CN117000178A - Preparation process and device of emulsified and crosslinked sodium hyaluronate particles - Google Patents
Preparation process and device of emulsified and crosslinked sodium hyaluronate particles Download PDFInfo
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- CN117000178A CN117000178A CN202310987355.3A CN202310987355A CN117000178A CN 117000178 A CN117000178 A CN 117000178A CN 202310987355 A CN202310987355 A CN 202310987355A CN 117000178 A CN117000178 A CN 117000178A
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- sodium hyaluronate
- particles
- crosslinked sodium
- emulsified
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Links
- 229920002385 Sodium hyaluronate Polymers 0.000 title claims abstract description 56
- 229940010747 sodium hyaluronate Drugs 0.000 title claims abstract description 56
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 title claims abstract description 56
- 239000002245 particle Substances 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title abstract description 13
- 238000003756 stirring Methods 0.000 claims abstract description 141
- 230000001804 emulsifying effect Effects 0.000 claims abstract description 39
- 238000004132 cross linking Methods 0.000 claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 9
- 239000000839 emulsion Substances 0.000 claims description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims description 9
- 229940057995 liquid paraffin Drugs 0.000 claims description 9
- 238000005303 weighing Methods 0.000 claims description 9
- 238000004945 emulsification Methods 0.000 claims description 8
- 230000003028 elevating effect Effects 0.000 claims description 7
- 239000012071 phase Substances 0.000 claims description 7
- 239000000243 solution Substances 0.000 claims description 7
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical group C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 claims description 6
- 239000007863 gel particle Substances 0.000 claims description 6
- 239000006228 supernatant Substances 0.000 claims description 6
- 239000003431 cross linking reagent Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 229940037003 alum Drugs 0.000 claims description 3
- 239000008346 aqueous phase Substances 0.000 claims description 3
- 238000004140 cleaning Methods 0.000 claims description 3
- 239000008055 phosphate buffer solution Substances 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 230000008961 swelling Effects 0.000 claims description 2
- 230000000712 assembly Effects 0.000 abstract description 11
- 238000000429 assembly Methods 0.000 abstract description 11
- 230000007246 mechanism Effects 0.000 abstract description 9
- 230000035484 reaction time Effects 0.000 abstract description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 17
- 229920002674 hyaluronan Polymers 0.000 description 16
- 229960003160 hyaluronic acid Drugs 0.000 description 16
- 230000000670 limiting effect Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 2
- 238000005265 energy consumption Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/18—Stationary reactors having moving elements inside
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0053—Details of the reactor
- B01J19/0066—Stirrers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/12—Powdering or granulating
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
Abstract
The application discloses a preparation process and a device for emulsifying crosslinked sodium hyaluronate particles, wherein the device comprises an emulsifying machine body and a stirring and lifting mechanism, the stirring and lifting mechanism is connected with the emulsifying machine body, the stirring and lifting mechanism comprises a support frame fixedly connected with the top of the emulsifying machine body, a stirring motor fixedly connected with the inner top wall of the support frame, a rotating shaft fixedly connected with the output end of the stirring motor, a positive and negative threaded rod fixedly connected with the bottom end of the rotating shaft, a pair of first stirring assemblies connected with the positive and negative threaded rod, a second stirring assembly connected with the pair of first stirring assemblies and a lifting adjusting assembly rotatably connected with the inner top wall of the emulsifying machine body, and the lifting adjusting assembly is connected with the pair of first stirring assemblies. The application can improve the uniformity of the crosslinking reaction, shorten the crosslinking reaction time, improve the preparation efficiency of the emulsified and crosslinked sodium hyaluronate particles and is not easy to influence the performance of the emulsified and crosslinked sodium hyaluronate particles.
Description
Technical Field
The application relates to the technical field of medical material preparation, in particular to a preparation process and a device of emulsified and crosslinked sodium hyaluronate particles.
Background
Hyaluronic Acid (HA), also known as hyaluronic acid, is a macromolecular acidic mucopolysaccharide formed by alternately connecting N-acetylglucosamine and glucuronic acid through glycosidic bonds. Hyaluronic acid is distributed in connective tissues and body fluids of mammals, and is a component constituting the skin cell matrix, and is usually present in the form of sodium hyaluronate. Hyaluronic acid is mainly prepared by two ways of animal tissue extraction and microbial fermentation. HA molecules contain more hydroxyl and carboxyl, so that the HA molecules have good moisture retention and free radical removal functions, and are widely used in cosmetics. However, hyaluronic acid is easy to diffuse and degrade between tissues, so that the in vivo residence time is short, the physical and chemical properties of the hyaluronic acid are difficult to fully develop, and the hyaluronic acid has a certain limitation in practical application. To compensate for these drawbacks, it is necessary to chemically modify or crosslink hyaluronic acid to obtain hyaluronic acid derivatives having more excellent properties.
At present, a plurality of methods for preparing crosslinked hyaluronic acid at home and abroad are generally to stir and mix hyaluronic acid and a crosslinking agent in an aqueous solution, and add the crosslinking agent to enable chemical bonds among hyaluronic acid polymer chains to be synthesized to prepare the crosslinked hyaluronic acid, and the obtained massive gel is generally crushed mechanically or pressed through a screen to obtain different particle size specifications, but the prepared crosslinked hyaluronic acid gel mostly has the problems of uneven crosslinking degree and low crosslinking efficiency, and affects the preparation efficiency and performance of emulsified crosslinked sodium hyaluronate particles. Therefore, a process and an apparatus for preparing emulsified crosslinked sodium hyaluronate particles are needed to solve the above technical problems.
Disclosure of Invention
This section is intended to outline some aspects of embodiments of the application and to briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section as well as in the description of the application and in the title of the application, which may not be used to limit the scope of the application.
The present application has been made in view of the above-mentioned problems associated with the conventional process and apparatus for producing emulsified and crosslinked sodium hyaluronate particles.
Therefore, the technical problem to be solved by the application is to provide a preparation process and a device for emulsifying and crosslinking sodium hyaluronate particles, and the purpose of the application is to solve the problems in the background technology.
In order to solve the technical problems, the application provides the following technical scheme: an apparatus for preparing emulsified and crosslinked sodium hyaluronate particles, which mainly comprises:
an emulsifying machine body;
stirring and elevating system, stirring and elevating system with the emulsion machine organism is connected, stirring and elevating system include with emulsion machine organism top fixed connection's support frame, with support frame inner roof fixed connection's agitator motor, with agitator motor's output fixed connection's axis of rotation, with axis of rotation bottom fixed connection's positive and negative threaded rod, with positive and negative threaded rod be connected a pair of first stirring subassembly, with a pair of first stirring subassembly be connected the second stirring subassembly and with emulsion machine organism inner roof rotate the lift adjustment subassembly of being connected, lift adjustment subassembly with a pair of first stirring subassembly is connected.
As a preferable mode of the apparatus for producing emulsified and crosslinked sodium hyaluronate particles according to the present application, there is provided: the rotating shaft is rotationally connected with the top of the emulsifying machine body through a bearing.
As a preferable mode of the apparatus for producing emulsified and crosslinked sodium hyaluronate particles according to the present application, there is provided: the positive and negative threaded rod is positioned in the emulsifying machine body.
As a preferable mode of the apparatus for producing emulsified and crosslinked sodium hyaluronate particles according to the present application, there is provided: the pair of first stirring components are symmetrically arranged on the positive and negative threaded rod, each first stirring component comprises a lifting disc which is spirally sleeved on the positive and negative threaded rod and a first stirring rod which is fixedly connected with the side face of the lifting disc, and the lifting disc is connected with the lifting adjusting component and the second stirring component.
As a preferable mode of the apparatus for producing emulsified and crosslinked sodium hyaluronate particles according to the present application, there is provided: the lifting disc is provided with a through groove which is communicated up and down, a fixed rod is fixedly connected inside the through groove, and a second stirring rod is fixedly connected on the fixed rod.
As a preferable mode of the apparatus for producing emulsified and crosslinked sodium hyaluronate particles according to the present application, there is provided: the second stirring assembly comprises a first supporting rod and a second supporting rod which are rotationally connected with the pair of lifting discs, and one end, far away from the lifting discs, of the first supporting rod is rotationally connected with one end, far away from the lifting discs, of the second supporting rod.
As a preferable scheme of the preparation process and the device of the emulsified and crosslinked sodium hyaluronate particles, the application comprises the following steps: and the first support rod and the second support rod are fixedly connected with a third stirring rod, and are symmetrically arranged.
As a preferable mode of the apparatus for producing emulsified and crosslinked sodium hyaluronate particles according to the present application, there is provided: the lifting adjusting assembly comprises a pair of guide slide bars, an outer gear ring, a first gear plate, a connecting shaft, a second gear plate and a driven gear, wherein the guide slide bars are in sliding connection with a lifting plate, the outer gear ring is in rotational connection with the inner top wall of an emulsifying machine body, the first gear plate is in meshed connection with one side of the outer gear ring, the connecting shaft is fixedly connected with the top of the first gear plate, the second gear plate is fixedly connected with the top of the connecting shaft, the driven gear is in meshed connection with one side of the second gear plate, the top ends of the guide slide bars are fixedly connected with the bottom of the outer gear ring, the outer gear ring is movably sleeved outside a rotating shaft, and the driven gear is fixedly sleeved outside the rotating shaft.
As a preferable mode of the apparatus for producing emulsified and crosslinked sodium hyaluronate particles according to the present application, there is provided: and the stirring motor is provided with a motor forward and reverse rotation controller for controlling forward and reverse rotation of the stirring motor.
The application also provides a preparation process of the emulsified crosslinked sodium hyaluronate particles, which comprises the following steps:
step one:
aqueous phase: weighing a certain amount of sodium hyaluronate dry powder, adding 1% sodium hydroxide solution for multiple times, stirring for 1h until sodium hyaluronate is completely dissolved, and observing no insoluble particles by naked eyes;
an oil phase: weighing a certain amount of liquid paraffin and span80, weighing the liquid paraffin and span80 according to a certain proportion, and uniformly stirring;
step two: transferring the dissolved sodium hyaluronate alkaline gel into an emulsifying machine body, setting the emulsifying rotating speed and time, then starting a stirring motor, and driving a positive and negative threaded rod and a driven gear to rotate by the stirring motor through a rotating shaft to enable a first stirring assembly to rotate up and down for stirring, and enabling a second stirring assembly to move left and right for stirring, so that an oil-water mixed phase can be emulsified;
step three: after emulsification is finished, adding a certain amount of crosslinking agent divinyl alum into an emulsifying machine body, stirring, and carrying out crosslinking reaction;
step four: and after the crosslinking reaction is finished, leading out the discharge port of the emulsion emulsifying machine body, after the emulsion is cooled, cleaning the emulsion by using ethyl acetate and absolute ethyl alcohol successively, standing for layering, pouring out supernatant, removing residual liquid paraffin and span80, dissolving the obtained gel particles in phosphate buffer solution, swelling overnight, pouring out supernatant, and collecting the lower-layer emulsified crosslinked sodium hyaluronate gel particles.
The application has the beneficial effects that:
1. when emulsification and crosslinking are carried out, the stirring motor drives the rotating shaft to rotate, the rotating shaft drives the positive and negative threaded rods and the driven gear to rotate, so that the first stirring assembly rotates up and down to stir, the second stirring assembly moves left and right to stir, the stirring range is wide, the efficiency is high, the oil-water mixed phase emulsification time can be shortened, the uniformity of crosslinking reaction can be improved, the crosslinking reaction time is shortened, the preparation efficiency of the emulsified crosslinked sodium hyaluronate particles is improved, and the performance of the emulsified crosslinked sodium hyaluronate particles is not easily affected.
2. When the stirring range is enlarged, the stirring device can be realized by only one driving motor, has low manufacturing cost and can reduce energy consumption.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings that are needed in the description of the embodiments will be briefly described below, it being obvious that the drawings in the following description are only some embodiments of the present application, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art. Wherein:
FIG. 1 is a schematic diagram showing the overall structure of an apparatus for producing emulsified and crosslinked sodium hyaluronate particles according to the present application.
FIG. 2 is a schematic internal perspective view of an apparatus for producing emulsified and crosslinked sodium hyaluronate particles according to the present application.
Fig. 3 is a schematic view showing an enlarged structure of a first view angle of a stirring and lifting mechanism of the apparatus for preparing emulsified and crosslinked sodium hyaluronate particles according to the present application.
Fig. 4 is a schematic view showing an enlarged structure of a second view angle of the stirring and lifting mechanism of the apparatus for preparing emulsified and crosslinked sodium hyaluronate particles according to the present application.
Fig. 5 is a schematic diagram showing a connection structure between a first stirring assembly and a front and back threaded rod of the apparatus for preparing emulsified and crosslinked sodium hyaluronate particles according to the present application.
Fig. 6 is a schematic structural view of a second stirring assembly of the apparatus for preparing emulsified and crosslinked sodium hyaluronate particles according to the present application.
Fig. 7 is a schematic structural view of a lifting adjusting assembly of the apparatus for preparing emulsified and crosslinked sodium hyaluronate particles according to the present application.
In the figure: 100. an emulsifying machine body; 200. a stirring and lifting mechanism; 201. a support frame; 202. a stirring motor; 203. a rotating shaft; 204. a positive and negative threaded rod; 205. a first stirring assembly; 205-1, lifting disk; 205-2, a first stirring rod; 205-3, through slots; 205-4, a fixed rod; 205-5, a second stirring rod; 206. a second stirring assembly; 206-1, a first strut; 206-2, a second strut; 206-3, a third stirring rod; 207. a lifting adjusting component; 207-1, a guide slide bar; 207-2, an external gear ring; 207-3, a first gear disc; 207-4, a connecting shaft; 207-5, a second gear disc; 207-6, driven gear.
Detailed Description
In order that the above-recited objects, features and advantages of the present application will become more readily apparent, a more particular description of the application will be rendered by reference to specific embodiments thereof which are illustrated in the appended drawings.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present application, but the present application may be practiced in other ways other than those described herein, and persons skilled in the art will readily appreciate that the present application is not limited to the specific embodiments disclosed below.
Further, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic can be included in at least one implementation of the application. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.
Further, in describing the embodiments of the present application in detail, the cross-sectional view of the device structure is not partially enlarged to a general scale for convenience of description, and the schematic is only an example, which should not limit the scope of protection of the present application. In addition, the three-dimensional dimensions of length, width and depth should be included in actual fabrication.
Example 1
Referring to fig. 1 to 7, in one embodiment of the present application, there is provided a process for preparing emulsified and crosslinked sodium hyaluronate particles and an apparatus therefor, the preparing apparatus comprising an emulsifying machine body 100 and a stirring and elevating mechanism 200;
as shown in fig. 1-4, the stirring and lifting mechanism 200 is connected with the emulsifying machine body 100, the stirring and lifting mechanism 200 comprises a supporting frame 201 fixedly connected with the top of the emulsifying machine body 100, a stirring motor 202 fixedly connected with the inner top wall of the supporting frame 201, a rotating shaft 203 fixedly connected with the output end of the stirring motor 202, a positive and negative threaded rod 204 fixedly connected with the bottom end of the rotating shaft 203, a pair of first stirring assemblies 205 connected with the positive and negative threaded rod 204, a second stirring assembly 206 connected with the pair of first stirring assemblies 205, and a lifting adjusting assembly 207 rotatably connected with the inner top wall of the emulsifying machine body 100, wherein the lifting adjusting assembly 207 is connected with the pair of first stirring assemblies 205, and a motor positive and negative rotation controller is installed on the stirring motor 202 and used for controlling the positive and negative rotation of the stirring motor 202.
When the stirring motor 202 is used, the stirring motor 202 rotates positively and overturns back and forth, the output end of the stirring motor 202 drives the positive and negative threaded rod 204 and the lifting adjusting component 207 to rotate through the rotating shaft 203, the pair of first stirring components 205 move along the positive and negative threaded rod 204 under the limiting and guiding actions of the lifting adjusting component 207 and move close to or away from each other, and the pair of first stirring components 205 rotate under the driving of the lifting adjusting component 207, so that the first stirring components 205 can rotate and stir and lift and stir, the emulsification and crosslinking efficiency can be improved, and the uniformity of emulsification and crosslinking reactions can be improved;
in addition, when the pair of first stirring assemblies 205 are close to or far from each other, the horizontal position of the second stirring assembly 206 is changed, so that the stirring can be performed by moving left and right, the stirring range is further increased, the stirring gap between the pair of first stirring assemblies 205 is made up, and the stirring can be performed better.
Specifically, as shown in fig. 2, the rotating shaft 203 is rotatably connected with the top of the emulsifying machine body 100 through a bearing, so that the rotating shaft 203 can be stably rotated, the forward and reverse threaded rod 204 can be stably rotated, and the forward and reverse threaded rod 204 is positioned in the emulsifying machine body 100.
Specifically, as shown in fig. 5, a pair of first stirring assemblies 205 are symmetrically arranged on the positive and negative threaded rod 204, the first stirring assemblies 205 comprise a lifting disc 205-1 which is spirally sleeved on the positive and negative threaded rod 204, and a first stirring rod 205-2 which is fixedly connected with the side surface of the lifting disc 205-1, and the lifting disc 205-1 is connected with a lifting adjusting assembly 207 and a second stirring assembly 206;
the lifting disc 205-1 is provided with a through groove 205-3 which is communicated up and down, a fixed rod 205-4 is fixedly connected inside the through groove 205-3, and a second stirring rod 205-5 is fixedly connected on the fixed rod 205-4.
Specifically, as shown in fig. 6, the second stirring assembly 206 includes a first strut 206-1 and a second strut 206-2 rotatably connected to the pair of lifting disks 205-1, and an end of the first strut 206-1 remote from the lifting disk 205-1 is rotatably connected to an end of the second strut 206-2 remote from the lifting disk 205-1;
a third stirring rod 206-3 is fixedly connected to the first supporting rod 206-1 and the second supporting rod 206-2, and the first supporting rod 206-1 and the second supporting rod 206-2 are symmetrically arranged.
Specifically, as shown in fig. 7, the lifting adjusting assembly 207 comprises a pair of guide sliding rods 207-1 slidably connected with the lifting disc 205-1, an external gear ring 207-2 rotatably connected with the inner top wall of the emulsifying machine body 100, a first gear plate 207-3 meshed with one side of the external gear ring 207-2, a connecting shaft 207-4 fixedly connected with the top of the first gear plate 207-3, a second gear plate 207-5 fixedly connected with the top end of the connecting shaft 207-4, and a driven gear 207-6 meshed with one side of the second gear plate 207-5, wherein the top ends of the pair of guide sliding rods 207-1 are fixedly connected with the bottom of the external gear ring 207-2, the external gear ring 207-2 is movably sleeved outside the rotating shaft 203, and the driven gear 207-6 is fixedly sleeved outside the rotating shaft 203.
When the stirring motor 202 operates, the forward and reverse threaded rod 204 and the driven gear 207-6 are driven to rotate by the rotating shaft 203, and the lifting disc 205-1 does not rotate along the forward and reverse threaded rod 204 under the guiding and limiting actions of the guiding slide rod 207-1 and moves along the forward and reverse threaded rod 204, so that the two lifting discs 205-1 move close to or away from each other, and the lifting disc 205-1 drives the first stirring rod 205-2 and the second stirring rod 205-5 to lift and stir;
when the two lifting plates 205-1 are close to or far away from each other, the included angle between the first supporting rod 206-1 and the second supporting rod 206-2 is reduced or increased, and when the included angle is changed, the third stirring rod 206-3 can move in a left-right inclined manner, so that the stirring range can be further enlarged, and the stirring gap between a pair of first stirring assemblies 205 can be filled up, so that a better stirring effect is achieved, and the uniformity of emulsification and crosslinking can be improved;
the driven gear 207-6 drives the second gear plate 207-5 to rotate when driven by the rotating shaft 203, the second gear plate 207-5 drives the first gear plate 207-3 to rotate through the connecting shaft 207-4, the first gear plate 207-3 drives the lifting plate 205-1 to rotate through the guide sliding rod 207-1, the lifting plate 205-1 drives the first stirring rod 205-2 and the second stirring rod 205-5 to rotate for stirring, and the lifting plate 205-1 drives the first stirring rod 205-2 and the second stirring rod 205-5 to lift and stir, so that the first stirring rod 205-2 and the second stirring rod 205-5 can lift and stir and rotate, the stirring range can be further improved, the emulsifying and crosslinking uniformity and the efficiency are further improved, and the emulsifying and crosslinking sodium hyaluronate particle emulsifying and crosslinking performances are not easy to influence;
in addition, the whole stirring range can be enlarged by only one stirring motor 202, the manufacturing cost is low, and the energy consumption can be reduced.
The preparation process of the preparation device for the emulsified and crosslinked sodium hyaluronate particles comprises the following steps:
step one:
aqueous phase: weighing a certain amount of sodium hyaluronate dry powder, adding 1% sodium hydroxide solution for multiple times, stirring for 1h until sodium hyaluronate is completely dissolved, and observing no insoluble particles by naked eyes;
an oil phase: weighing a certain amount of liquid paraffin and span80, weighing the liquid paraffin and span80 according to a certain proportion, and uniformly stirring;
step two: transferring the dissolved sodium hyaluronate alkaline gel into the emulsifying machine body 100, setting the emulsifying rotation speed and time, then starting the stirring motor 202, and driving the positive and negative threaded rod 204 and the driven gear 207-6 to rotate by the stirring motor 202 through the rotating shaft 203, so that the first stirring assembly 205 rotates up and down to stir, and the second stirring assembly 206 moves left and right to stir, thereby emulsifying the oil-water mixed phase;
step three: after emulsification is finished, a certain amount of crosslinking agent divinyl alum is added into the emulsifying machine body 100, and the mixture is stirred for crosslinking reaction;
step four: after the crosslinking reaction is finished, the discharge port of the emulsion emulsifying machine body 100 is led out, after the emulsion is cooled, ethyl acetate and absolute ethyl alcohol are sequentially used for cleaning the emulsion, standing and layering are carried out, supernatant liquid is poured out, residual liquid paraffin and span80 are removed, then the obtained gel particles are dissolved in phosphate buffer solution and swelled overnight, supernatant liquid is poured out, and the lower-layer emulsified crosslinked sodium hyaluronate gel particles are collected.
Notably, are: the whole device controls the realization of the device through the total control button, and because the equipment matched with the control button is common equipment, the device belongs to the prior art, and the electrical connection relation and the specific circuit structure of the device are not repeated here.
It should be noted that the above embodiments are only for illustrating the technical solution of the present application and not for limiting the same, and although the present application has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solution of the present application may be modified or substituted without departing from the spirit and scope of the technical solution of the present application, which is intended to be covered in the scope of the claims of the present application.
Claims (10)
1. An apparatus for producing emulsified and crosslinked sodium hyaluronate particles, comprising:
an emulsifying machine body (100);
stirring and elevating system (200), stirring and elevating system (200) with emulsion machine organism (100) are connected, stirring and elevating system (200) include with emulsion machine organism (100) top fixed connection's support frame (201), with support frame (201) inner roof fixed connection's agitator motor (202), with agitator motor (202) output fixed connection's axis of rotation (203), with axis of rotation (203) bottom fixed connection's positive and negative threaded rod (204), with positive and negative threaded rod (204) be connected a pair of first stirring subassembly (205), with a pair of first stirring subassembly (205) be connected second stirring subassembly (206) and with emulsion machine organism (100) inner roof rotation be connected lift adjustment subassembly (207), lift adjustment subassembly (207) with a pair of first stirring subassembly (205) are connected.
2. The apparatus for producing emulsified and crosslinked sodium hyaluronate particles as set forth in claim 1, wherein: the rotating shaft (203) is rotatably connected with the top of the emulsifying machine body (100) through a bearing.
3. The apparatus for producing emulsified and crosslinked sodium hyaluronate particles as set forth in claim 1, wherein: the positive and negative threaded rod (204) is positioned in the emulsifying machine body (100).
4. The apparatus for producing emulsified and crosslinked sodium hyaluronate particles as set forth in claim 1, wherein: the pair of first stirring components (205) are symmetrically arranged on the positive and negative threaded rod (204), the first stirring components (205) comprise a lifting disc (205-1) which is spirally sleeved on the positive and negative threaded rod (204), and a first stirring rod (205-2) fixedly connected with the side surface of the lifting disc (205-1), and the lifting disc (205-1) is connected with the lifting adjusting component (207) and the second stirring component (206).
5. The apparatus for producing emulsified and crosslinked sodium hyaluronate particles as set forth in claim 4, wherein: a through groove (205-3) which is communicated up and down is formed in the lifting disc (205-1), a fixing rod (205-4) is fixedly connected inside the through groove (205-3), and a second stirring rod (205-5) is fixedly connected to the fixing rod (205-4).
6. The apparatus for producing emulsified and crosslinked sodium hyaluronate particles as set forth in claim 4, wherein: the second stirring assembly (206) comprises a first supporting rod (206-1) and a second supporting rod (206-2) which are rotatably connected with the pair of lifting plates (205-1), and one end, far away from the lifting plates (205-1), of the first supporting rod (206-1) is rotatably connected with one end, far away from the lifting plates (205-1), of the second supporting rod (206-2).
7. The apparatus for producing emulsified and crosslinked sodium hyaluronate particles as set forth in claim 6, wherein: third stirring rods (206-3) are fixedly connected to the first supporting rods (206-1) and the second supporting rods (206-2), and the first supporting rods (206-1) and the second supporting rods (206-2) are symmetrically arranged.
8. The apparatus for producing emulsified and crosslinked sodium hyaluronate particles as set forth in claim 4, wherein: the lifting adjusting assembly (207) comprises a pair of guide sliding rods (207-1) which are in sliding connection with the lifting disc (205-1), an outer gear ring (207-2) which is in rotary connection with the inner top wall of the emulsifying machine body (100), a first gear disc (207-3) which is in meshed connection with one side of the outer gear ring (207-2), a connecting shaft (207-4) which is fixedly connected with the top of the first gear disc (207-3), a second gear disc (207-5) which is fixedly connected with the top of the connecting shaft (207-4) and a driven gear (207-6) which is in meshed connection with one side of the second gear disc (207-5), wherein the top ends of the pair of guide sliding rods (207-1) are fixedly connected with the bottom of the outer gear ring (207-2), the outer gear ring (207-2) is movably sleeved outside the rotating shaft (203), and the driven gear (207-6) is fixedly sleeved outside the rotating shaft (203).
9. The apparatus for producing emulsified and crosslinked sodium hyaluronate particles as set forth in claim 1, wherein: and a motor forward and backward rotation controller is arranged on the stirring motor (202) and used for controlling forward and backward rotation of the stirring motor (202).
10. A process for preparing emulsified and crosslinked sodium hyaluronate particles, characterized in that the apparatus for preparing emulsified and crosslinked sodium hyaluronate particles according to any one of claims 1 to 9 is used, comprising the steps of:
step one:
aqueous phase: weighing a certain amount of sodium hyaluronate dry powder, adding 1% sodium hydroxide solution for multiple times, stirring for 1h until sodium hyaluronate is completely dissolved, and observing no insoluble particles by naked eyes;
an oil phase: weighing a certain amount of liquid paraffin and span80, weighing the liquid paraffin and span80 according to a certain proportion, and uniformly stirring;
step two: transferring the dissolved sodium hyaluronate alkaline gel into an emulsifying machine body (100), setting the emulsifying rotating speed and time, then starting a stirring motor (202), and driving a positive and negative threaded rod (204) and a driven gear (207-6) to rotate by the stirring motor (202) through a rotating shaft (203), so that a first stirring assembly (205) rotates up and down to stir, and a second stirring assembly (206) moves left and right to stir, thereby emulsifying an oil-water mixed phase;
step three: after emulsification is finished, adding a certain amount of crosslinking agent divinyl alum into an emulsifying machine body (100), and stirring to perform crosslinking reaction;
step four: and after the crosslinking reaction is finished, leading out the discharge port of the emulsion emulsifying machine body (100), cleaning the emulsion by using ethyl acetate and absolute ethyl alcohol successively after the emulsion is cooled, standing for layering, pouring out supernatant, removing residual liquid paraffin and span80, dissolving the obtained gel particles in phosphate buffer solution, swelling overnight, pouring out supernatant, and collecting the lower-layer emulsified crosslinked sodium hyaluronate gel particles.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310987355.3A CN117000178A (en) | 2023-08-08 | 2023-08-08 | Preparation process and device of emulsified and crosslinked sodium hyaluronate particles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310987355.3A CN117000178A (en) | 2023-08-08 | 2023-08-08 | Preparation process and device of emulsified and crosslinked sodium hyaluronate particles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117000178A true CN117000178A (en) | 2023-11-07 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310987355.3A Pending CN117000178A (en) | 2023-08-08 | 2023-08-08 | Preparation process and device of emulsified and crosslinked sodium hyaluronate particles |
Country Status (1)
| Country | Link |
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| CN (1) | CN117000178A (en) |
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