技术领域Technical field
本发明属于隐形眼镜润滑液技术领域，具体涉及一种眼用润滑液组合物及其应用。The invention belongs to the technical field of contact lens lubricant, and specifically relates to an ophthalmic lubricant composition and its application.
背景技术Background technique
隐形眼镜以其光学矫正优势在增强视觉健康方面日益发挥着重要功能，尤其是软性隐形眼镜以其舒适、简便易用、受到越来越多近视患者的青睐，近年来其佩戴人群也在逐渐增加。Contact lenses are increasingly playing an important role in enhancing visual health with their optical correction advantages. In particular, soft contact lenses are favored by more and more myopic patients because of their comfort, simplicity and ease of use. In recent years, the number of people wearing them has also gradually Increase.
在佩戴隐形眼镜时，由于在眼睛多增加了两个接触面(由角膜一个界面增加到三个界面)，从而造成了加速泪水蒸发和降低泪水湿润现象，进而会出现如下症状，如：异物感和疲劳症状，刺激、痒、灼热，眨眼次数增加，结膜充血，眼睛存在黏液分泌物，对烟雾、空调以及环境因素过敏等。据报道，四分之三的隐形眼镜佩戴者会抱怨眼睛出现干涩现象。佩戴隐形眼镜出现的眼干是一种非常普遍的现象。研究表明，平均两个隐形眼镜佩戴者中会有一人出现眼干症状。佩戴隐形眼镜干燥也会导致镜片表面累积沉淀物、降低视力、降低镜片透氧性以及改变镜片规格等，严重影响了镜片的佩戴质量，并且镜片佩戴舒适感大大降低。这里描述的眼干症状，不是指临床上的裸眼干眼症，它是指许多隐形眼镜佩戴者在戴镜后出现的暂时性的眼睛干涩、异物感、易疲劳等症状。针对隐形眼镜佩戴者最典型的眼干症状，必须使用隐形眼镜专用的润滑液进行人工干预。When wearing contact lenses, two more contact surfaces are added to the eye (from one interface to the cornea to three interfaces), which accelerates tear evaporation and reduces tear moistening, and the following symptoms may occur, such as foreign body sensation. and fatigue symptoms, irritation, itching, burning, increased blinking, conjunctival congestion, mucus secretions in the eyes, allergies to smoke, air conditioning and environmental factors, etc. Three-quarters of contact lens wearers reportedly complain of dry eyes. Dry eyes are a very common phenomenon when wearing contact lenses. Research shows that on average, one in two contact lens wearers will experience symptoms of dry eyes. Wearing dry contact lenses will also lead to the accumulation of deposits on the lens surface, reduced vision, reduced lens oxygen permeability, and changes in lens specifications, which seriously affects the wearing quality of the lenses and greatly reduces the comfort of wearing the lenses. The dry eye symptoms described here do not refer to clinical naked eye dry eye syndrome, but refer to the temporary dry eyes, foreign body sensation, fatigue and other symptoms that many contact lens wearers experience after wearing glasses. For the most typical dry eye symptoms of contact lens wearers, manual intervention must be carried out using lubricants specially designed for contact lenses.
隐形眼镜在眼睛里的佩戴舒适度，在一定程度上取决于泪液与镜片基弧-角膜间泪液的流体交换。硬质隐形眼镜，由于上眼睑对镜片上部施加的压力而受到泵送作用，镜片上部起支点作用。这种泵送引起所希望的流体交换。然而，对于软质隐形眼镜，这样的“泵送”并不存在(参阅Mandel，“ContactLens Practice”(隐形眼镜实践)第三版，1981年，第512页)。因此，在软质隐形眼镜的佩戴者眼睛里，泪液交换减少。这种减少的泪水交换是不利的，因为它妨碍从镜片底下区域脱除废物和碎屑。这种废物和碎屑包括蛋白质、细胞、代谢产物及它们的碎片等，且会逐渐截留在镜片底下。所截留的废物和碎屑的积累，会造成佩戴者的不舒适，在极端的情况下可能对眼睛有害。同时，这还妨碍隐形眼镜外侧的所需要的泪液成分与镜片底下的眼睛相接触。虽然软质隐形眼镜不存在像硬质形眼镜那样的有效泵送作用，但由于上眼睑对镜片的压力，软质隐形眼镜在眼睛里仍有某种运动。这种运动使得能发生某种泪液交换，但并非能够足以避免废物和碎屑在镜片底下的积累。此外，镜片在眼睛中的这一种所希望的运动往往由于镜片脱水、收缩和更紧地贴在眼睛上，而随时间减少。The comfort of wearing contact lenses in the eyes depends to a certain extent on the fluid exchange between tears and the lens base curve-cornea. Rigid contact lenses are pumped due to the pressure exerted by the upper eyelid on the upper part of the lens, which acts as a fulcrum. This pumping causes the desired fluid exchange. However, with soft contact lenses, such "pumping" does not exist (see Mandel, "Contact Lens Practice" 3rd ed., 1981, p. 512). As a result, tear exchange is reduced in the eyes of soft contact lens wearers. This reduced tear exchange is disadvantageous because it prevents removal of waste and debris from the area beneath the lens. This waste and debris includes proteins, cells, metabolic products and their fragments, etc., and will gradually become trapped under the lens. The accumulation of trapped waste and debris can cause discomfort to the wearer and in extreme cases may be harmful to the eyes. At the same time, this also prevents the required tear components on the outside of the contact lens from coming into contact with the eye underneath the lens. Although soft contact lenses do not have the same effective pumping action as hard lenses, there is still some movement in the eye due to the pressure of the upper eyelid on the lens. This movement allows some tear exchange to occur, but is not sufficient to prevent waste and debris from accumulating underneath the lens. Furthermore, this desired movement of the lens in the eye often decreases over time as the lens dehydrates, shrinks, and becomes tighter against the eye.
用于提高硬性或软质隐形眼镜佩戴舒适度的润滑液早已有报道。润滑液作为隐形眼镜的护理产品，不同于润眼药(或滴眼药)。润眼药不可在佩戴隐形眼镜时使用，因其药物成分可能沉淀在镜片上，改变镜片的性状。而隐形眼镜专用润滑液是针对隐形眼镜佩戴者，用于改善和缓解佩戴隐形眼镜过程中的眼干以及提高戴镜舒适度的溶液；这种溶液一般包含：防腐剂、保湿剂、润滑剂、螯合剂、缓冲剂和等渗剂，用于在佩戴隐形眼镜时使用。目前市面上销量好的隐形眼镜润滑液产品含海昌隐形眼镜有限公司的水感觉款及锁水保湿型、爱尔康的傲滴型、博士伦的润明新概念、江苏中润光学眼镜有限公司的HA型、上海卫康光学眼镜有限公司的润滑液、博士伦有限公司的硬性透气角膜接触镜润滑液、雅培眼里健(杭州)制药有限公司的冰蓝型等产品。其中海昌隐形眼镜有限公司的水感觉款及锁水保湿型、爱尔康的傲滴型、博士伦的润明新概念、江苏中润光学眼镜有限公司的HA型和上海卫康光学眼镜有限公司的润滑液，仅适用于在佩戴软性隐形眼镜时使用；博士伦有限公司的硬性透气角膜接触镜润滑液仅适用于在佩戴硬性隐形眼镜时使用；雅培眼里健(杭州)制药有限公司的冰蓝型润滑液则适用于在佩戴软性和硬性隐形眼镜时使用。但是目前这些隐形眼镜用润滑液的保湿和润滑效果和戴镜舒适性并不令人满意。Lubricants used to improve the wearing comfort of hard or soft contact lenses have long been reported. As a care product for contact lenses, lubricant is different from eye drops (or eye drops). Eye moisturizers should not be used when wearing contact lenses, as the drug ingredients may precipitate on the lenses and change the properties of the lenses. The special lubricant for contact lenses is a solution for contact lens wearers to improve and relieve eye dryness during wearing contact lenses and improve the comfort of wearing lenses; this solution generally contains: preservatives, moisturizers, lubricants, Chelating agents, buffers, and isotonic agents used when wearing contact lenses. Currently, the best-selling contact lens lubricant products on the market include Haichang Contact Lens Co., Ltd.’s water-feeling and water-locking moisturizing types, Alcon’s AoDrip type, Bausch & Lomb’s Runming New Concept, and Jiangsu Zhongrun Optical Glasses Co., Ltd. The company's HA type, Shanghai Weikang Optical Glasses Co., Ltd.'s lubricant, Bausch & Lomb Co., Ltd.'s rigid gas permeable contact lens lubricant, Abbott Eyelijian (Hangzhou) Pharmaceutical Co., Ltd.'s ice blue type and other products. Among them, Haichang Contact Lens Co., Ltd.’s water-sensing type and water-locking and moisturizing type, Alcon’s Aodi type, Bausch & Lomb’s Runming new concept, Jiangsu Zhongrun Optical Glasses Co., Ltd.’s HA type and Shanghai Weikang Optical Glasses Co., Ltd. The company's lubricant is only suitable for use when wearing soft contact lenses; Bausch & Lomb Co., Ltd.'s rigid gas permeable contact lens lubricant is only suitable for use when wearing hard contact lenses; Abbott Eyes (Hangzhou) Pharmaceutical Co., Ltd. The ice blue lubricant is suitable for use when wearing soft and hard contact lenses. However, the moisturizing and lubricating effects of these current contact lens lubricants and the comfort of wearing the lenses are not satisfactory.
此外，以上产品均属于多剂量包装制剂，其均含有防腐剂。防腐剂是一类具有抑制微生物增殖或杀死微生物的化合物。虽然一些不含防腐剂的眼制剂产品逐渐上市，但由于一次性使用，其包装及生产设备较为独特，价格也较为昂贵。目前在润滑液产品中常用的防腐剂包括聚六亚甲基双胍盐酸盐(PHMB)、聚氨丙基双胍(PAPB)、聚季铵盐类、氯己胺葡萄酸盐和纯氯氧复合物；其中纯氯氧复合物，主要以NaClO的形式存在，见光分解成天然泪液成分NaCl和H2O，因此其包装需要特殊容器。另外，为提高佩戴隐形眼镜过程中润滑保湿和舒适度，润滑液产品的黏度值明显较高于常规款产品，如雅培冰蓝型和博士伦的硬性透气角膜接触镜润滑液黏度值都大于6以上。然而对于高粘和含有高含水量水溶性物质的溶液，其抗微生物防腐效果较差，常规控制措施是加大溶液中防腐剂的添加量或使用特殊防腐剂。大量的研究表明，高防腐剂含量的眼制剂易引起眼表毒性和/或刺激性。因此，在润滑液产品中如何控制防腐剂含量到最低水平，而又确保产品的防腐效果符合要求至关重要。In addition, the above products are all multi-dose packaged preparations, which contain preservatives. Preservatives are compounds that inhibit the proliferation of microorganisms or kill them. Although some preservative-free eye preparation products are gradually becoming available on the market, due to their one-time use, their packaging and production equipment are relatively unique and the price is relatively expensive. Currently commonly used preservatives in lubricant products include polyhexamethylene biguanide hydrochloride (PHMB), polyaminopropyl biguanide (PAPB), polyquaternium salts, chlorhexylamine glucate and pure chlorine-oxygen compound Among them, the pure chlorine-oxygen compound mainly exists in the form of NaClO, which decomposes into natural tear components NaCl and H2 O when exposed to light, so its packaging requires special containers. In addition, in order to improve lubrication, moisturizing and comfort during wearing contact lenses, the viscosity value of lubricant products is significantly higher than conventional products. For example, the viscosity values of Abbott Ice Blue and Bausch & Lomb rigid gas permeable contact lens lubricants are greater than 6 above. However, solutions with high viscosity and high water content and water-soluble substances have poor antimicrobial and preservative effects. Conventional control measures are to increase the amount of preservatives added to the solution or use special preservatives. Numerous studies have shown that ocular preparations with high preservative content may cause ocular surface toxicity and/or irritation. Therefore, it is crucial to control the preservative content in lubricant products to the lowest level while ensuring that the anti-corrosion effect of the product meets the requirements.
发明内容Contents of the invention
为了解决现有技术存在的以上问题，本发明提供了一种眼用润滑液组合物及其应用。本发明所述眼用润滑液组合物，能够安全有效地用于湿润和润滑隐形眼镜，改善和缓解眼干，提高戴镜舒适度；本发明所述眼用润滑液组合物中防腐剂含量较低，同时具有高效的防腐性和生物相容性。In order to solve the above problems existing in the prior art, the present invention provides an ophthalmic lubricating liquid composition and its application. The ophthalmic lubricating liquid composition of the present invention can be used to moisten and lubricate contact lenses safely and effectively, improve and relieve dry eyes, and increase the comfort of wearing glasses; the preservative content in the ophthalmic lubricating liquid composition of the present invention is relatively high. Low, while having high antisepsis and biocompatibility.
本发明所采用的技术方案为：The technical solutions adopted by the present invention are:
一种眼用润滑液组合物，原料组分包括：An ophthalmic lubricating liquid composition, the raw material components include:
透明质酸类化合物0.01～0.25重量份、聚乙烯基吡咯烷酮0.001～0.1重量份、聚乙二醇0.01～0.4重量份、氨丁三醇0.05～0.6重量份、依地酸二钠0.005～0.5重量份、双胍类防腐剂0.00004～0.00015重量份、泊洛沙姆0.01～0.5重量份、缓冲剂0.0001～0.5重量份、等渗剂0.5～1.5重量份；0.01-0.25 parts by weight of hyaluronic acid compounds, 0.001-0.1 parts by weight of polyvinylpyrrolidone, 0.01-0.4 parts by weight of polyethylene glycol, 0.05-0.6 parts by weight of trometamol, 0.005-0.5 parts by weight of disodium edetate 0.00004 to 0.00015 parts by weight of biguanide preservatives, 0.01 to 0.5 parts by weight of poloxamer, 0.0001 to 0.5 parts by weight of buffer, and 0.5 to 1.5 parts by weight of isotonic agent;
所述透明质酸类化合物为透明质酸、透明质酸盐、透明质酸衍生物、透明质酸盐衍生物中的一种或几种的混合物。The hyaluronic acid compound is one or a mixture of several of hyaluronic acid, hyaluronic acid salts, hyaluronic acid derivatives, and hyaluronic acid salt derivatives.
进一步优选所述眼用润滑液组合物的原料组分包括：It is further preferred that the raw material components of the ophthalmic lubricating liquid composition include:
透明质酸类化合物0.08～0.2重量份、聚乙烯基吡咯烷酮0.01～0.1重量份、聚乙二醇0.05～0.3重量份、氨丁三醇0.05～0.2重量份、依地酸二钠0.05～0.2重量份、双胍类防腐剂0.00006～0.00012重量份、泊洛沙姆0.01～0.1重量份、缓冲剂0.0001～0.5重量份、等渗剂0.5～1.5重量份。0.08-0.2 parts by weight of hyaluronic acid compounds, 0.01-0.1 parts by weight of polyvinylpyrrolidone, 0.05-0.3 parts by weight of polyethylene glycol, 0.05-0.2 parts by weight of trometamol, 0.05-0.2 parts by weight of disodium edetate 0.00006 to 0.00012 parts by weight of biguanide preservative, 0.01 to 0.1 parts by weight of poloxamer, 0.0001 to 0.5 parts by weight of buffer, and 0.5 to 1.5 parts by weight of isotonic agent.
所述透明质酸盐为透明质酸的钠盐、钾盐、钙盐、镁盐中的一种或几种的混合物。The hyaluronic acid salt is one or a mixture of sodium salt, potassium salt, calcium salt and magnesium salt of hyaluronic acid.
所述透明质酸类化合物为分子量为0.1×106Da～2.0×106Da的透明质酸钠。The hyaluronic acid compound is sodium hyaluronate with a molecular weight of 0.1×106 Da to 2.0×106 Da.
所述透明质酸类化合物为中分子量0.3×106Da～0.7×106Da透明质酸钠和高分子量0.8×106Da～1.5×106Da透明质酸钠的混合物。The hyaluronic acid compound is a mixture of sodium hyaluronate with a medium molecular weight of 0.3×106 Da to 0.7×106 Da and sodium hyaluronate with a high molecular weight of 0.8×106 Da to 1.5×106 Da.
所述中分子量透明质酸钠和高分子量透明质酸钠的重量比为1:(1～25)，优选为1:3。The weight ratio of the medium molecular weight sodium hyaluronate and the high molecular weight sodium hyaluronate is 1: (1-25), preferably 1:3.
透明质酸钠为一种从动物组织中提取或经微生物发酵生产的高分子粘多糖，简称HA，由D-葡萄糖醛酸和N-乙酰基-D-氨基葡萄糖双糖单位组成的高分子黏多糖。HA天然存在于人和动物体内，主要分布于关节、眼玻璃体、皮肤、脐带等，具有高度亲水性/保湿性、黏弹性、润滑性和良好的生物相容性。泪液及眼角膜上皮层表面均存在的天然保湿因子HA，具有保持角膜表面湿润、稳定泪液膜的作用，并有抗炎性能和促进创伤愈合、抗氧化损伤防护效应。Sodium hyaluronate is a high molecular mucopolysaccharide extracted from animal tissues or produced by microbial fermentation, referred to as HA. It is a high molecular mucopolysaccharide composed of D-glucuronic acid and N-acetyl-D-glucosamine disaccharide units. polysaccharide. HA naturally exists in human and animal bodies, mainly distributed in joints, vitreous body, skin, umbilical cord, etc. It has high hydrophilicity/moisturizing properties, viscoelasticity, lubrication and good biocompatibility. The natural moisturizing factor HA, which exists in tears and on the surface of the corneal epithelium, has the function of keeping the corneal surface moist and stabilizing the tear film. It also has anti-inflammatory properties, promotes wound healing, and protects against oxidative damage.
滴眼液中添加HA，可以增加眼部舒适度。HA具有良好的生物相容性及独特的大分子网状结构和非牛顿流体的特性，有效降低了佩戴接触镜的异物感及缓解佩戴接触镜后引起的干眼症。Adding HA to eye drops can increase eye comfort. HA has good biocompatibility, unique macromolecular network structure and non-Newtonian fluid characteristics, which can effectively reduce the foreign body sensation caused by wearing contact lenses and alleviate dry eye syndrome caused by wearing contact lenses.
现有技术中已有的隐形眼镜护理产品中一般只添加单一分子量的透明质酸钠，如博士伦有限公司的博乐纯隐形眼镜护理液中添加透明质酸钠的分子量为1.4×106Da。而本申请发明人在长期研究中创造性的发现，通过采用中分子量0.3×106Da～0.7×106Da和高分子量0.8×106Da～1.5×106Da的混合物作为透明质酸类化合物，并限定所述中分子量透明质酸钠和高分子量透明质酸钠的重量比为1:(1～25)，所述眼用润滑液组合物中透明质酸类化合物的总含量为0.01～0.25％时，能够有效提高润滑和保湿性能，提高佩戴舒适度。Existing contact lens care products in the prior art generally only add sodium hyaluronate with a single molecular weight. For example, the molecular weight of sodium hyaluronate added to Bausch & Lomb Co., Ltd.'s Bole Pure Contact Lens Care Solution is 1.4×106 Da. . The inventor of the present application creatively discovered during long-term research that by using a mixture of a medium molecular weight of 0.3×106 Da to 0.7×106 Da and a high molecular weight of 0.8×106 Da to 1.5×106 Da as a hyaluronic acid compound , and limit the weight ratio of the medium molecular weight sodium hyaluronate and the high molecular weight sodium hyaluronate to 1: (1 ~ 25), and the total content of hyaluronic acid compounds in the ophthalmic lubricant composition is 0.01 ~ At 0.25%, it can effectively improve lubrication and moisturizing properties and improve wearing comfort.
所述聚乙烯基吡咯烷酮为K15、K30、K60、K90中的一种或几种的混合物；优选聚乙烯基吡咯烷酮K30；聚乙烯基吡咯烷酮为一种非离子型高分子化合物，主要作为一种保湿剂，可以有效缓解眼部轻微刺激，缓解眼部干涩。根据分子量的不同，聚乙烯基吡咯烷酮有K15、K30、K60、K90，其代表的分子量为10000、40000、160000、360000；优选聚乙烯基吡咯烷酮K30。The polyvinylpyrrolidone is one or a mixture of K15, K30, K60 and K90; polyvinylpyrrolidone K30 is preferred; polyvinylpyrrolidone is a non-ionic polymer compound, mainly used as a moisturizing agent agent, can effectively relieve minor eye irritation and relieve eye dryness. According to different molecular weights, polyvinylpyrrolidone includes K15, K30, K60, and K90, with representative molecular weights of 10,000, 40,000, 160,000, and 360,000; polyvinylpyrrolidone K30 is preferred.
所述聚乙二醇为聚乙二醇300、聚乙二醇400、聚乙二醇600、聚乙二醇1000、聚乙二醇1500中的一种或多种的混合物。优选聚乙二醇400，聚乙二醇600和聚乙二醇1000，特别优选聚乙二醇400和聚乙二醇600。The polyethylene glycol is one or a mixture of polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 1000, and polyethylene glycol 1500. Polyethylene glycol 400, polyethylene glycol 600 and polyethylene glycol 1000 are preferred, with polyethylene glycol 400 and polyethylene glycol 600 being particularly preferred.
依地酸二钠作为螯合剂或者络合剂，可与重金属离子结合，避免重金属离子可能和或蛋白沉积物反应且沉积在镜片上；优选含量为0.005～0.5％，特别优选0.05～0.2％。As a chelating agent or complexing agent, disodium edetate can combine with heavy metal ions to prevent heavy metal ions from reacting with or protein deposits and depositing on the lens; the preferred content is 0.005 to 0.5%, particularly preferably 0.05 to 0.2%.
所述双胍类防腐剂为聚六亚甲基双胍盐酸盐和聚氨丙基双胍中的一种或多种的混合物。The biguanide preservative is one or a mixture of one or more of polyhexamethylene biguanide hydrochloride and polyaminopropyl biguanide.
眼用润滑液包括多次量和单次量。单次量无需关注防腐剂只需在初包装结构与形式上考量即可，多剂量则要关注防腐剂用量及防腐指标符合性问题。常规的眼用润滑液产品属于多次量使用产品，因此其防腐性指标应符合YY/T0719.4-2009《眼科光学接触镜护理产品第4部分：抗微生物防腐有效性试验及测定抛弃日期指南》要求。眼用润滑液中防腐剂应选用对眼部舒适、刺激较小和安全性高的物质。从产品安全方面考虑，一般主要权衡具体防腐种类和用量，而防腐效果和生物相容性相互矛盾，高浓度的防腐剂虽呈现出很好的防腐有效性，但是细胞毒性等生物相容性试验结果则不佳。目前对眼部刺激性较小和较常用的防腐剂优选双胍类，因而双胍类用量多少对产品的安全性影响较大。目前市面上获证的仅是低黏度的润滑液产品，其双胍的添加量已达到0.0001％～0.00018％，如海昌隐形眼镜有限公司生产的锁水保湿型隐形眼镜润滑液(黏度小于3.5)中含有0.00015％聚六亚基双胍盐酸盐，而获证的高黏度(黏度大于6)的润滑液产品使用的防腐剂为非双胍类，雅培冰蓝型润滑液使用的纯氯氧复合物，博士伦硬性润滑液则使用的聚季铵盐类和氯己胺葡萄酸盐。本发明所述眼用组合物中的防腐剂选用双胍类，可选用聚六亚甲基双胍盐酸盐(PHMB)和聚氨丙基双胍(PAPB)中的一种或多种，本发明中双胍的含量控制在0.00004～0.00015％，优选0.00006～0.00012％，其抗微生物活性及生物相容性均符合标准要求。Ophthalmic lubricants include multiple doses and single doses. There is no need to pay attention to the preservatives for a single dose. You only need to consider the structure and form of the initial packaging. For multiple doses, you need to pay attention to the amount of preservatives and compliance with preservative indicators. Conventional ophthalmic lubricant products are products that are used in multiple quantities, so their anti-corrosion indicators should comply with YY/T0719.4-2009 "Ophthalmic Optical Contact Lens Care Products Part 4: Antimicrobial Anti-corrosion Effectiveness Test and Determination of Disposal Date Guidelines" "Require. Preservatives in eye lubricants should be selected that are comfortable to the eyes, less irritating, and highly safe. From the perspective of product safety, the specific preservative type and dosage are generally weighed, and the preservative effect and biocompatibility are contradictory. Although high-concentration preservatives show good preservative effectiveness, biocompatibility tests such as cytotoxicity The results were not good. Currently, biguanides are the preferred preservatives that are less irritating to the eyes and are more commonly used. Therefore, the dosage of biguanides has a greater impact on the safety of the product. Currently, only low-viscosity lubricant products on the market have been certified, and the added amount of biguanide has reached 0.0001% to 0.00018%. For example, the water-locking and moisturizing contact lens lubricant produced by Haichang Contact Lens Co., Ltd. (viscosity less than 3.5) Contains 0.00015% polyhexamethylene biguanide hydrochloride, and the preservatives used in certified high-viscosity (viscosity greater than 6) lubricant products are non-biguanide, and the Abbott Ice Blue lubricant uses pure chlorine-oxygen complex , Bausch & Lomb hard lubricants use polyquaternium salts and chlorhexylamine glucate. The preservative in the ophthalmic composition of the present invention is biguanide, and one or more of polyhexamethylene biguanide hydrochloride (PHMB) and polyaminopropyl biguanide (PAPB) can be used. The content of biguanide is controlled at 0.00004-0.00015%, preferably 0.00006-0.00012%, and its antimicrobial activity and biocompatibility meet standard requirements.
所述泊洛沙姆为泊洛沙姆407、泊洛沙姆188、泊洛沙姆235的一种或多种的混合物。The poloxamer is one or a mixture of one or more of poloxamer 407, poloxamer 188, and poloxamer 235.
表面活性剂是指具有固定的亲水亲油基团，在溶液的表面能定向排列，并能使表面张力显著下降的物质。表面活性剂用于隐形眼镜护理产品中，一方面可用于清洁镜片表面污物，另一方面对镜片起润滑作用。表面活性剂包括阴离子表面活性剂、阳离子表面活性剂和非离子表面活性剂；非离子表面活性剂刺激性远低于阴离子、阳离子表面活性剂。在润滑液中添加表面活性剂，可有效降低隐形眼镜镜片与角膜直接的摩擦，进而提高戴镜的润滑感。本发明中所述的眼用组合物中的润滑剂选用非离子表面活性剂。比如，聚氧乙烯-聚氧丙烯嵌段共聚物，又称泊洛沙姆系列，如泊洛沙姆407、泊洛沙姆188和泊洛沙姆235；泊洛沙胺系列，如泊洛沙胺701和泊洛沙胺704；聚山梨酯系列，如吐温80；四丁酚醛(Tyloxapol)；聚氧乙烯氢化蓖麻油，如巴斯夫RH40。非离子表面活性剂可选自以上的一种或多种，更加优选泊洛沙姆系列，含量0.01～0.5％，更优选0.01～0.1％。Surfactant refers to a substance with fixed hydrophilic and lipophilic groups, which can be oriented and arranged on the surface of the solution and can significantly reduce the surface tension. Surfactants are used in contact lens care products. On the one hand, they can be used to clean dirt on the surface of the lens, and on the other hand, they can lubricate the lens. Surfactants include anionic surfactants, cationic surfactants and nonionic surfactants; nonionic surfactants are much less irritating than anionic and cationic surfactants. Adding surfactant to the lubricant can effectively reduce the direct friction between the contact lens lens and the cornea, thereby improving the lubrication of wearing the lenses. The lubricant in the ophthalmic composition described in the present invention is a nonionic surfactant. For example, polyoxyethylene-polyoxypropylene block copolymer, also known as poloxamer series, such as poloxamer 407, poloxamer 188 and poloxamer 235; poloxamine series, such as poloxamer Amine 701 and Poloxamine 704; polysorbate series, such as Tween 80; Tyloxapol; polyoxyethylene hydrogenated castor oil, such as BASF RH40. The nonionic surfactant can be selected from one or more of the above, more preferably the poloxamer series, with a content of 0.01 to 0.5%, more preferably 0.01 to 0.1%.
所述缓冲剂为盐酸、硼酸中的一种或两种的混合物。The buffering agent is one or a mixture of hydrochloric acid and boric acid.
所述组合物的pH值维持在6.5～7.5，其中优选7.0～7.4。缓冲剂包括磷酸缓冲剂、硼酸缓冲剂、碳酸缓冲剂、柠檬酸缓冲剂、N-(2-羟乙基)哌嗪-N'-2-乙烷磺酸(HEPES)缓冲剂、氨丁三醇缓冲剂、双(2-羟乙基)氨基(三羟甲基)甲烷(Bis-Tris)缓冲剂等。更具体的包括：磷酸氢二钠、磷酸二氢钠、磷酸二氢钾、硼酸、硼砂、碳酸、柠檬酸钠、HEPES、碳酸氢钠、氨丁三醇、盐酸、双(2-羟乙基)氨基(三羟甲基)甲烷(Bis-Tris)、氢氧化钠，以及它们的水合物，选自以上任意一种或多种化合物的组合。The pH value of the composition is maintained at 6.5 to 7.5, with 7.0 to 7.4 being preferred. Buffers include phosphate buffer, boric acid buffer, carbonic acid buffer, citric acid buffer, N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid (HEPES) buffer, tromethamine Alcohol buffer, bis(2-hydroxyethyl)amino(trihydroxymethyl)methane (Bis-Tris) buffer, etc. More specific include: disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, boric acid, borax, carbonic acid, sodium citrate, HEPES, sodium bicarbonate, tromethamine, hydrochloric acid, bis(2-hydroxyethyl) ) Amino(trimethylol)methane (Bis-Tris), sodium hydroxide, and their hydrates, selected from any one or a combination of more of the above compounds.
现有技术中润滑液产品中添加的缓冲剂大部分为磷酸盐体系或硼酸硼砂体系，本发明优选氨丁三醇和盐酸缓冲体系、氨丁三醇和硼酸缓冲体系。氨丁三醇，具体名称为2-氨基-2-羟甲基-1,3丙二醇，其名称也称为三(羟甲基)氨基甲烷和TRIS。氨丁三醇作为缓冲体系，不会发生像磷酸缓冲体系与钙、镁离子发生反应，也不会像硼酸硼砂缓冲体系因多种有机物的加入而复杂化。另一方面，氨丁三醇不仅有缓冲作用，还可以辅助杀菌，其消杀效果明显优于磷酸盐体系和硼酸硼砂体系，且毒性低。此外氨丁三醇能够有效降低接触镜上变性蛋白量，稳定蛋白防止变性。本发明中氨丁三醇的含量为0.05～0.6％，优选0.05～0.2％，再用盐酸或硼酸调整pH至7.0～7.4。Most of the buffers added to lubricant products in the prior art are phosphate systems or borate borax systems. In the present invention, tromethamine and hydrochloric acid buffer systems, and tromethamine and boric acid buffer systems are preferred. Tromethamine, whose specific name is 2-amino-2-hydroxymethyl-1,3 propanediol, is also known as tris(hydroxymethyl)aminomethane and TRIS. As a buffer system, tromethamine will not react with calcium and magnesium ions like a phosphate buffer system, nor will it be complicated by the addition of various organic substances like a borate borax buffer system. On the other hand, trometamol not only has a buffering effect, but can also assist in sterilization. Its sterilization effect is significantly better than that of the phosphate system and the borate borax system, and its toxicity is low. In addition, tromethamine can effectively reduce the amount of denatured proteins on contact lenses and stabilize proteins to prevent denaturation. In the present invention, the content of tromethamine is 0.05-0.6%, preferably 0.05-0.2%, and the pH is adjusted to 7.0-7.4 with hydrochloric acid or boric acid.
所述等渗剂(也称为渗透压调节剂)为氯化钠、氯化钾、氯化钙、氯化镁、葡萄糖、丙二醇、甘油中的一种或多种的混合物。The isotonicity agent (also called an osmotic pressure regulator) is one or a mixture of one or more of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glucose, propylene glycol, and glycerol.
本发明所述眼用润滑液组合物中的渗透压调节剂主要用于调节渗透压，调节组合物中渗透压接近于自然泪液。由于低渗和高渗均会引起眼部刺激和不舒适。其中渗透压调节剂可选自氯化钠、氯化钾、氯化钙、氯化镁、葡萄糖、丙二醇、甘油中的一种或多种，优选氯化钠、氯化钾，含量为0.5～1.5％，调节组合物中渗透压值为260～340mOsm/kg，优选300±10mOsm/kg。The osmotic pressure regulator in the ophthalmic lubricant composition of the present invention is mainly used to adjust the osmotic pressure, so that the osmotic pressure in the adjusted composition is close to that of natural tears. Both hypotonicity and hypertonicity can cause eye irritation and discomfort. The osmotic pressure regulator may be selected from one or more of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glucose, propylene glycol, and glycerin, preferably sodium chloride and potassium chloride, and the content is 0.5 to 1.5%. , adjust the osmotic pressure value in the composition to 260~340mOsm/kg, preferably 300±10mOsm/kg.
所述眼用润滑液组合物的pH为7.0～7.4，所述眼用润滑液组合物的渗透压为260～340mOsm/kg，优选为300±10mOsm/kg。The pH of the ophthalmic lubricating liquid composition is 7.0-7.4, and the osmotic pressure of the ophthalmic lubricating liquid composition is 260-340 mOsm/kg, preferably 300±10 mOsm/kg.
所述的眼用润滑液组合物在制备隐形眼镜润滑液中的应用，所述隐形眼镜为软性隐形眼镜、硬性隐形眼镜、彩色接触镜和硅水凝胶接触镜中的任意一种。所述的眼用润滑液组合物在佩戴隐形眼镜过程中使用，起润滑和保湿作用，提高佩戴舒适度，还可用于缓解戴镜时的眼干涩、眼疲劳或眼刺激等不适。Application of the described ophthalmic lubricating fluid composition in preparing lubricating fluid for contact lenses, the contact lenses being any one of soft contact lenses, hard contact lenses, colored contact lenses and silicone hydrogel contact lenses. The ophthalmic lubricant composition is used during the process of wearing contact lenses to lubricate and moisturize, improve wearing comfort, and can also be used to relieve discomfort such as dry eyes, eye fatigue, or eye irritation when wearing glasses.
本发明具体如下有益效果：The present invention has the following specific beneficial effects:
(1)本发明所述的眼用润滑液组合物，选择不同分子量的透明质酸钠进行复配，通过添加一定分子量范围的高分子量HA，其中高分子量的HA因其固有的特征黏性，“相对固定”在水合层中，可以延长水合层在泪液滞留时间及延长泪液的破裂时间(BUT)；高分子量的HA提高水分在镜片表面和/或角结膜的存留时间，持久保湿；高分子量HA中大量带负电的羧基与黏液成分中的羟基在镜片和/或角膜表面形成氢键，在镜片和/或角膜表面形成一层氢键缔合膜，使HA更易于与镜片和/或角膜亲和，赋予镜片和角膜优越的保湿性；再者，因HA的非牛顿流体的特性，呈假塑性特征，具有与生物泪液相同的黏滞性和伸缩性，接触眼表后眼睑仍可眨动自如；(1) The ophthalmic lubricant composition of the present invention is compounded by selecting sodium hyaluronate with different molecular weights and adding high molecular weight HA in a certain molecular weight range. High molecular weight HA has its inherent characteristic viscosity. "Relatively fixed" in the hydration layer can prolong the retention time of the hydration layer in tears and prolong the tear break-up time (BUT); high molecular weight HA improves the retention time of water on the lens surface and/or cornea and conjunctiva, providing long-lasting moisturizing; high molecular weight A large number of negatively charged carboxyl groups in HA form hydrogen bonds with the hydroxyl groups in the mucus components on the surface of the lens and/or cornea, forming a hydrogen bond association film on the surface of the lens and/or cornea, making it easier for HA to interact with the lens and/or cornea. Affinity, giving the lens and cornea superior moisturizing properties; in addition, due to the non-Newtonian fluid characteristics of HA, it has pseudoplastic characteristics and has the same viscosity and stretchability as biological tears. The eyelids can still blink after contacting the ocular surface. move freely;
另一方面，通过添加一定分子量范围的中分子量HA，中分子量HA在水合层中形成相对的“滑动层”。中分子量的HA的特征黏数低于高分子量的HA，故其在水合层中既可起到保湿作用也可有效降低镜片与角膜、眼睑的摩擦，从而提高镜片佩戴的舒适度；On the other hand, by adding medium molecular weight HA in a certain molecular weight range, the medium molecular weight HA forms a relative "sliding layer" in the hydration layer. The characteristic viscosity of medium molecular weight HA is lower than that of high molecular weight HA, so it can not only moisturize in the hydration layer, but also effectively reduce the friction between the lens and the cornea and eyelids, thereby improving the comfort of wearing the lens;
将高分子量HA和中分子量HA复配添加在组合物溶液中，两种不同分子量的水溶性高分子物质形成了互为贯穿的IPN结构。高分子量HA的“相对固定”和中分子量HA的“滑动层”在保湿的同时又显著增加组合物的流动性，有效改变了传统高含量HA溶液的黏连问题。High molecular weight HA and medium molecular weight HA are added to the composition solution, and the two water-soluble polymer substances with different molecular weights form an IPN structure that penetrates each other. The "relative fixation" of high molecular weight HA and the "sliding layer" of medium molecular weight HA significantly increase the fluidity of the composition while retaining moisture, effectively changing the adhesion problem of traditional high-content HA solutions.
(2)本发明所述的眼用润滑液组合物，通过选择不同分子量的透明质酸钠进行复配，并辅以适合重量配比的聚乙烯基吡咯烷酮和聚乙二醇，上述组分的协同作用下，起到保湿和增粘作用，表现出优异的润滑保湿性，并且可抑制眼干和提高戴镜舒适度；本申请发明人经过对比发现：通过在润滑液中使用不同分子量透明质酸钠、聚乙烯基吡咯烷酮和聚乙二醇，制得润滑液的润滑性、保湿性和舒适度均优于单一的透明质酸钠、单一的聚乙烯基吡咯烷酮、单一的聚乙二醇、单一透明质酸钠复配聚乙烯基吡咯烷酮体系、单一透明质酸钠复配聚乙二醇体系、聚乙烯基吡咯烷酮复配聚乙二醇体系。此外，本发明通过配合使用不同分子量透明质酸钠、聚乙烯基吡咯烷酮和聚乙二醇制得的润滑液，能有效抑制眼干，提高戴镜舒适度；(2) The ophthalmic lubricant composition of the present invention is compounded by selecting sodium hyaluronate with different molecular weights, and supplemented by polyvinylpyrrolidone and polyethylene glycol in a suitable weight ratio. Under the synergistic effect, it plays the role of moisturizing and thickening, showing excellent lubricating and moisturizing properties, and can inhibit eye dryness and improve the comfort of wearing glasses; the inventor of the present application found through comparison: by using hyaluronic acid with different molecular weights in the lubricant Using sodium hyaluronate, polyvinylpyrrolidone and polyethylene glycol, the lubricity, moisturizing and comfort of the lubricant produced are better than those of sodium hyaluronate, polyvinylpyrrolidone, polyethylene glycol alone. Single sodium hyaluronate compounded with polyvinylpyrrolidone system, single sodium hyaluronate compounded with polyethylene glycol system, polyvinylpyrrolidone compounded with polyethylene glycol system. In addition, the present invention can effectively inhibit dry eyes and improve the comfort of wearing glasses by combining the use of lubricating liquids prepared from sodium hyaluronate, polyvinylpyrrolidone and polyethylene glycol with different molecular weights;
本发明所述眼用润滑液组合物，通过采用聚乙烯基吡咯烷酮和不同分子量HA物质复配使用，显著增加了组合物溶液的黏度，一方面使得溶液中保湿剂(HA、聚乙烯基吡咯烷酮、聚乙二醇)与隐形眼镜和角膜接触时间延长，其次使得水分在镜片合角膜的保留时间也延长，此外，也加固了镜片与角膜之间的润滑保护层，使得保湿剂对镜片和角膜的保湿润滑效果极大化，并且提高了戴镜舒适度。The ophthalmic lubricant composition of the present invention uses polyvinylpyrrolidone and HA substances of different molecular weights in combination, which significantly increases the viscosity of the composition solution. On the one hand, the moisturizing agents (HA, polyvinylpyrrolidone, The contact time between polyethylene glycol (polyethylene glycol) and the contact lens and cornea is prolonged, which in turn prolongs the retention time of water in the lens and cornea. In addition, it also strengthens the lubricating protective layer between the lens and the cornea, making the moisturizer more effective on the lens and cornea. The moisturizing and lubricating effect is maximized and the comfort of wearing glasses is improved.
(3)本发明所述眼用润滑液组合物，采用双胍复配氨丁三醇和依地酸二钠的防腐体系，在不增加双胍含量的情况下，使润滑液仍具有高效的抗微生物防腐性；(3) The ophthalmic lubricant composition of the present invention adopts a preservative system of biguanide compounded with tromethamine and disodium edetate, so that the lubricant still has efficient antimicrobial antisepsis without increasing the biguanide content. sex;
单一防腐剂在含有高分子量HA及高含量水溶性物质的高黏度溶液中，所体现的抗微生物防腐效果较差，这是由于本申请发明人在长期研究中发现，高分子和/或高含量水溶性物质显著降低了防腐剂与微生物有效接触所致。通常，高分子量HA及高含量水溶性物质的高黏度润滑液要达到符合抗微生物防腐的标准要求，就需在配方中加大防腐剂的用量。但加大防腐剂用量的同时，会增大溶液的生物相容性不符合要求的风险及给使用者带来刺激感。本发明通过利用双胍类防腐剂与氨丁三醇、依地酸二钠进行复配，在三者的协同作用下，显著提高防腐剂与微生物的有效碰撞，可使在不加大双胍类防腐剂用量的情况下，这种含有高分子量HA及高含量水溶性物质的高黏度润滑液抗微生物防腐效果符合标准要求；A single preservative has a poor antimicrobial preservative effect in a high-viscosity solution containing high molecular weight HA and high content of water-soluble substances. This is because the inventor of the present application found in long-term research that high molecular weight and/or high content of water-soluble substances is not effective. Water-soluble substances significantly reduce the effective contact between preservatives and microorganisms. Usually, in order for high-viscosity lubricants with high molecular weight HA and high content of water-soluble substances to meet the antimicrobial anti-corrosion standards, it is necessary to increase the amount of preservatives in the formula. However, increasing the amount of preservatives will increase the risk of the solution's biocompatibility not meeting requirements and causing irritation to the user. The present invention uses biguanide preservatives to be compounded with trometamol and edetate disodium. Under the synergistic effect of the three, the effective collision between the preservatives and microorganisms is significantly improved, and the biguanide preservatives can be used without increasing the intensity of the biguanide preservatives. Under the condition of the dosage of the agent, the anti-microbial and anti-corrosion effect of this high-viscosity lubricant containing high molecular weight HA and high content of water-soluble substances meets the standard requirements;
另一方面本申请发明人还发现：依地酸二钠不仅可以作为螯合剂络合金属离子，避免金属离子与镜片上沉积和积聚的蛋白质反应，同时依地酸二钠与氨丁三醇复配使用后，可以明显起到协同增效杀菌作用。On the other hand, the inventor of the present application also found that disodium edetate can not only be used as a chelating agent to complex metal ions and prevent metal ions from reacting with proteins deposited and accumulated on the lens, but also disodium edetate can complex with tromethamine. When used together, it can obviously play a synergistic sterilization effect.
具体实施方式Detailed ways
为使本发明的目的、技术方案和优点更加清楚，下面将对本发明的技术方案进行详细的描述。显然，所描述的实施病例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动的前提下所得到的所有其它实施方式，都属于本发明所保护的范围。In order to make the purpose, technical solutions and advantages of the present invention clearer, the technical solutions of the present invention will be described in detail below. Obviously, the described implementation examples are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other implementations obtained by those of ordinary skill in the art without any creative work fall within the scope of protection of the present invention.
一、润滑性、保湿性和舒适度评价1. Evaluation of lubricity, moisturizing and comfort
实施例1和对比例1-10的配方组成如表1、表2所示。各组分的比例均为质量百分比。The formula compositions of Example 1 and Comparative Examples 1-10 are shown in Table 1 and Table 2. The proportions of each component are mass percentages.
表1-实施例1和对比例1-4的配方组成Table 1 - Formula composition of Example 1 and Comparative Examples 1-4
表2-对比例5-10的配方组成Table 2 - Formula composition of Comparative Examples 5-10
本发明所述润滑液组合物采用如下方法制备得到：The lubricating liquid composition of the present invention is prepared by the following method:
(1)按照表1-2的配方量分别称取各组分；(1) Weigh each component separately according to the formula amounts in Table 1-2;
(2)在容器内加入部分纯化水，然后分别加入泊洛沙姆407和聚乙二醇，再补入纯化水并搅拌30min；(2) Add some purified water to the container, then add poloxamer 407 and polyethylene glycol respectively, then add purified water and stir for 30 minutes;
(3)加入聚乙烯基吡咯烷酮、依地酸二钠、氨丁三醇、氯化钠和氯化钾，补入纯化水并搅拌50min；(3) Add polyvinylpyrrolidone, disodium edetate, tromethamine, sodium chloride and potassium chloride, add purified water and stir for 50 minutes;
(4)加入透明质酸钠，补入纯化水并搅拌90min；(4) Add sodium hyaluronate, add purified water and stir for 90 minutes;
(5)用盐酸调整料液pH，再加入聚六亚甲基双胍盐酸盐，补入纯化水并定容至100ml，搅拌15min，即得所述润滑液组合物。(5) Adjust the pH of the feed liquid with hydrochloric acid, then add polyhexamethylene biguanide hydrochloride, add purified water and adjust the volume to 100 ml, and stir for 15 minutes to obtain the lubricating liquid composition.
按照表1-2的配方制备得到的润滑液组合物，经过滤除菌后灌装在经灭菌处理后的聚乙烯瓶中，加上内塞和旋紧外盖。The lubricant composition prepared according to the formula in Table 1-2 is filtered and sterilized, then filled into a sterilized polyethylene bottle, with an inner stopper and a tightened outer cap.
选取40例隐形眼镜佩戴者的志愿者，试验用隐形眼镜为：FDAⅠ、Ⅳ、硅水凝胶镜片、彩色镜片、Menicon硬镜，试用表1-2中的润滑液，使用方法为：在佩戴隐形眼镜前，将配制的润滑液滴入每只镜片上1～2滴；然后在佩戴过程中，滴加同一配方的润滑液用于眼部。分别记录试用后的感受，并对试用后的润滑性、保湿性和舒适度进行评价，具体结果见表3。Select 40 volunteers who wear contact lenses. The contact lenses used for the test are: FDAⅠ,Ⅳ, silicone hydrogel lenses, colored lenses, and Menicon hard lenses. Try the lubricants in Table 1-2. The usage method is: while wearing Before wearing contact lenses, add 1 to 2 drops of the prepared lubricant to each lens; then, during the wearing process, add the same formula of lubricant to the eyes. The feelings after the trial were recorded respectively, and the lubricity, moisturizing and comfort after the trial were evaluated. The specific results are shown in Table 3.
表3-各示例佩戴隐形眼镜的润滑性能、保湿性能和舒适度评价Table 3 - Evaluation of lubrication performance, moisturizing performance and comfort of wearing contact lenses in each example
从表3可以看出，与对比例比较，实施例1感觉润滑、保湿和舒适的人数均多于对比例1-10，从而说明不同分子量透明质酸钠的复配物质与聚乙烯基吡咯烷酮、聚乙二醇混合使用配制的润滑液的润滑性,、保湿性和舒适度显著优于单一的透明质酸钠、单一的聚乙烯基吡咯烷酮、单一的聚乙二醇、单一透明质酸钠复配聚乙烯基吡咯烷酮体系、单一透明质酸钠复配聚乙二醇体系、聚乙烯基吡咯烷酮复配聚乙二醇体系配制的润滑液。It can be seen from Table 3 that compared with the comparative examples, more people in Example 1 felt lubricated, moisturized and comfortable than in Comparative Examples 1-10, which illustrates that the compound substances of sodium hyaluronate with different molecular weights and polyvinylpyrrolidone, The lubricant prepared by mixing polyethylene glycol has significantly better lubricity, moisturizing and comfort than single sodium hyaluronate, single polyvinylpyrrolidone, single polyethylene glycol, single sodium hyaluronate complex. Lubricant formulated with polyvinylpyrrolidone system, single sodium hyaluronate compounded with polyethylene glycol system, and polyvinylpyrrolidone compounded with polyethylene glycol system.
二、防腐有效性2. Anti-corrosion effectiveness
实施例1-3和对比例11-13的配方组成如表4所示。各组分的比例均为质量百分比。The formulation compositions of Examples 1-3 and Comparative Examples 11-13 are shown in Table 4. The proportions of each component are mass percentages.
表4-实施例1-3和对比例11-13的配方组成Table 4 - Formula compositions of Examples 1-3 and Comparative Examples 11-13
依据YY/T 0719.4-2009《眼科光学接触镜护理产品第4部分：抗微生物防腐有效性试验及测定抛弃日期指南》中的检测方法对表4中各实施例和对比例对金黄色葡萄球菌、绿脓杆菌、大肠杆菌和白色念珠菌的抗微生物防腐效果，具体结果如表5。According to the detection method in YY/T 0719.4-2009 "Ophthalmic Optical Contact Lens Care Products Part 4: Antimicrobial Preservative Effectiveness Test and Determination of Disposal Date Guidelines", the examples and comparative examples in Table 4 were tested for Staphylococcus aureus, The antimicrobial antiseptic effect of Pseudomonas aeruginosa, Escherichia coli and Candida albicans. The specific results are shown in Table 5.
表5-各示例所述的润滑液的防腐效果Table 5 - Anti-corrosion effect of the lubricating fluids described in each example
从表5可以看出，针对含有高分子量HA及高含量水溶性物质的高黏度润滑液，双胍复配氨丁三醇和依地酸二钠组成的防腐体系的抗微生物效果最佳，优于常用的硼酸硼砂和磷酸缓冲体系，并且将依地酸二钠与氨丁三醇复配使用后，可明显起到协同增效杀菌作用。It can be seen from Table 5 that for high-viscosity lubricants containing high molecular weight HA and high content of water-soluble substances, the antimicrobial effect of the antimicrobial system composed of biguanide compound trometamol and disodium edetate is better than that commonly used The borax borate and phosphate buffer system, and the combined use of edetate disodium and trometamol, can obviously play a synergistic bactericidal effect.
以上所述，仅为本发明的具体实施方式，但本发明的保护范围并不局限于此，任何熟悉本技术领域的技术人员在本发明揭露的技术范围内，可轻易想到变化或替换，都应涵盖在本发明的保护范围之内。因此，本发明的保护范围应以所述权利要求的保护范围为准。The above are only specific embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Any person familiar with the technical field can easily think of changes or substitutions within the technical scope disclosed in the present invention. should be covered by the protection scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claims.
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