string temp_str = "111,222,333,111,444,222";
temp_str = string.Join(",", Regex.Split(temp_str, @"[，,]").Distinct());//111,222,333,444

<script type="text/javascript" language="javascript">
    $(document).ready(
      function() {
        $('#txt_test').keyup(
          function() {
            var txt = $('#txt_test').val();
            var str = new Array();
            str = txt.split(",");
            var strc = txt.substring(txt.lastIndexOf(',') + 1, txt.length);
            for (var i = 0; i < str.length - 1; i++) {
              if (str[i] == strc) {
                alert(strc);
                var txt1 = txt.replace(txt.substring(txt.lastIndexOf(','), txt.length), "");
                $('#txt_test').val(txt1);
                break;
              }
            }
          }
        )
      }
    )
</script>

<asp:TextBox ID="txt_test" runat="server" TextMode="MultiLine"></asp:TextBox>