CN115139514B - Preparation method of degradable easily-separable microneedle array for 3D printing - Google Patents

Preparation method of degradable easily-separable microneedle array for 3D printing Download PDF

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CN115139514B
CN115139514B CN202210785834.2A CN202210785834A CN115139514B CN 115139514 B CN115139514 B CN 115139514B CN 202210785834 A CN202210785834 A CN 202210785834A CN 115139514 B CN115139514 B CN 115139514B
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printing
microneedle
code
speed
degradable
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CN115139514A (en
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韩晓筱
袁磊
陈锋
陆益栋
赵阳光
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Shanghai Heiyan Medical Technology Co ltd
Hunan University
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Shanghai Heiyan Medical Technology Co ltd
Hunan University
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/10Processes of additive manufacturing
    • B29C64/106Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
    • B29C64/118Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material using filamentary material being melted, e.g. fused deposition modelling [FDM]
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/30Auxiliary operations or equipment
    • B29C64/386Data acquisition or data processing for additive manufacturing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/30Auxiliary operations or equipment
    • B29C64/386Data acquisition or data processing for additive manufacturing
    • B29C64/393Data acquisition or data processing for additive manufacturing for controlling or regulating additive manufacturing processes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y10/00Processes of additive manufacturing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y50/00Data acquisition or data processing for additive manufacturing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y50/00Data acquisition or data processing for additive manufacturing
    • B33Y50/02Data acquisition or data processing for additive manufacturing for controlling or regulating additive manufacturing processes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y80/00Products made by additive manufacturing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29KINDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2067/00Use of polyesters or derivatives thereof, as moulding material
    • B29K2067/04Polyesters derived from hydroxycarboxylic acids
    • B29K2067/046PLA, i.e. polylactic acid or polylactide
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29KINDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2075/00Use of PU, i.e. polyureas or polyurethanes or derivatives thereof, as moulding material
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29LINDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
    • B29L2031/00Other particular articles
    • B29L2031/753Medical equipment; Accessories therefor

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Manufacturing & Machinery (AREA)
  • Physics & Mathematics (AREA)
  • Mechanical Engineering (AREA)
  • Optics & Photonics (AREA)

Abstract

The invention discloses a preparation method of a degradable easily-separable microneedle array for 3D printing, which comprises the following steps: s1, directly generating a G-code by utilizing the macro function of Excel, importing the G-code into Reetier-Host software to verify the shape of a graph, and determining the printing sequence and number of needle bodies, the height of a microneedle, the sizes of the top and the bottom and the distance between the needle bodies; s2, exporting the G-code from Repetier-Host software and guiding the G-code into a Raise3D Pro2 printer, wherein the left nozzle controls the printing of the bottom plate, the right nozzle realizes the printing of the microneedle body, the bottom plate is made of a flexible environment-friendly material, and the microneedle body is made of a degradable material; and S3, regulating and controlling parameters based on the setting of the G-code, realizing the rapid stretching of the filaments in the nozzle by utilizing the rapid movement of the nozzle, and finishing the manufacture of the micro-needle by utilizing the combination of a 3D printing process and a stretching method. The preparation method of the degradable easily-separable microneedle array for 3D printing ensures the precision of microneedles and simplifies the process of manufacturing separable microneedles by using a mold.

Description

Preparation method of degradable easily-separable microneedle array for 3D printing
Technical Field
The invention relates to the technical field of medicine and biological manufacturing, in particular to a preparation method of a degradable easily-separated microneedle array for 3D printing.
Background
The degradable microneedle is a polymer microneedle which can be automatically degraded in vivo after the microneedle is released, and has good biocompatibility and mechanical property. Because the microneedle can be degraded in vivo, the microneedle can not be broken, and the pollution to the tip can not be caused, so that the compliance of a patient is improved to a certain extent.
Since the degradable microneedles are mainly made of degradable polymers, there are many polymer choices and many choices in the manner of preparation. Currently, the most common preparation methods include: (1) processing a die: in this method, microneedles are manufactured using a high-precision template, but the manufacturing process of the mold is complicated, the manufacturing cost of the mold is high with high precision, and the microneedle array manufactured using the mold cannot be manufactured individually in terms of shape and the number of microneedles. (2) 3D printing and manufacturing: with the progress of technology, the 3D printing field is increasingly large, and products manufactured by 3D printing are also increasing.
In addition, fused Deposition Modeling (FDM) is also currently the most widely used, most commonly used printing equipment. At present, by utilizing the characteristics of more types of available materials and simultaneous working of multiple available nozzles, the publication No. CN 110693855A is named as a preparation method and application of a 3D printing microneedle patch, and the technology utilizes a double-nozzle fused deposition forming FDM 3D printer, wherein one nozzle prints a substrate of the microneedle patch, and the other nozzle prints a columnar array of the microneedle patch, and the columnar array contains insulin drugs capable of intelligently responding and adjusting blood sugar, so that the intelligent control of drug release is realized, and the problem that the number and other characteristic parameters of the existing microneedle array cannot be modified arbitrarily is solved. However, the method of modeling, slicing and remanufacturing cannot directly manufacture a microneedle array with a qualified size, and requires post-treatment (chemical treatment or physical treatment) to manufacture the microneedle array, and the microneedle array after the chemical treatment contains alkaline chemical substances, which may affect drug properties or human bodies.
In addition, most degradable microneedles are manufactured in a mode of facilitating separation of the microneedle body and the substrate, so that the microneedle can be used for keeping the needlepoint in the body after the microneedles are applied, and other parts are removed, so that the compliance of a patient is improved, and the safety of a wound is guaranteed.
At present, such a separate microneedle is mainly manufactured by a template method, but the whole operation process is complicated, and individualization in manufacturing cannot be realized. For example, publication number CN 110947085A entitled "a method for accelerating the forming and instant drug delivery of polyvinyl alcohol soluble microneedles and microneedles prepared thereby" adopts a template method to manufacture the microneedles, which is simple and rapid, and is convenient for mass production, but still cannot escape the disadvantage that the template method cannot be used for personalized manufacturing.
According to the manufacturing of the separated micro-needle, the material selection of the substrate and the needle body gradually moves from the same material to different materials, so that the degradability of the tip part can be ensured, the waste of the materials can be reduced, the flexible substrate also gradually becomes one of the selection of the micro-needle substrate, and the bonding of the needle body and the skin is improved.
Disclosure of Invention
The invention aims to provide a preparation method of a degradable easily-separable microneedle array by 3D printing, which solves the problem that the precision of microneedles can be ensured only by utilizing a post-treatment process, and can synchronously realize the preparation of separated microneedles by utilizing a 3D printing process.
In order to achieve the purpose, the invention provides a preparation method of a degradable easily-separated microneedle array for 3D printing, which comprises the following steps:
s1, directly generating a G-code by utilizing the macro function of Excel, importing the G-code into Reetier-Host software to verify the shape of a graph, and determining the printing sequence and number of needle bodies, the height of a microneedle, the sizes of the top and the bottom and the distance between the needle bodies;
s2, exporting the G-code from Repetier-Host software and guiding the G-code into a Raise3D Pro2 printer, wherein the left nozzle controls the printing of the bottom plate, the right nozzle realizes the printing of the microneedle body, the bottom plate is made of a flexible environment-friendly material, and the microneedle body is made of a degradable material;
and S3, regulating and controlling parameters of printing speed, idle stroke speed and printing temperature based on the G-code, realizing rapid stretching of filaments in the nozzle by utilizing rapid movement of the spray head, and finishing microneedle manufacturing by utilizing the combination of a 3D printing process and a stretching method.
Preferably, the specific operation in step S3 is as follows:
(1) The parameter regulation and control of the printing speed, the idle stroke speed and the printing temperature need to realize the matching among the parameters, thereby completing the regulation and control of the machine;
(2) The shape of the micro-needle is designed in relation to the moving speed of the nozzle, namely the idle stroke speed, which is also called as the stretching speed, so that the quality of the micro-needle is controlled, and the shape of the micro-needle can also be controlled.
Preferably, in the step S2, the flexible environment-friendly material is TPU, and is fed into a left spray head when in use; the degradable material is PLA, which is fed at the right jet when in use.
Preferably, in step S2, the flexible material includes, but is not limited to, TPU, and the degradable material includes, but is not limited to, PLA.
Preferably, in step S3, the printing speed is 800mm/min, the idle stroke speed range is 2000-10000mm/min, and the printing temperature is 210 ℃.
A microneedle patch prepared by the preparation method of the degradable easily-separable microneedle array based on 3D printing.
Preferably, the number of the microneedle arrays is 4 multiplied by 4, the height of the microneedles is 1500-2000 μm, the tip size is 70-100 μm, the bottom size is 500-1000 μm, and the distance between the needles is 5mm.
Therefore, the preparation method of the degradable easily-separable microneedle array by 3D printing is adopted, the stretching method is combined with the 3D printing technology, and the process of directly manufacturing the microneedles by using FDM equipment is realized by controlling parameters, so that the influence on medicines and patients caused by the post-treatment process is omitted. In addition, the shape of the microneedle can be controlled through the regulation and control of the 3D printing parameters, so that the 3D manufacturing of the easily separated microneedle is realized, and the process of manufacturing the separable microneedle by using the mold is simplified.
The technical solution of the present invention is further described in detail by the accompanying drawings and embodiments.
Drawings
Fig. 1 is a microscopic structure view of a 3D printed microneedle patch;
fig. 2 is a front view of a 3D printed microneedle patch;
fig. 3 is a top view of a 3D printed microneedle patch;
fig. 4 is an enlarged schematic view of a 3D printed microneedle patch;
FIG. 5 is a schematic view of microneedle shapes formed at different idle stroke speeds;
fig. 6 is a pictorial view of a microneedle patch;
fig. 7 is a schematic view of differently shaped microneedles.
Detailed Description
The technical scheme of the invention is further explained by the attached drawings and the embodiment.
Unless defined otherwise, technical or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein, and any reference signs in the claims are not intended to be construed as limiting the claim concerned.
Furthermore, it should be understood that although the present description refers to embodiments, not every embodiment may contain only a single embodiment, and such description is for clarity only, and those skilled in the art should integrate the description, and the embodiments may be combined as appropriate to form other embodiments understood by those skilled in the art. These other embodiments are also covered by the scope of the present invention.
It should also be understood that the above-mentioned embodiments are only for explaining the present invention, and the protection scope of the present invention is not limited thereto, and any person skilled in the art should be covered by the protection scope of the present invention by the technical solutions and the inventive concepts of the present invention equivalent substitutions or changes within the technical scope of the present invention disclosed by the present invention.
The use of the word "comprising" or "comprises" and the like in the present invention is intended to mean that the elements listed before the word cover the elements listed after the word and does not exclude the possibility that other elements may also be covered. The terms "inner", "outer", "upper", "lower", and the like indicate orientations or positional relationships based on those shown in the drawings, and are only for convenience in describing the present invention and simplifying the description, but do not indicate or imply that the referred devices or elements must have a specific orientation, be constructed and operated in a specific orientation, and thus are not to be construed as limiting the present invention, and when the absolute position of the described object is changed, the relative positional relationships may be changed accordingly. In the present invention, unless otherwise expressly stated or limited, the terms "attached" and the like are to be construed broadly, e.g., as meaning a fixed connection, a removable connection, or an integral part; either directly or indirectly through intervening media, either internally or in any other relationship. The specific meanings of the above terms in the present invention can be understood by those skilled in the art according to specific situations. The term "about" as used herein has the meaning well known to those skilled in the art, and preferably means that the term modifies a value within the range of ± 50%, ± 40%, ± 30%, ± 20%, ± 10%, ± 5% or ± 1% thereof.
All terms (including technical or scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs unless specifically defined otherwise. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.
Techniques, methods, and apparatus known to those of ordinary skill in the relevant art may not be discussed in detail but are intended to be part of the specification where appropriate.
The disclosures of the prior art documents cited in the present description are incorporated by reference in their entirety and are therefore part of the present disclosure.
The invention discloses a preparation method of a degradable easily-separated microneedle array for 3D printing, which comprises the following steps:
the G-code file is written before printing, so that the whole printing path is printed according to the requirement of the user in the printing process, and the direct writing can also reduce the slicing process, so that the influence of slicing software on the final printing result is reduced.
By applying the macro editing of Excel, the required structure is directly designed on the Excel interface, the printing parameters can be adjusted, the G-code is generated and then is detected by Repeter-Host software to be correct, the G-code can be led into a Raise3D Pro2 printer, the printing of the micro-needle structure is realized, if the printing result is unqualified, the structure can be directly modified on the Excel interface, so that the slicing link is reduced, and the manufacturing efficiency is improved.
The control of the printer of the present invention is as follows: the left nozzle adopts a TPU wire rod to control the printing of the bottom plate; and the right nozzle adopts PLA to realize the printing of the microneedle body. Whereas the parameters of the microneedles are as follows: the number of the microneedle arrays is 4 multiplied by 4, the height of the microneedles is 1500-2000 μm, the tip size is 70-100 μm, the bottom size is 500-1000 μm, and the distance between the needle bodies is 5mm.
The most critical of the whole printing process is the regulation and control of parameters, the optimal parameters are obtained mainly through experimental process tests, and the selection of the parameters is also carried out under the principle of following control variables.
For the regulation of printing parameters: (1) test for printing temperature: firstly, according to the glass transition temperature of the material and the suggested temperature of the wire rod which is 180-230 ℃, one temperature is taken every 10 ℃ to test the printing result, and the fact that when the temperature is 230 ℃, the liquid flows out too much and the curing time is long due to overhigh temperature is found; when the temperature is 180 ℃ and 190 ℃, the connection between the needle body and the bottom plate is not good during printing; when the temperature is 200 ℃, the phenomenon that the needle body is not well connected with the bottom plate still occurs in the printing process, and the printing effect is the best at 210-220 ℃. In order to ensure that the size of the tip of the microneedle is good, the microneedle printing temperature is set to be 210 ℃ according to the principle that the lower the temperature is, the faster the curing is.
(2) Determination of recovery value and recovery speed: in order to ensure the printing quality of the first layer and the stable combination of the layers, the recovery value and the recovery speed need to be determined, and the quality is optimal under the condition of matching the recovery value of 7mm with the recovery speed of 8000 mm/min.
(3) Selection of printing speed: the printing speed is a key parameter for determining the total printing quantity of the material and the quality of a printing result, and for the printing quality, the slower printing speed is better in the final printing result, so in order to ensure the printing quality, the reasonable printing speed range of the material is combined, the printing speed range of the constant microneedle volume is obtained by utilizing volume conservation, the printing speed is determined to be 800-10000mm/min, then 800mm/min and 1000mm/min are respectively taken, then a speed value is taken every 1000mm/min for detection, the printing quality with the speed of 800mm/min is the best under the matching of relevant parameters such as a recovery value (recovery speed) and printing temperature, and 800mm/min is selected as the printing speed.
(4) Selecting an idle stroke speed: the idle stroke speed refers to the speed of nozzle movement during unprinted events, and is the speed required for the stretching process of the microneedles after printing, and the speed directly determines the sharpness of the microneedles and the shape of the microneedles. By testing the speed range of 1000mm/min to 10000mm/min, one speed value is taken per 1000mm/min, after selecting the parameters according to the previous: the printing temperature is 210 ℃, the recovery value is 7 mm/recovery speed is 8000mm/min, the printing speed is 800mm/min, and a plurality of groups of experiments are carried out to determine the printing quality and the shape of the microneedle.
The final classification can be made according to different microneedle shapes: when the speed is 8000mm/min to 10000mm/min, the printed microneedle is a spindle-shaped microneedle, and the microneedle is convenient to separate a needle body from a base part, namely a separable microneedle; when the speed is 2000mm/min, the shape of the printed micro-needle is far larger than the tip part at the bottom, so that the micro-needle has enough strength, is suitable for manufacturing solid micro-needles or coating micro-needles and the like, and can prevent the micro-needle from breaking; at 1000mm/min, the micro-needle with the sharpness of 70-100 μm cannot be stretched due to the low speed, so the requirement is not met; and the shape of the microneedle is between that of the spindle microneedle and that of the large bottom microneedle when the speed is 2000mm/min to 8000 min/min.
Example one
As shown in fig. 1, 2, 3 and 6, the whole microneedle patch structure of the 3D printed microneedle patch mainly comprises three parts, namely a microneedle needle body (1), an adhesive patch (2) and a microneedle substrate (3). The micro-needle body is made of PLA which is a degradable material, the adhesive patch (such as a non-toxic acrylic coating, medical non-toxic water emulsion, medical non-toxic solvent adhesive and the like) is used for better adhering the skin and the micro-needle to prevent the micro-needle from falling off, and the micro-needle substrate is made of a flexible TPU material, so that the micro-needle can be more attached to the skin.
As shown in fig. 4, the microneedle has a monolithic structure, and it can be seen that the microneedle is enlarged to have a trapezoidal truncated cone structure, the top dimension is 70-100 μm, the bottom dimension is 500-1000 μm, and the entire height is 1500 μm. The micro-needle array is in a 4 multiplied by 4 array structure, and the distance between needle bodies is 5mm.
Example two
The structure of the needle body of the micro-needle is similar to a spindle structure, and the structure is mainly realized by adjusting the idle stroke speed. The dimensions of the respective portions of the microneedles formed at different stretching speeds (idle stroke speeds) and the dimensions of the central portions of the microneedles formed at different stretching speeds (idle stroke speeds) and the actual dimensions are shown in tables 1 and 2 and fig. 5.
TABLE 1 partial size table of microneedles formed at different draw speeds (idle stroke speeds)
Figure BDA0003728315680000081
Table 2 table of ratio of central dimension to actual dimension of theoretical microneedle formed at different stretching speeds (idle stroke speed)
Drawing speed (mm/min) RO (ratio of theory to reality)
2000 2.09
3000 1.86
4000 1.63
5000 1.81
6000 1.67
7000 1.16
8000 0.91
9000 0.95
10000 0.93
In order to achieve controllability of the microneedle arrangement, different arrangements are realized by adjusting the stretching speed (idle stroke speed), for which purpose it is convenient to indicate for the microneedle arrangement that the actual top is directly set to RT, the actual bottom dimension to RB and the actual middle dimension to RM. According to the trapezoidal median theory: the theoretical central dimension RM1 of the microneedle can be obtained by the central dimension = (upper dimension + lower dimension)/2, the ratio of the central dimension RM1 to the actual central dimension of the microneedle can be obtained and is set as R0, and the shape of the microneedle measured by the ratio and a microscope is as shown in a A, B, C microneedle monomer diagram in fig. 7, so that it can be clearly seen that when R0 > 2, the microneedle has a large bottom structure, as shown in fig. 7 (a); when R0 is more than 1 and less than or equal to 2, the structure is a common needle-shaped microneedle, as shown in figure 7 (b); when 1. Ltoreq.R 0, the structure is a spindle-shaped structure, as shown in FIG. 7 (c).
When the shape is matched with the stretching speed (idle stroke speed), when the idle stroke speed is 2000mm/min, the shape is a large bottom microneedle structure, as shown in fig. 7 (a); when the idle stroke speed is between 2000mm/min and 8000mm/min, the structure is a common conical microneedle, as shown in fig. 7 (b); when the idle stroke speed is more than 8000mm/min, the structure is a spindle-shaped structure, as shown in fig. 7 (c).
According to the method, the high-quality microneedle array is directly manufactured by using FDM, and the microneedles are manufactured by combining 3D printing with a traditional stretching method, so that the defects that a post-treatment process is needed after the 3D printing and the damage caused by the post-treatment process is overcome, and the defect that the traditional stretching method cannot control parameters such as stretching speed is overcome. Secondly, by applying the novel method, the microneedles with easily separated shapes can be manufactured by regulating and controlling the printing parameters, so that the separable microneedle array can be manufactured by the 3D printing technology.
Therefore, the preparation method of the degradable easily-separable microneedle array by 3D printing ensures the precision of the microneedles and simplifies the process of manufacturing the separable microneedles by using the mold.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solutions of the present invention and not for limiting the same, and although the present invention is described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that: modifications and equivalents may be made to the invention without departing from the spirit and scope of the invention.

Claims (4)

1. A preparation method of a degradable easily-separable microneedle array for 3D printing is characterized by comprising the following steps:
s1, directly generating a G-code by utilizing the macro function of Excel, importing the G-code into Reetier-Host software to verify the shape of a graph, and determining the printing sequence and number of needle bodies, the height of a microneedle, the sizes of the top and the bottom and the distance between the needle bodies;
s2, leading out the G-code from Repeter-Host software and guiding the G-code into a Raise3DPro2 printer, controlling the printing of a bottom plate by a left nozzle, realizing the printing of a microneedle body by a right nozzle, wherein the bottom plate is made of a flexible environment-friendly material, and the microneedle body is made of a degradable material;
s3, regulating and controlling parameters of printing speed, idle stroke speed and printing temperature based on the G-code, realizing rapid stretching of filaments in the nozzle by utilizing rapid movement of a spray head, and finishing microneedle manufacturing by utilizing the combination of a 3D printing process and a stretching method;
the specific operation in step S3 is as follows:
(1) The parameter regulation and control of the printing speed, the idle stroke speed and the printing temperature need to realize the matching among the parameters, thereby completing the regulation and control of the machine;
(2) The shape of the micro-needle is designed to be related to the moving speed of the nozzle, namely the idle stroke speed, which is also called as the stretching speed, so that the quality of the micro-needle is controlled, and the shape of the micro-needle can also be controlled;
in step S3, the printing speed is 800mm/min, the idle stroke speed range is 8000-10000mm/min, and the printing temperature is 210 ℃.
2. The preparation method of the degradable easily separable microneedle array for 3D printing according to claim 1, wherein: in the step S2, the flexible environment-friendly material is TPU, and is fed into a left spray head when in use; the degradable material is PLA, which is fed at the right hand jet when in use.
3. The preparation method of the degradable easily separable microneedle array according to claim 1, wherein the preparation method comprises the following steps: in step S2, the flexible material includes, but is not limited to, TPU, and the degradable material includes, but is not limited to, PLA.
4. A microneedle patch prepared based on the preparation method of the degradable easily separable microneedle array for 3D printing according to any one of claims 1 to 3.
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