US 3880996 A
An analgesic composition for the symptomatic relief of localized pain of musculo-skeletal etiology is adapted for topical application over affected areas and includes an analgesic, e.g., a salicylate, a local counter-irritant, and an organopolysiloxane.
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United States Patent Fisher Apr. 29, 1975 TOPICAL ANALGESIC PREPARATION AND Handbook of Non-Prescription Drugs, (1967), pp.
METHOD OF USING 63-66.
 Inventor: Arthur I. Fisher, Box 228 Herod Point Rd., Wading River, NY. Primary Examiner-Stanley J. Friedman l 1792 Attorney, Agent, or FirmNatter & Natter, Esqs.
 Filed: Mar. 11, 1974 ] Appl. No.: 449,765  ABSTRACT An analgesic composition for the symptomatic relief [22:] lJScCll 424/1846, 424/358 of localized pain of musculoskeletal etiology is f i f gg adapted for topical application over affected areas and l o earc l 8 3 includes an analgesic, e.g., a salicylate, a local coun- References Cited ter-irritant, and an organopolysiloxane.
OTHER PUBLICATIONS Merck Index, 7th Ed., (1960), p. 934.
8 Claims, N0 Drawings TOPICAL ANALGESIC PREPARATION AND METHOD OF USING BACKGROUND OF THE INVENTION 1. Field of the Invention The invention relates generally to topically applied analgesic preparations.
2. Brief Description of the Prior Art Local analgesics have been commonly used for the symptomatic relief of musculo-skeletal pain. Generally, these analgesic preparations have been available in the form of lotions, liniments and ointments for topical application and usually included an analgesic and a rubefacient, such as camphor, menthol, etc.
Although prior local analgesics have, in some instances, resulted in beneficial pain mitigation for mildly inflamed arthritic joints, the use of such preparations has provided but limited and short-lived relief. With most local analgesics, it is believed that the major factor attributable to their but limited efficacy was the inability to promote sufficient percutaneous absorption of the analgesic. A substantial factor in whatever pain relief was achieved is believed to have been the rubefacient which provided the source of counter-irritation resulting in localized heat sensation and concommitant psychological diversion or through the utilization of local anesthetics such as chloroform.
SUMMARY OF THE INVENTION An analgesic composition for local application includes a salicylate analgesic, e.g., glycol monosalicylate, a rubefacient, e.g., capsicum oleoresin, and a minor amount of organopolysiloxane (silicone). The composition can be employed with a suitable carrier or vehicle such as lanolin. The synergistic action of the composition results in enhanced salicylate absorption and alleviation of musculo-skeletal pain.
From the foregoing, it should be appreciated that it is an object of the present invention to provide an analgesic preparation of the general character described which is not subject to the disadvantages of preparations heretofore used.
It is a further object of the present invention to provide an analgesic preparation of the general character described which is adapted to provide effective alleviation of localized musculo-skeletal pain.
A further object of the present invention is to provide an analgesic preparation of the general character described having enhanced percutaneous analgesic absorption.
Another object of the present invention is to provide an analgesic preparation of the general character described which is well suited for topical application to provide alleviation of localized pain, inflammation and edema associated with arthritic joints.
Yet another object of the invention is to provide an analgesic preparation of the general character described which includes an analgesic, a rubefacient, and an organopolysiloxane in a suitable carrier for topical application.
Other objects and advantages of the invention in part will obvious and in part will be pointed out hereinafter.
With these ends in view, the invention resides in certain new and unique preparations and the synergistic action of the components thereof by which the said objects and certain other objects are hereinafter attained, all as fully described and the scope of which is more particularly pointed out and indicated in the appended claims.
DESCRIPTION OF THE PREFERRED EMBODIMENTS The analgesic preparation of the present invention comprises several of the basic constituents of presently known commercial topical preparations for use in musculo-skeletal pain alleviation to which a quantity of an organopolysiloxane is added. It was unexpectedly discovered, in accordance with the present invention, that the presence of the organopolysiloxane greatly enhanced the ability of the prior preparations to alleviate such pain and relieve the underlying irritation. Especially with instances of arthritic associated discomforts, the presence of the organopolysiloxane provides an analgesic preparation of increased efficacy, the use of which has achieved a marked improvement in joint mobility.
As is well known, organopolysiloxanes, popularly called silicones, are a group of compounds having the structural formula:
R R R I l l R-Si-O -Si-O -Si-R l l l R R R wherein R represents an organic radical such as an alkyl, aryl, alkaryl, aralkyl, including benzyl, phenyl, methyl, tolyl and the like. Enhanced results are obtained with and accordingly it is preferred to employ C,C dialkylpolysiloxanes such as dipropylpolysiloxane, dihexylpolysiloxane and the like. The length n of the polymer chain can be between 0 to 2,000 and determines the viscosity of the liquid and preferred results are obtained wherein the organopolysiloxane viscosity ranges between 50 200 centistokes. Suitable polysiloxanes are disclosed in US. Pat. Nos. 3,392,040 and 3,378,440, the contents of which are expressly incorporated herein.
Among the suitable organopolysiloxanes for use in the present invention are dimethylpolysiloxane liquids which can be generally represented as follows:
CH3 CH3 CH3 l l CH -Si-O -Si-O -Si-CH CH CH n CH In accordance with the present invention, a conventional analgesic ointment base comprising an analgesic salicylate such as methyl salicylate, glycol monosalicylate, trithamalamine salicylate and the like, and a rubefacient, such as capsicum oleoresin, camphor, chloroform, menthol, allyl isothiocyanate and the like, is formulated as an ointment, for example employing a conventional carrier or vehicle, such as a greaseless vehicle. In the analgesic ointment base, the rubefacients desirably provide a local vasodilation effect which may be further enhanced with such typical local vasodilators as methacholine chloride, histamine dihydrochloride and the like. Analgesic ointments of the foregoing nature ire commercially available and, as mentioned hereto- "ore, have met with but limited results. It is believed vhat mitigation of referred pain through these local anilgesics was ideally provided by percutaneous salicyate absorption which was designed to be facilitated .hrough the use of the rubefacient and/or vasodilator.
The analgesic composition of the present invention is achieved by the addition of an organopolysiloxane to he foregoing analgesic ointment base. It has been esablished that the admixture of the analgesic base com- )osition and the organopolysiloxane provides enianced effectiveness that can not be achieved from the tse of the individual constituents. For example, the :omposition of thepresent invention has provided a iefinite increase in pain relief of discomforts associated with arthritic symptoms as well as a marked reduction n edema and greater joint mobility as compared with 'outine use of the analgesic ointment base not containng the organopolysiloxane.
In general, an effective amount of the organopolysioxane is employed. Usually it is preferred to employ a ninor amount by total weight of the preparation. lf imounts significantly less than about percent by otal weight of the preparation are employed, no signifcant improvements, as compared to the analgesic ointnent base, are obtained and the organopolysiloxane lcts primarily as an emollient. Little, if any, synergistic nteraction is obtained.
Employing organopolysiloxane in amounts greater han about 40 percent by total weight of the preparaion unduly decreases the viscosity of the ointment )reparation to render it generally unacceptable for topcal use and also renders the ointment difficult to fornulate, package and apply. Best results are generally )btained employing the organopolysiloxane from about .3 percent by total weight of the preparation.
The analgesic preparation of the present invention is 'ormulated according to conventional procedures too vell known to the art to specifically describe. Of :ourse, other conventional additives commonly em- )loyed in topical ointments, e.g. pigments, stabilizers, lntioxidants and the like, can also be added in convenional amounts.
1n the following examples are described several of the )referred embodiments of the invention in an exemilary manner. It should be understood, however, that he invention is not intended to be limited to these spe- :ific embodiments.
EXAMPLE 1 Quite satisfactory results have been obtained utilizng, as an analgesic ointment base, a conventional anal- ;esic ointment containing the following constituent in- ;redients: glycol monosalicylate (approximately 10 iercent), capsicum oleoresin, histamine dihydrochlor- 11c, and methyl nicotinate in a lanolin carrier or vehile. An example of such analgesic preparation is the 'intment sold under the trademark Infra-Rub by Vhitehall Laboratories, New York, NY.
Commencing with a base of 3.3 oz. of this commerially available preparation, 0.6 oz. of silicone dimethlpolysiloxane (L-45 Union Carbide 100 cts.) was dded and mixed. A paste composition of uniform conistency resulted. The preparation was topically applied 9 the skin over arthritic joints once daily. With routine pplication, a marked decrease in inflammation was oted along with greater joint mobility after approximately three days. Concordant results have been obtained with 0.5 oz. silicone dimethylpolysiloxane 1-45 Union Carbide cts.) added to 3.3 oz. of an identical base.
While the precise reasons for the decrease in inflammation, concommitant pain relief and improved joint mobility are unknown, it has been established that the addition of the organopolysiloxane to the commercially available ointment base does result in a marked increase in percutaneous analgesic absorption.
Experiments were performed to determine the percutaneous salicylate absorption levels of a preparation similar to that of Example 1, with a 25 percent organopolysiloxane content. One hind rat foot was immersed in a vial containing the commercial ointment base preparation and compared with similar immersions in a vial containing the preparation of Example 1. The test animals were placed in a metabolic cage, a 24 hour urine specimen was collected, urine volume recorded and salicylate level measured. The following table outlines the testing results:
Ointment Base lmmersion Timc (min.) 7: salicylate in Urine Ointment Base with 257r L-45 Silicone 100 cts.)
Immersion Timc (min.) 7( salicylate in Urine It was thus determined that a substantial increase in percutaneous salicylate absorption has been achieved with the analgesic preparation of the present invention as compared with the commercial analgesic ointment base.
EXAMPLE 2 An analgesic ointment base of the following formulation was prepared:
ANALGESIC OlNTMENT BASE Salicylamidc 371 Dipropylcne glycol salicylate 3'7? Methyl nicotinate 0.571 Histamine dihydrochloride 0.057: Capsicum oleorcsin 0.0571 Stcaryl alcohol 3.7367: Glyceryl monostearatc 2.337571 Stcaric acid 4.68% Petrolatum 9.36% Mineral oil 4.687: Methyl parahcn 0.093671 Propyl parahcn 0.09367: Tricthanolamine 0.4687: Sodium lauryl sulfate-20% 0.468% Water 0.8.
An analgesic ointment of this general nature is presently manufactured by Ambix Laboratories, Inc. of North Bergen, NJ.
Commencing with a base of 3.3 oz. of this analgesic ointment base, 0.6 oz. of silicone dimethylpolysiloxane (L45 Union Carbide l00 cts.) was added to provide an ointment of uniform consistency in accordance with the present invention.
The composition was applied to locally inflamed areas over arthritic joints once daily. As with the composition of Example 1, a marked decrease in swelling inflammation accompanied by a decrease in pain and discomfort associated with the arthritic areas was noted with routine local application after approximately three days.
EXAMPLE 3 An analgesic ointment comprising methyl salicylate and menthol in a lanolin base was utilized as the analgesic ointment base. This ointment is generally available and sold under the trademark Ben-Gay by Pfizer, Inc. of New York, N.Y. To a base of 3.0 oz. of this ointment. 0.6 oz. of silicone dimethylpolysiloxane (L-45 Union Carbide 100 cts.) was added. In accordance with the present invention, the polysiloxane was admixed with the base to provide a paste of uniform consistency.
The preparation was topically applied over arthritic joint areas once daily. As in the previous examples, cessation of pain, a marked decrease in inflammation and greater joint mobility were noted after approximately 3 days.
EXAMPLE 4 An analgesic ointment comprising methyl salicylate, glycol monosalicylate, menthol, camphor and allyl isothiocyanate in a carrier of petrolatum and lanolin was utilized as the analgesic ointment base. A commercially available analgesic of this nature is sold under the trademark Musterole by Schering Plough Corp. of Bloomfield, NJ. To a base of 3.3 oz. of this ointment, 0.6 oz. of silicone dimethylpolysiloxane (L-45 Union Carbide I00 cts.) was added. The preparation thus formulated was topically applied over arthritic joint areas once daily. As in the previous examples, cessation of pain, decrease in inflammation and greaterjoint mobility were noted after approximately 3 days.
Results similar to those obtained in the foregoing examples are obtainable when other C -C dialkylpolysiloxanes such as dipropylpolysiloxane, dihexylpolysiloxane and the like are employed.
While the precise reason for the decrease in pain and discomfort as well as the reduction in inflammation and improved joint mobility when utilizing the composition of the present invention is unknown, it has been established that the polysiloxane definitely enhances the percutaneous salicylate absorption as compared with prior analgesic ointments. This phenomenon might be attributed to the lubricity of the polysiloxane in facilitating percutaneous passage through skin layers made receptive by the vasodilation effect of the rubefacients.
A further factor in improved salicylate absorption might be that the polysiloxane provides a barrier overlying the applied area which retards salicylate evaporation (generally accellerated by the rubefacients) to assure proper salicylate concentration in intimate skin contact.
It has been postulated that the polysiloxane itself may pass through the skin layers which have been affected by the rubefacients and vasodilators to provide direct joint lubrication in situ.
Thus, it will be seen that there is provided a topical analgesic preparation which achieves the various objects of the invention and which is well suited to meet the conditions of practical use.
As various changes might be made in the topical analgesic preparation as above set forth, it is to be understood that all matter herein described is to' be interpreted as illustrative and not in a limiting sense.
Having thus described the invention, there is claimed as new and desired to be secured by Letters Patent:
1. An analgesic preparation suitable for use in the mitigation of pain of musculo-skeletal etiology comprising:
a. an analgesic in an amount sufficient to alleviate musculo-skeletal pain,
b. a rubefacient in an amount sufficient to provide localized heat sensation, and
c. a polysiloxane having the formula:
R R R l R Si O Si O Si R l l l R R R wherein R represents an organic radical selected from the group consisting of alkyl, aryl, alkaryl, and aralkyl, and n is an integer between 0 and 2,000, said polysiloxane having a viscosity between 50 and 200 centistokes in a range from about 10 to 40 percent by weight of the total preparation,
whereby percutaneous absorption of the analgesic is enhanced.
2. An analgesic preparation in accordance with claim 1 wherein the analgesic is a salicylate.
3. An analgesic preparation in accordance with claim 1 wherein the analgesic is selected from the group consisting of methyl salicylate, glycol monosalicylate, trithamalamine salicylate, salicylamide and dipropylene glycol salicylate.
4. An analgesic preparation in accordance with claim 1 further including a vasodilator selected from the group consisting of methacholine chloride, histamine dihydrochloride, and methyl nicotinate.
5. An analgesic preparation suitable for use in the mitigation of pain of musculo-skeletal etiology comprising:
a. an analgesic in an amount sufficient to alleviate musculo-skeletal pain,
b. a rubefacient in an amount sufficient to provide localized heat sensation, and c. a C -C dialkylpolysiloxane in a range from about 10 to 40 percent by weight of the total preparation and of a viscosity from about 50 to 200 centistokes,
whereby percutaneous absorption of the analgesic is enhanced.
6. An analgesic preparation in accordance with claim 5 wherein the dialkylpolysiloxane is dimethylpolysiloxane.
7. A method of administering treatment for the alleviation of pain of musculo-skeletal etiology, said method comprising topically applying an analgesically effective amount of the preparation of claim 1.
8. A method of administering treatment for the alleviation of pain of musculo-skeletal etiology, said method comprising topically applying an analgesically effective amount of the preparation of claim 5.