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Accepted Dental Remedies
C O U N C IL O N D E N T A L TH ERAPEU TICS ACCEPTED D ENTAL REMEDIES The follow ing articles have been accepted as conforming to the rules of the Council on Dental Therapeutics of the American Dental Association for inclusion in the list of Accepted Dental Remedies. The Council desires dentists to understand that the admission of an article does not imply a recommendation. A copy of the rules which govern the Council in the con sideration of articles w ill be sent on request. S a m u e l M . G o r d o n , Secretary.
FIBRIN FERMENTS AND THROMBOPLASTIC SUBSTANCES Thromboplastic substances and fibrin ferments were introduced into medicine about fifteen years ago as aids in hastening the coagulation of blood. Preparations of this nature w ere introduced for local and intravenous use. In the meantime, evidence has been accumulating th at their intravenous use almost always pre sents grave danger; nor is there satisfactory evidence that they are effective when introduced subcutaneously. It seems improb able that when used in this w ay they are of any value in con trolling hemorrhage. I t is possible that local application may be of some value. (In this connection, the Council desires to point out that intravenous medication is in general fraught with many dangers. These dangers, anaphylaxis, shock, etc., are too great to compensate for the claimed advantages of this type of drug administration. Since intravenous injection of drugs disturbs a delicately balanced physiologic equilibrium, the Council suggests that this type of medication be resorted to only in cases of the gravest emergency, such as shock arising from certain anesthetic actions, and that it be used only when other measures have abso lutely failed.) T he clotting of blood may be regarded as the transformation of the fibrinogen of the circulating blood into the insoluble pro tein material, fibrin, of the blood clot. Different view s regarding this phenomenon have been advanced from time to time. It is generally agreed that the clotting of blood is due to the action of thrombin (the fibrin ferment) on the fibrinogen of the blood. Thrombin exists in the blood not as such but as prothrombin (the precursor of thrombin), which, when acted on by the calcium salts of the blood, is converted into the active agent, thrombin. (T his explains why oxalated blood does not clot; a fact of importance in blood chemistry.) Other factors in addi tion to calcium salts are necessary for clotting, since normal blood contains a sufficient amount of calcium salts, yet spontaneous clotting does not occur in the blood vessels, except in certain pathologic conditions (thrombosis, etc.)
Jour. A . D. A ., February, 1932.
325
T h e Journal of the American D ental Association T his other factor has been designated as “zymoplastic sub stance” by Schmidt, as “thrombokinase” by Morowitz, and as “thromboplastic substance” by H ow ell, who holds that blood does not coagulate in the vessels, since prothrombin exists there in combination with an inhibiting substance which prevents it from acting. He believes that w h en blood is shed or flows over in jured tissues, the thromboplastin derived from the blood cells, platlets or tissue cells, reacts in some undetermined manner with the inhibitor, liberating prothrombin from combination with the inhibiting agent. T he liberated prothrombin activated by the calcium salts converts the fibrinogen into fibrin, and initiates clotting. H ow ell has shown that thromboplastin or “thromboplastin substance” from every source which he has investigated contains the phospholipid cephalin ( see any standard textbook on physio logic chemistry) and that the accessory action of thromboplastin in coagulation is due to the action of cephalin. Cephalin (or kephalin) is soluble in ether, but insoluble in acetone or alcohol. In a solution or in solid form, cephalin gradually loses its power to hasten clotting of blood, owing, probably, to an oxidation o f the unsaturated fatty acids in the molecule. Because of this deterioration, only those products which bear a date of labeling should be used. Actions and Uses: Preparations containing thromboplastin are said to be useful when applied locally in the treatment of hemor rhage, especially hemorrhages from local surfaces and specifi cally after the extraction of teeth. It is also said to be useful in the treatment of scar tissues, in nose bleed and in surgery. It is reported that many surgeons are abandoning its use. It may w ell be questioned if simple m echanical means do not in most cases bring about a desired clotting action. T he intravenous administration is dangerous, and the sub cutaneous administration is irrational, as there is no satisfactory evidence that such administration is useful. Preparations should be standardized by testing on specimens of blood in vitro. Acceptable preparations should be able to re duce the coagulation period to about one-third of the original tim e; and they should be proved sterile. In view of their acceptance by clinical dentists for local ad ministration, the Council w ill accept thromboplastic preparations for inclusion in A. D. R. provided they are marketed with claims limited to their local application. T H R O M B O P L A ST IN L O C A L — S Q U IB B .— An extract of cattle brain in physiologic solution of sodium chlorid prepared according to the method of H ess. It complies with the product solution brain extract in physiologic solution of sodium chlorid prepared by the method of H ess ( /. A . M . A ., 66:558 {Feb. 19] 1916, Footnote 2 ). Actions and . Uses: Thromboplastin-Squibb, like other fibrin preparations, is ¡useful when applied locally in the treatment of hemorrhages, particularly on the oozing surfaces and in hemor rhage follow in g extraction o f teeth. It is applied by means of sterile tampons saturated w ith thromboplastin. (See foregoing paragraphs, “Fibrin Ferments and Thromboplastic Substances.” ) Dosage: See “Solution B rain Extract” (to be published).
Council on D ental Therapeutics Thromboplastin-Squibb is marketed in 20 c.c. vials. It is claimed that no loss of potency could be detected in unopened thromboplastin-Squibb more than three days old. Manufactured by E. R. Squibb and Sons. No U. S. patent or trade mark. Blood plasma is obtained by bleeding 45 c.c. of sheep’s blood into a tube containing 5 c.c. of 1 per cent sodium oxalate in physiologic solution of sodium chlorid, centrifuging the mixture to obtain the clear plasma and preserving this at a low temperature. A 0.5 per cent calcium chlorid solution is prepared by dissolving 0.5 gm. anhydrous calcium chlorid in 100 c.c. of physiologic solution o f sodium chlorid. Place 5 drops of blood plasma in a flat bottomed vial, add 3 drops of calcium chlorid solution and 2 drops of the thromboplastin-Squibb to be tested and mix the con tents by gentle rotation. Not more than sixty seconds should elapse before the vial may be completely inverted without loss of its contents.
V IO ST E R O L I N O IL 250-D , SQ U IB B . A brand o f Viosterol in oil 250-D, N. N. R. Actions and Uses: See Viosterol ( T h e J ou rn a l , 18:1786 [Sept.] 1931). Dosage: See Viosterol ( T h e J o u rn a l , 18:1786 [Sept.] 1931). Manufactured by E. R. Squibb and Sons, New York, under U. S. Patent 1,680,818 (Aug. 14, 1928, expires 1945), by license of the W is consin Alumni Research Foundation. Viosterol in Oil 250-D, Squibb is prepared by dissolving ergosterol in ether. The solution is then irradiated by exposure to ultraviolet rays. A fter assay of the irradiated ergosterol for its antirachitic potency, it is dissolved in maize oil and adjusted to have the potency of viosterol in oil 250-D, N. N. R.
SQ U IB B ’S C O D LIVER O IL W IT H V IO ST E R O L IO-D. A brand of cod liver oil with viosterol 10-D, N. N. R. Actions and Uses:
See Cod Liver Oil with Viosterol 10-D
( T h e J o u rn a l , 18:1787 [Sept.] 1931).
Dosage: See Cod Liver Oil w ith Viosterol 10-D ( T h e J o u rn a l , 18:1787 [Sept.] 1931). Manufactured by E, R. Squibb & Sons, New York, under U. S. Patent 1.680.818 (Aug. 14, 1928, expires 1945), by license of the Wisconsin Alumni Research Foundation. Irradiated ergosterol, prepared by the method described under viosterol in oil 250-D Squibb, is added to cod liver oil and the finished product is required to have a vitamin A potency of not less than 500 pharmacopeial units and to have the vitamin D potency of cod liver oil with viosterol 10-D, N. N. R.
SQ U IB B ’S C O D LIVER O IL W IT H V IO ST E R O L 10-D M IN T FLA V O R ED .—A brand of cod liver oil with viosterol 10-D, N. N. R., containing 0.67 per cent of oil of spearmint as flavoring. Actions and Uses: See Cod Liver Oil with Viosterol 10-D. Dosage: See Cod Liver Oil w ith Viosterol 10-D. Manufactured by E, R. Squibb & Sons, New York, under U. S. Patent 1.680.818 (Aug. 14, 1928; expires 1945), by license of the Wisconsin Alumni Research Foundation. Irradiated ergosterol, prepared by the method described under viosterol in oil 250-D Squibb, is added to cod liver oil containing 0.67 per cent of oil of spearmint as flavoring and the finished product is required to have a vitamin A:-potency of not less than 500 pharmacopeial units and ,to have the vitamin D potency of cod liver oil with viosterol 10-D, N. N. R.
FIBRIN FERMENTS AND THROMBOPLASTIC SUBSTANCES Thromboplastic substances and fibrin ferments were introduced into medicine about fifteen years ago as aids in hastening the coagulation of blood. Preparations of this nature w ere introduced for local and intravenous use. In the meantime, evidence has been accumulating th at their intravenous use almost always pre sents grave danger; nor is there satisfactory evidence that they are effective when introduced subcutaneously. It seems improb able that when used in this w ay they are of any value in con trolling hemorrhage. I t is possible that local application may be of some value. (In this connection, the Council desires to point out that intravenous medication is in general fraught with many dangers. These dangers, anaphylaxis, shock, etc., are too great to compensate for the claimed advantages of this type of drug administration. Since intravenous injection of drugs disturbs a delicately balanced physiologic equilibrium, the Council suggests that this type of medication be resorted to only in cases of the gravest emergency, such as shock arising from certain anesthetic actions, and that it be used only when other measures have abso lutely failed.) T he clotting of blood may be regarded as the transformation of the fibrinogen of the circulating blood into the insoluble pro tein material, fibrin, of the blood clot. Different view s regarding this phenomenon have been advanced from time to time. It is generally agreed that the clotting of blood is due to the action of thrombin (the fibrin ferment) on the fibrinogen of the blood. Thrombin exists in the blood not as such but as prothrombin (the precursor of thrombin), which, when acted on by the calcium salts of the blood, is converted into the active agent, thrombin. (T his explains why oxalated blood does not clot; a fact of importance in blood chemistry.) Other factors in addi tion to calcium salts are necessary for clotting, since normal blood contains a sufficient amount of calcium salts, yet spontaneous clotting does not occur in the blood vessels, except in certain pathologic conditions (thrombosis, etc.)
Jour. A . D. A ., February, 1932.
325
T h e Journal of the American D ental Association T his other factor has been designated as “zymoplastic sub stance” by Schmidt, as “thrombokinase” by Morowitz, and as “thromboplastic substance” by H ow ell, who holds that blood does not coagulate in the vessels, since prothrombin exists there in combination with an inhibiting substance which prevents it from acting. He believes that w h en blood is shed or flows over in jured tissues, the thromboplastin derived from the blood cells, platlets or tissue cells, reacts in some undetermined manner with the inhibitor, liberating prothrombin from combination with the inhibiting agent. T he liberated prothrombin activated by the calcium salts converts the fibrinogen into fibrin, and initiates clotting. H ow ell has shown that thromboplastin or “thromboplastin substance” from every source which he has investigated contains the phospholipid cephalin ( see any standard textbook on physio logic chemistry) and that the accessory action of thromboplastin in coagulation is due to the action of cephalin. Cephalin (or kephalin) is soluble in ether, but insoluble in acetone or alcohol. In a solution or in solid form, cephalin gradually loses its power to hasten clotting of blood, owing, probably, to an oxidation o f the unsaturated fatty acids in the molecule. Because of this deterioration, only those products which bear a date of labeling should be used. Actions and Uses: Preparations containing thromboplastin are said to be useful when applied locally in the treatment of hemor rhage, especially hemorrhages from local surfaces and specifi cally after the extraction of teeth. It is also said to be useful in the treatment of scar tissues, in nose bleed and in surgery. It is reported that many surgeons are abandoning its use. It may w ell be questioned if simple m echanical means do not in most cases bring about a desired clotting action. T he intravenous administration is dangerous, and the sub cutaneous administration is irrational, as there is no satisfactory evidence that such administration is useful. Preparations should be standardized by testing on specimens of blood in vitro. Acceptable preparations should be able to re duce the coagulation period to about one-third of the original tim e; and they should be proved sterile. In view of their acceptance by clinical dentists for local ad ministration, the Council w ill accept thromboplastic preparations for inclusion in A. D. R. provided they are marketed with claims limited to their local application. T H R O M B O P L A ST IN L O C A L — S Q U IB B .— An extract of cattle brain in physiologic solution of sodium chlorid prepared according to the method of H ess. It complies with the product solution brain extract in physiologic solution of sodium chlorid prepared by the method of H ess ( /. A . M . A ., 66:558 {Feb. 19] 1916, Footnote 2 ). Actions and . Uses: Thromboplastin-Squibb, like other fibrin preparations, is ¡useful when applied locally in the treatment of hemorrhages, particularly on the oozing surfaces and in hemor rhage follow in g extraction o f teeth. It is applied by means of sterile tampons saturated w ith thromboplastin. (See foregoing paragraphs, “Fibrin Ferments and Thromboplastic Substances.” ) Dosage: See “Solution B rain Extract” (to be published).
Council on D ental Therapeutics Thromboplastin-Squibb is marketed in 20 c.c. vials. It is claimed that no loss of potency could be detected in unopened thromboplastin-Squibb more than three days old. Manufactured by E. R. Squibb and Sons. No U. S. patent or trade mark. Blood plasma is obtained by bleeding 45 c.c. of sheep’s blood into a tube containing 5 c.c. of 1 per cent sodium oxalate in physiologic solution of sodium chlorid, centrifuging the mixture to obtain the clear plasma and preserving this at a low temperature. A 0.5 per cent calcium chlorid solution is prepared by dissolving 0.5 gm. anhydrous calcium chlorid in 100 c.c. of physiologic solution o f sodium chlorid. Place 5 drops of blood plasma in a flat bottomed vial, add 3 drops of calcium chlorid solution and 2 drops of the thromboplastin-Squibb to be tested and mix the con tents by gentle rotation. Not more than sixty seconds should elapse before the vial may be completely inverted without loss of its contents.
V IO ST E R O L I N O IL 250-D , SQ U IB B . A brand o f Viosterol in oil 250-D, N. N. R. Actions and Uses: See Viosterol ( T h e J ou rn a l , 18:1786 [Sept.] 1931). Dosage: See Viosterol ( T h e J o u rn a l , 18:1786 [Sept.] 1931). Manufactured by E. R. Squibb and Sons, New York, under U. S. Patent 1,680,818 (Aug. 14, 1928, expires 1945), by license of the W is consin Alumni Research Foundation. Viosterol in Oil 250-D, Squibb is prepared by dissolving ergosterol in ether. The solution is then irradiated by exposure to ultraviolet rays. A fter assay of the irradiated ergosterol for its antirachitic potency, it is dissolved in maize oil and adjusted to have the potency of viosterol in oil 250-D, N. N. R.
SQ U IB B ’S C O D LIVER O IL W IT H V IO ST E R O L IO-D. A brand of cod liver oil with viosterol 10-D, N. N. R. Actions and Uses:
See Cod Liver Oil with Viosterol 10-D
( T h e J o u rn a l , 18:1787 [Sept.] 1931).
Dosage: See Cod Liver Oil w ith Viosterol 10-D ( T h e J o u rn a l , 18:1787 [Sept.] 1931). Manufactured by E, R. Squibb & Sons, New York, under U. S. Patent 1.680.818 (Aug. 14, 1928, expires 1945), by license of the Wisconsin Alumni Research Foundation. Irradiated ergosterol, prepared by the method described under viosterol in oil 250-D Squibb, is added to cod liver oil and the finished product is required to have a vitamin A potency of not less than 500 pharmacopeial units and to have the vitamin D potency of cod liver oil with viosterol 10-D, N. N. R.
SQ U IB B ’S C O D LIVER O IL W IT H V IO ST E R O L 10-D M IN T FLA V O R ED .—A brand of cod liver oil with viosterol 10-D, N. N. R., containing 0.67 per cent of oil of spearmint as flavoring. Actions and Uses: See Cod Liver Oil with Viosterol 10-D. Dosage: See Cod Liver Oil w ith Viosterol 10-D. Manufactured by E, R. Squibb & Sons, New York, under U. S. Patent 1.680.818 (Aug. 14, 1928; expires 1945), by license of the Wisconsin Alumni Research Foundation. Irradiated ergosterol, prepared by the method described under viosterol in oil 250-D Squibb, is added to cod liver oil containing 0.67 per cent of oil of spearmint as flavoring and the finished product is required to have a vitamin A:-potency of not less than 500 pharmacopeial units and ,to have the vitamin D potency of cod liver oil with viosterol 10-D, N. N. R.