TW201330877A - Release capsules, manufacture and uses thereof - Google Patents
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本發明係關於釋放膠囊領域，該等膠囊尤其用於保護濕敏材料，例如鹽且尤其用於產生二氧化氯之組成物。本發明亦關於製造該等釋放膠囊之方法，且關於該等釋放膠囊之用途，尤其關於包含其之產物。 The invention relates to the field of release capsules, in particular for the protection of moisture-sensitive materials, such as salts, and in particular for the production of chlorine dioxide. The invention also relates to methods of making such release capsules, and to the use of such release capsules, and more particularly to products comprising the same.
常需要防止化學藥劑與其所在環境相互作用。然而，此等藥劑最終必須暴露於該環境以使其可展現其預定活性，例如在環境條件變得有利時或在需要指定作用時。 It is often necessary to prevent chemical agents from interacting with their environment. However, such agents must ultimately be exposed to the environment such that they exhibit their intended activity, such as when environmental conditions become favorable or when a specified effect is desired.
因此，經常嘗試使敏感藥劑與反應性環境分隔開。此僅當需要藥劑存在於反應混合物中時，才可例如藉由將該等藥劑投予包含反應混合物之反應器中來達成。或者，已嘗試使藥劑以封裝形式包括於反應混合物中，以便不再需要其他藥劑劑量。該等封裝可為例如包含反應混合物之各別成分於彼此機械隔開的個別區室中之多部分容器。在移除分隔該等區室之機械障壁後，可混合各成分且藥劑可發揮其作用。 Therefore, attempts are often made to separate sensitive agents from reactive environments. This can only be achieved, if the agent is required to be present in the reaction mixture, for example by administering the agents to a reactor comprising the reaction mixture. Alternatively, an attempt has been made to include the agent in a package in the reaction mixture so that no other agent dose is needed. The packages may be, for example, a multi-part container containing individual components of the reaction mixture that are mechanically separated from each other. After removing the mechanical barrier separating the compartments, the ingredients can be mixed and the agent can function.
就此而言，已嘗試用殼體囊封藥劑，以防止與反應性環境直接接觸。膠囊可呈具有一或多個殼層之核殼型粒子形式，或可為藥劑嵌入基質中之膠囊。亦已嘗試呈核殼型粒子形式之釋放膠囊，其中核心由嵌入有化學藥劑之基質製成。例如藉由基質及/或殼體材料之機械作用或機械崩解而自膠囊釋放藥劑。 In this regard, attempts have been made to encapsulate the agent with a shell to prevent direct contact with the reactive environment. The capsule may be in the form of core-shell particles having one or more shell layers or may be a capsule in which the agent is embedded in the matrix. Attempts have also been made to release capsules in the form of core-shell particles in which the core is made of a matrix embedded with a chemical agent. The agent is released from the capsule, for example, by mechanical action or mechanical disintegration of the matrix and/or shell material.
一個問題為化學藥劑之囊封過程本身不可使藥劑暴露於環 境，導致藥劑變質。舉例而言，溫度敏感型藥劑在囊封期間不應暴露於高溫，且濕敏型藥劑在囊封期間不應暴露於水。 One problem is that the encapsulation process of the chemical itself does not expose the agent to the ring. The environment causes the agent to deteriorate. For example, the temperature sensitive agent should not be exposed to high temperatures during encapsulation, and the moisture sensitive agent should not be exposed to water during encapsulation.
本發明已因此著手提供一種囊封化學藥劑之製造方法，其中該製造方法應允許在基本上不存在水的情況下進行。該製造方法亦應允許完整囊封且亦應允許實現囊封內容物甚至在浸入水中後亦能有長期防水效果。另外，本發明著手提供對應的釋放膠囊、其用途及尤其包含該等釋放膠囊之產物。 The present invention has therefore proceeded to provide a method of making an encapsulated chemical wherein the method of manufacture should be allowed to be carried out in the substantial absence of water. The method of manufacture should also permit complete encapsulation and should also allow for the long-term waterproofing of the encapsulated contents even after immersion in water. Additionally, the present invention proceeds to provide corresponding release capsules, uses thereof, and in particular products comprising such release capsules.
根據本發明，因此提供一種釋放膠囊，包含一具有欲最終釋放之藥劑的核心，該藥劑包含兩種或兩種以上不同物質或由兩種或兩種以上不同物質組成，該核心由一疏水性材料之殼體圍繞，且金屬氧化物材料沈積於該殼體中及/或沈積於該殼體上，其中金屬氧化物材料之量經選擇以使在該膠囊與液體水接觸後自該膠囊釋放50 wt.-%之該藥劑(亦即該藥劑之兩種或兩種以上不同物質之總重量/總含量)延遲至少24小時。 According to the present invention, there is thus provided a release capsule comprising a core having an agent to be finally released, the agent comprising two or more different substances or consisting of two or more different substances, the core being hydrophobic a shell of material surrounding and a metal oxide material deposited in the shell and/or deposited on the shell, wherein the amount of metal oxide material is selected such that the capsule is released from the capsule upon contact with liquid water 50 wt.-% of the agent (i.e., the total weight/total content of two or more different substances of the agent) is delayed by at least 24 hours.
現已驚訝地發現，疏水性殼體材料與沈積於該殼體中及/或沈積於該殼體上之金屬氧化物材料之組合允許使在釋放膠囊與液體水接觸後自該釋放膠囊之核心釋放50 wt.-%之藥劑延遲至少24小時。金屬氧化物材料之量較佳經選擇以便(a)使在該膠囊與液體水接觸後自該膠囊釋放75 wt.-%之該藥劑(亦即該藥劑之兩種或兩種以上不同物質之總重量/總含量)延遲至少24小時，且較佳地，(b)使在該膠囊與液體水接觸後自該膠囊釋放50 wt.-%之該藥劑(亦即該藥劑之兩種或兩種以上不同物質之總重量/總含量)延遲至少48小時。 It has now surprisingly been found that the combination of the hydrophobic shell material with the metal oxide material deposited in the shell and/or deposited on the shell allows the core of the capsule to be released after the release capsule is in contact with the liquid water. Release 50 wt.-% of the agent for at least 24 hours. Preferably, the amount of metal oxide material is selected to (a) release 75 wt.-% of the agent from the capsule after contact with the liquid water (ie, two or more different substances of the agent) The total weight/total content is delayed by at least 24 hours, and preferably, (b) releasing 50 wt.-% of the agent from the capsule after contact with the liquid water (ie, two or two of the agent) The total weight/total content of the above different substances is delayed by at least 48 hours.
術語「釋放」應解釋為意指藥劑或其各物質分別離開由疏水性材料之殼體圍繞且界定之(內部)區域且進入圍繞膠囊之介質，詳言之圍繞膠囊之液體或氣體介質，例如液體水。舉例而言，「離開」可發生在例如水流入釋放膠囊後，此會引起欲釋放藥劑溶解且釋放於水相環境中。視所用藥劑及任何圍繞膠囊之介質而定，若介質或其任何化合物滲入膠囊殼體且因此進入膠囊(內部)區域，因此藥劑或其一或多種物質可能與介質或其任何化合物反應，其中產生一或多種(其他)物質且之後自膠囊釋放，則亦可能發生「離開」。詳言之，離開可發生在周圍液體穿過殼體之擴散過程(關於分子擴散)的情況下，此可有助於核心之兩種不同物質之反應且形成氣態新組分，其接著可離開由殼體圍繞且界定之(內部)區域。 The term "release" is to be interpreted to mean that the agent or its substance separates from the (internal) region surrounded and defined by the shell of the hydrophobic material and enters the medium surrounding the capsule, in particular the liquid or gaseous medium surrounding the capsule, for example Liquid water. For example, "away" can occur, for example, after water has flowed into the release capsule, which causes the release of the agent to be dissolved and released into the aqueous environment. Depending on the agent used and any medium surrounding the capsule, if the medium or any compound thereof penetrates into the capsule shell and thus enters the capsule (internal) region, the agent or one or more substances thereof may react with the medium or any of its compounds, wherein "Leaving" may also occur if one or more (other) substances are released from the capsule. In particular, leaving can occur in the diffusion process of the surrounding liquid through the shell (with respect to molecular diffusion), which can contribute to the reaction of the two different substances of the core and form a gaseous new component, which can then leave An (internal) area surrounded and defined by the housing.
膠囊(如上所述)中所含之藥劑或其各物質各自釋放之量測較佳藉由使用例如雷射技術來進行：發送雷射束至浸於液體中之稜鏡，其中要研究核心藥劑或由兩種或兩種以上核心藥劑之反應形成之新組分的釋放(如上所述)。欲量測釋放之物質顯示在稜鏡與液體之間的界面處之繞射角對周圍液體中之物質濃度的函數依賴性。此依賴性可藉由添加確定的量至液體中且量測已自雷射器傳至稜鏡且隨後回至光學元件之光，亦即藉由量測回光(returning light)來校準。在該校準後，可將稜鏡浸於欲研究液體中，添加膠囊且可藉由量測回光(如上所述)之強度來研究核心藥劑之釋放。應注意，膠囊本身浸於液體中，但並未改變界面處之繞射角。根據本發明之一個較佳具體實例，量測(核心所釋放且)保留於水溶液中之任何物質(尤其鹽離子，例如Na+)對於繞射角之影響，而由核心藥劑反應形成之任何氣體(例如ClO2、CO2)(若合適時)將不會對量測有影響。儘管如此，由於核心藥劑之反應通常為已知的，故可校準且明確地量測釋放。因此，較佳對核心藥劑進行選擇，使得核心藥劑之反應(如上所述)已知或可分別預見。 The measurement of the release of each of the medicaments contained in the capsules (as described above) or their respective substances is preferably carried out by using, for example, a laser technique: sending a laser beam to a crucible immersed in a liquid, wherein the core medicament is to be studied Or the release of a new component formed by the reaction of two or more core agents (as described above). The substance to be measured is shown to exhibit a dependence of the diffraction angle at the interface between the hydrazine and the liquid on the concentration of the substance in the surrounding liquid. This dependency can be calibrated by adding a determined amount to the liquid and measuring the light that has passed from the laser to the helium and then back to the optical element, ie by measuring the returning light. After this calibration, the sputum can be immersed in the liquid to be studied, capsules added and the release of the core agent can be studied by measuring the intensity of the return light (as described above). It should be noted that the capsule itself is immersed in the liquid but does not change the diffraction angle at the interface. According to a preferred embodiment of the invention, any substance (especially released by the core) that remains in the aqueous solution (especially salt ions, such as Na+) is affected by the diffraction angle, and any gas formed by the reaction of the core agent is measured ( For example, ClO2, CO2) (if appropriate) will not affect the measurement. Nonetheless, since the reaction of the core agent is generally known, the release can be calibrated and unambiguously measured. Therefore, it is preferred to select the core agent such that the reaction of the core agent (as described above) is known or separately foreseen.
術語「具有藥劑之核心」應解釋為意指該核心包含至少一種，亦即一或多種(不同)如本文分別所述之藥劑。該「核心」較佳由第一及第二藥劑，及視情況選用之一或多種其他物質(諸如黏合劑、填充劑或其他藥劑)組成。若該核心包含一種以上藥劑，亦即如本文所述之兩種或兩種以上不同藥劑，則關於釋放延遲(如本文所述)之限制條件適用於所有核心藥劑。該(等)限制條件較佳適用於膠囊核心中所含之所有物質，尤其若膠囊之核心中所含之所有物質為水溶性物質時。 The term "core having a medicament" is to be interpreted to mean that the core comprises at least one, i.e. one or more (different) agents as described herein separately. Preferably, the "core" consists of the first and second agents, and optionally one or more other substances (such as adhesives, fillers or other agents). If the core comprises more than one agent, i.e., two or more different agents as described herein, the limitations on release delay (as described herein) apply to all core agents. The (etc.) limiting conditions are preferably applied to all of the materials contained in the core of the capsule, especially if all of the materials contained in the core of the capsule are water soluble.
若核心包含一種以上藥劑，亦即兩種或兩種以上藥劑，其中各藥劑包含兩種或兩種以上不同物質或由兩種或兩種以上不同物質組成，則應瞭解本文中鑒於核心之(至少一種)藥劑所述之態樣較佳適用於核心中所含之所有藥劑。 If the core contains more than one agent, that is, two or more agents, each of which contains two or more different substances or consists of two or more different substances, it should be understood that The at least one agent described above is preferably applied to all of the agents contained in the core.
(至少一種)藥劑較佳包含兩種或兩種以上不同物質或由兩種或兩種以上不同物質組成，該等物質能夠在與氣體或液體介質接觸後，例如在與(液體)水接觸後產生(亦即至少一種)其他物質，該其他物質不同於膠囊核心中所含之藥劑之物質，較佳不同於膠囊核心中所含之所有物質。亦即，藥劑之兩種或兩種以上不同物質較佳能夠在與氣體或液體介質或其任何化合物接觸後，較佳在與(液體)水接觸後產生(藉由化學反應來產生)該其他物質。與(氣體或液體)介質或其任何化合物接觸可發生在(a)膠囊釋放藥劑後或(b)若介質或其任何化合物滲入膠囊殼體且因此進入膠囊(內部)區域時(如上所述)。 The (at least one) agent preferably comprises two or more different substances or consists of two or more different substances which are capable of contacting the gas or liquid medium, for example after contact with (liquid) water. The other substance is produced (i.e., at least one) different from the substance of the agent contained in the core of the capsule, preferably different from all of the substances contained in the core of the capsule. That is, two or more different substances of the agent are preferably capable of being produced after contact with the gas or liquid medium or any of its compounds, preferably after contact with (liquid) water (produced by a chemical reaction). substance. Contact with a (gas or liquid) medium or any of its compounds may occur after (a) the capsule releases the agent or (b) if the medium or any of its compounds penetrates into the capsule shell and thus enters the capsule (internal) region (as described above) .
其中核心藥劑(較佳為各藥劑)為二氧化氯產生劑的本發明之釋放膠囊尤其較佳。較佳的二氧化氯產生劑將如下所述。 The release capsule of the present invention in which the core agent (preferably each agent) is a chlorine dioxide generator is particularly preferred. Preferred chlorine dioxide generators will be described below.
本發明之膠囊之核心中所含的藥劑較佳由兩種或兩種以上不同水溶性物質組成。尤其較佳為一種膠囊，其中該膠囊之核心中所含之所有物質為水溶性物質。 The agent contained in the core of the capsule of the present invention preferably consists of two or more different water-soluble substances. Particularly preferred is a capsule wherein all of the substances contained in the core of the capsule are water soluble.
較佳地，本發明之膠囊之核心中所含的藥劑為固體混合物，較佳為固體水溶性混合物。 Preferably, the agent contained in the core of the capsule of the present invention is a solid mixture, preferably a solid water-soluble mixture.
根據本發明之一個替代性具體實例，除如上所述之一或多種藥劑之外，膠囊之核心包含一或多種其他物質。根據本發明之一個較佳態樣，膠囊之核心中所含之所有物質為水溶性物質。 According to an alternative embodiment of the invention, the core of the capsule comprises one or more other substances in addition to one or more of the agents described above. According to a preferred aspect of the invention, all of the materials contained in the core of the capsule are water soluble.
因此，根據本發明之一個尤其較佳的具體實例，膠囊包含一具有一或多種藥劑(如上所述)之核心，該(等)藥劑包含兩種或兩種以上不同水溶性物質或由兩種或兩種以上不同水溶性物質組成，該等物質能夠在與氣體或液體介質接觸後產生一或多種其他物質(如上所述)，該(等)藥劑較佳為二氧化氯產生劑，該其他物質不同於該膠囊之核心中所含之所有物質，其中該膠囊之核心中所含之所有物質為水溶性物質。 Thus, in accordance with a particularly preferred embodiment of the invention, the capsule comprises a core having one or more agents (as described above), the agent comprising two or more different water soluble materials or by two Or consisting of two or more different water-soluble substances capable of producing one or more other substances (as described above) after contact with a gas or liquid medium, preferably the chlorine dioxide generating agent, the other The substance is different from all substances contained in the core of the capsule, wherein all substances contained in the core of the capsule are water-soluble substances.
較佳的製造該等釋放膠囊之方法、較佳的欲釋放藥劑、疏水性材料及金屬氧化物材料將詳細描述於下文中。 Preferred methods of making such release capsules, preferred release agents, hydrophobic materials, and metal oxide materials are described in detail below.
如上所述，本發明之較佳釋放膠囊包含二氧化氯產生劑作為欲釋放藥劑。一個尤其驚人的優勢為：本發明允許有效地在很長一段時間內使二氧化氯產生劑與液體水隔離，尤其允許使在膠囊與液體水接觸後自膠囊釋放50 wt.-%之二氧化氯產生劑延遲至少24小時，較佳允許(a)使在膠囊與液體水接觸後自膠囊釋放75 wt.-%之藥劑延遲至少24小時，且較佳地，(b)使在膠囊與液體水接觸後自膠囊釋放50 wt.-%之藥劑延遲至少48小時。 As described above, the preferred release capsule of the present invention contains a chlorine dioxide generator as a drug to be released. A particularly surprising advantage is that the present invention allows for effective isolation of the chlorine dioxide generator from liquid water over a long period of time, in particular allowing 50 wt.-% of oxidative release from the capsule after contact of the capsule with liquid water. The chlorine generating agent is delayed for at least 24 hours, preferably allowing (a) to delay release of 75 wt.-% of the agent from the capsule after contact with the liquid water for at least 24 hours, and preferably, (b) in the capsule and liquid A 50 wt.-% release of the agent from the capsule after contact with water is delayed for at least 48 hours.
二氧化氯(chlorodioxide/chlorine dioxide)為一種已知的消毒劑以及強氧化劑。二氧化氯因其具有殺細菌性、殺藻性、殺真菌性、漂白性及除臭性而尤其有用；參見US 6238643。二氧化氯之一個優勢為其可在不形成不希望有的副產物(諸如氯胺或氯化有機化合物)的情況下起作用，該等副產物不然會在利用元素氯進行消毒或薰蒸時產生。二氧化氯之一個 劣勢為在標準條件(亦即20℃、1013 hPa)下，二氧化氯為氣體且因此難以儲存。因此，為使用二氧化氯，此化合物常常必須如例如WO 2007/100531 A2及WO 2007/149906 A2中所述當場產生。然而，二氧化氯產生劑必須小心操作，因為二氧化氯會***分解成元素氯及氧。此外，當由鹽形成二氧化氯時，強制性地以無水形式儲存產生二氧化氯的鹽混合物，以免自發開始產生二氧化氯，由此導致二氧化氯損失或可能導致***性氣體形成。 Chlorodioxide/chlorine dioxide is a known disinfectant and a strong oxidant. Chlorine dioxide is particularly useful for its bactericidal, algicidal, fungicidal, bleaching and deodorizing properties; see US 6,238,643. One advantage of chlorine dioxide is that it can function without the formation of undesirable by-products such as chloramines or chlorinated organic compounds, which would otherwise be sterilized or fumigated with elemental chlorine. produce. One of chlorine dioxide The disadvantage is that under standard conditions (ie 20 ° C, 1013 hPa), chlorine dioxide is a gas and therefore difficult to store. Thus, in order to use chlorine dioxide, this compound must often be produced on the spot as described, for example, in WO 2007/100531 A2 and WO 2007/149906 A2. However, chlorine dioxide generators must be handled with care because chlorine dioxide decomposes into elemental chlorine and oxygen. Further, when chlorine dioxide is formed from a salt, it is mandatory to store a salt mixture which produces chlorine dioxide in an anhydrous form so as not to spontaneously start to generate chlorine dioxide, thereby causing loss of chlorine dioxide or possibly causing formation of an explosive gas.
現已驚訝地發現，可形成本發明之釋放膠囊以囊封用於產生二氧化氯之(鹽)混合物(在本文中稱為「二氧化氯產生劑」；該等混合物例如以商品名Aseptrol出售)，且更有價值的是：本發明之釋放膠囊可有效地使囊封的產生二氧化氯之混合物與水隔離。因此，本發明允許提供二氧化氯產生劑之一種安全儲存形式，且從而極大地拓寬二氧化氯之潛在應用範圍。 It has now surprisingly been found that the release capsules of the present invention can be formed to encapsulate a (salt) mixture for the production of chlorine dioxide (referred to herein as "chlorine dioxide generator"; such mixtures are sold, for example, under the trade name Aseptrol And, more valuablely, the release capsule of the present invention is effective to isolate the encapsulated chlorine dioxide-producing mixture from water. Thus, the present invention allows for a safe storage form of chlorine dioxide generating agent and thereby greatly broadens the potential range of application of chlorine dioxide.
適合二氧化氯產生劑及其物質例如描述於WO 2007/100531 A2及WO 2007/149906 A2中(尤其參見分別關於「產生二氧化氯之組成物」或「形成二氧化氯之組成物」及其對應成分之態樣)。 Suitable chlorine dioxide generating agents and their substances are described, for example, in WO 2007/100531 A2 and WO 2007/149906 A2 (see, in particular, "Composition of chlorine dioxide generating" or "Composition of chlorine dioxide forming" and Corresponding components)
本發明所用之包含兩種或兩種以上不同物質或由兩種或兩種以上不同物質組成的二氧化氯產生劑(如上所述)因此較佳包含以下物質或由以下物質組成：- 一或多種氧基-氯鹽，較佳為一或多種如WO/2007/149906 A2中所述之氧基-氯鹽，尤其為一或多種如其中描述為較佳者，尤其如其申請專利範圍中所述的氧基-氯鹽，較佳為金屬亞氯酸鹽，及- 一種酸源，較佳為如WO/2007/149906 A2中所述之酸源，更佳為如其中描述為較佳，尤其如其申請專利範圍中所述之酸源，(該(等)氧基-氯鹽，較佳為該金屬亞氯酸鹽及該酸源能夠在水中反應形成二氧化氯)， 及視情況選用之其他物質，亦即- 一或多種游離鹵素源，較佳為一或多種如WO/2007/149906 A2中所述之游離鹵素源，更佳為一或多種如其中描述為較佳，尤其如其申請專利範圍中所述之游離鹵素源，及/或- 一或多種用於緩和氧基-氯鹽之放熱反應之吸熱劑，較佳為一或多種如WO/2007/149906 A2中所述之吸熱劑，更佳為一或多種如其中描述為較佳，尤其如其申請專利範圍中所述之吸熱劑，及/或- 一或多種磷酸鹽，較佳為一或多種如WO/2007/100531 A2中所述之磷酸鹽，更佳為一或多種如其中描述為較佳，尤其如其申請專利範圍中所述之磷酸鹽，及/或- 一或多種界面活性劑，較佳為一或多種如WO/2007/100531 A2中所述之界面活性劑，更佳為一或多種如其中描述為較佳的界面活性劑，及/或- 一或多種其他物質，較佳為一或多種在WO 2007/100531 A2及/或WO 2007/149906 A2中分別結合「產生二氧化氯之組成物」或「形成二氧化氯之組成物」所述之其他物質。 The chlorine dioxide generating agent (as described above) comprising two or more different substances or consisting of two or more different substances used in the present invention preferably comprises or consists of the following substances: - a plurality of oxy-chlorine salts, preferably one or more oxy-chlorine salts as described in WO/2007/149906 A2, especially one or more as described therein as preferred, especially as claimed in the patent application The oxy-chlorine salt, preferably a metal chlorite, and - an acid source, preferably an acid source as described in WO/2007/149906 A2, more preferably as described therein. Particularly as the acid source described in the scope of the patent application, (the (etc.)oxy-chlorine salt, preferably the metal chlorite and the acid source are capable of reacting in water to form chlorine dioxide), And other materials selected as appropriate, i.e., one or more sources of free halogen, preferably one or more of the free halogen sources as described in WO/2007/149906 A2, more preferably one or more as described therein. Preferably, especially as the free halogen source described in the scope of the patent application, and/or one or more heat absorbing agents for tempering the exothermic reaction of the oxy-chlorine salt, preferably one or more, such as WO/2007/149906 A2 The heat absorbing agent described above is more preferably one or more of the heat absorbing agents as described therein, especially as described in the scope of the patent application, and/or one or more phosphates, preferably one or more such as WO. The phosphates described in /2007/100531 A2, more preferably one or more of which are preferably described therein, especially as described in the scope of their patent application, and/or one or more surfactants, preferably One or more surfactants as described in WO/2007/100531 A2, more preferably one or more surfactants as described therein, and/or one or more other substances, preferably one Or a plurality of combinations in WO 2007/100531 A2 and/or WO 2007/149906 A2 Other substances described in the composition of oxidized chlorine or "the composition forming chlorine dioxide".
當二氧化氯產生藥劑接觸水時，氧基-氯鹽提供二氧化氯。氧基-氯鹽可定義為一或多種含有亞氯酸根陰離子、氯酸根陰離子、或亞氯酸根陰離子與氯酸根陰離子之組合的固體材料。詳言之，術語氧基-氯鹽可指一或多種含有亞氯酸根陰離子或氯酸根陰離子中之任一者或兩者之金屬鹽。個別鹽、組合鹽及含有兩種或兩種以上個別鹽及/或組合鹽之任何組合的混合物可包括於術語氧基-氯鹽中。在一個較佳具體實例中，氧基-氯鹽可 溶於水。 The oxy-chlorine salt provides chlorine dioxide when the chlorine dioxide generating agent contacts water. The oxy-chlorine salt can be defined as one or more solid materials containing a chlorite anion, a chlorate anion, or a combination of a chlorite anion and a chlorate anion. In particular, the term oxy-chlorine salt may refer to one or more metal salts containing either or both of a chlorite anion or a chlorate anion. Mixtures of individual salts, combination salts, and any combination of two or more individual salts and/or combination salts may be included in the term oxy-chlorine salt. In a preferred embodiment, the oxy-chlorate salt can Dissolved in water.
金屬亞氯酸鹽之實例包括鹼金屬亞氯酸鹽，諸如亞氯酸鋰、亞氯酸鈉及亞氯酸鉀；及鹼土金屬亞氯酸鹽，諸如亞氯酸鈣及亞氯酸鎂。在一個較佳具體實例中，金屬亞氯酸鹽為亞氯酸鈉，尤其含有約80重量%之亞氯酸鈉及20重量%之其他鹽的乾燥工業級亞氯酸鈉。 Examples of metal chlorites include alkali metal chlorites such as lithium chlorite, sodium chlorite and potassium chlorite; and alkaline earth metal chlorites such as calcium chlorite and magnesium chlorite. In a preferred embodiment, the metal chlorite is sodium chlorite, especially dry industrial grade sodium chlorite containing about 80% by weight sodium chlorite and 20% by weight other salts.
金屬氯酸鹽之適合實例包括鹼金屬氯酸鹽，諸如氯酸鈉及氯酸鉀；及鹼土金屬氯酸鹽，諸如氯酸鎂。 Suitable examples of metal chlorates include alkali metal chlorates such as sodium chlorate and potassium chlorate; and alkaline earth metal chlorates such as magnesium chlorate.
在一個較佳具體實例中，酸源為乾燥固體酸源。該等乾燥固體酸源之實例包括無機酸鹽，諸如硫酸氫鈉及硫酸氫鉀；含有強酸陰離子及弱鹼陽離子之鹽，諸如氯化鋁、硝酸鋁、硝酸鈰及硫酸鐵；可在與水接觸時釋出質子於溶液中之固體酸，例如分子篩ETS-10(參見美國專利第4,853,202號)之酸性離子交換形式與氯化鈉之混合物；有機酸，諸如檸檬酸及酒石酸；及其混合物。在一個較佳具體實例中，固體酸源為固體無機酸源，例如硫酸氫鈉。本發明之釋放膠囊(尤其在欲釋放藥劑為二氧化氯產生劑時)之沈積金屬氧化物材料的量以該膠囊之總質量計，較佳為較佳小於10 wt.-%，較佳為小於2 wt.-%，尤其為0.1至1 wt.-%。現已發現，在金屬氧化物之該等量下，可有效地密封疏水性殼體材料之小孔或不規則處，防止例如水流入釋放膠囊中，此不然會導致欲釋放藥劑溶解且釋放於水相環境中。 In a preferred embodiment, the acid source is a dry solid acid source. Examples of such dry solid acid sources include inorganic acid salts such as sodium hydrogen sulfate and potassium hydrogen sulfate; salts containing strong acid anions and weak base cations such as aluminum chloride, aluminum nitrate, cerium nitrate and iron sulfate; A solid acid that releases protons in solution upon contact, such as a mixture of acidic ion exchange forms and sodium chloride of molecular sieve ETS-10 (see U.S. Patent No. 4,853,202); organic acids such as citric acid and tartaric acid; and mixtures thereof. In a preferred embodiment, the solid acid source is a solid inorganic acid source such as sodium bisulfate. The amount of the deposited metal oxide material of the release capsule of the present invention (especially when the agent to be released is a chlorine dioxide generator) is preferably preferably less than 10 wt.-%, preferably less than 10 wt.-%, based on the total mass of the capsule. Less than 2 wt.-%, especially 0.1 to 1 wt.-%. It has been found that at the same amount of metal oxide, the pores or irregularities of the hydrophobic shell material can be effectively sealed to prevent, for example, water from flowing into the release capsule, which would otherwise cause the release of the agent to be dissolved and released. In an aqueous environment.
欲沈積之金屬氧化物較佳呈粉末形式，其中粉末為由具有100μm以下、較佳為10μm以下之較佳平均尺寸的不同粒子組成的材料，該等平均尺寸可例如藉由標準雷射繞射量測(例如根據Malvern instruments)來量測，且粉末較佳選自由ZnO、SnO2、SiO2、Al2O3、AlOOH、ZrO2、Fe2O3、MgO、CaO及TiO2組成之群，較佳選自由ZnO、SiO2及TiO2組成之群。該金屬氧化物(粉末)之表面可藉由例如將(脂肪)酸基連接於表面，較 佳藉由將硬脂酸基連接於表面而產生疏水性。適用於本發明之金屬氧化物材料可例如為經疏水性處理之ZnO或TiO2。 The metal oxide to be deposited is preferably in the form of a powder, wherein the powder is a material consisting of different particles having a preferred average size of 100 μm or less, preferably 10 μm or less, which may be, for example, by standard laser diffraction. The measurement is measured (for example, according to Malvern instruments), and the powder is preferably selected from the group consisting of ZnO, SnO2, SiO2, Al2O3, AlOOH, ZrO2, Fe2O3, MgO, CaO and TiO2, preferably selected from the group consisting of ZnO, SiO2 and TiO2. a group of people. The surface of the metal oxide (powder) can be attached to the surface by, for example, a (fatty) acid group. Hydrophobicity is preferably achieved by attaching a stearic acid group to the surface. Metal oxide materials suitable for use in the present invention may, for example, be hydrophobically treated ZnO or TiO2.
金屬氧化物材料沈積於疏水性材料殼體中及/或沈積於疏水性材料殼體上。疏水性材料較佳為石蠟，其有利地賦予釋放膠囊機械強度及水密性；蠟材料；軟聚合物(如短直鏈聚乙烯或聚異丁烯)或蟲膠。疏水性材料較佳包含聚乙烯蠟、硬脂酸蠟、石蠟及/或脂肪酸蠟或由聚乙烯蠟、硬脂酸蠟、石蠟及/或脂肪酸蠟組成。疏水性材料較佳包含石蠟或由石蠟組成。 The metal oxide material is deposited in a hydrophobic material shell and/or deposited on a hydrophobic material shell. The hydrophobic material is preferably a paraffin wax which advantageously imparts mechanical strength and water tightness to the release capsule; a wax material; a soft polymer such as short linear polyethylene or polyisobutylene or shellac. The hydrophobic material preferably comprises or consists of a polyethylene wax, a stearic acid wax, a paraffin wax and/or a fatty acid wax or a polyethylene wax, a stearic acid wax, a paraffin wax and/or a fatty acid wax. The hydrophobic material preferably comprises or consists of paraffin wax.
本發明之釋放膠囊(較佳如上所述為較佳的釋放膠囊)較佳包含石蠟殼體(如上所述)，且更較佳的是使氧化鋅材料沈積於殼體中及/或沈積於殼體上(如上所述)。 The release capsule of the present invention, preferably a preferred release capsule as described above, preferably comprises a paraffin shell (as described above), and more preferably a zinc oxide material is deposited in the shell and/or deposited On the housing (as described above).
本發明之釋放膠囊，尤其包含二氧化氯產生劑之釋放膠囊，可用於殺細菌、殺藻、殺真菌、漂白及除臭目的。此外，由於其具有囊封作用，現有可能在用於局部施用於人體或動物體之化妝品或醫藥調配物中包括例如二氧化氯產生劑，以使得在使用調配物後產生二氧化氯。舉例而言，包含二氧化氯產生劑之本發明之釋放膠囊可包括於局部施用之調配物中，如個人衛生產品，例如肥皂、牙膏、***錠、消毒製品及傷口敷料。當局部施用該調配物時，本發明粒子之殼體可破裂以釋放二氧化氯產生劑且使其暴露於環境，由此產生二氧化氯且利用其漂白性及/或消毒性。 The release capsule of the present invention, especially comprising a release capsule of a chlorine dioxide generator, can be used for bactericidal, algicidal, fungicidal, bleaching and deodorizing purposes. Furthermore, due to its encapsulation, it is currently possible to include, for example, a chlorine dioxide generator in a cosmetic or pharmaceutical formulation for topical application to the human or animal body such that chlorine dioxide is produced after use of the formulation. For example, a release capsule of the present invention comprising a chlorine dioxide generating agent can be included in a topical formulation, such as a personal hygiene product such as a soap, a toothpaste, a buccal tablet, a disinfecting article, and a wound dressing. When the formulation is topically applied, the shell of the particles of the invention can be broken to release the chlorine dioxide generator and expose it to the environment, thereby producing chlorine dioxide and utilizing its bleaching and/or disinfecting properties.
本發明之釋放膠囊，尤其包含二氧化氯產生劑之釋放膠囊亦可包括於不局部施用於人體或動物體之產品中。詳言之，其可用作水淨化產品，以用於控制水應用(例如游泳池、儲水及廢水再循環、水管(如管及軟管)及工業冰機)中之生物膜及非殺滅性微生物(non-cidal microorganism)生長。該等膠囊可添加至與大氣冷卻水管路連通的溫室或冷卻塔中之水管中以免生物結垢(生物體生長)。在該情況下，例如所釋放(所 產生)的ClO2限制生物體生長與繁殖(對於本申請案，基於鉀之鹽為有利的，詳言之該等鹽不會損害植物以後的生長)。此外，包含二氧化氯產生劑之本發明之釋放膠囊可以呈粉末狀之乾燥形式使用，尤其用於表面衛生，例如用於地毯或洗滌。在該等應用中，可機械破裂釋放膠囊，例如在行走於撒有釋放膠囊之地毯上時，使得環境水分可與產生二氧化氯之調配物反應而產生二氧化氯。 The release capsule of the present invention, particularly a release capsule comprising a chlorine dioxide generator, may also be included in a product that is not applied topically to a human or animal body. In particular, it can be used as a water purification product for controlling biofilms and non-killing in water applications such as swimming pools, water storage and wastewater recycling, water pipes (such as pipes and hoses) and industrial ice machines. Non-cidal microorganisms grow. The capsules may be added to a water pipe in a greenhouse or cooling tower that is in communication with the atmospheric cooling water line to avoid biofouling (biomass growth). In this case, for example, released The resulting ClO2 limits the growth and reproduction of the organism (for the purposes of this application, potassium based salts are advantageous, in particular such salts do not impair the subsequent growth of the plant). Furthermore, the release capsules of the invention comprising a chlorine dioxide generating agent can be used in a dry form in powder form, especially for surface hygiene, for example for carpeting or washing. In such applications, the capsule can be mechanically ruptured, for example, when walking on a carpet with a release capsule, allowing ambient moisture to react with the chlorine dioxide-producing formulation to produce chlorine dioxide.
欲釋放藥劑(或各別藥劑)，較佳為二氧化氯產生劑之含量較佳為核心總質量之至少50 wt.-%，更佳為至少75 wt.-%且最佳為90-100 wt.-%。 Preferably, the chlorine dioxide generator is present in an amount of at least 50 wt.-%, more preferably at least 75 wt.-%, and most preferably 90-100. Wt.-%.
根據本發明之一個較佳具體實例，核心合計達膠囊總重量之至少50 wt.-%、較佳為至少66 wt.-%。尤其較佳的是本發明之釋放膠囊包含合計達該膠囊總重量之至少50 wt.-%、較佳為至少66 wt.-%之核心(如上所述)、合計達該膠囊總重量之10至40 wt.-%、較佳為10至20 wt.-%之殼體(如上所述)及合計達該膠囊總重量之10 wt.-%或10 wt.-%以下、較佳為2 wt.-%或2 wt.-%以下、尤其為0.1至1 wt.-%之金屬氧化物(如上所述)或由合計達該膠囊總重量之至少50 wt.-%、較佳為至少66 wt.-%之核心(如上所述)、合計達該膠囊總重量之10至40 wt.-%、較佳為10至20 wt.-%之殼體(如上所述)及合計達該膠囊總重量之10 wt.-%或10 wt.-%以下、較佳為2 wt.-%或2 wt.-%以下、尤其為0.1至1 wt.-%之金屬氧化物(如上所述)組成。 According to a preferred embodiment of the invention, the core is at least 50 wt.-%, preferably at least 66 wt.-%, based on the total weight of the capsule. It is especially preferred that the release capsule of the present invention comprises a core (as described above) totaling at least 50 wt.-%, preferably at least 66 wt.-%, based on the total weight of the capsule, totaling 10% of the total weight of the capsule. a shell of 40 wt.-%, preferably 10 to 20 wt.-% (as described above) and a total of 10 wt.-% or less than 10 wt.-%, preferably 2, of the total weight of the capsule a wt.-% or less than 2 wt.-%, especially 0.1 to 1 wt.-% of the metal oxide (as described above) or a total of at least 50 wt.-%, preferably at least the total weight of the capsule a core of 66 wt.-% (as described above), a total of 10 to 40 wt.-%, preferably 10 to 20 wt.-% of the total weight of the capsule (as described above) and a total of up to 10 wt.-% or less than 10 wt.-%, preferably 2 wt.-% or 2 wt.-% or less, especially 0.1 to 1 wt.-% of the total weight of the capsule (as described above) )composition.
由於根據本發明之一個具體實例，欲由本發明膠囊釋放之藥劑被有效地與環境水隔離開來，因此本發明之釋放膠囊之核心可有利地具有低含量的除欲釋放藥劑以外之材料，例如其他穩定化基質材料。因此，本發明允許製造具有高含量之欲釋放藥劑的特別小之膠囊。 Since the agent to be released from the capsule of the present invention is effectively isolated from the ambient water according to a specific example of the present invention, the core of the release capsule of the present invention may advantageously have a low content of materials other than the drug to be released, for example Other stabilizing matrix materials. Thus, the present invention allows the manufacture of particularly small capsules having a high level of drug to be released.
本發明之釋放膠囊，尤其為藥劑為二氧化氯產生劑之彼等釋放膠囊，尤其為如本文中所述為較佳之彼等釋放膠囊，較佳具有使膠囊在 用於產品(例如乳膏劑或糊劑)時不會被作為粒子而察覺到，尤其例如在使用或接觸該產品時不會被(人類)舌頭或皮膚察覺到的粒徑。本發明之釋放膠囊較佳具有2000μm或2000μm以下、較佳為1000μm或1000μm以下、更佳為500μm或500μm以下、更佳為100μm或100μm以下之尺寸。此外，膠囊較佳具有1μm或1μm以上之尺寸。因此，尤其較佳為1至1000μm、較佳為1至500μm、更佳為1至100μm之尺寸。膠囊更佳具有10μm或10μm以上之尺寸。因此，尤其較佳為10至500μm、尤其為10至100μm之尺寸。粒徑較佳藉由雷射繞射，例如Malvern Mastersize(參看上文)量測。對於粗略量測，可使用SEM及/或TEM。 The release capsules of the present invention, especially those in which the medicament is a chlorine dioxide generator, are particularly preferably released capsules as described herein, preferably having the capsules in place When used in products such as creams or pastes, it is not perceived as particles, especially for example, when used or contacted, the particle size that is not perceived by the (human) tongue or skin. The release capsule of the present invention preferably has a size of 2000 μm or less, preferably 1000 μm or less, more preferably 500 μm or less, more preferably 100 μm or less. Further, the capsule preferably has a size of 1 μm or more. Therefore, it is particularly preferably a size of from 1 to 1000 μm, preferably from 1 to 500 μm, more preferably from 1 to 100 μm. The capsule preferably has a size of 10 μm or more. Therefore, it is particularly preferable to have a size of 10 to 500 μm, particularly 10 to 100 μm. The particle size is preferably measured by laser diffraction, such as Malvern Mastersize (see above). For rough measurements, SEM and/or TEM can be used.
本發明亦提供包含本發明之釋放膠囊之產品。由於本發明之釋放膠囊具有防水性，因此該等產品可為水溶液或水分散液，且可具有達到產品總量之95 wt.-%、較佳為0-90 wt.-%之水含量，且對於實質上乾燥的產品，較佳具有0-10 wt.-%之水含量；在各種情況下，水含量係相對於產品總重量而給出。 The invention also provides a product comprising the release capsule of the invention. Since the release capsule of the present invention is water-repellent, the products may be aqueous solutions or aqueous dispersions, and may have a water content of 95 wt.-%, preferably 0-90 wt.-%, of the total amount of the product. And for a substantially dry product, preferably having a water content of from 0 to 10 wt.-%; in each case, the water content is given relative to the total weight of the product.
本發明之產品可為化妝品或醫藥組成物，包含如本文所述之本發明之釋放膠囊及化妝品及/或醫藥上可接受之載劑。該等組成物較佳用於局部施用於人體或動物體。尤其較佳的化妝品或醫藥組成物為本發明之釋放膠囊包含二氧化氯產生劑作為欲釋放藥劑之彼等化妝品或醫藥組成物。該等化妝品或醫藥組成物尤其適用於漂白、除臭及衛生處理；對應較佳的產品已描述如上。 The product of the invention may be a cosmetic or pharmaceutical composition comprising a release capsule of the invention as described herein and a cosmetic and/or pharmaceutically acceptable carrier. These compositions are preferably used for topical application to the human or animal body. Particularly preferred cosmetic or pharmaceutical compositions are the release capsules of the present invention comprising a chlorine dioxide generator as the cosmetic or pharmaceutical composition of the medicament to be released. Such cosmetic or pharmaceutical compositions are especially suitable for bleaching, deodorizing and sanitizing treatment; corresponding preferred products have been described above.
根據本發明，亦提供一種製造釋放膠囊、較佳為如上所述之釋放膠囊、更佳為如上所述為尤其較佳之釋放膠囊之方法，該方法包含以下步驟：(i)提供一具有欲最終釋放之藥劑的核心，該藥劑包含兩種或兩種以上不同物質或由兩種或兩種以上不同物質組成(較佳如上所述)， (ii)用疏水性材料(較佳為如上所述之疏水性材料)塗佈該核心，以形成一殼體，及(iii)將金屬氧化物材料，較佳為如上所述之金屬氧化物材料沈積於該殼體中及/或沈積於該殼體上，其中沈積金屬氧化物材料之量經選擇以使在該膠囊與液體水接觸後自該膠囊釋放50 wt.-%之該藥劑(亦即該藥劑之兩種或兩種以上不同物質之總重量/總含量)延遲至少24小時。 According to the present invention, there is also provided a method of making a release capsule, preferably a release capsule as described above, more preferably a capsule which is particularly preferred as described above, the method comprising the steps of: (i) providing a desired The core of the released drug, the agent comprising two or more different substances or consisting of two or more different substances (preferably as described above), (ii) coating the core with a hydrophobic material, preferably a hydrophobic material as described above, to form a shell, and (iii) a metal oxide material, preferably a metal oxide as described above Material is deposited in and/or deposited on the housing, wherein the amount of metal oxide material deposited is selected such that 50 wt.-% of the agent is released from the capsule after contact with the liquid water ( That is, the total weight/total content of two or more different substances of the agent is delayed by at least 24 hours.
所描述的本發明之製造方法尤其有利地允許在基本上不存在水的情況下以塗佈方法產生本發明之釋放膠囊。因此，較佳的是，在本發明之製造方法中，步驟(ii)中疏水性材料之水含量以用於塗佈核心之全部材料計為至多10 wt.-%、較佳為至多3 wt.-%、更佳為至多1 wt.-%且最佳為0-0.5 wt.-%。 The described manufacturing method of the present invention particularly advantageously allows the release capsule of the present invention to be produced by a coating process in the substantial absence of water. Therefore, preferably, in the production method of the present invention, the water content of the hydrophobic material in the step (ii) is at most 10 wt.-%, preferably at most 3 wt%, based on the total material for coating the core. .-%, more preferably at most 1 wt.-% and most preferably 0-0.5 wt.-%.
在本發明之製造方法中，較佳的欲最終釋放之藥劑、較佳疏水性材料及較佳金屬氧化物材料為如上所述者。使用該等材料可獲得對應優勢。以上關於膠囊成分較佳量之解釋以及以上定義因此適用。 In the production method of the present invention, preferred agents for final release, preferably hydrophobic materials and preferred metal oxide materials are as described above. The use of these materials gives you the advantage. The above explanation regarding the preferred amount of the capsule component and the above definition are therefore applicable.
因此，例如藥劑較佳包含兩種或兩種以上不同物質或由兩種或兩種以上不同物質組成，該等物質能夠在與氣體或液體介質接觸後產生其他物質(如上所述)，該其他物質不同於膠囊之核心中所含的藥劑之物質，較佳其中該藥劑為二氧化氯產生劑。 Thus, for example, the medicament preferably comprises two or more different substances or consists of two or more different substances which are capable of producing other substances (as described above) upon contact with a gaseous or liquid medium, the other The substance is different from the substance of the agent contained in the core of the capsule, and preferably the agent is a chlorine dioxide generator.
根據本發明之製造方法，將金屬氧化物材料沈積於步驟(ii)中形成之殼體中及/或沈積於該殼體上。金屬氧化物材料較佳以溶膠凝膠法或以凝聚法沈積。該等方法適用於沈積尤其細小的金屬氧化物粒子或層，有效密封可能存在於疏水性殼體中之顯微孔或裂縫。 According to the manufacturing method of the present invention, a metal oxide material is deposited in the casing formed in the step (ii) and/or deposited on the casing. The metal oxide material is preferably deposited by a sol-gel method or by a coacervation method. These methods are suitable for depositing particularly fine metal oxide particles or layers that effectively seal microscopic pores or cracks that may be present in the hydrophobic shell.
本發明方法之步驟(iii)中之沈積較佳在包含C1-C4醇及/或水或由C1-C4醇及/或水組成之沈積介質中實現。以沈積介質之總重量計，尤其較佳具有至多20 wt.-%、較佳為至多60 wt.-%、更佳為至多80 wt.-% 之水含量。根據本發明之一個較佳具體實例，沈積介質之水含量為100 wt.-%。替代性較佳沈積介質包含甲醇、乙醇、正丙醇、異丙醇、丁醇、異丁醇、第三丁醇或兩種或兩種以上此等醇之混合物及視情況選用之水，較佳為如上所述之量的水。其中，由乙醇及水組成之沈積介質尤其較佳，因為可能仍附著於由此產生之釋放膠囊的痕量乙醇一般可視為對本發明膠囊之其他加工且尤其亦對於包含該等釋放膠囊之本發明組成物之使用者的健康不具有危險性。 The deposition in step (iii) of the process of the invention is preferably effected in a deposition medium comprising C1-C4 alcohol and/or water or consisting of C1-C4 alcohol and/or water. It is particularly preferred to have up to 20 wt.-%, preferably up to 60 wt.-%, more preferably up to 80 wt.-%, based on the total weight of the deposition medium. Water content. According to a preferred embodiment of the invention, the deposition medium has a water content of 100 wt.-%. An alternative preferred deposition medium comprises methanol, ethanol, n-propanol, isopropanol, butanol, isobutanol, tert-butanol or a mixture of two or more such alcohols and, optionally, water. Preferably, the amount of water is as described above. Among them, a deposition medium composed of ethanol and water is particularly preferred, since trace amounts of ethanol which may still adhere to the resulting release capsule are generally regarded as other processing of the capsule of the present invention, and especially for the present invention comprising such released capsules. The health of the user of the composition is not dangerous.
在下文中藉助於實施例進一步詳細本發明。應注意，此等實施例不意欲限制以不同方式用於此說明書或申請專利範圍之表述的含義及範疇。 The invention is further detailed below by means of examples. It should be noted that the examples are not intended to limit the meaning and scope of the expressions used in this specification or the scope of the claims.
在下文中，使用模型組分一NaHCO3及酒石酸之鹽混合物(作為藥劑)進行製造。 In the following, the model component-a mixture of NaHCO3 and a mixture of tartaric acid (as a medicament) was used.
添加NaHCO3及酒石酸之粉末(如上文所定義) Add NaHCO3 and tartaric acid powder (as defined above)
a)至混合器(例如Somakon®混合器，其中該混合器僅為可使用之許多可能混合器的一個實例，諸如犁鏵或槳式混合器，例如Lödige、Ger.Ruberg；或環剪切混合器，例如Iödige、AVA-Hueb、Eirich混合器或類似混合器；所有該等混合器共有配備混合元件之旋轉混合軸(垂直或水平)，其在製備於混合室中之粉末層中誘發剪切應力)，或b)至流體化床(具有有孔底之腔室，其中空氣在確定的溫度下流經有孔底)。 a) to a mixer (such as a Somakon® mixer, where the mixer is only one example of many possible mixers that can be used, such as a ploughshare or paddle mixer, such as Lödige, Ger.Ruberg; or a ring shear mixer , for example, Iödige, AVA-Hueb, Eirich mixers or similar mixers; all of which have a rotating mixing shaft (vertical or horizontal) with mixing elements that induce shear stress in the powder layer prepared in the mixing chamber ), or b) to a fluidized bed (a chamber having a perforated bottom, wherein air flows through the perforated bottom at a determined temperature).
較佳經由噴嘴向此混合裝置a)或b)中添加合適流體及/或黏合劑(例如水(當使用水時，該方法較佳在85℃溫度下進行)及/或(若 適用時)熔融塗佈材料(如上所定義及描述，較佳為石蠟，例如稍後(亦)用於塗佈過程之材料))，且藉由壓力或二次加熱空氣/氮氣霧化。若適用時，可添加其他成分(例如一或多種填充劑)。在此操作期間，粉末必須在確定的速度下加以連續混合。混合剪切應力及(若適用時)流體及/或黏合劑(如上所述)之量影響粒度。另外，可將經加熱之空氣/氮氣送入混合室作為混合器中之流化氣體或二次氣體及/或可能加熱混合室之容器。經由此兩種方式，粉末層將具有低於塗佈材料熔融溫度之溫度，若適用時較佳低於熔融溫度5至20℃。 Preferably, a suitable fluid and/or binder is added to the mixing device a) or b) via a nozzle (for example water (when water is used, the method is preferably carried out at a temperature of 85 ° C) and/or (if Where applicable, the melt-coated material (as defined and described above, preferably paraffin, such as the material used later (also for the coating process)), is atomized by pressure or secondary heating air/nitrogen. Other ingredients (such as one or more fillers) may be added if applicable. During this operation, the powder must be continuously mixed at a determined speed. The amount of mixed shear stress and, if applicable, fluid and/or binder (as described above) affects the particle size. Alternatively, the heated air/nitrogen may be fed to the mixing chamber as a fluidizing gas or secondary gas in the mixer and/or a vessel that may heat the mixing chamber. In either of these ways, the powder layer will have a temperature below the melting temperature of the coating material, preferably from 5 to 20 ° C below the melting temperature, if applicable.
在顆粒形成後，可略微降低粉末層之溫度(亦即降低不到20 K)，(若適用時)或保持相同溫度來使用疏水性熔體(如上所定義及描述，較佳為石蠟)進行表面塗佈步驟。此在同一混合裝置中完成。 After the granules are formed, the temperature of the powder layer (ie, reduced by less than 20 K), if applicable, or at the same temperature, can be carried out using a hydrophobic melt (as defined and described above, preferably paraffin) Surface coating step. This is done in the same mixing device.
在混合器外部或在混合室內部之混合器緩慢操作期間冷卻(經塗佈)顆粒。 The particles are cooled (coated) during the slow operation of the mixer outside of the mixer or inside the mixing chamber.
若例如石蠟用於塗佈(參見上文)，則所獲得之顆粒/粒子可因石蠟塗佈而完全疏水，且由此可能需要經改質以更具親水性(較佳用濕潤劑)，以便能夠在此等粒子表面上進行例如ZnO塗佈。 If, for example, paraffin wax is used for coating (see above), the particles/particles obtained may be completely hydrophobic due to paraffin coating, and thus may need to be modified to be more hydrophilic (preferably a wetting agent), In order to be able to carry out, for example, ZnO coating on the surface of such particles.
濕潤劑可選自BASF界面活性劑、ex-Ciba濕潤劑及具有小分子量之商業界面活性劑，諸如Aerosol OT、At-lox4913、Pluronic F127、Inutec SP1、Sokalan CP 20、Sokalan HP25、Lutrol F68、Sokalan HP80、Luvitec K80、Luvitec K17、Sokalan PM70、Sokalan PA80S及EFKA系列。已發現Aerosol OT及Sokalan HP25可使石蠟塗佈粒子很好地再分散於水中。 The humectant may be selected from the group consisting of BASF surfactants, ex-Ciba humectants, and commercial surfactants having a small molecular weight such as Aerosol OT, At-lox 4913, Pluronic F127, Inutec SP1, Sokalan CP 20, Sokalan HP25, Lutrol F68, Sokalan HP80, Luvitec K80, Luvitec K17, Sokalan PM70, Sokalan PA80S and EFKA series. Aerosol OT and Sokalan HP25 have been found to allow good dispersion of paraffin-coated particles in water.
(例如)ZnO塗層(如上所述)之製備可例如在純乙醇、純水中或在乙醇與水之混合物中進行。可試驗不同反應參數以便發現最佳反 應條件且獲得最佳產品品質。欲變化之參數詳言之為(Zn2+-)鹽(ZnCl2、ZnSO4、Zn(NO3)2、Zn(AC)2)、以M為單位之Zn2+：OH-之比率(1：2、1：2.5、1：3、1：4)、乙醇：水之比率(純乙醇、1：1、2：1、4：1、8：1、純水)、反應時間(5、10、15、20、25、30分鐘)、作為加速ZnO沈澱及結晶之添加劑的各種聚合物(例如Sokalan PA、Sokalan HP系列)、多層(ZnO)沈積/塗佈之引入(單層、雙層、三層)及反應溫度(20、25、30、35、40℃)。 The preparation of, for example, a ZnO coating (as described above) can be carried out, for example, in pure ethanol, pure water or in a mixture of ethanol and water. Different reaction parameters can be tested to find the best anti- Condition and get the best product quality. The parameters to be changed are in detail the ratio of (Zn2+-) salt (ZnCl2, ZnSO4, Zn(NO3)2, Zn(AC)2), Zn2+:OH- in M (1:2, 1:2.5) , 1:3, 1:4), ethanol: water ratio (pure ethanol, 1:1, 2:1, 4:1, 8:1, pure water), reaction time (5, 10, 15, 20, 25, 30 minutes), various polymers (such as Sokalan PA, Sokalan HP series), multi-layer (ZnO) deposition/coating (single layer, double layer, three layers) and reaction as additives for accelerating ZnO precipitation and crystallization Temperature (20, 25, 30, 35, 40 ° C).
所獲得之產品可藉由使用XRD及REM來特性化。可在水中測試藥劑釋放。 The product obtained can be characterized by using XRD and REM. The release of the agent can be tested in water.
尤其合適之結果係藉由以下試驗來獲得：將0.5% Aerosol OT引入顆粒(於水中)，此舉後即刻為ZnO塗佈過程。ZnO塗佈較佳在以下條件下進行：ZnCl2：NaOH=2.5：1；添加1% Sokalan PA 15作為加速ZnO結晶之添加劑；反應時間=10 min；室溫。在N2氛圍中迅速乾燥產品。 Particularly suitable results were obtained by introducing 0.5% Aerosol OT into the granules (in water), immediately after the ZnO coating process. The ZnO coating is preferably carried out under the following conditions: ZnCl2: NaOH = 2.5:1; 1% Sokalan PA 15 is added as an additive for accelerating crystallization of ZnO; reaction time = 10 min; room temperature. Dry the product quickly in an N2 atmosphere.
應注意，鹽(藥劑)宜在ZnO塗佈過程期間留存於水溶液中。 It should be noted that the salt (agent) is preferably retained in the aqueous solution during the ZnO coating process.
根據以上實施例1中所述之指示產生含有NaHCO3及酒石酸(作為模型藥劑)之膠囊。已使用以下物質(以膠囊之總重量100 wt.-%計，其中石蠟1及2可為相同或不同的蠟)：
在Somakon混合器(如上所述)中，在500 rpm及50℃下進行顆粒製備，持續5分鐘(噴嘴Schlick壓力噴嘴0.8 mm，以電加熱)。 Particle preparation was carried out at 500 rpm and 50 ° C in a Somakon mixer (described above) for 5 minutes (nozzle Schlick pressure nozzle 0.8 mm, electrically heated).
在Somakon混合器(如上所述)中，在250 rpm及45℃下進行顆粒之(蠟)塗佈，持續10分鐘。 The granules (wax) were applied at 250 rpm and 45 ° C in a Somakon mixer (described above) for 10 minutes.
根據以上程序(參見實施例1)進行ZnO塗佈。 ZnO coating was carried out according to the above procedure (see Example 1).
在膠囊浸入水(10 g於200 mL中)中後之釋放(此處：核心：NaHCO3及酒石酸質量減少；假定石蠟及ZnO不溶解於水中)如下：20 min <10 wt.-%釋放 Release after immersion in water (10 g in 200 mL) (here: core: reduced mass of NaHCO3 and tartaric acid; assumed paraffin and ZnO are insoluble in water) as follows: 20 min <10 wt.-% release
12 h <40% wt.-%釋放 12 h <40% wt.-% release
24 h <50% wt-%釋放 24 h <50% wt-% release
藉由化學滴定測定CO2釋放。 CO2 release was determined by chemical titration.
根據以上實施例1中所述之指示產生含有NaHCO3及酒石酸(作為模型藥劑)之膠囊。然而，不進行金屬氧化物材料沈積。已使用以下物質(以膠囊之總重量100 wt.-%計，其中石蠟1及2可為相同或不同的蠟)：
在Somakon混合器(如上所述)中，在500 rpm及50℃下進 行顆粒製備，持續5分鐘(噴嘴Schlick壓力噴嘴0.8 mm，以電加熱)。 In the Somakon mixer (described above), at 500 rpm and 50 ° C The pellets were prepared for 5 minutes (nozzle Schlick pressure nozzle 0.8 mm, electrically heated).
在Somakon混合器(如上所述)中，在250 rpm及45℃下進行顆粒之(蠟)塗佈，持續10分鐘。 The granules (wax) were applied at 250 rpm and 45 ° C in a Somakon mixer (described above) for 10 minutes.
不施用ZnO塗佈。 No ZnO coating was applied.
在膠囊浸入水(10 g於200 mL中)中後之釋放(此處：核心：NaHCO3及酒石酸質量減少；假定石蠟及ZnO不溶解於水中)如下：20 min <50% wt.-%釋放 Release after capsule immersion in water (10 g in 200 mL) (here: core: reduced NaHCO3 and tartaric acid; assumed paraffin and ZnO are insoluble in water) as follows: 20 min <50% wt.-% release
12 h >80% wt.-%釋放 12 h >80% wt.-% release
24 h >90% wt.-%釋放 24 h >90% wt.-% release
僅在第一小時藉由化學滴定測定CO2釋放。 CO2 release was determined by chemical titration only in the first hour.
Claims (15)
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| US201161569800P | 2011-12-13 | 2011-12-13 | |
| EP11019320 | 2011-12-13 |
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| TW201330877A true TW201330877A (en) | 2013-08-01 |
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| TW101146580A TW201330877A (en) | 2011-12-13 | 2012-12-11 | Release capsules, manufacture and uses thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106455553A (en) * | 2014-09-19 | 2017-02-22 | 香港科技大学 | Antimicrobial coating for long-term disinfection of surfaces |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106455553A (en) * | 2014-09-19 | 2017-02-22 | 香港科技大学 | Antimicrobial coating for long-term disinfection of surfaces |
| CN106455553B (en) * | 2014-09-19 | 2020-10-30 | 香港科技大学 | Antimicrobial coatings for long term disinfection of surfaces |
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