US3260646A - Medication with mechanism to prevent overdosage - Google Patents

Medication with mechanism to prevent overdosage Download PDF

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US3260646A
US3260646A US231848A US23184862A US3260646A US 3260646 A US3260646 A US 3260646A US 231848 A US231848 A US 231848A US 23184862 A US23184862 A US 23184862A US 3260646 A US3260646 A US 3260646A
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overdosage
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A61K31/515—Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital

Definitions

  • emetics be used as a component in tablets, for example, to cause emesis at a certain level of overdosage.
  • Such emetics must be oral emetics, which have an effect which varies considerably with the stomach contents at the moment of ingestion. Not only is the action of such oral emetics quite variable, but the resultant vomiting provoked by overdosage often cannot be tolerated. For example, if an intoxicated patient is taking the tablets, a severe risk of inhalation of food particles, or even of suffocation, may result.
  • Another object is to provide medication containing means to prevent patient self overdosage which is not subject to avoidance by the patient.
  • a further object is to provide medication containing means for preventing patient self overdosage which may be easily adjusted to accommodate prescribed dosage levels.
  • a representative embodient of this invention involves the addition of 50 milligramsof nicotinic acid to each tablet.
  • a sedative tablet containing 400 milligrams of meprobamate and 50 milligrams of nicotinic acid was evaluated.
  • This dosage of meprobamate is appropriate to produce relief of tension in the normal dosage of one tablet three to four times daily.
  • the additional nicotinic acid will make it difficult or impossible to take the tablets at intervals more frequent than approximately three hours.
  • the simultaneous use of two or three tablets produces a rapidly appearing flush due to the peripheral vasodilation produced by the nicotinic acid. This flush increases markedly with any additional increase in dosage level.
  • This preparation was tried with ninety-two patients over a period of time sufficient to evaluate the clinical effect of this embodiment of the present invention.
  • the sample included thirty-five male patients and fifty-seven female patients. No difference in the effect between the two sexes was noted, so that the following data is not tabulated with respect to the sex of the patient.
  • the addition of the nicotinic acid was not found to have an adverse effect upon the therapeutic action of the sedative.
  • the therapeutic effect of the preparation containing nicotinic acid was clearly greater than that of meprobamate by itself. This improvement may have ocurred as a result of the effect of nicotinic acid upon vascular dilation and the vitmain effect.
  • overdosage control effects achieved with the above trial preparation according to the present invention when tested with the ninety-two patients were as follows. In the cases of all the nineteen patients who took or had been known to be taking overdosages, the trial preparation was successful in discouraging further use of the preparation in excessive amounts. Of the nineteen, fourteen were able to keep the prescribed dosage. The remaining five discontinued treatment altogether. The individual patients varied widely, from some who had been previously taking overdosages in the order to ten tablets a day to those who had been engaging in relatively moderate overdosage.
  • While my invention has been described in connection with clinical tests of an embodiment employing meprobamate and nicotinic acid, other drugs such as amphetamine or one of its derivatives, a barbiturate, or an opium alcaloid, may be used in conjunction with an agent capable of producing peripheral vasodilation.
  • other drugs such as amphetamine or one of its derivatives, a barbiturate, or an opium alcaloid, may be used in conjunction with an agent capable of producing peripheral vasodilation.
  • 40-60 milligrams of nicotinic acid per tablet is appropriate if the dosage is not to exceed three to four tablets daily. If 50 milligrams of nicotinic acid is used per tablet then 90% of the subjects will experience the flush if they exceed the prescribed dose and take two tablets simultaneously. If three tablets are taken simultaneously, substantially 100% of the patients will experience the flush.
  • vasodilators are suitable for use in tablets according to my invention.
  • tolazoline hydrochloride currently available under the tradename Priscoline
  • Priscoline is a suitable vasodilator.
  • Approximately 25 milligrams of tolazoline hydrochloride per tablet would give performance approximating that achieved with 50 milligrams of nicotinic acid per tablet.
  • Another suitable vasodilator is beta pyridil carbinol tartrate, currently available under the tradename of Roniacol.
  • beta pyridil carbinol tartrate is utilized as the vasodilator, the beta pyridil carbinol tartrate may be substituted for nicotinic acid on a one for one basis.
  • isoxsuprine currently available under the tradename of Vasodilan, is a suitable vasodilator. Relatively small amounts of isoxuprine are suitable, the amount of isoxsuprine necessary being approximately one tenth the amount of nicotinic acid needed to produce the same effect.
  • Isoxsuprine is suitable for use with all of the drugs listed with the exception of amphetamine. All of the above ratios are on a weight basis and all quantities for use in tablets have been expressed in terms of milligrams.
  • vasodilators may be used to form compositions according to my invention.
  • the drug with addiction forming tendencies will be accompanied by elements producing a tendency toward peripheral vasodilation. Twice the prescribed dosage will produce severe peripheral vasodilation.
  • a therapeutic composition adapted to prevent drug overdosage and adapted for oral administration comprising, in addition to therapeutic ingredients having addiction forming tendencies, a drug which causes peripheral vasodilation, the amount of said drug per unit of prescribed therapeutic dosage being approximately one-half the amount necessray to cause severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic composition adapted to prevent drug overdosage and adapted for oral administration comprising, in addition to therapeutic ingredients having addiction forming tendencies, nicotinic acid, the amount of said nicotinic acid per prescribed therapeutic dosage being approximately one-half the amount necessary to cause severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising, in addition to therapeutic ingredients having addiction forming tendencies, approximately 40 60 milligrams of nicotinic acid per tablet, whereby an overdose of said tablets will produce severe peripheral vasodilation as evidence by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising approximately 400 milligrams meprobamate and approximately 40-60 milligrams of nicotinic acid per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising a barbiturate and approximately 40-60 milligrams of nicotinic acid per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising amphetamine and approximately 40 60 milligrams of nicotinic acid per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising an amphetamine derivative and approximately 40-60 milligrams of nicotinic acid per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushmg.
  • a therapeutic tablet adapted to prevent drug overdosage comprising an opium alcaloid and approximately 40-60 milligrams of nicotinic acid per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic composition adapted to prevent drug overdosage and adapted for oral administration comprising in addition to therapeutic ingredients having addiction forming tendencies, tolazoline hydrochloride, the amount of said tolazoline hydrochloride per prescribed therapeutic dosage being approximately one-half the amount necessary to cause severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising in addition to therapeutic ingredients having addiction forming tendencies, approximately 25 milligrams of tolazoline hydrochloride per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidence by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising approximately 400 milligrams meprobamate and approximately 25 milligrams of tolazoline hydroohloride per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising a barbiturate and approximately 25 milligrams of tolazoline hydrochloride per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced'by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising an amphetamine composition and approximately 25 milligrams of tolazoline hydrochloride per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising an opium alcaloid and approximately 25 milligrams of tolazoline hydrochloride per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic composition adapted to prevent drug overdosage and adapted for oral administration comprising in addition to therapeutic ingredients having addiction forming tendencies, beta pyridil carbinol tartrate, the amount of said beta pyridil carbinol tartrate per prescribed therapeutic dosage being approximately one-half the amount necessary to cause severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic tablet adapted to prevent d-rug overdosage comprising in addition to therapeutic ingredients having addiction forming tendencies, approximately 50 milligrams of beta pyridil carbinol tartrate per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising approximately 400 milligrams rneprobamate and approximately 50 milligrams of beta pyridil ca-rbinol tartrate per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising a barbiturate and approximately 50 milligrams of beta pyridil carbinol tartrate per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushmg.
  • a therapeutic tablet adapted to prevent drug overdosage comprising an amphetamine composition and approximately 50 milligrams of beta pyridil carbinol tartrate per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising an opium alcaloid and approximately 50 milligrams of beta pyridil carbinol tartrate per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flush- 111g.
  • a therapeutic composition adapted to prevent drug overdosage and adapted for oral administration comprising in addition to therapeutic ingredients having addiction forming tendencies, isoxsuprine, the amount of said isoxsuprine per prescribed therapeutic dosage being approximately one-half of the amount necessary to cause severe peripheral vasodilation as evidenced by substantial flush- 22.
  • a therapeutic tablet adapted to prevent drug overdosage comprising in addition to therapeutic ingredients having addiction forming tendencies, approximately 5 milligrams of isoxsuprine per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising approximately 400 milligrams meprobamate and approximately 5 milligrams of isoxsuprine per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising a barbiturate and approximately 5 milligrams of isoxsuprine per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
  • a therapeutic tablet adapted to prevent drug overdosage comprising an opium alcaloid and approximate y 5 milligrams of isoxsuprine per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.

Description

United States Patent 3,260,646 MEDICATION WITH MECHANISM TO PREVENT OVERDOSAGE Frederik Paulsen, Malmo, Sweden, assignor, by mesne assignments, to Ferring AB, Malmo, Sweden, a corporation of Sweden No Drawing. Filed Oct. 19, 1962, Ser. No. 231,848 Claims. (Cl. 16752) This invention relates to medical compositions and more particularly to orally ingestible compositions with means to discourage overdosage.
Often tablets or other medications are administered by the patient himself away from medical supervision. In such circumstances the possibility of voluntary or involuntary overdosage by the patient presents serious problems. Some medication produces undersirable side effects when the prescribed dosage is exceeded. These problems have become especially severe with respect to the increasing use of tranquilizers, sedatives and stimulants during recent years. Investigations have shown that a very high percentageof patients do not follow the instructions received from their physicians but usually take higher doses. Severe addiction problems can thus result.
Two solutions to the overdosage problem have been suggested in the past. First, it has been suggested that emetics be used as a component in tablets, for example, to cause emesis at a certain level of overdosage. Such emetics must be oral emetics, which have an effect which varies considerably with the stomach contents at the moment of ingestion. Not only is the action of such oral emetics quite variable, but the resultant vomiting provoked by overdosage often cannot be tolerated. For example, if an intoxicated patient is taking the tablets, a severe risk of inhalation of food particles, or even of suffocation, may result.
The other solution suggested more recently is the addition of an atropin derivative. Overdosage of an atropin derivative which would result from overdosage of the tablets containing these derivatives tends to produce pronounced dryness in the throat. Unfortunately, experience has shown that addicts can take as much as twenty to twenty-five tablets daily instead of a prescribed three to four tablets, in spite of the resultant dryness to the mouth. The ability of addicts to develop a tolerance to the dryness of the mouth makes the atropin derivative technique relatively ineffective to prevent overdosage.
Acordingly, it is an object of the present invention to provide effective medication with means for preventing overdosage without the undesirable side effects present in prior methods.
Another object is to provide medication containing means to prevent patient self overdosage which is not subject to avoidance by the patient.
A further object is to provide medication containing means for preventing patient self overdosage which may be easily adjusted to accommodate prescribed dosage levels.
These and other objects are achieved by providing medication which produces severe peripheral vasodilation when taken in excess of the prescribed quantity.
A representative embodient of this invention involves the addition of 50 milligramsof nicotinic acid to each tablet. For example, a sedative tablet containing 400 milligrams of meprobamate and 50 milligrams of nicotinic acid was evaluated. This dosage of meprobamate is appropriate to produce relief of tension in the normal dosage of one tablet three to four times daily. However, the additional nicotinic acid will make it difficult or impossible to take the tablets at intervals more frequent than approximately three hours. Likewise, while a single tablet does not produce any unpleasant symptoms, the simultaneous use of two or three tablets produces a rapidly appearing flush due to the peripheral vasodilation produced by the nicotinic acid. This flush increases markedly with any additional increase in dosage level.
This preparation was tried with ninety-two patients over a period of time sufficient to evaluate the clinical effect of this embodiment of the present invention. The sample included thirty-five male patients and fifty-seven female patients. No difference in the effect between the two sexes was noted, so that the following data is not tabulated with respect to the sex of the patient. The addition of the nicotinic acid was not found to have an adverse effect upon the therapeutic action of the sedative. In fact, in certain cases, such as postraumatic myalgia, the therapeutic effect of the preparation containing nicotinic acid was clearly greater than that of meprobamate by itself. This improvement may have ocurred as a result of the effect of nicotinic acid upon vascular dilation and the vitmain effect.
In some cases, the patients experienced symptoms of hyperacidity, but it was found that this difficulty could be overcome by the administration of the normal alkaloid free antacids before means. These antacid tablets had no effect on the therapeutic effect of the trial preparation nor on the effectiveness of the nicotinic acid to limit overdosage. Unfortunately, the inclusion of the antacid preparation in the trial tablet composition itself did produce a reduction in both the therapeutic and the overdosage control effects. Therefore, the antacid should be preferably administered in separate tablets.
The overdosage control effects achieved with the above trial preparation according to the present invention when tested with the ninety-two patients were as follows. In the cases of all the nineteen patients who took or had been known to be taking overdosages, the trial preparation was successful in discouraging further use of the preparation in excessive amounts. Of the nineteen, fourteen were able to keep the prescribed dosage. The remaining five discontinued treatment altogether. The individual patients varied widely, from some who had been previously taking overdosages in the order to ten tablets a day to those who had been engaging in relatively moderate overdosage.
Thus, with the use of a preparation according to the present invention, it was possible to achieve spontaneous limitation of the use of the tablets. The clinical tests established that the patients for whom this medicine was prescribed preferred the occasional discomfort from increased nervous tension rather than to risk and unpleasant side effect which they knew they would experience if the prescribed dosage was exceeded. This result is primarily important in that the immediate undesirable effects of excessive dosage are avoided, and there is little possibility of addiction developing. In addition, a better long term therapeutic effect is achieved when a patient can be induced to hold sedative dosages to lower levels. It has previously been established that increased dosages of sedatives tend to produce a tolerance to the sedatives, with a lowered effect on the tension or other condition which is to be relieved.
Even those patients who discontinued treatment are considered to be successful examples of the use of preparations according to the present invention. The very fact that these patients refused to continue with these tablets and requested some other medication revealed to the physician the fact that they have a compulsive tendency to overdosage. Accordingly, the physician is enabled to direct his treatment and supervision of the patient properly. The tendency toward overdosages Patented July 12, 1965 might otherwise remain undetected until a serious condition had been created.
The only limitation found necessary in connection with the use of tablets according to my invention 'was a prohibition on the taking of tablets during fasting or together with coffee. While a normal percentage of patients either forgot or ignored these instructions from the physician, the resulting flush discouraged further violation of the prescribed procedures. No permanent effect or harm to the patient was incurred.
While my invention has been described in connection with clinical tests of an embodiment employing meprobamate and nicotinic acid, other drugs such as amphetamine or one of its derivatives, a barbiturate, or an opium alcaloid, may be used in conjunction with an agent capable of producing peripheral vasodilation. In each case 40-60 milligrams of nicotinic acid per tablet is appropriate if the dosage is not to exceed three to four tablets daily. If 50 milligrams of nicotinic acid is used per tablet then 90% of the subjects will experience the flush if they exceed the prescribed dose and take two tablets simultaneously. If three tablets are taken simultaneously, substantially 100% of the patients will experience the flush.
While nicotinic acid has been used as a preferred example, other vasodilators are suitable for use in tablets according to my invention. For instance, tolazoline hydrochloride, currently available under the tradename Priscoline, is a suitable vasodilator. Approximately 25 milligrams of tolazoline hydrochloride per tablet would give performance approximating that achieved with 50 milligrams of nicotinic acid per tablet. Another suitable vasodilator is beta pyridil carbinol tartrate, currently available under the tradename of Roniacol. If beta pyridil carbinol tartrate is utilized as the vasodilator, the beta pyridil carbinol tartrate may be substituted for nicotinic acid on a one for one basis. With certain drugs having addiction forming tendencies, isoxsuprine, currently available under the tradename of Vasodilan, is a suitable vasodilator. Relatively small amounts of isoxuprine are suitable, the amount of isoxsuprine necessary being approximately one tenth the amount of nicotinic acid needed to produce the same effect. Isoxsuprine is suitable for use with all of the drugs listed with the exception of amphetamine. All of the above ratios are on a weight basis and all quantities for use in tablets have been expressed in terms of milligrams.
The particular embodiments discussed above are i lustrative only and do not serve as limitations. Those skilled in the pharmaceutical arts will recognize that other vasodilators may be used to form compositions according to my invention. In each case the drug with addiction forming tendencies will be accompanied by elements producing a tendency toward peripheral vasodilation. Twice the prescribed dosage will produce severe peripheral vasodilation.
Having thus disclosed my invention and described in detail preferred embodiments thereof, I claim:
1. A therapeutic composition adapted to prevent drug overdosage and adapted for oral administration comprising, in addition to therapeutic ingredients having addiction forming tendencies, a drug which causes peripheral vasodilation, the amount of said drug per unit of prescribed therapeutic dosage being approximately one-half the amount necessray to cause severe peripheral vasodilation as evidenced by substantial flushing.
2. A therapeutic composition adapted to prevent drug overdosage and adapted for oral administration comprising, in addition to therapeutic ingredients having addiction forming tendencies, nicotinic acid, the amount of said nicotinic acid per prescribed therapeutic dosage being approximately one-half the amount necessary to cause severe peripheral vasodilation as evidenced by substantial flushing.
3. A therapeutic tablet adapted to prevent drug overdosage comprising, in addition to therapeutic ingredients having addiction forming tendencies, approximately 40 60 milligrams of nicotinic acid per tablet, whereby an overdose of said tablets will produce severe peripheral vasodilation as evidence by substantial flushing.
4. A therapeutic tablet adapted to prevent drug overdosage comprising approximately 400 milligrams meprobamate and approximately 40-60 milligrams of nicotinic acid per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
5. A therapeutic tablet adapted to prevent drug overdosage comprising a barbiturate and approximately 40-60 milligrams of nicotinic acid per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
6. A therapeutic tablet adapted to prevent drug overdosage comprising amphetamine and approximately 40 60 milligrams of nicotinic acid per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
7. A therapeutic tablet adapted to prevent drug overdosage comprising an amphetamine derivative and approximately 40-60 milligrams of nicotinic acid per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushmg.
8. A therapeutic tablet adapted to prevent drug overdosage comprising an opium alcaloid and approximately 40-60 milligrams of nicotinic acid per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
9. A therapeutic composition adapted to prevent drug overdosage and adapted for oral administration comprising in addition to therapeutic ingredients having addiction forming tendencies, tolazoline hydrochloride, the amount of said tolazoline hydrochloride per prescribed therapeutic dosage being approximately one-half the amount necessary to cause severe peripheral vasodilation as evidenced by substantial flushing.
10. A therapeutic tablet adapted to prevent drug overdosage comprising in addition to therapeutic ingredients having addiction forming tendencies, approximately 25 milligrams of tolazoline hydrochloride per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidence by substantial flushing.
11. A therapeutic tablet adapted to prevent drug overdosage comprising approximately 400 milligrams meprobamate and approximately 25 milligrams of tolazoline hydroohloride per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
12. A therapeutic tablet adapted to prevent drug overdosage comprising a barbiturate and approximately 25 milligrams of tolazoline hydrochloride per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced'by substantial flushing.
13. A therapeutic tablet adapted to prevent drug overdosage comprising an amphetamine composition and approximately 25 milligrams of tolazoline hydrochloride per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
14. A therapeutic tablet adapted to prevent drug overdosage comprising an opium alcaloid and approximately 25 milligrams of tolazoline hydrochloride per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
15. A therapeutic composition adapted to prevent drug overdosage and adapted for oral administration comprising in addition to therapeutic ingredients having addiction forming tendencies, beta pyridil carbinol tartrate, the amount of said beta pyridil carbinol tartrate per prescribed therapeutic dosage being approximately one-half the amount necessary to cause severe peripheral vasodilation as evidenced by substantial flushing.
16. A therapeutic tablet adapted to prevent d-rug overdosage comprising in addition to therapeutic ingredients having addiction forming tendencies, approximately 50 milligrams of beta pyridil carbinol tartrate per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
17. A therapeutic tablet adapted to prevent drug overdosage comprising approximately 400 milligrams rneprobamate and approximately 50 milligrams of beta pyridil ca-rbinol tartrate per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
18. A therapeutic tablet adapted to prevent drug overdosage comprising a barbiturate and approximately 50 milligrams of beta pyridil carbinol tartrate per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushmg.
19. A therapeutic tablet adapted to prevent drug overdosage comprising an amphetamine composition and approximately 50 milligrams of beta pyridil carbinol tartrate per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
29. A therapeutic tablet adapted to prevent drug overdosage comprising an opium alcaloid and approximately 50 milligrams of beta pyridil carbinol tartrate per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flush- 111g.
21. A therapeutic composition adapted to prevent drug overdosage and adapted for oral administration comprising in addition to therapeutic ingredients having addiction forming tendencies, isoxsuprine, the amount of said isoxsuprine per prescribed therapeutic dosage being approximately one-half of the amount necessary to cause severe peripheral vasodilation as evidenced by substantial flush- 22. A therapeutic tablet adapted to prevent drug overdosage comprising in addition to therapeutic ingredients having addiction forming tendencies, approximately 5 milligrams of isoxsuprine per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
23. A therapeutic tablet adapted to prevent drug overdosage comprising approximately 400 milligrams meprobamate and approximately 5 milligrams of isoxsuprine per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
24. A therapeutic tablet adapted to prevent drug overdosage comprising a barbiturate and approximately 5 milligrams of isoxsuprine per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
25. A therapeutic tablet adapted to prevent drug overdosage comprising an opium alcaloid and approximate y 5 milligrams of isoxsuprine per tablet whereby an overdose of said tablets will produce severe peripheral vasodilation as evidenced by substantial flushing.
References Cited by the Examiner American Drug Index, Lippincott Co., Philadelphia, Pa., 1960, pp. 45, 398, 445, 658.
Beckman: Pharmacology, the Nature, Action and Use of Drugs, Saunders Co., 2nd Ed., Philadelphia, Pa., November 1961, p. 647.
Krantz et al., The Pharmacologic Principles of Medical Practice, Bailliere, Tindall & Cox, Ltd., London, 1958, p. 1267.
Physicians Desk Reference, Medical Economics, Inc., 15th Ed., Oradell, N.J., 1961, pages 542, 649, 662, 711, P.O.S.L.
The Merck Index of Chemicals and Drugs, Merck and Co., Inc., Rahway, N.J., pp. 719-270, 7th edition (1960).
JULIAN S. LEVITT, Primary Examiner.

Claims (1)

  1. 9. A THERAPEUTIC COMPOSITION ADAPTED TO PREVENT DRUG OVERDOSAGE AND ADAPTED FOR ORAL ADMINISTRATION COMPRISING IN ADDITION TO THERAPEUTIC INGREDIENTS HAVING ADDITION FORMING TENDENCIES, TOLAZOLINE, HYDROCHLORIDE, THE AMOUNT OF SAID TOLOZOLINE HYDROCHLORIDE PER PRESCRIBED THERAPEUTIC DOSAGE BEING APPROXIMATELY ONE-HALF AND AMOUNT NECESSARY TO CAUSE SEVERE PERIPHERAL VASODILATION AS EVIDENCED. BY SUBSTANTIAL FLUSHING.
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