• Journal of Pharmaceutical Investigation
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• 제40권1호
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• pp.33-38
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• 2010

Sibutramine is a serotonin-norepinephrine reuptake inhibitor indicated for the management of obesity in conjunction with a reduced calorie diet. The oral administration of sibutramine is followed by its dose-related side effects. In this study, sibutramine was formulated into drug in adhesive (DIA) patches in an attempt to overcome these problems. The effects of different formulation variables including pressure-sensitive adhesive (PSA), loading amount of drug, thickness of matrix and enhancer on the skin permeation of the drug were evaluated using excised hairless mouse skin. In the acrylic adhesive with carboxyl functional group, low release of sibutramine was observed due to the strong interaction between carboxyl group of adhesive and amine group of sibutramine. The acrylic adhesive without functional group provided good adhesion force and allowed high drug loading. Changing drug load as well as thickness of the matrix was found to alter permeation rate. $Crovol^{(R)}$ PK40 and $Crovol^{(R)}$ A40, were found to be effective enhancers for sibutramine. The optimized patch contained 20% sibutramine, and 5% $Crovol^{(R)}$ A40 as permeation enhancer, in $80\;{\mu}m$ thick Duro-$Tak^{(R)}$ 87-9301 matrix.

• 대한임상독성학회지
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• 제10권2호
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• pp.111-117
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• 2012

Purpose: In Korea, few studies have examined the acute toxicity of anti-obesity drugs. The purpose of this study is to analyze the general characteristics and clinical aspect of acute anti-obesity drug intoxication. Methods: We retrospectively investigated patients admitted to the emergency department after anti-obesity drug intoxication between March, 2004 and February, 2012. The medical records of these patients were reviewed for demographic data, toxicologic history, time elapsed to presentation, clinical symptoms and signs, treatment, and outcome. Results: There were a total of 18 anti-obesity intoxication cases during the study period; of 16 which were included in our study. The purchasing route of the anti-obesity drug was mainly through a doctor's prescription (68.8%), however, some were obtained through the internet and the pharmacies. The mean time to The most commonly ingested antiobesity drug was sibutramine (31.3%) and many of the cases (62.5%) were multi-drug ingestions. The most common clinical manifestations were gastrointestinal symptoms (94%), but, CNS symptoms (75%) and cardiovascular symptoms (75%) were almost equally present. 13 patients (81%) were discharged after clearance of toxic symptoms and signs with a mean observational period of 7.0 hours. 3 patients were admitted for observation and treatment; of which 1 patient died due to fatal complications. Conclusion: Most anti-obesity intoxications show mild toxicity and a nonfatal clinical course. However, the recent trend toward prescribing psychostimulant anti-obesity medication, which can be fatal after an acute overdose, calls physicians' attention to treating of anti-obesity intoxications.

• 대한의생명과학회지
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• 제24권4호
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• pp.341-348
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• 2018

The polyherbal drug Gyeongshingangjeehwan 18 (GGEx18) from Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae) has traditionally been used as an antiobesity drug in Korean local clinics. This study investigates the effects of GGEx18 on pancreatic fibroinflammation in high-fat diet (HFD)-fed obese C57BL/6J mice and the molecular mechanism involved in this process. After HFD-fed obese C57BL/6J mice were treated with GGEx18 (125, 250, and 500 mg/kg) for 12 weeks, variables and determinants of obesity, pancreatic inflammation, and fibrosis were measured using histology, immunohistochemistry, and real-time polymerase chain reaction. Administration of GGEx18 at 500 mg/kg/day to obese mice decreased body weight gain, mesenteric adipose tissue mass, and adipocyte size. GGEx18 treatment not only reduced mast cells and CD68-immunoreactive cells, but also decreased collagen levels and ${\alpha}$-smooth muscle actin-positive cells in the pancreas of HFD-fed mice. Concomitantly, GGEx18 decreased the expression of genes for inflammation (i.e., CD68 and tumor necrosis factor ${\alpha}$) and fibrosis (i.e., collagen ${\alpha}1$ and transforming growth factor ${\beta}$) in the pancreas of obese mice. These results suggest that GGEx18 may inhibit visceral obesity and related pancreatic fibroinflammation in HFD-fed obese mice.

• 비만대사연구학술지
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• 제1권1호
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• pp.43-45
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• 2022

Intensive lifestyle modifications and anti-obesity medications are essential for obesity treatment. Antiobesity medications should be selected according to the patient's comorbidities, symptoms, and preferences. This case report describes the treatment of a morbidly obese patient with a history of depression, who complained of tingling and numbness after total thyroidectomy for papillary thyroid cancer. Very low-dose controlled-release phentermine/topiramate was prescribed and intensive lifestyle modifications were encouraged. As a result, the patient effectively lost weight and reached a near-normal weight without adverse drug effects. This implies that even an off-label anti-obesity medication low dose may be better for some patients, and the most important factor in obesity treatment is patient-tailored treatment.

• 비만대사연구학술지
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• 제2권1호
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• pp.17-24
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• 2023

Obesity is a major public health problem worldwide, with several methods having been proposed as a means of weight loss. If diet, exercise, and medication are insufficient, a healthcare professional may suggest weight loss treatments, including bariatric surgery or medical devices. Antiobesity medical devices are an option for patients who do not want to undergo bariatric surgery. Compared with bariatric surgery, medical devices have the advantage of being reversible and easier to operate. The U.S. Food and Drug Administration (FDA) regulates medical devices, including those used for weight loss and weight management. This article provides an overview of the FDA-regulated weight loss and weight management devices.

• 한국식품영양과학회지
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• 제38권11호
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• pp.1522-1527
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• 2009

우리는 고지방식이에 의해 유도된 비만 마우스의 몸무게, 부고환 지방조직 무게, 부고환 지방조직의 지방세포 크기 및 혈장 지질 농도에 약용식물 물 추출물들(MPWEs) 혼합식이가 어떤 영향들을 미치는지 연구하였다. MPWEs 혼합식이의 항비만 효과를 알아보기 위하여 C57BL/6J 마우스는 11주 동안 고지방식이를 섭취시켰다. 마지막 6주 동안, 계속해서 고지방식이(HFD)만 섭취시키거나 고지방식이에 MPWEs(5 g/kg, HFD＋MPWEs)이나 고지방식이에 orlistat[0.5 g/kg, HFD＋orlistat(항비만 약)]을 섞어 섭취시켰다. HF-free군은 11주 동안 일반 식이를 섭취시켰다. 11주간 고지방식이를 섭취한 군은 일반식이군과 비교하여 혈장 지질 수준, 몸무게, 간 무게 및 부고환 지방조직 무게가 현저하게 증가하였다. MPWEs를 함유하고 있는 식이는 몸무게, 간 무게 및 부고환 지방조직 무게와 마찬가지로 혈장 총콜레스테롤, LDL 콜레스테롤, 중성지방 그리고 혈당 농도를 현저하게 감소시켰다. 혈장 중성지방 수준은 6주 동안 orlistat를 함유한 고지방식이군(HFD＋orlistat)에서 현저히 낮았고 MPWEs를 함유한 고지방식이군(HFD＋MPWEs)의 그것과 유사하였다. 고지방식이군 마우스의 지방세포크기가 일반식이군의 그것에 비해 현저하게 증가하였고, MPWEs와 orlistat(positive control)는 부고환 지방세포 크기를 현저하게 감소시켰으나 orlistat가 MPWEs보다 약간 더 영향력이 있었다. 이들 결과들은 MPWEs 섭취는 몸무게 증가, 지방세포 형성 및 지방세포 크기 증가를 저해함으로써 항비만 효과가 있을 것이라는 것을 시사하고 있다.

• Journal of Applied Biological Chemistry
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• 제65권4호
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• pp.463-469
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• 2022

Cudrania tricuspidata (C. tricuspidata), a medicinal plant widely employed throughout Asia in ethnomedicine, has various bioactive properties, including antidiabetic, antiobesity, antitumor, and anti-inflammatory activities. In addition, the C. tricuspidata root extract reportedly inhibits platelet aggregation. Therefore, we focused on the active substances present in the C. tricuspidata extract. Sanggenon N (SN) is a flavonoid found in the root bark of C. tricuspidata. In the present study, we examined the inhibitory effects of SN on platelet aggregation, phosphoproteins, thromboxane A₂ generation, and integrin αIIbβ3 activity. SN inhibited collagen-induced human platelet aggregation in a dose-dependent manner without cytotoxicity. Furthermore, SN suppressed Ca²⁺ mobilization and influx through associated signaling molecules, such as inositol 1, 4, 5-triphosphate receptor I (Ser¹⁷⁵⁶), and extracellular signal-regulated kinase. In addition, SN inhibited thromboxane A₂ generation and associated signaling molecules, including cytosolic phospholipase A₂ and mitogen-activated protein kinase p38. Finally, SN could inhibit integrin (αIIb/β₃) activity by regulating vasodilator-stimulated phosphoprotein and Akt. Collectively, SN possesses potent antiplatelet effects and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

• Journal of Pharmaceutical Investigation
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• 제40권1호
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• pp.15-21
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• 2010

Sibutramine is an orally administered centrally-acting antiobesity agent and inhibits both noradrenaline(norephinephirine) and serotonin(5-HT) reuptake. These effects are contributed by its active metabolites, M1 and M2. However, as the free base form of sibutramine is an oil form in room temperature, it had the problem of handling and stability. Thus, this drug should be used in the form of acid salt form in the pharmaceutical application. Unfortunately, anhydrous sibutramine hydrochloride is highly hygroscopic and unstable. In order to solve the hygroscopicity of the anhydrous salt form, another sibutramine acid salt form must be developed as a hydrate form. In this study. to overcome these problems, various of sibutramine acid salt forms were prepared with the pharmaceutically available salts such as maleate, esylate, mandelate, camsylate, besylate, salicylate, tartrate, isethionate and malate forms, and their physicochemical properties were investigated. Sibutramine malate was selected for excellent solubility and stability among the listed salt forms above. Its pharmacokinetic parameters were evaluated in rats comparing with sibutramine HCl, resulting in similar parameters. In vitro dissolution study of sibutramine malate-loaded capsule was performed comparison with commercial product ($Reductil^{(R)}$) in pH 1.2, pH 4.0, pH 6.8 and water medium. Our results indicated that there were no significant differences in their dissolution profiles were similar in all tested medium. Thus, sibutramine malate-loaded capsule should be a potential candiate due to its excellent solubility, good stability and biosimilar absorption.

• Journal of Ginseng Research
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• 제39권2호
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• pp.141-147
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• 2015

Background: Adipocytes, which are the main cellular component of adipose tissue, are the building blocks of obesity. The nuclear hormone receptor $PPAR{\gamma}$ is a major regulator of adipocyte differentiation and development. Obesity, which is one of the most dangerous yet silent diseases of all time, is fast becoming a critical area of research focus. Methods: In this study, we initially aimed to investigate whether the ginsenoside Rf, a compound that is only present in Panax ginseng Meyer, interacts with $PPAR{\gamma}$ by molecular docking simulations. After we performed the docking simulation the result has been analyzed with several different software programs, including Discovery Studio, Pymol, Chimera, Ligplus, and Pose View. All of the programs identified the same mechanism of interaction between $PPAR{\gamma}$ and Rf, at the same active site. To determine the drug-like and biological activities of Rf, we calculate its absorption, distribution, metabolism, excretion, and toxic (ADMET) and prediction of activity spectra for substances (PASS) properties. Considering the results obtained from the computational investigations, the focus was on the in vitro experiments. Results: Because the docking simulations predicted the formation of structural bonds between Rf and $PPAR{\gamma}$, we also investigated whether any evidence for these bonds could be observed at the cellular level. These experiments revealed that Rf treatment of 3T3-L1 adipocytes downregulated the expression levels of $PPAR{\gamma}$ and perilipin, and also decreased the amount of lipid accumulated at different doses. Conclusion: The ginsenoside Rf appears to be promising compound that could prove useful in antiobesity treatments.

• Journal of Microbiology and Biotechnology
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• 제34권3호
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• pp.634-643
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• 2024

Juglans mandshurica Maxim. walnut (JMW) is well-known for the treatment of dermatosis, cancer, gastritis, diarrhea, and leukorrhea in Korea. However, the molecular mechanism underlying its antiobesity activity remains unknown. In the current study, we aimed to determine whether JMW can influence adipogenesis in 3T3-L1 preadipocytes and high-fat diet rats and determine the antioxidant activity. The 20% ethanol extract of JMW (JMWE) had a total polyphenol content of 133.33 ± 2.60 mg GAE/g. Considering the antioxidant capacity, the ABTS and DPPH values of 200 ㎍/ml of JMWE were 95.69 ± 0.94 and 79.38 ± 1.55%, respectively. To assess the anti-obesity activity of JMWE, we analyzed the cell viability, fat accumulation, and adipogenesis-related factors, including CCAAT-enhancer-binding protein alpha (C/EBPα), sterol regulatory element-binding protein-1c (SREBP1c), peroxisome proliferator-activated receptor-gamma (PPARγ), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). We found that total lipid accumulation and triglyceride levels were reduced, and the fat accumulation rate decreased in a dose-dependent manner. Furthermore, JMWE suppressed adipogenesis-related factors C/EBPα, PPARγ, and SREBP1c, as well as FAS and ACC, both related to lipogenesis. Moreover, animal experiments revealed that JMWE could be employed to prevent and treat obesity-related diseases. Hence, JMWE could be developed as a healthy functional food and further explored as an anti-obesity drug.