the occupants is minimised. An example of a tertiary preventiofrwould be the provision of a fast ambulance service so that the post injury sequelae are minimised. Obviously primary and secondary prevention measures are to be preferred, and of course where possible primary prevention is to be preferred over secondary prevention.

For example one form of prevention of childhood poisoning referred to as 'primary prevention* may include parents leaving distracting activities until the child's sleep time. Other forms of prevention such as a secondary (usually at the time of the event) or tertiary (after ingestion of a poison) prevention measure include limiting the damage caused to a child after the ingestion, of poison, for example giving the child milk after ingesting petroleum products or even providing of an antidote with a medicament formulation. Primary prevention is the preferred form of injury prevention generally, and of poison prevention specifically.

Various efforts have been made to prevent poisoning of infants by ingestion of insect repellents) and marking devices such as crayons. For example, in WO 2001/045506 (S, C. Johnson & Son Inc) there is described an insect mat including a heatable substrate, an insect control active material, and an . aversion-material. In this case the action of placing the mat into the oral cavity exposes an infant/toddler to ingestion a potentially injurious amount of the insect control material. The presence of an aversive material in an insect repellent mat however does not prevent an infant from ingesting the insecticide material in the first instance. Similarly, in Derwent Abstract Accession No. 2000-685100/67 (published 10 June 2000), there is disclosed adding an

Ozanne-Smith, J and Williams, F (199%) Injury research and prevention: a text Monash University aversive-flavouring to a crayon matrix. It is stated that the addition of an aversive to the crayon matrix would help prevent oral interactions with crayon products that could result in adverse health effects. It is evident however that the infant is still exposed to adverse health effects because ejection takes place after the infant has had an opportunity to interact with the crayon.

The problem with the prior art is that while they might reduce the amount of substance an infant/toddler ingests, said infant/toddler still access a potentially injurious substance in the first instance. These types of interventions are clearly secondary interventions, whereas primary interventions are very much preferred. Clearly further improvements are required to substantially prevent infant exposure to ox interactions with, a potentially hazardous chemical or product in the first instance. The aforementioned poisoning data and other independent data from around the world on infant injury clearly demonstrate that the problem of infant injury including poisoning still persists. Most if not all solutions tried to date are adult-centric and not child centric, because they assume that the primary method of examination is tactile (manual). The Haddon matrix is also useful, because it clearly demonstrates that primary and secondary prevention methods may be used together, that is synergistically.

In an alternative approach described in EP patent No. 997394 packaging was characterised in that it released an olfactory child deterrent means, which, in practice, Is released upon contact with sweat, or moisture.

The approach taken in EP 997394 represents a form of primary deterrent The aim of such an intervention was to prevent au infant/toddler from gaining access to an ingestible product, However, while mfant/toddlers may sense odours there is no conclusive evidence to show that infants and neonates can discriminate between pleasant and unpleasant odours [Engen and Lipsitt (1965)]. Research has for example shown that anise (pleasant) and asafoetida

(unpleasant) both elicit the same kind of mild startlement. Such evidence suggests that response to odour must be learned, A most important point to jbe .

Accident Research Centre, Melbourne 12 made is the differing roles that the sensory modalities play in the infant/toddler. Notably, there is a need to distinguish between the inflate single trial taste aversion learning that occurs with taste aversion, and the slower, underdeveloped learning of smell. The two sensory modalities have developed for two very different tasks, and while taste is particularly useful as a single trial aversion, olfaction is much less so, Olfaction is much more useful and informative for appealing or positive stimuli, such as the smell of food. This can be demonstrated with some very simple, yet powerful examples, in both children and adults. An example in adults is the durian fruit, which smells particularly foul, and yet which tastes delicious. The smell of the fruit does not stop people from eating and enjoying the fruit This would not be the case if olfactory aversion was as well developed. as taste aversion. Were the situation reversed (i.e. the fruit smelled delicious, but tasted foul) it would not be consumed. This simply demonstrates that smell aversion is a weaker and far less responsive modality than is taste aversion.

Smell attenuation or adaptation is also well recognised, and can start to operate even after a few breaths.

"In general, adaptation is defined as the waning of response with stimulus repetition. As in other sensory modalities, the decrease in sensitivity, or response to an odor stimulus following repetitive stimulation can be indexed using a variety of psychophysical or behavioral methods. For example, adaptation produces stimulus-speoific decreases in odor sensitivity and, in humans or animals, this decrease is most commonly measured by obtaining estimates of the absolute detection threshold before and after repetitive or prolonged exposure to an odor (Pryor et al, 1970 ). Adaptation also reduces the perceived intensity of an odor, a phenomenon that can be observed after even a few breaths of an odorant."

Dalton, P. (2000) Psychophysical and Behavioral Characteristics of Olfactory

Adaptation Chemical Senses, Volume 25, Number 4, Pp. 487-492 The outcome of this phenomenon is that an infant left alone with an olfactory aversive is more likely to adapt to or ignore the smell, and continue to explore the item at hand. This finding leads to the second example, that infants consistently ignore the sensory modality of olfaction, and place foul smelling items into their mouths for further tasting, happily ignoring the olfactory deterrent. The reason for this occurrence is that the infants/toddlers are equipped with a mechanism for detecting items "normally" found within their environment par excellence- the sensory modality of taste, and the mechanism is single trial taste aversion. To fully understand this mechanism, it is necessary to understand the ecological and evolutionary significance of the reflex. The mechanism and utility of single trial taste aversion learning is well documented and understood, Rescorla² discussed Pavlovian, or classical conditioning. He envisaged this type of learning as a rich and adaptive form of learning that quickly helps an organism adapt to the environment Interestingly Rescorla states that:

"Although conditioning can sometimes be slow, in fact most modern conditioning preparations routinely show rapid learning. One-trial learning is not confined to flavour aversion....."

It is interesting to note that taste aversion (not smell) is used as the classic example of single trail learning, a very powerful form of classical conditioning. The reason for this innate response is provided by understanding the adaptive significance of this feature, Taste aversion single trial learning is present across species- for example this paradigm was used by Ng³ in an ongoing series of studies across two decades with memory in day old chicks.

Essentially the development of the taste aversion arises because smell does not reliably provide information as to the toxicity of a potential food source, such as berries, etc. For example many poisonous plants do not produce an

² Rescorla, RA (1988) Pavlovian conditioning It's not what you think it is. American psychologist 43, 151-160

³ Gibbs MEHertz L,Ng KT, (2004) Inhibition of short-term memory formation in the chick by blockade of extracellular glutamate uptake. Neurobiol Learn Mem, 81 , 115-119. undesirable smell, But most poisons taste bitter, and so that modality is used by infants/toddlers to distinguish between potentially edible and potentially poisonous plants and berries in the "normal" environment It is important to understand what environment is considered "normal". Humans have developed to be hunter/gatherers, and so the "normal" environment to which they are adapted is that of the hunter/gatherer. In that environment, infants/toddlers stayed with women as they gathered foodstuffs for the day. The children were not closely monitored as they are in our 21^st century Western cultures, and so would wander, and opportunistically find interesting items, such as brightly coloured berries, some of which were palatable, and some of which were poisonous. The development of single trial taste aversion learning should then be viewed in that light. These finding can be considered in light of "bitter almond" which has a very mild smell, but which tastes quite bitter, and so is unpalatable. In this case the bitter taste warns of a potential poisoning from cyanide which can occur from ingestion of kernels from fruits such as almonds.

An olfactory deterrent therefore may not provide a sufficient barrier to prevent further investigation of a product.

To date, while EP 997304 might represent an alternative hi an aversive type packaging, the effect of an olfactory deterrent on infants is not optimal because an infant's olfactory sense is severely underdeveloped. The olfactory element is a most inadequate deterrent and restriction of access du to child resistant packaging if present , rather than any contribution made by the olfactory deterrent.

Further, referring to EP 997304, the child-deterrent effect of releasing a nasty smelling substance is initiated by contact with sweat, or water for example from a kitchen bench, this is clearly an undesirable effect since it allows release of odour in undesirable situations.

As indicated small children and particularly infants and toddlers are compelled to gnaw, and gnawing is largely independent of adult-centric behavioural factors such as food or water deprivation or satiation. For example:, infants chew on rubber or plastic articles as a means of easing pain and discomfort associated with or during tooth eruption. In fact the maximum levels of childhood poisoning occur at ages 18 months to 36 months, and this corresponds exactly with the timing of the eruption of the first and second deciduous molars. During tooth eruption children actively seek out and chew items to ease the significant pian associated with tooth eruption. During such, a growth phase if packages such as blister packs or bottles are within reach of an infant, the infant's instinctive reflex is to place the package in the mouth or at least to try to bite or suck on the article. This instinctive reflex exposes the infant to a potential poisoning hazard. The child might also, manually handle packaging, and consequently gain access to the contents of the packaging.

The foregoing discussion is not in any way an admission of the state of common general knowledge in this art.

A primary object is to cause an infant/toddler to lose interest in a container/packaging and discard it, so that the contents are not accessed by any means, such as using teeth or by manual handling.

A primary object of the present invention is therefore to provide an improved means for deterring a toddler or infant; automatic reflex to place packaging directly into iheir mouth.

A primary objective of the present invention is to provide an intervention that capitalises upon ubiquitous and unique developmental features of the "at risk" group.

A primary object of the present invention is therefore to provide an effective means for deterring a toddler or infant's automatic reflex to place packaging directly into their mouth, and thus to substantially prevent toddlers and infant children inadvertent access to, and ingestion of, packaging and/or its contents.

A further object is one-trial aversive learning to teach the child not to place packaging in the mouth, using a single trial taste aversive classical conditioning paradigm.

A further object of the invention is the provision of an effective means for deterring a toddler or infant's automatic reflex to place packaging directly into their mouth that readily complies with FDA or TGA regulations or regulations imposed by other similar legislative bodies.

A further object of the invention is the provision of an effective means for deterring a toddler or infant' s automatic reflex to place packaging directly into their mouth that is inexpensive.

Yet a further object of the invention is the provision of an effective, natural, organic means for reducing or preventing poisoning of infants and toddlers otherwise associated with a natural reflex to suck, bite and place packaging into their mouth.

A further object of this invention is the provision of effective means for reducing or preventing harm to infants and toddlers that may be applied to or incorporated within packaging material.

A further object of the invention is to cause the toddler/infant to cry, thus acting as an alerting mechanism for parent or care givers.

A further object of the invention, is to provide a useful and alternative or synergistic means for repelling and/or preventing infant access to articles contained in packaging which may cause damage or poison the infant/toddler.

A further object of the invention is to provide an intervention that effectively acts as primary prevention measure. SUMMARY OF THE INVENTION

The present invention is directed to a rion water soluble taste aversive container/packaging for substantially deterring an infant from accessing contents of the container, the container including a structure for storing a medicament or other potentially injurious substance, wherein the structure comprises a polymeric or other suitable matrix having incorporated therewithin an effective amount of a bitter taste aversive composition; wherein upon exposing a surface of the structure to sufficient moisture, the bitter taste aversive composition is released from the matrix at the exposed surface,

In a related aspect of the present invention there is disclosed a taste aversive container or packaging for substantially deterring an infani/toddler from accessing contents of the container/packaging, the container/packaging including a structure for storing a medicament or other potentially injurious agent,, wherein the structure comprises a polymeric or other type of non water soluble matrix having incorporated there within an effective amount of a bitter taste aversive composition; wherein upon exposing a surface of the structure to sufficient moisture, the bitter taste aversive composition is released from the matrix at the exposed surface.

In a related aspect, the present invention is directed to a container/packaging for storing a medicament or other potentially injurious agent and to substantially deter an infant from accessing contents of the package, the layer packaging film including:

a first or inner layer for encasing a unit of product, the first layer being a non- water soluble substrate;

a second layer of film formable on the first layer in a dispersion, the second film sheet being selected from a polymer or other suitable composition having a matrix adapted to retain an effective amount of a bitter taste aversive agent at or close to the surface thereof,

wherein bitter agent is removed from the second film sheet upon sufficient contact with moisture.

The packaging film can/may further, include a third layer applied to the second/intermediate film sheet, the third layer being selected from, for example, a hydrogel polymer composition which is adapted to erode/dissolve upon contact with saliva, in order to expose a surface of the second/intermediate, layer, wherein the bitter aversive agent at the exposed surface of the second/intermediate film elicits a response such that an infant's exploratory behaviour is deterred and eliminates exposure to package contents.

In a related aspect of the invention there is described a film forming liquid aversive composition for substantially deterring an infant from exploratory behaviour in a single trial learned response, the composition including between 0.5 and 2%w/v of a bitter or taste aversive agent and a solvent carrier system, wherein the composition is applied to at least a surface of an object such as a pharmaceutical package to form a localised film which releases an effective amount of the aversive agent to substantially elicit a learned deterrent response upon contact with saliva.

The solvent carrier system preferably localises film formation on at least a part of the surface. The film formed on at least a surface of the object, can be removable by water or aqueous solution/saliva.

The present invention has proved to be advantageous in substantially avoiding exposure of infants to potentially harmful products such as pharmaceuticals, which may present poisoning hazards.

A further advantage of the present invention is that the third layer does not undergo substantial erosion upon conventional handling. This means that adults may not ordinarily be exposed to transfer of the bitter aversive agent. Hence appropriate handling of the multi-layered packaging film does not immediately expose the person to transfer of bitter taste aversive agent to skin surfaces in contact with the multi-layer packaging film.

In a further related aspect of the present invention, there is disclosed a non water soluble container/packaging film for medication or other potentially injurious product and to substantially deter an infant from accessing contents of the package, the layer packaging film including:

a first layer for encasing a unit of product, the first layer being a non-water soluble substrate;

a polymeric or other suitable film formable on the first layer, the second film sheet being selected from a polymer or other suitable composition having a. matrix adapted to retain an effective amount of a bitter taste aversive agent at or close to the surface thereof,

wherein upon contact with sufficient moisture, bitter agent is selectively removed from a surface of the second film sheet.

In a related aspect of the present invention, there is described a container/packaging for a medicament or other potentially hazardous article, the container including a non water soluble receptacle structure made from a polymeric or other suitable matrix composition, wherein the polymeric matrix includes an effective amount of a bitter taste aversive composition dispersed therewithin;

a second film sheet applied to the polymeric structure, wherein the second sheet is selected firorn a polymer or other suitable composition adapted to erode or dissolve in contact with sufficient amounts of saliva wherein the area of erosion exposes a surface of the receptacle structure and releases the bitter taste aversive.

In this aspect of the invention the receptacle wall can include a plurality of structural recesses acting as a depot for housing aliquots of the bitter taste aversion composition.

The plurality of depots can include an erodable/soluble film sheet to encapsulate the bitter taste aversive within the each recesses.

Not only does the second film substantially prevent transfer of the bitter taste aversive composition during normal handling, there is sufficient loading of bitter taste aversive to provide repeat doses. This is clearly useful where a household may have more than one infant.

A saliva/chewing/sucking activated bitter taste or taste aversive container/packaging film for substantially deterring an infant from gaining access to contents contained therein, the packaging film including:

a non-water soluble container/packaging; and

an outer sacrificial sheet or coating selected from, for example, a hydrogel polymer composition, wherein the coating includes an effective amount of a bitter or taste aversive agent dispersed therein; and

wherein the container/packaging releases the bitter or taste aversive agent from the coating to a region of the surface thereof by sufficient exposure to saliva on mouthing, chewing or sucking.

An example of a taste aversive agent is quinine. Quinine can be present in the sacrificial layer in an amount ranging from 0.000] to 1.0 mg.

In a related aspect there is disclosed a saliva/chewing/sucking activated bitter or taste aversive packaging film comprising: a non-water soluble container/packaging; and

an intermediate sheet selected from, for example, a hydrogel polymer composition or other suitable formulation, applied to the non water soluble container/packaging, wherein the sheet includes an effective amount of a bitter or taste aversive agent dispersed therein; and

an external coating applied to the sacrificial sheet, wherein the external coating is selected to preferentially erode/dissolve upon contact with sufficient saliva/chewing/sucking and wherein when an area of the external coating erodes on contact with sufficient saliva/chewing/sucking the intermediate sheet is exposed; wherein the intermediate sheet is activated to release the bitter or taste agent at regions where the external coating has undergone erosion.

In a further related aspect of the present invention there is disclosed a non. water soluble taste aversive packaging as a primary aversive for behavioural learning deterrent in an infant, the packaging including: a receptacle structure for storing a medicament or other potentially injurious substance, wherein the structure comprises . a matrix having incorporated therewithin an effective amount of a bitter taste aversive composition; wherein the bitter taste aversive composition is released from a surface of the receptacle upon contact with sufficient moisture and wherein the contact surface is replenished with a surface concentration of the bitter taste aversive composition from within the matrix until the concentration of bitter agent within the matrix is depleted.

The taste aversive packaging as a primary aversive for behavioural learning deterrent in an infant can include: a receptacle structure for storing a medicament or other potentially injurious substance, wherein the structure is a polymeric matrix having at least one depot for receiving and releasing an amount of bitter taste aversive composition, the depot including a recess in the receptacle structure and an outer thin film layer, wherein the film encapsulates the amount of bitter taste aversive composition within, the recess, and wherein the film is adapted to rupture on contact to release a payload of the bitter agent composition,

In yet a further related aspect of the present invention there is described a non water soluble taste aversive layered packaging film as a primary aversive for initiating behavioural learning deterrent in an infant, said layered film being applied to a receptacle housing medication or other potentially injurious product, the layer packaging film including;

a first layer for encasing the receptacle, the first layer being non-water soluble; and

a film formable on the first layer, the film being selected from a polymer having a matrix adapted to retain an effective amount of a bitter taste aversive agent at or close to the surface thereof,

wherein upon contact with sufficient moisture, bitter agent is selectively released from the matrix of the polymeric film sheet to be present at the surface,

The non water soluble taste aversive layered packaging film can include a third layer. The third layer can be a hydrogel composition adapted to selectively erode upon contact with sufficient amounts of saliva, wherein erosion of the third layer exposes an infant to a surface of the second layer, and wherein the concentration of bitter aversive agent at the exposed surface of the second film sheet is effective to elicit a learned response such that an infent/toddler's exploratory behaviour is modified to substantially minimise risk of self exposure to medication or other potentially injurious product. In all aspects of the invention, the final inner layer of packaging will be non- water/saliva soluble, so that the pharmaceutical, chemical or other potentially injurious agent will not become available for ingestion by the infant/toddler. This aspect of the invention ensures that the invention will work as a primary prevention method. If the packaging were to be water/saliva soluble, then upon contact with the saliva of the infant/toddler the packaging is able to dissolve, and said infant/toddler is potentially able to access and ingest the contents of the packaging. Were this to occur the infant/toddler might reduce the amount of poison ingested- a secondary prevention, but the potential remains for the infant/toddler to be injured. This outcome is in contrast to the primary prevention which operates prior to, and prevents the poisoning.

There is further disclosed a method of deterring a child or infant from gaining access to contents of a container or package by means of a primary behavioural deterrent, the method including:

providing a non water soluble container for housing medicament or other potentially injurious material, applying a taste aversive agent in a film forming carrier composition to at least a surface portion of the container to form a first film portion, wherein the taste aversive agent is present in the first film in an effective amount to act as a primary deterrent for an infant child upon contact with a surface portion of the first film, and applying an outer coating layer to the taste aversive film layer, the outer coating being selected to preferentially erode/dissolve upon contact with sufficient saliva; wherein when an area of the external coating erodes/dissolves on contact with sufficient saliva, a portion of the taste aversive first film layer is exposed; and wherein the taste aversive film is activated by the exposure to moisture and releases bitter agent at the exposed surface in a sufficient amount to initiate a primary behavioural response and substantially prevent further exploratory behaviour of an infant and thus exposure to the package contents.

It is understood that the saliva/chewing/sucking activated bitter or taste aversive packaging film can be used for pharmaceuticals, chemicals and other potentially injurious substance or object and the like wherein the bitter or taste aversive agent is homogeneously or hcterogeneoυsly dispersed in the sacrificial sheet.

In a further related aspect of the invention there is disclosed a saliva/chewing/sucking activated bitter or taste aversive container/packaging for substantially deterring a child or infant from gaining access to contents of the package, the package including: a non water soluble container/packaging; and a bitter or taste taste aversive composition including, for example, quinine in a liquid film forming carrier, quinine being present in an effective amount to act as a deterrent for a child upon direct or indirect contact with a surface portion of the substrate, the composition being applied to at least a portion of the non water soluble container/packaging to form a coating on at least said portion; and an external coating applied to the bitter or taste aversive film, the coating being selected to preferentially erode/dissolve upon contact with sufficient saliva/chewing/sucking and wherein when an area of the external coating erodes on contact with sufficient saliva/chewing/sucking the bitter or taste aversive film is exposed; and wherein the bitter or taste aversive film is activated to release quinine at regions where the external coating has undergone erosion.

In a further related aspect of the present invention a bitter Or taste aversive packaging film is provided on the non water soluble container/packaging for substantially deterring a child or infant from gaining access to contents of the package, the packaging film containing a bitter or taste aversive deterrent agent. The deterrent agent can be selected from substances that provide an unpleasant taste for a child.

An example of a taste aversive deterrent agent is a bittering agent, Some bitter agents can be selected from extracts of plant or vegetable matter such as cynaropicrin, a plant species of the genus Cynara or chemicals such as but not limited to quinine or benzoic benzylamine amide. Generally it is understood that a child/infant is very inquisitive and e>tρlore their world using a substantially oral tactile sense. This is particularly so during eruption of the deciduous dentition where excessive saliva is generated as a consequence of gum inflammation and pain associated with the process commonly, called "teething". It is therefore a natural occurrence for an infant to want to touch and place objects into their mouth to try to relieve such symptoms. A packaging film or container, which incorporates or produces a bitter or taste aversion is naturally and instinctively discarded because of single trial taste aversion learning.

Packaging film suitable for use in the present invention include, but are not limited to, polymeric films such as blown film, oriented film, stretch and shrink film, heat shrinkable bags. Generally packaging films are flexible sheet materials with a thickness ranging between about 15 microns or less. Packaging films in accordance with the invention can include cellulosie material and thermoplastic stretch or shrink films and may be monolayer or multilayer films. Plastic films can be made from homo-polymers or copolymers of polyolefins such as polypropylene, polyethylene, or polyamides,

PET, PVC copolymers or ethylene-vinyl acetate copolymers or of proteinaceous material such as collagen, A surface of the polymeric film or substrate can be coated with a solution containing the bitter or taste aversive agent as a solute or dispersion, or by spraying a controlled amount in either dry or liquid form.

The aversive or bittering agent can be applied to a polymeric substrate, such as a film, by coating, for example, dipping, or spraying, brushing, roller application of a solution of the deterrent agent, or by impregnating the non water soluble substrate. Solution coating is preferred for placing very thin coatings on sheets, films and substrates, which have complex shapes swh as containers. The deterrent agent(s) utilised in accordance with the present invention can therefore be applied prior to or after formation of the polymer film/substrate to intersperse, coat and/or impregnate the polymeric substrate with a controlled amount of bitter or taste aversive agent per unit area of film. Mixtures of bitter or taste aversive agent can also be used or a plurality of agents can be applied serially. A bitter or taste aversive agent can also contain binding agents, emulsifiers and other additives.

In another aspect the bitter or taste averstve agent is ideally activated and soluble in saliva more so than water, so that the presence of saliva activates the aversive agent,

In a related aspect of the invention there is disclosed a non water soluble container/packaging for pharmaceuticals, chemicals other potentially injurious substance or object and the like, including a non water soluble container/packaging having a bitter or taste aversive agent applied thereto, wherein the taste aversive composition comprises a solvent carrier soluble in the polymer or other suitable substrate and microcapsules of a bitter or taste aversive agent and wherein the microcapsules adhere to a surface of the substrate and are disposed to burst on contact with moisture, such as saliva from an infant/toddler, so as to release an amount of bitter or taste aversive agent onto the surface of the substrate. In an alternative embodiment of this aspect the bitter or taste aversive agent can be homogeneously or heterogeneously dispersed in the polymer matrix. In a further related aspect of the invention there is disclosed a container for pharmaceuticals, chemieals other potentially injurious substance or object and the like, in which the container is formed from a no water soluble matrix in which there is dispersed an aversive composition containing micro-particles of said bitter or taste aversive agent, wherein bitter or taste aversive agent is released from or close to a surface layer of upon contact with a quantity of saliva..

In yet a further related aspect of the invention there is described a non water soluble container/packaging for a pharmaceutical, chemicals, other potentially injurious substance or object or the like, in which the container/packaging there is dispersed in or applied to an aversive composition containing microparticles of said bitter or taste aversive agent, the container further including an outer film layer applied to the substrate to seal the aversive composition, wherein the outer film layer is selected to be degradable in contact with saliva to expose an infant to at least an aversive surface portion of tihe substrate. When the outer layer is sufficiently degraded by the action of saliva, the bitter or taste aversive agent can be removed by further saliva contact

In a further related aspect of the present invention there is disclosed a structurally modified non water soluble container/packaging in which said package or container includes a single depot or plurality of spaced apart recesses, wherein at least one depot or recess(es) includes a quantity of a bitter or taste aversive agent. The depot or recess can be enclosed by a dissolvable film, gel or similar such that upon contact with saliva the bitter or taste aversive agent is available or is able to permeate a gel matrix upon breakdown of said gel matrix. One advantage of this aspect of the invention is that there is localised exposure to bitter or taste aversive agent in the area in which sucking takes place. If for example an infant opts to rotate the container to avoid an aversive taste experience, a fresh surface of bitter or taste aversive agent is ready to be exposed. Another major advantage of placing the bitter or taste aversive agents into recessed depots is that the bitter or taste aversive agent is less likely to contaminate the hands of adults who legitimately handle the packaging.

Still in a further related aspect of the invention there is described a non water soluble container/packaging for use in pharmaceutical, chemicals or other potentially injurious substance or product or the like including a first inert film layer on which there is applied a liquid coating composition of a bitter or taste aversive agent in a solvent carrier, a second degradable outer film layer applied to the coating of bitter or taste aversive agent, wherein the second layer is degradable upon sufficient exposure to wetting and exposes a surface of the bitter or taste aversive agent. The amount of bitter or taste aversive agent can vary widely depending on such factors the type of solvent, now the bitter or taste aversive agent is going to be applied (i:e. impregnated or surface coating), a desired time period of effectiveness. Water is a preferred solvent for preparing a solution for example in a dipping treatment The bitter or taste aversive agent applied to or impregnated within a polymeric substrate should be present in a sufficient length of time. Advantageously, the bitter or taste aversive agent would remain effective past opening of the package by the consumer and lifetime of the article(s) contained within the package. It is to be noted that a bitter or taste aversive agent that is coated on a siarfaoe of the non water soluble container/packaging, can exist as a surface coating or can penetrate the structure if the solvent used exhibits suitable solubility . characteristics in the substrate. Alternatively, the substrate can be a non- absorptive thermoplastic or a substrate on which a barrier coating has been applied or a multi-layer film or sheet that allows partial impregnation up to a barrier layer can be used,

In a related aspect there is described a child deterrent non water soluble container/packaging for substantially deterring a child or infant from gaining access to contents of the package, the package mcluding: a polymeric or other suitable substrate such as a film, sheet or container; and a bitter or taste aversive agent in a liquid film forming carrier, the composition being applied to at least a portion of the polymeric substrate to form a film coating on at least said portion, and wherein the bitter or taste aversive agent is present in an effective amount to act as a deterrent for a child upon direct oral contact with a surface portion of the substrate.

In use the bitter or taste aversive agent can be releasable from the substrate to a surface upon initiation by sufficient contact with moisture. Hence an infant/toddler who has a greater propensity to generate moisture or at least expose a package to high levels of moisture by mouth contact will preferentially initiate transfer or release of bitter or taste aversive agent from the substrate. Ih this aspect an adult opening a packaging sheet, film or container in which the deterrent composition has been applied generally supplies less moisture contact to initiate bitter or taste aversive agent transfer.

The present invention provides a practical and commercially effective means of deterring child access to contents of a packaged article by placing the article in a package according to the invention. In one commercial application of the instant invention, coating of a substrate with a bitter or taste aversive agent composition can be integrated into an existing manufacturing process.

Alternatively (a) a second package can be made to enclose a conventional packaged article or (b) a packaged article may be subject to a spray step to apply a coating to an existing package or article.

Articles for packaging, such as but not limited to pharmaceuticals, can be sealed in a package according to the present invention or alternatively an already sealed article can be inserted into an outer package according to the present invention.

A further advantage of the present invention is that the package can be sealed and readily opened by a tamper proof strip without significant contact with a surface of the bitter or taste aversive agent packaging. The tamper proof strip is typically shrink wrapped around a top end of the package.

The bitter or taste aversive agent can be a taste deterrent including a bitter agent selected from extracts from plant or vegetable matter and other chemicals, such as but not limited to: benzoic benzylamine amide; chemical compounds derived from chilli pepper plants; a plant species of the genus cynaro; denatonium benzoate; alkaloids; amino acids; trichloro anisole; methyl anthranilate, and quinine.

Quinine is a most preferable agent, Quinine as an agent is present in adult drinks such as bitter lemon and tonic water in amounts, which render the drink unpalatable to infants but will not be toxic Quinine is quite bitter enough and children are particularly sensitive to bitter agents.

In the amount to be used the potential dose of quinine would be negligible. It has been subject to extensive toxicity testing, and has been approved by the FDA for use in drinks, It is familiar and acceptable to the public. It is inexpensive, especially in small quantities used for this application, and easy to use.

In a related aspect there is described a child bitter or taste aversive agent composition for substantially deterring a child or infant from gaining access to contents of the package, the composition including:

a bitter or taste aversive agent in a liquid film forming carrier, the composition being applied to at least a portion of a non water soluble container/packaging on at least said portion, and wherein the bitter or taste aversive agent is present in an effective amount to act as a deterrent for a child when direct contact is made by the child with the surface portion of the substrate.

In a related aspect there is described a child deterrent non water soluble container/packaging for substantially deterring a child or infant from gaining access to contents of the package, the package including:

a non water soluble structure having impregnated therein a bitter or taste aversive agent in an effective amount in a liquid carrier such that upon liquid contact with a surface of the substrate the bitter or taste aversive agent is released from the structure network wherein the bitter or taste aversive ageitf is sufficient to substantially deter a child from further contact with the package, . In a related aspect there is described a method of substantially preventing a child from touching or gaining access to a packaged article, the method including providing a bitter or taste aversive agent composition containing. a carrier and a bitter or taste aversive agent such as quinine, the bitter or taste aversive agent being present in an effective amount to act as a deterrent for a child or infant from gaining access to the article, and applying the composition to a surface of the non water soluble container/packaging wherein on sufficient moisture contact with a surface of the packaging bitter or taste aversive agent is transferred to the infants taste buds, causing the infant to lose interest in, and consequently discard the packaging,

In a further related aspect there is described a child deterrent non water soluble container/packaging for substantially deterring a child or infant from gaining access to contents of the package, the package including:, a polymeric or other suitable substrate such as a film, sheet or container; and a bitter or taste aversive agent formable as a film on an external surface of the polymeric substrate, the bitter or taste aversive agent being formulated in a liquid carrier which effectively solubilises the bitter or taste aversive agent for application onto an external surface of the substrate; wherein the bitter or taste aversive agent is transferable to a contact surface upon initiation by sufficient moisture so that an effective amount of bitter or taste aversive agent is transferred to act as a repellent to infants/toddlers.

In yet a further related aspect there is described a child deterrent non water soluble container/packaging for substantially deterring a child or infant from gaining access to contents of the container/packaging;, the package including: a polymeric or other suitable substrate such as a film, sheet or container; and a bitter or taste aversive agent formable as a film on a surface of the polymeric or other substrate, the bitter or taste aversive agent being formulated in a liquid carrier which is effective to solubilise the bitter or taste aversive agent and allows penetration of the substrate; wherein the substrate acts as a depot for the bitter or taste aversive agent and the bitter or taste aversive agent undergoes diffusion and permeation through the polymeric substrate to a contact surface when a surface of the substrate is contacted with sufficient moisture wherein the bitter or taste aversive agent is transferable in a controlled and effective surface concentration so that the bitter or taste aversive agent is available for an extended period to act as a repellent for infants and children.

The bitter or taste aversive non water soluble container/packaging provided by the present invention has a sufficient surface concentration of a bitter or taste aversive agent after an initial period of permeation to act as a repellent for infants, whose natural reflex would ordinarily be to suck or try to place packaging into their mouth.

In the present invention an infant who desires to suck on the non water soluble packaging provided by the invention will be confronted with an undesirable/unpalatable bitter or taste aversive taste, which thereafter acts as a deterrent to further licking or sucking action. The present invention practically serves to teach an infant/toddler to avoid licking or sucking such packaging and hence items contained within such packaging are less likely to be accessed. It also causes an in infant/tøddler to lose interest in and discard the unpalatable container/packaging.

In a related aspect of the present invention there is disclosed a deterrent composition for substantially deterring a child or infant from gaining access to contents of the non water soluble container/packaging, the composition including an effective amount of a bitter or taste aversive agent; a liquid carrier for the bitter or taste aversive agent, wherein when the composition is applied to a polymeric or other suitable substrate the bitter or taste aversive agent is able to be transferred in an effective amount from me polymeric substrate upon surface contact with a sufficient initiating amount of moisture to act as a deterrent for a child or infant. .

The applicant has found that the bitter or taste aversive agent trialled has been effective without deleterious effects on infants. Preferred chemical compounds include quinine. Quinine solution was purchased from a pharmacy and placed upon the lid of a medicine container. When handled by two-year old infants, the objects were soon placed into the mouth.

Consequently, the infants immediately discarded the containers, and lost all interest in. attending to the containers.

An advantage of the invention is its use in redundant or "sacrificial" layers or coatings upon objects to be protected.

Yet another advantage of the invention is the ease of manufacture and relatively low cost.

Another advantage of the invention is that the targeted infant/toddler to be deterred is not harmed, and the quinine or other aversive agent at the concentration necessary for an effective deterrent is safe. Humans and non- targeted animals are not permanently or seriously harmed if they come in contact with objects treated with the invention.

Still another advantage of the invention is the potential for miscibility with various coatings and finishing substances and solvents.

Other objects, advantages and novel features, and further scope of applicability of the present invention will be set forth in part in the detailed description with reference to the example as set out previously.

In order that the invention is more readily understood. embodiments . will be described by way of illustration with reference to the drawings wherein: Diagram 1 is a diagrammatic overhead plan view of a blister pack form of an improved aversive safely packaging in accordance with a first embodiment of the invention;

Diagram 2 is a cross sectional view through A-B of Diagram 1;

Diagram 3 is a diagrammatic view of a further form of an improved, aversive safety packaging in accordance with a second embodiment of the invention having recesses on lid and body for placement of depots of aversive; Diagram 4 is a diagrammatic view of a further form of an improved aversive safety packaging in accordance with a third embodiment of the invention having sacrificial layers of aversive; and Diagram 5 is a cross sectional view through A-B of Diagram 4.

Detailed Description of the Present Invention-

Referring to Diagrams 1 and 2 there is shown a blister package 1 having a layer of bitter or taste aversive agent and sacrificial layer for substantially deterring a child or infant from gaining access to contents of the package. The package includes a blister film sheet 2 having disposed therealong a series of elliptical- shaped openings 3 configured transverse to the longitudinal direction of the sheet and arranged in parallel rows. The blister sheet includes a plurality of depressions for housing a dosage form of a medicament (not shown). The dosage form(s) are retained within the each depression by a lid or closure sheet to seal each dosage form within the separate depressions,

The package 1 further includes a sacrificial sheet 4 enclosing the blister film sheet 2. The sacrificial sheet 4 is a ph or saliva sensitive hydrogel polymer composition in which there is dispersed an effective amount of a bitter or taste aversive agent such that the sheet absorbs saliva on contact, which initiates slow and controlled release of the bitter or taste aversive agent to the surface of the sheet In this embodiment continued exposure of a surface of the sacrificial sheet to saliva initially diminishes surface concentration of the bitter or taste aversive agent, however this is replenished by diffusion gradient of bitter or taste aversive agent within the hydrogel composition.

Referring to Diagram 2, there is shown a cross-section corresponding to a line taken through the blister sheet indicated by AB. The cross-sectional view shows sacrificial sheet 4 enclosing the blister sheet .2. Between the sacrificial sheet 4 and blister sheet 2 there is shown a space 5, which accommodates each blister (not shown). Portions of the blister sheet 2 can have ridges to allow contact with the sacrificial sheet. Generally a force is required to be exerted on a blister to urge a dosage form out through the closure sheet. The blister package can further include a tamper proof strip so that the package can be opened without significant contact with a surface of the bitter or taste aversive agent packaging. The tamper proof strip is typically shrink wrapped around a top end of the package

Referring to Diagram 3 there is shown an aversive container 6 having a medicament receptacle 7 and a closure S each of which is conDiagramd to include a number of depots 9. The depots are formed in the body of ihe container at locations accessible to a child or infant and are shaped to receive a quantity of a bitter or taste aversive agent. The depots are enclosed by a film or hydrogel barrier through which the bitter or taste aversive agent in said composition is able to diffuse in effective concentrations upon exposure to saliva. The concentration of bitter or taste aversive agent within the depot can be saturated to maintain a surface concentration of the bitter or taste aversive agent at or close to the surface of the barrier,

Referring to Diagrams 4 and 5 there is shown a laminate taste aversive container 10 for substantially deterring a child or infant from gaining access to contents therein. The container 10 consists of a layered structure imchiding an inner wall 11 formed from plastic material and an inner layer film 12 and an outer layer film 13. Inner layer 12 is a saliva/water soluble film containing a bitter or taste aversive agent In this embodiment the bitter or taste aversive agent is captive within, the soluble film matrix and is released upon exposure to saliva or water. The inner layer film is surrounded by an outer protective: layer film 13, which degrades in contact with saliva at a contacted surface to expose a corresponding surface portion of the inner film layer.

In an alternative embodiment (not illustrated), the wall of the container is a polymeric network structure having impregnated therein a deterrent composition, the deterrent composition including an effective amount of a bitter or taste aversive agent composition such that when a surface of the structure is contacted with fluid/saliva, the bitter or taste aversive agent is released from the polymeric matrix network, When bitter or taste aversive agent is removed from the contacted surface, bitter or taste aversive agent from the matrix is urged towards the contacted surface by a diffusion gradient. So long as the concentration of bitter or taste aversive agent within the matrix is constant, the contacted/external surface of the structure continues to be replenished with fresh bitter or taste aversive agent from the matrix, The bitter or taste aversive agent concentration at the surface of the wall structure is sufficient to substantially deter an infant/toddler from further contact with the package.

In this embodiment the wall acts as a depot or matrix containing the bitter or taste aversive agent and the bitter or taste aversive agent undergoes diffusion and permeation through the polymeric substrate to a contact surface. When a surface of the substrate is contacted with sufficient moisture, the bitter or taste aversive agent is transferable in an effective surface concentration so that the bitter or taste aversive agent is available for a sustained period to act as a taste repellent for infants/toddlers.

In all aspects, placement of packaging within the mouth will cause the release of bitter or taste aversive agent, which will be available for the infant/toddler to taste- Bitter or taste aversion has been specifically identified as the sensory aversion of choice, because this process is specifically well developed in young children. The reason for this is that the reflex has adaptive significance because poisons are often bitter. Ecologically as humans developed, children could not be constantly monitored, and would be attracted to bright or colourful objects, such as berries on a. bush. The single trial taste aversion .learning is a very powerful learning experience which imparts a selective advantage upon those species which display the behaviour,

Claims

Claims:

1. A primary intervention article for an infant deterrent including a receptacle for storing a medicament or other potentially injurious agent, wherein the receptacle comprises a non water soluble matrix throughout which there is dispersed an effective amount of a bitter taste aversive composition; wherein the bitter taste aversive is released from the matrix upon exposure to a sufficient surface quantity of moisture,

2. A primary intervention method for an infant deterrent, said method including providing a film forming liquid aversive composition, the composition including a bitter or taste aversive agent and a solvent carrier system, wherein the composition is applied to at least a surface of an. object such as a pharmaceutical package to form a localised film which releases an effective amount of the aversive agent to substantially elicit a learned deterrent response upon contact with saliva,

3. A film forming liquid, aversive composition for substantially deterring an infant from exploratory behaviour in a single trial learned response, the composition including a bitter or taste aversive agent and a solvent carrier system, wherein the composition is applied to at least a surface of an object such as a pharmaceutical package to form a localised film which releases an effective amount of the aversive agent to substantially elicit a learned deterrent response upon contact with saliva.

4. Tlie film forming liquid aversive composition according to claim 3 wherein the solvent carrier system localises film formation on at least a part of the surface.

5. The film forming liquid aversive composition according to claim 3 wherein the taste aversive agent is present m the composition in an amount of between about 0.005% and 2.0%w/v.

6. The film forming liquid aversive composition according to claim 3 wherein the film formed on at least a surface of the object is. removable by water or aqueous solution/saliva.

7. The film form ing liquid aversive composition according to claim 3 wherein the bitter or taste aversive agent is selected from extracts of plant or vegetable matter,

8. The film forming liquid aversive composition according to claim 3 wherein the bitter or taste aversive agent is selected from non toxic synthetic chemicals.

9. The film forming liquid aversive composition according to claim 3 wherein the bitter or taste aversive agent is selected from non toxic amides such as benzoic benzylamine amide.

10. The film forming liquid aversive composition according to claim 3 wherein the film formed on at least a surface of the substrate is less than about 15 microns thick.

11. A method of deterring a child or infant from gaining access to contents of a container or package by a primary learned response behavioural deterrent, the method including:

providing a non water soluble container or package for housing medicament or other potentially injurious material, applying to at least a surface of the container a film forming liquid aversive composition according to any one of claims 3 to 10 to form a first film portion, wherein the taste aversive agent is present in the first film in an effective amount to act as a primary deterrent for an infant child upon contact with a surface portion of the first film portion.

12. A taste aversive container as a primary aversive for behavioural learning deterrent in an infant, the container including: a receptacle structure for storing a medicament or other potentially injurious substance, wherein the structure includes a non water soluble matrix having

5 one or more reservoir(s) in said structure, the reservoir including a recess in a surface portion of the receptacle structure for receiving an amount of bitter agent composition, and an outer thin film-layer, wherein the film encapsulates an effective amount of bitter agent composition within the recess, and wherein the film is adapted to erode or dissolve on. contact to release a payload of the

10 bitter agent composition.

13. A non water soluble taste aversive container as a primary aversive for behavioural learning deterrent in an infant, the container including: a receptacle structure for storing a medicament or other

1 5 potentially injurious substance, wherein the structure comprises a matrix having incorporated therewitbin an effective amount of a bitter taste aversive composition; wherein the bitter taste aversive composition is released from a surface of the matrix upon, contact with sufficient moisture and. wherein the contact surface

20. is replenished with a surface concentration of the bitter agent composition until the concentration of bitter agent within the matrix is depleted,

14. A non water soluble taste aversive layered packaging film as a primary aversive for initiating behavioural learning deterrerrt in an infant, said layered

25 film being applied to a receptacle housing medication or housing other potentially injurious product, the layer packaging film including:

a first layer for encasing the receptacle, the first layer being non^water soluble; and

30 a film formable on the first layer, the film being selected from a having a matrix adapted to retain an effective amount of a bitter taste aversive agent at or close to the surface thereof,

wherein upon contact with sufficient moisture, bitter agent is selectively released from the matrix to be present at the surface,

15. The non water soluble taste aversive layered packaging film according to claim 14 farther including a third layer applied to the film sheet, wherein the third layer is a composition adapted to selectively erode or dissolve upon contact with sufficient amounts of saliva, wherein erosion of the third layer exposes an infant to a surface of the second layer, and wherein the concentration of bitter aversive agent at the exposed surface of the second film sheet is effective to elicit a learned response such that an infant/toddler's exploratory behaviour is modified to substantially minimise risk of self exposure to medication or other potentially injurious product

16. The non water soluble taste aversive layered packaging film according to claim 15 wherein the third layer is a hydrogel.

17. A method of deterring a child or infant from gaining access to contents of a container or package by means of a primary behavioural deterrent, the method including:

18. An infant deterrent container, the container having a receptacle in which there is incorporated an aversive composition containing micro-particles of said bitter or taste aversive agent, wherein an initial burst of bitter or taste aversive agent is released from or close to a surface layer of the receptacle upon contact with a quantity of saliva, thereafter the surface layer is replenished,

19. An infant deterrent container according to claim 18 wherein the receptacle is selected from a polymeric matrix structure polymer matrix and wherein an initial burst of bitter or taste aversive agent is released from or close to a surface layer of the polymeric matrix upon contact with a quantity of saliva, thereafter the surface layer is replenished

20. An infant deterrent multi-layered packaging film for use in pharmaceutical, chemicals or other packaging to substantially prevent access of an infant to the package contents, the packaging film including a first inert film layer on which there is applied a liquid coating composition of a of bitter or taste aversive agent in a solvent carrier system, a second degradable outer film layer applied to the of bitter or taste aversive coating, wherein the second layer is degradable upon sufficient exposure to wetting to exposes a surface of the first layer from which the liquid coating composition is released,

21. A packaging film, or container or the like substrate for pharmaceuticals and other chemicals or injurious agents substantially deterring an infant child from opening the package or container, in accordance with claim 20 wherein the bitter or taste aversive agent can be applied to an internal or external surface of the polymeric substrate or film.

22. A child deterrent intervention safety package for substantially deterring a child or infant from gaining access to contents of the package, the package including: a polymeric substrate such as a film, sheet or container; and a deterrent composition in a liquid film forming carrier system, the composition being applied to at least a portion of the polymeric substrate to form a film coating on at least said portion, wherein the of bitter or taste aversive agent is present in. an effective amount to act as a deterrent for a child upon direct contact with a surface portion .of the substrate.

23. A non water soluble taste aversive container/packaging for substantially deterring an infant from accessing contents of the container, the container including a structure for storing a medicament or other potentially injurious substance, wherein the structure comprises a matrix having incorporated therewithal an effective amount of a bitter taste aversive composition; wherein upon exposing a surface of the structure to sufficient moisture, the bitter taste aversive composition is released from the matrix at the exposed surface.

24. The non water soluble taste aversive container/packaging for substantially deterring an infant from accessing contents of the container in accordance with claim 23 wherein the matrix is polymeric.

25. A non water soluble container/packaging film for medication or other potentially injurious product and to substantially deter an infant from accessing contents of the package, the layer packaging film including:

a polymeric or other suitable film formable on the first layer, the second film . sheet being selected from a polymer or other suitable. composition haying a . matrix adapted to retain an effective amount of a bitter taste, aversive: agent at or close to the surface thereof, wherein upon contact with sufficient moisture, bitter agent is selectively removed from a surface of the second film sheet.

26. The container/packaging according to claim 25 further including a third layer applied to the second film sheet, the third layer being selected from a hydrogel polymer or other suitable composition which is adapted to erode/dissolve with sufficient saliva contact to expose a surface of the second layer, wherein the concentration of bitter aversive agent at the exposed surface of the second film is effective to elicit a teamed response such that an infant/toddler's exploratory behaviour is modified, causing said infant/toddler to lose interest in and to discard the packaging containing potentially injurious agent, and so eliminate risk of self exposure to package contents.

27. A saliva/chewing/sucking activated bitter or taste aversive packaging film for substantially deterring a child or infant from gaining access to contents of the package, the package including: a non water soluble container/packaging; and a bitter or taste aversive composition in a liquid film forming carrier, the bitter agent being present in an effective amount to act as a deterrent for a child upon direct or indirect contact with a surface portion of the substrate, the composition being applied to at least a portion of the non-dissolvable polymeric or other suitable substrate to form a coating on at least said portion; and an external coating applied to the bitter or taste aversive film, the coating being selected to preferentially erode/dissolve upon contact with sufficient saliva/chewiug/sucking and wherein when an area of the external coating erodes/dissolves on contact with sufficient saliva/chewlng/sucking the bitter or taste aversive film is exposed; and wherein the bitter or taste aversive film is activated to release bitter agent in a sufficient amount at regions where the external coating has undergone erosion/dissolution to substantially prevent further exploratory behaviour of an infant and thus exposure to the package contents,

28. An aversive packaging film as substantially hereinbefore described with reference to the accon.pan.ying diagrams.

29. A saliva/chewing/suclung activated aversive packaging film for substantially deterring an infant from gaining access to contents contained therein, the packaging film including:

a non-dissolvable film sheet substrate; and

an outer sacrificial sheet or coating selected from a hydrogel polymer composition, wherein the coating includes an effective amount of a sensory deterrent agent dispersed therein; and

wherein the packaging film is activated to release deterrent agent from the coating to a region of the surface thereof by sufficient exposure to infant saliva or chewing or sucking.

30. A saliva/chewing/sucking activated aversive packaging film according to claim 29 including a sensory deterrent agent comprising a taste aversive agent.

30. A saliva/chewing/sucking activated aversive packaging film according to claim 30 wherein the taste aversive agent is quinine,

31. A saliva/chewing/sυcking activated aversive packaging film according to claim 30 wherein quinine is present in the sacrificial layer in an amount ranging from 0,005% to 2.0%w/v.

32. A saliva/chewing/sucking activated aversive packaging film including:

a non-dissolvable film sheet substrate; and

an intermediate sheet selected from a hydrogel polymer composition applied to the non-dissolvable film sheet substrate, wherein the sheet includes an . effective amount of a sensory deterrent agent dispersed therein; and

an external coating applied to the sacrificial sheet, wherein the external coating is selected to preferentially erode upon contact with sufficient saliva/chewing/sucking and wherein when an area of the external coating erodes on contact with sufficient saliva/chewing/sucking the intermediate sheet is exposed; wherein the intermediate sheet is activated to release the deterrent agent at regions where the external coating has undergone erosion.

33. A saliva/chewing/sucking activated aversive packaging film for pharmaceuticals, chemicals and other potentially injurious substance or object and the like according to claim 32 wherein the aversive agent is homogeneously or heterogeneously dispersed in the sacrificial sheet

34. A saliva/chewing/sucking activated aversive packaging film for substantially deterring a child or infant from gaining access to contents of the package, the package including: a non-dissolvable substrate such as a fiIm, sheet or container; and a taste aversive composition including quinine in a liquid film forming carrier, quinine being present in an effective amount to act as a deterrent for a child upon direct or indirect contact with a surface portion of the substrate, the composition being applied to at least a portion of the non-dissolvable substrate to form a coating on at least said portion; and an external coating applied to the taste aversive film, the coating being selected to preferentially erode upon contact with sufficient saliva/chewing/sucking and wherein when an area of the external coaling erodes on contact with sufficient saliva/chewing/sucking the taste aversive film is exposed; and wherein the taste aversive film is activated to release quinine at regions where the external coating has undergone erosion.