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US2853418A - Hypnotic composition comprising a barbiturate and beta, beta-methyl ethyl glutarimide - Google Patents

Hypnotic composition comprising a barbiturate and beta, beta-methyl ethyl glutarimide Download PDF

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US2853418A
US2853418A US578575A US57857556A US2853418A US 2853418 A US2853418 A US 2853418A US 578575 A US578575 A US 578575A US 57857556 A US57857556 A US 57857556A US 2853418 A US2853418 A US 2853418A
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barbiturate
glutarimide
methyl ethyl
barbiturates
beta
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Smith Robert Grenville
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Nicholas Pty Ltd
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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
    • A61K31/495—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

  • This invention relates to barbiturate pharmaceutical preparations, for example, tablets, capsules, elixirs, suspensions and the like, containing barbiturates.
  • Thebarbiturates comprise an important and valuable group of central nervous systemdepressants frequently prescribed by physicians and widely used by the laity. Reference to this appears in the textbook entitled, The Pharmacological Basis of Therapeutics, by Goodman and Gilman, page 126, published 1941 by the Macmillan Company, New York, U. S. A.
  • the barbiturates are used medically for several purposes, the most important of which are for producing sleep, inhibiting convulsions, anaesthesia, and sedation.
  • the general properties of barbiturates are possessed in varying degrees by individual members of the group andthis has led to a large number of different compounds being employed in medicine. Some are long acting, others intermediate and still others very short acting. Administration'may be oral or parenteral, but much more frequently the former.
  • the barbiturates are derivatives of barbituric acid, having the general structural formula as follows:
  • This barbiturate antagonist is fl,fl-methyl ethyl glutarimide, having the structural formula as follows:
  • the above identified glutarimide is outstanding for the purpose of treating barbiturate poisoning, and, unlike other aneleptics used in the treatment of barbiturate poisoning, appears to be a closer approach than hitherto to a true barbiturate antagonist. This has been shown to be the case with animal experiments and has since been confirmed clinically with success in curing many cases of barbiturate poisoning in humans both in Australia and England.
  • barbiturate poisoning can be prevented, rather than cured, by employing as a source of barbiturate a pharmaceutical preparation comprising a barbiturate and essentially a proportion of 5,,8-methyl ethyl glutarimide, insufiicient to intereral medical practice much safer by removing the risk of coma which follows ingestion of high doses at present.
  • the pharmaceutical preparation of the invention may embody an agent delaying the release of the 5,;8-rnethyl ethyl glutarimide in the" human gastro-intestinal tract.
  • the preparation may compriz'e granules havinginsoluble coatings for delaying the absorption of the 5,6- methyl ethyl glutarimide constituent of the mixture.
  • Another procedure which may be employed consistsin preparing multi-layer tablets in which a layer containing the barbiturate is compressed over a core containing the glutarimide, as hereinafter fully described in certain of the practical examples. Absorption rates (or release) of the drugs may thereby beartificially controlled, depending upon the rate of absorption, excretion and detoxicationof the ⁇ Le-methyl ethyl glutarimide in relation to the barbiturate prescribed.
  • Pharmaceutical preparations in accordancewith the invention may comprise; for example, any of the following medicinal barbiturates: Phenobarbitone (British Pharmacopoeia) or Phenobarbital (U. S. Pharmacopoeia); Amylobarbitone (British Pharmacopoeia) or Amobarbital (U. S. Pharmacopoeia); Butobarbitone (British Pharmacopoeia); Pentobarbitone Sodium (British Pharmacopoeia) or Pentobarbital Sodium (U. S. Pharmacopoeia); Quinalbarbitone Sodium (British Pharmacopoeia) or Secobarbital Sodium (U. S. Pharmacopoeia); and Hexobarbitone Sodium (British Pharmacopoeia) or Hexobarbital Sodium (U. S. National Fo-rmulary Vol. X, 1955).
  • Example I Tablets consisting of the following mixture were prepared:
  • the phenobarbitone, 5, ⁇ 3-methyl ethyl glutarimide, Lactose and sucrose all of 40 mesh size particles were mixed throughly in a blender, then massed by addinga mixture of equalparts of Industrial Spirit (alcohol 95%) and water.
  • the moistened mass was passed through a 16 mesh'sieve and-granules dried at 50 C.
  • the dried gran ules were passed through a 16 mesh sieve then mixedwith sodium carboxy methyl cellulose (40 mesh size particles) and magnesium stearate (.60 mesh size particles). Tablets were made diameter, weighing 200 mgm., and containing 30 mgm. of phenobarbitone.
  • Example 1 Grams Pentobarbitone 60 ⁇ LB-methyl ethyl glutarimide 12 Lactose 78 Sucrose 35 Sodium carboxy methyl cellulose 10 Magnesium stearate 5 The method of Example 1 was adopted,th e pentobar bi-i tone being of 40' mesh particles. Each 200 mgn'ntablet contains 60 mgm. of entobarbitone.
  • Example III Capsules (hard gelatine) were prapared containing the following:
  • Example IV An elixirwas: prepared consisting of the following:
  • Example V Multi-layer tablets for the delayed release or absorption of the drugs as indicated, were prepared consisting of the following:
  • the phenobarbitone and lactose were mixed thoroughly in a blender, then massed by adding gum acacia in aqueous solution.
  • the moistened mass was passed through- 16 mesh and the granules dried at 50 C.
  • the dried The fLfi-methyl ethyl glutarimide, lactose and icing sugar were granulated as in Example V and the dried granules passed through a 16 mesh then mixed with the sodium carboxy methyl cellulose and magnesium stearate. Tablets weighing 130 mgm. were so prepared.
  • Layer B Grams Amylobarbitone 2 Lactose 150 Icing sugar 56 Sodium carboxy methyl cellulose 16 Magnesium stearate 8 The granules were prepared as in Core A. Layer B was compressed on Core A to form a tablet weighing 560 mgm. and containing 200 mgm. amylobarbitone and 65 mgm. 5,5-methyl ethyl glutarimide.
  • Example VII Capsules (hard gelatine) were prepared containing the following:
  • the tap-methyl ethyl glutarimide, lactose, icing sugar and dextrin were granulated as in Example V.
  • the dried granules of 16 mesh size were coated with a solution of cellulose acetate phthalate 10% w/v in acetone.
  • the amount of coating was such that when the granules were tested in artificial intestinal juice, they disintegrated within one hour.
  • the dried, coated granules were mixed thoroughly with the phenobarbitone and the mixture was filled into hard gelatine capsules so that each capsule contained 19.5 mgm. 5,;3-methyl ethyl glutarimide and 130 mgm. phenobarbitone.
  • compositions comprising two or more barbiturates, such barbiturates being mixtures of short-acting, intermediate-acting, and/or long-acting drugs, e. g., mixtures of phenobarbitone and pentobarbitone.
  • the glutarimide should be incorporated in these compositions in an amount which is the desired percentage of the total weight of the mixture of barbiturates.
  • compositions comprising one or more barbiturates with mild stimulants such as caffeine or amphetamine to reduce the post-barbiturate depression usually encountered as an aftermath of barbiturate administration.
  • mild stimulants such as caffeine or amphetamine to reduce the post-barbiturate depression usually encountered as an aftermath of barbiturate administration.
  • the glutarimide should be incorporated in an amount which is the desired percentage of the weight of the barbiturate drug or drugs in the composition.
  • compositions comprising one or more barbiturates with other mild sedatives as, for example, sodium bromide.
  • the glutarimide should be incorporated in an amount which is the desired percentage of the weight of the barbiturate drug or drugs in the composition.
  • compositions comprising one or more barbiturates with other hypnotics as, for example, chloral or paraldehyde.
  • the glutarimide should be incorporated in an amount as already indicated. In compositions of this kind it will be appreciated that the advantage of the glutarimidemustbe assessed relative to any risk of death 'as a result of overdose of the other hypnotic.
  • compositions comprising one or more barbiturates with analgesics as, for example, aspirin, phenacetin, codeine.
  • analgesics as, for example, aspirin, phenacetin, codeine.
  • the glutarimide should be incorporated in an amount as already indicated.
  • compositions of this kind it will be appreciated that the presence of the glutarimide is limited to removing the toxic effect of the barbiturate in case of overdosage.
  • the toxic effect of the overdosage of the analgesic or analgesics remains.
  • compositions of this kind are usally such that this risk is very much less than the risk of barbiturate toxicity in the case of overdosage.
  • compositions comprising one or more barbiturates with antiasthmatics as, for example, ephedrine.
  • the glutarimide should be incorporated in an amount as already indicated.
  • compositions comprising one or more barbiturates with anticholinergic drugs acting on autonomic efiector cells as, for example, atropine.
  • the glutarimide should be incorporated as already indicated.
  • compositions comprising one or more barbiturates with anticonvulsants as, for example, the hydantoins.
  • the glutarimide should be incorporated as already indicated.
  • a pharmaceutical preparation comprising a medicinal barbiturate and a proportion of fLp-methyl ethyl glutarimide within the range of 5% to 30% by weight of the barbiturate.
  • a pharmaceutical preparation comprising a medicinal preparation
  • types of compositions containnal barbiturate and aproportion of [3, ⁇ 3-methyl ethyl glutarimidewithin the rangeyof 15% to 20% by Weight-of" thepbarbiturate.
  • a pharmaceutical preparation comprising-a barbiturate selected from thegroup' consisting of phenobarbital amobarbitol, butobarbitone, pentobarbital'sodiurn, secobarbital sodium andhexobarbital sodium, and a proportion of 13,,8-rnethyl ethyl glutarimide within therange of 0 portion of pig-methyl ethyl glutarirnide Within the range of 15% to"20% by weight of the barbiturate.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

United States Patent HYPNOTIC COMPOSITION COMPRISING A BAR- BITURATE AND QB-METHYL ETHYL GLUTAR- IMIDE NoDrawing. Application April 17, 1956 Serial No. 578,575
Claims priority, application Australia April 20, 1955 4 Claims. c1. 161-52 This invention relates to barbiturate pharmaceutical preparations, for example, tablets, capsules, elixirs, suspensions and the like, containing barbiturates.
Thebarbiturates comprise an important and valuable group of central nervous systemdepressants frequently prescribed by physicians and widely used by the laity. Reference to this appears in the textbook entitled, The Pharmacological Basis of Therapeutics, by Goodman and Gilman, page 126, published 1941 by the Macmillan Company, New York, U. S. A. The barbiturates are used medically for several purposes, the most important of which are for producing sleep, inhibiting convulsions, anaesthesia, and sedation. The general properties of barbiturates are possessed in varying degrees by individual members of the group andthis has led to a large number of different compounds being employed in medicine. Some are long acting, others intermediate and still others very short acting. Administration'may be oral or parenteral, but much more frequently the former.
Chemically, the barbiturates are derivatives of barbituric acid, having the general structural formula as follows:
wherein one or both'of the hydrogen atoms attached to the carbon atom numbered 5 or the hydrogen atom attached to the nitrogen atom numbered 3 are replaced by another group to produce a compound having special property in the field. Examples are diethyl barbituric acid or barbital,phenylethyl-barbituric acid or phenobarbital, and S-phenyl-S-ethyl-3-methyl barbituric acid or methyl-phenobarbitone. .Salts of these compoundscan England has appeared in Lancet, January 21, 1956 at page 150. This paper estimates that between 80,000 and 100,000 lbs. of barbiturates are prescribed annually in the United Kingdom. Approximately 9% of all prescriptions under the National Health Scheme in the United Kingdom were for barbiturates or preparations containing barbiturates. 6.4% of all prescriptions under the National Health Scheme in the United Kingdom in October 1954 contained barbiturates as the sole or principal therapeutic agent.
Since 1949 barbiturate poisoning in general has increased tremendously. The number of patients treated for barbiturate poisoning in England and Wales was 2800 in 1949; 3950 in 1951; and 4200 in 1953. Suicidal and accidental deaths from barbiturates have increased even more spectacularly. In 1946, the number of suicides was 78 and accidental deaths was 54, totalling 132; whilst in 1954 the suicides numbered 391 and accidental deaths 181, totalling 575. Since 1945 the total suicide rate from all agents has tended to oscillate but does not show a significant upward trend. however, have increased approximately six times and it has been concluded that a preference has been shown v lately for using barbiturates as suicidal agents rather than some other lethal means.
Research has recently disclosed a substance which exhibits outstanding antagonism towards barbiturates. This barbiturate antagonist is fl,fl-methyl ethyl glutarimide, having the structural formula as follows:
The above identified glutarimide is outstanding for the purpose of treating barbiturate poisoning, and, unlike other aneleptics used in the treatment of barbiturate poisoning, appears to be a closer approach than hitherto to a true barbiturate antagonist. This has been shown to be the case with animal experiments and has since been confirmed clinically with success in curing many cases of barbiturate poisoning in humans both in Australia and England.
The discovery has now been made that barbiturate poisoning can be prevented, rather than cured, by employing as a source of barbiturate a pharmaceutical preparation comprising a barbiturate and essentially a proportion of 5,,8-methyl ethyl glutarimide, insufiicient to intereral medical practice much safer by removing the risk of coma which follows ingestion of high doses at present. By combining with the barbiturate a proportion of [8,5- methyl ethyl glutarimide such that the effectiveness of the barbiturate at normal dosages is unimpaired but at high dosage levels approaching the usual coma dose, vital body functions are maintained-the usual depressive toxic effects of the barbiturate on such functions as pulse rate, blood pressure, and the like are reduced to a safe level. In this way it is possible to protect patients from accidental or deliberate overdosage of barbiturate.
Clinical trials have shown that 18,;3-methyl ethyl glutarimide may be present in the pharmaceutical preparation in a proportion of 5% to 30% by weight of the barbiturate without interfering with the therapeutic effect of the barbiturate, to overcome the toxic effects of overdose. The (MS-methyl ethyl glutarimide is, in this way Simultaneously ingested with the barbiturate to act as an Patented Sept. 23, 1958 Suicides from barbiturates,
longed in' action, hence'it is possible that the fi d-methyl" ethyl glutarimide would be absorbed and perhaps excreted'ins'om'e instances before being'active. Because of this the pharmaceutical preparation of the invention may embody an agent delaying the release of the 5,;8-rnethyl ethyl glutarimide in the" human gastro-intestinal tract. Thus, the preparation may compriz'e granules havinginsoluble coatings for delaying the absorption of the 5,6- methyl ethyl glutarimide constituent of the mixture. Another procedure which may be employed consistsin preparing multi-layer tablets in which a layer containing the barbiturate is compressed over a core containing the glutarimide, as hereinafter fully described in certain of the practical examples. Absorption rates (or release) of the drugs may thereby beartificially controlled, depending upon the rate of absorption, excretion and detoxicationof the {Le-methyl ethyl glutarimide in relation to the barbiturate prescribed.
Pharmaceutical preparations in accordancewith the invention may comprise; for example, any of the following medicinal barbiturates: Phenobarbitone (British Pharmacopoeia) or Phenobarbital (U. S. Pharmacopoeia); Amylobarbitone (British Pharmacopoeia) or Amobarbital (U. S. Pharmacopoeia); Butobarbitone (British Pharmacopoeia); Pentobarbitone Sodium (British Pharmacopoeia) or Pentobarbital Sodium (U. S. Pharmacopoeia); Quinalbarbitone Sodium (British Pharmacopoeia) or Secobarbital Sodium (U. S. Pharmacopoeia); and Hexobarbitone Sodium (British Pharmacopoeia) or Hexobarbital Sodium (U. S. National Fo-rmulary Vol. X, 1955).
Practical examples of pharmaceutical compositions in accordance with the invention are as follows, but it is to be understood that the invention is in no way limited thereto:
Example I Tablets consisting of the following mixture were prepared:
The phenobarbitone, 5,}3-methyl ethyl glutarimide, Lactose and sucrose all of 40 mesh size particles were mixed throughly in a blender, then massed by addinga mixture of equalparts of Industrial Spirit (alcohol 95%) and water. The moistened mass was passed through a 16 mesh'sieve and-granules dried at 50 C. The dried gran ules were passed through a 16 mesh sieve then mixedwith sodium carboxy methyl cellulose (40 mesh size particles) and magnesium stearate (.60 mesh size particles). Tablets were made diameter, weighing 200 mgm., and containing 30 mgm. of phenobarbitone.
Example 11 Tablets again were prepared consisting of the fol lowing:
Grams Pentobarbitone 60 {LB-methyl ethyl glutarimide 12 Lactose 78 Sucrose 35 Sodium carboxy methyl cellulose 10 Magnesium stearate 5 The method of Example 1 was adopted,,th e pentobar bi-i tone being of 40' mesh particles. Each 200 mgn'ntablet contains 60 mgm. of entobarbitone.
Example III Capsules (hard gelatine) were prapared containing the following:
Grams Amyl'obarbitone 200 mil-methyl ethyl glutarimide 25 Lactose 15 Mix the constituents eachof whichis of- 40 mesh sizeparticles and fill capsulesof suitable .size with.240. mgm'. of'the: mixture. Each capsule. v will contain.200 mgm. arnylobarbitone.
Example IV An elixirwas: prepared consisting of the following:
Dissolve thephenobarbitone, fi,fi-methyl ethyl glutarimide and orange oil in the alcohol and Tween 80, add the glycerin and syrup. Dissolve the tartrazine in sufficient distilled water, mix into the solution, make product up to volume with distilled water and filter. Each 5 ml. of this preparation contains 20 mgm. of phenobarbitone.
Example V Multi-layer tablets for the delayed release or absorption of the drugs as indicated, were prepared consisting of the following:
Core A: Grams [LB-methyl ethyl glutarimide 9.2 Lactose 26.55 Icing sugar 16.8 Dextrin 2.4 Magnesium stearate 0.05
The pLfi-methylethyl glutarimide, lactose, icing sugar and dextrin'are mixed thoroughly in a blender, then massed by, adding a mixture of equal parts of industrial spirit and water. The moistened mass was passed through a' 16 mesh and the granules dried at 50 C. The dried granules were passed through a 16' mesh then mixed with magnesium stearate. Tablets weighing 55 mgmz, and con- 5 taining 9.2 mgm. of Ftp-methyl ethyl glutarimide were so produced.
Layer B: Grams Phenobarbitone 65.75 Lactose 77 Gum acacia 1.5 Magnesium stearate 0.75
The phenobarbitone and lactose were mixed thoroughly in a blender, then massed by adding gum acacia in aqueous solution. The moistened mass was passed through- 16 mesh and the granules dried at 50 C. The dried The fLfi-methyl ethyl glutarimide, lactose and icing sugar were granulated as in Example V and the dried granules passed through a 16 mesh then mixed with the sodium carboxy methyl cellulose and magnesium stearate. Tablets weighing 130 mgm. were so prepared.
Layer B: Grams Amylobarbitone 2 Lactose 150 Icing sugar 56 Sodium carboxy methyl cellulose 16 Magnesium stearate 8 The granules were prepared as in Core A. Layer B was compressed on Core A to form a tablet weighing 560 mgm. and containing 200 mgm. amylobarbitone and 65 mgm. 5,5-methyl ethyl glutarimide.
Example VII Capsules (hard gelatine) were prepared containing the following:
Grams Phenobarbitone 130 B,fi-methyl ethyl glutarimide 19.5 Lactose 30.25 Icing sugar Dextrin 3 The tap-methyl ethyl glutarimide, lactose, icing sugar and dextrin were granulated as in Example V. The dried granules of 16 mesh size were coated with a solution of cellulose acetate phthalate 10% w/v in acetone.
The amount of coating was such that when the granules were tested in artificial intestinal juice, they disintegrated within one hour. The dried, coated granules were mixed thoroughly with the phenobarbitone and the mixture was filled into hard gelatine capsules so that each capsule contained 19.5 mgm. 5,;3-methyl ethyl glutarimide and 130 mgm. phenobarbitone.
Experimental work with animals and humans has been carried out employing phenobarbitone and pentobarbitone, which are the most widely used barbiturates. In all such clinical work the preparations were of the kind in which the lip-methyl ethyl glutarimide and'barbiturate (phenobarbitone or pentobarbitone) were available simultaneously for ingestion. Results in both animals and man showed that the particular barbiturate derivatives above identified act satisfactorily. Medicinal barbiturates generally may be employed in the compositions of the invention but persons concerned with the art will appreciate that no practical advantage will accrue with .those ultra-short acting barbiturates used for anaesthetic purposes only and administered by a qualified medical practitioner.
Persons concerned with the art will appreciate that the invention may also be applied in various kinds of barbiturate pharmaceutical compositions in which the barbiturate content normally constitutes a potential hazard in accidental or deliberate overdosage of barbiturate. ing barbiturates to which the invention may thus be adapted, to the extent that risk of death from overdosage may be minimised, are as follows:
(a) Compositions comprising two or more barbiturates, such barbiturates being mixtures of short-acting, intermediate-acting, and/or long-acting drugs, e. g., mixtures of phenobarbitone and pentobarbitone. The glutarimide should be incorporated in these compositions in an amount which is the desired percentage of the total weight of the mixture of barbiturates.
(b) Compositions comprising one or more barbiturates with mild stimulants such as caffeine or amphetamine to reduce the post-barbiturate depression usually encountered as an aftermath of barbiturate administration. The glutarimide should be incorporated in an amount which is the desired percentage of the weight of the barbiturate drug or drugs in the composition.
(c) Compositions comprising one or more barbiturates with other mild sedatives as, for example, sodium bromide. The glutarimide should be incorporated in an amount which is the desired percentage of the weight of the barbiturate drug or drugs in the composition.
(d) Compositions comprising one or more barbiturates with other hypnotics as, for example, chloral or paraldehyde. The glutarimide should be incorporated in an amount as already indicated. In compositions of this kind it will be appreciated that the advantage of the glutarimidemustbe assessed relative to any risk of death 'as a result of overdose of the other hypnotic.
(e) Compositions comprising one or more barbiturates with analgesics as, for example, aspirin, phenacetin, codeine. The glutarimide should be incorporated in an amount as already indicated. In compositions of this kind it will be appreciated that the presence of the glutarimide is limited to removing the toxic effect of the barbiturate in case of overdosage. The toxic effect of the overdosage of the analgesic or analgesics remains. In practise compositions of this kind are usally such that this risk is very much less than the risk of barbiturate toxicity in the case of overdosage.
(f) Compositions comprising one or more barbiturates with antiasthmatics as, for example, ephedrine. The glutarimide should be incorporated in an amount as already indicated.
(g) Compositions comprising one or more barbiturates with anticholinergic drugs acting on autonomic efiector cells as, for example, atropine. The glutarimide should be incorporated as already indicated.
(h) Compositions comprising one or more barbiturates with anticonvulsants as, for example, the hydantoins. The glutarimide should be incorporated as already indicated.
What is claimed is:
l. A pharmaceutical preparation comprising a medicinal barbiturate and a proportion of fLp-methyl ethyl glutarimide within the range of 5% to 30% by weight of the barbiturate.
2. A pharmaceutical preparation comprising a medici- Examples of types of compositions containnal barbiturate and aproportion of [3,}3-methyl ethyl glutarimidewithin the rangeyof 15% to 20% by Weight-of" thepbarbiturate.
3'. A pharmaceutical preparation comprising-a barbiturate selected from thegroup' consisting of phenobarbital amobarbitol, butobarbitone, pentobarbital'sodiurn, secobarbital sodium andhexobarbital sodium, and a proportion of 13,,8-rnethyl ethyl glutarimide within therange of 0 portion of pig-methyl ethyl glutarirnide Within the range of 15% to"20% by weight of the barbiturate.
References Cited in the file of this patent UNITED. STATES PATENTS.
Hermelin Feb. 28; 1956 OTHER REFERENCES Science News Letter, Apr. 25, 195 3, p. 259.
Harris: Lancet (London), vol. 268, Jan. 22, 1955. p. 181.
Shaw et.al.:. Nature, vol. 174, No..4426, Aug. 28, 1954, pp. 402-403.

Claims (1)

1. A PHARMACEUTICAL PREPARATION COMPRISING A MEDICINAL BARBITURATE AND A PROPORTION OF B-B-METYL ETHYL GLUTARIMIDE WITHIN THE RANGE OF 5% TO 30% BY WEIGHT OF THE BARBITURATE.
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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3051618A (en) * 1956-11-06 1962-08-28 Hoechst Ag Beta-hydroxy-butyric acid amide derivatives and process for their use as narcotics
US3051742A (en) * 1957-11-30 1962-08-28 Hoechst Ag beta-hydroxy-butyric acid amide derivatives and process of preparing them
US3145204A (en) * 1960-03-04 1964-08-18 Lab D Analyses Et De Rech S R Thienyl phenyl ethyl morpholy carbinol
US4526777A (en) * 1983-01-06 1985-07-02 Mylan Pharmaceuticals Inc. Pharmaceutical combination composition and associated method
US4547498A (en) * 1983-01-06 1985-10-15 Mylan Pharmaceuticals Inc. Pharmaceutical combination composition and associated method
US4804540A (en) * 1987-12-16 1989-02-14 G. D. Searle & Co. Process for preparing the combination products of triamterene and hydrochlorothiazide
US20060204578A1 (en) * 2001-11-06 2006-09-14 Vergez Juan A Dual controlled release dosage form

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2736682A (en) * 1954-10-11 1956-02-28 Victor M Hermelin Method of making a prolonged action medicinal tablet

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2736682A (en) * 1954-10-11 1956-02-28 Victor M Hermelin Method of making a prolonged action medicinal tablet

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3051618A (en) * 1956-11-06 1962-08-28 Hoechst Ag Beta-hydroxy-butyric acid amide derivatives and process for their use as narcotics
US3051742A (en) * 1957-11-30 1962-08-28 Hoechst Ag beta-hydroxy-butyric acid amide derivatives and process of preparing them
US3145204A (en) * 1960-03-04 1964-08-18 Lab D Analyses Et De Rech S R Thienyl phenyl ethyl morpholy carbinol
US4526777A (en) * 1983-01-06 1985-07-02 Mylan Pharmaceuticals Inc. Pharmaceutical combination composition and associated method
US4547498A (en) * 1983-01-06 1985-10-15 Mylan Pharmaceuticals Inc. Pharmaceutical combination composition and associated method
US4804540A (en) * 1987-12-16 1989-02-14 G. D. Searle & Co. Process for preparing the combination products of triamterene and hydrochlorothiazide
US20060204578A1 (en) * 2001-11-06 2006-09-14 Vergez Juan A Dual controlled release dosage form
US8329217B2 (en) 2001-11-06 2012-12-11 Osmotica Kereskedelmi Es Szolgaltato Kft Dual controlled release dosage form
US8591947B2 (en) 2001-11-06 2013-11-26 Osmotica Kereskedelmi és Szolgáltató KFT Dual controlled release dosage form

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