CN109529110A - Porous nano hydroxyapatite sustained-release gel preparation method - Google Patents
Porous nano hydroxyapatite sustained-release gel preparation method Download PDFInfo
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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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
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.
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
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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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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 |
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 |
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 |
BE1027375B1 (en) * | 2018-12-10 | 2021-01-26 | Shanghai Moyang Biotechnology Co Ltd | High porosity porous nanohydroxyapatite microsphere and its preparation process |
CN115137877A (en) * | 2022-03-25 | 2022-10-04 | 杭州诺嫣生物科技有限公司 | Injectable gel composition, 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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CN112500097B (en) * | 2020-12-28 | 2022-06-14 | 湖北工业大学 | Self-repairing steel slag-slag concrete and preparation method thereof |
CN115124753B (en) * | 2022-07-14 | 2023-07-25 | 元柔科技(北京)有限公司 | Porous flexible material and pressure sensor prepared from same |
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JPH03249911A (en) * | 1990-02-26 | 1991-11-07 | Central Glass Co Ltd | Ceramic filter for removing protein |
CN101343054B (en) * | 2008-08-19 | 2011-03-16 | 华南理工大学 | Preparation method of hydroxyapatite microsphere |
CN101361715B (en) * | 2008-09-11 | 2010-06-09 | 天津大学 | Preparation method of drug-carrying hydroxylapatite microspheres and bone cement composite porous microspheres |
US10914712B2 (en) * | 2014-03-03 | 2021-02-09 | Bio-Rad Laboratories, Inc. | Spherical porous hydroxyapatite sorbent and methods thereof |
CN105079876A (en) * | 2015-08-31 | 2015-11-25 | 华南理工大学 | Porous drug-loaded composite microsphere support material as well as preparation method and application thereof |
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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BE1027375B1 (en) * | 2018-12-10 | 2021-01-26 | Shanghai Moyang Biotechnology Co Ltd | High porosity porous nanohydroxyapatite microsphere and its preparation process |
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 |
CN115137877A (en) * | 2022-03-25 | 2022-10-04 | 杭州诺嫣生物科技有限公司 | Injectable gel composition, preparation method and application thereof |
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NL2023785A (en) | 2020-10-27 |
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