Deprecated: Creation of dynamic property wpdb::$categories is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/wp-db.php on line 760

Deprecated: Creation of dynamic property wpdb::$post2cat is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/wp-db.php on line 760

Deprecated: Creation of dynamic property wpdb::$link2cat is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/wp-db.php on line 760

Deprecated: Return type of WPCF7_FormTag::offsetExists($offset) should either be compatible with ArrayAccess::offsetExists(mixed $offset): bool, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/contact-form-7/includes/form-tag.php on line 542

Deprecated: Return type of WPCF7_FormTag::offsetGet($offset) should either be compatible with ArrayAccess::offsetGet(mixed $offset): mixed, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/contact-form-7/includes/form-tag.php on line 528

Deprecated: Return type of WPCF7_FormTag::offsetSet($offset, $value) should either be compatible with ArrayAccess::offsetSet(mixed $offset, mixed $value): void, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/contact-form-7/includes/form-tag.php on line 516

Deprecated: Return type of WPCF7_FormTag::offsetUnset($offset) should either be compatible with ArrayAccess::offsetUnset(mixed $offset): void, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/contact-form-7/includes/form-tag.php on line 552

Deprecated: Return type of WPCF7_Validation::offsetExists($offset) should either be compatible with ArrayAccess::offsetExists(mixed $offset): bool, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/contact-form-7/includes/validation.php on line 129

Deprecated: Return type of WPCF7_Validation::offsetGet($offset) should either be compatible with ArrayAccess::offsetGet(mixed $offset): mixed, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/contact-form-7/includes/validation.php on line 117

Deprecated: Return type of WPCF7_Validation::offsetSet($offset, $value) should either be compatible with ArrayAccess::offsetSet(mixed $offset, mixed $value): void, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/contact-form-7/includes/validation.php on line 98

Deprecated: Return type of WPCF7_Validation::offsetUnset($offset) should either be compatible with ArrayAccess::offsetUnset(mixed $offset): void, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/contact-form-7/includes/validation.php on line 139

Deprecated: Creation of dynamic property wpdb::$ewwwio_images is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/wp-db.php on line 760

Deprecated: Creation of dynamic property wpdb::$ewwwio_queue is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/wp-db.php on line 760

Deprecated: Return type of FS_Key_Value_Storage::offsetExists($k) should either be compatible with ArrayAccess::offsetExists(mixed $offset): bool, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/post-snippets/freemius/includes/managers/class-fs-key-value-storage.php on line 309

Deprecated: Return type of FS_Key_Value_Storage::offsetGet($k) should either be compatible with ArrayAccess::offsetGet(mixed $offset): mixed, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/post-snippets/freemius/includes/managers/class-fs-key-value-storage.php on line 317

Deprecated: Return type of FS_Key_Value_Storage::offsetSet($k, $v) should either be compatible with ArrayAccess::offsetSet(mixed $offset, mixed $value): void, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/post-snippets/freemius/includes/managers/class-fs-key-value-storage.php on line 301

Deprecated: Return type of FS_Key_Value_Storage::offsetUnset($k) should either be compatible with ArrayAccess::offsetUnset(mixed $offset): void, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/post-snippets/freemius/includes/managers/class-fs-key-value-storage.php on line 313

Deprecated: Return type of FS_Key_Value_Storage::current() should either be compatible with Iterator::current(): mixed, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/post-snippets/freemius/includes/managers/class-fs-key-value-storage.php on line 328

Deprecated: Return type of FS_Key_Value_Storage::next() should either be compatible with Iterator::next(): void, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/post-snippets/freemius/includes/managers/class-fs-key-value-storage.php on line 339

Deprecated: Return type of FS_Key_Value_Storage::key() should either be compatible with Iterator::key(): mixed, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/post-snippets/freemius/includes/managers/class-fs-key-value-storage.php on line 350

Deprecated: Return type of FS_Key_Value_Storage::valid() should either be compatible with Iterator::valid(): bool, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/post-snippets/freemius/includes/managers/class-fs-key-value-storage.php on line 362

Deprecated: Return type of FS_Key_Value_Storage::rewind() should either be compatible with Iterator::rewind(): void, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/post-snippets/freemius/includes/managers/class-fs-key-value-storage.php on line 375

Deprecated: Return type of FS_Key_Value_Storage::count() should either be compatible with Countable::count(): int, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/post-snippets/freemius/includes/managers/class-fs-key-value-storage.php on line 389

Deprecated: Return type of WordPressPopularPosts\Container\Container::offsetExists($key) should either be compatible with ArrayAccess::offsetExists(mixed $offset): bool, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/wordpress-popular-posts/src/Container/Container.php on line 50

Deprecated: Return type of WordPressPopularPosts\Container\Container::offsetGet($key) should either be compatible with ArrayAccess::offsetGet(mixed $offset): mixed, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/wordpress-popular-posts/src/Container/Container.php on line 83

Deprecated: Return type of WordPressPopularPosts\Container\Container::offsetSet($key, $value) should either be compatible with ArrayAccess::offsetSet(mixed $offset, mixed $value): void, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/wordpress-popular-posts/src/Container/Container.php on line 61

Deprecated: Return type of WordPressPopularPosts\Container\Container::offsetUnset($key) should either be compatible with ArrayAccess::offsetUnset(mixed $offset): void, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/wordpress-popular-posts/src/Container/Container.php on line 71

Deprecated: Creation of dynamic property POMO_FileReader::$is_overloaded is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 26

Deprecated: Creation of dynamic property POMO_FileReader::$_pos is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 29

Deprecated: Creation of dynamic property POMO_FileReader::$_f is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 160

Deprecated: Creation of dynamic property MO::$_gettext_select_plural_form is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/translations.php on line 292

Deprecated: Creation of dynamic property Automattic\Jetpack\Connection\Manager::$error_handler is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/jetpack_vendor/automattic/jetpack-connection/src/class-manager.php on line 93

Deprecated: Creation of dynamic property Automattic\Jetpack\Search\REST_Controller::$plan is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/jetpack_vendor/automattic/jetpack-search/src/class-rest-controller.php on line 46

Deprecated: Creation of dynamic property wpdb::$imagify_folders is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/wp-db.php on line 760

Deprecated: Creation of dynamic property wpdb::$imagify_files is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/wp-db.php on line 760

Deprecated: Creation of dynamic property Imagify\Job\MediaOptimization::$query_url is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/imagify/inc/classes/class-imagify-abstract-background-process.php on line 80

Deprecated: Creation of dynamic property WPCOM_REST_API_V2_Endpoint_Instagram_Gallery::$is_wpcom is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/_inc/lib/core-api/wpcom-endpoints/class-wpcom-rest-api-v2-endpoint-instagram-gallery.php on line 23

Deprecated: Creation of dynamic property WPCOM_REST_API_V2_Endpoint_Mailchimp::$wpcom_is_wpcom_only_endpoint is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/_inc/lib/core-api/wpcom-endpoints/class-wpcom-rest-api-v2-endpoint-mailchimp.php on line 26

Deprecated: Creation of dynamic property WPCOM_REST_API_V2_Endpoint_Publicize_Share_Post::$wpcom_is_wpcom_only_endpoint is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/_inc/lib/core-api/wpcom-endpoints/class-wpcom-rest-api-v2-endpoint-publicize-share-post.php on line 27

Deprecated: Creation of dynamic property WPCOM_REST_API_V2_Endpoint_Publicize_Share_Post::$is_wpcom is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/_inc/lib/core-api/wpcom-endpoints/class-wpcom-rest-api-v2-endpoint-publicize-share-post.php on line 30

Deprecated: Creation of dynamic property Automattic\Jetpack\Search\REST_Controller::$plan is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/jetpack_vendor/automattic/jetpack-search/src/class-rest-controller.php on line 46

Deprecated: Creation of dynamic property WPCOM_REST_API_V2_Endpoint_Tweetstorm_Gather::$wpcom_is_wpcom_only_endpoint is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/_inc/lib/core-api/wpcom-endpoints/class-wpcom-rest-api-v2-endpoint-tweetstorm-gather.php on line 21

Deprecated: Creation of dynamic property WPCOM_REST_API_V2_Endpoint_Tweetstorm_Gather::$is_wpcom is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/_inc/lib/core-api/wpcom-endpoints/class-wpcom-rest-api-v2-endpoint-tweetstorm-gather.php on line 22

Deprecated: Creation of dynamic property WPCOM_REST_API_V2_Endpoint_Gutenberg_Available_Extensions::$wpcom_is_site_specific_endpoint is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/_inc/lib/core-api/wpcom-endpoints/gutenberg-available-extensions.php on line 29

Deprecated: Creation of dynamic property WPCOM_REST_API_V2_Endpoint_Memberships::$wpcom_is_wpcom_only_endpoint is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/_inc/lib/core-api/wpcom-endpoints/memberships.php on line 23

Deprecated: Creation of dynamic property WPCOM_REST_API_V2_Endpoint_Memberships::$wpcom_is_site_specific_endpoint is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/_inc/lib/core-api/wpcom-endpoints/memberships.php on line 24

Deprecated: Creation of dynamic property WPCOM_REST_API_V2_Endpoint_Subscribers::$wpcom_is_wpcom_only_endpoint is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/_inc/lib/core-api/wpcom-endpoints/subscribers.php on line 22

Deprecated: Creation of dynamic property POMO_FileReader::$is_overloaded is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 26

Deprecated: Creation of dynamic property POMO_FileReader::$_pos is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 29

Deprecated: Creation of dynamic property POMO_FileReader::$_f is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 160

Deprecated: Creation of dynamic property MO::$_gettext_select_plural_form is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/translations.php on line 292

Deprecated: Creation of dynamic property POMO_FileReader::$is_overloaded is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 26

Deprecated: Creation of dynamic property POMO_FileReader::$_pos is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 29

Deprecated: Creation of dynamic property POMO_FileReader::$_f is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 160

Deprecated: Creation of dynamic property MO::$_gettext_select_plural_form is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/translations.php on line 292

Deprecated: Creation of dynamic property POMO_FileReader::$is_overloaded is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 26

Deprecated: Creation of dynamic property POMO_FileReader::$_pos is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 29

Deprecated: Creation of dynamic property POMO_FileReader::$_f is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 160

Deprecated: Creation of dynamic property MO::$_gettext_select_plural_form is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/translations.php on line 292

Deprecated: Creation of dynamic property POMO_FileReader::$is_overloaded is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 26

Deprecated: Creation of dynamic property POMO_FileReader::$_pos is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 29

Deprecated: Creation of dynamic property POMO_FileReader::$_f is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 160

Deprecated: Creation of dynamic property MO::$_gettext_select_plural_form is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/translations.php on line 292

Deprecated: Creation of dynamic property Yyi_Rinker_Plugin::$script_admin_rinker_url is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/yyi-rinker/yyi_rinker_main.php on line 57

Deprecated: Creation of dynamic property Yyi_Rinker_Plugin::$arrow_right_img_url is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/yyi-rinker/yyi_rinker_main.php on line 59

Deprecated: Creation of dynamic property Yyi_Rinker_Plugin::$arrow_left_img_url is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/yyi-rinker/yyi_rinker_main.php on line 60

Deprecated: Creation of dynamic property Yyi_Rinker_Plugin::$moshimo_amazon_id is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/yyi-rinker/yyi_rinker_main.php on line 66

Deprecated: Creation of dynamic property Yyi_Rinker_Plugin::$moshimo_yahoo_id is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/yyi-rinker/yyi_rinker_main.php on line 67

Deprecated: Creation of dynamic property Yyi_Rinker_Plugin::$moshimo_rakuten_id is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/yyi-rinker/yyi_rinker_main.php on line 68

Deprecated: Creation of dynamic property Yyi_Rinker_Plugin::$is_some_images is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/yyi-rinker/yyi_rinker_main.php on line 77

Deprecated: Creation of dynamic property Yyi_Rinker_Plugin::$rakuten_application_id is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/yyi-rinker/yyi_rinker_main.php on line 86

Deprecated: Creation of dynamic property Yoast\WP\SEO\Main::$helpers is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/wordpress-seo/lib/abstract-main.php on line 65

Deprecated: Creation of dynamic property Automattic\Jetpack\Sync\Queue::$random_int is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/jetpack_vendor/automattic/jetpack-sync/src/class-queue.php on line 40

Deprecated: Creation of dynamic property Automattic\Jetpack\Sync\Queue::$random_int is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/jetpack_vendor/automattic/jetpack-sync/src/class-queue.php on line 40

Deprecated: Creation of dynamic property Jetpack_Publicize::$modules is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/modules/publicize.php on line 36

Deprecated: Creation of dynamic property Automattic\Jetpack\Publicize\Publicize_UI::$in_jetpack is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/modules/publicize.php on line 102

Deprecated: Creation of dynamic property Jetpack_Likes::$in_jetpack is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/modules/likes.php on line 54

Deprecated: Creation of dynamic property Jetpack_Likes_Settings::$in_jetpack is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/modules/likes/jetpack-likes-settings.php on line 14

Deprecated: Creation of dynamic property Jetpack_Likes::$settings is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/modules/likes.php on line 55

Deprecated: Creation of dynamic property POMO_FileReader::$is_overloaded is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 26

Deprecated: Creation of dynamic property POMO_FileReader::$_pos is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 29

Deprecated: Creation of dynamic property POMO_FileReader::$_f is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 160

Deprecated: Creation of dynamic property MO::$_gettext_select_plural_form is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/translations.php on line 292

Deprecated: Creation of dynamic property POMO_FileReader::$is_overloaded is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 26

Deprecated: Creation of dynamic property POMO_FileReader::$_pos is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 29

Deprecated: Creation of dynamic property POMO_FileReader::$_f is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 160

Deprecated: Creation of dynamic property MO::$_gettext_select_plural_form is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/translations.php on line 292

Deprecated: Creation of dynamic property WPCOM_Widget_Goodreads::$shelves is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/jetpack/modules/widgets/goodreads.php on line 39

Deprecated: Creation of dynamic property WP_Block_Type::$skip_inner_blocks is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/class-wp-block-type.php on line 391

Deprecated: Creation of dynamic property WP_Block_Type::$skip_inner_blocks is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/class-wp-block-type.php on line 391

Deprecated: Creation of dynamic property POMO_FileReader::$is_overloaded is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 26

Deprecated: Creation of dynamic property POMO_FileReader::$_pos is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 29

Deprecated: Creation of dynamic property POMO_FileReader::$_f is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 160

Deprecated: Creation of dynamic property MO::$_gettext_select_plural_form is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/translations.php on line 292

Deprecated: Creation of dynamic property POMO_FileReader::$is_overloaded is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 26

Deprecated: Creation of dynamic property POMO_FileReader::$_pos is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 29

Deprecated: Creation of dynamic property POMO_FileReader::$_f is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 160

Deprecated: Creation of dynamic property MO::$_gettext_select_plural_form is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/translations.php on line 292

Deprecated: Creation of dynamic property POMO_FileReader::$is_overloaded is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 26

Deprecated: Creation of dynamic property POMO_FileReader::$_pos is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 29

Deprecated: Creation of dynamic property POMO_FileReader::$_f is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 160

Deprecated: Creation of dynamic property MO::$_gettext_select_plural_form is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/translations.php on line 292

Deprecated: Constant FILTER_SANITIZE_STRING is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/wordpress-seo/src/conditionals/third-party/elementor-edit-conditional.php on line 22

Deprecated: Constant FILTER_SANITIZE_STRING is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-content/plugins/wordpress-seo/src/conditionals/third-party/elementor-edit-conditional.php on line 28

Deprecated: Creation of dynamic property POMO_FileReader::$is_overloaded is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 26

Deprecated: Creation of dynamic property POMO_FileReader::$_pos is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 29

Deprecated: Creation of dynamic property POMO_FileReader::$_f is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/streams.php on line 160

Deprecated: Creation of dynamic property MO::$_gettext_select_plural_form is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/pomo/translations.php on line 292

Deprecated: Creation of dynamic property WP_Block_Type::$plan_check is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/class-wp-block-type.php on line 391

Deprecated: Creation of dynamic property WP_Block_Type::$plan_check is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/class-wp-block-type.php on line 391

Deprecated: Creation of dynamic property WP_Block_Type::$plan_check is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/class-wp-block-type.php on line 391

Deprecated: Creation of dynamic property WP_Block_Type::$plan_check is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/class-wp-block-type.php on line 391

Deprecated: Creation of dynamic property WP_Block_Type::$plan_check is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/class-wp-block-type.php on line 391

Deprecated: Creation of dynamic property WP_Block_Type::$plan_check is deprecated in /home/hatenko/ritouyakuzaishi.com/public_html/wp-includes/class-wp-block-type.php on line 391

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抗生物質と抗菌薬の違いを言えますか? | 離島薬剤師どっとこむ沖縄
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class="post-6691 post type-post status-publish format-standard has-post-thumbnail hentry category-175 tag-183 tag-184 article">

抗生物質と抗菌薬の違いを言えますか?


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いきなりですが、問題です。

以下の4つの薬剤の中で、「抗生物質(抗生剤)ではない」ものが1つ紛れています。それはどれでしょうか?

選択肢
A:ペニシリンG(注射用ペニシリンGカリウム)
B:アムホテリシンB(ファンギゾン®︎シロップ)
C:マイトマイシンC(マイトマイシン注用)
D:レボフロキサシン(クラビット®︎錠)
ん〜どれも抗生物質のような気がするけど、真菌感染症の治療に適応のある「アムホテリシンB」か、抗がん剤の「マイトマイシンC」が抗生物質ではないのでは?
サヤカさん、期待通りの解答をありがとうございます。

どちらも不正解です。

 

正解は『Dのレボフロキサシン』

 

え・・・えぇっっっっ〜〜〜!?
もし、間違えてしまった場合は、以下をしっかり読んでその違いを確認しましょう。
【PR】医師・薬剤師が利用する医療専門サイト『m3.com』

最新の医療ニュースや医薬品情報をチェックするなら『m3.com(エムスリー)』。
m3.com は薬剤師力を維持するために必ず登録したいアプリケーション
製薬会社からの広告収入により運営されており、製品紹介動画を見るだけで、商品券と交換できるm3 ポイントも貯まります

まだ登録していない方は忘れずにチェック → 詳しくはこちら

 

抗生物質と抗菌薬の違い

抗生物質と抗菌薬の違い
抗生物質とは

1947年に米国Rutgers大学のワックスマン(Waksman, Selman A.)博士は、抗生物質とは、「微生物が産生し、他の微生物の生育を阻害する物質」と定義しました。

つまり、

  1. 微生物が作る(放線菌、真菌、細菌など)
  2. 他の微生物の生育を阻害する

この2つの条件が当てはまれば「抗生物質」ということになります。ちなみに、薬である必要はありません。

身近な具体例を挙げますと、ペニシリンG、アムホテリシンB、バシトラシンはそれぞれ抗生物質になります。

ペニシリンGはは世界初の抗生物質で青カビ Penicillium chrysogenum が産生し、アムホテリシンBは放線菌 Streptomyces nodosus より、バシトラシンは Bacillus licheniformitis や Bacillus subtilisなどのバシラス属の細菌より産生されます。もちろん、それぞれ感染症の治療薬ですので抗菌活性があります。

 

そこで、先ほどクイズにもあった「レボフロキサシン(クラビット®︎錠)」を考えます。

レボフロキサシンはピリドンカルボン酸構造を基本骨格として人工的に完全合成して作られた化合物です。すなわち、「微生物の生育を阻害する」というのは正しいのですが、「微生物が作る」という点で抗生物質の定義から外れているのです。

したがって、レボフロキサシンなどを含むニューキノロン類は抗生物質とは別の呼び方をする必要があります。

 

抗生物質と抗菌薬の違い
抗菌薬とは

一方、抗菌薬は抗生物質のように定義のようなものは存在しませんが、言葉通り「細菌(真菌)を死滅させたり、増殖を抑える薬」と言ったところでしょう。

すなわち、

  1. 細菌(真菌)の生育を抑制する
  2. 医薬品である

これらが当てはまれば「抗菌薬」と言っても良いと考えられます。

 

先ほどのレボフロキサシンは上の条件に該当するので「抗菌薬」と呼ぶことが可能となるわけです。

レボフロキサシンのようなニューキノロン系抗菌薬の他に、完全合成で作られている抗菌薬は、

スルファメトキサゾール・トリメトプリム(ST合剤)、イソニアジド(抗結核薬)、リネゾリド(抗VRE,MRSA薬)、アゾール系抗真菌薬など数多くあります。(抗真菌薬を抗菌薬のくくりから外すこともあります。)

 

これまでの抗生物質と抗菌薬の関係性をわかりやすく表すと以下の図のようになります。広義に「抗菌薬」があり、その中に(自然から得られた)抗生物質があるイメージです。

作成:離島薬剤師どっとこむ沖縄

 

ちなみに、ビダラビンやバラシクロビル、オセルタミビルのような抗ウィルス薬は抗菌薬でもありません。ウィルスは菌ではありませんので。

 

抗生物質と抗菌薬の違い
半合成抗生物質

化合物の中には微生物が産生した抗生物質に人工的に修飾を与えて新たな化合物(誘導体)を作成することがあります。少しだけ合成しているので、ここでは半合成抗生物質とします。

例を挙げると、抗生物質であるペニシリンGの誘導体であるアモキシシリンがそれに該当します。

その他、放線菌 Streptomyces viridofaciensから産生されるテトラサイクリンの誘導体「ミノサイクリン」や放線菌 Streptomyces kanamyceticus から産生されるカナマイシンの誘導体「アルベカシン」は抗生物質を半合成して作られたものです。

微生物が産生していないので、狭義の意味では、抗生物質とは言えないのですが、天然物を化学修飾したもの含めて抗生物質という場合も多いです。

また、半合成された抗生物質のほとんどは抗生物質製剤として医薬品に使用されており、実際、それら医薬品の添付文書や商品箱にはしっかりと「抗生物質」と記されています。

 

抗生物質と抗菌薬の違い
抗腫瘍性抗生物質

抗腫瘍薬いわゆる抗がん剤の中にも、抗生物質が存在します。

例えば、放線菌 Streptomyces caespitosus の培養濾液中から単離されたマイトマイシンCや放線菌 Streptomyces verticillus から単離されたブレオマイシンなどがあり、それぞれ抗腫瘍活性の他に、グラム陽性菌・陰性菌に対する強力な抗菌作用を有しています 。

その他、「ダウノルビシン」や「ジノスタチンスチマラマー」などは抗生物質から半合成したものであり、その他にも多くの抗生物質である抗腫瘍剤が存在します。

なお、現在では、元々の抗生物質の定義にある「他の微生物の生育を阻害する物質」に癌細胞も加えるよう拡大解釈することで、抗腫瘍剤を抗生物質に含めるという考えもあるようですが、多くの抗腫瘍性化合物にはそもそも強い(細胞毒性による)抗菌活性があるので、ワックスマン博士が提唱した狭義の定義においても抗生物質と言えると私は思います。

 

スタチン系コレステロール降下剤も抗生物質?

これは極論かつ自論になりますが、私はプラバスタチン(メバロチン®︎)のようなスタチン系のコレステロール降下剤も抗生物質と考えています

医療従事者でそんなことを言う人はいないと思います。しかし、世界初のスタチン系化合物であるコンパクチンは青カビ Penicillium citrinum から単離されたものであり、プラバスタチン(メバロチン®︎)はその誘導体(アルカリ処理後、放線菌 Streptomyces carbophilus により微生物変換したもの)です。(FEBS Lett 1976 ; 72 : 323,J Antibiot 1976 ; 29 : 1346)

コンパクチンの抗菌活性についても、しっかり1976年にビーチャム社(現在のグラクソ・スミスクライン)の研究者が学術雑誌に化学構造と抗菌活性を報告している。(J Chem Soc Perkin 1976 ; I : 1165)

というのも、スタチン系化合物はメバロン酸合成の律速酵素である HMGA-CoA 還元酵素を阻害する作用を持つので、ユビキノンや細胞壁ペプチドグリカン生合成に重要なリピド中間体のリピド部分の生合成前駆体の生成を抑制するから抗菌作用があるのは理論的に当然と考えられます。

(余談ですが、メバロン酸経路を経由してリピド中間体を生成する生物はヒトや黄色ブドウ球菌、真核生物などであり、多くの病原性細菌は非メバロン酸経路を利用する。つまり、スタチン系は黄色ブドウ球菌の生育は抑えるが、大腸菌や緑膿菌には効かないということ。)

したがって、抗生物質の定義である「微生物が産生し、他の微生物の生育を阻害する物質」にスタチン系化合物は当てはまるので、私はスタチン系コレステロール降下剤を(半合成の)抗生物質と考えています。

 

現場では「抗菌薬」「抗生物質」どちらでも構わない

これまで、抗生物質と抗菌薬との違いを細かく説明してきましたが、薬剤師がそれら薬剤を患者に対してどう言うかは、ズバリ患者次第でしょう。

ただ患者に伝わればいい。たったそれだけ。

臨床における感染症のプロフェショナルと言われる人のほとんどは全てまとめて抗菌薬ということが多いですが、なぜか患者は抗生物質や抗生剤の方が馴染みのあるものであり、理解しやすい。

ただ、患者がその道の研究者であったり、有識の医師・薬剤師であった場合、レボフロキサシンを「抗生物質」と呼ぶのは、「大学でしっかり勉強してこなかったのかな」と思われたり信頼を損ねる可能性がないとも言えません。

したがって、まずは抗菌薬と抗生物質の違いをしっかりと理解し、そして患者を判断して、「抗菌薬」「抗生物質」をうまく使い分けて話すのが最良といえます。

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最新の医療ニュースや医薬品情報をチェックするなら『m3.com(エムスリー)』。
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製薬会社からの広告収入により運営されており、製品紹介動画を見るだけで、商品券と交換できるm3 ポイントも貯まります

まだ登録していない方は忘れずにチェック → 詳しくはこちら

 

感染症といえば沖縄

最後になりますが、当サイトは薬剤師のための転職情報サイトです。

亜熱帯海洋性気候の沖縄県は、一年中温暖で湿潤な気候特性から、本土と比較して感染症の患者が多い。

ノーベル賞を受賞した大村智先生が放線菌 Streptomyces avermetilis より発見したアベルメクチンの化学誘導体であるイベルメクチン(ストロメクトール®︎)は沖縄県では疥癬以外でも結構処方されます。

感染症に興味のある薬剤師の皆さん、美しい海が大好きな薬剤師の皆さん、沖縄で働きませんか?


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