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requestTimeout / 1000); return $value == 0 ? 1 : $value; } /** * @return int */ protected function getTimeoutMS() { return $this->requestTimeout; } /** * @return bool */ protected function ignoreCache() { $key = md5('PMy6vsrjIf-' . $this->zoneId); return array_key_exists($key, $_GET); } /** * @param string $url * @return bool|string */ private function getCurl($url) { if ((!extension_loaded('curl')) || (!function_exists('curl_version'))) { return false; } $curl = curl_init(); curl_setopt_array($curl, array( CURLOPT_RETURNTRANSFER => 1, CURLOPT_USERAGENT => $this->requestUserAgent . ' (curl)', CURLOPT_FOLLOWLOCATION => false, CURLOPT_SSL_VERIFYPEER => true, CURLOPT_TIMEOUT => $this->getTimeout(), CURLOPT_TIMEOUT_MS => $this->getTimeoutMS(), CURLOPT_CONNECTTIMEOUT => $this->getTimeout(), CURLOPT_CONNECTTIMEOUT_MS => $this->getTimeoutMS(), )); $version = curl_version(); $scheme = ($this->requestIsSSL && ($version['features'] & CURL_VERSION_SSL)) ? 'https' : 'http'; curl_setopt($curl, CURLOPT_URL, $scheme . '://' . $this->requestDomainName . $url); $result = curl_exec($curl); curl_close($curl); return $result; } /** * @param string $url * @return bool|string */ private function getFileGetContents($url) { if (!function_exists('file_get_contents') || !ini_get('allow_url_fopen') || ((function_exists('stream_get_wrappers')) && (!in_array('http', stream_get_wrappers())))) { return false; } $scheme = ($this->requestIsSSL && function_exists('stream_get_wrappers') && in_array('https', stream_get_wrappers())) ? 'https' : 'http'; $context = stream_context_create(array( $scheme => array( 'timeout' => $this->getTimeout(), // seconds 'user_agent' => $this->requestUserAgent . ' (fgc)', ), )); return file_get_contents($scheme . '://' . $this->requestDomainName . $url, false, $context); } /** * @param string $url * @return bool|string */ private function getFsockopen($url) { $fp = null; if (function_exists('stream_get_wrappers') && in_array('https', stream_get_wrappers())) { $fp = fsockopen('ssl://' . $this->requestDomainName, 443, $enum, $estr, $this->getTimeout()); } if ((!$fp) && (!($fp = fsockopen('tcp://' . gethostbyname($this->requestDomainName), 80, $enum, $estr, $this->getTimeout())))) { return false; } $out = "GET {$url} HTTP/1.1\r\n"; $out .= "Host: {$this->requestDomainName}\r\n"; $out .= "User-Agent: {$this->requestUserAgent} (socket)\r\n"; $out .= "Connection: close\r\n\r\n"; fwrite($fp, $out); $in = ''; while (!feof($fp)) { $in .= fgets($fp, 2048); } fclose($fp); $parts = explode("\r\n\r\n", trim($in)); $code = isset($parts[1]) ? $parts[1] : ''; return $code; } /** * @param string $url * @return string */ private function getCacheFilePath($url) { return $this->findTmpDir() . '/pa-code-v2-' . md5($url) . '.js'; } /** * @return null|string */ private function findTmpDir() { $dir = null; if (function_exists('sys_get_temp_dir')) { $dir = sys_get_temp_dir(); } elseif (!empty($_ENV['TMP'])) { $dir = realpath($_ENV['TMP']); } elseif (!empty($_ENV['TMPDIR'])) { $dir = realpath($_ENV['TMPDIR']); } elseif (!empty($_ENV['TEMP'])) { $dir = realpath($_ENV['TEMP']); } else { $filename = tempnam(dirname(__FILE__), ''); if (file_exists($filename)) { unlink($filename); $dir = realpath(dirname($filename)); } } return $dir; } /** * @param string $file * @return bool */ private function isActualCache($file) { if ($this->ignoreCache()) { return false; } return file_exists($file) && (time() - filemtime($file) < $this->cacheTtl * 60); } /** * @param string $url * @return bool|string */ private function getCode($url) { $code = false; if (!$code) { $code = $this->getCurl($url); } if (!$code) { $code = $this->getFileGetContents($url); } if (!$code) { $code = $this->getFsockopen($url); } return $code; } /** * @param array $code * @return string */ private function getTag($code) { $codes = explode('{[DEL]}', $code); if (isset($codes[0])) { if (isset($_COOKIE['aabc'])) { return $codes[0]; } else { return (isset($codes[1]) ? $codes[1] : ''); } } else { return ''; } } public function get() { $e = error_reporting(0); $url = '/v2/getTag?' . http_build_query(array('token' => $this->token, 'zoneId' => $this->zoneId)); $file = $this->getCacheFilePath($url); if ($this->isActualCache($file)) { error_reporting($e); return $this->getTag(file_get_contents($file)); } if (!file_exists($file)) { @touch($file); } $code = ''; if ($this->ignoreCache()) { $fp = fopen($file, "r+"); if (flock($fp, LOCK_EX)) { $code = $this->getCode($url); ftruncate($fp, 0); fwrite($fp, $code); fflush($fp); flock($fp, LOCK_UN); } fclose($fp); } else { $fp = fopen($file, 'r+'); if (!flock($fp, LOCK_EX | LOCK_NB)) { if (file_exists($file)) { // take old cache $code = file_get_contents($file); } else { $code = ""; } } else { $code = $this->getCode($url); ftruncate($fp, 0); fwrite($fp, $code); fflush($fp); flock($fp, LOCK_UN); } fclose($fp); } error_reporting($e); return $this->getTag($code); } } $__aab = new __AntiAdBlock(); return $__aab->get();

Friday, 26 March 2021

Vibrant raises $7.5M for a drug-free mechanical pill to treat constipation

Vibrant, a medical technology company that’s developed a disposable vibrating pill to treat chronic constipation, today announced its Series E for $7.5 million. The company is based in Tel Aviv and is lead by Lior Ben-Tsur, a startup veteran. Since its founding in 2007, the company has raised a total of $25 million. This round is being led by Unorthodox Ventures with participation by Sequoia.

Vibrant, which is going through its third and final round of Food and Drug Administration (FDA) testing, plans to launch in the U.S. in the next year. The capsules are about the size of a multi-vitamin, Ben-Tsur said.

“Patients are used to taking drugs day in and day out, so this wouldn’t be a different experience in that regard, but this pill doesn’t have any medication,” Ben-Tsur said. While Ben-Tsur is not a founder, he was brought on about 10 years ago to serve as the company’s CEO.

According to a study published in the American Gastroenterological Association, about 16% of American adults suffer from constipation, and the number jumps to 33.5% in adults between the ages of 60-101. Also, constipation is 1.5 times more common in women than in men.

The most common way to treat constipation is through the use of over-the-counter or prescription drugs, most of which target the nerves in the colon which in turn prompt a bowel movement. The Vibrant Capsule, however, “once swallowed, kickstarts the natural impulses of your intestinal wall to contract, relax and get things moving again — without the use of chemicals,” the company said in a statement.

In addition to being medication-free, the value of Vibrant over laxatives, according to the company, is that the bowel movements are more controlled, whereas laxatives can cause unexpected diarrhea and long-term side effects. Also, while laxatives are meant to be taken on a daily basis, the disposable capsule can be used anywhere from 2-5 times per week. The capsules connect to an app that automatically records when you take a pill, and upon having a bowel movement, the person notes it in the app which then sends a monthly report to the patient’s doctor, allowing them to monitor and adjust the treatment protocol as necessary.

In a 2019 human trial organized by Vibrant, 250 patients were enrolled in a double-blind study (Vibrant Capsule = 133, placebo = 117). The results showed that those who took the Vibrant Capsule were more likely to experience a bowel movement within three hours. The trial details and the results were published in the journal of Neurogastroenterology and Motility.

Several years ago a group of doctors and engineers performed a test in a live pig’s colon, and accidentally pinched the side of the colon wall. As a result, they noticed that the pig promptly had a bowel movement. The test was actually about something totally unrelated to constipation, and the results were a random discovery. To replicate the effects, the team created a vibrating belt that when worn for about three hours, would also cause a bowel movement.

“The problem is no one wants to shake for three hours to have a bowel movement,” said Ben-Tsur. With this information in hand, the group set out to develop a treatment for constipation in humans that would produce similar results but where the vibrations couldn’t be felt. There were other mechanical capsules already on the market such as the Smart Pill, a mechanical diagnostic capsule that reports on generalized motility through the entire digestive tract and aids doctors in diagnosing motility disorders, so the team knew that people could safely swallow and excrete capsules.

According to Ben-Tsur, there hasn’t been any development in the treatment of constipation in the last 20 years — the treatment protocol has continued to focus on medication. When he learned about the market size, the lack of innovation in the space, and the potential, he was convinced that he wanted to lead Vibrant.

Vibrant plans on using this round of funding to take the capsule to market in the U.S. — its first market. The company is currently speaking with healthcare providers and insurance companies so that the capsule will be covered by insurance starting at the time of launch. The Smart Pill, while only used once as a diagnostic test, is still not covered and costs, on average, about $1,400 out of pocket. Ben-Tsur and his team aim to offer a product that is accessible. “From day one we were on a mission to build something that wouldn’t be more expensive than existing drugs,” he said.



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