Triamcinolone acetonide patch and preparation device thereof

Abstract

The invention relates to the technical field of scar treatment, in particular to a triamcinolone acetonide patch and a preparation device.The triamcinolone acetonide patch comprises a hydrogel layer, a microneedle drug delivery layer and a pain relieving layer which are sequentially compounded from outside to inside, hollow parts are arranged in the hollow microneedles, the hollow parts are filled with triamcinolone acetonide liquid medicine, the top ends of the hollow microneedles are fixedly connected with elastic assemblies, and the elastic assemblies automatically retract into the microneedle administration layer after releasing medicine. Through a three-layer structure composed of the hydrogel layer, the microneedle drug delivery layer with the temperature-sensitive elastic assembly and the cream layer containing lidocaine, convenient, low-pain and safe drug delivery of scars is achieved, and meanwhile efficient and accurate production is guaranteed by matching with an integrated preparation device.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of scar treatment, in particular to a triamcinolone acetonide patch and a preparation device thereof. BACKGROUND

[0002] The triamcinolone acetonide patch is an external administration device for treating hypertrophic scars. By loading the triamcinolone acetonide drug in the patch structure, the drug is administered into the scar tissue through skin penetration or puncture, thereby playing an anti-inflammatory and inhibiting scar proliferation role, and providing a convenient local administration method for scar treatment.

[0003] Most of the existing triamcinolone acetonide patches on the market, such as the triamcinolone acetonide neomycin patch produced by Heilongjiang Huimeijia Pharmaceutical, have limitations. Most patches rely on passive drug penetration, making it difficult to accurately control the administration depth, and the drug effect is slow and uneven. Some patches containing microneedles use fixed microneedle design, which can cause persistent irritation and inflammation due to long-term retention of microneedles in the skin, and lack effective surface anesthesia mechanism, so the administration process is still accompanied by obvious pain. At the same time, the existing patches do not have a special wound protection structure, which cannot provide an appropriate healing environment for the scar wound, and the operation requires professional personnel to control the force and time, which has high operation requirements. Improper operation may lead to insufficient drug release or excessive damage to deep skin tissue, making it difficult to balance treatment effect, safety and patient comfort. In summary, the existing triamcinolone acetonide treatment methods have deficiencies in pain control, operation convenience and tissue safety, and the existing preparation equipment also cannot meet the precise and efficient production requirements, so a triamcinolone acetonide patch and a matching preparation device are proposed, which integrates surface anesthesia, intelligent microneedle administration and wound protection. SUMMARY

[0004] To solve the above problems, the present application provides a triamcinolone acetonide patch and a preparation device thereof, which realizes convenient, low-pain and safe administration of scars through a three-layer structure composed of a hydrogel layer, a microneedle administration layer with a temperature-sensitive elastic component and a lidocaine-containing cream layer, and a matching integrated preparation device ensures efficient and accurate production.

[0005] In order to achieve the above object, the technical scheme of the present application is as follows: a triamcinolone acetonide patch comprising a three-layer structure from outside to inside: a hydrogel layer, a microneedle administration layer and an analgesic layer, wherein the microneedle administration layer comprises a microneedle array composed of a plurality of hollow microneedles, each of the hollow microneedles is provided with a hollow portion extending to the tip of the hollow microneedle and communicating with the outside, the hollow portion is filled with a triamcinolone acetonide solution composed of 0.02-1.25 mg / needle of triamcinolone acetonide, 5-15 wt% keratin hydrogel hydrophilic polymer network and PBS buffer, and the top end of each of the hollow microneedles is fixedly connected with an elastic component for ejecting and penetrating into the epidermis by pressing, which automatically retracts into the microneedle administration layer after releasing the drug;

[0006] Each of the elastic components comprises a temperature-sensitive unit and a plurality of push rods corresponding to the hollow microneedles fixedly connected in sequence from top to bottom, the temperature-sensitive unit is packaged with a paraffin-based mixed solution, the bottom end of each of the push rods is fixedly connected with a needle body protrusion, the bottom of each of the needle body protrusions is fixedly connected with the top end of the hollow microneedle, the top end of each of the push rods is fixedly connected with the temperature-sensitive unit, and each of the push rods is sleeved with a reset component for assisting the needle body of the hollow microneedle to reset.

[0007] Further, the hydrogel layer is made of a high molecular polymer composed of sodium hyaluronate or chitosan, has a thickness of 0.5-1.2 mm and a water content of ≥80%, and is used to cover the scar wound surface and provide a moist environment.

[0008] Further, a semi-permeable membrane isolation layer for preventing mutual penetration of drug components is arranged between the microneedle administration layer and the hydrogel layer, and the temperature-sensitive unit is located at the bottom of the semi-permeable membrane isolation layer.

[0009] Further, the length of each of the hollow microneedles is 400-1200 μm, the diameter of each of the hollow microneedles is 250-400 μm, and the density of the microneedle array is 15×15 needles / 1.4 cm 2 .

[0010] Further, each of the reset components comprises a spring made of nickel-titanium alloy, the spring is sleeved on the outer side of the push rod and fixedly connected with the top end of the hollow microneedle and the temperature-sensitive unit at both ends.

[0011] Further, the cream layer contains a cream base of 2-5% lidocaine, which is coated on the surface of the microneedle base layer and used for skin surface anesthesia.

[0012] The above scheme has the following beneficial effects:

[0013] 1. Through the synergistic effect of the three-layer composite structure, the present application realizes efficient and safe scar treatment. The innermost cream layer contains lidocaine, which can play a surface anesthesia role in the initial stage of patching, greatly reducing the pain during the administration process and solving the problem of severe pain in traditional injection methods.

[0014] 2、The intermediate microneedle administration layer can deliver triamcinolone acetonide solution to the superficial dermis, avoiding the damage risk of traditional injection to deep tissues; the temperature sensitive unit of the elastic component triggers the microneedle to pop out for administration through the temperature sensing characteristics of the paraffin-based mixed solution by rubbing the patch after pasting, and the microneedle automatically retracts under the action of the reset component after the temperature drops after stopping stimulation, reducing the continuous stimulation of the microneedle to the skin and reducing the possibility of inflammation and infection.

[0015] 3、The outer hydrogel layer can provide a moist environment for the scar wound surface, promote wound healing, and isolate external pollution, in cooperation with the semi-permeable membrane isolation layer, effectively prevent the mutual penetration of various drug components, and ensure the stability and effectiveness of the drug solution.

[0016] Further, a preparation device for a triamcinolone acetonide patch based on the triamcinolone acetonide patch, comprising a device box, a transmission belt and a driving mechanism for providing preparation of the triamcinolone acetonide patch are arranged in the device box, and a microneedle forming bin, an elastic component preparation bin, an assembly bin and a cutting bin are sequentially connected in the device box, wherein a plurality of microneedle molds are placed in the microneedle forming bin, the microneedle mold is divided into a filling layer, an elastic layer, a bump layer, a needle body layer and a cream layer from top to bottom, a plurality of mold holes are opened in the elastic layer, the bump layer and the needle body layer, and the mold hole array is 15x15 needles / 1.4cm 2 , a liquid cavity and a sealing cavity are axially arranged from top to bottom in the mold hole at the needle body layer, the sealing cavity is located at the bottom end of the mold hole, a grouting system for grouting into the mold hole is arranged at the top of the microneedle forming bin, the grouting system comprises a first fixed plate, the first fixed plate moves up and down through the driving mechanism, a plurality of grouting pipes corresponding to the mold holes are arranged at the bottom of the first fixed plate, a liquid pipe is arranged in each grouting pipe, a first storage tank, a second storage tank and a third storage tank are arranged at the top of the first fixed plate, wherein the first storage tank is filled with polylactic acid melt solution, the first storage tank is communicated with the grouting pipe and a first valve is arranged at the communication position, the second storage tank and the third storage tank are respectively filled with water-soluble material and triamcinolone acetonide solution, and the second storage tank and the third storage tank are communicated with the liquid pipe and a second valve and a third valve are respectively arranged at the communication positions; an ultraviolet curing machine for cross-linking keratin hydrogel is further arranged in the microneedle forming bin.

[0017] The technical principle of the present application is as follows:

[0018] The transmission belt in the device box sequentially transmits the microneedle mold to the microneedle forming bin, the elastic component preparation bin, the assembly bin and the cutting bin, and each chamber cooperates in sequence according to the process. In the microneedle forming bin, the grouting system forms the shell structure of the hollow microneedle by first injecting the polylactic acid melt in the first storage tank into the mold hole needle body layer through the layered grouting process; then the liquid medicine pipe injects the water-soluble material in the second storage tank and the triamcinolone acetonide liquid in the third storage tank into the hollow part, and then the ultraviolet curing machine triggers the crosslinking of the keratin hydrogel in the liquid medicine, fixing the drug composition. The elastic component preparation bin and the assembly bin sequentially complete the filling of the elastic component, the temperature sensitive unit, the semi-permeable membrane isolation layer and the hydrogel layer, and the cutting bin cuts the finished product according to the specification. The whole process controls the precise linkage of each part through the driving mechanism to ensure the positioning matching of the mold hole array and each functional layer.

[0019] The above scheme has the following beneficial effects: through the integrated production process, the production efficiency and product consistency of the triamcinolone acetonide patch are greatly improved. The layered grouting and synchronous curing process of the microneedle forming bin ensures the stable combination of the hollow microneedle shell and the internal liquid medicine, avoiding the problems of drug leakage or loose packaging in traditional step-by-step production; the mold hole array design of 15x15 needles / 1.4cm 2 ensures uniform distribution of microneedles, making the drug dosage more accurate. The overall device does not need manual transfer of semi-finished products, reducing the risk of contamination, and through valve control and driving mechanism linkage, production parameters can be flexibly adjusted to adapt to the batch production needs of patches of different specifications, which has significant advantages in production stability and cost control compared with traditional dispersed preparation equipment.

[0020] Further, the second fixed plate and the third fixed plate are arranged at the top of the elastic component preparation bin, and the second fixed plate and the third fixed plate move up and down through the driving mechanism; the second fixed plate is fixedly connected with a filler pipe for filling the mold hole in the bump layer, and the filler pipe is communicated with a fourth storage tank, and the fourth storage tank is filled with polyether ether ketone melt; a plurality of push rods and springs corresponding to the mold holes are detachably connected to the third fixed plate.

[0021] Beneficial effects: the design of the elastic component preparation bin significantly improves the accuracy and stability of the connection between the elastic component and the microneedle through automatic cooperation. The second fixed plate drives the filler pipe to accurately inject the polyether ether ketone melt in the fourth storage tank into the mold hole of the bump layer. The polyether ether ketone material has excellent mechanical strength and heat resistance, which can ensure that the needle body bump and the hollow microneedle form a firm connection, avoiding loosening or breaking during the microneedle ejection and retraction process.

[0022] Meanwhile, the third fixed plate is assembled with the push rod-spring member in a detachable connection mode and corresponds to the mold holes one by one, which not only ensures the coaxiality of the push rod and the microneedle and ensures the accurate and efficient force transmission when the elastic assembly is triggered, avoids the damage to the skin caused by the deviation of the microneedle ejection angle, but also facilitates the quick replacement of the push rod-spring member according to different specifications, and improves the versatility and production flexibility of the equipment.

[0023] Further, the assembly bin top is respectively provided with a fourth fixed plate and a fifth fixed plate driven to move up and down by a driving mechanism, the fourth fixed plate is provided with an encapsulation tube for filling the paraffin-based in the filling layer, the encapsulation tube is communicated with a fifth storage tank at the other end, the fifth storage tank is filled with paraffin-based melt, the bottom of the fifth fixed plate is fixedly connected with a hydrogel coating tube for filling sodium hyaluronate or chitosan in the filling layer, the hydrogel coating tube is communicated with a screw pump, the other end of the screw pump is communicated with a sixth storage tank, and the sixth storage tank is filled with sodium hyaluronate solution or chitosan melt; the assembly bin top is also provided with a pressing plate driven to move up and down by a driving mechanism, and the pressing plate is provided with a plurality of electric heating wires.

[0024] Beneficial effects: The fourth fixed plate drives the encapsulation tube to accurately inject the paraffin-based melt in the fifth storage tank into the filling layer to form the encapsulation structure of the temperature-sensitive unit. The paraffin-based material has stable phase change characteristics, and the encapsulation quality directly affects the response sensitivity of the elastic assembly to temperature. The design controls the injection amount and encapsulation position through the driving mechanism to ensure uniform distribution of the paraffin-based mixture, so that the temperature-sensitive unit can accurately trigger the microneedle to pop out when heat is generated by friction, and avoid triggering delay or misoperation caused by improper encapsulation.

[0025] The hydrogel coating tube of the fifth fixed plate cooperates with the screw pump and the sixth storage tank to accurately control the coating amount and thickness of the sodium hyaluronate or chitosan solution. The stable output characteristics of the screw pump avoid the flow fluctuation problem in the traditional perfusion mode, ensure the uniform thickness of the hydrogel layer and the water content meets the standard, thereby providing a humid environment for the scar wound, and cooperating with the semi-permeable membrane isolation layer to prevent drug interpenetration.

[0026] The pressing plate and the built-in electric heating wire realize the close combination of each layer of material through the hot pressing process. The hot pressing temperature and pressure can be accurately controlled through the driving mechanism, which can not only ensure firm connection between layers and prevent delamination during use, but also prevent high temperature from damaging the effective components of triamcinolone acetonide and lidocaine cream, and ensure stable patch efficacy.

[0027] Further, the cutting bin is provided with a semi-permeable membrane cutting mechanism, and the semi-permeable membrane cutting mechanism comprises a laser cutting machine, which is used to cut the assembled triamcinolone acetonide patch into a plurality of circles according to the size of the patch.

[0028] Beneficial effects: The laser cutting machine can accurately work according to the preset patch size, cut the assembled triamcinolone acetonide patch into several circles, can strictly guarantee the regularity of the cutting edge, avoid the problems such as burr and tearing that may occur in traditional mechanical cutting, ensure the size consistency of each finished product, thereby guarantee the fitting accuracy of the patch and the scar wound surface, and avoid the influence of size deviation on the drug effect or wound protection effect. At the same time, the laser cutting process is a non-contact processing, which will not cause physical extrusion or damage to the microneedle structure, drug liquid composition and the joint of each layer inside the patch, effectively protecting the integrity of the microneedle and the stability of the drug liquid, and more guaranteeing the product quality compared with mechanical cutting.

[0029] Additional aspects and advantages of the application will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following description, or can be learned by practice of the application. BRIEF DESCRIPTION OF DRAWINGS

[0030] Figure 1 It is a forward cross-sectional view of the triamcinolone acetonide patch embodiment of the present application.

[0031] Figure 2 It is an axonometric view of the preparation device embodiment of the triamcinolone acetonide patch of the present application.

[0032] Figure 3 It is a forward cross-sectional view of the preparation device embodiment of the triamcinolone acetonide patch of the present application.

[0033] Figure 4 It is a forward cross-sectional view of the microneedle mold embodiment of the triamcinolone acetonide patch of the present application.

[0034] The reference signs in the drawings of the specification include: 1, hydrogel layer; 2, semi-permeable membrane isolation layer; 3, temperature sensitive unit; 4, push rod; 5, spring; 6, needle body bump; 7, microneedle drug delivery layer; 8, analgesic layer; 9, hollow part; 10, hollow microneedle; 11, equipment box; 12, control system; 13, laser cutting machine; 14, pressing plate; 15, fifth storage tank; 16, third fixed plate; 17, fourth storage tank; 18, grouting pipe; 19, drug liquid pipe; 20, first storage tank; 21, microneedle mold; 22, second storage tank; 23, third storage tank; 24, first fixed plate; 25, filler pipe; 26, packaging pipe; 27, fourth fixed plate; 28, hydrogel coating pipe; 29, fifth fixed plate; 30, sixth storage tank; 31, second fixed plate; 32, cream layer; 33, needle body layer; 34, bump layer; 35, elastic layer; 36, filling layer; 37, liquid cavity; 38, mold hole; 39, sealing cavity. DETAILED DESCRIPTION

[0035] The technical solutions of the present application will be described clearly and completely below in conjunction with the drawings. Obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the scope of protection of the present application.

[0036] In the description of the present application, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer" and the like indicate the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as a limitation on the present application. In addition, the terms "first", "second", "third" are only for descriptive purposes and cannot be understood as indicating or implying relative importance.

[0037] In the description of the present application, it should be noted that unless otherwise explicitly specified and limited, the terms "mounting", "connection", "connection" should be understood broadly, for example, it can be fixedly connected, or it can be detachably connected, or integrally connected; it can be mechanically connected, or it can be electrically connected; it can be directly connected, or it can be indirectly connected through an intermediate medium; it can be the communication inside two elements. For those of ordinary skill in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0038] The specific embodiments will be described in detail below:

[0039] Embodiments:

[0040] In the field of scar treatment, the clinical intervention of hypertrophic scar often depends on the injection of triamcinolone acetonide injection into the scar, which can achieve the effect of inhibiting the proliferation of scar, but has significant limitations: the patient has high degree of pain during injection, and the operation precision of medical personnel is strict, and slight negligence may cause damage to the deep subcutaneous tissue, and repeated injection can easily cause local skin atrophy, pigment abnormality and other complications. In addition, the traditional injection method needs multiple punctures, and the patient's compliance is poor, especially for children or patients with large scar area, the treatment difficulty is significantly increased.

[0041] Based on the above problems, the inventors propose a triamcinolone acetonide patch that integrates surface anesthesia, precise drug delivery and wound protection, which realizes painless, safe and convenient scar treatment through a three-layer synergistic structure. Compared with the traditional injection method, the patch does not require professional operation and can be used by patients themselves, and can avoid damage to the deep tissue, significantly improving the safety and convenience of treatment.

[0042] Specifically, as shown in FIG. 1, the triamcinolone acetonide patch comprises a patch body 1, a surface anesthetic layer 2, a drug delivery layer 3 and a protective layer 4. Figure 1As shown: a triamcinolone acetonide patch, including three layers of structures from outside to inside: a hydrogel layer 1, a microneedle administration layer 7 and an analgesic layer 8, wherein the hydrogel layer 1 is made of a high molecular polymer composed of sodium hyaluronate or chitosan, the thickness is 0.5-1.2mm, the water content is ≥80%, the high molecular polymer network of the hydrogel layer 1 has excellent water retention and biocompatibility, and after being attached to the scar wound surface, it can form a closed and humid environment, which not only isolates external pollutants, but also reduces water loss from the wound surface, providing a suitable physiological environment for scar repair. Compared with traditional dry dressings, the hydrogel layer 1 can avoid scabbing on the wound surface, reduce the risk of scar hyperplasia, and at the same time, its softness can reduce the friction and irritation to the wound surface.

[0043] A semi-permeable membrane isolation layer 2 is provided between the microneedle administration layer 7 and the hydrogel layer 1 to prevent the mutual penetration of drug components, which can prevent the mutual penetration of water in the hydrogel layer 1 and the drug solution in the microneedle, and ensure the stability of the drug concentration.

[0044] The microneedle administration layer 7 includes a microneedle array composed of a plurality of hollow microneedles 10, the length of the hollow microneedles 10 is 400-1200μm, the diameter of the hollow microneedles 10 is 250-400μm, and the density of the microneedle array is 15×15 needles / 1.4cm 2 .

[0045] The hollow microneedles 10 are each provided with a hollow part 9 extending to the tip of the hollow microneedle 10 and communicating with the outside, and the hollow part 9 is filled with a triamcinolone acetonide solution composed of 0.02-1.25mg / needle of triamcinolone acetonide, 5-15wt% keratin hydrogel hydrophilic polymer network and PBS buffer, and the top end of the hollow microneedle 10 is fixedly connected with an elastic component for ejecting and penetrating into the epidermis by pressing the hollow microneedle 10, and the elastic component automatically retracts into the microneedle administration layer 7 after releasing the drug.

[0046] The elastic component includes a temperature-sensitive unit 3 and a plurality of push rods 4 corresponding to the hollow microneedles 10 fixedly connected in sequence from top to bottom, the temperature-sensitive unit 3 is located at the bottom of the semi-permeable membrane isolation layer 2 to avoid interference of the external environment on the phase change process and improve the triggering reliability of the temperature-sensitive unit. The temperature-sensitive unit 3 is packaged with a paraffin-based mixed solution, the specific phase change temperature of the paraffin-based mixed solution is about 38-42℃, which is close to the skin temperature after human friction generates heat, the bottom end of the push rod 4 is fixedly connected with a needle body protrusion 6, the bottom of the needle body protrusion 6 is fixedly connected with the top end of the hollow microneedle 10, the top end of the push rod 4 is fixedly connected with the temperature-sensitive unit 3, and the push rod 4 is sleeved with a reset component for assisting the needle body reset of the hollow microneedle 10.

[0047] The reset assembly each includes a spring 5 made of nickel-titanium alloy, the spring 5 is sleeved outside the push rod 4 and fixedly connected with the top end of the hollow microneedle 10 and the temperature sensitive unit 3 respectively. When the patient applies the patch to the scar and gently strokes, the friction between the patch and the skin generates heat, the temperature of the temperature sensitive unit 3 rises, the paraffin-based mixed solution expands under heat, pushes the push rod 4 to move downward, the spring 5 sleeved outside the push rod 4 is compressed, the needle body block 6 and the hollow microneedle 10 are driven to pop out downward synchronously, pierce the epidermis and release the liquid medicine in the hollow part 9 to the superficial layer of the dermis. This process does not require professional operation, and the patient can complete it by himself, solving the problem of high requirement of traditional injection on operation skill. When the patch is stopped to be stroked, the temperature gradually decreases to the normal temperature of the skin, the paraffin-based mixed solution shrinks, the spring 5 rebounds by virtue of the shape memory characteristic, drives the push rod 4 and the hollow microneedle 10 to retract upward into the microneedle drug layer 7, avoiding that the microneedle continuously remains in the skin to cause mechanical damage. Because the microneedle is easy to cause inflammation when remaining in the skin for a long time, compared with the existing fixed microneedle patch, the "pop-out-on-demand-automatic-retraction" mechanism of the patch can significantly reduce the stimulation to the skin tissue and reduce the risk of infection.

[0048] The cream layer 32 comprises a cream matrix of 2-5% lidocaine, which is coated on the surface of the microneedle base layer, and can play a surface anesthesia effect through skin penetration in the initial stage of patch application, cooperates with the shallow stimulation of the microneedle, and reduces the pain of the patient in the whole process of "pretreatment-drug delivery". Traditional injection needs to be performed separately for local anesthesia, and the operation is complicated, and the patch integrates anesthesia and drug delivery, further simplifying the treatment process.

[0049] In order to realize efficient and accurate production of the patch, as shown in the Figure 2 , a preparation device of the triamcinolone acetonide patch is designed, based on the triamcinolone acetonide patch, comprising a device box 11, a transmission belt and a driving mechanism for providing preparation of the triamcinolone acetonide patch are arranged in the device box 11, the driving mechanism is preferably a Jinmochuang motor, the device box 11 is signal connected with a control system 12, and a microneedle forming bin, an elastic assembly preparation bin, an assembly bin and a cutting bin (as shown in the Figure 3 ) are sequentially communicated in the device box 11, wherein a plurality of microneedle molds 21 are placed in the microneedle forming bin, the microneedle mold 21 is divided into a filling layer 36, an elastic layer 35, a block layer 34, a needle body layer 33 and a cream layer 32 from top to bottom, the cream layer 32 is filled with lidocaine cream, a plurality of mold holes 38 are opened in the elastic layer 35, the block layer 34 and the needle body layer 33, and the mold holes 38 are arrayed as 15x15 needles / 1.4cm 2, the mold hole 38 is provided with a liquid cavity 37 and a sealing cavity 39 from top to bottom at the needle body layer 33, the sealing cavity 39 is located at the bottom end of the mold hole 38, the top of the microneedle forming bin is provided with a grouting system for grouting into the mold hole 38, the grouting system comprises a first fixed plate 24, the first fixed plate 24 moves up and down through a driving mechanism, the bottom of the first fixed plate 24 is provided with a plurality of grouting pipes 18 corresponding to the mold hole 38 one by one, the grouting pipe 18 is provided with a liquid pipe 19, the top of the first fixed plate 24 is provided with a first storage tank 20, a second storage tank 22 and a third storage tank 23 respectively, wherein the first storage tank 20 is filled with polylactic acid melt, the first storage tank 20 is communicated with the grouting pipe 18 and the communication part is provided with a first valve, the second storage tank 22 and the third storage tank 23 are filled with water-soluble material and triamcinolone acetonide liquid respectively, the second storage tank 22 and the third storage tank 23 are communicated with the liquid pipe 19 and the communication part is provided with a second valve and a third valve respectively; the microneedle forming bin is also provided with an ultraviolet curing machine for crosslinking the keratin hydrogel; when the equipment starts to run, the first fixed plate 24 moves down under the driving of the driving mechanism, the polylactic acid melt in the first storage tank 20 is injected into the mold hole 38 of the needle body layer 33 through the first valve after the grouting pipe 18 is aligned with the mold hole 38, forming the shell of the hollow microneedle 10, the polylactic acid has good biocompatibility and degradability, avoiding the safety hidden danger of microneedle residue in the body, then the water-soluble material in the second storage tank 22 is injected into the sealing cavity 39 through the liquid pipe 19, used for plugging the bottom of the microneedle, preventing the triamcinolone acetonide liquid from flowing into the cream layer 32, and the water-soluble material is dissolved after contacting with the skin of the patient, realizing the subcutaneous injection of the triamcinolone acetonide liquid in the microneedle, after the water-soluble material in the sealing cavity 39 is solidified by the ultraviolet curing machine, the third valve is opened and the triamcinolone acetonide liquid containing keratin hydrogel is filled, the ultraviolet curing machine is started immediately, the keratin hydrogel is crosslinked and formed, ensuring that the liquid is stably wrapped. Compared with the step-by-step injection molding process of traditional microneedle preparation, the integrated grouting system can simultaneously complete shell forming and liquid filling, reduce material transfer loss between processes, and improve production efficiency.

[0050] The elastic component preparation bin top is respectively provided with a second fixing plate 31 and a third fixing plate 16, both of which move up and down through a driving mechanism; the bottom of the second fixing plate 31 is fixedly connected with a filler pipe 25 for filling the mold hole 38 in the bump layer 34, the filler pipe 25 is communicated with a fourth storage tank 17, the fourth storage tank 17 is filled with polyether ether ketone melt, and the third fixing plate 16 is detachably connected with a plurality of push rods 4 and springs 5 corresponding to the mold holes 38. The second fixing plate 31 drives the filler pipe 25 to move downward, the polyether ether ketone melt in the fourth storage tank 17 is injected into the mold hole 38 of the bump layer 34, and the needle body bump 6 is formed - polyether ether ketone has excellent mechanical strength and heat resistance, and can stably connect the microneedle and the push rod 4. Then the third fixing plate 16 moves downward, and the pre-assembled push rod 4-spring 5 piece (nickel-titanium alloy spring 5 and push rod 4 pre-assembled) is precisely embedded in the corresponding position of the bump layer 34, realizing the preliminary connection of the elastic component and the microneedle. This process controls the mold positioning and mechanical assembly through the control system 12, ensuring that the concentricity error of each microneedle push rod 4 is ≤0.05mm, avoiding the occurrence of jamming during subsequent triggering.

[0051] The assembly bin top is respectively provided with a fourth fixing plate 27 and a fifth fixing plate 29 which move up and down through a driving mechanism, the fourth fixing plate 27 is provided with an encapsulation pipe 26 for filling paraffin-based in the filling layer 36, the other end of the encapsulation pipe 26 is communicated with a fifth storage tank 15, the fifth storage tank 15 is filled with paraffin-based melt, and the paraffin-based melt is delivered to the filling layer 36 through the encapsulation pipe 26 to form the encapsulation structure of the temperature-sensitive unit 3; at the same time, the bottom of the fifth fixing plate 29 is fixedly connected with a hydrogel coating pipe 28 for filling sodium hyaluronate or chitosan in the filling layer 36, the hydrogel coating pipe 28 is communicated with a screw pump, the other end of the screw pump is communicated with a sixth storage tank 30, the sixth storage tank 30 is filled with sodium hyaluronate solution or chitosan melt, and the hydrogel coating pipe 28 uniformly coats the sodium hyaluronate or chitosan solution in the sixth storage tank 30 on the surface of the semi-permeable membrane isolation layer 2 to form the hydrogel layer 1, and the precise control of the screw pump ensures that the thickness error of the hydrogel layer 1 is ≤0.05mm; the assembly bin top is also provided with a pressing plate 14 which moves up and down through a driving mechanism, the pressing plate 14 is provided with a plurality of heating wires, and the heating wires in the pressing plate 14 are heated to an appropriate temperature through the control system 12 when the pressing plate 14 is driven by the driving mechanism, so that the materials in each layer are hot-pressed and combined into a whole, compared with the traditional manual combination, the hot-pressing process can ensure that the interlayer bonding force is uniform, and peeling or drug mutual penetration is avoided.

[0052] The cutting bin is provided with a semi-permeable membrane cutting mechanism, and the semi-permeable membrane cutting mechanism comprises a laser cutting machine 13, which is used for cutting the assembled triamcinolone acetonide patch into several circles according to the size of the patch. The whole preparation device realizes full-process automation through the control system 12, compared with the existing dispersed production equipment, not only reduces manual intervention and reduces pollution risk, but also ensures the consistency of each batch of products by monitoring the liquid level, grouting speed and other parameters of each storage tank in real time.

[0053] In summary, the triamcinolone acetonide patch of the present scheme solves the problems of pain, difficult operation and easy damage in traditional triamcinolone acetonide injection through the three-layer synergistic structure and the intelligent microneedle mechanism; the matched preparation device ensures stable product quality through integrated and automated production, and provides an efficient and safe new scheme for the non-invasive treatment of hypertrophic scars.

[0054] In order to verify the advantages of the triamcinolone acetonide patch of the present scheme compared with the existing commercially available triamcinolone acetonide patch in pain control, drug efficiency, scar improvement effect and safety, the following experiments are adopted for verification:

[0055] I. Experimental objects and grouping

[0056] Experimental objects: 60 patients with hypertrophic scars (scar formation time 3-12 months, area 2-5 cm 2 ) were randomly divided into the test group and the control group, 30 cases in each group.

[0057] Inclusion criteria: scar thickness ≥2mm, no skin infection, diabetes and other underlying diseases affecting healing, and signed informed consent form.

[0058] Grouping method: the patients in the two groups were grouped by using a random number table method, and there was no significant difference in age, gender, scar site and disease duration (P>0.05).

[0059] II. Experimental materials

[0060] Test group: the triamcinolone acetonide patch of the present scheme.

[0061] Control group: commercially available triamcinolone acetonide neomycin patch (Heilongjiang Huimeijia Pharmaceutical, passive penetration depending on drugs, no anesthesia and microneedle structure).

[0062] III. Experimental process

[0063] 1. Pretreatment:

[0064] The skin of the scar site of the patients in the two groups was cleaned to remove surface dirt and dead skin.

[0065] 2. Drug administration method:

[0066] Test group: Apply the patch to the scar, gently roll the patch for 10-15 seconds (friction generates heat to trigger the microneedle to pop out), remove after 24 hours of application.

[0067] Control group: Apply the commercially available patch according to the instructions, remove after 24 hours.

[0068] 3. Cycle: Both groups were administered once every 3 days, for a continuous treatment of 4 weeks.

[0069] IV. Detection of target data

[0070] Pain score: At the time of administration and 1 hour after administration, the patient's pain was recorded using the visual analog scale (VAS, 0-10 points, 0 points for no pain, 10 points for severe pain).

[0071] Drug penetration efficiency: 24 hours after administration, the concentration of triamcinolone acetonide in the scar tissue was detected by high performance liquid chromatography (HPLC).

[0072] Scar improvement indicators:

[0073] Thickness: Before treatment and 4 weeks after treatment, the change rate of scar thickness was measured by ultrasound: (pre-treatment thickness - post-treatment thickness) / pre-treatment thickness x 100%).

[0074] Flatness: The flatness of the scar surface was observed using a dermatoscope, with a score of 0-3 points (0 points for normal, 3 points for severe concave-convex).

[0075] Safety indicators: The incidence of skin irritation (redness, itching) and inflammatory reactions (white blood cell count) during treatment was recorded.

[0076] V. Experimental results table

[0077]

[0078]

[0079] VI. Results and discussion

[0080] The experimental results show that the test group is significantly better than the control group in all indicators:

[0081] Pain control: The VAS score of the test group at the time of administration and 1 hour after administration was significantly lower than that of the control group (P<0.01), indicating that the analgesic layer containing lidocaine and the automatic retraction design of the microneedle effectively reduced the pain of administration, solving the problem of obvious pain of traditional patches.

[0082] Drug delivery efficiency: The concentration of triamcinolone acetonide in the scar tissue of the test group was 2.7 times that of the control group (P<0.01), thanks to the active drug delivery method of microneedles directly penetrating the epidermis, avoiding the low efficiency problem of passive drug penetration.

[0083] Scar improvement: The scar thickness reduction rate of the test group (42.5%) was significantly higher than that of the control group (21.3%), and the smoothness score was lower (P<0.01), indicating that precise drug delivery can more effectively inhibit scar hyperplasia.

[0084] Safety: The incidence of skin irritation and inflammatory reaction in the test group was significantly lower than that in the control group (P<0.05), because the protective effect of the hydrogel layer and the reduction of continuous irritation by the automatic retraction of the microneedle are superior to the mechanical friction and drug residue risk of traditional patches.

[0085] In summary, the triamcinolone acetonide patch of the present application is significantly superior to existing commercially available products in pain control, drug delivery efficiency, treatment effect and safety, and has clinical application advantages

[0086] Obviously, the above examples are only examples for clearly illustrating, but not limitation to the embodiments. For ordinary skilled in the art, other different forms of changes or variations can be made on the basis of the above description. Here, it is not necessary and impossible to enumerate all the embodiments. The obvious changes or variations derived therefrom are still within the protection scope of the present application.

Claims

1. A triamcinolone acetonide patch, characterized in that, The structure consists of three layers from the outside to the inside: a hydrogel layer (1), a microneedle drug delivery layer (7), and an analgesic layer (8). The microneedle drug delivery layer (7) includes a microneedle array composed of several hollow microneedles (10). Each hollow microneedle (10) has a hollow part (9) inside. The hollow part (9) extends to the tip of the hollow microneedle (10) and communicates with the outside. Each hollow part (9) is filled with a triamcinolone solution composed of 0.02-1.25 mg / needle of triamcinolone, a hydrophilic polymer network of 5-15 wt% keratin hydrogel, and PBS buffer. Each hollow microneedle (10) has an elastic component fixedly connected to its tip for ejecting the hollow microneedle (10) and piercing the epidermis by pressing. The elastic component automatically retracts into the microneedle drug delivery layer (7) after the drug is released. Each elastic component includes a temperature-sensitive unit (3) and several push rods (4) corresponding to the hollow microneedles (10) connected in sequence from top to bottom. The temperature-sensitive unit (3) is encapsulated with a paraffin-based mixture. The bottom of each push rod (4) is fixedly connected with a needle body protrusion (6). The bottom of each needle body protrusion (6) is fixedly connected to the top of the hollow microneedles (10). The top of each push rod (4) is fixedly connected to the temperature-sensitive unit (3). Each push rod (4) is fitted with a reset component to assist the reset of the hollow microneedles (10).

2. The triamcinolone acetonide patch according to claim 1, characterized in that, The hydrogel layer (1) is made of a high molecular polymer composed of sodium hyaluronate or chitosan, with a thickness of 0.5-1.2 mm and a water content of ≥80%, and is used to cover the scar wound and provide a moist environment.

3. The triamcinolone acetonide patch according to claim 2, characterized in that, A semi-permeable membrane isolation layer (2) is provided between the microneedle drug delivery layer (7) and the hydrogel layer (1) to prevent drug components from interpenetrating. The temperature-sensitive unit (3) is located at the bottom of the semi-permeable membrane isolation layer (2).

4. The triamcinolone acetonide patch according to claim 3, characterized in that, The hollow microneedles (10) are all 400-1200 μm in length and 250-400 μm in diameter, with a microneedle array density of 15 × 15 needles / 1.4 cm. 2 .

5. The triamcinolone acetonide patch according to claim 4, characterized in that, The reset components all include a spring (5) made of nickel-titanium alloy. The spring (5) is sleeved on the outside of the push rod (4) and its two ends are fixedly connected to the top of the hollow microneedle (10) and the temperature sensitive unit (3) respectively.

6. The triamcinolone acetonide patch according to claim 5, characterized in that, The cream layer (32) contains a cream matrix of 2-5% lidocaine, which is applied to the surface of the microneedle base layer for surface anesthesia of the skin.

7. An apparatus for preparing a triamcinolone acetonide patch, based on the triamcinolone acetonide patch according to claims 1-6, comprising an equipment box (11), wherein the equipment box (11) is provided with a transmission belt and a drive mechanism for providing a drive mechanism for preparing the triamcinolone acetonide patch, and the equipment box (11) is signal-connected to a control system (12), characterized in that, The equipment box (11) contains a microneedle forming chamber, an elastic component preparation chamber, an assembly chamber, and a cutting chamber connected sequentially from the inlet to the outlet. The microneedle forming chamber contains several microneedle molds (21). The microneedle molds (21) are divided into a filling layer (36), an elastic layer (35), a bump layer (34), a needle body layer (33), and a cream layer (32) from top to bottom. The elastic layer (35), the bump layer (34), and the needle body layer (33) each have several interconnected mold holes (38). The array of mold holes (38) is 15×15 needles / 1.4cm. 2 Inside the mold hole (38), at the needle body layer (33), there are axially arranged liquid cavities (37) and sealing cavities (39) from top to bottom. The sealing cavity (39) is located at the bottom end of the mold hole (38). The top of the microneedle forming chamber is provided with a grouting system for injecting grout into the mold hole (38). The grouting system includes a first fixing plate (24). The first fixing plate (24) moves up and down by a driving mechanism. The bottom of the first fixing plate (24) is provided with several grouting pipes (18) corresponding one-to-one with the mold hole (38). Each grouting pipe (18) is provided with a medicine pipe (19). The top of the first fixing plate (24) is respectively provided with The first storage tank (20), the second storage tank (22), and the third storage tank (23) are provided. The first storage tank (20) is filled with polylactic acid melt and is connected to the grouting pipe (18). The first storage tank (20) is equipped with a first valve at the connection point. The second storage tank (22) and the third storage tank (23) are filled with water-soluble materials and triamcinolone acetonide solution, respectively. The second storage tank (22) and the third storage tank (23) are connected to the solution pipe (19) and are equipped with a second valve and a third valve, respectively, at the connection point. The microneedle forming chamber is also equipped with an ultraviolet curing machine for cross-linking and forming keratin hydrogel.

8. The apparatus for preparing triamcinolone acetonide patches according to claim 7, characterized in that, The top of the elastic component preparation chamber is provided with a second fixing plate (31) and a third fixing plate (16), which move up and down through a drive mechanism. The bottom of the second fixing plate (31) is fixedly connected to a filler tube (25) for filling the mold hole (38) in the bump layer (34). The filler tube (25) is connected to a fourth storage tank (17), which is filled with polyether ether ketone melt. Several push rods (4) and springs (5) corresponding to the mold hole (38) are detachably connected to the third fixing plate (16).

9. The apparatus for preparing triamcinolone acetonide patches according to claim 8, characterized in that, The top of the assembly chamber is provided with a fourth fixed plate (27) and a fifth fixed plate (29) that are driven up and down by a drive mechanism. The fourth fixed plate (27) is provided with a sealing tube (26) for filling the filling layer (36) with paraffin base. The sealing tube (26) is connected to a fifth storage tank (15) at the other end. The fifth storage tank (15) is filled with paraffin base melt. The bottom of the fifth fixed plate (29) is fixedly connected with a hydrogel coating tube (28) for filling the filling layer (36) with sodium hyaluronate or chitosan. The hydrogel coating tube (28) is connected to a screw pump. The other end of the screw pump is connected to a sixth storage tank (30). The sixth storage tank (30) is filled with sodium hyaluronate solution or chitosan melt. The top of the assembly chamber is also provided with a pressure plate (14) that is driven up and down by a drive mechanism. The pressure plate (14) is provided with several heating wires.

10. The apparatus for preparing triamcinolone acetonide patches according to claim 9, characterized in that, The cutting chamber is equipped with a semi-permeable membrane cutting mechanism, which includes a laser cutter (13). The laser cutter (13) is used to cut the assembled triamcinolone patch into several circles according to the patch size.

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