CN114949344A

CN114949344A - Coating microneedle patch for skin filling

Info

Publication number: CN114949344A
Application number: CN202210384595.XA
Authority: CN
Inventors: 吴力波
Original assignee: Individual
Current assignee: Individual
Priority date: 2022-04-13
Filing date: 2022-04-13
Publication date: 2022-08-30

Abstract

The invention discloses a coated microneedle patch for skin filling. A microneedle patch is provided with a plurality of microneedles, and the number of the microneedles is determined by the dosage of the administered drugs and the acting skin area. The materials of the needle core and the patch substrate are polylactic acid, and the surface coating of the microneedle is hyaluronic acid. The microneedle patch can be pressed and implanted into the skin through a special device to release hyaluronic acid and partial polylactic acid in a dermis layer, and the coated microneedle is made of safe and biodegradable materials in cooperation with injection molding and dip coating. The density of the micro-needle on the micro-needle patch and the dosage of the drug can be customized in the preparation process. In addition, the drug release kinetics of the coated microneedle is discussed in the invention, so that an operator can understand and control the drug release efficiency.

Description

Coating micro-needle patch for skin filling

Technical Field

The invention belongs to the technical field of transdermal microneedle array equipment, and particularly relates to a coated microneedle patch for skin filling.

Background

The skin is the largest organ of the human body and also the barrier between the body and the external environment. Meanwhile, the skin has a great influence on the appearance of a person. The skin is composed of the epidermis, dermis, and subcutaneous tissues. The dermis consists of collagen, elastic fiber and matrix. During human growth, ultraviolet rays can penetrate the skin to reach the dermis layer, and matrix metalloproteases in the body are activated, and the enzymes can induce excessive degradation of collagen. Meanwhile, sugar ingested by the human body reacts with collagen in the skin to decompose the collagen. When the synthesis and loss speed of collagen in the skin are not kept in a balanced state any more, the skin has insufficient elasticity and loses support, so that the skin aging problems such as wrinkles and the like are generated.

Hyaluronic acid is a polysaccharide widely found in animals and humans. Hyaluronic acid is widely used in the therapeutic processes of humans or animals thanks to its biodegradability and biocompatibility. The molecular structure of hyaluronic acid makes it possible to support or capture the amount of water molecules about 1000 times its molecular weight. In human synovial fluid, hyaluronic acid has an average molecular mass of 4000 kDa.

Hyaluronic acid is naturally present in large quantities in the human dermis. The loss of hyaluronic acid or collagen in the human body causes a wrinkle phenomenon. Thus, non-toxic, non-irritating hyaluronic acid is typically used for injection into the dermis (as a dermal filler) to restore skin volume and minimize the appearance of wrinkles and nasolabial folds.

The degradation speed of the hyaluronic acid with large molecular weight in the skin is lower, the time of the hyaluronic acid with large molecular weight is longer, and therefore the filling effect of the hyaluronic acid with large molecular weight in the dermis layer is better. Molecules with molecular weights greater than 500Da penetrate very poorly through the epidermal layers. Thus, unlike the mode of application to the epidermis, the relying microneedles are effective in delivering relatively high molecular weight hyaluronic acid into the dermis. Simultaneously, compare in the mode of traditional injection, the micropin is put in and is had the operation degree of difficulty and little advantage of wound.

Polylactic acid is a degradable polymer, biodegradable and non-toxic. The polylactic acid with high molecular weight can be hydrolyzed into polylactic acid with low molecular weight or harmless lactic acid monomer under the catalysis of enzyme in human body. Meanwhile, the increase of the concentration of the lactic acid monomer in human tissues can not increase the risk of acidosis, and muscle tissues can also secrete lactic acid in the process of strenuous exercise of people. Lactic acid is metabolized in the human body and converted to glucose in the liver by the Cori cycle.

Elevated concentrations of lactic acid in the dermal layers are the primary signals for collagen synthesis and repair. The signal activates prolyl hydroxylase activity, up-regulates growth factor TGF-beta, and activates fibroblasts to secrete and synthesize more collagen. Thus, release of lactic acid monomers in the dermal layer also engorges the skin.

The micro-needle refers to a micron-sized needle-shaped structure, and the micro-needle administration is a novel transdermal administration mode. The micro-needle can carry the macromolecular drugs to pierce the epidermis layer of the human skin so as to release the macromolecular drugs to the dermis layer and then be absorbed by the tissue. Compared with the traditional transdermal drug delivery, the microneedle drug delivery improves the release efficiency of the drug. On the other hand, compared with the systemic administration such as intravenous injection or oral administration, the microneedle administration directly releases the drug in the skin layer to be treated, so that the drug administration efficiency is improved, and the toxicity risk of the drug to the human body is also reduced.

Microneedles can be classified as dissolvable microneedles, hollow microneedles, and coated microneedles. The whole needle body of the soluble microneedle is made of soluble material mixed with medicines, and the soluble microneedle starts to dissolve and release the medicines when meeting water after penetrating into a epidermal layer and reaching a dermal layer. The soluble microneedle has no residue after being released in the skin, so that the problem that the microneedle is broken in the skin and is difficult to treat is solved, and the recovery difficulty of medical wastes is reduced. However, due to the characteristic that the soluble microneedle can be dissolved after being wetted, the moisture environment has a great influence on the physical structure stability of the soluble microneedle, which also brings a challenge to the administration of the soluble microneedle in a moist tissue (oral cavity, eyeball, etc.). The hollow micro-needle is mainly made of silicon or photosensitive polymer, and the drug can be injected into the skin through a micro-cavity channel in the hollow micro-needle body structure, but the hollow structure also has the characteristic of weak overall structure, and potential safety hazards can be brought to people when the micro-needle made of non-biocompatible material is broken in the skin. The coated micro-needle can be divided into a needle body and a medicament, wherein the needle body is made of biodegradable materials, such as polylactic acid. The coating drug may be selected for different therapeutic applications. When the coated micro-needle penetrates into the dermis, the medicine is released from the surface of the needle body after meeting water. Compared with other microneedle types, the coated microneedle has stable mechanical structure, and the selection of the drug also has the characteristic of personalized customization. However, there is currently no commercial application of coated microneedles.

Disclosure of Invention

The purpose of the invention is as follows: aiming at overcoming the defects in the prior art and aiming at the requirements of the current medical and American markets on hyaluronic acid injection filling with low wound and high delivery rate, the invention provides the coated microneedle patch for skin filling.

The technical scheme is as follows: in order to realize the purpose, the invention adopts the technical scheme that:

a coated microneedle patch for skin filling comprises a substrate, microneedles standing on the substrate and a coating on the surface of the microneedles, wherein the microneedles and the substrate are both made of polylactic acid materials, the microneedles are of micron-sized conical structures, and the coating is hyaluronic acid coated on the surface of the microneedles.

Hyaluronic acid is widely present in connective, epithelial and neural tissues and is one of the major components of the extracellular matrix. The hyaluronic acid has the characteristics of no toxicity, low immunoreaction, high biocompatibility, biodegradability, absorbability for human bodies and the like, and can be used for eye surgery, intra-articular injection, wound healing and surgical anti-adhesion agents. With the development of medical and cosmetic industries, hyaluronic acid can also be used for filling wrinkles and adjusting facial tissues. In order to achieve better skin filling effect, the hyaluronic acid in the invention adopts hyaluronic acid with medium molecular weight (500 k-2000 kDa) to reduce the degradation rate of hyaluronic acid in the dermis layer and maintain the skin filling effect.

Polylactic acid is a thermoplastic aliphatic polyester, and is currently widely used in biomedical engineering as surgical sutures, bone screws, bone plates, and the like. Polylactic acid fillers were approved by the FDA in the united states for use in facial filling materials for aids patients in 2004, have gained wide acceptance over several years of clinical use, and were approved by the FDA in 2009 for use in aesthetic filling of humans. The polylactic acid in the invention adopts levorotatory polylactic acid. Compared with the dextro-polylactic acid, the degradation speed of the levo-polylactic acid is higher, so that the micro-needle can degrade more lactic acid monomers in a limited time of being implanted into the skin, the secretion of collagen in the dermis is promoted, and the filling degree of the skin is enhanced.

At present, the wrinkle removing modes in the medical and beauty fields are mainly divided into the steps of smearing hyaluronic acid on an epidermal layer, injecting polylactic acid microspheres subcutaneously and injecting hyaluronic acid subcutaneously. The macromolecular structure of hyaluronic acid is difficult to enter the dermis due to the barrier of the stratum corneum, which results in inefficient application of the epidermis. On the other hand, whether polylactic acid microspheres or hyaluronic acid, subcutaneous injection is performed under the operation of professional medical care personnel. At the same time, the subcutaneous injection mode risks irreversible trauma to the skin. The invention adopts the micro-needle to deliver the hyaluronic acid and the polylactic acid into the dermis at the same time, and compared with the traditional administration mode, the invention can deliver the medicine efficiently under the conditions of minimal invasion and no pain, thereby eliminating wrinkles in the skin.

Hyaluronic acid is uniformly coated on a polylactic acid needle body with high mechanical strength, and compared with a soluble microneedle and a hollow microneedle, the microneedle can stably pierce through wet human tissues so as to efficiently put medicines.

After the polylactic acid micro-needle coated with hyaluronic acid is penetrated into the dermis of a human body, the exposed polylactic acid needle body part begins to be degraded into lactic acid monomers under the catalysis of enzyme along with the release of the hyaluronic acid coating on the surface, and the lactic acid monomers can promote the secretion of collagen in the dermis, so that the skin is full.

In one embodiment of the invention, the microneedles and the substrate are both made of a levorotatory polylactic acid material.

The lactic acid monomer can be divided into D-lactic acid and L-lactic acid according to the chirality of the 3D structure, and the structural formula is shown as the formula (I). The structural formula of the polylactic acid polymerized by the lactic acid monomer is shown as the formula (II). Wherein, the degradation speed of the levorotatory polylactic acid in human body is obviously different from that of the dextrorotatory polylactic acid.

In order to improve the degradation speed of the polylactic acid micro-needle in the skin, the invention adopts the levorotatory polylactic acid. The levorotatory polylactic acid particles are matched with a metal mold obtained by precision processing to be made into a microneedle structure in an injection molding mode. The prepared micro-needle patch is dipped in a hyaluronic acid solution (with the concentration of 10-20% m/v) pool to dip hyaluronic acid, and the prepared micro-needle patch is matched with low-temperature air drying to finally obtain the polylactic acid micro-needle patch loaded with the hyaluronic acid coating.

In one embodiment of the invention, the microneedle has a conical structure, the height of the microneedle body is 500-1500 μm, the diameter of the needlepoint is less than 100 μm, and the diameter of the needle bottom is less than 500 μm, in consideration of the elastic resistance and deformation of the skin; the substrate has a thickness of 2000 μm, and the size and shape of the substrate are designed to reduce the pain caused by the penetration of the microneedle into the skin.

In one embodiment of the present invention, the molecular weight of the hyaluronic acid is 500 k-2000 kDa, which is a medium molecular hyaluronic acid. Hyaluronic acid is a polysaccharide widely present in human skin tissue and responsible for storing water to make the skin plump. Wherein, the cross-linking degree of the medium molecular hyaluronic acid is higher, and the aged skin can be plump again due to the filling and shaping functions of the medium molecular hyaluronic acid, so that wrinkles are counteracted.

In one embodiment of the present invention, the yield strength of the individual polylactic acid microneedles is up to 1100 mN.

In one embodiment of the invention, the hyaluronic acid has a thickness of 20 ± 2 μm.

In one embodiment of the present invention, a coated microneedle patch has a number of microneedles, which is determined by the dose of hyaluronic acid and the area of skin affected.

Another object of the present invention is to provide a method for preparing the coated microneedle patch for skin filling described above, comprising the steps of:

(1) preparing a substrate and microneedles by injection molding of polylactic acid raw materials;

(2) and coating the surface of the prepared microneedle with a hyaluronic acid solution to prepare the coated microneedle patch.

The polylactic acid micro needle can be prepared by a thermoplastic processing method, and the coating medicine is coated on the surface of the polylactic acid needle body in a dipping mode after the polylactic acid micro needle is prepared. The coated microneedle prepared by the two-step method can also be suitable for loading other high-temperature sensitive drugs.

In one embodiment of the present invention, in the step (2), the concentration of the hyaluronic acid solution is 10 to 20% m/v.

In one embodiment of the present invention, in the step (2), the hyaluronic acid solution is coated on the surface of the prepared polylactic acid microneedle by dip coating.

In one embodiment of the present invention, the polylactic acid microneedle is immersed in the hyaluronic acid solution for 5 to 10 seconds.

In one embodiment of the present invention, the polylactic acid microneedle is immersed in the hyaluronic acid solution for 5 to 8 seconds.

In one embodiment of the present invention, the microneedles and the substrate are integrally formed by injection molding.

In one embodiment of the invention, the injection molding temperature is 180-230 ℃.

In one embodiment of the invention, the injection molding temperature is 200 ℃.

In one embodiment of the present invention, step (2) is further followed by: air drying at low temperature of not higher than 20 deg.C.

In one embodiment of the present invention, step (2) is further followed by: and (3) air-drying at a low temperature of 15-20 ℃.

In one embodiment of the present invention, the present invention provides a method for preparing the microneedle patch, comprising:

(1) medical grade levorotatory polylactic acid granule is added injection moulding machine: injecting the levorotatory polylactic acid into a metal female die in a molten state, and cooling to obtain a polylactic acid microneedle patch;

(2) dipping the prepared polylactic acid microneedle patch in a hyaluronic acid solution pool for 5-8 seconds with the needle point facing downwards, so that the hyaluronic acid solution is coated on the surface of the polylactic acid microneedle;

(3) and (3) air-drying the hyaluronic acid solution on the surface of the polylactic acid microneedle at a low temperature of 15-20 ℃ to finally obtain the coated microneedle product.

The coated microneedle patch disclosed by the invention is penetrated into the skin by a special instrument, and the microneedle is separated from the instrument after penetrating into the skin epidermal layer of the skin. Hyaluronic acid in the coating begins to dissolve and release when meeting water in the dermis layer, promotes filling of hyaluronic acid and secretion of collagen in the dermis, and thus fills the skin. When the hyaluronic acid coating is dissolved and released, part of the L-polylactic acid is hydrolyzed and released under the action of enzyme in the dermis. The hydrolysate L-lactic acid can stimulate fibroblast to secrete type I and type III collagen of human body, so as to increase filling degree of dermis and improve facial wrinkles.

Has the advantages that: compared with the prior art, the polylactic acid micro-needle patch structure is prepared by adopting polylactic acid particles in an injection molding mode and matching with a metal mold obtained by precision processing, the prepared micro-needle patch is soaked in a hyaluronic acid solution (with the concentration of 10-20% m/v) pool to dip hyaluronic acid, and the polylactic acid micro-needle patch loaded with the hyaluronic acid coating is finally obtained by matching with low-temperature air drying. The micro-needle releases hyaluronic acid and lactic acid monomers within a certain period of time after being implanted into the skin, promotes hyaluronic acid filling and collagen secretion in the dermis, and thus fills the skin. According to the invention, the coating and air drying of the hyaluronic acid are completed under a low-temperature condition, so that the activity of the hyaluronic acid is effectively guaranteed.

Drawings

In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts.

Fig. 1 is a schematic illustration of coated microneedle patches releasing hyaluronic acid and lactic acid monomers in the dermal layer.

Fig. 2 is a representation of a polylactic acid microneedle patch. [A] Is a polylactic acid micro-needle patch prepared by injection molding technology. [B] Is a structural schematic diagram of a single polylactic acid microneedle. [C] The coated microneedle is prepared by dipping the polylactic acid microneedle in a hyaluronic acid solution and then air-drying at low temperature.

Fig. 3 is a mechanical strength test of polylactic acid microneedles. [A] Is a schematic diagram of polylactic acid microneedles before pressure testing. [B] The schematic diagram is shown after the polylactic acid microneedle is crushed and damaged. [C] The change curve of the pressure borne by the polylactic acid microneedle in the mechanical strength test process is shown.

Fig. 4 is a schematic structural diagram of the spring driving device.

Fig. 5 shows the release of drug from coated microneedles in pig skin. [A] Is a schematic diagram of the coated microneedle implanted into the pigskin under the pushing of a special injection apparatus. [B] The coated microneedles were removed 1 hour after the implantation of the pigskin and fluorescence imaging of the pigskin sections. [C] The drug release efficiency of the coated microneedle in the pigskin is improved.

Detailed Description

The invention will be further described with reference to the following figures and examples. The present invention will be better understood from the following examples. However, those skilled in the art will readily appreciate that the specific material ratios, process conditions and results thereof described in the examples are illustrative only and should not be taken as limiting the invention as detailed in the claims.

The invention discloses a coated microneedle patch for filling skin, in particular to a coated microneedle patch for filling facial skin, which has guiding significance for the industrialized development of a novel transdermal drug delivery technology. The microneedle is a short for micron needle structure. The surface of the coated microneedle is covered with the active pharmaceutical ingredient, and the microneedle firstly penetrates the epidermal layer of the outermost layer of human skin and then releases the surface active pharmaceutical ingredient into the dermal layer or the subcutaneous fat layer. The coated microneedle comprises a core and a drug covering the surface of the core. A microneedle patch is provided with a plurality of microneedles, and the number of the microneedles is determined by the dosage of the administered drugs and the acting skin area. The needle core and the substrate material of the patch are both polylactic acid, and the surface coating of the micro needle is hyaluronic acid.

The microneedle patch can be implanted into the skin through the spring driving device shown in fig. 4, so that hyaluronic acid and part of polylactic acid can be released in the dermis, and the coated microneedles are made of safe and biodegradable materials in cooperation with injection molding and dip coating. The density (i.e. the density, which refers to the number of microneedles on one patch) of the microneedles on the microneedle patch and the drug dosage (which refers to the total amount of drugs carried in all microneedle coating layers on one patch) can be customized in the preparation process, and are determined by the dosage of hyaluronic acid and the acting skin area. In addition, the drug release kinetics of the coated microneedle is discussed in the invention, so that an operator can understand and control the drug release efficiency.

Experimental materials: the polylactic acid used (6201D, NatureWorks) had an average molecular weight of 75 kDa. Hyaluronic acid was purchased from push pharmaceuticals, ltd, and had an average molecular weight of 1500 kDa. The fluorescent reagent rhodamine B is purchased from Sigma-Aldrich and has a molecular weight of 479 Da. The pigskin is stored in an environment of-80 ℃ and is unfrozen for one hour in a normal temperature environment before the experiment.

The confirmation that the hyaluronic acid can be coated on the surface of the polylactic acid microneedle to prepare the coated microneedle is provided.

According to previous studies, the force required for a single microneedle structure to penetrate human skin is at least 58 mN. The polylactic acid microneedles in the present invention have sufficient mechanical strength to pierce the skin.

In order to make the release and diffusion of hyaluronic acid in skin more obvious, a fluorescent reagent rhodamine B is added into a hyaluronic acid solution coated on the surface of a polylactic acid microneedle. The coated microneedle is implanted in the pig skin at a speed of 2m/s under the push of a special spring-driven device, namely a spring-driven injector, and waits for the release of the loaded drug.

When the coated microneedles are implanted in the pigskin for a specific time, the microneedles are pulled out. The extracted micro-needle is placed in water, so that the residual medicine on the surface of the micro-needle can be completely dissolved. The quantity of the residual drug on the surface of the microneedle can be calculated by using an enzyme-labeling instrument, so that the release efficiency of the drug in the skin can be calculated. The pigskin can be sliced after the micro-needle is taken out, and the pigskin is placed in a fluorescence microscope to observe the diffusion condition of the medicine.

Example 1

In the embodiment, polylactic acid is used as a microneedle material, and hyaluronic acid is used as a coating drug. The microneedle patch delivery pattern is shown in figure 1.

Preparation of coated microneedle patch for skin filling

Injecting polylactic acid particles into an injection molding machine, and processing according to a conventional polylactic acid injection molding process. And the temperature of injection molding is 200 ℃, the molten polylactic acid is poured into a metal mold, cooled and solidified, and the microneedle patch is taken out and dried for 12 hours at room temperature. The polylactic acid micro-needle patch prepared by injection molding is shown in fig. 2A and 2B, the height of the needle body of the obtained micro-needle is 1000 μm, the diameter of the needle point is 80 μm, and the diameter of the needle bottom is 400 μm; the thickness of the substrate was 2000. mu.m.

The coating medicine is coated on the surface of the micro-needle in a dipping mode. The coated microneedles were prepared by dipping the microneedles in hyaluronic acid (15% m/v) solution for 5 seconds, and then air-blowing and drying at 20 ℃ to obtain a coated microneedle, the thickness of the coating being 20 μm, as shown in fig. 2C. The prepared coated microneedle patch was stored in a sterile environment at 4 ℃.

The polylactic acid micro-needle prepared by the invention is measured for mechanical strength through a mechanical experiment of a force-displacement monitor. The sensor pressed the polylactic acid microneedles at a rate of 2 mm/min as shown in fig. 3A. The mechanical experiment was continued until after the polylactic acid microneedles were squeezed to full deformation, as shown in fig. 3B. In the mechanical experiment process, the pressure born by the polylactic acid microneedle is shown in fig. 3C, and it can be observed on an image that the force of 1100mN can make the microneedle yield and deform. The pilot study showed that 58mN is the minimum force required for a single microneedle to penetrate human skin. Thus, the microneedles in the present invention have sufficient mechanical strength to pierce the skin.

The coated microneedle of the present invention is implanted into the pigskin by a spring-driven injector, as shown in fig. 4 and 5A, the spring-driven injector is composed of a top end, a spring and a bottom end which are sequentially connected, the top end is used for contacting and connecting with the substrate of the coated microneedle patch, external pressure is applied by the bottom end of the spring-driven injector, the middle spring is compressed and extended to adjust the intensity and speed of the pressure, so that the top end is stably and effectively pushed at a speed of 2m/s to pierce the coated microneedle patch into the skin.

In order to make the observation effect more obvious, a rhodamine B fluorescent reagent is added into the coating medicine. The coated microneedles were pulled out one hour after implantation in the pigskin. The punctured section of the pigskin was sectioned and observed in a fluorescence microscope, as shown in fig. 5B. The coated drug may be released and diffused in the dermal layer by the microneedles. And (3) placing the drawn micro-needle in ultra-clean water for 2 hours to fully dissolve the rhodamine B remained on the surface of the micro-needle in the water. The concentration of rhodamine B in the solution can be measured by a microplate reader, so that the mass of the rhodamine B remained on the surface of the microneedle can be calculated, and the release efficiency of the drug loaded by the coated microneedle in the skin can be further calculated. As shown in fig. 5C, the drug release efficiency of the coated microneedle can reach about 35% after being implanted into the pigskin for 1 hour, and the drug release efficiency of the coated microneedle can reach 70% after being implanted into the pigskin for 2 hours. Considering that human body water content is more than that of the pigskin sample, the drug release efficiency should be higher in actual human skin.

As fully demonstrated by the above examples, the present invention prefers a polymer species, hyaluronic acid, which can be effectively coated on the surface of polylactic acid microneedles to make a coated microneedle patch. The polylactic acid micro-needle has enough mechanical strength to puncture the epidermal layer, so that the loaded medicament can be directly and effectively released into the dermal layer. Compared with the traditional smearing or subcutaneous injection administration mode, the coated microneedle patch provided by the invention can deliver the drug to a specified skin layer efficiently and in a targeted manner, and only causes less trauma to the skin. The painless microneedle patch which is possible to operate by itself has an important promoting effect on the future skin filling field and has an important significance on the development of a transdermal drug delivery system.

The above description is only of the preferred embodiments of the present invention, and it should be noted that: it will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the principles of the invention and these are intended to be within the scope of the invention.

Claims

1. The coated microneedle patch for skin filling is characterized by comprising a substrate, microneedles standing on the substrate and a coating on the surface of the microneedles, wherein the microneedles and the substrate are both made of polylactic acid materials, the microneedles are of micron-sized conical structures, and the coating is hyaluronic acid coated on the surface of the microneedles.

2. The coated microneedle patch for skin augmentation of claim 1, wherein said microneedles and said substrate are made of L-polylactic acid material.

3. The coated microneedle patch for skin augmentation of claim 1, wherein the molecular weight of hyaluronic acid is 500 k-2000 kDa.

4. The coated microneedle patch for skin augmentation of claim 1, wherein the microneedles are tapered, the height of the needles is 500-1500 μm, the diameter of the tips of the needles is less than 100 μm, and the diameter of the bottoms of the needles is less than 500 μm; the thickness of the substrate was 2000 μm.

5. The coated microneedle patch for skin augmentation of claim 1, wherein said single polylactic acid microneedle has a yield strength of up to 1100 mN.

6. The coated microneedle patch for skin augmentation of claim 1, wherein the thickness of hyaluronic acid is 20 ± 2 μm.

7. The coated microneedle patch for skin augmentation of claim 1, wherein a number of microneedles are provided on one coated microneedle patch, and the number is determined by the dose of hyaluronic acid and the area of skin affected.

8. The method of preparing a coated microneedle patch for skin augmentation of claim 1, comprising the steps of:

(1) preparing a base and microneedles by injection molding of a polylactic acid raw material;

9. The method according to claim 8, wherein in the step (2), the concentration of the hyaluronic acid solution is 10-20% m/v;

the hyaluronic acid solution is wrapped on the surface of the prepared polylactic acid microneedle in a dipping coating mode, and the dipping time of the polylactic acid microneedle in the hyaluronic acid solution is 5-10 s.

10. The method of claim 8, wherein the microneedles and the substrate are integrally formed by injection molding at a temperature of 180-230 ℃.

11. The method of claim 8, wherein step (2) is further followed by: air drying at low temperature of not higher than 20 deg.C.