201012481 九、發明說明： 【發明所屬之技術領域】 本發明是有關於一種生物性高分子材料與其製造方法 及其用途，特別是有關於一種微粒化生物性高分子材料與 其製造方法及其用途。 【先前技術】 膠原蛋白（collagen)及透明質酸（hyaluronic acid; © HA)是細胞外基質相當重要的組成分，同時亦可用於人體 器官組織修補（repair)及再生（regeneration)的生物性高 分子材料（biopolymer material)。隨著年齡增加，透明質 酸含量也會減少，使得皮膚與肌肉中的水分會減少而開始 老化。同時’原先真皮中膠原蛋白與其他蛋白交互構成有 規則的網目結構會逐漸崩解，最後導致皺紋、皮膚鬆弛、 晦暗、班點、粗糙。藉由飲食、化妝品或外用醫藥品可適 當補充皮膚之膠原蛋白及透明質酸。 Φ 膠原蛋白及透明質酸在應用於皮膚外用組成物時，通 常先溶於水相溶液中，再與其他成分混合。然而，在各種 形式之膠原蛋白及透明質酸中，僅有水溶性膠原蛋白及透 明質酸可應用於皮膚外用組成物，而且水溶性膠原蛋白及 透明質酸溶於水相溶液中的濃度亦受限，其濃度不超過約1 重量百分比’同時更增加皮膚外用組成物製程的步驟及時 間。 201012481 除了膠原蛋白及透明質酸之外，幾丁質及生物性約質 ’ 材料亦具有促進組織修補及再生特性，亦經常添加於皮膚 外用組成物或食品中。 習知技術有利用化學或酵素法處理上述生物性高分子 材料使其微粒化’而藉此提高其溶解於水相溶液之濃度。 惟以膠原蛋白為例，利用化學或酵素法處理所得之膠原蛋 白’其濃度最高不超過1重量百分比，且易造成膠原蛋白 的破壞或變性。另有以物理性研磨方式處理上述生物性高 β 分子材料，但上述生物性高分子材料除了幾丁質及生物性 鈣質材料之外，多為纖維狀或質地柔軟，較不易研磨，一 般研磨機器不易藉由研磨達到微粒化的效果，更難謂可藉 此提高其溶解於水相溶液之濃度。 有鏗於此，亟需提出一種微粒化生物性高分子材料及 其製造方法’藉以改善習知微粒化製程之種種缺點。 【發明内容】 ® 因此，本發明的觀點之一就是在提供一種微粒化生物 性高分子材料及其製造方法’其係將原本不溶且無法均勻 懸浮於水相溶液之生物性高分子材料，經由研磨介質物理 性研磨後’可得到平均粒徑介於300奈米至5微米之間、 且均勻懸浮於水相溶液中之微粒化生物性高分子材料。所 得之微粒化生物性高分子材料更可進一步添加於皮膚外用 , 組成物中。 根據本發明之上述觀點，提出一種微粒化生物性高分 子材料之製造方法，此方法包括提供生物性高分子材料， 201012481 其中生物性高分子材料可包括但不限於膠原蛋白、幾丁 質、透明質酸及生物性約質材料等。接著，進行至少一物 理性研磨步驟，其係於溫度介於攝氏5至4〇度之間的環境 下，利用平均粒徑介於〇·4毫米（mm)至M毫米之研磨 介質物理性研磨丨述生物性高分子材肖，以獲得平均粒徑 介於300奈米至5微米之間的微粒化生物性高分子材料。 之後，進行一分離步驟，以分離上述之微粒化生物性高分 子材料與研磨介質，其中微粒化生物性高分子材料可均勻 © 懸浮於水相溶液中。 依照本發明一較佳實施例，上述之生物性鈣質材料可 包括但不限於珍珠、牡蠣殼、貝殼或其任意組合。 依照本發明一較佳實施例，研磨介質之材料可包括但 不限於氧化锆、氧化釔或其任意組合。 根據本發明之上述觀點，更提出一種微粒化生物性高 刀子材料，此微粒化生物性高分子材料係於溫度介於攝氏5 至40度的環境下，利用平均粒徑介於〇 4毫米（瓜瓜）至 ® M毫米之研磨介質物理性研磨生物性高分子材料，使所得 之微粒化生物性高分子材料之平均粒徑介於3〇〇奈米至5 微米之間並均勻懸浮於水相溶液中。 根據本發明之上述觀點，再提出一種皮膚外用組成 物，其係含有如上所述之微粒化生物性高分子材料為有效 成分。依照本發明一較佳實施例，上述微粒化生物性高分 -子材料可以介於0.01重量百分比至50重量百分比之間添加 至基質中’且此基質可包括但不限於乳霜（Cream)、乳液 (L〇tl〇n )、精華液（Essence )或凝膠（Gel)。依照本發明 201012481 另一較佳實施例，上述微粒化生物性高分子材料亦可與敷 • 料結合，且此敷料可包括但不限於PE薄膜、護虜墊、紗布 或生物性敷料^ 應用本發明之微粒化生物性高分子材料及其製造方 法，其係將原本不溶且無法均勻懸浮於水相溶液之生物性 两分子材料，經由研磨介質物理性研磨後，可得到平均粒 徑介於300奈米至5微米之間、且均勻懸浮於水相溶液中 之微粒化生物性南分子材料β有別於習知技術利用酵素或 參 酸鹼等方式將生物性高分子材料微粒化，易造成生物牲高 分子材料的破壞或變性，本發明係於溫度例如介於攝氏5 至40度的環境，利用物理性研磨將其微粒化，所得之微粒 化生物性高分子材料不僅保留其生物活性，同時更可進一 步添加至皮膚外用組成物作為有效成分。 【實施方式】 承前所述，本發明提供一種微粒化生物性高分子材料 與其製造方法及其用途，係將原本不溶且無法均勻懸浮於 水相溶液之生物性高分子材料藉由物理性研磨予以微粒 化，所得之微粒化生物性高分子材料不僅保留其生物活 性，同時更可進一步添加至皮膚外用組成物作為有效成分。 根據本發明一較佳實施例，係提出一種微粒化生物性 高分子材料及其製造方法，包括首先提供生物性高分子材 料。本發明所指之生物性高分子材料係指原本不溶且無法 均勻懸浮於水相溶液者，一般可包括但不限於各種動物性 來源的膠原蛋白、幾丁質、透明質酸及生物性鈣質材料等。 201012481 在一實施例中，上述之生物性鈣質材料可包括但不限於珍 珠、牡蠣殼、貝殼或其任意組合。 接著，進行至少一物理性研磨步驟，其係於溫度例如 介於攝氏5至40度之間的環境下，利用平均粒徑介於〇4 毫米（mm )至ΐ·ι毫米之研磨介質，以介於例如每分鐘 至4000轉之研磨速度，藉由研磨介質之剪切力。“盯 force)、衝擊力（impaet f〇rce)等，物理性研磨上述生物 性高分子材料，其研磨時間可介於3〇分鐘至3小時，惟以 © 研磨約2小時為較佳。 在一實施例中，物理性研磨步驟可利用現有的研磨設 備進行’適合之研磨設備可例如攪拌介質研磨機（aghated media mill )、分散研磨機（diSpersi〇n min )、齒盤型研磨機 (toothed disc mill )、高剪式研磨機（high_shear mm )、球 磨機（ball mill)、氣流喷射研磨機（jet min)等。 其-人’研磨介質之材料可包括但不限於氧化錯、氧化 釔或其任意組合。在一實施例中，研磨介質可例如含有約 • 92重量百分比之氧化锆、約5重量百分比之氧化釔、以及 約3重量百分比之其他物質。 再者，物理性研磨步驟的研磨方式不拘，可以例如乾 磨或濕磨方式進行。在一實施例中，利用研磨介質乾磨上 述生物性高分子材料時，例如生物性鈣質材料之生物性高 分子材料可先進行清洗陰乾後，亦可選擇性先切割或粉碎 - 成較小片段，再直接利用研磨介質進行乾磨。在另一實施 例中，利用研磨介質乾磨上述生物性高分子材料時，例如 膠原蛋白、幾丁質、透明質酸等之生物性高分子材料可先 201012481 進行乾燥步驟，例如冷凍乾燥步驟或真空乾燥步驟，再直 接利用研磨介質進行乾磨。 除了乾磨方式之外，在又一實施例中，上述生物性高 刀子材料亦可進行濕磨。在一實施例中，利用研磨介質濕 磨上述生物性高分子材料時，可先將介於〇 〇1重量百分比 至10重量百分比之間的生物性高分子材料，加入酸鹼值介 於2.5至5.5之間的酸性水溶液中。適合之酸性水溶液可例 如醋酸水溶液、檸檬酸水溶液或鹽酸水溶液，而其適合之 ❹ 濃度以介於〇.11^至1河為宜，又以介於0.2]^至〇.8]^為 較佳。 進行上述物理性研磨步驟時，可進行至少一次，俾使 上述生物性高分子材料得以充分微粒化’以獲得平均粒徑 介於300奈米至5微米之間的微粒化生物性高分子材料。 此外’在進行上述物理性研磨步驟時，更可同步進行 分離步称，其係利用例如間隙分離、過渡分離、沉降分離、 離心分離等方式’以分離上述之微粒化生物性高分子材料 9 與研磨介質’其中所得之微粒化生物性高分子材料可均勻 懸浮於水相溶液中。 根據本發明另一較佳實施例’係提出一種皮膚外用組 成物’其係含有如上所述之微粒化生物性高分子材料為有 效成分。有別於習知技術利用酵素或酸鹼等方式將生物性 尚》分子材料微粒化’易造成生物性高分子材料的破壞或變 性’本發明係於溫度例如介於攝氏5至40度的環境，利用 研磨介質物理性研磨將其微粒化，因此所得之微粒化生物 性高分子材料不僅保留其生物活性，同時更可進一步添加 201012481 至皮膚外用組成物中，例如化妝品組成物或外用醫療組成 . 物。 在此實施例中，上述微粒化生物性高分子材料可以介 於0.01重量百分比至50重量百分比之間添加至基質中，且 此基質可包括但不限於乳霜（Cream)、乳液（L〇ti〇n )、精 華液（Essence)或凝膠（Gel)e根據本發明另一較佳實施 例，上述微粒化生物性高分子材料亦可與敷料結合，且此 敷料可包括但不限於PE薄膜、護膚墊、紗布或生物性敷料。 〇 值得一提的是，本發明係以物理性研磨將原本不溶且 無法均勻懸浮於水相溶液之生物性高分子材料予以微粒 化’其與一般習知微粒化之差異簡述如下。首先，一般以 化學或酵素法處理，其僅能以濕式法處理，且處理濃度不 高。舉例而言，以化學或酵素法處理所得之膠原蛋白，其 濃度最高不超過1重量百分比；然而以本發明物理性研磨 法處理所得之膠原蛋白，其濃度可達約6重量百分比以上。 其次’一般研磨主要乃針對硬質之無機材料，其研磨難度 ® 較低’相較之下，生物性高分子材料為纖維狀，且質地柔 軟’較不易研磨’一般研磨機器無法達到與本發明相同或 類似的效果。 以下利用數個實施例以說明本發明之應用，然其並非 用以限定本發明，本發明技術領域中具有通常知識者，在 不脫離本發明之精神和範圍内，當可作各種之更動與潤飾。 實施例一：利用濕磨製造微粒化生物性高分子材料 在本實施例中’係將約200公克（或公斤）的膠原蛋 12 201012481 白、幾丁質、透明質酸，分別加入酸鹼值約3的醋酸/檸檬 " 酸/鹽酸水溶液後，利用實驗級挽拌介質研磨機（laboratory agitated media mill > Model No. PML-H/V » Biihler & Drais GmbH，Germany)或其類似機型，連同平均粒徑介於0.4 毫米至1·1毫米之研磨介質，以介於例如每分鐘2000至 4000轉之研磨速度，分別濕磨上述膠原蛋白、幾丁質、透 明質酸，研磨約2小時。在進行上述物理性研磨步驟時， 可同步利用例如間隙分離、過濾分離或離心分離方式，分 Φ 離微粒化膠原蛋白、微粒化幾丁質、微粒化透明質酸與研 磨介質。所得之微粒化膠原蛋白、微粒化幾丁質、微粒化 透明質酸的濃度可分別達約6重量百分比、約3重量百分 比及約2重量百分比》 上述研磨分離所得之微粒化膠原蛋白更進一步利用例 如動態奈米光散射（Dynamic Light Scattering ; DLS )粒徑 分析儀，例如 Brookhaven 90Plus Nanoparticle Size Analyzer (Brookhaven Instruments Corp.，Holtsville，NY, USA)，進 • 行粒徑分析。經過DLS粒徑分析後，本實施例所得之微粒 化膠原蛋白的有效粒徑（effective diameter)為598.7±57.1 nm，半峰寬（half width)為 315.8±22.4 nm，多分散性 (polydiversity)為 0.278±0.21 ° 實施例二：製造含有微粒化生物性高分子材料之外用 醫療组成物 實施例一所得之微粒化膠原蛋白可以介於0.01重量百 分比至50重量百分比之間添加至添加至外用醫療組成物 13 201012481 中，例如醫療用乳霜。 在一實施例中，含有50重量百分比、20重量百分比或 0.1重量百分比之微粒化膠原蛋白的醫療用乳霜成份，如表 1所例示：201012481 IX. Description of the Invention: [Technical Field] The present invention relates to a biological polymer material, a method for producing the same, and a use thereof, and more particularly to a micronized biopolymer material, a method for producing the same, and a use thereof. [Prior Art] Collagen and hyaluronic acid (HA) are important components of the extracellular matrix, and can also be used for biological repair and regeneration of human organs. Biopolymer material. As the age increases, the hyaluronic acid content also decreases, causing the skin and muscles to reduce moisture and begin to age. At the same time, the collagen in the original dermis interacts with other proteins to form a regular mesh structure that gradually disintegrates, eventually leading to wrinkles, sagging skin, dullness, shifts, and roughness. Skin, collagen and hyaluronic acid can be properly supplemented by diet, cosmetics or topical medicines. Φ Collagen and hyaluronic acid are usually dissolved in an aqueous phase solution when applied to a skin external composition, and then mixed with other ingredients. However, among various forms of collagen and hyaluronic acid, only water-soluble collagen and hyaluronic acid can be applied to the external composition of skin, and the concentration of water-soluble collagen and hyaluronic acid dissolved in the aqueous phase solution is also Restricted, its concentration does not exceed about 1% by weight' while increasing the steps and time of the skin external composition process. 201012481 In addition to collagen and hyaluronic acid, chitin and bio-materials also promote tissue repair and regeneration, and are often added to skin external ingredients or foods. Conventional techniques have used a chemical or enzymatic method to treat the above-mentioned biopolymer material to be micronized, thereby increasing the concentration of the solution dissolved in the aqueous phase solution. In the case of collagen, for example, the collagen protein obtained by chemical or enzymatic treatment has a concentration of up to 1% by weight, and is liable to cause destruction or denaturation of collagen. In addition, the above-mentioned biological high-β molecular material is treated by physical grinding, but the above-mentioned biological polymer materials are mostly fibrous or soft in texture except for chitin and biological calcium materials, and are relatively difficult to grind, generally grinding. It is not easy for the machine to achieve the effect of micronization by grinding, and it is more difficult to increase the concentration of the solution dissolved in the aqueous phase. In view of this, there is a need to propose a microparticulated biopolymer material and a method of manufacturing the same to improve various disadvantages of the conventional micronization process. SUMMARY OF THE INVENTION Therefore, one of the viewpoints of the present invention is to provide a microparticulated biopolymer material and a method for producing the same, which are biopolymer materials which are originally insoluble and cannot be uniformly suspended in an aqueous phase solution, via After the grinding medium is physically ground, a micronized biopolymer material having an average particle diameter of between 300 nm and 5 μm and uniformly suspended in the aqueous phase solution can be obtained. The obtained micronized biopolymer material can be further added to the external composition of the skin. According to the above aspect of the present invention, a method for producing a microparticulated biopolymer material is provided, the method comprising providing a biopolymer material, 201012481 wherein the biopolymer material can include, but is not limited to, collagen, chitin, and transparency. Acidic and biological materials. Next, at least one physical grinding step is performed, which is performed under the environment of a temperature between 5 and 4 degrees Celsius, using a grinding medium having an average particle diameter of between 4 mm (mm) and M mm. The biological polymer material is described to obtain a micronized biopolymer material having an average particle diameter of between 300 nm and 5 μm. Thereafter, a separation step is performed to separate the above-mentioned micronized biopolymer material and the grinding medium, wherein the micronized biopolymer material can be uniformly suspended in the aqueous phase solution. According to a preferred embodiment of the invention, the biological calcium material may include, but is not limited to, pearls, oyster shells, shells or any combination thereof. In accordance with a preferred embodiment of the present invention, the material of the grinding media can include, but is not limited to, zirconia, cerium oxide, or any combination thereof. According to the above aspect of the present invention, there is further provided a micronized bio-high-material material which is used in an environment having a temperature between 5 and 40 degrees Celsius and an average particle diameter of 〇4 mm (瓜瓜) to ® M mm of grinding media physically grinding the biopolymer material, so that the obtained micronized biopolymer material has an average particle size of between 3 〇〇 and 5 μm and is uniformly suspended in water. In the phase solution. According to the above aspect of the present invention, there is further provided a composition for external use of skin comprising the microparticulated biopolymer material as described above as an active ingredient. In accordance with a preferred embodiment of the present invention, the micronized bio-high score-sub-material may be added to the matrix between 0.01 weight percent and 50 weight percent ' and the matrix may include, but is not limited to, cream, Emulsion (L〇tl〇n), Essence or Gel (Gel). According to another preferred embodiment of the invention 201012481, the micronized biopolymer material may also be combined with a dressing, and the dressing may include, but is not limited to, a PE film, an ankle pad, a gauze or a biological dressing. The microparticulated biopolymer material of the present invention and a method for producing the same, which are obtained by physically grinding a biological two-molecular material which is insoluble in the aqueous phase solution and is substantially insoluble in the aqueous phase solution, and has an average particle diameter of 300 The micronized biological southern molecular material β which is uniformly suspended in the aqueous phase solution between nanometers and 5 micrometers is different from the conventional technique in that the biological polymer material is micronized by means of enzymes or acid and alkali, which is easy to cause The invention destroys or denatures a biological polymer material, and the present invention is micronized by physical grinding at a temperature of, for example, 5 to 40 degrees Celsius, and the obtained micronized biopolymer material not only retains its biological activity, At the same time, it can be further added to the external composition for skin as an active ingredient. [Embodiment] As described above, the present invention provides a micronized biopolymer material, a method for producing the same, and a use thereof, wherein a biopolymer material which is originally insoluble and cannot be uniformly suspended in an aqueous phase solution is subjected to physical grinding. In the microparticulation, the obtained micronized biopolymer material not only retains its biological activity, but can be further added to the external composition for skin as an active ingredient. According to a preferred embodiment of the present invention, a micronized biopolymer material and a method of manufacturing the same are provided, which first provide a biopolymer material. The biological polymer material referred to in the present invention refers to those which are originally insoluble and cannot be uniformly suspended in the aqueous phase solution, and generally include, but are not limited to, various animal-derived collagen, chitin, hyaluronic acid and biological calcium. Materials, etc. 201012481 In an embodiment, the biological calcium material described above may include, but is not limited to, a precious bead, an oyster shell, a shell, or any combination thereof. Next, at least one physical grinding step is performed, which is carried out in an environment having a temperature of, for example, between 5 and 40 degrees Celsius, using a grinding medium having an average particle diameter of from 4 mm (mm) to ΐ·ι mm. For example, at a grinding speed of from 4,000 rpm to the shearing force of the grinding medium. "Being force", impact (impaet f〇rce), etc., physical polishing of the above biopolymer material, the grinding time can be from 3 to 3 hours, but it is better to grind for about 2 hours. In one embodiment, the physical grinding step can be performed using existing grinding equipment. Suitable grinding equipment can be, for example, an agated media mill, a dispersing mill (diSpersi〇n min), a toothed disc grinder (toothed). Disc mill ), high shear mill (high_shear mm ), ball mill, jet min, etc. The material of the human 'grinding medium may include, but is not limited to, oxidized erbium, cerium oxide or In any embodiment, the abrasive medium can, for example, contain about 92% by weight of zirconia, about 5% by weight of cerium oxide, and about 3% by weight of other materials. Further, the grinding method of the physical grinding step Alternatively, it may be carried out, for example, by dry grinding or wet grinding. In one embodiment, when the above-mentioned biopolymer material is dry-ground by a grinding medium, for example, a biological calcium material The physical polymer material may be firstly cleaned and dried, or may be selectively cut or pulverized into smaller fragments, and then directly ground using a grinding medium. In another embodiment, the above-mentioned biological high is dry-ground by using a grinding medium. In the case of molecular materials, biopolymer materials such as collagen, chitin, hyaluronic acid, etc. may be subjected to a drying step, such as a freeze drying step or a vacuum drying step, in 201012481, and then directly subjected to dry grinding using a grinding medium. In addition, in another embodiment, the biological high knife material may also be wet-ground. In an embodiment, when the biological polymer material is wet-ground by using a grinding medium, the first step may be between 〇〇1 The biopolymer material is between 10% by weight and the like, and is added to an acidic aqueous solution having a pH of between 2.5 and 5.5. Suitable acidic aqueous solutions may be, for example, aqueous acetic acid, aqueous citric acid or aqueous hydrochloric acid, and suitable for The concentration is preferably between 〇.11^ to 1 river, and preferably between 0.2]^ and 〇8]^. Perform the above physical grinding At least one time, at least once, the biopolymer material can be sufficiently micronized to obtain a micronized biopolymer material having an average particle diameter of between 300 nm and 5 μm. In the physical grinding step, the separation step can be simultaneously performed by using, for example, gap separation, transition separation, sedimentation separation, centrifugal separation, etc. to separate the above-mentioned micronized biopolymer material 9 and grinding medium. The micronized biopolymer material can be uniformly suspended in the aqueous phase solution. According to another preferred embodiment of the present invention, a skin external composition is proposed, which comprises the micronized biopolymer material as described above. Active ingredients. Different from conventional techniques, microbialization of biological materials by means of enzymes or acids and bases may cause damage or denaturation of biological polymer materials. The present invention is applied to an environment having a temperature of, for example, 5 to 40 degrees Celsius. The micronized biopolymer material obtained by the physical polishing of the grinding medium not only retains its biological activity, but also further adds 201012481 to the skin external composition, such as a cosmetic composition or a medical composition for external use. Things. In this embodiment, the micronized biopolymer material may be added to the matrix between 0.01% by weight and 50% by weight, and the matrix may include, but is not limited to, Cream, Emulsion (L〇ti 〇n), Essence or Gel e. According to another preferred embodiment of the present invention, the micronized biopolymer material may also be combined with a dressing, and the dressing may include but is not limited to a PE film. , skin pads, gauze or biological dressings.值得 It is worth mentioning that the present invention microscopically crystallizes a biological polymer material which is originally insoluble and cannot be uniformly suspended in an aqueous phase solution by physical polishing. The difference from the conventional micronization is briefly described below. First, it is generally treated by chemical or enzymatic methods, which can only be treated by a wet method, and the treatment concentration is not high. For example, the resulting collagen is treated chemically or enzymatically at a concentration of up to 1 weight percent; however, the collagen obtained by the physical milling method of the present invention may be present in a concentration of up to about 6 weight percent or more. Secondly, 'general grinding is mainly for hard inorganic materials, and its grinding difficulty is lower'. In comparison, biopolymer materials are fibrous, and the texture is soft 'less easy to grind'. Generally, the grinding machine cannot reach the same as the present invention. Or a similar effect. The following examples are used to illustrate the application of the present invention, and are not intended to limit the present invention. Those skilled in the art can make various changes without departing from the spirit and scope of the present invention. Retouching. Example 1: Preparation of micronized biopolymer material by wet grinding In this embodiment, about 200 grams (or kilograms) of collagen egg 12 201012481 white, chitin, hyaluronic acid are respectively added to the pH value. After about 3 acetic acid/lemon "acid/hydrochloric acid aqueous solution, a laboratory agitated media mill (Laboratory agitated media mill > Model No. PML-H/V » Biihler & Drais GmbH, Germany) or the like is used. Type, together with an abrasive medium having an average particle diameter of from 0.4 mm to 1.1 mm, wet-grinding the above-mentioned collagen, chitin, hyaluronic acid, and grinding, respectively, at a grinding speed of, for example, 2,000 to 4,000 rpm. 2 hours. In the above physical polishing step, micronized collagen, micronized chitin, micronized hyaluronic acid, and a grinding medium can be separated by, for example, gap separation, filtration separation, or centrifugation. The concentration of the obtained micronized collagen, micronized chitin, and micronized hyaluronic acid may be about 6 weight percent, about 3 weight percent, and about 2 weight percent, respectively. The micronized collagen obtained by the above grinding separation is further utilized. For example, a Dynamic Light Scattering (DLS) particle size analyzer, such as a Brookhaven 90Plus Nanoparticle Size Analyzer (Brookhaven Instruments Corp., Holtsville, NY, USA), is used for particle size analysis. After DLS particle size analysis, the effective diameter of the micronized collagen obtained in this example was 598.7±57.1 nm, the half width was 315.8±22.4 nm, and the polydispersity was 0.278±0.21 ° Example 2: Manufacturing a medical composition containing a micronized biopolymer material The micronized collagen obtained in Example 1 can be added between 0.01% by weight and 50% by weight to be added to a medical composition for external use. Item 13 201012481, for example, medical cream. In one embodiment, a medical cream composition containing 50% by weight, 20% by weight, or 0.1% by weight of micronized collagen is as illustrated in Table 1:
表1 内容物成分 微粒化膠原蛋白（重量百分比） 50.00 20.00 0.10 辛酸/癸酸三酸甘油酯 (Caprylic / Capric 17.00 17.00 17.00 Triglyceride ) 橄欖油山梨醇脂 (Cetearyl Olivate and 8.00 8.00 8.00 Sorbitan Olivate) 戊二醇 (Pentylene Glycol) 2.00 2.00 2.00 甘油（Glycerin ) 2.00 2.00 2.00 維他命E醋酸酯 (Tocopheryl Acetate) 1.00 1.00 1.00 苯曱酸甲酯 (Methylparaben ) 0.30 0.30 0.30 黃原膠（Xanthan Gum ) 0.20 0.20 0.20 純水（Aqua Purificata ) 加至 100.00 加至 100.00 加至 100.00 201012481 實施例三：製造含有微粒化生物性高分子材料之化妝 品乳霜 實施例一所得之微粒化膠原蛋白可以介於0.01重量百 分比至50重量百分比之間添加至添加至化妝品乳霜中。 在一實施例中’含有50重量百分比、2〇重量百分比或 0.1重量百分比之微粒化膠原蛋白的化妝品乳霜成份，如表 2所例示： 表2Table 1 Content components Micronized collagen (% by weight) 50.00 20.00 0.10 Caprylic / Capric 17.00 17.00 17.00 Triglyceride Olive oil sorbitol (Cetearyl Olivate and 8.00 8.00 8.00 Sorbitan Olivate) Pentylene Glycol 2.00 2.00 2.00 Glycerin 2.00 2.00 2.00 Tocopheryl Acetate 1.00 1.00 1.00 Methylparaben 0.30 0.30 0.30 Xanthan Gum 0.20 0.20 0.20 Pure Water ( Aqua Purificata ) Add to 100.00 Add to 100.00 Add to 100.00 201012481 Example 3: Manufacturing a cosmetic cream containing micronized biopolymer material The micronized collagen obtained in Example 1 may range from 0.01% by weight to 50% by weight. Add to add to cosmetic cream. In one embodiment, a cosmetic cream composition containing 50% by weight, 2% by weight or 0.1% by weight of micronized collagen, as exemplified in Table 2: Table 2
微粒化膠原蛋白（重量百分比） 一 ' ---- 内容物成分 50.00 20.00 0.1η 辛酸/癸酸三酸甘油酯 10.00 10.00 10.00 荷荷包油（Jojoba Oil) 5.00 5.00 5.0〇 橄欖油山梨醇脂 8.00 8.00 8.〇〇 戊二醇 2.00 2.00 2.〇〇 甘油（Glycerin) 2.00 2.00 2.〇〇Micronized collagen (% by weight) - ' Contents ingredients 50.00 20.00 0.1η Octanoic acid / citric acid triglyceride 10.00 10.00 10.00 Jojoba Oil 5.00 5.00 5.0 〇 olive oil sorbitol 8.00 8.00 8. 〇〇 pentanediol 2.00 2.00 2. Glycerin 2.00 2.00 2.〇〇
植物性角鯊烯 (Squalane, Vegetable) 2.00 2.00 2.00 神經酿胺（Ceramide) 1.00 1.00 1.0〇 維他命e醋酸酯 1.00 1.00 1.0〇 硬脂酸酸甘油酯 (Glyceryl Stearate) 0.80 0.80 〇.8〇 丁二醇 (1,3-Butylene Glycol) 0.50 0.50 〇.5〇 沒藥醇（α-Bisabolol) 0.50 0.50 〇.5〇 15 201012481 黃原膠 0.20 0.20 0.20 洋蘆薈（Aloe Vera) 0.30 0.30 0.30 苯甲酸甲酯 0.30 0.30 0.30 精油（Essential Oil) 0.02 0.02 0.02 純水 加至 100.00 加至 100.00 加至 100.00 實施例四：製造含有微粒化生物性高分子材料之化妝 品精華液 實施例一所得之微粒化膠原蛋白可以介於0.01重量百 分比至50重量百分比之間添加至添加至化妝品精華液中。 在一實施例中，含有50重量百分比、20重量百分比或 0.1重量百分比之微粒化膠原蛋白的化妝品精華液成份，如 表3所例示： 表3 内容物成分 微粒化膠原蛋白（重量百分比） 50.00 20.00 0.10 戊二醇 2.00 2.00 2.00 甘油（Glycerin) 2.00 2.00 2.00 大馬士革玫瑰花露 (Rosa Damascena 3.00 3.00 3.00 Flower Water ) 丁二醇 0.50 0.50 0.50 沒藥醇 0.50 0.50 0.50 16 201012481 黃原膠 0.20 0.20 0.20 苯甲酸甲酯 0.30 0.30 0.30 透明質酸鈉 (Sodium Hyaluronic 0.10 0.10 0.10 Acid ) 精油（Essential Oil) 0.02 0.02 0.02 純水 加至 100.00 加至 100.00 加至 100.00 比較例：利用習知技術製造微粒化生物性高分子材料 在本比較例中，係將200公克（或公斤）的膠原蛋白、 幾丁質、透明質酸，利用研磨機（Ling-Kwang Industrial Co.， Ltd.，台灣），以每分鐘24000轉之研磨速度，分別研磨上 述膠原蛋白、幾丁質、透明質酸，研磨約1小時。之後， 利用過濾分離微粒化膠原蛋白、微粒化幾丁質、微粒化透 明質酸與研磨介質。所得之微粒化膠原蛋白、微粒化幾丁 質、微粒化透明質酸的濃度分別約1重量百分比、約0.5 重量百分比及約0.5重量百分比。 根據習知技術之微粒化生物性高分子材料的粒徑分析 結果得知，比較例所得之微粒化膠原蛋白的平均粒徑介於 0.5微米至124微米之間。 惟需補充的是，本發明雖以特定生物性高分子材料、 特定研磨機型或研磨介質、特定用途作為例示，惟本發明 17 201012481 所屬技術領域中任何具有通常知識者可理解，在不脫離本 發明之精神和範圍内，亦可應用其他習知之生物性高分子 材料（例如幾丁質、透明質酸及生物性鈣質材料）、研磨機 型或研磨介質、或其他用途（例如添加至凝膠，或與PE薄 膜、護膚墊、紗布或生物性敷料等敷料結合）於本發明中， 故本發明並不園限於上述所舉。Squalane, Vegetable 2.00 2.00 2.00 Ceramide 1.00 1.00 1.0 〇Vitamin e acetate 1.00 1.00 1.0 G Glyceryl Stearate 0.80 0.80 〇.8 〇 Butanediol (1,3-Butylene Glycol) 0.50 0.50 〇.5 〇 药 醇 (α-Bisabolol) 0.50 0.50 〇.5〇15 201012481 Xanthan gum 0.20 0.20 0.20 Aloe Vera 0.30 0.30 0.30 methyl benzoate 0.30 0.30 0.30 Essential oil 0.02 0.02 0.02 Pure water added to 100.00 Add to 100.00 Add to 100.00 Example 4: Manufacture of cosmetic essence containing micronized biopolymer material The micronized collagen obtained in Example 1 can be Between 0.01% by weight and 50% by weight is added to the cosmetic essence. In one embodiment, the cosmetic essence component containing 50% by weight, 20% by weight, or 0.1% by weight of micronized collagen is as exemplified in Table 3: Table 3 Content Component Micronized Collagen (% by weight) 50.00 20.00 0.10 pentanediol 2.00 2.00 2.00 Glycerin 2.00 2.00 2.00 Damascus Rose Flower (Rosa Damascena 3.00 3.00 3.00 Flower Water ) Butanediol 0.50 0.50 0.50 Myrrholol 0.50 0.50 0.50 16 201012481 Xanthan gum 0.20 0.20 0.20 Benzoic acid Ester 0.30 0.30 0.30 Sodium Hyaluronic Acid (Sodium Hyaluronic 0.10 0.10 0.10 Acid ) Essential Oil 0.02 0.02 0.02 Pure water added to 100.00 Add to 100.00 Add to 100.00 Comparative Example: Micronized biopolymer material was prepared by conventional techniques In this comparative example, 200 grams (or kilograms) of collagen, chitin, and hyaluronic acid were ground by a grinder (Ling-Kwang Industrial Co., Ltd., Taiwan) at 24,000 rpm. Speed, separately grind the above collagen, chitin, hyaluronic acid, research About 1 hour. Thereafter, the micronized collagen, the micronized chitin, the micronized hyaluronic acid, and the grinding medium are separated by filtration. The concentration of the resulting micronized collagen, micronized chitin, and micronized hyaluronic acid was about 1 weight percent, about 0.5 weight percent, and about 0.5 weight percent, respectively. According to the particle size analysis of the microparticulated biopolymer material of the prior art, it was found that the average particle diameter of the micronized collagen obtained in the comparative example was between 0.5 μm and 124 μm. However, it should be added that the present invention is exemplified by a specific biopolymer material, a specific grinding machine type or a grinding medium, and a specific use, but it is understood by those having ordinary knowledge in the technical field of the present invention 17 201012481 that it does not deviate. Other conventional biopolymer materials (such as chitin, hyaluronic acid, and biological calcareous materials), grinders or grinding media, or other uses (eg, added to The gel, or in combination with a PE film, a skin pad, a gauze or a dressing such as a biological dressing, is in the present invention, and the present invention is not limited to the above.
由上述本發明較佳實施例可知，本發明之微粒化生物 性高分子材料及其製造方法，其優點在於將原本不溶且無 法均勻懸浮於水相溶液之生物性高分子材料，經由研磨介 質物理性研磨後，可得到平均粒徑介於3〇〇奈米至5微米 之間、且均勻懸浮於水相溶液中之微粒化生物性高分子材 料。有別於習知技術利用酵素或酸鹼等方式將生物性高分 子材料微粒化，易造成生物性高分子材料的破壞或變性， 本發明係於溫度例如介於攝氏5 1 4〇度的環境，利用物理 性研磨將其微粒化，所得之微粒化生物性高分子材料不僅 保留其生物活性’同時更可進一步添加至皮膚外用組成物 作為有效成分。 雖然本發明已以一較佳實施例揭露如上，然其並非用 以限定本發明’在本發明所屬技術領域中任何具有通常知 識者，在不脫離本發明之精神和範圍内，當可作各種之更 動與满飾’因此本發明之保護範圍當視後附之中請專 圍所界定者為準。 【圓式簡單說明] 201012481 【主要元件符號說明】According to the preferred embodiment of the present invention, the micronized biopolymer material of the present invention and the method for producing the same have the advantages of physico-polymer material which is originally insoluble and cannot be uniformly suspended in the aqueous phase solution, and is physically passed through the grinding medium. After the abrasive polishing, a micronized biopolymer material having an average particle diameter of between 3 Å and 5 μm and uniformly suspended in the aqueous phase solution can be obtained. Different from conventional techniques, microbial biomaterials are micronized by means of enzymes or acids and bases, which are liable to cause destruction or denaturation of biopolymer materials. The present invention is in an environment having a temperature of, for example, 515 degrees Celsius. The micronized biopolymer material is retained by physical polishing, and the obtained micronized biopolymer material not only retains its biological activity, but can be further added to the external composition for skin as an active ingredient. While the present invention has been described above in terms of a preferred embodiment, it is not intended to limit the invention, and the invention may be used in various forms without departing from the spirit and scope of the invention. The change and the full decoration 'The scope of protection of the present invention is subject to the definition of the exclusive scope. [Circular Simple Description] 201012481 [Main Component Symbol Description]