IE20100493U1 - A homeopathic complex - Google Patents

Abstract

ABSTRACT The present invention is directed to an anti-anxiety homeopathic complex and its use in the treatment of fear, phobias, anxiety or anxiety-related symptoms or mental health disorders. Ideally, the anti-anxiety homeopathic complex comprises a homeopathic tincture or dilutions thereof of Aconite, Avena Sativa, Passiflora incarnate, Scutellaria laterifolia, Stramrnonium, Valeriana and optionally Phosphorous and salts or acids . thereof.

Description

Introduction Anxiety is a complex combination of the feeling of fear, anticipation and apprehension/worry without apparent stimulus. It is often accompanied by physical sensations such as palpitations, chest pain and/or shortness of breath and physiological changes such as tachycardia. sweating, tremor in humans and drooling, pacing, panting in animals. It may exist as a primary brain disorder or may be associated with other medical problems including other psychiatric disorders.

Anxiety in animals can manifest itself as, for example. noise anxiety or phobia and can include anxiety related to thunderstorms, storms, fireworks, engines and other loud noises, separation anxiety or travel anxiety. In humans there are a huge range of anxiety phobias, which can be acute. chronic and/or anticipatory. These will be expanded on later.

There are many current methodologies for the treatment of anxiety or anxiety-related conditions. Usually, these treatments can involve one or more of the following conventional and non-conventional treatments: conventional anxiolytics drugs including benzodiazepines and non- benzodiazepines; psychotherapy including behavioural therapy; acupuncture or other alternative therapies; Chinese herbal remedies; herbal remedies including Bach flower remedies; and/or classical single remedy homeopathy such as Arsencium or in fact any single remedy matching the patient picture such as Amica Mental health disorders or psychiatric disorders include but are not limited to the following psychosomatic illness (psychophysiologic illness), hypochondria, obsessive- compulsive disorder, phobias many of which have an element of fear and anxiety.

However, none of these therapies is 100% effective on its own and, in practice, they are often used as part of an overall therapy often contributing a very small advantage over behavioural therapy.

In addition to the lack of effectiveness of some of these therapies, some therapies can have significant side-effects. Conventional drugs often have side-effects, ranging from mild to severe, which prevents their application to many patients. For example anti- anxiety drugs or anxiolytics have a slow onset time. In addition, many anxiolytics have either a sedative side effect or often other more hidden behavioural effects, such as dissociation, can occur. Conventional drugs may also be addictive and administration may result in the long term inability to cope without the drugs. in some cases, drugs used for the purposes of sedation have resulted in an aggravation of symptoms such as aggression following their use. For example, acepromazine/acetylpromazine (ACP) is used as a sedative/tranquilizer by veterinarians. it is a prescription only drug and can be used in the control of fear and anxiety symptoms in animals. The drug is also effective in alleviating vomiting caused by car or motion sickness. ACP is frequently used in combination with other sedatives and anaesthetics to provide smoother sedation and decreased doses of other anaesthetics. However, ACP can cause side effects, such as effects on blood pressure. In some cases the lower blood pressure remains long after the drug has been taken. Due to these severe side-effects, it may not be possible to administer ACP to some animals.

Therefore it is desirable to provide an anxiety treatment which addresses the significant side-effects associated with conventional drug therapies and is effective when used alone or in combination with other therapies.

Furthermore, another problem with current conventional methodologies is that no therapy is 100% effective across a population no matter what condition is targeted. Any therapy which can improve effectiveness across a wider range of subjects would be desirable.

Thus, there is a need for less expensive, safer and more user friendly therapeutic agents for use in the treatment of anxiety and anxiety-related conditions. Hence, the present invention is directed to specific homeopathic complexes which can treat anxiety and anxiety-related conditions without the negative side effect and costs issues usually associated with conventional pharmaceuticals.

Homeopathy is a form of alternative medicine and traditional homeopathy has been practiced for nearly two hundred years all over the world. Homeopathic medicine has its underpinnings in what is referred to as the Law of Similars or the similia principle.

The fundamental principle of homeopathy states that substances may be used to treat disorders whose manifestations are similar to those which they themselves produce in a healthy subject (Churchill Livingstone’s international Dictionary of Homeopathy Edited by Jeremy Swayne (2000) page 193. 1st Edition).

Homeopathic tinctures differ to herbal tinctures in their method of production, base ingredients used and their dilution.

Homeopathic tinctures are derived from many materials, whereas herbal tinctures are derived from plant materials only. Homeopathic mother tinctures are made following monographs laid down in the HAB (GHP- German Homeopathic Pharmacopeia), EP European Pharmacopeia, French Homeopathic Pharmacopeia BHP British Homeopathic Pharmacopeia HPUS Homeopathic Pharmacopeia of the United States.

While plants are the base ingredients for approximately 65% of homeopathic tinctures, the remainder are made from many mineral. animal or imponderable substance. Thus, the production of a homeopathic tincture involves the use of base ingredients from x- ray to diamond to Pulsatilla (the Wind flower).

A homeopathic mother tincture. comprising base ingredients such as for example fresh plants, is generally prepared by extracting the ingredients in a suitable solvent, followed by the steps of comminution. maceration and squeezing according to accepted homeopathic Pharmacopoeia. Suitable solvents inciude alcohol, water, water-alcohol mixtures, glycerine or isotonic sodium chloride solutions. Other techniques include tituration (grinding) with lactose to form a powdered dilution. On the contrary herbal tinctures are prepared in a different manner generally involving the use of a solvent to extract the base ingredient without the maceration or grinding steps. in homeopathy, a base preparation or mother tincture of a homeopathic remedy is made by liquid extraction (via maceration) of a herbal, mineral, animal or imponderable substance by dissolving the herbal, mineral, animal or imponderable in a solvent. In use, the mother tincture or 1x potency (1x10“ dilution) may be used as is, for example in diseases where the patient can benefit from the active principles within the tincture.

This assumes that the base tincture is not of a toxic nature. Optionally. the mother tincture may be further diluted. Essentially. a series of dilutions are prepared from the base preparation or mother tincture. This step is called potentization and involves a series of dilutions. Between each series the diluted substance is succussed (shaken in a vigorous manner). The process of dilution and succussion leads to a gradual loss of chemical toxicity while gradually increasing the homeopathic potency. The more dilute remedies being of greater potency.

Thus, homeopathic tinctures require a further dilution step in the production of the mother homeopathic tincture. This means that a homeopathic mother tincture is a 1x or 1 in 10 dilution of the base ingredient. Additionally, it is important to note that it is not possible to reconstitute a herbal mother tincture from a homeopathic mother tincture. Thus, what makes a tincture truly homeopathic is the additional dilution process to where the final mother tincture represents a dilution of 1:10 of the base ingredient.

Thus, homeopathic tinctures differ to herbal remedies in that a further dilution is required in the production of homeopathic tinctures so that the base material is 10% of the final mother tincture. As expanded on above a homeopathic mother tincture from fresh plants is prepared by extracting the ingredients in a suitable solvent, such as a alcohol, water-alcohol mixtures, water, glycerine or isotonic sodium chloride solution are used as a vehicle (solvent) followed by the steps of comminution, maceration and squeezing. Other techniques include tituration (grinding) with lactose to form a powdered dilution. On the other hand, herbal remedies are less dilute than homeopathic remedies and are prepared in a different manner merely involving the use of a solvent to extract the ingredient.

Homeopathic preparations as defined above must follow the monograph as laid down in the various homeopathic pharmacopoeias, for example the German Homeopathic Pharmacopeia (G.H.P. or H.A.B.), European Pharmacopeia (E.P.), French Homeopathic Pharmacopeia, British Homeopathic Pharmacopeia (B.H.P.) or the Homeopathic Pharmacopeia of the United States (H.P.U.S.).

I5 100493 -5? The dilution and sucussion level of homeopathic drugs are denoted as “x” or “d” for the decimal scale or centesimal ‘'0' scale or LM (Q) as 1:50.000 dilutions. This is expanded in Table 1 below.

For example, for a "3x' preparation, the mother tincture is diluted with nine parts of the desired diluent, in either liquid or powder form. The resultant mixture is then diluted a second time, in a ratio of one part mixture to ten parts solvent and the resulting mixture is diluted a third time in a ratio of one to ten. Therefore, the 3x or D3 potency is actually at 1x10"’ (1/1000) of the mother tincture. Similarly, a 6x potency dilution would be at 1x104’ of the original solution. In the "C scale" each dilution is done with ninety-nine parts diluent to the original mixture. Therefore, a 3G potency dilution is at 1x10‘ potency of the original mixture. ideally, x potency dilution is usually carried out with approximately 10 to 20 succussions, while C potency dilutions are carried out with anywhere from 10 to 100 succussions and in some cases 1000 sucussions between dilutions. The more stages of dilution and succussion a homeopathic solution has undergone, the higher the potency of that remedy.

These x and C scales are recognized by the main Homeopathic Pharmacopoeia such as the Gennan Homeopathic Pharmacopoeia (G.H.P.), French Homeopathic "5 700493 Pharmacopoeia British Homeopathic Pharmacopoeia, the Homeopathic Pharmacopeia of the United States (H.P.U.S.) and the European Homeopathic Pharmacopeia. when choosing the homeopathic remedy to administer, it is important to note that the homeopathic approach to treatment hypothesizes that the closer the matching of symptoms of the individual to be cured to those of the medicine being used. the greater the curing effect of the homeopathic treatment. This process is facilitated by these symptoms being catalogued in the homeopathic Materia Medica and various Homeopathic Fiepertories. The selection of the remedy is of prime importance in a successful homeopathic treatment. Of secondary importance, is the selection of the correct therapeutic potency. The potency of the medicine must be matched to the state of the patient and the state of the disease process. Thus. in a young healthy individual with an acute disease process a high potency medicine would generally be appropriate, whereas in an elderly patient with a chronic disease a low potency or even a diluted LM potency may be more appropriate.

In order to demonstrate the effectiveness of a homeopathic drug, the drug is tested by a "proving" in order to see how the drug will affect an otherwise healthy person.

Hundreds of compounds have been tested in this manner and these are catalogued in the various Homeopathic Fiepertories and Materia Medica. Homeopathic repertories generally provide listings of the human anatomy (or in some clinical repertories clinical conditions are listed) and list associated symptoms and treatments for these symptoms. Materia Medicae list homeopathic drugs and identify the maladies and symptoms each drug treats. The material in the Materia Medicae is derived from all the information about the homeopathic drug and includes data from homeopathic provings, toxicity, and clinical use. More over, where a repertory lists a symptom, it classifies possible treating compounds as either first, second or third degree and in some cases fourth degree remedies for that symptom. Typically, a homeopathic practitioner will prescribe homeopathic medicine that has the best overall recorded similarity to the overall disease picture in the patient. This also involves taking into account how important each symptom is in that picture especially the strange rare and peculiar symptom(s), mental, emotional, aetiological, general symptoms, local symptoms and modalities. A homeopathic medicine with first degree indications for a particular symptom picture is more likely to be used than a remedy with a similar second degree picture unless the second degree picture has a greater similarity to the overall patient picture. A homeopathic medicine with a third degree indication would be less likely to be used unless there was a greater similarity and particularly if there was IE 1 0 0 4 9 - 7- a strange rare and peculiar symptom present. Homeopathic tinctures and their derivative potencies or dilutions can be used in the treatment of a wide variety of diseases, conditions and or symptoms.

Classical homeopathy involves the administration of a homeopathic medicine based on a single ingredient. The use of a homeopathic complex comprising multiple different ingredients is contrary to conventional classical homeopathy teachings and in some pharmacopoeia this is not recommended (“Hahnemann Flevisited — A Textbook of Classical Homeopathy For the Professional” Luc Deschepper, First Edition 2001, “Achieving and Maintaining the Similimum Strategic Case Management for Successful Homeopathic Prescribing” LucDeSchepper, First Edition 2004. “The Organon of the Medical Art” by Samuel Hahnemann edited by Wenda Brewster O'Reilly First Edition, .) Thus, the present invention is directed to an alternative anxiety treatment addressing some of the problems outlined before and utilising homeopathic medicine.

Statements of the Invention According to a first general aspect of the invention, there is provided an anti-anxiety homeopathic complex comprising a homeopathic tincture or dilutions thereof of Aconite, Avena Sativa. Passiflora, Scutellaria, Stramonium and Valeriana.

Optionally, the anti-anxiety homeopathic complex may further comprise phosphorous [Phos] and salts or acids thereof. Such salts and acids include, but are not limited to Calcarea Phosphorioa [Calc Phos], Ferrum Phosphoricum [Ferr-P], Magnesia phosphorica [Mag-p]. Natrum phosphoricum [Nat-p], Phosphorous Acid and/or Zincum phosphoricum [Zinc-p]. when used in the treatment of general anxiety, the anti-anxiety homeopathic complex may further comprise a homeopathic tincture or dilutions thereof of one of more of the following ingredients Argentum Nitricum, Arsenicum Album, Belladonna, Borax, Calcarea Carbonica, Calcareas (preferably Calcarea Phosphorica) Caustlcum, Gelsemium, Hyoscamus, lgnathia, Lycopodium, Natrum and/or Chloride salts (preferably Nat Garb, Nat Mur, Nat Sulph and/or Aurum and salts thereof), Nux Vomica, Phosphorus and salts or acids thereof, Pulsatilla, Silicia, and/or Staphysagria.

When used in the treatment of travel anxiety, the anti-anxiety homeopathic complex may further comprise Apomorphine, Argentum nitricum, Arsencium Album, Borax, Cocculus lndlcus, Conium maculatum, Gelsemium sempervirens, Solanacea preferably Hyoscyamus niger, lpecacuanha, lgnathia Amara, Nux Vomica, Petroleum, Pulsatilla nigricans, Silica terra. Sepia succus, Tabacum, Veratrum album, and/or Zingiber otficinale. when used in the treatment of noise anxiety, the anti-anxiety homeopathic complex may further comprise Solanacea preferably Belladonna, Borax, phosphorous and salts or acids thereof (preferably Calcarea Phosphorica), Gelsemium sempervirens, Natrum salts (preferably Lycopodium clavatum, Natrum carbonicum, and Natrum muriatlcum), Phosphorus and salts or acids thereof, Rhododendron, Sllicia, and/or Staphysagria.

According to a second aspect of the present invention, there is provided a homeopathic complex comprising a homeopathic tincture or dilutions thereof as defined previously for use in the treatment of anxiety/fear or associated conditions or symptoms.

According to a third aspect of the present invention, there is provided the use of a homeopathic complex comprising a homeopathic tincture or dilutions thereof as defined previously in the manufacture of a medicament for the treatment of anxiety/fear or associated conditions or symptoms.

According to a fourth aspect of the present invention, there is provided a method of treating a mammal afflicted with an anxiety state comprising administering to said mammal a therapeutically effective amount of a composition comprising a homeopathic tincture or dilutions thereof as defined previously.

Detailed Description of the Invention In the specification the term “by weight” refers to the weight of the final composition and “by volume” refers to the volume of the final composition.

In this specification the term “homeopathic tincture and dilutions thereof” includes a homeopathic mother tincture and/or its various dilutions or potencies derived from the homeopathic mother tincture. It will also be understood that the homeopathic tincture comprises one or more extracts derived from plant. mineral, animal and/or imponderables.

Additionally, in the specification, it will be understood that the homeopathic ingredients can be referred to using different nomenclature or synonyms. The different nomenclature and synonyms are well known in the field and can be found in the homoeopathic literature.

Name OI‘ Remedy Abbreviation Nomenclaturelsynonyrn _MAl!£.E ’ ‘ - Aoonite., Monkshood. Wolfsbane. Common Aconitum napellus Acon. Aconlte. N. O. Ftanunculacee.

Avena., Common Oat. Oatstraw. N. 0.

Avena satlva Aven. Gramineae. Oatstraw.

Passiflora incarnate Passi. Passiflora. Passion flower. N. O. Passifioracee Scutellaria Iaterifolia Scut. Scutellaria. Skullcap. Mad-dog N. O. Labiatae Datura stramonium. Jimson weed.

Thornapple. Jamestown-weed. Stink-weed. N.

Stramonium Stram. 0. Solanaceae Valeriana offlcinalis Valer. VaIerlana., Valerian. N. 0. Valerianaceae.

MODIFIERS Agaricus.. Amanita muscarla. Fly Agaric. Bug Agaricus muscarlus Agar. Agaric. Champlgnon fou. N. O. Fungi.

Ambra. Ambergris. Morbid Secretion of the Ambra grisea Ambr. Whale.

Anacardium, Marking Nut. Malacca Bean.

Semecarpus Anacardium. N. 0.

Anacardium orientale. Anac. Anacardiacae. East indies.

Androctonus Androc Androctonus amurreuxl hebraeus Scroplon Apls melliiica. Apis. Apls-mel., Honey-Bee. N. O. lnsecta.

Apomophonlum muriatrlcum Apom-m Apomorphine Hydrochloride Argentum nitrlcum. Arg-n. Nitrate of Silver. Lunar Caustic Amica.. Leopard's Bane. Bruslewon. Fall Amica montana Am. Herb. N. 0. Composite.

Ars Alb., Arsen Alb., Arsencium Alb., Arsenic Trloxide. The white oxide of metallic Arsenic Arsenicum album Are. (Arsenicums) Artemisia , Muwort. Wormwood. N. 0.

Kali brorn. Bromide of Potassium. Potassium Kali bromatum Kali-br. Bromide.

Lac caninum Lao-o Lac can., Dog's milk.

Lachesis, Bushmaster snake, Lachesis muta.

Bushmaster. Surukuku. Trigonocephalous Lachesis mutus Lach. laohesis Lavendula Vera/Officionalls Lav-v Lavender Lupulus., Hops. N. 0. Cannabinacae of the Lupulus humulus. Lup. Urticacee i..ycopodium., Club moss. Muscus terrestris repens. Pes ursinus. Wolf's-claw. N. O.

L copodium ciavatum Lyo Lycopodlacee Magnesia phosphorica I393 Phosphate of Magnesia.

Mel Mel. Honey (& Honey with Salt Mel Cum Sale) Yellow clover. Sweet clover. Melilotus alba.

Melilotus otficinalis Mail. White and yellow varieties. N. O. Legininose.

Merc Soi., Mercurius Solublis Hahnemanni; Mercurius Mero-s., Merc.. also Metallic Mercurius Solubilus; Merc. Mercury Quioksilver.Argg1tum vivum Nat Carb.. Sodium carbonate. The common "Soda“ of the shops, purified, not the Natrum carbonioum. Nat-c. Bicarbonate of Soda.

Nat mur., Salt, Sodium chloride. Common Natrium muriaticum Nat-m. Rock Salt Natrum phosphoricum. Nat-p. Phosphate of Soda. Sodium Phosphate.

Nat Sulph.. Glauber's salt. Sodium Sulphate.

Natrum sulphuricum Nat~s. Sal Mirabiie. Soda vitriolata.

Nitricum acidum Nit—ac. Nitric acid. Aqua Fprtis. Solution.

Nux.. Poison nut. Strychnos Nux vomica. N.

Nux vomica Nux-v. O. Qggniacae.

Papaver somniferum. Poppy. N. O.

Opium. Op. Papaveraoee.

Petroleum Petr. Crude Rook oil. Oleum petrae. Coal Oil The Element Phosphorus ~ red amorphous Phosphorus Phos. Phosphorus Platinum metallicum Plat. Platina. An Element.

Lead the Element. Plum bum aceticum.

Acetate of Lead. Sugar of Lead. Plumbum carbonioum. Carbonate of lead. Pure White Plumbum metallicum Plb. Lead.

PuIsatilla., Pulsatllla nigricans. Pulsatilla pratensis. Anemone pratensis. Pasque-flower.

Pulsatilla pratensis Puts. Wind flower. N. O. Fianunc_ulaoeae Rhododendron . Siberian Rhododendron.

Rhododendron chrysanthurn Fihod. Yellow Snow Rose. N. O. Ericaoee.

Sepia.. Sepia succus. Cuttiefish ink. Sepia Sepia officinalis Sep oflicinalls. N. 0. Cephalopoda. J Silica terra Silloea Terra Silicea Flint. Sllex.

Silica terra Sil. Silicic anhydride. Silicon dioxide Sliicia in text Stannum metallicum. Stann. Stannum Tin. Trlturatlon of the pure metal Staphysagria. Delphinium staphysagrla.

Staphisagg Staph. Stavesacre. N. O. Ranunculaceae Strychninum. Strychnine. An alkaloid obtained from several species of Strychnos. Nux Stryohninum purum Stry. Vomlca.

Sulphur Sulph. Sulphur Sublimatum. Brimstone. Sublimed IE 100493 Sulphur Nicotiana tabacum. Tobacco. N. O.

Tabacum Tab. Sclanaceae Spanish tarentula. Lycosa tarantula. N. O.

Tarantula Hlspanica Tarent. Araneideae.

Thuja occidentalis Thu]. Thula., Arbor vitae. N. O. Coniferae Veratrum., Veratrum Alb., White heliebore.

White-flowered Veratrum. N. O. Melanthacae Veratrum album Verat. of the Lillaceae.

Zincum metallicum Zinc Zlncum Met. . Zinc. An Element. Zn.

Zinc Phcs.. Phosphide of Zinc. Zinc Zinc phosphoricum. Zinc-p. Phosphide.

Zingiber officinale Zing. Zingiber. Ginger. N. O. Zingiberaceae.

NQSODES A Tuberculosis Nosode. Bacillinum. A Baciilinum Bac. maceration made from a tubercular sputum.

Carcinosin Foubister. Carcinosin Burnett.

Carcinosinum. The nosode of Cancer.

Carcinosin was originally made from the Carcinosin Caro. discharge of a breast cancer Coiibacillinum 1 Call Collform Nosode Corynebacterlum Coryne A Corynebacterlum Nosode Distemperinum Dist‘ Nosode of Canine Distemper Colibaciliinum 2 E.CoIi Escherichia coll Lyssinum Lyss. Lyssin, Hydrophobinum. Nosode of rabies.

Gonorrhea nosode.. Glinicum. Potencies of Medorrhlnum Med. the Virus.

Staph Aureus Nosode Staphycoc Staphylococcus bacteria. Staphylococcinum.

Streptococcus Nosode Streptoc. Streptococcinum. Streptococcinum bacteria.

Avian tuberculosis - Chicken tuberculosis Tuberculinum Aviairae Tub- a. Tubercuiinum Avis Nosodes Bovine Tuberculosis - Tuberculinum Bovinum Tuberculinum Bovinum Tub Bov of Kent sometimes same as below Tuberculosis Nosode. The Tubercullnum Bovinum of Kent. Tuberculinum of Koch.

Liquid potencles. Nosode is prepared either from tubercular abscess or from a glycerine extract of pure cultivation of human tubercular Tubercullnum Koch Tub. bacillus. 1 According, to a first aspect of the invention there is provided an anti-anxiety ‘homeopathic complex comprising a homeopathic tincture or dilutions thereof of Aconite, Avena Sativa. Passiflora incarnate, Scutellaria iaterifolia, Strammonium, and Valeriana. This will be referred to as the “Main Core” within the specification. it will be understood that the homeopathic ingredients of the invention may be replaced or supplemented remedies with additional similar profiles. The main characteristic of the additional remedies is that they have similar profiles to the remedy they replace or supplement. iE1oo493 -13.

Furthermore, it will also be understood that these remedies of the invention may be replaced or supplemented with chemical equivalents or bioequivalents of the homeopathic remedies which essentially mimic the active moiety within the homeopathic remedy and ideally results in an agent with a similar profile to the homeopathic remedy. For example, venoms such as snake or spider remedies may be replaced by ammonium carbonate. Additionally and by way of non-limiting examples, the active agent within the Solanacea family (e.g. Belladonna, Strammonium, Hyoscyamus) are the alkaloids, particularly the tropane alkaloids, and the active agent within the Loganiaceae family (e.g. lganthia, Gelsemium, Nux Vomica) is strychnine (Strychnos). Other chemical equivalents or bioequivalents of homeopathic ingredients are well known in the field.

Phosphorous and salts or acids thereof may also be present in the Main Core. Such salts can be selected from the following Calcarea Phosphorica [Calc Phos], Ferrum Phosphoricum [Ferr-P]. Magnesia phosphorica [Mag-p], Natrum phosphoricum [Nat-p], Phosphorus [Phos] or Phosphoric Acid [Phos Ac] and/or Zincum phosphoricum [Zinc- Core A works on the majority of symptoms of anxiety. It was discovered through veterinary works and use with animals, however, we have found it is applicable to humans which demonstrate similar anxiety symptoms which may manifest in different ways. This aspect is expanded on later.

The Main Gore is targeted at calming underlying anxiety and tackling extreme responses to anxiety. Avena sativa, Passiflora, Scutellaria and Valerian provide the calming and prevention of side effects from psychotropic drug withdrawal, while the optional Phosphorus, salts and acids thereof and Stramonium provide a base level of reduction in extremes of fear and anxiety.

As stated above, the use of a homeopathic complex comprising multiple different ingredients is contrary to conventional classical homeopathy teachings and in some pharmacopoeia this is not recommended. Furthermore, it is also important to note there is no veterinary Materia Medica and if one followed a conventional Materia Medlca the combination of homeopathic ingredients in the Main Core would not be advised or expected to result in the anti-anxiety complex of the invention. .14.

The rhizomes and roots of Valeriana spp. (common name: Valerian; family Valerianaceae) have been used for medicinal purposes since ancient times. Valeriana is a genus of flowering plants in the family Valerianaceae. It includes a number of species of which the best known is the garden valerian Valeriana officinaiis. Valeriana is used as a herbal remedy to reduce tension and anxiety, over-excitability and hysterical states. It is calming without exerting too sedative an effect and is practically non-addictive. However, Valeriana is not conventionally used at homeopathic potencies.

The following table highlights the activity/"functionality of each ingredient of the Main Core. Phosphorous has been included in this table, even though it is an optional ingredient of the Main Core.

Main (‘tore Activltylfunctionality ingredient Aconite Treatment of fear, anxiety especially to sudden and acute stimuli.

Psychotropic activity, Non-addictive calming action lowers base level anxiety, Avena Sativa thus, decreasing sensitivity to external or sudden stim uii in general.

Passiflora Psychotropic activity, Non-addictive calming action lowers base level anxiety, lncamate thus, decreasing sensitivity to external or sudden stimuli in general.

Psychotropic activity. Non- addictive calming action lowers base level anxiety, Scutellaria thus, decreasing sensitivity to external or sudden stimuli in general. Can also Laterifolia be used to treat psychotropic drug withdrawal induced side-effects.

Combats fear/terror and mental health disorders ranging from anxiety in the Stramonium dark through terror to epilepsy.

Psychotropic activity, Non-addictive calming action lowers base level anxiety, Valeriana thus. decreasing sensitivity to external or sudden stimuli in general.

‘Phosphorus. salts and Combats general anxieties, for example fears already present which are acids thereof triggered by the slightest stimulus of any kind internal or external.

(Optional) Optionally, Lupulus Humulus may be added to the “Main Core” as defined above. .15..

It will be understood that the homeopathic complex of the present invention treats the general signs and symptoms of fear, phobia, anxiety and anxiety-related conditions and/or mental disorders in both humans and animals. Advantageously, the homeopathic complex of the invention possesses anxiolytic, antianoxic, sleep-inducing, hypnotic and anti-convulsant properties.

Furthermore, the homeopathic complex of the invention has an advantage in the treatment of psychiatric/mental health disorders, in that it is a non toxic, fast acting, non-sedating, non addictive treatment both for human and animals.

The homeopathic complex may be used as an anxiolytic in the treatment of psychiatric/mental health disorders in general, including but not limited to psychosomatic illness, hypochondria. obsessive-compulsive disorder or phobias. it has multiple applications across the spectrum of phobias in a spectrum of species. Not just does it have an application for specific phobic. it also has specific application for symptoms and syndromes presenting as a result of a phobia.

Anxiety symptoms, for example travel sickness, fear of thunder (loud noise) and .fear of narrow/confined spaces, are directly transposable from humans to animals. This means that objective symptoms of anxiety and fear in humans and animals can be correlated, however, the subjective component in animals can only be inferred. As homeopathy is good at targeting objective as well as subjective symptoms! components of anxiety and fear, we have been able to use human homeopathic repertoires for veterinarian use and can successfully infer the subjective symptoms from the objective symptoms. The following non-exhaustive table correlates general anxiety symptoms in humans to anxiety symptoms in animals.

Objective Symptom -- Human Objective Symptom - Animal Hiding " Hiding‘ Cowering * Cowering" Starting‘ Starting‘ Loquacity" Barking/vocalization‘ Screaming’ shrieking, barking, howling, nelghing vocalization‘ Wide eyed with fear Dilated pupils Shaking with fear/anxiety‘ ShaklngItrembIing' IE 100493 -13.

Sweating with fear Wet paw prints Involuntary urination - bed wetting etc‘ involuntary urination (eliminaticn)* Vomiting with fright — fear anxiety - travel sick Vomiting nausea. drooling. salivation -- travel sickness behaviour Diarrhoea with fright fear‘ Diarrhoea at show/vets etc (e|imination* Stage Fright Show fright Asthmatic breathing* Pantlng/asthmatic‘ Neurogenic cystitis Anxiety cystitis especially cats Hysteria Hysterical behaviour Biting‘ Biting* Picks at bed clothes. carphologia Tears bedding Fight — biting, punching Kicking biting scratching Flight - running away’ T3oIting' Self mutilation, hand wringing self destructive Hair pulling. lick granuloma Angioneuotio eruptions Hives urticaris from stress Pacing‘ Pacing‘ "l7igiting* FlestIessness* Vigilance’ Vigilance’ Destructive behaviour‘ Destructive behaviour‘ Paralysed by fear‘ Frozen‘ Grief Lick Granuloma, loquacity, isolation - wanting to be alone stares into walk. tear staining (Book ref when elephants cry) Obsessive Compulsive Disorder Excessive Grooming in a Cats, feather plucking in birds. Crib Biting, Box walking, Circling Windsucking in horses zoo animals etc e.g polar bears ADHD Attention Deficit Disorder/ Hyperactivity Disorder Hyperactive — disobedient animals (most often young animals) barking ignoring owners excessive energy (often related to high energy high carbohydrate foods) Company seeking‘ Owner seekinglrunning away to find people’ * = these symptoms were measured in the loud noise trials of the examples.

Combinations of the above symptoms can occur in response to any situation that produces or instigates a response, such as fear or anxiety. For example, a human with claustrophobia will react much like a dog with the same problem but the human can -17.. subjectively tell you they have claustrophobia apart from the fact that they sweat, panic, become hysterical and try to escape from the narrow space (even to the extent of pushing people out of the way and if necessary biting and scraping at them if they try to hold them in the narrow space) or they can simply freeze and deveiop rapid respiration. A dog, cat, horse or other animal when loaded into a small cage or horse box will react with exactly the same objective symptoms either they will freeze or they will panic developing rapid respiration, sweating, biting, kicking and trying to escape from the space. One is described as claustrophobia the other as loading or kennel phobia but effectively all are a fear of small spaces for one reason or another. The anti-anxiety formulations are useful in all the above cases as the main core and ancillary cores are designed to target ranges of symptoms exactly like this.

Thus, the homeopathic complex according to the present invention may be used trans- species in the treatment of fear-based conditions, depression, grief, home sickness, epilepsy, aggression and as a first aid treatment for anxiety and fear.

Specifically, the homeopathic complex may be use to treat animals suffering from noise phobia such as brontophobia (fear of thunder and lightening) or firework anxiety/fear/phobia, social anxiety phobia, bereavement, claustrophobia, autophobia, separation anxiety, aerophobia, necrophobia.

Noise phobia is common in canines. Noise phobia is an extreme fear to a defined stimulus characterized by sensitization, anticipation and flight. It is result of the interactions biological, genetic and environmental, being classified in specific or post- traumatic. The physio and psychopathology involve numerous conical structures, limbic and shaft brain, with participation of innate, learned and emotional components. The clinical signs consist of reactions of unjustified fear in front of an identifiable stimulus.

Noise phobia limited to a reduced group of stimuli as the fireworks, thunders, shots or explosions is the most common of the specific phobias in canines and felines. In contrast to the indispensable survival fear of the individual and the species, the phobia is a pathological behaviour of excessive fear that has lost its adaptive character. Noise phobia is an extreme, excessive and persistent fear unleashed by a definite stimulus (or group of narrowly related stimuli) normally presented in the environment and without real danger. it is accompanied by the sensitization processes, anticipation and avoidance. provoking a clinical significant discomfort that interferes with the normal behaviour.

J5 too 493 A further anxiety state is obsessive compulsive disorder which shows repetitive, persistent actions which are out of context. They interfere with normal behaviour and social interactions and deveiop harmful consequences that may be negative for the individual. Some causes are biological and behavioural factors, with central biochemical alterations. Associated anxiety signs may also be present These and other phobias may present with the following symptoms including destructive behaviour, self mutilation and/or ritualistic behaviours (pacing. circling in canines).

The homeopathic complex may also be used in the treatment of a wide range of phobias including, but not limited to the following: Arachnophobia ; Social anxiety phobia ; Aerophobia (including sickness); Agoraphobia ; Claustrophobia ; Autophobia ; Aerophobia ; Brontophobia ; Necrophobia ; Carcinophobia ; and/or Emetophboia. travel anxiety and motion Ideally, the homeopathic complex may be provided in any homeopathic dilution, for example from Mother Tincture onwards, including LM potencies. . Although, it will be understood that any homeopathic potency can be used provided that the dangers of toxicity with very low potencies or tinctures are taken into consideration and managed to remove any such danger from the final homeopathic preparation.

Suitable potency ranges for each ingredient of the Main Core are provided in the following table: ’5100493 Preferably, the potency of the homeopathic complex is from Mother Tincture to approximately 200C, preferably 300.

Ideally. the homeopathic complex according to the invention may be provided in a _ potency range from 1X to 12X, more preferably from 3X to 12X. This is ideal for the purposes of analytical traceability.

Ideally. Aconite is used at a potency of 3X. preferably 4X or greater. Stramonium and Phosphorus and salts or acids thereof are ideally present from 3x to 50M. Ideally, Stramonium is used at a potency of 3X, preferably 6X or greater. Ideally. Phosphorous and salts or acids thereof is used at a potency of 4X or greater. Conveniently, Acontite.

Stramonium and/or Phosphorous and salts or acids thereof are used at a potency range from 3x to 10M, preferably from 3x to 1M.

Avena, Passiflora, Scutellaria and Valeriana may be present from MT to 200C.

Advantageously, Avena, Passiflora, Scutellaria and Valerian are present from mother tincture to approximately 12x, preferably from approximately 4x to 12x.

Generally speaking, each ingredient is present in an amount from 0.1% to 20% v/v based on the volume of the total composition. ideally, each ingredient in the Main Core .20- is ideally combined in equal proportions, although other proportions/ratios may be used to achieve a similar effect.

According to one preferred embodiment, the Main Core comprises the following: IE100493.

Ideally, this homeopathic composition is in a form suitable for internal use, for example a liquid with typical excipients being alcohol and water.

The homeopathic ingredients are ideally combined from approximately 5 to 10%, preferably 6 to 7%. v/v based on the total volume of the final homeopathic composition.

Each ingredient is ideally combined in approximate equal proportions (1 :1 ratio) in the liquid excipient. Other proportions may be contemplated.

According to a preferred embodiment, a suitable ratio of Aconite:Avena:Passiflora:Phosphorous:Scutellariazstramonium:Valeriana is approximately 2:2:2:4:2:1:2. It will be understood that other ratios may be contemplated. it will also be understood that some homeopathic ingredients may be administered as a mother tincture, however, as explained before, for Regulatory reasons in some countries some homeopathic ingredients may not be administered as a mother tincture and must be diluted to 2x, preferably 4x, 6x or 8x or higher for administration.

Regulatory constraints will dictate the allowable potency.

To make an anti-anxiety homeopathic composition of the invention, each ingredient is made according to the potency range described above and this is done by different methods depending on whether it is a tincture or titurate. A titurate refers to the insoluble homeopathic ingredients which are diluted and potentised by grinding with for example, lactose. A tincture is as defined previously and is diluted and potentised in the usual manner by sucussion in an alcohol and water premix. The tincture and titurates are then combined with each other. These comments about tincture and titurates are relevant to all embodiments/compositions of the invention in use, the anti-anxiety composition may be administered as a liquid. to any mucous membrane of a subject to be treated, e.g. mouth, gum etc. Other alternative forms of administration are expanded on later. Water and alcohol are ideally used with the homeopathic complex of the invention. Daily dosage for subjects less than 20kg is approximately 5 drops/10 kg and for subjects greater than 20kg the dosage is approximately 15 drops. , it will be understood that the homeopathic complex according to the 'present invention is suitable trans-species, i.e. for both humans and animals. This invention is particularly applicable to domestic animals. such as cats and dogs, which frequently demonstrate anxiety conditions in response to traumatic events or loud noises.

Furthermore, the complex according to the invention has been used in clinical practice for horses and cattle with similar anxiety issues. Thus. it will be understood that the homeopathic complexes of the present invention may be used in the both human medical and veterinary applications and are trans-species in action. Indeed, the homeopathic complexes work in a wide variety of species, from companion animal (e.g. canines, felines to exotic parrot etc) to farm animals (e.g. equines and bovines etc) and to humans to name a few. ‘ Optionally, the Main Core may be supplemented with the following homeopathic ingredients: Apis mellifica, Lachesis and/or Hyoscyamus niger; or Thuja, Medorrhinum and/or Tarantula hispanica. when used in the treatment of bereavement/grief and obsessive compulsive disorder (000), the anti-anxiety homeopathic complex may further comprising a homeopathic tincture or dilutions thereof of one of more of the following ingredients,‘ Ambra Grisea Aurum and salts thereof, lgnathia . Calcium and salts thereof.

Kali salts (preferably potassium salts such as causticum), Lachesis, Natrum and salts therof, Pulsatilla, Staphysagria and/or Nosodes inc Bowel nosodes (e.g. Carcinosin Proteus Bach); or Agaricus Gresia, Argent Nit. Arsenicum Anacadium, Arum triphyllium.

Solanacea (such as Hyos), Chamomilla, Cocculus, Cuprum and salts thereof, lodium, Lilium Tig Lycopodium. Mercurius Nux Vomlca, Platina, Sulphur, Sulphur containing homeopathlcs and/or Nosodes including Bowel nosodes (such as Medorrhinum Tuberculinum Dysentry Co Lyssin).

Other homeopathic tinctures of various ingredients or dilutions thereof may also be added to the Main Core as indicated below. The addition of remedies around the Main Core results in a much wider range of signs and symptoms being alleviated. -23.

A These optional ingredients are listed below. it will be understood that each group of additional ingredients or ingredient per se may be added to the anti-anxiety complex comprising the main core on its own or in combination with any number of the different groups or ingredients. Thus. these additional groupings and ingredients are not mutually exclusive any may be combined in any manner.

The invention will now be described in relation to several further embodiments comprising the Main Core and optional groups of ingredients.

According to one embodiment, there is provided an anti-anxiety homeopathic complex for the treatment of general anxiety comprising the Main Core and a homeopathic tincture or dilutions thereof of one of more of the following ingredients Argentum Nitricum, Arsenicum Album. Belladonna, Borax, Calcarea Carbonica, Caicareas (preferably Calcarea Phosphorica) Causticum, Gelsemium, Hyoscamus, , lgnathia, Lycopodium, Natrum and Chloride salts (preferably Nat Carb, Nat Mur, Nat Sulph and/or Aurum and salts thereof), Nux Vomica, Phosphorus and salts or acids thereof, Pulsatilla, Silicia, and/or Staphysagria. Optionally, the complex may comprise.hypericum perforatum and/or nux moscha.

According to another embodiment there is provided an anti-anxiety homeopathic complex for the treatment of travel anxiety comprising the Main Core and a homeopathic tincture or dilutions thereof of one of more of the following ingredients Apomorphine. Argentum nitricum, Arsencium Album, Borax, Cocculus lndicus, Conium maculatum, Gelsemium sempervirens, Solanacea (preferably Hyoscyamus niger), lpecacuanha, lgnathia Amara, Nux Vomica, Petroleum, Pulsatiila nigricans, Silica tetra, Sepia succus, Tabacum, Veratrum album, and/or Zingiber officinale.

According to another embodiment, there is provided an anti-anxiety homeopathic complex for the treatment of loud noise anxiety comprising the Main Core and a homeopathic tincture or dilutions thereof of one of more of the following ingredients Soiancea (preferably Belladonna), Borax, phosphorous and salts or acids thereof (preferably Calcarea Phosphorica), Gelsemium sempervirens, Lycopodium clavatum, Natrum carbonicum, Natrum salts (preferably Natrum muriaticum), Rhododendron, Silicia, and/or Staphysagria.

According to another embodiment, there is provided an anti-anxiety homeopathic complex for the treatment of convulsive anxiety, including fits, epilepsy and hysteria, !E1oo 4 comprising the Main Core and/or any of the above embodiments with a homeopathic tincture or dilutions thereof of one of more of the following ingredients Cuprum metallicum, Zincum metallicum, Plumbum metallicum. Stannum metallicum, Agaricus, Artemsia Vulgarus, Bufo, Chamomiila, Cicuta virosa, Cina, Cocculus, Kali bromatum, Magnesia phosphorica, Sulphur and Sulphur containing homeopathlcs, Strychninum purum, Veratrum album, Hydrophobinium (equivalent to Lyssin) and/or Distemperinum Opium Proteus Bach. Kalis in general Kali Phos may also be added.

According to yet another embodiment there is provided an anti-anxiety homeopathic complex comprising the Main Core and/or any of the above embodiments with a homeopathic tincture or dilutions thereof of one of more of the following ingredients Acid Nitricum, Anacardium occidentale, Androctonus amurreuxi hebraeus, Arnica Montana. Aurum and salts thereof, Metallicum, Cenchris contortrix, Chamomilla matricaria, Falco peregrinus, Hepar sulphuris, Lac caninum, Lachesis Muta, Mercurius Solublis Hahnemanni (Mercurius vivus), Platina metallicum [Plat], Sepia succus [Sep] and/or Tarantula hispanica [Tarent].

According to yet another embodiment there is provided an anti-anxiety homeopathic complex comprising the Main Core and/or any of the above embodiments with a homeopathic tincture or dilutions thereof of one of more of the following ingredients Acid Nitricum [Nit-ac] [Ac-Nit], Anacardium occidentale [Anac-oc], Androctonus amurreuxi hebraeus [androc], Arnica Montana [Arn], Aurum Metallicum [Aur] and salts thereof, Cenchris contortrix [Cench], Chamomiila matricaria [Chem], Falco peregrinus [Falco-p.], Hepar sulphuris [Hep], Lac caninum [Lac-c]. Lachesis Muta [Lach]. Lyssin (Hydrophobinium) [Lyss], Mercurius Solublis Hahnemanni (Mercurius vivus) [Mere], Nux vomica [Nux-v], Platina metallicum [Plat], Sepia succus [Sep] and/or Tarentula hispanica.

According to yet another embodiment there is provided an anti-anxiety homeopathic complex comprising the Main Core and/or any of the above embodiments with a homeopathic tincture or dilutions thereof of one of more of the following Opium [Op], Cannabis indica [Cann-fl, Cannabis sativa [Cann-s], Chrysanthemum leucanthemum [Chrysan.], Cinnamon [Cinnam.] (preferably Cinnamomum Zeylanicum and/or Cinnamomum Cassia), Cypripedium pubescens [Cypr], Lavendula Oificinalis, Lavendula Vera [Lav-v], Melilotus officinalis [Meli], and/or Mels[Mel]; The homeopathic complex of the invention may further comprise Nosodes (including bowel nosodes) preferably present at a potency range from approximately 3X to 10M, preferably from 3X to 12X. it will be understood that Cenchris contortrix [Cench], Lachesis Muta [Lach] and/or Tarentula hispanica [Tarent] may be substituted with other snake or spider remedies of similar profile.

The homeopathic complex according to the present invention has many advantageous properties including safety, speed of action, ease of use and efficacy.

Furthermore, the homeopathic complex lacks toxicity and associated side effects. It is well tolerated and is compatible with many conventional pharmaceuticals. it provides for a rapid response time and is highly effective. In many cases administration led to immediate relief and the immediacy of this relief far exceeds current anxiolytic response times. Furthermore. the homeopathic complex is non-sedating. It can be administered to subjects even in a distressed state. It can be delivered in multiple formats from topical to oral to parental and there are minimal treatment requirements which increase patient compliance and enhancing successful outcomes. Furthermore, it provides for a consistent response and action across all species and across a wide range of conditions or even types of the same condition According to a preferred embodiment of the present invention. it will be understood that each ingredient is present in the anti-anxiety homeopathic complex at approximately equal proportions. Other proportions may also be used. ideally, the homeopathic complex is manufactured according to a competent homeopathic pharmacopeia such as the German, US, UK, EU and/or French Homeopathic Pharmacopeias.

Homeopathic complexes are generally prepared in liquid carrier solutions but may also be extracted in, for example, lactose by trituration and may thereafter be prepared in various delivery forms. For example, the extracted material of the homeopathic ingredient may be extracted in liquid form, using an alcohol and water solvent. This is then followed by comminution. percolation, maceration and squeezing techniques. when extracted in liquid form the resulting solution can contain anywhere from one part drug to three parts mother tincture although this strength can vary from 10 to 50% "$100493 .23.. depending on the monograph used. What makes a tincture truly homeopathic is the additional dilution process to where the final tincture represents a dilution of 1:10 of the drug, in effect a 1x dilution. The tincture or titurate may be combined with a base for use as a topical preparation or be used directly as a liquid oral preparation.

Alternatively, it may be sprayed or impregnated onto various solid mediums, such as a tablet. Alternatively, extraction of the homeopathic ingredient by tituration may take place using lactose for example to result in a solid or powder extract done up to ac or third centesimal dilution.

All the complexes according to the present invention may be used for topical including eye drops, oral, transdermal, implanted, suppository, or parenteral administration in a wide variety of forms such as gels, spray, liquids, powders, tablets, pillules, lotions, liniments, ointments to give just some examples. It will be understood that the homeopathic complex is made in the usually homeopathic manner according to homeopathic guidelines. It may then be administered as it is, or as a homeopathic dilution thereof. It may be administered in different ways by combining the complex with a delivery means, such as a cream or spray for topical use or a tablet for oral administration etc.

According to one specific embodiment of this aspect of the invention the homeopathic complex is in the form of an oral preparation, such as a dry dose form including a powder or tablet. Preferably, the homeopathic complex is provided in the form of a dosage unit form selected from a group consisting of tablets, capsules. pellets, gel caps, pills, pillules, globules, granules, crystals and suppositories. For example, tablets comprising lactose and sucrose may be used.

Alternatively, the homeopathic complex according to this aspect of the invention may be in the iorrn of a liquid preparation, such as a syrup or paste. spray or drops. Delivery of the liquid preparations may be in the form of injections, eyedrops. eardrops, nasal sprays, inhalers or diffusers.

According to another embodiment of this aspect of the invention the homeopathic complex may be in the form of a topical preparation such as an ointment, cream, lotion, oil, liniment, liquid and gel, such as a hydrophilic ointment.

E 10 o 4 9 3 Daily to twice or thrice administration of the homeopathic complex for a period of days is contemplated. it may be applied topically as needed, orally for daily dosage in unit dosage form or in liquid drops.

Conventional pharmaceutical excipients or cosmetic excipients suitable for the deliver system used can have the homeopathic complex incorporated into them or the homeopathic complex can be applied to the end product or packaged with the end product.

For solid dosage forms the accepted dose of medicating potency commonly used is two drops (0.2ml) to about 109 of the dose form giving a final remedy content of between 1 and 2% of the base material, whether homeopathic carrier such as lactose or a conventional tablet form. It is only necessary for each tablet to be coated with the alcoholic vapour carrying the homeopathic.

For creams, gels, ointments, lotions and liniments, the medicating liquid potency component can be 3% or less to 5% with efficacy being based more on the medicating tincture be it single remedy or complex suitability to the actual condition and patient rather than actual medicating potency percentage.

For liquid dose forms (such as injections. eye drops, oral liquid doses, nasal sprays and other spray forms) the homeopathic can either be made as part of the dilution process or the liquid can be medicated with about O.1ml of medicating potency to 1ml of liquid product.

Pharmaceutical excipients are substances other than the pharmacologically active drug or prodrug which are included in the manufacturing process or are contained in a finished pharmaceutical product dosage form. They are classified by the functions they perform in a pharmaceutical dosage form. Principal excipient classifications or functions include, but are not limited to the following: Binders; Dislntegrants; Fillers (dlluents); Lubricants; Glidants (flow enhancers); Compression aids; -' 551004 -23.

Colors; Sweeteners: Preservatives; Suspensing/dispersing agents; Film formers/coatings; and/or Flavors.

Some excipients, for example, comprise the product's delivery system. These transport the active drug to the site in the body where the drug is intended to exert its action.

Others will keep the drug from being released too early in the assimilation process in places where it could damage tender tissue and create gastric irritation or stomach upset. Others help the drug to disintegrate into particles small enough to reach the blood stream more quickly and still others protect the product's stability so it will be at maximum effectiveness at time of use. in addition, some excipients are used to aid the identification of a drug product. Last, but not least, some excipients are used simply to make the product taste and look better. This improves patient compliance, especially in children. Although technically "inactive" from a therapeutic sense, pharmaceutical excipients are critical and essential components of a modern drug product. In many products, excipients make up the bulk of the total dosage form. ideally, this formulation of the invention is provided in a form suitable for topical administration. As such, it may be delivered as a topical cream, lotion, gel, ointment, liniment, eyedrops, spray. skin patch/dressing or combined with a conventional topical medication or skin treatment.

For topical administration, the homeopathic formulation can be combined into any commercially available base. For example, the base may comprise approximately Lanolin from approximately 15 to 35%, preferably 25%; Mineral oil from approximately 5 to 35%, preferably 25%; and Petroleum from approximately 40 to 60%, preferably 50% at 2oz/lb.

Alternatively, the base may be a silcox base or a non-lanolin non-mineral oil aqueous cream.

According to one embodiment of the invention, there is provided a general anti-anxiety homeopathic complex as follows: -29.

EXAMPLE FINAL NAME OF REMEDY PREFERRED POTENCY RANGE POTENCY IN PRODUCT Aconitum napellus (gconlte) 4x to all potencies including LM’s 200c.1M,1OM Argentum Nitricum 4x to all potencies including LM’s 6cL30c,200c Arsenicum Album 6x (for safety) to all potencies inciudingt.M’s 6c.30c200c Avena Saliva MT to all potencies inc|udingLM's 2c,7x Belladonna 2x, 4x to all potencies including LM’s for safety 30c x to all potencies including i.M's in solid forms such as creams tablets x and above in Liquid and 9x and above in 90% Borax alcohol 6c,30c x to all potencies including LM’s in solid forms such as creams tablets x and above in Liquid and 9x and above in 90% Calc Carb alcohol 30c,200c x to all potencies including LM’s in solid forms such as creams tablets x and above in Liquid and 9x and above in 90% Calc Phos alcohol 30c,200c x to all potencies including LM’s in solid forms such as creams tablets x and above in Liquid and 9x and above in 90% Caustlcum alcohol 30c,200c Gelsemium 2x. 4x to all potencies including LM’s 6c,30c.200c Hyoscamus 2x. 4x to all potencies including LM’s 30c x to all potencies including LM’s in solid forms such as creams tablets -8x and above in Liquid and 9x and above in 90% _lgnathia alcohol 6c,30c,200c,1 M Lycopodiurn 2x to all potencies including LM’s 60.300 x to all potencies including LM’s in solid forms such as creams tablets x and above in Liquid and 9x and above in 90% Nat Carh alcohol 30c,200c x to all potencies including LM’s in solid forms such Nat Mur as creams 30c,200c,1 M Nux Vomica 2x, 4x to all potencies including LM’s 6c,30c,200c Passiflora MT to all potencies including LM’s 7x Phosphorus 4x to all potencies including LM’s 6c,30c.200c,1 M Pulsatilla 2x to all potencies including LM’s 30c.200c,1 M Scuteilaria MT to all potencies including LM’s 2c,7x Silicia 2x to all potencies including LM’s 300.2000 Stramonium 2x, 4x to all potencies including LM’s 30c Staphysagria 2x, 4x to all potencies including LM’s 6c,30c Vaieriana MT to all potencies incIudinJq LM’s 2c,7x,200c According to this embodiment of the invention, to make an anti-anxiety composition. each ingredient is made according to the potency range above. Each ingredient is then combined in approximately equal proportions in a water and alcohol excipient. _3o_‘ Generally speaking, each ingredient is present in an amount from 0.1% to 20% vlv based on the volume of the total composition. The anti-anxiety composition may be administered to the subject, whether human or animal as a liquid. to any mucous membrane. Other administration forms and means may be contemplated.

The above formulation is targeted at a broad range of anxieties such as stage fright, fear of appearing in public e.g. show tear in animals. fear of doctors visits in human and animals alike. separation anxiety and/or home sickness kennel problems in animals. it is also useful in grief and obsessive compulsive disorder According to another embodiment of the invention, there is provided a general anti- anxiety homeopathic complex. ideal for use in travel anxiety as follows: EXAMPLE WORKIN ANXIETY TRAVEL PREFERRED POTENCY RANGE FORMULATION Aconitum napellus (Aconite) 4x to all potencies including LM's 1M,10M Apomorphine 4x to all potencies including LM's 9x Argentum nltrlcum 4x to all potencies including LM's 4c.30c,200c Arsencium Album 6x (for safety) to all potencies including LM's 30c Avena Sativa MT to all potencies including LM's ' 2c,7x 2x to all potencies including LM's in solid forms such as creams tablets _. 6x and above in Liquid and 9x and above in 90% Borax alcohol 6c,30c Cocculus Indicus 2x to all potencies including LM’s 6c,30c Conium maculatum 4x (for safety)to all potencies including LM’s 4c.3oc Gelsemium sempervirens 2x, 4x to all potencies including LM's 6c.30c.200c Hyoscyamus niger 2x, 4X to all potencies includingLM's 30c.200c Ipecacuanha 2x, 4x to all potencies including LM's 6c 2x to all potencies including LM's in solid forms such as creams tablets 6-8:: and above in Liquid and 9x and above in _l_gnathia Amara 90% alcohol 300 Nux Vomica 2x.4x to all potencies including$M’s 8x,6c,30c Passiflora incamata MT to all potencies including LM's 2c,7x Petroleum 2x to all potencies including LM's 6c.30c,200c Phosphorus 4x to all potencies including LM's 30c Pulsatilla nlgricans 2x to all potencies including LM's 30c Scutellaria iaterifolia. MT to all potencies including LM's 2c.7x Silica terra 2x to all potencies includln;LM's 30c Sepia succus 2x to all potencies including LM's 6c Stramonium 2x, 4x to all potencies including LM's 30c Tabacum 2x to all potencies including_LM's 6c,30c.200c Valeriana officinalls MT to all potencies including LM's 2o,7x - 31 _ Veratrum album 2x, 4x to all potencies including LM's 30c Zinglber otficinale MT to all potencies including LM's 4:: According to this embodiment of the invention, to make an anti-anxiety composition, each ingredient is made according to the potency range above. Generally speaking, each ingredient is present in an amount from 0.1% to 20% v/v based on the volume of the total composition. In one non-limiting working embodiment each ingredient is then combined in equal proportions. in general. proportions are worked out for all the anxiety formulas based on the presence of the Main Core, increasing the percentage of the Main Core has very little effect on the resultant action of the formulation especially in owner perception of the improvement in anxiety symptoms. Flemedies from the other cores are used to broaden out the range of action and it is the proportion of these remedies which is important in modifying the Main Core action, for example, increasing stramonium and phosphorus increases the action of the formulation on the symptom of destructiveness in response to any stimulus, whether noise or abandonment.

The anti-anxiety composition may be administered to the subject, whether human or animal as a liquid. to any mucous membrane. Other administration forms and means may be contemplated.

According to another embodiment of the invention, there is provided a general anti- anxiety homeopathic complex, ideal for use in noise anxiety/phobia. such as storm stress anxiety or firework anxiety as follows: %vIv 0.5-1.0, 0.84 Aconite 6x to 24x11 2:: Avena 2-3. 2.10 -2. 1.24 -4, 4.12 -4. 4.12 , 4.1 -4, 3.29 -32. -4. 3.29 C TO 1 1 - 24xI12c . 0.82 .5-1. 0.82 x to 24x/12c 3-4. 4.12 SOC-1 2-3. 2.06 - 0 TO 2000 2010 TO 1 4C T01 MT TO Phophorus This treatment was used in Example 2 and is used in the treatment of storm stress, loud noise, firework anxiety. Example 3 shows an identical anti-anxiety compositions . with the same composition but different potencies.

According to this embodiment of the invention, to make an anti-anxiety composition for use in the treatment of loud noise anxiety. each ingredient is made according to the potency range above. Each ingredient is then combined in approximate equal proportions, although example proportions are given on the attached table. Generally speaking, each ingredient is present in an amount from 0.1% to 20% v/v based on the volume of the total composition.

According to a preferred embodiment of this aspect of the invention. the anti-anxiety complex for the treatment of loud noise/noise phobia/firework anxiety comprises the following ingredients: - IE 1 . . 00493 -%_ REMEDY PREFERRED PER ENTAG vlv POTENQY Aconite 6x-10x 0.5-1 .0, 0.83 Aconite 200C 0.5- 1.0. 0.83 Avena Sativa MT-2C 2.0-3.0. 2.07 . Avena Sativa 3x-7x 2.0-3.0, 2.0? : Beiladonna 30:: 1 .0—2.0, 1 .24 Borax 4c-Sc 4.0-5.0, 4.13 Borax 28c-30c 4.0-5.0, 4.13 Calc Phos 28c-30c 4.0-5.0. 4.13 Calc Phos 200:: 4.0-5.0, 4.13 Ge!semium 4c-Sc 3.0-4.0, 3.31 Gelsemiurn 30¢ 3.0-4.0, 3.31 Gelsemlum 2000 3.0-4.0. 3.31 Lycopodium 4c-6c 0.5-1 .0. 0.83 Lycopodlum 29c-30c 0.5-1.0, 0.83 Nat Carb 30c 4.0-5.0. 4.13 Nat Carb 200c 4.0-5.0, 4.13 Nat Mur 29c-30c 4.0-5.0, 2.07 Passiflora MT-2c 4.0-5.0. 2.07 Passiflora 3x-7x "4.0-5.0, 2.07 Phosphorus 5c-6c 8.0-9.0, 8.26 Phophorus 29c-30c 8.0-9.0, 8.26 Phophorus 199c- 200c 8.0-9.0, 8.26 Phosphorus 999c-1M 8.0-9.0, 8.26 Rhododendron 6c 2.0-3.0. 2.07 Scuttalria MT-2C 2.0-3.0, 2.07 Scuttalaria 3x-7x 2.0-3.0, 2.07 Silicia 29c-30c 0.5-1.0. 0.83 Silicia 1990-200c 0.5-1.0, 0.83 Stammonium 29c-30c 1.0-3.0. 1.24 Staphysagria 4c-6c 2.0-3.0, 2.0? Staphysagrla 28c-30c 2.0-3.0. 2.07 Valeriana MT-2c 2.0-3.0, 2.07 Valerlana 3x-7x 2.0-3.0. 2.07 PUFHFEED WATER 80% P 10 o 4 9 3 .3...

The anti-anxiety composition may be administered as a liquid to a subject via any mucous membrane.

In addition, any of the homeopathic complexes of the invention may be administered as a combination therapy, for example. at the same time as a conventional pharmaceutical, e.g. antibiotic, nutritional supplement or food.

In this specification the term “pharmaceutical” or “pharmaceutical composition” covers any chemical or biological substance. synthetic or non-synthetic which when taken by a subject will alter the function of that subject. Such substances ideally are intended for use in the treatment or prevention of disease in man or other animals. As such this term encompass more that conventional drugs or medicines and can also cover food, medicines, vitamins and minerals in general. Furthermore. the tenn “pharmaceutical” also the substance however it is made and, as such, encompasses biopharmaceuticals, biotechnology-derived treatments (including gene therapy) and phytotheraples. in this specification the term “combination therapy" is used broadly to cover the simultaneous administration of the homeopathic complex and the pharmaceutical composition. As such, the homeopathic tincture may be packaged separately. to the. pharmaceutical composition which is provided with a set of instructions for co- administration. The term “combination therapy” also covers the combination of the homeopathic complex with the pharmaceutical composition as a single entity. in this way, the homeopathic complex may be combined or integrated with the pharmaceuticai composition during or after manufacture. For example, the homeopathic complex when in liquid form may be sprayed onto the pharmaceutical composition. Alternatively. the homeopathic complex may be provided in liquid or powder form and may simply be combined or mixed with the pharmaceutical composition during manufacture. In this manner, the pharmaceutical composition acts as a delivery system for the homeopathic composition.

The co-administration of a conventional drug and a homeopathic according to the invention goes against Classical Homeopathic teachings and techniques. According to Classical/conventional homeopathic teachings, homeopathic complexes must be taken on their own at least 20 minutes after ingesting any food or drink. On the contrary the present invention dictates that the homeopathic complex is either part of a combination E10049; therapy or co-administered with a pharmaceutical composition. This would not be expected in the field of classical homeopathy.

According to a second aspect of the present invention, there is provided a homeopathic complex comprising a homeopathic tincture or dilutions thereof as defined previously for use in the treatment of anxiety/fear or associated conditions or symptoms.

According to a third aspect of the present invention, there is provided the use of a homeopathic complex comprising a homeopathic tincture or dilutions thereof as defined previously in the manufacture of a medicament for the treatment of anxiety/fear or associated conditions or symptoms.

According to a fourth aspect of the present invention. there is provided a method of treating a mammal afflicted with an anxiety state comprising administering to said mammal a therapeutically effective amount of a composition comprising a homeopathic tincture or dilutions thereof as defined previously.

The effect of the anti-anxiety complex can be demonstrated trans-species. The homeopathic complex of the invention may treat domestic and non-domestic animal such canines, porcines, felines etc. Humans may also be treated.

The invention will now be described by reference to the following non-limiting examples and figures. l-‘igure 1 outlines the improvement shown in each behavioural indicator of fear for dogs in both treatment groups in Example 2 (EN Study) Figures 2 to 4 outline the improvement shown in each behavioural indicator of fear for dogs in both treatment groups in Example 2 (NY Study) Figure 5 outlines the improvement shown in each behavioural indicator of fear for dogs during both study periods in Example 2 (Part III BN vs NY) Figure 6 shows that treatment B in Example 2 was responsible for a substantial reduction in the requirement for medication for fear of noise apart from being more effective than the placebo which had shown at least a 40% plus success rate in the lE1oo495 -36. previous trial with no side-effects noted in any of the trials by the participants. Thus, Treatment B has an anti-anxiety activity pre se. The results also shows that Treatment B has synergistic interaction with conventional medications and in fact reduces the‘ need or close of conventional medication thus enhancing the safety profile of the conventional medication.

Figure 7 shows the shows the median improvements in severity of behavioural signs of Example 3.

The following examples are representative and should not be construed to limit the scope of the invention in any way. In these examples, percentages are given as weight percents unless othenivise indicated.

EXAMPLES: General Background: Many trial types were brought forward for consideration including suspension in raised cages with exposure to light and dark, but these were all considered too traumatic to fit ' in with the homeopathic philosophy of "first do no harm”. Thus. it was not desirable to create a false trauma for the purposes of efficacy testing.

Canine noise phobia induced by loud noises such as fireworks and thunderstorms is a common concern reported by dog owners to veterinarians, who have few tools for treatment. None of these tools, which include tricyclic antidepressants, selective serotonin reuptake inhibitors and dog appeasing pheromone, all in combination with behavioral therapy, have been demonstrated as being effective under controlled study conditions. As a result. treatment is not instituted or is delayed while the problem becomes progressively worse. When severe, the pet can demonstrate panic behavior, with potentially disastrous consequences to itself and to the owner or the owner's property. Additionally, the pet may become hypersensitized to noises other than those that caused the initial problem.

Thus, within the context of noise phobia, a firework trial was chosen to test the anxiety composition. it was selected as being a cruelty free trial on the basis that this was a known pre-scheduled event that repeated at predetermined times every year where there were pets that would suffer fear and anxiety symptoms that the composition was IE 100493 designed to treat. The homeopathic compositions were tested in animals, canines and firework/loud noise anxiety was chosen to assess their efficacy.

Comgratlve Example 1 A double-blind placebo-controlled study into the efficacy of a homeopathic remedy for fear of firework noises in the dog‘ (canis familiaris) (published in The Veterinary Journal 177:80-88 (2008) Summary Seventy-five dogs that showed a fear response to fireworks participated in a double- blinded, placebo-controlled clinical trial to assess the efficacy of a homeopathic remedy for the alleviation of their behavioural signs. Dogs were randomly assigned to one of two treatments: a homeopathic treatment (TFLl\l® Homeopet) or a placebo treatment.

At the baseline assessments the owners identified the behavioural signs of fear that their dogs normally displayed in response to fireworks, rated their frequency and intensity, and assessed the global severity of their dog’s responses. These measures were repeated at the final assessment and owners also completed weekly diaries for the length of the trial.

Materials: Treatment A — Homeopathic complex {Homeopet TFLN®) Phosphorous, rhododendron, borax, theridion, chamomilla (GC and 300) in 20% USP alcohol in purified water.

Treatment B - Placebg: Alcohol and water Trlai Methodology This trial was set up as a placebo controlled, double blinded trial using both placebo and homeopathic complex (Homeopet TFLN®) as defined above. By examining the difference between responses of animals under the two treatments (real or “verum" and placebo) it is possible to determine how confident that any apparent effect is due to the treatment and not some other coincidental event.

The dogs in the study were chosen using the following criteria: IE 1 0 0 4 9 3" - as - - The dog was at least 6 months old - The dog was not receiving any medication to modify its behaviour or temperament - The dog was not currently receiving any homeopathic treatments - The dog’s diet excluded coffee, garlic and mint (inc peppermint) and sweets - The dog was not exposed to strong odours in the home such as essential oil aromatherapy . air fresheners or camphor based products (mothballs) etc - The treatment programme involved dosing the dog whilst it is afraid - The dog displayed fear responses to specific, identifiable firework noises.

- The fear response was reliably elicited by the naturally-occurring noise.

- The fear should not have generalised to the extent that the eliciting cues are too numerous to be identifiable and the dog rarely appears relaxed.

The trial involved the: 1. Daily dosing of the dog with the preparation supplied (either placebo or Homeopet TFLN®) 2. Daily record keeping and weekly monitoring.

These trials took place over a 2 year period (Year 1 and Year 2), covering Bonfire Night (BN1/BN2) and New Year (NY1/NY2) in both years.

Dosing lnstrugtions: The treatment was given by mouth once a day. ideally in the afternoon, preferably before any fireworks have started that evening. It the dog became anxious later on, the owner could repeat the closing up to a total of four times daily. These later doses were given at about 20 minute intervals. The dog owner kept a record of each day.

Results The data was analyzed using conventional statistical analysis techniques (Mann- Whitney test, chi-square tests etc).

There were significant improvements in the owners’ rating of 14/15 behavioural signs of fear in the placebo treatment group and all 15 behavioural signs in the homeopathic treatment group. Both treatment groups also showed significant improvement in the owners’ rating of the global severity of their dog's responses. However, there was no significant difference in the response seen between the two treatment groups. Thus, in lE1oo493 .39. this study it was found that Treatment A was no more effective than the placebo Treatment B.

Conclusion These results showed that both the placebo and the homeopathic complex (HomeoPet TFLN®)elicited a response.

It should be noted that the placebo effect in this trial would have been considered very high. The placebo effect was in excess of 40% with some very impressive changes on both sides. Many previous studies suggested a placebo effect in the 25 to 30% level.

Taking the fact that the homeopathic complex (Homeopet TFLN®) elicited a response in 40% plus of patients but no more than the placebo used in the trial it was decided to use the homeopathic complex (TFLN®) as the placebo in Example 2. On this basis HomeoPet TFLN® served as the placebo in Example 2.

Example 2 A Double Blind Study into the Efficacy of Two Homeopathic Formulations for Fear of Firework Noise: in the Dog (Canls famliiarls) Materlals Treatment A: PLACEBO Homeopet TFLN® (as per Example 1). In this trial Homeopet TFLN® is used as a placebo.

Treatment B: vena Sativa vena c 4c c 200c 4c lE1oo493 um 30c L 4c L 29c 30c Nat 2006 Nat Mur 29c MT 3x 5c ¢ 999c Rhododendron MT 3x Silicia 29c 199c Stammonium 29c 4c Valeriana 3x ml of the homeopathic mixture listed above was diluted in 100ml of an alcohol and water 20% alcohol and 80% water then the mixture was succussed 20 times. 1mI was then taken from this mixture and diluted in a further 100ml. Finally, 2.05mi of the base tincture was diluted in 100ml then this mixture was succussed 20 times. This provided a dilution of effectively 4X of the lowest potency.

Trial Methodology 39 dog owners were reused from Comparative Example 1 and 50 new dog owners were recruited. Dog owners were instructed that their participation would last through both bonfire night (BN) and New Year (NY) of Year 1 and Year 2.

Dog owners were informed that they would be trialling one of two homeopathic formulations during both periods, and that they wouldn't be aware of which treatment on either occasion.

Treatments were allocated by a researcher not involved in the study. Owners were asked to give details of their dogs response to fireworks prior to treatment. Owners were given instructions on how and when to does their dog. Owners were provided lE1oo493 _41_ with weekly record sheets and real exposure forms to monitor their dogs behaviour and response to treatment.

BN - Final assessment was conducted by mail and telephone after 4 weeks of treatment.

NY - Final assessment was conducted by telephone after 4 weeks of treatment Results: 1 0 Part I : Bonfire Night (BN) stud! Demograghig information (BN stugy) 1 5 Treatment A (n=-11) Treatment 3 (n=41) Mixed (10) Gundog (1 1) Gundog (8) Terrier (10) Pastoral (8) Mixed (8) Terrier (7) Pastoral (7) Hound (4) Hound (2) Utility (2) Utility (2) Working ( 1) Working (1) T0)’ (1) Toy (0) Mean age: 6.8 yrs Mean age: 6.4 yrs Male: 8 Male: 23 Female: 33 Female: 18 initial Final % change in P (% change uwmy severity severity in severity) (%) (96) -27.88 A (median) 32.16 18.82 (p=0.006) , 0.15 -42.62 B (median) 31.37 17.65 (p<0.0001) Table 1: Severity of Fear Response (BN study) lE1oo493 Fig 1 outlines the improvement shown in each behavioural indicator of fear for dogs in both treatment groups (BN study) A B ch?|I11ge chlalnge P (A '9" °' fear severity P severity P "39)’ (median) (median) Flunning around -1 <0.05 -2 <0.001 0.3 Drooling saliva -1 0.08 -1 0 0.62 Hiding 0 <0.05 -3 0 0.12 Destructiveness -1.5 0.29 -2 0.06 0.54 Cowering -3 0 -3 0 0.33 Flestiessness -1 .5 <0.05 -1 0 0.51 Freezing to the spot -2 <0.05 -2 0 0.28 Barking/whining/howling -1 0.09 -5 <0.001 0.02 Table 2: Change in severity of behavioural signs (BN study) A 5 Sign of fear Change In F Change In P P (A ve. severity severity B) (median) (median) Pantlng -2 <0.001 -3 0 0.42 Elimination -3.5 <0.05 -3.5 ‘ <0.05 0.8 Owner seeking 0 0.17 -1 <0.05 behaviour 0 45 Vigilance -2.5 <0.001 -1 <0.05 .22 Bolts -1 <0.05 -1 0 0.51 Exaggerated -2 <0.05 -3 0 startle 0.0 Shaking or ~1 <0.05 -3 <0.001 trembling .97 Table 3: Change in severity of behavioural signs (cont'd) (BN study) E 100 4 93’ N113‘; tt:':'°:_::a' Positlvse response? (chl (Mann-‘Whitney P) °‘"“'°" P’ Running around 0.09 0.81 Drooling 0.9 0.59 Cowering 0.81 0.12 Pacing 0.03 0.66 Vocalize 0.45 0.41 Pantlng 0.94 0.047 Owner seeking 0.6 0.38 Vigilance 0.3 0.16 Shaking 0.83 0.19 Hiding 0.9 0.19 Table 4: Analysis of recovery time following a typical exposure between groups (BN study) No si niflcant difference found between the 2 treatment rou BN stud with rggards to; o Owner's rating of dog's improvement when on treatment (A:-1, B=-2, p=0.12) o Difference in ‘before and after’ global fear scores given by owners ( =-2, B=-3, p=0.24) o No. of pieces of behavioural advice followed on FLE or D/D (RE A=6, B=6,p=0.16. D/D A=6, B=7, p=0.23) - The number of participants that reported some degree of improvement (A222, B=30, p=0.067) o The owners satisfaction rating (A=2. B=3, p=0.2) o The owners ‘use again’ rating (A23. A=3.p=O.26) o The owners rating of the treatment compared to last years n=39 (A=3, B=4, p=0.09) o The number of owners that used another form of treatment also (A=6, B=2, p=0.14) o The average number of firework exposures/week (A=1.5, B=1.25, p=0.97) o The number of doses given during a typical exposure (A=2, B=2, p=0.7) IE 1 o o 4 9 3 -44‘ Owner oomgllance (BN study) shown by: c No use of veterinary medication for fear during trial (91%) (A=5, B=2) o No use of other remedies or supplements for fear during trial (99%) (A=1. B=0) o No exposure to strong odours during the trial (100%) Results & conclusions : Main mints for Bonfire Night stug o Both treatment groups showed significant overall improvement. but no one group improved significantly more than the other o Most behaviours significantly improved in treatment group 8 (except destructiveness) - Less behaviours showed significant improvement in group A, with drooling, _ destructiveness. barking and owner seeking not reaching significance Generally no significant differences between groups with regards to the amount of improvement made in individual behaviours o Owners in group 8 reported a quicker recovery from pacing Significantly more owners in group B reported a positive improvement in the amount of time it took their dogs to stop panting Part ll : New Year study Demograghic information (NY Study) Treatment A (n=40) Treatment 3 (n=40) Mixed (9) Gundog (12) Pastoral (9) Terrier (10) Terrier (7) Mixed (7) Gundog (5) Pastoral (6) Hound (4) Hound (2) Utility (2) Utility (2) Working (2) Working (1) T0)! (2) Toy (0) Mean age: 6.7 yrs Mean age: 6.9 yrs Male: 8 Male: 21 Female: 32 Female: 19 -' 1E1oo493 45 Initial Flnal P (% severity severity ::3:'::'y9° '" change in (96) ($6) severity) . - . 6 A (median) 31.96 18.82 0232:0001) 0.17 . - 8.26 B (median) 31.57 17.65 (3410001) Table 5 : Severity of Fear Response (NY study) Figs 2 to 4 outline the improvement shown in each behavioural indicator of fear for dogs in both treatment groups (NY Study). Identical results were obtained in Figures 2 and 3 from year 1 to year 2.

A B Change Change In In P (A vs.

Sign of fear severity P severity P B) (median) (median Running around -1 <0.001 -2 <0.001 0.51 Drooling saliva -1 <0.05 -1 <0.0001 0.94 Hiding 0 <0.001 -3 <0.0001 0.32 Destructiveness -2 <0.05 -2.5 <0.05 0.68 Cowering -3 <0.0001 -6 <0.0001 0.16 Ftestlessness -2 <0.001 -3 <0.000'I 0.62 Freezing to the spot -2 <0.05 -2 <0.0001 0.43 Barking/whining/howling -2 <0.05 -6 <0.05 0.07 Table 6: Change in severity of behavioural signs (NY Study) i£1oo493 4*’ trembling 1 <0.001 -3 <0.0001 0.48 Table 7 : Change in severity of behavioural signs (cont'd) (NY Study) Elmo taken to return t ositlve response? (chi ormal (Mann-Whitney P) uared P) lfiunning around 0.08 1 Drooling 0.79 0.45 cowering 0.19 0.07 Pacing 0.04 0.82 Vocalize 0.49 0.19 Fantlng 0.99 o.oos Owner seeking 0.68 0.26 Vigilance 0.29 0.07 Shaking 0.84 0.28 Hiding 0.78 0.18 Table 8 : Analysis of recovery times following a typical exposure between groups (NY Study) ' fE1oo4 Differences also found between the 2 treatment groups [NY Study) with regards to: o Owner's rating of dogs improvement when on treatment (Aw1.25. B=- ,p=0.03) The owners satisfaction rating (A=2.5. B=3, p«—-0.04) Ng significant differences found between the 2 treatment groups (NY Study] with regards to: Difference in ‘before and after’ global fear scores given by owners (A=-2, B=-3. p=0.1) No. of pieces of behavioural advice followed on RE or DID (RE A=6, B=6.5,p=0.21. D/D A=6, B=7 p=0.19) The number of participants that reported some degree of improvement (A=24, B=32, p=0.051) The owners ‘use again’ rating (A=3, B.-.4, p=0.14) The owners rating of the treatment compared to last years n=39 (A=3. B=4. =o.25) The owners rating of the treatment compared to BN n=73(A=3, B=3, p=0.8) The number of owners that used another form of treatment also (A=4, B=1, p=0.17) The average number of firework exposures/week (A=1, B=0.7, p=o.08) The number of doses given during a typical exposure (A=2, B=2, p=O.43) own room Ii nce NY tud shown b : No use of veterinary medication for fear during trial (95%) (A=3. B=1) No use of other remedies or supplements for fear during trial (99%) (A=1, B=0) No exposure to strong odours during the trial (100%) Results & Conclusions : Main ggints for New Year study Again, both treatment groups showed significant overall improvement, but no one group improved significantly more than the other Owners in treatment group B reported a significantly higher rating of improvement Owners in treatment group B reported a significantly higher satisfaction rating Most behavioural signs significantly improved in both treatment groups (except for elimination and owner seeking in group A) but there was no difference E 100493 between the treatment groups with regards to the amount of improvement made (except for ‘exaggerated startle’ where group B made more improvement) o Owners in group B reported a quicker recovery from pacing o Significantly more owners in group B reported a positive improvement in the amount of time it took their dogs to stop panting Part III - Bonfire night Vs. New Year Demographic information - Included only those who took part in both studies (n=73) o Gundog (16) o Terrier (16) 0 Mixed (14) o Pastoral (14) o Hound (6) o Utility (4) Working (2) ° TOY (1) o Mean age: 6.8 yrs 0 Male: 25 - Female: 48 Initial Final severity % change In P (% severity (7.) (96) severity change In severity) -39.04 BN (median) 17.65 (p=0) 0.017 31 -75 -42.30 NY (median) 17.65 (p=0) Fig 5 outlines the improvement shown in each behavioural indicator of fear for dogs Tabie 9 : Severity of Fear Response during both study periods (Part III BN vs NY) IE 10 o 4 9 3 49 BN NY Change In Change In Sign of fear severity P severity P P (BN vs. NY) (median) (median Fiunning around -2 <0.001 -2 <0.0001 0.09 Drooling saliva -1 <0.0001 -1 <0.0001 0.83 Hiding -2 <0.0001 -2 <0.0001 0.74 Destructiveness -2 <0.05 -2 <0.001 0.37 Cowering -3 g <0.0001 -3 <0.0001 1 Fiestlessness -2 <0.0001 -2 <0.0001 0.22 Freezing to the spot -2 <0.0001 -2 <0.0001 0.3 Barking/whining/howling -2.5 <0.001 -2.5 <0.0001 0.58 Table 10 : Change in severity of behavioural signs BN NY Change In Change in Sign of fear severity P severity P P (EN vs. NY) (median) (median Panting -2 <0.0001 -2 <0.0001 0.72 Elimination 0 <0.05 0 <0.05 1 Owner seeking -4 <0.001 -4 <0.001 0.36 behaviour Vigilance -2 <0.0001 -2 <0.0001 0.059 Bolts ~1 <0.0001 -1.5 <0.0001 0.79 Exaggerated startle -2 <0.0001 -2.5 <0.0001 0.36 Shaking or -3 <0.0001 -3 <0.0001 0.18 trembling Table 11 :Change in severity of behavioural signs (cont’d) iE1oo493 5.0 taken to return response (wllooxon P) P) Table 12 : Analysis of recovery time following a typical exposure during both study periods Differences also found be_tw_gen the 2 study periods with regards to: Owner's rating of dog's improvement when on treatment (BN=-2, NY=-2, p=0.04) o The average number of firework exposures/week (BN=1.25, NY=1, p<0.0001) o The number of doses given during a typical exposure (BN=2. NY=2, p=0.02) No significant differences found between the 2 study periods with regards to; Difference in ‘before and after’ giobal fear scores given by owners (BN=-2, NY=-2, p=0.79) o No. of pieces of behavioural advice followed on RE or D/D (RE BN.-6, NY=6, p=1, D/D BN=7, NY=6, p=0.18) o The number of participants that reported some degree of improvement (BNM7, NY=50, p=O.59) o The owners satisfaction rating (BN=3, NY=3, p.-0.09) o The owners ‘use again’ rating (BN=3, NY=3, p=1) o The owners rating of the treatment compared to last years (BN=3.5, NY=4, p=0.1) o The number of owners that used another form of treatment also (BN=7, NY=4, p=0.35) lE1oo493 51 Owner compliance shown by: c No use of veterinary medication for fear during trial (85%) (BN=7, NY=4) o No use of other remedies or supplements for fear during trial (99%) (A=1, B=0) o No exposure to strong odours during the trial (100%) Results & Conclusions : Main goints from comparison of BN and NY studies o Owners reported significantly more overall improvement during the NY phase of the study than during the BN phase During both study periods participants showed significant improvement - The NY phase had significantly less firework exposures than the BN phase Owners used significantly less doses per exposure during the NY phase than during the BN phase 0 Owners rated their dogs to have shown significantly more improvement during the NY phase than during the BN phase 0 All behavioural signs significantly improved during both phases, but there was no difference between study periods with regards to the amount of improvement made Part IV: Results Year 1 Vs. Year 2 Original treatment (IFLN in Comg. Ex 1) Vs. Original treatment {TFLN in Ex 2) N=f1 (N = number of dogs allowing for randomization who received TFLN in Comparative Example 1 and Example 2) Difference in ‘before and after‘ global scores NY1 Vs. NY2 (NY1:-4, NY2:-3, p=O.4) Difference in % change in severity NY1 Vs. NY2 (NY1:-66.3. NY2=—35.1, p=0.13) Difference in ‘before and after‘ global scores NY1 Vs. BN1(NY1=-4, BN1:-1. p=0.31) Difference in % change in severity NY1 Vs. BN1 (NY1=~66.3, BN1=-1.2, p=0.053) Original treatment (IFLN in Comp. Ex 1) Vs. New treatment (Treatment B in Ex. 21 N=8 (N = number of dogs allowing for randomization who received TFLN in Comparative Example 1 and Treatment B in Example 2 at that particular time of year) Difference in ‘before and after’ global scores (NY1:-3, NY2:-3.5, p=0.18) Difference in % change in severity (NY1:-60.4, NY2:-39.64. p=0.36) Difference in ‘before and after global scores (NY1:-3, BN1-—-3, p=0.3) lE100493 52 Difference in % change in severity (NY1:-60.4. BN1:-40.83. p~—-0.29) Placebo (Como. Ex. 1] Vs. Original treatment (TFLN of Ex. 21- EXAMPLE 1 N=8 (N = number of dogs allowing for randomization who received Placebo in Comparative Example 1 and TFLN in Example 2) Difference in ‘before and after’ global scores (NY1:-1.5, NY2=-1, p=0.93) Difference in % change in severity (NY1=-39.6, NY2:-17, p=0.94) Difference in ‘before and after’ global scores (NY1:-1.5, BN1:-1, p=0.93) Difference in % change in severity (NY1=-39.6, BN1w23.5, p=0.83) Placebo (Comg. Ex. 1) Vs. New treatment (Treatment B of Example 2) N.-.8 (N = number of dogs allowing for randomization who received Placebo in Example 1 and Treatment B in Example 2) -Difference in ‘before and after’ global scores (NY1:-3, NY2:-4, p=O.27) Difference in % change in severity (NY1=-52, NY2=-49.52, p=0.94) Difference in ‘before and after’ global scores (NY1:-3. BN2:-4, p=0.27) Difference in % change in severity (NY1:-52, BN1:-45.57, p=1) Original treatment NY1 (Comg. Ex. 1) Vs. Original treatment NY2 (Example 21 NY1 n=35, NY2 n=41 Difference in ‘before and after’ global score (NY1:-2, NY2:-2, p=0.15) Difference in % change in severity (NY1:-38.2, NY2:-29.06, p-=0.23) Original treatment NY1 (Comg. Ex. 1) Vs. Originaltregtment BN1 (Examgle 1) NY1 n=35, BN1 n=40 Difference in ‘before and after’ global score (NY1:-2, BN1:-2, p=0.1) Difference in % change in severity (NY1:-38.2, BN1:-27.88, p=0.07) The rating scale for satisfaction was: Not at all satisfied 2 Slightly satisfied 3 Quite satisfied Very satisfied rlglorlg rlg lnew Placebo! orig lac I new TFLN fro (TFLNI (Placebo from Ex. 1 Placebo from Ex. 1! x. 1/ Placeb mple 2 -TFLN from Ex. 1) xample 2 — FLN) fro reatment 5) Treatment 3) Ex. 2) Better 4 4 3 7 Same 4 2 - 3 0 Worse 3 2 2 1 Table 13 : Owners comparison re Comparative Example 1 and Example 2 (Ex 2. New Year treatment vs. Comp. Example 1 New Year treatments) Fig 6 shows that treatment B was responsible for a substantial reduction in the requirement for medication for fear of noise apart from being more effective than the placebo which had shown at least a 40% plus success rate in the previous trial with no side-effects noted in any of the trials by the participants. Thus, Treatment B has an anti-anxiety activity per se. The results aiso shows that Treatment B has synergistic interaction with conventional medications and in fact reduces the need or dose of conventional medication thus enhancing the safety profile of the conventional medication.

Conclusion The above chart shows the considerable difference “Treatment B” made in Year 2.

“Treatment B" was given a much higher satisfaction ratings overall in relation to the following specific parameters exaggerated startle, pacing, panting and barking/whining/howling which are all prime signs of firework and thunder (brontophobia) phobias.

This success of these results are further indicated in that far fewer owners resorted to the use of supplementary conventional medication when their pets were on Treatment B demonstrating that Treatment B is not just more effective than placebo, but also resulted in a wider safety margin for patients given it due to the reduction in conventional therapeutics used (Figure 6). it is also worth noting that there was no adverse interaction with drugs used with the homeopathic formulations in the trial. No adverse reactions were reported for the homeopathic complexes themselves and all homeopathic treatments proved safe and side effect free during the trial. importantly, these symptoms of anxiety and fear are relatable across species including humans, thus. the present invention is applicable to humans and animals.

Example 3 Firework Anxieg Trials Materials Treatment A: (used for Bonfire Night (BN)) Ox Aconite 200C Avena 7x Belladonna 300 6c Borax 30c 28c Calc 200c Gelsemium c Nat 306 c .20 IE 100493 55 M Sc 2C Scuttalaria 7x :: Treatgent 3: (used for New Year (NY)) Remedy & Potency WV 1 Ox Aconite1 M Avena Avena IE 1 o o 4 9 3 56 "€r‘HANoL 20% PURIFIED WATER so°/.

Metnodolggg dog owners used from Example 2 ‘new’ dog owners recruited Dog owners instructed that their participation would last through both the BN and New Year firework periods Allowed consistency of owner reports to be examined Dog owners informed that they would be trialling one of two homeopathic formulations on each occasion All participants trialled treatment ‘A’ during the BN period and treatment ‘B’ during the New Year period, thus effectively increasing the sample size as a within subjects analysis could be performed Owners asked to re-rate the baseline severity of their dog's behavioural responses to fireworks and asked whether they had experienced fireworks since the last trial (Yes 57, No 12) Owners were: given instructions on how and when to close their dog provided with weekly record sheets and real exposure forms to monitor their dogs behaviour and response to treatment BN Final assessment conducted by mail New Year's Final assessment conducted by telephone Results Demographic data Same population participated in both periods 3 owners dropped out before NY (2 dogs on meds. 1 PTS) Population demographics (n=68) o Gundog (17) Mixed (16) Pastoral (15) Terrier (13) Hound (3) Utility (3) 0 Working (3) 0 Toy (1) - Median age: 7 yrs - Maie:23 - Female: 45 Severity of Fear Response initial severity Final Severity % Change In P (% change in (Median) (Median) Severity Severity) (Median) BN 81 46 (P=0) -37.5% 0.43 New Year 43 (P=0) -36.7% Conclusion from these results was that the response to both treatments in BN was not statistically different from the response in New Year (see Figure 7 which shows the Median improvements in severity of behavioural signs) 1 5 Change in severity of behavioural signs Sign of fear change in change In severity severity (median) (median) Running around -1 0 ~1 Drooling saliva . -1 Hiding Destructiveness Cowering fiestiessness Freezing to the spot Barking/whining/howling 53 A 5 Sign of fear change In P Change in P I5 (A vs. severity (median) severity B) (median) Self harm -1 <0.05 -2 <0.05 0.5 Aggression -1 <0.05 -1 <0.05 Not enough data Panting -3 0 -3 0 <0.05 Elimination -2 <0.05 -2 <0.05 0.8 Owner seeking -0.5 O 0 0 0.9 behaviour Vigilance -1 <0.05 -1 0 0.1 Bolts -1 0 -1 0 0.8 The conclusion from these results is that the response to both treatments were significantly different between BN and NY for Hiding, Cowering and Freezing. The P values do not appear to apply to a statistical between-treatment comparison. It also shows that Treatment B produced significant improvement Vs baseline only in Destructiveness, while Treatment A had significant improvement Vs baseline in Destructiveness, Freezing and Barking etc.

Differengg found between the 2 periods with regards tg: o Owner's rating of dog's improvement when on treatment (A:-2, B:-1, p=0.047) 0 Difference in ‘before and after’ global fear scores given by owners (A=-3, B:-3. p=0.008) H o The owner's satisfaction rating (A=3. B=2, p=0.005) IE 10 o 4 93 59 Analfiis of recovery time following a typical egposure between treatment grougs ‘Time taken to return to normal Positive rgggonse (Wllcoxon P) chi s uared P Running around 0.73 0.37 Drooling 0.4 0.73 Cowering 0.9 0.94 Pacing 0.96 0.35 Vocalize 0.63 0.89 Panting 0.7 0.96 Owner seeking 0.75 0.93 Vigilance 0.37 0.96 Shaking 0.8 0.58 Hiding 0.57 0.92 Conclusion These results show that Treatment A (the longer loud noise anxiety formula) works over a broader range of symptoms than Treatment B (the Main Core of the invention including phosphorus). Treatment B works very well for destructiveness, whereas . Treatment A works across 14 out of 16 symptoms. This shows that, despite Treatment B having a larger effect on a single symptom, owner perception was that Treatment A has an effect across a much broader group of symptoms and was in effect better at alleviating their pets expression of anxiety.

This shows that the core alone is very effective as an anti-anxiety treatment and that the additional remedies which are added to this core broaden out the action of the Main Core formulation.

Both these homeopathic treatments gave a high level of owner satisfaction with a consistent positive response over a broad range of anxiety symptoms. The treatment is safe, convenient and effective. In addition, we have found that. it's effects matches the effectiveness of other conventional products such as Dog Appeasing Pheromone (DAP) and clomipramine. in the specification, the terms “comprise. comprises, comprised and comprising" and any variation thereof and the terms “include, includes, included and including” and any so variation thereof are considered to be totally interchangeabie and they should all be afforded the widest interpretation.

The invention is not limited to the embodiments described above but may be varied within the scope of the claims.

Claims (5)

CLAIMS:

1. An anti-anxiety homeopathic complex comprising a homeopathic tincture or dilutions thereof of Aconite, Avena Sativa, Passiflora, Scuteliaria, Stramonium and Valeriana.

2. The anti-anxiety homeopathic complex as claimed in claim 1 further comprising a homeopathic tincture or dilutions thereof of one of more of the following ingredients Argentum Nitricum, Arsenicum Album, Belladonna, Borax, Caicarea Carbonica, Calcareas, Causticum, Gelsemium, Hyoscamus, lgnathia, Lycopodium, Natrum and/or Chloride salts , Nux Vomica, phosphorus [Phos} and salts or acids thereof including Calcarea Phosphorica [CaIc Phos], Ferrum Phosphoricum [Ferr-P], Magnesia phosphorica [Mag-p]. Natrum phosphoricum [Nat-p] and/or Zincum phosphoricum [Zinc-p], Pulsatilla, Silicia, and/or Staphysagria.

3. The anti-anxiety complex as claimed in any of the preceding claims wherein each homeopathic tincture or dilutions thereof are present at a potency range from Mother Tincture to approximately 2000.

4. The homeopathic complex as claimed in any of claims 1 to 3 for use in the treatment of fear, anxiety or anxiety-related conditions in humans and animals.

5. An anti-anxiety homeopathic complex as claimed in any of the preceding claims substantially as described herein with reference to the examples and figures. 31501lESD amended claims with track changes.28July2010