Process for the long term reduction of body fat stores, insulin resistance, hyperinsulinemia in vertebrates

• US 5,496,803 A
• Filed: 08/08/1994
• Issued: 03/05/1996
• Est. Priority Date: 05/10/1988
• Status: Expired due to Term

• Current Assignee: Louisiana State University Agricultural & Mechanical College (Louisiana State University System)
• Original Assignee: Louisiana State University Agricultural & Mechanical College (Louisiana State University System)
• Inventors: Cincotta, Anthony H., Meier, Albert H.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Touzeau, Lynn
• Application Number:
  US08/287,066
• Time in Patent Office: 575 Days
• Field of Search: 514/3, 514/4, 514/12
• US Class Current: 514/11.5
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/15 Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
• CPC Class Codes: A61K 31/166 having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/221 with compounds having an amino group, e.g. acetylcholine, acetylcarnitine
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/435 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4515 having a butyrophenone group in position 1, e.g. haloperidol pipamperone A61K31/4545
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/475 having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine vincamine A61K31/4375
• CPC Class Codes: A61K 31/48 Ergoline derivatives, e.g. lysergic acid, ergotamine
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/4985 : Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/54 : having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
• CPC Class Codes: A61K 31/5415 : ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 31/55 : having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/551 : having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/5513 : 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 31/695 : Silicon compounds
• CPC Class Codes: A61K 38/2257 : Prolactin
• CPC Class Codes: A61K 45/06 : Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/08 : for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: G01N 33/74 : involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

A process for the long-term modification and regulation of lipid metabolism--generally to reduce obesity, insulin resistance, and hyperinsulinemia (the three hallmarks of Type II diabetes)--by injections into the bloodstream of a vertebrate, animal or human, of prolactin, or both prolactin and a glucocorticosteroid. The injections are made over a limited period at a time of day dependent on the normal circadian rhythm of fat and lean members of a similar species. Decreases (or increases) in body fat deposits result by treatment of an obese species (lean species) on a daily timed sequence based on circadian rhythms of the peak prolactin, or peak prolactin and peak glucocorticosteroid, blood level established for lean members (or obese members) of a similar species. Insulin resistance, and hyperinsulinemia can also be controlled in humans on a long-term basis by treatment corresponding to that of the treatment for obesity. The short-term daily injections reset hormonal timing in the neural centers of the brain to produce long-term effects.

Claims

1. A method for modifying or resetting the phases of circadian oscillations of the brain which control circadian rhythms of prolactin levels in the bloodstream of said patient in need of the modification and resetting comprising

administering prolactin into the blood stream of said patient on a daily basis (i) at a time within the daily interval at which the prolactin level in the bloodstream of a lean insulin-sensitive human reaches its peak value and (ii) in an amount sufficient to increase the sensitivity of the patient to insulin;

continuing the daily administration of prolactin for a period of time sufficient to modify or reset the patient'"'"'s daily prolactin level cycle so that said cycle mimics in phase and amplitude the daily prolactin level cycle of a lean insulin-sensitive human.

2. The method of claim 1 wherein the modification persists after cessation of said prolactin administration.

3. The method of claim 1 further comprising administering a glucocorticosteroid to said patient.

4. The method of claim 3 wherein said glucocorticosteroid is administered daily at a second predetermined time of day, said second time being within the daily time interval at which the glucocorticosteroid level of lean insulin-sensitive human reaches its peak value.

5. The method of claim 1 wherein prolactin is administered once a day at dosage levels ranging from about 175 micrograms to about 2000 micrograms, per pound of body weight.

6. The method of claim 4 wherein the prolactin is administered at dosage levels ranging from about 175 micrograms to about 2000 micrograms per pound body weight, and glucocorticosteroid is administered at dosage levels ranging from about 175 micrograms to about 2000 micrograms, per pound of subject body weight.

7. The method of claim 4 wherein the glucocorticosteroid is cortisol.

8. A method for modifying or resetting the phases of circadian oscillations of the brain which control circadian rhythms of prolactin in the bloodstream of a human patient in need of said modification or resetting comprising:

a) determining the time of day at which the bloodstream level of prolactin peaks in a lean, insulin-sensitive human and the value of said peak level;

b) determining the time of day at which the bloodstream level of prolactin peaks in said patient and the value of said patient'"'"'s peak prolactin level; and

c) administering prolactin to said patient daily to modify or reset the patient'"'"'s daily prolactin cycle so that it mimics in both phase and amplitude the daily prolactin level cycle of a lean insulin-sensitive human.

9. The method of claim 8 wherein the modification persists after cessation of said prolactin administration.

10. The method of claim 8 wherein prolactin is administered once a day at dosage levels ranging from about 175 micrograms to about 2000 micrograms, per pound of body weight.

11. The method of claim 10 further comprising administering a glucocorticosteroid daily to said patient.

12. The method of claim 11 wherein the prolactin is administered at a first time during a 24 hour period, and glucocorticosteroid is administered at a second time during the same 24 hour period, said glucocorticosteroid being administered at dosage levels ranging from about 175 micrograms to about 2000 micrograms, per pound of body weight.

13. The method of claim 11 wherein said glucocorticosteroid is cortisol.