WO2002098415A1 - Medicine for treating obesity - Google Patents

Medicine for treating obesity Download PDF

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Publication number
WO2002098415A1
WO2002098415A1 PCT/KR2002/001072 KR0201072W WO02098415A1 WO 2002098415 A1 WO2002098415 A1 WO 2002098415A1 KR 0201072 W KR0201072 W KR 0201072W WO 02098415 A1 WO02098415 A1 WO 02098415A1
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WO
WIPO (PCT)
Prior art keywords
lipoic acid
obesity
present
treating obesity
olktf
Prior art date
Application number
PCT/KR2002/001072
Other languages
French (fr)
Inventor
Joong-Yeol Park
Sung-Kwan Hong
In Kyu Lee
Ki-Up Lee
Original Assignee
Joong-Yeol Park
Sung-Kwan Hong
In Kyu Lee
Ki-Up Lee
Priority date (The priority date 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 date listed.)
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Publication date
Application filed by Joong-Yeol Park, Sung-Kwan Hong, In Kyu Lee, Ki-Up Lee filed Critical Joong-Yeol Park
Publication of WO2002098415A1 publication Critical patent/WO2002098415A1/en

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring

Definitions

  • the present invention relates to novel anti-obesity agent, and more particularly, to the use of ⁇ -lipoic acid as anti-obesity agent.
  • Obesity is one of the most common medical disorders, which affects 30-40% of the population of which 10% may be severe and morbid.
  • Complications of obesity include insulin resistance, diabetes mellitus, hypertension, cardiovascular disease, pseudotumor cerebri, hyperlipidemia, sleep apnea, cancer, pulmonary hypertension, cholecystitis, and osteoarthritis.
  • current treatments of obesity are largely unsuccessful with a high failure rate.
  • obese patients try to reduce weight by diet and exercise, this failure may be due to the fact that the condition is strongly associated with genetically inherited factors that contribute to increased appetite, preference for highly caloric foods, increased lipid synthesis metabolism. Therefore, a new pharmacological agent to successfully reduce weight is needed.
  • ⁇ -lipoic acid C 8 H 1 O 2 S 2
  • ⁇ -lipoic acid was first isolated by Reed and coworkers and they named the compound ⁇ -lipoic acid after isolating trace element in liver, the structure of compound was elucidated by synthesis
  • ⁇ -lipoic acid was known as a new vitamin by the fact that unknown trace element in liver or yeast extract is a lactic acid bacteria growth factor
  • ⁇ -lipoic acid is known by a variety of names, including thioctic acid; l ,2-diethylene-3 pentanoic acid; and 6,8-thioctic acid.
  • ⁇ -lipoic acid and its reduced form, dihydrolipoic acid (DI I A). It is reported that ⁇ -lipoic acid, or its reduced form, DHLA, reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, peroxyl radicals, and singlet oxygen and it also protects cell membrane by reacting with vitamin C and glutathione.
  • ⁇ - lipoic acid administration has been shown to be beneficial in a number of oxidative stress besides.
  • the present invention has an object to provide ⁇ -lipoic acid as anti- obesity agent.
  • composition for treating obesity comprising ⁇ -lipoic acid, and a pharmaceutically acceptable carrier and additive.
  • a anti-obesity agent comprising ⁇ -lipoic acid.
  • ⁇ -lipoic acid may be used as anti-obesity agent of the present invention.
  • the anti-obesity agent in the present invention may be used with ⁇ -lipoic acid alone or mixed with other treatments of obesity. If necessary, the anti-obesity agent in the present invention may be mixed with various pharmaceutically acceptable additives such as excipients, disintergrants, freshners and lubricants.
  • the anti-obesity agent in the present invention may be oral or parenteral agents, but oral agents are desirable.
  • ⁇ -lipoic acid of the present invention is injected into OLKTF white rats as animal models having obese diabetes, the OLKTF rats are shown to reduce the amount of insulin and lose weight. Additionally, the mRNA expression of uncoupling protein 1 UCPI which emits energy as heat in brown and white adipose issues of the rats injected with ⁇ -lipoic acid significantly increases. It is shown from the above results that the effect of ⁇ -lipoic acid on obesity improvement results from induction of decrease in ingestion and the increase in expression of UCPI in brown and while adipose tissues.
  • Fig. 1 is a graph illustrating the effect of anti-obesity agent of the present invention on weight loss
  • Figs. 2a and 2b are a Northern blot and a graph illustrating the effect of anti- obesity agent of the present invention inhibiting UCPI expression in brown adipose tissues;
  • Figs. 3a and 3b are a Nothern blot and a graph illustrating the effect of anti- obesity agent of the present invention inhibiting UCPI expression in white adipose tissues.
  • the addition of at 0.6%> ⁇ -lipoic acid to normal rat feed was administrated to the OLKTF rats for 26 days in feeding group for ⁇ -lipoic acid(ALA group).
  • Normal rat feed was administrated to the OLKTF ' " rats of the control group and pair-feeding group for the same period.
  • ⁇ -lipoic acid of the present invention is highly effective material for treating obesity than other treating methods reducing amount of meals.
  • Kxample 2 Measuring UCPI mRNA in brown and white adipose tissues
  • Figs. 3a and 3b the result of white adipose tissue is shown in Figs. 3a and 3b.
  • the UCPI mRNA expression which emits energy as heat in brown adipose tissue, significantly increases in feeding group for ⁇ -lipoic acid in comparison with control group.
  • ALA group express UCPI in white adipose tissue which cannot express UCPI in normal condition.
  • ⁇ -lipoic acid as anti-obesity agent of the present invention is shown to have anti-obesity effect in OLKTF white rats. The effect results from decrease in ingestion and increase in expression of UCPI which emits energy as heat in brown and white adipose tissues. Accordingly, ⁇ -lipoic acid as anti-obesity agent of the present invention can be useful for excellent anti-obesity agent and appetite suppressant to various obese symptoms.

Abstract

The present invention relates to a new medicine for treating obesity, and more particularly to a medicine for treating obesity comprising α-lipoic acid. Moreover the present invention provides compositions for treating obesity or decreasing appetite comprising α-lipoic acid, pharmaceutically acceptable carriers and additives.

Description

MEDICINE FOR TREATING OBESITY
BACKGROUND OF THE INVENTION
1. Field of the Invention The present invention relates to novel anti-obesity agent, and more particularly, to the use of α-lipoic acid as anti-obesity agent.
2. Description of the Prior Art
Obesity is one of the most common medical disorders, which affects 30-40% of the population of which 10% may be severe and morbid. Complications of obesity include insulin resistance, diabetes mellitus, hypertension, cardiovascular disease, pseudotumor cerebri, hyperlipidemia, sleep apnea, cancer, pulmonary hypertension, cholecystitis, and osteoarthritis. As a result, keen attention is being paid to anti-obesity agent. Unfortunately, current treatments of obesity are largely unsuccessful with a high failure rate. Although obese patients try to reduce weight by diet and exercise, this failure may be due to the fact that the condition is strongly associated with genetically inherited factors that contribute to increased appetite, preference for highly caloric foods, increased lipid synthesis metabolism. Therefore, a new pharmacological agent to successfully reduce weight is needed.
A compound known as α-lipoic acid (C8H1 O2S2) was first isolated by Reed and coworkers and they named the compound α-lipoic acid after isolating trace element in liver, the structure of compound was elucidated by synthesis, α-lipoic acid was known as a new vitamin by the fact that unknown trace element in liver or yeast extract is a lactic acid bacteria growth factor, α-lipoic acid is known by a variety of names, including thioctic acid; l ,2-diethylene-3 pentanoic acid; and 6,8-thioctic acid. It functions as a thiamine related cofactor in the oxidative decarboxylation system of α-keto acids such as pyruvate, α-keto glutarate. Although admitted that α-lipoic acid is an essential material in metabolism, it is not clear that α-lipoic acid is necessary for food intake in higher animals. The experiment of lipoic acid deficiency for animals is still unsuccessful.
More recently, a great deal of attention has been given to possible antioxidant functions for α-lipoic acid, and its reduced form, dihydrolipoic acid (DI I A). It is reported that α-lipoic acid, or its reduced form, DHLA, reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, peroxyl radicals, and singlet oxygen and it also protects cell membrane by reacting with vitamin C and glutathione. α- lipoic acid administration has been shown to be beneficial in a number of oxidative stress besides.
However, it is not known α-lipoic acid use as anti-obesity agent.
SUMMARY OF THE INVENTION
Accordingly, the present invention has an object to provide α-lipoic acid as anti- obesity agent.
There is provided a composition for treating obesity comprising α-lipoic acid, and a pharmaceutically acceptable carrier and additive. In order to achieve the object of the present invention, a anti-obesity agent comprising α-lipoic acid.
Commercial α-lipoic acid may be used as anti-obesity agent of the present invention.
The anti-obesity agent in the present invention may be used with α-lipoic acid alone or mixed with other treatments of obesity. If necessary, the anti-obesity agent in the present invention may be mixed with various pharmaceutically acceptable additives such as excipients, disintergrants, freshners and lubricants.
The anti-obesity agent in the present invention may be oral or parenteral agents, but oral agents are desirable. When α-lipoic acid of the present invention is injected into OLKTF white rats as animal models having obese diabetes, the OLKTF rats are shown to reduce the amount of insulin and lose weight. Additionally, the mRNA expression of uncoupling protein 1 UCPI which emits energy as heat in brown and white adipose issues of the rats injected with α-lipoic acid significantly increases. It is shown from the above results that the effect of α-lipoic acid on obesity improvement results from induction of decrease in ingestion and the increase in expression of UCPI in brown and while adipose tissues.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention will be explained in terms of exemplary embodiments described in detail with reference to the accompanying drawings, which are given only by way of illustration and thus are not limitative of the present invention, wherein:
Fig. 1 is a graph illustrating the effect of anti-obesity agent of the present invention on weight loss;
Figs. 2a and 2b are a Northern blot and a graph illustrating the effect of anti- obesity agent of the present invention inhibiting UCPI expression in brown adipose tissues; and
Figs. 3a and 3b are a Nothern blot and a graph illustrating the effect of anti- obesity agent of the present invention inhibiting UCPI expression in white adipose tissues. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Kxample 1 : Weight change experiment
OLKTF rats(21 weeks) were classified into control group (n=6), feeding group for α-lipoic acid(n=6) and pair-feeding group (n^6). The addition of at 0.6%> α-lipoic acid to normal rat feed was administrated to the OLKTF rats for 26 days in feeding group for α-lipoic acid(ALA group). Normal rat feed was administrated to the OLKTF'" rats of the control group and pair-feeding group for the same period. The same amount of feed, which was administrated to the OLKTF rats of feeding group for α-lipoic acid on the previous day, was administrated to the OLKTF rats of pair-feeding group.
The weight change was observed by weighing the OLKTF rats every three days after weighing the OLKTF on the first day. Then, Table 1 and Fig. 1 shows the averaging results. [Table 1]
Figure imgf000005_0001
* P < 0.05 ** P < 0.05
As shown in Table 1 and Fig. 1. the three experimental groups show little difference in weight on the first day. However, the amount of feed intake in the OLKTF" rats of α-lipoic acid group significantly decreases in comparison with the control group. The weight of the OLKTF rats of α-lipoic acid group is shown to decrease on the 26th day than on the first day. The increase in body weight in α-lipoic acid is shown to be significantly small than that of Pair-fed group. Accordingly, it is suggested that α-lipoic acid of the present invention is highly effective material for treating obesity than other treating methods reducing amount of meals.
Kxample 2: Measuring UCPI mRNA in brown and white adipose tissues
After 26 days, OLKTF rats in control group (n=6), α-lipoic acid group (n=6) and pair-feeding group (n=6) were sacrificed. Then, their brown and white adipose tissues were isolated. After each adipose tissue was homogenized, RNA was isolated by using TR1ZOL solution (Life Technologies Co., Grand Island, NY, USA) with guanidium thiocyanate method using phenol/chloroform. From these RNAs, the degree of mRNA expression of UCPI in brown and white adipose tissues was measured by Northern blot analysis, respectively and quantitative analysis was performed with densitometry. Then the result of brown adipose tissue is shown in Figs. 2a and 2b, and the result of white adipose tissue is shown in Figs. 3a and 3b. As shown in Fig. 2a, the UCPI mRNA expression, which emits energy as heat in brown adipose tissue, significantly increases in feeding group for α-lipoic acid in comparison with control group.
As shown in Figs. 3a and 3b, ALA group express UCPI in white adipose tissue which cannot express UCPI in normal condition. As discussed earlier, α-lipoic acid as anti-obesity agent of the present invention is shown to have anti-obesity effect in OLKTF white rats. The effect results from decrease in ingestion and increase in expression of UCPI which emits energy as heat in brown and white adipose tissues. Accordingly, α-lipoic acid as anti-obesity agent of the present invention can be useful for excellent anti-obesity agent and appetite suppressant to various obese symptoms.

Claims

WHAT IS CLAIMED IS:
1. An anti-obesity agent comprising α-lipoic acid.
2. A composition for treating obesity comprising α-lipoic acid, and a pharmaceutically acceptable carrier and additive.
3. An appetite suppressant comprising α-lipoic acid.
4. A composition for suppressing appetite comprising α-lipoic acid, and a pharmaceutically acceptable carrier and additive.
PCT/KR2002/001072 2001-06-05 2002-06-05 Medicine for treating obesity WO2002098415A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2001-0031394A KR100427637B1 (en) 2001-06-05 2001-06-05 Agent increasing energy expenditure of the cell
KR2001/31394 2001-06-05

Publications (1)

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WO2002098415A1 true WO2002098415A1 (en) 2002-12-12

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107106540A (en) * 2015-10-13 2017-08-29 财团法人峨山社会福利财团 The fat prevention as active ingredient or therapeutic composition comprising alpha lipoic acid and N acetylcysteines

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997010808A1 (en) * 1995-09-20 1997-03-27 Perricone Nicholas V Lipoic acid in topical compositions
EP0935962A1 (en) * 1998-02-10 1999-08-18 BiRD Berolina innovative Research and Development GmbH Use of 5-(1,2-dithiolan-3-yl)valeric acid (alpha-lipoic acid) or its physiologically acceptable salts for treating lipid metabolism disorders
US5962030A (en) * 1997-03-07 1999-10-05 Akesis Pharmaceuticals, Inc. Dietary supplement and method of treatment for diabetic control
WO1999055331A1 (en) * 1998-04-25 1999-11-04 Skw Trostberg Aktiengesellschaft Use of alpha lipoic acid to reduce appetite and/or body weight

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU5725500A (en) * 1999-06-02 2000-12-18 Ashni Naturaceuticals, Inc. A dietary supplement containing vanadyl sulfate, alpha-lipoic acid, and taurine
GB9916536D0 (en) * 1999-07-14 1999-09-15 Scarista Limited Nutritional or pharmaceutical compositions

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997010808A1 (en) * 1995-09-20 1997-03-27 Perricone Nicholas V Lipoic acid in topical compositions
US5962030A (en) * 1997-03-07 1999-10-05 Akesis Pharmaceuticals, Inc. Dietary supplement and method of treatment for diabetic control
EP0935962A1 (en) * 1998-02-10 1999-08-18 BiRD Berolina innovative Research and Development GmbH Use of 5-(1,2-dithiolan-3-yl)valeric acid (alpha-lipoic acid) or its physiologically acceptable salts for treating lipid metabolism disorders
WO1999055331A1 (en) * 1998-04-25 1999-11-04 Skw Trostberg Aktiengesellschaft Use of alpha lipoic acid to reduce appetite and/or body weight

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