Medicines In Korea Research Articles

Public value judgments about the criteria for reimbursement of medicines in South Korea

ABSTRACT Objectives This study quantified the public value (PV) of the criteria and sub-criteria in the current drug reimbursement systems in South Korea and examined sociodemographic factors that associated with PV. Methods The Analytic Hierarchy Process (AHP) was used to quantify the PVs of criteria and sub-criteria. We developed a questionnaire to generate pairwise comparison matrices among criteria and sub-criteria. From 27 March to 1 April 2023, we recruited 1,000 study participants using a quota sampling method stratified by age, sex, and region based on Korean census data. Results The PVs for the criteria were highest for clinical usefulness (28.5%), followed by cost-effectiveness (27.1%), budget impact (24.3%), and reimbursement in other countries (20.1%). The sociodemographic characteristics of the participants had a significant impact on the PVs of the criteria. Willingness to pay additional premiums for national health insurance was negatively associated with PV for clinical usefulness and cost-effectiveness and positively associated with PV for reimbursement in other countries. Conclusions The public prioritized clinical usefulness and cost-effectiveness as the main criteria. However, the PVs of the criteria were divergent and associated with sociodemographic factors. Divergent public interests require an evidence-informed deliberative process for reimbursement decisions.

Establishment of Analyzing Method of Fenpropathrin Residue in Angelica dahurica Radix and Osterici Radix

Background: Angelica dahurica Radix and Osterici radix, are perennial herbs belonging to the family Umbelliferae, which were attacked by red spiders, thus fenpropathrin was registered. Fenpropathrin is important in improving productivity and quality of medicinal herbs due to timely pest control. However, residue may likely remain after harvest, and therefore, the residue analysis is important to ensure pesticides safety management. Objective: This study aimed to establish analysis method for fenpropathrin residues in A. dahurica Radix and O. radix using GLC-ECD and GC-MS/MS. Methods: Samples were moisturized with distilled-water and extracted with acetonitrile. The interferences were removed using SPE cartridges and analyzed by GLC-ECD and GC-MS/MS. Results: Based on pre-experiment results, the analysis method was optimized using double-cleanup method (SPE-GCB/NH2 & SPE silica cartridges). Fenpropathrin peak confirmed by GC-MS at the same retention time and with its mass numbers. Nevertheless, the cleanup processes are laborious and require a rather long time. Thus, additional effortless analysis method was developed using the d-SPE method that can apply to highly selective and sensitive GC-MS/MS. The LOD of GC-ECD and GC-MS/MS was 0.1 and 0.01 ng, respectively. While the LOQ was 0.04 mg/kg for both. Linearity (r2) was > 0.998 (GLC-ECD) and 0.999 (GC-MS/MS). The recoveries at three spiking levels ranged 83.6-103.1% and 89.6-98.0% for A. dahurica Radix and O. radix, respectively. Conclusion: Accuracy of the improved method met the standard of the Korean Ministry of Food and Drug Safety. Therefore, the developed methods expected to be used for analyzing pesticide residues in herbal medicines in Korea and other countries.

Chemical Constituents and Their Biological Activities from Genus Styrax.

Plants from the genus Styrax have been extensively used in folk medicines to treat diseases such as skin diseases and peptic ulcers and as an antiseptic and analgesic. Most Styrax species, especially Styrax tonkinensis, which is used as an expectorant, antiseptic, and analgesic in Chinese traditional medicine, could screen resin after external injury. Styrax is also used in folk medicines in Korea to treat sore throat, bronchitis, cough, expectoration, paralysis, laryngitis, and inflammation. Different parts of various Styrax species can be widely employed for ethnopharmacological applications. Moreover, for ethnopharmacological use, these parts of Styrax species can be applied in combination with other folk medicines. Styrax species consist of versatile natural compounds, with some of them exhibiting particularly excellent pharmacological activities, such as cytotoxic, acetylcholinesterase inhibitory, antioxidant, and antifungal activities. Altogether, these exciting results indicate that a comprehensive review of plants belonging to this genus is essential for helping researchers to continuously conduct an in-depth investigation. In this review, the traditional uses, phytochemistry, corresponding pharmacological activities, and structure-activity relationships of different Styrax species are clarified and critically discussed. More insights into potential opportunities for future research are carefully assessed.

National post-market surveillance assessment of veterinary medicines in Korea during 2018-2021

National post-market surveillance assessment of veterinary medicines in Korea during 2018-2021

Effects of Phellinus linteus extract on immunity improvement: A CONSORT-randomized, double-blinded, placebo-controlled trial.

Background:Immunity protects the body from external threats and prevents the development of cancer. Biological response modifiers extracted from natural sources are being actively studied, and the immunostimulatory and anticancer effects of various types of fungi have been reported. However, there are no previous clinical studies on the immune-enhancing effect of Phellinus linteus (PL). Lactate dehydrogenase cytotoxicity assay is a prerequisite in order to get approval for using PL as a raw material in functional supplements and medicines in Korea. However, due to the absence of precedent clinical trials, the use of PL in supplements has been hindered. but there is no precedent clinical trial using it. We conducted a randomized, double-blinded, placebo-controlled trial to confirm the efficacy and safety of PL extract for the improvement of immunity using the lactate dehydrogenase cytotoxicity assay.Methods:A total of 98 subjects were enrolled and randomly assigned to 2 groups. Subjects in the PL and placebo groups received 1000 mg of PL extract and 1000 mg of dextrin per day, respectively (one capsule, twice every day for 8 weeks). The primary outcome measured was the activity of natural killer cells. Secondary outcomes were the levels of TNF-α, IFN-γ, IL-1β, IL-2, IL-6, IL-12, IgG1, IgG2, and IgM. Safety was evaluated using laboratory tests.Results:NK cell activity was significantly increased in the PL group compared to the placebo group (P < .05). Despite the absence of significant changes in secondary outcomes, there was a tendency for improvement in the PL group. PL extract-related adverse outcomes, particularly in liver and renal function, were not observed.Conclusion:PL extract may improve immunity and is safe to be consumed orally.

Concurrent Use of Prescribed OTC · ETC Drugs and Herbal Medicines in South Korea: Exploring Potential Herb-drug Interactions

Herbal medicines have gained a reputation for being efficacious and safe over hundreds of years. Nowadays, people are easily exposed to drugs and herbal medications concurrently. Therefore, it is essential for regulatory authorities and physicians to closely monitor potential herb-drug interactions. The aim of this study was to determine (1) the prevalence of the concurrent use of drugs and herbal medications, (2) demographic and clinical characteristics of concurrent users, (3) risk factors associated with concurrent use, (4) prescription patterns, and (5) potential herb-drug interactions by using a nationwide insurance claims database. We included patients with herbal medicine records in 2010- 2015 from the National Health Insurance Service-National Sample Cohort 2.0. The herbal medicine users were divided into two groups: concurrent users who were prescribed both herbal and drug medications simultaneously and non-concurrent users. The proportion of concurrent use increased steadily from 2.5% in 2010 to 5.2% in 2015, and the growth rate in the elderly population aged 60-79 years was the highest, from 0.7% in 2010 to 2.8% in 2015. Concurrent users in 2015 were prone to be female; old; and have chronic diseases including hypertension (adjusted odds ratio [aOR], 4.89; 95% CI, 4.54-5.27), hyperlipidemia (aOR, 2.01; 1.89-2.14), and diabetes (aOR, 1.81; 1.67-1.98). The most common concurrently used combinations were Gunghatang-aspirin, Ojeoksan-aspirin, and Ojeoksan-atorvastatin. In this study, we investigated the herb-drug combinations that are used concurrently and related characteristics and elucidated the factors related to the concurrent use and the most common concurrently used herb-drug combinations.

BK002 Induces miR-192-5p-Mediated Apoptosis in Castration-Resistant Prostate Cancer Cells via Modulation of PI3K/CHOP.

BK002 consists of Achyranthes japonica Nakai (AJN) and Melandrium firmum Rohrbach (MFR) that have been used as herbal medicines in China and Korea. AJN and MFR have been reported to have anti-inflammatory, anti-oxidative, and anti-cancer activities, although the synergistic targeting multiple anti-cancer mechanism in castration-resistant prostate cancer (CRPC) has not been well reported. However, the drug resistance and transition to the androgen-independent state of prostate cancer contributing to CRPC is not well studied. Here, we reported that BK002 exerted cytotoxicity and apoptosis in CRPC PC3 cell lines and prostate cancer DU145 cell lines examined by cytotoxicity, western blot, a LIVE/DEAD cell imaging assay, reactive oxygen species (ROS) detection, quantitative real-time polymerase chain reaction (RT-PCR), and transfection assays. The results from our investigation found that BK002 showed more cellular cytotoxicity than AJN and MFR alone, suggesting that BK002 exhibited potential cytotoxic properties. Consistently, BK002 increased DNA damage, and activated p-γH2A.X and depletion of survivin-activated ubiquitination of pro-PARP, caspase9, and caspase3. Notably, live cell imaging using confocal microscopy found that BK002 effectively increased DNA-binding red fluorescent intensity in PC3 and DU145 cells. Also, BK002 increased the anti-proliferative effect with activation of the C/EBP homologous protein (CHOP) and significantly attenuated PI3K/AKT expression. Notably, BK002-treated cells increased ROS generation and co-treatment of N-Acetyl-L-cysteine (NAC), an ROS inhibitor, significantly preventing ROS production and cellular cytotoxicity, suggesting that ROS production is essential for initiating apoptosis in PC3 and DU145 cells. In addition, we found that BK002 significantly enhanced miR-192-5p expression, and co-treatment with BK002 and miR-192-5p inhibitor significantly reduced miR-192-5p expression and cellular viability in PC3 and DU145 cells, indicating modulation of miR-192-5p mediated apoptosis. Finally, we found that BK002-mediated CHOP upregulation and PI3K downregulation were significantly reduced and restrained by miR-192-5p inhibitor respectively, suggesting that the anti-cancer effect of BK002 is associated with the miR-192-5p/PI3K/CHOP pathway. Therefore, our study reveals that a combination of AJN and MFR might be more effective than single treatment against apoptotic activities of both CRPC cells and prostate cancer cells.

Improvement of Bronchial Immune Hypersensitivity Reaction Using Extracts from Chrysanthemum morifolium Ramatuelle and Scutellaria baicalensis Georgi.

Chrysanthemum morifolium Ramatuelle and Scutellaria baicalensis Georgi (skullcap) have been used as safe raw materials for drinking or as traditional medicines in Korea. In this study, we investigated the potential therapeutic effects of ovalbumin-induced asthma in a mouse model. After establishing the model, mice were treated with a mixture of chrysanthemum and skullcap extracts at different mixing ratios (6 : 4, 7 : 3, and 8 : 2). Immune cell counts and the production of various inflammatory cytokines were measured using biochemical tests. Among the mixtures tested, the 7 : 3 ratio (CS73) showed the most pronounced effects. CS73 significantly reduced the levels of the inflammatory cytokines interleukin- (IL-) 1β, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-17F, and IL-17E in the serum and bronchoalveolar lavage fluid of asthmatic mice. In addition, CS73 treatment significantly increased the production of IL-2 and interferon-γ and decreased the production of immunoglobulin E, histamine, and thymic stromal lymphopoietin in asthmatic mice compared to the control group. Our results suggest that the combination of chrysanthemum and skullcap extracts, especially at a 7 : 3 ratio, can be used to improve bronchial health and contribute to improved public health.

Analysis of the Korean generic medicine market: Factors affecting the market share of generic medicines.

This study probed the market share of generic medicines by patients’ age and sex, type of medical facilities, route of administration, number of generic brands, market size (drug expenditure), and therapeutic class and investigated factors associated with a high market share of generic medicines in Korea. We analyzed using national health insurance data between 2010 and 2019. The dependent variable was the generic medicine market share, measured as the number of prescriptions and expenditures. Multivariable regression analysis was conducted using the numbers of generic brands, market size by each ingredient and therapeutic class, relative price, the number of prescriptions, and therapeutic class. Total pharmaceutical expenditures have increased due to the high use of single‐source drugs. The number of prescriptions and expenditures for generic medicines were 0.3 billion prescriptions and $7.8 billion, respectively, accounting for 46.5% and 46% of the total market. Multivariate analysis showed that the number of prescriptions (>20 thousand) and the market size of main active ingredients (>$1 million) were associated with an increased market share, whereas the number of generic brands (compared to <3) was associated with reduced generic medicine market share. In conclusion, we found that supply policies to promote the market entry of generic medicines by mandating price consistency between generic medicines and off‐patent original medicines had limitations in increasing the generic medicine market share. Policy should be put in place both to ensure the timely market entry of generic medicines and to promote the use of cheaper generic medicines.

The additive memory and healthspan enhancement effects by the combined treatment of mature silkworm powders and Korean angelica extracts

Silkworm (Bombyx mori) and Korean angelica (KoAg; Angelica gigas Nakai) have been widely used as traditional oriental medicines in Korea, China, and Japan to treat various diseases such as anemia, cold, diabetes, palsy, stroke, etc. Steamed and freeze-dried mature silkworm powder, also known as HongJam (HJ), and extracts of KoAg root (KoAgE) are currently sold in Korea as functional foods to improve memory, cognition, and liver functions. However, the molecular and pharmacological basis for the improvement of brain functions of HJ and KoAgE has not yet been elucidated. This study aimed to elucidate the molecular basis underlying the memory-enhancing effects of HJ and KoAgE and determine whether administration of HJ and KoAgE complexes (HJ+KoAgC) has additive memory and healthspan-enhancing effects. The MCI mouse models generated by intraperitoneal injection of Scopolamine (Sco-IP) were orally administered with HJ and KoAgE alone or as complexes. Their memory-enhancing effects were examined on spatial, fear-aggravated, and social memories and compared with control or Donepezil (Dp) treatment. The activities of mitochondria complex (MitoCom) I-IV and acetylcholinesterase (AChE) and the amounts of ATP in the mouse brains were examined. The Drosophila model was used to investigate lifespan- and healthspan-promoting effects of HJ+KoAgC. Administration of HJ+KoAgC produced more memory-enhancing effects than administration of HJ or KoAgE alone or Dp. The increase in MitoCom I-IV activities and ATP amounts and the decrease in AChE activities in the mouse brains were the molecular basis for the memory enhancement. The greatest improvement in memory and mitochondrial function was observed when the mice were administered the 1:0.8 ratio of HJ+KoAgC. Administration of HJ+KoAgC to Drosophila prolonged the lifespan and the healthspan and increased the amounts of ATP. HJ+KoAgC had superior effects on memory improvement and healthspan extension by increasing mitochondrial activities and ATP amounts in treated animal models.

Risk of Cancer Following the Use of N-Nitrosodimethylamine (NDMA) Contaminated Ranitidine Products: A Nationwide Cohort Study in South Korea.

N-nitrosodimethylamine (NDMA), a known carcinogenic agent, was recently detected in some products of ranitidine. Several studies have investigated the detectability of NDMA, in drugs and their risks. However, only a few epidemiological studies have evaluated cancer risk from the use of such individual drugs. This study investigates the risk of cancer in ranitidine users. We conducted an observational population-based cohort study using the Health Insurance Review and Assessment databases, which contain information about the use of medicines in South Korea. The primary study cohort consisted of ranitidine users (n = 88,416). For controls, we enrolled users of famotidine, another H2-receptor antagonist in which no NDMA has been detected. A 4:1 matched cohort was constructed to compare cancer outcomes of the two groups. Our matched cohort comprised of 40,488 ranitidine users and 10,122 famotidine users. There was no statistical difference in the overall cancer risk between the ranitidine and famotidine groups (7.45% vs. 7.56%, HR 0.99, 95% CI 0.91–1.07, p = 0.716). Additionally, no significant differences were observed in the analysis of 11 single cancer outcomes. We found no evidence that exposure to NDMA through ranitidine increases the risk of cancer.

Application of the Health Technology Assessment in Korean Traditional Medicines.

Background: South Korea is the first Asian country to adopt health technology assessment (HTA) as a tool to support decision-making concerning pricing and reimbursement of drugs in 2007. Korean traditional medicines have been continuously marginalized in the modern paradigm of evidence-based medicine. To nurture Korean medicines, clinical practice guidelines for Korean medicines have been developed through government-led initiatives, and HTAs have been applied for the National Health Insurance coverage of Korean medicines. In this study, 27 diseases were selected for analyzing the evidence development of both clinical and economic values of Korean medicines. Methods: To investigate the status quo in application of HTA in Korean medicines, reports on the cost-effectiveness analysis project comprising 27 Korean medical interventions were reviewed. Results: All the selected studies were trial-based economic appraisals and their effectiveness was estimated with a subjective judgment tool, such as the quality of life measurement or visual analog scale. This study reconfirmed the limitations of Korean medicines, which included a short observation period, nonrandomized controlled trials, small sample size, subjective assessment for efficacy, selection bias, large uncertainty, and lack of evidence. Conclusions: Priorities should be placed on establishing the clinical evidence of Korean medicines, which will serve as the base for expanding the health coverage of Korean medicines and improving satisfaction and reliability of oriental medicines in Korea's health care system. Furthermore, the need to nurture the institutional environment in which both oriental and Western medicines can collaborate in Korea should be emphasized.

Anti-melanogenic effects of hot-water extracts from Torreya nucifera via MAPKs and cAMP signaling pathway on B16F10 cells.

Torreya nucifera is an evergreen tree in the family Taxaceae, the seeds, leaves, and stems of which have long been used as edible products and herbal medicines in Korea. Previous studies of biological activity have shown that T. nucifera has antioxidant and anti-inflammatory effects. However, the effect of T. nucifera leaves on melanogenesis are yet to be studied. In this investigation, we used B16F10 melanoma cells to test the efficacy of T. nucifera leaf hot water extract (TLWE). α-melanocyte stimulating hormone (α-MSH) stimulated B16F10 melanoma cells were treated with various concentrations of TLWE (50, 100, and 200 μg/mL). The results showed that TLWE reduced the melanin content and cellular tyrosinase activity in a concentration-dependent manner. It also inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38) and c-Jun N-terminal kinase (JNK) in the mitogen-activated protein kinase (MAPK) signaling pathway. The compounds catechin and ρ-coumaric acid, which are known to have a whitening effect on skin, were detected by HPLC analysis. These results suggest that TLWE has an anti-melanogenic effect. In addition, the safety of TLWE was tested. The results of the skin irritation test showed that TLWE is harmless to the human skin, even at higher concentrations than those used in the experiment. Therefore, we suggest that the water extract of T. nucifera leaves has potential for use as a skin-whitening agent.

Intestinal anti-inflammatory effects of fuzi-ganjiang herb pair against DSS-induced ulcerative colitis in mice

Ethnopharmacological relevanceFuzi and ganjiang are widely used as traditional Chinese medicines (TCM) in China, Korea, Japan, and many other southeast Asian countries for treating ulcerative colitis (UC), emesis and heart failure for more than 1800 years. However, the underlying mechanism of fuzi, ganjiang and fuzi-ganjiang herb pair is still unclear. In our study, we explored the therapeutic effects of fuzi, ganjiang and fuzi-ganjiang herb pair against dextran sulfate sodium (DSS)-induced UC in mice model, along with the relevant mechanism. Materials and methodsThe contents of each marker compound in fuzi decoction (FD), ganjiang decoction (GD) and fuzi-ganjiang decoction (FGD) were determined using LC-MS/MS. During the experiment, bodyweight changes in each group were monitored every 5 days. On the day of sacrifice, colonic length, disease activity index (DAI) and spleen weight were also evaluated and histopathological examination was performed through hematoxylin & eosin (H&E) staining. The levels of myeloperoxidase (MPO) and inflammatory cytokines in colon tissues were determined by enzyme-linked immunosorbent assay (ELISA), and then the relative mRNA productions of inflammatory mediators, such as MPO, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were measured by real-time polymerase chain reaction (PCR). Involvement of MAPK, STAT3 and NF-κB signaling pathways in the pathogenesis of UC was determined in each group using Western Blot (WB) analysis. ResultsCompared with fuzi and ganjiang single decoction, the content of the alkaloids derived from fuzi (especially the diester alkaloid with strong toxicity, hypaconitine) in fuzi-ganjiang herb pair decoction was reduced. Additionally, the 6-gingerol, which was not found in ganjiang single decoction, was retained in fuzi-ganjiang herb pair decoction. FD, GD, and FGD significantly restored the bodyweight reduction, colon shortening, DAI elevation, splenomegaly and histological score in DSS-induced UC mice. Furthermore, except for the failure of low dosage of ganjiang decoction (GD-L) on IL-17A, all FD, GD and FGD significantly inhibited the production of MPO and inflammatory cytokines, such as IFN-γ, TNF-α, IL-1β, IL-6, IL-10 and IL-17A, and suppressed the relative expression of inflammatory mediators, such as MPO, iNOS and COX-2 mRNA in colon tissues of DSS-induced mice. According to WB analysis, fuzi, ganjiang and fuzi-ganjiang combination inhibited the activation of MAPK, NF-κB and STAT3 signaling pathways. ConclusionsOur study demonstrated that fuzi, ganjiang and fuzi-ganjiang combination possess prominent anti-inflammatory activities against DSS-induced UC mice; the involved mechanism may be related to inhibition the activation of MAPK, NF-κB, and STAT3 signaling pathways.

Consumption of medicines used for gastric acid-related disorders in Australia and South Korea: a cross-country comparison

The study's aim was to compare the use of proton pump inhibitors (PPIs), histamine 2-receptor antagonists (H2RAs) and mucoprotective medicines (MPs) used for gastric acid-related disorders (GARD) in Australia and South Korea (Korea) from 2004 to 2017. Prescription data for PPIs, H2RAs and MPs for Australian outpatients were extracted from the Australian Statistics on Medicines annual reports, with dose-specific and expenditure data obtained from Medicare. Similar data were obtained from Korean National Health Insurance Service claims data. We analysed the volume and expenditure of medicines use annually using the defined daily dose per 1,000 population per day. We calculated which medicines accounted for 90% of use and estimated the proportions of use for low- and high-dose PPIs. While total utilisation for GARD medicines increased over time in both countries, patterns of use differed. Overall, use was somewhat higher in Australia but increased more rapidly in Korea. PPIs were used more extensively in Australia, while more MPs and H2RAs were used in Korea. Expenditure and use of low-dose PPIs is escalating in Korea. There were substantial differences in the use of GARD medicines in Australia and Korea over 14years. Both countries face similar challenges to promote rational medicines use and contain medical care costs. The discrepant prescribing patterns can be attributed to differences in healthcare systems, pharmaceutical policies and demographics. This study provides a baseline to influence more rational use of these medicines. It provides insight into medicines policies for other countries that face similar challenges.

Availability and drug lag of new medicines in South Korea

Abstract Introduction This study aims to capture the availability of new medicines, to measure drug lags for new medicines, and to demonstrate various factors affecting timely availability of new medicines in Korean market. Methods We construct two models for the analysis; logistic and Cox model. First, we provide the logistic regression to analyze the availability of new medicines in Korean market. Second, we are interested in the timely availability of new medicines in Korea. Therefore, we calculated the drug lag between the United States and South Korea, and applied an event history model for a statistical estimation. Results There have been 160 NDAs approved by the FDA in the United States between 2007 and 2015. Among 160 new drugs approved in the United States during the study period, 112 NDAs (70%) were also approved by the MFDS in Korea, while 48 new drugs (30%) are not currently available in the Korean market. In addition, we are interested in the order of timing for market approval for 112 NDAs that approved in both countries. Not surprisingly, 95 NDAs (85%) were approved in the United States, and then approved in Korea, while 17 NDAs (15%) were approved in Korea, and then approved in the United States. Conclusions Compared to the United States, a striking drug lag was observed in Korea. For the new drugs approved between 2007 and 2015, the median approval lag ranged from 1.72 years in 2013 to 5.84 years in 2007. Presence of the manufacturers in Korea and medicines belonging to the antineoplastic agents were not only positively associated with the availability in Korea, but also accelerated the time to approval in Korea compared to the reference. Key messages Compared to the United States, a striking drug lag was observed in Korea. Presence of the manufacturers in Korea were not only positively associated with the availability in Korea, but also accelerated the time to approval in Korea.

기허가 한약제제를 대상으로 한 인지장애 치료 유효 약물 탐색 - 인지장애 임상연구를 위한 예비연구

기허가 한약제제를 대상으로 한 인지장애 치료 유효 약물 탐색 - 인지장애 임상연구를 위한 예비연구

Gastroprotective Effects of Plants Extracts on Gastric Mucosal Injury in Experimental Sprague-Dawley Rats.

Rubus crataegifolius (black raspberry, RF), Ulmus macrocarpa (elm, UL), and Gardenia jasminoides (cape jasmine, GJ) are well known for hundreds of years as folk medicines in China and Korea to treat various gastrointestinal disturbance. The present study evaluated the gastroprotective effects of these plants either single or in combination against HCl/EtOH-induced gastritis and indomethacin-induced ulcer in rat model. Stomach ulcer was induced by oral ingestions of HCl/EtOH or indomethacin. Treatment with RF, UL, and GJ separately or in combination was done 1 h before ulcer induction. On HCl/EtOH-induced gastritis RF, UL, and GJ at a dose of 150 mg/kg showed comparable antigastritis effect (less than 50% inhibition) with lesion index of 94.97±8.05, 108.48±11.51, and 79.10±9.77 mm compared to cimetidine (45.33±23.73 mm). However, the combination of RF, UL, and GJ at a dose of 150 mg/kg with a ratio of 50:50:50 showed remarkable antigastritis effect with 77% inhibition. The observed lesion index at a ratio of 50:50:50 was 23.34±9.11 mm similar to cimetidine (18.88±19.88 mm). On indomethacin-induced ulcer, RF and GJ showed 38.28% and 51.8% inhibition whereas UL showed around 17.73% inhibition at 150 mg/kg. Combination of RF, UL, and GJ at 150 mg/kg showed strong antigastritis effect with 83.71% inhibition. These findings suggest strong gastroprotective effect of combined extract. In addition, these plants showed significant antioxidant activity in DPPH scavenging assay and antilipid peroxidation activity. Combination of black raspberry, elm, and cape jasmine might be a significant systemic gastroprotective agent that could be utilized for the treatment and/or protection of gastritis and gastric ulcer.

Does the Patent Linkage System Prolong Effective Market Exclusivity? Recent Evidence From the Korea-U.S. Free Trade Agreement in Korea.

This study evaluated the effect of the patent linkage system, fully introduced by the Korea-U.S. Free Trade Agreement in 2015, on patent challenges and the effective market exclusivity of new medicines in Korea. We used pharmaceutical approval data and pharmaceutical litigation data to detect new medicines and their counterparts, to collect patent challenges against new medicines, and to calculate effective market exclusivity for new medicines. Then, a nonparametric event history model was applied to statistically explain the duration of the market exclusivity of new medicines. Between 2007 and 2011, a total of 94 new medicines, consisting of 82 new chemical entities and 12 new biologics, were approved. The patent linkage system encouraged patent litigations to occur sooner, with a race to challenge the patents by various generic applicants. However, it was difficult to conclude that patent challenges had a significant impact on the prolongation of effective market exclusivity. The patent linkage system had a neutral effect on the effective market exclusivity of new medicines and encouraged patent challenges without abbreviating effective market exclusivity. In addition, this study highlights an important issue regarding biologics that has not been the subject of market competition, even for patent challenges.

PHP20 - Prescription Drug Use Monitoring to Check for Appropriate Use of Medicines in Korea vs. Japan and Taiwan

Prescription drug use monitoring to check for appropriate use of medicines is to ensure patients to receive appropriate medications for their clinical needs and to be safe from over/under-utilization of medications. This study aimed to compare the drug use monitoring policy between three Asian countries of Korea, Japan and Taiwan. Focusing on real-time drug use monitoring system and incentive/disincentive program for appropriate use of medicines, this study compared three Asian countries (Korea, Japan and Taiwan) based on a review of the literature (Database: Pubmed, Google Scholar, Respective institutional reports written in Korean, Japanese and English). Some sort of a real-time monitoring system is in place in all three countries. Japan collects patients’ drug records and allows physicians to review them for appropriate use. Taiwan has introduced Pharma Cloud in 2014 in order to let physicians access patients’ prescription records for prevention of overuse of medicines including duplicate prescriptions. Korea has implemented a real time drug utilization review (DUR) system to monitor for duplicate prescriptions and contraindicated combination drug therapy. Japan in 2016 has provided clinicians some incentives in place to monitor for polypharmacy. Taiwanese National Health Insurance Administration (NHIA) monitors for excessive prescribing/polypharmacy in drug therapy management of chronic diseases. NHIA adjusts medical reimbursement when physicians do not improve medication overuse. Korea in 2012 has implemented an incentive program for clinicians as well as for patients on drug therapy management of chronic diseases. Each country has a real-time drug use monitoring system and incentive/disincentive program in place to check for appropriate use of medicines. The real-time DUR system of Korea needs to include patients’ health records so that physicians’ prescribing practices improve in quality. Incentive program in Korea needs to relate effectively with quality evaluation.