Abstract:
Method of treating veterinary or human patients for relief of dermal or sub-dermal pain and inflammation by topical application of a therapeutic agent comprising propylene carbonate.

Description:
This is a continuation-in-part of U.S. patent application Ser. No. 439,620, filed Nov. 5, 1982, now abandoned. 
    
    
     BACKGROUND OF THE INVENTION 
     This invention pertains to a new method for treating pain, inflammation, trauma, allergy, and disease by the topical application of a therapeutic agent having previously unrecognized analgesic, anti-allergenic, and anti-inflammatory properties, or by the topical application of the same agent in combination with a second therapeutic agent, the effectiveness of which is enhanced by the first agent. 
     As stated in the publication of Texaco Chemical Company entitled &#34;Ethylene Carbonate-Propylene Carbonate,&#34; &#34;Propylene Carbonate is a clear, mobile, practically odorless liquid.&#34; It is 4-methyl 2-dioxolone, a cyclic organic ester which is a known solvent for a variety of polar and non-polar organic compounds and for many inorganic chemical and biological materials. Its chemical properties include low toxicity. The same publication further indicates that propylene carbonate is an excellent additive for certain clays and gel bases useful in cosmetic and personal care products. Still further, the publication refers to acute toxicity tests which indicate that propylene carbonate is practically non-toxic and is otherwise indicated to be non-offensive in subchronic dermal applications, skin sensitization tests and inhalation tests, though temporarily offensive to a minor degree to the eyes. 
     The Texaco publication also includes a extensive bibliography, including an applications section entitled &#34;Cosmetics and Personal Care,&#34; in which four patent references and three literature references are noted. 
     No indication whatsoever is found in the above-referenced Texaco publication to suggest, in any way, the possible utility of propylene carbonate as a therapeutic agent for treating pain, inflammation, trauma, allergy, or disease. 
     A search has been conducted in the U.S. Patent and Trademark Office to identify references relating to or disclosing the use of propylene carbonate for essentially any pharmaceutical purpose. Patents identified in this search were: 
     
         ______________________________________U.S. PAT. NO.     INVENTOR______________________________________4,017,615         Shastri, et al.4,279,901         Ronald M. Kudla3,924,004         Chang et al.4,273,770         Francisco Alvarez4,242,334         Stache et al.3,829,826         Gaetano D&#39;Alelio3,574,118         Wayne Otto Baker3,362,927         Edwin H. Lochridge3,185,627         Gus S. Kass3,178,352         Roy Erickson3,136,696         Benjamin Harrison3,472,931         R. B. Stoughton4,244,942         Kamishita et al.3,298,919         Jack L. Bishop, Jr.3,352,753         Leonard J. Lerner______________________________________ 
    
     The first three of the above-listed patents are listed in the Application-Cosmetics and Personal Care subsection of the bibliography in the above-referenced Texaco Chemical Company publication (page 24). The primary focus of Kudla is on ethylene carbonate rather than propylene carbonate. It will also be noted that the remaining references in that bibliography subsection all deal only with hair-treatment preparations. The patents on Chang, Shastri et al., and Kudla all relate to topical ointment compositions in which, generally, propylene carbonate or ethylene carbonate is combined with co-solvents or with other constituents, such that only a minor proportion of propylene carbonate is included in each composition, generally less than 40% in Chang and 30% in Shastri, for example. The compositions, in which propylene carbonate is incorporated in accordance with the teachings of these patents, each include specific therapeutic agents, such as anti-biotics, steroids, antihistamines, antiseptics, anesthetics, and corticosteroids. 
     The D&#39;Alelio patent relates to the use of propylene carbonate in removing dental calculus, relying on its non-toxic solvent function for swelling the organic binder phase of the calculus. 
     Alvarez is directed to novel anti-inflammatory agents. It indicates, however, that such agents may be combined with a &#34;pharmaceutically acceptable solvent,&#34; among particularly suitable examples of which is listed propylene carbonate. As in other applications of this type, the carbonate is generally carried in a semi-solid emulsion of oil and water, or water in oil including, for example, white petrolatum. 
     The Stache patent was cited apparently for its teaching of various carbonate-containing steroids useful in veterinary and human therapy. Notably absent, according to Applicants&#39; reading of this patent, is any suggestion of the use of propylene carbonate in any manner different than that suggested in the other prior art references, cited above. 
     In addition to the foregoing, Applicants are aware of certain unpublished non-clinical work of others. Applicants&#39; limited knowledge of this work prior to the present invention, indicated that propylene carbonate had been considered only for possible use as a rapid surface skin-penetrating carrier for a topically applied composition, namely suntan lotion, the objective of which was to eliminate the greasy surface feel commonly associated with existing suntan lotion. It is not known whether any such suntan lotion was ever prepared. 
     Notwithstanding prior knowledge of propylene carbonate and its limited use as a vehicle in topical medicaments, and notwithstanding the unpublished work of others suggesting propylene carbonate as a vehicle for suntan lotion, there remains a continuing need for more effective methods of therapy to relieve pain and inflammation and to treat trauma, allergy, and disease. This need has not been addressed in the art pertaining to propylene carbonate. 
     It is, therefore, the general object of the present invention to provide such a method by the topical application of a hitherto unrecognized therapeutic agent, either alone or in combination with a second agent, the therapeutic effectiveness of which is enhanced by the first agent. 
     BRIEF DESCRIPTION OF THE INVENTION 
     The present invention comprises a method to reduce pain and inflammation in surface tissue and in deep or sub-dermal tissue, such as bone, muscle, ligaments, or joints, of a human or veterinary patient by topical application, in the patient&#39;s skin or mucous membrane proximate the pain or inflammation, of a therapeutically effective amount of a medicament comprising propylene carbonate. The present invention also comprises a method to treat trauma, allergy or disease by the topical application of propylene carbonate, in combination with a second therapeutic agent appropriate to the trauma or allergy or disease, the effectiveness of which is enhanced by the propylene carbonate. 
    
    
     DETAILED DESCRIPTION OF INVENTION 
     As contrasted with prior art compositions in which limited amounts of propylene carbonate have been used as a vehicle or carrier for other pharmaceutical agents, the present invention involves a therapeutic method in which propylene carbonate is not merely a vehicle but a primary medicament. While the therapeutic composition used in the method of this invention may include other constituents, either as a stabilizer for the propylene carbonate or as a co-reactive medicament, the present invention has been found effective even in the absence of such stabilizers and co-reactive medicaments. 
     Thus, in most of the clinical tests described below, the effective therapeutical agent consisted essentially or entirely of propylene carbonate. These tests clearly demonstrate the hitherto unrecognized effectiveness of propylene carbonate as a therapeutic agent. Certain of the tests described below also demonstrate the effectiveness of propylene carbonate as a potentiating agent for a second or co-reactive medicament. 
     Technical explanations for the surprising results in the clinical tests of the present invention described below are speculative. Accordingly, Applicants do not wish to be bound by any such explanations. However, certain unique characteristics of propylene carbonate seem to be particularly significant. 
     First, the solvent properties of propylene carbonate are well known. Because of these properties, it has been used or proposed as a vehicle or carrier in a number of topically applied medicinal and cosmetic compositions. These same solvent properties, however, apparently based on the chemical affinity of propylene carbonate for a wide range of other chemical compounds, also make it appropriate as a penetrant. But enhanced penetrating properties due to the propylene carbonate constituent has not been a recognized characteristic of known propylene carbonate-containing medicinal and cosmetic compositions. Applicants now surmise this is because all such compositions include oils, fats, or emulsifiers, in addition to the propylene carbonate. These oils, fats, and emulsifiers are thought to inhibit the penetrating ability and mobility of propylene carbonate. In this respect, the &#34;Comparative Example&#34; discussed below is of interest. 
     As presently understood then, an important factor in the present invention is the absence, in the topically applied medicament used in this invention, of any penetration inhibiting constituent. This is believed to be important because it apparently enables the propylene carbonate, with its penetrating ability uninhibited, to migrate quickly to the sub-dermal region where its therapeutic value, and/or the therapeutic value of any co-reactive medicament with which it is combined, is expeditiously realized. 
     A second important characteristic of propylene carbonate, for purposes of the present invention, is thought to be the biological/chemical process by which it degrades through one or more free radical stages to non-toxic final products, namely propylene glycol and carbon dioxide. This may be of significance for two reasons. Primarily, if the final degradation products are innocuous, adverse long range side effects, caused by accumulated by-products, are unlikely. Secondly, the free radical intermediate products, through which propylene carbonate apparently degrades in the body, may function as metabolic accelerators and as nerve cell transmission blockers, resulting respectively in the enhancement of other normal bodily functions dependent on metabolic reactions and in the inhibition of neuro transmission of pain impulses to the brain. The latter may provide symptomatic relief of pain while the former may enhance the normal physiological tendency of a body member to counteract the abnormality, whether it be allergy, inflammation, trauma, or disease. 
     The accelerated metabolic activity associated with propylene carbonate degradation in the body may also be responsible for the enhanced effectiveness of other co-reactive medications administered in combination with propylene carbonate. For example, the clinical tests described below include several cases in which a solution of propylene carbonate with a co-reactive agent (namely aspirin, iodine, and penicillin, respectively, in separate tests) was used. Positive clinical therapeutic results were obtained in each case. The effectiveness of all three of these medications was apparently enhanced by the presence of propylene carbonate. The apparently improved pharmacologic responses suggest that only a reduced dosage of each medication would be needed in order to produce the desired therapeutic effect. An especially striking example was the case in which a solution of propylene carbonate and penicillin was applied locally to an abcessed tooth and gum (Test 73, below). 
     In Table I, below, are listed a number of clinical tests in which propylene carbonate was used alone, and in which almost immediate relief from pain, swelling, inflammation, and allergic phenomenon was obtained. Relief from pain usually lasted from 4 to 6 hours which coincides in general with the period of time believed to be required for the degradation of propylene carbonate in the body. In some of the clinical examples, repeated applications of propylene carbonate were necessary in order to obtain relief from pain; in others, prolonged relief was provided after only one application; in still others, continued use of propylene carbonate resulted in prolonged relief as more specifically indicated below. At least, temporary relief from pain, and at best, prolonged remission was obtained by the topical application of propylene carbonate alone. This was especially so in instances where pain and inflammation were associated with joint and muscle trauma, osteoarthritis, bursitis, tendonitis, sprains, hematomas, fractures, torn ligaments and muscles. In those instances where pain returned (although generally lessened) within 4 to 6 hours, repeated application of propylene carbonate seemed to hasten ultimate complete recovery. 
     
                                           TABLE I__________________________________________________________________________TestPatientGrade &amp; Date              Area of Topical                                    Time to    DurationNumberof Result        Age           Sex              Ailment     Application                                    Relieve Pain                                               of Effect__________________________________________________________________________ 1.  E - 5/18/82        56 F  Bursitis    Left Shoulder                                    2-3 Min.   8-10 Hours              (Chronic) (mild) 2.  G - 3 Applica-        24 M  Lower Back Pain                          Lumbar &amp; Sacral                                    20-25 Min. 6-8 Hourstions 5/22/82 (3 Week Duration)                          Regions5/29/80 6/5/82 3.  E - 3 Applica-        22 M  Infected Tooth                          Skin Over Left                                    2-3 Min. Pain                                               6-8 Hourstions 5/22/82 and Jaw     Mandibular                                    &amp; Swelling Re-5/23/82 5/25/82           Region    duced by 2nd                                    Application 4.  E - 3 Applica-        67 M  Osteo-Arthritis                          Hands &amp; Shoulder                                    5 Min.     4-6 Hourstions 5/18/825/20/82 5/25/82 5.  E - 4 Applica-        61 F  Osteo-Arthritis                          Hands &amp; Feet                                    3 Min.     4-6 Hourstions 5/25/825/26/82 5/27/825/28/82 6.  F - 6/7/82        18 F  Pulled Groin                          Left &amp; Right                                    5 Min. -   30 Min.                          Inguinal Region                                    Slight Effect                                    Vague Response 7.  E - 6/12/82        45 F  Foot Bones Broken                          Ventrum &amp; Dorsum                                    Immediate Ef-                                               30 Min.              Hematoma Right                          of Foot   fect - Com-              Foot                  plete Relief                                    From Pain 8.  E - 2 Applica-        43 M  Smashed Index                          Index Right                                    3-5 Min. Pain                                               6-8 Hourstions 6/16/82 -              Finger (Nail bed)                          Finger    Reduced; MovedAM and PM                           Finger Freely                                    With No Pain;                                    Healing Hastened 9.  G - 6/16/82        16 F  Osteo-Arthritis -                          Middle Finger                                    Two Appli-              Locked Middle         cations Need-              Finger                ed; Finger Un-                                    locked10.  E - 3 Applica-        31 F  Abcess Following                          Skin Over Right                                    5 Min. - Pain                                               6 Hourstions 6/19/82 Tooth Removal                          Mandible  Relieved6/20/82 6/21/82              Healing Hastened11.  N - 6/22/82        30 F  Sprained Wrist                          Wrist     Little or No Effect;                                    No Explanation Found;                                    Possibly Psychosomatic Symptoms12.  E - 4 Applica-        38 F  Osteo-Arthritis                          Both Knees                                    Within 10  10-12 Hourstions 6/24/82 of Knees              Min. Pain Gone                                               Used as Needed6/25/82 6/26/82                                for 2 mo. Period6/27/82                                        With Continued                                               Relief13.  E - 2 Applica-        74 F  Cervical Osteo-                          Cervical Neck                                    30 Min.    8 Hourstions 6/18/82 ArthritisAM &amp; PM14.  E - 6/22/82        20 F  Sprained Left                          Left Ankle                                    2-3 Min.   8-10 Hours              Ankle15.  G - 2 Applica-        35 F  (2 Teeth) Right                          Right Jaw Pain-                                    5 Min. Pain                                               8 Hourstions 6/24/82 Lower Jaw; Post                          ful &amp; Swollen                                    Relieved, also              Wisdom Tooth          Swelling Seem-              Extractions           ed Reduced16.  E - 6/24/82        67 M  Osteo-Arthritis                          Toes of Left                                    2 Min.     6-8 Hours              of Toes     Foot                 or Better17.  E - 3 Applica-        63 F  Osteo-Arthritis                          Left Thumb,                                    On Hand 4-5                                               8-12 Hourstions 6/28/82 Left Thumb &amp; Hip                          Hand, &amp; Hip                                    Min. - On Hip                                               Stiffness6/29/82 6/30/82                     15-20 Min. Down, Mo-                                               bility Up.                                               After Use                                               for 1 Week                                               Hip Pain                                               Gone - no                                               reapplica-                                               tion needed18.  G - 2 Applica-        59 M  Lower Back Muscle                          Lower Back 2                                    2-3 Hours  12 Hourstions 7/4/82  Sprain      Appl.19.  N 7/5/82        45 M  Lower Back Pain                          Lower Back 2                                    1st Appl. No                                               2-3 Min.              Chronic Inter-                          Appl.     effect. 2nd                                               Slight              mittent for 10        Appl. 4 Hours                                               Improve-              Years - No            Later      ment Only -              Diagnosis                        No Signifi-                                               cant Effect20.  N - 3 Applica-        80 F  Osteo Chronic Back                          (Reports are Uncertain) Leg Pain Remainedtions 7/8/82  &amp; Legs - 3 Ruptured                          the same. No measurable improvement7/9/82 7/10/82              Lumbar Discs21.  E - 2 Applica-        35 F  Chronic Pain of                          Lower Back                                    10-15 Min. 6-8 Hourstions 7/10/82 Severe Scoliosis                 Continued Use7/11/82       (Lumbar Region)                  for 6 Weeks, as                                               Needed, Gave                                               Consistent Re-                                               lief22.  E - 2 Applica-        27 F  Acute Tendonitis                          Right Wrist &amp;                                    10 Min.    8 Hourstions 7/13/82 Right Hand  Forearm              Repeated                                               Applica-                                               tions. Ef-                                               fective                                               over the                                               next week.23.  E - 7/15/82        47 M  Bursitis Right                          Wrist &amp; Shoulder                                    1-2 Min.   5-6 Hours              Wrist Left              Shoulder24.  E - 7/15/82        61 F  Osteo-Arthritis                          Left Knee &amp;                                    5 Min.     5 Hours              Left Knee &amp; Right                          Right Ankle              Ankle25.  E - 7/16/82        60 F  Osteo-Arthritis                          Distal &amp; Proximal                                    Stiffness Re-                                               4 Hours              Both Hands, Fingers                          Dip &amp; Pip duced 5 Min.;              Marked Deformity                          Joints    also Tenderness              of Pip Joints         Reduced on her Only                                    Tender Joint, Pip                                    Left Small Finger26.  F - 7/19/82        24 F  Herneated I.V.                          L.sub.1 -L.sub.5 Area                                    10-15 Min. 4 Hours              Disc (Lumbar) -       Pain in Back              Later Removed         &amp; Muscle Gone -                                    Radiated Pain                                    to Legs Un-                                    effected27.  E - 2 Applica-        56 F  Cervical Pain &amp;                          Cervical  Pain Gone in                                               Remaindertions 7/19/82 Stiffness in                          1-8       5 Min. -   of Day7/20/82       Morning               Refer to                                    #3328.  F - 7/19/82        24 M  Middle Toe, Right                          Pip × 2                                    Some Numbing                                               For 1 Week              Foot - Arthritis      of Mild Pain.                                               Afterwards              of Undetermined       Had taken  Toe was Mobile              Type                  Indocin that                                               at Joint Where                                    A.M. - Test                                               it was Pre-                                    Invalid    viously Fixed.29.  G - 7/24/82        50 M  Lower Back  Lumbo-Sacral                                    Pain Relief                                               5-6 Hours              Lumbo-Sacral                          Region    in 10 Min.30.  E - 7/28/82        86 F  Osteo-Arthritis                          Knees (P.C.                                    Pain Relief                                               4 Hours              Knees       With Aspirin)                                    1/2 Hour31.  Lidex Ointment Compared with 100% Propylene Carbonatea.   N - Lidex        61 F  Osteo-Arthritis                          Left Hand Lidex                                    No Reaction                                               100% P.C.6/19/82                                        Applied Over                                               Lidex -                                               Still No Reaction                                               in Left Handb.   E - 100% P.C.             Right Hand                                    2-3 Min.   4-6 Hours6/19/82                   Propylene Carbon-                          ate Only32.  N - 5/20/82        70 F  Osteo-Arthritis                          Hands Several                                    No Effect  Discovered That                          Appl.                Water had Con-                                               taminated P.C.33.  N - 7/25/82        56 F  Cervical Pain &amp;                          *1st Appl. effect    4 Hours              Stiffness Same                          Lasted Only 10 Min.              Pt. as #27  2nd Appl. 2-3 Min.                          for Effect With                          Fresh P.C.34.  E - 7/30/82        63 F  Osteo-Arthritis                          Applied P.R.N.                                    Less P.C. Needed              Hip, Knee &amp; Ankle                          for 6 wks.                                    and Quicker Response                                    After Repeated Use *Note: Suspect first application failed due to contamination of propylene carbonate.35.  E - 7/30/82        38 F  Night Cramps                          To Calves of                                    20 Min.    For the Night.              in Legs (Calf)                          Legs                 No Awakening                                               from Cramps36.  N to F - 8/5/82        69 M  Rheumatoid Arthritis                          Hands     P.C. - No Relief; Used 2 Times8/13/82 P.C.  Hands, Hip, &amp; Leg                          Daily for 1 Week. P.C.A. -8/13/82                   After 2 Days - Less StiffP.C.A.*                   Swelling Less, Mild Relief -                          No Significant Improvement37.  E - 8/13/82        27 F  T.sub.11 &amp; T.sub.12                          T.sub.11 &amp; T.sub.12 &amp;                                    10 Min. Relief                                               Back              Severe Sprain                          Dermatome            Improved              Intercostal                      After One              Pain - Rear                      Application              to Front38.  E - 8/15/82        56 F  Lower Back Pain                          Lower Back                                    20 Min. No Several              Sacrum                Pain       Applications                                               Over Period                                               of 2 Weeks;                                               Relief Each                                               Time39.  G - 8/23/82        16 M  Trauma to Right                          Fracture of                                    10-20 Min.              Wrist &amp; Forearm                          Radius &amp; Ulna                                    Swelling Down              Swollen &amp; Pain-                          Applied to Wrist                                    Pain Diminished on              ful         &amp; Forearm Forearm. Wrist                                    Slightly Numbed40.  G - 9/3/82        59 M  Hematoma on Right                          To Hematoma                                    Within 11/2                                               Swelling              Forearm Result of     Hour       Reduced,              Trauma                           Pain Diminished41.  E - 9/15/82        16 M  Trauma Left Fore-                          To Left Fore-                                    2-5 Min.   Pain Relieved;              finger, Jammed                          finger &amp;             Swelling Re-              Swollen Finger &amp;                          Hand                 duced in with-              Hand, Severe Pain                in 1/2 Hour.                                               Finger Freely                                               Movable With-                                               out Pain or                                               Limitation              Also Right Scapula                          To Skin over                                    2-5 Min.   Pain Com-              &amp; Trapezius Right                pletely Re-              Muscle Traumatized               lieved - Free-              Echymosis &amp; Hematoma             dom of Movement                                               Without Pain42.  E - 10/2/82        56 M  Tennis Elbow Right                          To Right Elbow                                    3-5 Min.   Pain Relieved                                               for 4-5 Hours43.  E - 10/11/82        56 F  Back Sprain To Lumbar-Sacral                                    10-20 Min. Pain Relieved                          Region               Remainder of Day44.  F - 10/16/82        44 M  T2-Rib Broken                          To Fracture Area                                    Within 5 Min.                                               Effective 1/2              With Referred                          and T2 Dermatome                                    the Referred                                               Hour              Pain                  Pain Was Absent                                    Movement on Site                                    of Fracture Pain                                    Confined though                                    Reduced45.  E - 10/17/82        67 M  Hemiplegia- To Painful Arm &amp;                                    5-10 Min.  Relieves Pain 4-5              Stroke, Pain                          Leg                  Hrs. Used Daily              in Arm &amp; Leg                     for 6-8 Weeks46.  E - 11/3/82        56 F  Bursitis Rt.                          1 Application                                    5 Min.     No Pain No Limit-              Shoulder    at Bedtime           ed Motion the                                               Next Morning47.  E - 11/4/82        16 M  Knee Trauma Rt.                          1 Application                                    10-15 Min. No Return of Pain              Knee Football                          to Rt. Knee                                    Pain Reduced                                               Or Swelling the                                    Swelling Down                                               Next Day48.  E - 11/10/82        32 F  &#34;Joggers&#34; Knee                          1 Application                                    Pain Diminish-                                               No Return of Pain              Pain        to Affected Knee                                    ed in 2-3 Min.                                               the Next Day                                    Absent After                                    1/2 Hour49.  E - 11/16/82        50 F  Sprained Ankle                          1 Application                                    Pain Gone in                                               No Return That Day              (Rt.)                 10-15 Min. Slightly Tender                                    Swelling   Next Day. PC                                    Reduced    Reapplied, No                                               Return of Pain                                               Rest of Day50.  E - 11/22/82        54 F  Unremitting Pain                          Applied to the                                    Within 10 Min.                                               No Return of              from Osteo-Arthritic                          Knees     Pain Remitted                                               Pain Rest of              Knees for 31/2 yrs.              Day51.  E - 11/21/82        24 F  1 Yr. Ago Broken                          Applied to Pain-                                    Swelling Re-                                               Pain Disappear-11/22/82      Ankle (left)                          ful Ankle on 3                                    lieved in  ed for the11/23/82      Pinned, Chronic                          Different Days                                    2-3 Min.   Entire Day on              Swelling &amp; Pain                  Each of the 3              for 1 Yr.                        Days52.  G - 11/25/82        23 F  Trauma to Lt.                          Lt. Small Toe                                    3-5 Min.   First Application -              Small Toe. Swollen                          2 Applications       Pain and Swelling              Purple &amp; Painful                          3 Hrs. Apart         Reduced. After 3                                               hrs., Some Swelling                                               &amp; Pain Returned.                                               Second Application -                                               Reduced Pain &amp;                                               Swelling53.  E - 11/27/82        22 M  L3, L4, &amp; L5                          Left Side L3, L4,                                    15 Min. Pain                                               1 Hr. - Pain Gone,              Torn Tendons Lt.                          &amp; L5, also Inser-                                    Diminished no Return of Pain or              Lat. Dorsal MM                          tions of Lt. Lat.    MM Spasm; Patient              Torn Ligament.                          Dorsal MM.           was Up and Around              Bed-fast 3 Days54.  E - 11/28/82        51 F  Post Oper. - 4 wks.                          On Incisional                                    10 Min.    Pain Gone in 10              Hysterectomy                          Scar, Inguinal       Min. with Return              Incision Pain on                          Regions &amp; Inner      in 8 hrs.; then Pain              Incision &amp; Bilateral                          Thighs               was Greatly Reduced              Inguinal Ligament &amp;              Inner Thighs55.  E - 11/29        27 F  Fractured Lt.                          Applied Directly                                    10 Min. Pain                                               Only Slight Tender-through       Clavicle Painful                          Over Swelling                                    Reduced    ness Remained Over12/12/82      &amp; Swollen. PC                    the Fracture; Pain              used Several ×/day         Reduced More After              for 2 wks.                       Each Application56.  G - 12/7/82        59 M  Toothache   Gum Area Sur-        After 3rd.                                               Application              Throbbing   rounding Tooth       in a Period of 2                                               Hrs.              Pain                             Pain was Gone57.  E - 12/7/82        33 F  Sprained Back                          Lumbo-Sacral         Response Good; Pain12/8/82       MM. Rt. Side                          Region &amp; Insertion   Diminished First                                               Day.12/9/82       Previous Episode                          of Rt. Lat. Dors.    Back Improved From              Took 2 wks. to                          MM. Applied 2-3      Each Application              Heal        times Daily for 3                          days58.  E - 12/20/82        38 M  Lower Back  Sprayed Entire                                    10 Min.    10 Min. Pain                                               Reduced.              Sprain (Lifted                          Lumbo-Sacral         20 Min. Pain Gone              Garage Door);                          Region of the        and Brace not Needed              wore a back brace                          back                 When Patient Walked                                               Out59.  E - 12/28/82        44 M  Lower Back Pain                          Lower Back                                    2-3 Min.   Relief Within12/29/82                  Over Painful Area    Minutes; Used Over12/20/82                                       the Period of 4 Days                                               With Good__________________________________________________________________________                                               Results GRADING KEY 54 E  Excellent, no pain or awareness at all during period 9 G  Good, relief from pain but an awareness of the area 5 F  Fair, relief from pain is not as definitive nor as striking as Excellent or Good 6 N  None, no change *Propylene carbonate with aspirin (15% solution) 
    
     In addition, a number of dermatologic conditions have been treated, as reported below in Table II (Tests 60-70 and 74) with propylene carbonate alone and with propylene carbonate in combination with a second therapeutic agent. 
     Test 73 involved treatment of a specific tooth and gum condition in a manner to demonstrate specifically the potentiating effect of propylene carbonate in combination with penicillin. 
     
                                           TABLE II__________________________________________________________________________TestPatientTest                                    Improvement TimeNumberGrade    Age       Sex          Condition Treatment  Days Used                                        &amp; Degree__________________________________________________________________________60.  E   60 F  Poison Ivy                    PC Application                               July 26 Applied                                        Poison Ivy on Arm to Which          on Both Arms                    to One Arm;                               Several Days                                        PC was Applied Cleared up                    Control Arm Not                               27th &amp; 28th                                        Rapidly. Untreated Arm Did                    Treated             Not Heal. Untreated Arm                                        Showed                                        Discolored Scars; PC                                        Treated                                        Arm no Discoloration, no                                        Scars61.  E   17 M  Acne, Chin &amp;                    P.C.I. (Polypy-                               8/1/82, 7 days                                        Pustules Gone in 1 Day;          Cheeks;   lene Carbonate-     Condomes Reduced in 2 Days;          Condomes, Iodine, 1000 PPM)   Face Cleared in 5 Days. PCI          Pustules  Applied 2-3 Times   Continued 1 mo. - Acne                                        Cleared.                    Daily               1 wk. Without Medication -                                        Acne                                        Returned; with Medication,                                        Face                                        Again Cleared Up62.  E   67 M  Forehead, Rash                    2 Applications                               8/17, 1 day                                        Itch Gone in Several Hours.          Allergy   PC                  Dermatitis Improved Within                                        Hours, Even Though it had                                        Grown Worse for Several                                        Days                                        Prior to Treatment63.  E   47 F  Poison Ivy                    2 Applications                               8/17, PC 1st Day, PC, Itch Gone          of Both Legs                    Rt. Leg - PC                               Worked as                                        Immediately; Redness Gone                    Lt. Leg - PCI                               Well as  PCI - Itch Gone                                        Immediately;                    (1000 PPM) PCI      Redness Gone 2 Days Follow-                                        ing; Poison Ivy Dried up on                                        Both Legs; no                                        Discoloration,                                        no Scars64.  E   21 M  Poison Ivy                    2 Applications                               8/26     1st Day Itch Relieved          of the Right leg                    Rt. Leg - PC        Immediately; Lesions Dried                                        up                                        and Spreading of Poison ivy                                        Prevented65.  E   35 F  Herpes Simplex                    Initially 2                               9/1 &amp; 9/2                                        Herpes Simplex Dried          I of Lips &amp;                    Applications                               &amp; 9/3    up; Lesions Cleared up;          Face; PriorPC; then PC3 Days    Compared to Lidex Which          Treatment With                    for 2 Subse-        Had no Effect          Lidex Ineffective                    quent days66.  E   24 F  Acne Vulgaris                    Daily Appli-                               9/4 through                                        Improvement Noted          of Forehead,                    cations for 3                               October, on Second Day of          Cheeks &amp; Chin                    Months; Beginning                               November;                                        PCI Use; Within          Moderate  on 9/4 - PCI                               Used Daily                                        One Week, Acne Was                    (1000 PPM)          Almost Cleared67.  E   26 F  Acne Vulgaris                    2 Times    10/14,   Improvement Began in          Moderate  Daily; PCI November,                                        a Few Days and in Two                    (2000 PPM) December,                                        Weeks Cleared Up                               198268.  E   59 M  First Degree                    Only one   11/1/82  Reduced Pain Immediately.          Burn Rt. Index                    Application         Within 2 Hours, There Were          Finger    PC                  No Redness, No Swelling,                                        and No Tenderness -                                        no evidence of burn at                                        all69.  E   20 F  Herpes Simplex                    2 Applications                               11/8, 11/9                                        Herpes Lesions Dried Up          of Lip - PC                    Daily      &amp; 11/10/82                                        First Day. Healed in 2-3                                        Days                                        (By Comparison, Previous                                        Bouts                                        of Herpes Lasted 10 Days to                                        2 Weeks in this patient)70.  E   27 F  Acne Vulgaris                    2 Applications                               11/29/82 -                                        Cleared Redness in 1 wk.          Mild Case Daily - PCI                               12/12/82 Papules &amp; Condomes Gone in                    (2000 PPM)          2 wks. Then Continued Use                                        as Needed71.  E   60 M  First Degree                    Immediate  12/24/82 Pain Stopped Immediately;          Burn of Thumb                    Application         Redness Diminished. There                                        was                    then 2 times        no Pain and the Formation                                        of                    Within One          Vessicle was Retarded                    Hour - PC72.  E   20 M  Acne Vulgaris                    P.C.I.     December Marked Improvement                    (2000 PPM) through  First 7 Days. Then on                    Applied Daily                               January  Medication for 6 Weeks,                               After a Test                                        Cleared Completely                               Period                               7 Days73.  Treatment of Pyorrhea of the gum and abscessed gum and molar tooth(1)    First treatment - Oral Tetracycline 250 mgm. b.i.d. for 15 days  No improvement of condition(2)    Second treatment - Oral SKF Pen VK 250 mgm. b.i.d. for 10 days  No improvement of condition(3)    Third treatment - Local topical application b.i.d. of 1/2 Tab. 250  mgm. of SKF VK in aqueous sol.  (dist. H.sub.2 O) for 7 days  No improvement of condition(4)    Fourth Treatment - PC local topical application b.i.d. for 7 days  Reduced suppuration and bleeding  Slight improvement - yet condition flared up during two day period  without any medication(5)    Fifth treatment regime -              Solution 1/4 of a 250 mgm. tablet of Pen VK in              solution with PC applied topically              to tooth &amp; gum b.i.d. for 7 days.              Suppuration and swelling completely reduced. Only              slight amount of bleeding remained -              no flare up during two day rest period without              medication(6)    Sixth treatment regime -              a repeat of 2 and 5 in combination, i.e., P.C. &amp; Pen              VK (1/4 Tab. 250 mgm.) topically              b.i.d. plus Pen VK 250 orally b.i.d. for 7 days.              Abcess healed - no reoccurrence after one month.              (i.e., December 31, 1982)74.  E   25 F  Infected  Applied 2 Times                               12/24-25-                                        First the Ulcers Dried Up          Ulcerations                    for 3 Days - PC;                               26/82    Then Swelling, Pain, and          Dorsum Rt.                    Previous Treatment  Redness Diminished; by the          Foot of 2 wks.                    with A &amp; D Ointment Third Day, Ulcers Were                                        Dried          Duration  and Furacin were to Up and Healed                    no Avail__________________________________________________________________________ 
    
     In general, the variety of clinical applications in which propylene carbonate has been tested and found to be useful include: as an anti-inflammatory, an anti-allergenic, a carrier of other therapeutic agents, and as a potentiating agent for other therapeutic agents. The types of co-reactive therapeutic agents with which propylene carbonate has been used include analgesics (e.g., aspirin), antibiotics (e.g., penicillin), and anti-septics (e.g., iodine). Other possible co-reactive medicaments include steroids, cortico-steriods, and anti-histamines. 
     In addition, the unusual effectiveness (i.e., quick remission) on virus infections and allergic manifestations noted to date suggests that propylene carbonate may have some special effects on histaminic and immunologic systems in the body, thereby, presaging an even wider spectrum of medical applications for this compound. 
     Among dermatologic and trauma-related conditions which may be treated with propylene carbonate, either alone or in combination with other drugs, are eczemas, burns, lesions, abrasions, incisions, allergies, and infectious disorders such as herpes, scabies, or even psoriatic conditions. 
     The results of Test 73 indicate that propylene carbonate, in combination with penicillin, is aparently more effective in the treatment of an abscessed tooth and gum (to cause remission of the infectious condition) than either penicillin or propylene carbonate alone. This occurred after the abscess remained resistant to systemic treatment with Tetracycline and SKF Pen VK penicillin. Upon topical application of a solution of propylene carbonate and Pen VK, the abscess showed signs of remission within a week. Upon a second application a week later in conjunction with systemic penicillin treatment, complete remission of the infection resulted. 
     The results of the other tests reported in Table II may be summarized as follows: 
     POISON IVY. Upon topical application of propylene carbonate, the poison ivy infected area dried in the same day and was prevented from spreading to other areas. Itching stopped within minutes; the condition healed within a few days without leaving the skin discoloration usually seen as a post-poison ivy condition. This also suggests that propylene carbonate, when applied to other types of lesions of the skin, may accelerate healing and help to minimize scarring. 
     HERPES SIMPLEX-1 (viral infection). Upon topical application of propylene carbonate to the affected skin area, healing occurred within a few days and did not spread to contiguous areas. Itching stopped immediately and the condition healed within a few days rather than in the usual 7 to 10 days, which occurs without treatment. This suggests the possible efficacy of the use of propylene carbonate in the treatment of the lesions of genital herpes, and the use of propylene carbonate in treating other virus-related conditions. 
     URTICARIA. Upon the topical application of propylene carbonate to urticaria of the face, the allergic manifestation disappeared within a few hours, apparently acting as an antihistamine. 
     BURNS. Propylene carbonate was applied topically to first degree burns; pain was immediately relieved, and blistering was prevented. Healing occurred within 2 days. 
     INFECTED SKIN ULCERATIONS. Upon topical treatment with propylene carbonate the condition healed over a period of 3 days with minimal scarring noted 3 weeks after healing. This condition had been resistant to healing with A &amp; D ointment &amp; Furacin for 2 weeks prior to the use of propylene carbonate. 
     ACNE VULGARIS (seven cases). By topical application of a solution of 1000 PPM Iodine in propylene carbonate or 2000 PPM Iodine in propylene carbonate, the Acne conditions showed considerable to complete remission. These clinical examples demonstrate the ability of propylene carbonate in combination with a second therapeutic agent, to act as a potentiator as well as a vehicle for that agent. 
     COMPARATIVE EXAMPLE 
     The only known medicament listed in the Physicians&#39; Desk Reference (Medical Economics Company, Inc., Oradell, NJ: 1982) which includes propylene carbonate is Lidex Ointment, manufactured and sold by Syntex, Inc. of Palo Alto, CA, the apparent assignee of the above-referenced Chang, Shastri, and Alvarez patents. According to the 1982 Physicians&#39; Desk Reference, and the literature distributed with Lidex Ointment, it is composed of &#34;Fluocinonide 0.5 mg/g, in a specially formulated ointment based consisting of Amerchol Cab (mixture of sterols and higher alcohols), white petrolatum, propylene carbonate, and propylene glycol. It provides the occlusive and emollient effects desirable in an ointment. In these formulations, the active ingredient is totally in solution.&#34; It is said to be effective in the relief of inflammatory manifestations of corticosteroid-responsive dermatoses. 
     For purposes of comparison with the present invention, Lidex Ointment was topically administered to test case #31-A 61 year old female with osteoarthritis of the hands (Test #31 in Table I above). No relief from the pain occurred when Lidex Ointment was applied to her left hand. Simultaneously, propylene carbonate was applied to her right hand resulting in immediate relief from pain. Additionally, when 100% propylene carbonate was applied over the Lidex Ointment on the left hand, no relief from the pain was obtained presumably because propylene carbonate could not penetrate the Lidex Ointment. 
     Thereafter, this same patient was made the subject of a clinical test of the present invention, with good results as indicated in Test #31b of Table I. 
     This significantly better result, obtained using the present invention, is considered to be a dramatic demonstration of the efficacy of the present invention. Moreover, this result is in sharp contrast to the result obtained using a composition, apparently typical of the prior art, in which propylene carbonate is present only in a minor amount and in combination with other solvents, vehicles, and medicaments. 
     While this invention has been described with reference to specific embodiments thereof, the appended claims are intended to be construed to extend not only to these embodiments and forms of the invention but to such other forms and embodiments as may be devised by those skilled in the art, without departing from the true spirit and scope of the invention.