Sodium hydroxide (naoh)

Regorafenib, 4‐[4‐ ({[4‐Chloro‐3‐(trifluoromethyl) phenyl]carbamoyl}amino)‐3‐fluorophenoxy]‐N‐methylpyridine‐2‐carboxamide monohydrate, was purchased from Selleck Chemicals Co., Ltd. and Active Biochem, Ltd.. Pazopanib, 5‐[[4‐[(2,3‐dimethylindazol‐6‐yl)‐methylamino]pyrimidin‐2‐yl]amino]‐2‐methylbenzenesulfonamide hydrochloride was purchased from SYNKinase Co., Ltd. Hydroxypropyl cellulose, sodium dihydrogen phosphate, sodium chloride and sodium hydroxide were purchased from FUJIFILM Wako Pure Chemical Corporation (Osaka, Japan). Light liquid paraffin and benzalkonium chloride were purchased from NACALAI TESQUE, Inc (Kyoto, Japan). Polysorbate 80 and D‐mannitol were purchased from Junsei Chemical Co., Ltd. Captisol was purchased from Ligand Pharmaceuticals, Inc. Aflibercept (40 mg/mL EYLEA^® Injection For Intravitreal Injection) was purchased from Bayer Yakuhin, Ltd. Mydrin‐P ophthalmic Solution was purchased from Santen Pharmaceutical Co., Ltd.. Scopisol solution was purchased from Senju Pharmaceutical Co., Ltd. (Osaka, Japan). Fluorescite Intravenous Injection 500 mg was purchased from Alcon Japan Ltd. (Tokyo, Japan).

The volatile standards used in this study are shown in Additional File 4: Table S1. First, 2,4-dichloroaniline (99.5% purity) was purchased from Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan) for the reagents. However, while n-heptyl β-D-glucopyranoside (98% purity) was purchased from Sigma-Aldrich, Inc. (St. Louis, MO, USA), dichloromethane (99.5% purity), liquid chromatography-mass spectrometry-grade methanol, citric acid, sodium phosphates, sodium fluoride (NaF), ascorbic acid, sodium hydroxide (NaOH) and 3-octanol (97% purity) were obtained from Wako Co. Ltd. (Osaka, Japan).

The medicinal herbs were purchased from Kojima Kampo (Osaka, Japan) in their cut, dried forms. Twenty kinds of medicinal herbs were used in the present study, and the IDs of those are as follows: 1, Glycyrrhizae Radix (Glycyrrhiza glabra Linné); 2, leaves of Stevia rebaudiana; 3, Saussureae Radix; 4, roots of Glycyrrhiza uralensis Fisher; 5, Scutellariae Radix; 6, Armeniacae Semen; 7, Sesami Semen; 8, Lili Bulbus; 9, Epimedii Herba; 10, Cnidii Rhizoma; 11, Polygoni Multiflori Radix; 12, Eriobotryae Folium; 13, Rhei Rhizoma; 14, Artemisiae Folium; 15, Atractylodis Lanceae Rhizoma; 16, Moutan Cortex; 17, Paeoniae Radix; 18, Persicae Semen; 19, Gardeniae Fructus; and 20, Lycium Fructus. Small pieces of herbs were suspended in distilled water to a final concentration of 5% (w/v) and then heat-treated at 105 °C for 30 min. The herbal debris was removed from the extracts by centrifugation, and the obtained supernatants were adjusted to pH 7.0 by adding sodium hydroxide (FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan) solution. After sterilization at 120 °C for 20 min, the extracts were used as cultivation media of the LABs.

Chemicals including calcium nitrate tetrahydrate (Ca(NO₃)₂·4H₂O, 98%), calcium chloride (CaCl₂, 95.0%), diammonium hydrogen phosphate ((NH₄)₂HPO₄, 98%), sodium hydroxide (NaOH, 97%), phosphoric acid (H₃PO₄, 85% aqueous solution), ammonia solution (25% aqueous solution), and acetic acid (99.7%), were purchased from FUJIFILM Wako Pure Chemical Corp., Osaka, Japan. Pyromellitic acid (98.0%) was purchased from Tokyo Chemical Industry Co., Ltd., Tokyo, Japan. Furthermore, calcium carbonate (CaCO₃ (calcite), 99.5%) and hydrochloric acid solution (HCl, 1.0 mol dm⁻³) were purchased from Nacalai Tesque Inc., Kyoto, Japan. All chemicals were used without further purification.