CA1224146A - Method for detoxification - Google Patents

Abstract

Abstract of the Disclosure Compositions for use in and a method for detoxifying chronic alcoholics and hard-line drug addicts while avoiding all of the major symptoms associated with alcohol and/or drug withdrawal, which comprises administering orally to such a subject an effec-tive amount of a formulation in dosage unit form having the following composition:
5-50 grams of at least one magnesium salt selected from the group consisting of magnesium chloride, magnesium sulfate, magnesium citrate and other suitable magnesium salts;
500 mgms. to 2 grams of at least one potassium salt selected from the group consisting of potassium citrate, potassium sulfate, potassium chloride, potassium bromide, potassium bitartrate and other suitable potassium salts;
and 50 mgms. to 5 grams of at least one salt selected from the group consisting of the citrates, ascorbates, chlorides, bromides, sulfates, carbonates, gluconates, lactates and bitartrates of calcium, sodium, zinc, copper and lithium.
The compositions can additionally contain vitamins, particu-larly the B vitamins, nutrients, sugars, flavoring and coloring agents, and are provided in powder form. Just prior to use, the compositions are introduced into a suitable diluent, preferably water in an amount suitable for dis-solving all of the powder and for being administered as a single dosage unit or may be provided for administration in the form of a prepared liquid:

Description

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1 i The present invention relates to therapeutic compositions and more particularly to therapeutic compositions adapted speci-fically for use in detoxifying chronic alcoholics and hard-line l drug addlcts while avoiding all of the majbr symptoms associated S I with alcohol and/or drug withdrawal.
According to a recent report of the Metropolitan Life Insur-ance Company, there are in the United States four million people who are alcoholics. Sometimes it appears that most estimates, including the one just noted have been made considering only the overt habitues of the skid rows~ Physicians however, are aware of another group of alcoholics which have been designated~as hidden alcoholics. These are-the individuals who drink surrepti.
¦ tiously and manage to keep their habituation secret. Many of ~ these people enjoy some occupational stability and some are l engaged in top level positions. It is estimated that only 6% of the alcoholic population is receiving treatment for the disease as such.
The follo.~ing steps have been suggested in the treatment of l acute aLcoholism or drunkenness:
~ l. Remove the liquor from the patient.
I I 2. Get the~alcohol out of the stomach and tissues. ~

I 3. Administer fluids and food to assist in restoration of water balance, vitamins and salts. For this purpose, it is 1 proposed that 1-2 liters of 10~ dextrines in isotonic salt solu-1 tion be injected slo~ly intraveneously. To ~his fluid there isadded 25 units of insulin and lO0 to 200 mgms. of thiamine hydro-chloride.
4. Reduce the blood levels of the alcoholic. This has been ¦ accomplished from the use of intraveneous injections of tri-.3a 1 iodothyronine. For reduoing the blood levels of alcohol inacutely intoxicated persons, there is injected a total dosage of . , ' ' '~

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1 l 200 mcg. of the hormone. A sobering effect occ~rs due to the ¦ accelerated alcohol metabolism.
l 5. Administer sedatives when indicated. For the purpose of ¦ sedation 60-120 mgms. of phenobarbital lS administed as an anti-S ¦I convulsant, 180 mgms. of diphenylhydantoin sodium may be desirable This treatment has to be continued for several hours.
6. Protect the patient so that he cannot injure himself or others. (See below for treatment of delirium tremens.) The treatment of the chronic alcoholic has heretofore been undertaken along the following lines:
1. Drug therapy I 2. Nutritional therapy i 3. Psychotherapy As drug therapy, thiamine hydrochloride 100 to 300 mgms.
lS intraveneously is used. The barbiturates such as pentobarbital ¦ sodium, 100 to 200 mgms. are administered. Diphenylhydantoin sodium, 100 to 200 mgms. is used to combat convulsive seizures.
Dextro-arnphe-tamine (Dexedrin sulfate) 5-50 mgms. 3 times a day is I also used in depressed alcoholics.
20 ~¦ Dietary measures are instituted using a diet with a high caloric intake supplemented by vitamins, especiall~ thiamine hydrochloride.
For treatment of delirium tremens, alcoholics' mental disease , characterized by visual hallucinations and accompani.ed by marked fear of the objects seen, confuslon, disorientatlon for time, place and in general keing out of contact or off the beam, the following steps have been suggested:
1. Withdraw alcohol abruptly;

2. Give 100 mgms- each of phenobarbital and diphenylhydantoi sodium orally as a sedative and anticonvulsant for several days~
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1 li 3. Inject 1-2 liters of 10% dextrose in normal salt solutior ¦ intraveneously.
4. Adminis-ter by slow intraveneous drip 100 to 200 mgms.
Il of thiamine hydrochloride and 25 units of insulin.
- S 1¦ Administer psychotropic drugs such as chlorpromazine, promazine and meprobromate. In the depressions that frequently are associated with the withdrawal of alcohol, d-amphetamines may be used to elevate the patient's mood. ~onitoring for hypotensior I and other side effects of these drugs and from their synergism 11 with alcohol must be carried out~ and also habituation to the - psychotropic drugs must be avoided.
The chronic alcoholic usually shows a distorted electrolyte balance. Thus, in connection with alcohol withdrawal, fluid and electrolyte therapy has received special attention.
Low serum potassium levels are commonl~ seen in withdrawal and may reflect total body potassium depletion. Hyperventilation may contribute to hypokalemia by causing-extracellular to intra-cellular potassium shifts. Thus, an assessmellt of serum potassiu~

1 as a guide to potassium requirements must be made.
¦ It has been proposed -that for each change in blood pH of 0.1 1¦ unit, the serum potassium~is adjusted 0.6 mEq/L in the opposite - direction. The rate of administration is critical since potassiu~
can cause cardiac arrhythmias.
- Statistics have shown most alcoholics to be magnesium 25 ¦ depleted regàrdless of their ser-~ levels. This deficiency may be 1-2 mEq/kg of body weight. Diminished dietary intake, vomi-tinc and an ethanol-medicated increase in urinary maynesium output are believed to contribute to this~deficiency.
Magnesium replacement therapy has been proposed and speci-ll fically 2 g MgSO4 (8 mEq/g) has been used.

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1 1l In adclition, for tile seizures and fevers accompanying alcoho ¦I withdrawal which are in part precipitated by hyperventilation and respiratory al]~alosis duriny the early period of abstinence it ~ has been proposed that benzodiazepine therapy and magnesium i~ replacement 1 to 2 grams magnesium sulfate intraveneously can be helpful in preventing such symptoms. If seizures do occur, intraveneous diazepines are used.
This use of magnesium and particularly magnesium sulfate for I producing the characteristic actions of magnesium ion and speci-li fically for its systemic action as an anticonvulsant is known as ¦¦ is its use for this purpose in connection with the muscu-lar Il tremors or delirium observed in alcoholics. For alleviating such ,¦ magnesium deficiency it has been recommended that there be given intramuscular injections of 2 grams of magnesium sulfate, as a ' 50% solution, 4 times daily for several days.
¦1 In United States Patent No. 3,829,569 a therapeutic composi-, tion for combatting the major symptoms resulting from the over ! indulgence of alcoholic beverages has been disclosed comprising a ¦,1 two-part formulation, one part of which contains aspirin and 20 ` ~¦ alumin~m hydroxide and the other part of which contains magnesium ¦ carbonate, magnesium trisilicate, nicotinamide, thiamine hydro-chloride and peppermint oil and elther or both of which contain ! caffeine. In this preparation, the magnesium trisilicate and -¦¦ magnesium carbonate are both present as antacids. From the 25 ¦¦ general formulation, it is apparent that the preparation disclosec ¦! is a "hàngover remedy" and that there is no concern with adjust-! ment of a magnesium deficiency such as is found in the chronic ¦l alcoholic.
1 In summary, in all of the proposals advanced heretofore ,I wh1ch recognlze an electrolyte imbalance in the alcoholic and ~2~

1 l~even in those case which suggest the use of magnesium carbonate and magnesium trisilicate as an antacid, there is no suggestion -to administer the magnesium compound in an amount contemplated by the applicant herein, of from 5 up to 50 grams per individual ¦dose. Further, it has not been recognized that for achieving the lldesired detoxification without concomitant withdrawal symptoms ¦~the other abnormal electrolyte levels have to be restored to ¦ normal levels and specifically this is true of the potassium levels if the detoxification is to be satisfactorily achieved.
It has now been found by the applicant that the administra-tion of megadoses of the essential electrolytes results in the substantial immediate restoration of the electrolyte levels of l body fluids.
¦ More specifically, the applicant has found that the adminis-'¦tration of magnesium in megadoses together with other electolytes il s~ch as potassium, calcium, sodlum, copper, zinc, lithium and others has a synergistic effect resulting in a marked improvement l~in the detoxification of the acute and chronic alcoholic and the lldrug addict as well.
~he detoxification in accordance with the invention is l~completed in 24 to 72 hours without any of the usually-encountered ¦~withdrawal effects. ' ~
¦¦ In accordance with the invention, compositions for use in ~ and a method for deto~ifying chronic alcoholics and hard-line I drug addicts while avoiding all of the major symptoms associated I I with alcohol and/or drug withdrawal are now proposed. The method I comprises administering orally to such a subject an effective ¦¦amount of a formulation in dosage unit form having the following composition:

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!, 1 11 5-50 grams of at least ~ne magnesium salt selected il from the group consisting of magnesium chloride, magnesium su~fate and magnesium citrate;
1 500 milligrams to 2 grams of at least one potassium S '1, salt selected from the group consisting of potassium citrate, potassium sulate, potassium chloride, potassiurn bromide ¦ and potassium bitartrate; and SO milligrams to 5 grams o at least one salt selected ¦ from the group consisting of the citrates, ascorbates, ¦~ chlorides, bromides, sulfates, carbonates, gluconates, lactates and bitartrates of calcium, sodium, zinc, copper and lithium. ~he compositions can additionally contain ¦ vitarnlns, particularly the B vitamins, nutrients, sugars, I flavoring and coloring agents and are provided in powder lS il form.

¦ The compositions are administered in the form of a prepared ¦liquid or just prior to use, are introduced into a suitable diluent, preferably water in an amount suitable for dissolving llall of the powder form components and for being readlly admlnister~ d ¦ 20 ` 1l as a single dosage unit.
¦ These compositions which are new, are administered orally ' in the orm of their solutions in water. Preferably the solutions - ! are taken under medical supervision. They are prepared by dis-1 solving the dry powder mixture in up to about 300 mls. of water.
If the patient cannot or will not drink the preparation, the composition can be administered~via a stomach tube. It is also ilpossible to administer the solutions parenterally but in this Iconnection the formulations must be speclfically prepared for 1 that type of administratlon.

The salt contents as set out herein are calculated for a singl~ dose. t can be appreci~ced that the powdery mixture can X~

1 Ibe made up in batches and aliquots to provide the desired quanti-¦¦ties, i.e., single dosage unit then taken from the master batch.
Each single dose is intended to be administered to the subject two to three times daily for from one to three days.

The general formulation of the compositions Gf the invention i can be seen from the following (the recited vitamins, flavoring agents, coloring agents, etc. are not critical but only preferred for improving the formulation): ~
5 to 50 grams total of magnesium chloride, magnesium sulfate, magnesium citrate or the like.
¦ 500 mgms. to 2 grams total of potassium citrate, ¦ potasslum sulfate, potass-ium chloride, potassium bromide, potassium bitartrate and the like.
50 mgms. to 5 grams total of at least one of calcium ll ascorbate, calcium pantothenate, calcium carbonate, calcium 1 lactate, sodium chloride, sodium ascorbate, sodium sulfate, I sodium citrate, zinc yluconate, zinc chloride, zinc sulfate and the like. Copper and lithium salts may also be present I but in this case in the indicated pharmaceutical ranges.
l 10 to 150 mgms. thiamine mononitrate (Vitamin Bl).

Il 1 to 20 mgms. riboflavin phosphate (Vitamin B2 phos-¦i phate).
1 to 250 mgms. pyridoxine hydrochlorlde (Vitamin B6~.

¦¦ 50 to~100 mgms. n~cinamide (Vitamin B3).
2S I 5 to 100 mgms. panthenol (Vitamin B5).

I ¦ Sugar, flavoring agents such as peppermint oil, licorice cherry, orange, grape and the like and coloring agents such as are conventionally used i.n pharmaceutical preparations.
This invention will appear more fully from the examples which follow. These examples are set forth by way of illustra-tion only, and it will be understood that the invention is not to . , .

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1 Ibe construed as limited in spirit or in scope by the detalls ,¦contained therein.

¦ Example 1 A formulation particularly suitable for use in detoxifying ~¦an alcoholic without onset of withdrawal symptoms is prepared by ~¦intimately admixing the following: ~
Magnesium sulfate10 gms.
Ij Potassium citrate 500 mgms.

,I Calcium ascorbate1 gm.
!l Sodium chloride 100 mgms.
il The dry mixture is prior to use dissolved in up to 250 ml.
Iwater. If desired a flavorant such as vanillin, cherry or mint ,Ican be added.
5 1¦ This solution is administered orally to the alcoholic as a ! single dose two or three times daily for from one to three days.
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Example 2 ¦ A mixture o-I Magnesium sulfate50 gms.
20 ~ !1 Potassium sulfate2 gms.
Sodium ascorbate2 gms.
Calclum pantothenate 500 mgms.
- llwas prepared.
i Prior to use in the treatment of an acute alcoholic or hard i line drug addict, the dry preparation can be converted to a ¦¦liquid dosage form.

Example 3.
jl The following ingredients were combined to provide a formu-30 ¦1 lation suitable for use in detoxifying an alcoholic or drug l~addict using only two (2) to nine ~9) doses:

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~L~241~1L6 agnesium sulfate 25 gms.' ¦ Potassium chloride l gm.
¦~ Calcium carbonate S gms.
,Sodium sulfa-te l gm.
S ,, Just prior to use, a flavorant such as peppermint oil and/
i or sugar can be added along with sufficient water to make up to 200 ml. of a llquid dosage form.

il Example 4 !! A powder formulation was prepared from the following:
Magnesium citra-te30 gms.
Potassium citrate500 mgms.
Calcium ascorbate l gm.
~¦ Sodium ascorbate500 mgms.

il Zinc sulfate 50 mgms.
i! Thiami!le mononitrate 100 mgms.
ii Riboflavin lO mgms.
i~ PyridG::ine HCl 50 mgms.

; I Example 5 A formulation in accordance with the invention was prepared by mixing together in the amounts indicated:
.~ Magnesium citrate50 gms.
jl Calcium ascorbate l gm.
I li Potassium sulfate 1 gm.
2S ~ ii Zinc chloride ' lO0 mgms.
¦¦ Sodium citrate 100 mgms. -The resulting dry mixture was introduced into 200 ml. water and stirred until dissolved. lO0 grams of sugar and 5 mg. of a flavo _ ,¦ ant such as licorice were then added unde~r stirring. The solutior 1l thereby obtained was suitable for use as a single dosage unit I for oral administration.
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l ~I Example 6 A mixture was prepared from the following dry inyredients:
Magnesium sulfate 25 gms.
Il Calcium lactate 2 gms.
s l! Potassium citrate~ 200 mgms.
ll Sodium ascorbate 500 mgms.
- I! This powder formulation in liquid oral dosage form was r! suitable for use in-the detoxification of alcoholics and hard ¦ line drug addicts.
, Example 7 The following dry ingredlents were combined to form a thera-¦ peutic composition to be taken orally as a single dose:
I Magnesium chlorlde50 gms.
` Caleium lactate5 gms.
j Potassium bitartrate l gm.
! Sodium chloride 500 mgms.

,¦ Example 8 'l The following specific ingredien-ts in the quantities reelted ~ ~¦ were combined to prepare a composltion for providing the thera-peutic effee~ts described above:
¦ ~lagnesium sulfate~ 50 gms.
~¦ Potassium bromide500 mgms.
'¦ Calcium ascorbate2 gms.
2S 1¦ . 'Zinc gluconàte50 mgms.

¦ E.Yample 9 ¦ A powder mixture of the following ingredients was prepared:
Magnesium sulfate50 gms.
¦ Potassium citrate1 gm.
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'lZZ4146 1 ll Sodium citrate500 mgms.
¦ Calcium lactate5 gms.
- ' Zinc sulfate100 mgms.
, Thiamine mononitrate 200 mgms.
S ll Rlboflavin 5 phosphate 50 mgms.
,I Pyridoxine HCl 100 mgms. .
'il Niacinamide ' 100 mgms.
l¦ ' ' Panthenol ' 100 mgms,.

' Cyanocobalamine 20 micrograms ¦ Sugar 125 gms.
The powder mixture was dissolved in sufficient water to ¦Iform 300 ml. of solution. ' Cherry flavor and a pharmaceutically acceptable red colorant l¦were then added.
I5 i' Il This single dosage preparation was administered twice a day ¦,for three days under supervision of medical personnel and was jlentirely efEective for detoxifying an alcoholic, no withdrawal , symptoms being observed.
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~I Example 10 ¦ The procedure of Example 9 was repeated using the followiny I , l ingredients in the amounts shown:
Magnesium sulfate 10 gms.
Calcium ascorbate 1 gm. ' 25 ll Potassium chlorlde 100 mgms.
! ~ ~inc,sulfate 50 mgms.
Sog~:~ 100 gms. :
¦¦ Water to 250 ml. .
¦ Grape flavorant and Ij suitable colorant Il .

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1 l This single dosage preparation was administered two to three times a day for two days and was an effective formulatlon for detoxifying an alcoholic and for providing the maximum therapeutic benefit without any evidence of withdrawal symptoms.
S l Accordingly, the compositions of the invention which provide the essential electrolytes and specifically megadosés of magnesium together with other electrolytes such as potassium, calcium, sodium, copper, lithlum, zinc and the like, can be used to de-l¦toxify alcoholics and drug addicts by restoring the electrolyte Illevels from their depleted state to normal without any of the iattendant severe withdrawal symptoms usually associated with such !Idetoxification.
l~ In its method of use aspect, this invention relates to the treatment of alcoholics and hard-line drug addicts for the purpose . lS 1l of restoring to normal the electrolyte levels of the body fluids thereby avoiding withdrawal symptoms. Results of experiments indicate that the composition administered two to three times j,daily for a period of one to three days are effective in the li treatment of chronic alcoholics and hard-line drug addicts while -jlsubstantial].y les~sening, i.e., eliminating the otherwise behav-ioral and physiological changes observed in such subjects duringdetoxificatlon and being attributable to loss of magnesium and ¦ potassium levels in their body fluids.
In medical practice, the compositions according to the ¦present lnventlon can be admlnistered orally and also parenter-ally. Oral administra~ion is pref~rred and has been described ;l above. It lS understood however that the compositions can be jl made up for parenteral adminis-tration, using a suitable liquid ¦Idiluent capable of dissolving all of the ingredients, with pre-cautions, including sterilization beillg taken vis-a-vis such .: : .

method of administration. In either case, the magnesium is supplied so as to provide the same in a mega amount, the other ~ electr~lytes being supplied in an amount effective to restore the I same to their normal physiological levels.
S ! The formulation of the medicinal agents of this invention is accomplished in the conventional manner by processing the salts, nutriments, vitamins, etc. together so as to form a dry, stable àdmixture.
This dry admixture is then introduced into the diluent, i.e., the water together with the flavor accelerating substance, colorant, and the like customary in galenic pharmacy and con-verted into the desired form for application such as solutions suitable for oral administration and flasks, glass ampules and the like suitable for parenteral administration.
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Claims (16)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A composition, for the detoxification of chronic alcoholics and drug addicts, which, in unit dosage form, contains as essential components:
(a) from 5 to 50 grams of at least one magnesium salt selected from the group consisting of magnesium chloride, mag-nesium sulfate, and magnesium citrate;
(b) from 500 mg to 2 g of at least one potassium salt selected from potassium citrate, potassium sulfate, potassium chloride, potassium bromide, and potassium bitartrate, and (c) from 50 mg to 5 g of at least one salt selected from the group consisting of the citrates, ascorbates, chlorides, bromides, sulfates, carbonates, gluconates, lactates, panto-thenates, and bitartrates of calcium, sodium, zinc, copper and lithium;
together with, if desired, a pharmaceutically acceptable carrier.

2. A composition according to claim 1 wherein water is used as the pharmaceutically acceptable carrier to provide the composition in the form of a solution or suspension.

3. A composition according to claim 1 further including vitamins, nutrients, sugars, flavoring agent(s) and coloring agent(s).

4. A composition according to claim 3 containing B vitamins.

5. A composition according to claim 1 wherein component (c) comprises at least one salt selected from calcium ascorbate, calcium pantothenate, calcium carbonate, calcium lactate, sodium chloride, sodium ascorbate, sodium sulfate, sodium citrate, zinc gluconate, zinc chloride, and zinc sulfate.

6. A composition according to claim 4 which contains:
thiamine mononitrate 10-150 mgm riboflavin phosphate 1-20 mgm pyridoxine hydrochloride; 1-250 mgm niacinamide 50-100 mgm , and panthenol 5-100 mgm

7. A composition according to claim 1 which comprises:
magnesium sulfate 10 gm potassium citrate 500 mgm calcium ascorbate 1 gm sodium chloride 100 mgm

8. A composition according to claim 1 which comprises:
magnesium sulfate 50 gms potassium sulfate 2 gms sodium ascorbate 2 gms calcium pantothenate 500 mgms

9. A composition according to claim 1 which comprises:
magnesium sulfate 25 gms potassium chloride 1 gm calcium carbonate 5 gms sodium sulfate 1 gm

10. A composition according to claim 1 which comprises:
magnesium citrate 30 gms potassium citrate 500 mgms calcium ascorbate 1 gm sodium ascorbate 500 mgms zinc sulfate 50 mgms thiamine mononitrates 100 mgms riboflavin 10 mgms pyridoxine HCl 50 mgms

11. A composition according to claim 1 which comprises:
magnesium citrate 50 gms calcium ascorbate 1 gm potassium sulfate 1 gm zinc chloride 100 mgms sodium citrate 100 mgms

12. A composition according to claim 1 which comprises:
magnesium sulfate 25 gms calcium lactate 2 gms potassium citrate 200 mgms sodium ascorbate 500 mgms

13. A composition according to claim 1 which comprises:
magnesium chloride 50 gms calcium lactate 5 gms potassium bitartrate 1 gm sodium chloride 500 mgms

14. A composition according to claim 1 which comprises:
magnesium sulfate 50 gms potassium bromide 500 mgms calcium ascorbate 2 gms zinc gluconate 50 mgms

15. A composition according to claim 2 which comprises:
magnesium sulfate 50 gms potassium citrate 1 gm sodium citrate 500 mgms calcium lactate 5 gms zinc sulfate 100 mgms thiamine mononitrate 200 mgms riboflavin 5 phosphate 50 mgms pyridoxine HCl 100 mgms niacinamide 100 mgms panthenol 100 mgms cyanocobalamine 20 micrograms sugar 125 gms water q.s. 250 mls

16. A composition according to claim 1 which comprises:
magnesium sulfate 10 gms calcium ascorbate 1 gm potassium chloride 100 mgms zinc sulfate 50 mgms sugar 100 gms