Figure S1. Changes in laser Doppler perfusion imaging results before and after NXCL-4950 application.

Figure S2. (a) Hands were placed in iced water for 1.5 min, either before treatment, or after treatment with placebo or active lotion. (b,c) Thermoscan images of (b) untreated hands and (c) hands treated with NXCL-4950 (N) or placebo (P) ROI, region of interest.

Figure S3. (a) Target fingernail used for nailfold capillaroscopy, wih (b) close-up view of nailfold. Microvessel pattern (Left panels) before and (right panels) after application of NXCL-4950, showing changes in both width and colour of vessels.

Figure S4. Nailfold capillaroscopy images from (a) a normal adult and (b) a patient with peripheral vascular disorder. (b) Images acquired (upper panels) before and (lower panels) 30 min after application of NXCL-4950 application. Black arrows indicate areas in which the blood vessel diameter particularly increased after the application of NXCL-4950. Original magnification ×  400.

Figure S5. Output of the MC-500 software, using a datum (pivot) point (indicated by the red circle) and the target point (or white matter) (indicated by the blue circle).

Figure S6. Images of skin from 10 volunterrs 24 h after the NXCL-4950 patch test, which gave a very low irritation score.

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