技术领域Technical field
本发明涉及组织填充材料技术领域，尤其是涉及一种注射填充剂及其复溶方法。The present invention relates to the technical field of tissue filling materials, and in particular to an injection filler and its reconstitution method.
背景技术Background technique
随着抗老意识增强，人们开始致力于找到一种合适的软组织填充剂用于矫正局部凹陷的软组织缺损。相较时效较短的传统填充产品，再生材料由于填充效果自然、渐进且长效而受到广泛关注。With the increasing awareness of anti-aging, people have begun to focus on finding a suitable soft tissue filler to correct local depressed soft tissue defects. Compared with traditional filling products that have a shorter life span, recycled materials have attracted widespread attention due to their natural, gradual and long-lasting filling effects.
目前，传统的临床用再生填充剂多为以脂肪族聚酯微球为主要成分的干粉剂型，通常需在注射前数小时前用无菌水复溶。传统的临床用再生填充剂不仅复溶时间长，复溶后分散性差、微球容易聚集沉积进而导致注射过程中堵塞针头、注射痛感增加甚至注射后引起皮下结节，且由于无菌水能快速被吸收，注射后无法即刻显现填充效果。At present, most of the traditional clinical regenerative fillers are dry powder dosage forms with aliphatic polyester microspheres as the main component, which usually need to be reconstituted with sterile water several hours before injection. Traditional clinical regenerative fillers not only take a long time to dissolve, but also have poor dispersion after reconstitution, and the microspheres are easy to aggregate and deposit, which can lead to clogging of the needle during the injection process, increased injection pain, and even subcutaneous nodules after injection. In addition, because sterile water can quickly It is absorbed and the filling effect cannot be seen immediately after injection.
凝胶剂型是另一种常见的填充剂型，将干粉剂替换成凝胶剂型可以部分解决上述问题，但微球在凝胶中不能长时间稳定存在，这就导致凝胶剂型产品的保质期较短。Gel dosage form is another common filling dosage form. Replacing dry powder with gel dosage form can partially solve the above problems, but the microspheres cannot exist stably in the gel for a long time, which results in a shorter shelf life of gel dosage products. .
发明内容Contents of the invention
基于此，有必要提供一种可以解决上述问题的注射填充剂。Based on this, it is necessary to provide an injectable filler that can solve the above problems.
此外，还有必要提供一种上述注射填充剂的复溶方法。In addition, it is necessary to provide a reconstitution method for the above-mentioned injectable filler.
一种注射填充剂，包括注射填充微球和水溶性凝胶干粉，所述注射填充微球的粒径为10μm～100μm，所述水溶性凝胶干粉的粒径为1nm～10μm。An injection filler includes injection-filled microspheres and water-soluble gel dry powder. The particle size of the injection-filled microspheres is 10 μm to 100 μm, and the particle size of the water-soluble gel dry powder is 1 nm to 10 μm.
在一个实施例中，所述注射填充微球和所述水溶性凝胶干粉的质量比为30～50：7～15。In one embodiment, the mass ratio of the injection-filled microspheres and the water-soluble gel dry powder is 30-50:7-15.
在一个实施例中，所述注射填充微球为无机微球、有机高分子微球或无机/有机复合微球。In one embodiment, the injection-filled microspheres are inorganic microspheres, organic polymer microspheres or inorganic/organic composite microspheres.
在一个实施例中，所述无机微球为羟基磷灰石微球；所述有机高分子微球为脂肪族聚酯微球或凝胶微球。In one embodiment, the inorganic microspheres are hydroxyapatite microspheres; the organic polymer microspheres are aliphatic polyester microspheres or gel microspheres.
在一个实施例中，所述脂肪族聚酯微球的材料选自PCL、PLA、PLLA、PLGA、PHA、PLGA-PEG、PLA-PEG、PLLA-PEG、PCL-PEG、PLGA-PEG-PLGA、PLA-PEG-PLGA、PLLA-PEG-PLGA、PCL-PEG-PLGA、PLGA-PEG-PLA、PLA-PEG-PLA、PLLA-PEG-PLA、PCL-PEG-PLA、PLGA-PEG-PLLA、PLA-PEG-PLLA、PLLA-PEG-PLLA、PCL-PEG-PLLA、PLGA-PEG-PCL、PLA-PEG-PCL、PLLA-PEG-PCL和PCL-PEG-PCL中的至少一种；In one embodiment, the material of the aliphatic polyester microspheres is selected from PCL, PLA, PLLA, PLGA, PHA, PLGA-PEG, PLA-PEG, PLLA-PEG, PCL-PEG, PLGA-PEG-PLGA, PLA-PEG-PLGA, PLLA-PEG-PLGA, PCL-PEG-PLGA, PLGA-PEG-PLA, PLA-PEG-PLA, PLLA-PEG-PLA, PCL-PEG-PLA, PLGA-PEG-PLLA, PLA- At least one of PEG-PLLA, PLLA-PEG-PLLA, PCL-PEG-PLLA, PLGA-PEG-PCL, PLA-PEG-PCL, PLLA-PEG-PCL and PCL-PEG-PCL;
所述凝胶微球为明胶微球、壳聚糖微球、海藻酸钠微球、丝素蛋白微球、透明质酸微球和胶原蛋白微球中的至少一种。The gel microspheres are at least one of gelatin microspheres, chitosan microspheres, sodium alginate microspheres, silk fibroin microspheres, hyaluronic acid microspheres and collagen microspheres.
在一个实施例中，所述水溶性凝胶干粉的材料选自明胶、壳聚糖、海藻酸钠、丝素蛋白、透明质酸、胶原蛋白及其衍生物中的至少一种。In one embodiment, the water-soluble gel dry powder is made of at least one material selected from the group consisting of gelatin, chitosan, sodium alginate, silk fibroin, hyaluronic acid, collagen and derivatives thereof.
一种注射填充剂的复溶方法，包括如下步骤：A method for reconstitution of injectable filler, including the following steps:
提供上述的注射填充剂，所述注射填充剂包括注射填充微球和水溶性凝胶干粉，所述注射填充微球的粒径为10μm～100μm，所述水溶性凝胶干粉的粒径为1nm～10μm；The above-mentioned injectable filler is provided, the injectable filler includes injectable filled microspheres and water-soluble gel dry powder, the particle size of the injectable filled microspheres is 10 μm to 100 μm, and the particle size of the water-soluble gel dry powder is 1 nm. ~10μm;
将所述注射填充剂和水性溶剂混合均匀，使得所述注射填充微球分散均匀，并且使所述水溶性凝胶干粉溶解，从而使得整个体系形成胶体凝胶。The injectable filler and the aqueous solvent are mixed evenly so that the injectable filled microspheres are evenly dispersed and the water-soluble gel dry powder is dissolved, so that the entire system forms a colloidal gel.
在一个实施例中，将所述注射填充剂和水性溶剂混合均匀的操作为：用注射器推注所述注射填充剂和所述水性溶剂若干次，直至所述注射填充剂和所述水性溶剂混合均匀。In one embodiment, the operation of uniformly mixing the injectable filler and the aqueous solvent is: using a syringe to inject the injectable filler and the aqueous solvent several times until the injectable filler and the aqueous solvent are mixed. Evenly.
在一个实施例中，将所述注射填充剂和水性溶剂混合均匀的操作中，所述水溶性凝胶干粉和所述水性溶剂的比例为7g～15g：100mL。In one embodiment, in the operation of uniformly mixing the injectable filler and the aqueous solvent, the ratio of the water-soluble gel dry powder and the aqueous solvent is 7g-15g:100mL.
在一个实施例中，所述水性溶剂为生理盐水或磷酸盐缓冲液。In one embodiment, the aqueous solvent is physiological saline or phosphate buffer.
本发明的注射填充剂包括注射填充微球和水溶性凝胶干粉，即本发明的注射填充剂属于干粉剂，相对于凝胶剂型产品，本发明的注射填充剂的保质期较长，不会出现因为注射填充微球发生降解，导致的形变和坍塌。The injectable filler of the present invention includes injection filled microspheres and water-soluble gel dry powder, that is, the injectable filler of the present invention belongs to dry powder. Compared with gel dosage products, the injectable filler of the present invention has a longer shelf life and will not cause Because the injection-filled microspheres degrade, resulting in deformation and collapse.
本发明的注射填充剂在复溶时，只需要与适量水性溶剂混合均匀，即可得到粘稠度均一的胶体凝胶。水溶性凝胶干粉可以快速溶解，从而可以提供即刻填充效果，水溶性凝胶干粉与水性溶剂结合形成的胶体凝胶具有剪切变稀特性，在注射后粘度提高，强度增加以在组织中提供填充和支撑作用，使注射填充微球均匀分布，避免迁移。When the injectable filler of the present invention is reconstituted, it only needs to be mixed evenly with an appropriate amount of aqueous solvent to obtain a colloidal gel with uniform viscosity. The water-soluble gel dry powder can dissolve quickly, thus providing an immediate filling effect. The water-soluble gel dry powder combined with the aqueous solvent forms a colloidal gel that has shear-thinning properties. After injection, the viscosity increases and the strength increases to provide in the tissue. Filling and supporting functions enable the injected filled microspheres to be evenly distributed and avoid migration.
与传统的干粉剂型产品相比，本发明的注射填充剂可以在复溶后形成胶体凝胶，从而大大提高了注射填充微球的分散性，避免了由于微球分散性差、微球容易聚集沉积导致的一系列问题。Compared with traditional dry powder dosage products, the injectable filler of the present invention can form a colloidal gel after reconstitution, thereby greatly improving the dispersion of the injection-filled microspheres and avoiding the easy aggregation and deposition of the microspheres due to poor dispersion of the microspheres. resulting in a series of problems.
对比现有技术，本发明的注射填充剂显著提高了复溶效率，节约了时间成本，降低了染菌风险。Compared with the existing technology, the injectable filler of the present invention significantly improves the reconstitution efficiency, saves time and cost, and reduces the risk of bacterial contamination.
优选的，本发明的注射填充剂在复溶时，可以在注射器中通过反复推注，即可实现注射填充微球分散均匀，其使用起来极为方便。Preferably, when the injectable filler of the present invention is reconstituted, it can be injected repeatedly in a syringe to achieve uniform dispersion of the injection-filled microspheres, which is extremely convenient to use.
附图说明Description of the drawings
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。In order to explain the embodiments of the present invention or the technical solutions in the prior art more clearly, the drawings needed to be used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings in the following description are only These are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without exerting creative efforts.
其中：in:
图1为实施例1制备的注射填充剂复溶后的剪切变稀特性图。Figure 1 is a shear thinning characteristic diagram of the injectable filler prepared in Example 1 after reconstitution.
图2为实施例1制备的注射填充剂复溶后的高弹特性图。Figure 2 is a graph showing the high elastic properties of the injectable filler prepared in Example 1 after reconstitution.
具体实施方式Detailed ways
下面将结合本发明具体实施例，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施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作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to specific embodiments of the present invention. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts fall within the scope of protection of the present invention.
需要说明，本发明实施例中所有方向性指示(诸如上、下、左、右、前、后……)仅用于解释在某一特定姿态下各件之间的相对位置关系、运动情况等，如果所述特定姿态发生改变时，则所述方向性指示也相应地随之改变。It should be noted that all directional indications (such as up, down, left, right, front, back...) in the embodiments of the present invention are only used to explain the relative positional relationship, movement, etc. between various parts in a specific posture. , if the specific posture changes, the directional indication also changes accordingly.
另外，在本发明中涉及“第一”、“第二”等的描述仅用于描述目的，而不能理解为指示或暗示其相对重要性或者隐含指明所指示的技术特征的数量。由此，限定有“第一”、“第二”的特征可以明示或者隐含地包括至少一个所述特征。另外，各个实施例之间的技术方案可以相互结合，但是必须是以本领域普通技术人员能够实现为基础，当技术方案的结合出现相互矛盾或无法实现时应当认为这种技术方案的结合不存在，也不在本发明要求的保护范围之内。In addition, descriptions involving "first", "second", etc. in the present invention are for descriptive purposes only and cannot be understood as indicating or implying their relative importance or implicitly indicating the number of indicated technical features. Thus, features defined as "first" and "second" may explicitly or implicitly include at least one of the described features. In addition, the technical solutions in various embodiments can be combined with each other, but it must be based on the realization by those of ordinary skill in the art. When the combination of technical solutions is contradictory or cannot be realized, it should be considered that such a combination of technical solutions does not exist. , nor within the protection scope required by the present invention.
本发明公开了一实施方式的注射填充剂，包括注射填充微球和水溶性凝胶干粉，注射填充微球的粒径为10μm～100μm，水溶性凝胶干粉的粒径为1nm～10μm。The invention discloses an injectable filler in one embodiment, which includes injection-filled microspheres and water-soluble gel dry powder. The particle size of the injection-filled microspheres is 10 μm to 100 μm, and the particle size of the water-soluble gel dry powder is 1 nm to 10 μm.
本发明的注射填充剂包括注射填充微球和水溶性凝胶干粉，即本发明的注射填充剂属于干粉剂，相对于凝胶剂型产品，本发明的注射填充剂的保质期较长，不会出现因为注射填充微球发生降解，导致的形变和坍塌。The injectable filler of the present invention includes injection filled microspheres and water-soluble gel dry powder, that is, the injectable filler of the present invention belongs to dry powder. Compared with gel dosage products, the injectable filler of the present invention has a longer shelf life and will not cause Because the injection-filled microspheres degrade, resulting in deformation and collapse.
本发明的注射填充剂在复溶时，只需要与适量水性溶剂混合均匀，即可得到粘稠度均一的胶体凝胶。水溶性凝胶干粉可以快速溶解，从而可以提供即刻填充效果，水溶性凝胶干粉与水性溶剂结合形成的胶体凝胶具有剪切变稀特性，在注射后粘度提高，强度增加以在组织中提供填充和支撑作用，使注射填充微球均匀分布，避免迁移。When the injectable filler of the present invention is reconstituted, it only needs to be mixed evenly with an appropriate amount of aqueous solvent to obtain a colloidal gel with uniform viscosity. The water-soluble gel dry powder can dissolve quickly, thus providing an immediate filling effect. The water-soluble gel dry powder combined with the aqueous solvent forms a colloidal gel that has shear-thinning properties. After injection, the viscosity increases and the strength increases to provide in the tissue. Filling and supporting functions enable the injected filled microspheres to be evenly distributed and avoid migration.
与传统的干粉剂型产品相比，本发明的注射填充剂可以在复溶后形成胶体凝胶，从而大大提高了注射填充微球的分散性，避免了由于微球分散性差、微球容易聚集沉积导致的一系列问题。Compared with traditional dry powder dosage products, the injectable filler of the present invention can form a colloidal gel after reconstitution, thereby greatly improving the dispersion of the injection-filled microspheres and avoiding the easy aggregation and deposition of the microspheres due to poor dispersion of the microspheres. resulting in a series of problems.
对比现有技术，本发明的注射填充剂显著提高了复溶效率，节约了时间成本，降低了染菌风险。Compared with the existing technology, the injectable filler of the present invention significantly improves the reconstitution efficiency, saves time and cost, and reduces the risk of bacterial contamination.
优选的，本实施方式中，注射填充微球和水溶性凝胶干粉的质量比为30～50：7～15。Preferably, in this embodiment, the mass ratio of injection-filled microspheres and water-soluble gel dry powder is 30-50:7-15.
优选的，本实施方式中，注射填充微球为无机微球、有机高分子微球或无机/有机复合微球。Preferably, in this embodiment, the injection-filled microspheres are inorganic microspheres, organic polymer microspheres or inorganic/organic composite microspheres.
具体来说，无机微球可以为羟基磷灰石微球；有机高分子微球可以为脂肪族聚酯微球或凝胶微球。Specifically, the inorganic microspheres can be hydroxyapatite microspheres; the organic polymer microspheres can be aliphatic polyester microspheres or gel microspheres.
特别的，脂肪族聚酯微球的材料选自PCL、PLA、PLLA、PLGA、PHA、PLGA-PEG、PLA-PEG、PLLA-PEG、PCL-PEG、PLGA-PEG-PLGA、PLA-PEG-PLGA、PLLA-PEG-PLGA、PCL-PEG-PLGA、PLGA-PEG-PLA、PLA-PEG-PLA、PLLA-PEG-PLA、PCL-PEG-PLA、PLGA-PEG-PLLA、PLA-PEG-PLLA、PLLA-PEG-PLLA、PCL-PEG-PLLA、PLGA-PEG-PCL、PLA-PEG-PCL、PLLA-PEG-PCL和PCL-PEG-PCL中的至少一种。In particular, the material of aliphatic polyester microspheres is selected from PCL, PLA, PLLA, PLGA, PHA, PLGA-PEG, PLA-PEG, PLLA-PEG, PCL-PEG, PLGA-PEG-PLGA, PLA-PEG-PLGA , PLLA-PEG-PLGA, PCL-PEG-PLGA, PLGA-PEG-PLA, PLA-PEG-PLA, PLLA-PEG-PLA, PCL-PEG-PLA, PLGA-PEG-PLLA, PLA-PEG-PLLA, PLLA - at least one of PEG-PLLA, PCL-PEG-PLLA, PLGA-PEG-PCL, PLA-PEG-PCL, PLLA-PEG-PCL and PCL-PEG-PCL.
优选的，水溶性凝胶干粉的材料选自明胶、壳聚糖、海藻酸钠、丝素蛋白、透明质酸、胶原蛋白及其衍生物中的至少一种。Preferably, the material of the water-soluble gel dry powder is selected from at least one of gelatin, chitosan, sodium alginate, silk fibroin, hyaluronic acid, collagen and their derivatives.
特别的，本实施方式中，水溶性凝胶干粉为纳米明胶颗粒。In particular, in this embodiment, the water-soluble gel dry powder is nano gelatin particles.
本发明的注射填充剂作为一种可注射填充剂，有效避免了微球在分散剂中沉降和团聚，并且通过简单的操作快速地使填充剂由干粉状转化为可注射状态，具有效率高、可操作性强等优势。As an injectable filler, the injectable filler of the present invention effectively avoids the sedimentation and agglomeration of microspheres in the dispersant, and quickly converts the filler from dry powder to an injectable state through simple operations, with high efficiency. , strong operability and other advantages.
本发明的注射填充剂的配方简单，不涉及复杂改性过程，易于扩大生产。The injection filler of the present invention has a simple formula, does not involve complex modification processes, and is easy to expand production.
本发明还公开了一实施方式的上述注射填充剂的复溶方法，包括如下步骤：The invention also discloses a method for redissolving the above-mentioned injectable filler in one embodiment, which includes the following steps:
S10、提供上述的注射填充剂，注射填充剂包括注射填充微球和水溶性凝胶干粉。S10. Provide the above-mentioned injectable filler, which includes injectable filling microspheres and water-soluble gel dry powder.
其中，注射填充微球的粒径为10μm～100μm，水溶性凝胶干粉的粒径为1nm～10μm。Among them, the particle size of the injection-filled microspheres is 10 μm to 100 μm, and the particle size of the water-soluble gel dry powder is 1 nm to 10 μm.
优选的，本实施方式中，注射填充微球和水溶性凝胶干粉的质量比为30～50：7～15。Preferably, in this embodiment, the mass ratio of injection-filled microspheres and water-soluble gel dry powder is 30-50:7-15.
优选的，本实施方式中，注射填充微球为无机微球、有机高分子微球或无机/有机复合微球。Preferably, in this embodiment, the injection-filled microspheres are inorganic microspheres, organic polymer microspheres or inorganic/organic composite microspheres.
具体来说，无机微球可以为羟基磷灰石微球；有机高分子微球可以为脂肪族聚酯微球或凝胶微球。Specifically, the inorganic microspheres can be hydroxyapatite microspheres; the organic polymer microspheres can be aliphatic polyester microspheres or gel microspheres.
特别的，脂肪族聚酯微球的材料选自PCL、PLA、PLLA、PLGA、PHA、PLGA-PEG、PLA-PEG、PLLA-PEG、PCL-PEG、PLGA-PEG-PLGA、PLA-PEG-PLGA、PLLA-PEG-PLGA、PCL-PEG-PLGA、PLGA-PEG-PLA、PLA-PEG-PLA、PLLA-PEG-PLA、PCL-PEG-PLA、PLGA-PEG-PLLA、PLA-PEG-PLLA、PLLA-PEG-PLLA、PCL-PEG-PLLA、PLGA-PEG-PCL、PLA-PEG-PCL、PLLA-PEG-PCL和PCL-PEG-PCL中的至少一种。In particular, the material of aliphatic polyester microspheres is selected from PCL, PLA, PLLA, PLGA, PHA, PLGA-PEG, PLA-PEG, PLLA-PEG, PCL-PEG, PLGA-PEG-PLGA, PLA-PEG-PLGA , PLLA-PEG-PLGA, PCL-PEG-PLGA, PLGA-PEG-PLA, PLA-PEG-PLA, PLLA-PEG-PLA, PCL-PEG-PLA, PLGA-PEG-PLLA, PLA-PEG-PLLA, PLLA - at least one of PEG-PLLA, PCL-PEG-PLLA, PLGA-PEG-PCL, PLA-PEG-PCL, PLLA-PEG-PCL and PCL-PEG-PCL.
优选的，水溶性凝胶干粉的材料选自明胶、壳聚糖、海藻酸钠、丝素蛋白、透明质酸、胶原蛋白及其衍生物中的至少一种。Preferably, the material of the water-soluble gel dry powder is selected from at least one of gelatin, chitosan, sodium alginate, silk fibroin, hyaluronic acid, collagen and their derivatives.
特别的，本实施方式中，水溶性凝胶干粉为纳米明胶颗粒。In particular, in this embodiment, the water-soluble gel dry powder is nano gelatin particles.
S20、将S10得到的注射填充剂和水性溶剂混合均匀，使得注射填充微球分散均匀，并且使水溶性凝胶干粉溶解，从而使得整个体系形成胶体凝胶。S20. Mix the injection filler obtained in S10 and the aqueous solvent evenly, so that the injection filling microspheres are evenly dispersed, and the water-soluble gel dry powder is dissolved, so that the entire system forms a colloidal gel.
优选的，本实施方式中，将注射填充剂和水性溶剂混合均匀的操作为：用注射器推注注射填充剂和水性溶剂若干次，直至注射填充剂和水性溶剂混合均匀。Preferably, in this embodiment, the operation of mixing the injection filler and the aqueous solvent evenly is: using a syringe to inject the injection filler and the aqueous solvent several times until the injection filler and the aqueous solvent are evenly mixed.
通过注射器的通过反复推注，即可实现注射填充微球分散均匀，本发明的注射填充剂使用起来极为方便。By repeatedly injecting the syringe, the injection-filled microspheres can be evenly dispersed, and the injectable filler of the present invention is extremely convenient to use.
注射器的具体推注次数可以根据实际情况确定，一般为十次以上。The specific number of injections of the syringe can be determined according to the actual situation, and is generally more than ten times.
优选的，本实施方式中，将注射填充剂和水性溶剂混合均匀的操作中，水溶性凝胶干粉和水性溶剂的比例为7g～15g：100mL。Preferably, in this embodiment, during the operation of uniformly mixing the injection filler and the aqueous solvent, the ratio of the water-soluble gel dry powder and the aqueous solvent is 7g to 15g:100mL.
优选的，本实施方式中，水性溶剂为生理盐水或磷酸盐缓冲液。Preferably, in this embodiment, the aqueous solvent is physiological saline or phosphate buffer.
更优选的，水性溶剂中还含有10wt％～20wt％的利多卡因。More preferably, the aqueous solvent also contains 10wt% to 20wt% lidocaine.
本发明的注射填充剂在复溶后，水溶性凝胶干粉水化后形成的胶体凝胶具有良好的生物相容性和剪切变稀特性，可以在注射器中通过反复推注使微球分散均匀；且在注射后粘度提高，强度增加以在组织中提供填充和支撑作用，使微球均匀分布，避免迁移。After the injectable filler of the present invention is reconstituted and the water-soluble gel dry powder is hydrated, the colloidal gel formed has good biocompatibility and shear thinning properties, and the microspheres can be dispersed through repeated injection in a syringe. Uniform; and after injection, the viscosity increases and the strength increases to provide filling and support in the tissue, so that the microspheres are evenly distributed and avoid migration.
以下为具体实施例。The following are specific examples.
实施例中，纳米明胶颗粒购于深圳华诺生物科技有限公司；羟基磷灰石微球购于上海伊普瑞生物科技有限公司，粒径为25μm～45μm；PCL微球由溶剂挥发法制备得到：将含5wt％PCL的二氯甲烷溶液分散于2wt％的PVA溶液中，高速搅拌乳化后低速搅拌固化，制备得到PCL微球，洗涤干燥后备用。In the examples, nano-gelatin particles were purchased from Shenzhen Huanuo Biotechnology Co., Ltd.; hydroxyapatite microspheres were purchased from Shanghai Yipuri Biotechnology Co., Ltd., with a particle size of 25 μm to 45 μm; PCL microspheres were prepared by a solvent evaporation method. : Disperse a methylene chloride solution containing 5wt% PCL in a 2wt% PVA solution, stir at high speed to emulsify, and then stir at low speed for solidification to prepare PCL microspheres, which are washed and dried before use.
实施例1Example 1
1)配制注射填充剂1) Preparation of injectable filler
在无菌环境下称量0.1g PCL微球和0.25g纳米明胶颗粒，并混合均匀，得到注射填充剂。Weigh 0.1g PCL microspheres and 0.25g nanogelatin particles in a sterile environment and mix them evenly to obtain an injectable filler.
2)注射填充剂的使用2) Use of injectable fillers
将注射填充剂与2.5mL生理盐水共混，通过注射器反复推注15次，至混合物粘稠度均一。Blend the injectable filler with 2.5 mL of physiological saline and inject it repeatedly through a syringe 15 times until the mixture has a uniform consistency.
实施例2Example 2
1)配制注射剂1) Preparation of injections
在无菌环境下称量0.1g羟基磷灰石微球和0.20g纳米明胶颗粒，并混合均匀，得到注射填充剂。Weigh 0.1g hydroxyapatite microspheres and 0.20g nanogelatin particles in a sterile environment and mix them evenly to obtain an injectable filler.
2)注射剂的使用2) Use of injections
将微球混合颗粒与2.5mL生理盐水共混，通过注射器反复推注12次，至混合物粘稠度均一。Blend the microsphere mixed particles with 2.5 mL of physiological saline and inject it repeatedly through a syringe 12 times until the mixture has a uniform viscosity.
实施例3Example 3
1)配制注射填充剂1) Preparation of injectable filler
在无菌环境下称量0.161g PCL微球和0.375g纳米明胶颗粒，并混合均匀，得到注射填充剂。Weigh 0.161g PCL microspheres and 0.375g nano-gelatin particles in a sterile environment and mix them evenly to obtain an injectable filler.
2)注射填充剂的使用2) Use of injectable fillers
将注射填充剂与2.5mL生理盐水共混，通过注射器反复推注25次，至混合物粘稠度均一。Blend the injectable filler with 2.5 mL of physiological saline and inject it repeatedly through a syringe 25 times until the mixture has a uniform consistency.
实施例4Example 4
1)配制注射填充剂1) Preparation of injectable filler
在无菌环境下称量0.175g PCL微球和0.175g纳米明胶颗粒，并混合均匀，得到注射填充剂。Weigh 0.175g PCL microspheres and 0.175g nano-gelatin particles in a sterile environment and mix them evenly to obtain an injectable filler.
2)注射填充剂的使用2) Use of injectable fillers
将注射填充剂与2.5mL生理盐水共混，通过注射器反复推注10次，至混合物粘稠度均一。Blend the injectable filler with 2.5 mL of physiological saline and inject it repeatedly through a syringe 10 times until the mixture has a uniform consistency.
测试例1Test example 1
对实施例1得到的混合物进行流变分析，得到图1。The mixture obtained in Example 1 was subjected to rheological analysis, and Figure 1 was obtained.
结合图1可以看出，随着应变增加，剂型的黏度降低，具有剪切变稀特性。It can be seen from Figure 1 that as the strain increases, the viscosity of the dosage form decreases and has shear thinning characteristics.
对实施例1得到的混合物在37℃下进行振荡频率扫描(0.1Hz～10Hz；1％应变)，以显示G’储存模量和G”损耗模量，得到图2。The mixture obtained in Example 1 was subjected to oscillation frequency scanning (0.1 Hz to 10 Hz; 1% strain) at 37°C to display the G' storage modulus and G" loss modulus, and Figure 2 was obtained.
结合图2可以看出，微球注射剂的高弹特性，储存模量G’约1000Pa。It can be seen from Figure 2 that the microsphere injection has high elastic properties and the storage modulus G’ is about 1000Pa.
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对申请专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。The above-described embodiments only express several implementation modes of the present invention, and their descriptions are relatively specific and detailed, but they should not be construed as limiting the scope of the patent application. It should be noted that, for those of ordinary skill in the art, several modifications and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the scope of protection of the patent of the present invention should be determined by the appended claims.
| Application Number | Priority Date | Filing Date | Title |
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| CN202310648732.0ACN116808290A (en) | 2023-06-02 | 2023-06-02 | Injection filler and redissolution method thereof |
| Application Number | Priority Date | Filing Date | Title |
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| CN202310648732.0ACN116808290A (en) | 2023-06-02 | 2023-06-02 | Injection filler and redissolution method thereof |
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| CN116808290Atrue CN116808290A (en) | 2023-09-29 |
| Application Number | Title | Priority Date | Filing Date |
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| CN202310648732.0APendingCN116808290A (en) | 2023-06-02 | 2023-06-02 | Injection filler and redissolution method thereof |
| Country | Link |
|---|---|
| CN (1) | CN116808290A (en) |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118436851A (en)* | 2024-04-17 | 2024-08-06 | 中科之光生物科技(河北省)有限公司 | Active medical beauty injection filling material and preparation method thereof |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111617315A (en)* | 2020-01-14 | 2020-09-04 | 北京四环制药有限公司 | Biodegradable injection filler, preparation method and application thereof |
| CN111840638A (en)* | 2020-07-21 | 2020-10-30 | 华熙生物科技股份有限公司 | Preparation method of crosslinked hyaluronic acid filler for injection |
| CN113117142A (en)* | 2020-01-14 | 2021-07-16 | 北京四环制药有限公司 | Biodegradable injection filler, preparation method and application thereof |
| CN114099771A (en)* | 2020-08-27 | 2022-03-01 | 杭州协合医疗用品有限公司 | Gradient injection containing mixed polymer microspheres |
| CN114209887A (en)* | 2021-08-24 | 2022-03-22 | 杭州协合医疗用品有限公司 | Injection gel containing controllable degradable polyester microspheres |
| CN114269327A (en)* | 2019-06-01 | 2022-04-01 | 纳诺米公司 | Monodisperse absorbable polyester polymer compositions |
| WO2022205645A1 (en)* | 2021-04-02 | 2022-10-06 | 长春圣博玛生物材料有限公司 | Injectable dermal filler and preparation method therefor |
| CN115414530A (en)* | 2022-10-24 | 2022-12-02 | 深圳市致美生物科技有限公司 | Injectable filler for accelerating collagen regeneration induction and preparation and application thereof |
| CN115531607A (en)* | 2022-10-21 | 2022-12-30 | 北京安奇生物医药科技有限公司 | Preparation method of mixed degradable material microsphere and composite preparation |
| CN116617456A (en)* | 2023-03-03 | 2023-08-22 | 天津宏达未来科技有限公司 | Injectable dermal filler |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114269327A (en)* | 2019-06-01 | 2022-04-01 | 纳诺米公司 | Monodisperse absorbable polyester polymer compositions |
| CN111617315A (en)* | 2020-01-14 | 2020-09-04 | 北京四环制药有限公司 | Biodegradable injection filler, preparation method and application thereof |
| CN113117142A (en)* | 2020-01-14 | 2021-07-16 | 北京四环制药有限公司 | Biodegradable injection filler, preparation method and application thereof |
| CN111840638A (en)* | 2020-07-21 | 2020-10-30 | 华熙生物科技股份有限公司 | Preparation method of crosslinked hyaluronic acid filler for injection |
| CN114099771A (en)* | 2020-08-27 | 2022-03-01 | 杭州协合医疗用品有限公司 | Gradient injection containing mixed polymer microspheres |
| WO2022205645A1 (en)* | 2021-04-02 | 2022-10-06 | 长春圣博玛生物材料有限公司 | Injectable dermal filler and preparation method therefor |
| CN114209887A (en)* | 2021-08-24 | 2022-03-22 | 杭州协合医疗用品有限公司 | Injection gel containing controllable degradable polyester microspheres |
| CN115531607A (en)* | 2022-10-21 | 2022-12-30 | 北京安奇生物医药科技有限公司 | Preparation method of mixed degradable material microsphere and composite preparation |
| CN115414530A (en)* | 2022-10-24 | 2022-12-02 | 深圳市致美生物科技有限公司 | Injectable filler for accelerating collagen regeneration induction and preparation and application thereof |
| CN116617456A (en)* | 2023-03-03 | 2023-08-22 | 天津宏达未来科技有限公司 | Injectable dermal filler |
| Title |
|---|
| 张新著: "《现代医学美容教学理论与实践探索》", 31 May 2022, 西安：陕西科学技术出版社, pages: 196* |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118436851A (en)* | 2024-04-17 | 2024-08-06 | 中科之光生物科技(河北省)有限公司 | Active medical beauty injection filling material and preparation method thereof |
| Publication | Publication Date | Title |
|---|---|---|
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