WO2015092539A1

WO2015092539A1 - System comprising ophiocordyceps and a sleep apnea treatment device for treating sleep apnea or snoring, method and use thereof.

Info

Publication number: WO2015092539A1
Application number: PCT/IB2014/002965
Authority: WO
Inventors: Ilya BENNETT; Jack Gerschman; Joel GERSCHMAN
Original assignee: Sleepapp Holdings Limited
Priority date: 2013-12-18
Filing date: 2014-12-18
Publication date: 2015-06-25
Also published as: WO2015092538A1

Abstract

A system comprises an extract or fraction, derivative or chemically synthesized or modified form of any one or more components of Ophiocordyceps or a genetically modified or phenotypically adapted strain thereof, and sleep apnea treatment device. The system acts in synergy to reduce Cortisol levels and increase oxygen saturation, utilization and/or absorption levels. In particularly, the extract is Cs-4 or fraction, derivative or chemically synthesized or modified form of any one or more components. The sleep apnea treatment device comprises a mouthpiece including a vestibular locator and an airway conduit.

Description

System comprising Ophiocordyceps and a sleep apnea treatment device for treating sleep apnea or snoring, method and use thereof.

FILING DATA

(000J J Thi application is associated with and claims priority from Australian Provisional Patent Application No. 2013904946, filed on 18 December, 2013, entitled "A. method of treatment", the entire contents of which, are incorporated herein by reference.

FIELD

[0002] The present specification relates generally to the field of therapeutic protocols for the treatment of inter alia sleeping disorders, metabolic diseases, cardiovascular diseases and neurological conditions.

BACKGROUND

[0003] Bibliographic details of the publications referred to by author in this specification are collected alphabeticall at the end of the description.

[Θ004| Reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that this prior art forms part of the common general knowledge in an country.

[0005] Stress management is a major field of study worldwide. Stress can result from a range of environmental, psychological, endocrino ogical and physiological factors. One feature associated with some forms of stress is elevation of Cortisol (hydrocortisone) and this can lead to a variet of conditions which can exacerbate further stress levels. For example, sleep apnea is a potentiall debilitating condition resulting from partial or complete closure of the posterior airway space which is situated between the back of the tongue and the throat. The degree of severity of sleep apne can be referred to as the apnea hypopnea index (AHI). There are different forms of sleep apnea including mild, where there is cessation of breathing for at least 10 seconds for from 5 to 15 times per hour (mild AHI); moderate AHI, where there is cessation of breathing for at least 10 seconds for fro 15 to 30 times per hour; and severe AHI, where cessation of breathing occurs for from 10 seconds to over 60 seconds. There is also a hypopnea where there is cessation of breathing for less than 1 seconds which ca also be mild, moderate or severe. Sleep apnea has been associated with adverse cardiovascular events and poor aerobic fitnes (Beitler et at (2014) J. Clin. Sleep Med. 10(1 199-1204). Snoring is also commonly associated with sleep apnea.

[0006] Sleep apnea has received some attention in Western populations but generally in relation to the social effects on partners of people who experience sleep apnea. For various cultural reasons, studies on the effects of sleep apnea in Chinese, Indian, Russian and some South American populations on work output have received less attention.

[0007] Sleep apnea can lead to substantial risks to workers due to fatigue, reduced concentration and poor work performance. There are also neurocognitive consequences (Lau et- !. (2013) Sleep Disor 2: 1 -6), Snoring associated with sleep apnea can also add significant pressures on personal relationships.

[0008] In the transport industry, fatigue can have catastrophic consequences especially when there is cessation of breathing during microsleep periods. There is a need to provide protocols tor dealing with sleep disorders such as arising from abnormal respiratory patterns i cluding snoring,

[0009] Western medicine has had an enormously important and successful impact on improving health outcomes in human medicine, This impact often detracts from the benefits of herbal medicines which predate Western medicine by thousands of years. One such herbal medicine is an extract of Ophio ordyceps sinensis (formally known as Cordyceps sinensis). Ophiacordyceps is an ascomycete fungus (sac fungus) that is mainly parasitic on insects and arthropods (Bao ( 1995) J, Admin. Trad. Chinese Med. 5 (Suppl6)). [0010] This organism has been highly valued in China as a tonic and herbal medicine (Zhu et al. (1998) J, AUem Complement Med (3J :289-303). Extracts of this fungus have been shown to have beneficial effects as an oxygen-free radical scavenger, and in age-related mitigation, endocrine function, hypolipidemia and in various other conditions (Zhu et al.

[0011] In accordance with the present disclosure, it is proposed to utilize an extract of Ophiocordyceps spp to treat human subjects in an integrated approach with Western medicine practice to reduce adverse respiratory conditions and associated metabolic, cardiovascular and neurological conditions which can further exacerbate, or be exacerbated by, stress levels. In particular, a protocol to treat subjects with sleep apnea and wh snore is provided.

SUMMARY

|0012] The present specification teaches a multifaceted approach to treat a human based on a combination of a herbal medicine and a sleep apnea treatment device. The combination of a herbal medicine and sleep apnea devi ce can also be used to treat snoring. The multifaceted approach is referred to as a "therapeutic protocol". The herbal component of the therapeutic protocol is an extract of a species of Qphiocordyceps (formally known as Confyceps) and extends to fractions, derivatives and chemically synthesized or modified forms of the extract. Qphiocordyceps is a fungus. The benefits of using fungi are multifactorial including ease of growth, genetic stability and the ability to produce substantial mycelial biomass. Production of extracts of Qphiocordyceps is described in International Patent Publication No. WO 99/21 61 which is incorporated herein i its entirety by reference. Reference to an "extract" includes an isolated compound, family of compounds and a mixture of compounds. The extract may also be referred to as a herbal formulation, medicinal, medicament, nutraceutical, myochemical, phytochemical, biochemopreyentative, functional or designer food or dietary supplement. Any of these terms can be used to describe the Qphiocordyceps extract. As indicated above, reference to "extract" includes fractions, derivatives and chemically synthesized or modified forms thereof A "modified" form includes forms augmented with other compounds such as digoxin, hydrochlorothiazide, dopamine, debutamine, Rhodiola and/or erythropoietin (EPO), A "modified" form also includes where one or more components are added or substituted for another component.

(0013] In. an embodiment, the device treats sleep apnea and can also be applied separately, to treat snoring , the device being a component of the therapeutic protocol comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing said ambient air through the airway conduit. In another embodiment, the sleep apnea device component is intended for use i breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending betwee the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing said ambient air through the airway conduit.

[00.14] Reference to a "sleep apnea device" or "sleep apnea treatment device" encompasses a "snoring device" and a "snoring treatment device".

[0015] The therapeutic protocol is useful in the amelioration of symptoms of respiratory disorders, metabolic conditions, cardiovascular conditions and neurological conditions which exacerbate or are exacerbated by stress levels or neurodegeneration. The respiratory condition or disorder may result in respiratory patterns leading to sleep disorders such as sleep apnea and snoring. Metabolic conditions include Type 1 and 2 diabetes. Cardiovascular conditions include cardiac disorders and heart failure. Neurological conditions include depression, epilepsy and neurodegeneration. The present method is particularly applicable to reducing stress levels exacerbated by fatigue, metabolic disorders, cardiovascular conditions and neurological conditions. The subject protocol further results in normalization or enhancement of oxygen saturation, utilization and/or absorption and this has beneficial effects in terms of an improved cardiovascular system, aerobic fitness, sexual performance and prevention of adverse consequences of hypoxia such as resulting from heart failure or asphyxia (e.g. from drowning). A surprising benefit is the use of the protocol by astronauts for deep space travel for prolong periods or deep sea divers.

[0016] Without intending to limit the present invention to any one theor or mode of action, it is proposed that the combination of Ophiocorcfyceps. extract and the sleep apnea device has beneficial effects on Cortisol -based pathways and increases oxygen saturation, utilization and/or

in the blood system and organs including the brai of the subject being treated. In an embodiment, the combination of the extract and the device elevates or normalizes oxygen saturation to 90% or greater during sleeping periods as well- as increasing oxygen utilization and/or absorption, By "90% or greater" includes 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%. This is based on a "normal"^' oxygen saturation of about 96 to 98% under walking conditions. It is proposed herein that elevated Cortisol can lead to respiratory patterns causing sleep disorders such as sleep apnea and snoring as well as metabolic conditions such as Type 1 and 2 diabetes, cardiovascular disease such as heart failure and neurological disorders such as depression, epilepsy or neurodegeneration. Any or all of these conditions can lead to, or exacerbate, stress. Furthermore, a combination of Cortisol level modification and improved oxygen saturation,, utilization and/or absorption can lead to a range of therapeutic benefits. These include alleviating sexual dysfunction and improving recovery following hypoxic events. The protocol is also useful for astronauts under prolonged deep space flight conditions and deep sea divers,

[001.7] Accordingly, one aspect of the present invention provides a therapeutic protocol for treating a human subject with a Cortisol -based disorder or condition or with the potential for developing a Cortisol -based disorder or condition, the method comprising, in either order or simultaneously, the administration to the subject of an effective amount of an extract of a species of Ophioeordyceps and insertion of a sleep apnea treatment device into the subject's mouth for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user ϊηίβφθΒβά between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit mai ntains fluid communication of the mouth vestibule with ambi ent air to facilitate the user breathing the ambient air through the airway conduit. In a embodiment, the vestibular locator is a flange having an inner surface and an outer surface. I an embodiment, the airway conduit extends through the flange. In an embodiment, the device is a singularly constructed device. In another embodiment, it is a multi -component such as a 2-part device comprising a mouth piece and a mask portion in the form of a flexible flap. Furthermore, the treatment process or protocol may be monitored or managed using art electronic health (eHealth) system.

[001.8] In an embodiment, the present invention provides a method for treating a huma subject with a respiratory pattern leading to a sleep disorder such as sleep apnea or snoring, the method comprising the administration to the subject in either order or simultaneously an effective amount of an extract of a species of Ophwcwxfyceps and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit,

[001.9] In a related embodiment, the present invention provides a method for treating a human with a metabolic disorder such as Type 1 or 2 diabetes, the method comprising the administration to the subject in either order or simultaneously an effective amount of an extract of a species of ' Ophiocordyc ps and the insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed betwee the lips and teeth of the user, the vestibul ar locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending betwee the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0020] In a related embodiment, the present invention provides a method for treating a human with cardiovascular disorder, the method comprising the administration to the subject in either order or simultaneously an effective amount of an extract of a species of Ophiocortfy eps and the insertion into a subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0021] In a further related embodiment, the present inventio contemplates a method for alleviating the symptoms of a neurological condition, such as depression, epilepsy or neurodegeneration, the method comprising the administration to the subject in either order or simultaneously an effective amount of an extract of a species of Ophiocordyeeps and the insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communicatio of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit,

[0022] These aspects are further associated with the treatment of stress i a human subject, the method comprising the administration to the subject in either order or simultaneously, of an effective amount of art extract of a species of Ophiocordyeeps and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit,

(0023] The therapeutic protocol is also useful for enhancing or normalizing oxygen saturation, utilization and/or absorption in a human subject, the method comprising the administration to the subject in either order or simultaneously, of an effective amount of an extract of a species of Qphiocordyceps and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed, between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit. The latter method has a range of beneficial outcomes including addressing sexual dysfunction and treating subjects exposed to hypoxic conditions such as following heart failure, asphyxia and/or astronauts on a. prolonged, deep space flight or deep sea divers.

[0024] In an embodiment, the device includes a formation for engagement with a lower j w of the user to retain the lower jaw^r in a forward position. The formation may be adapted to be engaged with the lower jaw of the user to retain the lower jaw. In an embodiment, the forward position is designed in a degree of advancement of the Sower jaw relative to the upper jaw. In one aspect, the formation includes a retaining protrusion. In an embodiment, the formation includes a plurality of retaining protrusions,

(0025] In. an embodiment, the device includes an abutment for abutting the upper jaw such that force imparted to the device from the lower jaw is transferred to the upper jaw.

[0Q26| In an embodiment, the airway conduit terminates to minimise protrusion beyond the lips of the user. In an embodiment, the airway conduit terminates at a opening, and the opening is supported by the lips of the user. The opening may be formed in a mask portion, in the form of a flexible fla of the device, and the mask portion abuts an external surface of the user's face surrounding the user's mouth.

(0027] In one aspect, the sleep apnea treatment device includes an arcuate bite platform to distribute force to the teeth of the wearer. For example,- the arcuate bite platform extends either side of the airway conduit. In one form, the arcuate bite platform extends as a shelf from the inner surface of the vestibular locator. The arcuate bite platform may be formed of a solid ledge at either side of the airway conduit. The arcuate bite platform may be integrally formed as a unitary structure with the mouthpiece. The arcuate bite platform may also be arranged to support jaws of the wearer apart b rear teeth of the wearer so as to prevent the jaws from closing the airway conduit, in one example, the arcuate bite platform is configured to contact all teeth of the wearer.

[0028] The subject method may also be augmented by the selective administration of ^'other active agents such as cortisol-lowermg agents or agents which further facilitate oxygen saturation in the blood stream and/or improve oxygen saturation, utilization and/or absorption. Other agents useful in combination with the extract component of the therapeutic protocol include digoxin, hydrochlorothiazide, dopamine, dobutamine and/or Rhodiola. In addition, a sleep disorder sensor such as comprising a microchip may be employed to detect the level or severity of the sleep disorder. Alternatively or in addition, the treatment is based on or monitored by aft eHealt system. Oxygen saturation, utilization and/or absorption in the brain can also be readily monitored. Without limiting the present invention to any one theory or mode of action, th combination of medicinal and device can lead to synergy between Cortisol level modification and oxygen saturation, utilization and/or absorption.

[0029] In accordance with another aspect of the present invention, there is provided a system for treating sleep apnea, comprising a device as described above, and a medicament for increasing oxygen saturation, utilization and/or absorption of a user's blood or organ and/or lowering Cortisol levels, the medicament comprising an extract of a species of Opkwcor yeeps. [0030] In accordance with another aspect of the present invention, there is provided a method of treating sleep apnea comprising the steps of wearing a sleep apnea treatment device as described above, and breathing ambient air through the sleep apnea treatment device while sleeping and administering an extract of a species of Ophiocordyceps,.

[0031] In accordance with another aspect of the present invention, there is provided a method of treating sleep apnea including the steps of a user selecting from a range of predetermined sizes of sleep apnea treatment devices from a retail outlet including an online outlet, and the user wearing the selected sleep apnea treatment device, wherein each of the sleep apnea treatment devices in the range of predetermined sizes is a sleep apnea treatment device as described above and taking an extract of Ophiocordyceps.

[0032] Yet a further aspect contemplated herein is a method for controlling snoring comprising th steps of wearing a sleep apnea treatment device as described above, and breathing ambient air through the sleep apnea treatment device while sleeping and administering an extract of a species of Ophiocordyceps.

[0033] Still yet another aspect contemplated herein is a method for controlling snoring including the steps of a user selecting from a range of predetermined sizes of sleep apnea treatment devices from a retail outlet including an on-line outlet, and the user wearing the selected sleep apnea treatment device, wherein each of the sleep apnea treatment devices in the range of predetermined sizes is a sleep apnea treatment device as described above and taking an extract of Ophiocordyceps.

(0 34J The importance of managing stress via downstream effects of cortisol-based pathways cannot be underestimated in countries such as China, India, Russia and some South American countries which rely heavily on transport and agriculture. Managing metabolic disorders such as diabetes, cardiovascular disorders, neurological conditions, behavior patterns and/or fatigue due to abnormal sleep patterns have enormous benefits to work output. It is also important for controlling snoring to facilitate more harmonious relationships between individuals during sleeping periods. There are other beneficial outcomes in terms of normalizing or enhancing oxygen saturation, utilization and/or absorption which facilitates improved fitness, mental health, sexual performance and is useful in the treatment of patients exposed to hypoxic conditions suc as following heart failure, asphyxia (e.g. drowning). The protocol is also useful for better management of oxygen for astronauts on deep space flights and deep sea divers.

(0035] Administration of the extract may be by any convenient means including administration via intra-nasal inhalation, spray or drops or as a dietary supplement or as a pill or tablet, cream lotion and/or patch. Nanoparticles are also a useful delivery modality. Alternatively, the seep apnea device contains a slow release mechanism to administer the extract over a period of time such as overnight while the subject sleeps.

[0036] The respirator condition includes any condition affecting sleep patterns. In an embodiment, the respiratory condition is sleep apnea or snoring. The metabolic condition includes Type 1 and 2 diabetes. Cardiovascular conditions include heart disease such as heart failure. The neurological condition includes depression, epilepsy and neurodegenerative disorders. Hence, an "effective amount'^' includes an amount effective to prevent, reduce or ameliorate stress patterns leading to the sleep disorder, metabolic disease, cardiovascul r disease and/or to treat neurological conditions including adverse (e.g. anti-social) psychological behavior, depression, and neurodegeneration. An effective amount may also be measured in terms of oxygen saturation, utilization and/or absorption levels,

[0037] In an embodiment, the species of Ophiocord eps is Ophiocordyceps sinensis.

[0038] Reference to a "subject" includes a human of any age and may be referred to inter alia as a patient, individual, recipient or user. A "subject" may also be an astronaut or deep sea diver,

[0039] Another aspect of the present invention contemplates the use of a species of Ophiocordyceps in the manufacture of a medicament to treat stress or a symptom of stress in a human subject together with the use of a sleep apne device as described herein.

(0040] Contemplated herein is the use of an extract of Ophioco dycep sinensis in the manufacture of a medicament in the treatment of stress or a symptom of stress in a human subject together with the use of a sleep apnea device as described herein.

(^'0041] Symptoms of stress include a sleep disorder such a sleep apnea and snoring, a metabolic, disorder such as Type 1 or 2 diabetes, cardiovascular disease and a neurological condition such as depressio or iieurodegeneration,

(0042] In an embodiment, the Ophiocordycep extract is Cs-4 (also referred to as Cordyceps from Ophiocordyceps sinensis). Cs-4 is described in Chen et al, (2010) J Alierri Complement Med 16(5):5 5~590. Fractions, derivatives, chemically synthesized or modified forms of Cs-4 or any of its components are also contemplated herein and are contemplated by the term "Cs-4" or "Cordyceps". The Cs-4 may also be augmented with other components such as digoxin, hydrochlorothiazide, dopamine, dohutamiiie and/or Rhodiola,

[0043] The present invention further provides an integrated eHea!th platform comprising a protocol for dealing with stress management. Such a platform comprises all or part of a mandibular device component comprising a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular loeator supporting the airway conduit in place relative to the user's mouth with the .airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibuie with ambient air to facilitate the user breathing the ambient air through the airway conduit, a pharmaceutical component and optionally a monitoring component.

[0044] Hence, enabled herein is a therapeutic protocol which comprises two main components:

(a) a medicinal component comprising an extract of Ophiocordyceps or a fraction, derivative or chemically synthesized or modified form of the extract; and

(b) physical component comprising a sleep apnea device as herein described,

[0045] It is proposed, without intending on limiting the present invention to any one theon' or mode of action, that the medicinal and physical components act in synergy to achieve clinicall and biochemically measurable outcomes including reduced Cortisol levels and/or normalization or enhancement of oxygen saturation utilization and/or absorption. These have downstream advantages including ameliorating the adverse effects of stress, metabolic disease, cardiovascular disease and neurological conditions. The therapeutic protocol also leads to a grater capacity for a subject to engage in physical exercise and hence promotes aerobic fitness and to reduce symptoms such as snoring, improve sexual performance and promote mental health.

BRIEF DESCRIPTION OF THE FIGURES

[0046] The sleep apnea device component of the present invention is described, by way of non-limiting example only, with reference to the accompanying drawings, in which:

(0047] Figure 1 shows an anterior view of a mouthpiece in accorda ce with an example of the present inventi on.

[0048] Figure 2 shows a posterior vi ew of the mouthpiece of Figure 1.

[0049] Figure 3 shows a top view of the mouthpiece, depicted with a support flap in place.

[0050] Figure 4 shows a posterior view of the support flap.

[O05J] Figure 5 shows a perspective rear view of a mouthpiece in accordance wit another example of the present invention.

[0052] Figure 6 shows a top view of the mouthpiece of Figure 5.

[0053] Figure 7 shows a front perspective view of a mouthpiece in. accordance with another example of the present invention.

[0054] Figure 8 shows a rear perspective view of the mouthpiece of Figure 7. [0055] Figure 9 shows a rear view of the mouthpiece of Figure 7. [0056] Figure 10 show^?s a top view of the mouthpiece of Figure 7, [0057] Figure 11 shows a bottom view of the mouthpiece of Figure 7. [0058] Figure .1 shows a side view of the mouthpiece of Figure 7. [0059| Figure 13 shows a front view of the mouthpiece of Figure 7,

[0060] Figure 14 shows a front view of a two-part device in accordance with another example of the present invention, comprising a mouthpiece and a mask portion in the form of a flexible flap, in a disassembled condition.

[0061] Figure 15 shows a rear view of the two-part device of Figure 14,

[0062] Figure 16 shows the mouthpiece of the two-part device in situ i a mouth of a user.

[0063] Figure 17 shows the mouthpiece in situ in the mouth of the user, wit the mask portion coupled to the mouthpiece,

[0064] Figure 18 shows a top view of the mouthpiece shown in Figures 5 and 6. [0065] Figure 19 shows a side view of the mouthpiece shown in Figures 5 and 6. [0066] Figure 20 shows a rear view of the mouthpiece shown in Figures 5 and 6.

DETAILED DESCRIPTION j0067] Throughout this specification, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element or integer or method step or group of elements or integers or method steps but not the exclusion of any other element or integer or method steps or group of elements or i ntegers or method steps.

[0068] As used in the subject specification,, the singular forms "a", "an" and "the" include plural aspects unless the context clearly dictates otherwise. Thus, for example, reference to "a mushroom species" includes a single mushroom species, as well as two or more mushroom species; reference to "an extract" includes a single extract, as well as two or more extracts; reference to "the disclosure" includes a single and multiple aspect taught by the disclosure; and so forth. Aspects taught and enabled herein are encompassed by the term "i nvention " . Al l such aspects are enabl ed withi n the width of the present i nvention.

[0069] The terms "compound", "agent", "active agent", "chemical agent", "pharmacologicall active agent", "medicament", "active" and "drug" are used interchangeably herein to refer to an extract of Ophioconfyceps which, in combination with a sleep apnea device induces a desired pharmacological and/or physiological effect such as preventing, reducing or inhibiting the adverse affects of stress such as a respiratory pattern which could lead to a sleep disorder such as sleep apnea or other condition such as metabolic disease (e.g. Type 1 or 2 diabetes), cardiovascular disease (e.g. heart failure) or a neurological condition such as depression, epilepsy or neurodegeneration. Other terms used interchangeably herein include herbal formulation, medicinal, neutraceutical, myochemicah ph tochemical, biochemopreventative, functional or designer food or dietary supplement. It is proposed that the combined use of the extract and mandibular device leads to normalization or enhancement of oxygen saturation, utilization and/or absorption. This has various beneficial side effects including facilitating good mental health, ameliorating sexual dysfunction and improving outcomes for subjects exposed to hypoxic conditions such as following asphyxia (e.g. drowning). In a surprising benefit, the improved or more efficient oxygen utilizatio is useful for astronauts on deep space prolonged flight missions and deep sea divers,

[0070] Taught herein is a therapeutic protocol comprising a medicinal component and a physical component. The medicinal compound encompasses an extract of Ophiocordyceps or pharmaceutically aceeptable and pharmacologically active ingredients of this extract mentioned herein including but not limited to salts, esters, amides, prodrugs, active metabolites, analogs and the like of any components in the extract The term "extract" includes fractions, derivatives and chemically synthesized or modified forms. For example, one or more components of the extract may be chemically synthesized or substituted by natural or chemically synthesized counterparts or augmented with other components such as digoxin. hydrochlorothiazide, dopamine, dobutamine or Rhodiola. The physical component comprises a mandibular device in the form of a sleep apnea device as herein described. The term "apnea" is an Americanized form of "apnoea". Either term may be used interchangeably in this specification and means the same condition. Reference to "sleep apnea" or "sleep apnoea", includes "hypopnea" or "hypopnoea".

[00711 The terms "sleep apnea device" and "sleep apnea treatment device" is not to imply any limitation which would exclude the device being a "snoring device" or "snoring treatment device" or a device to facilitate nor alization of or enhanced oxygen saturation, utilization and/or absorption. The therapeutic protocol facilitates a desired pharmacological or physiological effect which includes preventing, reducing or inhibiting sleep disorders or associated conditions such as metabolic diseases (e.g. Type 1 or 2 diabetes), cardiovascular disease or a neurological condition such as depression, epilepsy or anti-social behavior or neurodegeneration. Other related conditions include improved mental health, amelioratio of sexual dysfunction and protection from hypoxia such as following asphyxia (e.g. drowning) or, more surprisingly, for use by astronauts on prolonged dee space flights or for use by deep sea divers. In the case of the latter, use of the treatment protocol may be useful after a dive to prevent the bens. The pharmacological or physiological effect also includes enhanced aerobic perfonnance and protect from heart failure. The present invention extends to a combinatio of extracts from one or more species of Qphiocordyceps. The extract is used in. an integrated approach to improving sleep patterns through use of a mandibular device in tire form of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airwa conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit and optionally monitored by an electronic health (eHealth) system. Reference to an "extract" includes a fraction, derivative or chemically synthesized or modified form thereof.

[0072] The device component may be in the form of a singularly constructed device or in multi-component form such as a 2-part device comprising a mouth component and a mask component in the form of a flexible flap.

[0073] Without limiting the present invention to any theory or modification, it is proposed in an embodiment herein that the medicinal and physical components act in synergy to, inter alia reduce Cortisol level and/or to improve oxygen saturation, utilization and/or absorption in a subject's blood system and organs including the brain. There is a variability in oxygen saturation levels during polysomnography and these are expressed in terms such as average oxygen saturation (A0₂) and lowest oxygen saturation (L0₂) and the percent of total time with oxygen saturation level l ower than 90% (T<90%). AO 2 has been reported as 92.7 + 5.6; L0₂ as 68.5 ± 19.3 and T 90% as 15.7 + 24.2 T<90% (Chaudhary t at. (1998) CHEST J .13:719-722). Haemoglobin (Hb) bound to oxygen is referred to as oxygenated haemoglobin (Hb0₂). When Hb does not have any oxygen bound to it, the Hb is deoxygenated (referred to as "Hb"). The oxygen saturation is the ratio of HbO .Hb.

% Oxygen saturation [HbQ₂J x 100

[Hb0₂] [Hb] At sea level, healthy individuals exhibit oxygen saturation levels of 96-9.9%. Sleep apnea can occur in mild to severe forms when the oxygen saturation level is from 90% (mild) to 80-89% (moderate) to less than 80% (severe) [website for Harvard University, Healthy Sleep - sleep apnea/diagnosing].

[0074] In an embodiment, Cortisol level modification and/or enhanced oxygen saturation, utilization and/or absorption act in synergy to facilitate and promote a range of clinical benefits. In an embodiment the combination of the extract and the device elevates or normalizes oxyge saturation to 90% or greater during sleeping periods as well as increasing oxyge utilization and/or absorption. By "90% or greater' include 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% and, 99% . This is based on a "normal" oxygen saturation of about 96 to 98% under walking conditions. Put in other terms. The T<90% is maintained at a level of 24 or less such as from 1 to 24 which includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, .1 1, 12, 13, 14, 15, 16, 1.7, 18, 19, 20, 21, 22, 23 or 24. An oxygen saturation of 90% corresponds to a PaC value of 60 mmHg (Chaudhary et al (1998) supra). Reference to "synergy" means that th effect of a given Ophiocordyeeps extract and mandibular device is greater when used together compared to the use of either or alone. Greco et al. (1995) Pharmacol Rev. ¥7:331-385 define a category of synergy on the basis that the use of two components in combination has greater activity relative to the use of one agent alone. Hence, the definition adopted herei includes all such situations provided that the combined effeet of the extract and the mandibular device acting together is greater than the sum of the individual components acting alone. This can be measured, for example, by Cortisol levels, blood oxygen concentration, oxygen utilization and/or absorption, insulin levels, sugar levels or symptom relief. Furthermore, a combination of components is deemed synergistic, a the term is intended herein, if there exists a set of conditions, including but not limited to application strategy, where the combined effect of the components of the therapeutic protocol acting together is greater than the sum of the individual components acting atone. Richer (1987) Pestic Sci :3.09-315 describes a mathematical approach to establish proof of synergy. Modifying Limpel's formula, there is an observed level of a biochemical or symptom parameter (P) in the combined presence of the extract (X) and mandibular device (Y), with an expected additive effect (Ee) resulting from each X or Y acting separately as used to measure their combined effect. Additive percent clearance, Ee, is calculated as X + Y - XY/IOQ where X and Y are expressed as percent inhibition. Synergism exits where P > Ee. Put in another way, the concentration of Ophiocordyceps extract or length of that required for the use of the sleep apnea device is less hen both components are used in combination compared to the use of either component alone,

[0075] The extract includes proteins, peptides or essential amino acids, polyamines including 1,3-diamino propane, cadaverine, spermidine and putrescme, saccharides and sugar derivatives (e.g. D-roan toi), sterols including ergosterol, A^J-ergosterol peroxide, β- sitosterol, daueosterol and compasterol, nucleosides including adenine, uracil, uridine, guanosine, thymidine and deoxyuridine, fatty acids and other organic acids, vitamins B l, B2, B12, E and K and inorganics including , a, Ca, Mg, Fe, Cu, Mn, n, Pi, Se, Al, Si, Ni, Sr, Ti, Cr, Ga, V and Zr. In an embodiment, the Subject extract includes all or a sufficient quantity of adenosine, adenine, uracil, uridine, mannitol, β-sitosterol, oligosaccharides, polysaccharides, amino acids, zinc, potassium, manganese, phosphorous, selenium, vitamin B 1, vitamin B2 and/or vitamin E. In a embodiment, the extract is Cs-4 from Ophiocordyceps sinensis (Che et al. (2010) supra). Cs-4 is also known as Cordyceps. Generation of the extract is described inter alia in International Patent Publication No. WO 99/21 1, the contents of which are incorporated herein by reference.

[0076] Reference to Ophiocordyceps includes Ophiocordyceps sinensis, Ophiocordycep acicuiaris, Ophiocordyceps agiiotidis, Ophiocordyceps ainicios, Ophiocordyceps amazonica, Ophiocordyceps amazonica var. neoamazonica, Qphiocordy ps aphodii, Ophioeordyeeps appendicidaia, Ophiocordyceps arachneicola, Ophiocordyceps arbitscirfa, Ophiocordyceps armewaea, Ophiocordyceps asy e is, Ophiocordyceps cmmntia, Ophiocordyceps australis, Ophiocordyceps hamesH, Ophiocordycep hicephala, Ophiocordyceps hrimmipwwtaia, Ophiocordyceps hispor , Ophiocordyceps bkittae, Ophiocordyceps caloceroides, Ophiocordyceps canthare (hides, Ophiocordyceps carabidicola, Ophiocordycep cicadicol , Ophiocordyceps elavaia, Ophiocordycep clayulata, Ophiocordyceps cocck!iicoia, Ophiocordyceps coccigena, Ophiocordyceps^' cochlidiicola, Ophiocardyceps communis, Ophiocardyceps corall0my^~c.es, Ophiocordyceps crassispora, Ophiocordyceps crinalis, Ophiocordyceps cuboidea, Ophiocordyceps cucimrispora, Ophiocordyceps cucimtispora var. dotichoderi, Ophiocardyceps curculianwn_?- Ophiocordyceps cyUndrostromata^ Ophiocordyceps dayiemis-, Ophiocordyceps dermapterigena, Ophiocordyceps dipterigena, Ophiocordyceps discoideieapitaia, Ophiocordyceps ditmarii, Ophiocordyceps dovei, Ophiocordyceps eiateridicola, Ophiocordyceps elongaia, Ophiocordyceps ek gaiiperifheciata, Ophiocordyceps ehmgatistromaia, Ophioconfyceps emeiensis, Ophiocardyceps englerkma, Ophiocordyceps entomarrhiza, Ophiocordyceps evdogeorgiae, Ophiocordyceps fakata, Ophiocordyceps fakaioides, Ophiocordyceps fascictdatistromafct, Ophiocordyceps ferrugmosa, Ophiocordyceps filijormis, Ophiocordyceps form^' icartoffi, Ophiocordyceps fof fuignanii jOphiocordyceps fiircic udata, Ophiocordyceps gamuensis, Ophiocordyceps genicuktta, Ophiocordyceps geritilis, Ophiocordyceps gkiziovii, Ophiocordyceps goniophora, Ophiocardyceps gr cilioides, Ophiocordyceps gracilis, Ophiocordyceps gryiiotoipae, Ophiocordyceps halabalaensis, -Ophiocordyceps heteropoda, Ophiocardyceps hirsuteliae, Ophiocordyceps hhtgensis, Ophiocordyceps huheriana, Ophiocordyceps humhertU, Ophiocordyceps imigms, Ophiocordyceps irangiensis, Ophiocordyceps japonensis, Ophiocordyceps jiangxiensis, Ophiocordyceps jinggengshanerisis, Ophiocordyceps kangdmgensis, Ophiocardyceps kniphofioides, Ophiocordyceps kniphofi ides var. doiichoden, Ophiocordyceps kniphofioides var. monacidis, Ophioconfycep kniphofioides var, ponerinamm, Ophiocordycep koningshergeri, Ophiocordycep koimoana, Ophiocordyceps lachnopoda, Ophiocordyceps iaojimshanemis, Ophiocordyceps Iarvamm, Ophiocordyceps larvicola, Ophiocordyceps Uoydii, Ophiocordyceps Uoydii var. binaia, Ophiocordyceps ngissima_* Ophiocardyceps lutea, Ophiocordyceps macular is, Ophiocordyceps wieiolonthae, Ophiocordycep meiok thae var. rickii, Ophiocordyceps michiganensis, Ophiocordycep mimttissima, Ophiocordyceps monticola, Ophiocordyceps mrciemis; Ophioconfyceps mtdtiaxialis, Ophiocordyceps mwmecophikt, Ophiocordyceps neovolkkma, Ophiocordyceps nepalensis, Ophiocordyceps nigra, Ophiocordyceps nigreffa, Ophiocordyceps mgripes, Ophiocordyceps nutans _t Ophiocordyceps obt sa, Ophiocordycep actospora, Ophiocordyceps odonatae , Ophiocordyceps osmumontana, Ophiocordyceps owariensis, Ophiocordyceps owariemis f. viridescem, Ophiocordyceps oxycephat , Ophiocordyceps pciksdosa, Ophiocordyceps p racuboidea, Ophiocordyceps pentatomae, Ophiocordyceps petchii, Ophiocordyceps proUferans, Ophiocordyceps prolifica, Ophiocordyceps prtdnosa, Ophiocordyceps pseudoHoydii, Ophiocordyceps pseudolongissima, Ophiocordyceps pntvin ta, Ophiocordyceps purpureosiromata, Ophiocordyceps purpureostromaia f. recurv i , Ophiocordyceps ravemlii, Ophiocordyceps rhizoidea, Ophiocordyceps ridieyi, Ophiocordyceps roherisii, Ophiocordyceps rubripunctata, Ophiocordycep rubigittosip ritheciai , Ophiocordyceps ryogamiensis, Ophiocordyceps saiebrosa, Ophiocordyceps seoitiana, Ophiocordyceps sefkirkii, Ophiocordyceps sichua ensis-, Ophiocordyceps smithii, Ophiocordyceps soholifera, Ophiocordyceps sphecocephala^ Ophiocordyceps stipiUata, Ophiocordyceps siylophora, Ophiocordyceps subflavid , Ophiocordyceps su btmitateralis, Ophiocordyceps superficialis, Ophiocordyceps superficia!is f, cmsiacea, Ophiocordyceps takao mis, Ophiocordyceps tay rii, Ophiocordyceps thyrsoides, Ophiocordyceps tricentri , Ophiocordyceps iruncaia, Ophiocordyceps chiy m e, Ophiocordyceps um!atemlis, Ophiocordyceps imilateraHs var. ek ata, Ophiocordyceps variabilis, Ophiocordyceps voeltzkowii, Ophiocordyceps voikimm, Ophiocordyceps wuyishanensis, Ophiocordyceps yetkusimemis and Ophiocordyceps zh ngji jiemis as well as closely genetically or functionally related genera, species and strains thereof. In addition, a genetically modified or phenotypically adapted strain of the species or strain of Ophiocordycep may be developed or utilized.

[0077] In an example, the Ophiocordyceps is Ophiocordyceps sinensis and the extract is Cs-4 (Cordyceps) or a derivati ve or fraction thereof or a chemically or partially chemically synthesized form thereof An equivalent or related genus, species or strain may be selected for use in a particular country or region where the material is to be grown. A genetically modified or phenotypically adapted Ophiocordyceps sinensis ma be developed or utilized such as a strain which produces a more efficacious Cs-4 product or which grows more efficiently or utilizes a particular nutrient. genetically modified form includes a genetically modified part of the Ophiocordyceps. Reference to "Cs-4" includes a chemically synthesized or partially chemically synthesized form or a Cs-4 to which additional or substitute components have been added. [0078] Enabled herein is a process for producing a Cordyceps fermentation product which comprises fermenting a species of Ophiocordyceps or a genetically modified or phenotypically adapted strain thereof under aerobic conditions in a culture medium and recovering Cordyceps mycelia from the culture medium for use in combination with a mandibular device.

[0079] hi an embodiment, the process comprises:

(a) inoculating a culture medium with at least one fungal strain and cultuiing under aerobic conditions for about 2 to 5 days at about 24°C;

(b) cultuiing the fungus in fresh medium under aerobic conditions for about 2 to 3 days at about 24°C;

(c) repeating step (b) such that there is a sufficient amount of fungus to start a Cordycep fermentation in a large-scale fermentor;

(d) cultuiing the fungus from step (c) in fresh medium in a large-scale fermentor under aerobic conditions for about 5 days at about 24°C; and

(e) recovering the Cordyceps fermentation product by removing the medium and drying the Cordyceps mycelia.

[0080] Reference to an extract or component or components in an extract includes combinations of two or more extracts or components. A "combination" also includes multi-part compositions where the extracts or components are provided separately and given or dispensed separately or admixed together prior to dispensation. For example, a multi-part pack may have two or more active extracts separately maintained. In an embodiment, the multi-part pack comprises Cs-4 (Cordyceps) from Ophiocordyceps^' sinensis. I another embodiment, the pack comprises a sensor device to monitor breathing patterns. I another embodiment, the pack is sold with the mandibular device in the form of the sleep apnea device to facilitate breathing. The Ophiocordyceps extract and that mandibular device are used in concert, i.e. in combination. The mandibular device is in the form of a sleep apnea treatment, device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit. The device may also be referred to as a snoring treatment device. The pack or its use may be packaged for sale or license in an eHealth system.. The term "extract" does not imply that the extract is not chemically synthesized or a component or two or more components is not substituted by a natural or chemically synthesized substitute. In addition, other components may be added to the extract or given together with the extract. Examples include digoxin, hydrochlorothiazide, dopamine, dobutamine and Rhodiola.

[0081] The terms- "effective amount" and "therapeutically effective amount" of an agent as used herein mea a sufficient mnount of the agent (i.e. Ophiocorefyceps extract) to provide the desired therapeutic or physiological effect or outcome which includes ameliorating the effect of a respirator pattern which leads to a sleep disorder such as sleep apnea or snoring, a metabolic disease such as Type 1 or 2 diabetes, cardiovascular disease or a neurological condition such as depression, epilepsy or neurodegeneration or other beneficial clinical outcomes when used in combination with the sleep apnea device. Undesirable effects, e.g. side effects, are sometimes manifested along with the desired therapeutic effect; hence, a practitioner or user balances the potential benefits against the potential risks in determining what is an appropriate "effective amount". The exact amount required will vary from subject to subject, depending on the age and general condition of the subject, mode of administration and the like. Thus, it may not be possible to specify an exact "effective amount". However, an appropriate "effective amount" in any individual case may be determined b one of ordinar skill in the art using onl routine experimentation. The effective amount may also be measured in terms of maintaining or improving oxygen saturation to 90%. or greater and/or to improve oxygen utilization and/or absorption. The effective amount may also be influenced by the outcome of a monitoring algorithm within the context of an eHealth platform . |0082| Hence, as used herein, an "effective amount" refers to an amount of Qphiocortlyceps extract that provides the desired effect of preventing, reducing or inhibiting a corti sol -based condition such as stress or symptoms leading to stress including a sleep disorder such as sleep apnea or snoring, a metabolic condition such as Type 1 or 2 diabetes, cardiovascular disease or a neurological condition such as depression, epilepsy or neurodegeneration when administered according to a suitable dosing regime, in combination ^'with a subject having the sleep apnea device inserted into the subject's mouth. Other clinical outcomes include normalization or enhancement of oxygen saturation, utilization and/or absorption, improved mental health, improved sexual performance and prevention or reduction of damage following hypoxia conditions such as after asphyxiation. In a surprising benefit, the protocol is useful for astronauts on deep space (e.g. interplanetary) missions and for deep sea divers. Dosing may occur at intervals of several minutes, hours, days, weeks or months or may occur j ust prior to normal sleeping times. Dosing may al so depend on the readout of a sleep monitor device and the use of the mandibular device. In an embodiment, the dose of extract is from lOOpg to lOOg per day or per two days or per week. Reference to "100μ§ to lOOg" includes from lOOug to Img, Img to !GOrng, J OOmg to Ig and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 , 52, 53, 54, 55, 56, 57, 58, 59, 60, 61 , 62, 63, 64, 65, 66, 67, 68, 69, 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88. 89, 90, 91 , 92, 93, 94, 95, 96, 97, 98, 99 or lOOg. In an embodiment, 0.0 Ig to Ig/kg body weight is administered including 0,01, 0,02, 0,03, 0.04, 0,05, 0,06, 0.07, 0.08, 0.09, 0, 1, 0.2, 0,3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 or Ig kg body weight. Split dosing may also be utilized where the total daily amount of the extract is given over a period of from 1 to 24 hours in different or evenly proportioned amounts, For example, two half doses every 12 hours. Administration may be b any means including nasal or inhalation spray, dietary supplement, tablet, pill, cream, lotion, gel and/or patch or via nanoparticl.es·. The sleep apnea device may also be modified to include a slow release component for the extract. The medicinal and the device may be used in either order or simultaneously and the device may be used each night and the extract given at different times or days. As indicated above, the extract may be an extract of the Ophiocord ceps or an extract of a genetically modified Ophioeordyceps or a chemically or partially chemically synthesized or complemented form.

[0083] The extract may also contain a pharmaceutically acceptable carrier, excipient, diluent or additive.

(0084] By a "pharmaceutically acceptable" carrier, excipient, diluent or additive is meant a vehicle comprised of a material that is not biologically or otherwise undesirable, i.e. the material may be administered to the human subject along with the selected extract without causing any or a substantial adverse reaction. Carriers may include excipients and other additives such as diluents, detergents, coloring agents, wetting or emulsifying agents, pH buffering agents, preservatives, and dietary additives and the like.

[0085] Conveniently, the therapeutic protocol is available over the counter or by on-line sales as a package comprising the sleep apnea device and a course of medicament being the extract from Ophioeordyceps in an appropriate formulation.

[0086] It is proposed herein that the sleep apnea treatment device be used with the Ophioeordyceps extract for decreasing cytosol levels and increasing oxygen saturation, utilization and/or absorption of the user's blood, orga (e.g. brain) and cardiovascular system thereby managing stress levels. The sleep apnea treatment device is used in a. method of treating sleep apnea which includes the steps of wearing the sleep apnea treatment device and breathing ambient air through the sleep apnea treatment devic while sleeping while taking, in either order or simultaneously, the extract from Ophioeordyceps. The sleep apnea device is also used to control snoring which: includes the steps of wearing the slee apnea treatment device and breathing ambient air through the sleep apnea treatment device while sleeping while taking, in either order or simultaneo sly, the extract from Ophioeordyceps. Advantageously, as the device is not connected to a machine for pumping pressurised air into the user, the user has greater freedom to move during sleeping, for example rolling in bed, which may promote greater adherence of the user to the treatment. Furthermore, the external surface of the masked portion ma be curved so as to minimise interference with movement of the user during sleeping.

(0087] The sleep apnea treatment device may be produced in a range of sizes which may include a larger (medium-large) size and a smaller (small-medium) size available from a pharmacy or other retail outlet such that the user does not need to consult a dentist or physician to obtain the product. In this way, the cost to the user in obtaining the product may be minimised to encourage the user to obtain the product. Accordingly; the method of treating sleep apnea includes the user selecting for themselves from a range of predetermined sizes of sleep apnea treatment devices from a retail outlet, and the user wearing the selected sleep apnea treatment device. A indicated above, the device may be integral comprising a singularly constructed device or it may be of a multi -component type such as a 2-part device comprising a mouth portion and a mask portion in the form of a flexible flap.

[0088] The terms "treating" and "treatment" as used herein refer to reduction in severity and/or frequency of symptoms of the Cortisol -based disorder being treated, elimination of symptoms and/or underlying cause, prevention of the occurrence of symptoms of the condition and/or their underlying cause and improvement or remediation or amelioratio of damage following a condition. Hence, an human subject may be treated in advance of any symptoms of a disorder such a sleep apnea or snoring, a metabolic disease such as Type 1 or 2 diabetes, cardiovascular disease or a neurological condition such as depression, epilepsy or neurodegeneration. The user may also desire greater aerobic capacity and physical fitness and/or suffer from less fatigue. Furthermore, the combination of medicinal and device leads to enhanced or normalized oxyge saturation, utilization and/or absorption and to lower levels of Cortisol. Either of these or in combination can have many clinical beneficial effects including improved mental health, treatment of sexual dysfunction and improved outcomes following hypoxic conditions (e.g. after heart failure, asphyxia and conditions) requirin efficient oxygen control (e.g. deep space travel and dee sea diving).

[0089] "Treating" a human subject may occur as a routine procedure prior to engaging to work practices even if there are no symptoms to treat. For example, if the subject, engages in transport or agricultural activities then prior to the initiation of these activities the subject would use the mandibular device and take the extract from Ophiocor fyceps. As indicated above, the term "extract" is not to limit the composition to a biological extract bu may contain some or all components which are chemically synthesized or added. In terms of snoring, reference is made to "controlling" snoring which includes treating, reducing the intensity, preventing and the like. Alternatively, the treatment protocol is part, of an eHealth platform.

[0090] A "subject" as used herein refers to a human of any age who can benefit from the formulations and methods of the present invention. A subject may also be referred to as a patient, host, recipient person, individual, user and the like.

[0091] The present invention is predicated in part on a determination that a formulated extract from Ophioeordyceps acts in synergy with the sleep apnea device as described herein to ameliorate the symptoms of adverse elevated Cortisol -based disorders which lead or which have the potential to lead to sleep disorders such as sleep apnea or snoring, metabolic disorders such as Type 1 or 2 diabetes, cardiovascular disease or a neurological condition such as depression, epilepsy or neurodegenerati n. Overall, these conditions can lead to stress or exacerbate stress levels. As indicated above, the treatment protocol can also lead to greater aerobic fitness and other clinically beneficial outcomes.

[0092] .Exemplary conditions include sleep apnea, snoring, Type 1 or 2 diabetes, cardiovascular disease (e.g. heart failure), depression and neurodegenerative disorders. Other conditions include improving aerobic fitness and enhanced or normalized oxygen saturation, utilization and/or absorption.

[0093] Accordingly, a aspect of the present invention provides a method for treating a huma subject with a cortisol-based disorder or condition or with the potential for developing the disorder or condition, the method comprising the admini strati on to the subject in either order or simultaneously an effective amount of an extract of a species of Ophiocordyceps and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0094] In an embodiment, the present invention provides a method for treating a human subject with a respiratory pattern leading to a sleep disorder such as sleep apnea or snoring, the method comprising the administration to the subject in either order or simultaneousl an effective amount of an extract of a species of Ophiocordyceps and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit mai ntains fluid communication of the mouth vestibule wit ambient air to facilitate the user breathing the ambient air through the airwa conduit.

[0095] In an embodiment, the present invention provides a method for treating a human subject with a metabolic disease such as Type .1. or 2 diabetes, the method comprising the admini stration to the subject in either order or simultaneously an effective amount of an extract of a species of Ophiocordyceps and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit i place relative to the user's mouth wi th the airway conduit extending betwee the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

(0096] In an embodiment, the present invention provides a method for treating a human subject with a cardiovascular disease, the method comprising the administration to the subject i either order or simultaneously an effective amount of an extract of a species of Ophiocordyeeps and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0097] In an embodiment, the present invention provides a method for treating a human subject with a neurological condition such as depression, epilepsy or neurodegeneration, the method comprising the administration to the subject in either order or simultaneously an effective amount of an extrac of a species of Ophiocordyeeps and insertion into the subject's mouth of a sleep apnea treatment device for use i breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airwa conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit,

[0098] In an embodiment, the present invention provides a method fo treatin human subject with stress, the method comprising the administration to the subject in either order or simultaneously of an effective amount of an extract of a species of Ophiocordyeeps and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit,

[0099] In an embodiment, the present invention encompasses a method for treating a huma subject requiring normalization or enhancement of oxygen saturation, utilization and/or absorption, the method comprising the administration to the subject in either order or simultaneously of an effective amount of an extract of a species of Qphiocordyceps and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

|0100] I accordance with another aspect of the present invention, there is provided a system for treating sleep apnea, comprising a sleep apnea device as described herein, and a medicament for increasing oxygen saturation and/or utilization, the medicament comprising an extract of a species of Ophiocordyceps.

[0101] I accordance with another aspect of the present invention, there is provided a method of treating sleep apnea compri sing the steps of wearing a sleep apnea treatment device as described herein, and breathing ambient air through the sleep apnea treatment device while sleeping and administering an extract of a species of Ophiocordyceps. - 5J -

[0.1.02] In accordance with another aspect of the present invention, there is provided a method of treating sleep apnea including the steps of a user selecting from a range of predetermined sizes of slee apnea treatment devices from a retail outlet including an online outlet, and the user wearing the selected sleep apnea treatment device, wherein each of the sleep apnea treatment devices in the range o predetermined sizes is a sleep apnea treatment device as described herein and taking a extract of Ophiocordyceps.

[0103] hi accordance with another aspect of the present invention, there is provided a system for controlling snoring, comprising a sleep apnea device as described herein, and a medicament for increasing oxygen saturation and/or utilization, the medicament comprising an extract of a species of Ophtocordyeeps .

[0104] In accordance with another aspect of the present invention, there is provided a method of controlling snoring comprisin the steps of wearing a sleep apnea treatment device as described herein, and breathing ambient air through the sleep apnea treatment device while sleeping and administering an extract of a species of Ophiocordyceps.

[0105] In accordance with another aspect of the present invention, there is provided a method of controlling snoring including the steps of a user selecting from a range of predetermined, sizes of sleep apnea treatment devices from a retail outlet including an online outlet, and the user wearing the selected sleep- apnea treatment device, wherein each of the slee apnea treatment devices in the range of predetermined sizes is a sleep apnea treatment device as described herein and taking an extract of Ophiocordyceps.

(0106] The instant method may also be augmented by the administration of other agents useful in modulating levels of Cortisol and/or oxygen saturation, utilization and/or absorption and/or the treatment or outcome may be monitored by or integrated within an e Health . platform.

[0107] Generally, the respiratory disorder is a sleeping disorder such as sleep apnea or snoring. The sleeping disorder may also be detected by sensor means. Generally, the metabolic disorder is Type 1 or 2 diabetes. Generally, the cardiovascular disease is a heart condition such as heart failure. Generally, the neurological condition is depression, epilepsy or is a neurodegenerative disorder. The depression may be from mild t severe and includes drug resistant depression. The combination therapy can also lead to improved mental health and to reduce adverse psychological behaviors such as anti-social behavior. The neurodegenerative disorder includes Parkinson's disease, Alzheimer's disease, Huntington' disease and multiple sclerosis. Other beneficial outcomes include improved sexual performance and enhanced neurological protection following hypoxia or exposure to hypoxic conditions,

[01081 As indicated above, the "effective amount" is the amount of extract required to prevent, reduce or inhibit the adverse consequences of elevated Cortisol or poor oxygen utilization and/or saturation when used in synergy with the sleep apnea device. Hence, the subject method is also useful for managing stress levels. In an embodiment, the Ophiocordyceps is Ophiocordyceps sinemis or a genetically modified or phenotypically adapted form thereof.

[0109] Accordingly, taught herein is a method for treating a human subject with a sleeping disorder or condition or with a potential of developing the sleeping disorder or condition such as sleep apnea or snoring, the method comprising the administration to the subject in either order or simultaneously a effective amount of an. extract of Ophiocordyceps sinensis and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted, for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communicati on of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit. [0.110] Enabled herein is a method for treating human subject with a metabolic disease such as Type 1 or 2 diabetes or with a potential of developing the metabolic disease, the method comprising the administration to the subject in either order or simultaneously an effective amount of an extract of Ophiocordyceps sinensis and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in. the mouth vestibule of a user interposed between the li ps and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communicatio of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit,

[0111] Enabled herein is a method for treating a human subject with a cardiovascular disease or with a potential of developing the cardiovascular disease, the method comprising the administration to the subject in either order or simultaneousl an effective amount of an extract of Ophiocordyceps sinensis and i sertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airwa conduit in place relative to the user's mouth with the airway conduit extending betwee the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

(0112] The present specification is also instructional for a method for treating a human subject with a neurological condition such as depression, epilepsy or neurodegeneration or with a potential of developing a neurological condition such as depression, the method comprising the administration to the subject in either order or simultaneousl an effective amount of an extract of Ophiocordyceps sinensis and insertion into the subject's mouth of a sleep apnea treatment, device for use in breathing ambient air, the device comprising mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teet of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0113] Enabled herein is a method far treating a human subject with stress or with a potential of developing stress or stress-related conditions, the method comprising the administration to the subject in either order or simultaneously an effective amount of an extract of Ophiocordyceps sinensis and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0114] Taught herein is a method for treating a human subject requiring normalization or enhancement of oxygen saturation, ^'utilization and/or absorption the method comprising the administration to the subject in either order or simultaneously an effective, amount of an extract of Ophiocordyceps sinensis and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the m outh vestibule of a user interposed b etween the l ips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit mai ntains fluid communication of the mouth vestibule wi th ambi ent air to facilitate the user breathing the ambient air through the airway conduit . [0115] In a particular embodiment, the extract is referred to Cs-4 or Cordyceps from Qpkiocordyceps sinensis or is a derivative or fraction thereof or an extract from a genetically modified or phenotypically adapted form of the Ophioeordyceps. sinensis or a Cs-4 which comprises all or some components chemically synthesized or added or substituted for existing components.

[0116] Accordingly, taught herein is a method for treating a human subject having a respiratory pattern leadin to a sleep disorder such as sleep apnea or snorin or with a potential of developing the sleeping disorder or condition, the method comprising the administration to the subject in either order or simultaneously an effective amount of Cs-4 or a fraction or derivative or chemically synthesized or modified form thereof and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airwa conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0117] Enabled herein is a method for treating a human subject having a metabolic disease such as Type 1 or 2 diabetes or with a potential of developing the metabolic disease, the method comprising the administration to the subject in either order or simultaneously an effective amount of Cs-4 or a fraction or deri vative or chemically synthesized or modified form thereof and insertion into the subject's mouth of a sleep apnea treatment device tor use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airwa conduit, the vestibular locator being adapted for positioning in. the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

(01 IS] Enabled herein is a method for treating a human subject having a cardiovascular disease or with a potential of developing cardiovascular disease, the method comprising the administration to the subject in either order or simultaneously an effective amount of C^'s-4 or a fraction or derivative or chemically synthesized or modified form thereof and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airwa conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the ai way conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule wit ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0119] Taught herei is a method for treating a human subject having a neurological condition such as depression or neurodegeneration or with a potential of developing the neurological condition, the method comprising the administration to the subject in either order or simultaneously an effective amount of Cs-4 or a fraction or derivative or chemically synthesized or modified form thereof and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed betwee the lips and teeth of the user, the vestibul ar locator supporting the airway conduit i place relati ve to the user's m outh wi th the airway conduit extending bet ween the lips of the user whereby the aii-way conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0120] The present specification is instructional for treating a human subject having stress or with a potential o developing stress or a stress-related condition, the method comprising the administration to the subject in either order or simultaneously an effective amount of Cs-4 or a fraction or derivative or chemically synthesized or modified form thereof and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teet of the user, the vestibular locator supporti g the airway conduit in place relative to the user's mo th with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[Q121| Enabled herein is a method for treating a subject requiring normalization or enhancement of oxygen saturation, utilization and/or absorption, the method comprising the administration to the subject in either order or simultaneously an effective amount of Cs-4 or a fraction or derivative or chemically synthesized or modified form thereof and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator a id an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between th li ps and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit,

[0122] Administration of the Ophiocordyceps extract may be by any convenient means including as a dietary supplement the extract may be in the form of aerosol spray, droplets, nasal swab, inhalation via nose or mouth, vapor, dry powder, nanoparticles and the like including a pill or tablet, cream, gel, lotion and/or patch and/or using nanoparticles. The sleep apnea device may also be modified to include a slow release component of the medicinal extract.

[0123] Another aspect enabled herein is a method for treating sleep apnea or a related condition including snoring i a human subject, the method comprising the administration, to the subject in either order or simultaneously as a dietary supplement an amount of an extract of a species of Ophiocordyceps effective to prevent, reduce or inhibi t the sym tom s of sleep apnea together with insertion into a subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to faci litate the user breathing the ambient air through the airway conduit.

[0124] In a related embodiment, taught herein is a method for treating sleep apnea or snoring i a human subject, the method comprising the administration to the subject in either order or simultaneously an effective amount of an extract from Ophiocofdyceps sinensis and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, th vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between, the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

(0125] In. an embodiment, enabled herein is a method for treating sleep apnea or snoring in a human subject, the method comprising the administration to the subject in either order or simultaneously an effective amount of Cs-4 or a fraction or derivative or chemically synthesized or modified form thereof and insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication, of the mouth vestibule with, ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0126] In an embodiment, enabled herein is a method for treating; a metabolic condition such as Type 1 or 2 diabetes in. a huma subject, the method comprising the administration to the subject in either order or simultaneously as a dietary supplement an extract of a species of Ophiocordyceps together with insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway condui the vestibular locator being adapted for posi tioning in the mouth vestibule of a user i nterposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0127] In an embodiment enabled herein is a method for treating a metabolic disease or related condition in a human subject, the method comprising the administration to the subject in either order or simultaneously an extract of Ophiocordyceps sinensis and insertio into the subjeGt's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathi g the ambient air through the airway conduit,

[0128] In an embodiment, enabled herein is a method for treating metabolic disease in human subject the method comprising the administration to the subject in either order or simultaneously Cs-4.or a fraction or derivative or chemically synthesized or modified form and the insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed betwee the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between th lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0129] In an embodiment, enabled herein is a method for treating cardiovascular disease in a human subject, the method comprising the admi istration to the subject in either order or simultaneously as a dietary supplement an extract of a species of Ophiocordyceps and the insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between, the l ips and teeth of the user, the vesti bular locator supporting the airway conduit in place relative to the user's mouth with the airwa conduit extending between the lips of the user whereby the ai way conduit maintains fluid communicatio of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit,

[0130] In an embodiment, enabled herein is a method for treating cardiovascular disease or a related condition in a human subject, the metliod comprising the administration to the subject by either order or simultaneously an extract of Ophiocordyceps sinensis and the insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air. the device comprising a mouthpiece including a vestibular locator and a airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit, in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0131] In an embodiment, enabled herein is a method for treating cardiovascular disease in a human subject, the method comprising the administration in either order or simultaneously Cs-4 or a fraction or derivative or chemically synthesized or modified form, and the insertion into the subject's mout of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extendin betwee the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit

[0132] In an embodiment, enabled herein i s a method for treating a neurological condition such as depression, epilepsy or neurodegeneration or a related condition in a human subject, the method comprising the administration to the subject in either order or simultaneously an of extract of a species of Ophiocordyceps and the insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airwa conduit.

[0133] In an embodiment, enabled herein is a method for treating a neurological condition such as depression, epilepsy or neurodegeneration in a human subject, the method comprising the administration in either order or simultaneously .an extract of Ophiocordyceps sinensis and the insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid com muni cation of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit,

[0134] In an embodiment, enabled herein is a method for treating a neurological condition such as depression, epilepsy or neurodegeneration in a human subject, the method comprising the administration in either order or simultaneously Cs-4 or a fraction or derivative or chemicall synthesized or modified form and the insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit,

|0135] I an embodiment, enabled herei is a method for treating a huma subject in need of normalization or enhancement of oxygen saturation, utilization and/or absorption, the method comprising the administration to the subject in either order or simultaneously a of extract of a species of Qphiocordyceps and the insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning i the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid comrnunication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit. [0136] In an embodiment, enabl d herei is a method for treating a human subject in need of normalization or enhancement of oxygen saturation, utilization and/or absorption, the method comprising the administration in either order or simultaneously an extract of Qphiocordyceps sinensis and the insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and .an airway conduit, the vestibuiar locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0137] In an embodiment, enabled herein is a method fo treating a human subject in need of normalization or enhancement of oxygen saturation, utilization and/or absorption, the method comprising the administration in either order or simultaneousl Cs-4 or a fraction or derivative or chemically synthesized or modified form and the insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular l ocator being adapted for positioning in the mouth vestibul e of a user interposed between the lips and teeth of the user, the vestibuiar locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereb the airway conduit maintains fluid com munication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0138] The Opkioc rdyeeps extract includes any molecules which have a beneficial effect in ameliorating the symptoms of a respirator)' condition or disorder leading to a sleep disorder or a metabolic disorder such as Type 1 or 2 diabetes or cardiovascular disease or neurological condition such as depression, epilepsy or neurodegeneration when used in conjunction with the sleep apnea disorder herein described. The extract includes proteins, peptides or essential amino acids, polyamin.es including 1 ,3 -diamine propane, cadaverine, spermidine and putrescine, saccharides and sugar derivatives (e.g. D.-manrtitol), sterols includin ergosterol, A^J~ergosterol peroxide, β-sitosterol, daucosterol and compasterol., nucleosides including adenine, uracil, uridine, guanosine, thymidine and deoxyuridme, fatty acids and other organic acids, vitamins Bl, B2, B12, E and K and inorganics including K, Na, Ca, Mg, Fe, Cu, Mn, Zii, Pi, Se, Al, Si, Ni, Sr, Ti, Cr, Ga, V and Zr. In an embodiment, the Ophiacordyceps extract comprises all or a sufficient number or quantity of adenosine, adenine, uracil uridine, mannitol, β-sitosterol, oligosaccharides, polysaccharides, amino acids, zinc, potassium, manganese, phosphorous, selenium, vitami Bl, vitamin B2 and/or vitamin E. In an embodiment, the extract is Cs-4 (Cordyceps) from Qphiocordyceps sinensis (see Chen et at. (2010) supra) or from a genetically modified or phenotypically adapted Qphiocordyceps sinensis or a traction or derivative or chemically synthesized or modified form of the Cs-4. The extract may be produced Following fermentation such as described by WO 99/21961, th contents oF which are incorporated herein in their entirety,

(0139] The present invention is further directed to a method of treating a human subject with a respiratory pattern which leads to a sleeping disorder or for the potential for developing same such as sleep apnea or snoring, the method comprising administering to the subject in either order or simultaneously an effective amount of an agent comprising all or a sufficient number of adenosine, adenine, uracil, uridine, mannitol, β-sitosterol, oligosaccharides, polysaccharides, amino acids, zinc, potassium, manganese, phosphorous, selenium, vitamin Bl, vitamin B2 and/or vitamin E or chemically synthesized or modified forms of any one or more components together with insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an .airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the tips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit. [0.140] Enabled herein is a method of treating a human subject with a metabolic disease such as Type 1 or 2 diabetes or for the potential of developing same, the method comprising administering to the subject in either order or simultaneously an effective amount of an agent comprising all or a sufficient number of adenosine, adenine, uracil, uridine, mannitol, β~ sit sterol, oligosaccharides, polysaccharides, amino acids, zinc, potassium, manganese, phosphorous, selenium, vitamin Bl , vitamin B2 and/or vitamin E or chemicall synthesized or modified forms of any one or more components together wit insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mout with the airway conduit extending betwee the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[01.41] Enabled herein is a method of treating a human subject with a cardiovascular disease or for the potential of developing same, the method comprising administering to the subject in either order or simultaneously an effecti ve amount of a agent comprising all or a sufficient number of adenosine, adenine, uracil, uridine, mannitol, β-sitosterol, oligosaccharides, polysaccharides, amino acids, zinc, potassium, manganese, phosphorous, selenium, vitamin Bl, vitamin B2 and/or vitamin E or chemically synthesized or modified forms of any one or more components together with insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a. mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the Hps and teeth of the user, the vestibular locator supporting the airway conduit in. place relative to the user's mouth with the airway conduit extending between the lips of the user whereb the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit. [0142J Taught herein is a method of treating a human subject with a neurological condition such as depression, epileps or neurodegeneration or for the potential tor developing same, the method comprising administering to the subject in either order or simultaneously an effective amount of an agent comprising all or a sufficient number of adenosine, adenine, uracil, uridine, mannitol, β-sitosterot, oligosaccharides, polysaccharides, amino acids, zinc, potassium, manganese, phosphorous, selenium, vitamin Bl, vitamin B2 aiid/or vitamin E or chemically synthesized or modified forms of any one or more components together with insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending betwee the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0143] Taught herein is a method of normalizing or enhancing oxygen saturation, utilization and/or absorption in a human subject, the method comprising administering to the subject in either order or simultaneously an effective amount of an agent comprising all or a sufficient number of adenosine, adenine, uracil, uridine, mannitol, β-sitosterol, oligosaccharides, polysaccharides, amino acids, zinc, potassium, manganese, phosphorous, selenium, vitamin Bl, vitamin B2 afld/or vitamin E or chemically synthesized or modified forms of any one or more components together with insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the Hps and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit. [0144J The Ophiocardyceps extract contemplated for use herein include naturally occurring or synthetic or modified forms. A "modified form" includes a component added or supplemented or substituted for an existing component In general, the extract comprises all or a sufficient number or quantity of adenosine, adenine, uracil, uridine, mannitoi, β-sitosterol, oligosaccharides, polysaccharides, amino acids, zinc, potassium, manganese, phosphorous, selenium, vitami Bl , vitamin B2 and/or vitamin E or chemically synthesized or modified forms of any one or more components. In an embodiment, the extract is Cs-4 (Cordyceps) or chemically synthesized or modified forms of any one or more components.

[0145] A therapeutic protocol is hence provided to deal with sleeping disorders such as sleep apnea or snoring. This can lead to metabolic conditions such as Type 1 or 2 diabetes, cardiovascular disease or depression. The protocol involves the regular administration of an extract of Ophiocardyceps together with use of a sleep apnea device as herein described. The extract ma also be integrated into an eHealth platform.

[0146) The present invention is further directed to the use of an extract of a species Ophiocordyceps in the manufacture of a medicament for the treatment of a sleeping disorder such as sleep apnea or snoring in a human subject together with use of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning i the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to faci litate the user breathing the ambient air through the airway conduit.

(0147] Enabled herein is the use of an extract of a species Ophiocordyceps in the manufacture of a medicament for the treatment of metabolic disease in a human subject together with use of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece includin a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

(0148] Enabled herein is the use of an extract of a species Qphiocordyceps in the manufacture of a medicament for the treatment of cardiovascular disease in a human subject together with use of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0149] Taught herein is the use of an extract of a species Qphiocordyceps in the manufacture of a medicament for the treatment of a neurological condition such as depression, epilepsy or neurodegeneration in a human subject together with use of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibul ar locator supporting the airway conduit in place relati ve to the user's mouth wi th the .airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[ 1 SO] Enabled herein is the use of an extract of a species of Qphiocordyceps in the manufacture of a medicament for the treatment of a subject to normalize or enhance oxygen saturation, utilization and/or absorption, in a human subject together with use of a sleep apnea treatment device for use in breathing ambient air. the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communieation of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit,

[0151] The present invention further contemplates the use of an extract of Ophiocordyceps sinensis in the manufacture of a medicament for the treatment of sleeping disorder such as sleep apnea or snoring in a human subject together with use of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0152] Enabled herein is the use of an extract of Ophiocordyceps sinensis in the manufacture of a medicament for the treatment of a metabolic disease such as Type 1 or 2 diabetes in a human subject together with the use of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0153] Enabled herein is the use of an extract of Ophiocordyceps sine mis in the manufacture of a medicament for the treatment of cardiovascular disease in a huma subject together with the use of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an air vay conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the Hps and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airvvay conduit extending betwee the lips of the user whereby the airway coiiduit maintains fluid, communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit,

[0154 J The present specification is instructional on the use of an extract of Ophioc rdyceps sinensis in the manufacture of a medicament for the treatment of a neurological condition such as depression, epilepsy or neurodegeneration in a human subject together with use of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airvvay conduit,

[0155] The present specification enables the use of an extract of Ophiocordyceps sinensis in the manufacture of a medicament for the treatment of a subject to normalize or enhance oxygen saturation, utili zation and/or absorption, in. -a human subject together ^'with use of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit i place relative to the user's mouth wi th the airway conduit extending betwee the lips of the user whereby the airvvay conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

(0156] In another embodiment, enabled herein is the use of Cs-4 or Cordyceps or chemically synthesized or modified forms of any one or more components in the manufacture of a medicament for the treatment of a sleeping disorder such as sleep apnea or snoring in a human subject together with use of a sleep apnea treatment device for use in breathing ambient air, th device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0157] Taught herein is the use of Cs-4 or Cordyceps or chemically synthesized or modtfied forms of any one or more components in the manufacture of a medicament for the treatment of metabolic disease in a human subject together with use of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the Tips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0158] Taught herein is the use of Cs-4 or Cordyceps or chemically synthesized or modified forms of any one or more components in the manufacture of a medicament for the treatment of cardiovascular disease in a human subject together with use of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0159] Enabled herein is the use of Cs-4 or Cordyeeps or chemically synthesized or modified forms of any one or more components in the manufacture of a medicament for the treatment of a neurological condition such as depression or neurodegeneration in a human subject together with use of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the li s and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user ^'whereb ^' the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0160] Taught herein is the use of Cs-4 or Cordyeeps or chemically synthesized or modified forms of any one or more components in the manufacture of a medicament for the treatment of a subject to normalize or enhance oxygen saturation, utilization and/or absorption in a human subject together with use of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the .airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibuie with ambient air to facilitate the user breathing the ambient air through the airway conduit.

[0161] The present invention further provides a treatment or monitor algorithm-based eHealth system for use in conjunction with a therapeutic protocol comprising an Ophiocortfy eps extract (herbal/medicinal/chemicai extract) and a sleep apnea device. Generally, input data are collected based on Cortisol levels, dissolved oxygen levels, oxygen utilizatio potential, sleeping patterns, psychological questionnaire answers, sugar levels and/or insulin levels and subjected to an algorithm to assess the statistical significance of any change in parameters of stress -which information is then output data. Computer software and hardware for assessing input data are encompassed by the present invention.

[0162] Another aspect of the present invention contemplates an eHealth platform for treating a patient with a cortisol-disorder or conditio such as stress, a sleep disorder, a metabolic disease, cardiovascular disease or a neurological condition, the method comprising subjecting the patient to a diagnostic assa to determine an index of probability of the patient having the condition, and where the risk of the patient having the condition, subjecting the patient to a treatment comprising the administration of an extract of Ophiocordyceps such as Ophiocordyceps sinensis (e.g. Cs-4 or chemically synthesized or modified forms of any one or more components) together with a sleep apnea device; and then monitoring index of probability over time, in an embodiment, the subject is tested for inter alia Cortisol levels, dissolved oxygen levels, oxygen utilization capacity, oxygen absorption, sleeping patterns, psychological questionnaire answers, sugar levels and/or insulin levels.

[0163] The assay of the present invention permits integration into existing or newly developed pathology architecture or platform systems. For example, the present inventio contemplates a method of allowing a user to determine the status of a subject with respect to the Cortisol -based condition or disorder, the method including:

(a) receiving data from the user via a communications network;

(b) processing the subject data via a algorithm or data processing which provides a disease inde value;

(c) determining the status of the subject in accordance with the results of the disease index value i comparison with predetermined values; and

(d) transferring an indication of the status of the subject to the user via the communicati ons network.

(0164] Conveniently, the method generally further includes:

(a) having the user determine the dat using a remote end station; and

(b) transferring the data from the end station to the base station via the communications network,

[0165] The base station can include first and second processing systems, in which case the method can include:

(a) transferring the data to the first processing system;

(b) transferring the data to the second processing system; and

(c) causing the first processing system to perform the algorithmic function or data processing function to generate the disease index value,

[0166] The method may also include:

(a) transferring the results of the algorithmic function to the first processing system; and

(h) causing the first processing s stem to determine the status of the subject. [0167] In this case, the method also includes at least one of:

(a) transferring the data between the communications network and the first processing system through a first firewall; and

(b) transferring the data between the first and the second processing systems through a second firewall,

[0168] The second processing system may be coupled to a database adapted to store predetermined data and/or an algorithm and/or to perform data processing, the method include:

(a) querying the database to obtain at least selected predetermined data or access to the algorithm from the database; and

(b) comparing the selected predetermined data to the subject data or generating a predicted probability index.

(0169] The second processing system can be coupled to a database, the method including storing the data in the database.

[0170] The present invention also provides a base station for determining the status of a subject with respect to a Cortisol -based disorder or condition, the base station including;

(a) a store method;

(b) processing system, the processing system being adapted to:

(i) receive subject data from the user via a communications network; (ii) performing an algorithmic function including comparing the data to predetermined data;

(iii) determining the status of the subject in accordance with the results of the algorithmic function or data processing function including the comparison; and

(e) output an indication of the status of the subject to the user via the communications network.

[0171] The processing system can be adapted to receive data from a remote end station adapted to determine the data.

|01 2] The processing system may include:

(a) a first processing system adapted to:

(i) recei ve the data; and

(ii) determine the status of the subject in accordance with the results of the algorithmic function or data processing function including com aring the data; and

(b) a second processing system adapted to:

(i) receive the data from the processing system;

(ii) perform the algorithmic function or data processing function including the comparison; and

(iii) transfer the results to the first processing system. [0.173] The base station typically includes:

(a) a first firewall for coupling the first processing system to the communications network; and

(b) a second firewall for coupling the first and the second processing systems.

[0174] The processing system can be coupled to a database, the processing system being adapted to store the data in the database.

[0175] Reference to an "algorithm" or "algorithmic functions" includes the performance of a multivariate analysis function. A range of different architectures and pi at forms may be implemented in addition to those described above. It will be appreciated that any form of architecture suitable for implementing the present invention may be used. However, one beneficial technique is the use of distributed architectures, Reference to an "algorithm" includes a computer program comprising an algorithm. The term "data processing" includes a computer program which may not necessarily involve an algorithmic function.

[01 6] It will also be appreciated that in one example, the end stations can be hand -held devices, such as PDAs, mobile phones, tablets, smart phones, computers, or the like, which are capable of transferring the subject data to the base station via a communications network such as the Internet, and receiving the reports.

[0177] In the above aspects, the term "data" means the levels or concentrations of the biomarkers such as sugar levels, insuli levels, results of a psychological or fatigue questionnaire or other parameters. The "communications network" includes the internet. When a server is used, it is generally a client server or more particularly a simple object application protocol (SOAP).

[0178] A therapeutic protocol is provided comprising the use of Ophi cordyceps extract and the mandibular device in the form of the sleep apnea device. Advantageously, in an example of the presen t in vention :

The medicinal extract is Cs-4 or a fraction, derivative or chemically synthesized or modified form of any one or more com onents.

The slee apnea device is a n o -customized, self-fitted, self-adaptable in^'tra-oral mandibular advancement splint designed to manage snoring and mild sleep apnea. Together, the combination of extract and device delivers all of the following benefits: clinically effective outcomes, affordable cost, ease of use, comfort and easy accessibility without measurement/fitti g by a clinician.

The device is placed in the mouth inside the lips, resting gently over the front upper and lower teeth, just prior to sleep.

This will eradicate or reduce snoring, thereby reducing the extremely common conflict/tension between partners caused by the noise levels of snorers, which interrupt partners' sleep.

It will also eradicate or reduce mild sleep apnea or snoring pattern, thereby producing refreshing sleep, significantly reducing daytime tiredness/fatigue and reducing the risk of developing other serious health conditions.

As a result, it will also increase quality of life, reduce impairment of work school performance and decrease work-related and motor vehicle accidents.

The synergy between the extract and the device levels to one or more of reduced cytosol levels, reduced stress, improved cardiovascular performance, reduced adverse metabolic disease outcomes such as diabetes Type I or Π, amelioration of feelings of depression and repair or amelioration of other neurological conditions such as neurodegeneratio.n and/or enhanced oxygen utilization, and/or saturation.

The user's adherence may also be associated with activated acupuncture points in the mouth l eading to a feeling of physiological comfort.

The protocol improves Sa<¾ levels.

The protocol improves Sp( )> levels.

The protocol improves oxygen saturation, utilization and/or absorption.

The protocol improves mental, cardiovascular and metabolic health.

The protocol improves sexual performance and reduces erectile dysfunction.

The protocol improves oxygen saturation, utilization and/or absorption in organs including the brai n.

The protocol elevates oxygen saturation to greater than 90%. The protocol enables Cs- or like medicament to cross blood brain barrier or to produce an equilibrium gradient shift to remove toxic elements in the brain (e.g. pathogenic form s of amyloid beta.

The protocol improves survival rates in heart failure patients.

The protocol has the ability to facilitate survive longer under hypoxic conditions (e.g. following drowning or asphyxia).

The protocol allows better oxygen saturation, utilization and/or absorption b astronauts in deep space travel and/or by deep sea divers.

The protocol facilitates greater aerobic fitness.

Customer needs/ motivation

[0179] The primary customer needs/motivations are:

As noted above, the primary customer need or motivation is to alleviate the significant social problems caused by Cortisol medicated stress such as resulting from snoring noises, often resulting in the snoring partner having to slee in a different room or the listening partner suffering from sleep deprivation, fatigue, irritability and at times depression.

In addi tion, the snorer him/herself often experiences even greater sleep deprivation, fatigue, cognitive impairment, and associated significant medical problems (as noted above), all of which serve to motivate a customer to seek improved quality of life through treatment.

Once a customer has resolved to seek treatment, customers are often looking for solutions that are: low cost; easily accessible (over the counter rather than custom fitted via dental consultation); highly effective; comfortable to wear (big bulky devices have low adherence rates); easy to use; and portable. - 6ί -

Value of the therapeutic protocol

[0180] The therapeutic protocol addresses some or all of the following problems for consumers:

It eradicates or reduces snoring, thereby reducing the extremely common conflict tension betwee partners caused by the noise levels of snorers, which interrupt partners' sleep.

It eradicates or reduces mild to moderate sleep apnea, thereby producing refreshing sleep, significantly reducing day time tiredness/fatigue and reducing the risk of developing other serious health conditions (e.g. heart attack, stroke, sudden death., depression, memory loss, as noted above).

As a result, it also increases quality of life, reduce impairment of work/school performance and decrease the likelihood of work-related accidents and motor vehicle accidents.

Competitive advantages / Differentiators

[0181] Reduce cost: It is inexpensive to purchase, as the design of device is user-friendly and made from inexpensive materials - namely rubber/silicon or a material which enables slow release of the extract. Also, the device does not need manufacturing by a dental technician or impressions, fitting and adjustments/titrations by a Dentist, which are time- consuming and significantly increase costs. Production of the device by a 3D printer is possible.

[0182] Easy to access: Both the extract and the device can be purchased over the counter at pharmacies and online. It does not need fitting by a specialist, as it can be purchased in two different sizes, unlike other custom-fitted splints.

[0183] Easy to use: The device does not require special fitting, boiling or customized manufacturing and can simply be purchased and worn immediately - unlike customized splints or boil-and-bite devices. This also increases low adherence rates of other devices.

[0184] Portable: The device and the herbal medicine are small, light and extremely portable - including for traveling.

(0185] Comfortable to wear: Com ared to competitors (like custom -fitted splints), the device is less bulky and causes minimal hyper salivation, oral dryness, tooth sensitivity, jaw/muscle pain or jaw joint disorders - all of which reduce adherence rates. This is because it is small, made of flexible rubber/silicon material and is primarily held by the lips and cheek muscles rather than the teeth like other splints (which is the source of the above-mentioned complaints). In an embodiment the combination of the medicinal and device may activate acupuncture sites in the mouth leading to a feeling of comfort and this may also have beneficial endocrinology implications.

[0186] Side effects: The therapeutic protocol avoids adverse side effects or medicinal extracts. The device does not cause tooth movement, permanent protrusion of the lower jaw, permanent changes in the bite, soreness in teeth and gums, and mild-severe temporomandibular disorders (jaw joint disorders). Similarly, the boil and bite process can result in associated side effects, including burning of the oral tissues. The extract is safe and effective.

[0187] Adherence: Given .enhanced comfort and reduced side effects, adherence rates for the combination of extract and device are anticipated to be high.

[0188] Efficacy: The therapeutic protocol is expected to be significantly more effective than other therapeutic protocols and has muiti -beneficial outcomes.

[0189] Use with dentures: The device used in the therapeutic protocol may be easily worn by patients wearing full upper and l u^der dentures or an upper or a lower denture alone, whereas typical mandibular advancement splints are difficult (or even impossible) to fit on dentures.

[0190] In summary, examples of the present invention will provide a therapeutic protocol for reducing Cortisol levels leading the beneficial clinical outcomes such as treating slee apnea, improving metabolic conditions, improving respiratory performance, improving overall cardiovascular health and treating neurological conditions. It enables normalization of oxygen saturation, utilization and/or absorption leading to a range of beneficial chemical outcomes, it has practical uses for astronauts and deep sea divers. It can also be used as a point of care procedure for asphyxia or heart failure patients.

[0191] While vaiious embodiments of the present in vention have been described above, it. should be understood that they have been presented by way of example only, and not by way of limitation. It will be apparent to a person skilled in the relevant art that various changes in form and detail can be made therein without departing from the spirit and scope of the invention. Thus, the present invention should not be limited b any of the above described exemplary embodiments.

EXAMPLE 1

Extract of Ophiocordyceps

[0192] An Ophiocordyceps extract is prepared by standard protocols including fermentation, vibration-extraction such as b sonif!cation followed by a drying process. The extract includes proteins, peptides or essential amino acids, polyamines including 1,3- diamirio propane, cadavenne, spermidine and putrescine, saccharides and sugar derivatives (e.g. D-mannitol), sterols including ergosterol, A³-ergosterol peroxide, β-sitosterol, daucosterol and compasterol, nucleosides including adenine, uracil, uridine, guanosine, thymidine and deoxyuridine, fatty acids and other organic acids, vitamins B ! , B.2, B12, E and and inorganics including , Na, Ca, Mg, Fe, Cu, Mn, Zn, Pi, Se, Al, Si, Ni, Sr, Ti, Cr, Ga, V and Zr. In an embodiment, the extract comprises all or a sufficient number of adenosine, adenine, uracil, uridine, mannitol, β-sttosterol, oligosaccharides, polysaccharides, amino acids, zinc, potassium, manganese, phosphorous, selenium, vitamin Bl , vitamin B2 and vitamin E, In the case of Cs-4 or Cordyceps from Ophiocordyceps sinensis, this can be purchased from Jiangxi GuoYao Company, Jiangxi China as supplied by Pharmanax, toe. In an embodiment, 0,01 to lg/kg body weight is administered. In addition, the extract may be modified by the addition or substitution of alternative or compatible components sourced by chemically synthetic or natural means. Hence, reference to "Cs-4" or "Cordyceps" includes or chemically synthesized or modified forms of any one or more components as well as a fraction or derivative thereof.

[01 3] In an embodiment, the Cs-4 extract is generated using the method published in WO 99/21 61, the contents of which are incorporated by reference in their entirety. This includes a fermentation process.

[ 1 4] For example, the first order seed culture is prepared as follows:

1. Culture medium: in a total of 21.. in water

glucose 40g

sucrose 40g

peptone lOg Bran* 1 OOg

* Boiled 5% w/v Bran for 30 minutes, followed by filtering with gauze, and the filtrate was used in the culture medium.

2, 20 flasks (size; 500m:L), each is filled, with only lOOmL culture medium. The flasks with medium are sterilized, cooled to 25°C, and adjusted to pH 6.4. Each flask is inoculated with the Cs-4 strain from a slant-surface culture.

3. The inoculated cultures are incubated for 4 days, at 25°c, in a shaking incubator at a speed of 90rpm.

[0195] The second order seed culture is prepared as follows:

1. Culture medium; in a total of 2QL in water (formula; the same in proportion as described above for a first order seed culture).

glucose 400g

sucrose 400g

peptone 10Og

Bran* lOOOg

2. 20 flasks (size: 5L), each is filled with 1.0L culture medium. The flasks with medium are sterilized, and each is inoculated with one flask of first-order seeds of Cs-4 strain.

3. The second seed cultures are incubated for 4 days, at 25°C, in a shaking incubator at a speed of 90 rpra. [0196] The first order fermentor fermentation is carried out as follows:

1. Fermentor fermentation medium: a total of 2GGL in water is made in a 300L fermentor.

glucose 2% 4,000g

sucrose 2% 4,000g

powder of soya-bean cake 2% 4,oooa

MgS0₄ 0,075% 15Qg

soya-bean oil 0,01% 20raL

The culture medium is sterilized, cooled to 25 C, and adjusted to pH 6.4. The 2QL second-order seeds for Cs-4 strain is added to the fermentor.

4, Fermentation is carried out for 3 days, at 23°C, with agitation at a speed of 150 rpm and ventilation Ί ,8nvVh.

[0197] This method can be scaled up using multi-ton fermentors.

[0198] In an embodiment, the Cs-4 comprises:

1 D-mannitol 70-80mg/g

2 Polysaccharide 5-30% w/v

3 Protein 15-40% w/v

4 Vitamin A 0.1-lg

5 Vitamin B 1.2 0.005-0. Img/g

6 Zinc 5-30ppm/g

7 Copper I - ] Oppm/g

[0199] Nucleosides are one of the major ingredients in Cs-4. More than 10 nucleosides and their related components, including adenine, adenosine, .cytidrne, cytosine, guanine, guanosine, uracil, uridine, hypoxanthine, inosine, thymine, thymidine, 2'-deoxyuridine, 2'- deoxyadenosine, cordycepm, N -methyladenosine, and 6-hydraxyethyl-adenosine, have been isolated and or identified in C.s-4 (Lu and Li (2011) Chapter 5, Herbal Medicine: Bmmoleci ar and Clinical Aspects, 2?^α Edition. Benzie, IFF and Wachtel-Galors Editors : CRC Press). Adenosine Ai, A2A, A2B, and A3 receptors are distributed in the brain, lung, heart, iiver, and kidney, and are involved i central nervous system (CNS)-mediated events such as sleep and cardiovascular function, I a non-limiting proposal, Cs-4 ma exhibit beneficial effects via adenosine receptors.

EXAMPLE 2

Delivery ofOph cordyceps extract

[0200] The extract can be provided to human subjects as a dietary supplement, pill or tablet or as a nasal inhaler or by other convenient means such as a gel, lotion, cream and/or patch or via nanoparticles. It can also be incorporated as a slow release formulation associated with or separate to the mandibular device.

EXAMPLE 3

Sleep apnea device - 1

|020J ] Figures .1 to 4 show a sleep apnea treatment device which is non-customized, self- adaptable and self-fitting which is used in conjunction with the medicinal extract from Ophiocordyceps or chemically synthesized or modified forms of any one or more components. The device is an intra-oral appliance for the management of snoring and mild sleep apnea and acts in synergy with the medicinal extract to reduce Cortisol levels, manage stress and elevate dissolved blood oxygen levels. Advantageousl , the device is in the form of a stand-alone mouthpiece which is not connected to ventilatio machine which results in a lower expense and also greater adherence by the user. The device advances the mandible of the user during sleep to facilitate breathing of ambient air by the user through the device. [02.02] More specifically, Figures 1 to 4 show a sleep apnea treatment device 10 comprising a mouthpiece 12 including a vestibular locator 14 and an airway conduit 16. The vestibular locator 14 is adapted for positioning in the vestibule of a user interposed between the lips and teeth of the user, the vestibular locator 14 locating supporting the airway conduit 16 in place relative to the user's mouth with the airway conduit 16 extending between the lips of the user. The airway conduit 16 maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit 16, Advantageously, the device 10 does not require connection to a machine to drive pressurised air into the user's mouth - rather, the device 10 is used to facilitate the breathing of ambient air surrounding the user's mouth at ambient pressure.

[0203] With reference to Figure 1 which shows an anterior view of the device 10 and Figure 2 which shows a posterior view of the device 10, the vestibular locator 14 is a flange 18 having an inner surface 20 and an outer surface 22. The airway conduit 16 extends through the flange 18. When in use, the inner surface 20 of the flange 18 may abut against a front surface of teeth of the user and the outer surface. 22 may abut against an inside of the Hps of the user.

[0204] With reference to Figure 2, the device 10 includes a formation 24 for engagement with a lower jaw^J of the user to retain the lower jaw in a forward position. The formation 24 may be adapted to be engaged with the lower j aw of the user to retain the lower jaw in a plurality of forward positions selectable by the user. The plurality of selectable forward positions may range in a degree of advancement of the lower jaw relative to the upper jaw. The formation 24 may include a retaining protrusion or, more preferably, a plurality of retaining protrusions. In one form, the formation 24 may include a plurality of flexible protrusions over which the teeth of the lower jaw may be selectively engaged to allow the mandible to be positioned i two positions, including a first position which is slightly forward (3mm to 4mm from a normal position) and a second position which is further forward (5mm to 9mm from the normal position). [0205 j The device 10 may include an abutment 26 for abutting the upper jaw such that force imparted to the device 10 from the lower jaw is transferred to the upper jaw by the abutment 26. The abutment 26 may be in the form of a flexible wall which is configured to position the front upper teeth of the upper jaw.

[0206] The airway conduit 16 may terminate to minimise protrusion beyond the lips of the user. With reference to Figure 3, the airway conduit 16 may terminate at an opening 28, and the opening 28 may be supported by the face of the user. More specifically, the opening 28 may be formed in a mask portion 30 of the device 10, and the mask portion 30 may abut an external surface of the user's face surrounding the user's mouth. The mask portion 30 may be in the form of a flexible flap which is able to be resiliency snapped forward to facilitate fitment of the device 10 and is able to be snapped rearward into the position shown in Figure 3 such that the mask portion 30 abuts the user's face. Specifically,, as shown in Figure 3 and Figure 4, the mask portion 30 may include side wings 32 which extend either side of the opening 28, the wings 32 curving inwardly toward the face of the user so as to cover the device 10 and to snap r ear ward! y over the mouth, lips and cheeks of the user. The mask portion 30 also may be provided with apertures 34 for ventilation. The flexible flap also holds the upper and lower jaw together through suction on the upper and lower lips and adjacent skin above the upper lip, below the lower lip and bilaterally at the side of the lips, thereby preventing the lower jaw from dropping duri g sleep.

[Q2G7] Also as shown in Figure 3, the device 10 may include a connector 36 betwee the flange 18 and the masked portion 30, and the airway conduit 16 may include a rear portion 38 which extends rear ardly behind the flange 18 such that, in use, the rear portion 38 sits between the upper teeth and the lower teeth of the user. The rear portion 38 may also have mounted thereon a protrusion 40 for locating the front top teeth of the user.

[0208] It is proposed herein that the sleep apnea treatment device 10 may be used with the Ophiovordyeeps extract for increasing oxygen saturation of the user's blood and/or reducing cytosol levels and managing stress levels. The sleep apnea treatment device 10 may be used in a method of treating sleep apnea which includes the steps of wearing the sleep apnea treatment device 10 and breathing ambient air through the sleep apnea treatment device while sleeping while taking, in either order or simultaneously, the herbal/medicinal extract. Advantageously, as the device 10 is not connected to a machine for pumping pressurised air into the user, the user has greater freedom to move during sleeping, for example rolling in bed, which may promote greater adherence of the user to the treatment. Furthermore, as shown in. Figure 3, the external surface of the masked portion 30 may he curved so as to minimise interference with movement of the user during sleeping.

[0^'209| The sleep apnea treatment device 10 ma be produced in a range of sizes which may include a larger (Medium-Large) size and a smaller (Small -Medium) size available from a pharmacy or other retail outlet suc that the user does not need to consult a dentist to obtain the product. In this way, the cost to the user in obtaining the product may be minimised t encourage the user to obtain the product. Accordingly, the method of treating sleep apnea may include the user selecting for themselves from a range of predetermined sizes of sleep apnea treatment devices from a retai l outlet, and the user wearing the selected sleep apnea treatment device.

EXAMPLE 4

Sleep apnea device - II

[0210] With reference to Figures 5 to 17, there are shown other sleep apnea devices 10 for use in either order or simultaneously with the extract from Qphiocordycep or chemically synthesized or modified forms of any one or more components in accordance with examples of the present invention. The devices shown in. Figures 5 to 17 have features similar to the features of the device shown in Fi ures 1 to A, and like features are indicated with like reference numerals. More specifically, the devices 10 shown in Figures 5 to 17 differ most notably in that they are provided with an arcuate bite platform 42 to distribute force to the teeth of the wearer more broadly. In particular, with reference to Figures 5 to 13, the mouthpiece 12 has an arcuate bile platform 42 which extends either side of the airway conduit 16. m particular, the arcuate bite platform 42 extends as a shelf from the inner surface 20 of the vestibular locator 14, The arcuate bite platform 42 may be formed of a solid ledge at either side of the airway conduit 16 and may be integrally formed as a unitary structure with the remainder of the mouthpiece 1.2. The arcuate bite platform 42 may be arranged so as to support j aws of the wearer apart by rear teeth of the wearer so as to prevent the jaws from closing the airway conduit 16. In one form, the arcuate bite platform 42 may be configured to contact, al l teeth of the wearer .

[0211] Advantageously, the arcuate bite platform 42 may serve to prevent unwanted teeth movement. The arcuate bite platform 42 may be in the form of a simple flat shelf which is not specifically precision fitted to the teeth of the wearer - the mouthpiece 12 may be held in pl ace by the gum s of the wearer.

[0212] The mouthpiece 12 may be formed as a unitary part made from silicone. The silicone may be food grade silicone or medical grade silicone. Alternatively, TPE (Thermoplastic Elastomer) material may be used. In examples of the invention, the material may have a shore hardness of between 20 and 40, and possibly betwee 25 and 35, The shore hardness is to be chosen such that the material is not too hard and not too soft. If the materia] is too hard, the mouthpiece may not fit around the gum s, may cut the gums/frenum, may hurt the teeth, and may not allow the teeth to sink elasticaily into the material of the bite platform 4:2. On the other hand, if the material is too soft, the teeth may make an impression in the mouthpiece 12 and/or the wearer may bite off part of the mouthpiece 12. It is preferable for the mouthpiece 12 to be comfortable without allowing the material to be bitten through. To protect/accommodate the frenum, the mask portion 30 may also be provided with a central indentation in an upper edge thereof, as shown in the drawings:,

[0213] As can be seen in Figure 6, the mouthpiece 12 protrudes sufficiently forward from the vestibular locator 14 to support the lips of the wearer as shown in Figure 1 . The front protrusion may tefminate in a flange 44 to assist in retaining the mask portion 30 in the form of a flexibl e fl ap shown i n Figures 34, 15 and 17.

[0214] Figures 18 to 19 show further views of the example shown in Figures 5 and 6, and the same reference numerals are used to identify features of the device 10. More specifically. Figure 18 shows a top view of the device 10, Figure 1 shows a side view of the device 10 and Figure 20 shows a rear view of the device 10.

EXAMPLE 5

Procedure

[0215] A protocol is developed where human subjects are provided either a placebo or Cs-4 or a derivative or fraction thereof together with a sleep apnea device comprising a sleep apnea treatment device intended for breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway condui in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing the ambient air through the airway conduit and then subjected to sleeping pattern analysis, Cortisol levels may also be tested such as in a saliva test. Aerobic capacity is assessed including the presence of an sleeping disorders or fatigue. Assessment is also made of throat surface epithelium. The protocol is similar to that described b Chen etaL (2010) supra. Sugar levels may also be determined as well as insulin levels. A questionnaire may also be used to determine fatigue levels or stress levels or levels of depression. Oxygen saturation, utilization and/or absorption in the body including the blood stream or an organ and/or cardiovascular system may also be monitored.

EXAMPLE 6

Outcomes

[0216] Human subjects who take Cs-4 in combination with the sleep apnea treatment device are expected to exhibit reduced sleeping disorders and hence suffer from less fatigue. Sugar levels are also expected to be controlled. Enhanced aerobic fitness and reduced Cortisol levels are also expected together with enhanced blood oxygen saturation and/or absorption.

EXAMPLE 7

Measuremen t of oxygen

[0217] Oxygen saturation is measured by any number of means including using a pulse oximeter (e.g. KonicaMinolta Sensing Inc.). Levels of oxygen saturation of peripheral oxygen (or percutaneous oxygen saturation) [Sp0₂] range from 96 to 99% in healthy individuals. The percentage of oxygen saturation is calculated by the equation:

% Oxygen saturation ~ [HbOj x 100

[Hb0₂] + [Mb ]

Hemoglobin (Hb) is present in deoxygenated and oxygenated forms. Oxygenated Hb comprise 4 molecules of oxygen (H Oj). Oxygen saturation is assessed by SaOi or SpO¾ wherein SaOj is oxygen saturated in arterial blood and S Qz is percutaneous saturation detected by the pulse oximeter.

[Q2I&I A pulse oximeter is useful to measure SpO? during a sleep period to determine the frequency of hypoxemia events (oxygen desaturation index) as well as the duration of desaturation. Outcomes are expected to confirm that individuals on the combination of Cs- 4 or a fraction, derivative or chemically synthesized or modified forms thereof and the mandibular device will exhibit an S 0 above 90% and approaching 96 to 99% with a reduced number of hypoxemic events. A 90% oxygen saturation corresponds to a Pa0₂ of 60mm Hg. Oxygen saturation levels lower than 88% generally corresponds to a PaOi of 55mm Hg (Chaudhary etal. (1998) supra).

EXAMPLE 8

Oxygen utilization

(0219] Under conditions of stimulated oxygen consumption, subcutaneous injections have been provided to hypoxic mice. This is described in Lou et at, (1987) Current Genet 7:473-480; Zhu etal, (1998) supra; Zhu et at. (1998) J. Atiern Complement Med 4(4)429- 457. It is proposed herein that Cs-4 and the mandibular device in combination will significantly reduce oxygen consumption from between 40-50% within a 10 minute period and prolong survival of brain cells which would otherwise die due to the hypoxia. The combination of Cs-4 and mandibular device means greater tolerance to hypoxia-induced acidosis and represents a point of care option in situations of drowning or asphyxia. It also represents a useful tool for prolonged, deep space exploration by astronauts and/or for use by deep sea divers.

EXAMPLE 9

Comparison of mandibular device and CPAP machine

[0220] A comparative trial is conducted on two groups of sleep apnea patients: Group (1): Cs-4 and the mandibular device of the present invention; Group (ii): a CPAP (continuous positive airway pressure) machine alone. It is anticipated that Group (i) sleep apnea patients will exhibit higher oxygen saturation, utilization and/or absorption levels than the Group (ii). Measurement of an apnea hypopnea index (AHI) ma be used as a criteria wherein:

Healthy AHI: no to minimal sleep apnea or hypoxic events.

Mild AHI: cessation of breathing for at least 10 seconds for from 5 to 15 times per hour.

Moderate AHI: cessation of breathing for at least 10 seconds for from 15 to 30 times per hour.

Severe AHI: cessation of breathing for from 10 seconds to over 60 seconds. In addition or al tentatively, SaQz or SpG₂ is determined.

EXAMPLE 10

Effects of combination therapy

[0221] Use of the extract and mandibular device is expected to result in an elevation of oxygen saturation levels to 90% or greater (i.e. from 90 to 98%). Oxyge utilization may also be elevated. Hence, the combined effects of extract or chemically synthesized or modified forms of any one or more components and device leads to improved sleep patterns and other health benefits. EXAMPLE Π

Measurement of brain oxygen

[0222] Cerebral oxygenation can be measured using near-infrared spectroscopy. The details are as described by Hausser-Haulu et l. (2000) Neurophysioi Clin 13-118. Patients undergoing combination therapy are expected to show elevated cerebral oxygenation or at least normalization, o oxygen levels in apneie patients. This will also have beneficial neurological outcomes.

EXAMPLE 12

Combinatio therapy with additional agents

[0223] The combination protocol of Cs-4 and mandibular device is complemented with Rhodiola, Results are expected to show elevated erythropoietin (EPO) sensitivity, decreased Cortisol levels and enhanced cardiovascular fitness.

[0224] Those skilled in the art will appreciate that aspects of aspects described herein are susceptible to variations and modifications other than those specifically described. It is to be understood that these aspects include all such variations and modifications. These aspects also include all of the steps, features, compositions and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations of any two or more of the steps or features.

BIBLIOGRAPHY

Bao (1995) J Admin, Trad. Chinese Med, 5(Suppl6) &r et al. (20 ! ) J. Clin. Sleep Med. 10(J 1 ): l 199- \ 204 Chaudhary et ai. (1998) CHEST 1. 13:719-722 Chen et ai. (2 1.0) J A hem Complement Med 16(5) ':585-590 Greco et al. (1995) Pharmacol Rev. ^7:33 1-385 Bausser-Hauki et al. (2000) Neurophysiol Clin 30(2): 113-1 18 Lau et al. (2013) J Sleep Disor 2: 1 -6 Lou et i. ( 1987) Current Genet 7:473-480

Lu and Li (201 1 ) Chapter 5. Herbal Medicine: Biomolecutar and Clinical Aspects. 2' Edition. Benzie, IFF and Wachtel-Ga!ors Editors: CRC Press

Richer (1987) Pestic Sci /.9:309-315

Wagner et al Veterinary Immunology and Immimopathology 105(1-2) : 1 -14, 2005 Zhu et al. (1998) J. Altern Complement Med 4(3):2S9-303 Zhu e al. (1998) 1 Altern Complement Med 4(4)429-451

Claims

CLAIMS:

1 , A method for treating human subject with a cortisol-based disorder or condition or with the potential for -developing a cortisol-based disorder or condition, said method comprising the administration to the subject in either order or simultaneously an effective amount of an extract or a fraction, derivative or chemically synthesized or modified form of any one or more components of a species Qphiocord ceps or a genetically modified or phenotypically adapted strain thereof together with insertion into the subject's mouth of a sleep apnea treatment device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communicatio of the mo th vestibule with ambient air to facilitate the user breathing said ambient air through the airway conduit.

2, A method for treating human subject with a cortisol-based disorder or conditio or with the potential for developing a cortisol-based disorder or condition, said method comprising the■administration to the subject in either order or simultaneously an effective amount of an extract or a fraction, derivative or chemicall synthesized or modified form of any one or more components of a species Qphwcorcfyceps or a genetically modified or phenotypicall adapted strain thereof together with insertion into the subject's mouth of a sleep apnea treatment device for use in breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereb the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing said ambient air through the airway conduit.

3, The method of Claim 1 or 2 wherein the species of Ophiocordyceps is selected from the listing consisting of Opchiocordyceps sinensis, Ophiocordyceps cicul ris, Ophiocordyceps agiiotidis, Ophiocordyceps aimctos,. Ophiocordycep am omm, Ophiocordycep m zonica var. neoammanica, Ophiocordyceps aphodii, Ophiocordyceps apperidiculata, Ophiocordyceps arachneicola₁ Ophiocordyceps arbuscula, Ophiocordyceps mmeniac , Ophiocordyceps asyuemis, Ophiocordycep aur nti , Ophiocordyceps australis, Ophiocordyceps hamesii, Ophiocordyceps bicephala, Ophiocordyceps brimmipitnetaia, Ophiocordyceps Mspora, Ophiocordyceps Mattae, Ophiocordyceps caloceroides, Ophiocordyceps cantharelloides, Ophiocordyceps corabidicola, Ophiocordyceps cic dicola^ Ophiocordyceps clavata, Ophiocordyceps ciavulata, Ophiocordyceps coccidiicola, Ophiocordyceps coccigena, Ophiocordyceps cocMidiicoia, Ophiocordyceps communis, Ophiocordyceps corallomyces, Ophiocordyceps crassispora, Ophiocordyceps crinalis, Ophiocordyceps cuhoidea, Ophiocordyceps cucumispora, Ophiocordyceps cucumispora var, doUchoderi, Ophiocordyceps curculionum, Ophiocordyceps cyihukostromata, Ophiocordyceps d yiemis, Ophiocordyceps derm pterigena, Ophiocordyceps dipterigena, Ophiocordyceps discoideicapricti , Ophiocordycep ditmarii, Ophiocordyceps dovei, Ophiocordyceps e!citeridicola, Ophiocordyceps elongata, Ophiocordyceps efongatiperifheci ta, Ophiocordyceps elo gaiisiro ia, Ophiocordyceps emeietisis, Ophiocordyceps engiericma, Ophiocordyceps e omorrhiza, Ophiocordyceps evdogeorgiae, Ophiocordyceps f iccti , Ophiocordyceps, faicatoides, Ophiocordyceps. fascicid tistrofnata, Ophiocordyceps fermgmosct, Ophiocordyceps filifo , Ophiocordyceps formicarum, Ophiocordyceps

Ophiocordyceps gamuensis, Ophiocordyceps geniculata, Ophiocordycep gentitis, Ophiocordyceps gkiziovii, Ophiocordyceps goniophor , Ophiocordyceps gr cilioides, Ophiocordyceps gracilis, Ophiocordyceps gryllotalpae, Ophiocordyceps h lahik mis, Ophiocordycep heierapoda, Ophiocordyceps hirsute lia , Ophiocordyceps hiugens s, Ophiocordyceps uheriana, Ophiocordyceps humhertii, Ophiocordyceps insignis, Ophiocordyceps irangiensis, Ophiocordyceps japonemis, Ophiocordyceps flangxiensis,. Ophiocordyceps jinggangshanemis, Ophiocordyceps hwigdingemis, Ophiocordyceps kniphofioides, Ophiocordyceps kniphofioides var. dolichoderi, Ophiocordyceps kmphofioides var. mo tcidis, Ophiocordyceps kniphofioides var. pomrma m, Ophiocordyceps - SI - komngshergeri^ Ophiocordyceps komtaana, Ophiocordyceps hchnopoda, Ophiocordyceps ktojimshahensis, Ophiocordyceps iarv rum, Ophiocordyceps larvicoia, Ophiocordyceps lloydii, Ophiocordyceps lloydii var, binata, OpPriocordyceps iongissima, Ophiocordyceps luiea, Ophiocordyceps macularis, Ophiocordyceps mehkmthae, Ophiocordyceps melolonthae var. rickii, Ophiocordyceps michfganemis, Ophiocordyceps minutissima, Ophiocordyeeps monticola, Ophiocordyceps mrciemis _s Ophiocordyceps multiaxialis, Ophiocordyceps myrmecophila , Ophiocordyceps movolkkma, Ophiocordyceps mpalemis_x Ophiocorcfyceps nigra, Ophiocordyceps mgre a_t Ophiocordyceps nigripes, Ophiocordyceps nutans _t Ophiocordyceps obt sa, Ophiocordyceps ociospom, Ophiocordyceps odonatae, Ophiocordyceps osuzumontana, Ophiocordyceps ow ri sis, Ophiocordyceps owariensis f. viridescens, Ophiocordyceps oxyceph i , Ophiocordyceps pal dos , Ophiocordyceps paraeuboidea, Ophiocordyceps pmtatomae, Ophiocordyceps peichii, Ophiocordyceps protiferam, Ophiocordycep prolific , Ophiocordyceps pruinosa , Ophiocordyeeps pseudolloydii , Ophiocordyceps pseudolongissima, Ophiocordyceps pidvinata, Ophiocordyceps ptirpureostramatcL Ophiocordyeeps^' pwpureostromata f. recurvaia, Ophiocordycep ravemlii, Ophiocordyeeps rhizoidea, Ophiocordyceps ridieyi, Ophiocordycep robertsii, Ophiocordyeeps ruhriptmetata, Ophiocordyceps ruhiginosiperiiheciafa, Ophiocordyceps ryogamiensis, Ophiocordyceps salebrosa, Ophiocordyeeps seattiana, Ophiocordyceps selkirkii, Ophiocordyceps sichu emis, Ophiocordyceps smithii, Ophiocordyceps sobolifefa, Ophiocordyceps sphecoeephala, Ophiocordyceps stipiUala, Ophiocordyceps sfylophora, Ophiocordyceps s hflavida, Ophiocordyceps subtmiiateralis, Ophiocordycep superficialis, Ophiocordyceps superficialis f. Crustacea, Ophiocordyceps takaoensis, Ophiocorcfyceps tayiorii, Ophiocordyceps thyrsoides, OpMocordyceps tricentri, Ophiocordyceps truncate, Ophiocordyceps uchiyamae, Ophiocordycep imi lateralis, Ophiocordyceps t ikUeraii var. etavata, Ophiocordyceps variabilis, Ophiocordyeeps voeltzk -ti, Ophiocordyceps volkiana, Ophiocordyceps wuyishcmensis, Ophiocordyceps yakusimemis and Ophiocordyceps zhangjkijiensis or a genetically modified or phenotypically adapted strain thereof.

4. The method of Claim 3 wherein the extract is from Ophiocordycep sinensis or a genetically modified or phenofyptcally adapted strain thereof.

5. The method of Claim 3 or 4 wherein the extract comprises all or a sufficient number of adenosine, adenine, uracil, uridine, mannitol, β-sitosterol, oligosaccharides, polysaccharides, amino acids, zinc, potassium, manganese, phosphorous, selenium, vitami Bl, vitamin B2 and vitamin E or chemically synthesized or modified fonn of any one or more components.

6. The method of Claim 4 wherein the extract is Cs-4 or Cordyeeps or a fraction, derivative or chemically synthesized or modified form of any one or more components.

7. The method of Claim 6 wherein the extract is Cs-4 or Cordyeeps,

8. The method of Claim 1 or 2, wherein the vestibular locator is a flange having an inner surface and an outer surface.

9. The method of Claim 8, wherein the airway conduit extends through the flange.

10. The method of Claim 1 or 2 or 8 or 9, wherein the device includes a formation for engagement with a lower jaw of the user to retain the lower jaw in a forward position.

1 1. The method of Claim 10, wherein the formation is adapted to be engaged with the lower jaw of the user to retain the lower jaw in a plurality of forward positions selectable by the user.

12. The method of Claim 1.1, wherein the plurality of selectable forward positions range in a degree of advancement of the lower j aw relative to the upper j aw.

13. The method of any one of Claims 10 to 12. wherein the formation includes retaining protrusion.

14. The method of Claim 13, wherein the formation includes a plurality of retaining protrusions,

15. The method of Claim 13 or 14, wherein the device includes an abutment for abutting the upper jaw such that force from retaining the lower jaw is transferred to the upper jaw.

16. The method of Claims 1, 2 or 8 to 15, wherein the airway conduit terminates to minimise protrusion beyond the Hps of the user.

17. The method of Claim 16, wherein the airway conduit terminates at an opening, a d the opening is supported by the face of the user.

18. The method of Claim 17, wherein the opening is formed in a mask portion of the device, and the mask portion abuts an external surface of the user's face surrounding the User's mouth.

19. The method of Claim 1 wherein the device is in multi -component form comprising a mouth component and a mask component in the form of a flexible flap.

20. The method of Claim 1 or 2, wherein the Cortisol -based disorder or condi tion i s stress-related.

21. The method of Claim 1 or 2, wherein the Cortisol -based disorder or condition is a sleeping disorder such as sleep apnea or snoring.

22. The method of Cl im 1 or 2. wherein the Cortisol -based di sorder or condition is a metabolic disease such as Type 1 or 2 diabetes.

23. The method of Clai m 1 or 2, wherein the Cortisol -based disorder or condition i s cardiovascular disease including heart failure.

24. The method of Claim 1 or 2, wherein the Cortisol -based disorder or condition is a neurological condition such as depression, epilepsy or neurodegeneration.

25. The method of Claim 1 or 2 wherein the subject exhibits normalization or enhancement of oxygen saturation, utilization and/or absorption.

26. A system for treating sleep apnea or snoring in a subject comprising use of an extract or a fraction, derivate of Ophiocordyceps or a geneticall modified or phenotypically adapted strain thereof or chemically synthesized or modified form of any one or more components and a sleep apnea device.

27. The system o Claim 24 wherein the subject's Cortisol levels are reduced and/or there is an increase in oxygen saturation, utilizatio and/or absorption in the blood and/or an organ.

28. The system of Claim 27 wherein the organ is the brain,

29. A method of treating sleep apnea comprising the steps of wearing a sleep apnea treatment device and breathing ambient air through the sleep apnea treatment device while sleeping and, in either order, taking an extract or a fraction, derivative or chemically synthesized or modified form of any one or more components of Ophiocordyceps or a genetically modified or phenotypically adapted strain thereof.

30. A method of controlling snoring comprising the steps of wearing a sleep apnea treatment device and breathing ambient air through the sleep apnea treatment device while sleeping and, in either order, taking an extract or a fraction, derivative or chemically synthesized or modified forms of any one or more components of Ophiocordyceps or a genetically modified or phenotypically adapted strain thereof.

31. The system of Claim 26 or 27 or 28 or method of Claim 29 wherein the extract of Ophiocortfyceps is Cs-4 or a fraction, derivative or chemically synthesized or modified form of an one or more components,

32. The method of any one of Claims 1 to 24 or 29 or system of Claim 31 integrated into an electronic health (eHealth) platform.

33. The method of Claim I or 2, wherein from O.Olg to I g'kg body weight of Ophiocorcfyceps extract or fraction, derivative, or chemically synthesized or modified form of any one or more components is administered.

34. The method of Claim I or 2 wherei administration is b intra-nasal inhalation, dietar supplement, tablet, pill, cream, lotion, gel, patch and/or a slow release component of the sleep apnea treatment device.

35. Use of an extract or fraction, derivative or chemically synthesized or modified form of any one or more components of a species Ophiocorcfyceps or geneticall modifi ed or phenotypically adapted strain thereof in the manufacture of a medicament for the treatment of a sleeping disorder such as sleep apnea or snoring in a human subject togethe with the use of a sleep apnea treatment device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the Hps and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing said ambient air through the airway conduit.

36. Use of an extract or fraction, derivative or chemically synthesized or modified form of any one or more components of a species Ophiocordyceps or a genetically modified or phenotypically adapted form thereof in the manufacture of a medicament for the treatment of a sleeping disorder such as sleep apnea or snoring in a human subject together with the use of a sleep apnea treatment device intended for breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the Vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mout vestibule with ambient air to facilitate the user breathing said ambient air through the airway conduit,

37. Use of an extract or fraction, derivative or chemically synthesized or modified form of any one or more components of Ophiocordyceps sinensis or a genetically modified or phenotypically adapted form thereof in the manufacture of a medicament for the treatment of a sleeping disorder such as sleep apnea or snoring in human subject together with use of a sleep apnea treatment device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supportmg the airwa conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing said ambient air through the airway conduit.

38. Use of an extract or fraction, deri vative or chemically synthesized or modified form of any one or more components of Ophiocordyceps sinensis or a genetically modified or phenotypically adapted form thereof in the manufacture of a medicament for the treatment of a sleeping disorder such as sleep apnea or snoring in a human subject together with use of a sleep apnea, treatment device intended for breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning i the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with ambient air to facilitate the user breathing said ambient air through the airway conduit.

39. Use of Cs-4 or Cordyceps or fraction, derivative or chemically synthesized or modified form of any one or more components in the manufacture of a medicament for the treatment of a sleeping disorder such as sleep apnea or snoring in a human subj ect together with use of a sleep apnea treatment device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the Hps and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communicati on of the mouth vestibule with ambient air to facilitate the user breathing said ambient air through the airway conduit.

40. Use of Cs-4 or fraction, derivative or chemically synthesized or modified form of any one or more components in the manufacture of a medicament for the treatment of a sleeping disorder such as slee apnea or snoring in a human subject together with use of a sleep apnea treatment device intended for breathing ambient air, the device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular locator supporting the airway conduit in place relative to the user's mouth with the airway conduit extending between the lips of the user whereby the airway conduit maintains fluid communication of the mouth vestibule with, ambient air to facilitate the user breathing said ambient air through the airway conduit.

41. A method of normalizing or enhancing oxygen saturation, utilization and/or absorption in a human subject, said method comprising the administration to the subject in either order or simultaneousl an effective amount of an extract or a fraction, derivative or chemically synthesized or modified form of any one or more components of a species Ophiocordyceps or a genetically modified or phenotypically adapted strain thereof together with insertion into the subject's mouth of a sleep apnea treatment device comprising a mouthpiece including a vestibular locator and an airway conduit, the vestibular locator being adapted for positioning in the mouth vestibule of a user interposed between the lips and teeth of the user, the vestibular- locator supporting the airway conduit in place relative to the user's mouth with the ai rway conduit extendi ng between the lips of the user whereby the airway conduit maintains fluid communication, of the mouth vestibule with, ambient air to facilitate the user breathing said ambient air through the airway conduit.

42. The method of Claim 41 wherei the method results in improved mental health, aerobic fitness and/or an amelioration of sexual dysfunction.

43. The method of Claim 43 wherein the method facilitates protection of the brain from hypoxic conditions,

44. The method of Claim 41 for us by astronauts during prolong deep space flying or by deep sea divers.