Biomass substrate microneedle and method of making the same

Abstract

The application discloses a biomass substrate microneedle and a preparation method thereof. The preparation method comprises the following steps: dissolving, dissolving a first seed powder by using a urea / strong alkali aqueous solution, and then adjusting the pH of the solution to 6.8-7.2 to obtain a biomass dissolving solution; mixing, mixing the biomass dissolving solution with a second seed powder to obtain a microneedle injection mold liquid; and forming, injecting the microneedle injection mold liquid into a mold, and then drying and demolding to obtain a biomass microneedle. The application takes seed powder as a raw material for preparing the microneedle, and has the advantages of natural raw material, good biocompatibility, wide material selection and suitability for large-scale production.

Description

Technical Field

[0001] This invention relates to the field of microneedle technology, and more specifically, to biomass matrix microneedles and their preparation methods. Background Technology

[0002] Microneedles are mainly used to create micron-sized drug delivery channels on the surface of skin and mucous membranes, enabling transmembrane drug delivery to organisms. Their main applications are in biomedical fields such as medical drug delivery, physical condition monitoring, disease screening, and beauty and health care, with broad application prospects.

[0003] Microneedles are mainly classified into four types according to their drug delivery method: solid microneedles, hollow microneedles, topical microneedles, and dissolving microneedles.

[0004] 1. Solid microneedles: Solid microneedles are inserted into the skin, removed, and then applied to the skin for drug delivery. They can be reused, but the operation is complicated and there is a risk of needle tip breakage and residue in the tissue. Disinfection is required before reuse.

[0005] 2. Hollow microneedles: Drugs are delivered through the pores of hollow microneedles, which can achieve continuous drug delivery or physical condition testing. However, the pore diameter is limited and blockage has occurred. With long-term use, rejection is likely to occur due to the incompatibility between the material and the tissue.

[0006] 3. Apply medication to the microneedle. After the microneedle is inserted into the skin, the medication is released. This method can release medication quickly and efficiently at specific points. However, the surface area of ​​the needle tip is limited, so the total amount of medication carried is limited.

[0007] 4. Dissolving microneedles: Microneedles are manufactured using a drug-containing matrix solution, and then inserted into the skin to release the drug. This process can carry a large amount of drug and achieve sustained and controlled release, but the microneedles need to have sufficient strength and stability.

[0008] Among the four types of microneedles mentioned above, dissolving microneedles are relatively convenient to use, have high drug loading capacity, and good sustained release properties. However, the preparation process of dissolving microneedles in the prior art is relatively complex, and the raw material cost is also relatively high. In view of this, the present invention is proposed. Summary of the Invention

[0009] The purpose of this invention is to provide biomass matrix microneedles and their preparation method, overcoming the problems of relatively high raw material costs and relatively complex processes in the preparation of microneedles in the prior art.

[0010] This invention is implemented as follows:

[0011] In a first aspect, the present invention provides a method for preparing biomass matrix microneedles, comprising the following steps:

[0012] Dissolving: The first seed powder was dissolved in a urea / strong alkali aqueous solution, and then the pH of the solution was adjusted to 6.8-7.2 to obtain a biomass dissolution solution;

[0013] Mixing: The biomass solution is mixed with the second seed powder to obtain a microneedle injection solution;

[0014] The molding process involves injecting the microneedle molding liquid into a mold, then drying and demolding to obtain biomass microneedles.

[0015] In some optional embodiments, the urea / strong alkali aqueous solution contains 1-15 wt% urea, 1-8 wt% strong alkali, NaOH, and the temperature of the urea / strong alkali aqueous solution is 0-25°C.

[0016] In some alternative embodiments, both the first seed powder and the second seed powder are powders of cereal seeds.

[0017] In some alternative embodiments, the first seed powder is at least one of corn flour, wheat flour, glutinous rice flour, millet flour, and rice flour.

[0018] In some alternative embodiments, the second seed powder is at least one of corn flour, wheat flour, glutinous rice flour, millet flour, and rice flour.

[0019] In some alternative embodiments, the mass ratio of the first seed powder to the second seed powder is 1:0.5-1.5.

[0020] In some alternative embodiments, the particle size of the first seed powder and the second seed powder is less than 100 mesh.

[0021] In some alternative embodiments, the dissolution step is performed at a temperature of 0-25°C for 2-24 hours, and the pH of the solution is adjusted to 6-8 with hydrochloric acid after dissolution.

[0022] In some optional embodiments, during the dissolution step, the amount of the first seed powder added accounts for 5-10.0 wt% of the total mass of the biomass dissolution solution.

[0023] In some optional embodiments, during the mixing step, the biomass solution is mixed with the second seed powder at 8-35°C for 60-2400 min to obtain a microneedle injection solution.

[0024] In some optional embodiments, the mold is a polydimethylsiloxane microneedle mold, and the needle shape of the mold is conical, cylindrical, triangular pyramidal or square pyramidal, with a needle base diameter of 100-1000μm, a needle height of 50-1000μm and a needle tip diameter of 5-20μm.

[0025] In some optional embodiments, during the molding step, the microneedle injection molding fluid is injected into the mold in two separate injections, with the mass ratio of the two injections being 1:0.5-1.5.

[0026] In some alternative embodiments, after the microneedle injection fluid is injected into the mold for the first time, the mold containing the microneedle injection fluid is centrifuged, the main purpose of which is to fill the needle tip cavity with the solution.

[0027] In some alternative embodiments, the centrifugation step is performed at 1500-3000 g / min for 5-20 min.

[0028] Secondly, the present invention provides a biomass matrix microneedle prepared by any of the methods described in any of the foregoing embodiments.

[0029] The present invention has the following beneficial effects:

[0030] This application uses seed powder as a raw material for microneedle preparation, which has the advantages of natural raw materials, good biocompatibility, wide availability, and suitability for large-scale production. Attached Figure Description

[0031] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0032] Figure 1 A flowchart of a method for preparing biomass matrix microneedles;

[0033] Figure 2 The in vitro dissolution of the five biomass matrix microneedles prepared in Example 2;

[0034] Figure 3 The results show the DPPH free radical scavenging activity evaluation of the five biomass matrix microneedles prepared in Example 2;

[0035] Figure 4 The results are the biocompatibility evaluation results of the five biomass matrix microneedles prepared in Example 2;

[0036] Figure 5 The results are the adhesion evaluation results of the five biomass matrix microneedles prepared in Example 2;

[0037] Figure 6 The results are the evaluation results of the skin penetration performance of the five biomass matrix microneedles prepared in Example 2;

[0038] Figure 7 The results are the evaluation results of the mechanical properties of biomass matrix microneedles prepared from corn seeds in Example 2 and Comparative Example 4.

[0039] Figure 8 The results are the evaluation results of the mechanical properties of biomass matrix microneedles prepared from wheat seeds in Example 2 and Comparative Example 4.

[0040] Figure 9 The results are the evaluation results of the mechanical properties of the biomass matrix microneedles prepared from glutinous rice seeds in Example 2 and Comparative Example 4.

[0041] Figure 10 The results are the evaluation results of the mechanical properties of the biomass matrix microneedles prepared from millet seeds in Example 2 and Comparative Example 4.

[0042] Figure 11 The results show the mechanical properties of the biomass matrix microneedles prepared from rice seeds in Example 2 and Comparative Example 4. Detailed Implementation

[0043] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0044] One embodiment of this application provides a method for preparing biomass matrix microneedles, such as... Figure 1 As shown, it includes the following steps:

[0045] Dissolving: The first seed powder was dissolved in a urea / strong alkali aqueous solution, and then the pH of the solution was adjusted to 6.8-7.2 to obtain a biomass dissolution solution;

[0046] Mixing: The biomass solution is mixed with the second seed powder to obtain a microneedle injection solution;

[0047] The molding process involves injecting the microneedle molding liquid into a mold, then drying and demolding to obtain biomass microneedles.

[0048] The first step is to add the first seed powder to dissolve it under strong alkaline conditions, then adjust the pH value to neutral, and then add the second seed powder. Since the solution pH is 6-8 when the second seed powder is added, the second seed powder will not dissolve.

[0049] The first step, dissolving, is to provide the base solution for preparing microneedles. The second step, adding a second seed powder and mixing, can improve the mechanical properties of the microneedles and increase their toughness.

[0050] Microneedling is a minimally invasive transdermal drug delivery method that significantly increases the transdermal delivery of small molecules, biomacromolecules, and exosomes by creating micropores in the dermis. Dissolving microneedles are typically made of polymers that gradually dissolve or decompose upon insertion into the skin, releasing the drug. Previous reports on purely plant-based microneedles are scarce. Plant-based microneedles are nearly harmless to the skin and, using the most basic materials, can shorten wound healing time by more than 20% compared to no medication.

[0051] The microneedles prepared by this process not only have antioxidant and wound-healing effects, but also possess high drug loading capacity, suitable mechanical strength, good release depth, and rapid solubility, which facilitates penetration through the skin surface and achieves good therapeutic effects. The method of this invention is rationally designed, uses widely available raw materials, is low in cost, has low sensitization potential, is simple to operate, highly practical, and has a wide range of applications.

[0052] In some optional embodiments, the urea / strong alkali aqueous solution contains 1-15 wt% urea, 1-8 wt% strong alkali, NaOH, and the temperature of the urea / strong alkali aqueous solution is 0-25°C.

[0053] In some alternative embodiments, both the first seed powder and the second seed powder are powders of cereal seeds, which have low allergenicity.

[0054] In some alternative embodiments, the first seed powder is at least one selected from corn flour, wheat flour, glutinous rice flour, millet flour, and rice flour;

[0055] In some alternative embodiments, the second seed powder is at least one selected from corn flour, wheat flour, glutinous rice flour, millet flour, and rice flour;

[0056] In some alternative embodiments, the mass ratio of the first seed powder to the second seed powder is 1:0.5-1.5.

[0057] In some alternative embodiments, the particle size of the first seed powder and the second seed powder is less than 100 mesh.

[0058] In some alternative embodiments, the dissolution step is performed at a temperature of 0-25°C for 2-24 hours, and the pH of the solution is adjusted to 6-8 with hydrochloric acid after dissolution.

[0059] In some optional embodiments, during the dissolution step, the amount of the first seed powder added accounts for 5-10.0 wt% of the total mass of the biomass dissolution solution.

[0060] In some optional embodiments, during the mixing step, the biomass solution is mixed with the second seed powder at 8-35°C for 60-2400 min to obtain a microneedle injection solution.

[0061] In some optional embodiments, the mold is a polydimethylsiloxane microneedle mold, and the needle shape of the mold is conical, cylindrical, triangular pyramidal or square pyramidal, with a needle base diameter of 100-1000μm, a needle height of 50-1000μm and a needle tip diameter of 5-20μm.

[0062] In this embodiment, the size of the mold and the density of the microneedles can be determined according to the actual situation. Specifically, the mold area can be any value from 0.5*0.5cm to 10*10cm, and the microneedles are arranged in an array of 5*5 to 200*200.

[0063] In some optional embodiments, during the molding step, the microneedle injection fluid is injected into the mold in two separate injections, with the mass ratio of the two injections being 1:0.5-1.5.

[0064] The microneedle molding fluid is injected in two stages. This is because after the first injection, centrifugation is required. If too much fluid is added at once, the liquid will fly out during centrifugation, resulting in loss. Distributed injection ensures that the liquid fills the needle tip and is not wasted during centrifugation. The second injection replenishes the liquid volume of the substrate, which can produce microneedles with complete shape and uniform mechanical properties.

[0065] In some alternative embodiments, after the microneedle injection fluid is injected into the mold for the first time, the mold containing the microneedle injection fluid is centrifuged, the main purpose of which is to fill the needle tip cavity with the solution.

[0066] In some alternative embodiments, the centrifugation step is performed at 1500-3000 g / min for 5-20 min.

[0067] Secondly, the present invention provides a biomass matrix microneedle prepared by any of the methods described in any of the foregoing embodiments.

[0068] Example 1

[0069] This embodiment provides a method for preparing biomass matrix microneedles, including the following steps:

[0070] S1. Dissolve urea and NaOH in deionized water to obtain a 3% urea / 2% sodium hydroxide aqueous solution, then pre-cool to 4°C. Select cereal seeds (corn, wheat, glutinous rice, millet, and rice) as microneedle materials. Weigh out each of the five powders and slowly and evenly add them to the stirred urea / sodium hydroxide aqueous solution. Mix thoroughly by shaking and store at 4°C for 12 hours to allow the powders to dissolve completely. Then, adjust the solution to neutral using 1M hydrochloric acid to obtain a 5% (w / w) cereal seed solution. Slowly add the corresponding cereal seed powder to the above solution until the cereal seed powder mass fraction reaches 6%. Mix on a four-dimensional rotary mixer for 2 hours to obtain the microneedle injection solution.

[0071] S2. The above-mentioned injection solution is added to the polydimethylsiloxane (PDMS) microneedle mold (the needles are conical, with a base diameter of 250 μm, a height of 300 μm, a tip diameter of 5 μm, a mold size of 1 cm * 1 cm, and an array of 10 * 10) in two separate additions. The first addition is 170 mg of injection solution to the mold, and the mold is centrifuged at 2000 g / min for 10 min to fill the needle tip cavity with the solution. Then, another 150 mg of injection solution is added to the microneedle mold, and the mold is placed in a drying oven to air dry. After demolding, the plant microneedle array is obtained.

[0072] Example 2

[0073] This embodiment provides a method for preparing biomass matrix microneedles, including the following steps:

[0074] S1. Dissolve urea and NaOH in deionized water to obtain a 7% urea / 4% sodium hydroxide aqueous solution, then pre-cool to 4°C. Select cereal seeds (corn, wheat, glutinous rice, millet, and rice) as microneedle materials. Weigh out each of the five powders and slowly and evenly add them to the stirred urea / sodium hydroxide aqueous solution. Shake to mix thoroughly and store at 4°C for 12 hours to allow complete dissolution. Then, adjust the solution to neutral using 1M hydrochloric acid to obtain a cereal seed solution with a mass concentration of 6.7%. Slowly add the corresponding cereal seed powder to the above solution until the mass fraction of cereal seed powder reaches 10%. Mix on a four-dimensional rotary mixer for 2 hours to obtain the microneedle injection solution.

[0075] S2, same as Example 1.

[0076] Example 3

[0077] This embodiment provides a method for preparing biomass matrix microneedles, including the following steps:

[0078] S1. Dissolve urea and NaOH in deionized water to obtain a 10% urea / 4% sodium hydroxide aqueous solution, then pre-cool to 4°C. Select cereal seeds (corn, wheat, glutinous rice, millet, and rice) as microneedle materials. Weigh out each of the five powders and slowly and evenly add them to the stirred urea / sodium hydroxide aqueous solution. Shake to mix thoroughly and store at 4°C for 12 hours to allow complete dissolution. Then, adjust the solution to neutral using 1M hydrochloric acid to obtain a 10% cereal seed solution. Slowly add the corresponding cereal seed powder to the above solution until the cereal seed powder mass fraction reaches 16%. Mix on a four-dimensional rotary mixer for 2 hours to obtain the microneedle injection solution.

[0079] S2, same as Example 1.

[0080] Example 4

[0081] This embodiment provides a method for preparing biomass matrix microneedles, including the following steps:

[0082] S1. Dissolve urea and NaOH in deionized water to obtain a 12% urea / 6% sodium hydroxide aqueous solution, then pre-cool to 4°C. Select cereal seeds (corn, wheat, glutinous rice, millet, and rice) as microneedle materials. Weigh out each of the five powders and slowly and evenly add them to the stirred urea / sodium hydroxide aqueous solution. Shake to mix thoroughly and store at 4°C for 12 hours to allow complete dissolution. Then, adjust the solution to neutral using 1M hydrochloric acid to obtain a cereal seed solution with a mass concentration of 15%. Slowly add the corresponding cereal seed powder to the above solution until the mass fraction of cereal seed powder reaches 22%. Mix on a four-dimensional rotary mixer for 2 hours to obtain the microneedle injection solution.

[0083] S2, same as Example 1.

[0084] Comparative Example 1

[0085] Urea was dissolved in deionized water to obtain a 7% urea aqueous solution, which was then pre-cooled to 4°C. Cereal seeds—corn, wheat, glutinous rice, millet, and rice—were selected as microneedle materials. Five powders were weighed separately and slowly and evenly added to the stirring urea aqueous solution. The mixture was shaken and stirred until homogeneous, then stored at 4°C for 12 hours to dissolve the powder. If the powder did not dissolve, it could not be used as a molding liquid.

[0086] Comparative Example 2

[0087] Urea and NaOH were dissolved in deionized water to obtain a 1% urea / 1% sodium hydroxide aqueous solution, which was then pre-cooled to 4°C. Cereal seeds—corn, wheat, glutinous rice, millet, and rice—were selected as microneedle materials. Five powders were weighed separately and slowly and evenly added to the stirred urea / sodium hydroxide aqueous solution. The mixture was shaken and incubated at 4°C for 12 hours to allow complete dissolution. The solution was then adjusted to neutral using 1M hydrochloric acid, yielding a 3% (w / w) cereal seed solution. The corresponding cereal seed powder was then slowly added to the above solution until the cereal seed powder mass fraction reached 2.5%. The mixture was then mixed for 2 hours in a four-dimensional rotary mixer to obtain the microneedle injection solution.

[0088] The molding solution was added in two stages to a polydimethylsiloxane (PDMS) microneedle mold (conical needle shape, 250 μm base diameter, 300 μm height, 5 μm tip, 1cm x 1cm mold, 10 x 10 array). The first stage involved adding 170 mg of molding solution to the mold and centrifuging at 2000 g / min for 10 min to fill the needle tip cavity. Then, another 150 mg of molding solution was added to the microneedle mold, and the mold was placed in a drying oven to air dry. After drying, the microneedles failed to form intact structures; the substrate crumbled, making demolding impossible.

[0089] Comparative Example 3

[0090] Urea and NaOH were dissolved in deionized water to obtain a 15% urea / 8% sodium hydroxide aqueous solution, which was then pre-cooled to 4°C. Cereal seeds—corn, wheat, glutinous rice, millet, and rice—were selected as microneedle materials. Five powders were weighed separately and slowly and evenly added to the stirred urea / sodium hydroxide aqueous solution. The mixture was shaken and incubated at 4°C for 12 hours to allow complete dissolution. The solution was then adjusted to neutral using 1M hydrochloric acid, yielding a 20% (w / w) cereal seed solution. The corresponding cereal seed powder was then slowly added to the above solution until the cereal seed powder concentration reached 30%. The mixture was then stirred in a four-dimensional rotary mixer for 2 hours to obtain the microneedle injection solution.

[0091] The above-mentioned injection molding solution was added to the polydimethylsiloxane (PDMS) microneedle mold (conical needle shape, 250 μm base diameter, 300 μm height, 5 μm tip, 1 cm*1 cm mold, 10*10 array) in two batches. The first batch consisted of 170 mg of injection molding solution added to the mold and centrifuged at 2000 g / min for 10 min to fill the needle tip cavity with solution. Then, another 150 mg of injection molding solution was added to the microneedle mold and placed in a drying oven to dry naturally. Urea crystals precipitated after drying.

[0092] Comparative Example 4

[0093] This comparative example provides a method for preparing biomass matrix microneedles, including the following steps:

[0094] S1. Dissolve urea and NaOH in deionized water to obtain a 7% urea / 4% sodium hydroxide aqueous solution, then pre-cool to 4°C. Select cereal seeds (corn, wheat, glutinous rice, millet, and rice) as microneedle materials. Weigh out each of the five powders and slowly and evenly add them to the stirring urea / sodium hydroxide aqueous solution. Mix well by shaking and store at 4°C for 12 hours to allow the powders to dissolve completely. Then, adjust the solution to neutral using 1M hydrochloric acid to obtain a cereal seed solution with a mass concentration of 6.7%.

[0095] S2, same as Example 1.

[0096] The five biomass matrix microneedles obtained in Example 2 were placed on phosphate-buffered saline (PBS, pH = 7.4) moistened rabbit skin for in vitro dissolution experiments to simulate the in vivo dissolution of the microneedle patches upon skin contact. The results are as follows: Figure 2 As shown, from Figure 2 As can be seen, the microneedle tips of all test patches dissolved or deformed rapidly within 120 seconds.

[0097] The DPPH free radical scavenging activity of the five biomass matrix microneedles obtained in Example 2 was tested, and the test results are as follows: Figure 3 As shown, the DPPH radical scavenging activity of all samples increased gradually in a concentration-dependent manner. When the microneedle solid sample was prepared into a solution of 100 mg / mL, suspended in a four-dimensional rotary suspending apparatus for 2 h, and centrifuged at 8000 g / min to obtain a supernatant concentration of 10 mg / mL, the DPPH radical scavenging rates of corn, wheat, glutinous rice, millet, and rice were 56.42%, 42.60%, 43.41%, 34.07%, and 44.07%, respectively, indicating that all samples exhibited antioxidant activity.

[0098] The biocompatibility of the five biomass matrix microneedles obtained in Example 2 was evaluated using the MTT assay, and the results are as follows: Figure 4 The microbes are almost non-toxic to 3T3-NIH cells and have good biocompatibility.

[0099] The adhesion properties of the five biomass matrix microneedles obtained in Example 2 were evaluated through skin and visceral adhesion experiments. The results are as follows: Figure 5 The microparticles exhibit good adhesion to bent skin and mouse hearts.

[0100] The skin penetration performance of the five biomass matrix microneedles obtained in Example 2 was investigated by microneedle pressure and skin penetration experiments, followed by H&E staining and fluorescence staining experiments. The results are as follows: Figure 6As shown, microneedles can create noticeable indentations on the skin, demonstrating transdermal penetration.

[0101] The mechanical properties of ten biomass matrix microneedles obtained in Example 2 (M+F group) and Comparative Example 4 (M group) were tested using a universal testing machine. The results are as follows: Figure 7-11 As shown, in Example 2, the force on the microneedle tip can reach more than 0.05N, which enables it to penetrate the skin.

[0102] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for preparing biomass matrix microneedles, characterized in that, Includes the following steps: The first seed powder is dissolved in a urea / strong alkali aqueous solution, and then the pH of the solution is adjusted to 6.8-7.2 with hydrochloric acid to obtain a biomass dissolving solution. In the urea / strong alkali aqueous solution, the mass fraction of urea is 1-15 wt%, the mass fraction of strong alkali is 1-8 wt%, the strong alkali is NaOH, and the temperature of the urea / strong alkali aqueous solution is 0-25℃. The first seed powder is one of corn flour, wheat flour, glutinous rice flour, millet flour, and rice flour, and the amount of the first seed powder added accounts for 5-10.0 wt% of the total mass of the biomass dissolving solution. The temperature of the dissolving step is 0-25℃, and the time is 2-24 hours. The biomass solution is mixed with the second seed powder at 8-35℃ for 60-2400 min to obtain a microneedle injection solution; the second seed powder is one of corn flour, wheat flour, glutinous rice flour, millet flour and rice flour, and the mass ratio of the first seed powder and the second seed powder is 1:0.5-1.5; the first seed powder and the second seed powder are the same type. The molding process involves injecting the microneedle molding liquid into a mold, then drying and demolding to obtain biomass microneedles.

2. The method for preparing biomass matrix microneedles according to claim 1, characterized in that, The particle size of the first seed powder and the second seed powder is less than 100 mesh.

3. The method for preparing biomass matrix microneedles according to claim 1, characterized in that, The mold is a polydimethylsiloxane microneedle mold, and the needle shape of the mold is conical, cylindrical, triangular pyramidal or square pyramidal, with a needle base diameter of 100-1000μm, a needle height of 50-1000μm and a needle tip diameter of 5-20μm.

4. The method for preparing biomass matrix microneedles according to claim 1, characterized in that, In the molding step, the microneedle injection liquid is injected into the mold in two parts, and the mass ratio of the two injections of microneedle injection liquid is 1:0.5-1.

5.

5. The method for preparing biomass matrix microneedles according to claim 4, characterized in that, After the microneedle injection fluid is injected into the mold for the first time, the mold containing the microneedle injection fluid is centrifuged.

6. The method for preparing biomass matrix microneedles according to claim 5, characterized in that, The centrifugation step involves centrifuging at 1500-3000g / min for 5-20 minutes.

7. A biomass matrix microneedle prepared by the method according to any one of claims 1-6.

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