CA2316330A1 - Estrone and estrone esters as growth- and fat-deposition promoting compounds in humans - Google Patents
Estrone and estrone esters as growth- and fat-deposition promoting compounds in humans Download PDFInfo
- Publication number
- CA2316330A1 CA2316330A1 CA002316330A CA2316330A CA2316330A1 CA 2316330 A1 CA2316330 A1 CA 2316330A1 CA 002316330 A CA002316330 A CA 002316330A CA 2316330 A CA2316330 A CA 2316330A CA 2316330 A1 CA2316330 A1 CA 2316330A1
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- Prior art keywords
- compound
- estrone
- compound according
- humans
- fat
- 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.)
- Abandoned
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/566—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol having an oxo group in position 17, e.g. estrone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nutrition Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Child & Adolescent Psychology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Mycology (AREA)
- Obesity (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
A compound with the general formula of estrone (3-hydroxy-estra-1, 3, 5(10)-trien-17-one) and its 3-acyl ester is effective for dietary and medical uses to promote growth and fat-deposition in humans.
Description
Page 2 of fi AK19794P
ESTRONE AND ESTRONE ESTERS AS GROWTH- AND FAT-DEPOSITION
PROMOTING COMPOUNDS IN HUMANS
BACKGROUND OF THE INVENTION
1. Field of Invention The present invention relates to medicament for the treatment of humans afflicted with eating disorders due to malabsorption, cachexia and anorexia.
ESTRONE AND ESTRONE ESTERS AS GROWTH- AND FAT-DEPOSITION
PROMOTING COMPOUNDS IN HUMANS
BACKGROUND OF THE INVENTION
1. Field of Invention The present invention relates to medicament for the treatment of humans afflicted with eating disorders due to malabsorption, cachexia and anorexia.
2. Prior Art The body weight maintenance system relies in part on the equilibrium of free and oleoyl-ester of estrone. Adipose tissue takes up estrone and stores it as oleoyl ester. Non-adipose tissues break down oleoyl estrone to yield estrone (Sanchis, D. et al., 1997.
Mol. Cell. Chem., 177:153-157). Equilibrium between circulating levels of oleoyl estrone and free estrone represents also an equilibrium between fat and lean body mass. The increase in either fat or lean body mass results in the brain ordering a counteracting metabolic adjustment to re-establish equilibrium. An excess in estrone is interpreted as predominance of lean body mass, i.e., insufficient fat, and fat storage is stimulated (Fernandez- Lopez, J.A. et al., 2000. Nutr, Obes., 3:26-35).
Thus, the intake of large amounts of estrone may destabilize the weight control system including fat accumulation. Conversely, the intake of large amount of intact oleoyl estrone would induce the loss of fat (Sanchis, D. et al., 1996. Int. J. Obes., 20:588-594).
Estrone, mainly in the form of oleoyl estrone, is present in many common foods at levels ranging up to 12 micromols per kilogram (Remesar, X. et al., 1999. Eur. J.
Nutr., 38:247-253). Its presence in dairy products is especially high, and it is speculated that this presence helps suckling to improve energy efficiency and prioritize growth. Over consumption of estrone ester-laden foods, may destabilize the body weight control system inducing the same effect of growth and fat deposition in suckling.
Although milk is the preferred food for growth induction, much of its content such as lactose and saturated fats are functionally intolerable by many persons. Thus, the on-purpose addition of oleoyl estrone to foods would be particularly beneficial, especially to those persons with cachexic and undernourished conditions.
Page 3 of 6 AK19794P
In US Patent 5,314,182, Pantic et al. teach the use of a mixture of estradiol ester and progesterone ester to treat meat-producing animals to improve yield and to increase the proportion of lean to fat meat. In US Patent 5,861,391, Yen et al., teach the use of dehydroepiandrosterone to treat humans with andrenal insufficiency due to acquired immune deficiency syndrome.
Estrone (3-hydroxy-estra-1, 3, 5(10)-17-one) is an approved prescription drug for use in the treatment of vasomotor syndrome associated with menopause and palliative therapy of advanced prostatic carcinoma. Its use has not hereunto found to be surprising useful for the promotion of tissue growth and fat-deposition in mammalian subjects.
SUMMARY OF THE INVENTION
The presence of estrone and acyl estrone in limited amounts in food, either concentrated naturally or added specifically, has been discovered to induce growth of live matter in mammals when such foods are ingested. This invention is particularly useful to induce tissue growth and fat deposition in undernourished children and persons suffering from severe eating disorders. Moreover, this invention is useful for counteracting severe cachexia-inducing pathologies in persons afflicted with such ailments as cancer and acquired immune deficiency syndrome.
DETAILED DESCRIPTION OF THE INVENTION
The practice of the present invention is illustrated by the following examples, without limiting the general applicability of the present invention:
Example 1 Wistar female rats (Fa/?) weighing initially 245 to 255 grams were used in groups of five animals. A preparation of free estrone in a 20% isotonic lipid suspension (Intralipid, manufactured by Pharmacia & Upjohn, Sant Cugat, Barcelona, Spain) was used to fill up osmotic pumps (Model 2ML2, Alza Corp., Los Angeles, CA). The pumps were inserted in the back of the rats under anesthesia, and were connected via short capillary tube to the left jugular vein. The mini-pump released 0.12 milliliters per day, at a constant rate, of the suspension into the rat blood stream. The daily dose of free estrone was set at 3.5 nanomols per gram of initial body weight, for a period of 14 days.
Free estrone was found to increase the body weight of the test rats substantially.
Page 4 of 6 AK19794P
of initial weieht, after 14 days Control (no estrone) 6.3+0.8 Test (with estrone) 12.3+1.9 Example 2 Zucker lean rats (Fa/?) weighing initially 200 to 215 grams were used in groups of five animals. The test rats were fed a hyperlipidic powdered diet (18.6 MJ/kg), in which lipids accounted for 38% of the energy content, protein accounted for 17%, and balance being sugars and starches. This diet was intended to simulate a typical human diet.
The content of total estrone of the control diet was 0.9+0.3 nanomols per gram.
The test diet with oleoyl estrone (3-oleoyl-estra- 1, 3, 5(10)-men-17-one) added had a content of total estrone of 1.4~0.3 nanomols per gram. The test results after 16 days of feeding showed that the test group weight was substantially greater than the control group.
Avg foodconsumed, Total Estrone % of initial weight g/day over the 16 ingested, nmol/kg days over the 16 days Control 13.1 +1.1 53 106+4 Test 14.5+1.1 90 114+3 Example 3 Female mice weighing initially 19 to 21 grams were used in groups of five animals. The mice were injected daily, subcutaneously in the back, with 0.2 milliliters of a preparation of oleoyl estrone {3-oleoyl-estra-1, 3, 5(10)-trien-17-one) dissolved in a 20%
isotonic liquid suspension (Intralipid, manufactured by Pharmacia & Upjohn, Sant Cugat, Barcelona, Spain). Four groups were studied for dose response. The tests were continued for 14 days. The results showed that test mice achieved substantial gain in body weight. The results also indicated that higher dosing does not necessarily result in greater gain in body weight, cf. Group B versus Group C at Day 5.
Page 5 of 6 AK19794P
of initial weight Daily Dosage of Day 5 Day 14 Total Estrone, nmol/g Control 0.0 102.6+1.5 105.7 +1.8 Group A 1.5 112.8_+0.6 _ not tested Group B 3.5 116.8_+0.6 125.5 +0.9 Group C 7.0 110.6+1.4 _ not tested
Mol. Cell. Chem., 177:153-157). Equilibrium between circulating levels of oleoyl estrone and free estrone represents also an equilibrium between fat and lean body mass. The increase in either fat or lean body mass results in the brain ordering a counteracting metabolic adjustment to re-establish equilibrium. An excess in estrone is interpreted as predominance of lean body mass, i.e., insufficient fat, and fat storage is stimulated (Fernandez- Lopez, J.A. et al., 2000. Nutr, Obes., 3:26-35).
Thus, the intake of large amounts of estrone may destabilize the weight control system including fat accumulation. Conversely, the intake of large amount of intact oleoyl estrone would induce the loss of fat (Sanchis, D. et al., 1996. Int. J. Obes., 20:588-594).
Estrone, mainly in the form of oleoyl estrone, is present in many common foods at levels ranging up to 12 micromols per kilogram (Remesar, X. et al., 1999. Eur. J.
Nutr., 38:247-253). Its presence in dairy products is especially high, and it is speculated that this presence helps suckling to improve energy efficiency and prioritize growth. Over consumption of estrone ester-laden foods, may destabilize the body weight control system inducing the same effect of growth and fat deposition in suckling.
Although milk is the preferred food for growth induction, much of its content such as lactose and saturated fats are functionally intolerable by many persons. Thus, the on-purpose addition of oleoyl estrone to foods would be particularly beneficial, especially to those persons with cachexic and undernourished conditions.
Page 3 of 6 AK19794P
In US Patent 5,314,182, Pantic et al. teach the use of a mixture of estradiol ester and progesterone ester to treat meat-producing animals to improve yield and to increase the proportion of lean to fat meat. In US Patent 5,861,391, Yen et al., teach the use of dehydroepiandrosterone to treat humans with andrenal insufficiency due to acquired immune deficiency syndrome.
Estrone (3-hydroxy-estra-1, 3, 5(10)-17-one) is an approved prescription drug for use in the treatment of vasomotor syndrome associated with menopause and palliative therapy of advanced prostatic carcinoma. Its use has not hereunto found to be surprising useful for the promotion of tissue growth and fat-deposition in mammalian subjects.
SUMMARY OF THE INVENTION
The presence of estrone and acyl estrone in limited amounts in food, either concentrated naturally or added specifically, has been discovered to induce growth of live matter in mammals when such foods are ingested. This invention is particularly useful to induce tissue growth and fat deposition in undernourished children and persons suffering from severe eating disorders. Moreover, this invention is useful for counteracting severe cachexia-inducing pathologies in persons afflicted with such ailments as cancer and acquired immune deficiency syndrome.
DETAILED DESCRIPTION OF THE INVENTION
The practice of the present invention is illustrated by the following examples, without limiting the general applicability of the present invention:
Example 1 Wistar female rats (Fa/?) weighing initially 245 to 255 grams were used in groups of five animals. A preparation of free estrone in a 20% isotonic lipid suspension (Intralipid, manufactured by Pharmacia & Upjohn, Sant Cugat, Barcelona, Spain) was used to fill up osmotic pumps (Model 2ML2, Alza Corp., Los Angeles, CA). The pumps were inserted in the back of the rats under anesthesia, and were connected via short capillary tube to the left jugular vein. The mini-pump released 0.12 milliliters per day, at a constant rate, of the suspension into the rat blood stream. The daily dose of free estrone was set at 3.5 nanomols per gram of initial body weight, for a period of 14 days.
Free estrone was found to increase the body weight of the test rats substantially.
Page 4 of 6 AK19794P
of initial weieht, after 14 days Control (no estrone) 6.3+0.8 Test (with estrone) 12.3+1.9 Example 2 Zucker lean rats (Fa/?) weighing initially 200 to 215 grams were used in groups of five animals. The test rats were fed a hyperlipidic powdered diet (18.6 MJ/kg), in which lipids accounted for 38% of the energy content, protein accounted for 17%, and balance being sugars and starches. This diet was intended to simulate a typical human diet.
The content of total estrone of the control diet was 0.9+0.3 nanomols per gram.
The test diet with oleoyl estrone (3-oleoyl-estra- 1, 3, 5(10)-men-17-one) added had a content of total estrone of 1.4~0.3 nanomols per gram. The test results after 16 days of feeding showed that the test group weight was substantially greater than the control group.
Avg foodconsumed, Total Estrone % of initial weight g/day over the 16 ingested, nmol/kg days over the 16 days Control 13.1 +1.1 53 106+4 Test 14.5+1.1 90 114+3 Example 3 Female mice weighing initially 19 to 21 grams were used in groups of five animals. The mice were injected daily, subcutaneously in the back, with 0.2 milliliters of a preparation of oleoyl estrone {3-oleoyl-estra-1, 3, 5(10)-trien-17-one) dissolved in a 20%
isotonic liquid suspension (Intralipid, manufactured by Pharmacia & Upjohn, Sant Cugat, Barcelona, Spain). Four groups were studied for dose response. The tests were continued for 14 days. The results showed that test mice achieved substantial gain in body weight. The results also indicated that higher dosing does not necessarily result in greater gain in body weight, cf. Group B versus Group C at Day 5.
Page 5 of 6 AK19794P
of initial weight Daily Dosage of Day 5 Day 14 Total Estrone, nmol/g Control 0.0 102.6+1.5 105.7 +1.8 Group A 1.5 112.8_+0.6 _ not tested Group B 3.5 116.8_+0.6 125.5 +0.9 Group C 7.0 110.6+1.4 _ not tested
Claims (16)
- What is claimed is:
A compound with the general formula of estrone (3-hydroxy-estra-1, 3, 5(10)-trien-17-one) and its acyl ester is used for the promotion of tissue growth and fat-deposition in humans. - 2. A compound according to claim 1 in which the acid moiety of the said acyl ester is an organic acid.
- 3. A compound according to claim 2 in which the organic acid is a fatty acid containing 1 carbon to 26 carbons
- 4. A compound according to claim 3 in which the degree of unsaturation of the fatty acid is between 1 and 10.
- 5. A compound according to claim 3 in which the fatty acid moiety is saturated
- 6. A compound according to claim 2 in which the fatty acid is oleic acid.
- 7. A compound according to claim 1 in which the said compound is used in a food preparation to facilitate its absorption in the human intestine.
- 8. A preparation according to claim 7 in which the said compound of claim 1 is emulsified in a food substrate with the aid of a surfactant and/or dispersing agent.
- 9. A compound according to claim 1 in which the dosing of the said compound is set lower than that inducing eventual estrone overload and unwanted estrogenic side effects.
- 10. A compound according to claim 1 in which the said chemical is used in a medicinal preparation to facilitate its absorption in the human intestine.
Page 6 of 6 - 11. A preparation according to claim 9 is a pill, tablet, capsule or tonic.
- 12. A preparation according to claims 9 and 10 is a dietary supplement.
- 13. A compound according to claim 1 in which the said compound is used for the treatment of malnutrition, insufficient growth or lack of fat reserve as caused by hyponutrition or chronic ailments.
- 14. A compound according to claim 1 in which the said compound is used to treat cachexia and malnutrition.
- 15. A method according to claim 14 in which cachexia is present in humans with acquired immune deficiency syndrome.
- 16. A method according to claim 14 in which cachexia is present in humans with eating disorders.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002316330A CA2316330A1 (en) | 2000-08-09 | 2000-08-09 | Estrone and estrone esters as growth- and fat-deposition promoting compounds in humans |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002316330A CA2316330A1 (en) | 2000-08-09 | 2000-08-09 | Estrone and estrone esters as growth- and fat-deposition promoting compounds in humans |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2316330A1 true CA2316330A1 (en) | 2002-02-09 |
Family
ID=4166921
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002316330A Abandoned CA2316330A1 (en) | 2000-08-09 | 2000-08-09 | Estrone and estrone esters as growth- and fat-deposition promoting compounds in humans |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2316330A1 (en) |
-
2000
- 2000-08-09 CA CA002316330A patent/CA2316330A1/en not_active Abandoned
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| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |