U.S. patent application number 12/138300 was filed with the patent office on 2008-12-18 for topicial composition for treating pain.
Invention is credited to Arnold L. Oronsky, Bryan T. Oronsky, Neil C. Oronsky.
Application Number | 20080311217 12/138300 |
Document ID | / |
Family ID | 40132558 |
Filed Date | 2008-12-18 |
United States Patent
Application |
20080311217 |
Kind Code |
A1 |
Oronsky; Bryan T. ; et
al. |
December 18, 2008 |
TOPICIAL COMPOSITION FOR TREATING PAIN
Abstract
Topical compositions having as the active ingredient a lipid,
fatty acid ester, natural wax, sterol, or combinations thereof
referred to herein as "lipophilic vehicle" or "LV" and methods of
use, have been developed for the amelioration or prevention of pain
or the sequelae of pain. The composition may be in the form of an
ointment, cream, gel, lotion, spray, foam, paste, patch, suspension
or dispersion. In the preferred embodiment, the formulation is a
gel. The LV may contain a penetration enhancer, most preferably one
with membrane disruptive properties. The formulation may be applied
to or impregnated into a gauze, wrap, bandage, cotton-tipped stick,
adhesive bandage strip, or other support wrap or medical bandage or
wound cover. For example, the compositions may be are incorporated
onto or into disposables such as hemorrhoid wipes, sponge, mouth
guards, dental trays; needles or catheters; adult diapers; gloves,
socks or wrist bands, for ease of application. The composition is
applied topically to a site at or adjacent to a painful region. The
composition is reapplied as necessary. Pain relief is typically
obtained within minutes and lasts for periods of variable duration
ranging from minutes to several hours and even, in some cases,
days. The composition is variably effective to treat visceral,
somatic and neuropathic pain both acute and chronic as well as
muscle pain and stiffness and joint pain and stiffness.
Inventors: |
Oronsky; Bryan T.; (Los
Altos Hills, CA) ; Oronsky; Neil C.; (Los Altos
Hills, CA) ; Oronsky; Arnold L.; (Los Altos Hills,
CA) |
Correspondence
Address: |
MORRISON & FOERSTER LLP
755 PAGE MILL RD
PALO ALTO
CA
94304-1018
US
|
Family ID: |
40132558 |
Appl. No.: |
12/138300 |
Filed: |
June 12, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11851241 |
Sep 6, 2007 |
|
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12138300 |
|
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60943552 |
Jun 12, 2007 |
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Current U.S.
Class: |
424/537 ;
424/725; 424/766; 514/169; 514/552; 514/78 |
Current CPC
Class: |
A61K 31/01 20130101;
A61P 29/02 20180101; A61P 17/00 20180101; A61P 11/00 20180101; A61K
31/19 20130101; A61K 31/215 20130101; A61K 31/23 20130101; A61K
31/045 20130101; A61K 31/685 20130101; A61P 21/00 20180101; A61K
31/56 20130101; A61K 9/0014 20130101; A61P 25/04 20180101; A61P
1/14 20180101; A61P 29/00 20180101; A61P 11/08 20180101; A61P 25/00
20180101; A61K 9/0009 20130101; A61P 3/04 20180101; A61P 19/02
20180101 |
Class at
Publication: |
424/537 ; 514/78;
514/552; 514/169; 424/725; 424/766 |
International
Class: |
A61K 36/00 20060101
A61K036/00; A61K 31/685 20060101 A61K031/685; A61K 31/23 20060101
A61K031/23; A61K 35/00 20060101 A61K035/00; A61P 11/00 20060101
A61P011/00; A61K 31/56 20060101 A61K031/56; A61K 36/185 20060101
A61K036/185; A61K 36/87 20060101 A61K036/87 |
Claims
1. A composition for treating a breathing disorder comprising a
lipophilic vehicle, wherein the lipophilic vehicle itself is
capable of treating the breathing disorder.
2. The composition of claim 1 wherein the breathing disorder is
asthma, chronic obstructive pulmonary disease, dyspnea, obstructive
sleep apnea, or wheezing.
3. The composition of claim 2 wherein the breathing disorder is
obstructive sleep apnea.
4. The composition of claim 1 further comprising a penetration
enhancer.
5. The composition of claim 4 wherein the penetration enhancer
comprises a sulphoxide, an azone, a pyrrolidone, an alcohol, an
alkanol, an ether, a glycol, a surfactant, a terpene, or a
combination thereof.
6. The composition of claim 1 wherein the lipophilic vehicle
comprises a lipid, a phospholipid, a glycolipid, a fatty acid
ester, a natural wax, a sterol, a seed oil, or a combination
thereof.
7. The composition of claim 6 wherein the lipophilic vehicle
comprises a phospholipid.
8. The composition of claim 7 wherein the phospholipid comprises
lecithin.
9. The composition of claim 6 wherein the lipophilic vehicle
comprises a fatty acid ester.
10. The composition of claim 9 wherein the fatty acid ester
comprises isopropyl myristate.
11. The composition of claim 6 wherein the lipophilic vehicle
comprises a natural wax.
12. The composition of claim 11 wherein the natural wax comprises
beeswax or lanolin.
13. The composition of claim 6 wherein the lipophilic vehicle
comprises a seed oil.
14. The composition of claim 13 wherein the seed oil comprises
macadamia nut oil, grape seed oil, cottonseed oil, or sesame
oil.
15. The composition of claim 1 further comprising a hydrophilic
polymer.
16. The composition of claim 15 wherein the hydrophilic polymer
comprises polyethylene glycol.
17. The composition of claim 1 wherein the composition is in the
form of an ointment, cream, gel, lotion, spray, foam, paste,
suspension, or dispersion.
18. The composition of claim 1 further comprising an antimicrobial
or disinfectant.
19. A device for treating a breathing disorder comprising: a) a
substrate; and b) a composition comprising a lipophilic vehicle on
or impregnated within the substrate, wherein the lipophilic vehicle
itself is capable of treating the breathing disorder.
20. The device of claim 19 wherein the breathing disorder is
asthma, chronic obstructive pulmonary disease, dyspnea, obstructive
sleep apnea, or wheezing.
21. The device of claim 20 wherein the breathing disorder is
obstructive sleep apnea.
22. The device of claim 19 wherein the substrate comprises a
bandage, gauze, an adhesive strip, a wipe, a wrap, a sponge, a
swab, a patch, a dressing, or an article of clothing.
23. The device of claim 19 wherein the substrate is configured for
placement around the neck of an individual.
24. A method for treating a breathing disorder comprising topically
applying a lipophilic vehicle at or adjacent to a site associated
with the breathing disorder, wherein the lipophilic vehicle itself
is capable of treating the breathing disorder.
25. The method of claim 24 wherein the breathing disorder is
asthma, chronic obstructive pulmonary disease, dyspnea, obstructive
sleep apnea, or wheezing.
26. The method of claim 24 wherein the breathing disorder is
obstructive sleep apnea.
27. The method of claim 24 wherein the lipophilic vehicle is
topically applied using a substrate.
28. The method of claim 27 wherein the lipophilic vehicle is
applied to the substrate prior to topical application.
29. The method of claim 27 wherein the lipophilic vehicle is
impregnated within the substrate.
30. The method of claim 27 wherein the substrate comprises a
bandage, gauze, an adhesive strip, a wipe, a wrap, a sponge, a
swab, a patch, a dressing, or an article of clothing.
31. The method of claim 27 wherein the substrate is configured for
placement around the neck of an individual.
32. The method of claim 24 further comprising use of a separate
device with the lipophilic vehicle to treat the breathing
disorder.
33. The method of claim 24 further comprising application of
electrotherapy, heat, laser, radiation, ultrasound, or combinations
thereof.
34. The method of claim 24 further comprising topically reapplying
the lipophilic vehicle.
35. A kit comprising: a) a composition comprising a lipophilic
vehicle, wherein the lipophilic vehicle itself is capable of
treating a breathing disorder; and b) optionally, one or more
substrates for applying the composition to a treatment site.
36. The kit of claim 35 wherein the breathing disorder is
obstructive sleep apnea and the one or more optional substrates is
configured for placement around the neck of an individual.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser.
No. 11/851,241, filed Sep. 6, 2007, which claims the benefit of
U.S. Provisional Application Ser. No. 60/943,552, filed Jun. 12,
2007, each of which is hereby incorporated by reference in its
entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to a topical treatment of
acute and chronic pain, which is somatic, visceral, or neuropathic,
as well as joint and muscle stiffness. This treatment also
addresses to some degree the psychologic, vegetative and
medication-induced sequelae of pain (usually chronic) which can
include fatigue, decreased alertness, weight gain, decreased
exercise tolerance, and dyspnea.
BACKGROUND OF THE INVENTION
[0003] Pain is a sensation and a perception that is comprised of a
complex series of mechanisms. In its most simple construction, it
is a signal from the firing of nociception, touch and pressure
receptors in the periphery that is transmitted to the spinal cord
and finally to lower and higher centers of the brain. However, this
signal can be modified in a multitude of ways at each level of the
pain pathway. See e.g. Millan, M. J. (1999) The Induction of Pain:
An Integrative Review, Progress in Neurobiology, 57, 1-164
(Pergamon Press) for an in depth review.
[0004] There are primarily three types of pain, somatic, visceral
and neuropathic which can be acute and chronic. Somatic pain is
caused by the activation of pain receptors in either the cutaneous
or musculoskeletal tissues. In contrast to surface somatic pain
which is usually described as sharp and may have a burning or
pricking quality, deep somatic pain is usually characterized as a
dull, aching but localized sensation Somatic pain may include
fractures in the vertebrae, joint pain (deep somatic pain) and
postsurgical pain from a surgical incision (surface pain).
Inflammatory pain shares elements in common with somatic, visceral
and neuropathic pain since these conditions can induce inflammatory
events. Inflammatory pain is related to tissue damage which can
occur in the form of penetration wounds, burns, extreme cold,
fractures, inflammatory arthropathies as seen in many autoimmune
conditions, excessive stretching, infections, vasoconstriction and
cancer.
[0005] Visceral pain is caused by activation of pain receptors in
internal areas of the body that are enclosed within a cavity. An
example of visceral pain, usually described as pressure-like,
poorly localized and deep, is pancreatitis.
[0006] Neuropathic pain, caused by neural damage, is usually
described as burning, tingling, shooting or stinging but can also
manifest itself as sensory loss either as a result of compression,
infiltration, chemical, metabolic damage or idiopathic. Examples of
neuropathic pain are heterogenous and include medication-induced
neuropathy and nerve compression syndromes such as carpal tunnel,
radiculopathy due to vertebral disk herniation, post-amputation
syndromes such as stump pain and phantom limb pain, metabolic
disease such as diabetic neuropathy, neurotropic viral disease from
herpes zoster and human immunodeficiency virus (HIV) disease, tumor
infiltration leading to irritation or compression of nervous
tissue, radiation neuritis, as after cancer radiotherapy, and
autonomic dysfunction from complex regional pain syndrome
(CRPS).
[0007] Acute pain, termed nociception, is the instantaneous onset
of a painful sensation in response to a noxious stimulus. It is
considered to be adaptive because it can prevent an organism from
damaging itself. For example, removing a hand from a hot stove as
soon as pain is felt can prevent serious burns. The second type of
pain is persistent pain. Unlike acute pain, it usually has a
delayed onset but can last for hours to days. It is predominately
considered adaptive because the occurrence of persistent pain
following injury can prevent further damage to the tissue. For
example, the pain associated with a sprained ankle will prevent the
patient from using the foot, thereby preventing further trauma and
aiding healing. A third category of pain is chronic pain. It has a
delayed onset and can last for months to years. In contrast to
acute and persistent pain, chronic pain is considered maladaptive
and is associated with conditions such as arthritis, nerve injury,
AIDS and diabetes. Yet another type of pain can be termed
breakthrough pain. This is a brief flare-up of severe pain lasting
from minutes to hours that can occur in the presence or absence of
a preceding or precipitating factor even while the patient is
regularly taking pain medication. Many patients experience a number
of episodes of breakthrough pain each day.
[0008] Many types of pain control are systemic in nature. These
also have systemic side effects, such as stomach ulcers in the case
of some of the non-steroidal anti-inflammatories ("NSAIDS"),
hepatotoxicity from acetaminophen, constipation, CNS effects,
respiratory depression, drug tolerance, dependence, and addiction
from opioid narcotics and impotence and decreased libido from
antidepressants. In the case of chronic pain, the side effects from
these systemic medications sometimes can be controlled only with
the addition more systemic medications which in turn have their own
side effects such as the psychostimulant Ritalin to help counteract
the symptoms of opioid-related drowsiness. In addition, the
psychologic component of chronic pain can lead to fatigue, weight
gain, increased appetite, decreased concentration and awareness,
decreased energy, and psychomotor retardation which often require
further adjunctive therapy such as antidepressants and stimulants.
Associated comorbid conditions such as COPD, asthma, and
hypertension can lead to dyspnea and decreased exercise tolerance,
thereby exacerbating the downward spiral and depression which often
characterizes chronic pain syndromes and necessitates further
adjunctive treatment. Moreover, most topical treatments to control
pain are of limited efficacy or last only for a few minutes, such
as the lidocaine sprays and patches and benzocaine ointments.
[0009] Pain of all types can be debilitating both psychologically
and physically and exacts an enormous toll in dollars, decreased
productivity, and quality of life. Therefore, formulations for
prevention or alleviation of pain that are effective, safe, allow
for increased levels of patient control, and in some measure affect
the important psychologic, vegetative and medication-related
sequelae of pain symptoms and treatment are needed in order to
increase functionality and decrease the use of systemic medications
with their attendant side effects.
[0010] It is therefore an object of the present invention to
provide topical formulations providing pain relief for periods of
varying durations lasting from minutes, to hours to days depending
on the patient and the type of pain and painful lesion or
syndrome.
SUMMARY OF THE INVENTION
[0011] Topical compositions having as the active ingredient one or
more of a lipid, fatty acid ester, natural wax, sterol, or
combinations thereof referred to herein as "lipophilic vehicle" or
"LV" and methods of use, have been developed for the amelioration
or prevention of pain or the sequelae of pain. The composition may
be in the form of an ointment, cream, gel, lotion, spray, foam,
paste, patch, suspension or dispersion. In the preferred
embodiment, the formulation is a gel. The LV may contain a
penetration enhancer, most preferably one with membrane disruptive
properties.
[0012] The formulation may be applied to or impregnated into a
gauze, wrap, bandage, cotton-tipped stick, adhesive bandage strip,
or other support wrap or medical bandage or wound cover. For
example, the compositions may be are incorporated onto or into
disposables such as hemmorhoid wipes, sponge, mouth guards, dental
trays; needles or catheters; adult diapers; gloves, socks or wrist
bands, for ease of application.
[0013] The composition is applied topically to a site at or
adjacent to a painful region. The composition is reapplied as
necessary. Pain relief is typically obtained within minutes and
lasts for periods of variable duration ranging from minutes to
several hours and even, in some cases, days. The compounds are
applied such that the dosage is sufficient to provide an effective
dose in the painful area or immediately adjacent areas, to
ameliorate or eliminate pain. The composition is variably effective
to treat visceral, somatic, inflammatory and neuropathic pain both
acute and chronic as well as muscle pain and stiffness and joint
pain and stiffness. Examples demonstrate pain relief in human
patients for a wide number of conditions, including joint, muscle
and tendon pain, joint, muscle and tendon immobility, inflammatory
pain, neuropathies, muscle spasms, osteoarthritis, breathing
disorders such as wheezing, hunger pains, some types of headaches,
dysphagia, fibromyalgia, autoimmune disorders, dysmennorhea,
post-surgical pain, anal fissures and visceral pain resulting from
chronic and pancreatitis.
DETAILED DESCRIPTION OF THE INVENTION
I. Definitions
[0014] "Water Soluble" as used herein refers to substances that
have a solubility of greater than or equal to 5 g/100 ml water.
[0015] "Lipid Soluble" as used herein refers to substances that
have a solubility of greater than or equal to 5 g/100 ml in a
hydrophobic liquid such as castor oil.
[0016] "Hydrophilic" as used herein refers to substances that have
strongly polar groups that readily interact with water.
[0017] "Lipophilic" refers to compounds having an affinity for
lipids.
[0018] "Amphiphilic" refers to a molecule combining hydrophilic and
lipophilic (hydrophobic) properties
[0019] "Hydrophobic" as used herein refers to substances that lack
an affinity for water; tending to repel and not absorb water as
well as not dissolve in or mix with water.
[0020] An "oil" is a composition containing at least 95% wt of a
lipophilic substance. Example lipophilic substances include but are
not limited to naturally occurring and synthetic oils, fats, fatty
acids, lecithins, triglycerides and combinations thereof.
[0021] An "emulsion" is a composition containing a mixture of
non-miscible components homogenously blended together. In
particular embodiments, the non-miscible components include a
lipophilic component and an aqueous component. An emulsion is a
preparation of one liquid distributed in small globules throughout
the body of a second liquid. The dispersed liquid is the
discontinuous phase, and the dispersion medium is the continuous
phase. When oil is the dispersed liquid and an aqueous solution is
the continuous phase, it is known as an oil-in-water emulsion,
whereas when water or aqueous solution is the dispersed phase and
oil or oleaginous substance is the continuous phase, it is known as
a water-in-oil emulsion. Either or both of the oil phase and the
aqueous phase may contain one or more surfactants, emulsifiers,
emulsion stabilizers, butters, and other excipients. Preferred
excipients include surfactants, especially non-ionic surfactants;
emulsifying agents, especially emulsifying waxes; and liquid
non-volatile non-aqueous materials, particularly glycols such as
propylene glycol. The oil phase may contain other oily
pharmaceutically approved excipients. For example, materials such
as hydroxylated castor oil or sesame oil may be used in the oil
phase as surfactants or emulsifiers.
[0022] "Emollients" are an externally applied agent that softens or
soothes skin and are generally known in the art and listed in
compendia, such as the "Handbook of Pharmaceutical Excipients", 4th
Ed., Pharmaceutical Press, 2003. These include, without limitation,
almond oil, castor oil, ceratonia extract, cetostearoyl alcohol,
cetyl alcohol, cetyl esters wax, cholesterol, cottonseed oil,
cyclomethicone, ethylene glycol palmitostearate, glycerin, glycerin
monostearate, glyceryl monooleate, isopropyl myristate, isopropyl
palmitate, lanolin, lecithin, light mineral oil, medium-chain
triglycerides, mineral oil and lanolin alcohols, petrolatum,
petrolatum and lanolin alcohols, soybean oil, starch, stearyl
alcohol, sunflower oil, xylitol and combinations thereof. In one
embodiment, the emollients are ethylhexylstearate and ethylhexyl
palmitate.
[0023] "Surfactants" are surface-active agents that lower surface
tension and thereby increase the emulsifying, foaming, dispersing,
spreading and wetting properties of a product. Suitable non-ionic
surfactants include emulsifying wax, glyceryl monooleate,
polyoxyethylene alkyl ethers, polyoxyethylene castor oil
derivatives, polysorbate, sorbitan esters, benzyl alcohol, benzyl
benzoate, cyclodextrins, glycerin monostearate, poloxamer, povidone
and combinations thereof. In one embodiment, the non-ionic
surfactant is stearyl alcohol.
[0024] "Emulsifiers" are surface active substances which promote
the suspension of one liquid in another and promote the formation
of a stable mixture, or emulsion, of oil and water. Common
emulsifiers are: metallic soaps, certain animal and vegetable oils,
and various polar compounds. Suitable emulsifiers include acacia,
anionic emulsifying wax, calcium stearate, carbomers, cetostearyl
alcohol, cetyl alcohol, cholesterol, diethanolamine, ethylene
glycol palmitostearate, glycerin monostearate, glyceryl monooleate,
hydroxpropyl cellulose, hypromellose, lanolin, hydrous, lanolin
alcohols, lecithin, medium-chain triglycerides, methylcellulose,
mineral oil and lanolin alcohols, monobasic sodium phosphate,
monoethanolamine, nonionic emulsifying wax, oleic acid, poloxamer,
poloxamers, polyoxyethylene alkyl ethers, polyoxyethylene castor
oil derivatives, polyoxyethylene sorbitan fatty acid esters,
polyoxyethylene stearates, propylene glycol alginate,
self-emulsifying glyceryl monostearate, sodium citrate dehydrate,
sodium lauryl sulfate, sorbitan esters, stearic acid, sunflower
oil, tragacanth, triethanolamine, xanthan gum and combinations
thereof. In one embodiment, the emulsifier is glycerol
stearate.
[0025] A "lotion" is an emulsion having a viscosity of between 100
and 1000 centistokes.
[0026] A "cream" is an emulsion having a viscosity of greater than
1000 centistokes, typically in the range of 20,000-50,000
centistokes.
[0027] A "paste" is a liquid or emulsion having solid material
homogenously suspended therein, typically in a lotion cream or
gel.
[0028] A "gel" is a composition containing a thickening agent or
polymeric material dissolved or suspended in a liquid. The liquid
may include a lipophilic component, an aqueous component or both.
Some emulsions may be gels or otherwise include a gel component.
Some gels, however, are not emulsions because some do not contain a
homogenized blend of immiscible components.
[0029] "Penetration enhancers" are used to promote transdermal
delivery of drugs across the skin, in particular across the stratum
corneum. These can be chemical penetration enhancers or physical
penetration enhancers, such as ultrasound.
[0030] Skin protectants can be included in compositions formulated
for topical administration. Such agents not only soothe the site of
infection but may also aide in maintaining the integrity of the
skin to prevent additional damage. Suitable skin protectants
include allantoin; cocoa butter; dimethicone; kaolin; shark liver
oil; petrolatum; lanolin; vegetable oils; ethoxylated oils and
lipids; polymers such as polyalkylene oxides, polyvinylpyrrolidone,
polyvinyl alcohol, poly(meth)acrylates, ethylvinyl acetate,
polyalkylene glycols; polysaccharides and modified polysaccharides
such as hyaluronic acid, cellulose ethers, cellulose esters,
hydroxypropyl methylcellulose, crosscarmelose, and starch; natural
gums and resins which may be gelling or non-gelling such as
alginates, carrageenans, agars, pectins, glucomannans (guar, locust
bean, etc.), galactomannans (e.g. konjac), gum arabic, gum
traganth, xanthan, schleroglucan and shellac; and colloidal
insolubles such as zinc oxide and other insoluble zinc salts,
talcum powder and other micronized natural minerals; and colloidal
silicas, aluminas and other metal oxides.
[0031] Buffers are used to control pH of a composition. Preferably,
the buffers buffer the composition from a pH of about 4 to a pH of
about 7.5, more preferably from a pH of about 4 to a pH of about 7,
and most preferably from a pH of about 5 to a pH of about 7. In a
preferred embodiment, the buffer is triethanolamine.
[0032] Preservatives can be used to prevent the growth of fungi and
microorganisms. Suitable antifungal and antimicrobial agents
include, but are not limited to, benzoic acid, butylparaben, ethyl
paraben, methyl paraben, propylparaben, sodium benzoate, sodium
propionate, benzalkonium chloride, benzethonium chloride, benzyl
alcohol, cetypyridinium chloride, chlorobutanol, phenol,
phenylethyl alcohol, and thimerosal.
II. Compositions
[0033] As demonstrated by the examples, it has been discovered that
certain lipophilic vehicles can alleviate or prevent pain from a
variety of different souces, when applied topically. Although the
vehicles can also be used for drug delivery, drug is not required
for efficacy.
[0034] A. Lipophilic Vehicles
[0035] Topical compositions having as the active ingredient a lipid
(e.g., glycolipids, phospholipids), fatty acid ester, natural wax,
sterol, and combinations thereof referred to herein as a
"lipophilic vehicle" ("LV") have been developed and tested for
alleviation of a variety of different types of pain. The
formulation typically includes excipients that are amphiphilic,
hydrophobic, lipophilic and/or surface active. These are used to
form an ointment, cream, gel, lotion, spray, foam, paste, patch,
suspension or dispersion, for topical application to the skin or
mucosal surface. In the preferred embodiment, the formulation is a
gel. The gel is preferably an organo gel.
[0036] The active ingredient can be a hydrophilic polymer, such as,
in combination with a lipid, fatty acid ester, or sterol, or
combinations thereof (e.g., PLO) or mono or diesters of a
hydrophilic polymer (e.g., polyoxyl 40 stearate). Suitable LVs
include Pluronic.RTM. F-127 gel containing lecithin and isopropyl
myristate; Van Pen.RTM.; PCCA cosmetic HRT cream; a 50:50 mixture
of ACAI Berry Blend and Aquaphor; mixtures of polyethylene glycol
("PEG"), glycerin, and isopropyl myristate; mixtures of lecithin
and isopropyl myristate; pluronic gel; sesame oil; cottonseed oil;
ointment base containing beeswax and lanolin; and detergents, such
as Dawn.RTM.. Pluronic.RTM. F-127 is a polaxamer surfactant which
is an ABA-type block copolymer containing 70% polyethylene oxide
(PEO). The molecular weight is 12,500 Daltons. Upon cooling,
Pluronic.RTM. F-127 becomes a liquid, while at higher temperatures,
the material is a solid or semi-solid. DMSO and lecitihin/isopropyl
plamitate can be added to Pluronic.RTM. F-127 to increase
absorption through the skin.
[0037] Additional LVs that provided pain relief include 20%
pluronic gel+lecithin/isopropyl
myristate+PEG+glycerin+pharmaceutical grade sesame oil; Oleic
acid+AQUAPHOR.TM., VersaBase cream PCCA ("Professional Compounding
Centers of America"), and PCCA Emollient Cream.
[0038] Lecithin
[0039] Lecithin is a mixture of glycolipids, triglycerides, and
phospholipids (e.g. phosphatidylcholine, phosphatidylethanolamine,
and phosphatidylinositol). Lecithin is also used as a synonym for
pure phosphatidylcholine, a phospholipid which is the major
component of a phosphatide fraction which may be isolated from
either egg yolk or soy beans from which it is mechanically or
chemically extracted using hexane.
[0040] Lecithin is regarded as a well-tolerated and non-toxic
surfactant. It is approved by the United States Food and Drug
Administration for human consumption with the status "Generally
Recognized As Safe" (GRAS). Lecithin is an integral part of cell
membranes, and can be completely metabolized by the body. Lecithin
is used commercially in substances requiring a natural emulsifier
and/or lubricant, from pharmaceuticals to protective coverings.
[0041] Isopropyl Myristate
[0042] Isopropyl myristate is the ester of isopropanol and myristic
acid. It is a simple 12 carbon fatty acid ester. Isopropyl
myristate is used in cosmetic and topical medicinal preparations
where good absorption through the skin is desired.
[0043] Van Pen.RTM.
[0044] Van Pen.RTM. is a commercially available pharmaceutical base
which contains soya lecithin, isopropyl palmitate, stearic acid,
glycerol monostearate, isopropyl myristate, and polyoxyl 40
stearate. Soya lecithin and isopropyl myristate are described
above.
[0045] Isopropyl palmitate is the ester of isopropanol and palmitic
acid. Palmitic acid, is one of the most common saturated fatty
acids found in animals and plants. As its name indicates, it is a
major component of the oil from palm trees (palm oil and palm
kernel oil). Palmitic acid is the first fatty acid produced during
lipogenesis (fatty acid synthesis) and from which longer fatty
acids can be produced. Palmitate negatively feeds back on
acetyl-CoA carboxylase (ACC) which is responsible for converting
acetyl-ACP to malonyl-ACP on the growing acyl chain, thus
preventing further palmitate generation.
[0046] Glycerol fatty acid esters are used as emulsifiers or oiling
agents for foods, spin finishes and textiles; antifoaming and
antistatic agents for plastics; and lubricants, water treatment,
metal working fluids, and dispersing agents. End applications
include cosmetics, foods, personal care products, medicine,
pesticides, paper making, plastics and paints.
[0047] Polyoxyl 40 Stearate is a mixture of the monostearate and
distearate esters of a condensation polymer,
H(OCH2CH2)n-OCOC.sub.16H.sub.32CH.sub.3 (n is approximately 40). It
is a nonionic surface-active agent used as an emulsifying agent in
hydrophilic ointments and other emulsions.
[0048] PCCA Cosmetic HRT Cream
[0049] HRT cream is a base used for the formulation of cosmetics.
HRT cream contains caprylic triglycerides; macadamia oil; grapeseed
oil; and vitamin A palmitate.
[0050] Caprylic/capric triglyceride (CCT) is a mixture of triesters
of caprylic and capric acids, is a highly refined medium chain
triglyceride (MCT) oil possessing excellent oxidation stability
with an almost indefinite shelf life. CCT is a desirable emollient
with quick skin penetration. CCT is colorless, odorless, and
tasteless.
[0051] Macadamia oil (or Macadamia nut oil) is a non-volatile oil
expressed from the nut meat of the macadamia (Macadamia
integrifolia) tree. Macadamia oil is sometimes used in food as a
frying or salad oil, and in cosmetic formulations as an emollient
or fragrance fixative. Macadamia oil contains approximately 60%
oleic acid, 19% palmitoleic acid, 2.8% Linoleic acid and 1%
Linolenic acid. It also contains 3% omega-6 and 3% omega-3.
Although macadamia is cultivated in many different parts of the
world, the oil's fatty acid profile is not greatly influenced by
environmental factors. The oil displays chemical properties typical
of a vegetable triglyceride oil.
[0052] Grape seed oil (also called grapeseed oil or grape oil) is a
vegetable oil pressed from the seeds of various varieties of Vitis
vinifera grapes, an abundant by-product of winemaking. Grape seed
oil is used for in salad dressings, marinades, deep frying,
flavored oils, baking, massage oil, sunburn repair lotion, hair
products, body hygiene creams, lip balm and hand creams.
[0053] Grape seed oil is a preferred cosmetic ingredient for
damaged and stressed tissues, possessing regenerative and
restructuring qualities which allow for better control of skin
moisturization. Grape seed oil can help skin retain the normal
structure of epithelium cells and nerve cells via supporting the
cell membranes. It is noted to be especially effective for repair
of the skin around the eyes. Used as an all-over skin moisturizer,
grape seed oil is known to reduce the look of stretch marks. A
light, thin oil, grape seed oil leaves a glossy film over the skin
when used as a carrier oil for essential oils in aromatherapy.
[0054] Grape seed oil contains 69-78% omega-6 (linoleic acid);
15-20% omega-9 (oleic acid); 5-11% palmitic acid; 3-6% stearic
acid; 0.1-3% omega-3 (linolenic acid); and 0.5-0.7% palmitoleic
acid. Grape seed oil contains more linoleic acid than many other
carrier oils.
[0055] Retinyl palmitate, or vitamin A palmitate, is a common
vitamin supplement, having the formula C.sub.36H.sub.60O.sub.2. It
is available in both oral and injectable forms for treatment of
vitamin A deficiency, under the brand names Aquasol A.RTM. and
Palmitate A.RTM.. [0056] 50:50 ACAI Berry Blend+Aquaphor
[0057] This blend contains omega-6 and omega-9, which are discussed
above. The blend also contains phytonutrients, phytosterols,
polyphenolics and anthocyanins, vitamins, minerals, amino acids,
antioxidants, anti-inflammatories, anti-mutagenics and
anti-bacterials derived from the berry extracts. Aquaphor is a
formulation containing 95% petrolatum.
[0058] Sesame Oil
[0059] Sesame Oil. (also known as gingerly oil and til oil) is an
organic oil derived from sesame. Sesame oil is composed of the
following fatty acids:
TABLE-US-00001 Fatty acid Nomenclature Minimum Maximum Palmitic
C16:0 7.0% 12.0% Palmitoleic C16:1 trace 0.5% Stearic C18:0 3.5%
6.0% Oleic C18:1 35.0% 50.0% Linoleic C18:2 35.0% 50.0% Linolenic
C18:3 trace 1.0% Eicosenoic C20:1 trace 1.0%
[0060] Sesame oil is known for its ability to penetrate the skin
easily, nourishing and detoxifying even the deepest tissue layers.
Sesame oil is unique in that, it has the highest concentration of
omega-6 fatty acids. The most common omega-6 fatty acids are
linoleic, gamma-linolenic acid, eicosadienoic,
dihomo-gamma-linoenic acid, arachidonic acid, docosadieoic acid,
adrenic acid, and docosapentanoic acid. At the same time, the oil
contains two natural-occurring preservatives, sesamol and sesamin.
As a result, sesame oil is the only oil which has a high percentage
of polyunsaturates that also keeps at room temperature.
[0061] Cottonseed Oil
[0062] Cottonseed oil is a vegetable oil extracted from the seeds
of the cotton plant after the cotton lint has been removed. It must
be refined to remove gossypol, a naturally occurring toxin that
protects the cotton plant from insect damage. Therefore, unrefined
cottonseed oil is sometimes used as a pesticide. In its natural
unhydrogenated state, cottonseed oil, like all vegetable oils, has
no cholesterol. It also contains no trans fatty acids. However, it
does contain over 50% Omega-6 fatty acids and trace amounts of
Omega-3 fatty acids. Cottonseed oil is rich in palmitic acid
(22-26%), oleic acid (15-20%), linoleic acid (49-58%) and 10%
mixture of arachidic acid, behenic acid and lignoceric acid.
[0063] Beeswax and Lanolin Ointment Base
[0064] Beeswax is obtains bee hives, specifically the hive of any
species of honey bee (the genus Apis). The main components of
beeswax are palmitate, palmitoleate, hydroxypalmitate and oleate
esters of long-chain (30-32 carbons) aliphatic alcohols, with the
ratio of triacontanylpalmitate
CH.sub.3(CH.sub.2).sub.29O--CO--(CH.sub.2).sub.14CH.sub.3 to
cerotic acid CH.sub.3(CH.sub.2).sub.24COOH, the two principal
components, being 6:1.
[0065] Lanolin, also known as Adeps Lanae, wool wax, wool fat, or
wool grease, is a greasy yellow substance obtained from
wool-bearing animals. Lanolin is useful as a skin ointment, a
water-proofing wax, and a raw material (such as in shoe
polish).
[0066] Lanolin is chiefly a mixture of cholesterol and the esters
of several fatty acids. Crude (non-medical) grades of lanolin also
contain wool alcohols, which are an allergen for some people.
Recent studies also indicate that antibiotics are present in the
lanolin. The extract is insoluble in water, but forms an emulsion.
At one point, the name Lanolin was trademarked as the generic term
for a preparation of sheep fat and water.
[0067] Medical grade lanolin is used as a cream to soothe skin. It
is pure, hypoallergenic, and bacteriostatic. This grade of lanolin
can also be used to treat chapped lips, diaper rash, dry skin,
itchy skin, rough feet, minor cuts, minor burns and skin abrasions.
As an ointment base, it readily absorbs through skin, facilitating
absorption of the medicinal chemicals it carries.
[0068] Lanolin is classified chemically as a wax, containing a
complex mixture of naturally occurring esters and poly-esters of 33
high molecular weight alcohols (principally sterols) and 36 fatty
acids. It is 98% ester minimum, of which the fatty alcohols and
fatty acids comprise an approximately 50/50 ratio.
[0069] The typical composition of lanolin is shown below:
[0070] Esters of sterols and triterpene alcohols 35.4%
[0071] Esters of aliphatic alcohols 23.7%
[0072] Monohydroxyesters of sterols and of triterpene and aliphatic
alcohols 20.0%
[0073] Di- and polyhydroxyesters and free diols 7.9%
[0074] Free aliphatic alcohols 5.6%
[0075] Free Sterols 4.1%
[0076] Free hydrocarbons 0.6%
[0077] Free fatty acids 0.5%
[0078] Unknowns 2.2%
[0079] In a preferred embodiment, the LV penetrates into the skin.
The LV may contain a penetration enhancer, most preferably one with
membrane disruptive properties. One long-standing approach for
improving transdermal drug delivery uses penetration enhancers
(also called sorption promoters or accelerants) which penetrate
into skin to reversibly decrease the barrier resistance. Numerous
compounds have been evaluated for penetration enhancing activity,
including sulphoxides (e.g., dimethylsulfoxide ("DMSO") and
decylmethylsulfoxide (C10MSO)), Azones (e.g. laurocapram),
pyrrolidones (for example 2-pyrrolidone, 2P), alcohols and alkanols
(ethanol, or decanol), glycols (for example propylene glycol, PG, a
common excipient in topically applied dosage forms), surfactants
(also common in dosage forms) and terpenes. Many potential sites
and modes of action have been identified for skin penetration
enhancers, such as the intercellular lipid matrix in which the
accelerants may disrupt the packing motif, the intracellular
keratin domains, or through increasing drug partitioning into the
tissue by acting as a solvent for the permeant within the membrane.
Further potential mechanisms of action, for example with the
enhancers acting on desmosomal connections between corneocytes or
altering metabolic activity within the skin, or exerting an
influence on the thermodynamic activity/solubility of the drug in
its vehicle are possible.
[0080] Preferred penetration enhancers include the sulfoxide
decylmethylsulfoxide (C.sub.10MSO); ethers such as diethylene
glycol monoethyl ether, dekaoxyethylene-oleylether, and diethylene
glycol monomethyl ethers; surfactants, fatty acids such as C8-C22
and other fatty acids, C8-C22 fatty alcohols, and polyols. Other
suitable penetration enhancers include, but are not limited to,
urea, (carbonyldiamide), imidurea, N,N-diethylformamide,
N-methyl-2-pyrrolidine, 1-dodecal-azacyclopheptane-2-one, calcium
thioglycate, 2-pyyrolidine, N,N-diethyl-m-toluamide, oleic acid and
its ester derivatives, such as methyl, ethyl, propyl, isopropyl,
butyl, vinyl and glycerylmonooleate, sorbitan esters, such as
sorbitan monolaurate and sorbitan monooleate, other fatty acid
esters such as isopropyl laurate, isopropyl myristate, isopropyl
palmitate, diisopropyl adipate, propylene glycol monolaurate,
propylene glycol monooleatea and non-ionic detergents such as
Brij.RTM. 76 (stearyl poly(10 oxyethylene ether), Brij.RTM. 78
(stearyl poly(20)oxyethylene ether), Brij.RTM. 96 (oleyl
poly(10)oxyethylene ether), and Brij.RTM. 721 (stearyl poly (21)
oxyethylene ether) (ICI Americas Inc. Corp.). Fatty acids such as
linoleic acid, capric acid, lauric acid, and neodecanoic acid,
which can be in a solvent such as ethanol or propylene glycol, can
be used as lipid bilayer disrupting agents. DMSO is not a
particularly preferred penetration enhancer due to its strong odor
and the fact that it is not approved for use in humans by the Food
and Drug Administration.
[0081] Detergents such as Dawn.RTM. detergent contain sodium lauryl
sulfate, sodium pareth-23. Sodium dodecyl sulfate (or sulphate)
(SDS or NaDS) (C.sub.12H.sub.25NaO.sub.4S), also known as sodium
lauryl sulfate (SLS), is an ionic surfactant that is used in
household products such as toothpastes, shampoos, shaving foams and
bubble baths for its thickening effect and its ability to create a
lather. The molecule has a tail of 12 carbon atoms, attached to a
sulfate group, giving the molecule the amphiphilic properties
required of a detergent.
[0082] C. Drugs
[0083] The LV containing the penetration enhancer can be
administered alone or in combination with another penetration
enhancer or with a pharmaceutical agent, for example, one or more
of vasodilators and antihypertensives, anticonvulsant, membrane
stabilizer, and/or psychoactive drugs (for example,
anti-depressants). Other classes of bioactives include
chemotherapeutic agents for treatment of cancer. The LVs can be
used in combination with antibiotics in cutaneous application to
enhance delivery of antibiotic to wounds and to simultaneously
provide pain relief. The LVs can be used in combination with
chemotherapeutic agents in cutaneous application to enhance
delivery of chemotherapeutic agents and to provide pain relief. The
LVs can be used in combination with minerals such as calcium and
phosphorus in cutaneous application in the treatment of
osteoporosis or bone fractures to provide enhanced diffusion and
pain relief. The LVs can be used in combination with adrenaline or
noradrenaline in a cutaneous application to reduce pain and to
cause localized vasoconstriction in order to keep another drug or
substance in a localized space. The LVs can be used in combination
with other appetite-suppressants and obesity medications such as
phenteramine to enhance appetite-suppressing effects of LVs.
Alternatively, the LVs can be used in combination with other
appetite-stimulating medications such as Megace, corticosteroids,
and Marinol to counteract appetite-suppressing effects of LVs. The
LVs can be used in combination with bronchodilators, mucolytics,
expectorants to enhance bronchodilating effects of LVs. The LVs can
be used in combination with other decongestants and antihistamines
both nasal and systemic to enhance decongestant effects of LVs. LVs
can also be used in combination with other stimulant medications
such as Provigil.RTM., caffeine and Ritalin.RTM., Adderal.RTM.l and
Concerta.RTM. in order to enhance wakefulness-promoting effects of
LVs. LVs can also be used in combination with other hypnotic or
sedating medications to counteract wakefulness-promoting effects of
LVs. LVs can be used in combination with other medications that
increase the tightness of bladder neck sphincter such as Detrol to
enhance the anti-incontinence effects of LVs. Alternatively, the
LVs can be used in combination with other medications such as
alpha-2 blockers to counteract the urinary retention induced by
LVs. LVs can be administered in combination with immunosuppresive
agents in cutaneous application directly over joints in autoimmune
diseases and inflammatory arthropathies to provide diffusion of
these agents directly into the joint or joints and to provide pain
relief. LVs can be administered in combination with vasodilators in
cutaneous application for anginal pain both to provide enhanced
diffusion of these agents and to provide enhanced pain relief. LVs
can be administered in combination with BoTox and other therapeutic
toxins and antitoxins to provide localized pain relief and enhanced
penetration. Finally, LVs can be administered in combination with
corticosteroids and antihistamines in cutaneous application over
joints, nerves and skin lesions such as psoriasis, eczema,
scleroderma, urticaria to provide enhanced penetration and pain
relief. In one embodiment, the LVs are provided in combination with
dyes and other markers to provide enhanced penetration of dyes and
markers along with pain relief.
[0084] The LVs may be applied topically directly before, after or
simultaneously with a beta-2 agonist like albuterol or an
anticholinergic like ipratropium bromide to enhance the effects of
the LV.
[0085] An effective amount is generally in the range of 10% by
weight or less, more preferably 5% by weight or less, most
preferably in the range equivalent to 2% by weight of a nitrate
such as nitroglycerin.
[0086] D. Formulations
[0087] The LVs can be administered directly or used in combination
with a composition, device or formulation. For example, the LV can
be impregnated onto or into bandages or adhesive strips such as
Band-Aids.RTM.. These will then alleviate pain, prevent sticking to
the wound, and allow the absorbent material to absorb liquid and
protect the injury.
[0088] The LVs can be administered as a gauze, sponge, cotton swab
(one or two sided or ended), wrap, patch, dressing, medication pad,
tissue, pain-relief gel pack, lip balm, poultice, plaster, or
compress.
[0089] The LVS can be applied within, on or in devices such as
gloves, socks, wrist bands. The LVs can be impregnated into a wipe
for use in alleviating pain from hemorrhoids or anal fissures. The
gloves, socks or wristbands may have the formulation applied to the
inside as a coating, impregnated into the fibers, or provided as a
separate applicator for administration at the time of application.
They may be applied as built-in or attach-on disposable pads to
mattresses and pillows such as cervical pillows. The LVs may be
applied to cushioned insoles and corn and bunion pads to help
alleviate pain in the feet. The LVs may be applied on, in or to
compression stockings such as TED hose or Jobst stockings to
alleviate the pain of varicose veins and superficial
thrombophlebitis.
[0090] The LVs may be used in facial tissues to soothe or prevent
the sore or chapped skin under or around the nose with allergies or
upper respiratory infections.
[0091] They may be used to coat medical instruments to ease the
pain of their insertion and simultaneously to provide lubrication
such as with a catheter.
[0092] They may be used to coat metal-containing items such as
jewelry, hooks, zippers, pens, snaps and tools for individuals who
have metal allergies and in particular nickel sensitivity.
[0093] They may be applied to mechanical braces, sleeves, corsets
and girdles, splints, casts, prostheses and the like to provide
analgesia along with the functional and positional support provided
by the orthoses.
[0094] They may be applied as built-in or attach-on disposable pads
to superficial heating devices such as electric heating pads,
rubber hot water bottles, warm fluid heat packs, chemical hot packs
and therapeutic cold modalities such as ice packs or added to
vapocoolant sprays. They may be used in concert with modalities of
electrotherapy such as iontophoresis, TENS, muscle stimulation, and
diathermy or applied to the electrodes of these devices. They may
be used in concert with radiation therapy such as infrared,
ultraviolet and cold laser.
[0095] Examples of disposables include patches, hemorrhoid wipes,
medication pads, dressings, gauze, sponges, bandages, tissues,
wraps, pain-relief gel packs and beds, swabsticks and Q-tips,
poultices, plasters and compresses; devices and equipment for
injury protection, increased mobility, functional and positional
support and correction such as orthotics, braces, TED hose and
other support stockings, crutches, casts, splints, prosthetics,
girdles and corsets, hot water bottles, inserts, insoles and arch
supports, pads (e.g. corn and bunion) exercise equipment, cooling
or heating devices, mattresses, pillows, chucks and bed liners and
mouth guards; medical, dental and surgical implants, equipment and
supplies such as dental trays, dental bridges, dentures, crowns,
floss, picks, needles, lancets, rods, stents, blades, probes,
stylets, tubes, scissors, clamps, retractors, forceps, endoscopes,
mammography compression plates, cannulas or catheters; articles of
clothing and footwear including shoes, shoelaces, socks, gloves,
caps, scarves, leotards, head bands, wrist bands, gloves and adult
diapers, pads, guards and liners. Additional materials include
patches, bandages or dressings for use around the neck to decrease
obstructive sleep apnea.
[0096] The LVs may be applied as built-in or attach-on disposable
pads to mattresses and pillows such as cervical pillow. The LVs may
be applied to bed underpads and chucks to alleviate the pain of bed
sores and to promote continence. The LVs may be applied to
cushioned insoles and corn and bunion pads to help alleviate pain
in the feet. The LV may be applied on, in or to compression
stockings such as TED hose or Jobst stockings to alleviate the pain
of varicose veins and superficial thrombophlebitis.
[0097] The LVs may be applied to one end of a two-sided swabstick.
The other end of the swabstick could contain a disinfectant like
alcohol or iodine or an antihistamine or anti-inflammatory as well
as antibiotics, chemotherapeutic agents, minerals and vitamins,
appetite-suppressants and obesity medications such as phenteramine
or appetite-stimulating medications such as Megace,
immunosuppresive agents, vasodilators like nitrates, BoTox and
other therapeutic toxins and antitoxins, dyes and other markers.
The LVs may be applied to one side of a two-sided patch. The other
side can contain antibiotics, chemotherapeutic agents, minerals and
vitamins, appetite-suppressants and obesity medications such as
phenteramine or appetite-stimulating medications such as Megace,
corticosteroids, immunosuppresive agents, vasodilators like
nitrates, BoTox and other therapeutic toxins and antitoxins,
corticosteroids, antihistamines, dyes and other markers.
[0098] The may be used to coat a device such as a mouth guard, tray
for whitening teeth or taking teeth impressions. Typically these
will be applied as a paste, gel or film to the device at the time
of use.
[0099] The LVs can be incorporated into cosmetics or makeup, to
reduce inflammation or alleviate pain at the same time as covering
up the inflammation or painful site.
[0100] The LVs can be incorporated into or onto or in a kit with
needles or catheters or ports. This may be particularly
advantageous with tattoo needles or piercing jewelry. These may be
in the form of wipes or sponges that are applied to the skin at the
time of or immediately before application of the needle, or even
added to the tattoo ink or applied as a coating to the needle.
II. Methods of Treatment or Prevention
[0101] A. Methods of Administration
[0102] The composition is applied topically to a site at or
adjacent to a painful region for both localized and systemic
effects. The composition is reapplied as necessary. Pain relief is
typically obtained within minutes and lasts for variable periods
depending on the patient and type of pain symptoms. The compounds
are applied such that the dosage is sufficient to provide an
effective dose in the painful area or immediately adjacent areas,
to ameliorate or eliminate one or more symptoms causing pain, or
pain. The LV is applied to the skin, which may be rubbed in using
an applicator, to the site of pain, as needed. Ultrasound or heat
may also be applied to increase transdermal penetration and to
increase local vasodilation.
[0103] As used herein, topical includes injection or infusion at
the site of administration, for example, subcutaneously, and can
include administration to mucosal surfaces, as well as
trans-rectal, intra-peritoneal, intra-uterine and
intra-articular.
[0104] Coadministration with an inhaled sympathomimetic such as
albuterol or an inhaled parasympathomimetic such as ipratropium
bromide tends to enhance the effects of the topical
application.
[0105] B. Therapeutic Indications
[0106] The composition is generally effective to treat visceral,
somatic and neuropathic pain both acute and chronic as well as
muscle pain and stiffness and joint pain and stiffness. Examples
include joint, muscle and tendon pain, joint, muscle and tendon
immobility, inflammatory pain, neuropathies, muscle spasms,
osteoarthritis, breathing disorders such as wheezing, hunger pains,
some types of headaches, dysphagia, fibromyalgia, autoimmune
disorders, and pancreatitis.
[0107] The composition also has an effect on some of the
psychological and vegetative symptoms of pain, especially chronic
pain, since in several patients, the LV alone without any active
ingredient, applied to different areas on the skin can produce
beneficial systemic effects such as decreased appetite, a feeling
of heightened alertness, decongestion, increased energy and
decreased fatigue, bronchodilation, urinary retention, and a
sensation of decreased work of breathing. The composition has been
demonstrated to provide pain relief in human patients for a wide
number of conditions
[0108] Indications for which the present formulations can be used
include, but are not limited to, inflammatory arthropathies
including rheumatoid arthritis, lupus and Reiter's syndrome,
neuropathies including those resulting from pressure, medication
and diabetes, bursitis, tendinopathies, sprains and muscle strains,
joint pains and arthralgias, muscle stiffness and overuse
syndromes, pancreatitis, dyspnea, wheezing and chest tightness
induced by asthmas, atelectasis, high blood pressure, obesity and
chronic obstructive pulmonary disease (COPD), tension headaches,
pain from anal fissures, hunger pain, fractures or compression of
lumbar vertebrae, fibromyalgia, chronic coccygeal pain, reflex
sympathetic dystrophy, polyneuropathy, TMJ dysfunction, and
osteoarthritis/degenerative joint disease, spondylosis.
[0109] The present invention will be further understood by
reference to the following non-limiting examples. In the examples
cited there was most often a significant decrease in the reported
neuropathic pain, joint pain and stiffness, muscle pain and
stiffness leading to increased mobility and range of motion of
subjects receiving treatment of topically applied compounds as
compared to subjects receiving placebo therapy. Also in subjects
receiving treatment of topically applied compounds as compared to
subjects receiving placebo therapy, a rubifacient effect on the
skin, ranging from mild to pronounced in some cases, was also often
observed. The first set of examples refers to treatment of patients
with an LV usually in combination with an active agent. The second
set of examples refers to treatment of patients with an LV alone
and with an emphasis on the systemic effects observed both after
administration of the LV to the affected painful area and to
different non-involved cutaneous areas.
EXAMPLE 1
Administration of LV with/without an Active Agent to Normal Control
Human Patient
[0110] Methods and Materials
[0111] a) Pluronic 20% with 750 mg lactose (Weise compounding
pharmacy)
[0112] b) Vanpen (Weise compounding company)
[0113] c) PLO gel (Weise compounding company)-combination of soy
lecithin (PCCA) dissolved in 20% pluronic gel made from 405 powder
in a ratio of 25% lecithin to 75% pluronic gel
[0114] d) Lecithin soya dissolved in isopropyl myristate (Weise
compounding company)
[0115] e) PLO (Advanced Rx compounding pharmacy)-combination of
lactose (750 mg) with propylene glycol to we, 9 mL soy lecithin
isopropyl palmitate and 20% pluronic gel (30 mg)
[0116] Atenolol (Advanced Rx compounding pharmacy)
[0117] Clonidine (Advanced Rx compounding pharmacy)
[0118] Nitrobid
[0119] Surgilube (applied as control)
[0120] Formulations were applied to skin with a tongue
depressor.
[0121] Treatment and Observation
[0122] Application of (a) on skin resulted in numbness similar to
that produced by lidocaine.
[0123] Application of (b) on skin led to slight numbness.
[0124] Application of (c) on skin resulted in pronounced numbness
similar to lidocaine.
[0125] Application of (d) on skin had no effect.
[0126] Application of (e) on skin had a strong numbing effect but
only after several minutes.
EXAMPLE 2
Administration of LV with/without an Active Agent to Human Patient
with Neck Pain
[0127] Materials and Methods
[0128] Formulations were as in Example 1.
[0129] Patient presented with stiff neck with an inability to
rotate it past 70 degrees to the right and a rotator cuff
tendinopathy. Pain Level -4/10. Stiffness with an inability to move
her shoulder past 70 degrees.
[0130] Treatment and Observation
[0131] Adding (e) resulted in a very slight effect on the
shoulder.
[0132] Adding (c) reduced the pain to 3/10 and made shoulder more
mobile. Adding (d) seemed to have no effect.
[0133] Adding (e) plus Atenolol 25 mg dissolved in lactose,
propylene glycol, soy lecithin/isopropyl palmitate, 20% pluronic
gel had a strong effect reducing pain to 0.5/10 and made her
shoulder much more mobile.
[0134] Adding to (e) clonidine 0.8 mg dissolved in lactose,
propylene glycol, soy lecithin/isopropyl palmitate, 20% pluronic
gel mixed with 2% nitrobid made the pain disappear completely and
restored full mobility. In addition, the skin on her shoulder was
red and patient stated that her shoulder felt flushed, warm and
"good." Her neck became more mobile when (e) was then applied to it
and she was able to turn her neck to 85 degrees. Subsequently
applying (c) had no additional effect on mobility although it made
the skin feel "numby." Adding clonidine 0.6 mg+nitrobid restored
full 90 degrees mobility. Her pain-free interval and increased
mobility lasted 1.5 weeks
EXAMPLE 3
Administration of LV with/without an Active Agent to Human Patient
with Shoulder and Neck Pain from Tendonopathy
[0135] Materials and Methods
[0136] Formulations were the same as in Example 1.
[0137] The patient presented with Pain level=9/10 on shoulder/neck
pain from a rotator cuff tendonopathy and inability to move his
shoulder past the horizontal. Pain Level=7/10 left knee pain due to
patellofemoral syndrome; Pain level=9/10 from a left sacroiliac
strain.
[0138] Treatments and Observation
[0139] Shoulder: Applying 25 mg Atenolol dissolved in (e) decreased
pain to 5/10 and patient noted that his skin felt warm and mobility
was improved.
[0140] The clonidine+nitrobid combination was added with no
change.
[0141] Then VanPen gel was added and pain disappeared with full
mobility remaining.
[0142] Knee: Adding (e) decreased pain to 2/10 with no change in
mobility. Clonidine 0.6 mg+nitrobid (2% nitrate) were applied with
no change in pain or mobility.
[0143] Back (sacroiliac strain): Applied (e) and pain decreased to
5/10. Added clonidine+nitrobid and pain decreased to 4/10. Added
VanPen and pain decreased to 3/10.
EXAMPLE 4
Administration of LV with an Active Agent to Human Patient with
Pain from Hammer Toes and Halux Valgus and Rigiditus
[0144] Materials and Methods
[0145] The same formulations were used as in Example 1.
[0146] Patient presented with a pain level of 7/10 for hammer toes
and halux valgus and rigiditus. Because of the hallux rigiditus
(rigid big toe) patient displayed virtually no movement in big
toe.
[0147] Treatment and Observation:
[0148] After administering compound (e) patient's pain decreased to
5/10 and patient was able to move the big toe where she previously
could not. After adding Atenolol patient reported no effect. VanPen
was then added and pain decreased to 3/10. Then nitrobid and 0.6 mg
Clonidine were added and pain disappeared. Patient noted that for
the first time in years she was able to walk without her cane.
EXAMPLE 5
Administration of LV with an Active Agent to Human Patient with
Pain from Trochanteric Bursitis, Knee Osteoarthritis
[0149] Materials and Methods
[0150] The same formulations were used as in Example 1.
[0151] The patient presented with a pain Level of 8/10 from
trochanteric bursitis, and a pain level of 8/10 from knee
osteoarthritis.
[0152] Treatment and Observation
[0153] Atenolol to hip reduced the pain level to 6/10. After
applying clonidine 0.8 mg+nitrobid patient noted no change in pain
level but the patient felt that the hip was much "looser."
Application of Atenolol to knee decreased the pain level to 5/10.
Overlying skin was flushed and patient stated that overall she felt
"wonderful" and "better" than she had "in years."
EXAMPLE 6
Administration of LV without an Active Agent to Human Patient with
Pain from Tarsal Tunnel Syndrome
[0154] Materials and Methods
[0155] The same formulations were used as in Example 1.
[0156] The 37 year old male patient presented with a pain Level of
5/10 from symptoms consistent with tarsal tunnel syndrome.
[0157] Treatment and Observation
[0158] Lecithin Soya dissolved in isopropyl palmitate was applied
to the patient's foot and the patient reported that the foot went
numb to the point where it felt like it might "fall off" and pain
was reduced to 0/10. Patient called 3 hours later to say that it
was still numb.
EXAMPLE 7
Administration of LV with/without an Active Agent to Human Patient
with Pain from Fibromyalgia
[0159] Materials and Methods
[0160] The same formulations were used as in Example 1.
[0161] The 45 year old female patient with severe melancholic
depression presented with Pain level=7/10 fibromyalgia with
multiple bilateral tender sore spots.
[0162] Treatment and Observation
[0163] Applied different combinations of creams to different spots
and overall patient stated that her pain level decreased to
5.75/10. Each of the creams either alone or in combination seemed
to have varying effects working in some areas but not in
others.
EXAMPLE 8
Administration of LV with an Active Agent to Human Patient with
Pain from Trochanteric Bursitis
[0164] Materials and Methods
[0165] The same formulations were used as in Example 1.
[0166] The 71 year old female patient presented with Pain
level=8/10 from trochanteric bursitis; Pain level=10/10 from
meralgia parsthetica or lateral femoral cutaneous neuropathy; Pain
level=10/10 from right sacroiliac strain; and Pain level=5/10 from
left rotator cuff tendinitis with almost no mobility.
[0167] Treatment and Observation
[0168] To 1 (hip) added Atenolol with no change. Then added VanPen
and pain disappeared after several minutes.
[0169] To 2 (lat cut fern neuropathy) added pluronic acid 50%.
Initially no change. Added 0.6 mg Clonidine+nitrobid and pain
decreased to 5/10.
[0170] To 3 (back) added clonidine 0.6 mg and pain decreased to
5-6/10. Added VanPen and after several minutes pain
disappeared.
[0171] To 4 (shoulder) added clonidine 0.6 mg+nitrobid and pain
decreased to 4/10. Added VanPen and pain decreased to 3/10. Also
patient was able to fully move shoulder where she could not
before.
[0172] In all cases after application of compounds the overlying
skin took on a flushed, mottled appearance
EXAMPLE 9
Administration of LV with an Active Agent to Human Patient with
Pain from Right Sacroiliac Strain
[0173] Materials and Methods
[0174] The same formulations were used as in Example 1.
[0175] The 30 year old female patient presented with Pain
level=6/10 from right sacroiliac strain, with radiation into the
gluteal area and down right leg to the calf.
[0176] Treatment and Observation
[0177] After adding Clonidine 0.6 mg+nitrobid pain decreased to
3/10 with no soreness down leg. Patient noted a "deep numbing
penetration." After adding VanPen patient noted complete numbness
with no pain. Stated she felt "like dancing."
EXAMPLE 10
Administration of LV with an Active Agent to Human Patient with
Pain from Thoracalgia
[0178] Materials and Methods
[0179] The same formulations were used as in Example 1.
[0180] The 45 year old female patient presented with a pain level
of 5/10 on both sides from thoracalgia versus costochondritis and
symmetrical sore spots across her flanks radiating backwards
circumferentially.
[0181] Treatment and Observation
[0182] VanPen was administered to the left side initially. Patient
stated pain decreased to 3/10. Atenolol was administered to the
right side and pain decreased to 2/10. Atenolol was then
administered to the left side and VanPen administered to the right
side, and pain completely disappeared from both sides as well as
radiation around to back.
EXAMPLE 11
Administration of LV with/without an Active Agent to Human Patient
with Pain from Right Sacroiliac Strain
[0183] Materials and Methods
[0184] The same formulations were used as in Example 1.
[0185] The 51 year old African-American female patient presented
with amputated right arm and a right arm neuroma with phantom limb
with a pain level of 4/10.
[0186] Treatment and Observation
[0187] After applying VanPen, patient noted numbness and "dulling"
of the pain to 2/10. After adding Clonidine 0.8 mg pain completely
disappeared.
EXAMPLE 12
Administration of LV with an Active Agent to Human Patient with
Pain from Osteoarthritis
[0188] Materials and Methods
[0189] Clonidine paste was applied at a dose of about 0.3 mg per
site, Nitrobid paste was applied from around 0.5 inches to 1 inch
per site, viscous lidocaine 2% and topical capsaicin (which did not
have much of an effect except in a few patients) were applied
without regard to amount.
[0190] Treatment and Observation
[0191] The 70 year old female presented with right knee
osteoarthritis with a pain level of 10/10. Nitrobid paste was
applied to the knee. The pain level decreased to 0 in about 5
minutes. Patient remained pain-free for about 1 week.
EXAMPLE 13
Administration of LV with an Active Agent to Human Patient with
Pain from Cervical Strain
[0192] Materials and Methods
[0193] The formulations were as described in Example 1.
[0194] The 47 year old female presented with cervical strain with a
pain level of 9/10. Nitrobid paste was applied to the neck.
[0195] Treatment and Observation
[0196] Pain decreased to 0 within 10 minutes and had not yet
returned in over a month
EXAMPLE 14
Administration of LV with an Active Agent to Human Patient with
Pain from Osteoarthritis
[0197] Materials and Methods
[0198] The formulations were as described in Example 1.
[0199] The 45 year old female presented with bilateral knee
osteoarthritis with a pain level of 10/10. Nitrobid paste was
applied to the knees
[0200] Treatment and Observation
[0201] The pain decreased to 0 within 10 minutes. Pain relief
lasted for 12 hours.
EXAMPLE 15
Administration of LV with an Active Agent to Human Patient with
Pain from Trochanteric Bursitis
[0202] Materials and Methods
[0203] The formulations were as described in Example 1.
[0204] The 50 year old male patient presented with right
trochanteric bursitis (hip) with a pain level of 7/10, and lateral
epicondylitis (elbow) with a pain level of 8/10. Nitrobid paste was
applied to lateral epicondyle and greater trochanter.
[0205] Treatment and Observation
[0206] The pain decreased to 0 in the hip and elbow within 10
minutes. Patient stated his hip felt so much better he wanted to
"dance." Patient was pain-free for about 6 hours.
EXAMPLE 16
Administration of LV with an Active Agent to Human Patient with
Pain from Torticollis
[0207] Materials and Methods
[0208] The formulations were as described in Example 12.
[0209] The 42 year old male patient presented with torticollis. The
pain level was 9/10 with extreme stiffness and inability to turn
head more than 20 degrees to either side. Nitrobid cream was
applied to neck.
[0210] Treatment and Observation
[0211] Pain decreased from 9/10 to 6/10. Patient's neck also became
more supple and range of movement went from about 20 degrees
turning to either side to over 70 degrees. No follow-up available
as yet.
EXAMPLE 17
Administration of LV with an Active Agent to Human Patient with
Pain from Bursitis
[0212] Materials and Methods
[0213] The formulations were as described in Example 12.
[0214] A 36 year old male presented with a left rotator cuff
impingement and bursitis with a pain level of 5/10.
[0215] Treatment and Observation
[0216] Pain disappeared with 0.8 mg of clonidine.
[0217] Table 1 shows the application of nitrobid paste and
clonidine paste in series.
TABLE-US-00002 TABLE 1 Administration of nitrobid and clonidine
paste I. Treatment with nitronid (NB) followed by clonidine paste
(CD) 0.3 mg Pain Level Patient Patient Complain Initial NB CD 1
Migraines and tension headaches 6/10 5/10 0/10 2 Sacroiliac strain
810 7/10 3/10 .sup.a3.sup. Neck Spondylosis 5/10 3/10 0/10 4
Sacroiliac strain 9/10 6/10 5/10 .sup.b5.sup. Sacroiliac strain
6/10 5/10 4.75/10 .sup.b6.sup. Torn rotator cuff 6/10 3/10 0/10 II.
Treatment with clonidine paste (CD) followed by nitrobid paste (NB)
Initial CD NB 1 Neck spondylosis 5/10 3/10 0/10 2 Osteoarthritis
10/10 7/10 3.5/10 3 Osteonecrosis of hip 9/10 6/10 3/10
.sup.aPatient later developed a splitting headache as a side effect
.sup.bPatient also had increased flexibility; overlying skin became
flushed
EXAMPLE 18
Administration of LV with an Active Agent to Human Patient with
Pain from Torn ACL and Meniscus
[0218] Materials and Methods
[0219] The formulations were as described in Example 12.
[0220] A 45 year old female presented with torn right ACL and torn
meniscus in right knee and anterior tarsal tunnel syndrome (a
compressive neuropathy) in right ankle. Capsaicin and lidocaine
were applied to knee and ankle.
[0221] Treatment and Observation
[0222] There was a decrease in pain from 8/10 to 7.5/10 in the knee
and no change in pain level in the ankle. After nitrobid paste was
added, pain decreased in the knee to 5/10, and pain and
paresthesias disappeared in ankle to 0/10.
EXAMPLE 19
Administration of LV with an Active Agent to Human Patient with
Pain from Torn Rotator Cuff
[0223] Materials and Methods
[0224] The formulations were as described in Example 1.
[0225] The 51 year old male presented with osteoarthritis
bilaterally of knees and a torn right rotator cuff and frozen
shoulder. The pain level was 10/10 in left knee, 7/10 right knee
and 5/10 in right shoulder. The right shoulder demonstrated
decreased abduction of about 50 degrees and decreased external
rotation of about 60 degrees.
[0226] Treatment and Observation
[0227] After addition of a mixture of topical capsaicin and 2%
viscous lidocaine, patient's pain decreased to 7/10 in left knee,
to 3/10 in right knee and 3/10 in right shoulder. With addition of
nitrobid paste, pain further decreased to 5/10 in left knee, and to
0/10 in right knee and right shoulder. Furthermore, patient had
increased mobility and range of movement of shoulder increased in
abduction to about 70 degrees and increased external rotation to
about 80 degrees.
EXAMPLE 20
Administration of LV with an Active Agent to Human Patient with
Pain from Joint Pain
[0228] Materials and Methods
[0229] The formulations were as described in Example 1.
[0230] A 55 year old female presented with a right knee replacement
with patellofemoral syndrome and osteoarthritis, with a pan level
of 8/10, patellofemoral syndrome and likely osteochrondritis
dessicans (loose body) in left knee with a pain level of 9/10,
carpal tunnel syndrome of right wrist with complaints of pain and
paresthesias in 1st two fingers of hand, with a pain level of 9/10,
ischial gluteal bursitis with a pain level of 9/10 and trochanteric
bursitis with a pain level of 9/10. Nitropaste was added to left
knee and right wrist.
[0231] Treatment and Observation
[0232] Pain in the left knee went from a 9/10 to a 4/10 after about
10 minutes. Pain in the right wrist (carpal tunnel) went to 4/10
after about 20 minutes. At about 30 minutes, clonidine paste was
added to right wrist and left knee, and pain decreased to 3/10 in
the wrist and 0/10 in left knee. For right knee osteoarthristis,
left trochanteric bursitis and ischial gluteal bursitis, clonidine
was first added to right knee, left greater trochanter and ischial
tuberosity and pain decreased in right knee from 9/10 to 8/10, in
ischial tuberosity from 9/10 to 5/10, and greater trochanter from
9/10 to 5/10 all within 10 minutes. Then nitropaste was applied and
pain from ischial gluteal bursitis decreased 1/10, pain from
trochanteric bursitis decreased to 1/10 and pain from right knee
osteoarthritis decreased to 6/10. The overlying skin where
compounds were applied became red and mottled.
EXAMPLE 21
Administration of LV with an Active Agent to Human Patient with
Pain from Bilateral Sacroiliac Strain
[0233] Materials and Methods
[0234] The formulations were as described in Example 12.
[0235] The 70 year old female presented with bilateral sacroiliac
strain. Pain level was 9/10 and patient had abnormal Scober test
with stiffness to lumbosacral region.
[0236] Treatment and Observation
[0237] Nitrobid paste was applied to sacroiliac joints bilaterally
and pain level decreased to 6/10 within 10 minutes. Then Clonidine
paste was applied and pain level decreased to 5/10. Patient also
had improved mobility and range of motion and was able to bend
forward almost touching her toes
EXAMPLE 22
Administration of LV with an Active Agent to Human Patient with
Pain from Bilateral Rotator Cuff Tear
[0238] Materials and Methods
[0239] The formulations were as described in Example 12.
[0240] A 65 year old male presented with a bilateral rotator cuff
tear with a pain level of 8.5/10.
[0241] Treatment and Observation
[0242] Clonidine alone applied on right shoulder and nitrobid on
left shoulder separately had no effect. When clonidine and nitrobid
were combined in a single formulation and applied on both
shoulders, the patient reported a decrease in pain level to 7/10 in
both shoulders.
EXAMPLE 23
Administration of LV with an Active Agent to Human Patient with
Pain from Thoracalgia with No Efficacy
[0243] Materials and Methods
[0244] The formulations were as described in Example 12.
[0245] A 51 year old patient presented with thoracalgia with a pain
level of 8/10.
[0246] Treatment and Observation
[0247] He reported no effect with application of either the
clonidine or nitrobid or capsaicin and lidocaine or a combination
of all three.
EXAMPLE 24
Administration of LV with an Active Agent to Human Patient with
Pain from Patellofemoral Syndrome
[0248] Materials and Methods
[0249] The formulations were as described in Example 12.
[0250] A 46 year old male with left patellofemoral syndrome
presented with a pain level of 7/10.
[0251] Treatment and Observation
[0252] Application of Nitrobid reduced pain to 5/10 and then
application of clonidine 0.8 mg reduced further reduced the pain to
3/10. A day later patient reported that his knee pain was still
reduced
EXAMPLE 25
Administration of LV with an Active Agent to Human Patient with
Pain from Trochanteric Bursitis
[0253] Materials and Methods
[0254] The formulations were as described in Example 12.
[0255] A 64 year old man presented with left trochanteric bursitis
with a pain level of 7/10, low back pain secondary to a lumbar
compression fracture with a pain level of 7/10 and right thumb
osteoarthritis with a pain level 2/10.
[0256] Treatment and Observation
[0257] With application of clonidine 0.8 mg, thumb pain stayed the
same after 5 minutes but with application of nitrobid 2% it
disappeared. With a combination of nitrobid and clonidine back pain
also disappeared. Trochanteric bursitis disappeared with just
application of clonidine.
EXAMPLE 26
Administration of LV with an Active Agent to Human Patient with
Pain from Compression Fracture of Vertebra
[0258] Materials and Methods
[0259] The formulations were as described in Example 12.
[0260] A 49 year old female presented with a vertebral compression
fracture of L3 with a pain level of 6/10.
[0261] Treatment and Observation
[0262] 1.6 mg of clonidine was applied to lower back and pain level
decreased to a 4/10. No change was observed with application of
nitropaste. The improvement lasted 6 hours and the patient reported
that she was able to sit for a prolonged period for the first time
in several months.
EXAMPLE 27
Administration of LV with an Active Agent to Human Patient with
Pain from Neck Stiffness
[0263] Materials and Methods
[0264] The formulations were as described in Example 12.
[0265] A 41 year old male presented with neck stiffness and pain
secondary to radiculopathy. Pain level was about 6/10.
[0266] Treatment and Observation
[0267] After application of clonidine 0.8 mg pain disappeared but
patient was only able to rotate head 70 to left and 75 degrees to
right. After application of nitropaste patient was able to rotate
head 85 degrees to the right and 80 degrees to left
EXAMPLE 28
Administration of LV with an Active Agent to Human Patient with
Pain from Osteoarthritis
[0268] Materials and Methods
[0269] The formulations were as described in Example 12.
[0270] A 50 year old female presented with bilateral osteoarthritis
and patellofemoral syndrome of knees with a pain level of 6/10 in
both knees and inability to flex the knees because of pain.
[0271] Treatment and Observation
[0272] Clonidine was applied to the right knee and pain decreased
to 3/10. To left knee nitrobid was added and pain level stayed
roughly the same. After addition of nitrobid to right knee pain
disappeared and ability to flex knee became much improved. After
addition of clonidine to left knee pain also disappeared and
patient demonstrated improved flexibility. 2 days later the patient
was still pain-free.
EXAMPLE 29
Administration of LV with an Active Agent to Human Patient with
Pain from Lupus and Disc Bulges
[0273] Materials and Methods
[0274] The formulations were as described in Example 12.
[0275] A 40 year old woman presented with systemic lupus and
multilevel disc bulges with a pain level of 6/10 on
presentation.
[0276] Treatment and Observation
[0277] With application of 0.8 mg clonidine and 2% nitrobid paste
to back, pain diminished to 5/10 and patient reported slightly
improved flexibility.
EXAMPLE 30
Administration of LV with an Active Agent to Human Patient with
Pain from Neuropathy
[0278] Materials and Methods
[0279] The formulations were as described in Example 12.
[0280] A 51 year old diabetic with lower extremity neuropathy and
severe vascular stenosis presented with a pain level of 7/10.
[0281] Treatment and Observation
[0282] Clonidine 0.8 mg was applied to legs and pain level
decreased to 5/10 in 5 minutes. Then, nitrates were added and pain
disappeared.
EXAMPLE 31
Administration of LV Combined with an Active Agent to Human Patient
with Pain from Cluster Headache
[0283] Materials and Methods
[0284] The formulations were as described in Example 12.
[0285] A 50 year old man presented with cluster headaches with an
intractable headache and wearing dark sunglasses with a pain level
of 10/10.
[0286] Treatment and Observation
[0287] Application of Clonidine 1.6 mg combined with 2 inches of 2%
nitroglycerin lead to complete disappearance of headache
EXAMPLE 32
Administration of LV with an Active Agent to Human Patient with
Pain from Headache
[0288] Materials and Methods
[0289] The formulations were as described in Example 12.
[0290] A 94 year old female presented with a unilateral migraine
characterized by photophobia, phonophobia, nausea, vomiting and
with a pain level of 10/10. She stated that the headache originated
from her neck.
[0291] Treatment and Observation
[0292] Clonidine 0.1 mg combined with 0.5 inches of 2% Nitrobid
applied to back of neck resulted in diminishment of pain from
headache to 3/10
EXAMPLE 33
Administration of LV with an Active Agent to Human Patient with
Pain from TMJ
[0293] Materials and Methods
[0294] The formulations were as described in Example 12.
[0295] A 41 year old male presented with trigeminal neuralgia,
temporal mandibular joint dysfunction and hemicrania continua. The
pain level was 8/10. Treatment and Observation Premixed cream was
applied and within 10 minutes patient's pain level decreased to
2/10.
EXAMPLE 34
Administration of LV with an Active Agent to Human Patients
[0296] I. Administration of Atenolol in PLO
[0297] (a) Administration to a patient with pain from rotator cuff
tendinopathy
[0298] Male patient presented with rotator cuff tendinopathy and
shortness of breath. The pain level was 8/10.
[0299] Atenolol in PLO was applied to shoulder, and back and pain
level decreased to 0/10. Patient also noted that breathing
improved.
[0300] (b) Administration to a patient with wheezing
[0301] Female African-american patient presented in visible
respiratory distress, audibly wheezing and using an albuterol
inhaler every few minutes.
[0302] Atenolol in PLO gel was applied to back and chest. Within a
few minutes the wheezing abated and patient no longer needed to use
the inhaler for at least 20 minutes while the patient was in the
office
[0303] II. Administration of 0.6 mg Clonidin+nitrobid
[0304] (a) Administration to a Patient with Pain from Biceps
Insertionitis
[0305] African-american male patient presented with biceps
insertionitis. The pain level was 6/10.
[0306] Clonidine 0.6 mg+nitrobid were premixed and applied to the
biceps tendon. Pain level decreased to 1/10 and patient noted that
his arm felt much more mobile.
[0307] (b) Administration to a Patient with Bilateral Sacroiliac
Strain
[0308] Male patient presented with low back pain, with a pain level
of 6/10.
[0309] Clonidine 0.6 mg premixed with nitrobid was applied to
sacroiliac joints. Patient's pain diminished from 6/10 to 2/10 only
2-3 hours later but the interval with diminished pain lasted 24
hours.
[0310] (c) Administration to a Patient with Patient with a Left
Rotator Cuff Tendinopathy
[0311] Male patient presented shoulder pain, with a pain level of
6/10.
[0312] Application of Clonidine 0.6 mg premixed with nitrobid
followed by VanPen cream and further followed by Pluronic gel 20%
with lecithin soya/isopropyl myristate had no effect on patient's
pain.
[0313] III. Administration Pluronic Gel+Nitrobid
[0314] (a) Administration to a patient with back and leg pain
[0315] Male patient presented with severe pain in back and legs.
The pain level was 10/10.
[0316] Pluronic gel 20% with lecithin soya and nitrobid were
premixed and applied to both of the patients' legs. Patient stated
that there was no change in pain level.
[0317] (b) Administration to Patients with Joint Pain
[0318] Female patient presented with malaise, weakness, myalgias,
tendinopathies and extreme diffuse joint pain, with a pain level of
10/10.
[0319] Pluronic gel 20% with lecithin soya/isopropyl myristate
premixed with nitrobid was applied to shoulders, neck, hips,
wrists, hands, knees and ankles. Patient reported that her pain
dissipated to 0/10 and lasted for 4 hours before returning. She
also noted that during these 4 hours, she felt more alert and
awake, breathed easier and was less hungry.
[0320] Male patient with severe rheumatoid arthritis presented with
diffuse joint pain, with a pain level of 10/10.
[0321] Pluronic gel 20% with lecithin soya/isopropyl myristate
premixed with nitrobid was applied to shoulders, hands, wrists, and
elbows. Patient reported that his pain in these joints dissipated
to 0/10 and lasted for about 7.5 hours before returning. He also
noted that he felt more alert and awake.
[0322] (c) Administration to Patient with Thoracalgia
[0323] Male patient with pain in the chest. The pain level was
6/10.
[0324] Pluronic gel 20% with lecithin soya/isopropyl myristate
premixed with nitrobid was applied to mid/upper back. Patient
reported that his back pain disappeared.
[0325] IV. Administration of Orajel
[0326] (a) Administration to a patient a teeth pain and diabetic
neuropathy
[0327] Female patient presented with mouth pain with a pain level
of 10/10 and painful diabetic neuropathy with a pain level of
7/10.
[0328] After administration of Orajel (PEG+benzocaine), patient
noted not only decreased mouth pain but also markedly decreased
pain in his lower extremities from 7/10 to 2/10. The relief in his
lower extremities lasted about 30 minutes before returning.
[0329] (b) Administration to a Patient with Wrist and Neck Pain
[0330] Male patient presented with wrist pain with a pain level of
7/10 and neck pain with a pain level of 5/10.
[0331] Oragel applied to the gums decreased his neck pain from 2/10
(brought to these levels by administration of PEG) to 1/10.
[0332] V. Administration of PLO Gel Followed by Albuterol and/or
Ipratropium Bromide (Atrovent)
[0333] (a) Administration to a Patient with Diabetic
Nephropathy
[0334] Patient presented with diabetic nephropathy complained of
stinging, shooting, lacinating pains in bilateral lower extremities
worse over the heels in intensity. The pain level was 8/10.
[0335] PLO gel was applied to right heel and pain level dropped to
5/10, with no change in left heel. 5 minutes later patient was
given albuterol inhaler, within 30 seconds pain in right heel
dropped to 4/10 and pain in left heel dropped to 6/10. 5 minutes
later he was given an Atrovent inhaler and within 30 seconds pain
in right heel dropped to 3/10 and pain in left heel dropped to
5/10. He was given albuterol inhaler again and pain in right heel
dropped to 2/10 and pain left heel dropped to 3/10. No further
change occurred with inhalers but patient noted that, although a
deep, aching pain was still present, the burning sensation was
totally gone.
[0336] (b) Administration to a Patient with Porphyria
[0337] Patient presented with lower extremity neuropathy from
porphyria.
[0338] PLO gel was applied to legs. The pain level was 8/10. After
ten minutes there was a small change to in pain, to 7.5/10. She was
given several alternating inhalations of atrovent and albuterol and
pain level dropped to 4/10. Patient noted that although deep pain
was still present the stinging superficial pain had disappeared
[0339] (c) Administration to a Patient with Neck Pain and
Stiffness
[0340] Patient presented with neck pain and stiffness with a pain
level of 5/10 and lower back pain over the coccyx with a pain level
of 8/10.
[0341] She was given Atrovent and noted that along with decreasing
her neck pain to 3/10, her neck was much looser. There was no
change in her back pain. PLO cream was applied to her back without
change. Ultrasound was used with PLO cream on her back over the
affected area but patient did not note a change in her pain level.
Albuterol inhaler was given and, although there was no change in
her back pain, her neck pain decreased to 2/10. Atrovent was then
given and her neck pain decreased to 1/10. Patient also noted that
her mobility in her neck was greatly improved
[0342] (d) Administration to a Patient with Multiple Sclerosis and
Sacroiliac Strain
[0343] Patient presented with multiple sclerosis and sacroiliac
strain with radiation into her legs. The pain level was 5/10.
[0344] PLO cream was applied to back and pain decreased to 2/10.
She was given an Atrovent inhaler and pain disappeared
completely
[0345] (e) Administration to a Patient Sacroiliac Strain
[0346] Patient presented with sacroiliac strain with a pain level
of 8.5/10.
[0347] Patient was given PLO cream and pain level decreased to 5/10
and remained stable for over 5 minutes. Patient was given an
Albuterol inhaler and pain level decreased to 4/10. Then he was
given an Atrovent inhaler and pain level decreased to 3/10
[0348] (f) Administration to a Patient Sacroiliac Strain
[0349] Patient presented with midback pain with a pain level of
7/10.
[0350] PLO cream was administered to back with no change in pain
level. Albuterol and Atrovent inhalers were given without any
change
[0351] (g) Administration to a Patient with Bilateral Plantar
Fasciitis
[0352] Patient with a diagnosis of bilateral plantar fasciitis with
a pain level of 5/10 in both feet.
[0353] PLO cream was applied to right foot and pain level decreases
to 0/10 in right foot, while pain in the left foot remained at
5/10. Patient was given Atrovent and pain in the left for decreased
to 0/10.
[0354] (h) Administration to a Patient with Pain from Compression
Fractures
[0355] Patient presented with pain from T11 and T12 compression
fractures 6/10.
[0356] PLO cream was applied to her back and pain level dropped to
0/10. No inhalers were used
[0357] Patient presented with a possible lower lumbar compression
fracture 5/10.
[0358] PLO cream was applied to back with no change in pain level.
Albuterol inhaler was given and pain level dropped to 6/10.
[0359] The Examples below and Tables 2, 3, 4 and 5 show treatments
which do not employ an active agent other than the lipophilic
vehicle.
TABLE-US-00003 TABLE 2 Administration of LV's alone Patient (site
of Pain Level application) Patient Complain Before After I.
Treatment with HRT Base .sup.a1 (left shoulder and Rotator cuff
tendinopathy 9/10 0/10 back) Low Back pain 4/10 3/10 .sup.b2 (back)
Low back pain 4/10 0/10 .sup.c3 (left should) Supraspinatus Tendon
tear 4/10 2/10 4 (breast) Nipple pain 6/10 0/10 5 (inguinal region)
Lateral cutaneous femoral nerve 4/10 0/10 syndrome 7 Shingles 10/10
0/10 8 (thumb) Gout 7/10 0/10 II. Treatment with Pluronic gel 20%
with lecithin soya/isopropyl myristate 1 (back) Chest pain 7/10
7/10 2 (shoulder and low Rotator cuff tendinopathy 10/10 0/10 back)
Radicular back pain 10/10 10/10 3 (neck) Neck pain 5/10 0/10 4
(ankle) Ankle osteoarthritis 7/10 0/10 5 (ankle) Ankle
osteoarthritis 7/10 0/10 III. Treatment with VanPen *1 (left
sacroiliac Bilateral sacroilitis 10/10 5/10 joint **2 (shoulder)
Reflex sympathetic dystrophy 8/10 5.5/10 3 (scar on wrist) Wrist
pain from hypertrophic 7/10 0/10 scar IV Treatment with PLO gel 1
(scrotum and feet) Bilateral tarsal tunnel syndrome 7/10 0/10
Surgery to the scrotum 10/10 0/10 2 (leg) Reflex sympathetic
dystrophy 7/10 5/10 V. Treatment with VersaCream 1 Superficial
thrombophlebitis 10/10 0/10 2 Pain in big toe from gout 8/10 1/10
.sup.aPatient 1 noted that she felt more awake, lost her appetite
and was breathing easier. .sup.bPatient 2 experienced 30-40
increasing shoulder mobility. He also presented with nasal
secretions which dried up with HRT base treatment. .sup.cPatient 3
also presented with a greenish-black nipple discharge which
disappeared with HRT treatment. She also noted that she felt much
more alert, less congested, could breathe easier and was producing
more saliva. *Surgilube (placebo) treatment had no effect.
Additional treatment with 20% pluronic gel decreased pain from 5/10
to 0/10. **Patient noted increased salivation. Administration of
Pluronic gel 20% decreased pain level from 5.5/10 to 4/10 and
appetite went away. No additional effect was observed with this
patient upon administration of treatment II. (i) Patient noted
marked loosening of neck and shoulders and increased ability to
move them.
[0360] HRT was applied to a patient with rash and it took away the
all itching for over 12 hours. No effect was observed upon
administration of HRT to one patient with neck stiffness and
itching.
[0361] The materials described in the table above generally contain
compounds which are amphiphilic (i.e., contain polar and non-polar
moieties within the molecule). For example, fatty acids, fatty acid
esters, and lecithin are compounds which contains hydrophobic
moiety (e.g. non-polar tail) and a hydrophilic moiety (e.g.,
carboxylic acid group, ester group, phosphate group). Lanolin is a
complex mixture of esters of sterols, triterpene alcohols, and
aliphatic alcohols. Oils which appear to have activity are rich in
Omega 6 and/or Omega fatty acids.
[0362] Other molecules to evaluate include other fatty acids,
cholesterol derivatives, and any materials rich in Omega 6 and
Omega 9 fatty acids.
EXAMPLE 35
Additional Treatments with Pluronic Gel 20% with Lecithin
Soya/Isopropyl Myristate
[0363] (a) Administration to a Patient with Cardiac Asthma and
Hunger Pains
[0364] Male hypertensive patient presented with labored breathing.
Patietn stated "I'm very hungry because I haven't eaten all
day."
[0365] Pluronic gel 20% with lecithin soya/isopropyl myristate was
applied to stomach and abdominal wall. Patient experienced 2 hours
without any hunger pains or cravings. He also was breathing
noticeably better. His peak flow meter measured 500 L/min before
application of the cream and 600 L/min after its application. He
also stated he felt much more awake and alert and his breathing
remained better for the whole rest of the day (about 12 hours).
[0366] (b) Administration to a Patient with Shortness of Breath
Materials and Methods
[0367] Female patient with shortness of breath and hunger
pains.
[0368] Before Pluronic gel 20% with lecithin soya/isopropyl
myristate was applied to abdomen, patient's peak expiratory flow
was 240 L/min. After application of cream to abdomen and thorax,
the patient's peak expiratory flow increased to 370 L/min. She also
noted that she was able to breathe more deeply and easier. She also
felt more awake as well as hot and sweaty and completely lost her
appetite.
[0369] (c) Administration to a Patient with Hunger Pains
[0370] Female patient presented with hunger pains.
[0371] Treatment and Observation
[0372] Pluronic gel 20% with lecithin soya/isopropyl myristate was
applied to stomach and abdominal wall. Patient noted that she was
more awake and no longer hungry.
[0373] (d) Administration to a Patient with Shortness of Breath
Female Asthmatic Patient Presented with Audible Wheezing and
Shortness of Breath
[0374] Before Pluronic gel 20% with lecithin soya/isopropyl
myristate was applied to thorax, patient's peak expiratory flow was
180 L/min. After application of cream to thorax, the patient's peak
expiratory flow increased to 240 L/min. She noted that she was able
to breathe more easily and she was no longer wheezing. She also
felt more awake as well as hot and sweaty and completely lost her
appetite.
[0375] (e) Administration to a Patient with Hunger Pains
[0376] Female patient presented with hunger pains
[0377] After administration of Pluronic gel 20% with lecithin
soya/isopropyl myristate to abdominal wall, patient noted that she
completely lost her appetite.
[0378] (f) Administration Following a Fingerstick
[0379] (i) Patient was given a fingerstick on right index finger
without pluronic gel, which was painful; (blood sugar:123 mg/dl),
fingerstick on left index finger with pluronic gel 15% stick was
less painful (blood sugar measured 132 mg/dl).
[0380] (ii) 15% pluronic was applied on the right index finger of a
patient, and nothing was placed on the left index finger. A
fingerstick was done on both fingers. The patient barely felt the
needlestick on the right index finger, while on the left index
finger he felt a sharp pain and discomfort which lingered even
after the fingerstick. Applying 15% pluronic gel over this finger
completely eliminated the discomfort. His glycemia measured on the
left was 128 and on the right it was 114. When the blood was
remeasured on other fingers without the gel, it was 109 on the left
and 102 on the right.
[0381] iii) Finger sticks were performed on 20 patients using the
TheraSense device glucometer. Although this device requires the
smallest drop of blood and produces the least discomfort, it still
results in a noticeable pain which lasts about ten to twenty
minutes. To perform the finger stick, finger was cleaned with and
alcohol wipe, allowed to dry, then a stick was performed and the
glucose concentration measured. Using the same finger Pluronic gel
15%, allowed to dry, and a stick was performed. The pain was so
reduced as to be barely noticeable and the meter reading was within
10% of the initial stick. Of note if the is the fact that the
specifications for these meters allows for 20% variation for the
device.
EXAMPLE 36
Additional Treatments with PLO Cream and HRT Base
[0382] (a) A patient presented with psoriasis. PLO cream on
psoriatic plaques on back of hands and shins given over 1 month
reduced their size.
[0383] (b) A patient presented with atopic dermatitis complaining
of extreme pruritis. HRT cream base applied to rashy areas took
away all itching for about 4-5 hours. Treatments using oils are
shown in table 3 below.
TABLE-US-00004 TABLE 3 Treatment with oils; Overall analgesic
effect with oils was immediate but duration of analgesia was
significantly less than with creams. Pain Level Patient Patient
Complain Before After I. Treatment with Oil of Cloves 1 Neck,
shoulder and lower back pin 0/10 2 Subscapular Bursitis secondary
to Rotator cuff 3/10 0/10 tendinopathy 3 Hip Bursitis 8/10 0/10 4
Neck pain and stiffness 7/10 0/10 *5 Bilateral flank pain 9/10 9/10
II. Treatment with Peppermint oil .sup.a1.sup. SI Strain 8/10 2/10
.sup.b2.sup. Coccygodynia 5/10 0/10 Neck stiffness and pain 4/10
0/10 .sup.c3.sup. Menstrual Cramps 8/10 4/10 .sup.d4.sup. Pain from
Meniscal tear 8/10 4/10 .sup.e5.sup. Pain from Meniscal tear 8/10
0/10 .sup.f6.sup. Neck Pain 8/10 2/10 Headache 8/10 2/10 7
Atherosclerotic peripheral vascular disease 9/10 0/10 .sup.g8.sup.
Neck pain and Stiffness 5/10 5/10 .sup.h9.sup. Carpal tunnel
Syndrome 7/10 0/10 All oils used were pharmaceutical grade oils
*Additional PLO gel administration did not reduce pain level
.sup.aPatient noted decongestion, increased alertness, sweating and
a sense of well being .sup.bPatient noted numbness, decongestion,
increased alertness, and loss of appetite .sup.cPatient felt more
awake, alert, and decongested (could breathe easier and more
deeply) .sup.dPatient felt more alert, awake and decongested
.sup.ePatient felt more mobile .sup.fPatient felt more awake,
decongested and was sweating .sup.gApplication of PLO eliminated
the pain .sup.hPatient started visibly sweating and her appetite
disappeared
EXAMPLE 37
Treatment Using Combinations of Oil and LV's
[0384] (a) Administration of VanPen with PLO to a Patient with Pain
from Neuroma and Trochanteric Bursitis.
[0385] A female patient presented with pain from a neuroma in her
amputated stump in visible acute distress, and trochanteric
bursitis. The pain level from the neuroma was 10+++/10 and from the
trochanteric bursitis, 4/10.
[0386] VanPen mixed with PLO was applied to the stump. The pain
level decreased to 5/10. When Sesame oil was applied to the stump,
the pain decreased to 0. The patient stated that "The oil worked
the best." Similarly, when Sesame oil was applied to the hip the
pain disappeared.
[0387] (b) Application to a Patient with Pain from Inguinal
Lymphadenopathy
[0388] A patient presented with an 8/10 pain level in the groin
from right inguinal lymphadenopathy.
[0389] Application of PLO gel to groin eliminated all pain.
Patient's blood sugar was also taken from two separate finger
sticks. On one finger right pluronic gel 15% was applied on the
other finger left nothing was applied. On the finger with pluronic
gel the patient didn't feel the pain of the finger stick, on the
other finger the patient felt the pain of the needlestick
intensely. After application of pluronic gel to this finger the
pain and sensitivity of the needlestick went away. The patient's
blood sugar measured 116 mg/dl on the right and 111 mg/dl on the
left. Additional treatment combinations are shown in table 4.
EXAMPLE 38
Administration of Oils Alone or in Combination with Other LV's
[0390] Table 5 shows the observations when oils were applied either
alone or in combination with other LVs to human patients.
TABLE-US-00005 TABLE 4 Administration of Pluronic acid 20% (PA),
lecithin/isopropyl myristate (L/I), Glycerin pure (GP) polyethylene
glycol (PEG) and anhydrous Lanolin (LAN) alone or in combination
Complaint (pain Treatment Patient level) PA L/I GP PEG LA
Observation 1 Neck pain and + + + + .sup.xPain reduced to 2/10
Stiffness (4/10) + + + + .sup.yPain reduced to 1/10 2 Neck pain and
Stiffness + + *No effect 3 Tarsal tunnel + + + Pain reduced to 0/10
syndrome (8/10 **4 Bilateral SI + + + Pain reduced 0/10 strain
(8.5/10) 5 Pain in big toe (8/10 + No effect + Pain reduced 4/10
.sup.a6 Knee Osteoarthritis + + Pain reduced 0/10 (4/10) Rotator
Cuff + + Pain reduced 1/10 Impingement (10/10) 7 Neck pain + Pain
disappeared .sup.b8 Rotator cuff + + Small to no effect
tendinopathy Coccydynia + + Small to no effect .sup.c9 Carpal
tunnel + Pain reduced 2/10 syndrome (4/10) Hip bursitis (4/10) +
Pain reduced 2/10 Neck pain and + Pain reduced 2/10 stiffness
(6/10) .sup.d10 Bilateral + + Pain reduced 6/10 costochondritis
(8/10 .sup.e11 Systemic Lupus + + + Pain reduced to 4/10
Erythematosis (6/10 .sup.xTreatment included ultrasound
application; Patient could not rotate head to the right past 70
degrees without pain .sup.yTreatment included sesame oil; rotation
to the right improved to about 88 degrees *Treatment also included
application of motor oil and grapeseed oil **Patient had initially
been hoarse. Treatment eliminated hoarseness, he felt less
congested and more awake .sup.aPatients pain level from
osteoarthritis had been reduced from 6/10 to 4/10 by the
administration of GP and then LAN .sup.bWith subsequent
administration of PLO, shoulder pain disappeared .sup.cprior
administration of GP had no effect .sup.dPain level further
decreased to 4/10 with VanPen administration. No further change was
observed with a combination of VanPen and PLO or PLO alone.
.sup.eThere was no effect on pain when cottonseed oil was added to
the combination treatment
TABLE-US-00006 TABLE 5 Application of oils in combination with
other LVs Patient Complaint (pain level) Treatment Observation 1
Costalgia (7/10) and L3 Olive, Peanut No effect radiculopathy to
knee (5/10) or Canola oil Burts Bees An effect, too small to
quantify Bag Balm An effect, too small to quantify Lecithin + PEG +
Both pains decreased by 50%. PLO Increased briskness of patellar
reflex 2 Trigeminal neuralgia (TN) Tween 80 *Decreased TN pain to
1/10 and (2/10) and frontal headache headache to 0/10 (1/10) 3
Coccygodynia (5/10) SDS 20% **Reduced pain to 0/10 4 Low back pain
(4/10) Peanut or Olive No effect Rotator Cuff Syndrome oil (4/10)
Cotton seed oil 50% reduction in pain; wore off in 10 min 5 Pain
from neck spasm (5/10) Cotton seed oil Pain decreased to 3/10;
effect wore off in 10 minutes .sup.a6.sup. Plantar fascitis and
neck Cotton seed oil Reduced pain in neck to 1/10; stiffness
(2-3/10) no effect on plantar fascitis 7 Lumbar radiculopathy
Cotton seed oil ***No effect (4/10) 8 Rotator cuff syndrome
Propylene No effect (6/10) Knee Osteoarthritis glycol (6/10)
Glycerin Shoulder pain decreased from 6-4/10 No effect on knee 9
Neck stiffness (4/10) Tween 80 No effect 10 Neck pain (5/10) Tween
80 More mobility; no decrease in pain SDS 20% No change in pain or
mobility Triton x100 Slight increase in mobility; no change in pain
Tween 20 Increased mobility; no change in pain Glycerin pure Pain
decreased to 1/10; Increased mobility for 1 hour Propylene No
effect glycol *Effect lasted for 5 minutes upon first
administration, but lasted until patient left upon second
administration **patient was jittery for several minutes, lost
appetite and breathed better ***VanPen application resulted in a
heating feeling with a 20-30% reduction in pain which lasted 5-6
hours .sup.aPatellar reflex were more brisk while ankle reflexes
were less brisk
EXAMPLE 39
Administration of SDS, Tween and Dawn Dishwashing Liquid
[0391] (a) A patient presented with congestion, wheezing and
hunger. Application of SDS and Tween 80 led to an improvement in
breathing. Administration of Dawn Hand Dishwashing Liquid led to a
strong improvement in breathing. Patient completely lost appetite
for over 8 hours.
[0392] (b) A Patient presented with a 5-6 tension headache and
nuchal stiffness with 65 degree range of motion from side to side.
With application of Dawn Hand Dishwashing Liquid, the patient was
breathing easier, felt more awake, pain in neck and head were gone,
and experienced greatly improved mobility with head turning almost
reaching 90 degrees on each side
[0393] (c) A patient presented with an 8/10 SI joint pain. Patient
was taking Atenolol. Treatment with Dawn Hand Dishwashing Liquid
had no effect.
[0394] (d) A patient presented with a 7/10 low back pain, abdominal
cramps from menses, flank pain from Urinary Tract infection.
[0395] With application of Dawn Hand Dishwashing Liquid, patient
was breathing better, awakened, less congested, pain decreased from
7/10 to 3/0. Dawn was applied to abdomen, right flank and low
back.
EXAMPLE 40
Administration of MonaVie Juice in Aquaphor Cream 50:50: Mixture
(Made by Weise Compounding Pharmacy)
[0396] A mixture of MonaVie juice in aquaphor cream was
administered to patients with different conditions. The results are
shown in table 6.
TABLE-US-00007 TABLE 6 Administration of MonaVie Juice in aquafor
cream Pain level Patient Complaint Before After 1 Coccygodynia 8/10
6/10 .sup.a2.sup. Right rotator cuff tendinopathy 7/10 0/10
Radicular low back pain 5/10 4/10 3 Low back pain and stiffness
5/10 0/10 Right ankle bruise from trauma 4/10 1/10 4 SI Strain 7/10
5/10 Neuroma in amputated thumb 5/10 0/10 5 Rotator cuff
tendinopathy 7/10 0/10 L5 radiculopathy 9/10 9/10 .sup.aPatient
also presented with congestion and wheezing which was decreased
with cream application. Subsequent application of PLO cream reduced
pain on shoulder with no effect on lower back.
[0397] A summary of the treatments for pain, categorized by
conditions treated is shown in table 7 below.
TABLE-US-00008 TABLE 7 SUMMARY TO TREATMENTS EFFECT ON PAIN LEVEL/
% Change in PT TREATMENT % change Pain level 1(a) PLO Very slight
effect PLO gel From 4/10 to 3/10 25% 2(a) Clonidine 0.6 mg + NB
From 5/10 to 4/10 20% VanPen From 4/10 to 3/10 25% 3(a) Clonidine
0.8 mg From 5/10 to 0/10 100% 4(a) Atenolol in PLO to back From
8/10 to 0/10 100% and shoulder 5(a) Clonidine 0.6 mg + NB, No
effect 0 then VanPen, Pluronic gel 20% with L/IM 6(b) Clonidine No
effect 0 Clonidine combined with From 8.5/10 to 7/10 18.75%
nitrobid 7(b) Nitropaste From 6/10 to 3/10 50% Clonidine paste From
3/10 to 0/10 100% 8(c) HRT From 9/10 to 0/10 100% 9(b) HRT From
4/10 to 2/10 50% 10(a) Pluronic gel 20% with LS/IM From 10/10 to
0/10 100% 11(a) PEG From 9/10 to 0/10; 100% 12 Oil of cloves From
3/10 to 0/10 (from 100% subscapular bursitis); 13 Glycerin pure +
LAN From 10/10 to 1/10 90% (rotator cuff impingement) 14(a) MJ/AQ
cream in 50:50 From 7/10 to 0/10 100% 15 Cottonseed oil From 4/10
to 2/10; 50% rotator cuff impingement) no effect with olive/peanut
oil Summary: 9 patients experienced a 1-5 change in pain level, 6
patients a 7-10 change. 2 had no change (a) Rotator Cuff
Tendinopathy (b) rotator cuff tear (c) shoulder pain Fibromyalgia 1
Diiferent combinations of From 7/10 to 5.75/10 17.85% creams
Summary: Change in pain was 2.25 1(a) 0.8 mg clonidine 2% NB From
6/10 to 5/10 16.7% paste 2(b) HRT base From 7/10 to 0/10 100% 3(c)
Pluronic gel + LS/IM From 10/10 to 0/10 100% 4(b) Versa cream From
8/10 to 1/10 87.5% Summary: 1 patient experienced a change in pain
level of 1, and 3, a change of 7-10 (a) Lupus (b) Gout (c)
rheumatoid arthritis Tronchanteric Bursitis 1 Atenolol From 8/10 to
6/10 25% Clonidine 0.8 mg + NB No change; hip looser 0 2 Clonidine
From 8 to 5-6/10 31.25% 3 NB to trochanter From 7/10 to 0/10 100% 4
Clonidine 8 mg From 7/10 to 0/10 100% Summary: 1 patient
experienced a 2-3 change in pain level, 2 patients a 7 change. 1
had no change. Sacroiliac Strain 1 Atenolol No change 0 VanPen From
10/10 to 0/10 100% 2 Clonidine 0.6 mg + From 6/10 to 3/10 50%
nitrobid 3 Nitrobid From 8/10 to 7/10 12.5% 4 Nitrobid From 9/10 to
6/10 33% Clonidine paste From 6/10 to 5/10 16.7%; *44% 5 Nitrobid
From 6/10 to 5/10 16.7% Clonidine paste From 5/10 to 4.75/10 5%;
*37.5% 6 Clonidine 0.6 mg + From 6/10 to 2/10 66.7% Nitrobid 7 PLO
cream From 8.5/10 to 5/10 41% Albuterol inhaler From 5/10 to 4/10
20% Atrovent inhaler From 4/10 to 3/10 23%; *64.7% 8 PLO cream then
No change in 7/10 pain 0 albuterol, then atrovent 9 PLO cream From
5/10 to 2/10 60% 10 PLO cream, then From 8.5/10 to 4/10, to 53% to
albuterol, then atrovent 3/10 *64.7% 11(b) VanPen, then Pluronic
From 10/10 to 5/10 to 50% to 20% 0/10 (left joint) *100% Pluronic
60% From 10/10 to 9/10 10% (right joint) 12 Pluronic acid 20%/LS/IM
From 8.5/10 to 0/10 100% 13 Peppermint oil From 8/10 to 2/10 75% 14
MJ/AQ cream 50:50 From 7/10 to 5/10 28.6% Summary: 10 patients
experienced a 1-5 change in pain level, 8 experienced a 6-10
change, and 1, no change (b) Bilaterial sacroilitis Thoracalgia 1
VanPen to left side From 5/10 to 3/10 40% Atenolol to right side
Pain decreased to 2/10 60% Atenolol to left side and Pain
disappeared 100% VanPen to right side completely 2 Pluronic gel 20%
with From 6/10 to 0/10 100% LS/IM + NB 3 Pluronic gel 20% with No
change in 7/10 pain 0 LS/IM Summary: 2 patients experienced a 5-6
change in pain level; 1 patient had no change. Osteoarthritis 1
Atenolol to knee From 8/10 to 5/10 37.5% 2 Nitrobid paste to knee
From 10/10 to 0/10 100% 3 Nitrobid paste to knee From 10/10 to 0/10
100% 4 Clonidine paste From 10/10 to 7/10 30% Nitrobid paste to
knee From 7/10 to 3.5/10 50%; *65% 5 Clonidine 8 mg No change 0
Nitrobid 2% to thumb From 2/10 to 0/10 100% 6 Clonidine to right
knee From 6/10 to 3/10 50% Nitro to right knee From 3/10 to 0/10
*100% Nitro to left knee No change 0 Clonidine to left knee 6/10 to
0/10 100% 7 Mix of Capsaicin + 2% From 10/10 to 7/10 (left 30%
viscous lidocaine knee) From 7/10 to 3/10 (right 57% knee) Nitrobid
paste From 7/10 to 5/10 (left 28.5% *50% knee) From 3/10 to 0/10
(right *100% knee) 8 Nitrobid paste From 9/10 to 4/10 (left 55.5%
knee) Clonidine paste Pain went to zero *100% 9 Pluronic gel 20%
with From 7/10 to 0/10 100% LS/IM (ankle) 10 Pluronic gel 20% with
From 7/10 to 0/10 100% LS/IM (ankle) 11 PEG From 9/10 to 0/10 100%
(knee) 12 Glycerin pure From 6/10 to 5/10 (right 16.7% knee)
Anhydrous lanolin From 6/10 to 4/10 (left 33% knee) Glycerin pure +
Pain disappeared in both *100% anhydrous lanolin knees 13 Clonidine
paste From 5/10 to 3/10 40% (spondylosis) Nitrobid paste 2% Pain
went to zero *100% Summary: 5 patients experienced a 2-6 change in
pain, 8 patients experienced a 7-10 change Bilateral plantar
fascitis 1 PLO cream From 5/10 to 0/10 (right 100%; 0 foot); no
change on left Atrovent Pain dropped from 5/10 100% to 0/10 (left)
Summary: Total change in pain was 5 Compression Fracture of
Vertebra 1 1.6 mg Clonidine From 6/10 to 4/10, No 33% change with
NB 2 PLO cream Pain dropped to zero 100% (no initial value)
Summary: One patient experienced a total change in pain of 2 Neck
Pain and stiffness 1 Clonidine 0.8 mg From 6/10 to 0/10 100% 2 PEG,
then Oragel (to From 5/10 to 2/10, then *80% gums) to 1/10 3
Atrovent inhaler, then From 5/10 to 3/10, to *80% albuterol
inhaler, then 2/10, to 1/10 atrovent 4 Pluronic gel 20% with From
5/10 to 0/10 100% LS/IM 5 PEG to gums From 5/10 to 2/10 60% 6 Oil
of cloves From 7/10 to 0/10 100% 7 Glycerin pure + Pluronic No
change in pain level 0 acid 20% + motor oil + grapeseed oil 8
Peppermint oil From 4/10 to 0/10 100% 9 Peppermint oil; then PLO No
change, then From 0; then 100% 5/10 to 0/10 (PLO) 10 Peppermint oil
From 8/10 to 0/10 100% 11 Glycerin pure, then No effect (glycerin),
Lanolin (LAN) From 6/10 to 3/10 (LAN) 12* Cottonseed oil From 5/10
to 3/10 40% (*neck spasm) 13 Nitrobid cream From 9/10 to 6/10 33%
(Torticollis) 14 Nitrobid paste to neck From 9/10 to 0/10 100%
(cervical strain) Summary: 10 patients experienced a 2-5 change in
pain, 3 experienced a 7-9 change, 1 experienced no change
Patellofemoral Syndrome 1 Nitrobid From 7/10 to 5/10 28.6%
Clonidine 0.8 mg From 5/10 to 3/10 40%; *57% 2 PEG to gums No
change in 7/10 pain 0 Summary: One patient experienced a total
change in pain of 4, one patient experienced no change 1(a)(b) NB
paste, then clonidine From 6/10 to 5/10, to *100% paste 0/10 2(c)
Clonidine (1.6 mg) + 2% From 10/10 to 0/10 100% NG 3(d) Clonidine
(0.1 mg) + 2% From 10/10 to 3/10 70% NG 4(d) Peppermint oil From
8/10 to 2/10 75% Summary: Two patients experienced a change in pain
of 6, two, a change in pain of 7-8 (a) Migraine, (b) tension
Headache, (c) cluster headache, (d) headache 1(a) Lecithin Soya in
IM From 5/10 to 3/10 40% 2(c) VanPen From 7/10 to 0/10 100% 3(b)
Nitrobid paste to wrist From 9/10 to 4/10 55.6% 4(c) PEG to gums No
change in 7/10 pain 0 5(c) PEG to wrist From 8/10 to 0/10 100%
(DeQuervains tenosynovitis) 6(a) PLO gel From 7/10 to 0/10 100%
7(a) Glycerin pure + Pluronic From 8/10 to 0/10 100% acid 20%/LS/IM
8(b) Peppermint oil From 7/10 to 0/10 100% 9(b) Glycerin pure, then
No effect (glycerin); 0, then 50% lanolin From 4/10 to 2/10 (LAN)
Summary: 3 patients experienced a change in pain level of 2-5, 5, a
change of 7-8 and 1, no change (a) Tarsal Tunnel Syndrome (b)
Carpal Tunnel Syndrome (c) wrist pain Torn ACL and Meniscus 1
Capsaicin and Lidocaine From 8/10 to 7.5/10 6% Nitrobid paste From
7.5/10 to 5/10 33%; *37.5% (knee) and 0/10 (ankle) (knee); *100%
(ankle) Summary: the total change in pain was 3 at the knee and 8
at the ankle 1(a)(b) Pluronic gel 20%, LS/IM No change in 10/10
pain 0 mixed with NB 2(c) Pluronic gel 20%, LS/IM From 10/10 to
0/10 100% mixed with NB 3(c) Pluronic gel 20%, LS/IM From 10/10 to
0/10 100% mixed with NB 4(a) HRT From 4/10 to 3/10 25% 5(a) HRT
From 4/10 to 0/10 100% 6(a) PEG From 9/10 to 0/10 (low 100% back)
7(c) PEG to gums From 7/10 to 4.5/10 35.7% 8(d) Oil of cloves From
8/10 to 0/10 100% 9(e) Glycerin pure, the No Change, then from 0,
then 50% Lanolin (LAN) 8/10 to 4/10 (LAN) 10(f) Peppermint oil From
8/10 to 4/10 50% (meniscal tear) 11(f) Peppermint oil From 8/10 to
0/10 100% (meniscal tear) 12(a) MJ/AQ cream 50:50 From 5/10 to 0/10
100% 13(a) MJ/AQ cream 50:50 From 5/10 to 4/10 20% (radicular pain)
14(a) MJ/AQ cream 50:50 No effect on 9/10 0 radiculopathy pain
15 MJ/AQ cream 50:50 From 4/10 to 1/10 75% (ankle bruise) 16(a)
Cottonseed oil From 4/10 to 2/10; no 50%; 0 effect with
Peanut/olive oil Summary: 9 patients experienced a 1-5 change in
pain, 6, a 7-10 change, and 2, no change (a) Back (b) Leg Pain or
(c) Join pain (d) hip pain (e) toe pain (f) knee pain 1(a) Oragel
to gums From 7/10 to 2/10 71% 2(a) PLO gel (heels) From 8/10 to
5/10 37.5% (right); no change on left Albuterol inhaler (5 min From
5/10 to 4/10 20%; 25% later) (right); 8/10 to 6/10 (left) Atrovent
inhaler (5 min 4/10 to 3/10 (right); 25%; 16.7% later) 6/10 to 5/10
(left) Albuterol inhaler (5 min 3/10 to 2/10 (right); 33%; 40%
later) 5/10 to 3/10 (right) 3(b) PLO gel From 8/10 to 7.5/10 6%
Alternating atrovent and From 7.5/10 to 4/10 46.7%; *50% albuterol
inhalers 4(c) MJ/AQ cream 50:50 From 5/10 to 0/10 100% (amputated
thumb) 5(c) VanPen mixed with PLO From 10+++/10 to 5/10 ++++50%
(amputated stump) Sesame oil From 5/10 to 0/10 *100% Summary: 4
patients experienced a 1-5 change in pain level, and 1, a 10 change
(a) Diabetic neuropathy (b) Porphyric neuropathy (c) neuroma 1(a)
HRT From 6/10 to 0/10 100% 2(b) PLO gel From 7/10 to 0/10 100% 3(c)
Peppermint oil From 10/10 to 0/10 100% 4(d) PLO gel From 8/10 to
0/10 100% Reflex Sympathetic dystrophy Summary: one patient
experienced a 6 change in pain level, 3, a 7-10 change (a) Nipple
pain (b) Scrotal pain (c) Menstrual Cramps (d) groin pain 1 VanPen,
then Pluronic From 8/10 to 5.5/10, to 43.7% to 20% with LS/IM to
4/10 *50% abdomen 2 PLO cream From 7/10 to 5/10 28.6% Summary: Both
patients experienced a 2-4 change in pain level Peripheral vascular
disease 1 Peppermint oil 9/10 to 0/10 100% Summary: There was a
pain level change of 9 Coccygodynia 1 MJ/AQ cream 50:50 From 8/10
to 6/10 25% Summary: Patient experienced a pain level change of 2
Superficial Thrombophlebitis 1 Versa cream From 10/10 to 0/10 100%
Summary: Patient experienced a pain level change of 10 Shingles 1
PLO cream, then HRT worse (PLO), then From 0; then 100% 10/10 to
0/10 (HRT) 2 Combination of different None of the creams 0 creams
used worked Summary: Patient experienced a pain level change of 10
Bilateral Costochondritis 1 Lanolin + glycerin pure, From 8/10 to
6/10, to 25% to *50% then sesame oil 4/10 Summary: Patient
experienced a pain level change of 4
[0398] Modifications and variations will be obvious to those of
skill in the art from the foregoing detailed description of the
invention and are intended to come within the scope of the
following claims.
* * * * *