Drugs in R & D

, Volume 5, Issue 2, pp 63–71 | Cite as

Improvement of Cutaneous Microcirculation and Oxygen Supply in Patients with Chronic Venous Insufficiency by Orally Administered Extract of Red Vine Leaves AS 195

A Randomised, Double-Blind, Placebo-Controlled, Crossover Study
  • Ulrich Kalus
  • Juergen Koscielny
  • Alexandre Grigorov
  • Eckhard Schaefer
  • Hubertus Peil
  • Holger Kiesewetter
Original Research Article



To investigate the effect of the red vine leaf extract AS 195 on cutaneous microvascular blood flow, transcutaneous oxygen pressure (tcpO2), and leg oedema in patients with chronic venous insufficiency (CVI).

Design and patients

The study was a randomised, double-blind, placebo-controlled, crossover trial for which 129 men and women, aged ≥18 years, with CVI stage I or II were screened. Seventy-one fulfilled the inclusion criteria and were randomised.


A total of 71 patients were divided into two groups. The first group (n=36) received AS 195 360mg once daily during a first 6-week treatment period, followed by a 4-week placebo washout period and then placebo during the second 6-week treatment period. The second group (n=35) started with placebo and received AS 195 360mg after the placebo washout. The cutaneous microvascular blood flow in the malleolar region was measured using a newly developed laser Doppler device. TcpO2 was measured using a solid-state electrode.


After 6 weeks, patients in the AS 195 group had increased microvascular blood flow values (+241.8±18.7 arbitrary units [AU] versus a decrease of −41.0±18.7AU in the placebo group; p < 0.0001). Oxygen increased to 1.35±0.97mm Hg (placebo: decrease of −7.27±0.97mm Hg; p < 0.0001). After 6 weeks of treatment the leg circumference was decreased (ankle level: by −0.39±0.09cm versus +0.29±0.09cm; p < 0.0001; calf level: by −0.54±0.05cm versus +0.14±0.05cm; p < 0.0001).


The administration of AS 195 improved objective symptoms of CVI and may prevent CVI deterioration.


Hesperidin Isoquercitrin Microvascular Blood Flow Chronic Venous Insufficiency Chronic Venous Insufficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study was funded by Boehringer Ingelheim, Ingelheim am Rhein, Germany. Holger Kiesewetter was the principal investigator and recruited the patients. He contributed to the design and coordinated the study. Day-to-day conduct of the study, record keeping, and assessment of patients was the responsibility of UK, JK and AG. Overall analysis of data and statistical analysis was the responsibility of HP. ES and HP set up the trial protocol and the paper. All authors reviewed both documents and approved the final version.

The clinical investigations were in compliance with the current relevant German laws. HK has a consultancy agreement with the sponsor. ES and HP are employees of the sponsor.


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Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Ulrich Kalus
    • 1
  • Juergen Koscielny
    • 1
  • Alexandre Grigorov
    • 1
  • Eckhard Schaefer
    • 2
  • Hubertus Peil
    • 3
  • Holger Kiesewetter
    • 1
  1. 1.Institute for Transfusion MedicineUniversity Clinic CharitéBerlinGermany
  2. 2.Consumer Health CareBoehringer Ingelheim GmbHIngelheim am RheinGermany
  3. 3.Medical Data ServicesBoehringer Ingelheim Pharma GmbH&Co KGIngelheim am RheinGermany

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