U.S. patent application number 16/992631 was filed with the patent office on 2020-12-03 for compositions of psilocybin and analogs.
The applicant listed for this patent is Paul Edward STAMETS. Invention is credited to Paul Edward STAMETS.
Application Number | 20200375967 16/992631 |
Document ID | / |
Family ID | 1000005016473 |
Filed Date | 2020-12-03 |
United States Patent
Application |
20200375967 |
Kind Code |
A1 |
STAMETS; Paul Edward |
December 3, 2020 |
COMPOSITIONS OF PSILOCYBIN AND ANALOGS
Abstract
Methods and compositions are disclosed for enhancing
neurogenesis, resolving neuropathy and improving neurological
health and functioning using fungal extracts and their active
ingredients, including species of mushrooms and mycelia containing
psilocybin and psilocin, combined with erinacines and hericenones
or fungal extracts containing those active ingredients, with the
addition of nicotinic acid. The compositions may optionally be
combined with nervine plants.
Inventors: |
STAMETS; Paul Edward;
(Shelton, WA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
STAMETS; Paul Edward |
Shelton |
WA |
US |
|
|
Family ID: |
1000005016473 |
Appl. No.: |
16/992631 |
Filed: |
August 13, 2020 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
16211281 |
Dec 6, 2018 |
|
|
|
16992631 |
|
|
|
|
15494503 |
Apr 23, 2017 |
|
|
|
16211281 |
|
|
|
|
62365982 |
Jul 23, 2016 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 31/455 20130101;
A61K 31/4045 20130101; A61K 31/675 20130101; A61K 36/07
20130101 |
International
Class: |
A61K 31/455 20060101
A61K031/455; A61K 31/4045 20060101 A61K031/4045; A61K 31/675
20060101 A61K031/675; A61K 36/07 20060101 A61K036/07 |
Claims
1. A composition comprising: psilocybin, psilocin, baeocystin,
norbaeocystin, salts thereof, or combinations thereof; an
erinacine, a hericenone, or a combination thereof.
2. The composition of claim 1, further comprising: niacin.
3. The composition of claim 1, further comprising one or more
pharmaceutically acceptable excipients comprising selected from
buffering agents, antimicrobial preservatives, antioxidants,
suspension agents, a tablet or capsule diluent, or a tablet
disintegrant.
4. The composition of claim 1, further comprising one or more
Bacopa species (Bacopa monnien), Gotu kola (Centella asiatica),
Gingko (Gingko biloba), Ginger (Zingiber officinale), Holy Basil
(Ocimum sanctum), Hu Zhang (Polygonum cuspidatum), Oregano
(Origanum vulgare, Origanum onites), Rosemary (Rosmarinus
officinalis, Rosmarinus eriocalyx, Rosmarinus species), Turmeric
(Curcuma longa), Green Tea (Camellia sinensis), lavender (Lavandula
spica and Lavandula species), skullcap (Scutellaria lateriflora),
oat straw (Avena sativa and Avena byzantine), Diviner's Sage
(Salvia divinorum), ayahuasca (Banisteriopsis caapi and Psychotria
species), Tabernanthe iboga, Voacanga africana, Tabernaemontana
undulate, peyote (Lophophora williamsii), morning glory (Ipomoea
tricolor, Argyreia nervosa), Cannabis sativa, Cannabis indica or
Cannabis ruderalis, extracts thereof, or combinations thereof.
5. The composition of claim 1, wherein the composition further
comprises: mycelia, fruitbodies, or extracts thereof of Antrodia,
Beauveria, Copelandia, Cordyceps, Ganoderma, Grifola, Hericium,
Inonotus, Isaria, Panaeolus, Phellinus, or combinations
thereof.
6. A method for treating or improving neurological functioning or
mental health in a subject in need thereof comprising
administration of an effective amount of the composition of claim 1
to the subject in need thereof.
7. The method of claim 6, where the neurological or mental health
conditions comprise depression, memory loss, dementia, cognitive
dysfunction, hearing loss, vision loss, neurologic pain, or
combinations thereof.
8. A composition comprising: psilocybin, psilocin, baeocystin,
norbaeocystin, salts thereof, or combinations thereof; an
erinacine, a hericenone, or a combination thereof; and niacin.
9. The composition of claim 8, further comprising one or more
Bacopa species (Bacopa monnien), Gotu kola (Centella asiatica),
Gingko (Gingko biloba), Ginger (Zingiber officinale), Holy Basil
(Ocimum sanctum), Hu Zhang (Polygonum cuspidatum), Oregano
(Origanum vulgare, Origanum onites), Rosemary (Rosmarinus
officinalis, Rosmarinus eriocalyx, Rosmarinus species), Turmeric
(Curcuma longa), Green Tea (Camellia sinensis), lavender (Lavandula
spica and Lavandula species), skullcap (Scutellaria lateriflora),
oat straw (Avena sativa and Avena byzantine), Diviner's Sage
(Salvia divinorum), ayahuasca (Banisteriopsis caapi and Psychotria
species), Tabernanthe iboga, Voacanga africana, Tabernaemontana
undulate, peyote (Lophophora williamsii), morning glory (Ipomoea
tricolor, Argyreia nervosa), Cannabis sativa, Cannabis indica or
Cannabis ruderalis, extracts thereof, or combinations thereof.
10. A method for treating or improving neurological functioning or
mental health in a subject in need thereof comprising
administration of an effective amount of the composition of claim 8
to the subject in need thereof.
11. The method of claim 10, wherein the neurological or mental
health conditions comprise depression, memory loss, dementia,
cognitive dysfunction, hearing loss, vision loss, neurologic pain,
or combinations thereof.
12. A composition comprising: 4-phospho-N,N-dimethyltryptamine
(4-PO-DMT; psilocybin), 4-hydroxy-N,N-dimethyltryptamine (4-HO-DMT;
psilocin), 4-phospho-N-methyl tryptamine (baeocystin),
4-phospho-tryptamine (4-PO-T, norbaeocystin), 1-methylpsilocin,
N,N-dimethyltryptamine (DMT), 5-hydroxytryptamine (5-HT;
serotonin), 5-hydroxytryptophan (5-HTP),
4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT),
4-acetoxy-N-methyl-N-ethyltryptamine (4-AcO-MET),
4-acetoxy-N,N-diethyltryptamine (4-AcO-DET),
4-acetoxy-N-methyl-N-propyltryptamine (4-AcO-M PT),
4-acetoxy-N-methyl-N-isopropyltryptamine (4-AcO-MIPT),
4-acetoxy-N,N-dipropyltryptamine (4-AcO-DPT),
4-acetoxy-N,N-diisopropyltryptamine (4-AcO-DI PT),
4-hydroxy-N-methyl-N-ethyltryptamine (4-OH-MET),
4-hydroxy-N-methyl-N-propyltryptamine (4-OH-MPT),
4-hydroxy-N-methyl-N-isopropyltryptamine (4-OH-MI PT),
4-hydroxy-N,N-diethyltryptamine (4-OH-DET),
4-hydroxy-N,N-dipropyltryptamine (4-OH-DPT),
4-hydroxy-N,N-diisopropyltryptamine (4-OH-DI PT),
4-hydroxy-N,N-diallyltryptamine (4-OH-DALT), N-dimethyltryptamine
(DMT), N-methyl-N-ethyltryptamine (MET),
N-methyl-N-propyltryptamine (MPT), N,N-diethyltryptamine (DET),
N,N-dipropyltryptamine (DPT), N,N-isopropyltryptamine (DIPT),
N-methyl-N-isopropyltryptamine (MIPT), .alpha.-methyltryptamine
(AMT), N-ethyl-N-isopropyltryptamine (EIPT),
N-methyl-N-butyl-tryptamine (MBT), N,N-dimethyl-5-hydroxytryptamine
(5-OH-DMT), 5-methoxy-.alpha.-methyltryptamine (5-MeO-.alpha.MT),
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; bufotenin),
5-methoxy-N,N-diethyltryptamine (5-MeO-DET),
5-methoxy-N,N-dipropyltryptamine (5-MeO-DPT),
5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT),
5-methoxy-N-ethyl-N-isopropyltryptamine (5-MeO-EIPT),
2,.alpha.-dimethyltryptamine (2,.alpha.-DMT),
.alpha.,N-dimethyltryptamine (.alpha.,N-DMT),
.alpha.-ethyltryptamine (.alpha.-ET),
2-methyl-N,N-dimethyltryptamine (2-Me-DMT),
2-methyl-N,N-diethyltryptamine (2-Me-DET), 12-methoxyibogamine
(ibogaine), salts thereof, or combinations thereof; and an
erinacine, a hericenone, or a combination thereof.
13. The composition of claim 12, further comprising: niacin.
14. The composition of claim 12, comprising one or more Bacopa
species (Bacopa monnien), Gotu kola (Centella asiatica), Gingko
(Gingko biloba), Ginger (Zingiber officinale), Holy Basil (Ocimum
sanctum), Hu Zhang (Polygonum cuspidatum), Oregano (Origanum
vulgare, Origanum onites), Rosemary (Rosmarinus officinalis,
Rosmarinus eriocalyx, Rosmarinus species), Turmeric (Curcuma
longa), Green Tea (Camellia sinensis), lavender (Lavandula spica
and Lavandula species), skullcap (Scutellaria lateriflora), oat
straw (Avena sativa and Avena byzantine), Diviner's Sage (Salvia
divinorum), ayahuasca (Banisteriopsis caapi and Psychotria
species), Tabernanthe iboga, Voacanga africana, Tabernaemontana
undulate, peyote (Lophophora williamsii), morning glory (Ipomoea
tricolor, Argyreia nervosa), Cannabis sativa, Cannabis indica or
Cannabis ruderalis, extracts thereof, or combinations thereof.
15. A method for treating or improving neurological functioning or
mental health in a subject in need thereof comprising
administration of an effective amount of the composition of claim
12 to the subject in need thereof.
16. The method of claim 15 wherein the neurological or mental
health conditions comprise depression, memory loss, dementia,
cognitive dysfunction, hearing loss, vision loss, neurologic pain,
or combinations thereof.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 16/211,281, filed on Dec. 6, 2018, which is a
continuation of U.S. patent application Ser. No. 15/494,503, filed
Apr. 23, 2017, which claims priority to U.S. Provisional Patent
Application No. 62/365,982, filed Jul. 23, 2016, each of which is
hereby incorporated by reference in its entirety.
BACKGROUND
[0002] The present invention relates to neuroregenerative
compositions based upon constituents isolated from or contained
within mushroom fruitbodies or mycelia, or the corresponding
synthetic molecules, combined with niacin.
BRIEF SUMMARY
[0003] The current invention describes novel contributions to the
field of medicinal mushroom research, particularly discoveries
pertaining to neuroregeneration.
[0004] The tragedy of aging is the loss of accumulated knowledge
due to neuropathy, especially related to dementia, Alzheimer's, and
other neurological disorders. The cause of these disorders is a
matter of dispute, ranging from free radical damage to exposure to
toxins to inability of neurons to regenerate in the numbers and
quality necessary for healthy mental functioning. In addressing a
disease complex with multifactoral causes, offering a combination
of elements that can synergistically repair and improve
neurological function is an important step in helping cognitive and
motor skills, in particular, as humans age and/or when exposed to
neurotoxins, stress or head trauma. Not only are benefits realized
from multiple active principle ingredients activating neurogenesis,
but the compositions and methods below may additionally help
mitigate and/or reverse ocular and cochlear nerve degeneration.
[0005] A composition including psilocybin
(4-phosphoryloxy-N,N-dimethyltryptamine) or psilocin
(4-hydroxy-N,N-dimethyltryptamine) in pure form or extracts from
Psilocybe and psilocybin containing mushrooms combined with
erinacines or hericenones, or extracts from Hericium mushroom
species, and niacin (nicotinic acid or 3-pyridinecarboxylic acid,
also known as vitamin B3), uniquely aids in repairing and improving
neurologic functioning and signaling. Schartner et al. (2017)
reported substantial increased global neural signal diversity in a
psilocybin-human clinical study (Nature Scientific Reports,
7:46421). Additionally, niacin is known to be a neural
anti-inflammatory, and, in itself, has been implicated in improving
neural functioning. As niacin activates nerve endings, the inventor
suggests that the addition of niacin contributes an added benefit
by enhancing the neurogenic effects of psilocybin, psilocin,
erinacines and hericenones by helping these nootropics cross the
blood brain barrier, and migrate throughout the nervous systems,
and to its end points. Moreover, niacin is a vasodilator improving
blood flow in the brain by relaxing constricted blood vessels. This
unique combination not only rebuilds myelin upon the axons, it also
activates new astrocyte/astroglial cells and neuronal nodes of
crossings such as the synaptic regions, particularly in the
hippocampus. Other medicinal mushroom species also can be added,
particularly species of Antrodia, Beauveria, Copelandia, Cordyceps,
Ganoderma, Grifola, Inonotus, Isaria, Panaeolus, Phellinus, and
other medicinal mushrooms and their mycelia whose unique
neurogenerative properties may add benefits to this basic
formulation. An excellent summary of the prior art related to the
use of mushrooms as "brain foods" can be found in Phan et al.
(2017), "Edible and Medicinal Mushrooms: Emerging Brain Food for
the Mitigation of Neurodegenerative Diseases," Journal of Medicinal
Foods 20(1): 1-10. Lion's Mane (Hericium erinaceus), Bear's Head
(H. coralloides), or Comb Tooth (H. ramosum) mushrooms and mycelium
have also been well studied and reported to regenerate myelin on
the axons of nerves. Two particular families of compounds are most
noteworthy--erinacines and hericenones. Erinacines, including known
erinacines A-K, P and Q, are cyanthane terpenes isolated from the
mycelia of Hericium erinaceus that promote NGF (nerve growth
factor) synthesis. Hericenones, including known hericenones C--H,
are cyanthane terpenes located in both the mycelia and fruiting
body of Hericium erinaceus that promote NGF synthesis. Friedman et
al. (2015) summarizes these activities in "Chemistry, Nutrition,
and Health-Promoting Properties of Hericium erinaceus (Lion's Mane)
Mushroom Fruiting Bodies and Mycelia and Their Bioactive
Compounds," Journal of Agricultural and Food Chemistry 63:
7108-7123.
[0006] Although Phan et al. describes many species with potential
neurogenerative properties, the psilocybin or psilocybian species
(i.e. "psilocybin-containing," from the use of "psilocybienne" as
described by the French mycologist, Roger Heim, with R. Gordon
Wasson, in 1957 in Les champignons hallucinogene du mexique. Paris:
Museum de historie naturelle; 1958, pp. 268-71) are not mentioned,
either alone or in combinations with the edible and medicinal
mushroom species described by Phan. A good summary of the role of
psilocybin in humans can be found in Passie et al. (2002), "The
Pharmacology of Psilocybin," Addiction Biology 7: 357-364. That
psilocybin has neurogenerative properties was elucidated by Catlow
et al. (2013), "Effects of psilocybin on hippocampal neurogenesis
and extinction of trace fear conditioning," Experimental Brain
Research 228: 481-491.
[0007] The present nootropic invention can benefit those suffering
from age or trauma related neuropathologies including but not
limited to tinnitus, organophosphates, and other toxic compounds),
heavy metals, prions, amyloid plaque formation, demyelination,
nerve signaling, neurotoxic viruses, stress and numerous other
agents causing neuropathies. Psilocybian mushrooms, their enzymes
and their indole alkaloids may counteract and reduce the toxicity
of methyl phosphonates--the core structure of Sarin, a potent
neurotoxin, used in nerve gases. Moreover, the use of psilocin and
psilocybin in the compositions described here may help block the
neurotoxicity effects of chemical nerve toxins and lead to
protecting and healing military and civilians exposed to sarin and
other neurotoxic agents. The use of fungal extracts also
potentially enables neurogenesis by removing agents harmful to
neurological health, including but not limited to parasites such as
nematodes, protozoa, pathogenic bacteria, including Borrelia
species and other spirochetes, and other infectious organisms or
viruses. The benefits of this invention to the nervous system is
hard to overstate. Additional benefits are conferred not only to
humans challenged with diseases or neurotoxins, but also in healthy
humans, including but not limited to increased cognitive function
in students, scientists, computer coders, hackers, Big Data
specialists, mathematicians, astronomers, strategic planners (i.e.,
such as in the U.S. Defense Department), gamers, linguists,
writers, futurists, Mensa members, athletes, soldiers, religious
leaders, politicians, business leaders or anyone benefiting from
increased memory, intelligence, imagination, cognition,
clairvoyance, motor skills, spatial navigation, athleticism,
ability to more quickly respond to and process stimuli, balance,
neuroplasticity, state of mind, longevity and mental health.
Various benefits are also expected in vertebrate animals including
mammals, carnivores, omnivores, herbivores, pets including cats and
dogs and companion animals, farm and produce animals, laboratory
animals, zoo animals, reptiles, fish, and birds. The compounds of
the present invention may also be useful for bees, including those
suffering from pesticides, viruses or at risk from Colony Collapse
Disorder, and various other invertebrates.
DETAILED DESCRIPTION
[0008] Niacin (nicotinic acid) has long been reported to counteract
the effects of psilocybin and LSD, helping those experiencing
adverse reactions or "bad trips" to return to a non-psychoactive
state of mind, by reversing the excitement of nerve receptors.
Therefore, the prior art teaches away from using niacin to excite
nerve endings using psilocybin or psilocin. Hence,
counter-intuitively, this invention uniquely combines niacin with
psilocin/psilocybin and erinacines/hericenones for neurological
restructuring and improved neurological health. By adding niacin
into a psilocybin-centered neuroregenerative nootropic
nutraceutical, vitamin complex or medicine in sufficient quantities
to cause extreme discomfort for those who might try to abuse a
therapeutic combination containing psilocin or psilocybin, this
invention provides improved methods and compositions to prevent
potential abuse by those wishing to get "high." Analogous to
effects of Antabuse (disulfiram), which induces an unpleasant
experience for those abusing alcohol, the addition of sufficient
quantities of niacin, which likewise causes extreme discomfort,
with psilocybin/psilocin will help prevent the abuse of the
described neurogenic formulas.
[0009] As little as 10-35 mg per day of niacin causes flushing
redness on the skin, itchiness, burning and unpleasant tingling.
Higher doses can lead to liver damage. 500 mg. per day is
considered the top tier for safe use unless prescribed by a
physician who closely monitors the patient for adverse effects.
Some cholesterol-lowering products contain up to 500 milligrams of
niacin and these levels can interfere with the metabolism of other
medicines. 3,000 milligrams per day is clearly toxic. Upon
hydrolysis, a drug called Picamilon produces GABA and niacin,
allowing the inhibitory neurotransmitter GABA to pass through the
blood-brain barrier. The addition of niacin to GABA to form
nicotinyl-.gamma.-aminobutyric acid or N-nicotinoyl-GABA also aids
the passage of GABA across the blood-brain barrier. The stacking of
niacin, psilocybin (or psilocin), GABA, erinacines and hericenones
is an additional embodiment of this invention. Further embodiments
include the addition of vanillic acid, trans-ferulic acid,
trans-cinnamic acid, or other antiviral, anti-inflammatory
polyphenols to reverse neuropathies, especially in those harmed by
viruses such as, but not limited to, herpes simplex viruses (HSV),
human papilloma viruses (HPV), polio, pox and other neurotoxic and
inflammatory viruses.
[0010] Moreover, by using psilocin or psilocybin at levels
equivalent to what is colloquially known as "microdoses," i.e.,
<1 mg per day for a 70 kg individual, compounding effects can be
realized over time. Such low doses have no noticeable consciousness
altering effects on the person ingesting, and moreover, it is well
know that tolerance to any perceived effects in altering one's
consciousness is achieved very quickly from daily dosing of even
higher levels, such as 10 mg of psilocin or psilocybin per day for
a 70 kg person. Johns Hopkins researchers found the "sweet spot"
for full-blown therapeutic doses to be around 35 mg of
psilocybin/psilocin for a 70 kg person. (Note that psilocybin is
dephosphorylated into psilocin, which passes through the
blood-brain barrier.)
[0011] The term "effective amount" or "therapeutic amount" refers
to an amount sufficient to have neurogenerative activity. This
amount may vary to some degree depending on the mode of
administration but will be in the same general range. The exact
effective amount necessary could vary from subject to subject,
depending on the compound, preventative treatment or condition
being treated, the mode of administration, etc. The appropriate
effective amount may be determined by one of ordinary skill in the
art using only routine experimentation or prior knowledge in the
art in view of the present disclosure. Note that effective
ranges/dosages are not expected to be precisely the same for all
compounds. Dosages may be optimized with each compound when the
pharmacokinetics are studied to see how each compound is
metabolized, which may alter the dose ranges. Nevertheless, given
these factors, this neuro-enhancing invention is best managed in
consultation with a skilled medical professional.
[0012] A suggested formula containing optional nervine plants that
serves the purpose of neurological benefit but below any noticeable
level of intoxication could be a 550 mg delivery dose via an
ingestible capsule or by any means known to the art of drug
delivery:
TABLE-US-00001 Neurogenesis Formula 1 Psilocin or psilocybin 1 mg
Erinacines or hericenones 50 mg Niacin per day 200 mg Extract of
Hericium erinaceus, H. coralloides, H. abietis 199 mg mycelium
and/or fruitbodies of medicinal mushrooms Extracts of plants with
neurogenic properties* 100 mg
[0013] Plant extracts with known neuroregenerative properties
include but are not limited to: Bacopa species (Bacopa monnien),
Gotu kola (Centella asiatica), and Gingko (Gingko biloba).
Additional plants with anti-inflammatory properties include but are
not limited to: Ginger (Zingiber officinale), Holy Basil (Ocimum
sanctum), Hu Zhang (Polygonum cuspidatum), Oregano (Origanum
vulgare, Origanum onites), Rosemary (Rosmarinus officinalis,
Rosmarinus eriocalyx, species in the genus Rosmarinus), Turmeric
(Curcuma longa), Green Tea (Camellia sinensis), lavender (Lavandula
spica and related species in the genus Lavandula), skullcap
(Scutellaria lateriflora), and oat straw (Avena sativa, Avena
byzantina). Moreover, Salvia divinorum, aka Diviner's Sage,
ayahuasca, a concoction made from Banisteriopsis caapi and
Psychotria species, and plants containing ibogaine (Tabernanthe
iboga, Voacanga africana and Tabernaemontana undulate), peyote
(Lophophora williamsii), the seeds of morning glory (Ipomoea
tricolor and related species) and Hawaiian baby wood rose (Argyreia
nervosa), and Cannabis (Cannabis sativa, C. indica, and C.
ruderalis), can be incorporated as well. Any nervine agents from
natural products may also be incorporated, including, for example,
cordycepin (or Cordyceps extracts containing such) or amyloban
(found in Lion's mane).
[0014] Depending on individual factors such as variations in
metabolism, neurotransmitters and preventative treatment or
condition, such a regimen of 500-1000 mg of intake, once to three
times daily may produce measurable effects in one year, or the
regimen may extend for up to a year or more before noticeable
neurological benefits are evident. Since psilocybin converts to
psilocin and is typically not detectable in the urine in 24 hours,
the long-term use of this nootropic formulation sustains psilocin
as a serotonin agonist, while not activating dopamine
receptors.
[0015] In another embodiment, the composition comprises one or more
of ethyl 7-chloro-2-oxo-4-phenyl-2H-chromen-3-carboxylate, vanillic
acid, chrysin, quercetin hydrate, rutin hydrate, syringic acid,
trans-cinnamic acid, trans-ferulic acid, salts thereof, esters
thereof, or combinations thereof, and thereby has an antiviral
effect against a pathogenic virus comprising one or more of herpes
Varicella zoster virus, Epstein-Barr virus, herpes simplex I and II
viruses, human papillomaviruses (HPV), poliovirus, or viruses which
contribute to neuropathies.
[0016] As ranges of these active ingredients can vary, the inventor
anticipates the ranges giving benefits will include:
TABLE-US-00002 Neurogenesis Formula 2 (based on a 70 kg, 154 lb
person) Psilocin or psilocybin 0.1 mg to 0.6 mg Erinacines or
hericenones 1 mg to 20 mg Niacin per day 1 to 50 mg Neurogenesis
Formula 3 Psilocin or psilocybin 0.6 mg to 0.9 mg Erinacines or
hericenones 20 mg to 50 mg Niacin per day 50 mg to 100 mg
Neurogenesis Formula 4 Psilocin 0.9 mg to 10 mg Erinacines or
hericenones 50 mg to 200 mg Niacin per day 100 mg to 200 mg
Neurogenesis Formula 5 Psilocin or psilocybin 0.1 mg to 10 mg
Erinacines or hericenones 1 mg to 200 mg Niacin per day 1 mg to 200
mg Neurogenesis Formula 6 Psilocin or psilocybin 1 mg to 10 mg
Erinacines or hericenones 50 mg to 200 mg Niacin per day 101 mg to
200 mg Neurogenesis Formula 7 Psilocybin mushroom @ 0.1 g to 1 g 1%
psilocin or psilocybin Lion's mane mushroom @ 50 mg to 200 mg 1%
erinacines or hericenones Niacin per day 101 mg to 200 mg
[0017] Compounds naturally produced by the mycelium of psilocybian
mushrooms and their mycelium includes baeocystin, norbaeocystin,
N,N-dimethyltryptamine, 5-hydroxytryptamine (serotonin),
5-hydroxytryptophan, psilocybin and psilocin. These compounds,
their precursors and immediate derivatives are candidates for
neurogenesis. Synthetic or natural prodrugs, congeners and analogs
of psilocybin, psilocin, baeocystin and norbaeocystin may offer
similar benefits. Congeners are chemical substances related to each
other by origin, structure, or function. Analogs (or analogues or
structural analogs) are compounds having a structure similar to
another but differing from it in respect of a certain substituent
in which one or more atoms or functional groups which are replaced
with other atoms or groups or substituents. Psilocybin and psilocin
prodrugs and analogs that may similarly prove useful include those
where the hydroxyl group is modified, or the methyl groups of the
terminal amine nitrogen have been modified. Example hydroxyl group
substituents include alkyl and aryl ethers and esters, for example
methoxy and ethoxy ethers and acetyl esters, halogens including
fluoro-, chloro- and bromo-substituents, and thio groups such as
methylthio or benzothio. Example nitrogen group substituents
include one or both methyl groups substituted with ethyl, propyl,
isopropyl, butyl, isobutyl, secbutyl, tertbutyl, amyl or allyl
groups and the N-trimethyl analogs. The corresponding phosphate
esters, namely psilocybin and baeocystin analogs, may also prove
useful, as may analogs where one or more hydrogen atom is replaced
by fluorine, chlorine, or bromine. Also preferred, where possible,
are the salts of the tryptamine compounds, for example
hydrochloride, fumarate, maleate, picrate, oxalate, tartrate, and
sulfate salts, which are typically more stable. Also preferred are
the zwitterionic forms, particularly of the phosphate esters and
quaternary ammonium compounds. Preferred analogs include:
4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT or O-acetyl psilocin)
the acetylated form of the psilocin (4-OH-DMT). It is a possible
prodrug of psilocin (as are other 4-alkyl-esters), more stable than
psilocin, and has a longer shelf life;
4-acetoxy-N-methyl-N-ethyltryptamine (4-AcO-MET), a psilocin analog
substituted at R4 of its indole heterocycle with an acetoxy (AcO or
CH3COO--) functional group which also contains a methyl group and
an ethyl chain bound to the terminal amine nitrogen of its
tryptamine backbone. 4-AcO-MET is an acetate ester analog of
4-OH-MET and a N-substituted ethyl homolog of 4-AcO-DMT;
4-acetoxy-N,N-diethyltryptamine (4-AcO-DET);
4-acetoxy-N-methyl-N-propyltryptamine (4-AcO-MPT);
4-acetoxy-N-methyl-N-isopropyltryptamine (4-AcO-MIPT);
4-acetoxy-N,N-dipropyltryptamine (4-AcO-DPT) and
4-acetoxy-N,N-diisopropyltryptamine (4-AcO-DI PT);
4-hydroxy-N-methyl-N-ethyltryptamine (4-OH-MET, metocin, or
methylcybin), a 4-hydroxy N-substituted structural analog of
psilocin and the with a methyl and an ethyl group bound to the
terminal amine nitrogen of the tryptamine structure;
4-hydroxy-N-methyl-N-propyltryptamine (4-OH-MPT);
4-hydroxy-N-methyl-N-isopropyltryptamine (4-OH-MI PT);
4-hydroxy-N,N-diethyltryptamine (4-OH-DET);
4-hydroxy-N,N-dipropyltryptamine (4-OH-DPT);
4-hydroxy-N,N-diisopropyltryptamine (4-OH-DI PT); and
4-hydroxy-N,N-diallyltryptamine (4-OH-DALT); analogs where the 4-OH
group has been removed, such as N,N-dimethyltryptamine (DMT),
N-methyl-N-ethyltryptamine (MET), N-methyl-N-propyltryptamine
(MPT), N,N-diethyltryptamine (DET), N,N-dipropyltryptamine (DPT),
N,N-isopropyltryptamine (DIPT), N-methyl-N-isopropyltryptamine
(MIPT), .alpha.-methyltryptamine (AMT),
N-ethyl-N-isopropyltryptamine (EIPT), N-methyl-N-butyl-tryptamine
(MBT) or analogs substituted at other positions such as
N,N-dimethyl-5-hydroxytryptamine (5-OH-DMT or bufotenine),
5-methoxy-.alpha.-methyltryptamine (5-MeO-aMT),
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT),
5-methoxy-N,N-diethyltryptamine (5-MeO-DET),
5-methoxy-N,N-dipropyltryptamine (5-MeO-DPT),
5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT),
5-methoxy-N-ethyl-N-isopropyltryptamine (5-MeO-EI PT),
2,.alpha.-dimethyltryptamine (2,.alpha.-DMT),
.alpha.,N-dimethyltryptamine (.alpha.,N-DMT),
.alpha.-ethyltryptamine (.alpha.-ET),
2-methyl-N,N-dimethyltryptamine (2-Me-DMT),
2-methyl-N,N-diethyltryptamine (2-Me-DET), 1-methylpsilocin and
ibogaine (a complex tryptamine). In general, equimolar amounts of
an analog may be used in place of psilocybin and/or psilocin in the
formulas above, or amounts producing equivalent functional effects
may be utilized. See TiHKAL: The Continuation by Alexander Shulgin
and Ann Shulgin (1997, Transform Press) for an in-depth discussion
of both "legal" analogs and "chemical" analogs, and synthesis and
effects of various psilocybin and psilocin analogs.
[0018] Additional pharmaceutical excipients useful for the
compositions as described herein include, for example, the
following: acidifying agents (acetic acid, glacial acetic acid,
citric acid, fumaric acid, hydrochloric acid, diluted hydrochloric
acid, malic acid, nitric acid, phosphoric acid, diluted phosphoric
acid, sulfuric acid, tartaric acid); alkalizing agents (ammonia
solution, ammonium carbonate, diethanolamine, diisopropanolamine,
potassium hydroxide, sodium bicarbonate, sodium borate, sodium
carbonate, sodium hydroxide, trolamine); antifoaming agents
(dimethicone, simethicone); antimicrobial preservatives
(benzalkonium chloride, benzalkonium chloride solution,
benzethonium chloride, benzoic acid, benzyl alcohol, butylparaben,
cetylpyridinium chloride, chlorobutanol, chlorocresol, cresol,
dehydroacetic acid, ethylparaben, methylparaben, methylparaben
sodium, phenol, phenylethyl alcohol, phenylmercuric acetate,
phenylmercuric nitrate, potassium benzoate, potassium sorbate,
propylparaben, propylparaben sodium, sodium benzoate, sodium
dehydroacetate, sodium propionate, ascorbic acid, thimerosal,
thymol); antioxidants (ascorbic acid, ascorbyl palmitate, butylated
hydroxyanisole, butylated hydroxytoluene, hypophosphorous acid,
monothioglycerol, propyl gallate, sodium formaldehyde sulfoxylate,
sodium metabisulfite, sodium thiosulfate, sulfur dioxide,
tocopherol, tocopherols excipient); buffering agents (acetic acid,
ammonium carbonate, ammonium phosphate, boric acid, citric acid,
lactic acid, phosphoric acid, potassium citrate, potassium
metaphosphate, potassium phosphate monobasic, sodium acetate,
sodium citrate, sodium lactate solution, dibasic sodium phosphate,
monobasic sodium phosphate); chelating agents (edetate disodium,
ethylenediaminetetraacetic acid and salts, edetic acid); coating
agents (sodium carboxymethylcellulose, cellulose acetate, cellulose
acetate phthalate, ethylcellulose, gelatin, pharmaceutical glaze,
hydroxypropyl cellulose, hydroxypropyl methylcellulose,
hydroxypropyl methylcellulose phthalate, methacrylic acid
copolymer, methylcellulose, polyvinyl acetate phthalate, shellac,
sucrose, titanium dioxide, carnauba wax, microcrystalline wax,
zein); colorants (caramel, red, yellow, black or blends, ferric
oxide); complexing agents (ethylenediaminetetraacetic acid and
salts (EDTA), edetic acid, gentisic acid ethanolamide, oxyquinoline
sulfate); desiccants (calcium chloride, calcium sulfate, silicon
dioxide); emulsifying and/or solubilizing agents (acacia,
cholesterol, diethanolamine (adjunct), glyceryl monostearate,
lanolin alcohols, mono- and di-glycerides, monoethanolamine
(adjunct), lecithin, oleic acid (adjunct), oleyl alcohol
(stabilizer), poloxamer, polyoxyethylene 50 stearate, polyoxyl 35
castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 10 oleyl
ether, polyoxyl 20 cetostearyl ether, polyoxyl 40 stearate,
polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80,
diacetate, monostearate, sodium lauryl sulfate, sodium stearate,
sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate,
sorbitan monostearate, stearic acid, trolamine, emulsifying wax);
filtering aids (powdered cellulose, purified siliceous earth);
flavors and perfumes (anethole, benzaldehyde, ethyl vanillin,
menthol, methyl salicylate, monosodium glutamate, orange flower
oil, peppermint, peppermint oil, peppermint spirit, rose oil,
stronger rose water, thymol, tolu balsam tincture, vanilla, vanilla
tincture, vanillin); humectants (glycerol, hexylene glycol,
sorbitol); plasticizers (e.g., castor oil, diacetylated
monoglycerides, diethyl phthalate, glycerol, mono- and
di-acetylated monoglycerides, propylene glycol, triacetin, triethyl
citrate); polymers (e.g., cellulose acetate, alkyl celluloses,
hydroxyalkyl, acrylic polymers and copolymers); solvents (acetone,
alcohol, diluted alcohol, amylene hydrate, benzyl benzoate, butyl
alcohol, carbon tetrachloride, chloroform, corn oil, cottonseed
oil, ethyl acetate, glycerol, hexylene glycol, isopropyl alcohol,
methyl alcohol, methylene chloride, methyl isobutyl ketone, mineral
oil, peanut oil, propylene carbonate, sesame oil, water for
injection, sterile water for injection, sterile water for
irrigation, purified water); sorbents (powdered cellulose,
charcoal, purified siliceous earth); carbon dioxide sorbents
(barium hydroxide lime, soda lime); stiffening agents (hydrogenated
castor oil, cetostearyl alcohol, cetyl alcohol, cetyl esters wax,
hard fat, paraffin, polyethylene excipient, stearyl alcohol,
emulsifying wax, white wax, yellow wax); suspending and/or
viscosity-increasing agents (acacia, agar, alginic acid, aluminum
monostearate, bentonite, purified bentonite, magma bentonite,
carbomer, carboxymethylcellulose calcium, carboxymethylcellulose
sodium, carboxymethylcellulose sodium carrageenan, microcrystalline
and carboxymethylcellulose sodium cellulose, dextrin, gelatin, guar
gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl
methylcellulose, magnesium aluminum silicate, methylcellulose,
pectin, polyethylene oxide, polyvinyl alcohol, povidone, alginate,
silicon dioxide, colloidal silicon dioxide, sodium alginate,
tragacanth, xanthan gum); sweetening agents (aspartame, dextrates,
dextrose, excipient dextrose, fructose, mannitol, saccharin,
calcium saccharin, sodium saccharin, sorbitol, solution sorbitol,
sucrose, compressible sugar, confectioner's sugar, syrup);
surfactants (simethicone); tablet binders (acacia, alginic acid,
sodium carboxymethylcellulose, microcrystalline cellulose, dextrin,
ethylcellulose, gelatin, liquid glucose, guar gum, hydroxypropyl
methylcellulose, methylcellulose, polyethylene oxide, povidone,
pregelatinized starch, syrup); tablet and/or capsule diluents
(calcium carbonate, dibasic calcium phosphate, tribasic calcium
phosphate, calcium sulfate, microcrystalline cellulose, powdered
cellulose, dextrates, dextrin, dextrose excipient, fructose,
kaolin, lactose, mannitol, sorbitol, starch, pregelatinized starch,
sucrose, compressible sugar, confectioner's sugar); tablet
disintegrants (alginic acid, microcrystalline cellulose,
croscarmellose sodium, crospovidone, polacrilin potassium, sodium
starch glycolate, starch, pregelatinized starch); tablet and/or
capsule lubricants (calcium stearate, glyceryl behenate, magnesium
stearate, light mineral oil, sodium stearyl fumarate, stearic acid,
purified stearic acid, talc, hydrogenated vegetable oil, zinc
stearate); thickening agents (gelatin having a bloom strength of
50-100); tonicity agent (dextrose, glycerol, mannitol, potassium
chloride, sodium chloride); vehicle: flavored and/or sweetened
(aromatic elixir, compound benzaldehyde elixir, iso-alcoholic
elixir, peppermint water, sorbitol solution, syrup, tolu balsam
syrup); vehicle: oleaginous (almond oil, corn oil, cottonseed oil,
ethyl oleate, isopropyl myristate, isopropyl palmitate, mineral
oil, light mineral oil, myristyl alcohol, octyl dodecanol, olive
oil, peanut oil, persic oil, sesame oil, soybean oil, squalane);
vehicle: solid carrier (sugar spheres); vehicle: sterile
(bacteriostatic water for injection, bacteriostatic sodium chloride
injection); viscosity-increasing (see suspending agent); water
repelling agents (cyclomethicone, dimethicone, simethicone); and/or
solubilizing agent (benzalkonium chloride, benzethonium chloride,
cetylpyridinium chloride, docusate sodium, nonoxynol 9, nonoxynol
10, octoxynol 9, poloxamer, polyoxyl 35 castor oil, polyoxyl 40,
hydrogenated castor oil, polyoxyl 50 stearate, polyoxyl 10 oleyl
ether, polyoxyl 20, cetostearyl ether, polyoxyl 40 stearate,
polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80,
sodium lauryl sulfate, sorbitan monolaurate, sorbitan monooleate,
sorbitan monopalmitate, sorbitan monostearate, tyloxapol). This
list is not meant to be exclusive, but instead merely
representative of the classes of excipients and the particular
excipients that may be used in oral dosage forms as described
herein.
[0019] Another embodiment is methods for manufacturing a dosing
form for treating, ameliorating, mitigating, alleviating, reducing
and curing a nerve damage from neurotoxic virus infection
comprising: formulating a composition into a dosage form comprising
sprays, capsules, tablets, elixirs, emulsions, lozenges,
suspensions, syrups, pills, lotions, epidermal patches,
suppositories, inhalers, or injectables. Any methods known to the
art for formulating extracts or active principal ingredients into
lotions, soaps, etc. may be utilized.
[0020] Using blue light stimulation in the 280-400 nm wavelength
range, precursor molecules to psilocybin and psilocin production
can be elicited from the mycelium, primordia or fruitbodies of
psilocybian or their close non-psilocybian relatives, to induce the
formation of neurogenic compounds, including those that are not
illegal, and therefore would not violate statutes in the United
States or other countries. The goal here is to employ legal
neurogenic precursor, congener or analog compounds related to
psilocybin and psilocin.
[0021] Induction of bioactive compounds from mycelium through light
stimulation is a method that can be used for discovering
synergistic neurogenic compounds. Blue light activates shikimic
acid production in mycelium, and antioxidant polyphenols, while
also stimulating tyrosinase leading to melanization while
inhibiting laccase and other enzymatic pathways, simultaneously
inducing the production of psilocin, psilocybin, and other
tryptamines from mycelium in psilocybin active mushrooms and their
relatives. Modifying the wavelength (i.e., blue light for 12 hours,
red light for 12 hours, per day) and frequency of light exposure,
including "pulsing" of the light, can help articulate the
expression of active neurogenic ingredients. The shikimic acid
pathway gives rise to aromatic amino acids (phenylalanine,
tyrosine, and tryptophan), which are precursors for the formation
of ergot alkaloids, lysergic acid, psilocybin, and psilocin (Isaac,
Fungal-Plant Interactions, Springer Netherlands, 1992). The
inventor postulates that light stimulation evoking the
transformation of ergosterol to vitamin D will also influence the
pathways where light induces neurogenic compounds from mycelium.
These pathways are interrelated and can be used for creating
medically significant novel compositions whose synergy is useful
for repairing the neuropathic damage by promoting neurogenesis and
synaptic integrations. Exposure of mycelium to select wavelengths
of light, especially blue and red spectra, may induce indole
alkaloids related to psilocin analogues that have distinct
antiviral and neuroprotective properties.
[0022] The biosynthesis of psilocybin from tryptophan involves
enzymatic decarboxylation, methylation at the N.sup.9 position,
4-hydroxylation, and O-phosphorylation. Light stimulation triggers
the production of psilocybin and psilocin in the mycelium of, for
instance Psilocybe azurescens, Psilocybe cyanescens and Psilocybe
cubensis, possibly by stimulation of the enzymatic reactions. The
"off/on" production of psilocybin, psilocin, baeocystin (the
N-demethylated analog of psilocybin,
4-phosphoryloxy-N-methyltryptamine), norbaeocystin (the
N-demethylated analog of psilocin, 4-phosphoryloxy-tryptamine) and
other associated alkaloids from the mycelium caused by light
exposure (particularly UV) are interrelated to the production of
p-coumaric acid and the resultant metabolic expression of
tyrosinase coding for melanin, especially prior to, during and
after the time of primordia formation. The transition of the
mycelium upon controlled light exposure, especially blue and UV
light in the 280-420 nanometers ranges, affords the development of
a customized suite of active ingredients, from which an extract be
created or combined with active pharmacological molecules for a net
benefit for the patient that consumes this unique combination.
[0023] Compositions and methods utilizing combinations of psilocin
or psilocybin, and their immediate precursors, derived from
mycelium that is exposed to light, particularly in the blue
spectrum, additionally combined with erinacines or hericenones,
with or without the addition of niacin, can result in medically
significant, deliverable formulations for human consumption
supporting neurogenesis.
[0024] This inventor reported Psilocybe azurescens to be the most
potent psilocybian mushrooms in the world. (Stamets, P., Psilocybin
Mushrooms of the World, 1996, Ten Speed Press.) A common side
effect of taking this psychoactive mushroom species is loss of
coordination and in some occasions, temporary paralysis. This
mushroom contains ingredients related to psilocybin that may swamp
receptor fields to cause these conditions. In medicine, the
difference between a toxin and a medicine is often the dose. As
such, this inventor suggests that other potent neurologically
active ingredients are within Psilocybe azurescens (and to a lesser
degree, Psilocybe cyanescens, and Psilocybe subaeruginosa), which
are likely useful for neurogenesis when presented or isolated at
proper dosages.
[0025] Exposing mycelium grown on rice to blue and ultraviolet
light in the 280-420 nanometer wavelengths, for a short window of
time, lasting for a short duration of only 1-5 days, can help
create and potentiate the neuroregenerative agents described
herein. The intensity of light can range from 50-1,000 lux. By
incubating the sterilized rice being actively colonized by the
mycelium in plastic bags, which have grown out for a minimum of 1
week and up to 16 weeks, UV light exposure lights can be placed
directly above and below horizontally shaped bags for maximum light
exposure. The plastic bags or glass vessels can be selected for
allowing these blue light wavelengths to reach the mycelium. The
mycelium can undergo a phase change in response to light stimuli
into producing derivative neuroregenerative agents (it is to be
expected that during this transitional period, the mycelium may
contain varying mixtures of active compounds). This method and
derivative improvements can potentiate the production of
neuroregenerative molecules, some of which are intermediates during
the melanization pathways activated by light exposure at specific
wavelengths. This opens possibilities for customizing the output of
specific active molecules using precise wavelengths, exposure times
and intensities of light for manufacturing and potentiating
production from mycelium. Lights can be pulsed and/or sequenced
with varying wavelengths for exposing mycelium. The mycelium can
also be subsequently agitated to cause new growth spurts, causing
differentiation of hyphae with multiple nuclei per cell and
hyper-expression of extracellular metabolites. Moreover, active
molecules may be emitted differentially over time, allowing for
windows of harvesting by washing the mycelium using cold EtOH and
H.sub.2O or other solvents and processes known to the art of
natural product extraction.
[0026] Serotonin is the fundamental neurotransmitter all animals
use. That serotonin and psilocybin co-occur within
psilocybin-containing ("psilocybian" as used herein) mushrooms, and
that psilocybin is a serotonin agonist, substituting for serotonin
in the human brain and exciting neurotransmission, underscores the
value of exploring these pathways for neurogenic compounds.
Utilizing specific wavelengths of light--both blue and red
spectra--can induce or suppress expression of these compounds,
allowing customization of neurogenic compounds which can be useful
medically. Exposure of red-light spectra on maturing mycelium of
psilocybin active mushroom species--which naturally would generate
psilocybin and psilocin in its mycelium--can be used to acquire
compounds useful for neurogenesis. Moreover, this unique
combination of compounds can be incorporated into other therapies
with such combinations providing unique advantages for medically
significant advancements in repairing neurons, removing amyloid
plaques, improving mental health, cognition, agility, and improving
overall the ecology of consciousness. The inventor foresees
utilizing such compounds in helping amputees activate their
articulable prostheses. Such derivatives can help the improve
cyborg technologies, allowing for neurons to grow into and mesh
computer interfaces.
[0027] Moreover, the production of active principle ingredients
from mycelium can be additionally enhanced by vibrational actions,
including but not limited to pulsed sonic
vibration--sonification--in combination with active principal
ingredients stimulating UV wavelengths. Specific UV spectra and
vibrations can be customized for enhancing yields.
[0028] Psilocybin dephosphorylates into psilocin in the liver,
which then passes through the blood-brain barrier. Subsequent to
enzymatic conversion and liver metabolism, psilocin is further
degraded along at least one pathway, one rendition of which is
featured below. These derivative compounds have neurogenic
potential and are anticipated to be useful in nootropic
formulations.
##STR00001##
Adapted from Psilocybin, Wikipedia, The Free Encyclopedia.
[0029] Moreover, since psilocin and its analogs are
neurotransmitters, and substitute for serotonin, acting as an
agonist exciting serotonin receptors, their ability to enhance
neurotransmission while in combination with nerve growth factors
such as erinacines and hericenones, provides a unique opportunity
for spurring neurogenesis. When combined with niacin, which causes
nerve ending excitement, and additionally combined with mushroom
and plant extracts, compounded neurogenic benefits are anticipated
by this inventor.
[0030] The inventor claims rights to obvious embodiments of this
invention, including using delivery systems, compositions,
combinations and solvent extraction methods as outlined in this
author's previous patents and patent applications, which are a
matter of record at the United States Patent and Trademark Office
as well as methods and compositions known to the art of
pharmaceutical science and drug discovery.
[0031] It will be apparent to one of ordinary skill in the relevant
art that suitable modifications and adaptations to the
compositions, formulations, methods, processes, and applications
described herein can be made without departing from the scope of
any embodiments or aspects thereof. The compositions and methods
provided are exemplary and are not intended to limit the scope of
any of the specified embodiments. All of the various embodiments,
aspects, and options disclosed herein can be combined in any and
all variations or iterations. The scope of the compositions,
formulations, methods, and processes described herein include all
actual or potential combinations of embodiments, aspects, options,
examples, and preferences herein described. The exemplary
compositions and formulations described herein may omit any
component, substitute any component disclosed herein, or include
any component disclosed elsewhere herein. The ratios of the mass of
any component of any of the compositions or formulations disclosed
herein to the mass of any other component in the formulation or to
the total mass of the other components in the formulation are
hereby disclosed as if they were expressly disclosed. Should the
meaning of any terms in any of the patents or publications
incorporated by reference conflict with the meaning of the terms
used in this disclosure, the meanings of the terms or phrases in
this disclosure are controlling. Furthermore, the foregoing
discussion discloses and describes merely exemplary embodiments.
All patents and publications cited herein are incorporated by
reference herein for the specific teachings thereof.
[0032] No limitations with respect to the specific embodiments and
examples disclosed herein are intended or should be inferred, as
the examples and embodiments are representative only. While
examples and preferred embodiments of the present invention have
been shown and described, it will be apparent to those skilled in
the art, or ascertainable using no more than routine
experimentation, that many changes and modifications may be made
without departing from the invention in its broader aspects. The
appended claims are therefore intended to cover all such changes,
modifications, and equivalents as fall within the true spirit and
scope of the invention.
* * * * *