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Styptysate—Not Acceptable for A.D.R.
STYPTYSATE—NOT ACCEPTABLE FOR A.D.R. The Council has authorized publication of the following report. S am uel
M.
G o rd o n ,
Secretary.
Styptysate is marketed by E rnst Bischoff Company, New York City, as a “de pendable non-toxic hemostatic.” Advertising to dentists states it to be . . . indicated in hemorrhage control. Prophylactically, wherever a tendency to bleeding is suspected or known to exist. Before complicated by hemorrhage. Also in Uterine, Gastric, Renal, Nasal and Pulmonary hemorrhages and even true Hemophilia. In dysmenorrhea its analgesic action is very pronounced.
I t is supplied in liquid and in tablet form ; it may be administered orally or topically. Shortly after the W ar, Styptysate was advertised to the medical profes sion w ith the following claims: The Remedy for Hemorrhages . . . Superior to Ergot and Hydrastis . . . of par ticular advantage in Menorrhagia and Metorrhagia . . . found of great value in vesical hemorrhages and hemorrhages from mucous membranes in général.
T h e Council on Pharmacy and Chemistry in 1922 examined the available evi dence for the product and found it not acceptable for N .N .R . T h e best th at could be said for the product was that, during a shortage of ergot in Germ any in wartime, it was used in place of that established drug. (Styptysate, N ot Admissible to New and Nonofficial Remedies, J.A .M .A ., 7 8 :450 [Feb. 11] 1922.) T his appraisal of the product is further borne out by a review of the Q uarterly Cumulative Index Medicus and the Q uarterly Cumulative Index from 1918 to 1932 (A p ril). W hile several references on Styptysate and Shepherd’s purse (the plant from which the product is made) appeared in 1920 and 1922, none appeared after 1922. I t thus would seem that a little used drug already generally discarded by the medical profession is resurrected and advertised to dentists. According to recent advertising Styptysate is a “dialized (sic) fluid Extract of Capsella Bursa Pastoris,” which “reduces both clotting and bleeding time without increase of blood pressure as it is purely hemic in action.” N o statement of com position other than “Dialysate of Capsella Bursa Pastoris” . . . Alcohol, 14 per cent.” “ Non-narcotic hemostatic” appears on the package. Capsella bursa pastoris is commonly known as Shepherd’s purse. T h e following appears in advertising: In the revised edition of his work, A T extbook of E xodontia, D r. Leo W inter'writes as follows: “In addition to packing the socket, hemostatics should be administered internally. O f the numerous hemostatics offered to the profession a most effective one has recently claimed our attention. Th e drug is a dialyzed fluid extract of Capsella Bursa pastoris, mar keted under the trade name of S T Y P T Y S A T E . It is not a vasoconstrictor, so does not raise blood pressure. Bleeding time and clotting time are both greatly reduced and remain so for about twenty-four hours.”
Before consideration of the product was taken up in June of 1932, communica tions were sent to the firm inviting them to place before the Council a statement 1532
Council on D ental Therapeutics
1533
of source and preparation of the product; a Statement of the active ingredients, as far as possible in quantitative term s; chemical or physiologic assays for con trolling the uniform ity of the product and any carefully controlled experimental evidence, laboratory or clinical, as to the usefulness of the product in dental prac tice. A representative of the firm promised to send this information, but although nearly twelve months have passed, the information has not been received. D r. W in ter was requested to make available to the Council the scientific or carefully controlled evidence upon which the statement accredited to him rested, and asked if the firm had his permission to quote from his textbook. Sometime later, after a second letter was sent, D r. W in ter wrote in part as follow s: D r. Newcomb, describing himself as a representative of the Bischoff Company, came to see me at the clinic and told me that they were manufacturers of Alpha-lobelin and other approved preparations and that they were desirous of my experimentation with a new prod uct for the control of bleeding. M y procedure in this case was the one which we follow generally: first, ascertain the standing of the concern; second, inquire as to whether or not animal experimentation has been done with the product; third, attempt to determine the basic ingredients in order that we may not produce an irreparable injury on human being. Being satisfied with D r. New comb’s statement in this regard, we proceeded to try it and found that when applied locally, Styptysate did seem to have an action which appeared to be equally as good as Adrenalin Chloride 1:1000 or Suprarenin. No controls were used in the experimentation of the drug for the reason that no case presented itself out of the 100 or more upon which it was tried where we had the same character of bleeding on both sides of the mouth that would enable us to see which of the drugs was most effective. M y statement was merely to the effect that Styptysate was another drug which could be used in the control of persistent capillary ooz ing, and I did not desire to have it given any further meaning. Th e illustration which appears in my textbook was only a part of a gracious act and due to the persistent calling of this individual. Not seeing any possible detrimental action, I ac ceded to his request. This was not based upon any commercial arrangement with the Bischoff Company for I have none, nor with any other concern.
In this connection, it is an interesting fact that not one of the preparations of the E rnst Bischoff Company, N ew Y ork City, stands accepted in the latest edition of N ew and NonoiEcial Remedies, published by the Council on Pharmacy and Chemistry of the American M edical Association. T h e grounds on which the rep resentative of the firm claims that they m arket approved preparations is not known. Therefore, the following is presented for the information of the dental profession: Shepherd’s purse is a weed common in the U nited States and in Europe. Like most other common plants, it was formerly used in domestic medicine. Shepherd’s purse does not receive extensive consideration as a hemostatic from authors of stand ard textbooks on m ateria medica, pharmacology and therapeutics.1 I t has not been extensively studied, either chemically or pharmacologically. T h e active constituents, if any, are ill-defined, variable and uncertain. Its action also is indefinite and un certain. Investigators attribute some of its effects on strips of excised uterus to the potassium salts present, others to “bursic acid” and still others to the presence of fungi. Kochmann, whose investigation represents the most critical yet cursory 1. Sollmann (Manual of Pharmacology, 4th ed. p. 483) lists it as an oxytoxic of minor importance. Myer-Gottlieb-Henderson (Experimental Pharmacology, Ed. 2) devotes a few lines to it for its action on the uterus and the literature cited contains no evidence of a hemo static action on this organ, the results on excised strips being controversial and irrelevant.
1534
T he Journal of the American D ental Association
work on the weed, finds that it causes contraction of the excised uterus, but the activity of the drug collected at different periods yields different results, and he {joints out the need for further investigation of the drug w ith reference to place, time of harvesting, method of drying, etc. T h e articles in support of its use as a hemostatic for menorrhagia and uterine hemorrhage are uncritical and do not furnish enough data for critical analysis.2 T he drug, at best, cannot possibly compare in effect w ith ergot or pituitary. It is probable th at at one time Styptysate may have contained cotarnine, to which it may have owed its styptic effect, if any. I t is improbable that cotarnine is now contained in the preparation; otherwise, a narcotic blank would be required for its purchase. Cotarnine is being generally discarded as a uterine hemostatic. I t actually increases the flow of blood. N o evidence is available that Styptysate is efficient as a blood coagulant or hemo static when administered orally, that it is useful locally or that it possesses ad vantages not obtainable w ith epinephrine or readily available inorganic hemostatics or thromboplastic agents. In view of the foregoing, Styptysate is declared inadmissible to A .D .R .; because its composition is semi-secret and indefinite, there is no evidence that its uniformity and strength are controlled (Rules 1 and 2 ), the therapeutic claims advanced for its use in dental practice are unw arranted (R ule 6) and no evidence has been advanced that it occupies a useful place in the control of hemorrhages when other useful drugs are available (R ule 10, essentially useless articles). 2. Walther: Capsella Bursa Als Secelersatz, Med. Klin. 622 (June 17) 1920. Kroeber: Ueber Capsella Bursa Pastoris.L, Muenchen. Med. Wochenschr., 67:752 (June 25) 1920. Oppenheim: Styptysat, Ein Neues Uterinum, Med. Klin. 902 (Sept. 2) 1920. Report of Council on Pharmacy and Chemistry, J.A .M .A ., 78:450 (Feb. 11) 1922.
M.
G o rd o n ,
Secretary.
Styptysate is marketed by E rnst Bischoff Company, New York City, as a “de pendable non-toxic hemostatic.” Advertising to dentists states it to be . . . indicated in hemorrhage control. Prophylactically, wherever a tendency to bleeding is suspected or known to exist. Before complicated by hemorrhage. Also in Uterine, Gastric, Renal, Nasal and Pulmonary hemorrhages and even true Hemophilia. In dysmenorrhea its analgesic action is very pronounced.
I t is supplied in liquid and in tablet form ; it may be administered orally or topically. Shortly after the W ar, Styptysate was advertised to the medical profes sion w ith the following claims: The Remedy for Hemorrhages . . . Superior to Ergot and Hydrastis . . . of par ticular advantage in Menorrhagia and Metorrhagia . . . found of great value in vesical hemorrhages and hemorrhages from mucous membranes in général.
T h e Council on Pharmacy and Chemistry in 1922 examined the available evi dence for the product and found it not acceptable for N .N .R . T h e best th at could be said for the product was that, during a shortage of ergot in Germ any in wartime, it was used in place of that established drug. (Styptysate, N ot Admissible to New and Nonofficial Remedies, J.A .M .A ., 7 8 :450 [Feb. 11] 1922.) T his appraisal of the product is further borne out by a review of the Q uarterly Cumulative Index Medicus and the Q uarterly Cumulative Index from 1918 to 1932 (A p ril). W hile several references on Styptysate and Shepherd’s purse (the plant from which the product is made) appeared in 1920 and 1922, none appeared after 1922. I t thus would seem that a little used drug already generally discarded by the medical profession is resurrected and advertised to dentists. According to recent advertising Styptysate is a “dialized (sic) fluid Extract of Capsella Bursa Pastoris,” which “reduces both clotting and bleeding time without increase of blood pressure as it is purely hemic in action.” N o statement of com position other than “Dialysate of Capsella Bursa Pastoris” . . . Alcohol, 14 per cent.” “ Non-narcotic hemostatic” appears on the package. Capsella bursa pastoris is commonly known as Shepherd’s purse. T h e following appears in advertising: In the revised edition of his work, A T extbook of E xodontia, D r. Leo W inter'writes as follows: “In addition to packing the socket, hemostatics should be administered internally. O f the numerous hemostatics offered to the profession a most effective one has recently claimed our attention. Th e drug is a dialyzed fluid extract of Capsella Bursa pastoris, mar keted under the trade name of S T Y P T Y S A T E . It is not a vasoconstrictor, so does not raise blood pressure. Bleeding time and clotting time are both greatly reduced and remain so for about twenty-four hours.”
Before consideration of the product was taken up in June of 1932, communica tions were sent to the firm inviting them to place before the Council a statement 1532
Council on D ental Therapeutics
1533
of source and preparation of the product; a Statement of the active ingredients, as far as possible in quantitative term s; chemical or physiologic assays for con trolling the uniform ity of the product and any carefully controlled experimental evidence, laboratory or clinical, as to the usefulness of the product in dental prac tice. A representative of the firm promised to send this information, but although nearly twelve months have passed, the information has not been received. D r. W in ter was requested to make available to the Council the scientific or carefully controlled evidence upon which the statement accredited to him rested, and asked if the firm had his permission to quote from his textbook. Sometime later, after a second letter was sent, D r. W in ter wrote in part as follow s: D r. Newcomb, describing himself as a representative of the Bischoff Company, came to see me at the clinic and told me that they were manufacturers of Alpha-lobelin and other approved preparations and that they were desirous of my experimentation with a new prod uct for the control of bleeding. M y procedure in this case was the one which we follow generally: first, ascertain the standing of the concern; second, inquire as to whether or not animal experimentation has been done with the product; third, attempt to determine the basic ingredients in order that we may not produce an irreparable injury on human being. Being satisfied with D r. New comb’s statement in this regard, we proceeded to try it and found that when applied locally, Styptysate did seem to have an action which appeared to be equally as good as Adrenalin Chloride 1:1000 or Suprarenin. No controls were used in the experimentation of the drug for the reason that no case presented itself out of the 100 or more upon which it was tried where we had the same character of bleeding on both sides of the mouth that would enable us to see which of the drugs was most effective. M y statement was merely to the effect that Styptysate was another drug which could be used in the control of persistent capillary ooz ing, and I did not desire to have it given any further meaning. Th e illustration which appears in my textbook was only a part of a gracious act and due to the persistent calling of this individual. Not seeing any possible detrimental action, I ac ceded to his request. This was not based upon any commercial arrangement with the Bischoff Company for I have none, nor with any other concern.
In this connection, it is an interesting fact that not one of the preparations of the E rnst Bischoff Company, N ew Y ork City, stands accepted in the latest edition of N ew and NonoiEcial Remedies, published by the Council on Pharmacy and Chemistry of the American M edical Association. T h e grounds on which the rep resentative of the firm claims that they m arket approved preparations is not known. Therefore, the following is presented for the information of the dental profession: Shepherd’s purse is a weed common in the U nited States and in Europe. Like most other common plants, it was formerly used in domestic medicine. Shepherd’s purse does not receive extensive consideration as a hemostatic from authors of stand ard textbooks on m ateria medica, pharmacology and therapeutics.1 I t has not been extensively studied, either chemically or pharmacologically. T h e active constituents, if any, are ill-defined, variable and uncertain. Its action also is indefinite and un certain. Investigators attribute some of its effects on strips of excised uterus to the potassium salts present, others to “bursic acid” and still others to the presence of fungi. Kochmann, whose investigation represents the most critical yet cursory 1. Sollmann (Manual of Pharmacology, 4th ed. p. 483) lists it as an oxytoxic of minor importance. Myer-Gottlieb-Henderson (Experimental Pharmacology, Ed. 2) devotes a few lines to it for its action on the uterus and the literature cited contains no evidence of a hemo static action on this organ, the results on excised strips being controversial and irrelevant.
1534
T he Journal of the American D ental Association
work on the weed, finds that it causes contraction of the excised uterus, but the activity of the drug collected at different periods yields different results, and he {joints out the need for further investigation of the drug w ith reference to place, time of harvesting, method of drying, etc. T h e articles in support of its use as a hemostatic for menorrhagia and uterine hemorrhage are uncritical and do not furnish enough data for critical analysis.2 T he drug, at best, cannot possibly compare in effect w ith ergot or pituitary. It is probable th at at one time Styptysate may have contained cotarnine, to which it may have owed its styptic effect, if any. I t is improbable that cotarnine is now contained in the preparation; otherwise, a narcotic blank would be required for its purchase. Cotarnine is being generally discarded as a uterine hemostatic. I t actually increases the flow of blood. N o evidence is available that Styptysate is efficient as a blood coagulant or hemo static when administered orally, that it is useful locally or that it possesses ad vantages not obtainable w ith epinephrine or readily available inorganic hemostatics or thromboplastic agents. In view of the foregoing, Styptysate is declared inadmissible to A .D .R .; because its composition is semi-secret and indefinite, there is no evidence that its uniformity and strength are controlled (Rules 1 and 2 ), the therapeutic claims advanced for its use in dental practice are unw arranted (R ule 6) and no evidence has been advanced that it occupies a useful place in the control of hemorrhages when other useful drugs are available (R ule 10, essentially useless articles). 2. Walther: Capsella Bursa Als Secelersatz, Med. Klin. 622 (June 17) 1920. Kroeber: Ueber Capsella Bursa Pastoris.L, Muenchen. Med. Wochenschr., 67:752 (June 25) 1920. Oppenheim: Styptysat, Ein Neues Uterinum, Med. Klin. 902 (Sept. 2) 1920. Report of Council on Pharmacy and Chemistry, J.A .M .A ., 78:450 (Feb. 11) 1922.