3,257.276 United States Patent Office Patented June 21, 1966 1. 2 nounced, chloral hydrate, a powerful hypnotic, has been 3,257.276 utilized. The use of the more potent local anesthetic ORAL ANALGESEC PREPARATION compounds have been deplored because of their pro Robert H. Broh-Kahn, Hastings on Hudson, and Ernest. nounced tendency to cause allergic reactions. Sasmor, Yonkers, N.Y., assignors to Laboratories fo Painful conditions peculiar to the gingivae and mucosal Pharmaceutical Development, Inc., a corporation of membranes in and about the oral cavity are well known. New York Relief of pain associated with these conditions has been No Drawing. Filed Apr. 26, 1962, Ser. No. 190,235 an especially difficult problem. Thus, the commonly 8 Claims. (C. 167-65) practiced dental, surgical procedure of multiple extraction This invention relates to an improved medicinal com of diseased teeth has created problems of effective pain position adapted for use on the gingival and lip surfaces 10 control during the post-operative period. A wide area as well as on the mucosa of the buccal and oral cavity of gingival tissue becomes painful and generally exhibits in general, said surfaces and mucosa being referred to a local inflammatory response to the Surgical trauma. herein as the “oral mucosa," in order to achieve relief of When a large number of teeth are extracted at one time, pain. In particular, it is concerned with the use of or 5 the practice of suturing the wound in order to prevent ex ganic or inorganic water soluble salicylates, as for ex cessive bleeding, gives rise to prolonged pain during the ample, choline salicylate, sodium salicylate, potassium postoperative period. This practice is further compli salicylate, calcium salicylate and morpholine salicylate, cated by other advances in dental science which now per dissolved in a special vehicle which modifies the penetra mit the immediate insertion of new dentures after Sur tion of the active moiety in order to permit the attainment 20 gery. It is an extremely difficult process to achieve pain of therapeutically significant blood levels and, at the same relief in these conditions. Local anesthetic agents are time, to permit high local concentrations of the active generally not utilized because of their transient period of compound. It is by virtue of this special property of activity as well as the great danger of allergic reactions the absorption of the active moiety as well as the attain arising from their multiple use. ment of high local concentrations, that affords maximal 25 The modern use of artificial dentures to replace missing pain relief with minimal amounts of the Water Soluble or extracted teeth is another cause of painful conditions salicylate used. Thus, through this double action, the of the mouth. A new dental technique permits the den effective concentration of the therapeutically active Sub ture to be inserted into the patient's mouth as soon as the stance of this new product is materially less than would teeth have been extracted, and this technique is known be required to produce an equal pharmacologic effect 30 as “immediate denture method.” Under this practice, the through a systemic action. gums are sutured after extraction of the teeth in order to Eruption of deciduous teeth in infants is often aSSO lessen the healing time required as well as to prevent ex ciated with much pain and suffering. The gingivae at the cessive blood loss and the previously prepared denture is point of emergence of the new deciduous teeth, may be immediately inserted. It is the usual practice to permit come swollen, inflamed and sensitive to contact and pres 35 this denture to remain in the mouth substantially continu sure, thereby producing irritability, fretfulness, disturbed ously during the first seventy-two hour period Subsequent sleep and excessive salivation. On occasion, an eruptive to extraction in order to minimize the excessive swelling gingivitis during teething may become complicated by of the gingival tissue and to insure that healing will take the development of a hemorrhagic cyst which is visible in place in the same contour as had previously existed. the area overlying the emerging tooth. The infant's re 40 Maintaining these artificial dentures during the first sev sponse depends largely upon the severity of the pain. In enty-two hours is often a painful experience. an article appearing in the Journal of Dentistry of Chil A similar problem exists with the older procedure of dren (volume 19, page 127-132, 1952), it was reported utilizing dentures, to replace missing teeth. These are that, “the emotionality of the baby between the ages of inserted four to six weeks after the extraction of teeth, six months and 30 months may be traced by the cutting 45 subsequent to substantial healing of the alveolar ridges of teeth. Each new tooth is accompanied by some physical of the gums. These new dentures often result in pain to upset, even though it may be of a minor sort, and this pre the patient during the initial period of adaptation since disposes the baby to general irritability.' it is virtually impossible to prepare a prosthetic appliance Deciduous teeth are twenty in number and first appear which corresponds exactly to the contour and shape of the at six to eight months of age. The teething process lasts 50 gingival surface. up to approximately 30 months of age and it appears that Still another painful condition arises in the oral cavity many infants are in need of some comfort of irritating which involves the oral mucosal membrances and these symptomatology resulting from this physiologic process are those local inflammations and abraded areas as a for approximately the first two and one-half years of their result from ecrtain infections, as for example, the com life. 55 mon cold sore, the fever-blister or herpes simplex, which Lancing the gingivae over the bulging, emerging tooth arises predominantly on the lips. Included among these was a common practice for many centuries. During the painful conditions are mechanical irritations resulting from 19th century, the practice of providing soothing powders accidental biting of the internal membranes of the mouth and syrups containing various preparations of opium, Such and also local infections of the mucosal surface, per se. as tincture of opium, became common. In more recent 60 Relief of pain may be achieved through four funda years the use of sedatives, hypnotics and other analgesic mental methods. These are: (a) removing the under substances have been suggested. These are generally lying cause of the pain; (b) blocking the pathway of the frowned upon because of the high order of toxicity and painful impulses; (c) raising the pain threshold; or (d) addiction resulting from the injudicious use of these potent Suppressing the pain reaction by depressing the cortical substances. 65 area of the brain. The removal of the cause of the pain Present therapy appears to depend largely upon the is the most desirable method of pain relief, but this is severity of the accompanying symptomatology. Small not always possible. Thus, pain, after surgery, arises doses of sedatives and antipyretics under physician con from the trauma to the tissues and will disappear when trol, have been utilized. Local massage with aromatic this injury has been resolved. During the period of heal compounds as well as the application to the gingival sur 70 ing, however, pain will be present as a natural consequence face of small doses of alcohol has also been suggested. to surgery. On the other hand, in certain infectious Where the discomfort and irritability are more pro states, the pain may be relieved to a very great degree 3,257.276 3 4. merely by controlling the infection or by providing ade used in attempts to obtain relief from painful conditions quate drainage to the area. It should be recognized that in the mouth through their local application. Thus, pain during the postoperative phase is a necessary adjunct the authoritative Second Edition of "Pharmacology in to the Surgery and requires special techniques for effective Medicine” edited by Victor Drill, Ph.D., M.D., at page 293 control. states, "Careful studies in man have shown that when as Blocking the pathway of the painful impulse is perhaps pirin is placed in the mouth absorption is negligible if the the most widely used method to manage pain arising in patients are warned not to swallow their saliva.” and about the buccal cavity. The use of local anesthetics Since it is obviously very difficult to make certain that a which are injected into the tissue about the nerve is the patient does not swallow his saliva and thus enable a accepted and most common anesthetic procedure for O salicylate originally present in his oral cavity to be ab dental Surgery pain control. Although local anesthetics Sorbed via the stomach, the unique property of our inven are used almost exclusively for the operative period and tion was demonstrated as follows: Five ml. of a hydro have, on occasion, been used for acute painful states be alcoholic gel containing 436 mg. choline salicylate were cause of their short period of pain relief, these agents do placed in the buccal cavity of each of two anesthetized not lend themselves to continuous or multiple and repeated 5 rabbits in whom the esophagus had previously been ligated applications. to prevent accidental swallowing of the preparation and The use of large amounts of systemic analgesics to de in whom a tracheal cannula was inserted both to provide press the pain reaction has as its principal drawback, the proper ventilation and to insure that none of the prepara fact that a general systemic effect is achieved when only a tion could be aspirated into the bronchial tract from which local action is desired.