阅读说明：本技术 一种小分子透明质酸的制备方法 (Preparation method of micromolecular hyaluronic acid ) 是由 陈宁生 于 2021-10-15 设计创作，主要内容包括：本发明公开了一种小分子透明质酸的制备方法,属于透明质酸制备领域,一种小分子透明质酸的制备方法,在制备过程中需要干燥时,通过磁动兜的设置,在通电时,随动绳受到吸附力与电磁板吸附,并随电磁板移动,从而扯动随动兜凸起,进而迫使其上方的小分子透明质酸受到翻动,在断电后,随动兜迅速恢复原位,从而产生抖动,进一步提高对其翻动效果,在多组的随动绳作用下,有效保证小分子透明质酸的翻动均匀性,同时增大其与通入的热风的接触面积,相较于现有技术,显著提高得到的小分子透明质酸干粉含水率的均匀性,同时加快干燥效率,进而使整体的制备效率得到提高。(The invention discloses a preparation method of micromolecular hyaluronic acid, belonging to the field of hyaluronic acid preparation, in particular to a preparation method of micromolecular hyaluronic acid, when drying is needed in the preparation process, the follow-up rope is adsorbed with the electromagnetic plate by the adsorption force and moves along with the electromagnetic plate when the magnetic moving pocket is electrified, thereby pulling the following pocket bulge to force the micromolecule hyaluronic acid above the following pocket bulge to be turned over, after power failure, the follow-up pocket is quickly restored to the original position, thereby generating jitter and further improving the turning effect, under the action of the multiple groups of follow-up ropes, the turning uniformity of the micromolecule hyaluronic acid is effectively guaranteed, meanwhile, the contact area between the micromolecule hyaluronic acid and introduced hot air is increased, compared with the prior art, the uniformity of the water content of the obtained micromolecule hyaluronic acid dry powder is obviously improved, meanwhile, the drying efficiency is accelerated, and further the overall preparation efficiency is improved.)

1. A preparation method of small molecular hyaluronic acid is characterized by comprising the following steps: the method comprises the following steps:

s1, adding hyaluronidase into the purified water, then adding the high-molecular hyaluronic acid in portions while stirring, and thus carrying out enzyme digestion reaction;

s2, sequentially carrying out enzyme inactivation, activated carbon adsorption impurity removal and microporous membrane filtration on the product obtained after the enzyme digestion reaction in the step S1 to obtain micromolecular hyaluronic acid;

s3, putting the micromolecular hyaluronic acid into the magnetic drying furnace, continuously controlling the power on and off, and enabling the magnetic pocket in the magnetic drying furnace to be in a fluctuating state continuously, so that the micromolecular hyaluronic acid is turned over, and meanwhile, hot air is introduced for drying to obtain micromolecular hyaluronic acid dry powder with uniform water content.

2. The method of claim 1, wherein the method comprises: after hyaluronidase is added in the step S1, the pH is adjusted to 5-8, and the temperature is kept at 25-40 ℃.

3. The method of claim 1, wherein the method comprises: the temperature of the hot air in the step S3 is not higher than 70 ℃ and not lower than 45 ℃.

4. The method of claim 1, wherein the method comprises: magnetomotive drying furnace includes furnace body (1) and covers bell (2) of establishing on furnace body (1), the equal fixedly connected with breather pipe (3) in both ends about furnace body (1), furnace body (1) inner wall from the bottom up fixedly connected with magnetism in proper order bumps board, magnetomotive pocket, limiting plate (43) and electronic slide rail (6), the electric connection has electromagnetic plate (7) on electronic slide rail (6), magnetomotive pocket upper end fixedly connected with multiunit follow-up rope, follow-up rope upper end activity run through limiting plate (43) and with limiting plate (43) upper end contact.

5. The method for preparing a small molecule hyaluronic acid according to claim 4, wherein: follow-up rope includes stay cord (91) and connects at magnetic control piece (92) of stay cord (91) upper end, horizontal slot hole has been dug on limiting plate (43), horizontal slot hole is run through in stay cord (91), magnetic control piece (92) and horizontal slot hole inner wall contact.

6. The method of claim 5, wherein the small hyaluronic acid molecule is selected from the group consisting of: the length and the width of the magnetic control block (92) are both larger than the width of the transverse long hole, the magnetic control block (92) is made of a ferromagnetic material, the pull rope (91) is made of a non-elastic structure, and the length of the pull rope (91) is just equal to the distance between the magnetic control block (92) and the magnetic moving pocket.

7. The method of claim 6, wherein the small hyaluronic acid molecule is selected from the group consisting of: the magnetic motion pocket comprises a drying plate (42) and a follow-up pocket (8) which are fixedly connected with the inner wall of the furnace body (1), a pre-through ball point is arranged at the joint of the lower end of the pull rope (91) and the follow-up pocket (8), the follow-up pocket (8) is in contact with the upper surface of the drying plate (42), and the upper surface of the follow-up pocket is not higher than the plane of the left end and the right end of the follow-up pocket (8) when the micromolecular hyaluronic acid is dried.

8. The method of claim 5, wherein the small hyaluronic acid molecule is selected from the group consisting of: the magnetic collision plate comprises a lower fixed plate (41) fixed on the inner wall of the furnace body (1) and a plurality of magnetic collision elastic rod balls (5) fixedly connected to the upper end of the lower fixed plate (41), and the upper end of each magnetic collision elastic rod ball (5) is made of ferromagnetic materials.

9. The method of claim 7, wherein the small hyaluronic acid molecule is selected from the group consisting of: the pre-passing ball point comprises a half sealing piece (102) fixedly connected with the follow-up pocket (8) and a ventilation hemisphere (101) connected inside the half sealing piece (102), and the pull rope (91) is fixedly connected with the middle part of the half sealing piece (102).

10. The method of claim 9, wherein the small hyaluronic acid molecule is selected from the group consisting of: the ventilation hemisphere (101) is of a multi-way through hole structure, the lower end part of the semi-sealing piece (102) is fixed to the outer surface of the ventilation hemisphere (101), the upper end part of the semi-sealing piece (102) is attached to the surface of the ventilation hemisphere (101), the longitudinal span end of the fixing part is not smaller than 1/3 of the radius of the ventilation hemisphere (101), and the semi-sealing piece (102) of the attaching part is of an elastic microporous structure.

Technical Field

The invention relates to the field of hyaluronic acid preparation, and particularly relates to a preparation method of small-molecule hyaluronic acid.

Background

Hyaluronic acid, also known as hyaluronic acid, has the molecular formula of (C14H21NO11) N, and is a disaccharide glycosaminoglycan composed of D-glucuronic acid and N-acetylglucosamine. It has high clinical value, and may be used widely in various ophthalmic operations, such as crystal implantation, cornea transplantation, glaucoma resisting operation, etc. It can also be used for treating arthritis and promoting wound healing. The skin care cosmetic has unique skin protection effect, can keep skin moist, smooth, fine, tender and elastic, and has the effects of preventing wrinkles, resisting wrinkles, beautifying, protecting health and recovering physiological functions of the skin.

Chinese patent No. CN201910164881.3 discloses a method for preparing small molecular hyaluronic acid or its salt, which uses spray drying during the preparation process, and takes away the moisture on the small molecular hyaluronic acid by circulating the inlet and outlet air continuously to realize drying, but in the actual drying process, the small molecular hyaluronic acid is stacked, and the small molecular hyaluronic acid on the surface or above is more fully contacted with the inlet air, resulting in uneven drying of the stacked small molecular hyaluronic acid, i.e. the part near the surface is dried quickly and the part near the lower part is dried slowly, resulting in long time and low efficiency of the overall complete drying, affecting the overall preparation efficiency, and causing uneven moisture content of the obtained dry powder of small molecular hyaluronic acid.

Disclosure of Invention

1. Technical problem to be solved

Aiming at the problems in the prior art, the invention aims to provide a preparation method of small-molecule hyaluronic acid, wherein when drying is needed in the preparation process, through the arrangement of a magnetic pocket, when power is on, a follow-up rope is adsorbed by an electromagnetic plate under the action of adsorption force and moves along with the electromagnetic plate, so that a protrusion of the follow-up pocket is pulled, the small-molecule hyaluronic acid above the follow-up pocket is forced to be turned, and after power is off, the follow-up pocket is rapidly restored to the original position, so that shaking is generated, the turning effect of the follow-up pocket is further improved, the turning uniformity of the small-molecule hyaluronic acid is effectively ensured under the action of multiple groups of follow-up ropes, the contact area between the small-molecule hyaluronic acid and introduced hot air is increased, compared with the prior art, the uniformity of the water content of the obtained small-molecule hyaluronic acid is remarkably improved, the drying efficiency is accelerated, and the whole preparation efficiency is further improved.

2. Technical scheme

In order to solve the above problems, the present invention adopts the following technical solutions.

A preparation method of small molecular hyaluronic acid comprises the following steps:

s1, adding hyaluronidase into the purified water, then adding the high-molecular hyaluronic acid in portions while stirring, and thus carrying out enzyme digestion reaction;

s2, sequentially carrying out enzyme inactivation, activated carbon adsorption impurity removal and microporous membrane filtration on the product obtained after the enzyme digestion reaction in the step S1 to obtain micromolecular hyaluronic acid;

s3, putting the micromolecular hyaluronic acid into the magnetic drying furnace, continuously controlling the power on and off, and enabling the magnetic pocket in the magnetic drying furnace to be in a fluctuating state continuously, so that the micromolecular hyaluronic acid is turned over, and meanwhile, hot air is introduced for drying to obtain micromolecular hyaluronic acid dry powder with uniform water content.

Further, after adding hyaluronidase in the step S1, the pH is adjusted to 5 to 8, and the temperature is maintained at 25 to 40 ℃.

Further, the temperature of the hot air in the step S3 is not higher than 70 ℃ and not lower than 45 ℃.

Further, magnetomotive drying furnace includes the furnace body and covers the bell of establishing on the furnace body, the equal fixedly connected with breather pipe in both ends about the furnace body, furnace body inner wall from the bottom up fixedly connected with magnetism bumps board, magnetomotive pocket, limiting plate and electronic slide rail in proper order, the electric connection has the electromagnetic plate on the electronic slide rail, magnetomotive pocket upper end fixedly connected with multiunit follow-up rope, follow-up rope upper end activity run through the limiting plate and with the contact of limiting plate upper end.

Further, the follow-up rope includes the stay cord and connects the magnetic control piece at the stay cord upper end, horizontal slot hole has been dug on the limiting plate, horizontal slot hole is run through to the stay cord, the magnetic control piece contacts with horizontal slot hole inner wall.

Furthermore, the length and the width of the magnetic control block are both larger than the width of the transverse long hole, the magnetic control block is made of a ferromagnetic material, the pull rope is made of a non-elastic structure, and the length of the pull rope is just equal to the distance between the magnetic control block and the magnetic moving pocket.

Furthermore, the magnetic pocket comprises a drying plate and a follow-up pocket which are fixedly connected with the inner wall of the furnace body, a pre-through ball point is arranged at the joint of the lower end of the pull rope and the follow-up pocket, the follow-up pocket is in surface contact with the upper surface of the drying plate, and the upper surface of the follow-up pocket is not higher than the plane where the left end and the right end of the follow-up pocket are located when the micromolecular hyaluronic acid is dried.

Further, the board is bumped to magnetism includes that the board is fixed with the furnace body inner wall down decides the board and a plurality of fixed connection decide the board upper end down the magnetism of board upper end and bump the pin ball, magnetism is bumped pin ball upper end and is made for ferromagnetic material.

Furthermore, it includes the half mounting and connects the ventilation hemisphere at half mounting inside with follow-up pocket fixed connection to lead to the ball point in advance, and stay cord and half mounting middle part fixed connection.

Furthermore, the ventilation hemisphere is of a multi-pass through hole structure, the lower end part of the semi-sealing piece is fixed to the outer surface of the ventilation hemisphere, the upper end part of the semi-sealing piece is attached to the surface of the ventilation hemisphere, the longitudinal span end of the fixing part is not smaller than 1/3 of the radius of the ventilation hemisphere, and the semi-sealing piece of the attaching part is of an elastic microporous structure.

3. Advantageous effects

Compared with the prior art, the invention has the advantages that:

(1) this scheme is when the preparation in-process needs the drying, through the setting of magnetic pocket, when the circular telegram, the follow-up rope receives adsorption affinity and electromagnetic plate absorption, and move along with the electromagnetic plate, thereby tear follow-up pocket arch, and then force the micromolecule hyaluronic acid of its top to receive and turn, after the outage, the follow-up pocket resumes the normal position rapidly, thereby produce the shake, further improve the effect of turning it, under the follow-up rope effect of multiunit, effectively guarantee the homogeneity of turning of micromolecule hyaluronic acid, increase its and the hot-blast area of contact who lets in simultaneously, compare in prior art, show the homogeneity that improves the micromolecule hyaluronic acid dry powder moisture content that obtains, accelerate drying efficiency simultaneously, and then make holistic preparation efficiency obtain improving.

Drawings

FIG. 1 is a schematic diagram of the main flow structure of the present invention;

FIG. 2 is a schematic three-dimensional structure of a magnetomotive drying oven according to the present invention;

FIG. 3 is a schematic structural view of the front face of the magnetomotive drying oven of the present invention;

FIG. 4 is a schematic view of the invention at a limiting plate;

FIG. 5 is a schematic diagram of a variation structure of the magnetomotive drying oven after being electrified;

FIG. 6 is a schematic diagram of the present invention showing the change of the current supply and the current interruption to the next follow-up rope;

FIG. 7 is a schematic view of the structure at the pre-ball point of the present invention;

FIG. 8 is a schematic diagram of the configuration of the pre-clearing bulb after pulling force of the heated follower string of the present invention.

The reference numbers in the figures illustrate:

1 furnace body, 2 furnace covers, 3 vent pipes, 41 lower fixed plates, 42 drying plates, 43 limit plates, 5 magnetic catch bouncing rod balls, 6 electric sliding rails, 7 electromagnetic plates, 8 follow-up pockets, 91 pull ropes, 92 magnetic control blocks, 101 ventilation hemispheres and 102 semi-sealing pieces.

Detailed Description

The drawings in the embodiments of the invention will be combined; the technical scheme in the embodiment of the invention is clearly and completely described; obviously; the described embodiments are only some of the embodiments of the invention; but not all embodiments, are based on the embodiments of the invention; all other embodiments obtained by a person skilled in the art without making any inventive step; all fall within the scope of protection of the present invention.

In the description of the present invention, it should be noted that the terms "upper", "lower", "inner", "outer", "top/bottom", and the like indicate orientations or positional relationships based on those shown in the drawings, and are only for convenience of description and simplification of description, but do not indicate or imply that the referred device or element must have a specific orientation, be constructed in a specific orientation, and be operated, and thus should not be construed as limiting the present invention. Furthermore, the terms "first" and "second" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.

In the description of the present invention, it should be noted that, unless otherwise explicitly specified or limited, the terms "mounted," "disposed," "sleeved/connected," "connected," and the like are to be construed broadly, e.g., "connected," which may be fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meanings of the above terms in the present invention can be understood in specific cases to those skilled in the art.

Example 1:

referring to fig. 1, a method for preparing small molecule hyaluronic acid includes the following steps:

s1, adding hyaluronidase into the purified water, then adding the high-molecular hyaluronic acid in portions while stirring, and thus carrying out enzyme digestion reaction;

s2, sequentially carrying out enzyme inactivation, activated carbon adsorption impurity removal and microporous membrane filtration on the product obtained after the enzyme digestion reaction in the step S1 to obtain micromolecular hyaluronic acid;

s3, putting the micromolecular hyaluronic acid into the magnetic drying furnace, continuously controlling the power on and off, and enabling the magnetic pocket in the magnetic drying furnace to be in a fluctuating state continuously, so that the micromolecular hyaluronic acid is turned over, and meanwhile, hot air is introduced for drying to obtain micromolecular hyaluronic acid dry powder with uniform water content.

After adding hyaluronidase in step S1, adjusting pH to 5-8, and maintaining the temperature at 25-40 deg.C, and the temperature of hot air is not higher than 70 deg.C and not lower than 45 deg.C in step S3.

Referring to fig. 2-3, the magnetic drying furnace includes a furnace body 1 and a furnace cover 2 covering the furnace body 1, the left and right ends of the furnace body 1 are fixedly connected with a vent pipe 3, the inner wall of the furnace body 1 is fixedly connected with a magnetic collision plate, a magnetic pocket, a limit plate 43 and an electric slide rail 6 from bottom to top, the electric slide rail 6 is electrically connected with an electromagnetic plate 7, the upper end of the magnetic pocket is fixedly connected with a plurality of groups of follow-up ropes, please refer to fig. 6, when the electromagnetic plate 7 moves to a second follow-up rope, the power is off, the former follow-up rope recovers to the original position, then the power is on to adsorb the second follow-up rope, the follow-up pocket 8 is repeatedly pulled, in the process that the electromagnetic plate 7 moves along the electric slide rail 6, the uniform turning over of the small molecule hyaluronic acid in the drying process is realized, the drying is more uniform, the water content is more uniform, the upper end of the follow-up rope movably penetrates through the limit plate 43 and contacts with the upper end of the limit plate 43, the magnetic collision plate comprises a lower fixed plate 41 fixed with the inner wall of the furnace body 1 and a plurality of magnetic collision elastic rod balls 5 fixedly connected with the upper end part of the lower fixed plate 41, the upper end part of each magnetic collision elastic rod ball 5 is made of ferromagnetic materials, so that when the electric slide rail 6 drives the electromagnetic plate 7 to move left and right on the magnetic collision elastic rod ball 5, the magnetic collision elastic rod balls 5 quickly bounce upwards under the action of magnetic attraction when the electromagnetic plate 7 passes through the magnetic collision elastic rod balls 5, and further impact on the drying plate 42, so that the small molecular hyaluronic acid is always in a dynamic state, compared with a static state, the contact with hot air is better, and the drying efficiency is higher;

in order to ensure the accuracy of the power-on and power-off node, a displacement sensor can be arranged on the electromagnetic plate 7, so that the power-on and power-off can be carried out once when the electromagnetic plate transversely passes through a group of follow-up ropes.

The magnetomotive pocket comprises a drying plate 42 and a follow-up pocket 8 which are fixedly connected with the inner wall of the furnace body 1, a pre-through ball point is arranged at the joint of the lower end part of the pull rope 91 and the follow-up pocket 8, the follow-up pocket 8 is in surface contact with the upper surface of the drying plate 42, and the upper surface of the small molecular hyaluronic acid is not higher than the plane where the left end part and the right end part of the follow-up pocket 8 are located when the small molecular hyaluronic acid is dried, so that the accumulation thickness of the small molecular hyaluronic acid is not too large when the small molecular hyaluronic acid is dried, and the drying uniformity is better.

As shown in fig. 4, a in the drawing shows a transverse long hole, the follow-up rope comprises a pull rope 91 and a magnetic control block 92 connected to the upper end of the pull rope 91, a transverse long hole is cut in the limiting plate 43, the pull rope 91 penetrates through the transverse long hole, the magnetic control block 92 is in contact with the inner wall of the transverse long hole, the length and the width of the magnetic control block 92 are both greater than the width of the transverse long hole, after the magnetic control block 92 is effectively ensured to be adsorbed by the electromagnetic plate 7, when the power failure occurs, the magnetic control block 92 is not easy to directly penetrate through the transverse long hole and fall off from the limiting plate 43, the magnetic control block 92 is made of a ferromagnetic material, the pull rope 91 is made of an inelastic structure, the length of the pull rope 91 is just equal to the distance between the magnetic control block 92 and the magnetic control pocket, when the magnetic control block 92 is adsorbed by the electromagnetic plate 7, the follow-up pocket 8 can be pulled up to be in an undulating shape, and the effect of turning over the small molecular hyaluronic acid is achieved.

Referring to fig. 7, the pre-passing ball point includes a half-sealing piece 102 fixedly connected to the follower pocket 8 and a ventilation hemisphere 101 connected to the inside of the half-sealing piece 102, and the pull cord 91 is fixedly connected to the middle portion of the half-sealing piece 102, the ventilation hemisphere 101 is a multi-pass structure, the lower end portion of the half-sealing piece 102 is fixed to the outer surface of the ventilation hemisphere 101, the upper end portion of the half-sealing piece 102 is attached to the surface of the ventilation hemisphere 101, the longitudinal span end of the fixed portion is not less than 1/3 of the radius of the ventilation hemisphere 101, and the half-sealing piece 102 of the attached portion is an elastic microporous structure, as shown in fig. 8, when the follower pocket 8 is pulled by the follower cord, the attached portion of the half-sealing piece 102 is directly stressed to be separated from the ventilation hemisphere 101, and the surface micropores are expanded under the action of pulling force, at this time, external hot air enters between the drying plate 42 and the follower pocket 8 along the gap, and during the process that the follower pocket 8 is restored to its original position at each time of power failure, the hot air is pressed to gradually overflow from the ball point, so that the follow-up pocket 8 gradually collapses in the gas overflow process to further play a role in turning, and on the other hand, the overflowed gas passes through the gaps between the micromolecule hyaluronic acids from the lower part to overflow, and is matched with most of the hot air to dry the micromolecule hyaluronic acids above, so that the bidirectional drying is realized, and the efficiency is higher.

When drying is needed in the preparation process, through the arrangement of the magnetic pocket, as shown in fig. 5-6, when power is on, the follow-up rope is adsorbed by the electromagnetic plate 7 and moves along with the electromagnetic plate 7, so that the follow-up pocket 8 is pulled to protrude, the micromolecule hyaluronic acid above the follow-up pocket is forced to be turned, after power is off, the follow-up pocket 8 is rapidly restored to the original position, shaking is generated, the turning effect on the micromolecule hyaluronic acid is further improved, the turning uniformity of the micromolecule hyaluronic acid is effectively ensured under the action of the plurality of groups of follow-up ropes, meanwhile, the contact area between the micromolecule hyaluronic acid and introduced hot air is increased, compared with the prior art, the uniformity of the water content of the obtained micromolecule hyaluronic acid dry powder is remarkably improved, the drying efficiency is accelerated, and the overall preparation efficiency is improved.

The above; but are merely preferred embodiments of the invention; the scope of the invention is not limited thereto; any person skilled in the art is within the technical scope of the present disclosure; the technical scheme and the improved concept of the invention are equally replaced or changed; are intended to be covered by the scope of the present invention.