• Journal of Pharmaceutical Investigation
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• 제41권5호
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• pp.279-288
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• 2011

The Dexamethasone (DEX) loaded chitosan microspheres were prepared by thermal denaturation and chemical cross-linking method using a dierent concentration of glutaraldehyde as chemical cross-linking agent. The prepared microspheres were evaluated for the percentage of Drug Loading (DL), Encapsulation Efficiency (EE) and surface morphology by Scanning Electron Microscopy (SEM). DL and EE were found to be maximum range of 10.0 to 10.79 % and 58.19 to 64.73 % respectively. The SEM Photographs of the resultant microspheres exhibited fairly smooth surfaces and predominantly spherical in appearance. In addition, Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) shown that there was no interaction between the drug and polymer. In vitro and in vivo release studies revealed that the release of dexamethasone was sustained and extended up to 63 days and effectively controlled by the extent of cross-linking agent. Non-clinical parameters such as paw volume, hematological parameters like Erythrocyte Sedimentation Rate (ESR), Paced Cell Volume (PCV), Total Leucocytes Count (TLC), Hemoglobin (Hb), Differential Cell Count (DCC) were investigated in Fruend's Complete Adjuvant (FCA) induced arthritic rats. Radiology and histopathological studies were also performed in order to evaluate the therapeutic efficacy of the DEX-loaded microspheres in extenuating the rat arthritic model.

• 생약학회지
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• 제25권4호통권99호
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• pp.363-367
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• 1994

For developing plant anti-inflammatory agents, extracts from Lonicera japonica were obtained and evaluated for their anti-inflammatory and analgesic activities using acute/chronic inflammatory models and writhing tests. It was found that the extracts with a modified extraction method showed higher anti-inflammatory and analgesic activities than those of the extracts based on the ancient literatures.

• 생약학회지
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• 제27권3호
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• pp.282-287
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• 1996

Cnidii rhizoma is one of the most important crude drugs used particularly for the treatment of female genital inflammatory diseases in traditional oriental medicine. In this study, its anti-inflammatory and analgesic activities were examined employing animal models. It was found that $H_2O$ extract and n-BuOH fraction inhibited significantly the edema formation after the subplantar injection of carrageenin at oral doses of 100 and 200 mg/kg in a dose-dependent fashion, where MeOH extract showed significant anti-inflammatory activity at a oral dose of 200 mg/kg. In Freund's complete adjuvant-induced arthritis, H2O extract and n-BuOH fraction exerted their significant inhibitory activity on the edema formation at oral doses of 100 and 200 mg/kg. The $H_2O$ extract and n-BuOH fraction also showed significant analgesic activity in a dose-dependent manner in acetic acid-induced writhing test.

• 대한한의학회지
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• 제23권1호
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• pp.92-99
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• 2002

Objectives : To investigate the role of Meridian flow on acupuncture effect, we observed the therapeutic effects of electroacupuncture (EA) after Meridian blocking with pressure in arthritic rats. Methods : To make reliable and local monoarthritis, $40{\;}{\mu}l$ complete Freund's adjuvant was injected into the tibio-tarsal joint. EA was applied on acupoint GB30 while 5 Pascal pressure was added to the middle of the Gall bladder Meridian around GB31 between acupoint GB30 and arthritic foci (ipsilateral meridian blocking: IB) or opposite part of IB (contralateral part blocking: CB). To observe the change of arthritis, extension and flexion pain scores and circumferential differences were evaluated once a week. Results : EA stimulation without blocking reduced arthritic pain significantly. IB abolished the acupuncture effects and there was no statistical difference with the arthritic control group, whereas the CB group still showed the therapeutic effects of acupuncture. Conclusions : This finding strongly supports that the Meridian blocking with local pressure reduced the therapeutic effect of EA.

• Archives of Pharmacal Research
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• 제21권4호
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• pp.406-410
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• 1998

Biflavonoid is one of unique classes of naturally-occurring bioflavonoids. Certain biflavonoids including amentoflavone were previously reported to have inhibitory effect on the group 11 phospholipase $A_2$ activity. Amentoflavone was also found to inhibit cyclooxygenase from guinea-pig epidermis without affecting lipoxygenase. In this study, anti-inflammatory and analgesic activities of amentoflavone were evaluated. When amentoflavone was administered intraperitoneally, it showed a potent anti-inflammatory activity as determined by amelioration of croton-oil induced mouse ear edema. It also showed a potent anti-inflammatory activity in the rat carrageenan paw edema model ($ED_{50}$=42 mg/kg) compared to the activity of prednisolone (35 mg/kg) and indomethacin (10 mg/kg). However, amentoflavone did not show a significant inhibitory activity against rat adjuvant-induced arthritis, a chronic inflammatory model. In addition, amentoflavone was found to possess a potent analgesic activity in the acetic acid writhing test ($ED_{50}$=9.6 mg/kg) compared to the activity of indomethacin (3.8 mg/kg). These results suggest that amentoflavone may be a potential lead for a new type of anti-inflammatory agents having dual inhibitory activity of group 11 phospholipase $A_2$ and cyclooxygenase.

• Toxicological Research
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• 제30권4호
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• pp.277-282
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• 2014

To develop a composition for enhancing immunity, based on alcohol extracts of the bumblebee as an active ingredient, bumblebee ethanol extracts were evaluated for their protective effect in chronic models of inflammation, adjuvant induced rat arthritis. B. terrestris worker extract (SDIEX) and, B. hypocrita sapporoensis lava and pupa extract (SPDYBEX), significantly decreased paw edema in arthritic rats, at a dose 100 mg/kg, respectively. The cytokine levels related inflammation of COX-2, $sPLA_2$, VEGF, and TNF-${\alpha}$, were decreased, compared to positive control, indomethacin (5 mg/kg). Histopathological data demonstrated decreases inflammatory activity, hind paw edema, and repaired hyaline articular cartilage in DRG over a 2 wk administration. HPLC and GC-MS analysis of SDIEX and SPDYBEX revealed the presence of cantharidin.

• 생약학회지
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• 제34권4호통권135호
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• pp.327-334
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• 2003

We evaluated the anti-arthritic effect of a new diet-supplement product containing red ginseng, glucosamine, shark cartilage, ascorbic acid and manganese chloride for the relieving arthritic symptoms. Anti-inflammatory activities of the aqueous extract of red ginseng (250 and 500 mg/kg), glucosamine (240 mg/kg) and shark cartilage (240 mg/kg) were tested individually on vascular permeability and carrageenan-induced paw edema. Glucosamine and shark cartilage showed the inhibition of vascular permeability by 29.6 and 32.9%, respectively. Red ginseng (500 mg/kg) and shark cartilage showed the inhibition of carrageenan-induced paw edema at 0.5, 1, 2 and 3 hr. The supplement (red ginseng mixture: RGM) composed of red ginseng (43.5%), glucosamine (25.0%), shark cartilage (25.0%), ascorbic acid (5.0%) and manganese chloride (1.5%) was prepared and its inhibitory activities including vascular permeability and carrageenan-induced paw edema were comparable to anti-inflammatory drugs such as diclofenac and ibuprofen. It was also tested on adjuvant-induced arthritis in rats as one of chronic arthritic tests and Randall-Selitto assay as an analgesic test. RGM showed the inhibition against the swelling of rat paws induced by Mycobacterium tuberculosis at a dose of 1,500 mg/kg. Determination of cytokines of the sera sampled from arthritis-induced animals indicated that RGM increased the levels of $interferon-{\gamma}$ and interleukin-6, representing the immunostimulatory effect by red ginseng. RGM treatment moderately reduced the production of NO in RAW 264.7 cells in a dose-dependent manner. Taken together, these results support that RGM can be applicable for the improvement of arthritic as a new diet-supplement.

• 한방재활의학과학회지
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• 제19권2호
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• pp.125-156
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• 2009

Objectives : To research the trend of studies related to rheumatoid arthritis and to indicate the hereafter direction for its study in oriental medicine and its treatment. Methods : I reviewed 75 domestic oriental medical journals, and 50 medical journals about rheumatoid arthritis published after 2004, and comparative analysis was made. And these theses were classified by college, year, field of study, subject. Results : The following are the results of this study. 1. Classified by oriental medical college, Dae-jeon college published the most theses, followed by Dong-guk, Kyung-hee, Se-myung and Dong-shin college. Han-yang college published the most theses among college of medicine. 2. Classified by type of thesis, experimental theses(70 pieces, 94%) showed higher rate than that of clinical theses(4 pieces, 5%) in oriental medical studies. However, in medical studies, clinical theses(34 pieces, 68%) showed higher rate than that of experimental theses(15 pieces, 30%). 3. Analyzed by subject, the most dealt subject in oriental medicine was herb medication, followed by herbal acupuncture, single herb, electroacupuncture, sasang & gene, acupuncture & moxibustion, complex accordingly. The most dealt subject in medical clinical journals was standards of diagnosis & prognosis, followed by medication, gene analysis, pathogenesis, clinical pattern, operative treatment and complication accordingly. 4. In theses related to herb medication, most of the subject was to evaluate anti-inflammatory and immunoregulatory effects of herb medication with geopungseup, jibitong, hwalhyeolgeoer function. The tendency of experimental methods was focusing on understanding anti-inflammatory and immunoregulatory mechanisms through molecular biologic methods by analyzing cytokine and gene. 5. Most of theses related to herbal acupuncture were experimental studies verifying ant-inflammatory and immnoregulatory effects through methods observing change of cytokine and immunoregulatory factors. Regarding remedies for herbal acupuncture, Ulmus davidiana Planch was most preferred, followed by bee venom. 6. In theses related to single herb, Boik-yak was most prefered, followed by Geopungseup-yak and Hwalhyeolgeoer-yak. Regarding methods of research, there were tendency of shifting from methods verifying travail, anti-inflammatory and anti-pyretic effects through a test of behavior, morphometry, serology and temperature measurement of the rectum and the skin into verifying anti-inflammatory and immunoregulatory effects through observing inflammatory cytokine in the joint and cells of spleen. 7. In theses related to electroacupuncture, ST36 and adjuvant were most preferred as acupoints and induced factor. The tendency of experimental methods was turning from verifying mechanism of travail effect to analyzing inflammation and pain inducing factors. 8. Diverse medical clinical studies were published. Subjects such as diagnosis and prognosis, medication, gene analysis, clinical pattern, operational treatment, complication and pathogenesis were published. Especially, studies about standards of early diagnosis, and research on possible parallel medications with methotrexate were actively inquired. 9. Most of theses related to medical experimental studies was about mediators and receptors related to inflammatory induction and osteoclasia mechanism. Also, it was presented blockage of them can be effective on rheumatoid arthritis. Conclusions : The oriental medicine studies have merit in its diversity of treatment, but it clinical studies is lacking compared to experimental studies. Also, more diversity of subjects is necessary. Therefore, complementary measures are needed. Hereafter, oriental medicine research about rheumatoid arthritis needs more clinical research verifying the effectiveness and safety in clinical field. Also, we require oriental medical standard of diagnosis and researches on pathological generation which would make early checkup and prognosis possible.

• Journal of Pharmaceutical Investigation
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• 제31권2호
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• pp.125-130
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• 2001

Bucillamine is a novel cysteine derivative with two free intramolecular sulfhydryl groups, and has a preventive and therapeutic effect on adjuvant arthritis, suggesting its antirheumatic action. With respect to the effect on the immune system, bucillamine-exerted such immunoregulating actions are to nomalize an excessive reduction or acceleration in immune reaction. It is useful not only in patients with early stage of rheumatoid arthritis (RA) but also in those with active RA retained for more than 10 years. The purpose of the present study was to evaluate the bioequivalence of two bucillamine tablets, $Rimatil^{TM}$ (Chong Kun Dang Pharmaceutical Co., Ltd.) and $Bucilin^{TM}$ (Kuhn Il Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $23.67{\pm}2.09$ years in age and $65.03{\pm}6.73\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After three tablets containing 100 mg of bucillamine per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of bucillamine in serum were determined using GC/MS with mass selective detector. Pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, $C_{max}\;and\;T_{max}$ between two tablets were -0.29%, -3.20% and 8.22%, respectively, when calculated against the $Rimatil^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t\;and\;C_{max}$ were 84.31 % and 91.16%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.10$ and $1-{\beta}=0.8$ were less than 20% (e.g., 18.58% and 16.51% for $AUC_t\;and\;C_{max}$, respectively). The 90% confidence intervals were within ${\pm}20%$ (e.g.,$-12.77{\sim}12.20$ for $AUC_t$ and $-14.30{\sim}7.90$ for $C_{max}$). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Bucilin^{TM}$ tablet is bioequivalent to $Rimatil^{TM}$ tablet.

• 대한한의학회지
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• 제28권2호통권70호
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• pp.93-113
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• 2007

Objective : To research Trends of studies about anti-inflammation and pain relief, obesity, and safety of herbal acupuncture therapy by analyzing domestic theses, published since 2001, about herbal acupuncture therapy. Methods : Domestic theses, published since 2001, mentioning anti-inflammation or pain relief, obesity, or safety of herbal acupuncture therapy were reviewed and analyzed. These theses were then classified by university, year, and subject. Results : The following results were obtained in this study. 1. Among published theses related to anti-inflammation effects of herbal-acupuncture, studies about arthritis comprised the most part, 52. In theses relating to causes of arthritis, 16 were about adjuvant, which was the most, followed by Type II collagen, LPS and carrageenan. Blood test, reactions of inflammation and revelation of cytokine and immune cellswere methods for evaluating anti-inflammation effect. The tendency of experimental methods was to focus on molecular biologic method. 2. In theses related to pain relief, many clinical attempts with herbal injection were carried out, and Carthami Flos and Scolopendrawere used most. Observing reduction of pain inducing factor and checking behavioral change were methods for evaluating pain relief. 3. In theses related to obesity, research focused on effects in association with spots on the body suitable for acupuncture. There were also attempts comparing effectiveness between single injections and complex injections. Astraball Radix, Angelica Gigantis Radix, Coicis Semen and Taeumjowetang were used. Evaluation of anti-obesity effects were by weight loss, food efficiency, blood lipid profile and evaluation of liver function. 4. In theses related to safety of herbal-acupuncture, Herba Chelidonii Chaenonelis Fructus, Clematis Florida Thunb, Corydalidis Tuber, Paeoniae Radix, and Carthami Flos which marked 2 theses each were most studied. Methods of evaluating safety were mostly by observing liver and kidney functions based on blood test, and by applying herbal injections to clinical treatment. Conclusion : Herbal acupuncture is being used in various ways associating with its anti-inflammation, pain relief and anti-obesity effect. Studies on efficacy and mechanism of herbal acupuncture are being conducted even at the molecular biology level.