KR-20260067327-A - ANTIVIRAL PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OR PREVENTION OF PORCINE EPIDEMIC DIARRHEA VIRUS, METHOD FOR PREPARING THE SAME, AND METHOD FOR TREATING OR PREVENTING PORCINE EPIDEMIC DIARRHEA VIRUS USING THE SAME

KR20260067327AKR 20260067327 AKR20260067327 AKR 20260067327AKR-20260067327-A

Abstract

According to one embodiment, an antiviral pharmaceutical composition for the treatment or prevention of porcine epidemic diarrhea virus (PEDV) comprising a drug GS-441524 and a clay-based drug delivery system may be provided, and a method for preparing the same may be provided. Additionally, a method for treating or preventing PEDV may be provided using the above antiviral pharmaceutical composition for the treatment or prevention of PEDV.

Inventors

김재환
강일모
서성만
김원일
김대영
노상건

Assignees

한국지질자원연구원

Dates

Publication Date: 20260512
Application Date: 20251029
Priority Date: 20241105

Claims (13)

A drug represented by the following Formula 1; and clay-based drug delivery systems An antiviral pharmaceutical composition for the treatment or prevention of porcine epidemic diarrhea virus (PEDV) comprising [Equation 1]
In paragraph 1, The clay-based drug delivery system described above is, Illite, sericite, bentonite, smectite, montmorillonite, notronite, saponite, mica, muscovite, lepidolite, biotite, kaolinite, dikite, nacrite, halloysite, vermiculite, chlorite, clinochlore, chamosite, cookeite, ripidolite, sudoite, baileychlore, borocookeite, donbassite, pennantite, zeolite, and Containing one or more of diatomites, Antiviral pharmaceutical composition for the treatment or prevention of PEDV.
In paragraph 1, The drug represented by Formula 1 above is included in an amount of 14 to 34 weight percent based on the total weight of the antiviral pharmaceutical composition for the treatment or prevention of PEDV, and The clay-based drug delivery system is included in an amount of 66 to 86 weight percent relative to the total weight of the antiviral pharmaceutical composition for the treatment or prevention of PEDV, Antiviral pharmaceutical composition for the treatment or prevention of PEDV.
In paragraph 1, The weight ratio of the clay-based drug delivery system and the drug represented by Formula 1 is 2:1 to 6:1, Antiviral pharmaceutical composition for the treatment or prevention of PEDV.
In paragraph 1, The weight ratio of the clay-based drug delivery system and the drug represented by Formula 1 is 4:1, Antiviral pharmaceutical composition for the treatment or prevention of PEDV.
A step of preparing a drug solution by dissolving a drug represented by Formula 1 below in a solvent; A step of preparing a suspension comprising a clay-based drug delivery system; and A step of mixing the above drug solution and the suspension comprising the above clay-based drug delivery system including, Method for preparing an antiviral pharmaceutical composition for the treatment or prevention of PEDV. [Equation 1]
In paragraph 6, The above solvent comprises one or more of dimethyl sulfoxide (DMS0), dimethylformamide (DMF), acetonitrile, methanol, ethanol, purified water, physiological saline, phosphate-buffered saline (PBS), glycerol, ethanol, and polyethylene glycol (PEG). Method for preparing an antiviral pharmaceutical composition for the treatment or prevention of PEDV.
In paragraph 6, The drug represented by Formula 1 above is included in an amount of 14 to 34 weight percent based on the total weight of the antiviral pharmaceutical composition for the treatment or prevention of PEDV, and The clay-based drug delivery system comprises 66 to 86 weight percent of the total weight of an antiviral pharmaceutical composition for the treatment or prevention of PEDV, Method for preparing an antiviral pharmaceutical composition for the treatment or prevention of PEDV.
In paragraph 6, The weight ratio of the clay-based drug delivery system and the drug represented by Formula 1 is 2:1 to 6:1, Method for preparing an antiviral pharmaceutical composition for the treatment or prevention of PEDV.
In paragraph 6, The weight ratio of the clay-based drug delivery system and the drug represented by Formula 1 is 4:1, Method for preparing an antiviral pharmaceutical composition for the treatment or prevention of PEDV.
A step comprising administering the antiviral pharmaceutical composition for the treatment or prevention of PEDV described in claim 1 to a subject other than a human, Methods for treating or preventing PEDV.
In Paragraph 11, The step of administering the above antiviral pharmaceutical composition for the treatment or prevention of PEDV comprises the step of orally administering 1 to 3 capsules of the above antiviral pharmaceutical composition per day at a concentration of 80 to 120 mg/capsule. Methods for treating or preventing PEDV.
In Paragraph 11, The step of administering the above antiviral pharmaceutical composition for the treatment or prevention of PEDV is A step comprising the first administration of an antiviral pharmaceutical composition within 3 days after infection of the subject with porcine epidemic diarrhea virus, Methods for treating or preventing PEDV.

Description

Antiviral pharmaceutical composition for the treatment or prevention of porcine epidemic diarrhea virus, method for preparing the same, and method for treating or preventing PEDV using the same The following various embodiments relate to an antiviral pharmaceutical composition for the treatment or prevention of porcine epidemic diarrhea virus (PEDV) comprising a clay-based drug delivery system, a method for preparing the same, and a method for the treatment or prevention of porcine epidemic diarrhea virus using the same. Porcine epidemic diarrhea virus (PEDV) is a coronavirus that infects the cells lining the small intestine of pigs. The virus replicates in the epithelial cells of the small and colon, as well as in the mesenteric lymph nodes, causing severe diarrhea and dehydration. Although PEDV occurs regardless of the age of the pig, piglets, in particular, exhibit a very high mortality rate, generally dying within five days of infection. Due to its high transmissibility, it causes significant economic losses to the global pig industry. Transmission of PEDV primarily occurs via the fecal-oral route, and feces, vomit, or contaminated objects (such as transport trailers and feeders) can serve as major sources of transmission. It takes approximately 7 to 9 days for the virus to be shed from infected pigs. PEDV remains stable in environments ranging from 4°C to a maximum of 60°C, after which it begins to lose infectivity. Therefore, the porcine epidemic diarrhea virus can survive in various farm environments depending on temperature, pH, and humidity. Meanwhile, GS-441524 is a nucleoside analog antiviral developed by Gilead Sciences. It is a major plasma metabolite of the antiviral prodrug remdesivir and is known as an effective treatment for feline coronavirus, which causes feline infectious peritonitis (FIP). GS-441524 is activated after intracellular metabolism into triphosphate, which serves as a pseudo-substrate for viral RNA-dependent RNA polymerase, thereby acting as an inhibitor that functions as the termination sequence of the viral RNA chain. Consequently, GS-441524 triphosphate interferes with the viral transcription process, preventing the virus from replicating further. Meanwhile, bentonite is a layered silicate mineral formed by the transformation of volcanic ash and is composed mainly of smectite minerals, as well as clay of montmorillonite minerals. Its microstructure consists of stacked plate structures. Each plate is composed of three sandwiched layers : a central octahedral alumina ( Al₂O₃ ) layer and two tetrahedral silica ( SiO₂ ) layers. The characteristics of bentonite include a large interlayer space, cation exchange capacity, antimicrobial activity, drug transport and release, swelling and hygroscopicity, gel formation, and the ability to act as cell center adsorption sites that enhance cell attachment and cell proliferation. Currently, the utilization of these clay minerals as raw materials for pharmaceuticals in Korea is relatively low. Although bentonite is deposited in significant quantities domestically, it contains impurities such as quartz, feldspar, mica, iron oxides, and silica hydrate, and has a low montmorillonite content, so it is used only restrictively for purposes such as molding sand, binders, and civil engineering. However, recently, attempts have been made to develop basic materials for pharmaceuticals from mineral resources to turn them into raw materials for medicines. In particular, bentonite is receiving attention as it is expected to be utilized as a high-value mineral resource of the future. Many antiviral drug candidates for PEDV have been proposed and their efficacy has been proven through cell experiments, but it is necessary to verify their efficacy in actual target animals, and there is also a need to develop drug adjuvants or administration methods to maximize the efficacy of the drug in oral administration. Figure 1 is the result of measuring the daily weight gain for one embodiment. FIG. 2 is a figure showing (a) fecal virus concentration and (b) fecal score evaluation results for one embodiment. Figure 3 is a diagram showing (a) fecal virus concentration and (b) fecal score results for Comparative Example 1. Figure 4 is a diagram showing (a) fecal virus concentration and (b) fecal score results for Comparative Example 2. Figure 5 is a diagram showing the results of the intestinal virus titer evaluation for one example and a comparative example. Figure 6 is a figure showing the villus length to crypt length ratio (Villus:Crypt ratio) for one embodiment and a comparative example. Figure 7 is a diagram showing the results of an antiviral titration assay for one embodiment. Figure 8 is a diagram showing the results of the cytotoxicity evaluation (MTT assay) of the drug GS-441524 against the PEV virus. Figure 9 is a diagram showing the results of evaluating the daily weight gain for one example and a comparative example. Figure 10 is a diagram showing the