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Home , Butacaine, Isobucaine, Ketocaine

||||||||||I|| USOO5276.032A United States Patent (19) 11 Patent Number: 5,276,032 King et al. 45) Date of Patent: Jan. 4, 1994

54 VISION AD AND ANESTHETC 56) References Cited COMPOSTON U.S. PATENT DOCUMENTS 1,907,392 5/1933 Stover ...... 514/535 76) Inventors: O. Newton King, 2524 Yale Rd.; 2,382,546 8/1945 Curtis ...... 54/535 X Henry W. Buck, 306 Homestead Dr., 2,803,582 8/1957 Cherney...... S4/535 X both of, Lawrence, Kans, 66049 3,019,163 1/1962 Harnist et al. ... 54/535 X 4,748,022 5/1988 Busciglio ...... 424/95. FOREIGN PATENT DOCUMENTS 21 Appl. No.: 788,932 460629 1/1937 United Kingdom . Primary Examiner-Frederick E. Waddell 22) Fied: Nov. 7, 1991 Assistant Examiner-T. J. Criares 57 ABSTRACT Related U.S. Application Data A new visualizing and composition and the process for the preparation thereof. The composition, 63 Continuation of Ser. No. 458,300, Dec. 28, 1989, aban generally as a gel, contains an effective amount of a doned. topical anesthetic, an effective amount of a visualizing agent and a pharmaceutically acceptable gelling reser 51 Int. Cl...... A61K 31/535; A61K 31/445; voir as a heat exchanger and/or a light transmitter. The A61K 31/24; A61K 47/00 composition is useful for topical application to a region (52) U.S. C...... 514/239.2; 514/317; of mammalian skin to supply visualization to a lesion 514/535; 514/626, 514/536; 514/781; 514/944; therein and to anesthetize the region for a subsequent 514/967; 514/969 destructive therapy. 58 Field of Search ...... 514/817, 818, 535, 617, 514/619, 626, 317, 239.2 9 Claims, No Drawings 5,276,032 1. 2 combination of both events. M. Coppleson, "Colpo VISION AD AND ANESTHETIC COMPOSITION scopic Features of HPV in the Female Genital Tract' in Obstetrics and Gynecology Clinics of North America, R. The present application is a continuation of U.S. pa Reid, Ed., Vol. 14/2, June 1987, page 476, R. Reid and tent application Ser. No. 07/458,300 filed Dec. 28, 1989, P. Scalzi, Am. J. Obstet. Gynecol., Vol. 153, pages now abandoned. 611-618 (1985). In addition to visualizing the lesion for therapy, some BACKGROUND OF THE INVENTION topical or local must also be used for the 1. Field of the Invention comfort of the patient being treated. The use of these The present invention relates to a new visualizing and 10 anesthetics is particularly desirable when treating sites anesthetic composition, and the process for the prepara which are located on the extremely sensitive external tion thereof, which composition possesses useful visual genitalia of either males or females. izing and anesthetic activities, and, more particularly, composition is well known in the this composition is useful for topical application to a art. U.S. Pat. No. 2,004,891 to Goldberg teaches anes region of mammalian skin to supply visualization to a 15 thetic solution containing acetate and epineph lesion therein and to anesthetize the region for a subse rin. U.S. Pat. No. 3,038,835 to Endres et al. discloses quent destructive therapy. derivatives of 2,6-Xylidine as surface anesthetic. Like History of the Prior Art wise, RESOLVE(R) is a commercially available prod Certain viruses and bacteria are known to cause le uct that produces surface anesthesia when applied topi sions on mammalian skin. Lesions caused by, and associ 20 cally to inflamed or abraded skin or to mucous mem ated with, the human papillomavirus (HPV) are com brane, such as cold sores. Each gram of RESOLVE (R) monly known as genital warts, venereal warts or condy contains 10 mg of dycionine hydrochloride (4"butoxy-3- loma acuminata. HPV is transmitted sexually. Areas piperidinopropiophenone hydrochloride). commonly affected include the cervix, vagina and ex Traditionally, the visualizing agent and the local an ternal genitalia of both the female and male. Diseased 25 esthetic agent are applied separately to the regions to be tissues also develop secondary to the HPV infection. subjected to destructive therapy. Commonly, the re The incidence of HPV infections has increased mark gions are "washed' with an aqueous solution of acetic edly. Untreated, HPV infection can cause severe com acid to visualize the lesion. Then a topical anesthetic plications. gel/ointment is applied to the same regions to prepare Most of the histopathologic features of HPV-related 30 the regions for therapy. Occasionally, a solution of local lesions correspond to the cytopathic effects of HPV on anesthetic is injected into the regions before the ther squamous epithelium in different stages of differentia apy. The separate application of these agents, however, tion. Other features include degenerative nuclear alter causes undesirable problems and complications. If the ations (wrinkling, pyknosis, and binucleation) of granu aqueous acetic acid is applied first to visualize the lesion lar cells and production of excess keratin (hyperkerato 35 and then followed by the application of topical anes sis), particularly in cutaneous warts. These genital warts thetic agent to induce local anesthesia, the visualizing or lesions are generally treated by destructive therapy, effect of the acetic acid is hampered by the subsequent such as cryotherapy or laser vaporization in an office application of the anesthetic agent. Consequently, the setting. visualization of lesions previously detected is lost. In The prefix "cryo” denotes very low temperature. 40 fact, even in the absence of any other agent, the visualiz Extremely low temperature can destroy abnormal tis ing effect of the aqueous acetic acid is short-lived. If sue. For example, cooling tissue to a temperature of more acetic acid is reapplied to the region, the effective -80° C. will cause the treated tissue to shed off and concentration of the topical anesthetic is reduced, less slough away over time, producing a watery discharge. ening its anesthetic effect and causing the patient to In most cases, not only the visible lesions, but also the 45 suffer unnecessary pain. "invisible' lesions caused by HPV must be treated. The An alternate way to apply the two agents separately "invisible' lesions normally reside in normal appearing is to first apply the topical anesthetic agent to the sus tissue adjacent to the visible lesions. Also, these "invisi pected region to induce topical anesthesia followed by ble' lesions are often flat, not elevated above the surface the application of the aqueous acetic acid to visualize of the skin. These "invisible' lesions must first be visual 50 the lesion. However, this is also not an ideal way. Intro ized before they can be treated by any destructive ther ducing aqueous acetic acid to some topical anesthetic apy. agent usually creates a messy mix on the skin, reducing HPV infection affects the orientation of keratin fila the effectiveness of the acetic acid and further obscur ments within the superficial layers of infected squamous ing the treatment site. epithelium. Application of dilute acetic acid (about 55 The effect of the traditional way of applying the 3-5%) to such areas causes the areas to turn white-the visualizing agent and the local anesthetic agent sepa so-called acetowhite epithelium. In fact, benign HPV rately is loss of visualization of lesions, dilution of the related infections, the various grades of dysplasia, and anesthetic effect, and obscuring the surgical field. The carcinomas in situ all manifest acetowhite epithelium, net result is less effective treatment of the patient ac particularly as seen under colposcopic visualization. It companied by suffering greater pain than necessary. has been postulated that acetowhitening of high-grade The present invention overcomes the prior art prob lesions probably occurs because the osmotic dehydra lems as discussed above. tion accentuates the high content of optically dense chromatin in cervical intraepitheline neoplasia. On the SUMMARY OF THE INVENTION other hand, acetowhitening of minor lesions is probably 65 The present invention relates to a composition for attributable to some transient reaction between acetic topical application to a region of mammalian skin to acid and abnormal envelope proteins in HPV-infected supply visualization to a lesion therein and to anesthe keratinocytes. Other grades of lesion could reflect a tize the region for a subsequent destructive therapy. 5,276,032 3 4. Broadly, the composition contains: An effective amount thetics, and their acid addition salts, of the amide type of a topical anesthetic to impart local anesthesia around include: hydrochloride ((-)-(1-butyl-2- the region; an effective amount of a visualizing agent to piperidyl)formo-2',6'-xylidide hydrochloride monohy visualize and recognize the lesion; and a pharmaceuti drate); (dibucaine, or 2-butoxy-N (2-die cally acceptable gelling reservoir to give the desired thylaminoethyl)-quinoline-4-carboxamide); consistency and to provide the necessary heat exchange (E)-2-(N-ethylpropylamino)butyro-2', 6'-xylidide hy interface and/or light transmitter. drochloride); lignocaine (); (1- It is, therefore, an object of the present invention to methyl-2-piperidyl)formo-2',6'-xylidide hydrochloride); provide a new water base gel containing an effective and (propylaminopropiono-o-toluidide hy amount of topical anesthetic and an effective amount of O drochloride). Other local anesthetics, and their acid visualizing agent. When applied to a region of a mam addition salts, include: sulphate (3- malian skin, the new water base gel supplies visualiza dibutylaminopropyl 4-aminobenzoate sulphate; butanili tion to a lesion therein, anesthetizes the region, and caine phosphate (2-butylamino-6'-chloroaceto-o-tolui provides the necessary medium, namely, a heat transfer dide dihydrogen phosphate); butyl aminobenzoate interface or a light transmitter for a subsequent cryo 15 (butyl 4-aminobenzoate); carticaine hydrochloride therapy or laser ablation, respectively. (methyl 4-methyl-3-(2-propylaminopropionamido)thio It is a further object of the present invention to pro phene-2-carboxylate hydrochloride; vide a gel that is a visual aid and is also an anesthetic hydrochloride (2-diethylaminoethyl 4-amino-2- agent. The gel is characterized in that it is clear and it chlorobenzoate hydrochloride); sul allows transmissions of light and trans-visualization. 20 phate (3-(2-methylpiperidino)-propyl 4-cyclohexylox It is another object of the present invention to pro ybenzoate hydrogen sulphate); dimethisoquin hydro vide a visual aid and anesthetic gel with a consistency chloride (2-(3-butyl-1-isoquinolyloxy)-NN-dime that allows the gel to remain where applied, even on a thylethyl- hydrochloride); diperodon (3- vertical surface or the underside of a surface. piperidinopropylene bis(phenylcarbamate) monohy It is still another object of the present invention to 25 drate); dyclonine hydrochloride (4'-butoxy-3- provide a visual aid and anesthetic gel that has a reason piperidinopropiophenone hydrochloride); ethyl chlo able shelf-life and that can retain its integrity after appli ride (); euprocin hydrochloride (9R)- cation on skin surfaces. The gel maintains its therapeutic 10, 11-dihydro-6'-(3-methylbutoxy)cinchonan-9-ol di properties after having been applied on body surfaces hydrochloride monohydrate); fomocaine (4-3-(alphap for about one hour. It resists drying and also maintains 30 henoxy-p-tolyl)propylimorpholine); hydro its therapeutic properties necessary for subsequent cry chloride (2-cyclohexylamino-1-methylethyl benzoate otherapy. Further, the gel retains its therapeutic proper hydrochloride); hydrochloride (2- ties after storage at room temperature for a reasonable isobutylamino-2-methylpropyl benzoate hydrochlo period of time. ride); hydrochloride (2'-(2-di-iso 35 DESCRIPTION OF PREFERRED propylaminoethoxy) hydrochloride); EMBODIMENTS leucinocaine mesylate (2-diethylamino-4-methylpentyl In accordance with this invention there is provided a 4-aminobenzoate methanesulphonate); hy composition for use in locally visualizing and anesthe drochloride (2-methyl-2-propylaminopropyl benzoate tizing a region on a mammalian skin having a lesion hydrochloride); myrtecaine (2-2-(10-norpin-2-en-2- therein for subsequent destructive therapy. Broadly, the yl)ethoxy)triethylamine); octacaine hydrochloride (3- composition contains, an effective amount of a topical diethylaminobutyranilide hydrochloride); oxybu anesthetic, an effective amount of visualizing agent, and procaine hydrochloride (2-diethylaminoethyl 4-amino a heat exchange interface or a light transmitter in the 3-butoxybenzoate hydrochloride); pramoxine hydro form of a pharmaceutically acceptable gelling reservoir. 45 chloride (4-3-(4-butoxyphenoxy)propyl)morpholine Topical anesthetics are compounds which block hydrochloride); and hydrochloride nerve conduction when applied topically to nerve tissue (2-diethylaminoethyl 3-amino-4-propoxybenzoate hy in appropriate concentrations. They produce reversible drochloride). loss of sensation by preventing or diminishing the con The "effective amount” or "pharmacologically effec duction of sensory nerve impulses near the site of their tive amount' of a local anesthetic in a unit dose of com application or action. Their main site of action is the cell position depends upon a number of factors. Included membrane. Local anesthetics could also be described as among those factors are the quantity of gelling reservoir local analgesics as they are most often used to produce used, the amount of visualizing agent present, the quan loss of pain without loss of nervous control. A preferred tity of other ingredients when used, and the tolerance local anesthetic should not be irritating to the tissue to 55 for the active ingredient of anesthetic. Effective amount which it is applied, nor should it cause any permanent of local anesthetic ranges from about 0.5% to about damage to nerve structure. It should have low systemic 30% by weight based on the total weight of the final toxicity because it is eventually absorbed from its site of composition. The section on Local Anaesthetics, Mar application. The time required for the onset of anesthe tindale, the Extra Pharmacopoeia, 29th Edition, J. E. F. sia should be as short as possible. Furthermore, the 60 Reynolds (ed.), Pharmaceutical Press, London, (1989), action must last long enough to allow time for the con offers a guide as to suitable ranges of topical anesthetics templated surgery or therapy, yet not so long as to under each entry. Ranges of representative topical anes entail an extended period of recovery. Local anesthet thetics are given below: ics, and their acid addition salts, of the ester type suit able for this invention include: Amethocaine (tetra 65 Suitable Range Preferred Range caine, or 2-dimethylaminoethyl 4-butylaminobenzoate); Anesthetic Weight Percent Weight Percent (ethyl aminobenzoate, or ethyl 4-aminoben lidocaine HC 0.5-30 2-25 zoate); and (cocainium chloride). Local anes dyclonine HC 0.5-3 0.5-2 5,276,032 5 6 -continued Suitable Range Preferred Range Suitable Range Preferred Range Anesthetic Weight Percent Weight Percent" Gelling Reservoir Weight Percent Weight Percent" pranoxine HCl 0.5-3 0.5-2 5 hydroxypropyl 0.5-10 0.5-5 benzocaine 0.5-2S 0.5-20 methylcellulose HC 0.5-3 0,5-2 carboxymethylcellulose 0.5-10 0.5-5 dibucaine HC 0.25-3 0.25-1 ("C.M.C.") dimethisoquin HCl 0.2-2 0.3-0.5 sodium C.M.C. 0.5-10 0.5-5 lidocaine base 0.5-30 2-2S polyvinylpyrrolidone 0.5-20 0.5-30 cocaine 2-20 4-0 O Weight percent of the total weight of the final composition. weight percent of the total weight of the final composition. Other agents can be added to the composition to At proper concentrations, the visualizing agents are impart additional desirable properties. Thus, for exam not excessively irritating to a mammalian skin. They ple, a vehicle and/or a humectant may be used. A typi cause color change where the lesions are found so the 15 cal vehicle includes water. It is usually added to make lesions can be visualized and recognized. Visualizing up the weight or volume. A humectant is an agent agents that are useful include acetic acid and hydro known to promote the retention of moisture. Glycerin chloric acid. The most preferred visualizing agent is and propylene glycol are suitable humectants. A pre acetic acid. Suitable range of glacial acetic acid is from ferred humectant for this invention is glycerin. Glycerin about 0.1% to about 15% by weight based on the total 20 is relatively inert. It helps to retain the moisture in the weight of the final composition. The pH of the composi final composition of the present invention, particularly tion is reduced by the use of the acidic visualizing agent. when water is used as a carrier or vehicle. Suitable and Suitable and effective range of the pH is from about 2 to effective amounts of glycerin range from about 1% to 5, and preferably around 3. about 20% by weight based on the total weight of the Among other functions, the gelling reservoir acts as 25 final composition. an interface which is required to provide an efficient The following non-limiting preferred examples illus means for heat transfer between the cryoprobe and the trate the present invention. The weight percent ex skin to be treated. The gelling reservoir is a heat ex pressed for each ingredient is the weight percent based change interface. The gelling reservoir also acts as a on the total weight of the final composition. means to allow transmission of light and to aid in pro 30 viding the final composition with a desired consistency. EXAMPLE 1. Generally, this gelling reservoir is in the form of gel, ointment, lotion, paste, jelly, spray, solution, cream, or Ingredient Weight Percent aerosol. The gelling reservoir is preferably made up of 35 lidocaine HC 20 a water-soluble gum or resin, which may have to be glacial acetic acid 5 dissolved in water if necessary. Water-soluble resins are hydroxypropyl methylcellulose 1.5 polymeric materials whose composition enables them glycerin 10 either to dissolve or to swell in water. A wide variety of Water qs. to 100' these polymeric compositions are known. They may be 40 *q.s. as much as suffices classified as nonionic, anionic cationic, or amphoteric, The final composition was prepared by first adding according to their electrolytic behavior in solution, and glycerin with stirring to water heated to about 75 C. as natural or synthetic, according to the method by Meanwhile, lidocaine HCI, in powder form, and hy which they are obtained. They alter the properties of droxypropyl methylcellulose were mixed to obtain a aqueous solutions or form films. Functions include dis homogenous mixture. The mixture was then added to persion, rheology control, binding, coating, floccula the stirred heated water solution containing the glyc tion, emulsification, foam stabilization and protective erin. The resultant mixture was cooled to room temper colloid action. Representative of these water-soluble ature, about 25 C. Glacial acetic acid was then added gums and resins include: acacia, agar, alginates, alkyl SO to the cooled mixture. The final mixture was cooled to and hydroxyalkylalkylcellulose, bentonite, carbomer, about 5 C. After about overnight to about 24 hours at carboxymethylcellulose ("C.M.C.”), carboxymethyl this temperature, the final mixture turned into a stable cellulose sodium ("sodium C.M.C.'), carrageenan, gel. The gel could then be stored at room temperature powdered cellulose, , gelatin, guar gum, until use. gum agar, gum arabic, gum ghatti, gun karaya, gum 55 The finished gel possessed all the desired properties. tragacanth, hydroxyethylcellulose, hydroxypropylcel The finished gel was clear, and allowed transmission of lulose, hydroxypropyl methylcellulose, locust bean light and trans-visualization. The gel had a consistency gum, methylcellulose, octoxynol 9, oleyi , pec that allowed it to remain at a vertical surface when tins, polyacrylamide, poly(acrylic acid) and its homo applied to the surface. The viscosity of the finished gel logs, polyethylene glycol, poly(ethylene oxide), polyvi also allowed it to remain, and not flow or drop, when it nyl alcohol, polyvinylpyrrolidone, propylene glycol was applied to an underside of a surface. The finished monostearate, sodium lauryl sulfate, sorbitan esters, gel also retained its integrity in that it maintained its stearyl alcohol, starch and its modifications, tamarind characteristics when stored at room temperature for gum, tragacanth, and xanthan gun. Suitable ranges of days or when place on body surfaces, resisting drying gelling reservoir vary from about 0.5% to about 10%. 65 and maintaining its gel properties necessary for trans by weight based on the total weight of the final compo mitting heat for cryotherapy from the time of applica sition. Ranges of representative gelling reservoir are tion to the time of treatment, usually from about 5 min given below: utes to about 15 minutes. 5,276,032 7 8 EXAMPLE 2 -continued Example 1 was repeated replacing the glacial acetic Ingredient Weight Percent acid with a sufficient amount of 0.1% of hydrochloride Wate qs, to 100' acid to reach a similar pH of about 3. s The finished gel had similar characteristics and prop erties as the one prepared according to the method EXAMPLE 8 described for Example 1. Example 1 was repeated using the ingredients in the Ingredient Weight Percent following examples. The finished gel had similar char- dyclonine HC acteristics and properties as the one prepared according glacial acetic acid 5 to the method described for Example 1. carboxymethylcellulose 1.5 glycerin O EXAMPLE 3 Water qs. to 100' 15 'q.S. as much as suffices ingredient Weight Percent Ordinarily, only a thin layer of the gel of the present dyclonine HC invention is needed to prepare a region on the skin, the glacial acetic acid 5 treatment site, for cryotherapy. After application of the EPropy methylcellulose 20 gel, a physician should wait for about 8-10 minutes Yin qs. to 100" before reexamination and undertaking cryotherapy. The continuous effect of the gel of the present invention qs. as much as suffices will enhance the ability to locate lesions. Enough mois ture usually remains on skin to provide interface for EXAMPLE 4 25 cryotherapy. If, however, loss of moisture should oc cur, an additional thin layer of the gel should be applied. Total anesthesia will not occur. Patients will experience Ingredient Weight Percent a "stinging" sensation which is quite tolerable and of pramoxine HC short duration, not more than a few minutes. Treatment glacial acetic acid 5 30 sites can then be viewed under magnification (colpo droxypropyl methylcellulose scope). After treatment, the gel of the present invention in qs to 100 should be allowed to remain to continue topical anes thesia. q.s. as much as suffices Evaluation routines and use of the gel from the pres The following examples can be repeated as in Exam- 35 ent invention in the treatment of external HPV lesions ple 1 using the ingredients given below. The finished gel are given below. has similar characteristics and properties as the one EVALUATION AND TREATMENT FEMALE prepared according to the method described for Exam To locate the general area of lesions, if any, apply 5% ple 1. 40 acetic acid to vulva, including vestibule and anus. EXAMPLE 5 Before the evaporation of 5% acetic solution, inspect vulva and anus with magnification (colposcope), possi ble biopsy (do not mistake papillosis of vestibule for Ingredient Weight Percent HPV lesions). tetracaine HC 2 45 Iflesions are found, apply a thin layer of the gel of the glacial acetic acid 5 present invention-use Q-tip (R) in urethral hydroxypropyl methylcellulose 5 meatus-to prepare for cryo. glycerin 10 Flood vagina with 5% acetic acid to evaluate cervix Water qs. to 100 and vagina. 50 Perform colposcopy with ECC and biopsy of suspi cious areas; Monsel's solution. EXAMPLE 6 Inspect vagina, possible biopsy (spiking, micropapil lations, etc.). Ingredient Weight Percent Treat vulva, vestibule, and anus with cryo. dibucaine HC 55 EVALUATION AND TREATMENT-MALE glacial acetic acid s hydroxypropyl methylcellulose 1.5 To locate the general area of lesions, if any, apply 5% glycerin 10 acetic acid to penis and scrotum. Watet qs, to 100' Before the evaporation of the 5% acetic acid, inspect 60 penis, including urethral meatus, possible biopsy (do not mistake papillosis of corona for HPV lesions). EXAMPLE 7 Inspect scrotum. If lesions found, apply a thin layer of the gel of the Ingredient Weight Percent 65 present invention-use Q-tip (R) in urethral cocaine HCl O meatus-to prepare for cryo. glacial acetic acid 5 Apply 5% acetic acid to anus to evaluate the general hydroxypropyl methylcellulose S region. Inspect before the evaporation of the 5% acetic glycerin 0 acid, possible biopsy. 5,276,032 10 If lesions found, apply a thin layer of the gel of the caine HCL, dyclonine HCL, pramoxine HCL, present invention to prepare for cryo. tetracaine HCL, dibucaine HCL, and cocaine HCL Treat lesions with cryo. to impart local anesthesia around said region; Clinical studies have shown that patients treated with (b) from about 0.1% to about 15% by weight, based the new composition reported less pain and shorter upon total weight of said composition, of a visualiz duration of residual discomfort as compared with those ing agent selected from the group consisting of treated with the conventional method of separately acetic acid and hydrochloric acid to visualize and applying anesthetic agent and visualizing agent on the recognize said lesion; skin region having the lesion therein. Thus, it is seen (c) a pharmaceutical gelling reservoir comprising that the gel of the present invention is a great improve O hydroxypropyl methylcellulose, glycerin, and ment over the prior art discussed in that it is effective water in an amount of about 0.5% to 10% by and easy to use. weight, based upon the total weight of said compo Each and every publication, patent or otherwise, sition; and specifically identified in this specification represents a (d) said compositions having a pH in the range of teaching of the understanding of those skilled in the art 15 about 2 to about 5. at the time this invention was made and is herein indi 2. The composition of claim 1 wherein said topical vidually incorporated by reference to the same extent as anesthetic is 1% by weight dyclonine HCL, said visual if it had been physically reproduced in the location and izing agent is 5% by weight of glacial acetic acid, said for the purpose as identified by the context in which it gelling reservoir is 1.5% by weight of hydroxypropyl is found. 20 methycellulose and 10% by weight of glycerin and It is thus believed that the operation and construction Water. of the present invention will be apparent from the fore 3. The composition of claim 2 wherein said glacial going description. Although the composition and acetic acid is replaced with a sufficient amount of 0.1% method shown and described have been characterized of hydrochloric acid to reach a pH of about 3. as being preferred, it will be obvious that various 25 4. The composition of claim 2 wherein said topical changes and modifications may be made therein with anesthetic is about 5% by weight of lidocaine HCL. out departing from the spirit and scope of the invention 5. The composition of claim 2 wherein said topical as defined in the following claims. anesthetic is about 1% by weight of pramoxine HCL. We claim: 6. The composition of claim 2 wherein said topical 1. A composition for topical application to a region of 30 anesthetic is about 2% by weight of tetracaine HCL. mammalian skin to supply visualization to a lesion 7. The composition of claim 2 wherein said topical therein and to anesthetize said region for a subsequent anesthetic is about 1% by weight of dibucaine HCL. destructive therapy, said lesion being characterized as 8. The composition of claim 2 wherein said topical human papillomavirus related, said composition com anesthetic is about 10% by weight of cocaine HCL. prising: 35 9. The composition of claim 4 wherein said hydroxy (a) from about 1% to about 20% by weight, based on propyl methylcellulose is replaced with carboxymethyl total weight of said composition, of a topical anes cellulose. thetic selected from the group consisting of lido k k SE k k

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