GB2203941A - Anti-obesity agent - Google Patents
Anti-obesity agent Download PDFInfo
- Publication number
- GB2203941A GB2203941A GB08809833A GB8809833A GB2203941A GB 2203941 A GB2203941 A GB 2203941A GB 08809833 A GB08809833 A GB 08809833A GB 8809833 A GB8809833 A GB 8809833A GB 2203941 A GB2203941 A GB 2203941A
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- Prior art keywords
- dha
- derivative
- obesity
- dehydroepiandrosterone
- rats
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- 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
-
- 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
- A61P3/06—Antihyperlipidemics
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
Dehydroepiandrosterone (DHA) or a derivative thereof e.g. DHA conjugated with sulphuric acid, is orally administered to inhibit the activity of enzymes closely related with steatogenesis in respective tissues, thereby obtaining anti-obesity activity with no side effects.
Description
ANTI-OBESITY AGENT
The present invention relates to an anti-obesity agent and more particularly relates to an anti-obesity agent to be used for the remedy and prevention of obesity in human or animal cases.
Obesity is defined as the condition where neutral fats are abnormally accumulated in fat tissues, especially in subcutaneous tissues and body weight is increased beyond the limits of skeletal or physiological functions. Practically, obesity in a clinical sense is defined as the-condition where the body weight is increased by more than 20% of the standard weight as shown in Table 1 for a given sex and body height.
Table 1 Standard Body weight for Japanese
male female male female body body body body body body weight height weight weight height weight
(kg) (cm) - (kg) (kg) (cm) (kg) 70.9 180 59.1 164 58.3 70.1 179 58.5 163 57.7 69.3 178 57.9 162 57.1 68.5 177 57.3 161 56.5 67.7 176 56.7 160 55.9 66.9 175 56.1 159 55.3 66.1 174 55.5 158 54.7 65.4 173 55.0 157 54.1 64.7 172 54.5 156 53.5 64.0 171 54.0 155 53.0 63.3 170 154 52.5 62.6 169 62.4 153 52.0 61.9 168 61.3 152 51.5 61.2 167 60.3 151 51.0 60.5 166 59.6 150 50.5 59.8 165 58.9 149 50.1
148 49.7 normal limits :+ 10% obesity : more than.+ 20%
Neutral fats are accumulated n subcutaneous fat tissues normally in the following sequence: cheeks, chest, thighs and abdominal wall.The causes of obesity are divided into : (1) Overeating and lack of exercise and physical movement, (2) hereditary factors, (3) psychogenic factors, (4) constitution (physical factors), and (5) endocrine disorders. The obesity caused by (1) is called extrinsic or simple obesity, and the obesity caused by (2) - (5) is called intrinsic obesity.
Extrinsic obesity is found overwhelmingly more than intrinsic obesity and tends to occur when energy is excessively taken in by overeating or when energy use or consumption is too little because of lack of exercise. However, it is not entirely deniable that intrinsic factors may be related with this extrinsic obesity. Fat tissues expand as we get older and the number of cells increases accordingly. Extrinsic obesity is most likely to occur when the number of cells is too numerous from congenital reasons. Also, extrinsic obesity tends to occur due to ecological factors. Specific food taste at home or racial difference are also related to it.
Hereditary factors and physical constitution, causing intrinsic obesity, are not known in detail at present. -These factors depend upon the personal difference in fat tissues, appetite regulatory mechanism and endocrine functions. Psychogenic factors may cause obesity, while obesity may aggravate psychogenic factors-.
The appetite centre is located at the ventromedial nucleus and the lateral nucleus of hypothalamus and appetite is balanced by competition of these two nuclei. It is believed that emotion, sentiment, stomach function, blood sugar etc. are all related to this centre. Obesity is also caused by brain tumour, encephalitis or by sequela of meningitis or sequela of trauma on the head.
It is said that obesity caused by endocrine ( and metabolic) factors is comparatively rare. A typical example is Cushing's syndrome. Laurence-Moon-Biedl syndrome and Frohlich's syndrome are specific examples and are supposed to be caused by a disorder in the hypothalamus.
The long-term administration of steroids causes iatrogenic obesity. Obesity is often apt to be combined with other diseases such as diabetes, coronary artery sclerosis, cholelithiasis, fat liver, renal diseases, etc. Psychological anomalies are often caused by obesity.
As conventional treatments for obesity, there are: (1) alimentary therapy to reduce food, (2) exercise therapy to increase the consumption energy by exercise, (3) pharmacotherapy to treat with drugs, and (4) surgical therapy.
In pharmacotherapy, there are drugs to control appetite primarily by giving effects on hypothalamus, and drugs to reduce body weight by acting on organs other than hypothalamus. Amphetamine, mazindol, fenfluramine etc. belong to the former, while the latter includes thyroid hormone, dinitrophenol, etc.
In alimentary therapy, patients must try to control calorie intake by radically changing their alimentary habits and must also endure hunger for a long period. Exercise therapy requires patients to perform a considerably degree of exercise for a long time. Patients must hav a strong will and determination because severe physical and mental burdens are involved. In cities, patients may have difficulty in finding places for such exercise. Also, they may not be able to perform exercise because of their physical condition. Furthermore, exercise stimulates the appetite. Energy intake is thus increased and efforts to reduce body weight are rarely obtained in most cases.
The above mentioned drugs in pharmacotherapy have undesirable side effects and occupy only supplementary positions in the treatment of obesity.
After years of biochemical research on obesity, the present inventors have found that DHA has very good anti-obesity effects. Based on these findings, DHA preparations were prepared to perform therapeutic experiments with human subjects. The drug was given to patients with obesity, and the effects and side effects were studied. The results of the study revealed that
DHA preparations had no side effects and it was confirmed that DHA can provide an excellent antiobesity agent not known in the past.
According to the invention, there is provided the use of Dehydroepiandrosterone (DHA) or a derivative thereof in the preparation of an anti-obesity agent.
Preferably, the derivative is an ester on the third hydroxyl radical of the DHA which may be DHA conjugated with sulphuric acid. The use may be on humans or on animals such as domestic and zoo animals.
A typical dosage might be 25 to 75 mg/day of the
DHA or its derivative for a human. It might be orally administered, possibly in tablet, capsule or powder form, or as granules.
The invention also extends to an anti-obesity agent having DHA or a derivative thereof as its effective ingredient, preferably together with a pharmaceutically or veterinarily acceptable carrier.
The derivative may be as outlined above.
The invention may be carried into practice in various ways and some embodiments will now be specifically described with reference to the accompanying drawings and Examples.
Figure 1 shows a synthetic course of adrenal cortext steroids; and
Figure 2 shows a metabolic mechanism of dehydroepiandrosterone.
The present invention relates to an anti-obesity agent having DHA or a derivative as its effective component. DHA derivatives in this case include DHA conjugated with sulphuric acid and similar products.
DHA as mentioned herein is a chemical substance already known. It is one of the steroid hormones produced and secreted by the adrenal cortex. A suitable derivative of DHA is an ester on the third hydroxyl radical of DHA. A typical example is DHA conjugated with sulphuric acid which is a urophanic type of DHA. However, it is not limited to this and synthesised derivatives may be used.
In the following, the properties of DHA and DHAsodium sulphate, which are effective components according to the present invention, will be described. (1) Dehydroepiandrosterone (DHA)
Chemical name : 3B-hydroxy-5-androsten-17-one Molecular formula : C19H2802
Molecular weight : 288.43
Structural formula:
Melting Point
Needle crystals :140 - 141 OC Leaflet-crystals :152 - 153 OC Solubility : Easily soluble in benzene,
alcohol and ether;
Hardly soluble in chloroform
and petroleum ether.
(2) Dehydroepiandrosteronesodium sulphate (DHA-S)
Chemical name : 3)3-hydroxy-5-androsten-17- one-sodium sulphate dihydrate
Molecular formula : C19H27NaO5s 2H2O Molecular weight : 426.50
Structural
Melting point : approx. 1540C (decomposed)
Property : white crystals or crystalline
powder with no odour and
bitter taste.
Solubility : A little easily soluble in
methanol, hardly soluble in
water, hardly soluble in
dehydrated ethanol, and
substantially insoluble in
acetone, ether, chloroform
or benzene.
pH : 4.0 - 7.0
(0.5 W/V% aqueous solution)
Normal dosage of DHA or its derivative based on this invention is 25 - 75 mg/day in oral administration. The dosage may be adjusted according to sex, age, degree of obesity, and other symptoms.
As pharmaceutical preparations for oral administration, the product may be prepared in tablets, capsules, granules, powder, etc. The preparations can be produced by normal pharmaceutical procedures.
An approximate synthetic course of adrenal cortex steroids is shown in Figure 1. About 50 different steroid hormones biosynethesized with adrenal cortex have been isolated up to now. As shown in Table 2, they are roughly divided into glucocorticoid biochemically related with saccharometabolism (e.g.
cortisol), mineralocorticoid related with electrolyte metabolism (e.g. aldosterone) and androgen (DHA and DHA conjugated with sulphuric acid (DHA-S)].
Table 2 Steroid Secreted from Human Adrenal Cortex
Group Compound mean secreted,
amount of adult
per day
cortisol 15-20 mg glucocorticoid
corticosterone 2-5 mg
adosterone 50-150 sg mineralocorticoid 11-deoxycorticosterone trace
dehydroepiandrosterone 15-20 mg androgens A4-androstenedione 0-10 mg 11 -OH androstenedione 0-10 mg
pregnenolone 0.5-0.8 mg progestin
17-OH pregnenoldne 0.2-0.4 mg estrogen estradiol trace
DHA is produced from DHA-S. For this.reason,
DHA-S is called a storage type hormone of DHA. DHA is a steroid, which can be a biosynthetic origin of androgenic hormones - testosterone and estradiol, but testosterone and estradiol are synthesised in the adrena cortex only in small quantities.
DHA has very few effects as a sex hormone. It has effects on lipometabolism and protein metabolism and also exerts an influence on the metabolism of salts such as phosphoric acid, potassium, sodium, etc. It is excreted into urine- as DHA-S as shown in Figure 2. It is also excreted in the form of androsterone or etiocholanolone conjugated with sulphuric acid or glucuronic acid through androstenedione. All of these substances can be determined as 17-KS (ketosteroids).
In the case of women (not pregnant), almost all of these 17-KS's are said to be. derived from the adrenal cortex. In the case of men, 2/3 to 3/4 of them are derived from the adrenal cortex, while the remaining 1/3 to 1/4 come from the testes.
It can be experimentally demonstrated that metabolic products of DHA as excreted into the urine (17-KS in urine) from a patient with obesity are low in quantity. When diabetes or other diseases are combined with the obesity, they are found in extremely low quantities.
DHA and DHA-S (storage type of DHA) exist abundantly in the blood of younger people (20 - 30 years old), but the values gradually decrease as they get older. In contrast, cortisol is secreted in almost constant quantities (15 - 20mg per day) irrespective of age and 17-OHCS (hydroxycorticoid) is excreted into the urine as its metabolite.
DHA inhibits the synthesis of lipids and reduces cholesterol and lipids in the blood, whereas excessive secretion of cortisol, coupled with excessive secretion of insulin against it, enhances the synthesis of lipids. Accordingly, when DHA secretion decreases due to age or.other reasons, cortisol and insulin cannot be controlled or inhibited any more and lipids begin, to accumulate gradually in fat tissues. This results in obesity, causes troubles in the production and secretion-of insulin, and finally induces diabetes.
DHA has effects which inhibit and control the production of insulin and cortisol at the same time.
In addition, it hinders blood coagulation and the aggregation of platelets.
When given orally, DHA reaches the intestine and is converted to DHA-S there. It is then moved to various tissues in this form where it is returned again to DHA. This inhibits the activity of the enzyme, glucose-6-phosphate dehydrogenase (G6PDH), which is closely related with steatogenesis. This gives antiobesity effects. Another excellent feature of DHA. is that no side effects have been observed during experiments
The anti-obesity effects of DHA appear not only in human cases but also in animals kept at home or in a zoo. It is therefore useful as an anti-obesity agent both for human and animal cases.
Product examples of anti-obesity agents according to the present invention, animal experiments, acute toxicity tests and a clinical test will now be described. It should be understood that this invention is not limited to the exact details of this description.
Production Example 1 DHA tablet
Composition of a tablet:
DHA (dehydroepiandrosterone) 25mg
Lactose 80mg
Starch 12.5mg
Polyvinyl pyrrolidone-K30 5mg
Magnesium stearate 2.5mg
Total 125mg
Tablet production method : Wet granule method
Table diameter : 7mm
Appearance : White tablet
Production Example 2 DHA-S Tablet
Composition of a tablet
DHA-S (dehydroepiandrosterone
sodium-sulphate) 35mg
Lactose 70mg
Starch 12.5mg
Polyvinyl pyrrolidone-K30 5mg
Magnesium stearate 2.5mg Total 125mg
Tablet production method : Wet granule method
Table diameter : 7mm
Appearance : White tablet 35mg of DHA-S is equivalent to 25mg of DHA.
Animal Test 1
This test was performed with 24 female Zucker rats (8 skinny control rats, 4 obese control rats, 8 skinny test rats, and 4 obese test rats). Powdery feed with
DHA added at the rate of 0.6% was given to the DHAadministered group, and the same powdery feed was given t6 the control group for 23 weeks. The tests were then performed on them.
Table 3 shows body weight, feed intake, serum glucose and insulin.
TABLE 3 DHA- increment
DHA- increment Item control administered or
group group decrement
body decreased
weight (g) 212 181 by 15% skinny feed decreased rats intake (g) 2,319 2,170 by 6%
amount of substant
glucose 101 103 ially
(mg/dl) unchanged
body decreased
weight (g) 324 251 by 22% obese feed increased rats intake (g) 2,513 2,591 by 2% (with same amount of decreased feed glucose 121 108 by 10% intake) (mg/dl)
amount of decreased
insulin (ng/ml) 4.33 1.96 by 55%
The weight of fat in the extracted tissue is as shown in Table 4.
TABLE 4
DHA
extracted control administ- decrement
tissues group ered group
periuterus (g) 2.0 1.0 decreased
Skinny by 508 rats posteroperi
toneum (g) 1.3 0.7 decreased
by 46%
Obese decreased rats periuterus (g) 14.0 6.6 by 52% with same feed posteroperi- decreased intake toneum (g) 6.7 3.1 by 53%
Animal Test 2
20 adult SD rats (10 male rats and 10 female rats} were used, dividing them into a control group and a test group. The feed containing DHA (0.6%) was given to the test group-and the feed without DHA was given to the control group for 11 weeks. The rats were then tested.
Table 5 shows the effects of DHA on feed intake, body weight, and heat metabolism at 6th and 11th we-'ek.
TABLE 5
Sex Male (n=5) Female (n=5) Week 6 1 11 6 1 11 Feed intake I -3 I Body weight I I Heat Metabolism 5 Heat Metabolism t\ I I NOTE:
increased
extremely increased decreased extremely decreased
substantially unchanged
The composition of the rat body in the DHAadministered group is as given in Table 6.
TABLE 6
Sex Male (n=5) Female (N=5)
DHA- DHAgroup control administered control administered
group group group group body weight (g) 526 445 288 268 water % 58.3 62.2 60.3 64.6 protein % 51.5 56.2 49.3 59.0 fat % 36.8 33.2 37.4 24.0
Experiments were performed on the effects of DHA to determine liver weight, G6PDH activity in liver tissue and triglycerides in serum. The results were as shown in Table 7.
TABLE 7
Sex male female
DHA- DHAgroup control administered control administered
group group group group liver weight (g) 0.45 0.77 0.37 0.51 G6PDH activity (um/mg protein) 0.0486 0.0301 0.0473 0.0303 triglycerides in serum (mg/dl) 295 215 290 190
Acute Toxicity Test
DHA was given subcutaneously or orally to male and female ICR mice and SD rats and LD50 (mg/kg) was determined. The results are given in Table 8.
TABLE 8
mouse rat route male female male female subcutaneous administration 900 1,060 1,000 1,015 oral administration > 10,000 > 10,000 > 10,000 > 10,000
In the chronic toxicity test with mice and rats, no pathological change was observed in the livers.
Clinical Test
A clinical test was performed on 5 patients with obesity. The age, sex, body height, body weight, etc.
are shown in Table 6. The drug used for the test was
DHA in tablet form, each containing 25mg of DHA. One tablet was given at every meal, 3 times per day (75mg of DHA given per day). The administration period varied from 3 to 5 months according to the symptoms.
Use of other drugs was avoided during this period.
Table 9 shows the body weights of the patients after the administration.
TABLE 9 test number 1 2 3 4 5 age 64 52 56 48 44 sex man woman man woman man body height (cm) 165 153 162 159 170 body weight (kg) 81 63 74 64 78
Standard body weight* (for ref.) 60 52 58 55 63
DHA administration period (months) 5 4 4 3 4 body weight upon completion of test (kg) 73 58 68 60 72 ratio relative to standard body weight 1.22 1.12 1.17 1.09 1.14 decrement in body weight (%) 9.87 7.93 8.11 6.25 7.69 * see Table 1
Table 10 gives biochemical data of the blood of the patients before and after the clinical test with
DHA tablets.
TABLE 10
Test Number 1 2 3 4 5
age 64 52 56 48 44
sex man woman man woman man
total choles
terol (mg/dl) 290 250 280 260 300 before adminis- triglyceride tration (neutral fats).
(mg/dl) 257 270 260 260 280
free fatty acid (uEq/1 ) 720 590 680 580 690
total choles
terol (mg/dl) 205 230 190 210 210 after adminis- triglyceride tration (neutral fats)
(mg/dl) 150 130 140 120 150
free fatty acid
(pEq/1) 510 430 490 450 530
As described above, when the anti-obesity agent based on the present invention is given to patients, its effective component DHA (or derivative) inhibits the production of insulin and cortisol, reduces cholesterol and lipids in blood, or inhibits the activity of enzymes closely related with steatogenesis.
As a result, the drug gives excellent anti-obesity effects in human and animal cases.
Claims (11)
1. The use of Dehydroepiandrosterone (DHA) or a derivative thereof in the preparation of an antiobesity agent.
2. A use as claimed in Claim 1 in which the derivative is an ester on the third hydroxyl radical of the DHA.
3. A use as claimed in Claim 2 in which the derivative is DHA conjugated with sulphuric acid.
4. A use as claimed in any preceding claim in which the DHA or its derivative is administered to a human.
5. A use as claimed in any of Claims 1 to 3 in which the DHA or its derivative is administered to animals kept in the home or in a zoo.
6. A use as claimed in Claim 4 in which the dosage of the DHA or its derivative is 25 - 75 mg/day.
7. A use as claimed in any preceding claim in which the DHA or its derivative is administered orally.
8. A use as claimed in Claim 7 in which the DHA or its derivative is in the form of tablets, capsules, granules or powder.
9. The use of dehydroepiandrosterone or a derivative thereof, substantially as herein specifically described with reference to the accompanying Examples.
10. An anti-obesity agent having dehydroepiandrosterone or a derivative thereof as an active component.
11. An anti-obesity agent comprising dehydroepiandrosterone or a derivative thereof together with a pharmaceutically or veterinarily acceptable carrier.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP62104064A JPS63267722A (en) | 1987-04-27 | 1987-04-27 | Anti-obesity agent |
Publications (2)
Publication Number | Publication Date |
---|---|
GB8809833D0 GB8809833D0 (en) | 1988-06-02 |
GB2203941A true GB2203941A (en) | 1988-11-02 |
Family
ID=14370739
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB08809833A Withdrawn GB2203941A (en) | 1987-04-27 | 1988-04-26 | Anti-obesity agent |
Country Status (3)
Country | Link |
---|---|
JP (1) | JPS63267722A (en) |
KR (1) | KR920000309B1 (en) |
GB (1) | GB2203941A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2803519A1 (en) * | 2000-01-12 | 2001-07-13 | Assist Publ Hopitaux De Paris | ORAL USE OF DEHYDROEPIANDROSTERONE, ITS PRECURSORS AND DERIVATIVES THEREOF FOR IMPROVING THE SKIN ASPECT OF THE SKIN |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE275957T1 (en) * | 1993-01-19 | 2004-10-15 | Endorech Inc | THERAPEUTIC USES AND ADMINISTRATION SYSTEMS OF DEHYDROEPIANDROSTERONE |
JP2698865B2 (en) * | 1994-08-08 | 1998-01-19 | 仲昭 大澤 | Agent for myotonic dystrophy |
JPH10114789A (en) * | 1996-10-14 | 1998-05-06 | Kanebo Ltd | Therapeutic agent for chronic fatigue syndrome |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1246639A (en) * | 1967-10-04 | 1971-09-15 | Schering Ag | Dehydroepiandrosterone esters |
US4005200A (en) * | 1975-07-17 | 1977-01-25 | Kanebo, Ltd. | Method for improving the maturity of the parturient canal and the sensitivity to oxytocin |
EP0189738A1 (en) * | 1982-08-16 | 1986-08-06 | Norman Orentreich | Topical compositions for preventing or treating dry skin |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES8706717A1 (en) * | 1983-08-02 | 1987-07-01 | Research Corp | Steroids and therapeutic compositions containing same. |
-
1987
- 1987-04-27 JP JP62104064A patent/JPS63267722A/en active Pending
-
1988
- 1988-04-25 KR KR1019880004683A patent/KR920000309B1/en not_active IP Right Cessation
- 1988-04-26 GB GB08809833A patent/GB2203941A/en not_active Withdrawn
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1246639A (en) * | 1967-10-04 | 1971-09-15 | Schering Ag | Dehydroepiandrosterone esters |
US4005200A (en) * | 1975-07-17 | 1977-01-25 | Kanebo, Ltd. | Method for improving the maturity of the parturient canal and the sensitivity to oxytocin |
EP0189738A1 (en) * | 1982-08-16 | 1986-08-06 | Norman Orentreich | Topical compositions for preventing or treating dry skin |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2803519A1 (en) * | 2000-01-12 | 2001-07-13 | Assist Publ Hopitaux De Paris | ORAL USE OF DEHYDROEPIANDROSTERONE, ITS PRECURSORS AND DERIVATIVES THEREOF FOR IMPROVING THE SKIN ASPECT OF THE SKIN |
WO2001051023A1 (en) * | 2000-01-12 | 2001-07-19 | Assistance Publique - Hopitaux De Paris | Use of orally administered dehydroepiandrosterone, precursors and derivatives thereof in order to improve the papery aspect of the skin |
Also Published As
Publication number | Publication date |
---|---|
KR920000309B1 (en) | 1992-01-11 |
JPS63267722A (en) | 1988-11-04 |
KR880012232A (en) | 1988-11-26 |
GB8809833D0 (en) | 1988-06-02 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |