US3298915A - Vascular headache treatment - Google Patents

Vascular headache treatment Download PDF

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Publication number
US3298915A
US3298915A US345558A US34555864A US3298915A US 3298915 A US3298915 A US 3298915A US 345558 A US345558 A US 345558A US 34555864 A US34555864 A US 34555864A US 3298915 A US3298915 A US 3298915A
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vascular headache
alpha
acid
picolinic acid
vascular
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US345558A
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Spencer M Fossel
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Unimed Inc
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Unimed Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides

Definitions

  • This application relates to the treatment of vascular headache, and more particularly to new compositions for v a and method of achieving relief of vascular headache.
  • Vascular headache is an extremely widespread condition which is responsible for great economic loss and personal difiiculty among-thosewho suffer from the same. Most commonly, vascular headache takesthe form of a migraine attack.
  • Analgesics such as salicylates, e.g. aspirin, phenacetine, etc., increase the pain threshold of the body, and in this way somewhat combat the condition but do not have any lasting effect. In addition, after continued use, larger and larger doses are necessary to achieve any pain relieving effect.
  • the present invention mainly comprises as a composition for combating vascular headache and the like, an efiective amount of an alpha-picolinic acid diloweralkyl-arnide, and a pharmaceutical carrier.
  • the most preferred active agent for the treatment of vascular headache is alpha-picolinic acid diethylamide.
  • the pharmaceutical carrier used for the purposes of the present invention may either be a solid material or a sterile parenteral liquid.
  • compositions of this invention take the form of tablets, powders, capsules, or other dosage forms. It is a particular advantage of the present invention that the compositions may be administered orally, although it is also possible to prepare liquid forms thereof with liquid diluents for administration by injection.
  • suitable pharmaceutical carriers may be mentioned cornstarch, lactose, talc, stearic acid, magnesium stearate, gums, or the like. Any of the tableting materials commonly used in pharmaceutical manufacturing may be employed, so long as there is no incompatibility of the same with the particular alpha picolinic acid diloweralky-amide which is employed.
  • alpha-picolinic acid diloweralkyl-amides per se as agent for combating vascular headache
  • these compounds in the form of their non-toxic acid addition salts; for example, acid addition cal 3,293,915 Patented Jan. 1.7, 1967 salts thereof with hydrochloric acid, sulphuric acid,'fumaric'acid, etc.
  • V V d The compounds which are used according to the present invention have the following general formula:
  • R is a lower alkyl
  • compositions containingthe same are quite effective in combating the symptoms of migraine and the syndrome of interim migraine.
  • the unit dose form of the active ingredients of the present invention is between about 0.1-1 mg. administered three times a day.
  • alpha-picolinic acid diloweralkyl-amides and particularly alpha-picolinic acid diethylamide are very well tolerated, and there is a large margin of safety between the toxic dose and the effective therapeutic dose.
  • Example I Grams Alpha-picolinic acid diethylamide 1 Lactose 300
  • the above mixture is comminuted in a mixer and utilized to make 1000 #2 capsules packed so that each contains 300 mg. of the mixture; i.e., 1 mg. each of the active ingredients.
  • Example II Alpha-picolinic acid diethylamide mg Lactose grms 200 Gum arabic do 10 Talc do 50 Stearic acid powder do 50 The above formula is utilized after mixing with sufficient alcohol to granulate, for the purpose of manufacturing tablets, each tablet to contain 0.1 mg. of the active ingredient.
  • Example III Alpha-picolinic acid diethylamide mg 500 Beta-lactose grams 300
  • the above mixture is used to make 1000 capsules of (#2) containing 0.5 mg. of active ingredient in each capsule, the total weight of the contents of each capsule being 300 mg.
  • Example 1V Capsules are prepared as in Example I, however using alpha-picolinic acid diethylamide-hydrochloride as the active ingredient.
  • Example V Capsules are prepared as in Example I, however using alpha-picolinic acid-dimethylamide as the active ingredient.
  • Method of treating the sufferings of vascular headache which comprises administering to a patient suffering from the same an effective amount of at least one compound selected from the group consisting of alphapicolinic acid diloweralkyl-amide and non-toxic acid addition sales thereof.
  • Method of treating the sufferings of vascular headache which comprises administering to a patient suffering from the same and effective dose of alpha-picolinic acid diethylamide.
  • Method of treating the sufferings of vascular headache which comprises administering to a patient suffering from the same an effective dose of a non-toxic acid addition salt of alpha-picolin'ic acid diethylamide.
  • Method of treating the sufferings of vascular headache which comprises orally administering to a patient suffering from the same an effective amount of at least one compound selected from the group consisting of alpha-picolinic acid diloweralkyl-amide and non-toxic acid addition salts thereof.
  • Method of treating the sufferings of vascular headache which comprises orally administering to a patient suffering from the same a unit dose of about 0.11 mg. of at least one compound selected from the group consisting of alpha-picolinic acid diloweralkylamide and nontoxic acid addition salts thereof.

Description

United States. Patent v 5 Claims. -(cl. 161-65 This application relates to the treatment of vascular headache, and more particularly to new compositions for v a and method of achieving relief of vascular headache.
' Vascular headache is an extremely widespread condition which is responsible for great economic loss and personal difiiculty among-thosewho suffer from the same. Most commonly, vascular headache takesthe form of a migraine attack.
It causes auro, dizziness, and other manifestations along with the very strong headache, which may even lead to nausea, vomiting, gastrointestinal upset and vasomotor imbalance.
Analgesics such as salicylates, e.g. aspirin, phenacetine, etc., increase the pain threshold of the body, and in this way somewhat combat the condition but do not have any lasting effect. In addition, after continued use, larger and larger doses are necessary to achieve any pain relieving effect.
It is a primary object of the present invention to provide new compositions for the treatment of vascular headache which are highly effective in the relief of the suffering of vascular headache, as well as in relieving the suffering of related conditions which require a circulatory stimulant (but not a vasodilator), such as angina, Mnieres syndrome, and Raynors disease.
It is still another object of the present invention to provide a method of treating these conditions.
Other objects and advantages of the present invention will be apparent from a further reading of the specification and of the appended claims.
With the above and other objects in view, the present invention mainly comprises as a composition for combating vascular headache and the like, an efiective amount of an alpha-picolinic acid diloweralkyl-arnide, and a pharmaceutical carrier. The most preferred active agent for the treatment of vascular headache is alpha-picolinic acid diethylamide.
The pharmaceutical carrier used for the purposes of the present invention may either be a solid material or a sterile parenteral liquid.
The compositions of this invention take the form of tablets, powders, capsules, or other dosage forms. It is a particular advantage of the present invention that the compositions may be administered orally, although it is also possible to prepare liquid forms thereof with liquid diluents for administration by injection.
Among the suitable pharmaceutical carriers, may be mentioned cornstarch, lactose, talc, stearic acid, magnesium stearate, gums, or the like. Any of the tableting materials commonly used in pharmaceutical manufacturing may be employed, so long as there is no incompatibility of the same with the particular alpha picolinic acid diloweralky-amide which is employed.
In addition to the possibility of using alpha-picolinic acid diloweralkyl-amides per se as agent for combating vascular headache in accordance with this invention, it is possible to use these compounds in the form of their non-toxic acid addition salts; for example, acid addition cal 3,293,915 Patented Jan. 1.7, 1967 salts thereof with hydrochloric acid, sulphuric acid,'fumaric'acid, etc. V V d The compounds which are used according to the present invention have the following general formula:
wherein R is a lower alkyl.
- The. alpha-picolinic acid diloweralkyl-amides and their acid. addition salts have been found to be particularly effective in combating vascular headaches. Compositions containingthe same are quite effective in combating the symptoms of migraine and the syndrome of interim migraine.
As little as 0.1 mg. per day may be used in the treatment of vascular headaches. In general, the unit dose form of the active ingredients of the present invention is between about 0.1-1 mg. administered three times a day.
The alpha-picolinic acid diloweralkyl-amides and particularly alpha-picolinic acid diethylamide are very well tolerated, and there is a large margin of safety between the toxic dose and the effective therapeutic dose.
The following examples are given to further illustrate the present invention. The scope of the invention is not, however, meant to be limited to the specific details of the examples.
Example I Grams Alpha-picolinic acid diethylamide 1 Lactose 300 The above mixture is comminuted in a mixer and utilized to make 1000 #2 capsules packed so that each contains 300 mg. of the mixture; i.e., 1 mg. each of the active ingredients.
Example II Alpha-picolinic acid diethylamide mg Lactose grms 200 Gum arabic do 10 Talc do 50 Stearic acid powder do 50 The above formula is utilized after mixing with sufficient alcohol to granulate, for the purpose of manufacturing tablets, each tablet to contain 0.1 mg. of the active ingredient.
Example III Alpha-picolinic acid diethylamide mg 500 Beta-lactose grams 300 The above mixture is used to make 1000 capsules of (#2) containing 0.5 mg. of active ingredient in each capsule, the total weight of the contents of each capsule being 300 mg.
Example 1V Capsules are prepared as in Example I, however using alpha-picolinic acid diethylamide-hydrochloride as the active ingredient.
1' Example V Capsules are prepared as in Example I, however using alpha-picolinic acid-dimethylamide as the active ingredient.
Without further analysis, the foregoing will so fully reveal the gist of the present invention that others can, be applying current knowledge, readily adapt it for various applications Without omitting features that, from the standpoint of prior art, fairly constitute essential characteristics of the generic or specific aspects of this invention and, therefore, such adaptations should and are intended to be comprehended within the meaning and range of equivalence of the following claims.
What is claimed as new and desired to be secured by Letters Patent is:
1. Method of treating the sufferings of vascular headache, which comprises administering to a patient suffering from the same an effective amount of at least one compound selected from the group consisting of alphapicolinic acid diloweralkyl-amide and non-toxic acid addition sales thereof.
2. Method of treating the sufferings of vascular headache, which comprises administering to a patient suffering from the same and effective dose of alpha-picolinic acid diethylamide.
3. Method of treating the sufferings of vascular headache, which comprises administering to a patient suffering from the same an effective dose of a non-toxic acid addition salt of alpha-picolin'ic acid diethylamide.
4. Method of treating the sufferings of vascular headache, which comprises orally administering to a patient suffering from the same an effective amount of at least one compound selected from the group consisting of alpha-picolinic acid diloweralkyl-amide and non-toxic acid addition salts thereof.
5. Method of treating the sufferings of vascular headache, which comprises orally administering to a patient suffering from the same a unit dose of about 0.11 mg. of at least one compound selected from the group consisting of alpha-picolinic acid diloweralkylamide and nontoxic acid addition salts thereof.
References Cited by the Examiner UNITED STATES PATENTS 10/1958 Carrara 260295 OTHER REFERENCES Chem. Abstracts, vol. 28, p. 47917 (1934). Merck Index, 7th ed. (1960), Merck & Co. Rahway, N. 1., pp. 720-1.
SAM ROSEN, Primary Examiner. MARTIN J. COHEN, S. J. FRIEDMAN, Examiners.

Claims (1)

1. METHOD OF TREATING THE SUFFERINGS OF VASCULAR HEADACHE, WHICH COMPRISES ADMINISTERING TO A PATIENT SUFFERING FROM THE SAME AN EFFECTIVE AMOUNT OF AT LEAST ONE COMPOUND SELECTED FROM THE GROUP CONSISTING OF ALPHAPICOLINIC ACID DILOWERALKYL-AMIDE AND NON-TOXIC ACID ADDITION SALES THEREOF.
US345558A 1964-02-18 1964-02-18 Vascular headache treatment Expired - Lifetime US3298915A (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2858317A (en) * 1953-10-22 1958-10-28 Lepetit Spa Process for preparing isonicotinic acid diethylamide

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2858317A (en) * 1953-10-22 1958-10-28 Lepetit Spa Process for preparing isonicotinic acid diethylamide

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