CA2012395A1 - Topical analgesic composition - Google Patents
Topical analgesic compositionInfo
- Publication number
- CA2012395A1 CA2012395A1 CA002012395A CA2012395A CA2012395A1 CA 2012395 A1 CA2012395 A1 CA 2012395A1 CA 002012395 A CA002012395 A CA 002012395A CA 2012395 A CA2012395 A CA 2012395A CA 2012395 A1 CA2012395 A1 CA 2012395A1
- Authority
- CA
- Canada
- Prior art keywords
- solution
- trolamine
- mixture
- acid
- parahydroxybenzoic acid
- 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
- 230000000202 analgesic effect Effects 0.000 title claims abstract description 4
- 239000000203 mixture Substances 0.000 title claims 8
- 230000000699 topical effect Effects 0.000 title 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims abstract description 12
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229960004418 trolamine Drugs 0.000 claims abstract description 8
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 230000009969 flowable effect Effects 0.000 claims abstract description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims abstract 15
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims abstract 9
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 claims abstract 6
- 125000005907 alkyl ester group Chemical group 0.000 claims abstract 4
- 229960004889 salicylic acid Drugs 0.000 claims abstract 4
- -1 alkylene glycol Chemical compound 0.000 claims abstract 3
- 238000000034 method Methods 0.000 claims abstract 3
- 238000002360 preparation method Methods 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 5
- 239000007864 aqueous solution Substances 0.000 claims 3
- 229960004063 propylene glycol Drugs 0.000 claims 3
- 235000013772 propylene glycol Nutrition 0.000 claims 3
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 238000001556 precipitation Methods 0.000 claims 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 239000002253 acid Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 2
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
- 241001535291 Analges Species 0.000 description 1
- 244000287680 Garcinia dulcis Species 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/618—Salicylic acid; Derivatives thereof having the carboxyl group in position 1 esterified, e.g. salsalate
- A61K31/621—Salicylic acid; Derivatives thereof having the carboxyl group in position 1 esterified, e.g. salsalate having the hydroxy group in position 2 esterified, e.g. benorylate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
ABSTRACT OF
THE
DISCLOSURE
Flowable, aqueous, analgesic solutions containing substantially equimolar quantities of trolamine and salicylic acid together with a lower alkanol, a lower alkylene glycol and a lower alkyl ester of parahydroxybenzoic acid and water, and method for the preparation thereof.
THE
DISCLOSURE
Flowable, aqueous, analgesic solutions containing substantially equimolar quantities of trolamine and salicylic acid together with a lower alkanol, a lower alkylene glycol and a lower alkyl ester of parahydroxybenzoic acid and water, and method for the preparation thereof.
Description
r-Trolamlne sali~ylat- ha~ long b-sn known a~ a topl~-l ~n~lge~lc for temporary ~Qll~f o~ mu~culo~kol~t-l ~ch-~ and paln-q ~peclally tho~e a~soci~ted wlth tra~n~, ~praln~, brulo-~ or ov~r-xcrtion, t ha~ alno b-on recomm-nd-d ~or ~empo~ary allovlation o~ arthritlc ~nd rh~umatlc paln oDp~cially ln th-h~nds and ~--t. It 18 ~peclally favor~d by atnlete~
Trolamine ~allcylAte 1~ a l:l complex formad by r-actlon o~
~qulmo~ar qu~ntitl~ of ~allcyllc acld ~nd trol~mlne (t~l-th~nol amln~ ho analgesic a~-nt 18 the ~allcyllc acld which fo~m~ tn JltU when th- Jalt cro~ th~ ~kln barrl-r, The prlnclpal da~ld-ratum of toplcal analge~lc~ 1~ r~pld p-n-tr~tlon of the ~ln barrler to th- r-glon of th~ paln. To thlJ cnd, a variety o~ toplcal cr-am-~ lotiono, ~02m~ and othar vl~cou~ oomposltlon~ hav- ~oon provid-d contalning a larg- numbe~
o~ omoli-nt-, suopon~lng agent~, eh-lating agents, ~t~ nlng ag-nt~, omulsirl~r6, olls, buf~-rln~ agent4 and oth-r component~
lnc~udlng, 80 call-d ol~agonou~ v-hlcle~ hav~ bo-n provlded, app~r~ntly in tho b-lle~ ~hat ~uch lngr~d~ont~ ~ro n0cos~ary ~or r-pld penotrEtlon o~ th- ~kin barr~-r.
Th~- vl~cou~ compo-ltion~ ar- o~ten di~flcult to apply and r~qulre xt~nslv~ "ru~blng ln". Thl~ may be burd~n~om~, -p-clally lf ~oth hands ar~ ~ff-cted, o~ lf th- aff-cted ar~a 1 h-rd to r-ach ~uch ~Q the ~r of th~ ~houlter ar-~.
Addltlo~ally~ the cr~am may 1~aY~ un-~ght~y raoldu~ on ths 4~1n or thoy may tain th~ clothl~g. Oft-n, -p~clally lf u~-d by nn athl-t~ ~urlng comp~tltlon thoy may ab~orb ~lr-~orn~ du~t and p-rtlcles and b-com~ n more unst~htly~ Mor-o w r, on~ or mor-of the compon-nt~ m~y b- allorg~nlc.
. .
20~3~5 .
Th~ a~t h~ long ~earch-d ~or compo~ltlon- whlch can b~
u~erully mploy~d whil~ avoiding th~ ~bove mentionod icultl~.
' .
It ha~ now b--n dl~cov-r-d that ~ ~eapito th- lndl~atlon~
from the ~rt, aqu-ou~ oolutlon~ con~inin~ t~ol~m~n- ~all~yla~e n--d ~ot contaln the larg- numbo~ of lngr-dl-~t~ pr~vlo~ly mployed, but th~t th~ anAl~o~lc may b~ promptly and e~ ien~ly d-llver~d to tho ~lt~ wh~ro it i3 naed6d ~rom ~ Garrlor baYe that contain~ only w~tor, ~ pr~a-r~ti~e, ~ low~r alkanol, ~nd A low mol-c~ wolght glycol. Th~ ~ctlv- l~gr~dlent w~ll r~pldly ~ -pon~trate th- ~ln barrl~r to prov~ a prompt ~oothlng analgeoic aetlon de~plt- tho absenc- o~ the oll~, ~mulsl~lar~ ~nd oth~r xcipient~ norm~lly employ-d with trolamln- ~-licylAt-.
~ h~ compo~itlon. o~ th- inYentlon ar- ~low~bl- ~ompo~ltlon~
wlth a vl~co~ty at dmbl-nt t~mper~ture whloh 1~ ~out th~t of w~ter, 1,~. ~bout 0.58 to 1.2 time~ th~ v~co~ity o~ water.
B~cau~e th-y are re~dlly flowable, 1.~., "llk- wat~r", tney may be ~a~lly And convonl-ntly ~ppll~d by a ~-ry brief rubblng. Th-y are r-~d~ly appll-~ ~om ea~lly d-~gn-d cont~l~er8 ~uch ~
~-rosol, bru~h or spongo ~ppllcator~. Tha volum- Or ~olutlon p-e~lng through tho Appllcator c~n be controll~ by ~ny o~
numbe~ o~ v~lve mean~ w-ll known to tho~ d in tno art, Some appllc~tor~ may ov-n ellminat- th- n-~d ~or touchlng th~
compo~ltlon~ of tho in~ent~on ~urtng ~ppllcat~on.
Tho ~ormatlo~ of th- trol~mine ~allcyl~t- ~omplsx ~3 ~n qulmolar r~ctlon. Acco~dlngly the compo~ltlon~ will ~ontaln ~ub~t~ntlally e~ulmol~r quantlt~a~ o~ the ~n~lg-~lc ~Cld and th- :~
b-Jo. ~t 1- pro~rre~ to omploy ~ ght molsr xc~o~, 4ay 1~ to Z01~39S
10~, o~ th~ ba9e to insur~ th~t all 4~ the acld will r4act an~
301ubillz~, The amount of trolamlne wlll vAry ~rom ~bout 5 to 12~, and of ~allcylic acid from about 3 to lO~ by w~i~ht bo~ed on tho total volum- o~ ~o oompo~tlon.
In thl- dl3closu~0 ond clolm~, all de~ined amount~ Aro tn p-rcont by w-ight ba~ad on tho total volume.
Tho alkonol dmployod in th~ oomposltlonJ will contaln two o~
~hree corbon atom~ ~nd b~ misclbl- wlth wat~r. Such alcohols hsve Low ~o~ling polnta and hlgh vapor p~e~sura. Th-y promo~e ropld ~vaporation of th~ carrier v~hiol- ot ~he compo~ltion. The amou~t o~ alcohol employed lo typlo~lly ~rom about 3 to 6~.
Th- pref~rr~d alkanol i~ l~opropyl alcohol. M~xtures of alcohol~ w~ich ~oy contoln eth~nol moy b~ ~m~loy~d.
Tho compoJltion- ol the inv~ntlon wSll al~o cont-in A
pre~orv~ttve. Th- pr~o~tly pr-~-rr-d pre~rv~tlv-~ arc low~r al~yl -ter~ of psrAhydroxyb-nzolc ocid, typlo~lly contalning up to thræe carbon atom~, Th~ ~mount of pr-~arvatlv~ normally employed will b~ ~rom about 0.1 to 0.5~, olthough wld- vorlation~
~re po~lble wlthout adverse re~ult~. The ~Jtar~ may be ~mploy-d lngly, but lt i~ pr-~rr~d to u~- a mlxture o~ m-thyl and propyl o~ter~ o~ p~rahydroxyben201c acl~ ~lnce tho mlxturo app~ar~ to ~e moro ctlve than lt~e~ e~t~r t~ken ~lono.
Propyleno glycol~ or mlxtures ther~o~ are UtlllZ-~ ~n the compo~ltlons o~ tho lnventlon ~- a ~olublll2~r for th~
pro~orvative ~y-t-m ln an amount of from ~out 2.5 to 6~. The compo~ltlon8 of thl~ invontlon are solution~. It i~ lmport~nt th~t ~11 of th- ~olid compon-~to dlJ~olv-~ A su~ficl-nt amount of glycol 1~ mployed to ln~ure ~uch ~olublllty, but too much - . ~ " j . . .
~ \
glycol m~y incr~a~ the vi~co~ty of the composltion and ~tlll decr~a~- the rata o~ evaporatlon rom ~he skln. ~h- pro~errod g~ycol 1~ 1,2-propan~ dlol.
~ g lndlcAted abov-, the c~mpon-nt~ Or the mlxtur~ mu~t rorm a oolutlon. It ha~ b--n dl~ov~r-d th~t th~ ~ethod o mlxlng i~
very lmport~nt to pr-v-nt pr~lplt~t~on o~ the ~olld compon-nt~.
In th~ pr-~orred procod~ro, th~ trol~mln- And ~allcyllo a~ld ~r-~dded ~t amb~-nt temp~r~ture to th~ ct-d quantlty of wat~r, which may be ~ll of th~ water employ~d ln th- compo~lt~on, and the mlxtur~ 18 allow-~ to stand untll complete ~olut~on 1~
e~f~ct~d. A socond mlxtura contalnlng th~ aelect~d quantltl~s of glycol and al~yl ~te~(~) o~ p~r~hydroxybenzolc acld, ~.q., mlxture o~ ~h- m~thyl and propyl estor 1~ ~-p~r~t~ly prep~r~d ~nd ~lowly adde~ to th- ~lr~t ~olutlon. I~ lt 1~ added too rapi~ly, lt wlll c~u3e preclpltation o~th- ~llcyl~c acid ~nd/or the alkyl o~ter o~ parahydroxyb-nzoic acid. Th~ glycollpreoe~vatlv-m$xtu~e may con~in ~omo o~ tho water of th- ~lnal compo~lt~on.
Th- select~d quantlty o~ alkanol 1~ th~n ~ddcd ~o ehe mlxtur-.
Th~ p~ o~ th~ composlt~on~ oS thl~ inventlon ar- preSerably a~ clo~c to n~utr~l a8 po4~1bl-, but a range oS 6 to 8, or evan ~llghtly wld~r c~n be to1crat-d.
It 1~ surprl~l~g to ob-~rve how qulckly the actlve ln~r-dlent penotr~tes th~ a~ln basrl~r ~rom th- ~olutlon~ o~ thls lnvention. Athl-t-~ hav~ b--n partlcul~rly ~-tl~led. ~h~y hdv~
ob~-rv-d rel~o~ ~rom musoular paln o~ the arm~ sn~ leg~ withln few mlnute4 a~t-r toplcal ppllcation.
The.~ollowlng ~ormulatlon~ A ~nd B axo repre~ntatlv~ o~ the ~n-lgo~lc compo~ltlon~ o~ the i~vontlon.
, 1 ' ' ' . ' . ' ' '' " ' ' '' '" ' ' ' "' ' ; ' . , ' ' ~ :
Trolamine ~allcylAte 1~ a l:l complex formad by r-actlon o~
~qulmo~ar qu~ntitl~ of ~allcyllc acld ~nd trol~mlne (t~l-th~nol amln~ ho analgesic a~-nt 18 the ~allcyllc acld which fo~m~ tn JltU when th- Jalt cro~ th~ ~kln barrl-r, The prlnclpal da~ld-ratum of toplcal analge~lc~ 1~ r~pld p-n-tr~tlon of the ~ln barrler to th- r-glon of th~ paln. To thlJ cnd, a variety o~ toplcal cr-am-~ lotiono, ~02m~ and othar vl~cou~ oomposltlon~ hav- ~oon provid-d contalning a larg- numbe~
o~ omoli-nt-, suopon~lng agent~, eh-lating agents, ~t~ nlng ag-nt~, omulsirl~r6, olls, buf~-rln~ agent4 and oth-r component~
lnc~udlng, 80 call-d ol~agonou~ v-hlcle~ hav~ bo-n provlded, app~r~ntly in tho b-lle~ ~hat ~uch lngr~d~ont~ ~ro n0cos~ary ~or r-pld penotrEtlon o~ th- ~kin barr~-r.
Th~- vl~cou~ compo-ltion~ ar- o~ten di~flcult to apply and r~qulre xt~nslv~ "ru~blng ln". Thl~ may be burd~n~om~, -p-clally lf ~oth hands ar~ ~ff-cted, o~ lf th- aff-cted ar~a 1 h-rd to r-ach ~uch ~Q the ~r of th~ ~houlter ar-~.
Addltlo~ally~ the cr~am may 1~aY~ un-~ght~y raoldu~ on ths 4~1n or thoy may tain th~ clothl~g. Oft-n, -p~clally lf u~-d by nn athl-t~ ~urlng comp~tltlon thoy may ab~orb ~lr-~orn~ du~t and p-rtlcles and b-com~ n more unst~htly~ Mor-o w r, on~ or mor-of the compon-nt~ m~y b- allorg~nlc.
. .
20~3~5 .
Th~ a~t h~ long ~earch-d ~or compo~ltlon- whlch can b~
u~erully mploy~d whil~ avoiding th~ ~bove mentionod icultl~.
' .
It ha~ now b--n dl~cov-r-d that ~ ~eapito th- lndl~atlon~
from the ~rt, aqu-ou~ oolutlon~ con~inin~ t~ol~m~n- ~all~yla~e n--d ~ot contaln the larg- numbo~ of lngr-dl-~t~ pr~vlo~ly mployed, but th~t th~ anAl~o~lc may b~ promptly and e~ ien~ly d-llver~d to tho ~lt~ wh~ro it i3 naed6d ~rom ~ Garrlor baYe that contain~ only w~tor, ~ pr~a-r~ti~e, ~ low~r alkanol, ~nd A low mol-c~ wolght glycol. Th~ ~ctlv- l~gr~dlent w~ll r~pldly ~ -pon~trate th- ~ln barrl~r to prov~ a prompt ~oothlng analgeoic aetlon de~plt- tho absenc- o~ the oll~, ~mulsl~lar~ ~nd oth~r xcipient~ norm~lly employ-d with trolamln- ~-licylAt-.
~ h~ compo~itlon. o~ th- inYentlon ar- ~low~bl- ~ompo~ltlon~
wlth a vl~co~ty at dmbl-nt t~mper~ture whloh 1~ ~out th~t of w~ter, 1,~. ~bout 0.58 to 1.2 time~ th~ v~co~ity o~ water.
B~cau~e th-y are re~dlly flowable, 1.~., "llk- wat~r", tney may be ~a~lly And convonl-ntly ~ppll~d by a ~-ry brief rubblng. Th-y are r-~d~ly appll-~ ~om ea~lly d-~gn-d cont~l~er8 ~uch ~
~-rosol, bru~h or spongo ~ppllcator~. Tha volum- Or ~olutlon p-e~lng through tho Appllcator c~n be controll~ by ~ny o~
numbe~ o~ v~lve mean~ w-ll known to tho~ d in tno art, Some appllc~tor~ may ov-n ellminat- th- n-~d ~or touchlng th~
compo~ltlon~ of tho in~ent~on ~urtng ~ppllcat~on.
Tho ~ormatlo~ of th- trol~mine ~allcyl~t- ~omplsx ~3 ~n qulmolar r~ctlon. Acco~dlngly the compo~ltlon~ will ~ontaln ~ub~t~ntlally e~ulmol~r quantlt~a~ o~ the ~n~lg-~lc ~Cld and th- :~
b-Jo. ~t 1- pro~rre~ to omploy ~ ght molsr xc~o~, 4ay 1~ to Z01~39S
10~, o~ th~ ba9e to insur~ th~t all 4~ the acld will r4act an~
301ubillz~, The amount of trolamlne wlll vAry ~rom ~bout 5 to 12~, and of ~allcylic acid from about 3 to lO~ by w~i~ht bo~ed on tho total volum- o~ ~o oompo~tlon.
In thl- dl3closu~0 ond clolm~, all de~ined amount~ Aro tn p-rcont by w-ight ba~ad on tho total volume.
Tho alkonol dmployod in th~ oomposltlonJ will contaln two o~
~hree corbon atom~ ~nd b~ misclbl- wlth wat~r. Such alcohols hsve Low ~o~ling polnta and hlgh vapor p~e~sura. Th-y promo~e ropld ~vaporation of th~ carrier v~hiol- ot ~he compo~ltion. The amou~t o~ alcohol employed lo typlo~lly ~rom about 3 to 6~.
Th- pref~rr~d alkanol i~ l~opropyl alcohol. M~xtures of alcohol~ w~ich ~oy contoln eth~nol moy b~ ~m~loy~d.
Tho compoJltion- ol the inv~ntlon wSll al~o cont-in A
pre~orv~ttve. Th- pr~o~tly pr-~-rr-d pre~rv~tlv-~ arc low~r al~yl -ter~ of psrAhydroxyb-nzolc ocid, typlo~lly contalning up to thræe carbon atom~, Th~ ~mount of pr-~arvatlv~ normally employed will b~ ~rom about 0.1 to 0.5~, olthough wld- vorlation~
~re po~lble wlthout adverse re~ult~. The ~Jtar~ may be ~mploy-d lngly, but lt i~ pr-~rr~d to u~- a mlxture o~ m-thyl and propyl o~ter~ o~ p~rahydroxyben201c acl~ ~lnce tho mlxturo app~ar~ to ~e moro ctlve than lt~e~ e~t~r t~ken ~lono.
Propyleno glycol~ or mlxtures ther~o~ are UtlllZ-~ ~n the compo~ltlons o~ tho lnventlon ~- a ~olublll2~r for th~
pro~orvative ~y-t-m ln an amount of from ~out 2.5 to 6~. The compo~ltlon8 of thl~ invontlon are solution~. It i~ lmport~nt th~t ~11 of th- ~olid compon-~to dlJ~olv-~ A su~ficl-nt amount of glycol 1~ mployed to ln~ure ~uch ~olublllty, but too much - . ~ " j . . .
~ \
glycol m~y incr~a~ the vi~co~ty of the composltion and ~tlll decr~a~- the rata o~ evaporatlon rom ~he skln. ~h- pro~errod g~ycol 1~ 1,2-propan~ dlol.
~ g lndlcAted abov-, the c~mpon-nt~ Or the mlxtur~ mu~t rorm a oolutlon. It ha~ b--n dl~ov~r-d th~t th~ ~ethod o mlxlng i~
very lmport~nt to pr-v-nt pr~lplt~t~on o~ the ~olld compon-nt~.
In th~ pr-~orred procod~ro, th~ trol~mln- And ~allcyllo a~ld ~r-~dded ~t amb~-nt temp~r~ture to th~ ct-d quantlty of wat~r, which may be ~ll of th~ water employ~d ln th- compo~lt~on, and the mlxtur~ 18 allow-~ to stand untll complete ~olut~on 1~
e~f~ct~d. A socond mlxtura contalnlng th~ aelect~d quantltl~s of glycol and al~yl ~te~(~) o~ p~r~hydroxybenzolc acld, ~.q., mlxture o~ ~h- m~thyl and propyl estor 1~ ~-p~r~t~ly prep~r~d ~nd ~lowly adde~ to th- ~lr~t ~olutlon. I~ lt 1~ added too rapi~ly, lt wlll c~u3e preclpltation o~th- ~llcyl~c acid ~nd/or the alkyl o~ter o~ parahydroxyb-nzoic acid. Th~ glycollpreoe~vatlv-m$xtu~e may con~in ~omo o~ tho water of th- ~lnal compo~lt~on.
Th- select~d quantlty o~ alkanol 1~ th~n ~ddcd ~o ehe mlxtur-.
Th~ p~ o~ th~ composlt~on~ oS thl~ inventlon ar- preSerably a~ clo~c to n~utr~l a8 po4~1bl-, but a range oS 6 to 8, or evan ~llghtly wld~r c~n be to1crat-d.
It 1~ surprl~l~g to ob-~rve how qulckly the actlve ln~r-dlent penotr~tes th~ a~ln basrl~r ~rom th- ~olutlon~ o~ thls lnvention. Athl-t-~ hav~ b--n partlcul~rly ~-tl~led. ~h~y hdv~
ob~-rv-d rel~o~ ~rom musoular paln o~ the arm~ sn~ leg~ withln few mlnute4 a~t-r toplcal ppllcation.
The.~ollowlng ~ormulatlon~ A ~nd B axo repre~ntatlv~ o~ the ~n-lgo~lc compo~ltlon~ o~ the i~vontlon.
, 1 ' ' ' . ' . ' ' '' " ' ' '' '" ' ' ' "' ' ; ' . , ' ' ~ :
2 01~ 3 95 ~ w/v trol~mln- 99~ N.F. 5.76 ~allcylle ~ld U.S.P. 4~1 m~thyl parahydroxyb~201c aci~, N,F. 0.2 propyl p~rahydroxybenzoic acid, N.F, 0.1 propylane ~lycol U.S.P. 3.0 lsopropyl ~lcohol U.S.P. 3.0 wat~r U.S.P. ~3.13 qr~ms trolaml~e 9g~ N.F. 28. ~0 salleyllc ~ld U.~P. 2~05 methyl par~hydroxybenzole ~c~d, N.F. 1,00 propyl par~hydroxyben20~e ~cld~ N~F. 0.50 propylen~ glyeol U.~.P. 15.00 i~opropyl ~lcohol U.S.P. lS,00 wat~r U,S,P, ~1S.6S ~:.
For com~o~ltlon A, th- trolamlne, 50~ o~ th~ volume of wat~r ~nd thc ~llcjlic ael~ ~-ro ~tirro~ ~t room t-mporatur~ uns1l th- . :
~alleylic ~eid dl~-olv d. In ~ s~par~t- v~ l, th~
pr~J-rvatlve~ war- d~ol~d in propylo~e qlycol and th~
~olution ~d~ed ~lowly to th~ ~lr~t mlxtu~e wlth ~t~:rlng. ~hen ~:~
th~ addlt~on wa~ compl-t~, tho alcohol w~ ~dd~d ~ollowod by th- ::
b~l~ne- o~ tho w-t-r whlle contlnually Jtlrring. :
- 5 ~
20~239.~
CompoNltlon B tqa~ ~imil~rly prepar~d.
For com~o~ltlon A, th- trolamlne, 50~ o~ th~ volume of wat~r ~nd thc ~llcjlic ael~ ~-ro ~tirro~ ~t room t-mporatur~ uns1l th- . :
~alleylic ~eid dl~-olv d. In ~ s~par~t- v~ l, th~
pr~J-rvatlve~ war- d~ol~d in propylo~e qlycol and th~
~olution ~d~ed ~lowly to th~ ~lr~t mlxtu~e wlth ~t~:rlng. ~hen ~:~
th~ addlt~on wa~ compl-t~, tho alcohol w~ ~dd~d ~ollowod by th- ::
b~l~ne- o~ tho w-t-r whlle contlnually Jtlrring. :
- 5 ~
20~239.~
CompoNltlon B tqa~ ~imil~rly prepar~d.
Claims (9)
1. A flowable, analgesic, aqueous solution having a pH
of from about 6 to 8, a viscosity of from about 0.98 to 1.2 times that of water and containing, from, about 5 to 12% trolamine, about 3 to 10% salicylic acid, about 0.1 to 0.5% of a lower alkyl ester of parahydroxybenzoic acid, abut 2.5 to 5% of a propylene glycol or mixtures thereof, and about 3 to 6% of an alkanol containing two or three carbon atoms, the salicyclic acid and trolamine being present in substantially equimolar quantities.
of from about 6 to 8, a viscosity of from about 0.98 to 1.2 times that of water and containing, from, about 5 to 12% trolamine, about 3 to 10% salicylic acid, about 0.1 to 0.5% of a lower alkyl ester of parahydroxybenzoic acid, abut 2.5 to 5% of a propylene glycol or mixtures thereof, and about 3 to 6% of an alkanol containing two or three carbon atoms, the salicyclic acid and trolamine being present in substantially equimolar quantities.
2. A solution of claim 1 containing from 1% to 10%
molar excess of trolamine.
molar excess of trolamine.
3. A solution of claim 1 or 2 wherein the alkyl group of the lower alkyl ester of parahydroxybenzoic acid contains up to three carbon atoms.
4. A solution of claim 1 or 2 wherein the propylene gylcol in 1,2-propane diol.
5. A solution of claim 1 or 2 containing a mixture of methyl and propyl esters of parahydroxybenzoic acid.
6. A solution of claim 1 or 2 containing a mixture of ethyl and isopropyl alcohol.
7. A solution of claim 1 or 2 containing a mixture of methyl and propyl parahydroxybenzoic acid together with, isopropyl alcohol, and 1,2-propane diol.
8. A method for the preparation of an aqueous solution of claim 1 dissolving the trolamine and salicylic acid in a portion of the total water of the solution which will dissolve all of the trolamine and salicylic acid to form a first mixture, separately forming a second mixture containing the lower alkyl ester of parahydroxybenzoic acid and the alkylene glycol;
combining the first and second mixtures at a rate which is insufficient to cause precipitation of any solid and thereafter adding the alkanol and any additional water necessary to form the said aqueous solution.
combining the first and second mixtures at a rate which is insufficient to cause precipitation of any solid and thereafter adding the alkanol and any additional water necessary to form the said aqueous solution.
9. A method of claim 8 employing from 1% to 10% molar excess of trolamine.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US32491289A | 1989-03-17 | 1989-03-17 | |
US07/324,912 | 1989-03-17 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2012395A1 true CA2012395A1 (en) | 1990-09-17 |
Family
ID=23265643
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002012395A Abandoned CA2012395A1 (en) | 1989-03-17 | 1990-03-16 | Topical analgesic composition |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0417245A4 (en) |
JP (1) | JPH03504610A (en) |
AU (1) | AU5341390A (en) |
CA (1) | CA2012395A1 (en) |
WO (1) | WO1990011014A1 (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8697043B1 (en) * | 2013-01-08 | 2014-04-15 | Chattem, Inc. | Odor suppression of volatile organic analgesic compounds and method of use |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA613768A (en) * | 1961-01-31 | P. Modderno John | Topical analgesic compositions | |
US4353896A (en) * | 1981-06-08 | 1982-10-12 | Levy Michael A | Penetrating topical medicament |
US4511563A (en) * | 1983-07-15 | 1985-04-16 | Basf Wyandotte Corporation | Clear analgesic gels with reduced tackiness |
-
1990
- 1990-03-15 WO PCT/US1990/001419 patent/WO1990011014A1/en not_active Application Discontinuation
- 1990-03-15 JP JP2505255A patent/JPH03504610A/en active Pending
- 1990-03-15 EP EP19900905333 patent/EP0417245A4/en not_active Withdrawn
- 1990-03-15 AU AU53413/90A patent/AU5341390A/en not_active Abandoned
- 1990-03-16 CA CA002012395A patent/CA2012395A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
JPH03504610A (en) | 1991-10-09 |
WO1990011014A1 (en) | 1990-10-04 |
AU5341390A (en) | 1990-10-22 |
EP0417245A1 (en) | 1991-03-20 |
EP0417245A4 (en) | 1991-09-18 |
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