OneSignalSDK.js

!function(e){var t={};function n(i){if(t[i])return t[i].exports;var r=t[i]={i:i,l:!1,exports:{}};return e[i].call(r.exports,r,r.exports,n),r.l=!0,r.exports}n.m=e,n.c=t,n.d=function(e,t,i){n.o(e,t)||Object.defineProperty(e,t,{configurable:!1,enumerable:!0,get:i})},n.r=function(e){Object.defineProperty(e,"__esModule",{value:!0})},n.n=function(e){var t=e&&e.__esModule?function(){return e.default}:function(){return e};return n.d(t,"a",t),t},n.o=function(e,t){return Object.prototype.hasOwnProperty.call(e,t)},n.p="",n(n.s=91)}([function(e,t,n){"use strict";var i=this&&this.__awaiter||function(e,t,n,i){return new(n||(n=Promise))(function(r,o){function s(e){try{u(i.next(e))}catch(e){o(e)}}function a(e){try{u(i.throw(e))}catch(e){o(e)}}function u(e){e.done?r(e.value):new n(function(t){t(e.value)}).then(s,a)}u((i=i.apply(e,t||[])).next())})},r=this&&this.__generator||function(e,t){var n,i,r,o,s={label:0,sent:function(){if(1&r[0])throw r[1];return r[1]},trys:[],ops:[]};return o={next:a(0),throw:a(1),return:a(2)},"function"==typeof Symbol&&(o[Symbol.iterator]=function(){return this}),o;function a(o){return function(a){return function(o){if(n)throw new TypeError("Generator is already executing.");for(;s;)try{if(n=1,i&&(r=i[2&o[0]?"return":o[0]?"throw":"next"])&&!(r=r.call(i,o[1])).done)return r;switch(i=0,r&&(o=[0,r.value]),o[0]){case 0:case 1:r=o;break;case 4:return s.label++,{value:o[1],done:!1};case 5:s.label++,i=o[1],o=[0];continue;case 7:o=s.ops.pop(),s.trys.pop();continue;default:if(!(r=(r=s.trys).length>0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]0)for(var s=0;s0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]=0;i--){n[i]===t&&n.splice(i,1)}},e}();t.WorkerMessengerReplyBuffer=p;var h=function(){function e(e,t){void 0===t&&(t=new p),this.context=e,this.replies=t,this.debug=!0}return e.prototype.broadcast=function(e,t){return i(this,void 0,void 0,function(){var n,i,o,s;return r(this,function(r){switch(r.label){case 0:return u.default.getWindowEnv()===l.WindowEnvironmentKind.ServiceWorker?[3,1]:[2];case 1:return[4,self.clients.matchAll({type:"window",includeUncontrolled:!0})];case 2:for(n=r.sent(),i=0,o=n;i Page] Broadcasting '"+e.toString()+"' to window client "+s.url+"."),s.postMessage({command:e,payload:t});r.label=3;case 3:return[2]}})})},e.prototype.unicast=function(e,t,n){return i(this,void 0,void 0,function(){return r(this,function(i){switch(i.label){case 0:if(u.default.getWindowEnv()!==l.WindowEnvironmentKind.ServiceWorker)return[3,1];if(!n)throw new a.InvalidArgumentError("windowClient",a.InvalidArgumentReason.Empty);return f.default.debug("[Worker Messenger] [SW -> Page] Unicasting '"+e.toString()+"' to window client "+n.url+"."),n.postMessage({command:e,payload:t}),[3,4];case 1:return[4,this.isWorkerControllingPage()];case 2:return i.sent()||f.default.debug("[Worker Messenger] The page is not controlled by the service worker yet. Waiting...",self.registration),[4,this.waitUntilWorkerControlsPage()];case 3:i.sent(),f.default.debug("[Worker Messenger] [Page -> SW] Unicasting '"+e.toString()+"' to service worker."),navigator.serviceWorker.controller.postMessage({command:e,payload:t}),i.label=4;case 4:return[2]}})})},e.prototype.listen=function(e){return i(this,void 0,void 0,function(){return r(this,function(t){switch(t.label){case 0:return d.default.supportsServiceWorkers()?u.default.getWindowEnv()!==l.WindowEnvironmentKind.ServiceWorker?[3,1]:(self.addEventListener("message",this.onWorkerMessageReceivedFromPage.bind(this)),f.default.debug("[Worker Messenger] Service worker is now listening for messages."),[3,3]):[2];case 1:return[4,this.listenForPage(e)];case 2:t.sent(),t.label=3;case 3:return[2]}})})},e.prototype.listenForPage=function(e){return i(this,void 0,void 0,function(){return r(this,function(t){switch(t.label){case 0:return e?[3,3]:[4,this.isWorkerControllingPage()];case 1:return t.sent()||f.default.debug("("+location.origin+") [Worker Messenger] The page is not controlled by the service worker yet. Waiting...",self.registration),[4,this.waitUntilWorkerControlsPage()];case 2:t.sent(),f.default.debug("("+location.origin+") [Worker Messenger] The page is now controlled by the service worker."),t.label=3;case 3:return navigator.serviceWorker.addEventListener("message",this.onPageMessageReceivedFromServiceWorker.bind(this)),f.default.debug("("+location.origin+") [Worker Messenger] Page is now listening for messages."),[2]}})})},e.prototype.onWorkerMessageReceivedFromPage=function(e){var t=e.data;if(t&&t.command){var n=this.replies.findListenersForMessage(t.command),i=[],r=[];f.default.debug("[Worker Messenger] Service worker received message:",e.data);for(var o=0,s=n;o=0;a--){var u=i[a];this.replies.deleteListenerRecord(t.command,u)}for(var c=0,l=r;c=0;a--){var u=i[a];this.replies.deleteListenerRecord(t.command,u)}for(var c=0,l=r;c0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1] to the first element in ."))}},e.getNotificationTypeFromOptIn=function(e){return 1==e||null==e?1:-2},e.wasHttpsNativePromptDismissed=function(){return"dismissed"===d.default.getItem("onesignal-notification-prompt")},e.markHttpPopoverShown=function(){sessionStorage.setItem("ONESIGNAL_HTTP_PROMPT_SHOWN","true")},e.isHttpPromptAlreadyShown=function(){return"true"==sessionStorage.getItem("ONESIGNAL_HTTP_PROMPT_SHOWN")},e.checkAndTriggerNotificationPermissionChanged=function(){return i(this,void 0,void 0,function(){var e,t;return r(this,function(n){switch(n.label){case 0:return[4,c.default.get("Options","notificationPermission")];case 1:return e=n.sent(),[4,OneSignal.getNotificationPermission()];case 2:return t=n.sent(),e===t?[3,5]:[4,l.triggerNotificationPermissionChanged()];case 3:return n.sent(),[4,c.default.put("Options",{key:"notificationPermission",value:t})];case 4:n.sent(),n.label=5;case 5:return[2]}})})},e.getNotificationIcons=function(){return i(this,void 0,void 0,function(){var t,n,i;return r(this,function(r){switch(r.label){case 0:return[4,e.getAppId()];case 1:if(!(t=r.sent()))throw new s.InvalidStateError(s.InvalidStateReason.MissingAppId);return n=u.default.getOneSignalApiUrl().toString()+"/apps/"+t+"/icon",[4,fetch(n)];case 2:return[4,r.sent().json()];case 3:if((i=r.sent()).errors)throw f.default.error("API call %c"+n,l.getConsoleStyle("code"),"failed with:",i.errors),new Error("Failed to get notification icons.");return[2,i]}})})},e.getSlidedownPermissionMessageOptions=function(){var e=OneSignal.config.userConfig.promptOptions;return e?e&&!e.slidedown?e:{actionMessage:e.slidedown.actionMessage,acceptButtonText:e.slidedown.acceptButtonText,cancelButtonText:e.slidedown.cancelButtonText}:null},e.getFullscreenPermissionMessageOptions=function(){var e=OneSignal.config.userConfig.promptOptions;return e?e&&!e.fullscreen?e:{autoAcceptTitle:e.fullscreen.autoAcceptTitle,actionMessage:e.fullscreen.actionMessage,exampleNotificationTitleDesktop:e.fullscreen.title,exampleNotificationTitleMobile:e.fullscreen.title,exampleNotificationMessageDesktop:e.fullscreen.message,exampleNotificationMessageMobile:e.fullscreen.message,exampleNotificationCaption:e.fullscreen.caption,acceptButtonText:e.fullscreen.acceptButton,cancelButtonText:e.fullscreen.cancelButton}:null},e.getPromptOptionsQueryString=function(){var t="";if(e.getFullscreenPermissionMessageOptions())for(var n=e.getPromptOptionsPostHash(),i=0,r=Object.keys(n);i0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]{{prompt.native.grant}}{{prompt.native.grant}} to receive notifications"),this.text["message.action.unsubscribed"]||(this.text["message.action.unsubscribed"]="You won't receive notifications again"),this.text["dialog.main.title"]||(this.text["dialog.main.title"]="Manage Site Notifications"),this.text["dialog.main.button.subscribe"]||(this.text["dialog.main.button.subscribe"]="SUBSCRIBE"),this.text["dialog.main.button.unsubscribe"]||(this.text["dialog.main.button.unsubscribe"]="UNSUBSCRIBE"),this.text["dialog.blocked.title"]||(this.text["dialog.blocked.title"]="Unblock Notifications"),this.text["dialog.blocked.message"]||(this.text["dialog.blocked.message"]="Follow these instructions to allow notifications:"),this._launcher=N,this.state=e.STATES.UNINITIALIZED,this._ignoreSubscriptionState=!1,b.default.emitter.on(e.EVENTS.SUBSCRIBE_CLICK,function(){x.dialog.subscribeButton.disabled=!0,x._ignoreSubscriptionState=!0,b.default.setSubscription(!0).then(function(){return x.dialog.subscribeButton.disabled=!1,x.dialog.hide()}).then(function(){return x.message.display(h.default.TYPES.MESSAGE,x.text["message.action.resubscribed"],h.default.TIMEOUT)}).then(function(){return x._ignoreSubscriptionState=!1,x.launcher.clearIfWasInactive(),x.launcher.inactivate()}).then(function(){return x.updateState()})}),b.default.emitter.on(e.EVENTS.UNSUBSCRIBE_CLICK,function(){x.dialog.unsubscribeButton.disabled=!0,b.default.setSubscription(!1).then(function(){return x.dialog.unsubscribeButton.disabled=!1,x.dialog.hide()}).then(function(){return x.launcher.clearIfWasInactive(),x.launcher.activate()}).then(function(){return x.message.display(h.default.TYPES.MESSAGE,x.text["message.action.unsubscribed"],h.default.TIMEOUT)}).then(function(){return x.updateState()})}),b.default.emitter.on(e.EVENTS.HOVERING,function(){x.hovering=!0,x.launcher.activateIfInactive(),x.message.shown||x.dialog.shown?x.hovering=!1:x.message.contentType!==h.default.TYPES.MESSAGE?new Promise(function(e){if(x.message.queued.length>0)return x.message.dequeue().then(function(t){x.message.content=t,x.message.contentType=h.default.TYPES.QUEUED,e()});x.message.content=c.decodeHtmlEntities(x.message.getTipForState()),x.message.contentType=h.default.TYPES.TIP,e()}).then(function(){return x.message.show()}).then(function(){x.hovering=!1}):x.hovering=!1}),b.default.emitter.on(e.EVENTS.HOVERED,function(){x.message.contentType!==h.default.TYPES.MESSAGE&&x.dialog.hidden&&(x.hovering&&(x.hovering=!1,x.message.waitUntilShown().then(function(){return c.delay(h.default.TIMEOUT)}).then(function(){return x.message.hide()}).then(function(){x.launcher.wasInactive&&x.dialog.hidden&&(x.launcher.inactivate(),x.launcher.wasInactive=null)})),x.message.shown&&x.message.hide().then(function(){x.launcher.wasInactive&&x.dialog.hidden&&(x.launcher.inactivate(),x.launcher.wasInactive=null)}))}),b.default.emitter.on(b.default.EVENTS.SUBSCRIPTION_CHANGED,function(t){return i(x,void 0,void 0,function(){var n,i=this;return r(this,function(r){switch(r.label){case 0:return 1!=t?[3,2]:(this.badge.shown&&this.options.prenotify&&this.badge.hide(),null!==this.dialog.notificationIcons?[3,2]:[4,u.default.getNotificationIcons()]);case 1:n=r.sent(),this.dialog.notificationIcons=n,r.label=2;case 2:return b.default.getNotificationPermission(function(n){i.setState(t?e.STATES.SUBSCRIBED:"denied"===n?e.STATES.BLOCKED:e.STATES.UNSUBSCRIBED,i._ignoreSubscriptionState)}),[2]}})})}),b.default.emitter.on(e.EVENTS.STATE_CHANGED,function(t){x.launcher.element&&(t.to===e.STATES.SUBSCRIBED?x.launcher.inactivate():(t.to===e.STATES.UNSUBSCRIBED||e.STATES.BLOCKED)&&x.launcher.activate())}),b.default.emitter.on(b.default.EVENTS.NATIVE_PROMPT_PERMISSIONCHANGED,function(){x.updateState()}),this.updateState()}}return Object.defineProperty(e,"EVENTS",{get:function(){return{STATE_CHANGED:"notifyButtonStateChange",LAUNCHER_CLICK:"notifyButtonLauncherClick",BELL_CLICK:"notifyButtonButtonClick",SUBSCRIBE_CLICK:"notifyButtonSubscribeClick",UNSUBSCRIBE_CLICK:"notifyButtonUnsubscribeClick",HOVERING:"notifyButtonHovering",HOVERED:"notifyButtonHover"}},enumerable:!0,configurable:!0}),Object.defineProperty(e,"STATES",{get:function(){return{UNINITIALIZED:"uninitialized",SUBSCRIBED:"subscribed",UNSUBSCRIBED:"unsubscribed",BLOCKED:"blocked"}},enumerable:!0,configurable:!0}),Object.defineProperty(e,"TEXT_SUBS",{get:function(){return{"prompt.native.grant":{default:"Allow",chrome:"Allow",firefox:"Always Receive Notifications",safari:"Allow"}}},enumerable:!0,configurable:!0}),e.prototype.showDialogProcedure=function(){var e=this;this.dialog.shown||this.dialog.show().then(function(){c.once(document,"click",function(t,n){e.dialog.element.contains(t.target)||(n(),e.dialog.shown&&e.dialog.hide().then(function(){e.launcher.inactivateIfWasInactive()}))},!0)})},e.prototype.create=function(){return i(this,void 0,void 0,function(){var e,t,n,i,o=this;return r(this,function(r){switch(r.label){case 0:return this.options.enable?[4,b.default.context.dynamicResourceLoader.loadSdkStylesheet()]:[2];case 1:return 0!==r.sent()?(g.default.debug("Not showing notify button because styles failed to load."),[2]):(this.container&&c.removeDomElement("#onesignal-bell-container"),c.addDomElement("body","beforeend",'
'),c.addDomElement(this.container,"beforeend",'
'),c.addDomElement(this.launcher.selector,"beforeend",'
'),c.addDomElement(this.launcher.selector,"beforeend",'
'),c.addDomElement(this.launcher.selector,"beforeend",'
'),c.addDomElement(this.message.selector,"beforeend",'
'),c.addDomElement(this.launcher.selector,"beforeend",'
'),c.addDomElement(this.dialog.selector,"beforeend",'
'),c.addDomElement(this.button.selector,"beforeEnd",''),[4,b.default.isPushNotificationsEnabled()]);case 2:return e=r.sent(),[4,b.default.getSubscription()];case 3:return t=r.sent(),[4,u.default.wasHttpsNativePromptDismissed()];case 4:return n=r.sent(),i=e?"small":this.options.size,[4,this.launcher.resize(i)];case 5:if(r.sent(),"bottom-left"===this.options.position)c.addCssClass(this.container,"onesignal-bell-container-bottom-left"),c.addCssClass(this.launcher.selector,"onesignal-bell-launcher-bottom-left");else{if("bottom-right"!==this.options.position)throw new Error("Invalid OneSignal notify button position "+this.options.position);c.addCssClass(this.container,"onesignal-bell-container-bottom-right"),c.addCssClass(this.launcher.selector,"onesignal-bell-launcher-bottom-right")}if("default"===this.options.theme)c.addCssClass(this.launcher.selector,"onesignal-bell-launcher-theme-default");else{if("inverse"!==this.options.theme)throw new Error("Invalid OneSignal notify button theme "+this.options.theme);c.addCssClass(this.launcher.selector,"onesignal-bell-launcher-theme-inverse")}return this.applyOffsetIfSpecified(),this.setCustomColorsIfSpecified(),this.patchSafariSvgFilterBug(),g.default.info("Showing the notify button."),[4,(e?this.launcher.inactivate():c.nothing()).then(function(){return b.default.getSubscription()}).then(function(t){return!e&&t||null!==o.dialog.notificationIcons?c.nothing():u.default.getNotificationIcons().then(function(e){o.dialog.notificationIcons=e})}).then(function(){return c.delay(o.options.showLauncherAfter)}).then(function(){return c.isUsingSubscriptionWorkaround()&&t&&!0!==n&&!e&&!0===b.default.config.userConfig.autoRegister&&!u.default.isHttpPromptAlreadyShown()?(g.default.debug("Not showing notify button because popover will be shown."),c.nothing()):o.launcher.show()}).then(function(){return c.delay(o.options.showBadgeAfter)}).then(function(){return o.options.prenotify&&!e&&b.default._isNewVisitor?o.message.enqueue(o.text["message.prenotify"]).then(function(){return o.badge.show()}):c.nothing()}).then(function(){return o.initialized=!0})];case 6:return r.sent(),[2]}})})},e.prototype.patchSafariSvgFilterBug=function(){if(!(s.default.safari&&Number(s.default.version)>=9.1)){var e="drop-shadow(0 2px 4px rgba(34,36,38,0.35));",t="drop-shadow(0 2px 4px rgba(34,36,38,0));",n="drop-shadow(0px 2px 2px rgba(34,36,38,.15));";this.graphic.setAttribute("style","filter: "+e+"; -webkit-filter: "+e+";"),this.badge.element.setAttribute("style","filter: "+t+"; -webkit-filter: "+t+";"),this.dialog.element.setAttribute("style","filter: "+n+"; -webkit-filter: "+n+";")}s.default.safari&&this.badge.element.setAttribute("style","display: none;")},e.prototype.applyOffsetIfSpecified=function(){var e=this.options.offset;e&&(this.launcher.element.style.cssText="",e.bottom&&(this.launcher.element.style.cssText+="bottom: "+e.bottom+";"),"bottom-right"===this.options.position?e.right&&(this.launcher.element.style.cssText+="right: "+e.right+";"):"bottom-left"===this.options.position&&e.left&&(this.launcher.element.style.cssText+="left: "+e.left+";"))},e.prototype.setCustomColorsIfSpecified=function(){var e=this.dialog.element.querySelector("button.action"),t=this.button.element.querySelector(".pulse-ring");this.graphic.querySelector(".background").style.cssText="";for(var n=this.graphic.querySelectorAll(".foreground"),i=0;i0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]0))for(var n=0,i=t.buttons;n0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]OneSignal: This page cannot be directly opened, and must be opened as a result of a subscription call."),[2,Promise.resolve()]):((e=i({},this.options)).appId=e.appId,e.subdomainName=e.subdomain,e.origin=e.origin,OneSignal.config=e||{},[4,(new c.default).getAppConfig(e)]);case 1:return t=r.sent(),OneSignal.context=new u.default(t),OneSignal.context.workerMessenger.listen(!0),OneSignal.initialized=!0,this.loadPromise={},this.loadPromise.promise=new Promise(function(e,t){n.loadPromise.resolver=e,n.loadPromise.rejector=t}),this.establishCrossOriginMessaging(),[2,this.loadPromise.promise]}})})},e.prototype.establishCrossOriginMessaging=function(){},e.prototype.dispose=function(){this.messenger.destroy()},e.prototype.finishInitialization=function(){this.loadPromise.resolver()},e.prototype.subscribe=function(){return r(this,void 0,void 0,function(){var e,t;return o(this,function(n){switch(n.label){case 0:return[4,OneSignal.isPushNotificationsEnabled()];case 1:return e=n.sent(),t=opener||parent,e?t&&window.close():a.default.registerForPush(),[2]}})})},e}();t.default=l},function(e,t,n){"use strict";var i,r,o;Object.defineProperty(t,"__esModule",{value:!0}),(i=t.ConfigIntegrationKind||(t.ConfigIntegrationKind={})).TypicalSite="typical",i.WordPress="wordpress",i.Shopify="shopify",i.Blogger="blogger",i.Magento="magento",i.Drupal="drupal",i.SquareSpace="squarespace",i.Joomla="joomla",i.Weebly="weebly",i.Wix="wix",i.Custom="custom",(r=t.NotificationClickMatchBehavior||(t.NotificationClickMatchBehavior={})).Exact="exact",r.Origin="origin",(o=t.NotificationClickActionBehavior||(t.NotificationClickActionBehavior={})).Navigate="navigate",o.Focus="focus"},function(e,t,n){"use strict";var i=this&&this.__importDefault||function(e){return e&&e.__esModule?e:{default:e}};Object.defineProperty(t,"__esModule",{value:!0});var r=n(1),o=i(n(6)),s=i(n(2)),a=i(n(35)),u=function(){function e(e,t,n,i,r,o,s){void 0===i&&(i="shown"),void 0===r&&(r=["opacity","transform"]),void 0===s&&(s=500),this.selector=e,this.showClass=t,this.hideClass=n,this.state=i,this.targetTransitionEvents=r,this.nestedContentSelector=o,this.transitionCheckTimeout=s}return e.prototype.show=function(){var t=this;return this.hidden?new Promise(function(n){if(t.state="showing",o.default.trigger(e.EVENTS.SHOWING,t),t.hideClass&&r.removeCssClass(t.element,t.hideClass),t.showClass&&r.addCssClass(t.element,t.showClass),0==t.targetTransitionEvents.length)return n(t);var i=setTimeout(function(){s.default.debug("Element did not completely show (state: "+t.state+").")},t.transitionCheckTimeout);r.once(t.element,"transitionend",function(s,a){if(s.target===t.element&&r.contains(t.targetTransitionEvents,s.propertyName))return clearTimeout(i),a(),t.state="shown",o.default.trigger(e.EVENTS.SHOWN,t),n(t)},!0)}):Promise.resolve(this)},e.prototype.hide=function(){var t=this;return this.shown?new Promise(function(n){if(t.state="hiding",o.default.trigger(e.EVENTS.HIDING,t),t.showClass&&r.removeCssClass(t.element,t.showClass),t.hideClass&&r.addCssClass(t.element,t.hideClass),0==t.targetTransitionEvents.length)return n(t);r.once(t.element,"transitionend",function(i,a){var u=setTimeout(function(){s.default.debug("Element did not completely hide (state: "+t.state+").")},t.transitionCheckTimeout);if(i.target===t.element&&r.contains(t.targetTransitionEvents,i.propertyName))return clearTimeout(u),a(),t.state="hidden",o.default.trigger(e.EVENTS.HIDDEN,t),n(t)},!0)}):Promise.resolve(this)},e.prototype.waitUntilShown=function(){var t=this;return"shown"===this.state?Promise.resolve(this):new Promise(function(n){a.default.emitter.once(e.EVENTS.SHOWN,function(e){if(e===t)return n(t)})})},e.prototype.waitUntilHidden=function(){var t=this;return"hidden"===this.state?Promise.resolve(this):new Promise(function(n){a.default.emitter.once(e.EVENTS.HIDDEN,function(e){if(e===t)return n(t)})})},Object.defineProperty(e,"EVENTS",{get:function(){return{SHOWING:"animatedElementShowing",SHOWN:"animatedElementShown",HIDING:"animatedElementHiding",HIDDEN:"animatedElementHidden"}},enumerable:!0,configurable:!0}),Object.defineProperty(e.prototype,"content",{get:function(){return this.nestedContentSelector?this.element.querySelector(this.nestedContentSelector).innerHTML:this.element.innerHTML},set:function(e){this.nestedContentSelector?this.element.querySelector(this.nestedContentSelector).innerHTML=e:this.element.innerHTML=e},enumerable:!0,configurable:!0}),Object.defineProperty(e.prototype,"element",{get:function(){return 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Date).getTime()>=t.expirationTime||(new Date).getTime()>=o)]}})})},e.prototype.getSubscriptionState=function(){return i(this,void 0,void 0,function(){var t,n,i,o;return r(this,function(r){switch(r.label){case 0:if(e.isSafari())return[2,this.getSubscriptionStateForSecure()];switch(t=y.default.getWindowEnv(),t){case v.WindowEnvironmentKind.ServiceWorker:return[3,1]}return[3,4];case 1:return[4,self.registration.pushManager.getSubscription()];case 2:return n=r.sent(),[4,S.default.getSubscription()];case 3:return i=r.sent().optedOut,[2,{subscribed:!!n,optedOut:i}];case 4:return[4,y.default.getIntegration()];case 5:switch(o=r.sent(),o){case P.IntegrationKind.Secure:return[3,6];case P.IntegrationKind.SecureProxy:return[3,7];case P.IntegrationKind.InsecureProxy:return[3,11]}return[3,13];case 6:return[2,this.getSubscriptionStateForSecure()];case 7:switch(t){case v.WindowEnvironmentKind.OneSignalProxyFrame:case v.WindowEnvironmentKind.OneSignalSubscriptionPopup:case v.WindowEnvironmentKind.OneSignalSubscriptionModal:return[3,8]}return[3,9];case 8:return[2,this.getSubscriptionStateForSecure()];case 9:return[4,OneSignal.proxyFrameHost.runCommand(OneSignal.POSTMAM_COMMANDS.GET_SUBSCRIPTION_STATE)];case 10:return[2,r.sent()];case 11:return[4,this.getSubscriptionStateForInsecure()];case 12:return[2,r.sent()];case 13:throw new a.InvalidStateError(a.InvalidStateReason.UnsupportedEnvironment)}})})},e.prototype.getSubscriptionStateForSecure=function(){return i(this,void 0,void 0,function(){var t,n,i,o,s,a,u,c,l;return r(this,function(r){switch(r.label){case 0:return[4,S.default.getSubscription()];case 1:return t=r.sent(),n=t.deviceId,t.subscriptionToken,i=t.optedOut,e.isSafari()?(o=window.safari.pushNotification.permission(this.config.safariWebId),[2,{subscribed:!("granted"!==o.permission||!o.deviceToken||!n),optedOut:i}]):[4,this.context.serviceWorkerManager.getActiveState()];case 2:return s=r.sent(),[4,navigator.serviceWorker.getRegistration()];case 3:return a=r.sent(),[4,this.context.permissionManager.getNotificationPermission(this.context.appConfig.safariWebId)];case 4:return u=r.sent(),c=s===E.ServiceWorkerActiveState.WorkerA||s===E.ServiceWorkerActiveState.WorkerB,a?[4,a.pushManager.getSubscription()]:[2,{subscribed:!1,optedOut:i}];case 5:return l=r.sent(),[2,{subscribed:!!(l&&n&&u===h.NotificationPermission.Granted&&c),optedOut:i}]}})})},e.prototype.getSubscriptionStateForInsecure=function(){return i(this,void 0,void 0,function(){var e,t,n,i,o;return r(this,function(r){switch(r.label){case 0:return[4,S.default.getSubscription()];case 1:return e=r.sent(),t=e.deviceId,n=e.subscriptionToken,i=e.optedOut,[4,this.context.permissionManager.getNotificationPermission(this.context.appConfig.safariWebId)];case 2:return o=r.sent(),[2,{subscribed:!(!t||!n||o!==h.NotificationPermission.Granted),optedOut:i}]}})})},e.prototype.registerFailedSubscription=function(e,t){return i(this,void 0,void 0,function(){return r(this,function(n){return 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e>0?t.bell.badge.show():Promise.resolve(t)}).then(e(n)):(t.bell.badge.decrement(),e(n))})},t}(a.default);t.default=l},function(e,t,n){"use strict";var i=this&&this.__assign||Object.assign||function(e){for(var t,n=1,i=arguments.length;n0&&r[r.length-1])&&(6===o[0]||2===o[0])){s=0;continue}if(3===o[0]&&(!r||o[1]>r[0]&&o[1]=63&&(a.default.tablet||a.default.mobile)?[4,OneSignal.privateShowHttpPrompt()]:[3,8];case 7:return n.sent(),[3,10];case 8:return[4,y.default.registerForPush()];case 9:n.sent(),n.label=10;case 10:return[3,12];case 11:OneSignal._sessionInitAlreadyRunning=!1,n.label=12;case 12:return[3,16];case 13:return!0!==OneSignal.config.userConfig.autoRegister&&A.default.debug("OneSignal: Not automatically showing popover because autoRegister is not specifically true."),S.default.isHttpPromptAlreadyShown()&&A.default.debug("OneSignal: Not automatically showing popover because it was previously shown in the same 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loading...

Preparaty liposomowe - nadzieją na skuteczniejsze leczenie raka, m.in. trzustki

Nad preparatami liposomowymi, które pomogą dostarczać do komórek nowotworowych leki w kombinacji z naturalnym substancjami bioaktywnymi z roślin, pracują naukowcy z Wrocławia. Takie rozwiązania pomogą zwiększyć skuteczność terapii, np. raka trzustki.

zdjęcie:pixabay/ Preparaty liposomowe - nadzieją na skuteczniejsze leczenie raka, m.in. trzustki
zdjęcie:pixabay/ 
Preparaty liposomowe - nadzieją na skuteczniejsze leczenie raka, m.in. trzustki

Dzięki takiemu połączeniu można stosować większą dawkę tych substancji, niż gdybyśmy użyli tylko klasycznych leków, stosowanych w terapii nowotworowej. To sprawia, że przy większym ich stężeniu, a jednocześnie mniejszej toksyczności dla organizmu, uzyskujemy dużo lepszy efekt terapeutyczny – powiedział PAP dr hab. Jerzy Gubernator, kierownik Zakładu Lipidów i Liposomów na Wydziale Biotechnologii Uniwersytetu Wrocławskiego.

Wrocławscy naukowcy poszukują zwłaszcza nowych leków na nowotwór trzustki. Opracowali m.in. liposomową postać epirubicyny - klasycznego leku przeciwnowotworowego, a także preparaty liposomowe zawierające kurkuminę czy berberynę. Wyniki testów na zwierzętach świadczą o większej skuteczności takich substancji liposomalnych. "Rzeczywiście podanie tych substancji liposomalnych zwiększa wyraźnie skuteczność terapii w porównaniu z wolnymi substancjami" - podkreślił naukowiec.

Liposomy to małe pęcherzyki lipidowe zbudowane najczęściej z fosfolipidów. Mogą być wielkości bakterii albo wirusów. Do badań nad nowotworami naukowcy używają liposomów wielkości wirusów. Tak małe cząstki mogą dostać się do miejsca, w którym obecny jest np. stan zapalny (który często towarzyszy również nowotworom) - i się tam akumulować.

"Dzięki temu, że liposomy są tak małe, możemy uzyskać efekt ich kumulacji w tkance nowotworowej. A ponieważ naczynia krwionośne w nowotworach mają większą przepuszczalność różnych cząstek, to w ten sposób uzyskuje się większy efekt terapeutyczny" - wyjaśnił.

Liposomy bardzo długo pozostają w krwiobiegu – dla niektórych typów połowiczny czas krążenia we krwi wynosi nawet 50 godzin. W związku z tym nawet po tygodniu od podania liposomów część z nich wciąż krąży w krwiobiegu i może kumulować się w tkance nowotworowej.

Dr Gubernator informuje, że naukowcy pracują przede wszystkim nad połączeniem różnych substancji, które mają szerokie spektrum terapeutyczne albo różne mechanizmy działania. To daje perspektywę skuteczniejszego leczenia.

Bardzo często używają oni klasycznych leków przeciwnowotworowych w połączeniu z naturalnym substancjami bioaktywnymi pochodzenia roślinnego. Wiele substancji znajdujących się np. w warzywach czy przyprawach, codziennie spożywanych, ma bowiem silne właściwości przeciwnowotworowe. Jest to np. kurkumina - jeden ze składników kurkumy, czy związki obecne w roślinach krzyżowych, choćby kapuście.

"Jeżeli zwiążemy je razem z nośnikiem liposomowym i użyjemy razem z lekiem przeciwnowotworowym, wtedy ten efekt terapeutyczny może być bardzo wyraźnie wzmocniony. Istotne jest także to, że substancje naturalne często mają większą selektywność wobec komórek nowotworowych, niż klasyczne chemoterapeutyki" - opowiada ekspert.

Kluczowe jest też opracowanie metod uwalniania substancji z liposomów. "Pracujemy nad tym, aby po pierwsze substancje, które zamknięte są w liposomach, działały na różne sposoby, a po drugie, żeby sposób ich uwalniania był kontrolowany. Żeby można było w jednostce czasu uzyskać jak największe stężenie substancji terapeutycznych w guzie nowotworowym, co pozwala na skuteczną terapię" - wyjaśnił badacz.

Naukowcy z Zakładu Lipidów i Liposomów UWr poszukują przede wszystkim nowych możliwości w leczeniu raka trzustki. To jeden z najtrudniejszych do leczenia nowotworów. Związana z nim śmiertelność jest bardzo wysoka, a średni czas przeżycia pacjentów wynosi zaledwie 9-10 miesięcy.

Same badania rozpoczynają się od wyboru substancji, które mają być zamknięte w liposomach. "Robimy selekcję, czyli tzw. screeningi różnych substancji, które mogłyby być stosowane w przypadku nowotworu trzustki. Badamy zarówno klasyczne chemoterapeutyki, jak i naturalne substancje. Następnie robimy kombinacje tych substancji ze sobą, badamy efekt synergii. Jeśli go uzyskujemy, to dokładamy kolejną substancję w celu kolejnego zwiększenia tego efektu. I w ten sposób możemy doprowadzić do tego, że 98-99 proc. komórek rakowych jesteśmy w stanie zabić" - podkreślił dr hab. Jerzy Gubernator.

Po przeprowadzeniu badań in vitro - czyli na hodowlach komórkowych, naukowcy przygotowują liposomowe wersje tychże substancji, które następnie badają na zwierzętach, przede wszystkim na myszach. Opracowali m.in. preparaty liposomowe zawierające kurkuminę czy berberynę - naturalne substancje roślinne, które mogą być stosowane do leczenia raka trzustki, a także lipomową postać epirubicyny, klasycznego leku przeciwnowotworowego.

Mówiąc o pierwszych wynikach tych badań dr Gubernator przyznaje, że podanie tak przygotowanych substancji liposomalnych wyraźnie zwiększa skuteczność terapii w porównaniu z substancjami wolnymi.

"Jeżeli np. porównamy zwierzę leczone klasycznymi lekami w postaci wolnej, jak i liposomalnymi, ten efekt jest kilkukrotnie większy. Czyli przeżycie zwierząt jest większe i guzy rozwijają się wielokrotnie wolniej. Więc efekt kumulacji, a potem kontrolowanego uwalniania tych substancji jest rzeczywiście widoczny i pozytywny" - podkreślił naukowiec.

Jeżeli badania na zwierzętach ostatecznie zakończą się sukcesem, trzeba będzie przeprowadzić badania kliniczne. To jest jednak długa i kosztowana droga – podsumował dr hab. Jerzy Gubernator z UWr.

PAP - Nauka w Polsce, Kamil Szubański
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