Efficacy of mecasin for treatment of amyotrophic lateral sclerosis: A phase IIa multicenter randomized double-blinded placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder characterized by progressive paralysis of voluntary muscles. Mecasin, the extract of modified jakyakgamchobuja-tang-a herbal preparation comprising of Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Aconiti Lateralis Preparata, Radix Salviae Miltiorrhizae, Rhizoma Gastrodiae, Radix Polygalae, Curcuma Root, Fructus Chaenomelis, and Rhizoma Atractylodis Japonicae-shows neuroprotective and anti-neuroinflammatory effects and alleviates the symptoms in patients with ALS. AIM OF THE STUDY: This trial aimed to evaluate the efficacy and safety of mecasin in these patients. MATERIAL AND METHODS: Patients were randomized to receive mecasin 1.6 g daily, mecasin 2.4 g daily, or placebo for 12 weeks. The primary endpoint was the Korean version of ALS Functional Rating Scale-Revised (K-ALSFRS-R) score. The secondary endpoints were muscular atrophy measurements, pulmonary function test results, creatine kinase levels, body weight, safety, and scores of the Medical Research Council (MRC) scale for muscle strength; Visual Analog Scale for pain (VAS pain); Hamilton Rating Scale for Depression; and Fatigue Severity Scale. RESULTS: Among the 30 patients randomized, 24 completed the follow-up. Significant between-group differences were detected in the primary endpoint using the omnibus F-test. The changes in the K-ALSFRS-R score between 12 weeks and baseline were -0·25, -1·32, and -2·78 in the mecasin 1.6 g, mecasin 2.4 g, and placebo groups, respectively. The difference in the K-ALSFRS-R score between the mecasin 1.6 g and placebo groups was 2·53 points (95% confidence interval [CI]: 0·61-4·45), and that between the 2.4 g and placebo groups was 1·46 points (95% CI: 0·48-3·40). However, no significant differences were detected in the secondary endpoints (MRC: dyspnea, p = 0·139; VAS pain, p = 0·916; forced vital capacity, p = 0·373). The incidence of adverse events was similar and low in all groups. CONCLUSIONS: Mecasin may retard symptomatic progression without major adverse effects. A phase IIb study to evaluate its long-term effects in ALS is ongoing.

26-Week Repeated Dose Oral Toxicity Study of KCHO-1 in Sprague-Dawley Rats.

OBJECTIVES: KCHO-1(Mecasin), also called Gamijakyakgamchobuja-tang originally, is a combination of some traditional herbal medicines in East Asia. This medicine has been used mainly for alleviating neuropathic pains for centuries in Korean traditional medicine. KCHO-1 was developed to treat pain, joint contracture and muscular weakness in patients with amyotrophic lateral sclerosis. This study was carried out to investigate the chronic toxicity of KCHO-1 oral administration in rats for 26 weeks. METHODS: Sprague-Dawely rats were divided into four groups and 10 rats were placed in the control group and the high-dose group, respectively. Group 1 was the control group and the remaining groups were the experimental groups. In the oral toxicity study, 500 mg/kg, 1,000 mg/kg, and 2,000 mg/kg of KCHO-1 were administered to the experimental group, and 10 ml/kg of sterile distilled water was administered to the control group. Survival rate, body weight, feed intake, clinical signs, and visual findings were examined. Urinalysis, ophthalmologic examination, necropsy, organ weight, hematologic examination, blood chemical examination and histopathologic examination were performed. RESULTS: Mortality and toxicological lesions associated with the administration of test substance were not observed in all groups. CONCLUSION: NOAEL(No observed adverse effect level) of KCHO-1 is higher than 2000 mg/kg/day. And, the above findings suggest that treatment with KCHO-1 is relatively safe.

Analytical Method Validation of Gamijakyakgamchobuja-Tang (KCHO-1, Mecasin) Preparation.

Previous studies have confirmed that KCHO-1 (Mecasin) was developed to alleviate the symptoms of Amyotrophic Lateral Sclerosis (ALS). And its toxicity test has also been carried out. The aim of this study is confirming the validation and stability of concentration analysis method of the Mecasin preparations using HPLC. As a conclusion, we found that the preparations at the concentrations of 50mg/ml and 200mg/ml in sterilized distilled water were homogeneous and it was stable for 4 hours at room temperature and 7 days refrigerated condition (2~8°C). And this method for analyzing the concentration of the Mecasin preparations has been found to be suitable. This study is helpful to promote development of reliable manufacturing medicine and good researches through definitive quality control of Mecasin as complex herbal medicine, aiming to provide help for the treatment of ALS.

Case Series Study on the Use of BU Pharmacopuncture Treatment in Patients with Acute Lumbar Sprain.

OBJECTIVE: The purpose of this study was to investigate the clinical effects of BU pharmacopuncture therapy consisting of bear's gall(fel ursi) and ox bezoar(bovis calculus) on acute lumbar sprain. METHODS: 12 patients diagnosed as acute lumbar sprain in 6 designated local Korean medicine clinics from October 2017 to February 2018 were treated by BU pharmacopuncture. Several acupoints in abdomen and lumbar region were selected by clinicians at their own discretion. The effectiveness of the therapy was evaluated using VAS and ODI. After that we reviewed the medical records of all these patients to evaluate the effectiveness and safety of the therapy. RESULTS: The VAS and ODI scales were significantly decreased after BU pharmacopuncture therapy. And no major complications and adverse effects were reported. CONCLUSION: BU pharmacopuncture showed rapid pain relief in patients with acute lumbar sprain. It is possible to shorten the treatment period of acute lumbar sprain and prevent progressing to chronic back pain in advance. To establish the effects of BU pharmacopuncture therapy, more succeeding clinical and laboratory studies are needed.

The Use of Korean Medicine to Treat Patients with Spinobulbar Muscular Atrophy, Kennedy's Disease - A Case Study.

OBJECTIVES: Studies involving patients with spinobulbar muscular atrophy (SBMA), which is often referred to as Kennedy's disease, similar to those involving patients with progressive muscular disease (PMD), are rare. This paper reports a case study involving the use of Korean medicine to treat a patient with SBMA. METHODS: We treated a patient with SBMA with unique symptoms by using various kinds of pharmacopuncture and herbal medicines for about two and a half years. After the treatment had ended, we evaluated the patient's conditions and the side effects of the treatment. RESULTS: After treatment, the patient's symptoms were stabilized, and the patient suffered no abnormalities or side effects. No special changes in condition were noted during treatment period, and the patient was very satisfied with his response to treatment. CONCLUSION: Existing treatments have some considerable after effects and are difficult to apply in domestic clinics. In this regard, our findings should open possibilities for new clinical guidelines. Nevertheless, the limitations associated with this case study should be resolved, and more studies need to be conducted.

Study on the Single Dose Toxicity of ShinEumHur Pharmacopuncture Injected into the Muscles of Rats.

OBJECTIVES: This study was carried out to analyze the single dose toxicity of ShinEumHur (SEH) pharmacopuncture injected into the muscles of Sprague-Dawley rats. METHODS: The SEH pharmacopuncture was made in a clean room at the Korean Pharmacopuncture Institute (K-GMP). After the mixing process with sterile distilled water had been completed, the pH was controlled to between 7.0 and 7.5. All experiments were conducted at Biotoxtech, an institution authorized to perform non-clinical studies under the Good Laboratory Practice (GLP) regulations. Sprague-Dawley rats were chosen for the pilot study. Doses of SEH pharmacopuncture, 0.25, 0.5 and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. We examined the survival rate, weights, clinical signs, mean hematology parameters, mean clinical chemistry, necropsy and histopathological findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. RESULTS: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. CONCLUSION: The above findings suggest that treatment with SEH pharmacopuncture is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

Single-dose Toxicity of ShinYangHur Herbal Acupuncture.

OBJECTIVES: This study was carried out to analyze the single-dose toxicity of ShinYangHur (SYH) herbal acupuncture injected into the muscles of Sprague-Dawley (SD) rats. METHODS: The SYH herbal acupuncture was made in a clean room at the Korean Pharmacopuncture Institute (KPI, Korea-Good Manufacturing Practice, K-GMP). After the mixing process with sterile distilled water, the pH was controlled to between 7.0 and 7.5. Then, NaCl was added to make a 0.9% isotonic solution by using sterilized equipment. All experiments were conducted at Biotoxtech, an institution authorized to perform non clinical studies under the regulations of Good Laboratory Practice (GLP). SD rats were chosen for the pilot study. Doses of SYH herbal acupuncture, 0.25, 0.5, and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. RESULTS: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To check for abnormalities in organs and tissues, we used microscopy was used to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. CONCLUSION: The above outcomes suggest that treatment with SYH herbal acupuncture is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

Toxicity of Eun-bi San Pharmacopuncture Injection in the Muscle of Rats.

OBJECTIVES: This study was carried out to analyze the single-dose toxicity of Eun-Bi San pharmacopuncture injected into the muscle of Sprague-Dawley (SD) rats. METHODS: All experiments were performed at Biotoxtech, an institution certified to conduct non-clinical studies under the Good Laboratory Practice (GLP) regulations. Six week old SD rats reared by ORIENTBIO were chosen for this pilot study. The reason SD rats were chosen is that they have been widely used in safety tests in the field of medicine, so the results can be easily compared with many other databases. The Eun-Bi San pharmacopuncture was made in a clean room at the Korean Pharmacopuncture Institute (KPI, K-GMP). The constituents of the Eun-Bi San pharmacopuncture are Angelicae gigantis radix, Strychni semen and Glycyrrhizae radix. These were extracted at low temperature and low pressure in an aseptic room at the KPI. Doses of Eun- Bi San pharmacopuncture, 0.25, 0.5 and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was performed under the approval of the Institutional Animal Ethics Committee of Biotoxtech Co., Ltd. RESULTS: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To determine if abnormalities existed in any organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. CONCLUSION: The results of this study suggest that treatment with Eun-Bi San pharmacopuncture is relatively safe and that its clinical use may be beneficial. Further evaluations and studies on this subject will be needed to provide more concrete evidence in support of these conclusions.

A 4-week Repeated dose Oral Toxicity Study of Mecasin in Sprague-Dawley Rats to Determine the Appropriate Doses for a 13-week, Repeated Toxicity Test.

OBJECTIVES: In this study, we investigated the 4-week repeated-dose oral toxicity of gami-jakyak gamcho buja decoction (Mecasin) to develop safe treatments. METHODS: In order to investigate the 4-week oral toxicity of Mecasin, we administered Mecasin orally to rats. Sprague-Dawley (SD) rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of Mecasin of 500, 1,000, and 2,000 mg/kg of body weight were administered to the experimental groups, and a dose of normal saline solution of 10 mL/kg was administered to the control group. We examined the survival rate, weight, clinical signs, and gross findings for four weeks. This study was conducted under the approval of the Institutional Animal Ethics Committee. RESULTS: No deaths occurred in any of the four groups. No significant changes in weights or food consumption between the control group and the experimental groups were observed. Serum biochemistry revealed that some groups showed significant decrease in inorganic phosphorus (IP) (P < 0.05). During necropsy on the rats, one abnormal macroscopic feature, a slight loss of fur, was observed in the mid dosage (1,000 mg/ kg) male group. No abnormalities were observed in any other rats. In histopathological findings, the tubular basophilia and cast of the kidney and extramedullary hematopoiesis of the spleen were found. However, those changes were minimal and had occurred naturally or sporadically. No other organ abnormalities were observed. CONCLUSION: During this 4-week, repeated, oral toxicity test of Mecasin in SD rats, no toxicity changes due to Mecasin were observed in any of the male or the female rats in the high dosage group. Thus, we suggest that the doses in a 13-week, repeated test should be 0, 500, 1,000, and 2,000 mg/kg respectively.