CN116370715A - Shapable porous biological composite bone filling material containing statin drugs and preparation method thereof - Google Patents
Shapable porous biological composite bone filling material containing statin drugs and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/446—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/422—Anti-atherosclerotic agents
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Abstract
The invention relates to the technical field of bone filling materials, in particular to a mouldable porous biological composite bone filling material containing statin drugs and a preparation method thereof. The preparation method comprises the following steps: (1) The anhydrous calcium sulfate powder and the statin powder are weighed according to a proportion, then the anhydrous calcium sulfate powder and the statin powder are mixed and placed on a mixing plate, and after being mixed repeatedly by a cutter adjusting level at normal temperature, the mixture is mixed repeatedly up and down; wherein, the weight ratio of the anhydrous calcium sulfate powder to the statin powder is 1: 0.005-0.01; (2) Rapidly weighing the end-removed polypeptide collagen gel in proportion at normal temperature, wherein the end-removed polypeptide collagen gel is in a solid jelly shape; the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and statin mixed powder is 1: 2-2: 1, a step of; (3) Placing the weighed end-removed polypeptide collagen gel on a stirring plate, and repeatedly pressing and stirring by a knife at normal temperature to obtain the mouldable porous biological composite bone filling material containing statin drugs.
Description
Technical Field
The invention relates to the technical field of bone filling materials, in particular to a shapable porous biological composite bone filling material and a preparation method thereof.
Background
Bone tissue is one of the most widely distributed and common organs of the human body, and loss of function is one of the main causes of the reduction of quality of life. Currently, massive bone resorption and defects due to severe trauma, infection, bone tumor and other factors are increasingly becoming a significant challenge for clinicians. As the aging population becomes more and more severe, the incidence of bone diseases (e.g., osteoporosis, osteoarthritis, and osteomyelitis) and trauma related injuries caused by primary tumor resection and orthopedic surgery (e.g., total joint replacement and implant fixation) increases, which results in an increasing demand for bone filling and repair materials.
At present, the most main method for treating bone defect is autologous or allogeneic bone grafting, but the problems of lack of a donor, great surgical traumatism, high cost, limitation of the shape of the bone defect part and the like are caused, and great difficulties are brought to patients and clinicians. About 200 tens of thousands of bone grafting procedures for the spine, pelvic and other trunk bones are internationally available each year, however, about 50% of implants, whether autogenous or allograft, are faced with failure for a variety of reasons. High incidence of bone and joint related diseases such as osteoporosis, arthritis, obesity, diabetes, cancer, etc., causes damage to bone tissue, and ultimately affects the health and function of human bones. Therefore, how to reduce the success rate of surgery for patients with bone defects, reduce the economic burden of patients, and improve the life quality of patients is an urgent problem to be solved.
The damage to the patient caused by the oral bone defect is also obvious. Firstly, the teeth of the patient are lost, so that the vomiting, the unclear pronunciation, the soft tissue defect and the eating of the patient are influenced, the appearance of the patient is possibly changed, and finally the psychological and mental burden of the patient is caused. Missing teeth can seriously affect the function and beauty of chewing and auxiliary pronunciation of a patient, and can also affect the health of the oral and jaw system and the psychological health of the patient. Tooth loss has been shown to be a risk factor for obesity, diabetes, cardiovascular disease, part of the tumor types and Alzheimer's disease.
Autologous bone grafting (the grafting of tissue from one location to another in the same patient's body) is the most successful treatment of bone defects, and is also the gold standard. It faces many limitations such as: poor availability of harvested tissue, chronic donor site pain, morbidity and complications, and the like. Moreover, significant injury and pain can occur during additional complex procedures, while bone removal can lead to donor site morbidity. Allogeneic bone (tissue is transplanted from a patient with different genotypes to another patient) and xenograft (tissue is transplanted from a donor of another species) are also one of the more widely used alternative materials in clinic at present, but the application prospect is limited to a certain extent due to the disadvantages of immune-mediated rejection, risk of infectious disease transmission, inability to meet the treatment of massive bone defects and the like.
For the above reasons, the discovery of synthetic materials has opened a new era in the field of bone graft medicine. Such biomaterials are receiving increasing attention for their excellent biocompatibility, absorbability, bone conductivity, plasticity, etc., including polymethyl methacrylate (PMMA), calcium Phosphate Cement (CPC), calcium sulfate (CAS), etc. Especially, the calcium-phosphorus artificial bone biological material can be injected into bone defect positions with various geometric shapes for in-situ shaping and curing due to the advantages of good biocompatibility, in-situ curing, injectability and the like, thereby greatly improving the success rate of the bone defect treatment in clinic. However, with the clinical application and the deep research, problems such as: PMMA has the defects of high polymerization temperature, poor biocompatibility, nondegradability and the like; CPC has the disadvantages of long bone formation time, poor mechanical properties and the like. On the other hand, the material is mostly used for plastic surgery, orthopaedics and the like, and the injectable bone biological material has little application in the oral cavity.
Injectable calcium phosphate and calcium sulfate bone substitutes are the most common calcium-phosphorus biomaterials. The composite material is degraded while providing space and guiding support for the growth of blood vessels and osteoblasts, namely the degradation and absorption process is synchronous with the crawling replacement process of bones, and the bone substitute absorption time is consistent with the clinical healing time of fracture. Especially because of its injectability, it is especially convenient for the treatment of bone defects in the oral cavity. The method is simple to operate, and the risk of infection is reduced by transmucosal injection or minimally invasive fenestration injection, so that the physical and psychological burden of a patient is further reduced.
Calcium sulfate (CAS) has potential for minimally invasive surgery in surgical reconstructive surgery in stomatology, orthopedics, etc., due to its biocompatibility and bone conduction characteristics, and its low price and injectability. Moreover, because it is stiffer and more supportive than CPC, it has become a clinically common replacement for bone defects. CAS has been used as a bone defect filling repair material for centuries, but the purity of CAS is not high due to limitations of the manufacturing process of early CAS, resulting in poor clinical use. However, with the continued development of technology, CAS has been made to exist in an ultra-high purity crystal structure. Studies have shown that CAS has good histocompatibility, does not produce inflammation and irritation to surrounding tissues, and more importantly, CAS has a degradation time of 1-4 months in vivo, which is consistent with the formation time of new bone, which also creates favorable conditions for regeneration of new bone. On the other hand, studies have shown that the CAS osteogenesis mechanism includes two aspects: CAS fills the bone defect, restores bone appearance, prevents soft tissue ingrowth, and provides space and conductive scaffolding for vascular and osteoblast ingrowth while degrading. The CAS degradation and absorption process is synchronous with the crawling replacement process of the bone, and finally continuous bone tissues are formed in the bone grafting area; CAS has osteoinductive activity by locally forming a slightly acidic environment during the degradation and absorption process of CAS, causing the release of osteogenic factors by local decalcification and bone matrix. The CAS forms a high-calcium environment locally during in-vivo degradation, provides a calcium source for new bone formation, and simultaneously can promote osteoblast proliferation and differentiation. Therefore, CAS is an osteogenic material that has bone conductivity, osteoinductive properties, and osteogenic action, is nontoxic, has no immunogenicity, and can be completely biodegraded in a short time.
However, there are also studies showing that CAS has a disadvantage in that it is cured at a high rate to inhibit bone regeneration. Therefore, in order to greatly exploit the advantages of CAS, there is a need to develop a novel composite material that combines other materials.
Statins play a role in stimulating bone regeneration via the mevalonate pathway, they inhibit 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and thereby affect growth factors in osteoblasts, for example: up-regulating BMP-2 and VEGF expression. Research shows that the statin medicine can promote bone healing, form New Bone (NB), strengthen bone strength, increase bone volume, etc. In addition, it has been found that statins promote bone formation around implants when injected systemically or locally. However, the effect of statins can only be maintained for 5 days when used alone without an effective Drug Delivery System (DDS). There is also a need for a better drug release material that allows for the stable release of a biologically active substance in vivo over a prolonged period of time.
CN106390192a discloses a biological bone cement, which consists of powder and liquid, wherein the weight percentage of the powder is: 0.1-50% of calcium sulfate; 0.01-10% of hydrophilic biological material; 0.1-50% of acrylic resin; 1.0-30% of developer; initiator 0.001-5%; the liquid comprises the following components in percentage by weight: 10-99% of acrylic monomer; 0.01-5% of promoter; 0-1% of antioxidant. However, the calcium sulfate in the material is not a main material and is only used as an additive; the fracture strength is too high, the application range is that the bone of the body is used, and the bone can not be used for the jawbone of the oral cavity. Moreover, the release temperature of the material during the reaction is at least 48 ℃, and if the material is placed at the bone defect during the reaction, the cell death around the wound is easy to cause; in addition, it has a long curing time.
The atelopeptide collagen has high moisturizing ability and excellent biocompatibility, and is often used as a tissue engineering scaffold for culturing cells. On the other hand, atelocollagen has a positive effect of guiding tissue regeneration, and it can promote osteoblast differentiation and type I collagen production, thereby playing a role in inducing bone regeneration. Thus, the inventors' research team utilized these features to improve and enhance CAS performance using atelocollagen as a solvent to mix with CAS.
The research team in which the inventors participated in was in Injectable Porous Bioresorbable Composite Containing Fluvastatin for Bone Augmentation (ACS biomatter. Sci. Eng.2019,5, 5422-5429) used calcium sulfate, liquid atelocollagen and fluvastatin, but the test was performed after the samples were left at 37 ℃ for 7 days. The product has long hardening time, and soft tissue pressure can deform the material during suturing, so that the material treatment effect is reduced, and the possibility of use during operation is reduced.
Therefore, how to improve the above materials is one of the technical problems to be solved in the art.
Disclosure of Invention
Aiming at the problems, the invention aims to provide a mouldable porous biological composite bone filling material containing statin drugs and a preparation method thereof.
In order to solve the technical problems, the application provides the following technical scheme:
a preparation method of a statin-containing shapeable porous biological composite bone filling material comprises the following steps:
(1) The anhydrous calcium sulfate powder and the statin powder are weighed according to a proportion, then the anhydrous calcium sulfate powder and the statin powder are mixed and placed on a mixing plate, and after being mixed repeatedly by a cutter adjusting level at normal temperature, the mixture is mixed repeatedly up and down; wherein, the weight ratio of the anhydrous calcium sulfate powder to the statin powder is 1: 0.005-0.01;
(2) Rapidly weighing the end-removed polypeptide collagen gel in proportion at normal temperature, wherein the end-removed polypeptide collagen gel is in a solid jelly shape; the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and statin mixed powder is 1: 2-2: 1, a step of;
(3) Placing the weighed end-removed polypeptide collagen gel on a stirring plate, and repeatedly pressing and stirring by a knife at normal temperature to obtain the mouldable porous biological composite bone filling material containing statin drugs.
In the step (1), the horizontal repeated mixing is carried out for 20-30s by using a cutter at a speed of 1-3 times/s, and then the vertical repeated mixing is carried out for 20-30s.
Wherein in the step (3), the cutter is repeatedly pressed and stirred for 25-90s at the speed of 0.5-1 times/s.
Wherein the purity of the anhydrous calcium sulfate powder is more than or equal to 99.99 percent.
Wherein the purity of the statin powder is more than or equal to 98 percent.
Wherein, the origin of the polypeptide collagen gel with the end removed is cow or pig, the purity is more than 99 percent, and the fat content is less than 1 percent; the molecular weight is 270-300KD, and the storage temperature is 2-8deg.C.
Wherein the temperature at normal temperature is 18-37 ℃.
Wherein the statin comprises fluvastatin or rosuvastatin.
Compared with the prior art, the statin drug-containing shapable porous biological composite bone filling material and the preparation method thereof have at least the following beneficial effects:
the statin medicine-containing shapable porous biological composite bone filling material can reach the compressive strength of 20Mpa in 1 hour (the actual solidification time is less than 30 minutes, and the test is completed in 30 minutes after solidification), can be hardened (with a certain supporting property) in a very short time when being applied to clinical treatment and placed at a bone defect, so that the soft tissue pressure can not deform the material when being sutured, the material treatment effect is improved, and the possibility of using the material during operation is greatly improved.
The prolonged operation time and the curing speed of the material are relatively contradictory properties, and the material of the invention well solves the contradiction. The material increases the operation time in the process of filling the bone defect part, and shortens the self-curing time after the filling operation is finished.
The statin medicine-containing shapable porous biological composite bone filling material has the characteristics of shapable property, absorbability, porous carrying property, prolonged operation time, shortened material curing speed, improved bone formation level and the like, and can play a role in guiding bone regeneration well.
The following describes the statin-containing plastic porous biological composite bone filling material and the preparation method thereof with reference to the accompanying drawings.
Drawings
FIG. 1 is a photograph showing the process of formulating a statin-containing moldable porous biocomposite bone filler material; wherein A: schematic diagram before material mixing; b: schematic of the gel of the polypeptide collagen with the end removed before mixing; c: schematic of the morphology of the mixed materials; d: material filling to a circular glass mold schematic;
FIG. 2 is a photograph showing the temperature of the process of compounding a statin-containing moldable porous biocomposite bone filler material; wherein A: measuring the temperature at the beginning of material mixing; b: measuring the highest temperature in the mixing process of materials; c: measuring the temperature when the material is not solidified; d: measuring the temperature of the solidified material; e: measuring the temperature after the material is solidified for 1 hour;
FIG. 3 is a photograph of a compressive strength test;
FIG. 4 is a statistical graph of the experimental results of examples 1-10.
Detailed Description
Example 1
Referring to fig. 1-2, a method for preparing a fluvastatin-containing shapable porous biological composite bone filler material comprises the following steps:
(1) The anhydrous calcium sulfate powder and the fluvastatin powder are weighed according to the proportion, then the anhydrous calcium sulfate powder and the fluvastatin powder are mixed and placed on a mixing plate, a stainless steel knife is used for mixing for 20-30s at the speed of 1-3 times per second at the normal temperature (18-37 ℃), and then the mixture is mixed up and down repeatedly for 20-30s. Wherein, the weight ratio of the anhydrous calcium sulfate powder (the purity is more than or equal to 99.99%) to the fluvastatin powder (the purity is more than or equal to 98%) is 1:0.005;
(2) Rapidly weighing the end-removed polypeptide collagen gel in proportion at normal temperature (18-37 ℃), wherein the end-removed polypeptide collagen gel is in a solid jelly shape; the weight ratio of the terminal polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 1:1, a step of;
(3) Placing the weighed end-removed polypeptide collagen gel on a stirring plate, repeatedly pressing and stirring at a speed of 0.5-1 time/s for 25-90s by using a stainless steel knife at normal temperature to obtain the fluvastatin-containing mouldable porous biological composite bone filling material, namely filling the bone defect part.
Wherein the source of the polypeptide collagen gel is cow or pig, the purity is more than 99%, the fat content is less than 1%, the molecular weight is 270-300KD, and the storage temperature is 2-8deg.C.
Example 2
Compared with example 1, the difference is that: the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 3:2.
example 3
Compared with example 1, the difference is that: the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 2:1.
example 4
Compared with example 1, the difference is that: the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 2:3.
example 5
Compared with example 1, the difference is that: the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 1:2.
example 6
Compared with example 1, the difference is that: the weight ratio of the anhydrous calcium sulfate powder (the purity is more than or equal to 99.99%) to the fluvastatin powder (the purity is more than or equal to 98%) is 1:0.01.
example 7
Compared with example 1, the difference is that: the weight ratio of the anhydrous calcium sulfate powder (the purity is more than or equal to 99.99%) to the fluvastatin powder (the purity is more than or equal to 98%) is 1:0.01; the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 3:2.
example 8
Compared with example 1, the difference is that: the weight ratio of the anhydrous calcium sulfate powder (the purity is more than or equal to 99.99%) to the fluvastatin powder (the purity is more than or equal to 98%) is 1:0.01; the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 2:1.
example 9
Compared with example 1, the difference is that: the weight ratio of the anhydrous calcium sulfate powder (the purity is more than or equal to 99.99%) to the fluvastatin powder (the purity is more than or equal to 98%) is 1:0.01; the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 2:3.
example 10
Compared with example 1, the difference is that: the weight ratio of the anhydrous calcium sulfate powder (the purity is more than or equal to 99.99%) to the fluvastatin powder (the purity is more than or equal to 98%) is 1:0.01; the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 1:2.
the shapeable time, setting time, average temperature, maximum temperature, compressive strength (measurement completed within 30 minutes after setting) and new bone formation rate of examples 1 to 10 were tested, the compressive strength test is shown in fig. 3, and the results are shown in fig. 4 and table 1.
TABLE 1
Note that: CAS: anhydrous calcium sulfate; FS: fluvastatin; ACG: an end-removed polypeptide collagen gel.
Compared with the product of the inventor in Injectable Porous Bioresorbable Composite Containing Fluvastatin for Bone Augmentation (ACS biomatter. Sci. Eng.2019,5, 5422-5429), the solidification time of the product prepared by the invention is greatly shortened, and other indexes are improved to different degrees.
Anhydrous calcium sulfate was identified in 2019: the optimal result is 3:2, but the setting time still needs 34 minutes, and researches show that the setting time is most suitable in clinical treatment. Other proportions, although short in setting time, have poor physical properties and cannot be used. In oral clinical treatment, the operation time is not too long,the setting time of the material should not be too long. If the bone filler material is used to suture the wound before it is not coagulated, the material is easily deformed by external conditions such as soft tissue, resulting in an unsatisfactory therapeutic effect. In the experiment of the invention, the solidification time is greatly shortened under the condition that the performance precursors of other aspects of the material are not influenced, and in the optimal scheme (the proportion of 1:1 of the embodiment 1), the solidification time is shortened to about 11 minutes. The mechanism of analysis is roughly: the gel is susceptible to cations and the gel strength increases with increasing cation concentration over a range. When the gel contacts Ca 2+ When Ca is 2+ Induces formation of a good uniform network structure, and Ca 2+ The repulsive force among macromolecules in the gel can be reduced, so that the inside of the gel is twisted and wound to form a network structure, and anhydrous calcium sulfate particles are better wrapped, so that the reaction of the gel and the anhydrous calcium sulfate particles is faster and more uniform, and the material performance is improved due to the mutual influence of the gel and the anhydrous calcium sulfate particles.
In addition, in order to achieve the desired effect, the in vitro experiments in 2019 publication were performed after the materials were synthesized and left to stand at 37℃for 7 days (see, e.g., 2.3.1, 2.3.2, and 2.4, respectively, for example, 2.3.1, for "7 days in a 37℃vacuum oven", 2.3.2, respectively, for mechanical properties (i.e., compressive strength) for "cylindrical test specimen made as described above", and 2.2, for "mold was placed in a 37℃vacuum oven", for which the solidification conditions were more stringent and complicated than the present invention.
The above examples are only illustrative of the preferred embodiments of the present invention and are not intended to limit the scope of the present invention, and various modifications and improvements made by those skilled in the art to the technical solution of the present invention should fall within the scope of protection defined by the claims of the present invention without departing from the spirit of the present invention.
Claims (10)
1. The preparation method of the statin-containing shapeable porous biological composite bone filling material is characterized by comprising the following steps:
(1) The anhydrous calcium sulfate powder and the statin powder are weighed according to a proportion, then the anhydrous calcium sulfate powder and the statin powder are mixed and placed on a mixing plate, and after being mixed repeatedly by a cutter adjusting level at normal temperature, the mixture is mixed repeatedly up and down; wherein, the weight ratio of the anhydrous calcium sulfate powder to the statin powder is 1: 0.005-0.01;
(2) Rapidly weighing the end-removed polypeptide collagen gel in proportion at normal temperature, wherein the end-removed polypeptide collagen gel is in a solid jelly shape; the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and statin mixed powder is 1: 2-2: 1, a step of;
(3) Placing the weighed end-removed polypeptide collagen gel on a stirring plate, and repeatedly pressing and stirring by a knife at normal temperature to obtain the mouldable porous biological composite bone filling material containing statin drugs.
2. The method for preparing the statin-containing shapable porous biological composite bone filler material according to claim 1, wherein the method comprises the following steps: in the step (1), the cutter is used for horizontally and repeatedly stirring for 20-30s at the speed of 1-3 times/s, and then the cutter is used for repeatedly stirring for 20-30s up and down.
3. The method for preparing the statin-containing shapable porous biological composite bone filler material according to claim 1, wherein the method comprises the following steps: in the step (3), the mixing is repeatedly pressed and stirred for 25-90s at the speed of 0.5-1 times/s by a cutter.
4. The method for preparing the statin-containing shapable porous biological composite bone filler material according to claim 1, wherein the method comprises the following steps: the purity of the anhydrous calcium sulfate powder is more than or equal to 99.99 percent.
5. The method for preparing the statin-containing shapable porous biological composite bone filler material according to claim 1, wherein the method comprises the following steps: the purity of the statin powder is more than or equal to 98 percent.
6. The method for preparing the statin-containing shapable porous biological composite bone filler material according to claim 1, wherein the method comprises the following steps: the source of the end-removed polypeptide collagen gel is cattle or pigs, the purity is more than 99%, and the fat content is less than 1%.
7. The method for preparing the statin-containing plastic porous biological composite bone filler material according to claim 6, wherein the method comprises the following steps: the molecular weight of the polypeptide collagen gel with the end removed is 270-300KD, and the storage temperature is 2-8 ℃.
8. The method for preparing the statin-containing shapable porous biological composite bone filler material according to claim 1, wherein the method comprises the following steps: the temperature at the normal temperature is 18-37 ℃.
9. The method for preparing the statin-containing shapable porous biological composite bone filler material according to claim 1, wherein the method comprises the following steps: the statin comprises fluvastatin or rosuvastatin.
10. The moldable porous biocomposite bone filler material containing statin prepared by the method of any of claims 1-9.
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