U.S. patent application number 13/744072 was filed with the patent office on 2016-03-24 for topical transdermal method for delivering nutrients through the skin for expeditied wound healing and skin rejuvenation.
This patent application is currently assigned to Neville Pharmaceutical, Inc.. The applicant listed for this patent is Neville Pharmaceutical, Inc.. Invention is credited to Donald P. Orofino.
Application Number | 20160082068 13/744072 |
Document ID | / |
Family ID | 51165314 |
Filed Date | 2016-03-24 |
United States Patent
Application |
20160082068 |
Kind Code |
A9 |
Orofino; Donald P. |
March 24, 2016 |
Topical Transdermal Method for Delivering Nutrients Through the
Skin for Expeditied Wound Healing and Skin Rejuvenation
Abstract
The present invention relates to liquid application for skin
rejuvenation created from specific amino acids, lipids, nucleic
acids and vitamins. This collection of molecules delivers precisely
the factors necessary to a specific site requiring healing; a
direct intervention system to most expeditiously remodel skin with
building blocks. This delivery is a transdermal topical delivery
and healing is via specific molecules that engender a false
autocoid reaction rapidly followed by an incremental
healing-anti-inflammatory response augmented by very specific GRAS
ingredients in the invention and also recruited from the body to
this needy site. Energy is brought to site by transdermally
delivered protons and enhanced by the local vascular flow initiated
by transdermal molecules. This delivery system bypasses digestion
and dilution. Key is a lipophilic carrier with nuclear and
mitochondrial ligands that rapidly penetrate and permeate all
membranes and truncates the inflammatory site quickly manifesting
curation. Other delivered molecules expedite healing at every
level.
Inventors: |
Orofino; Donald P.; (Port
Washington, NY) |
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Applicant: |
Name |
City |
State |
Country |
Type |
Neville Pharmaceutical, Inc. |
Albany |
NY |
US |
|
|
Assignee: |
Neville Pharmaceutical,
Inc.
|
Prior
Publication: |
|
Document Identifier |
Publication Date |
|
US 20140199367 A1 |
July 17, 2014 |
|
|
Family ID: |
51165314 |
Appl. No.: |
13/744072 |
Filed: |
January 17, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13552920 |
Jul 19, 2012 |
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13744072 |
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61509559 |
Jul 19, 2011 |
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Current U.S.
Class: |
424/443 ;
128/200.14; 424/630; 424/639; 424/682; 424/744; 514/356; 514/458;
514/56; 514/560; 514/77; 514/89 |
Current CPC
Class: |
A61K 31/355 20130101;
A61K 31/727 20130101; A61K 2300/00 20130101; A61K 2300/00 20130101;
A61K 2300/00 20130101; A61K 2300/00 20130101; A61K 2300/00
20130101; A61K 2300/00 20130101; A61K 2300/00 20130101; A61K
2300/00 20130101; A61K 2300/00 20130101; A61K 2300/00 20130101;
A61K 31/664 20130101; A61K 31/675 20130101; A61K 45/06 20130101;
A61K 31/727 20130101; A61K 36/886 20130101; A61K 33/06 20130101;
A61K 33/34 20130101; A61K 36/886 20130101; A61K 31/201 20130101;
A61K 9/0014 20130101; A61K 31/198 20130101; A61K 31/455 20130101;
A61K 33/24 20130101; A61K 31/4172 20130101; A61K 31/675 20130101;
A61K 31/355 20130101; A61K 31/4172 20130101; A61K 33/06 20130101;
A61M 11/00 20130101; A61K 31/455 20130101; A61K 31/198 20130101;
A61K 33/34 20130101; A61K 31/201 20130101; A61K 45/00 20130101 |
International
Class: |
A61K 36/886 20060101
A61K036/886; A61K 33/24 20060101 A61K033/24; A61K 33/06 20060101
A61K033/06; A61K 31/727 20060101 A61K031/727; A61M 11/00 20060101
A61M011/00; A61K 31/675 20060101 A61K031/675; A61K 31/455 20060101
A61K031/455; A61K 31/355 20060101 A61K031/355; A61K 31/201 20060101
A61K031/201; A61K 45/00 20060101 A61K045/00; A61K 33/34 20060101
A61K033/34; A61K 31/664 20060101 A61K031/664 |
Claims
1. A method for supplying and applying a therapeutic agent locally
to a wound site on the body of a patient that is comprised of a
homogenized blend of a carrier and a treatment agent transdermally
to said wound site, wherein said carrier comprises methyl
nicotinate and beta alanine, said methyl nicotinate delivering
energy to said wound site by delivering protons to said wound site,
said energy provided by said protons allowing for the self-repair
of the tissue at said wound site, and wherein said beta alanine
defuses the inflammatory response of the patient's body to allow
the anti-inflammatory response of the patient's body to occur more
quickly and promote the healing of the tissue at said wound
site.
2. (canceled)
3. The method according to claim 38 wherein said treatment agent
comprises vitamins.
4. The method according to claim 7 wherein said vitamins further
comprise one or more of alpha and gamma tocopherols or blends
thereof.
5. The method according to claim 3 wherein said vitamins are one or
more B-complex vitamins.
6. The method according to claim 5 wherein said B-complex vitamin
is a nicotinic acid and/or niacinamide.
7. The method according to claim 6 wherein said B-complex vitamin
further comprises pyridoxal-5-phosphate (P-5-P).
8. The method according to claim 42 wherein said amino acid is
histidine, taurine or blends thereof.
9. The method according to claim 40 wherein the trace minerals are
copper, magnesium or blends thereof.
10. The method according to claim 5 wherein the blend further
comprises an excipient.
11. The method according to claim 10 wherein the excipient is
polysorbate 20.
12. The method according to claim 5 wherein said blend further
comprises glycerol and derivatives thereof.
13. The method according to claim 12 wherein the derivative of
glycerol is a medium chain triglyceride.
14. The method according to claim 13 wherein the triglyceride is
oleic acid.
15. The method according to claim 12 wherein the derivative of
glycerol is glycerophosphocholine ("gpc").
16. The method according to claim 5 wherein the blend further
comprises a solvent.
17. The method according to claim 16 wherein said solvent is
propylene glycol.
18. The method according to claim 5 wherein the blend is applied
using a radiating pump dispenser.
19. The method according to claim 5 wherein the blend is applied as
a salve or balm rubbed into the skin.
20. The method according to claim 5 wherein the blend is a gel.
21. The method according to claim 20 further comprising aloe vera
and vitamin E.
22. The method according to claim 5 wherein said blend is applied
as a wound cleansing rinse.
23. The method according to claim 5 wherein said blend is applied
as a burn cleansing rinse.
22-23. (canceled)
24. The method according to claim 5 wherein said blend is packaged
in an individually hermetically sealed package with and wherein
said composition has been dehydrated and can be reconstituted with
water.
25. The method according to claim 5 wherein said blend is applied
as a powder comprised of micronized, freeze dried material.
26. The method according to claim 25 where said blend is used to
treat pressure ulcers.
27. The method according to claim 25 where said blend is used to
treat diabetic wounds.
28. The method according to claim 5 where said blend is applied by
a time-released epidermal/topical patch for staged and sequential
delivery of said composition for site-specific application.
29. The method according to claim 5 wherein the treatment agent is
an anticoagulant.
30. The method according to claim 29 wherein said anticoagulant is
heparin.
31. The method according to claim 5 wherein the treatment agent
causes an autocoid that engenders dermal healing.
32. The method according to claim 1 wherein the treatment agent is
an antioxidant.
33. The method according to claim 1 wherein the treatment agent is
an anti-inflammatory agent.
34. The method according to claim 1 wherein the treatment agent is
applied to keratinocytes and causes accelerated new dermal
growth.
35. The method according to claim 1 wherein the carrier further
comprises copper peptide.
36. The method according to claim 35 wherein the carrier further
comprises P-5-P.
37. The method according to claim 36 wherein the carrier further
comprises niacinamide.
38. The method according to claim 36 wherein the carrier further
comprises nicotinic acid.
39. (canceled)
40. The method according to claim 5 wherein the treatment agent
further comprises trace minerals.
41. The method according to claim 5 wherein the treatment agent
further comprises fats.
42. The method according to claim 5 wherein the treatment agent
further comprises amino acids.
43. The method according to claim 5 wherein said blend is applied
by a roll on applicator.
44. The method according to claim 5 wherein said blend is applied
by a blend impregnated mini-sponge.
45. The method according to claim 5 wherein said methyl nicotinate
is in an amount of from about 0.1% to about 1.0% of said blend,
said beta aniline in an amount of from about 1.0% to about 3.0% of
said blend, and wherein said blend further comprises arachidonic
acid in an amount of from about 0.5% to about 2.0% of said blend,
ascorbyl palmitate in an amount of from about 0.5% to about 2.0% of
said blend, hypoxanthine riboside in an amount of from about 0.25%
to about 1.75% of said blend, phosphatidylcholine in an amount of
from about 0.5% to about 2.0% of said blend and lysophosphatidyl
choline in an amount of from about 0.01% to about 0.05% of said
blend.
Description
CROSS-REFERENCE TO A RELATED APPLICATION
[0001] This application is a continuation-in-part of U.S.
application Ser. No. 13/552,920, filed on Jul. 19, 2012, which
claimed priority on U.S. Provisional Patent Application No.
61/509,559, filed Jul. 19, 2011, the full disclosures of which are
incorporated by reference.
BACKGROUND OF THE INVENTION
[0002] Methylation is the key to the epigenetic perfect expression,
peak maintenance and re-assembly of all genes (DNA/RNA). On the
skin surface or wound site, methylation can be part of the energy
cycle to facilitate in the epigenome's perfect retooling; the
Methyl Nicotinate molecule (MN) is present to affect this
reassembly on the skin surface or wound site. This process occurs
without any systemic dilution or metabolic transformation that
would occur by the oral or parenteral administration of the
administered substance. Methyl Nicotinate molecules are lipophilic
in nature and at the cellular level easily traverse through the
plasma membrane. The methyl group provides energy directly to the
site of application on the order of 3 protons (H+). Additional
energy from increased NAD, increased NADP, increased cAMP and
opening the calcium channel for increasing ATP manufacturing occurs
with every molecule of MN. Once in the cytosol, it can readily
enter the nucleus, delivering the Nicotinate ligand and energy.
This Methyl donor energy interacts with the gene (DNA/RNA) via
multiple venues; one is the histone sheath. This exposes more of
the gene (DNA/RNA), now expressing its increased function and/or
repair, and/or gene silencing, and/or its activation of apoptosis.
The genome (DNA/RNA) is thus rebooted by the MN thereby allowing
epigenetically more of the phenotypic aspects of the gene (DNA/RNA)
to facilitate a renewed, reorganized and enhanced structure within
the cell. The repaired gene can now perform with greater
efficiency, and the repaired cell containing this gene (DNA)
becomes more efficient in its innate cellular functions. There is a
special energy balancing synergy to maintain perfect structure and
function that requires the delicate pre-programming of the
following cellular pathways: cAMP, PGC1A, Ppars, Foxo1, PARP1a,
peroxisomes and proteasomes. These pathways work in synergy, aiding
and contributing to optimize each individual cellular mechanism.
The protons/ATP, seamlessly delivered, assist with the process of
cellular respiration and maintain the balance of NAD, NADH, FAD and
FADH.
[0003] Whether the gene is carrying out its normal functions or
effecting self-repair, it can now do so expediently due to this
delivery of energy that is both transdermally applied and
systemically recruited via specific nutrients. Where RNAi or the
gene has been silenced, or is malfunctioning, the increased energy
delivered can retool this nuclear function. If the malfunction is
not fixable, this energy can allow the cell to have PARP (parp1 in
this case) induce apoptosis or autophagy via demethylization. When
and if the cell rejuvenates, in turn, the energy and the nicotinate
ligand for the nuclear super family of transcriptional regulated
genes (NSFTRG) will induce the nucleus to engender increased
production of mitochondria, proteasomic activity, Ppars, PGC1a and
Sirtuin activations to continue their ever-vigilant maintenance of
the gene (DNA).
[0004] Through the use of Methyl Nicotinate, the nicotinate ligand,
as a promoter of the nuclear super family of transcriptionally
regulated genes (NSFTRG), is attracting cytoplasmic organelles into
the cytosol for increased mitochondria activity.
[0005] Within the barrier of the skin where the wound begins, the
nicotinate molecule functions as a false analog, creating a false
injury (an autocoid response) that is quickly recognized by the
body and is quelled more rapidly than a true injury, then
stimulating an anti-inflammatory healing process. The delivered
beta alanine also defuses the inflammatory response allowing the
anti-inflammatory response to occur more quickly.
[0006] With the absorption and transfer of the array of
accompanying materials for rebuilding cellular tissue (dermis),
Methyl Nicotinate causes GPRA1 activation. The event of G-protein
coupled receptor A-1 activation is via skin, neurons, or immune
cells release of their local free fatty acids (FFA), Phospholipase
A1 (PLA1) and including arachidonic acid (AA) that recruits both
the LOX cascades and COX cascades, along with a myriad of other
cytokines and chemokines. (PLA1 enables AA production.) These
enable local inflammation at the cell/wound site. There is also a
local transformation of stem cells to mast cells with the increased
production of histamine and heparin and their powerful antioxidant
and anticoagulation effects at the cell site due to this local
false inflammatory reaction.
[0007] Arachidonic acid by-products are legend. The body will
transform AA to leukotriene via LOX interaction with AA resulting
in LTA4 that hydrates to LTB4. Then glutathione helps engender LTC4
from B4. Removal of specific amino acids manifests D4 and E4 from
C4. The healing cascade is as follows: B4 causes adhesion,
chemotaxis and Superoxide dismutase (SOD) manufacture and, in
general, invites systemic cells to come to this site to assist in a
quick/short false inflammatory response. AA via COX influence
produces prostanoids that have both pro-inflammatory and
anti-inflammatory effect. The manufacture of PGD2 and PGE2 results
in nicotinic acids vasodilatory effect that enhances local blood
flow with oxygen, nutrients and cellular cleansing. PGI2 is created
via COX and AA enabling an anti-inflammatory response. Both the COX
and LOX truncated autocoid response enable the treated skin site to
be rejuvenated. This is followed by a dedicated anti-inflammatory
healing response. The addition of omega-3's: decosahexanoic acid
(DHA), eicosopentanoic acid (EPA), with adjunctive acetylsalicylic
acid AND the removal of MCT's and/or Emu oil enables the production
of lipoxins, epilipoxins, protectins, resolvins and maresins to
rapidly enhance this response by Specialized Proresolving Mediators
(SPM)--autocoid production.
[0008] The nutrients delivered to the wound site with Methyl
Nicotinate are specific for wound/skin healing. This action
truncates inflammation and expedites the cellular healing
process.
[0009] The amino acid L-Histidine is a delivered nutrient whose
safety, pharmaceutical evaluation, bioavailability, physiology,
metabolism, medical usage and physiologic impact are well
documented in the scientific and biomedical literature. Histidine
functions as a safe anti-inflammatory and antioxidant. Histidine on
its own permeates the skin (integument) to reach the full dermis,
down to the keritinocytes, where it renders several restorative
functions. Methyl Nicotinate, described above, further enhances
tissue penetration and saturation of Histidine while its redox
properties allow metal cations, singlet oxygen and hydroxyl groups
to be reduced and/or neutralized, and rendered non-toxic. Free
Histidine (HD) is found in all tissue. As HD is decarboxylated to
histamine (HA), beta-alanine can combine with HA in the presence of
carcinine synthetase forming carcinine (CA). Alternately, HD may
combine with beta-alanine, in the presence of carnosine synthetase,
to become carnosine.
[0010] Carnosine (CS) is important in protein manufacturing and
diminishing glycosylation and carbonylation. By the modes of
actions of HA/HD/CS/CA cells may restore their intrinsic resting
electrical potential. This energizing effect further creates within
the epidermal and subdermal layers of the skin the re-scaffolding
needed for new tissue formation and for the building from
connective tissues using CS, an integral component, along with
glycine and imidizole acetic acid (IAA), which are needed to
provide for the collagen and elastin formation.
[0011] While in the re-scaffolding process, reactive oxygen species
(ROS) and nitric oxide synthase (NOS) need suitable blockade
occurring via the HD, HA, CA and CS molecules that prevents the
oxidative deterioration and weakening of the newly formed
scaffolding. In fact, all the nutrients and molecules being
delivered to skin/wound have an increased shelf life because of
these antioxidant molecules. Quintessentially, HD opens the
aquaporine channels (AQP0). Specifically, aquaporine increases the
PH within the cell as a signaling mechanism and turns on the
calcium channel-signaling pathway (nicotinic acid assisted) that
provides cellular hydration directly through aquaglyceroporin
channels, as well as a milieu to enhance cellular respiration and
increase energy manufacturing. Induced Carcinine (CA): HA, derived
from HD, can be biochemically changed to CA via HA combining with
beta alanine and P-5-P in the presence of Carcinine synthase. CA is
an analog of CS. Although CA is best produced in the central
nervous system (CNS) at a rate of 15-fold greater saturation than
found in any other tissue, its mode of action for healing is mainly
seen through the cardiovascular system. The Epiphenomenon permits
CS and CA to work directly to influence an increased blood flow and
cardiac output to heal injured tissues. Deep tissue (muscle and
fascia) restoration relates to CS presence that is essential with
deep wound healing. CA directly decreases and/or reverses skin
aging. The transdermal mechanism allows application and delivery to
the exact area of injury of HD, HA, MN, CS, CA, amino acetic acid
(AAA), IAA, glycine, P-5-P, Copper (Cu++), and the medium chain
triglycerides (MCT) molecules that the integument requires for
repair. These restorative nutrient components are either applied to
the site of repair or are biochemically and/or physiologically
produced in situ or alternatively delivered to the site by locally
increased circulation and/or local neurologic discharge.
[0012] Additional concentrations of HA and HD pool at injury sites
acutely by proximal neural firing. This effects increased HD and HA
locally. HA and HD may then be oxidized along with beta alanine to
amino acetic acid, and/or imidazole acetic acid (IAA), and/or they
can be methylated. Pain at the N-Methyl D-Aspartate (NMDA) sites
may be mitigated by IAA occupying the glycine receptor adjacent to
the glutamate site. HD is ubiquitous and creates special
prostaglandins of the 2 series (PGE2) at the inflammatory sites,
which assist in creating accelerated tissue growth. HD and HA, with
their bio-degratory amino acetic acids (AAA) are integral in
nucleic acid production, essential for new cell growth and
replenishment.
[0013] Energy for healing is essential. Methyl Nicotinate, a
nicotinic acid (B3) with a methyl group attached for its
lipophilicity, transports and transfers energy locally. Nicotinate
increases the surface temperature of the skin (warming) and causes
a significant release of prostaglandins (PGE 2) from the skin. It
stimulates histamine release from mast cells in the tissue, thereby
initiating the autacoid response of the specific immune system.
Methyl Nicotinate, a forerunner of NADPH and NADH are the keys in
glucose metabolism. They are required for the energy production
needed for healing. This action is accomplished through the
donation of an electron, resulting in increased energy for rapid
and repeatable cellular tissue repair.
[0014] Methyl nicotinate synergizes with pyridoxal-5-phosphate
(P-5-P) and Cu++ to promote scaffolding for the collagen/elastin
infrastructure and to efficiently reassemble "big "collagen
(potential scarring) to normal collagen. The direct infusion of
Cu++ increases skin growth and matrix molecules for faster
keritinocyte growth, thereby yielding faster dermal growth. P-5-P
with nicotinic acid are necessary for keritinocyte and skin
regrowth, as PARP and Sirtuins both require NAD as an essential
substrate. They enable new undamaged dermal regrowth. Including
both MN and NA in this formula promotes a two-pronged both "time
release" effect on energy enhancement required for new skin
generation via NAD, cAMP, cytosolic Ca++ regulation, increased
efficiency of CAC with diminished ROS.
[0015] Pyridoxal-5-phosphate (P-5-P) with MN assists in energy
production, and in wound/skin methylation by direct application to
the site of injury. Like Methyl nicotinate it bypasses per oral
digestion and systemic dilution, locally empowering this wound/skin
site to grow and heal more rapidly than normal. P-5-P directly
facilitates copper in the proper redox state to avoid toxicity,
thereby increasing the reactive oxygen species (ROS) being
neutralized. The increased bioavailability of the vitamin C for
tissue factors (e.g. Glycosaminoglycan) is enhanced by healthy
copper at the wound site. P-5-P is a critical factor for the supply
of energy, materials and preparation required for on site
healing.
[0016] Ceramide manufacture, engendered by niacin, increases skin
production along with signaling molecules for apoptosis, cell
growth and/or cell differentiation.
[0017] Medium Chain Triglycerides (MCT's) are structured lipids C-6
through C-12 that are applied topically to the wound to assist in
energy, cell wall manufacture and healing.
[0018] Heat Shock Proteins (HSP). The induced local inflammatory
site engenders heat shock proteins (HSP) to assist in the
chaperoning of specific molecules to their necessary destination of
skin and soft tissue remanufacturing sites. Additionally, heat
shock factors (HSF1) partner in this same process.
[0019] Ribosome switches, or Ribo switches, are now recognized as
one of the major metabolite controlling systems that account for
about two percent (2%) of genetic regulation in bacteria. They
respond to various metabolites, including co-enzymes, sugars,
nucleotide bases, amino acids and cations. With Thiamine, Methyl
donor groups, glycine and B-alanine, the ribo-like switches can be
turned on, off and incrementally speed up the healing of
skin/wounds, bypassing part of the molecular networking that could
impede this process.
[0020] Sirtuins are necessarily activated by the upstream and
downstream energy circuitry that is engendered by multiple
networking molecules (CREB, CREM, cAMP, FOXO1, FOXO3a, PPARS, and
PGC1a). PGC1a becomes a special additional immediate fuel source
for SIRTS by its manifold acetylated lysines. This entire energy
loop is the source for wound healing. The above is engendered in
part or all by the methylation process and redox upregulation by
Methyl Nicotinate, P-5-P, Cu++ and Inosine (a nucleoside).
[0021] Inosine is a necessary precursor of cellular energy and
efficiency. It sustains cellular and extra cellular ATP for
integument maintenance and growth. In new skin formation it enables
oxygenation and new ATP manufacture essential for growth. Its neuro
protectant application is essential for preservation and regrowth
of neural tissue in the healing wound. Inosine is commonly found in
tRNA that impacts on RNA editing and RNAi for maximal cellular
integrity.
[0022] Additional transdermal nutrient delivery molecules in this
invention that augment efficacy and potency of this invention are
(1-5): [0023] 1. ALA (alpha lipoic acid) a thiol and antioxidant
that interacts with lipid and water-soluble antioxidants increases
peak longevity of these several nutrients. ALA reboots vitamin C,
vitamin E, ubiquinone and glutathione thereby reducing ROS yet
increasing local nutrient bioavailability. ALA architecturally
undergirds new dermal growth with glycine and imidizole acetic acid
(IAA) allowing dermal structure to emerge under the scrutiny of a
genetic cleavage system (caspase proteases) under the protection of
the above antioxidants. It also increases eNOS (endothelial nitric
oxide synthase) and increases nitric oxide vasodilation. [0024] 2.
Beta-alanine, above biochemically discussed and applied in earlier
text here, is key to the remodeling of injured, diseased or aged
skin, suppresses leukotriene (LT) especially LT (B4) thereby
diminishing the circadia of the false inflammatory autocoid
response of methyl nicotinate (MN) and thus more rapidly engenders
an anti-inflammatory healing response. [0025] 3. Glycerol,
propylene glycol and polysorbate 20 allow more efficient
transdermal penetration of molecular substrate. These hydroscopic
nutrients with medium chain triglycerides (MCT's) enable enhanced
dermal permeation and therefore expedited dermal regrowth. [0026]
4. Thiamine enables pyruvate dehydrogenase activity to increase by
energizing all cellular rejuvenatory capacity via the CAC cycle and
thus defusing neuropathy, myopathy, vasculopathy and
endocrinopathy. [0027] 5. Riboflavin, in addition to its manifold
attributes, provides the litmus test of transdermal penetration of
this invention by the increased yellow intensity of the urine as
absorption crescendos and later decrescendos. It visually depicts
the transdermal invention as it transits through your body.
[0028] All of these nutrients, whether supplied transdermally or
recruited to the site, play an important role in the accelerated
healing and/or rejuvenation that takes place with this unique
formulation and delivery system.
[0029] Aquaporins ("AQPs") constitute a major conduit for movement
of water across plasma membranes. AQP0 is expressed in the fiber
cells. AQP0, engendered by Histidine, is critical for cell
homeostasis. Several cellular functions have been attributed to
AQP0. In vitro and ex vivo experiments have confirmed the water
permeability function of AQP0. It is my belief that AQP0 performs
cell-to-cell adhesion. There is strong support and empirical data
validating the possible structural role of AQP0 as a cell-to-cell
adhesion protein influencing subdermal ceramides.
BRIEF SUMMARY OF THE INVENTION
[0030] The present invention relates to therapeutic composition
that is comprised of a blend of active and inactive ingredients
that includes specific and highly selective proteins, amino acids,
and nucleic acid molecules. This therapeutic composition has
sequences encoding such proteins, nutrient catalyzing cofactors,
antibodies and short antisense-like molecules existing and innate
within the sub dermal layer. Also included in the present invention
are specific functional methods to enable and utilize such
polypeptides to modulate healing, apoptosis, riboswitch-like
activation and curation of wounds. The active ingredients are all
GRAS ("generally regarded as safe") and all natural. They are
factors in the apoptotic cascade, and in the control and modulation
of said bodily processes specifically present for the purpose of
wound curation and truncation of the insult/injury cycle. The
inherent synergy between components provides for an internal milieu
that utilizes the body's own recovery cycle and the antisense-like
technology underscored by this invention. The present invention
provides a time-staged delivery of beneficial nutrients
transdermally through the medium of a methyl carrier for the
purpose of cellular remodeling, as well as cleavage by a variety of
different caspase proteases that are capable of inhibiting
apoptosis. The amount of nutrients delivered may depend on a
variety of factors, including the molecular size of the nutrients,
the solubility of the nutrients, the condition of the skin that is
being treated, the ambient temperature, the medical condition of
the patient, and whether any other medications or skin ointments
are also being taken by the patient.
[0031] Mitogen-activated protein kinase kinase kinase 1 is an
enzyme that in humans is encoded by the MAP3K1 gene. MAP3K, or MEK
kinase, is a serine/threonine kinase that occupies a pivotal role
in a network of phosphorylating enzymes integrating cellular
responses to a number of mitogenic and metabolic stimuli, including
insulin and many growth factors. Mouse genetics has revealed that
the kinase is important in correct embryogenesis, keratinocyte
migration, T cell cytokine production and B cell antibody
production.
DETAILED DESCRIPTION OF INVENTION
[0032] I have discovered that a variety of nutrients (i.e.
vitamins, trace minerals, fats and select amino acids) delivered
transdermally/topically in a staged and sequential manner, through
the conveyance of a methyl carrier, i.e., a carrier for the methyl
group which can preferably be methyl nicotinate, provide a
meaningful, measureable and significant way to both induce and
transport these active healing substances. This combination of
nutrients, such as amino acids and mineral cofactors, function as a
therapeutic composition and enables the body's own healing and
innate immune system to recreate a healed dermis now in
homeostasis. [0033] 2. The components of the therapeutic
composition include but are not limited to alpha and gamma
tocopherols, B-complex vitamins. Preferably, the composition
includes nicotinic acid, the amino acids glycine and histidine,
histamine, beta-alanine and taurine, copper and magnesium, P-5-P,
polysorbate 20, glycerol, medium chain triglycerides,
glycerophosphocholine ("gpc"), propylene glycol, oleic acid, MN,
Inosine, and water.
Representative Formulation of Ingredients--Percent & Volume
[0034] The therapeutic composition of the present invention
preferably comprises at least one active ingredient component and
at least one inactive ingredient component. The composition is also
preferably a solution that includes as an active component a methyl
nicotinate component in an amount of about 0.1% to about 1.0%, more
preferably from 0.2% to 0.8%, and most preferably from 0.25% to
0.5%. There can be additional active components. These active
components can preferably include one or more of the following:
TABLE-US-00001 Arachidonic Acid ~0-~3%, preferably 0.25%-2.5%, more
preferably 0.5%-2.0%, and most preferably 0.75%-1.5% Amino Acidic
Acid ~0-~5%, preferably 0.5%-4.5%, more preferably 1.0%-4.0%, and
most preferably 1.75%-3.5% Histidine ~0-~8%, preferably 1.5%-7.25%,
more preferably 3.0%-6.0%, and most preferably 4.5%-5.5% Copper
Peptide ~0-~5%, preferably 0.5%-4.5%, more preferably 1.0%-4.0%,
and most preferably 1.75%-3.5% Ascorbyl Palmitate ~0-~3%,
preferably 0.25%-2.5%, more preferably 0.5%-2.0%, and most
preferably 0.75%-1.5% Niacinamide/ ~0-~3%, preferably 0.1%-2.5%,
Nicotinic Acid more preferably 0.3%-2.0%, and most preferably
0.4%-1.5% Histamine ~0-~5%, preferably 0.5%-4.5%, more preferably
1.0%-4.0%, and most preferably 1.75%-3.5% Beta Alanine ~0-~4%,
preferably 0.5%-3.5%, more preferably 1.0%-3.0%, and most
preferably 1.5%-2.5% Hypoxanthine ~0-~2%, preferably 0.25%-1.75%,
Riboside more preferably 0.5%-1.5%, and most preferably 0.75%-1.25%
Mixed Tocopherols ~0-~2%, preferably 0.25%-1.75%, (Vitamin E) more
preferably 0.5%-1.5%, and most preferably 0.75%-1.25% P-5-P ~0-~5%,
preferably 0.5%-4.5%, more preferably 1.0%-4.0%, and most
preferably 1.75%-3.5% Glycine ~0-~2%, preferably 0.1%-1.75%, more
preferably 0.3%-1.5%, and most preferably 0.4%-1.25% Taurine
~0-~2%, preferably 0.25%-1.75%, more preferably 0.5%-1.5%, and most
preferably 0.75%-1.25%
[0035] Conditional Ingredients that may be used include Alpha
Lipoic Acid, Carnosine, and Inosine. The amount of conditional
ingredients used may range from about 0% to about 5% of the
therapeutic composition. Preferably, the amount of conditional
ingredients may range from 0.01% to 2%. However, for wound care
applications, the amount of conditional ingredients may preferably
range from 0.1% to 5%.
[0036] In addition to the active components there is preferably at
least one inactive component in the composition. The inactive
component can include one or more of the following:
TABLE-US-00002 Glycerol ~0-~2%, preferably 0.1%-1.75%, more
preferably 0.3%-1.5%, and most preferably 0.4%-1.25%
Caprylic/Caprylate ~0-~3%, preferably 0.5%-2.75%, Triglycerides
(MCT) more preferably 1.0%-2.5%, and most preferably 1.5%-2.25%
Polysorbate 20 ~0-~1%, preferably 0.1%-0.9%, more preferably
0.2%-0.8%, and most preferably 0.3%-0.7% (sufficient to mix
oils/H20 to give emulsion): preferred is a natural source such as
coconut Propylene Glycol ~0%-~15%, preferably 0.1%-13.75%, more
preferably 0.2%-12.5%, and most preferably 0.3%-11.25% (solvent in
cosmetics) Phosphatidylcholine ~0-~3%, preferably 0.25%-2.5%, more
preferably 0.5%-2.0%, and most preferably 0.75%-1.5%
Lysophosphatidylcholine ~0-~0.1%, preferably 0.005%-0.075%, more
preferably 0.01%-0.05%, and most preferably 0.015%-0.05% Ethanol an
amount sufficient to pass a Micro biological Assay test Glyceryl
Stearate ~0-~1% (emulsifier), preferably 0.1%-0.9%, more preferably
0.2%-0.8%, and most preferably 0.3%-0.7% Oleic Acid (sufficient to
pass thru the dermis only) Tetrasodium EDTA 50-200 ppm (.ltoreq.2%
by weight) preferably (stabilizer) 70-180 ppm, more preferably
90-160 ppm, and most preferably 110-140 ppm Deionized Water balance
of solution
[0037] An example of a preferred composition is as follows wherein
the ingredients are in the form volume percent:
TABLE-US-00003 Active Ingredients (~26.5%-~27%) Methyl Nicotinate
~0.25%-~1% Arachidonic Acid ~1% Amino Acidic Acid ~3% Histidine ~5%
Copper Peptide ~3% Ascorbyl Palmitate ~1% Niacinamide/Nicotinic
Acid ~0.5%-~1% Histamine ~3% Beta Alanine ~2% Hypoxanthine Riboside
~1% Mixed Tocopherols (Vitamin E) ~1% P5P ~3% Glycine ~0.5%-~1%
Taurine ~1%
TABLE-US-00004 Conditional Ingredients Alpha Lipoic Acid,
Carnosine, ~1%, or increase to and/or Inosine ~3% for wound care
only
TABLE-US-00005 Inactive Ingredients Deionized Water balance of
solution Glycerol ~0.5%-~1% Caprylic/Caprylate ~2% Triglycerides
(MCT) Polysorbate 20 ~0.5% (sufficient to mix oils/H20 to give
emulsion), e.g. natural source coconut Propylene Glycol ~0.5%-~10%
max (solvent in cosmetics) Phosphatidylcholine ~1%
Lysophosphatidylcholine ~0.02% Ethanol an amount sufficient to pass
Micro biological Assay test Glyceryl Stearate ~0.5% (emulsifier)
Oleic Acid sufficient to pass thru the dermis only Tetrasodium EDTA
50-200 ppm (stabilizer) (.ltoreq.2% by weight)
[0038] Water is the overall solvent for many of the ingredients,
but to formulate the spray most effectively water and fat-soluble
emulsions must be homogenized for best transdermal bioavailability
and application.
[0039] The components of this mixture are used in a combination in
range used to treat non-medical as well as medical conditions.
Topical and/or transdermal treatment is preferred for local control
of disease states and inflammatory cascade states to insure that
any disapparate and/or unwanted side effects are minimized and
curtailed.
[0040] Varieties or combinations of this therapy include, though
are not limited to the following: [0041] (a) A topical/transdermal
spray using a radiating pump dispenser; [0042] (b) A
topical/transdermal salve/balm rubbed into the skin; [0043] (c) A
topical/transdermal gel w/aloe vera and vitamin E rubbed into the
skin; [0044] (d) A topical/transdermal wound/burn cleansing rinse;
[0045] (e) A topical/transdermal roll-on for pain relief; [0046]
(f) An impregnated mini-sponge individually hermetically sealed
with said composition that can be reconstituted with water; [0047]
(g) A wound powder composed of micronized, freeze dried material
used for pressure ulcers and diabetic wounds, and [0048] (h) A
time-released epidermal/topical patch for staged and sequential
delivery of said composition for site-specific application.
[0049] The therapeutic composition may preferably be administered
about 1-4 times per day on a daily basis until the wound is healed
as desired and/or the skin rejuvenated as desired. In addition, the
therapeutic composition may alternatively be administered on a
bi-weekly, tri-weekly, weekly or monthly basis until the wound is
healed as desired and/or the skin rejuvenated as desired.
Furthermore, the administration may initially begin on a daily
basis and then, in response to clinical improvement, transition to
a weekly, monthly, etc. administration. Rather than being used
solely as a treatment aid, the composition of the present invention
may also be used to maintain a user's skin in good condition.
[0050] The most convenient method of applying the compound is to
spray the compound on the desired site of a user's skin with no
covering or other compounds applied to the location. It is
preferable to leave the compound exposed to air for 15 to 30
minutes after having been applied to the skin. An
osmotic/absorptive gradient can wean the composition from the skin
to the dressing, thereby depriving composition content from the
needy delivery site. Wound cover can be applied as clinically
required.
* * * * *