1363634 .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（hyalur〇nic acid; 鲁 HA )疋細胞外基質相當.重要的組成分’同時亦可用於人體 器g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、皮膚鬆他、 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。 • 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。 6 除了夥原蛋白及透明質酸之外，幾丁質及生物性㈣ 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#原蛋白㈣’利用化學或酵素法處理所得之夥原蛋 白，其濃度最高不超過i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 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^藉由研磨達到微粒化的效果，更難謂可藉 此提兩其溶解於水相溶液之濃度。 有鑑於此，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 眭间刀子材料及其製造方法，其係將原本不溶且無法均句 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。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， 1363634 其中生物性高分子材料可包括但不限於膠原蛋白 質、透明質酸及生物性舞質材料等。接著，進行至少 陡研磨步帮’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（職）至i」毫米之研磨 介質物理性研磨上述生物性高分子材料以獲得平均粒徑 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-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，吏提出一種微粒化生物性高 分子材料，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（mm)至 1.1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300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 (Lotion)、精華液（Essence)或凝膠（Gel)。依照本發明 8 1363634 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。 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 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。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 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 均勻懸汗於水相溶液者，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。 9 1363634 在一實施例中，上述之生物性㈣材料可包括但不限於珍 珠、牡螺殼、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，利用平均粒經介於〇 4 毫米（mm)至1.1毫米之研磨介質，以介於例如每分鐘〇 至4000轉之研磨速度，藉由研磨介質之剪切力（如肛 f⑽）、衝擊力umpactforce)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-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授拌介f研磨機 media mill)、分散研磨機（dispersi〇nmin)、齒盤型研磨機 (diSC miU )、高剪式研磨機（high-shear mill )、球 磨機（ballmill)、氣流喷射研磨機（jetmill)等。 其次，研磨介質之材料可包括但不限於氧化锆、氧化 紀或其任意組合H施例中，研磨介質可例如含有約 92重量百分比之氧化鍅、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-實施例中，利用研磨介質乾磨上 述生物性咼分子材料時，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 勝原蛋白、幾丁質、透明質酸等之生物性高分子材料可先 10 進灯乾燥步称，例如冷涞乾燥步驟或真空乾燥步驟再直 接利用研磨介質進行乾磨。 了乾磨方式之外，在又一實施例中上述生物性高 分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0.01重量百分比 至10重里百分比之間的生物性高分子材料，加人酸驗值介 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 濃度以介於Ο.1 M至1 Μ為宜，又以介於0.2 M至〇_8 M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微求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 分離步驟’其係利用例如間隙分離、過滤分離、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 研磨η質，其中所仔之微粒化生物性高分子材料可均勾 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 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 1363634 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（Lotion)、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。 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 化子或酵素法處理，其僅能以濕式法處理，且處理濃度不 同。舉例而§，以化學或酵素法處理所得之膠原蛋白其 濃度最高不超過i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’-般研磨主要乃針對硬質之無機材料，其研磨難度 -相較之下，生物性尚分子材料為纖維狀，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。 J •利用濕磨製造微粒化生物性高分子材料 在本實施例中，係將約公克（或公斤）的膠原蛋 12 1363634 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，利用實驗級攪拌介質研磨機（laboratory agitated media mill，Model No. PML-H/V，Btihler & 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 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 醫療組成物 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 1363634 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：1363634. IX. Description of the Invention: [Technical Field] The present invention relates to a biopolymer material, a method for producing the same, and a use thereof, and more particularly to a micronized biopolymer material and a method of manufacturing the same Its use. [Prior Art] Collagen (collagen) and hyaluronic acid (hyalur〇nic acid; Lu HA) 相当 extracellular matrix is equivalent. The important component 'can also be used for human body tissue repair (repair) and regeneration (regeneration ) a 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. Finally, it causes wrinkles, loose skin, dullness, stagnation, and roughness. Skin, collagen and hyaluronic acid can be properly supplemented by diet, cosmetics or topical medicines. • When applied to skin external ingredients, collagen and hyaluronic acid are usually dissolved in an aqueous solution and 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, the concentration does not exceed about 1% by weight, and at the same time increases the steps and time of the skin external composition process. 6 In addition to collagen and hyaluronic acid, chitin and biological (4) materials also promote tissue repair and regeneration characteristics, and are often added to skin external compositions 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. However, the raw protein obtained by chemical or enzymatic treatment with #原蛋白(四)' is not more than i by weight, and is liable to cause destruction or denaturation of collagen. In addition, the above-mentioned biological polymer material is treated by physical polishing, but the above-mentioned biological polymer material is mostly fibrous or soft in texture except for chitin and biological calcium material, and is relatively difficult to grind, and generally grinding machine It is not difficult to achieve the effect of microparticulation by grinding, and it is more difficult to mention the concentration of the two dissolved in the aqueous phase solution. In view of the above, 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 micronized biological intercondylar knife material and a method for producing the same, which are a biological polymer material which is originally insoluble and cannot be uniformly suspended in an aqueous phase solution, via After the polishing medium is physically ground, a micronized biopolymer material having an average particle diameter of between 3 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 for 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, 1363634 wherein the biopolymer material can include, but is not limited to, collagen protein, hyaluronic acid, and living organisms. Sexual dance materials, etc. Next, at least a steep grinding step is performed in an environment where the temperature is between 5 and 4 degrees Celsius, and the grinding medium is physically ground using an average particle diameter of between 4 mm and 2 mm. The above biopolymer material is obtained to obtain a micronized biopolymer material having an average particle diameter of between 300 nm and 5 μm. Thereafter, a carry-off step is performed to separate the above-mentioned micronized biopolymer material from the grinding medium, wherein the micronized biopolymer material can be uniformly suspended in the aqueous phase solution. According to a preferred embodiment of the present invention, the biological calcium material may include, but is not limited to, a pearl, an oyster shell, a shell or any combination thereof. According to a preferred embodiment of the present invention, the material of the grinding medium may include but is not limited to Zirconia, cerium oxide or any combination thereof. According to the above aspect of the present invention, a micronized biopolymer material is proposed which is used in an environment having a temperature between 5 and 40 degrees Celsius and an average particle diameter of 〇4 mm ( Mm) to 1.1 mm of the grinding medium physically grinds the biopolymer material, so that the obtained micronized biopolymer material has an average particle diameter of between 300 nm and 5 μm and is uniformly suspended in the aqueous phase solution. According to the above aspect of the present invention, there is further proposed a composition for external use on skin which contains the microparticulated biopolymer material as described above as an active ingredient. According to a preferred embodiment of the present invention, 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 ( Lotion), Essence or Gel. According to another preferred embodiment of the invention 8 1363634, the micronized biopolymer material may also be combined with a dressing' and the dressing may include, but is not limited to, a PE film, a skin pad, a gauze or a biological dressing. The micronized biopolymer material of the present invention and a method for producing the same are used, wherein a biological polymer material which is insoluble in the aqueous phase solution and which is not insoluble in the aqueous phase solution is physically ground through a grinding medium, and an average particle size is obtained. A micronized biopolymer material between 300 nm and 5 μm and uniformly suspended in an aqueous phase solution. 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, 5 to 40 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. [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 a material which is originally insoluble and cannot be uniformly suspended in an aqueous phase solution, and generally includes, but is not limited to, various animal-derived collagen, chitin, hyaluronic acid and biological calcium. Material, etc. 9 1363634 In one embodiment, the biological (four) material described above may include, but is not limited to, a pearl, a snail shell, a shell, or any combination thereof. Next, performing at least one physical grinding step, which is carried out in an environment having a temperature of, for example, between 5 and 40 degrees Celsius, using an average particle size of between 〇4 mm (mm) and 1.1 mm of the grinding medium to For example, the grinding speed of 4,000 to 4,000 rpm, the grinding of the medium (such as anal f (10)), impact force umpactforce, etc., physical polishing of the above biopolymer material, the grinding time can be between 3 〇 minutes It is preferred to grind for about 2 hours to 3 hours. In an embodiment, the physical grinding step can be carried out using an existing grinding apparatus, such as a grinding mill media mill, a dispersing mill (dispersi〇nmin), a sprocket type grinding machine (diSC). miU), high-shear mill, ballmill, jetmill, and the like. Secondly, the material of the grinding medium may include, but is not limited to, zirconia, oxidized or any combination thereof. In the embodiment, the grinding medium may, for example, contain about 92% by weight of cerium oxide, about 5% by weight of cerium oxide, and about 3 weights. Percentage of other substances. Further, the polishing method of the physical polishing step is not limited and can be carried out, for example, by dry grinding or wet milling. In the embodiment, when the biological bismuth molecular material is dry-ground by using a grinding medium, the biological polymer material such as the biological calcium material may be firstly cleaned and dried, or may be selectively cut or pulverized into smaller fragments. Then, the grinding medium is directly used for dry grinding. In another embodiment, when the above bio-based polymer material is dry-ground by using a grinding medium, biopolymer materials such as phenylpropolis, chitin, hyaluronic acid, etc. may be first subjected to a light drying step, such as cold sputum. The drying step or the vacuum drying step is followed by dry grinding directly using the grinding medium. In addition to the dry milling method, in still another embodiment, the above bio-based polymer material may be subjected to wet milling. In an embodiment, when the above-mentioned biopolymer material is wet-ground by using a grinding medium, the biopolymer material between 0.01% by weight and 10% by weight may be first added, and the acid value is between 2.5 and 5.5. Between acidic aqueous solutions. Suitable acidic aqueous solutions may, for example, be aqueous acetic acid, aqueous citric acid or aqueous hydrochloric acid, and suitable concentrations are preferably between 0.1 M and 1 Torr, and preferably between 0.2 M and 〇8 M. In the physical polishing step, the biopolymer material may be sufficiently micronized at least once to obtain a micronized biopolymer material having an average particle diameter of between 300 nm and 5 μ. Further, in the above-described physical polishing step, the separation step may be simultaneously performed by using, for example, gap separation, filtration separation, sedimentation separation, centrifugation, or the like to separate the above-mentioned microparticulated biopolymer material from n-mass. The micronized biopolymer material of the seed can be suspended in the aqueous solution. According to another preferred embodiment of the present invention, there is provided a skin external composition comprising the micronized biopolymer material as described above as an active ingredient. 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, 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 1363634 to the external composition for skin 'for example, a cosmetic composition or a topical medical composition. 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 not limited to, Cream, Lotion, 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 not limited to, a PE film, a skin pad, Gauze or biological dressing. It is worth mentioning that the present invention micronizes a biological polymer material which is originally insoluble and cannot be uniformly suspended in an aqueous phase solution by physical polishing, and the difference from the conventional micronization is briefly described as follows. First, it is generally treated by a chemical or enzyme method, which can only be treated by a wet method, and the treatment concentration is different. For example, §, the collagen obtained by chemical or enzymatic treatment is at a concentration not exceeding i by weight; 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, 'the general grinding is mainly for hard inorganic materials, and the grinding difficulty is compared. The biological molecular material is fibrous, and the soft texture is 'not easy to grind'. Generally, the grinding machine cannot achieve the same or similar to the present invention. 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. J: The use of wet grinding to produce a micronized biopolymer material. In this embodiment, approximately gram (or kilograms) of collagen egg 12 1363634 white, chitin, hyaluronic acid are added to a pH of about 3, respectively. After the acetic acid/citric acid/hydrochloric acid aqueous solution, an experimental agitated media mill (Model No. PML-H/V, Btihler & Drais GmbH, Germany) or the like is used together with the average particle size. The above-mentioned collagen, chitin, hyaluronic acid is wet-milled for about 2 hours at a grinding rate of, for example, from 2,000 to 4,000 rpm at a grinding medium of 0.4 mm to 1.1 mm. In the above physical polishing step, microparticulated collagen, micronized chitin, micronized hyaluronic acid, and a grinding medium can be separated by, for example, gap separation, filtration separation, or centrifugation. The resulting micronized collagen, micronized chitin, and micronized hyaluronic acid may each have a concentration of 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 subjected to granules using, for example, a Dynamic Light Scattering (DLS) particle size analyzer such as a Brookhaven 90 Plus Nanoparticle Size Analyzer (Brookhaven Instruments Corp., Holtsville, NY, USA). Path analysis. After the DLS particle size analysis, the effective diameter of the micronized collagen obtained in the present example was 598·7±57·1 nm, and the half width was 315.8±22.4 nm, and the polydispersity was obtained. (polydiversity) was 0.278 ± 0·21. Example 2: Production of 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 the external medical composition 13 1363634. For example, medical creams. 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 苯甲酸甲酯 (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 1363634 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) is added to 100.00 to 100.00 to 100.00 1363634. Example 3: Manufacturing a cosmetic cream containing micronized biopolymer material. The micronized collagen obtained in Example 1 may be between 0.01% by weight and 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
内容物成分 微粒化膠白（重量百分比 50.00 on ηπ η 1ΛContent component micronized gel white (weight percentage 50.00 on ηπ η 1Λ
辛酸/癸酸三酸甘油酯 10.00 10.00 10.C 荷荷芭油（Jojoba Oil ) 5.00 5.00 5.C 撖欖油山梨醇脂 8.00 8.00 戊二醇 2.00 2.00 2.C 甘油（Glycerin) 2.00 2.00 2.C 植物性角鯊烯 (Squalane, Vegetable)Caprylic/capric triglyceride 10.00 10.00 10.C Jojoba Oil 5.00 5.00 5.C eucalyptus oil 8.00 8.00 pentanediol 2.00 2.00 2.C Glycerin 2.00 2.00 2. C squalane, Vegetable
2.00 2.00 2.0〇 神經酿胺（Ceramide) 1.00 1.00 維他命e醋酸酯 1.00 1.00 1.0〇 ι.〇〇 硬脂酸酸甘油酯 (Glyceryl Stearate) 0.80 0.80 °*8〇 二醇 1,3-Butylene Glycol) 0.50 0.50 〇.5〇 沒藥醇（α-Bisabolol) 0.50 0.50 0.50 Ϊ363634 黃原膠 0.20 0.20 0.20 洋蘆薈（Aloe Vera) 0.30 0.30 0.30 多甲酸甲酯 0.30 0.30 0.30 精油（Essential Oil ) 0.02 0.02 0.02 純水 加至 加至 加至 100.00 100.00 100.002.00 2.00 2.0〇Ceramide 1.00 1.00 Vitamin e acetate 1.00 1.00 1.0〇ι.〇〇Glyceryl Stearate 0.80 0.80 °*8〇diol 1,3-Butylene Glycol) 0.50 0.50 〇.5〇Bisabolol 0.50 0.50 0.50 Ϊ363634 Xanthan gum 0.20 0.20 0.20 Aloe Vera 0.30 0.30 0.30 Polymethyl carboxamide 0.30 0.30 0.30 Essential oil (Essential Oil) 0.02 0.02 0.02 Pure water plus Add to 100.00 100.00 100.00
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〇 〇1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、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精華液成份，如 表3所例示： 表3Example 4: Production of Cosmetic Essence Containing Micronized Biopolymer Material The micronized collagen obtained in Example 1 can be added to the cosmetic essence from 重量1% by weight to 50% by weight. In one embodiment, the composition of the cosmetic serum containing 50% by weight, 2% by weight or 0.1% by weight of micronized collagen, as exemplified in Table 3: Table 3
内容物成分 !二醇 2.00 一甘油（Glycerin ) — 丨― 2.00 大馬士革玫塊花露 -----~~~ (Rosa Damascena 3.00 Flower Water) 丁二醇 0.50 沒藥醇 0.50 _^化膠重量百分比 50.00 20.00 0.10 2.00 2.00 3.00 0.50 2.00 2.00 3.00 0.50 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 Acid ) 0.10 0.10 0.10 精油（Essential Oil ) 0.02 0.02 0.02 加至 加至 加至 純水 100.00 100.00 100.00 1363634 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，研磨約丨小時。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、約〇5 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、料料料例*，惟本發明 17 1363634 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， 故本發明並不囿限於上述所舉。 由上述本發明較佳實把例可知’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，經由珥磨介 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至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申請專利範 圍所界定者為準。 【圖式簡單說明】 無 1363634 【主要元件符號說明】Contents ingredients! Glycol 2.00 Glycerin - 丨 - 2.00 Damascus rose flower dew-----~~~ (Rosa Damascena 3.00 Flower Water) Butanediol 0.50 Myrrholol 0.50 _^ Gel weight percentage 50.00 20.00 0.10 2.00 2.00 3.00 0.50 2.00 2.00 3.00 0.50 Xanthan gum 0.20 0.20 0.20 methyl benzoate 0.30 0.30 0.30 sodium hyaluronic acid 0.10 0.10 0.10 essential oil (Essential Oil ) 0.02 0.02 0.02 Add to add to Pure water 100.00 100.00 100.00 1363634 Comparative example: Production of micronized biopolymer material by conventional techniques In this comparative example, 200 g (or kg) of collagen, chitin, hyaluronic acid, using a grinder (Ling-Kwang Industrial Co., Ltd. 'Taiwan), grinding the above collagen, chitin, hyaluronic acid at a polishing rate of 24,000 rpm, and grinding for about 丨 hours. Thereafter, the micronized collagen, the micronized chitin, the micronized hyaluronic acid, and the grinding medium are separated by filtration. The obtained micronized collagen, micronized chitin, and micronized hyaluronic acid have a concentration of about 1% by weight, about 5% by weight, and about 0.5% by weight, respectively. The micronized biopolymer material according to the prior art. As a result of the particle size analysis, 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 although the present invention is based on a specific biopolymer material, a specific grinding machine type or a grinding medium, and a material material*, it is understood by those having ordinary knowledge in the technical field of the invention 17 1363634, Other conventional biopolymer materials (eg, chitin, hyaluronic acid, and biological calcareous materials), grinders or grinding media, or other uses (eg, additions) may also be utilized without departing from the spirit and scope of the present invention. To the gel, or in combination with a dressing such as a pE film, a skin pad, a gauze or a biological dressing, the present invention is not limited to the above. According to the above preferred embodiment of the present invention, the microparticulated biopolymer material of the present invention and the method for producing the same have the advantage that the biopolymer material which is originally insoluble and cannot be uniformly suspended in the aqueous phase solution is honed. After the medium is physically ground, a micronized biopolymer material having an average particle diameter of between 3 nm 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, 5 to 4 degrees Celsius. 'Micronized by physical polishing, 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 present invention, and it is to be understood by those skilled in the art without departing from the spirit and scope of the invention. The scope of protection of the present invention is therefore defined by the scope of the appended claims. [Simple description of the diagram] None 1363634 [Description of main component symbols]