US20200390790A1 - Pain reliever composition - Google Patents
Pain reliever composition Download PDFInfo
- Publication number
- US20200390790A1 US20200390790A1 US16/862,469 US202016862469A US2020390790A1 US 20200390790 A1 US20200390790 A1 US 20200390790A1 US 202016862469 A US202016862469 A US 202016862469A US 2020390790 A1 US2020390790 A1 US 2020390790A1
- Authority
- US
- United States
- Prior art keywords
- composition
- pain
- amount
- inventive composition
- sodium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 225
- 229940124641 pain reliever Drugs 0.000 title description 13
- 235000000346 sugar Nutrition 0.000 claims abstract description 30
- 150000005846 sugar alcohols Chemical class 0.000 claims abstract description 28
- 230000003113 alkalizing effect Effects 0.000 claims abstract description 26
- 239000003795 chemical substances by application Substances 0.000 claims description 29
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 21
- 235000002639 sodium chloride Nutrition 0.000 claims description 21
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 20
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 19
- 239000008121 dextrose Substances 0.000 claims description 19
- 239000011780 sodium chloride Substances 0.000 claims description 12
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 10
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 229930195725 Mannitol Natural products 0.000 claims description 8
- 239000000594 mannitol Substances 0.000 claims description 8
- 235000010355 mannitol Nutrition 0.000 claims description 8
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 8
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 claims description 7
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 7
- 239000000839 emulsion Substances 0.000 claims description 7
- 239000003921 oil Substances 0.000 claims description 7
- 235000019198 oils Nutrition 0.000 claims description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 6
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 6
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 5
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 5
- 150000001768 cations Chemical class 0.000 claims description 5
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 5
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 claims description 5
- 239000000194 fatty acid Substances 0.000 claims description 5
- 229930195729 fatty acid Natural products 0.000 claims description 5
- 150000003904 phospholipids Chemical class 0.000 claims description 5
- 239000000811 xylitol Substances 0.000 claims description 5
- 235000010447 xylitol Nutrition 0.000 claims description 5
- 229960002675 xylitol Drugs 0.000 claims description 5
- 239000011701 zinc Substances 0.000 claims description 5
- 229910052725 zinc Inorganic materials 0.000 claims description 5
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 claims description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 4
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims description 4
- UNXHWFMMPAWVPI-QWWZWVQMSA-N D-threitol Chemical compound OC[C@@H](O)[C@H](O)CO UNXHWFMMPAWVPI-QWWZWVQMSA-N 0.000 claims description 4
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 claims description 4
- 239000004386 Erythritol Substances 0.000 claims description 4
- 229930091371 Fructose Natural products 0.000 claims description 4
- 239000005715 Fructose Substances 0.000 claims description 4
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 4
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 4
- 235000019414 erythritol Nutrition 0.000 claims description 4
- 229940009714 erythritol Drugs 0.000 claims description 4
- FBPFZTCFMRRESA-GUCUJZIJSA-N galactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-GUCUJZIJSA-N 0.000 claims description 4
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 claims description 4
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 claims description 4
- 239000011777 magnesium Substances 0.000 claims description 4
- 229910052749 magnesium Inorganic materials 0.000 claims description 4
- 229940091250 magnesium supplement Drugs 0.000 claims description 4
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 claims description 4
- HEBKCHPVOIAQTA-ZXFHETKHSA-N ribitol Chemical compound OC[C@H](O)[C@H](O)[C@H](O)CO HEBKCHPVOIAQTA-ZXFHETKHSA-N 0.000 claims description 4
- 239000001509 sodium citrate Substances 0.000 claims description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 4
- 235000011083 sodium citrates Nutrition 0.000 claims description 4
- 239000005720 sucrose Substances 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 3
- HEBKCHPVOIAQTA-QWWZWVQMSA-N D-arabinitol Chemical compound OC[C@@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-QWWZWVQMSA-N 0.000 claims description 3
- OXQKEKGBFMQTML-UHFFFAOYSA-N D-glycero-D-gluco-heptitol Natural products OCC(O)C(O)C(O)C(O)C(O)CO OXQKEKGBFMQTML-UHFFFAOYSA-N 0.000 claims description 3
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims description 3
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 claims description 3
- SKCKOFZKJLZSFA-UHFFFAOYSA-N L-Gulomethylit Natural products CC(O)C(O)C(O)C(O)CO SKCKOFZKJLZSFA-UHFFFAOYSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 3
- XJCCHWKNFMUJFE-CGQAXDJHSA-N Maltotriitol Chemical compound O[C@@H]1[C@@H](O)[C@@H](O[C@@H]([C@H](O)[C@@H](O)CO)[C@H](O)CO)O[C@H](CO)[C@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 XJCCHWKNFMUJFE-CGQAXDJHSA-N 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
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- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 3
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 3
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 3
- 150000004665 fatty acids Chemical class 0.000 claims description 3
- 229930182830 galactose Natural products 0.000 claims description 3
- 229960000367 inositol Drugs 0.000 claims description 3
- 239000000905 isomalt Substances 0.000 claims description 3
- 235000010439 isomalt Nutrition 0.000 claims description 3
- HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 claims description 3
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- 239000008101 lactose Substances 0.000 claims description 3
- JCQLYHFGKNRPGE-FCVZTGTOSA-N lactulose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 JCQLYHFGKNRPGE-FCVZTGTOSA-N 0.000 claims description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 3
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- 229960003975 potassium Drugs 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 claims description 3
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims description 3
- 239000000600 sorbitol Substances 0.000 claims description 3
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- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 2
- AEQDJSLRWYMAQI-UHFFFAOYSA-N 2,3,9,10-tetramethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline Chemical compound C1CN2CC(C(=C(OC)C=C3)OC)=C3CC2C2=C1C=C(OC)C(OC)=C2 AEQDJSLRWYMAQI-UHFFFAOYSA-N 0.000 claims description 2
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 claims description 2
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- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 2
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- 229910021538 borax Inorganic materials 0.000 claims description 2
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- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
Definitions
- Pain is one of the most frequent symptoms for which patients seek medical intervention. Pain may be classified as acute or chronic. Acute pain may be generally associated with excessive noxious stimulus resulting in a severe distressful sensation whereas chronic pain may be associated with physiological changes resulting from tissue or nerve injury leading to hyperalgesia, an increased amount of pain associated with a mild noxious stimulus, or allodynia, a pain induced by a non-noxious stimulus.
- Neurogenic pain is a neurological disorder caused by insult to peripheral nerves, resulting in chronic pain and varying combinations of sensory symptoms, including paresthesia, loss of sensation, and even motor weakness. Neurogenic pain may be long-lasting, and may develop days or month following the injury. Often, this type of chronic pain may be observed in diseases affecting the peripheral nervous system, such as nerve compression syndromes, cutaneous sensory neuropathies and polyneuropathies (of which diabetic neuropathy may be the most well-known).
- Neurogenic pain involves alterations in the function of both the peripheral and central nervous system, postulated to be caused by changes in mechano-insensitive peptidergic nociceptors referred to as “silent” or “sleeping” nociceptors, which are chemo-sensitive and respond to noxious chemicals typically released in response to tissue or nerve trauma.
- the phenotype of the nociceptors can be altered, whereby the formerly “silent” or “sleeping” nociceptors become “polymodal” or “awake” nociceptors (C fibers), which release significant amounts of pro-inflammatory neuropeptides, such as calcitonin gene-related peptide (CGRP) or substance P (SP), initiating neurogenic inflammation in combination with enhancing action potentials, thereby resulting in increased nociception.
- CGRP calcitonin gene-related peptide
- SP substance P
- peripheral sensitization which is mediated by increased expression of the transient receptor potential (TRP) family of non-specific cation channels, including transient receptor potential cation channel subfamily V member 1 (TRPV1), which is expressed in C fibers and ⁇ fibers.
- TRP transient receptor potential
- TRPV1 transient receptor potential cation channel subfamily V member 1
- Another mechanism leading to peripheral sensitization includes the accumulation of voltage-gated sodium channels at the site of the injured nerve and at the dorsal root ganglion, resulting in abnormal ectopic excitability of afferent neurons. These changes may be perceived as spontaneous positive sensations, such as paresthesia (a sensation of tingling, burning, pricking, or numbness of skin) or dysthesia (an unpleasant, abnormal sense of touch).
- Central sensitization defined as the activation of second order nociceptive neurons in the dorsal horn of the spinal cord by peripheral nerve damage, results from the release of glutamate, SP, or other transmitters or cytokines, such as adenosine-5′-triphosphate (ATP), chemokine (C-C motif) ligand 2 (CCL2), or interferon gamma (INF ⁇ ), from the central terminals of primary nociceptive afferents in the dorsal horn.
- cytokines such as adenosine-5′-triphosphate (ATP), chemokine (C-C motif) ligand 2 (CCL2), or interferon gamma (INF ⁇ )
- ATP-activated microglial P2X4 and P2X7 receptors stimulate the p38 mitogen-activated protein kinases (p38-MAPK) signalling cascade, resulting in release of substances such as brain-derived neurotrophic factor (BNDF), down-regulation of potassium/chloride cotransporters, and diminished inhibitory neurotransmission (GABAergic inhibition).
- BNDF brain-derived neurotrophic factor
- GABAergic inhibition diminished inhibitory neurotransmission
- various inflammatory substances such as histamines, prostaglandins, or cytokines, may be released from inflammatory cells which have migrated through the blood to the site of the injured tissue.
- the peripheral terminals of sensory neurons may be activated, resulting in inflammation characterized by the release of neuropeptides, such as CGRP, SP, or calcitonin, from the C fiber terminal, which can lead to vasodilation, edema, or pain.
- neurogenic inflammation plays an integral role in the pathophysiology of neurogenic pain.
- U.S. patent application Ser. No. 12/895,200 (US 2011/0076327 A1) by Lomax teaches herbal pain killer compositions, one of which comprises 50 mg each of the following ingredients formed into an approximately 600 mg tablet for oral administration to a mammal: Boswellia serrata , Tumeric, White Wilow, Harpagophytum Procumbens, Phellodendron Amurense, Paullinia Tomentosa , Milkberry, Mimosa Pudica, Lactuca Virosa , Naringen, 6-7 Dihydroxybergamottin, and Yerba mate.
- U.S. patent application Ser. No. 12/874,038 (US 2011/0117175 A1) by Rosenbaum teaches a pain reliever composition for medical procedures treatments comprising a sweet analgesic and a delivery vehicle, wherein the delivery vehicle is suitable for intra-oral delivery, and the sweet analgesic comprises sucrose, glucose, fructose, dextrose, maltodextrin, corn syrup, high fructose corn syrup, cyclamate, aspartame, sucralose, xylitol, cyclamate, stevia , brazzein, curculin, erythritol, glycyrrhizin, honey, luo han gua, mabinlin, monatin, miraculin, monellin, pentadia, thaumatin, acesulfame potassium, alitame, salt of aspartame-acesulfame, dulcin, glucin, neohyesperidin di
- U.S. patent application Ser. No. 11/305,552 (US 2008/0102107 A1) by Lewellyn teaches a transdermal joint pain therapy composition comprising (a) from about 2.5% to about 15%, based on the total weight of said transdermal joint therapy composition, of glutamine; (b) from about 0.04% to about 0.5%, based on the total weight of said transdermal joint pain therapy composition, of hyaluronic acid; (c) from about 2.55 to about 10.0%, based on the total weight of said transdermal joint pain therapy composition, of methylsulfonylmethane; and (d) from about 70% to about 95%, based on the total weight of said transdermal joint pain therapy composition, of a transdermal delivery agent.
- An objective of the present disclosure is to develop an alternate form of pain relief composition using different active ingredients and in different quantities that is applied to the epidermis of mammals.
- the invention can relate to a pain reliever composition comprised of some or all of the following ingredients: dextrose, aloe vera concentrate, propylene glycol, caprylic/capric tryglicerides, sodium chloride (or acetic acid), a homeopathic anti-inflamatory extract, Dimethyl Sulfone (or methylsulfonylmethane (MSM)), cetyl myristoleate, and a pitcher plant extract.
- the inventive pain reliever composition can comprise a pain relief composition applied to the epidermis of mammals in form of a water-based solution and gels comprising dextrose and aloe vera concentrate, and further comprising some or all of the following ingredients: propylene glycol, caprylic/capric tryglicerides, sodium chloride (or acetic acid), a homeopathic anti-inflamatory extract, such as Traumeel®, Dimethyl Sulfone (or Methyl sulfonylmethane (MSM)), cetyl myristoleate, lipoderm base, distilled water, and a pitcher plant extract, such as Sarapin.
- a homeopathic anti-inflamatory extract such as Traumeel®, Dimethyl Sulfone (or Methyl sulfonylmethane (MSM)
- MSM Methyl sulfonylmethane
- the lipoderm base can be substituted by any of the following; (1) lecthicin or other fat soluble granules (2) PLO (Pluronic Lecithin Organogel) (3) Urea, (4) Oleic acid, (5) Liposomes, (6) Niosomes, or (7) Nanotechnology, namely, any one of the following chosen from a group consisting of nanocrystals, liposomes, nanoparticle-protein conjugates, magnetic nanoparticles, nanogels and biodegradable nanoparticlea.
- An embodiment comprises aloe vera concentrate, propylene glycol, sterile water, and sodium chloride, in amounts ranging from 0.01% to 75% of the composition, but preferably comprising at least 5% anhydrous dextrose or 1% to 50% hypertonic saline (preferably 20%), at least 10% aloe vera concentrate, and at least 10% propylene glycol.
- An embodiment comprises aloe vera concentrate, propylene glycol, caprylic/capric triglycerides, ultrasound gel, and simple-gel (Hawkins), also in amounts ranging from 0.01% to 75% of the composition, but preferably comprising at least 5% anhydrous dextrose or 1% to 50% hypertonic saline (preferably 20%), at least 10% aloe vera concentrate, at least 10% propylene glycol, and at least 10% caprylic/capric triglycerides.
- An embodiment comprises anhydrous dextrose, aloe vera concentrate, ethoxy diglycol reagent, caprylic/capric triglycerides, lipoderm base, and cetyl myristoleat, in amounts ranging from 0.01% to 75%, but preferably comprising at least 20% anhydrous dextrose, at least 10% aloe vera concentrate, at least 10% caprylic/capric triglycerides, and at least 10% caprylic/capric triglycerides.
- the third embodiment should further comprise at least 10% dimethyl sulfone or Methylsulfonylmethane (MSM), at least 10% pitcher plant extract, distilled water, and a homeopathic anti-inflammatory extract.
- a broad object of a particular embodiment of the invention can be to provide an inventive composition including an amount of sugar or sugar alcohol, an amount of alkalizing agent, and an amount of vehicle; whereby the inventive composition is formulated for transdermal administration.
- Another broad object of a particular embodiment of the invention can be to provide a method of using the inventive composition, the method including transdermally administering the inventive composition to alleviate one or more disorder symptoms, for example neurogenic pain, or to treat one or more disorders, for example neurogenic inflammation.
- Another broad object of a particular embodiment of the invention can be to provide a method of producing an inventive composition, the method including combining an amount of sugar or sugar alcohol, an amount of alkalizing agent, and an amount of vehicle; and formulating the inventive composition for transdermal administration.
- a method of using a particular embodiment of the inventive composition including an amount of sugar or sugar alcohol, an amount of alkalizing agent, and an amount of vehicle, whereby the inventive composition is formulated for transdermal administration can include administering the inventive composition to an external surface of a body to alleviate one or more disorder symptoms, for example neurogenic pain, or to treat one or more disorders, for example neurogenic inflammation.
- sugar for the purposes of this invention means any carbohydrate or saccharide, including monosaccharides, disaccharides, oligosaccharides, or polysaccharides.
- sugar alcohol for the purposes of this invention means any polyol (or polyhydric alcohol) derived from a sugar.
- the polyol can typically include an alcohol group (CH 2 OH) in place of an aldehyde group (CHO) of the parent sugar.
- alkalizing agent for the purposes of this invention means an agent capable of adjusting a pH from a lesser alkalinity toward a greater alkalinity.
- symptoms for the purposes of this invention means any discomfort or combination of discomforts associated with a disorder. Without limiting the breadth of the foregoing, symptoms can include: pain, dyesthesia, paresthesia, sensory loss, allodynia, hyperpathia, reduced range-of-motion, motor weakness, or the like, or combinations thereof.
- a disorder for the purposes of this invention means a physical or mental condition which may not be normal or healthy.
- a disorder can include: known compressive mononeuropathies (such as carpal tunnel syndrome, cubital tunnel syndrome, or tarsal tunnel syndrome), regional pain conditions (such as sub-occipital neuralgia, facial neuralgias, headache, neck pain, or back pain), acute joint injury which may include a component of nerve inflammation (such as ankle sprain or strain), tendinopathies potentially promoted or aggravated by concomitant neurogenic components (such as Achilles tendonosis, lateral epicondylosis, or medial epicondylosis), or isolated inflammation of any one or more peripheral nerves (such as cranial and upper cervical nerve branch derivatives of the face and cranium).
- known compressive mononeuropathies such as carpal tunnel syndrome, cubital tunnel syndrome, or tarsal tunnel syndrome
- regional pain conditions such as sub-occipital neuralgia, facial neuralgias, headache
- topical administration or transdermal administration for the purposes of this invention means the administration of one or more components of a composition or compound to and typically, but not necessarily, through the epidermis on any external surface of a body.
- topical administration or transdermal administration can mean the administration of one or more components of a composition or compound to the epidermis on any external surface of a body and typically, but not necessarily, through the dermis.
- one or more components of the composition or compound may or may not be systemically bioavailable.
- the trade name material or the trademark material is understood to have the chemicals or ingredients in the amounts or combinations as described below.
- the trade name material or trademark material or a substantially equivalent product or combination of chemicals or ingredients can be utilized in embodiments of the inventive composition. It is further understood that where a trade name material or trademark material is utilized in a table or figure that substantially equivalent chemicals or ingredients in the amounts and combinations as indicated below can be utilized in substitution of the trade name material or trademark material.
- a person of ordinary skill in the art can convert the weight percentages shown in the tables or figures to determine the amount of each chemical or ingredient to mix when the equivalent of the trade name material or trademark material is prepared.
- embodiments of the inventive composition can include formulations having raw materials admixed in the exemplary weight percentages (“Weight Percent”) shown in column two of Table 1.
- Weight Percent exemplary weight percentages
- Numerous embodiments of the inventive composition can be prepared by altering the weight percentages of the raw materials within the range weight percentages (“Range Weight Percent”) shown in column three of Table 1 with an amount of vehicle making up the balance.
- the sugar can include a monosaccharide, such as ribose (CAS No: 50-69-1), xylose (CAS No: 58-86-6), fructose (CAS No: 57-48-7), dextrose (glucose) (CAS No: 50-99-7), galactose (CAS No: 59-23-4), mannose (CAS No: 31103-86-3), sorbose (CAS No: 87-79-6), or the like, or combinations thereof, all of which can be obtained from Sigma-Aldrich, 3050 Spruce Street, St. Louis, Mo., USA.
- ribose CAS No: 50-69-1
- xylose CAS No: 58-86-6
- fructose CAS No: 57-48-7
- dextrose glucose
- galactose CAS No: 59-23-4
- mannose CAS No: 31103-86-3
- sorbose CAS No: 87-79-6
- the sugar can include a disaccharide, such as sucrose (CAS No: 57-50-1), maltose (CAS No: 69-79-4), lactose (CAS No: 63-42-3), lactulose (CAS No: 4618-18-2), trehalose (CAS No: 99-20-7), cellobiose (CAS No: 528-50-7), or the like, or combinations thereof, all of which can be obtained from Sigma-Aldrich, 3050 Spruce Street, St. Louis, Mo., USA.
- a disaccharide such as sucrose (CAS No: 57-50-1), maltose (CAS No: 69-79-4), lactose (CAS No: 63-42-3), lactulose (CAS No: 4618-18-2), trehalose (CAS No: 99-20-7), cellobiose (CAS No: 528-50-7), or the like, or combinations thereof, all of which can be obtained from Sigma-Aldrich, 3050 Spruce Street, St. Louis, Mo., USA
- the sugar can be generally included in an amount of about 2% to about 30% by weight of the inventive composition; however, greater or lesser weight percents of the sugar can be included depending on the disorder symptom to be alleviated or the disorder to be treated.
- the amount of sugar included in the inventive composition can be selected from the group including or consisting of: between about 5% to about 30% by weight of the inventive composition; between about 10% to about 30% by weight of the inventive composition; between about 15% to about 30% by weight of the inventive composition; and between about 20% to about 30% by weight of the inventive composition.
- the amount of sugar, for example dextrose, included can be about 20% by weight of the inventive composition.
- the amount of sugar included in the inventive composition can be influenced by factors such as user anatomy, physiology, or biochemistry of the epidermis or underlying tissue; disorder symptom targeted for alleviation; disorder targeted for treatment; observable effect(s) of the application of the inventive composition; or the like; or combinations thereof; but not so much as to cause discomfort to the user or irritation to the epidermis or underlying tissue.
- the sugar alcohol can include a polyol derived from a monosaccharide or a disaccharide, including glycerol (CAS No: 56-81-5), erythritol (CAS No: 10030-58-7), threitol (CAS No: 2418-52-2), arabitol (CAS No: 7643-75-6), xylitol (CAS No: 87-99-0), adonitol (CAS No: 488-81-3), mannitol (CAS No: 69-65-8), sorbitol (CAS No: 50-70-4), dulcitol (CAS No: 608-66-2), fucitol (CAS No: 13074-06-1), iditol (CAS No: 488-45-9), inositol (CAS No: 87-89-8), volemitol (CAS No: 30635-52-0), isomalt (CAS No: 64519-82-0), maltitol (CAS No: 585-88-6),
- the sugar alcohol can be generally included in an amount of about 2% to about 30% by weight of the inventive composition; however, greater or lesser weight percents of the sugar alcohol can be included depending on the disorder symptom to be alleviated or the disorder to be treated.
- the amount of sugar alcohol included in the inventive composition can be selected from the group including or consisting of: between about 5% to about 30% by weight of the inventive composition; between about 10% to about 30% by weight of the inventive composition; between about 15% to about 30% by weight of the inventive composition; and between about 20% to about 30% by weight of the inventive composition.
- the amount of sugar alcohol, for example mannitol, included can be about 20% by weight of the inventive composition.
- the amount of sugar alcohol included in the inventive composition can be influenced by factors such as user anatomy, physiology, or biochemistry of the epidermis or underlying tissue; disorder symptom targeted for alleviation; disorder targeted for treatment; observable effect(s) of the application of the inventive composition; or the like; or combinations thereof; but not so much as to cause discomfort to the user or irritation to the epidermis or underlying tissue.
- the alkalizing agent can include any agent capable of adjusting a pH from a lesser alkalinity toward a greater alkalinity, such as sodium bicarbonate (CAS No: 144-55-8), potassium citrate (CAS No: 866-84-2), calcium carbonate (CAS No: 471-34-1), calcium acetate (CAS No: 62-54-4), or the like, or combinations thereof, all of which can be obtained from Sigma-Aldrich, 3050 Spruce Street, St. Louis, Mo., USA.
- sodium bicarbonate CAS No: 144-55-8
- potassium citrate CAS No: 866-84-2
- calcium carbonate CAS No: 471-34-1
- calcium acetate CAS No: 62-54-4
- the alkalizing agent can include a salt.
- the salt can include a monovalent cation, a divalent cation, or a trivalent cation, including but not limited to sodium, calcium, potassium, zinc, iron, magnesium, or the like, or combinations thereof.
- the salt can include an anion, including but not limited to chloride, acetate, ascorbate, bicarbonate, citrate, formate, fumarate, phosphate, succinate, borate, gluconate, lactate, malate, trimalate, panthothenate, thiocyanate, glycinate, sulphate, or the like, or combinations thereof.
- the salt can be selected from the group including or consisting of: sodium chloride, sodium acetate, sodium bicarbonate, sodium citrate, sodium phosphate, sodium dihydrogen phosphate, sodium hydrogen phosphate, sodium succinate, sodium borate, sodium gluconate, sodium citrate, sodium lactate, calcium citrate, calcium chloride, calcium pantothenate, calcium gluconate, calcium phosphate, potassium chloride, monopotassium phosphate, dipotassium phosphate, tripotassium phosphate, potassium gluconate, magnesium sulphate, magnesium chloride magnesium gluconate, magnesium acetate, magnesium malate, magnesium glycinate, magnesium lactate, zinc chloride, zinc sulphate and zinc acetate.
- Other exemplary salts may be formed from any combination of anions and cations listed above and may include, anhydrous, hydrates, dehydrates, or the like, or combinations thereof.
- the alkalizing agent can be generally included in an amount of about 0.1% to about 15% by weight of the inventive composition; however, greater or lesser weight percents of the alkalizing agent can be included depending on the disorder symptom to be alleviated or the disorder to be treated. As to particular embodiments, the amount of alkalizing agent included in the inventive composition can be in a range of between about 6.5% to about 15% by weight of the inventive composition.
- the amount of alkalizing agent included in the inventive composition can be selected from the group including or consisting of: between about 1% to about 15% by weight of the inventive composition, between about 1% to about 15% by weight of the inventive composition, between about 2.5% to about 15% by weight of the inventive composition, between about 5% to about 15% by weight of the inventive composition, between about 7.5% to about 15% by weight of the inventive composition, between about 10% to about 15% by weight of the inventive composition, and between about 12.5% to about 15% by weight of the inventive composition.
- the amount of alkalizing agent, for example sodium bicarbonate, included can be about 5% by weight of the inventive composition.
- the amount of alkalizing agent included in the inventive composition can be influenced by factors such as user anatomy, physiology, or biochemistry of the epidermis or underlying tissue; disorder symptom targeted for alleviation; disorder targeted for treatment; observable effect(s) of the application of the inventive composition; or the like; or combinations thereof; but not so much as to cause discomfort to the user or irritation to the epidermis or underlying tissue.
- the vehicle can include one or more excipients in which the sugar or sugar alcohol can be solubilized or suspended.
- the excipient can render the inventive composition suitable for topical application or transdermal application, whereby the vehicle can facilitate the transdermal administration of a portion of the amount of sugar or sugar alcohol and a portion of the amount of alkalizing agent.
- the inventive composition including the amount of sugar or sugar alcohol, amount of alkalizing agent, and the amount of vehicle can take the form of lotion, cream, emulsion, ointment, gel, foam, paste, oil, lipid delivery system, spray, drops, or the like, or combinations thereof.
- the amount of vehicle included in the inventive composition can be influenced by factors such as user anatomy, physiology, or biochemistry of the epidermis or underlying tissue; disorder symptom targeted for alleviation; disorder targeted for treatment; observable effect(s) of the application of the inventive composition; or the like; or combinations thereof; but not so much as to cause discomfort to the user or irritation to the epidermis or underlying tissue.
- the vehicle can include an emulsion base, which can have an oil phase.
- the oil phase can include vegetable oils, animal oils, mineral oils, silicone oils, synthetic oils, fatty acids, fatty alcohols, phospholipids, paraffin waxes, or the like, or combinations thereof.
- the vehicle can further include one or more solubilizing agents, such as cyclodextrins, surfactants, organic solvents, alcohols, polysorbates, or the like, or combinations thereof.
- solubilizing agents such as cyclodextrins, surfactants, organic solvents, alcohols, polysorbates, or the like, or combinations thereof.
- the vehicle can further include one or more viscosity-increasing agents, such as microcrystalline cellulose, carboxymethylcellulose sodium, propylene glycol alginate, xanthan gum, polyacrylic acid, or the like, or combinations thereof.
- viscosity-increasing agents such as microcrystalline cellulose, carboxymethylcellulose sodium, propylene glycol alginate, xanthan gum, polyacrylic acid, or the like, or combinations thereof.
- the vehicle can further include one or more emulsifying or co-emulsifying agents, such as non-ionic surfactants, polyethylene glycol esters, polyoxypropylene glycol ethers, sorbitan esters, ethoxylated sorbitan esters, poly esters, or the like, or combinations thereof.
- emulsifying or co-emulsifying agents such as non-ionic surfactants, polyethylene glycol esters, polyoxypropylene glycol ethers, sorbitan esters, ethoxylated sorbitan esters, poly esters, or the like, or combinations thereof.
- the vehicle can further include one or more emulsion stabilizing agents, such as abietic acid, hydrogenated lanolin alcohol, calcium myristate, hydroxyaluminium distearate, aluminum isostearate, aluminum stearate, 7, 8-didehydrocholesterol, aluminum magnesium hydroxide, stearic acid, lauryl alcohol, hydroxyethyl cellulose, or the like, or combinations thereof.
- emulsion stabilizing agents such as abietic acid, hydrogenated lanolin alcohol, calcium myristate, hydroxyaluminium distearate, aluminum isostearate, aluminum stearate, 7, 8-didehydrocholesterol, aluminum magnesium hydroxide, stearic acid, lauryl alcohol, hydroxyethyl cellulose, or the like, or combinations thereof.
- the vehicle can further include one or more preservatives or preserving agents, such as sorbic acid, methyl paraben, propyl paraben, benzoic acid, sodium benzoate cetrimide, phenoxyethanol, chlorphenisin, methylchloroisothiazolinone, or the like, or combinations thereof.
- preservatives or preserving agents such as sorbic acid, methyl paraben, propyl paraben, benzoic acid, sodium benzoate cetrimide, phenoxyethanol, chlorphenisin, methylchloroisothiazolinone, or the like, or combinations thereof.
- the vehicle can further include one or more penetration enhancers, such as alcohols, sulphoxides, azone, pyrrolidones, urea, disubstituted aminoacetates, glycols (for example, propylene glycol), surfactants, terpenes, terpenoids, fatty acids, esters, cyclodextrins, phospholipids, or the like, or combinations thereof.
- penetration enhancers such as alcohols, sulphoxides, azone, pyrrolidones, urea, disubstituted aminoacetates, glycols (for example, propylene glycol), surfactants, terpenes, terpenoids, fatty acids, esters, cyclodextrins, phospholipids, or the like, or combinations thereof.
- the vehicle can further include water (CAS No: 7732-18-5), which can be filtered, de-ionized, distilled, or water otherwise filtered or purified.
- water CAS No: 7732-18-5
- the vehicle can include Pentravan®, having fatty acid alcohols, acids, esters, phospholipids, antioxidants, skin-feel enhancer, natural humectant, natural preservatives, nonionic emulsifiers, anionic emulsifiers, and buffer, which can be obtained from Fagron, 2400 Pilot Knob Road, St Paul, Minn. 55120, USA.
- Pentravan® having fatty acid alcohols, acids, esters, phospholipids, antioxidants, skin-feel enhancer, natural humectant, natural preservatives, nonionic emulsifiers, anionic emulsifiers, and buffer, which can be obtained from Fagron, 2400 Pilot Knob Road, St Paul, Minn. 55120, USA.
- the vehicle can include Versatile®, having waters, fatty acid esters, alcohols, paraffinic silicone replacement, glidant, plant-derived emollient, vitamin E, nonionic emulsifiers, pro-liposomal phospholipids, and preservatives, which can be obtained from Fagron, 2400 Pilot Knob Road, St Paul, Minn. 55120, USA.
- Versatile® having waters, fatty acid esters, alcohols, paraffinic silicone replacement, glidant, plant-derived emollient, vitamin E, nonionic emulsifiers, pro-liposomal phospholipids, and preservatives, which can be obtained from Fagron, 2400 Pilot Knob Road, St Paul, Minn. 55120, USA.
- the vehicle can include VersaPro Cream BaseTM, which can be obtained from Medisca, 661 Route 3, Unit C, Plattsburgh, N.Y. 12901, USA.
- the inventive composition can further include an amount of magnesium.
- the amount of magnesium can be provided by magnesium chloride, magnesium sulfate, or the like, or combinations thereof.
- the inventive composition can further include an amount of Aesculus hippocastanum .
- the amount of Aesculus hippocastanum can be in a range of between about 0.25% to about 2% by weight of the inventive composition.
- the amount of Aesculus hippocastanum can include an amount of aescin.
- the inventive composition can further include an amount of quercetin.
- the amount of quercetin can be in a range of between about 0.1% to about 1% by weight of the inventive composition.
- the inventive composition can further include an amount of acetyl-L-carnitine.
- the amount of acetyl-L-carnitine can be in a range of between about 0.025% to about 3% by weight of the inventive composition.
- the inventive composition can further include an amount of zinc.
- the amount of zinc can be in a range of between about 0.025% to about 3% by weight of the inventive composition.
- the amount of zinc can be provided by zinc oxide, zinc sulfate, or the like, or combinations thereof.
- inventive composition can further include one or more colorants, fragrances, or the like, as persons of ordinary skill in the art would understand.
- a method of using the inventive composition can include transdermally administering the inventive composition including an amount of sugar or sugar alcohol, an amount of alkalizing agent, and an amount of vehicle, whereby the inventive composition is formulated for transdermal administration.
- the method of using the inventive composition can further include transdermally administering the inventive composition to an external surface of a body to alleviate one or more disorder symptoms, for example to decrease neurogenic pain, or to treat one or more disorders, for example to decrease neurogenic inflammation.
- the method of using the inventive composition can further include transdermally administering the inventive composition along a nerve pathway of a nerve to decrease neurogenic pain or to decrease neurogenic inflammation of the nerve.
- transdermally administering the inventive composition can alkalize a perineural environment proximate the nerve by adjusting a pH of the perineural environment from a lesser alkalinity toward a greater alkalinity.
- transdermally administering the inventive composition can decrease an amount of hydrogen ions (H+) in the perineural environment proximate the nerve.
- H+ hydrogen ions
- TrpV1 transient receptor potential cation channel subfamily V member
- transdermally administering the inventive composition can decrease a viscosity of hyaluronic acid (also known as hyaluronan, hyaluronate, or HA), which is an anionic, nonsulfated glycosaminoglycan widely distributed throughout connective, epithelial, and neural tissues.
- hyaluronic acid can be found between fascial layers, acting as a lubricant to facilitate fascial glide.
- peripheral nerves especially superficial sensory nerves, can typically be enveloped between fascial layers, decreasing the viscosity of hyaluronic acid may decrease friction or mechanical irritation of the nerves by the fascia.
- the method of using the inventive composition can further include transdermally administering the inventive composition formulated as a fluid, such as a lotion, cream, emulsion, ointment, gel, foam, paste, oil, lipid delivery system, spray, drops, or the like, or combinations thereof, to the external surface of the body to alleviate one or more disorder symptoms or to treat one or more disorders.
- a fluid such as a lotion, cream, emulsion, ointment, gel, foam, paste, oil, lipid delivery system, spray, drops, or the like, or combinations thereof
- the method of using the inventive composition can further include administering one or more physical skin penetration enhancement techniques before, during, or after transdermally administrating the inventive composition to the external surface of the body to alleviate one or more disorder symptoms or to treat one or more disorders.
- physical skin penetration enhancement techniques can include phonophoresis, sonophoresis, iontophoresis, electroporation, radiofrequency-driven skin microchanneling, microneedles, massage, occlusion, heating, cooling, or the like, or combinations thereof.
- the inventive composition included dextrose in an amount of about 20% by weight of the inventive composition, sodium bicarbonate in an amount of about 5% by weight of the inventive composition, and vehicle in an amount of about 75% by weight of the inventive composition.
- the method of transdermally administering the particular embodiment of the inventive composition included: i) identifying the site of one or more symptoms, typically pain, and having the subject assess their perceived pain level on a scale ranging from 0 to 10, with 0 being the least amount of pain and 10 being the greatest amount of pain (indicated in column three as “Pre-Admin Pain Level”); ii) determining the cutaneous nerve branch(es) or main nerve trunk(s) liable for the one or more symptoms; iii) confirming the liability of the cutaneous nerve branch(es) or main nerve trunk(s) for the one or more symptoms by palpation; and iv) transdermally administering the inventive composition along the nerve pathway of the cutaneous nerve branch(es) or main nerve trunk(s) liable for the one or more symptoms, focusing on areas where the cutaneous nerve branch(es) or main nerve trunk(s) emerge superficially from deeper regions.
- the inventive composition was transdermally administered for a time period of about sixty seconds. Following, the subject reassessed their perceived pain level at about five minutes after the transdermal administration of the inventive composition (indicated in column four as “5 Minutes Post-Admin Pain Level”) and again at about twenty-four hours after the transdermal administration of the inventive composition (indicated in column six as “24 Hours Post-Admin Pain Level”).
- the mean pre-administration perceived pain level was 5.7/10 whereas the mean five minutes post-administration perceived pain level was 0.4/10, resulting in a mean 95% reduction in perceived pain level (each subject's percent reduction in perceived pain level indicated in column five as “Percent Reduction in Pain Level”) in relation to the pre-administration perceived pain level.
- the mean twenty-four hour post-administration perceived pain level was 1/10, resulting in a mean 84% reduction in perceived pain level (each subject's percent reduction in perceived pain level indicated in column seven as “Percent Reduction in Pain Level”) in relation to the pre-administration perceived pain level.
- the inventive composition included dextrose in an amount of about 20% by weight of the inventive composition, sodium bicarbonate in an amount of about 5% by weight of the inventive composition, and vehicle in an amount of about 75% by weight of the inventive composition.
- the method of transdermally administering the particular embodiment of the inventive composition included: i) identifying the site of one or more symptoms, typically pain, and having the subject assess their perceived pain level on a scale ranging from 0 to 10, with 0 being the least amount of pain and 10 being the greatest amount of pain (indicated in column three as “Pre-Admin Pain Level”); ii) determining the cutaneous nerve branch(es) or main nerve trunk(s) liable for the one or more symptoms; iii) confirming the liability of the cutaneous nerve branch(es) or main nerve trunk(s) for the one or more symptoms by palpation; and iv) transdermally administering the inventive composition along the nerve pathway of the cutaneous nerve branch(es) or main nerve trunk(s) liable for the one or more symptoms, focusing on areas where the cutaneous nerve branch(es) or main nerve trunk(s) emerge superficially from deeper regions.
- the inventive composition was transdermally administered for a time period of about sixty seconds. Following, the subject reassessed their perceived pain level at about one minute after the transdermal administration of the inventive composition (indicated in column four as “1 Minute Post-Admin Pain Level”).
- the mean pre-administration perceived pain level was 6.4/10 whereas the mean one minute post-administration perceived pain level was 1.2/10, resulting in a mean 77% reduction in perceived pain level (each subject's percent reduction in perceived pain level indicated in column five as “Percent Reduction in Pain Level”) relative to the pre-administration perceived pain level.
- the inventive composition included dextrose in an amount of about 20% by weight of the inventive composition, sodium bicarbonate in an amount of about 5% by weight of the inventive composition, and vehicle in an amount of about 75% by weight of the inventive composition.
- the method of transdermally administering the particular embodiment of the inventive composition included: i) identifying the site of one or more symptoms, typically pain, and having the subject assess their perceived pain level on a scale ranging from 0 to 10, with 0 being the least amount of pain and 10 being the greatest amount of pain (indicated in column three as “Pre-Admin Pain Level”); ii) determining the cutaneous nerve branch(es) or main nerve trunk(s) liable for the one or more symptoms; iii) confirming the liability of the cutaneous nerve branch(es) or main nerve trunk(s) for the one or more symptoms by palpation; iv) transdermally administering the inventive composition along the nerve pathway of the cutaneous nerve branch(es) or main nerve trunk(s) liable for the one or more symptoms, focusing on areas where the cutaneous nerve branch(es) or main nerve trunk(s) emerge superficially from deeper regions; and v) administering ultrasound to enhance skin penetration of the inventive composition.
- the inventive composition was transdermally administered for a time period of about sixty seconds and ultrasound was administered for a time period of about five minutes. Following, the subject reassessed their perceived pain level at about one minute after the ultrasound administration (indicated in column four as “1 Minute Post-Admin Pain Level”).
- the mean pre-administration perceived pain level was 5.6/10 whereas the mean one minute post-administration perceived pain level was 0.4/10, resulting in a mean 93% reduction in perceived pain level (each subject's percent reduction in perceived pain level indicated in column five as “Percent Reduction in Pain Level”) relative to the pre-administration perceived pain level.
- Table 5 which evidences the results of the transdermal administration of a particular embodiment of the inventive composition, a first compound, a second compound, and a third compound (as detailed in column one) to a subject who presented with lower back pain in four distinct regions (a first region, a second region, a third region, and a fourth region) along superior cluneal nerves, as detailed in column two.
- the inventive composition, first compound, second compound, and third compound were transdermally administered to the first, second, third, and fourth regions, respectively.
- the inventive composition included dextrose in an amount of about 20% by weight of the inventive composition, sodium bicarbonate in an amount of about 5% by weight of the inventive composition, and vehicle in an amount of about 75% by weight of the inventive composition.
- the first compound included dextrose in an amount of about 10% by weight of the first compound, tannic acid in an amount of about 2% by weight of the first compound, aloe vera in an amount of about 0.75% by weight of the first compound, and vehicle in an amount of about 87.25% by weight of the first compound.
- the second compound included mannitol in an amount of about 20% by weight of the second compound and vehicle in an amount of about 80% by weight of the second compound.
- the third compound included dextrose in an amount of about 20% by weight of the third compound and vehicle in an amount of about 80% by weight of the third compound.
- the method of transdermally administering the particular embodiment of the inventive composition and each of the first, second, and third compounds included: i) identifying the first, second, third, and fourth regions of pain symptoms; ii) applying 2.5 kg/cm′ of pressure via an algometer to each of the first, second, third, and fourth regions of pain symptoms and having the subject assess their perceived pain level on a scale ranging from 0 to 10, with 0 being the least amount of pain and 10 being the greatest amount of pain (indicated in column three as “Pre-Admin Pain Level”); iii) determining the cutaneous nerve branch(es) or main nerve trunk(s) liable for the pain symptoms in each of the first, second, third, and fourth regions; iv) confirming the liability of the cutaneous nerve branch(es) or main nerve trunk(s) for the pain symptoms in each of the first, second, third, and fourth regions by palpation; and v) transdermally administering the inventive composition along the nerve pathway liable for the pain symptoms
- the inventive composition and each of the first, second, and third compounds were transdermally administered for a time period of about sixty seconds.
- 2.5 kg/cm′ of pressure was applied via an algometer to each of the first, second, third, and fourth regions of pain symptoms at about five minutes after the transdermal administration and the subject reassessed their perceived pain level (indicated in column four as “5 Minutes Post-Admin Pain Level”) and again at about fifteen minutes after the transdermal administration, 2.5 kg/cm′ of pressure was applied via an algometer to each of the first, second, third, and fourth regions of pain symptoms and the subject reassessed their perceived pain level (indicated in column six as “15 Minutes Post-Admin Pain Level”).
- the subject reported an 89% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and an 89% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level.
- the subject reported a 50% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 50% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level.
- the subject reported a 56% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 66% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level.
- the subject reported a 70% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and an 80% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level.
- the greatest percent reduction in perceived pain level at both five minutes post-administration and fifteen minutes post-administration was observed following transdermal administration of the inventive composition.
- Table 6 which evidences the results of the transdermal administration of a particular embodiment of the inventive composition, the first compound, the second compound, and the third compound (as detailed in column one) to a subject who presented with knee pain in four distinct regions (a first region, a second region, a third region, and a fourth region) along cutaneous branches of the femoral nerve, as detailed in column two.
- the subject was medicating with oxycodone/acetaminophen (5/325 milligrams every four to six hours), yet still reported significant perceived pain.
- the inventive composition, first compound, second compound, and third compound were transdermally administered to the first, second, third, and fourth regions, respectively.
- the inventive composition included dextrose in an amount of about 20% by weight of the inventive composition, sodium bicarbonate in an amount of about 5% by weight of the inventive composition, and vehicle in an amount of about 75% by weight of the inventive composition.
- the first compound included dextrose in an amount of about 10% by weight of the first compound, tannic acid in an amount of about 2% by weight of the first compound, aloe vera in an amount of about 0.75% by weight of the first compound, and vehicle in an amount of about 87.25% by weight of the first compound.
- the second compound included mannitol in an amount of about 20% by weight of the second compound and vehicle in an amount of about 80% by weight of the second compound.
- the third compound included dextrose in an amount of about 20% by weight of the third compound and vehicle in an amount of about 80% by weight of the third compound.
- the method of transdermally administering the particular embodiment of the inventive composition and each of the first, second, and third compounds included: i) identifying the first, second, third, and fourth regions of pain symptoms; ii) applying 2.5 kg/cm′ of pressure via an algometer to each of the first, second, third, and fourth regions of pain symptoms and having the subject assess their perceived pain level on a scale ranging from 0 to 10, with 0 being the least amount of pain and 10 being the greatest amount of pain (indicated in column three as “Pre-Admin Pain Level”); iii) determining the cutaneous nerve branch(es) or main nerve trunk(s) liable for the pain symptoms in each of the first, second, third, and fourth regions; iv) confirming the liability of the cutaneous nerve branch(es) or main nerve trunk(s) for the pain symptoms in each of the first, second, third, and fourth regions by palpation; and v) transdermally administering the inventive composition along the nerve pathway liable for the pain symptoms
- the inventive composition and each of the first, second, and third compounds were transdermally administered for a time period of about sixty seconds.
- 2.5 kg/cm′ of pressure was applied via an algometer to each of the first, second, third, and fourth regions of pain symptoms at about five minutes after the transdermal administration and the subject reassessed their perceived pain level (indicated in column four as “5 Minutes Post-AdminPain Level”) and again at about fifteen minutes after the transdermal administration, 2.5 kg/cm′ of pressure was applied via an algometer to each of the first, second, third, and fourth regions of pain symptoms and the subject reassessed their perceived pain level (indicated in column six as “15 Minutes Post-Admin Pain Level”).
- the subject reported a 90% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 100% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level.
- the subject reported a 50% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 50% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level.
- the subject reported a 72% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 72% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level.
- the subject reported an 86% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and an 86% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level.
- the greatest percent reduction in perceived pain level at both five minutes post-administration and fifteen minutes post-administration was observed following transdermal administration of the inventive composition.
- Table 7 which evidences the results of the transdermal administration of a first inventive composition, a second inventive composition, a first compound, and a second compound (as detailed in column one) to a subject who presented with lower back pain in four distinct regions (a first region, a second region, a third region, and a fourth region), as detailed in column two.
- the subject Upon presentation, the subject was having a trochanteric shot administered every four weeks.
- the subject was medicating with a steroid pak, celecoxib (200 milligrams every twenty-four hours), and oxycodone/acetaminophen (10/325 milligrams every four hours), yet still reported significant perceived pain.
- the first inventive composition, the second inventive composition, the first compound, and the second compound were transdermally administered to the first, second, third, and fourth regions, respectively.
- the first inventive composition included dextrose in an amount of about 25% by weight of the first inventive composition, sodium bicarbonate in an amount of about 2.5% by weight of the first inventive composition, and vehicle in an amount of about 72.5% by weight of the first inventive composition.
- the second inventive composition included dextrose in an amount of about 20% by weight of the second inventive composition, sodium bicarbonate in an amount of about 10% by weight of the second inventive composition, and vehicle in an amount of about 70% by weight of the second inventive composition.
- the first compound included sodium bicarbonate in an amount of about 2.5% by weight of the first compound and vehicle in an amount of about 97.5% by weight of the first compound.
- the second compound included mannitol in an amount of about 2.5% by weight of the second compound and vehicle in an amount of about 97.5% by weight of the second compound.
- the method of transdermally administering the particular embodiment of the inventive composition and each of the first, second, and third compounds included: i) identifying the first, second, third, and fourth regions of pain symptoms; ii) applying 2.0 kg/cm′ of pressure via an algometer to each of the first, second, third, and fourth regions of pain symptoms and having the subject assess their perceived pain level on a scale ranging from 0 to 10, with 0 being the least amount of pain and 10 being the greatest amount of pain (indicated in column three as “Pre-Admin Pain Level”); iii) determining the cutaneous nerve branch(es) or main nerve trunk(s) liable for the pain symptoms in each of the first, second, third, and fourth regions; iv) confirming the liability of the cutaneous nerve branch(es) or main nerve trunk(s) for the pain symptoms in each of the first, second, third, and fourth regions by palpation; and v) transdermally administering the inventive composition along the nerve pathway liable for the pain symptoms
- each of the first inventive composition, the second inventive composition, the first compound, and the second compound were transdermally administered for a time period of about sixty seconds.
- 2.5 kg/cm′ of pressure was applied via an algometer to each of the first, second, third, and fourth regions of pain symptoms at about five minutes after the transdermal administration and the subject reassessed their perceived pain level (indicated in column four as “5 Minutes Post-Admin Pain Level”) and again at about fifteen minutes after the transdermal administration, 2.5 kg/cm′ of pressure was applied via an algometer to each of the first, second, third, and fourth regions of pain symptoms and the subject reassessed their perceived pain level (indicated in column six as “15 Minutes Post-Admin Pain Level”).
- the subject reported a 57% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 57% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level.
- the subject reported an 83% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and an 83% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level.
- the subject reported an 11% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 22% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-AdminPain Level”) in relation to the pre-administration perceived pain level.
- the subject reported a 50% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 50% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level.
- the greater percent reduction in perceived pain level at both five minutes post-administration and fifteen minutes post-administration was observed following transdermal administration of the first and second inventive compositions, with the greatest percent reduction in perceived pain level at both five minutes post-administration and fifteen minutes post-administration observed following transdermal administration of the second inventive composition.
- the inventive pain reliever can comprise anhydrous dextrose and aloe vera concentrate, and some or all of the following ingredients: propylene glycol, caprylic/capric tryglicerides, sodium chloride (or acetic acid), a homeopathic anti-inflamatory extract, such as Traumeel®, Dimethyl Sulfone (or Methylsulfonylmethane (MSM)), cetyl myristoleate, lipoderm base, distilled water, and, optionally, a pitcher plant extract, such as Sarapin.
- a homeopathic anti-inflamatory extract such as Traumeel®, Dimethyl Sulfone (or Methylsulfonylmethane (MSM)
- MSM Methylsulfonylmethane
- Sarapin a pitcher plant extract
- the Lipoderm base may be substituted by any of the following:
- lecthicin or other fat soluble granules in the range of 0.001 to 75% (w/w) of the composition, preferably 5%;
- PLO Pluronic Lecithin Organogel
- Oleic acid in the range of 0.001 to 70% of the composition, preferably 5%;
- Liposomes in the range of 0.01% to 75% of the composition
- Niosomes in the range of 0.01% to 75% of the composition.
- Nanotechnology in the range of 0.01 to 75%, namely, any one of the following chosen from a group consisting of nanocrystals, liposomes, nanoparticle-protein conjugates, magnetic nanoparticles, nanogels and biodegradable nanoparticles.
- anhydrous dextrose can be substituted in approximately the same concentration by any of the following:
- a. sugar alcohols such as:
- Inositol (6-carbon; a cyclic sugar alcohol);
- An embodiment is a water-based solution to be applied through iontophoresis. This embodiment comprises the following ingredients:
- aloe vera concentrate freeze dried 40 ⁇ powder
- the active ingredients can vary in range from 0.01% to 75% of the total volume of the solution.
- the active ingredients in the embodiment are anhydrous dextrose, aloe vera concentrate, and propylene glycol.
- Another embodiment is a gel which can be applied directly to the epidermis using an ultra sound machine, and can be absorbed faster than the first embodiment.
- This embodiment comprises the following ingredients:
- aloe vera concentrate freeze dried 40 ⁇ powder
- caprylic/capric triglycerides 0.5-5 ml of caprylic/capric triglycerides
- the active ingredients can vary in range from 0.01% to 75% of the total volume of the solution.
- the active ingredients in the embodiment are anhydrous dextrose, aloe vera concentrate, propylene glycol, and caprylic/capric triglycerides.
- Another embodiment is also a gel which can be applied directly to the epidermis without the use an ultra sound machine or iontophoresis, and can be absorbed faster than the first and second embodiment.
- This embodiment comprises the following ingredients:
- aloe vera concentrate freeze dried 40 ⁇ powder
- caprylic/capric triglycerides 0.5-5 ml of caprylic/capric triglycerides
- MSM dimethyl sulfone
- pitcher plant extract (1:2 solution), such as Sarapin®;
- a homeopathic anti-inflamatory extract such as Traumeel®.
- the active ingredients can vary in range from 0.01% to 75% of the total volume of the solution.
- the active ingredients in the embodiment are anhydrous dextrose, aloe vera concentrate, caprylic/capric triglycerides, ethoxy diglycol reagent, lipoderm base, and cetyl myristoleate.
- the recommended percentage of the solution or gel can be as follows:
- dextrose at least 5% or 1-50%, preferably 20%, or of hypertonic saline;
- MSM dimethyl sulfone
- pitcher plant extract such as Sarapin® 10%.
- the embodiments may be combined with shampoo, soap, or water, without losing their effectiveness.
- a pain reliever can be comprised of dextrose, aloe vera concentrate, and some or all of the following ingredients: propylene glycol, caprylic/capric tryglicerides, sodium chloride (or acetic acid), a homeopathic anti-inflamatory extract, Dimethyl Sulfone (or Methylsulfonylmethane (MSM)), cetyl myristoleate, and, optionally, a pitcher plant extract.
- the resulting compositions can be a water-based solution and gel composition applied to the epidermis of mammals for relieving pain.
- a method of producing a particular embodiment of the inventive composition can include combining an amount of sugar or sugar alcohol, an amount of alkalizing agent, and an amount of vehicle; and formulating the inventive composition for transdermal administration.
- the term “combination or combining” refers to any method of putting two or more materials together. Such methods include, but are not limited to, mixing, blending, commingling, concocting, homogenizing, ultrasonic homogenizing, incorporating, intermingling, fusing, joining, shuffling, stirring, coalescing, integrating, confounding, joining, uniting, creating a stable suspension of two immiscible liquids via any number of means such as emulsions, or the like.
- the method of producing a particular embodiment of the inventive composition can include combining the sugar or sugar alcohol, alkalizing agent, and vehicle, whereby each can be combined in an amount as described above.
- the method of producing a particular embodiment of the inventive composition can further include combining one or more additional components to formulate the inventive composition, whereby the one or more additional components can be as described above or can be other additional components.
- the basic concepts of the present invention may be embodied in a variety of ways.
- the invention involves numerous and varied embodiments of a pain relieving system and methods for making and using such pain relieving systems including the best mode.
- each element of an apparatus or each step of a method may be described by an apparatus term or method term. Such terms can be substituted where desired to make explicit the implicitly broad coverage to which this invention is entitled. As but one example, it should be understood that all steps of a method may be disclosed as an action, a means for taking that action, or as an element which causes that action. Similarly, each element of an apparatus may be disclosed as the physical element or the action which that physical element facilitates.
- the term “a” or “an” entity refers to one or more of that entity unless otherwise limited. As such, the terms “a” or “an”, “one or more” and “at least one” can be used interchangeably herein.
- each of the pain relieving systems herein disclosed and described ii) the related methods disclosed and described, iii) similar, equivalent, and even implicit variations of each of these devices and methods, iv) those alternative embodiments which accomplish each of the functions shown, disclosed, or described, v) those alternative designs and methods which accomplish each of the functions shown as are implicit to accomplish that which is disclosed and described, vi) each feature, component, and step shown as separate and independent inventions, vii) the applications enhanced by the various systems or components disclosed, viii) the resulting products produced by such systems or components, ix) methods and apparatuses substantially as described hereinbefore and with reference to any of the accompanying examples, x) the various combinations and permutations of each of the previous elements disclosed.
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Abstract
An inventive composition including an amount of sugar or sugar alcohol, an amount of alkalizing agent, and an amount of vehicle; whereby the inventive composition is formulated for transdermal administration to alleviate one or more disorder symptoms, for example neurogenic pain, or to treat one or more disorders, for example neurogenic inflammation.
Description
- This United States Patent Application is a continuation of U.S. patent application Ser. No. 15/910,983, filed Mar. 2, 2018, and titled PAIN RELIEVER COMPOSITION, which is a continuation of U.S. patent application Ser. No. 15/697,324, filed Sep. 6, 2017, and titled PAIN RELIEVER COMPOSITION, which is a continuation of U.S. patent application Ser. No. 14/612,006, filed Feb. 2, 2015, and titled PAIN RELIEVING SYSTEM, which is a continuation-in-part of U.S. patent application Ser. No. 14/294,034, filed Jun. 2, 2014, and titled PAIN RELIEVER COMPOSITION, which is a continuation of U.S. patent application Ser. No. 13/479,998, filed May 24, 2012, and titled PAIN RELIEVER COMPOSITION, which is a continuation-in-part of U.S. patent application Ser. No. 13/417,053, filed Mar. 9, 2012, and titled PAIN RELIEVER COMPOSITION, which is a continuation-in-part of U.S. patent application Ser. No. 13/295,010, filed Nov. 11, 2011, and titled PAIN RELIEVER COMPOSITION. Each of the above-identified applications is hereby incorporated by reference herein.
- Pain is one of the most frequent symptoms for which patients seek medical intervention. Pain may be classified as acute or chronic. Acute pain may be generally associated with excessive noxious stimulus resulting in a severe distressful sensation whereas chronic pain may be associated with physiological changes resulting from tissue or nerve injury leading to hyperalgesia, an increased amount of pain associated with a mild noxious stimulus, or allodynia, a pain induced by a non-noxious stimulus.
- Neurogenic pain is a neurological disorder caused by insult to peripheral nerves, resulting in chronic pain and varying combinations of sensory symptoms, including paresthesia, loss of sensation, and even motor weakness. Neurogenic pain may be long-lasting, and may develop days or month following the injury. Often, this type of chronic pain may be observed in diseases affecting the peripheral nervous system, such as nerve compression syndromes, cutaneous sensory neuropathies and polyneuropathies (of which diabetic neuropathy may be the most well-known).
- Amongst the various types of chronic pain, understanding and management of neurogenic pain remains a considerably challenging task for researchers and clinicians. Despite the rapid development of neuroscience and the discovery of new pharmaceutical compounds, a need continues to exist for an effective treatment based on a basic understanding of the contributing molecular mechanisms of neurogenic pain.
- Neurogenic pain involves alterations in the function of both the peripheral and central nervous system, postulated to be caused by changes in mechano-insensitive peptidergic nociceptors referred to as “silent” or “sleeping” nociceptors, which are chemo-sensitive and respond to noxious chemicals typically released in response to tissue or nerve trauma. Once sensitized, the phenotype of the nociceptors can be altered, whereby the formerly “silent” or “sleeping” nociceptors become “polymodal” or “awake” nociceptors (C fibers), which release significant amounts of pro-inflammatory neuropeptides, such as calcitonin gene-related peptide (CGRP) or substance P (SP), initiating neurogenic inflammation in combination with enhancing action potentials, thereby resulting in increased nociception.
- Following nerve injury, increased excitability and sensitivity is observed in the cell body of the injured dorsal root ganglia neurons and neighboring intact afferent neurons. This enhanced stimulation involving the primary afferent neurons is defined as peripheral sensitization, which is mediated by increased expression of the transient receptor potential (TRP) family of non-specific cation channels, including transient receptor potential cation channel subfamily V member 1 (TRPV1), which is expressed in C fibers and Δδ fibers. Another mechanism leading to peripheral sensitization includes the accumulation of voltage-gated sodium channels at the site of the injured nerve and at the dorsal root ganglion, resulting in abnormal ectopic excitability of afferent neurons. These changes may be perceived as spontaneous positive sensations, such as paresthesia (a sensation of tingling, burning, pricking, or numbness of skin) or dysthesia (an unpleasant, abnormal sense of touch).
- Central sensitization, defined as the activation of second order nociceptive neurons in the dorsal horn of the spinal cord by peripheral nerve damage, results from the release of glutamate, SP, or other transmitters or cytokines, such as adenosine-5′-triphosphate (ATP), chemokine (C-C motif) ligand 2 (CCL2), or interferon gamma (INFγ), from the central terminals of primary nociceptive afferents in the dorsal horn. The overall effect of these changes may be prolonged excitability of the spinal cord neurons (long-term potentiation).
- Further contributing factors to the development of neurogenic pain include the involvement of spinal cord microglia and astrocytes in enhancing pain, whereby ATP-activated microglial P2X4 and P2X7 receptors stimulate the p38 mitogen-activated protein kinases (p38-MAPK) signalling cascade, resulting in release of substances such as brain-derived neurotrophic factor (BNDF), down-regulation of potassium/chloride cotransporters, and diminished inhibitory neurotransmission (GABAergic inhibition).
- Additionally, following an injury, various inflammatory substances such as histamines, prostaglandins, or cytokines, may be released from inflammatory cells which have migrated through the blood to the site of the injured tissue. When the injury results in nerve damage, the peripheral terminals of sensory neurons may be activated, resulting in inflammation characterized by the release of neuropeptides, such as CGRP, SP, or calcitonin, from the C fiber terminal, which can lead to vasodilation, edema, or pain. As such, neurogenic inflammation plays an integral role in the pathophysiology of neurogenic pain.
- Successful treatment of neurogenic pain requires direct targeting of the receptors and transmitters involved. Conventional therapeutic strategies aim to reduce neuron excitability through alterations in ion channel activity, which may be targeted by compounds such as gabapentin or lidocaine, or modulate central neurotransmission, which may be targeted by compounds such as opioids or tricyclic antidepressants. Despite consistent efficacy observed in randomized trials and meta-analyses, the use of these agents may be limited due to debilitating side effects, such as sedation, somnolence, dry mouth, urinary retention, erythema, ataxia, or the like, or combinations thereof. Moreover, patients using these compounds must be closely monitored and dose tapering may be required to prevent withdrawal symptoms. Accordingly, a need exists for a novel alternative characterized by maximal therapeutic efficacy, minimal toxicity, and low incidence of side effects.
- Some pain reliever compositions are known. For example, U.S. patent application Ser. No. 12/895,200 (US 2011/0076327 A1) by Lomax teaches herbal pain killer compositions, one of which comprises 50 mg each of the following ingredients formed into an approximately 600 mg tablet for oral administration to a mammal: Boswellia serrata, Tumeric, White Wilow, Harpagophytum Procumbens, Phellodendron Amurense, Paullinia Tomentosa, Milkberry, Mimosa Pudica, Lactuca Virosa, Naringen, 6-7 Dihydroxybergamottin, and Yerba mate.
- Further, U.S. patent application Ser. No. 12/874,038 (US 2011/0117175 A1) by Rosenbaum teaches a pain reliever composition for medical procedures treatments comprising a sweet analgesic and a delivery vehicle, wherein the delivery vehicle is suitable for intra-oral delivery, and the sweet analgesic comprises sucrose, glucose, fructose, dextrose, maltodextrin, corn syrup, high fructose corn syrup, cyclamate, aspartame, sucralose, xylitol, cyclamate, stevia, brazzein, curculin, erythritol, glycyrrhizin, honey, luo han gua, mabinlin, monatin, miraculin, monellin, pentadia, thaumatin, acesulfame potassium, alitame, salt of aspartame-acesulfame, dulcin, glucin, neohyesperidin dihydrochalcone, neotame, P-4000, saccharin, or a combination thereof.
- Finally, U.S. patent application Ser. No. 11/305,552 (US 2008/0102107 A1) by Lewellyn teaches a transdermal joint pain therapy composition comprising (a) from about 2.5% to about 15%, based on the total weight of said transdermal joint therapy composition, of glutamine; (b) from about 0.04% to about 0.5%, based on the total weight of said transdermal joint pain therapy composition, of hyaluronic acid; (c) from about 2.55 to about 10.0%, based on the total weight of said transdermal joint pain therapy composition, of methylsulfonylmethane; and (d) from about 70% to about 95%, based on the total weight of said transdermal joint pain therapy composition, of a transdermal delivery agent.
- An objective of the present disclosure is to develop an alternate form of pain relief composition using different active ingredients and in different quantities that is applied to the epidermis of mammals.
- The invention can relate to a pain reliever composition comprised of some or all of the following ingredients: dextrose, aloe vera concentrate, propylene glycol, caprylic/capric tryglicerides, sodium chloride (or acetic acid), a homeopathic anti-inflamatory extract, Dimethyl Sulfone (or methylsulfonylmethane (MSM)), cetyl myristoleate, and a pitcher plant extract.
- The inventive pain reliever composition can comprise a pain relief composition applied to the epidermis of mammals in form of a water-based solution and gels comprising dextrose and aloe vera concentrate, and further comprising some or all of the following ingredients: propylene glycol, caprylic/capric tryglicerides, sodium chloride (or acetic acid), a homeopathic anti-inflamatory extract, such as Traumeel®, Dimethyl Sulfone (or Methyl sulfonylmethane (MSM)), cetyl myristoleate, lipoderm base, distilled water, and a pitcher plant extract, such as Sarapin.
- The lipoderm base can be substituted by any of the following; (1) lecthicin or other fat soluble granules (2) PLO (Pluronic Lecithin Organogel) (3) Urea, (4) Oleic acid, (5) Liposomes, (6) Niosomes, or (7) Nanotechnology, namely, any one of the following chosen from a group consisting of nanocrystals, liposomes, nanoparticle-protein conjugates, magnetic nanoparticles, nanogels and biodegradable nanoparticlea.
- An embodiment comprises aloe vera concentrate, propylene glycol, sterile water, and sodium chloride, in amounts ranging from 0.01% to 75% of the composition, but preferably comprising at least 5% anhydrous dextrose or 1% to 50% hypertonic saline (preferably 20%), at least 10% aloe vera concentrate, and at least 10% propylene glycol.
- An embodiment comprises aloe vera concentrate, propylene glycol, caprylic/capric triglycerides, ultrasound gel, and simple-gel (Hawkins), also in amounts ranging from 0.01% to 75% of the composition, but preferably comprising at least 5% anhydrous dextrose or 1% to 50% hypertonic saline (preferably 20%), at least 10% aloe vera concentrate, at least 10% propylene glycol, and at least 10% caprylic/capric triglycerides.
- An embodiment comprises anhydrous dextrose, aloe vera concentrate, ethoxy diglycol reagent, caprylic/capric triglycerides, lipoderm base, and cetyl myristoleat, in amounts ranging from 0.01% to 75%, but preferably comprising at least 20% anhydrous dextrose, at least 10% aloe vera concentrate, at least 10% caprylic/capric triglycerides, and at least 10% caprylic/capric triglycerides. Preferably, the third embodiment should further comprise at least 10% dimethyl sulfone or Methylsulfonylmethane (MSM), at least 10% pitcher plant extract, distilled water, and a homeopathic anti-inflammatory extract.
- A broad object of a particular embodiment of the invention can be to provide an inventive composition including an amount of sugar or sugar alcohol, an amount of alkalizing agent, and an amount of vehicle; whereby the inventive composition is formulated for transdermal administration.
- Another broad object of a particular embodiment of the invention can be to provide a method of using the inventive composition, the method including transdermally administering the inventive composition to alleviate one or more disorder symptoms, for example neurogenic pain, or to treat one or more disorders, for example neurogenic inflammation.
- Another broad object of a particular embodiment of the invention can be to provide a method of producing an inventive composition, the method including combining an amount of sugar or sugar alcohol, an amount of alkalizing agent, and an amount of vehicle; and formulating the inventive composition for transdermal administration.
- Naturally, further objects of the invention are disclosed throughout other areas of the specification, drawings, and claims.
- A method of using a particular embodiment of the inventive composition including an amount of sugar or sugar alcohol, an amount of alkalizing agent, and an amount of vehicle, whereby the inventive composition is formulated for transdermal administration, can include administering the inventive composition to an external surface of a body to alleviate one or more disorder symptoms, for example neurogenic pain, or to treat one or more disorders, for example neurogenic inflammation.
- The term “sugar” for the purposes of this invention means any carbohydrate or saccharide, including monosaccharides, disaccharides, oligosaccharides, or polysaccharides.
- The term “sugar alcohol” for the purposes of this invention means any polyol (or polyhydric alcohol) derived from a sugar. The polyol can typically include an alcohol group (CH2OH) in place of an aldehyde group (CHO) of the parent sugar.
- The term “alkalizing agent” for the purposes of this invention means an agent capable of adjusting a pH from a lesser alkalinity toward a greater alkalinity.
- The term “symptom” for the purposes of this invention means any discomfort or combination of discomforts associated with a disorder. Without limiting the breadth of the foregoing, symptoms can include: pain, dyesthesia, paresthesia, sensory loss, allodynia, hyperpathia, reduced range-of-motion, motor weakness, or the like, or combinations thereof.
- The term “disorder” for the purposes of this invention means a physical or mental condition which may not be normal or healthy. Without limiting the breadth of the foregoing, a disorder can include: known compressive mononeuropathies (such as carpal tunnel syndrome, cubital tunnel syndrome, or tarsal tunnel syndrome), regional pain conditions (such as sub-occipital neuralgia, facial neuralgias, headache, neck pain, or back pain), acute joint injury which may include a component of nerve inflammation (such as ankle sprain or strain), tendinopathies potentially promoted or aggravated by concomitant neurogenic components (such as Achilles tendonosis, lateral epicondylosis, or medial epicondylosis), or isolated inflammation of any one or more peripheral nerves (such as cranial and upper cervical nerve branch derivatives of the face and cranium).
- The term “topical administration or “transdermal administration” for the purposes of this invention means the administration of one or more components of a composition or compound to and typically, but not necessarily, through the epidermis on any external surface of a body. As to particular embodiments, topical administration or transdermal administration can mean the administration of one or more components of a composition or compound to the epidermis on any external surface of a body and typically, but not necessarily, through the dermis. Following topical administration or transdermal administration, one or more components of the composition or compound may or may not be systemically bioavailable.
- Where trade names or trademarks are utilized herein, whether in Table 1 through Table 7, or any table, figure, or portion of the description, the trade name material or the trademark material is understood to have the chemicals or ingredients in the amounts or combinations as described below. The trade name material or trademark material or a substantially equivalent product or combination of chemicals or ingredients can be utilized in embodiments of the inventive composition. It is further understood that where a trade name material or trademark material is utilized in a table or figure that substantially equivalent chemicals or ingredients in the amounts and combinations as indicated below can be utilized in substitution of the trade name material or trademark material. A person of ordinary skill in the art can convert the weight percentages shown in the tables or figures to determine the amount of each chemical or ingredient to mix when the equivalent of the trade name material or trademark material is prepared.
- Where the constituents of a particular trade name material or trademark material have been set out a first time in the description below, each applies to the subsequent uses of the trade name material or trademark material in the description, tables and figures.
- Now referring primarily to Table 1, embodiments of the inventive composition can include formulations having raw materials admixed in the exemplary weight percentages (“Weight Percent”) shown in column two of Table 1. Numerous embodiments of the inventive composition can be prepared by altering the weight percentages of the raw materials within the range weight percentages (“Range Weight Percent”) shown in column three of Table 1 with an amount of vehicle making up the balance.
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TABLE 1 Raw Material Weight Percent Range Weight Percent Sugar or Sugar Alcohol 20 2 to 30 Alkalizing Agent 5 0.1 to 15 Vehicle 75 55 to 97.9 - As to particular embodiments, the sugar can include a monosaccharide, such as ribose (CAS No: 50-69-1), xylose (CAS No: 58-86-6), fructose (CAS No: 57-48-7), dextrose (glucose) (CAS No: 50-99-7), galactose (CAS No: 59-23-4), mannose (CAS No: 31103-86-3), sorbose (CAS No: 87-79-6), or the like, or combinations thereof, all of which can be obtained from Sigma-Aldrich, 3050 Spruce Street, St. Louis, Mo., USA. As to other particular embodiments, the sugar can include a disaccharide, such as sucrose (CAS No: 57-50-1), maltose (CAS No: 69-79-4), lactose (CAS No: 63-42-3), lactulose (CAS No: 4618-18-2), trehalose (CAS No: 99-20-7), cellobiose (CAS No: 528-50-7), or the like, or combinations thereof, all of which can be obtained from Sigma-Aldrich, 3050 Spruce Street, St. Louis, Mo., USA.
- The sugar can be generally included in an amount of about 2% to about 30% by weight of the inventive composition; however, greater or lesser weight percents of the sugar can be included depending on the disorder symptom to be alleviated or the disorder to be treated.
- As to particular embodiments, the amount of sugar included in the inventive composition can be selected from the group including or consisting of: between about 5% to about 30% by weight of the inventive composition; between about 10% to about 30% by weight of the inventive composition; between about 15% to about 30% by weight of the inventive composition; and between about 20% to about 30% by weight of the inventive composition. As to the particular embodiment of the inventive composition shown in Table 1, the amount of sugar, for example dextrose, included can be about 20% by weight of the inventive composition.
- The amount of sugar included in the inventive composition can be influenced by factors such as user anatomy, physiology, or biochemistry of the epidermis or underlying tissue; disorder symptom targeted for alleviation; disorder targeted for treatment; observable effect(s) of the application of the inventive composition; or the like; or combinations thereof; but not so much as to cause discomfort to the user or irritation to the epidermis or underlying tissue.
- The sugar alcohol can include a polyol derived from a monosaccharide or a disaccharide, including glycerol (CAS No: 56-81-5), erythritol (CAS No: 10030-58-7), threitol (CAS No: 2418-52-2), arabitol (CAS No: 7643-75-6), xylitol (CAS No: 87-99-0), adonitol (CAS No: 488-81-3), mannitol (CAS No: 69-65-8), sorbitol (CAS No: 50-70-4), dulcitol (CAS No: 608-66-2), fucitol (CAS No: 13074-06-1), iditol (CAS No: 488-45-9), inositol (CAS No: 87-89-8), volemitol (CAS No: 30635-52-0), isomalt (CAS No: 64519-82-0), maltitol (CAS No: 585-88-6), lactitol (CAS No: 585-86-4), maltotriitol (CAS No: 32860-62-1), or the like, or combinations thereof, all of which can be obtained from Sigma-Aldrich, 3050 Spruce Street, St. Louis, Mo., USA.
- The sugar alcohol can be generally included in an amount of about 2% to about 30% by weight of the inventive composition; however, greater or lesser weight percents of the sugar alcohol can be included depending on the disorder symptom to be alleviated or the disorder to be treated.
- As to particular embodiments, the amount of sugar alcohol included in the inventive composition can be selected from the group including or consisting of: between about 5% to about 30% by weight of the inventive composition; between about 10% to about 30% by weight of the inventive composition; between about 15% to about 30% by weight of the inventive composition; and between about 20% to about 30% by weight of the inventive composition. As to the particular embodiment of the inventive composition shown in Table 1, the amount of sugar alcohol, for example mannitol, included can be about 20% by weight of the inventive composition.
- The amount of sugar alcohol included in the inventive composition can be influenced by factors such as user anatomy, physiology, or biochemistry of the epidermis or underlying tissue; disorder symptom targeted for alleviation; disorder targeted for treatment; observable effect(s) of the application of the inventive composition; or the like; or combinations thereof; but not so much as to cause discomfort to the user or irritation to the epidermis or underlying tissue.
- The alkalizing agent can include any agent capable of adjusting a pH from a lesser alkalinity toward a greater alkalinity, such as sodium bicarbonate (CAS No: 144-55-8), potassium citrate (CAS No: 866-84-2), calcium carbonate (CAS No: 471-34-1), calcium acetate (CAS No: 62-54-4), or the like, or combinations thereof, all of which can be obtained from Sigma-Aldrich, 3050 Spruce Street, St. Louis, Mo., USA.
- As to particular embodiments, the alkalizing agent can include a salt. As to particular embodiments, the salt can include a monovalent cation, a divalent cation, or a trivalent cation, including but not limited to sodium, calcium, potassium, zinc, iron, magnesium, or the like, or combinations thereof. As to other particular embodiments, the salt can include an anion, including but not limited to chloride, acetate, ascorbate, bicarbonate, citrate, formate, fumarate, phosphate, succinate, borate, gluconate, lactate, malate, trimalate, panthothenate, thiocyanate, glycinate, sulphate, or the like, or combinations thereof.
- As to particular embodiments, the salt can be selected from the group including or consisting of: sodium chloride, sodium acetate, sodium bicarbonate, sodium citrate, sodium phosphate, sodium dihydrogen phosphate, sodium hydrogen phosphate, sodium succinate, sodium borate, sodium gluconate, sodium citrate, sodium lactate, calcium citrate, calcium chloride, calcium pantothenate, calcium gluconate, calcium phosphate, potassium chloride, monopotassium phosphate, dipotassium phosphate, tripotassium phosphate, potassium gluconate, magnesium sulphate, magnesium chloride magnesium gluconate, magnesium acetate, magnesium malate, magnesium glycinate, magnesium lactate, zinc chloride, zinc sulphate and zinc acetate. Other exemplary salts may be formed from any combination of anions and cations listed above and may include, anhydrous, hydrates, dehydrates, or the like, or combinations thereof.
- The alkalizing agent can be generally included in an amount of about 0.1% to about 15% by weight of the inventive composition; however, greater or lesser weight percents of the alkalizing agent can be included depending on the disorder symptom to be alleviated or the disorder to be treated. As to particular embodiments, the amount of alkalizing agent included in the inventive composition can be in a range of between about 6.5% to about 15% by weight of the inventive composition. As to particular embodiments, the amount of alkalizing agent included in the inventive composition can be selected from the group including or consisting of: between about 1% to about 15% by weight of the inventive composition, between about 1% to about 15% by weight of the inventive composition, between about 2.5% to about 15% by weight of the inventive composition, between about 5% to about 15% by weight of the inventive composition, between about 7.5% to about 15% by weight of the inventive composition, between about 10% to about 15% by weight of the inventive composition, and between about 12.5% to about 15% by weight of the inventive composition. As to the particular embodiment of the inventive composition shown in Table 1, the amount of alkalizing agent, for example sodium bicarbonate, included can be about 5% by weight of the inventive composition.
- The amount of alkalizing agent included in the inventive composition can be influenced by factors such as user anatomy, physiology, or biochemistry of the epidermis or underlying tissue; disorder symptom targeted for alleviation; disorder targeted for treatment; observable effect(s) of the application of the inventive composition; or the like; or combinations thereof; but not so much as to cause discomfort to the user or irritation to the epidermis or underlying tissue.
- The vehicle can include one or more excipients in which the sugar or sugar alcohol can be solubilized or suspended. As to particular embodiments, the excipient can render the inventive composition suitable for topical application or transdermal application, whereby the vehicle can facilitate the transdermal administration of a portion of the amount of sugar or sugar alcohol and a portion of the amount of alkalizing agent. As illustrative examples, the inventive composition including the amount of sugar or sugar alcohol, amount of alkalizing agent, and the amount of vehicle can take the form of lotion, cream, emulsion, ointment, gel, foam, paste, oil, lipid delivery system, spray, drops, or the like, or combinations thereof.
- The amount of vehicle included in the inventive composition can be influenced by factors such as user anatomy, physiology, or biochemistry of the epidermis or underlying tissue; disorder symptom targeted for alleviation; disorder targeted for treatment; observable effect(s) of the application of the inventive composition; or the like; or combinations thereof; but not so much as to cause discomfort to the user or irritation to the epidermis or underlying tissue.
- As to particular embodiments, the vehicle can include an emulsion base, which can have an oil phase. As illustrative examples, the oil phase can include vegetable oils, animal oils, mineral oils, silicone oils, synthetic oils, fatty acids, fatty alcohols, phospholipids, paraffin waxes, or the like, or combinations thereof.
- As to particular embodiments, the vehicle can further include one or more solubilizing agents, such as cyclodextrins, surfactants, organic solvents, alcohols, polysorbates, or the like, or combinations thereof.
- As to particular embodiments, the vehicle can further include one or more viscosity-increasing agents, such as microcrystalline cellulose, carboxymethylcellulose sodium, propylene glycol alginate, xanthan gum, polyacrylic acid, or the like, or combinations thereof.
- As to particular embodiments, the vehicle can further include one or more emulsifying or co-emulsifying agents, such as non-ionic surfactants, polyethylene glycol esters, polyoxypropylene glycol ethers, sorbitan esters, ethoxylated sorbitan esters, poly esters, or the like, or combinations thereof.
- As to particular embodiments, the vehicle can further include one or more emulsion stabilizing agents, such as abietic acid, hydrogenated lanolin alcohol, calcium myristate, hydroxyaluminium distearate, aluminum isostearate, aluminum stearate, 7, 8-didehydrocholesterol, aluminum magnesium hydroxide, stearic acid, lauryl alcohol, hydroxyethyl cellulose, or the like, or combinations thereof.
- As to particular embodiments, the vehicle can further include one or more preservatives or preserving agents, such as sorbic acid, methyl paraben, propyl paraben, benzoic acid, sodium benzoate cetrimide, phenoxyethanol, chlorphenisin, methylchloroisothiazolinone, or the like, or combinations thereof.
- As to particular embodiments, the vehicle can further include one or more penetration enhancers, such as alcohols, sulphoxides, azone, pyrrolidones, urea, disubstituted aminoacetates, glycols (for example, propylene glycol), surfactants, terpenes, terpenoids, fatty acids, esters, cyclodextrins, phospholipids, or the like, or combinations thereof.
- As to particular embodiments, the vehicle can further include water (CAS No: 7732-18-5), which can be filtered, de-ionized, distilled, or water otherwise filtered or purified.
- As an illustrative example, the vehicle can include Pentravan®, having fatty acid alcohols, acids, esters, phospholipids, antioxidants, skin-feel enhancer, natural humectant, natural preservatives, nonionic emulsifiers, anionic emulsifiers, and buffer, which can be obtained from Fagron, 2400 Pilot Knob Road, St Paul, Minn. 55120, USA.
- As an additional illustrative example, the vehicle can include Versatile®, having waters, fatty acid esters, alcohols, paraffinic silicone replacement, glidant, plant-derived emollient, vitamin E, nonionic emulsifiers, pro-liposomal phospholipids, and preservatives, which can be obtained from Fagron, 2400 Pilot Knob Road, St Paul, Minn. 55120, USA.
- As yet an additional illustrative example, the vehicle can include VersaPro Cream Base™, which can be obtained from Medisca, 661 Route 3, Unit C, Plattsburgh, N.Y. 12901, USA.
- As to particular embodiments, the inventive composition can further include an amount of magnesium. As to particular embodiments, the amount of magnesium can be provided by magnesium chloride, magnesium sulfate, or the like, or combinations thereof.
- As to particular embodiments, the inventive composition can further include an amount of Aesculus hippocastanum. As to particular embodiments, the amount of Aesculus hippocastanum can be in a range of between about 0.25% to about 2% by weight of the inventive composition. As to particular embodiments, the amount of Aesculus hippocastanum can include an amount of aescin.
- As to particular embodiments, the inventive composition can further include an amount of quercetin. As to particular embodiments, the amount of quercetin can be in a range of between about 0.1% to about 1% by weight of the inventive composition.
- As to particular embodiments, the inventive composition can further include an amount of acetyl-L-carnitine. As to particular embodiments, the amount of acetyl-L-carnitine can be in a range of between about 0.025% to about 3% by weight of the inventive composition.
- As to particular embodiments, the inventive composition can further include an amount of zinc. As to particular embodiments, the amount of zinc can be in a range of between about 0.025% to about 3% by weight of the inventive composition. As to particular embodiments, the amount of zinc can be provided by zinc oxide, zinc sulfate, or the like, or combinations thereof.
- As to particular embodiments, the inventive composition can further include one or more colorants, fragrances, or the like, as persons of ordinary skill in the art would understand.
- A method of using the inventive composition can include transdermally administering the inventive composition including an amount of sugar or sugar alcohol, an amount of alkalizing agent, and an amount of vehicle, whereby the inventive composition is formulated for transdermal administration.
- As to particular embodiments, the method of using the inventive composition can further include transdermally administering the inventive composition to an external surface of a body to alleviate one or more disorder symptoms, for example to decrease neurogenic pain, or to treat one or more disorders, for example to decrease neurogenic inflammation.
- As to particular embodiments, the method of using the inventive composition can further include transdermally administering the inventive composition along a nerve pathway of a nerve to decrease neurogenic pain or to decrease neurogenic inflammation of the nerve.
- As to particular embodiments, transdermally administering the inventive composition can alkalize a perineural environment proximate the nerve by adjusting a pH of the perineural environment from a lesser alkalinity toward a greater alkalinity. As to particular embodiments, transdermally administering the inventive composition can decrease an amount of hydrogen ions (H+) in the perineural environment proximate the nerve.
- Research suggests an association between tissue acidity and neurogenic inflammation whereby hydrogen ions (H+) may prime the transient receptor potential cation channel subfamily V member (TrpV1), thereby increasing neurogenic inflammation and corresponding neurogenic pain. Accordingly, decreasing the amount of hydrogen ions (H+) by adjusting the perineural environment from a lesser alkalinity toward a greater alkalinity may be beneficial for alleviating neurogenic pain or treating neurogenic inflammation.
- As to particular embodiments, transdermally administering the inventive composition can decrease a viscosity of hyaluronic acid (also known as hyaluronan, hyaluronate, or HA), which is an anionic, nonsulfated glycosaminoglycan widely distributed throughout connective, epithelial, and neural tissues. Particularly, hyaluronic acid can be found between fascial layers, acting as a lubricant to facilitate fascial glide. As peripheral nerves, especially superficial sensory nerves, can typically be enveloped between fascial layers, decreasing the viscosity of hyaluronic acid may decrease friction or mechanical irritation of the nerves by the fascia. Research suggests that adjusting the pH of a perineural environment from a lesser alkalinity toward a greater alkalinity may result in a conformational change in the hyaluronic acid molecule resulting from a degradation of attraction forces between hyaluronic acid molecules, thereby increasing the flexibility of the hyaluronic acid polymer and correspondingly decreasing the viscosity of hyaluronic acid.
- As to particular embodiments, the method of using the inventive composition can further include transdermally administering the inventive composition formulated as a fluid, such as a lotion, cream, emulsion, ointment, gel, foam, paste, oil, lipid delivery system, spray, drops, or the like, or combinations thereof, to the external surface of the body to alleviate one or more disorder symptoms or to treat one or more disorders.
- As to particular embodiments, the method of using the inventive composition can further include administering one or more physical skin penetration enhancement techniques before, during, or after transdermally administrating the inventive composition to the external surface of the body to alleviate one or more disorder symptoms or to treat one or more disorders. As illustrative examples, physical skin penetration enhancement techniques can include phonophoresis, sonophoresis, iontophoresis, electroporation, radiofrequency-driven skin microchanneling, microneedles, massage, occlusion, heating, cooling, or the like, or combinations thereof.
- Now referring primarily to Table 2, which evidences the results of a method of transdermally administering a particular embodiment of the inventive composition to twenty-six subjects (indicated in column 1 as “Subject Number”) who presented with various pain-related complaints (indicated in column 2 as “Primary Complaint”). As to this particular embodiment, the inventive composition included dextrose in an amount of about 20% by weight of the inventive composition, sodium bicarbonate in an amount of about 5% by weight of the inventive composition, and vehicle in an amount of about 75% by weight of the inventive composition.
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TABLE 2 Percent Percent 5 Minutes Reduction 24 Hours Reduction Subject Pre-Admin Post-Admin in Pain Post-Admin in Pain Number Primary Complaint Pain Level Pain Level Level Pain Level Level 1 Post-surgical knee pain 4 0 100% 1 75% 2 Idiopathic knee pain 3 0 100% 1 67% 3 Radiating leg pain 4 0 100% 1 75% 4 Post-surgical knee pain 8 0 100% 2 75% 5 Iliotibial band pain 2 0 100% 0 100% 6 Post-surgical hip pain 3 0 100% 0 100% 7 Elbow pain 4 0 100% 0 100% 8 Severe low back & leg pain 8 0 100% 1 88% 9 Neck pain & face paresthesia 8 0 100% 0 100% 10 Elbow/forearm pain 4 0 100% 1 75% 11 Shoulder pain 4 0 100% 1 75% 12 Post-surgical knee pain 8 2 75% 2 75% 13 Post-surgical back pain 9 2 78% 2 78% 14 Plantar fasciitis 4 0 100% 1 75% 15 Plantar fasciitis 3 0 100% 1 67% 16 Post-surgical knee pain 7 0 100% 1 86% 17 Acute lower back pain 6 0 100% 0 100% 18 Severe low back & leg pain 10 2 80% 3 70% 19 Shoulder pain & restriction 4 0 100% 0 100% 20 Post-surgical shoulder pain 5 0 100% 0 100% 21 Chronic shoulder pain 5 0 100% 0 100% 22 Acute upper back pain 6 0 100% 0 100% 23 Acute shoulder pain 6 2 67% 2 67% 24 Chronic shoulder pain 9 1 89% 3 67% 25 Neck & shoulder pain 8 1 88% 3 63% 26 Chronic headache/migraine 6 0 100% 0 100% Mean 5.7 0.4 95% 1 84% - Again referring primarily to Table 2, the method of transdermally administering the particular embodiment of the inventive composition included: i) identifying the site of one or more symptoms, typically pain, and having the subject assess their perceived pain level on a scale ranging from 0 to 10, with 0 being the least amount of pain and 10 being the greatest amount of pain (indicated in column three as “Pre-Admin Pain Level”); ii) determining the cutaneous nerve branch(es) or main nerve trunk(s) liable for the one or more symptoms; iii) confirming the liability of the cutaneous nerve branch(es) or main nerve trunk(s) for the one or more symptoms by palpation; and iv) transdermally administering the inventive composition along the nerve pathway of the cutaneous nerve branch(es) or main nerve trunk(s) liable for the one or more symptoms, focusing on areas where the cutaneous nerve branch(es) or main nerve trunk(s) emerge superficially from deeper regions. Generally, the inventive composition was transdermally administered for a time period of about sixty seconds. Following, the subject reassessed their perceived pain level at about five minutes after the transdermal administration of the inventive composition (indicated in column four as “5 Minutes Post-Admin Pain Level”) and again at about twenty-four hours after the transdermal administration of the inventive composition (indicated in column six as “24 Hours Post-Admin Pain Level”).
- Again referring primarily to Table 2, the mean pre-administration perceived pain level was 5.7/10 whereas the mean five minutes post-administration perceived pain level was 0.4/10, resulting in a mean 95% reduction in perceived pain level (each subject's percent reduction in perceived pain level indicated in column five as “Percent Reduction in Pain Level”) in relation to the pre-administration perceived pain level. The mean twenty-four hour post-administration perceived pain level was 1/10, resulting in a mean 84% reduction in perceived pain level (each subject's percent reduction in perceived pain level indicated in column seven as “Percent Reduction in Pain Level”) in relation to the pre-administration perceived pain level.
- Now referring primarily to Table 3, which evidences the results of a method of transdermally administering a particular embodiment of the inventive composition to twelve subjects (indicated in column 1 as “Subject Number”) who presented with various pain-related complaints (indicated in column 2 as “Primary Complaint”). As to this particular embodiment, the inventive composition included dextrose in an amount of about 20% by weight of the inventive composition, sodium bicarbonate in an amount of about 5% by weight of the inventive composition, and vehicle in an amount of about 75% by weight of the inventive composition.
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TABLE 3 1 Minute Percent Subject Primary Pre-Admin Post-Admin Reduction Number Complaint Pain Level Pain Level in Pain Level 1 Abdominal pain 6 1 83% 2 Knee pain 6 1 83% 3 Metacarpal- 6 0.5 92% phalangeal joint pain 4 Carpal tunnel pain 6 0 100% 5 Supraspinatus 10 2 80% tendon pain 6 Wrist rheumatoid 3 3 0% arthritis 7 Lower back pain 9 3 67% 8 Foot complex 3.4 1.5 56% regional pain syndrome 9 Knee pain 5 0 100% 10 Achilles tendon pain 6 1 83% 11 Wrist pain 9 0 100% 12 Lower back pain 7 1.5 79% Mean 6.4 1.2 77% - Again referring primarily to Table 3, the method of transdermally administering the particular embodiment of the inventive composition included: i) identifying the site of one or more symptoms, typically pain, and having the subject assess their perceived pain level on a scale ranging from 0 to 10, with 0 being the least amount of pain and 10 being the greatest amount of pain (indicated in column three as “Pre-Admin Pain Level”); ii) determining the cutaneous nerve branch(es) or main nerve trunk(s) liable for the one or more symptoms; iii) confirming the liability of the cutaneous nerve branch(es) or main nerve trunk(s) for the one or more symptoms by palpation; and iv) transdermally administering the inventive composition along the nerve pathway of the cutaneous nerve branch(es) or main nerve trunk(s) liable for the one or more symptoms, focusing on areas where the cutaneous nerve branch(es) or main nerve trunk(s) emerge superficially from deeper regions. Generally, the inventive composition was transdermally administered for a time period of about sixty seconds. Following, the subject reassessed their perceived pain level at about one minute after the transdermal administration of the inventive composition (indicated in column four as “1 Minute Post-Admin Pain Level”).
- Again referring primarily to Table 3, the mean pre-administration perceived pain level was 6.4/10 whereas the mean one minute post-administration perceived pain level was 1.2/10, resulting in a mean 77% reduction in perceived pain level (each subject's percent reduction in perceived pain level indicated in column five as “Percent Reduction in Pain Level”) relative to the pre-administration perceived pain level.
- Now referring primarily to Table 4, which evidences the results of a method of transdermally administering a particular embodiment of the inventive composition to nine subjects (indicated in column 1 as “Subject Number”) who presented with various pain-related complaints (indicated in column 2 as “Primary Complaint”). As to this particular embodiment, the inventive composition included dextrose in an amount of about 20% by weight of the inventive composition, sodium bicarbonate in an amount of about 5% by weight of the inventive composition, and vehicle in an amount of about 75% by weight of the inventive composition.
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TABLE 4 1 Minute Percent Subject Primary Pre-Admin Post-Admin Reduction Number Complaint Pain Level Pain Level in Pain Level 1 Neck pain 6 1 83% 2 Plantar fasciitis 6 0 100% 3 Carpal tunnel pain 6 0 100% 4 Plantar fasciitis 6 2 67% pain 5 Bilateral ankle 4 0 100% pain 6 Carpal tunnel pain 4 0 100% 7 Extensor ligament 4 0 100% pain 8 Achilles tendon 8 1 88% pain 9 Knee pain 6 0 100% Mean 5.6 0.4 93% - Again referring primarily to Table 4, the method of transdermally administering the particular embodiment of the inventive composition included: i) identifying the site of one or more symptoms, typically pain, and having the subject assess their perceived pain level on a scale ranging from 0 to 10, with 0 being the least amount of pain and 10 being the greatest amount of pain (indicated in column three as “Pre-Admin Pain Level”); ii) determining the cutaneous nerve branch(es) or main nerve trunk(s) liable for the one or more symptoms; iii) confirming the liability of the cutaneous nerve branch(es) or main nerve trunk(s) for the one or more symptoms by palpation; iv) transdermally administering the inventive composition along the nerve pathway of the cutaneous nerve branch(es) or main nerve trunk(s) liable for the one or more symptoms, focusing on areas where the cutaneous nerve branch(es) or main nerve trunk(s) emerge superficially from deeper regions; and v) administering ultrasound to enhance skin penetration of the inventive composition. Generally, the inventive composition was transdermally administered for a time period of about sixty seconds and ultrasound was administered for a time period of about five minutes. Following, the subject reassessed their perceived pain level at about one minute after the ultrasound administration (indicated in column four as “1 Minute Post-Admin Pain Level”).
- Again referring primarily to Table 4, the mean pre-administration perceived pain level was 5.6/10 whereas the mean one minute post-administration perceived pain level was 0.4/10, resulting in a mean 93% reduction in perceived pain level (each subject's percent reduction in perceived pain level indicated in column five as “Percent Reduction in Pain Level”) relative to the pre-administration perceived pain level.
- Now referring primarily to Table 5, which evidences the results of the transdermal administration of a particular embodiment of the inventive composition, a first compound, a second compound, and a third compound (as detailed in column one) to a subject who presented with lower back pain in four distinct regions (a first region, a second region, a third region, and a fourth region) along superior cluneal nerves, as detailed in column two. The inventive composition, first compound, second compound, and third compound were transdermally administered to the first, second, third, and fourth regions, respectively.
- As to this particular embodiment, the inventive composition included dextrose in an amount of about 20% by weight of the inventive composition, sodium bicarbonate in an amount of about 5% by weight of the inventive composition, and vehicle in an amount of about 75% by weight of the inventive composition.
- The first compound included dextrose in an amount of about 10% by weight of the first compound, tannic acid in an amount of about 2% by weight of the first compound, aloe vera in an amount of about 0.75% by weight of the first compound, and vehicle in an amount of about 87.25% by weight of the first compound.
- The second compound included mannitol in an amount of about 20% by weight of the second compound and vehicle in an amount of about 80% by weight of the second compound.
- The third compound included dextrose in an amount of about 20% by weight of the third compound and vehicle in an amount of about 80% by weight of the third compound.
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TABLE 5 Inventive Percent Percent Composition 5 Minutes Reduction 15 Minutes Reduction and Distinct Pre-Admin Post-Admin in Pain Post-Admin in Pain Compounds Region Pain Level Pain Level Level Pain Level Level Inventive First Region 9 1 89% 1 89% Composition First Second Region 10 5 50% 5 50% Compound Second Third Region 9 4 56% 3 66% Compound Third Fourth Region 10 3 70% 2 80% Compound - Again referring primarily to Table 5, the method of transdermally administering the particular embodiment of the inventive composition and each of the first, second, and third compounds included: i) identifying the first, second, third, and fourth regions of pain symptoms; ii) applying 2.5 kg/cm′ of pressure via an algometer to each of the first, second, third, and fourth regions of pain symptoms and having the subject assess their perceived pain level on a scale ranging from 0 to 10, with 0 being the least amount of pain and 10 being the greatest amount of pain (indicated in column three as “Pre-Admin Pain Level”); iii) determining the cutaneous nerve branch(es) or main nerve trunk(s) liable for the pain symptoms in each of the first, second, third, and fourth regions; iv) confirming the liability of the cutaneous nerve branch(es) or main nerve trunk(s) for the pain symptoms in each of the first, second, third, and fourth regions by palpation; and v) transdermally administering the inventive composition along the nerve pathway liable for the pain symptoms proximate the first region; vi) transdermally administering the first compound along the nerve pathway liable for the pain symptoms proximate the second region; vii) transdermally administering the second compound along the nerve pathway liable for the pain symptoms proximate the third region; and viii) transdermally administering the third compound along the nerve pathway liable for the pain symptoms proximate the fourth region. Generally, the inventive composition and each of the first, second, and third compounds were transdermally administered for a time period of about sixty seconds. Following, 2.5 kg/cm′ of pressure was applied via an algometer to each of the first, second, third, and fourth regions of pain symptoms at about five minutes after the transdermal administration and the subject reassessed their perceived pain level (indicated in column four as “5 Minutes Post-Admin Pain Level”) and again at about fifteen minutes after the transdermal administration, 2.5 kg/cm′ of pressure was applied via an algometer to each of the first, second, third, and fourth regions of pain symptoms and the subject reassessed their perceived pain level (indicated in column six as “15 Minutes Post-Admin Pain Level”).
- Again referring primarily to Table 5, regarding the inventive composition transdermally administered to the first region, the subject reported an 89% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and an 89% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level. Regarding the first compound transdermally administered to the second region, the subject reported a 50% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 50% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level. Regarding the third compound transdermally administered to the third region, the subject reported a 56% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 66% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level. Regarding the fourth compound transdermally administered to the fourth region, the subject reported a 70% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and an 80% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level. Overall, of the inventive composition, and first, second, and third compounds, the greatest percent reduction in perceived pain level at both five minutes post-administration and fifteen minutes post-administration was observed following transdermal administration of the inventive composition.
- Now referring primarily to Table 6, which evidences the results of the transdermal administration of a particular embodiment of the inventive composition, the first compound, the second compound, and the third compound (as detailed in column one) to a subject who presented with knee pain in four distinct regions (a first region, a second region, a third region, and a fourth region) along cutaneous branches of the femoral nerve, as detailed in column two. Upon presentation, the subject was medicating with oxycodone/acetaminophen (5/325 milligrams every four to six hours), yet still reported significant perceived pain. The inventive composition, first compound, second compound, and third compound were transdermally administered to the first, second, third, and fourth regions, respectively.
- As to this particular embodiment, the inventive composition included dextrose in an amount of about 20% by weight of the inventive composition, sodium bicarbonate in an amount of about 5% by weight of the inventive composition, and vehicle in an amount of about 75% by weight of the inventive composition.
- The first compound included dextrose in an amount of about 10% by weight of the first compound, tannic acid in an amount of about 2% by weight of the first compound, aloe vera in an amount of about 0.75% by weight of the first compound, and vehicle in an amount of about 87.25% by weight of the first compound.
- The second compound included mannitol in an amount of about 20% by weight of the second compound and vehicle in an amount of about 80% by weight of the second compound.
- The third compound included dextrose in an amount of about 20% by weight of the third compound and vehicle in an amount of about 80% by weight of the third compound.
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TABLE 6 Inventive Percent Percent Composition 5 Minutes Reduction 15 Minutes Reduction and Distinct Pre-Admin Post-Admin in Pain Post-Admin in Pain Compounds Region Pain Level Pain Level Level Pain Level Level Inventive First Region 10 1 90% 0 100% Composition First Second Region 8 4 50% 4 50% Compound Second Third Region 7 2 72% 2 72% Compound Third Fourth Region 7 1 86% 1 86% Compound - Again referring primarily to Table 6, the method of transdermally administering the particular embodiment of the inventive composition and each of the first, second, and third compounds included: i) identifying the first, second, third, and fourth regions of pain symptoms; ii) applying 2.5 kg/cm′ of pressure via an algometer to each of the first, second, third, and fourth regions of pain symptoms and having the subject assess their perceived pain level on a scale ranging from 0 to 10, with 0 being the least amount of pain and 10 being the greatest amount of pain (indicated in column three as “Pre-Admin Pain Level”); iii) determining the cutaneous nerve branch(es) or main nerve trunk(s) liable for the pain symptoms in each of the first, second, third, and fourth regions; iv) confirming the liability of the cutaneous nerve branch(es) or main nerve trunk(s) for the pain symptoms in each of the first, second, third, and fourth regions by palpation; and v) transdermally administering the inventive composition along the nerve pathway liable for the pain symptoms proximate the first region; vi) transdermally administering the first compound along the nerve pathway liable for the pain symptoms proximate the second region; vii) transdermally administering the second compound along the nerve pathway liable for the pain symptoms proximate the third region; and viii) transdermally administering the third compound along the nerve pathway liable for the pain symptoms proximate the fourth region. Generally, the inventive composition and each of the first, second, and third compounds were transdermally administered for a time period of about sixty seconds. Following, 2.5 kg/cm′ of pressure was applied via an algometer to each of the first, second, third, and fourth regions of pain symptoms at about five minutes after the transdermal administration and the subject reassessed their perceived pain level (indicated in column four as “5 Minutes Post-AdminPain Level”) and again at about fifteen minutes after the transdermal administration, 2.5 kg/cm′ of pressure was applied via an algometer to each of the first, second, third, and fourth regions of pain symptoms and the subject reassessed their perceived pain level (indicated in column six as “15 Minutes Post-Admin Pain Level”).
- Again referring primarily to Table 6, regarding the inventive composition transdermally administered to the first region, the subject reported a 90% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 100% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level. Regarding the first compound transdermally administered to the second region, the subject reported a 50% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 50% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level. Regarding the third compound transdermally administered to the third region, the subject reported a 72% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 72% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level. Regarding the fourth compound transdermally administered to the fourth region, the subject reported an 86% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and an 86% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level. Overall, of the inventive composition, and first, second, and third compounds, the greatest percent reduction in perceived pain level at both five minutes post-administration and fifteen minutes post-administration was observed following transdermal administration of the inventive composition.
- Now referring primarily to Table 7, which evidences the results of the transdermal administration of a first inventive composition, a second inventive composition, a first compound, and a second compound (as detailed in column one) to a subject who presented with lower back pain in four distinct regions (a first region, a second region, a third region, and a fourth region), as detailed in column two. Upon presentation, the subject was having a trochanteric shot administered every four weeks. In addition, the subject was medicating with a steroid pak, celecoxib (200 milligrams every twenty-four hours), and oxycodone/acetaminophen (10/325 milligrams every four hours), yet still reported significant perceived pain. The first inventive composition, the second inventive composition, the first compound, and the second compound were transdermally administered to the first, second, third, and fourth regions, respectively.
- As to this particular embodiment, the first inventive composition included dextrose in an amount of about 25% by weight of the first inventive composition, sodium bicarbonate in an amount of about 2.5% by weight of the first inventive composition, and vehicle in an amount of about 72.5% by weight of the first inventive composition.
- The second inventive composition included dextrose in an amount of about 20% by weight of the second inventive composition, sodium bicarbonate in an amount of about 10% by weight of the second inventive composition, and vehicle in an amount of about 70% by weight of the second inventive composition.
- The first compound included sodium bicarbonate in an amount of about 2.5% by weight of the first compound and vehicle in an amount of about 97.5% by weight of the first compound.
- The second compound included mannitol in an amount of about 2.5% by weight of the second compound and vehicle in an amount of about 97.5% by weight of the second compound.
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TABLE 7 Inventive Percent Percent Composition 5 Minutes Reduction 15 Minutes Reduction and Distinct Pre-Admin Post-Admin in Pain Post-Admin in Pain Compounds Region Pain Level Pain Level Level Pain Level Level First First Region 7 3 57% 3 57% Inventive Composition Second Second Region 6 1 83% 1 83% Inventive Composition First Third Region 9 8 11% 7 22% Compound Second Fourth Region 6 3 50% 3 50% Compound - Again referring primarily to Table 7, the method of transdermally administering the particular embodiment of the inventive composition and each of the first, second, and third compounds included: i) identifying the first, second, third, and fourth regions of pain symptoms; ii) applying 2.0 kg/cm′ of pressure via an algometer to each of the first, second, third, and fourth regions of pain symptoms and having the subject assess their perceived pain level on a scale ranging from 0 to 10, with 0 being the least amount of pain and 10 being the greatest amount of pain (indicated in column three as “Pre-Admin Pain Level”); iii) determining the cutaneous nerve branch(es) or main nerve trunk(s) liable for the pain symptoms in each of the first, second, third, and fourth regions; iv) confirming the liability of the cutaneous nerve branch(es) or main nerve trunk(s) for the pain symptoms in each of the first, second, third, and fourth regions by palpation; and v) transdermally administering the inventive composition along the nerve pathway liable for the pain symptoms proximate the first region; vi) transdermally administering the first compound along the nerve pathway liable for the pain symptoms proximate the second region; vii) transdermally administering the second compound along the nerve pathway liable for the pain symptoms proximate the third region; and viii) transdermally administering the third compound along the nerve pathway liable for the pain symptoms proximate the fourth region. Generally, each of the first inventive composition, the second inventive composition, the first compound, and the second compound were transdermally administered for a time period of about sixty seconds. Following, 2.5 kg/cm′ of pressure was applied via an algometer to each of the first, second, third, and fourth regions of pain symptoms at about five minutes after the transdermal administration and the subject reassessed their perceived pain level (indicated in column four as “5 Minutes Post-Admin Pain Level”) and again at about fifteen minutes after the transdermal administration, 2.5 kg/cm′ of pressure was applied via an algometer to each of the first, second, third, and fourth regions of pain symptoms and the subject reassessed their perceived pain level (indicated in column six as “15 Minutes Post-Admin Pain Level”).
- Again referring primarily to Table 7, regarding the first inventive composition transdermally administered to the first region, the subject reported a 57% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 57% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level. Regarding the second inventive composition transdermally administered to the second region, the subject reported an 83% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and an 83% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level. Regarding the first compound transdermally administered to the third region, the subject reported an 11% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 22% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-AdminPain Level”) in relation to the pre-administration perceived pain level. Regarding the second compound transdermally administered to the fourth region, the subject reported a 50% reduction in perceived pain level at five minutes post-administration (indicated in column five as “5 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level and a 50% reduction in perceived pain level at fifteen minutes post-administration (indicated in column five as “15 Minutes Post-Admin Pain Level”) in relation to the pre-administration perceived pain level. Overall, of the first inventive composition, the second inventive composition, the first compound, and the second compound, the greater percent reduction in perceived pain level at both five minutes post-administration and fifteen minutes post-administration was observed following transdermal administration of the first and second inventive compositions, with the greatest percent reduction in perceived pain level at both five minutes post-administration and fifteen minutes post-administration observed following transdermal administration of the second inventive composition.
- The inventive pain reliever can comprise anhydrous dextrose and aloe vera concentrate, and some or all of the following ingredients: propylene glycol, caprylic/capric tryglicerides, sodium chloride (or acetic acid), a homeopathic anti-inflamatory extract, such as Traumeel®, Dimethyl Sulfone (or Methylsulfonylmethane (MSM)), cetyl myristoleate, lipoderm base, distilled water, and, optionally, a pitcher plant extract, such as Sarapin. Each of the below-described embodiments are described in relation to a 100 gram composition.
- In all embodiments, the Lipoderm base may be substituted by any of the following:
- (1) lecthicin or other fat soluble granules in the range of 0.001 to 75% (w/w) of the composition, preferably 5%;
- (2) PLO (Pluronic Lecithin Organogel) in the range of 0.001 to 75% of the composition in gel form, preferably 30%;
- (3) Urea in the range of 1-50% of the composition, preferably 10%;
- (4) Oleic acid in the range of 0.001 to 70% of the composition, preferably 5%;
- (5) Liposomes in the range of 0.01% to 75% of the composition;
- (6) Niosomes in the range of 0.01% to 75% of the composition; or
- (7) Nanotechnology in the range of 0.01 to 75%, namely, any one of the following chosen from a group consisting of nanocrystals, liposomes, nanoparticle-protein conjugates, magnetic nanoparticles, nanogels and biodegradable nanoparticles.
- Also, in all embodiments anhydrous dextrose can be substituted in approximately the same concentration by any of the following:
- a. sugar alcohols such as:
- Glycol (2-carbon);
- Glycerol (3-carbon);
- Erythritol (4-carbon);
- Threitol (4-carbon);
- Arabitol (5-carbon);
- Xylitol (5-carbon);
- Ribitol (5-carbon);
- Mannitol (6-carbon);
- Sorbitol (6-carbon);
- Dulcitol (6-carbon);
- Fucitol (6-carbon);
- Iditol (6-carbon);
- Inositol (6-carbon; a cyclic sugar alcohol);
- Volemitol (7-carbon);
- Isomalt (12-carbon);
- Maltitol (12-carbon);
- Lactitol (12-carbon); and
- Polyglycitol; or
- b. other Sugars, such as:
- xylitol;
- ribose;
- fructose;
- galactose;
- lactose;
- maltose;
- raffinose; and
- sucrose.
- An embodiment is a water-based solution to be applied through iontophoresis. This embodiment comprises the following ingredients:
- 2-50 grams of anhydrous dextrose;
- 0.5-10 grams of aloe vera concentrate (freeze dried 40× powder);
- 1-20 ml of propylene glycol;
- 10-100 ml of sterile water; and
- 1-20 grams of sodium chloride (granular) (or acetic acid).
- While the above measurements are ideal, the active ingredients can vary in range from 0.01% to 75% of the total volume of the solution. Among the active ingredients in the embodiment are anhydrous dextrose, aloe vera concentrate, and propylene glycol.
- Another embodiment is a gel which can be applied directly to the epidermis using an ultra sound machine, and can be absorbed faster than the first embodiment. This embodiment comprises the following ingredients:
- 2-50 grams of anhydrous dextrose;
- 0.5-10 grams of aloe vera concentrate (freeze dried 40× powder);
- 1-20 ml of propylene glycol;
- 0.5-5 ml of caprylic/capric triglycerides;
- 10-100 grams of ultrasound gel; and
- 0.25-5 ml of simple-gel (Hawkins) gel.
- While the above measurements are ideal, the active ingredients can vary in range from 0.01% to 75% of the total volume of the solution. Among the active ingredients in the embodiment are anhydrous dextrose, aloe vera concentrate, propylene glycol, and caprylic/capric triglycerides.
- Another embodiment is also a gel which can be applied directly to the epidermis without the use an ultra sound machine or iontophoresis, and can be absorbed faster than the first and second embodiment. This embodiment comprises the following ingredients:
- 2-50 grams of anhydrous dextrose;
- 0.5-10 grams of aloe vera concentrate (freeze dried 40× powder);
- 0.5-5 ml of caprylic/capric triglycerides;
- 1-10 ml of ethoxy diglycol reagent;
- 5-10 grams of a lipoderm base; and
- 0.1-5 grams of cetyl myristoleate.
- The following optional ingredients may be added:
- 0.5-5 grams of dimethyl sulfone (or MSM);
- 0.5-5 ml of pitcher plant extract (1:2 solution), such as Sarapin®;
- 1-20 ml of distilled water; and
- 0.5-20 tablets of a homeopathic anti-inflamatory extract, such as Traumeel®.
- While the above measurements are ideal, the active ingredients can vary in range from 0.01% to 75% of the total volume of the solution. Among the active ingredients in the embodiment are anhydrous dextrose, aloe vera concentrate, caprylic/capric triglycerides, ethoxy diglycol reagent, lipoderm base, and cetyl myristoleate.
- Whenever the following ingredients are used in any of the above embodiments, the recommended percentage of the solution or gel can be as follows:
- dextrose at least 5% or 1-50%, preferably 20%, or of hypertonic saline;
- aloe vera concentrate 10%;
- propylene glycol 10%;
- caprylic/capric triglycerides 10%;
- sodium chloride (or acetic acid) 10%;
- homeopathic anti-inflamatory extract, such as Traumeel® 10%;
- dimethyl sulfone (or MSM) 10%;
- cetyl myristoleat 10%; and
- pitcher plant extract, such as Sarapin® 10%.
- The embodiments may be combined with shampoo, soap, or water, without losing their effectiveness.
- A pain reliever can be comprised of dextrose, aloe vera concentrate, and some or all of the following ingredients: propylene glycol, caprylic/capric tryglicerides, sodium chloride (or acetic acid), a homeopathic anti-inflamatory extract, Dimethyl Sulfone (or Methylsulfonylmethane (MSM)), cetyl myristoleate, and, optionally, a pitcher plant extract. The resulting compositions can be a water-based solution and gel composition applied to the epidermis of mammals for relieving pain.
- Although preferred embodiments have been shown and described, various modifications and substitutions may be made thereto without departing from the spirit and scope of the invention. Accordingly, it is to be understood that the present disclosure has been described by way of illustration and not limitation.
- A method of producing a particular embodiment of the inventive composition can include combining an amount of sugar or sugar alcohol, an amount of alkalizing agent, and an amount of vehicle; and formulating the inventive composition for transdermal administration.
- As used herein, the term “combination or combining” refers to any method of putting two or more materials together. Such methods include, but are not limited to, mixing, blending, commingling, concocting, homogenizing, ultrasonic homogenizing, incorporating, intermingling, fusing, joining, shuffling, stirring, coalescing, integrating, confounding, joining, uniting, creating a stable suspension of two immiscible liquids via any number of means such as emulsions, or the like.
- As to particular embodiments, the method of producing a particular embodiment of the inventive composition can include combining the sugar or sugar alcohol, alkalizing agent, and vehicle, whereby each can be combined in an amount as described above.
- As to particular embodiments, the method of producing a particular embodiment of the inventive composition can further include combining one or more additional components to formulate the inventive composition, whereby the one or more additional components can be as described above or can be other additional components.
- As can be easily understood from the foregoing, the basic concepts of the present invention may be embodied in a variety of ways. The invention involves numerous and varied embodiments of a pain relieving system and methods for making and using such pain relieving systems including the best mode.
- As such, the particular embodiments or elements of the invention disclosed by the description or shown in the figures or tables accompanying this application are not intended to be limiting, but rather exemplary of the numerous and varied embodiments generically encompassed by the invention or equivalents encompassed with respect to any particular element thereof. In addition, the specific description of a single embodiment or element of the invention may not explicitly describe all embodiments or elements possible; many alternatives are implicitly disclosed by the description and figures.
- It should be understood that each element of an apparatus or each step of a method may be described by an apparatus term or method term. Such terms can be substituted where desired to make explicit the implicitly broad coverage to which this invention is entitled. As but one example, it should be understood that all steps of a method may be disclosed as an action, a means for taking that action, or as an element which causes that action. Similarly, each element of an apparatus may be disclosed as the physical element or the action which that physical element facilitates. As but one example, the disclosure of a “combination” should be understood to encompass disclosure of the act of “combining”—whether explicitly discussed or not—and, conversely, were there effectively disclosure of the act of “combining”, such a disclosure should be understood to encompass disclosure of a “combination” and even a “means for combining”. Such alternative terms for each element or step are to be understood to be explicitly included in the description.
- In addition, as to each term used it should be understood that unless its utilization in this application is inconsistent with such interpretation, common dictionary definitions should be understood to included in the description for each term as contained in the Random House Webster's Unabridged Dictionary, second edition, each definition hereby incorporated by reference.
- All numeric values herein are assumed to be modified by the term “about”, whether or not explicitly indicated. For the purposes of the present invention, ranges may be expressed as from “about” one particular value to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value to the other particular value. The recitation of numerical ranges by endpoints includes all the numeric values subsumed within that range. A numerical range of one to five includes for example the numeric values 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, and so forth. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. When a value is expressed as an approximation by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. The term “about” generally refers to a range of numeric values that one of skill in the art would consider equivalent to the recited numeric value or having the same function or result. Similarly, the antecedent “substantially” means largely, but not wholly, the same form, manner or degree and the particular element will have a range of configurations as a person of ordinary skill in the art would consider as having the same function or result. When a particular element is expressed as an approximation by use of the antecedent “substantially,” it will be understood that the particular element forms another embodiment.
- Moreover, for the purposes of the present invention, the term “a” or “an” entity refers to one or more of that entity unless otherwise limited. As such, the terms “a” or “an”, “one or more” and “at least one” can be used interchangeably herein.
- Thus, the applicant(s) should be understood to claim at least: i) each of the pain relieving systems herein disclosed and described, ii) the related methods disclosed and described, iii) similar, equivalent, and even implicit variations of each of these devices and methods, iv) those alternative embodiments which accomplish each of the functions shown, disclosed, or described, v) those alternative designs and methods which accomplish each of the functions shown as are implicit to accomplish that which is disclosed and described, vi) each feature, component, and step shown as separate and independent inventions, vii) the applications enhanced by the various systems or components disclosed, viii) the resulting products produced by such systems or components, ix) methods and apparatuses substantially as described hereinbefore and with reference to any of the accompanying examples, x) the various combinations and permutations of each of the previous elements disclosed.
- The background section of this patent application provides a statement of the field of endeavor to which the invention pertains. This section may also incorporate or contain paraphrasing of certain United States patents, patent applications, publications, or subject matter of the claimed invention useful in relating information, problems, or concerns about the state of technology to which the invention is drawn toward. It is not intended that any United States patent, patent application, publication, statement or other information cited or incorporated herein be interpreted, construed or deemed to be admitted as prior art with respect to the invention.
- The claims set forth in this specification, if any, are hereby incorporated by reference as part of this description of the invention, and the applicant expressly reserves the right to use all of or a portion of such incorporated content of such claims as additional description to support any of or all of the claims or any element or component thereof, and the applicant further expressly reserves the right to move any portion of or all of the incorporated content of such claims or any element or component thereof from the description into the claims or vice-versa as necessary to define the matter for which protection is sought by this application or by any subsequent application or continuation, division, or continuation-in-part application thereof, or to obtain any benefit of, reduction in fees pursuant to, or to comply with the patent laws, rules, or regulations of any country or treaty, and such content incorporated by reference shall survive during the entire pendency of this application including any subsequent continuation, division, or continuation-in-part application thereof or any reissue or extension thereon.
- Additionally, the claims set forth in this specification, if any, are further intended to describe the metes and bounds of a limited number of the preferred embodiments of the invention and are not to be construed as the broadest embodiment of the invention or a complete listing of embodiments of the invention that may be claimed. The applicant does not waive any right to develop further claims based upon the description set forth above as a part of any continuation, division, or continuation-in-part, or similar application.
Claims (21)
1. A composition comprising:
an amount of sugar or sugar alcohol;
an amount of alkalizing agent; and
an amount of vehicle;
wherein said composition is formulated for transdermal administration.
2. The composition of claim 1 , wherein said amount of sugar or sugar alcohol is in a range of between about 2% to about 30% by weight of said composition.
3. The composition of claim 2 , wherein said amount of sugar or sugar alcohol is in a range selected from the group consisting of: between about 5% to about 30% by weight of said composition; between about 10% to about 30% by weight of said composition; between about 15% to about 30% by weight of said composition; and between about 20% to about 30% by weight of said composition.
4. The composition of claim 2 , wherein said sugar is one or more selected from the group consisting of: ribose, xylose, fructose, dextrose, galactose, mannose, sorbose, sucrose, maltose, lactose, lactulose, trehalose, and cellobiose.
5. The composition of claim 2 , wherein said sugar comprises dextrose.
6. The composition of claim 2 , wherein said sugar alcohol is one or more selected from the group consisting of: glycerol, erythritol, threitol, arabitol, xylitol, adonitol, mannitol, sorbitol, dulcitol, fucitol, iditol, inositol, volemitol, isomalt, maltitol, lactitol, and maltotriitol.
7. The composition of claim 2 , wherein said sugar alcohol comprises mannitol.
8. The composition of claim 2 , wherein said amount of alkalizing agent is in a range of between about 0.1% to about 15% by weight of said composition.
9. The composition of claim 8 , wherein said amount of alkalizing agent is in a range of between about 6.5% to about 15% by weight of said composition.
10. The composition of claim 8 , wherein said alkalizing agent is one or more selected from the group consisting of: sodium bicarbonate, potassium citrate, calcium carbonate, and calcium acetate.
11. The composition of claim 8 , wherein said alkalizing agent comprises sodium bicarbonate.
12. The composition of claim 8 , wherein said alkalizing agent comprises a salt.
13. The composition of claim 12 , wherein said salt comprises a cation selected from the group consisting of: sodium, calcium, potassium, zinc, iron, and magnesium.
14. The composition of claim 12 , wherein said salt comprises an anion selected from the group consisting of: chloride, acetate, ascorbate, bicarbonate, citrate, formate, fumarate, phosphate, succinate, borate, gluconate, lactate, malate, trimalate, panthothenate, thiocyanate, glycinate, and sulphate.
15. The composition of claim 12 , wherein said salt is selected from the group consisting of: sodium chloride, sodium acetate, sodium bicarbonate, sodium citrate, sodium phosphate, sodium dihydrogen phosphate, sodium hydrogen phosphate, sodium succinate, sodium borate, sodium gluconate, sodium citrate, sodium lactate, calcium citrate, calcium chloride, calcium pantothenate, calcium gluconate, calcium phosphate, potassium chloride, monopotassium phosphate, dipotassium phosphate, tripotassium phosphate, potassium gluconate, magnesium sulphate, magnesium chloride, magnesium gluconate, magnesium acetate, magnesium malate, magnesium glycinate, magnesium lactate, zinc chloride, zinc sulphate and zinc acetate.
16. The composition of claim 8 , wherein said amount of sugar or sugar alcohol is solubilized in said vehicle.
17. The composition of claim 8 , wherein said amount of sugar or sugar alcohol is suspended in said vehicle.
18. The composition of claim 8 , wherein said vehicle facilitates said transdermal administration of a portion of said amount sugar or sugar alcohol and a portion of said amount of alkalizing agent.
19. The composition of claim 18 , wherein said vehicle comprises an emulsion base.
20. The composition of claim 19 , wherein said emulsion base comprises an oil selected from the group consisting of: vegetable oils, animal oils, mineral oils, silicone oils, synthetic oils, fatty acids, fatty alcohols, phospholipids, and paraffin waxes.
21.-60. (canceled)
Priority Applications (1)
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US16/862,469 US20200390790A1 (en) | 2011-11-11 | 2020-04-29 | Pain reliever composition |
Applications Claiming Priority (8)
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US13/295,010 US20130122116A1 (en) | 2011-11-11 | 2011-11-11 | Pain reliever composition |
US13/417,053 US20130236530A1 (en) | 2012-03-09 | 2012-03-09 | Pain reliever composition |
US13/479,998 US20130236577A1 (en) | 2012-03-09 | 2012-05-24 | Pain reliever composition |
US14/294,034 US20140271828A1 (en) | 2012-05-24 | 2014-06-02 | Pain Reliever Composition |
US14/612,006 US9757401B2 (en) | 2011-11-11 | 2015-02-02 | Method for relieving neurogenic pain |
US15/697,324 US9907808B2 (en) | 2011-11-11 | 2017-09-06 | Method for relieving neurogenic pain |
US15/910,983 US20180185400A1 (en) | 2011-11-11 | 2018-03-02 | Pain Reliever Composition |
US16/862,469 US20200390790A1 (en) | 2011-11-11 | 2020-04-29 | Pain reliever composition |
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US15/910,983 Continuation US20180185400A1 (en) | 2011-11-11 | 2018-03-02 | Pain Reliever Composition |
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US15/910,983 Abandoned US20180185400A1 (en) | 2011-11-11 | 2018-03-02 | Pain Reliever Composition |
US16/862,469 Abandoned US20200390790A1 (en) | 2011-11-11 | 2020-04-29 | Pain reliever composition |
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US15/910,983 Abandoned US20180185400A1 (en) | 2011-11-11 | 2018-03-02 | Pain Reliever Composition |
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US9757401B2 (en) | 2011-11-11 | 2017-09-12 | Nova Neura, Llc | Method for relieving neurogenic pain |
IT201700076321A1 (en) * | 2017-07-06 | 2019-01-06 | Mm Farma Srl Semplificata A Socio Unico | COMPOSITIONS CONTAINING L-ACETYLCARNITINE FOR THE USE IN THE TREATMENT OF PAINFUL SYMPTOMS ASSOCIATED WITH THE SHOULDERS OF THE SHOULDER |
US20230201550A1 (en) * | 2020-06-08 | 2023-06-29 | Nova Neura, Llc | Systems and methods for treating persistent pain of neurogenic origin and complex injury |
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US5383324A (en) | 1993-04-23 | 1995-01-24 | Baxter International Inc. | Method for manufacturing and storing stable bicarbonate solutions |
US5420114A (en) | 1993-07-07 | 1995-05-30 | Clodman; Percy B. | Methods for the treatment of skin disorders |
US6586000B2 (en) * | 1999-12-16 | 2003-07-01 | Dermatrends, Inc. | Hydroxide-releasing agents as skin permeation enhancers |
US6579543B1 (en) * | 2002-02-22 | 2003-06-17 | Jackie H. McClung | Composition for topical application to skin |
US20030175328A1 (en) | 2002-03-06 | 2003-09-18 | Adi Shefer | Patch for the controlled delivery of cosmetic, dermatological, and pharmaceutical active ingredients into the skin |
US20030175333A1 (en) | 2002-03-06 | 2003-09-18 | Adi Shefer | Invisible patch for the controlled delivery of cosmetic, dermatological, and pharmaceutical active ingredients onto the skin |
US7700626B2 (en) | 2004-06-04 | 2010-04-20 | Adolor Corporation | Compositions containing opioid antagonists |
US7625586B2 (en) | 2004-10-28 | 2009-12-01 | Md Scientific, Llc | Method for mitigating injury to a kidney resulting from an ischemic event |
US20080146672A1 (en) * | 2006-12-08 | 2008-06-19 | Denton Marcia Marye | Topical Eutectic Anesthetic Composition for Oral or Dermal Tissue |
CN101822818B (en) * | 2010-05-13 | 2012-06-27 | 多力坤·马木特 | Composition of Chinese yam polysaccharide and Chinese yam protein and application thereof |
US8512770B2 (en) * | 2010-08-04 | 2013-08-20 | Dominion Resources Unlimited, Llc | Skin penetration composition |
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US9168281B2 (en) | 2011-03-09 | 2015-10-27 | Charles E. Worden, SR. | Kit for treating a wound |
US9757401B2 (en) | 2011-11-11 | 2017-09-12 | Nova Neura, Llc | Method for relieving neurogenic pain |
US20130236530A1 (en) | 2012-03-09 | 2013-09-12 | Howard Rosen | Pain reliever composition |
US20130236577A1 (en) | 2012-03-09 | 2013-09-12 | Howard Rosen | Pain reliever composition |
US20130122116A1 (en) | 2011-11-11 | 2013-05-16 | Howard Rosen | Pain reliever composition |
US9351985B2 (en) * | 2013-04-29 | 2016-05-31 | Helene Bertrand | Topical formulation for pain relief |
-
2015
- 2015-02-02 US US14/612,006 patent/US9757401B2/en active Active
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2017
- 2017-09-06 US US15/697,324 patent/US9907808B2/en active Active
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2018
- 2018-03-02 US US15/910,983 patent/US20180185400A1/en not_active Abandoned
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2020
- 2020-04-29 US US16/862,469 patent/US20200390790A1/en not_active Abandoned
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US9757401B2 (en) | 2017-09-12 |
US9907808B2 (en) | 2018-03-06 |
US20150148429A1 (en) | 2015-05-28 |
US20180185400A1 (en) | 2018-07-05 |
US20170360814A1 (en) | 2017-12-21 |
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