US3867539A - Method of producing anorexia as a treatment for obesity - Google Patents
Method of producing anorexia as a treatment for obesity Download PDFInfo
- Publication number
- US3867539A US3867539A US355296A US35529673A US3867539A US 3867539 A US3867539 A US 3867539A US 355296 A US355296 A US 355296A US 35529673 A US35529673 A US 35529673A US 3867539 A US3867539 A US 3867539A
- Authority
- US
- United States
- Prior art keywords
- histidine
- zinc
- daily
- appetite
- patient
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
Definitions
- the internal administration to human patients of the amino acid histidine has an anorexigenic or appetite-suppressing effect without producing the undersirablc side effects associated with the previously employed anorexigenic agents, and hence is highly effective in the treatment of obesity.
- the histidine which is preferably L-histidine but may also be D-histidine, DL-histidine or mixtures thereof, may be employed either as the free base or in the form of various pharmaceutically acceptable, non-toxic, water-soluble salts thereof.
- examples of such salts are the monoor di-hydrochlorides, sulphates and phosphates, and such non-toxic alkaline metal salts as the potassium and sodium salts.
- Anorexigenic pharmaceutical preparations may conveniently and easily be produced by compounding the histidine or a pharmaceutically acceptable salt thereof with conventional inert pharmaceutical carriers into dosage forms which are suitable for oral or parenteral administration, in accordance with conventional manufacturing processes common in the art.
- dosage forms include tablets, capsules, suspensions, solutions, and the like.
- various pharmaceutical carriers that may be employed for this purpose are lactose, starch, gelatin, talc, magnesium stearate, stearic acid, gums, water, saline solution, glucose solution, and the like.
- the daily dosage of histidine which are-effective in producing anorexia may be varied within a relatively wide range and, to some extent, are dependent upon the needs and requirements of the individual patient. It has been found, however, that as a general rule, the daily administration of from about 1 to about 32 grams of histidine, calculated as free base, will prove .to be effective.
- the histidine is orally administered to the patient in suitable dosage forms containing from about 0.5 to about 16 grams of histidine per dosage unit, one to three times a day as conditions demand, desirably before meals.
- a suitable oral dosage form containing about 8.1 grams of histidine, administered twice a day before meals for a total daily dose of about 16.2 grams will prove to be effective for producing anorexia without any undesirable side effects.
- normal appetite will generally return within 24 to 48 hours following discontinuation of the treatment.
- histidine produces anorexia. It is believed to be at least in part related to the ability of histidine to complexrloosely bound zinc in the plasma, thereby upsetting normal zinc transport and storage processes in the body. Such reaction is evidenced by increased urinary zinc excretion observed in patients treated with histidine in accordance with the invention.
- Example 1 A patient was placed on a constant 9 mEq Na diet with 100 mEq of Na added in a salt shaker and a fixed amount of distilled water, the daily amount set by the patient. The patient was then studied for two control days during which two daily blood samples and total excretion of urine for all 24 hour periods were collected and zinc and copper measured. Mean control values for serum zinc and copper concentrations were and 130 rig/100 ml, respectively; mean control values for urinary zinc and copper excretion were 950 and 35 ag/24 hours, respectively.
- 8.1 gm L-histidine was administered orally, once daily, in pears, without any resultant change in either serum zinc or copper concentrations but with a significant increase in urinary zinc excretion to 1123 ug/24 hours. No change in any clinical parameters occurred at the end of these two days.
- 8.1 gm L-histidine was administered orally, twice daily, in pears, for a total daily dose of.
- Example 2 A patient wasplaced on a constant 9 mEq NA diet with 100 mEq of Na added in a salt shaker and a fixed amount of distilled water, the daily amount set by the patient. The patient was then studied for two control days during which two daily blood samples and total excretion of urine for all 24 hour periods were collected and zinc and copper measured. Mean control values for serum zinc and copper concentrations were 77 and ag/ ml, respectively; mean control values for urinary zinc and copper excretion were 550 and 34 #g/24 hours, respectively.
- Example 3 A patient was placed on a constant 9 mEq Na diet with 100 mEq of Na added in a salt shaker and a fixed amount of distilled water, the daily amount set by the patient. The patient was then studied for two control days during which two daily blood samples and total excretion of urine for all 24 hour periods were collected and zinc and copper measured. Mean control values for serum zinc and copper concentrations were 100 and 102 ug/IOO ml, respectively; mean control values for urinary zinc and copper excretion were 315 and 41 ,ug/24 hours, respectively.
- 8.1 gm L-histidine was administered orally, once daily, in pears, with a decrease in serum zinc concentration to 89 ug/lOO ml and an increase in urinary zinc excretion to 630 ug/24 hours. No change in any clinical parameters occured at the end of these two days.
- 8.1 gm L-histidine was administered orally, twice daily, in pears, for a total daily dose of 16.2 gm, without any significant change in serum zinc concentration to 87 p-g/l00 ml and a further increase in urinary zinc excretion to 950 ,ug/24 hours.
- On the evening of the sixth day of the study at dinner. the patient became aware of a marked loss of appetite resulting in his wish to avoid food. This symptom was very unusual for him. Following discontinuation of the L-histidine urinary zinc excretion and appetite returned to normal within 2448 hours. No other side effects were noted.
- a method for suppressing the appetite of humans which consists essentially of internally administering to an obese patient an effective anorexigenic amount of histidine or a pharmaceutically acceptable non-toxic salt thereof.
- histidine is administered orally in a dosage of from about 1 to about 32 grams, calculated as free base, daily.
Abstract
A method of suppressing the appetite as a treatment for obesity by internally administering histidine or a pharmaceutically acceptable non-toxic salt thereof.
Description
United States Patent [1 1 Henkin [451 Feb. 18,1975
[54] METHOD OF PRODUCING ANOREXIA AS A TREATMENT FORIOBEISITY [52] U.S. Cl. 424/273, 424/319 [51] Int. Cl A61k 27/00 [58] Field of Search 424/269, 319, 273
[56] References Cited UNITED STATES PATENTS 3,632,774 l/1972 Gerber 424/319 3,697,287 10/1972 Winitz 424/319 Primary Examiner-Stanley J. Friedman Assistant Examiner-Norman A. Drezin [57] ABSTRACT A method of suppressing the appetite as a treatment for obesity by internally administering histidine or a pharmaceutically acceptable non-toxic salt thereof.
2 Claims, No Drawings METHOD OF PRODUCING ANOREXIA AS A TREATMENT OF OBESITY This invention relates to anorexigenic agents and to a method for suppressing appetite by the internal administration thereof.
Various therapeutic agents have previously been employed in the treatment of obese individuals in order to decrease their appetite so as to assist them in enduring a weight-reducing program. The most widely used agent for this purpose has been d-amphetamine. This compound, however, being a central nervous system stimulant, produces some undersirable and unpleasant side effects, including, for example, nervous tension, insomnia, headache, palpitations and elevation of blood pressure. Hence, this compound has been found to be unsuitable for use with many patients.
In accordance with the present invention, it has been found that the internal administration to human patients of the amino acid histidine has an anorexigenic or appetite-suppressing effect without producing the undersirablc side effects associated with the previously employed anorexigenic agents, and hence is highly effective in the treatment of obesity.
The histidine, which is preferably L-histidine but may also be D-histidine, DL-histidine or mixtures thereof, may be employed either as the free base or in the form of various pharmaceutically acceptable, non-toxic, water-soluble salts thereof. Examples of such salts are the monoor di-hydrochlorides, sulphates and phosphates, and such non-toxic alkaline metal salts as the potassium and sodium salts.
Anorexigenic pharmaceutical preparations may conveniently and easily be produced by compounding the histidine or a pharmaceutically acceptable salt thereof with conventional inert pharmaceutical carriers into dosage forms which are suitable for oral or parenteral administration, in accordance with conventional manufacturing processes common in the art. Such dosage forms include tablets, capsules, suspensions, solutions, and the like. Among the various pharmaceutical carriers that may be employed for this purpose are lactose, starch, gelatin, talc, magnesium stearate, stearic acid, gums, water, saline solution, glucose solution, and the like.
The daily dosage of histidine which are-effective in producing anorexia may be varied within a relatively wide range and, to some extent, are dependent upon the needs and requirements of the individual patient. It has been found, however, that as a general rule, the daily administration of from about 1 to about 32 grams of histidine, calculated as free base, will prove .to be effective. Preferably the histidine is orally administered to the patient in suitable dosage forms containing from about 0.5 to about 16 grams of histidine per dosage unit, one to three times a day as conditions demand, desirably before meals. Under ordinary circumstances, a suitable oral dosage form containing about 8.1 grams of histidine, administered twice a day before meals for a total daily dose of about 16.2 grams, will prove to be effective for producing anorexia without any undesirable side effects. Moreover, at this dosage level, normal appetite will generally return within 24 to 48 hours following discontinuation of the treatment.
Although the precise mechanism by which the administration of histidine produces anorexia is not fully understood. it is believed to be at least in part related to the ability of histidine to complexrloosely bound zinc in the plasma, thereby upsetting normal zinc transport and storage processes in the body. Such reaction is evidenced by increased urinary zinc excretion observed in patients treated with histidine in accordance with the invention.
As illustrative embodiments of the invention, the following examples are presented to illustrate the anorexigenic effect produced in patients treated with histidine in accordance with this invention.
Example 1 A patient was placed on a constant 9 mEq Na diet with 100 mEq of Na added in a salt shaker and a fixed amount of distilled water, the daily amount set by the patient. The patient was then studied for two control days during which two daily blood samples and total excretion of urine for all 24 hour periods were collected and zinc and copper measured. Mean control values for serum zinc and copper concentrations were and 130 rig/100 ml, respectively; mean control values for urinary zinc and copper excretion were 950 and 35 ag/24 hours, respectively. On the third and fourth days of the study 8.1 gm L-histidine was administered orally, once daily, in pears, without any resultant change in either serum zinc or copper concentrations but with a significant increase in urinary zinc excretion to 1123 ug/24 hours. No change in any clinical parameters occurred at the end of these two days. On the fifth and sixth days of the study, 8.1 gm L-histidine was administered orally, twice daily, in pears, for a total daily dose of.
16.2 gm, without any significant change in either serum zinc or copper concentrations but with a further increase in urinary zinc excretion to 1,490 ag/24 hours. On the morning of the sixth day of the study, at breakfast, the patient became aware of a marked loss of appetite resulting in his wish to avoid food. This symptom was very unusual for him. Following discontinuation of the L-histidine, urinary zinc excretion and appetite returned to normal within 24-48 hours. No other side effects were noted.
Example 2 A patient wasplaced on a constant 9 mEq NA diet with 100 mEq of Na added in a salt shaker and a fixed amount of distilled water, the daily amount set by the patient. The patient was then studied for two control days during which two daily blood samples and total excretion of urine for all 24 hour periods were collected and zinc and copper measured. Mean control values for serum zinc and copper concentrations were 77 and ag/ ml, respectively; mean control values for urinary zinc and copper excretion were 550 and 34 #g/24 hours, respectively. On the third and fourth days of the study, 8.1 gm L-histidine was administered orally, once daily, in pears, without any resultant change in either serum zinc or copper concentrations but with a significant increase in urinary zinc excretion to 765 ag/24 hours. On the fourth day of the study, while on 8.1 gm L-histidine daily, the patient at lunchtime noted the onset of anorexia which caused him to omit eating his potatoes, something he had never done before, while well, in his life. On the fifth and sixth days of the study, 8.1 gm L-histidine was administered orally, twice daily, in pears, for a total daily dose of 16.2 gm, without any significant change in either serum zinc or copper concentrations but with a further increase in urinary zinc excretion to 1,100 ug/24 hours. The patients anorexia persisted during these two days of the study but did not increase in severity. Following discontinuation of the L-histidine urinary zinc excretion and appetite returned to normal within 24-48 hours. No other side effects were noted.
"Example 3 A patient was placed on a constant 9 mEq Na diet with 100 mEq of Na added in a salt shaker and a fixed amount of distilled water, the daily amount set by the patient. The patient was then studied for two control days during which two daily blood samples and total excretion of urine for all 24 hour periods were collected and zinc and copper measured. Mean control values for serum zinc and copper concentrations were 100 and 102 ug/IOO ml, respectively; mean control values for urinary zinc and copper excretion were 315 and 41 ,ug/24 hours, respectively. On the third and fourth days of the study, 8.1 gm L-histidine was administered orally, once daily, in pears, with a decrease in serum zinc concentration to 89 ug/lOO ml and an increase in urinary zinc excretion to 630 ug/24 hours. No change in any clinical parameters occured at the end of these two days. On the fifth and sixth days of the study, 8.1 gm L-histidine was administered orally, twice daily, in pears, for a total daily dose of 16.2 gm, without any significant change in serum zinc concentration to 87 p-g/l00 ml and a further increase in urinary zinc excretion to 950 ,ug/24 hours. On the evening of the sixth day of the study, at dinner. the patient became aware of a marked loss of appetite resulting in his wish to avoid food. This symptom was very unusual for him. Following discontinuation of the L-histidine urinary zinc excretion and appetite returned to normal within 2448 hours. No other side effects were noted.
In addition to the mechanism previously stated with respect to the manner by whic histidine functions in the product of anorexia histidine also accumulates in hypothalamic regions of the brain in and near area which exercise some control over appetite and food intake. ln this sense histidine may suppress appetite and food intake either by a direct inhibitor effect on these brain centers or through an indirect effect on zinc levels in these areas of the brain.
What is claimed is:
l. A method for suppressing the appetite of humans which consists essentially of internally administering to an obese patient an effective anorexigenic amount of histidine or a pharmaceutically acceptable non-toxic salt thereof.
2. The method of claim 1 wherein said histidine is administered orally in a dosage of from about 1 to about 32 grams, calculated as free base, daily.
Claims (2)
1. A METHOD FOR SUPPRESSING THE APPETITE OF HUMANS WHICH CONSISTS ESSENTIALLY OF INTERNALLY ADMINISTERING TO AN OBESE PATIENT AN EFFECTIVE ANOREXIGENIC AMOUNT OF HISTIDINE OR A PHAMACCUTICALLY ACCEPTABLE NON-TOXIC SALT THEREOF.
2. The method of claim 1 wherein said histidine is administered orally in a dosage of from about 1 to about 32 grams, calculated as free base, daily.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US355296A US3867539A (en) | 1973-04-27 | 1973-04-27 | Method of producing anorexia as a treatment for obesity |
FR7414640A FR2227006B1 (en) | 1973-04-27 | 1974-04-26 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US355296A US3867539A (en) | 1973-04-27 | 1973-04-27 | Method of producing anorexia as a treatment for obesity |
Publications (1)
Publication Number | Publication Date |
---|---|
US3867539A true US3867539A (en) | 1975-02-18 |
Family
ID=23396952
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US355296A Expired - Lifetime US3867539A (en) | 1973-04-27 | 1973-04-27 | Method of producing anorexia as a treatment for obesity |
Country Status (2)
Country | Link |
---|---|
US (1) | US3867539A (en) |
FR (1) | FR2227006B1 (en) |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4032676A (en) * | 1973-12-24 | 1977-06-28 | Henkel & Cie G.M.B.H. | N-polyhydroxyalkyl-amino acids, their manufacture and skin treating agents containing the same |
US4500540A (en) * | 1979-12-26 | 1985-02-19 | Hoffmann-La Roche Inc. | Thromboxane synthase inhibitors as insulin lowering agents and antionbesity agents |
US4731363A (en) * | 1979-12-26 | 1988-03-15 | Hoffmann-La Roche Inc. | Thromboxane synthase inhibitors as insulin lowering agents and antiobesity agents |
US5635535A (en) * | 1996-04-05 | 1997-06-03 | Wagstaff; Robert K. | Method for increasing blood glucose levels |
WO1998002165A1 (en) * | 1996-07-17 | 1998-01-22 | Nutracorp Scientific, Inc. | Appetite suppression |
US5900418A (en) * | 1997-02-10 | 1999-05-04 | Synapse Pharmaceuticals International, Inc. | Method for treatment of obesity |
WO1999052363A1 (en) * | 1998-04-15 | 1999-10-21 | Nutriceutical Technology Corporation | Method of regulating appetite and metabolism |
US20070269490A1 (en) * | 2004-02-12 | 2007-11-22 | Shigeru Nakajima | Material for Processed Food for Weight Reduction Diets and Weight Reduction Dietary Processed Food Using Thereof |
US20070298025A1 (en) * | 2004-11-15 | 2007-12-27 | Obe Therapy Biotechnology S.A.S. | Pharmaceutical Compositions and Methods for Reducing Body Fat |
US20090209613A1 (en) * | 2005-06-13 | 2009-08-20 | Yeda Researc And Development Co. Ltd. At The Weizmann Institute Of Science | Use of allymercaptocaptopril for treating or preventing obesity and obesity related diseases |
US9481709B2 (en) | 2007-12-03 | 2016-11-01 | Obe Therapy Biotechnology | Boropeptide inhibitors of enteropeptidase and their uses in treatment of obesity, overweight and/or diseases associated with an abnormal fat metabolism |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2199243A (en) * | 1986-09-17 | 1988-07-06 | Natural Vitality Ltd | Pharmaceutical compositions comprising ornithine and arginine |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3632774A (en) * | 1970-03-30 | 1972-01-04 | Donald A Gerber | Method of treating rheumatoid arthritis with histidine |
US3697287A (en) * | 1969-01-28 | 1972-10-10 | Morton Norwich Products Inc | Amino acid food composition |
-
1973
- 1973-04-27 US US355296A patent/US3867539A/en not_active Expired - Lifetime
-
1974
- 1974-04-26 FR FR7414640A patent/FR2227006B1/fr not_active Expired
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3697287A (en) * | 1969-01-28 | 1972-10-10 | Morton Norwich Products Inc | Amino acid food composition |
US3632774A (en) * | 1970-03-30 | 1972-01-04 | Donald A Gerber | Method of treating rheumatoid arthritis with histidine |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4032676A (en) * | 1973-12-24 | 1977-06-28 | Henkel & Cie G.M.B.H. | N-polyhydroxyalkyl-amino acids, their manufacture and skin treating agents containing the same |
US4500540A (en) * | 1979-12-26 | 1985-02-19 | Hoffmann-La Roche Inc. | Thromboxane synthase inhibitors as insulin lowering agents and antionbesity agents |
US4731363A (en) * | 1979-12-26 | 1988-03-15 | Hoffmann-La Roche Inc. | Thromboxane synthase inhibitors as insulin lowering agents and antiobesity agents |
US5635535A (en) * | 1996-04-05 | 1997-06-03 | Wagstaff; Robert K. | Method for increasing blood glucose levels |
WO1998002165A1 (en) * | 1996-07-17 | 1998-01-22 | Nutracorp Scientific, Inc. | Appetite suppression |
US5900418A (en) * | 1997-02-10 | 1999-05-04 | Synapse Pharmaceuticals International, Inc. | Method for treatment of obesity |
WO1999052363A1 (en) * | 1998-04-15 | 1999-10-21 | Nutriceutical Technology Corporation | Method of regulating appetite and metabolism |
KR20010052257A (en) * | 1998-04-15 | 2001-06-25 | 뉴트리슈티컬 테크놀러지 코아포레이션 | Method of regulating appetite and metabolism |
US20070269490A1 (en) * | 2004-02-12 | 2007-11-22 | Shigeru Nakajima | Material for Processed Food for Weight Reduction Diets and Weight Reduction Dietary Processed Food Using Thereof |
US20070298025A1 (en) * | 2004-11-15 | 2007-12-27 | Obe Therapy Biotechnology S.A.S. | Pharmaceutical Compositions and Methods for Reducing Body Fat |
US20090209613A1 (en) * | 2005-06-13 | 2009-08-20 | Yeda Researc And Development Co. Ltd. At The Weizmann Institute Of Science | Use of allymercaptocaptopril for treating or preventing obesity and obesity related diseases |
US9481709B2 (en) | 2007-12-03 | 2016-11-01 | Obe Therapy Biotechnology | Boropeptide inhibitors of enteropeptidase and their uses in treatment of obesity, overweight and/or diseases associated with an abnormal fat metabolism |
Also Published As
Publication number | Publication date |
---|---|
FR2227006B1 (en) | 1977-11-04 |
FR2227006A1 (en) | 1974-11-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Molad | Update on colchicine and its mechanism of action | |
US4868179A (en) | Method of reducing mortality associated with congestive heart failure using hydralazine and isosorbide dinitrate | |
US3867539A (en) | Method of producing anorexia as a treatment for obesity | |
US4315028A (en) | Method of treatment of rheumatoid arthritis | |
EP0234733A1 (en) | Pharmaceutical compositions | |
US4435449A (en) | Treatment of minimal brain dysfunction (MBD) | |
US4487780A (en) | Method of treatment of rheumatoid arthritis | |
Malkinson et al. | Hydroxychloroquine treatment of porphyria cutanea tarda | |
US4438138A (en) | Reduction of cholesterol with meta-chloro α-t-butylaminopropiophenone | |
RU2039556C1 (en) | Pharmaceutical antialcoholic composition stimulating energy metabolism, secretory function of gastric mucous membrane and producing halioprotective and antitumor effect; method of prevention and treatment of alcoholic intoxication and alcoholic abstinence syndrome; method for stimulating energy metabolism; method for stimulating and diagnosing acid-forming and secretory functions of gastric mucosa; method for protecting warm-blooded animals from radiation injury | |
US6433015B1 (en) | Method for reducing body weight | |
JPS63270626A (en) | Antiulcer agent | |
US2789938A (en) | Method of producing a diuretic effect with p-carboxybenzenesulfonamide | |
Haberman | Malignant hyperthermia: An allergic reaction to thioridazine therapy | |
JPH0699310B2 (en) | Acetaldehyde antidote | |
US4414212A (en) | Method of treatment of pre-menstrual syndrome | |
AU651824B2 (en) | Pharmaceutical composition | |
JPH0354644B2 (en) | ||
US5534523A (en) | Anti-aids virus composition | |
US4565830A (en) | Method of ameliorating the subjective symptoms and objective signs in congestive heart failure | |
Selmanowitz | Lithium, leukocytes, and lesions | |
US4032650A (en) | Method of treating fatigue by administering a gulonic acid salt | |
US4271191A (en) | Method of treating hyperuricemia and gout | |
US4466978A (en) | Bodyweight reducing method | |
EP0321556A1 (en) | Use of c-5 mono-substituted barbiturates to treat disorders of uric acid metabolism |