WO2023216069A1 - Composition orthopédique plastique présentant une résistance à l'érosion - Google Patents

Composition orthopédique plastique présentant une résistance à l'érosion Download PDF

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Publication number
WO2023216069A1
WO2023216069A1 PCT/CN2022/091740 CN2022091740W WO2023216069A1 WO 2023216069 A1 WO2023216069 A1 WO 2023216069A1 CN 2022091740 W CN2022091740 W CN 2022091740W WO 2023216069 A1 WO2023216069 A1 WO 2023216069A1
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Prior art keywords
composition
calcium sulfate
orthopedic
bone
plastic
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PCT/CN2022/091740
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English (en)
Chinese (zh)
Inventor
方旭伟
蒋孝鸿
苏真莹
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台北科技大学
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Priority to PCT/CN2022/091740 priority Critical patent/WO2023216069A1/fr
Publication of WO2023216069A1 publication Critical patent/WO2023216069A1/fr

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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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/02—Surgical adhesives or cements; Adhesives for colostomy devices containing inorganic materials
    • 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
    • A61L27/02—Inorganic materials
    • 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
    • A61L27/02—Inorganic materials
    • A61L27/12—Phosphorus-containing materials, e.g. apatite
    • 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
    • A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix

Definitions

  • the present invention relates to a bone filling material, and in particular to a plastic orthopedic composition with erosion resistance.
  • Calcium sulfate has been used to help bone repair for a long time. Because of its good osteoconductivity and biocompatibility, it is mainly used as a cavity filler. It can help restore the shape and contour of the bone and prevent the invasion of soft tissue and its degradation. The rate can match the rate of new bone formation and aid vascular infiltration.
  • the dissociated calcium ions on the surface reach a specific concentration gradient and will combine with the phosphate ions normally present in the body to produce calcium phosphate precipitation.
  • phosphate precipitation produces secondary osteoconductivity, allowing osteoblasts to adhere.
  • Calcium sulfate can be divided into calcium sulfate dihydrate (CaSO 4 ⁇ 2H 2 O), calcium sulfate hemihydrate (CaSO 4 ⁇ 0.5H 2 O) and anhydrous calcium sulfate (Calcium sulfate hemihydrate, CaSO 4 ⁇ 0.5H 2 O) according to the amount of crystal water.
  • Calcium sulfate Dehydrate three kinds, calcium sulfate dihydrate can be called raw gypsum, calcium sulfate hemihydrate can also be called gypsum of paris. Both calcium sulfate dihydrate and calcium sulfate hemihydrate can be used in bone filling materials.
  • hydroxylapatite is the main inorganic component of human bones and has good biocompatibility. Its calcium-to-phosphorus ratio is 1.67, which is consistent with that of bones.
  • the mineral composition is very similar and can bond with the bone and become part of the bone.
  • the mechanical strength is too low. Therefore, when used as a composite material with calcium sulfate, increasing the proportion of calcium sulfate will increase the mechanical strength of the implant [4 ], and when calcium sulfate degrades, holes will also be created for new bone to grow in.
  • Calcium sulfate hemihydrate adds acellular bone matrix: In addition to providing biocompatibility and osteoconductivity, acellular bone matrix also has osteoinductivity and growth factors [7], but its main disadvantage is poor mechanical strength. , infection risks and sources of acquisition, etc. Therefore, composite aggregates adding calcium sulfate hemihydrate can provide initial mechanical strength and have the effect of initial vascular infiltration [8].
  • calcium sulfate products are mostly injection type. Calcium phosphate is available in tablet, sheet, columnar, injection and other dosage forms. There are also some bioglass (calcium silicate), polymer materials ( Polylactic acid, polyglycolic acid) are added to bone filling materials. Usually for injection-type or hydration-type materials, you need to mix powder and liquid into a paste before use, and then add it to the injection container or a thicker clay-like material that can match the shape of the affected area, mold it into the desired shape, and then fill it in. .
  • bioglass calcium silicate
  • polymer materials Polylactic acid, polyglycolic acid
  • the powder and water are not mixed evenly, which may cause changes in material properties, causing changes in the original curing time, injection properties, and mechanical properties.
  • the mixing methods of currently commercially available products are different.
  • Product A requires mixing the powder and water evenly within the specified time of one minute, and then waiting for three minutes before it can be filled into the affected area.
  • Product B needs to be soaked in powder and water for three minutes and mixed for one minute before it can be filled into the affected area.
  • premixed dosage forms are produced.
  • Premixed dosage forms generally refer to the fact that when doctors open the package, they can directly fill it without the complicated mixing of powder and water. The mixing time of powder and water can be omitted, which not only facilitates the doctor's Use can also reduce the risk of disease.
  • the inventor of the present invention has conducted relevant research and improvement on orthopedic compositions based on years of research experience; therefore, the main purpose of the present invention is to provide a plastic orthopedic composition with erosion resistance and its Preparation.
  • a plastic orthopedic composition with good erosion resistance is provided.
  • the present invention is about providing a plastic orthopedic composition, which includes: a powder composition, which includes calcium sulfate hemihydrate (CaSO 4 ⁇ 0.5H 2 O), tricalcium phosphate ( ⁇ -tricalcium phosphate ( ⁇ -TCP) and hydroxypropyl methylcellulose (HPMC); and a solvent including glycerol (Glycerol) and water.
  • a powder composition which includes calcium sulfate hemihydrate (CaSO 4 ⁇ 0.5H 2 O), tricalcium phosphate ( ⁇ -tricalcium phosphate ( ⁇ -TCP) and hydroxypropyl methylcellulose (HPMC); and a solvent including glycerol (Glycerol) and water.
  • the ratio of the calcium sulfate hemihydrate to the tricalcium phosphate is about 1:1 (g/g).
  • the weight percentage of hydroxypropyl methylcellulose is 1 to 6%.
  • the weight percentage of hydroxypropyl methylcellulose is 1 to 4%.
  • the volume percentage of glycerin is about 70-99%.
  • the volume percentage of glycerol is about 85%.
  • a bone filling kit which includes the moldable orthopedic composition according to the present invention stored in a separate container.
  • a plastic orthopedic composition is further provided for medical use in treating bone defects.
  • Figure 1 shows the washout percentage of orthopedic compositions that both contain 70% glycerol (Glycerol), but contain different proportions of hydroxypropyl methylcellulose (HPMC), immersed in simulated body fluids for 15 minutes or 1 hour.
  • **P ⁇ 0.01 is the difference between soaking for 15 minutes and 1 hour for the same formula.
  • Figure 2 shows the washout percentage of orthopedic compositions that both contain 85% glycerol (Glycerol), but contain different proportions of hydroxypropyl methylcellulose (HPMC), immersed in simulated body fluids for 15 minutes or 1 hour.
  • Glycerol 85% glycerol
  • HPMC hydroxypropyl methylcellulose
  • Figure 3 shows the erosion percentage of bone filling materials, which all contain 99% glycerol (Glycerol) but contain different proportions of hydroxypropyl methylcellulose (HPMC), soaked in simulated body fluids for 15 minutes or 1 hour. Using t test statistics, there is no statistical difference between soaking for 15 minutes and 1 hour.
  • Glycerol 99% glycerol
  • HPMC hydroxypropyl methylcellulose
  • the term "about” is used to indicate that a numerical value includes errors in material proportions, drug concentration values, or variations that exist between experimental subjects. Typically the term is intended to cover greater or less than 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14 %, 15%, 16%, 17%, 18%, 19% or 20% variability, as appropriate.
  • orthopedic composition include, but are not limited to, joint implants, spinal implants, craniofacial implants, dental implants, foot and ankle implants, or trauma implants. Objects (bone plates, bone nails), etc.
  • injected include the administration of any composition, such as injection, immersion or delivery to an individual via any delivery device .
  • the object of the present invention is to provide a plastic orthopedic composition, which includes: a powder composition, which includes calcium sulfate hemihydrate (CaSO 4 ⁇ 0.5H 2 O), tricalcium phosphate ( ⁇ -tricalcium phosphate, ⁇ -TCP) and hydroxypropyl methylcellulose (Hydroxypropyl Methylcellulose, HPMC); and a solvent including glycerol (Glycerol) and water.
  • a powder composition which includes calcium sulfate hemihydrate (CaSO 4 ⁇ 0.5H 2 O), tricalcium phosphate ( ⁇ -tricalcium phosphate, ⁇ -TCP) and hydroxypropyl methylcellulose (Hydroxypropyl Methylcellulose, HPMC); and a solvent including glycerol (Glycerol) and water.
  • the ratio of calcium sulfate hemihydrate to tricalcium phosphate is approximately 1:1 (g/g).
  • the weight percentage of hydroxypropyl methylcellulose in the powder composition is about 1 to 6%, preferably about 1 to 4%, and most preferably about 2 to 4%.
  • the weight percentage of hydroxypropyl methylcellulose exceeds 6%, the orthopedic composition of the present invention will be excessively sticky, resulting in poor operability and failure to become a plastic orthopedic composition.
  • the optimal liquid-to-powder ratio of the powder composition of the present invention and the solvent is about 0.35 ml/g.
  • the weight percentage of calcium sulfate hemihydrate in the powder composition of the present invention is about 47, 47.5, 48, 48.5, 49, 49.5%, preferably about 48, 48.5, 49, 49.5%, most preferably about 48, 48.5, 49%;
  • the weight percentage of tricalcium phosphate is about 47, 47.5, 48, 48.5, 49, 49.5%, preferably about 48, 48.5, 49, 49.5%, most preferably about 48, 48.5, 49%; hydroxyl
  • the weight percentage of propyl methylcellulose is about 1, 2, 3, 4, 5, 6%, preferably about 1, 2, 3, 4%, and most preferably about 2, 3, 4%.
  • the volume percentage of glycerin in the solvent is about 70% to 99%, preferably about 85%.
  • the volume percentage of glycerin is less than 70%, the orthopedic composition of the present invention is prone to disintegration and cannot be effectively formed, and will disintegrate within one day and cannot be formed.
  • the orthopedic composition of the present invention may need to further add a dispersant for uniformly dispersing the powder, a suspension stabilizer for maintaining the suspended state of the powder particles, and pharmaceutical agents (for example, bone cell formation/differentiation accelerator, angiogenesis accelerator, etc.), nutrients, antibacterial agents, antibiotics or additives (such as curing accelerator, curing retardant, etc.).
  • a dispersant for uniformly dispersing the powder for example, bone cell formation/differentiation accelerator, angiogenesis accelerator, etc.
  • pharmaceutical agents for example, bone cell formation/differentiation accelerator, angiogenesis accelerator, etc.
  • nutrients for example, antibacterial agents, antibiotics or additives (such as curing accelerator, curing retardant, etc.).
  • Another object of the present invention is to provide a bone filling kit, which includes the moldable orthopedic composition according to the present invention stored in a separate container.
  • the inner diameter of the injection port of a traditional bone filling syringe that is currently commonly used is about 3mm. Therefore, the particle size of the above-mentioned calcium sulfate hemihydrate, tricalcium phosphate and hydroxypropyl methylcellulose will also affect the injection of the orthopedic composition. of liquidity. In order to make the orthopedic composition of the present invention have better fluidity, it can be easily extruded.
  • the calcium sulfate hemihydrate that can be used in the present invention preferably has an average particle size of 20 to 40 ⁇ m
  • the tricalcium phosphate preferably has an average particle size of 20 to 40 ⁇ m
  • the hydroxypropyl methylcellulose preferably has an average particle size of 100 ⁇ 200 ⁇ m average particle size.
  • Another object of the present invention is to provide a plastic orthopedic composition for medical use in the treatment of bone defects.
  • the preparation method of the orthopedic composition is based on the weight percentage shown in Table 1, adding calcium sulfate hemihydrate (average particle size 20-40 ⁇ m), tricalcium phosphate (average particle size 20-40 ⁇ m) and hydroxypropyl methylcellulose After the powder (average particle size 100-200 ⁇ m) is fully mixed, mix glycerol and water thoroughly according to the volume percentage of the solvent shown in Table 1, and add it to the powder at room temperature, stir evenly with a spoon to form a Shapeable orthopedic composition with erosion resistance.
  • the moldable orthopedic composition was placed in a 304 stainless steel mold (diameter 6 mm, height 3 mm) to form a cylinder and weighed. It is then immersed in the center of the bottom of a cylinder containing simulated body fluids.
  • the cylinder has a diameter of 20 mm and a height of 20 mm, and is placed in an environment of 37 degrees Celsius.
  • the ratio of orthopedic composition and simulated body fluid is 0.2 g of bone filling material/1 ml of simulated body fluid.
  • the reason for using simulated body fluid is that its ion concentration is similar to that of human plasma [12].
  • the simulated body fluid is removed, 1 ml of 99.5% alcohol is added, and left at room temperature for 30 seconds. Then remove the alcohol, place the main body of the undisintegrated bone filling material (a cylinder with a diameter of 6 mm), and the disintegrated debris into an oven at 50 degrees Celsius for 3 days. Weigh the main body of the undisintegrated bone filling material to The weight loss is obtained by subtracting the weight of the main body of the undisintegrated bone filling material from the weight before the experiment, and then divided by the weight before the experiment to obtain the erosion percentage. Therefore, the lower the erosion percentage, the better the erosion resistance of the formula.
  • the orthopedic composition when the proportion of glycerol is less than 70%, that is, when the glycerol is 50% or 30%, the orthopedic composition cannot be stored for more than 1 day, that is, it will disintegrate within 1 day and cannot be formed.
  • the orthopedic composition When the glycerol ratio is higher than 70%, the orthopedic composition has the ability to be molded and can be stored at room temperature for at least 21 days.
  • the orthopedic composition of the present invention As shown in Table 7, compared with commercially available Gurai bone meal ( Compared with Bone Graft Substitute), the orthopedic composition of the present invention has slightly higher erosion resistance than Gurai bone powder. It shows that the orthopedic composition of the present invention has good erosion resistance and plasticity.
  • the present invention has a plastic orthopedic composition with erosion resistance, which is mainly composed of calcium sulfate and calcium phosphate (tetracalcium phosphate and dicalcium phosphate), and is added with citric acid and hydroxypropyl methyl fiber. After conditioning, it can achieve effective anti-erosion effect and have better repair function.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
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  • Engineering & Computer Science (AREA)
  • Composite Materials (AREA)
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  • Materials For Medical Uses (AREA)

Abstract

La présente invention concerne une composition orthopédique plastique présentant une résistance à l'érosion et comprenant : une composition de poudre comprenant de l'hémihydrate de sulfate de calcium, du phosphate tricalcique et de l'hydroxypropylméthylcellulose ; et un solvant comprenant du glycérol et de l'eau. La composition orthopédique présente une bonne résistance à l'érosion. La présente invention concerne également un procédé de préparation de ladite composition orthopédique, ainsi qu'un kit de comblement osseux comprenant la composition.
PCT/CN2022/091740 2022-05-09 2022-05-09 Composition orthopédique plastique présentant une résistance à l'érosion WO2023216069A1 (fr)

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Application Number Priority Date Filing Date Title
PCT/CN2022/091740 WO2023216069A1 (fr) 2022-05-09 2022-05-09 Composition orthopédique plastique présentant une résistance à l'érosion

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PCT/CN2022/091740 WO2023216069A1 (fr) 2022-05-09 2022-05-09 Composition orthopédique plastique présentant une résistance à l'érosion

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118022050A (zh) * 2024-01-26 2024-05-14 北京纳通医学研究院有限公司 一种钉道增强用骨水泥

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6793725B2 (en) * 2001-01-24 2004-09-21 Ada Foundation Premixed calcium phosphate cement pastes
CN101366971A (zh) * 2008-10-15 2009-02-18 苗军 可注射防水型磷酸钙骨水泥
CN101668550A (zh) * 2007-04-20 2010-03-10 创新生物陶瓷公司 预混合的生物学水凝性粘固粉糊剂组合物及其应用
CN103349793A (zh) * 2005-09-09 2013-10-16 阿格诺沃斯健康关爱公司 复合骨移植替代物水泥以及由其制得的制品
EP1622843B1 (fr) * 2003-04-08 2015-06-03 Ada Foundation Pates pour greffe osseuse autodurcissantes premelangees

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6793725B2 (en) * 2001-01-24 2004-09-21 Ada Foundation Premixed calcium phosphate cement pastes
EP1622843B1 (fr) * 2003-04-08 2015-06-03 Ada Foundation Pates pour greffe osseuse autodurcissantes premelangees
CN103349793A (zh) * 2005-09-09 2013-10-16 阿格诺沃斯健康关爱公司 复合骨移植替代物水泥以及由其制得的制品
CN101668550A (zh) * 2007-04-20 2010-03-10 创新生物陶瓷公司 预混合的生物学水凝性粘固粉糊剂组合物及其应用
CN101366971A (zh) * 2008-10-15 2009-02-18 苗军 可注射防水型磷酸钙骨水泥

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118022050A (zh) * 2024-01-26 2024-05-14 北京纳通医学研究院有限公司 一种钉道增强用骨水泥

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