CN109529110A - Porous nano hydroxyapatite sustained-release gel preparation method - Google Patents

Porous nano hydroxyapatite sustained-release gel preparation method Download PDF

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Publication number
CN109529110A
CN109529110A CN201811502474.0A CN201811502474A CN109529110A CN 109529110 A CN109529110 A CN 109529110A CN 201811502474 A CN201811502474 A CN 201811502474A CN 109529110 A CN109529110 A CN 109529110A
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porous nano
nano hydroxyapatite
hydroxyapatite
preparation
sustained
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林光明
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Shanghai Moyang Biotechnology Co Ltd
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Shanghai Moyang Biotechnology Co Ltd
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Priority to CN201811502474.0A priority Critical patent/CN109529110A/en
Publication of CN109529110A publication Critical patent/CN109529110A/en
Priority to CN201910323669.7A priority patent/CN110538346B/en
Priority to BE20195545A priority patent/BE1027074B1/en
Priority to BE20195546A priority patent/BE1027375B1/en
Priority to NL2023785A priority patent/NL2023785B1/en
Pending legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
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    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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    • 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
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
    • 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
    • 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
    • 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
    • A61L27/58—Materials at least partially resorbable by the body
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    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602—Type of release, e.g. controlled, sustained, slow
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    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/12—Materials or treatment for tissue regeneration for dental implants or prostheses

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Abstract

The invention proposes a kind of porous nano hydroxyapatite sustained-release gel preparation methods.Hydroxyapatite composite microspheres even size distribution obtained by the method for the present invention, 10-100 μm of particle size distribution, 20-60 μm of medium particle diameter.The suspension stability of suspension can effectively be enhanced by increasing organic phase in hybrid technique, and prepared Microsphere Size is evenly distributed and partial size is big compared with Microsphere Size made from conventionally spray-dried method, can be used as injection inner support material；Microballoon is spherical preferably, have high hole can reinforcing material syringeability, be conducive to the metabolism time for accelerating drug, maintain vivo medicine concentration to stablize effectively, drug release property is good.

Description

Porous nano hydroxyapatite sustained-release gel preparation method
Technical field
The invention belongs to field of material technology more particularly to a kind of porous nano hydroxyapatite sustained-release gel preparation sides Method.
Background technique
Hydroxyapatite (HAP) is since its structure and ingredient are all very close to body bone tissue, so as to cause biology Material and the extensive concern of medical expert.HAP is applied to orthopaedics, the department of stomatology and plastic surgery as filling material of bone, in addition HAP The carriers such as growth factor, drug are also act as, and show good sustained release performance.To meet different clinical demands, study Personnel prepare the HAP of different shapes such as rodlike, dumbbell shaped, spherical, sheet.Ball shaped hydroxy-apatite due to its mobility is strong, Large specific surface area, bulk density are high, have been now subjected to great concern.
There are many kinds of the methods for preparing hydroxyapatite micro-sphere, such as hydro-thermal method, emulsion-crosslinking method, microwave method, spray drying Method.Wherein emulsion-crosslinking method is chiefly used in the preparation of organo-mineral complexing hydroxyapatite micro-sphere, but there are microballoons easily to roll into a ball for the method Poly-, crosslinking agent is difficult to remove the problems such as complete.Spray drying process have it is easy to operate, without adding toxic reagent, easily industrialize The advantages that, but its there is also microballoons it is in irregular shape, size distribution is wide the defects of.And the method for preparing porous hydroxyapatite has Chemical blowing process, pore creating material method, Polymeric sponge method, organic formwork method.When chemical blowing process prepares porous hydroxyapatite It is more difficult to control for the aperture and voidage of porous material, and the hole of porous material that this method obtains is largely closing , the perforation rate of stomata is poor.Porous hydroxyapatite porosity obtained by pore creating material method is not high, and pore diameter range distribution compared with It is wide.Polymeric sponge method easily generates fine crack during drying and sintering on biomaterial, reduces porous The intensity of hydroxyapatite.Organic formwork method needs to select suitable surfactant, and selected surface is living in some cases Property agent may it is toxic, need to remove at high temperature, this reduces the bioactivity of porous hydroxyapatite.
Summary of the invention
To overcome the problems of the prior art, the invention proposes a kind of systems of porous nano hydroxyapatite sustained-release gel Preparation Method, which is characterized in that the preparation method includes the following steps:
Step 1: nanometer hydroxyapatite powder is added to the water the hydroxyapatite slurry for being formulated as content 10-40% (w/v) Material；
Step 2: hydroxyapatite slurry, pore creating material and oleic acid three are mixed in proportion, put ball milling 6- in the ball mill 24 hours, uniform suspension is obtained after ball milling；
Step 3: suspension addition organic compounding agent is mixed in proportion, is then placed in 30-80 DEG C of water-bath Interior stirring and dissolving；
Step 4: the suspension being uniformly dissolved carries out spray drying granulation, obtains solidification microballoon；
Step 5: solidification microballoon obtained is subjected to high temperature dewaxing treatment, then is calcined under the high temperature conditions, high hole is made Gap rate porous nano hydroxyapatite micro-sphere；
Step 6: drug is embedded in the high porosity porous nano hydroxyapatite micro-sphere；
Step 7: prepare evenly dispersed has water soluble algae hydrochlorate and high porosity porous nano hydroxyapatite micro- respectively The mixing suspension of ball, and configuration water-soluble calcium saline solution；
Step 8: water-soluble calcium saline solution is added in mixing suspension in a manner of spraying droplet, makes the mixing It after suspension pension gelation, then immerses in water-soluble calcium salting liquid 10 minutes~24 hours, it is slow to obtain porous nano hydroxyapatite Release gel.
Preferably, the weight ratio of the hydroxyapatite slurry and pore creating material is 80~95:20~5.
Preferably, the organic compounding agent is gelatin, Arabic gum, chitosan, sodium alginate, polylactic acid, natural fiber One of element or a variety of any combination.
Preferably, the pore creating material is any one or more of any combination of carbon dust, graphite powder, acetylene black.
Preferably, the stirring rate 200-600r/min of water-bath, dissolution time 2-5h.
Preferably, the temperature of dewaxing is 800~1500 DEG C, and the dewaxing treatment time is 30~120min.
Preferably, the high-temperature calcination temperature is 1000~1500 DEG C, and calcination time is 45~180min.
Preferably, 250-500 degrees Celsius of vapo(u)rizing temperature, charging rate 10-30ml/min, atomisation pressure 0.05-0.1MPa.
Preferably, in the mixing suspension, the molar concentration of water soluble algae hydrochlorate is 0.01~10 mol/L.
Preferably, the mass ratio of the high porosity porous nano hydroxyapatite micro-sphere and water soluble algae hydrochlorate is 1: 10~10:1.
Compared with prior art, beneficial effects of the present invention: hydroxyapatite composite microspheres obtained by the method for the present invention Even size distribution, 10-100 μm of particle size distribution, 20-60 μm of medium particle diameter.Increasing organic phase in hybrid technique can be effective Enhance the suspension stability of suspension, prepared Microsphere Size is evenly distributed and partial size is compared with microballoon made from conventionally spray-dried method Size is big, can be used as injection inner support material；Microballoon is spherical preferably, have high hole can reinforcing material syringeability, favorably In the metabolism time for accelerating drug, vivo medicine concentration is maintained to stablize effectively, drug release property is good.
Detailed description of the invention
Fig. 1 is the different time drug accumulation release curve synoptic diagram of embodiment 1.
Fig. 2 is the different time drug accumulation release curve synoptic diagram of embodiment 2.
Fig. 3 is the different time drug accumulation release curve synoptic diagram of embodiment 3.
Specific embodiment
Below in conjunction with schematic diagram to the preparation method of porous nano hydroxyapatite sustained-release gel proposed by the present invention into Row more detailed description, which show the preferred embodiment of the present invention, it should be appreciated that those skilled in the art can modify The present invention of this description, and still realize advantageous effects of the invention.Therefore, following description should be understood as this field Technical staff's is widely known, and is not intended as limitation of the present invention.
Embodiment 1
A kind of porous nano hydroxyapatite sustained-release gel preparation method of the present embodiment, the method include following step It is rapid:
Step 1: nanometer hydroxyapatite powder is added to the water the hydroxyapatite slurry for being formulated as content 10-40% (w/v) Material；
Step 2: hydroxyapatite slurry, pore creating material and oleic acid three are mixed in proportion, wherein the hydroxyapatite The weight ratio of slurry and pore creating material is 80:20.It puts ball milling 6-24 hours in the ball mill, is uniformly suspended after ball milling Liquid；Pore creating material is carbon dust.
Step 3: suspension addition organic compounding agent is mixed in proportion, is then placed in 80 DEG C of water-baths Stirring and dissolving；Organic compounding agent is the combination of gelatin, Arabic gum, chitosan, sodium alginate.The stirring rate of water-bath 600r/min, dissolution time 5h.
Step 4: the suspension progress spray drying granulation being uniformly dissolved, 250 degrees Celsius of vapo(u)rizing temperature, charging rate 10ml/min, atomisation pressure 0.05MPa obtain solidification microballoon；
Step 5: carrying out high temperature dewaxing treatment for solidification microballoon obtained, and the temperature of dewaxing is 800 DEG C, when dewaxing treatment Between be 120min；It is calcined under the high temperature conditions again, high-temperature calcination temperature is 1000 DEG C, calcination time 120min, and institute is made The high porosity porous nano hydroxyapatite micro-sphere stated.High porosity porous nano hydroxyapatite obtained by the present embodiment 1 20~75 μm of microsphere particle size distribution, 20~60 μm of medium particle diameter, porosity 78%.
Step 6: drug is embedded in the high porosity porous nano hydroxyapatite micro-sphere；
Step 7: prepare evenly dispersed has water soluble algae hydrochlorate and high porosity porous nano hydroxyapatite micro- respectively The mixing suspension of ball, and configuration water-soluble calcium saline solution；
Step 8: water-soluble calcium saline solution is added in mixing suspension in a manner of spraying droplet, makes the mixing It after suspension pension gelation, then immerses in water-soluble calcium salting liquid 10 minutes~24 hours, it is slow to obtain porous nano hydroxyapatite Release gel.Through testing, the different time drug accumulation release curve synoptic diagram of the porous nano hydroxyapatite sustained-release gel As shown in Figure 1.
Embodiment 2
A kind of porous nano hydroxyapatite sustained-release gel preparation method of the present embodiment, the method include following step It is rapid:
Step 1: nanometer hydroxyapatite powder is added to the water the hydroxyapatite slurry for being formulated as content 10-40% (w/v) Material；
Step 2: hydroxyapatite slurry, pore creating material and oleic acid three are mixed in proportion, wherein the hydroxyapatite The weight ratio of slurry and pore creating material is 85:15.It puts ball milling 6-24 hours in the ball mill, is uniformly suspended after ball milling Liquid；Pore creating material is carbon dust.
Step 3: suspension addition organic compounding agent is mixed in proportion, is then placed in 50 DEG C of water-baths Stirring and dissolving；Organic compounding agent is the combination of gelatin, Arabic gum, chitosan, sodium alginate.The stirring rate of water-bath 250r/min, dissolution time 5h.
Step 4: the suspension progress spray drying granulation being uniformly dissolved, 250 degrees Celsius of vapo(u)rizing temperature, charging rate 10ml/min, atomisation pressure 0.05MPa obtain solidification microballoon；
Step 5: carrying out high temperature dewaxing treatment for solidification microballoon obtained, and the temperature of dewaxing is 1500 DEG C, when dewaxing treatment Between be 60min；It is calcined under the high temperature conditions again, high-temperature calcination temperature is 1000 DEG C, calcination time 180min, is made described High porosity porous nano hydroxyapatite micro-sphere.High porosity porous nano hydroxyapatite obtained by the present embodiment 2 is micro- 60~85 μm of ball particle size distribution, 20~60 μm of medium particle diameter, porosity 78%.
Step 6: drug is embedded in the high porosity porous nano hydroxyapatite micro-sphere；
Step 7: prepare evenly dispersed has water soluble algae hydrochlorate and high porosity porous nano hydroxyapatite micro- respectively The mixing suspension of ball, and configuration water-soluble calcium saline solution；
Step 8: water-soluble calcium saline solution is added in mixing suspension in a manner of spraying droplet, makes the mixing It after suspension pension gelation, then immerses in water-soluble calcium salting liquid 10 minutes~24 hours, it is slow to obtain porous nano hydroxyapatite Release gel.Through testing, the different time drug accumulation release curve synoptic diagram of the porous nano hydroxyapatite sustained-release gel As shown in Figure 2.
Embodiment 3
A kind of porous nano hydroxyapatite sustained-release gel preparation method of the present embodiment, the method include following step It is rapid:
Step 1: nanometer hydroxyapatite powder is added to the water the hydroxyapatite slurry for being formulated as content 10-40% (w/v) Material；
Step 2: hydroxyapatite slurry, pore creating material and oleic acid three are mixed in proportion, wherein the hydroxyapatite The weight ratio of slurry and pore creating material is 95:5.It puts ball milling 6-24 hours in the ball mill, uniform suspension is obtained after ball milling； Pore creating material is carbon dust.
Step 3: suspension addition organic compounding agent is mixed in proportion, is then placed in 50 DEG C of water-baths Stirring and dissolving；Organic compounding agent is the combination of gelatin, Arabic gum, chitosan, sodium alginate.The stirring rate of water-bath 250r/min, dissolution time 5h.
Step 4: the suspension progress spray drying granulation being uniformly dissolved, 250 degrees Celsius of vapo(u)rizing temperature, charging rate 10ml/min, atomisation pressure 0.1MPa obtain solidification microballoon；
Step 5: carrying out high temperature dewaxing treatment for solidification microballoon obtained, and the temperature of dewaxing is 1500 DEG C, when dewaxing treatment Between be 60min；It is calcined under the high temperature conditions again, high-temperature calcination temperature is 1000 DEG C, calcination time 180min, is made described High porosity porous nano hydroxyapatite micro-sphere.High porosity porous nano hydroxyapatite obtained by the present embodiment 3 is micro- 50~85 μm of ball particle size distribution, 20~60 μm of medium particle diameter, porosity 89%.High porosity manufactured in the present embodiment is more The porosity of hole nanometer hydroxyapatite microballoon is high, almost penetrates through, mechanical strength is moderate.
Step 6: drug is embedded in the high porosity porous nano hydroxyapatite micro-sphere；
Step 7: prepare evenly dispersed has water soluble algae hydrochlorate and high porosity porous nano hydroxyapatite micro- respectively The mixing suspension of ball, and configuration water-soluble calcium saline solution；
Step 8: water-soluble calcium saline solution is added in mixing suspension in a manner of spraying droplet, makes the mixing It after suspension pension gelation, then immerses in water-soluble calcium salting liquid 10 minutes~24 hours, it is slow to obtain porous nano hydroxyapatite Release gel.Through testing, the different time drug accumulation release curve synoptic diagram of the porous nano hydroxyapatite sustained-release gel As shown in Figure 3.
The above is only a preferred embodiment of the present invention, does not play the role of any restrictions to the present invention.Belonging to any Those skilled in the art, in the range of not departing from technical solution of the present invention, to the invention discloses technical solution and Technology contents make the variation such as any type of equivalent replacement or modification, belong to the content without departing from technical solution of the present invention, still Within belonging to the scope of protection of the present invention.

Claims (10)

1. a kind of preparation method of porous nano hydroxyapatite sustained-release gel, which is characterized in that the preparation method includes such as Lower step:
Step 1: nanometer hydroxyapatite powder is added to the water the hydroxyapatite slurry for being formulated as content 10-40% (w/v)；
Step 2: hydroxyapatite slurry, pore creating material and oleic acid three are mixed in proportion, and it is small to put ball milling 6-24 in the ball mill When, uniform suspension is obtained after ball milling；
Step 3: suspension addition organic compounding agent is mixed in proportion, is then placed in 30-80 DEG C of water-bath and stirs Mix dissolution；
Step 4: the suspension being uniformly dissolved carries out spray drying granulation, obtains solidification microballoon；
Step 5: solidification microballoon obtained is subjected to high temperature dewaxing treatment, then is calcined under the high temperature conditions, high porosity is made Porous nano hydroxyapatite micro-sphere；
Step 6: drug is embedded in the high porosity porous nano hydroxyapatite micro-sphere；
Step 7: prepare evenly dispersed has water soluble algae hydrochlorate and high porosity porous nano hydroxyapatite micro-sphere respectively Mixing suspension, and configuration water-soluble calcium saline solution；
Step 8: water-soluble calcium saline solution is added in mixing suspension in a manner of spraying droplet, makes the mix suspending It after pension gelation, then immerses in water-soluble calcium salting liquid 10 minutes~24 hours, it is solidifying to obtain porous nano hydroxyapatite sustained release Glue.
2. the preparation method of porous nano hydroxyapatite sustained-release gel according to claim 1, which is characterized in that described The weight ratio of hydroxyapatite slurry and pore creating material is 80~95:20~5.
3. the preparation method of porous nano hydroxyapatite sustained-release gel according to claim 1, which is characterized in that described Organic compounding agent is one of gelatin, Arabic gum, chitosan, sodium alginate, polylactic acid, native cellulose or a variety of timess Meaning combination.
4. the preparation method of porous nano hydroxyapatite sustained-release gel according to claim 1, which is characterized in that described Pore creating material is any one or more of any combination of carbon dust, graphite powder, acetylene black.
5. the preparation method of porous nano hydroxyapatite sustained-release gel according to claim 1, which is characterized in that water-bath The stirring rate 200-600r/min, dissolution time 2-5h of pot.
6. the preparation method of porous nano hydroxyapatite sustained-release gel according to claim 1, which is characterized in that dewaxing Temperature be 800~1500 DEG C, the dewaxing treatment time be 30~120min.
7. the preparation method of porous nano hydroxyapatite sustained-release gel according to claim 1, which is characterized in that described High-temperature calcination temperature is 1000~1500 DEG C, and calcination time is 45~180min.
8. the preparation method of porous nano hydroxyapatite sustained-release gel according to claim 1, which is characterized in that spraying 250-500 degrees Celsius of temperature, charging rate 10-30ml/min, atomisation pressure 0.05-0.1MPa.
9. the preparation method of porous nano hydroxyapatite sustained-release gel according to claim 1, which is characterized in that described In mixing suspension, the molar concentration of water soluble algae hydrochlorate is 0.01~10 mol/L.
10. the preparation method of porous nano hydroxyapatite sustained-release gel according to claim 1, which is characterized in that institute The mass ratio for stating high porosity porous nano hydroxyapatite micro-sphere and water soluble algae hydrochlorate is 1:10~10:1.
CN201811502474.0A 2018-12-10 2018-12-10 Porous nano hydroxyapatite sustained-release gel preparation method Pending CN109529110A (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
CN201811502474.0A CN109529110A (en) 2018-12-10 2018-12-10 Porous nano hydroxyapatite sustained-release gel preparation method
CN201910323669.7A CN110538346B (en) 2018-12-10 2019-04-22 Preparation method of porous nano hydroxyapatite sustained-release gel
BE20195545A BE1027074B1 (en) 2018-12-10 2019-08-20 Process for preparing a porous nanohydroxyapatite sustained release gel
BE20195546A BE1027375B1 (en) 2018-12-10 2019-08-20 High porosity porous nanohydroxyapatite microsphere and its preparation process
NL2023785A NL2023785B1 (en) 2018-12-10 2019-09-06 Preparation Method for Porous Nano-hydroxyapatite Sustained Release Gel

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CN110538347A (en) * 2018-12-12 2019-12-06 上海摩漾生物科技有限公司 High-porosity porous nano hydroxyapatite microspheres and preparation method thereof
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Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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US10914712B2 (en) * 2014-03-03 2021-02-09 Bio-Rad Laboratories, Inc. Spherical porous hydroxyapatite sorbent and methods thereof
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CN106565974B (en) * 2016-10-20 2018-09-28 中国科学院上海硅酸盐研究所 Alginate/hydroxyapatite overlong nanowire composite hydrogel

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CN110538347A (en) * 2018-12-12 2019-12-06 上海摩漾生物科技有限公司 High-porosity porous nano hydroxyapatite microspheres and preparation method thereof
CN110182779A (en) * 2019-05-07 2019-08-30 湖南雅城新材料有限公司 The preparation method of ferric phosphate duct material
CN112028044A (en) * 2020-08-11 2020-12-04 浙江拜尔克生物科技有限公司 Apatite microcarrier and preparation method and application thereof
CN115926198A (en) * 2021-09-23 2023-04-07 四川大学 Injectable tissue regeneration type filler and preparation method thereof
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