United States Patent [191 [11] Patent Number: 4,582,705 Primes et al.‘ [45] Date of Patent: Apr. 15, 1986

[54] COMPOSITION FOR DETOXIFICATION alcohol and/or drug withdrawal, which comprises ad- I [76] Inventors: Leonard Primes, 230 Juniper Cir. ministering orally to such a subject an effective amount No., Lawrence, NY. 11559; Thomas of a formulation in dosage unit form having the follow Young, 5 Beach 119th St., Rockaway ing composition: Point, NY. 11694 , 5-50 grams of at least one magnesium salt selected from the group consisting of magnesium chloride, [21] App]. No.: 575,537 magnesium sulfate, magnesium citrate and other [22] Filed: Apr. 26, 1984 suitable magnesium salts; 500 mgms. to 2 grams of at least one potassium salt Related US. Application Data selected from the group consisting of potassium [63] Continuation of Ser. No. 397,420, Jul. 12,1982, aban citrate, potassium sulfate, potassium chloride, po doned. tassium bromide, potassium bitartrate and other suitable potassium salts; and [51] Int. Cl.4 ...... A61U 31/34; A61U 33/06; 50 mgms. to 5 grams of at least one salt selected from A61U 33/20; A6lU 33/30; A61U 33,34 the group consisting of the citrates, ascorbates, [52] US. Cl...... 424/ 141; 424/145; 424/ 149; 424/ 153; 424/ 154; 514/474 chlorides, bromides, sulfates, carbonates, gluco [58] Field of Search ...... 424/ 149, 153, 154, 145, nates, lactates and bitartrates of calcium, sodium, 424/141; 514/474 zinc, copper and lithium. The compositions can, additionally contain vitamins, particularly the B [56] References Cited vitamins, nutrients, sugars, ?avoring and coloring U.S. PATENT DOCUMENTS agents, and are provided in powder form. Just prior to use, the compositions are introduced into a suit 4,167,564 9/1979 Jensen ...... 424/177 4,322,407 3/1982 K0 ...... 424/128 able diluent, preferably water in an amount suitable for dissolving all of the powder and for being ad Primary Examiner-Stanley J. Friedman ministered as a single dosage unit or may be pro Attorney, Agent, or Firm-Evelyn M. Sommer vided for administration in the form of a prepared [57] _ ABSTRACT liquid. 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 14 Claims, No Drawings 4,582,705 1 2 out of contact or off the beam, the following steps have COMPOSITION FOR DETOXIFICATION been suggested: 1. Withdraw alcohol abruptly. This is a continuation of application Ser. No. 397,420, 2. Give 100 mgms. each of phenobarbital and diphenyl ?led July 12, 1982, now abandoned. hydantoin sodium orally as a sedative and anticonvul The present invention relates to therapeutic composie sant for several days. ' tions and more particularly to therapeutic compositions 3. Inject l-2 liters of 10% dextrose in normal salt solu adapted speci?cally for use in detoxifying chronic alco tion intraveneously. holics and hard-line drug addicts while avoiding all of 4. Administer by slow intraveneous drip 100 to 200 the major symptoms associated with alcohol and/or mgms. of thiamine hydrochloride and 25 units of drug withdrawal. insulin. According to a recent report of the Metropolitan Life Administer psychotropic drugs such as chlorproma Insurance Company, there are in the United States four zine, promazine and meprobromate. In the depressions million people who are alcoholics. Sometimes it appears that frequently are associated with the withdrawal of that most estimates, including the one just noted have alcohol, d~amphetamines may be used to elevate the been made considering only the overt habitues of the patient’s mood. Monitoring for hypotension and other skid rows. Physicians however, are aware of another side effects of these drugs and from their synergism group of alcoholic which have been designated as hid with alcohol must be carried out and also habituation to den alcoholics. These are the individuals who drink the psychotropic drugs must be avoided. surreptitiously and manage to keep their habituation The chronic alcoholic usually shows a distorted elec secret. Many of these people enjoy some occupational trolyte balance. Thus, in connection with alcohol with stability and some are engaged in top level positions. It drawal, ?uid and electrolyte therapy has received spe is estimated that only 6% of the alcoholic population is ~ cial attention. receiving treatment for the disease as such. Low serum potassium levels are commonly seen in The following steps have been suggested in the treat withdrawal and may re?ect total body potassium-deple ment of acute alcoholism or drunkenness: tion. Hyperventilation may contribute to hypokalemia 1. Remove the liquor from the patient. by causing extracellular to intracellular potassium 2. Get the alcohol out of the stomach and tissues. shifts. Thus, an assessment of serum potassium as av 3. Administer ?uids and food to assist in restoration of guide to potassium requirements must be made. water balance, vitamins and salts. For this purpose, it 30 It has been proposed that for each change in blood is proposed that 1-2 liters of 10% dextrines in isotonic pH of 0.1 unit, the serum potassium is adjusted 0.6 salt solution be injected slowly intraveneously. To ' mEq/L in the opposite'direction. The rate of adminis this ?uid there is added 25 units of insulin and 100 to tration is critical since potassium can cause cardiac 200 mgms. of thiamine hydrochloride. arrhythmias. . 35 Statistics have shown most alcoholics to be magne 4. Reduce the blood levels of the alcoholic. This has sium depleted regardless of their serum levels. This been accomplished from the use of intraveneous in de?ciency may be l-2 mEq/kg of body weight. Dimin jections of triiodothyronine. For reducing the blood ished dietary intake, vomiting and an ethanol-medicated I levels of alcohol in acutely intoxicated persons, there increase in urinary magnesium output are believed to is injected a total dosageof 200 mcg. of the hormone. contribute to this de?ciency. A sobering effect occurs due to the accelerated alco Magnesium replacement therapy has been proposed hol metalbolism. and speci?cally 2 g MgSO4 (8 mEq/g) has been used. 5. Administer sedatives when indicated. For the pur In addition, for the seizures and fevers accompanying pose of sedation 60-120 mgms. of phenobarbital is alcohol withdrawal which are in part precipitated by administed as an anti-convulsant, 180 mgms. of diphe~ hyperventilation and respiratory alkalosis during the nylhydantoin sodium may be desirable. This treat early period of abstinence it has been proposed that ment has to be continued for several hours. benzodiazepine therapy and magnesium replacement 1 6. Protect the patient so that he cannot injure himself or to 2 grams magnesium sulfate intraveneously can be others. (See below for treatment of delirium tremens.) helpful in preventing such symptoms. If seizures do The treatment of the chronic alcoholic has heretofore 50 occur, intraveneous diazepines are used. been undertaken along the following lines: This use of magnesium and particularly magnesium 1. Drug therapy sulfate for producing the characteristic actions of mag 2. Nutritional therapy nesium ion and speci?cally for its systemic action as an 3. Psychotherapy _ anticonvulsant is known as is its use for this purpose in As drug therapy, thiamine hydrochloride 100 to 300 connection with the muscular tremors or delirium ob mgms. intraveneously is used. The barbiturates such as served in alcoholics. For alleviating such magnesium pentobarbital sodium, 100 to 200 mgms. are adminis de?ciency it has been recommended that there be given tered. Diphenylhydantoin sodium, 100 to 200 mgms. is intramuscular injections of 2 grams of magnesium sul used to combat convulsive seizures. Dextro-ampheta fate, as a 50% solution, 4 times daily for several days. mine (Dexedrin sulfate) 5-50 mgms. 3 times a day is also 60 In US. Pat. No. 3,829,569 a therapeutic composition used in depressed alcoholics. . for combatting the major symptoms resulting from the Dietary measures are instituted using a diet with a overindulgence of alcoholic beverages has been dis high caloric intake supplemented by vitamins, espe closed comprising a two-part formulation, one part of v cially thiamine hydrochloride. ' which contains aspirin and aluminum hydroxide and the For treatment of delirium tremens, alcoholics’ mental 65 other part of which contains magnesium carbonate, disease, characterized by visual hallucinations and ac magnesium trisilicate, nicotinamide, thiamine hydro companied by marked fear of the objects seen, confu chloride and peppermint oil and either or both of which sion, disorientation for time, place and in general being ‘ contain caffeine. In this preparation, the magnesium 4,582,705 3 4 trisilicate and magnesium carbonate are both present as administered via a stomach tube. It is also possible to antacids. From the general formulation, it is apparent administer the solutions parenterally but in this connec that the preparation disclosed in a “hangover remedy” tion the formulations must be speci?cally prepared for and that there is no concern with adjustment of magne that type of administration. sium de?ciency such as is found in the chronic alco The salt contents as set out herein are calculated for holic. a single dose. It can be appreciated that the powdery In summary, in all of the proposals advanced hereto mixture can be made up in batches and aliquots to pro fore which recognize an electrolyte imbalance in the vide the desired quantities, i.e., single dosage unit then alcoholic and even in those case which suggest the use taken from the master batch. Each single dose is in of magnesium carbonate and magnesium trisilicate as an tended to be administered to the subject two to three antacid, there is no suggestion to administer the magne times daily for from one to three days. sium compound in an amount contemplated by the ap The general formulation of the compositions of the plicant herein, of from 5 up to 50 grams per individual invention can be seen from the following (the recited dose. Further, it has not been recognized that for vitamins, ?avoring agents, coloring agents, etc. are not achieving the desired detoxi?cation without concomi critical but only preferred for improving the formula tant withdrawal symptoms the other abnormal electro tion): lyte levels have to be restored to normal levels and 5 to 50 grams total of magnesium chloride, magne speci?cally this is true of the potassium levels if the sium sulfate, magnesium citrate or the like. detoxi?cation is to be satisfactorily achieved. 500 mgms. to 2 grams total of potassium citrate, po It has now been found by the applicant that the ad 20 tassium sulfate, potassium chloride, potassium bro ministration of megadoses of the essential electrolytes mide, potassium bitartrate and the like. results in the substantial immediate restoration of the electrolyte levels of body ?uids. 50 mgms. to 5 grams total of at least one of calcium More speci?cally, the applicant has found that the ascorbate, calcium pantothenate, calcium carbon ate, calcium lactate, sodium chloride, sodium as administration of magnesium in megadoses together 25 with other electolytes such as potassium, calcium, so corbate, sodium sulfate, sodium citrate, zinc gluco dium, copper, zinc, lithium and others has a synergistic nate, zinc chloride, zinc sulfate and the like. Cop effect resulting in a marked improvement in the detoxi per and lithium salts may also be present but in this ?cation of the acute and chronic alcoholic and the drug case in the indicated pharmaceutical ranges. addict as well. 10 to 150 mgms. thiamine mononitrate (Vitamin B1). The detoxi?cation in accordance with the invention 1 to 20 mgms. riboflavin phosphate (Vitamin B2 phos is completed in 24 to 72 hours without any of the usual phate). ly-encountered withdrawal effects. l to 250 mgms. pyridoxine hydrochloride (Vitamin In accordance with the invention, compositions for B6). use in and a method for detoxifying chronic alcoholics 35 50 to 100 mgms. niacinamide (Vitamin B3). and hard-line drug addicts while avoiding all of the 5 to 100 mgms. panthenol (Vitamin B5). major symptoms associated with alcohol and/or drug Sugar, flavoring agents such as peppermint oil, lico withdrawal are now proposed. The method comprises rice, cherry, orange, grape and the like and color administering orally to such a subject an effective ing agents such as are conventionally used in phar amount of a formulation in dosage unit form having the 40 maceutical preparations. following composition: This invention will appear more fully from the exam 5-50 grams of at least one magnesium salt selected ples which follow. These examples are set forth by way from the group consisting of magnesium chloride, of illustration only, and it will be understood that the magnesium sulfate and magnesium citrate; invention is not to be construed as limited in spirit or in 500 milligrams to 2 grams of at least one potassium 45 scope by the details contained therein. salt selected from the group consisting of potas sium citrate, potassium sulfate, potassium chloride, EXAMPLE 1 potassium bromide and potassium bitartrate; and A formulation particularly suitable for use in detoxi 50 milligrams to 5 grams of at least one salt selected fying an alcoholic without onset of withdrawal symp from the group consisting of the citrates, ascor toms is prepared by intimately admixing the following: bates, chlorides, bromides, sulfates, carbonates, Magnesium sulfate: 10 gms. gluconates, lactates and bitartrates of calcium, so Potassium citrate: 500 mgms. dium, zinc, copper and lithium. The compositions Calcium ascorbate: 1 gm. can additionally contain vitamins, particularly the Sodium chloride: 100 mgms. B vitamins, sugar, ?avoring and coloring agents 55 The dry mixture is prior to use dissolved in up to 250 and are provided in power form. ml. water. If desired a ?avorant such as vanillin, cherry The compositions are administered in the form of a or mint can be added. prepared liquid or just prior to use, are introduced into This solution is administered orally to the alcoholic as a suitable diluent, preferably water in an amount suit a single dose two or three times daily for from one to able for dissolving all of the powder form components 60 three days. and for being readily administered as a single dosage unit EXAMPLE 2 These compositions which are new, are administered A mixture of orally in the form of their solutions in water. Preferably Magnesium sulfate: 50 gms. the solutions are taken under medical supervision. They 65 Potassium sulfate: 2 gms. are prepared by dissolving the dry powder mixture in Sodium ascorbate: 2 gms. up to about 300 mls. of water. If the patient cannot or Calcium pantothenate: 500 mgms. will not drink the preparation, the composition can be was prepared. 5 4,582,705 6 Prior to use in the treatment of an acute alcoholic or hard line drug addict, the dry preparation can be con EXAMPLE 8 verted to a liquid dosage form. The following speci?c ingredients in the quantities ' recited were combined to prepare a composition for EXAMPLE 3 5. providing the therapeutic effects described above: The following ingredients were combined to provide Magnesium sulfate: 50 gms. a formulation suitable for use in detoxifying an alcoholic Potassium bromide: 500 mgms. or drug addict using only two (2) to nine (9) doses: Calcium ascorbate: 2 gms. Magnesium sulfate: 25 gms. ‘ Zinc gluconate: 5O mgms. Potassium chloride: 1 gm. EXAMPLE 9 Calcium carbonate: 5 gms. Sodium sulfate: 1 gm. A powder mixture of the following ingredients was Just prior to use, a ?avorant such as peppermint oil prepared: and/or sugar can be added along with’ suf?cient water Magnesium sulfate: 50 gms. 15 Potassium citrate: 1 gm. to make up to 200 ml. of a liquid dosage form. Sodium citrate: 500 mgms. EXAMPLE 4 Calcium lactate: 5 gms. Zinc sulfate: 100 mgms. A powder formulation was prepared from the follow Thiamine mononitrate: 200 mgms. mg: 20 Ribo?avin 5 phosphate: 50 mgms. Magnesium citrate: 30 gms. Pyridoxine HCl: 100 mgms. Potassium citrate: 500 mgms. Niacinamide: 100 mgms. Calcium ascorbate: 1 gm. Panthenol: 100 mgms. Sodium ascorbate: 500 mgms. Cyanocobalamine: 20 micrograms Zinc sulfate: 50 mgms. 25 Sugar: 125 gms. Thiamine mononitrate: 100 mgms. The powder mixture was dissolved in suf?cient water Ribo?avin: l0 mgms. to form 300 ml. of solution. Pyridoxine HCl: 50 mgms. Cherry flavor and a pharmaceutically acceptable red colorant were then added. ' EXAMPLE 5 This single dosage preparation was administered A formulation in accordance with the invention was twice a day for three days under supervision of medical prepared by mixing together in the amounts indicated: personnel and was entirely effective for detoxifying an Magnesium citrate: 50 gms. alcoholic, no withdrawal symptoms being observed. Calcium ascorbate: 1 gm. Potassium sulfate: 1 gm. 35 EXAMPLE 10 Zinc chloride: 100 mgms. The procedure of Example 9 was repeated using the Sodium citrate: 100 mgms. following ingredients in the amounts shown: The resuting dry mixture was introduced into 200 ml. Magnesium sulfate: 10 gms. water and stirred until dissolved. 100 grams of sugar Calcium ascorbate: 1 gm. and 5 mg. of a ?avorant such as licorice were then Potassium chloride: lOO mgms. added under stirring. The solution thereby retained was Zinc sulfate: 50 mgms. suitable for use as a single dosage unit for oral adminis Sugar: 100 gms. tration. ' Water to: 250 ml. Grape ?avorant and suitable colorant. EXAMPLE 6 45 This single dosage preparation was administered‘two A mixture was prepared from the following dry in to three times a day for two days and was an effective gredients: ‘ . formulation for detoxifying an alcoholic and for provid Magnesium sulfate: 25 gms. ing the maximum therapeutic bene?t without any evi dence of withdrawal symptoms. Calcium lactate: ' A mixture was prepared from the following dry in 50 Accordingly, the compositions of the invention gredients: which provide the essential electrolytes and specifically Magnesium sulfate: 25 gms. megadoses of magnesium together with other electro lytes such as potassium, calcium, sodium, copper, lith Calcium lactate: 2 gms. ium, zinc and the like, can be used to detoxify alcoholics Potassium citrate: 200 mgms. 55 and drug addicts by restoring the electrolyte levels Sodium ascorbate: 500 mgms. ‘from their depleted state to normal without any of the This power formulation in liquid oral dosage form attendant severe withdrawal symptoms usually associ was suitable for use in the detoxi?cation of alcoholics ated with such detoxi?cation. and hard line drug addicts. In its method of use aspect, this invention relates to EXAMPLE 7 the treatment of alcoholics and hard-line drug addicts for the purpose of restoring to normal the electrolyte ' The following dry ingredients were combined to levels of the body ?uids thereby avoiding withdrawal form a therapeutic composition to be taken orally as a _ symptoms. Results of experiments indicate that the single dose: composition administered two to three times daily for a Magnesium chloride: 50 gms. 65 period of one to three days are effective in the treatment Calcium lactate: 5 gms. of chronic alcoholics and hard-line drug addicts while Potassium bitartrate: 1 gm. , substantially lessening, i.e., eliminating the otherwise Sodium chloride: 500 mgms. behavioral and physiological changes observed in such 4,582,705 7 8 subjects during detoxi?cation and being attributable to Sodium ascorbate: 2 gms loss of magnesium and potassium levels in their body Calcium pantothenate: 500 mgms. ?uids. 7. Method according to claim 1 wherein said compo~ In medical practice, the compositions according to sition comprises: the present invention can be administered orally and 5 Magnesium sulfate: 25 gms also parenterally. Oral administration is preferred and Potassium chloride: 1 gm has been described above. It is understood however that Calcium carbonate: 5 gms the compositions can be made up for parenteral admin Sodium sulfate: 1 gm. istration, using a suitable liquid diluent capable of dis 8. Method according to claim 1 wherein said compo solving all of the ingredients, with precautions, includ 10 sition comprises: ing sterilization being taken vis~a-vis such method of Magnesium citrate: 30 gms administration. In either case, the magnesium is supplied Potassium citrate: 500 mgms so as to provide the same in a mega amount, the other Calcium ascorbate: 1 gm electrolytes being supplied in an amount effective to Sodium ascorbate: 500 mgms restore the same to their normal physiological levels. Zinc sulfate: 50 mgms The formulation of the medicinal agents of this inven Thiamine mononitrate: 100 mgms tion is accomplished in the conventional manner by processing the salts, nutriments, vitamins, etc. together Pyridoxine HCl: 50 mgms, so as to form a dry, stable admixture. 9. Method according to claim 1 wherein said compo This dry admixture is then introduced into the dilu sition comprises: ent, i.e., the water together with the ?avor accelerating Magnesium citrate: 50 gms substance, colorant, and the like customary in galenic Calcium ascorbate: 1 gm pharmacy and converted into the desired form for ap Potassium sulfate: 1 gm plication such as solutions suitable for oral administra Zinc chloride: 100 mgms tion and ?asks, glass ampules and the like suitable for 25 Sodium citrate: 100 mgms. parenteral administration. 10. Method according to claim 1 wherein said com What is claimed is: position comprises: 1. Method for detoxifying a chronic alcoholic or hard Magnesium sulfate: 25 gms line drug addict while avoiding all of the symptoms Calcium lactate: 2 gms associated with alcohol and/or drug withdrawal which 30 Potassium citrate: 200 mgms comprises administering orally to such a subject a com Sodium ascorbate: 500 mgms. position in dosage unit form comprising: 11. Method according to claim 1 wherein said com 5-50 grams of at least one magnesium salt selected position comprises: ' from the group consisting of magnesium chloride, Magnesium chloride: 50 gms magnesium sulfate and magnesium citrate; 35 Calcium lactate: 5 gms 50 milligrams 2 grams of at least one potassium salt Potassium bitartrate: 1 gm selected from the group consisting of potassium Sodium chloride: 500 mgms. citrate, potassium sulfate, potassium chloride, po 12. Method according to claim 1 wherein said com tassium bromide and potassium bitartrate; and position comprises: 50 milligrams to 5 grams of at least one salt selected 40 Magnesium sulfate: 50 gms from the group consisting of the citrates, ascor Potassium bromide: 500 mgms bates, chlorides, bromides, sulfates, carbonates, Calcium ascorbate: 2 mgs lactates, gluconates and bitartrates of calcium, so Zinc gluconate: 5O mgms. dium, zinc, copper and lithium. 13. Method according to claim 1 wherein said com 2. Method according to claim 1, which comprises 45 position comprises: administering said composition one to three times daily Magnesium sulfate: 50 gms for from one to three days. Potassium citrate: 1 gm 3. Method for detoxifying chronic alcoholics and Sodium citrate: 500 mgms hard-line drug addicts while avoiding all of the major Calcium lactate: 5 gms symptoms associated with alcohol and/or drug with Zinc sulfate: 100 mgms drawal comprising administering orally to such a sub Thiamine mononitrate: 200 mgms ject a composition according to claim 1 in the form of Ribo?avin S-phosphate: 5O mgms its solution in water. Pyridoxine HCl: 100 mgms 4. Method according to claim 3 which comprises Niacinamide: 100 mgms administering such composition two to three times daily Panthenol: 100 mgms for from one to three days. Cyanocobalamine: 20 micrograms 5. Method according to claim 1 wherein said compo Sugar: 125 gms sition comprises: Water q.s.: 250 mls. Magnesium sulfate: 10 gms 14. Method according to claim 1 wherein said com Potassium citrate: 500 mgms position comprises: Calcium ascorbate: 1 gm Magnesium sulfate‘: 10 gms: Sodium chloride: 100 mgms. Calcium ascorbate: 1 gm: 6. Method according to claim 1 wherein said compo Potassium chloride: 100 mgms: sition comprises: Zinc sulfate: 50 mgms: Magnesium sulfate: 50 gms 65 Sugar: 100 gms. Potassium sulfate: 2 gms I8 * lk it it