Blood vessel induction gel suspension as well as preparation method and application thereof
By providing a vascular induced gel suspension containing porous microspheres, salt solutions and gels, the problem of inability to effectively guide vascular growth and promote collagen tissue repair and regeneration in the prior art is solved, and the risk of foreign body rejection is achieved.
Patent Information
- Application Number
- CN202510251138.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-03-04
- Publication Date
- 2025-06-13
Smart Images
Figure CN120132048A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of medical materials, and particularly to a vascular induction gel suspension and its preparation method and application. Background Art
[0002] Among the existing subcutaneous filling injection products, hyaluronic acid-based products can achieve immediate and long-term filling. However, due to their poor biological activity, they will form fibrous encapsulation and fibrous hyperplasia under the skin, which will cause persistent local inflammation in the long term. Collagen-based products can achieve immediate filling, and some cross-linked products can achieve long-term filling. However, due to the problems of animal-derived components and xenogeneic sources, there is a risk of rejection reaction after implantation under the skin. Other composite suspension products based on microspheres can improve the biocompatibility of gel preparations to a certain extent. However, existing commercial products generally use solid microspheres, such as polylactic acid microspheres, polycaprolactone microspheres, etc., which cannot effectively guide blood vessel ingrowth and ultimately cannot promote the repair and regeneration of lost collagen. There are also some existing technologies that use hollow microspheres as raw materials, which can promote tissue growth, but it is often difficult to avoid the damage to the human body caused by harmful substances generated by degradation, affecting the growth of new tissues. Summary of the Invention
[0003] The main object of the present invention is to provide a vascular induction gel suspension and its preparation method and application, aiming to solve the technical problems that the existing subcutaneous filling injection products cannot effectively guide blood vessel ingrowth, are difficult to promote the repair and regeneration of lost collagen, and are prone to degradation to produce toxic and harmful substances, which damage human health and affect the growth of new tissues.
[0004] To achieve the above object, the present invention provides a vascular induction gel suspension, which includes porous microspheres, a salt solution, and a gel, and the porous microspheres include biodegradable natural macromolecules and / or biodegradable synthetic macromolecules.
[0005] In some embodiments of the present application, the biodegradable synthetic macromolecules are selected from at least one of polylactic acid, poly(lactic-co-glycolic acid), polycaprolactone, polyglycolide, polydioxanone, dipropyl fumarate polyesters, polyanhydrides, polyhydroxybutyrate, polyethylene glycol and its derivatives, polyamides, polylysine, polystyrene, polypropylene, polypyrrole, poly(N-isopropylacrylamide) and its derivatives, polyorthoesters, and polyacetals;
[0006] and / or, the natural macromolecules are selected from at least one of alginate, chitosan and its derivatives, dextran and its derivatives, chitosan oligosaccharide and its derivatives, hyaluronic acid and its derivatives, pullulan polysaccharide and its derivatives, collagen, recombinant collagen, silk and its derivatives, gelatin and its derivatives, and extracellular matrix.
[0007] In some embodiments of the present application, the average particle size range of the porous microspheres is 20 - 200 μm.
[0008] In some embodiments of the present application, the pore size range of the porous microspheres is 5 - 50 μm.
[0009] In some embodiments of the present application, the porosity range of the porous microspheres is 30% - 80%.
[0010] In some embodiments of the present application, the molecular weight range of the porous microspheres is 200KDa - 800KDa.
[0011] In some embodiments of the present application, the water content of the porous microspheres is below 10%.
[0012] In some embodiments of the present application, the compressive strength range of the porous microspheres is 0.01 - 0.10 Mpa.
[0013] In some embodiments of the present application, calculated by mass percentage, the mass percentage of the porous microspheres is 1% - 50%.
[0014] In some embodiments of the present application, the gel includes at least one of a hyaluronic acid-based gel, a collagen-based gel, and a polymer gel.
[0015] In some embodiments of the present application, the salt solution includes at least one of a sodium chloride solution, a sodium carbonate solution, a sodium bicarbonate solution, and a potassium chloride solution.
[0016] In addition, to achieve the above object, the present invention also provides a preparation method of the vascular induction gel suspension as described above, and the preparation method includes the following steps:
[0017] Mix the porous microspheres, the salt solution, and the gel to obtain the vascular induction gel suspension.
[0018] The present invention also provides an application of the vascular induction gel suspension of the present invention as described above in inducing blood vessel ingrowth and collagen tissue repair and regeneration. The vascular induction gel suspension of the present invention can effectively induce blood vessel ingrowth in a subcutaneous filling scenario, and ultimately achieve the repair and regeneration of collagen tissue, and can effectively reduce the in vivo foreign body rejection reaction.
[0019] The beneficial effects that the present invention can achieve:
[0020] The vascular induction gel suspension provided by the present invention comprises porous microspheres, a gel and a salt solution. The porous microspheres of the present invention are degradable, non-toxic, not likely to cause harm to the human body, have good biocompatibility, can effectively reduce the risk of foreign body rejection in the body, and moreover, the porous microspheres provide a special porous structure that can provide a scaffold for the crawling of endothelial cells, ultimately enabling blood vessels to grow into the injection area, truly realizing the repair and regeneration of the lost collagen tissue. In addition, the salt solution can maintain the stability of the vascular induction gel suspension, enable the crawling scaffold to be evenly distributed in the injection area, promote the uniform growth of blood vessels and the repair and regeneration of collagen tissue, and reduce the risk of subcutaneous formation of fibrous capsules and fibrous hyperplasia. Description of the Drawings
[0021] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following briefly introduces the drawings required for use in the description of the embodiments or the prior art. Obviously, the following-described drawings are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can be obtained based on the structures shown in these drawings.
[0022] Figure 1 SEM images of the porous microspheres in Example 1 of Test 1 and the solid microspheres in Comparative Example 1, wherein, Figure 1 A and Figure 1 B are the SEM images of the porous microspheres, Figure 1 C is the SEM image of the solid microspheres.
[0023] Figure 2 Macrophotographs of the rats in Comparative Example 3 and the control group in Test 2 on the 0th day, 4th day, and 8th day after injection of the injection.
[0024] Figure 3 Anatomical diagrams of the rats in Comparative Example 3 and the control group in Test 2 on the 8th day after injection of the injection.
[0025] Figure 4 Macrophotographs of the rats in Example 1, the control group, and Comparative Example 1 in Test 3 on the 0th day after injection of the injection.
[0026] Figure 5 Morphological diagrams of the gels used in Example 1, the control group, and Comparative Example 1 in Test 3 and macrophotographs of the rats 1 month after injection of the injection.
[0027] Figure 6 Stained tissue section diagrams of the anatomical samples of the rats in Example 1, the control group, and Comparative Example 1 in Test 3 1 month after injection of the injection.
[0028] Figure 7Tissues from the dissection of rats in Example 1, the control group, and Comparative Example 1 in Test 3, one month after injection of the injection.
[0029] Figure 8 Stained tissue section diagram of the dissection sample of the rats in Example 2 in Test 4, three weeks after injection of the injection.
[0030] Figure 9 Stained tissue section diagram of the dissection sample of the rats in Comparative Example 2 in Test 4, three weeks after injection of the injection.
[0031] Figure 10 Macrographs of the rats in Example 3 and the control group in Test 5 on the 0th day, 1st week, 2nd week, and 3rd week after injection of the injection.
[0032] Figure 11 Stained tissue diagram of the dissection of the rats in Example 3 and the control group in Test 5 on the 8th day after injection of the injection.
[0033] The realization, functional features, and advantages of the object of the present invention will be further described in conjunction with the embodiments with reference to the accompanying drawings. Detailed implementation manners
[0034] It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.
[0035] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention.
[0036] In the present invention, descriptions such as "first" and "second" are only for descriptive purposes and cannot be understood as indicating or implying their relative importance or implicitly indicating the quantity of the indicated technical features. Thus, features defined with "first" and "second" may explicitly or implicitly include at least one such feature. In addition, the technical solutions between the various embodiments can be combined with each other, but it must be based on the fact that those of ordinary skill in the art can implement them. When the combination of technical solutions appears to be contradictory or unable to be implemented, it should be considered that such a combination of technical solutions does not exist and is not within the scope of protection required by the present invention.
[0037] Scientific research has confirmed that collagen is the basis of life, and life is a reaction system of collagen. However, with the aging of the body, the slowdown of metabolism, and the decline of collagen synthesis ability, everyone will inevitably experience "aging" caused by collagen loss. In recent years, with the pursuit of high-quality life by people, it has also given rise to the development of the anti-aging, medical aesthetics, and beauty industries. Among them, injectable gel products have become one of the mainstays of global fashion consumption because they can achieve minimally invasive treatment, immediate effect, and long-term retention.
[0038] Injectable gel products mainly have three major categories, namely collagen-based products, hyaluronic acid-based products, and polymer-based products. The main function of these products under the skin is immediate filling to supplement the lost collagen. Some products may have the effect of stimulating fibroblast proliferation, but generally do not have the effect of stimulating collagen tissue regeneration. The core of collagen tissue repair and regeneration is the ingrowth of blood vessels, and the ingrowth of blood vessels has certain requirements for the tissue microenvironment, such as a porous structure suitable for endothelial cell crawling, appropriate porosity and pore size, and suitable material mechanical properties. Only when all indicators are relatively balanced and stay under the skin for a period of time can the effective ingrowth of blood vessels be achieved, thereby stimulating collagen tissue repair and regeneration. Using hollow microspheres as raw materials can promote tissue growth, but there are often harmful substances produced by material degradation, which cause damage to the human body.
[0039] In view of this, the present invention provides a vascular induction gel suspension, which includes porous microspheres, a salt solution, and a gel. The porous microspheres include biodegradable natural macromolecules and / or biodegradable synthetic macromolecules.
[0040] The porous microspheres of the present invention are selected from biodegradable natural macromolecules and / or biodegradable synthetic macromolecules, which can meet the requirements of subcutaneous implantation, have good biocompatibility, are beneficial to reducing the risk of rejection reaction, and are not easily degraded to produce toxic and harmful substances that cause damage to the human body.
[0041] In some embodiments, the biodegradable synthetic macromolecules are selected from at least one of polylactic acid, poly(lactic-co-glycolic acid), polycaprolactone, polyglycolide, polydioxanone, poly(dipropyl fumarate), polyanhydride, polyhydroxybutyrate, polyethylene glycol and its derivatives, polyamide, polylysine, polystyrene, polypropylene, polypyrrole, poly(N-isopropylacrylamide) and its derivatives, polyorthoester, and polyacetal.
[0042] And / or, the biodegradable natural macromolecules are selected from at least one of alginate, chitosan and its derivatives, dextran and its derivatives, chitosan oligosaccharide and its derivatives, hyaluronic acid and its derivatives, pullulan polysaccharide and its derivatives, collagen, recombinant collagen, silk and its derivatives, gelatin and its derivatives, and extracellular matrix.
[0043] The vascular induction gel suspension of the present invention has porous microspheres with a special structure, which can provide a crawling scaffold for endothelial cells and a suitable tissue microenvironment for blood vessel ingrowth. In the subcutaneous filling scenario, it can effectively achieve the ingrowth of blood vessels into the injection area and truly realize the repair and regeneration of the lost collagen tissue.
[0044] In some embodiments, the average particle size range of the porous microspheres is 10 - 200 μm. Specifically, the average particle size of the porous microspheres can be any value within the range of 10 - 200 μm, such as 10 μm, 20 μm, 30 μm, 40 μm, 50 μm, 60 μm, 90 μm, 100 μm, 110 μm, 130 μm, 150 μm, 180 μm, 200 μm, etc. The porous microspheres with the above particle size range can form a suspended state in the vascular induction gel suspension of the present invention, enabling the porous microspheres providing the blood vessel crawling scaffold to be evenly distributed in the subcutaneous injection area, which is beneficial to promoting the uniform ingrowth of blood vessels into the injection area and stimulating the repair and regeneration of collagen tissue.
[0045] In some embodiments, the pore size range of the porous microspheres is 20 - 50 μm. Specifically, the pore size of the porous microspheres can be any value within the range of 20 - 50 μm, such as 20 μm, 25 μm, 30 μm, 40 μm, 45 μm, or 50 μm. As the blood vessel crawling scaffold for blood vessel ingrowth, if the pore size is too small, it cannot induce blood vessels to grow into the subcutaneous injection area, and thus cannot promote the repair and regeneration of the lost collagen tissue; if the pore size is too large, it is easy to cause uneven distribution of newly formed blood vessels in the injection area, and thus affect the repair effect of the lost collagen tissue, which is not conducive to the recovery of the body in the subcutaneous filling scenario. When the porous microspheres have a pore size within the above range of 20 - 50 μm, it is beneficial to promote the uniform ingrowth of blood vessels into the injection area, enable the newly formed blood vessels to be evenly distributed in the injection area, and promote the regeneration and repair of the lost collagen tissue.
[0046] In some embodiments, the porosity of the porous microspheres is 30% - 80%. Specifically, the porosity of the porous microspheres can be any value within the range of 30% - 80%, such as 30%, 40%, 50%, 60%, 70%, or 80%. Within the porosity range of 30% - 80% above, it is more conducive to inducing blood vessels to grow into the injection area to promote the repair and regeneration of the lost collagen tissue.
[0047] The molecular weight of the porous microspheres affects the residence time of the vascular induction gel suspension under the skin, and the residence time under the skin in turn affects the ingrowth of blood vessels and the repair and regeneration of the lost collagen tissue. In some embodiments, the molecular weight range of the porous microspheres is 200KDa - 800KDa. Within this molecular weight range, it is beneficial to control the residence time of the vascular induction gel suspension under the skin for more than 14 days. The porous microspheres will not be absorbed by the body prematurely, which is more conducive to promoting the ingrowth of blood vessels and enabling the repair and regeneration of collagen tissue.
[0048] In some embodiments, the water content of the porous microspheres is below 10%. If the water content of the porous microspheres is too high, they are easily degraded prematurely, and the residence time of the porous microspheres under the skin is too short. They will be degraded before the blood vessels grow into the injection area and cannot stimulate the regeneration and repair of collagen tissue.
[0049] In some embodiments, the compressive strength range of the porous microspheres is 0.01 - 0.10 MPa. Within this range, the porous microspheres include three cases of low mechanical strength, medium mechanical strength, and high mechanical strength, which can meet various shaping requirements in the subcutaneous filling scenario. For example, the porous microspheres with low mechanical strength are softer in texture, are easily absorbed, and have a shorter residence time, and can be used for injection and implantation in the relatively shallow area under the skin; the porous microspheres with medium mechanical strength have a moderate hardness, a slightly longer residence time, and can be used for injection and implantation in the deep area under the skin; the porous microspheres with high mechanical strength are harder in texture, are more conducive to cross-linking and shaping, have a more lasting shaping effect, and have a longer residence time, and can be injected into the deeper area under the skin. That is, the porous microspheres in the vascular induction gel suspension of the present invention have the above compressive strength range value, can meet the shaping requirements of most subcutaneous fillings, and have a wide application range.
[0050] It can be understood that the above limiting conditions for various physical and chemical properties and mass percentage contents of the porous microspheres can be satisfied simultaneously or only one of them can be satisfied. However, satisfying them simultaneously is more conducive to obtaining a vascular induction gel suspension that can induce the ingrowth of blood vessels, stimulate the repair and regeneration of collagen tissue, does not induce the formation of fibrous capsules and fibrous hyperplasia, and is not easily degraded to produce toxic and harmful substances that cause damage to the human body.
[0051] The present invention does not limit the content of the porous microspheres in the above-mentioned vascular induction suspension. In some embodiments, calculated by mass percentage, the mass percentage of the porous microspheres in the vascular induction gel suspension can be any value within the range of 1% - 50%, such as 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 13%, 15%, 18%, 20%, 25%, 28%, 30%, 34%, 35%, 38%, 40%, 42%, 45%, 49% or 50%. Under the limitation of the above mass percentage, the porous microspheres providing a crawling scaffold for endothelial cells can be evenly distributed in the injection area, inducing the uniform growth of blood vessels, and then stimulating the regeneration of collagen tissue.
[0052] The present invention does not limit the content of the salt solution and the gel in the above-mentioned vascular induction suspension. Calculated by mass percentage, the mass percentage of the salt solution is 20% - 80%, and the mass percentage of the gel is 20% - 80%. Combined with the porous microspheres, a vascular induction gel suspension in a suspended state can be formed. The suspended state is conducive to the uniform distribution of the porous microspheres, evenly distributing the crawling scaffold in the injection area, facilitating the growth of new blood vessels into the injection area, then stimulating the regeneration of collagen tissue, and reducing the occurrence of fibrous encapsulation and fibrous hyperplasia.
[0053] The present invention does not limit the type of the salt solution. The salt solution mainly promotes the formation of a suspended state of the suspension and maintains the stability of the vascular induction gel. In some embodiments, the salt solution includes at least one of a sodium chloride buffer solution, a sodium carbonate buffer solution, a sodium bicarbonate buffer solution, and a potassium chloride buffer solution.
[0054] The present invention does not limit the type of the gel, which is mainly an injectable gel product, including but not limited to hyaluronic acid-based gels, collagen-based gels, and polymer gels. The above types of gels can be in a cross-linked state or a non-cross-linked state, and can be mixed with the porous microspheres and the salt solution to form a vascular induction gel suspension in a suspended state.
[0055] The vascular induction gel suspension of the present invention is implanted into the subcutaneous tissue by means of injection and stays for more than 14 days. Further, according to the depth of the subcutaneous injection area and the shaping requirements, the vascular induction gel suspension can be adjusted to stay in the subcutaneous tissue for 14 days, 3 weeks, 1 month, etc., without being unable to induce the growth of blood vessels into the injection area due to too short a residence time, which affects the repair and regeneration of collagen tissue.
[0056] To achieve the above object, the present invention also provides a preparation method of the above-mentioned vascular induction gel suspension, including the following steps:
[0057] Mix the porous microspheres, the salt solution and the gel to obtain the vascular induction gel suspension.
[0058] In some embodiments, calculated by mass percentage, the mass percentage of the porous microspheres is 1%-50%, the mass percentage of the salt solution can be 20%-80%, and the mass percentage of the gel is 20%-80%.
[0059] In some embodiments, the porous microspheres, the salt solution, and the gel can be mixed evenly by stirring, which is more conducive to obtaining a vascular induction gel suspension in a suspended state. Specifically, the stirring speed can be 1000-1500 rpm, and the stirring time can be 20 min-60 min.
[0060] The vascular induction gel suspension obtained in the present invention can be applied to induce blood vessel ingrowth and stimulate the repair and regeneration of collagen tissue. In particular, it is applied to the field of aesthetic medicine. In the subcutaneous filling scenario, it can effectively induce blood vessels to grow into the injection area and ultimately achieve true repair and regeneration of collagen tissue. It also has good biocompatibility, can reduce the in vivo foreign body rejection reaction, and is not likely to produce toxic and harmful substances that cause damage to the human body after degradation.
[0061] The technical solutions of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following specific embodiments are only used to explain the present invention and are not used to limit the present invention.
[0062] Examples 1-3
[0063] The preparation method of a vascular induction gel suspension in this example includes the following steps:
[0064] Mix the porous microspheres, the gel, and the salt solution according to Table 1 and stir evenly at a speed of 1000 rpm to obtain a vascular induction gel suspension.
[0065] Comparative Example 1
[0066] Comparative Example 1 prepared a gel suspension with reference to Example 1. However, the difference is that in Comparative Example 1, alginate solid microspheres were used instead of the alginate porous microspheres in Example 1.
[0067] Comparative Example 2
[0068] Comparative Example 2 prepared a gel suspension with reference to Example 2. However, the difference is that the material of the porous microspheres used in Comparative Example 2 is polyurethane.
[0069] Comparative Example 3
[0070] Comparative Example 3 prepared a gel suspension with reference to Example 1. However, the difference is that the compressive strength of the microspheres is 0.005 MPa.
[0071] Table 1 Raw material composition of the vascular induction gel suspension in the examples
[0072]
[0073] Note: "Content %" in the table refers to the mass percentage based on the vascular induction gel suspension.
[0074] Performance Test
[0075] All the rats selected for the following performance tests are male rats with a rat age of 12 weeks and a body weight of 250 g ± 50 g.
[0076] Test 1 - Example 1 and Comparative Example 1
[0077] The porous microspheres of Example 1 were characterized by an electron scanning electron microscope, and the characterization results are shown in Figure 1 A and Figure 1 B. It was found that the porous microspheres had a porous structure that could provide for the crawling growth of blood vessels.
[0078] The solid microspheres of Comparative Example 1 were characterized by an electron scanning electron microscope, and the characterization results are shown in Figure 1 C. The solid microspheres did not have a porous structure that could provide for the crawling growth of blood vessels.
[0079] Test 2 - Comparative Example 3 and Control Group
[0080] The vascular induction gel suspension of Comparative Example 3 was used as an injection agent and injected subcutaneously into the back of rats, and sodium hyaluronate gel was used as the injection agent for the control group and injected subcutaneously into the back of another group of rats.
[0081] The macroscopic effect diagrams of the injection areas of the rats in Comparative Example 3 and the control group on day 0, day 4, and day 8, as well as the anatomical effect diagram of the injection area on day 8, were observed. Specifically, they are shown in Figure 2 and Figure 3 .
[0082] From Figure 2 it can be seen that after day 8, the sodium hyaluronate gel, porous microspheres in the injection area of the rats in Comparative Example 3, and the sodium hyaluronate gel in the control group all disappeared. Combining with Figure 3 the anatomical effect diagram, it was found that after day 8, no new tissue was found in the injection areas of the rats in Comparative Example 3 and the control group, indicating that the gel and porous microspheres in Comparative Example 3 could not induce the ingrowth of blood vessels and thus could not complete the repair and regeneration of collagen tissue.
[0083] From Test 2, it can be known that the compressive strength of the microspheres in the gel suspension of Comparative Example 3 was only 0.005 MPa, and degradation occurred on day 8, and it could not induce the ingrowth of blood vessels.
[0084] Test 3 - Example 1, Comparative Example 1 and Control Group
[0085] The products of Example 1 and Comparative Example 1 were respectively used as injection agents and injected subcutaneously into the backs of different rats, and sodium hyaluronate gel was used as the control injection agent and injected subcutaneously into the backs of rats.
[0086] The macroscopic effects of the rats in Example 1, Comparative Example 1, and the control group were observed on the 0th day after injection. See specifically Figure 4 , and the macroscopic pictures, stained anatomical tissue section pictures of the injection area, and omics stained pictures of the anatomical tissue section of the injection area were observed 1 month after injection. See specifically Figures 5 to 7 .
[0087] From Figure 4 it can be seen that there were obvious bulges on the backs of the rats in Example 1, Comparative Example 1, and the control group, indicating that the injection agent was effectively implanted.
[0088] From Figure 5 it can be seen that 1 month after injection, the bulges on the backs of the rats in Example 1, Comparative Example 1, and the control group gradually disappeared.
[0089] From Figure 6 it can be seen that 1 month after injection, obvious vascular structures appeared in the injection area of the rats in Example 1 in the stained anatomical tissue section pictures of the injection area of the backs of the rats in Example 1, Comparative Example 1, and the control group, while a fibrous membrane wrapping appeared in the control group, and no vascular structures appeared in Comparative Example 1, and only the wrapped fibrous tissue was observed.
[0090] From Figure 7 it can be seen that 1 month after injection, new blood vessels appeared in the injection area of the rats in Example 1.
[0091] It can be known from Test 3 that the vascular induction gel suspension of Example 1 can effectively promote the ingrowth of blood vessels into the injection area.
[0092] Test 4 - Example 2 and Comparative Example 2
[0093] The products of Example 2 and Comparative Example 2 were respectively used as injection agents and injected subcutaneously into the backs of different rats, and the stained anatomical tissue section pictures of the injection areas of the rats in Example 2 and Comparative Example 2 were observed at the 1st month. See specifically Figure 8 and Figure 9 , Figure 8 is the stained anatomical tissue section picture of the anatomical sample of the rats in Example 2 1 month after injection of the injection agent in Test 4, Figure 9 is the stained anatomical tissue section picture of the anatomical sample of the rats in Comparative Example 2 1 month after injection of the injection agent in Test 4.
[0094] From Figure 8It can be seen that the anatomical tissue section staining effect diagrams of the rats in Example 2 and Comparative Example 2 after 3 weeks of subcutaneous injection. After 3 weeks, new tissues appeared in the injection area of the rats in Example 2, indicating that it can promote the ingrowth of blood vessels into the injection area and stimulate the repair and growth of collagen tissue. The polyurethane microspheres implanted in Comparative Example 2 may produce toxicity due to degradation, affecting the growth of new blood vessels, and there are fewer blood vessels growing into the injection area.
[0095] Test 5 - Example 3 and the control group
[0096] The vascular induction gel suspension of Example 3 was used as an injection agent and injected subcutaneously into the back of rats, and sodium hyaluronate gel was used as the injection agent for the control group and injected subcutaneously into the back of another group of rats. The macroscopic effect diagrams of the injection areas of the rats in Example 3 and the control group on the 0th day, 1st week, 2nd week, and 3rd week were observed, and the anatomical tissue section staining effect diagrams of the injection areas of the rats in the 3rd week were observed. Specifically, see Figure 10 and Figure 11 .
[0097] It can be seen from Figure 10 that after 3 weeks of subcutaneous injection of the rats in Example 3 and the control group, both the sodium hyaluronate gel and the porous microspheres disappeared. Combining with the anatomical tissue section staining effect diagrams of Figure 11 , new tissues appeared in the injection area of the rats in Example 3 after 3 weeks, indicating that it can promote the ingrowth of blood vessels into the injection area and stimulate the repair and growth of collagen tissue. No new tissues grew in Comparative Example 3.
[0098] The above are only the preferred embodiments of the present invention, and do not limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made by using the content of the specification and drawings of the present invention, or directly or indirectly applied to other related technical fields, shall be equally included in the patent protection scope of the present invention.
Claims
1. A vascular induction gel suspension, characterized in that: The vascular induction gel suspension comprises porous microspheres, a salt solution and a gel, wherein the porous microspheres comprise degradable natural macromolecules and / or degradable artificially synthesized macromolecules.
2. The vascular inducing gel suspension according to claim 1, characterized in that The degradable synthetic macromolecule comprises at least one of polylactic acid, polylactic acid-co-glycolic acid, polycaprolactone, polyglycolide, polydioxanone, polydihydroxypropyl fumarate, polyanhydride, polyhydroxybutyric acid, polyethylene glycol and its derivatives, polyamide, polylysine, polystyrene, polypropylene, polypyrrole, poly(N-isopropylacrylamide) and its derivatives, polyorthoesters and polyacetals; And / or, the degradable natural macromolecules include at least one of alginate, chitosan and its derivatives, dextran and its derivatives, chitosan oligosaccharides and their derivatives, hyaluronic acid and its derivatives, pullulan and its derivatives, collagen, recombinant collagen, silk and its derivatives, gelatin and its derivatives, and extracellular matrix.
3. The vascular inducing gel suspension according to claim 1, characterized in that The average particle size of the porous microspheres ranges from 10 μm to 200 μm; And / or, the pore size of the porous microspheres is in the range of 20-50 μm; And / or, the porosity of the porous microspheres ranges from 30% to 80%; And / or, the molecular weight range of the porous microspheres is 200 KDa-800 KDa.
4. The vascular inducing gel suspension according to claim 1, characterized in that: The water content of the porous microspheres is less than 10%.
5. The vascular inducing gel suspension according to claim 1, characterized in that: The compressive strength of the porous microspheres ranges from 0.01 MPa to 0.10 MPa.
6. The vascular inducing gel suspension according to claim 1, characterized in that: The mass percentage of the porous microspheres is 1%-50%.
7. The vascular inducing gel suspension according to claim 1, characterized in that: The gel includes at least one of a hyaluronic acid-based gel, a collagen-based gel, and a polymer gel.
8. The vascular inducing gel suspension according to claim 1, characterized in that: The salt solution includes at least one of a sodium chloride buffer solution, a sodium carbonate buffer solution, a sodium bicarbonate buffer solution, and a potassium chloride buffer solution.
9. A method for preparing the vascular inducing gel suspension according to any one of claims 1 to 8, characterized in that: The following steps are involved: The porous microspheres, saline solution and gel are mixed to obtain the angiogenic gel suspension.
10. Use of the vascular induction gel suspension according to any one of claims 1 to 8 in inducing vascular ingrowth and promoting collagen tissue repair and regeneration.