Microneedle

Abstract

A microneedle for transdermal drug delivery includes an input channel extending through the microneedle along a longitudinal axis of the microneedle, the input channel defining a sidewall, a first end and a second end, the input channel configured to receive fluid input into the microneedle. The microneedle includes one or more outlet channels extending between an inner surface of the sidewall and an outer surface of the sidewall such that each of the one or more outlet channels defines a fluid path between the input channel and the outer surface of the sidewall. The one or more outlet channels are at an angle greater than 0 DEG and less than 90 DEG with respect to the longitudinal axis of the microneedle.

Description

Technical Field

[0001] The present invention relates generally to microneedles. More particularly, but not exclusively, the present invention relates to microneedles for transdermal drug delivery. Background Art

[0002] Traditionally, drugs are delivered into the body orally using a hypodermic needle, or through other means such as pulmonary drug delivery devices.

[0003] Oral delivery of drugs into the human body is problematic primarily due to drug degradation in the gastrointestinal tract. Drugs that are administered orally (as opposed to intravenous, intramuscular, sublingual, or transdermal) must first travel from the intestine to the liver before reaching the systemic circulation. Therefore, for many drugs, xenobiotic metabolism reduces the dose before reaching body tissues. Some drugs are metabolized by intestinal flora or digestive enzymes.

[0004] In addition, the use of hypodermic needles to deliver medications is often painful for the patient and is not suitable for long-term, continuous delivery or self-administration. Many patients suffer from needle phobia, making it difficult for medical professionals to inject patients. Injections with hypodermic needles often result in bruising, and infection may occur at the insertion point of the needle.

[0005] Another method of delivering drugs into the human body is to use a transdermal patch. However, drug delivery via a transdermal patch is severely limited by the inability of most drugs to enter the body through the skin at therapeutic rates. The drug delivery rate is limited by the outer layer of the skin (the stratum corneum), which is approximately 10-30 μm thick and consists of keratinized dead cells and scales. If the stratum corneum is damaged, the permeability of the skin is greatly increased. In order to damage this layer, many different methods have been studied, ranging from chemical / lipid enhancers, to electric fields using iontophoresis and electroporation, to pressure waves generated by ultrasound or photoacoustic effects. To date, these enhancement methods have had only limited impact on medical practice. Chemical methods can negatively affect the skin and the drug being delivered. In addition, other methods require the use of complex systems.

[0006] Microneedles are effective at creating micropores in the stratum corneum. In addition, they do not chemically react with the skin or the drug being delivered. Therefore, microneedles are considered a promising minimally invasive drug delivery device that can replace pills / tablets, traditional needles, and transdermal patches. Compared with traditional hypodermic needles, the reduced size of microneedles (typical width and length are tens to hundreds of microns) reduces or eliminates the pain experienced by patients during treatment, such as when used for intravenous and intramuscular injections.

[0007] Currently, the biggest problem associated with microneedle drug delivery is that the applicable dose of the drug is too small. Typically, most current microneedles are configured to deliver small doses of drug to patients, such as between 0.3ml and 1ml of drug, and the dose is usually limited to less than 2ml. Therefore, it is difficult to deliver certain therapeutic levels of drugs using current microneedle technology. Simply increasing the number of microneedles used simultaneously will result in a significant increase in the difficulties and costs associated with the production of microneedle devices, and does not solve the problem of rapid saturation of the skin caused by delivering drug liquids to small areas of the same skin layer at the same time.

[0008] Hollow microneedles allow for continuous delivery of drug solutions due to the presence of internal microchannels. The complex design of hollow microneedles leads to manufacturing difficulties, and cost-effective manufacturing remains a major challenge for microneedle device producers. Given the high costs and difficulties associated with manufacturing, as well as concerns about potential rapid saturation of the injected skin layer, most hollow microneedle arrays include a limited number of microneedles, such as 1, 3, or 12 microneedles, which commercial systems have adopted.

[0009] The present invention has been devised in view of the above circumstances. Summary of the invention

[0010] According to one aspect of the present invention, a microneedle for transdermal drug delivery is provided. The microneedle includes an input channel extending through the microneedle along a longitudinal axis of the microneedle. The input channel defines a sidewall, a first end, and a second end. The input channel is configured to receive a fluid input into the microneedle. The fluid can be a liquid, such as a liquid medicament. The longitudinal axis extends between the first end and the second end of the microneedle.

[0011] The microneedle includes one or more outlet channels. Each of the one or more outlet channels can define a fluid path between the input channel and the outer surface of the microneedle.

[0012] The outlet channel may extend between the inner surface of the sidewall and the outer surface of the sidewall. The outer surface of the sidewall may be the outer surface of the microneedle. Each of the one or more outlet channels may define a fluid path between the input channel and the outer surface of the sidewall.

[0013] One or more outlet channels are angled relative to the longitudinal axis of the microneedle at an angle greater than 0° and less than 90°. In this manner, the microneedle can be configured such that fluid enters the input channel and travels along an input direction directed toward the longitudinal axis (i.e., at 0°). The outlet channel is inclined relative to the input direction at an angle greater than 0° and less than 90° relative to the input direction.

[0014] The outlet channel can be formed in the side wall instead of at the second end of the microneedle. Providing the outlet channel in the side wall reduces the hydrostatic pressure that the fluid delivered through the microneedle needs to overcome to enter the patient's body. In addition, when the outlet channel is at the second end of the microneedle, it reduces the high resistance applied by the skin at the needle tip that hinders drug delivery. In this way, forming the outlet channel in the side wall of the microneedle increases the drug delivery rate of the microneedle. The outlet channel formed in the side wall can be called a lateral outlet channel.

[0015] The angle of the outlet channel relative to the longitudinal axis is greater than 0° but less than 90°. When the fluid enters one or more outlet channels from the input channel, it changes the direction of flow. If the outlet channel is at a 90° angle, i.e., perpendicular to the longitudinal axis of the microneedle, the fluid will experience a sudden change. The sudden change in the direction of fluid flow may cause blockage and potentially reduce the fluid flow rate. Using off-axis outlet channels that are angled relative to the longitudinal axis reduces the change in flow direction. Therefore, compared to outlet channels that are angled at 90° relative to the longitudinal axis, this arrangement helps to reduce blockage and maintain a greater fluid flow rate.

[0016] An outlet channel at an angle of 0° relative to the longitudinal axis of the microneedle will extend parallel to the longitudinal axis and will be formed at one end (e.g., the second end) of the microneedle rather than on the sidewall. As described above, such a microneedle requires the fluid to overcome greater resistance (e.g., due to a hydrostatic pressure difference) when entering a patient's body compared to an outlet channel formed in the sidewall and at an angle greater than 0° relative to the longitudinal axis of the microneedle.

[0017] The angle between the outlet channel and the longitudinal axis may be between 10° and 70°. The angle between the outlet channel and the longitudinal axis may be between 20° and 60°. The angle may be greater than 45 degrees.

[0018] The microneedle may include one or more outlet channels disposed in the sidewall as described above, and a vertical outlet channel disposed at the needle tip.

[0019] The fluid may be received through the first end of the input channel. The second end of the input channel may be far from the first end of the microneedle, and the first end of the input channel may be close to the first end of the microneedle.

[0020] The outlet channel may have curved edges. Having curved edges makes the change in fluid flow direction less abrupt, which helps reduce the chance of clogging and increases fluid flow rate.

[0021] The first end of the input channel may be open. The open first end of the input channel may be configured such that a fluid may enter the input channel through the first end of the input channel.

[0022] The second end of the input channel can be closed. The closed second end can prevent fluid from passing through. The needle tip can be disposed on the second closed end of the inlet channel. The needle tip can be configured to penetrate the patient's skin. In embodiments where the needle tip is disposed at the second end of the input channel, the second end of the input channel is not the end of the microneedle. In other arrangements, the second end of the input channel can be the second end of the microneedle. The first end of the input channel can be the first end of the microneedle.

[0023] The microneedle may include multiple outlet channels. The location of the outlet channels on the microneedle may be referred to as a pattern (of outlets).

[0024] Having multiple exit channels increases the drug delivery rate because the liquid drug can enter the body through more paths. In addition, different numbers of exit channels can be used to control the total area from which the drug liquid is discharged. Likewise, if one of the exit channels is blocked, the microneedle is still operable.

[0025] The outlet channels may be offset relative to each other along the longitudinal axis of the microneedle. The outlet channels may be angularly offset relative to each other around the longitudinal axis of the microneedle. The outlet channels may be uniformly angularly offset relative to each other around the longitudinal axis so that the outlet channels are evenly distributed around the longitudinal axis.

[0026] Having outlet channels at different locations along the microneedle helps reduce the effects of saturation. Once an area of ​​the body has absorbed / absorbed a certain amount of liquid drug without sufficient diffusion outward, it cannot absorb any more and any further drug delivered to that area will be ineffective. Staggering the locations of the outlet channels along and around the longitudinal axis at angles ensures that each outlet channel delivers fluid to a different part of the skin. For example, the outlet channels can deliver fluid to different skin layers. In addition, having multiple outlets that are angularly offset from each other around the longitudinal axis directs the liquid drug in different directions. This controls the diffusion of the drug in the skin to avoid oversaturation.

[0027] The presence of the outlet channels reduces the structural strength of the microneedle. Distributing the outlet channels uniformly at angles around the longitudinal axis improves the structural strength of the microneedle relative to microneedles with outlet channels clustered together. The offset of the outlet channels along the longitudinal axis of the microneedle prevents the formation of weak areas of the microneedle that are susceptible to fracture and / or breakage.

[0028] The width of the input channel can vary along the longitudinal axis of the microneedle. The width of the input channel can be constant along the longitudinal axis of the microneedle. The input channel can have a tapered profile, a sinusoidal profile, a staggered profile, a stepped profile, or an irregular profile.

[0029] Having a 3D internal structure allows the designer to optimize fluid flow based on the exit channel location. The 3D internal structure refers to the changing / unchanging profile of the input channel and the changing / unchanging profile of the exit channel. Variations in the width of the input channel can be used to adjust the pressure drop and fluid velocity across the input channel. Varying the width of the input channel also allows the designer to expand or shrink the drug delivery path relative to a microneedle with a constant width input channel.

[0030] The width of the microneedle can vary along the longitudinal axis. The varying width of the microneedle can define the shape of the microneedle. The microneedle can be a cylinder, a tapered cylinder, a pyramid, a tetrahedron, or a cone. The shape of the microneedle can be configured to increase the strength and durability of the microneedle to reduce the likelihood of microneedle breakage.

[0031] The microneedle may be formed of or include a polymer material. The microneedle may be formed of or include a high-strength biocompatible polymer material, such as polyglycolide (PGA), polylactic acid (PLA), polymethyl methacrylate (PMMA), cyclic olefin copolymer (COC), polycarbonate (PC) or liquid crystal polymer (LCP).

[0032] Alternatively or additionally, the microneedles may be formed from or include a metal, a ceramic, or a semiconductor.

[0033] In some arrangements, the one or more outlet channels include a first end formed in the inner surface of the side wall and a second end formed in the outer surface of the side wall. One or more of the one or more outlet channels may be tapered such that a dimension of the first end of the one or more outlet channels is not equal to a dimension of the second end of the outlet channel.

[0034] The size of the first end of one or more outlet channels and the size of the second end of one or more outlet channels can be a cross-sectional size. The first end of the outlet channel can be larger than the second end of the outlet channel. Alternatively, the second end of the outlet channel can be larger than the first end of the outlet channel. The outlet channel can be a smooth taper so that the size of the outlet channel gradually changes between the first and second ends. The outlet channel can have an internal structure of a 3D profile between the first and second ends so that the size of the outlet channel changes between the first and second ends.

[0035] Having a tapered outlet channel allows the microneedle to be configured to increase or decrease the cross-sectional area of ​​the flow path in the outlet channel, for example to affect the flow rate. This flexibility enables the manufacture of microneedles customized for specific applications. Variations in the width of the outlet channel can be used to adjust pressure drop and fluid velocity.

[0036] The microneedle may include a combination of tapered and non-tapered outlet channels. The microneedle may include only tapered outlet channels. The microneedle may not include any tapered outlet channels.

[0037] According to another aspect of the present invention, a microneedle array device is provided. The microneedle array device includes a base. The microneedle array device includes one or more microneedles. The microneedles may be the microneedles of the above aspects of the present invention. The one or more microneedles may be disposed on a first side of the substrate. The microneedle array device includes a drug inlet. The drug inlet may be disposed on a second side of the base. The microneedle array device may include a hollow chamber within the base. The hollow chamber may form a fluid connection between the one or more microneedles and the drug inlet.

[0038] The microneedle array device allows a clinician, other medical professional, or patient to easily inject fluids (e.g., liquid drugs / medicaments) into the body. A syringe or other device can be used to deliver the fluid into and through the microneedle array device via the drug inlet. The one or more microneedles are small enough to easily penetrate the patient's skin without causing much pain or discomfort.

[0039] The first side of the base may be opposite to the second side of the base. Alternatively, the first side of the base may be adjacent to the second side.

[0040] The hollow chamber can connect a first side of the microneedle array device to a second side. The hollow chamber can provide a fluid pathway between a drug inlet on the first side and an input channel of a microneedle located on the second side.

[0041] The drug inlet may include a connection device. The connection device may connect the microneedle array device to a syringe or a container. The connection device may be or include a tapered hole. The connection device may be or include an elastic sealing ring or other type of sealing component.

[0042] The connection device reduces the chance of a syringe or other device slipping out of position when fluid is delivered into the microneedle array device. This makes it easier for the user to inject the fluid into the patient. This makes the microneedle array device more flexible when connecting to external devices. In addition, it enables the microneedle array device to be connected to a variety of external devices such as syringes. When injecting the drug into the body, the connection device reduces the chance of fluid leakage.

[0043] The one or more microneedles may include a first microneedle comprising one or more outlet channels and a second microneedle comprising one or more outlet channels.

[0044] The one or more outlet channels of the first microneedle may be distributed in a first pattern, and the one or more outlet channels of the second microneedle may be distributed in a second pattern.

[0045] The first pattern may be different from the second pattern.

[0046] As discussed above, if fluid is delivered to the same area of ​​the body, fluid absorption will be reduced due to saturation. Using different exit channel patterns between different microneedles allows fluid to be delivered to a range of different areas to avoid the saturation effect.

[0047] One of the one or more outlet channels distributed in the first pattern can have a different position along the longitudinal axis of the microneedle than one of the one or more outlet channels distributed in the second pattern.

[0048] One or more outlet channels in the first pattern may have the same position along the longitudinal axis as one or more outlet channels in the second pattern.

[0049] One of the one or more outlet channels distributed in the first pattern can have a different position along the longitudinal axis of the microneedle than each of the one or more outlet channels distributed in the second pattern.

[0050] Each of the one or more outlet channels distributed in the first pattern can have a different position along the longitudinal axis of the microneedle than each of the one or more outlet channels distributed in the second pattern.

[0051] One of the one or more outlet channels distributed in the first pattern may have a different angular position about the longitudinal axis of the microneedle than one of the one or more outlet channels distributed in the second pattern.

[0052] One of the one or more outlet channels distributed in the first pattern may have a different angular position about the longitudinal axis of the microneedle than each of the one or more outlet channels distributed in the second pattern.

[0053] One or more outlet channels in the first pattern may have the same angular position about the longitudinal axis as one or more outlet channels in the second pattern.

[0054] Each of the one or more outlet channels distributed in the first pattern can have a different angular position about the longitudinal axis of the microneedle than each of the one or more outlet channels distributed in the second pattern.

[0055] One of the one or more microneedles may include one or more outlet channels that are distributed in the same pattern as the outlet channels of one or more other microneedles. Alternatively, each microneedle in the one or more microneedles may include a unique outlet channel pattern.

[0056] A first microneedle in the plurality of microneedles may have a different length than at least one other microneedle in the plurality of microneedles. Each microneedle in the plurality of microneedles may have a different length from one another. In some embodiments, each microneedle in the microneedle array device may have the same length.

[0057] Microneedles with different lengths allow the microneedle array device to form a microneedle array with a shaped surface pattern. The surface pattern can be designed to match the shape / surface of the patient's skin.

[0058] In some arrangements, microneedles positioned in the central region of the microneedle array device can be longer than microneedles positioned in the outer region, such that the surface pattern defines a protruding region. In other arrangements, microneedles positioned in the outer region of the microneedle array device can be longer than microneedles positioned in the central region, such that the surface pattern defines a jagged region.

[0059] More advantageously, microneedles having different lengths enable the microneedles to penetrate to different depths within the patient's body to ensure that the fluid is delivered to the desired area and to reduce the chance of saturation occurring at a single depth. In addition, microneedles of different lengths can more perfectly match the contours of the human body and prevent leakage from the patient's body due to oversaturation of the patient's tissue or insufficient penetration of the microneedles in certain areas.

[0060] According to another aspect of the present invention, a method for manufacturing a microneedle is provided, which can be used to manufacture the microneedle of the above aspect of the present invention, or the microneedle array device of the above aspect of the present invention.

[0061] The method may include providing a mold. The method may include providing a polymer material. The method may include injection molding the polymer material using the mold to form the microneedle.

[0062] Injection molding allows manufacturers to produce polymer microneedles on a large scale in a cost-effective manner.

[0063] Advantageously, the injection molding process for producing microneedle array devices enables manufacturers to produce microneedle array devices with integral microneedles.

[0064] The method may include forming one or more outlet channels during the injection molding step.

[0065] Forming the outlet channels during the injection molding step reduces the complexity associated with manufacturing compared to some other conventional manufacturing processes. No further steps are required to produce the microneedles.

[0066] The method may also include the step of removing one or more portions of the sidewall to form one or more outlet channels of the microneedle. This step may be performed after the injection molding step. Removing one or more portions of the sidewall may include laser cutting. Removing one or more portions of the sidewall may include direct polymer cutting. Removing one or more portions may include any other suitable method.

[0067] Forming the microneedles without the exit channels during the injection molding step reduces the complexity of the injection molding process. This allows manufacturers to use simple molds. In addition, this enables manufacturers to mass-produce microneedles using the same mold because the exit channels can be added later.

[0068] Due to the low cost of injection molding, any device including microneedles made using the method of this aspect can be disposable (single-use) when desired. Due to the small size and complex structure of the microneedle device, it is difficult to thoroughly clean the microneedle device, so for some patients to use self-administration devices, cleaning and disinfection of the microneedle device may not be practical, so a disposable, single-use microneedle device is needed.

[0069] According to another aspect of the present invention, a microneedle for transdermal drug delivery is provided. The microneedle includes an input channel extending through the microneedle along the longitudinal axis of the microneedle. The input channel defines a sidewall, a first end, and a second end. The input channel is configured to receive a fluid input into the microneedle. The fluid can be a liquid, such as a liquid medicament. The longitudinal axis extends between the first and second ends of the microneedle. The microneedle includes one or more outlet channels. The outlet channel can extend between the inner surface of the sidewall and the outer surface of the sidewall. The one or more outlet channels can include a first end formed in the inner surface of the sidewall and a second end formed in the outer surface of the sidewall. One or more of the one or more outlet channels can be tapered so that the size of the first end of the one or more outlet channels is not equal to the size of the second end of the outlet channel.

[0070] The size of the first end of one or more outlet channels and the size of the second end of one or more outlet channels can be a cross-sectional size. The first end of the outlet channel can be larger than the second end of the outlet channel. Alternatively, the second end of the outlet channel can be larger than the first end of the outlet channel. The outlet channel can be a smooth taper so that the size of the outlet channel gradually changes between the first and second ends. The outlet channel can have an internal structure of a 3D profile between the first and second ends so that the size of the outlet channel changes between the first and second ends.

[0071] Having a tapered outlet channel allows the microneedle to be configured to increase or decrease the cross-sectional area of ​​the flow path in the outlet channel, for example to affect the flow rate. This flexibility enables the manufacture of microneedles customized for specific applications. Variations in the width of the outlet channel can be used to adjust pressure drop and fluid velocity.

[0072] The microneedle may include a combination of tapered and non-tapered outlet channels. The microneedle may include only tapered outlet channels. The microneedle may not include any tapered outlet channels.

[0073] Optional features of any of the above aspects may be combined with features of any other aspect in any combination. For example, features described in conjunction with the microneedles of the above aspects may have corresponding features definable with respect to the methods of the above aspects, and vice versa, and these embodiments are specifically contemplated. According to any other aspect of the invention, a microneedle array device of one aspect of the invention may include one or more microneedles. Features described in the context of the invention or in separate aspects and embodiments may be used together and / or interchangeable where possible. Similarly, for the sake of brevity, features are described in the context of a single embodiment, which may also be provided separately or in any suitable sub-combination. BRIEF DESCRIPTION OF THE DRAWINGS

[0074] The present invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0075] Figure 1 shows a perspective side view of a microneedle according to the present invention, showing the internal structure of the microneedle;

[0076] Figure 2 shows a perspective side view of another microneedle according to the present invention, showing the internal structure of the microneedle;

[0077] Figure 3a and 3b 1 and 2 show a perspective side view of another microneedle according to the present invention, Figure 3b The internal structure of the microneedle is shown;

[0078] Figure 4a and 4b shows a side view of a microneedle, Figure 4c shows a side view of a microneedle according to the present invention, in which the location of the outlet channel is clearly shown;

[0079] Figure 5a and 5b shows a side view of another microneedle according to the present invention, Figure 5a The internal structure of the microneedle is shown;

[0080] Figure 6a shows a perspective side view of a microneedle according to the present invention, showing the internal structure of the microneedle; Figure 6b Shows Figure 6a A plan view of the microneedle;

[0081] Figure 6c shows a perspective side view of a microneedle according to the present invention, showing the internal structure of the microneedle;

[0082] Figure 7a and 7b Showing views of the first and second sides of a microneedle array device according to the present invention, respectively;

[0083] Figure 8 A schematic cross-sectional view of a microneedle array device according to the present invention is shown;

[0084] Fig. 9 shows a schematic cross-sectional view of a microneedle array device including a connection device according to the present invention;

[0085] Fig.10 shows a schematic cross-sectional view of a microneedle array device according to the present invention, which includes microneedles having outlet channels arranged according to different patterns;

[0086] Fig.11 shows a schematic cross-sectional view of a microneedle array device according to the present invention, which includes microneedles of different lengths;

[0087] Fig.12 shows a microneedle array device comprising two types of microneedles according to the present invention;

[0088] Fig.13a and 13b The following are shown in more detail: Fig.12 A perspective view and a side view of various types of microneedles of a microneedle array device;

[0089] Fig.14 Shows Fig.12 A plan view of a microneedle array device showing the direction facing the outlet;

[0090] Fig.15 An overall flow chart of a method for manufacturing microneedles and microneedle array devices is shown;

[0091] Fig.16 shows a perspective view of a microneedle array device according to the present invention;

[0092] Fig.17 a and 17b show schematic side views of a microneedle array device according to the present invention; and

[0093] Fig.18 18a and 18b show schematic side views of a microneedle array device according to the present invention. DETAILED DESCRIPTION

[0094] Figure 1 A perspective view of a microneedle 10 is shown. The microneedle 10 includes an input channel 12 extending through the microneedle 10 along a longitudinal axis (A) of the microneedle 10. The input channel 12 defines a sidewall 16, a first end 11, and a second end 13. The longitudinal axis (A) of the microneedle 10 is the longitudinal axis of the input channel 12.

[0095] The side wall 16 includes an inner surface 20 and an outer surface 18. The outer surface 18 of the side wall 16 is the outer surface of the microneedle 10. The inner surface 20 of the side wall 16 defines the width of the input channel 12. Figure 1 In the embodiment of the present invention, the outer surface 18 is concentric with the inner surface 20. In other embodiments, the outer surface 18 may not be concentric with the inner surface 20. Figure 1 In some embodiments, the width of the sidewall 16 is uniform across the microneedle 10. In other embodiments, the width of the sidewall 16 varies at different portions of the microneedle 10. For example, in some embodiments, the width of the sidewall 16 varies along the longitudinal axis (A) of the microneedle 10.

[0096] exist Figure 1 In the embodiment, the input channel 12 is a hollow input channel. In other embodiments, the input channel 12 may not be completely hollow. For example, the input channel 12 may include one or more support structures. The support structure may be a frame configured to strengthen the microneedle internally.

[0097] The input channel 12 is concentric with the outer surface 18 of the microneedle 10 and passes through the center of the microneedle 10. In other embodiments, the input channel 12 can be offset from the center of the longitudinal axis (A) of the microneedle 10. Figure 1 In the embodiment of the present invention, the input channel 12 passes through the entire microneedle 10, so that the length of the input channel 12 is equal to the length of the microneedle 10. In other embodiments, the input channel 12 may only pass through a portion of the microneedle 10.

[0098] The microneedle 10 includes an outlet channel 14. The outlet channel 14 is a hollow channel extending between the inner surface 20 of the sidewall 16 and the outer surface 18 of the sidewall 16. The outlet channel 14 provides a fluid path between the input channel 12 and the outer surface 18 of the sidewall 16. The outlet channel 14 provides a fluid path for delivering fluid from the inlet channel 12 to the outside of the microneedle 10. In use, the microneedle is inserted through the skin of a patient, and a fluid such as a liquid medication is delivered from the input channel 12 through the outlet channel 14 into the patient's body.

[0099] The outlet channel 14 is angled relative to the longitudinal axis (A) of the microneedle 10. More specifically, the longitudinal axis of the outlet channel is angled relative to the longitudinal axis (A) of the microneedle 10. The outlet channel 14 is angled relative to the longitudinal axis (A). The angle (θ) is the angle between the longitudinal axis of the outlet channel and the longitudinal axis of the inlet channel 12. The angle (θ) is greater than 0° and less than 90°. An angle (θ) of 90° corresponds to the outlet channel 14 being parallel to the transverse axis of the microneedle 10, i.e., perpendicular to the longitudinal axis (A) of the microneedle. In some embodiments, the angle (θ) is greater than 45° and less than 90°. Figure 1 In the embodiment of the present invention, the angle (θ) is 65°.

[0100] Obviously, the outlet channel 14 at an angle of 0° relative to the longitudinal axis (A) of the microneedle 10 will not be located in the side wall 16 of the microneedle 10, but in the second end 13 of the microneedle 10, otherwise the outlet channel 14 will not form a fluid channel between the inner surface 20 and the outer surface 18 of the microneedle 10. As explained earlier in the specification, the outlet channel 14 in the second end 13 of the microneedle 10 requires the fluid to overcome a greater resistance (e.g., hydrostatic pressure) when entering the patient's body than the outlet channel 14 formed in the side wall 16 and at an angle greater than 0° relative to the longitudinal axis (A) of the microneedle 10.

[0101] exist Figure 1 In some embodiments, the microneedle 10 includes a single outlet channel 14. In other embodiments, the microneedle 10 may include multiple outlet channels 14.

[0102] The outlet passage 14 has an inner edge 15. The inner edge 15 defines a boundary between the outlet passage 14 and an inner surface 20 of the side wall 16. Figure 1 In the embodiment, the edge 15 is sharp, which means that there is an instantaneous change in angular direction between the inner surface 20 of the side wall 16 and the outlet passage 14. In other embodiments, the edge 15 can be smooth (e.g., rounded), which means that there is a gradual change between the outlet passage 14 and the inner surface 20 of the side wall 16. A smooth edge 15 can be defined as a curved edge 15.

[0103] The first end 11 of the input channel 12 is open. The open first end 11 is configured to allow fluid to enter the input channel 12. The second end 13 of the input channel 12 is closed. The closed second end 13 is configured to prevent fluid from passing therethrough.

[0104] The microneedle 10 is formed of a polymer material, or includes a polymer material. The microneedle 10 may be formed of a high-strength biocompatible polymer material, or include a high-strength biocompatible polymer material. The microneedle 10 may be formed of one or more of polyglycolide (PGA), polylactic acid (PLA), polymethyl methacrylate (PMMA), cycloolefin copolymer (COC), polycarbonate (PC) and liquid crystal polymer (LCP), or include one or more of these. In other embodiments, the microneedle 10 may be formed of a metal, ceramic or semiconductor, or include a metal, ceramic or semiconductor.

[0105] Figure 2 A perspective view of another microneedle 10' is shown. Figure 1 The microneedle 10 of FIG. 1 is substantially the same, but it includes two outlet channels 14 a ′, 14 b ′.

[0106] The first outlet channel 14a' is at an angle θa relative to the longitudinal axis (A) of the microneedle 10'. Figure 2 , θa is 55. , the first outlet channel 14a' is tapered so that the first end 14a-1' of the outlet channel 14a' is larger than the second end 14a-2' of the outlet channel 14a'. The first end 14a-1' of the outlet channel 14a' is formed on the inner surface 20' of the side wall 16'. The second end 14a-2' of the outlet channel 14a' is formed on the outer surface 18' of the side wall 16'. The cross-sectional area of ​​the first end 14a-1' is larger than the cross-sectional area of ​​the second end 14a-2'. This is consistent with Figure 1 In contrast to the outlet channel 14 of the microneedle 10, Figure 1 In the microneedle 10, the outlet channel 14 is not tapered.

[0107] When referring to a tapered outlet channel, the angle of the outlet channel relative to the longitudinal axis of the microneedle refers to the angle of the longitudinal axis of the outlet channel extending through the outlet channel relative to the longitudinal axis of the microneedle.

[0108] An angle θa between 0° and 90° means that the first outlet channel 14a' is tilted away from the first end 11' of the microneedle 10' and toward the second end 13' of the microneedle 10', such that the second end 14a-2' of the outlet channel 14a' is farther from the first end 11' of the microneedle 10' than the first end 14a-1' of the outlet channel 14a'. An angle θa between 90° and 180° will correspond to the outlet channel 14a' tilted toward the first end 11' of the microneedle 10', such that the second end 14a-2' of the outlet channel 14a' is closer to the first end 11' of the microneedle 10' than the first end 14a-1' of the outlet channel 14a'.

[0109] The second outlet channel 14b' is at an angle θb relative to the longitudinal axis (A) of the microneedle 10'. Figure 2 , θb is 90°. The second outlet channel 14b' is not tapered so that the first end 14b-1' of the outlet channel 14b' is the same size as the second end 14b-2' of the outlet channel 14b'. The first end 14b-1' of the outlet channel 14b' is formed on the inner surface 20' of the side wall 16'. The second end 14b-2' of the outlet channel 14b' is formed on the outer surface 18' of the side wall 16'. The area of ​​the first end 14b-1' is equal to the area of ​​the second end 14b-2'.

[0110] Figure 2 The microneedle 10' includes a combination of tapered and non-tapered outlet channels 14a', 14b'. In other embodiments, all outlet channels 14a', 14b' are tapered, or none of the outlet channels 14a', 14b' are tapered.

[0111] exist Figure 1 and Figure 2In the drawings, for the sake of clarity, the microneedles 10, 10' are shown without needle tips, but it should be understood that such devices typically include needle tips.

[0112] Figure 3a and 3b A perspective view of a microneedle 110 is shown. Figure 3b Provided Figure 3a A partially transparent view of the microneedle 110 shows the internal structure. Except for the number of outlet channels 114a-c, the microneedle 110 substantially corresponds to Figure 1 Microneedle 10.

[0113] The microneedle 110 includes three outlet channels 114a-c. In other embodiments, the microneedle 110 may include any other number of outlet channels.

[0114] The outlet channels 114a-c are offset relative to each other along the longitudinal axis (A) of the microneedle 110. Figure 3a and 3b In some embodiments, the outlet channels 114a-c are evenly spaced, such that the distance between consecutive outlet channels 114a-c is consistent. In other embodiments, the spacing between the outlet channels 114a-c may be irregular, such that the distance between consecutive outlet channels 114a-c varies.

[0115] exist Figure 3a and 3b In the embodiment of the present invention, the outlet channels 114a-c are also angularly offset relative to each other around the longitudinal axis (A) of the microneedle 110. The outlet channels 114a-c are uniformly angularly offset around the longitudinal axis (A). In the arrangement shown in FIG. 3 , there are three outlet channels 114a-c, and the angle between consecutive outlet channels 114a-c is 120°.

[0116] In other embodiments, for example, in a system having four outlet channels 214a-d, Figure 4a In -c, the angle between consecutive channels 214a-d around the longitudinal axis is 90°.

[0117] exist Figure 4c In the embodiment, four outlet channels 214a-d are evenly spaced along the longitudinal axis. The distance between consecutive outlet channels (eg, the distance between 214a and 214b, the distance between 214b and 214c, etc.) is constant.

[0118] In other embodiments, the outlet channels 114a-c are not uniformly angularly distributed around the longitudinal axis (A) of the microneedle 110. For example, for embodiments including three outlet channels, the first and second outlet channels 114a, 114b can be angularly offset from each other by a first angle θ1, the second and third outlet channels 114b, 114c can be angularly offset from each other by a second angle θ2, and the first and third outlet channels 114a, 114c can be angularly offset from each other by a third angle θ3, wherein the values ​​of θ1, θ2, and θ3 are different from each other.

[0119] Two or more outlet channels 114a-c may be aligned at an angle. For example, an outlet channel 114a-c may be aligned with one or more other outlet channels 114a-c and may be angularly offset from one or more other outlet channels 114a-c. An example of such an embodiment is Figure 5a and 5b . The microneedle 310 includes four outlet channels 314. The first pair of outlet channels 314a are angularly aligned on a first side of the microneedle 310, and the second pair of outlet channels 314b are angularly aligned on a second side of the microneedle 310. The term "angularly aligned" herein means that the pair of outlet channels 314 are not angularly displaced from each other around the longitudinal axis (A). The first pair of outlet channels 314a and the second pair of outlet channels 314b are offset 180 degrees relative to each other around the longitudinal axis (A).

[0120] exist Figure 3a and 3b In the embodiment, each outlet channel 114a-c forms the same angle (θ) with respect to the longitudinal axis (A). In other embodiments, one or more outlet channels 114a-c may form a first angle (θ) with the longitudinal axis (A) of the microneedle 110, and one or more other outlet channels 114a-c may form a different second angle (θ) with the longitudinal axis (A) of the microneedle 110. For example, the first outlet channel may be 50° with respect to the longitudinal axis (A), and the second outlet channel may be 45° with respect to the longitudinal axis (A). In other embodiments, each outlet channel 114a-c may form a different angle (θ) with respect to the longitudinal axis (A).

[0121] Figure 3a and 3b The microneedle 110 further includes a needle tip 121. The needle tip 121 is disposed on the second end 113 of the microneedle 110. The needle tip 121 seals the second end 113 of the input channel 112. Figure 3a and 3bIn the embodiment of the present invention, the needle tip 121 is integrally formed with the side wall 116 of the microneedle 110. In other embodiments, the needle tip 121 can be a separate component connected to the side wall 116. The needle tip 121 forms a sufficiently sharp tip to penetrate the patient's skin. In other embodiments, the microneedle 110 may not include the needle tip 121.

[0122] Figure 6a and 6c A perspective view of microneedles 410 and 510 according to another embodiment is shown. Figure 6b Shows Figure 6a 4 is a plan view of a cross section of a microneedle 410. For clarity, the outlet channel and the needle tip are not shown in these figures.

[0123] The microneedle 410 includes an input channel 412 whose width varies along the longitudinal axis (A) of the microneedle 410. The width of the input channel 412 refers to the distance between opposite sides of the inner surface 420 of the sidewall 416 along a transverse plane perpendicular to the longitudinal axis (A) of the microneedle 410. The width of the input channel 412 varies between Figure 6b The winning bid is "W1".

[0124] exist Figure 6a In the example of FIG. 4 , the input channel 412 tapers toward the second end 413 of the microneedle 410. In other embodiments, the input channel 412 may taper toward the first end 411 of the microneedle 410. In other embodiments, the input channel 412 may have a sinusoidal profile, a staggered profile, a stepped profile, or an irregular profile.

[0125] The width of the microneedle 410 refers to the distance between opposite sides of the outer surface 418 of the sidewall 416 along a transverse plane perpendicular to the longitudinal axis (A) of the microneedle 410. Figure 6b The winning bid is "W2".

[0126] exist Figure 6a In the embodiment of the present invention, the width of the microneedle 410 is constant. The microneedle 410 is cylindrical because its width is constant.

[0127] The microneedle 510 includes an input channel 512 whose width is constant along the longitudinal axis (A) of the microneedle 510. The width of the microneedle 510 varies along the longitudinal axis (A).

[0128] exist Figure 6c In the example of FIG. 5 , the microneedle 510 tapers toward the second end 513 of the microneedle 510. In other embodiments, the microneedle 510 may taper toward the first end 511 of the microneedle 510. In other embodiments, the microneedle 510 may have a sinusoidal profile, a staggered profile, a stepped profile, or an irregular profile.

[0129] The shape of the microneedle 510 is defined by the outer surface 518 of the sidewall 516. In some embodiments, the shape of the microneedle 510 can be cylindrical (e.g. Figure 6a As shown), conical cylindrical (as Figure 6c as shown), pyramidal, tetrahedral, cone or any other shape.

[0130] In some embodiments, both the width of the microneedle and the width of the input channel vary relative to the longitudinal axis of the microneedle.

[0131] An experiment was conducted to test the mechanical strength of the microneedles formed according to the present invention. A microneedle array device comprising 100 microneedles was used for the experiment. A combined force of 22 N was applied to the 100 microneedles, so that a force of 0.22 N was applied to each microneedle. When subjected to this force, none of the microneedles broke. According to "Park, J.-H., Allen, MG and Prausnitz, MR's Biodegradable Polymer Microneedles: Fabrication, Mechanics and Transdermal Delivery. J. Controlled Release. 104, 51–66 (2005)", the minimum microneedle strength required to penetrate the skin is 0.058 N.

[0132] Figure 7a and 7b A first side and a second side of a microneedle array device 600 are shown. Figure 8 A schematic cross-sectional side view of a microneedle array device 600 is shown. The microneedle array device 600 includes a base 630, a plurality of microneedles 610, a drug inlet 650, and a hollow chamber 660.

[0133] The microneedles 610 are disposed on the first side 632 of the substrate 630. In different embodiments, the number of microneedles may be different. In some embodiments, the microneedle array device 600 may include one microneedle 610. In some typical embodiments, the array device may include 10-30 microneedles, or more than 100 microneedles. The microneedles 610 may be Figure 1 Any microneedle shown in -6 and described herein. Figure 8 As shown, microneedles 610 are integrally formed with array device 600. In other embodiments, microneedles may be connected to array device 600 without being integrally formed with array device 600.

[0134] exist Figure 7a and 7b In the embodiment, the microneedles 610 form a square array. In other embodiments, the microneedles can form a circular, rectangular, or triangular array. In addition, the microneedles 610 can form an array without a defined shape. The distance between the microneedles (the center-to-center distance between the microneedles) can be uniform or non-uniform.

[0135] The drug inlet 650 is disposed on the second side 634 of the base. The second side 634 of the base is opposite the first side 632. In other embodiments, the drug inlet 650 can be disposed on any side of the base.

[0136] A hollow chamber 660 is formed inside the base 630. The hollow chamber 660 forms a fluid connection between one or more microneedles 610 and the drug inlet 650. The hollow chamber 660 forms a continuous fluid path between the drug inlet 650 and the microneedle 610. In use, the user injects one or more fluids through the drug inlet 650 (for example, using a syringe). The hollow chamber 660 provides a fluid path that delivers the liquid entering through the drug inlet 650 to the input channel 612 of the microneedle 610. The input channel 612 of the microneedle 610 is in fluid communication with a fluid channel 661 extending through the first side 632 of the microneedle array device 600 into the hollow chamber 660. The fluid enters the input channel 612 of the microneedle 610 from the hollow chamber 660 through the fluid channel 661. The fluid then leaves the microneedle 610 via the outlet channel 614.

[0137] exist Figure 8 In the embodiment, each microneedle 610 has the same width. In other embodiments, the width of each microneedle 610 can be different from one or more other microneedles 610. Each microneedle 610 can have a unique width.

[0138] exist Figure 8 In one embodiment, each microneedle 610 has the same input channel width. In other embodiments, the input channel width of each microneedle 610 can be different from one or more other microneedles 610. Each microneedle 610 can have a unique input channel width. Figure 8 In the embodiment, each microneedle 610 has the same outlet channel width. In other embodiments, the outlet channel width of each microneedle 610 can be different from one or more other microneedles 610. Each microneedle 610 can have a unique outlet channel width.

[0139] Fig. 9 A microneedle array device 700 is shown in which a drug inlet 750 includes a connection device. The connection device is formed of two parts. The first part of the connection device is that the drug inlet 750 has a tapered inlet. In use, when a syringe (or other fluid delivery device) is placed in the drug inlet 750, the tapered surface abuts the syringe to secure it in place. The drug inlet 750 includes a second part of the connection device, which is an elastic sealing ring 760. The elastic sealing ring 760 can be elastically deformed to receive and hold the syringe (or other fluid delivery device) and prevent liquid drug from leaking from the microneedle array device 700. Although the two parts of the connection device are Fig. 9In the embodiment shown together, but in other embodiments they can be used separately. In addition, some embodiments can use one or more components of the connection device in combination with other connection devices.

[0140] exist Figure 8 and Fig. 9 In the microneedle array device 600, 700 of FIG. 1 , each microneedle 610, 710 is identical to the other microneedles 610, 710. In contrast, in Fig.10 and 11 In the microneedle array device 800 , 900 , each microneedle 810 , 910 is different from at least one other microneedle 810 , 910 .

[0141] exist Fig.10 In the embodiment of the present invention, the number of outlet channels 814a-c varies between microneedles 810. A microneedle 810 within an array device 800 may have a different number of outlet channels 814a-c than one or more other microneedles 810 within the array device. Fig.10 In FIG. 8 , microneedle 810a includes one outlet channel 814a, while microneedle 810b includes two outlet channels 814b and 814c.

[0142] exist Fig.10 810. In the embodiment of the present invention, the position of the outlet channels 814a-c on each microneedle 810 is offset relative to the position of the outlet channels 814a-c of at least one other microneedle 810. The position of the outlet channels 814a-c is unique for each microneedle in the array device 800. The positions of the outlet channels 814a-c of the microneedle 810 are offset along the longitudinal axis of the microneedle 810. The positions of the outlet channels 814a-c of the microneedle 810 are angularly offset around the longitudinal axis of the microneedle 810.

[0143] In other embodiments, the location of the outlet channel is not unique for each microneedle in the array device 800. For example, for each microneedle, the location of the outlet channel can be the same as one or more other microneedles in the microneedle array device.

[0144] In some embodiments, the location of the outlet channels differs only between adjacent microneedles 810. For example, the location of the outlet channels of a microneedle 810 may differ from the location of the outlet channels of other microneedles 810 surrounding it. In some embodiments, the location of the outlet channels of microneedles 810 may form a repeating pattern.

[0145] In some embodiments, the outlet channels of each microneedle 810 are positioned so that they do not face the outlet channels of another microneedle 810. The outlet channels of a microneedle can be offset along the longitudinal axis relative to the outlet channels of an adjacent microneedle 810. The outlet channels of a microneedle can face a different angular direction around the longitudinal axis than the outlet channels of an adjacent microneedle 810.

[0146] Fig.11 A microneedle array device 900 is shown in which the lengths of the microneedles 910a-e are different. The length of the microneedle is defined as the distance between the location where the microneedles 911a, b are connected to the first side 932 of the base 930 and the needle tips 921a, b. The length of each microneedle 910a-e is different from the length of at least one other microneedle 910a-e. For example, the distance between 911b and 921b is less than the distance between 911a and 921a. In some embodiments, the length of each microneedle 910 is different from the length of each other microneedle 910.

[0147] exist Fig.11 In some embodiments, the center microneedles 910b-d are shorter than the edge microneedles 910a and 910e. In other embodiments, the center microneedles 910b-d are longer than the edge microneedles 910a and 910e. The distribution of the length of the microneedles 910 on the microneedle array device can form a surface pattern. In some embodiments, the surface pattern can be an angled, pyramidal or sinusoidal surface pattern. The surface pattern can include protruding portions and / or recessed portions.

[0148] Fig.12 A microneedle array device 1000 is shown. The microneedle array device 1000 includes a first type of microneedle 1010a and a second type of microneedle 1010b. There are 12 first type microneedles 1010a forming an outer ring. There are 6 second type microneedles 1010b arranged to form an inner ring. This inner ring is surrounded by an outer ring.

[0149] Fig.13a The first type of microneedle 1010a is shown in more detail in The first type of microneedle 1010a is 1.5 mm high and includes a single angled outlet channel 1014a.

[0150] Fig.13b The second type of microneedle 1010b is shown in more detail in The second type of microneedle 1010b is 1.0 mm high and includes a single outlet channel 1014b.

[0151] exist Fig.13b In the illustrated arrangement, the outlet channels of the second type of microneedles 1010b are angled at θ = 90°. However, in other arrangements, all microneedles (first and second types) may have inclined outlet channels with angles less than θ = 90° and greater than θ = 0°, or only the second type may have inclined outlet channels with angles less than θ = 90° and greater than θ = 0°.

[0152] Using a microneedle array device 1000 including microneedle types 1010a, 1010b having different heights allows the microneedle array device 1000 to more reliably penetrate the skin because a patient's skin is generally rounded rather than flat.

[0153] like Fig.14 As shown, each microneedle 1010a, 1010b of the microneedle array device 1000 is arranged so that their outlets face radially outward in directions different from each other. Fig.14 The arrow 1070 in FIG. 1 indicates the direction in which the outlet of each microneedle 1010a, 1010b faces. This design helps minimize interference between different microneedles and spreads the drug / fluid more evenly in the skin layer.

[0154] The lengths of the first type of microneedles 1010a and the second type of microneedles 1010b are different so that the liquid drug can be delivered to different skin layers to minimize interference between the microneedles, thereby avoiding rapid saturation.

[0155] Fig.16 A perspective view of a microneedle array device 1100 is shown. The device 1100 includes five microneedles 1110. Four microneedles 1110-1 are arranged in a square configuration (referred to as "outer" microneedles), and a fifth microneedle 1110-2 is located in the center of the other microneedles 1110-1 (referred to as the "center" microneedle).

[0156] Each microneedle 1110 includes two outlet channels 1114. The first outlet channel 1114 of each microneedle 1110 is formed in the side wall of the microneedle 1110. The first outlet channel 1114 of each of the four outer microneedles 1110-1 is arranged to face away from the other outer microneedles 1110-1. In other words, the first outlet channel 1114 of each outer microneedle 1110-1 is located on the side of the microneedle 1110-1 opposite to the central microneedle 1110-2.

[0157] The second outlet channel 1114 of each microneedle 1110 is formed in the tip of the microneedle 1110. The second outlet channel 1114 of each outer microneedle 1110 is arranged to face the central microneedle 1110.

[0158] In other embodiments, the first and / or second outlet channels 1114 may be arranged differently and face in any direction. In other embodiments, the outer microneedles 1110 - 1 do not form a square configuration. In other embodiments, there may be any number of microneedles 1110 .

[0159] In use Fig.16 During experiments using the microneedle array device 1100, mice injected with drugs suffered fewer breaks in their skin than when using traditional needles.

[0160] Fig.17(a) and (b) show a microneedle array device 1200, 1300, which includes microneedles 1210, 1310, and the microneedles 1210, 1310 have exit channels disposed on the sidewalls and tips of the microneedles.

[0161] like Fig.17 As shown in (a), the microneedle 1210 includes a first outlet channel 1214-1 disposed in the side wall of the microneedle 1210 and a second outlet channel 1214-2 disposed in the tip. Fig.17 In (a), the first outlet channel 1214-1 is at a 90° angle relative to the longitudinal axis of the microneedle 1210, and the second outlet channel 1214-2 is at a 45° angle relative to the longitudinal axis.

[0162] Fig.17 (a) is intended to illustrate the location and direction of the outlet channel, not the angle of the outlet channel. The outlet channel 1214-1 in the side wall can be at an angle greater than 0° and less than 90° relative to the longitudinal axis of the microneedle. Fig.16 , 17 (b) and Fig.18 The same is true for (a) and (b), and the outlet channels of these figures may also be at an angle greater than 0° and less than 90° relative to the longitudinal axis of the microneedle.

[0163] exist Fig.17 In the microneedle array device 1200 of (a), the first outlet channels 1214-1 are all away from the center of the device 1200. The second outlet channels 1214-2 are all facing the center of the device 1200.

[0164] Fig.17 (b) shows Fig.17 (a) An alternative microneedle array device 1300 in which the outlet channels face in different directions. Fig.17 (a), the outlet channels of the central microneedle 1310 face in opposite directions to provide a different drug delivery profile.

[0165] Fig.18 (a) shows a microneedle array device 1400 including a microneedle 1410 including a first outlet channel 1414-1 disposed in the sidewall of the microneedle 1410 and a second outlet channel 1414-2 disposed in the tip. Fig.18 In the embodiment of (a), the first outlet channel 1414-1 is at an angle of 90° relative to the longitudinal axis of the microneedle 1410. The second outlet channel 1414-2 is at an angle of 45° relative to the longitudinal axis.

[0166] Fig.18 The microneedle array device 1400 of (a) is similar to Fig.17(a) but with different lengths of microneedles 1410. The length of the center microneedle 1410 is shorter than the length of the outer microneedles 1410. In other embodiments, the lengths of the microneedles may vary according to different patterns.

[0167] Fig.18 (b) shows a microneedle array device 1500, which combines Fig.17 18(b) and 18(a) 1300, 1400. The microneedle array device 1500 includes microneedles 1510 having different lengths and outlets facing in selectable directions, i.e., each microneedle 1510 has an outlet channel facing in the opposite direction to its adjacent microneedle 1510.

[0168] Fig.17 (a) and (b) and Fig.18 (a) and (b) are provided as examples only, and in other embodiments, the length of one or more microneedles may be unique or equal to the length of one or more other microneedles. The direction facing the outlet channel of one or more microneedles may be unique or the same as that of one or more other microneedles.

[0169] Fig.15 An overview of a method 2000 for making a microneedle array device is shown. The method 2000 includes steps 210-2110. The method can be used to make the microneedle array device described herein and Figure 1 -6, or the microneedle array device shown in Figures 7-14.

[0170] Step 2010 includes designing the microneedle. For example, a person practicing the method needs to determine the parameters of the microneedle, such as the number of outlet channels, the location of the outlet channels, and the angle of the outlet channels relative to the longitudinal axis.

[0171] Step 2020 includes selecting a polymer for making the microneedle. The person practicing the method can select from a range of high-strength biocompatible polymer materials. For example, the person practicing the method can select one or more from polyglycolide (PGA), polylactic acid (PLA), polymethyl methacrylate (PMMA), cyclic olefin copolymer (COC), polycarbonate (PC) and liquid crystal polymer (LCP).

[0172] Step 2030 includes designing and manufacturing a mold. The mold can be a two-piece mold. The mold can be a three-piece mold. The mold can be formed of one or more parts, or include one or more parts.

[0173] In some embodiments, the mold is designed to form one or more outlet channels in the microneedle during the injection molding process. In other embodiments, the microneedles are formed without outlet channels, and they are formed after the injection molding process is completed. The complexity of the mold can be determined based on these factors.

[0174] Step 2040 includes assembling the mold into an injection molding machine. Step 2040 may include assembling one or more components of the mold into the injection molding machine. In some embodiments, the injection molding machine is a micro injection molding machine. In some embodiments, customized modifications may be made on the injection molding machine to accommodate more complex molds.

[0175] Step 2050 includes feeding polymer pellets into an injection molding machine. The pellets are formed from or include the polymer material selected in step 2020.

[0176] After the pellets are fed into the injection molding machine, steps 2060 and 2070 include plasticizing / melting of the pellets and injecting the molten polymer material into the mold, respectively.

[0177] Step 2080 includes packaging and cooling the molten polymer material within the mold. Step 2080 solidifies the polymer material to form one or more microneedles and / or a base.

[0178] Step 2090 includes opening the mold to release the one or more microneedles.

[0179] Method 2000 can produce a "2D line" of microneedles, referred to as a "microneedle line", for subsequent modular assembly. For example, a mold can be designed to produce a row of microneedles. These microneedles in the same row can have the same length or different lengths. Compared to traditional manufacturing techniques, producing a long string of microneedles reduces the complexity of the required mold, thereby reducing the time and cost associated with manufacturing. The microneedles can then be rearranged or assembled into a specific pattern to form a 2D / 3D microneedle array and mounted into a base according to their desired use to form a microneedle array device. Arranging the microneedles in an array is an optional step, as shown in step 2100. Therefore, during the modular assembly process, manufacturers can adjust the number and distribution pattern of microneedles in each unit by selecting an appropriate microneedle string, which provides greater flexibility for product changes.

[0180] After the step 2100 of assembling and packaging, the method may include testing 2110 and sterilization, as required.

[0181] In some embodiments, method 2000 produces a microneedle comprising an input channel and one or more outlet channels. To achieve this, the mold is configured to form a microneedle comprising an outlet channel. In other embodiments, the microneedle produced by method 2000 comprises an input channel but does not comprise an outlet channel.

[0182] In some embodiments, in the case where the injection molding process produces a microneedle without an outlet channel, the method further comprises the step of removing one or more portions of the sidewall of the molded microneedle to form one or more outlet channels. Removing one or more portions of the sidewall may include laser cutting, direct polymer cutting, both, or other applicable manufacturing techniques.

[0183] In some embodiments, one or more of steps 2010-2110 may be optional. For example, steps 2010-2030 may be performed once as part of the design process, and subsequent manufacturing steps may be performed repeatedly to produce a large number of microneedles. This would eliminate the need for the manufacturer to repeatedly select polymers and molds.

[0184] In some embodiments, method 2000 can be used to produce a microneedle array device, rather than one or more microneedles. In such embodiments, the microneedles will be integrally formed with the base of the microneedle array device. One or more connecting devices can be subsequently added to the microneedle array device. Alternatively, one or more connecting devices can be integrally formed with the base.

[0185] In the examples above, the microneedles are shown as having a length of approximately 0.8 mm, 1.0 mm, or 1.5 mm. However, the microneedles may have a length in the range of 0.5 to 2 mm.

[0186] By reading this disclosure, other changes and modifications will be apparent to the skilled person. Such changes and modifications may include equivalent features and other features known in the art of microneedles, microneedle array devices or injection molding processes, and these features may be used to replace or be added to the features already described herein.

[0187] Although the attached claims are directed to specific combinations of features, it should be understood that the scope of the disclosure of the present invention also includes any novel feature or any novel combination of features disclosed explicitly or implicitly herein, or any generalization thereof, regardless of whether it relates to the same invention currently claimed in any claim and regardless of whether it alleviates any or all technical problems similar to the present invention.

[0188] Features described in the context of separate embodiments may also be provided in combination in a single embodiment. Conversely, various features described in the context of a single embodiment for the sake of brevity may also be provided separately or in any suitable subcombination. Applicants hereby declare that new claims may be formulated to such features and / or combinations of such features during the prosecution of this application or of any further application derived therefrom.

[0189] For the sake of completeness, it is also stated that the term "comprising" does not exclude other elements or steps, the term "a" or "an" does not exclude a plurality, a single processor or other unit may fulfill the functions of several means recited in the claims, and any reference signs in the claims should not be construed as limiting the scope of the claims.

Claims

1. A microneedle for transdermal drug delivery, the microneedle comprising: an input channel extending through the microneedle along a longitudinal axis of the microneedle, the input channel defining a first end and a second end, the input channel configured to receive a fluid input into the microneedle; as well as one or more outlet channels, each of the one or more outlet channels defining a fluid path between the input channel and an outer surface of the microneedle; The one or more outlet channels are at an angle greater than 0° and less than 90° relative to the longitudinal axis of the microneedle.

2. The microneedle according to claim 1, wherein The input channel further defines a side wall; And wherein the one or more outlet channels extend between an inner surface of the sidewall and an outer surface of the sidewall such that each of the one or more outlet channels defines a fluid path between the input channel and the outer surface of the sidewall.

3. The microneedle according to claim 1 or 2, wherein: A first end of the input channel is open so that fluid can enter the input channel.

4. The microneedle according to any one of the preceding claims, wherein The second end of the input channel is closed so that fluid cannot pass through.

5. The microneedle according to any one of the preceding claims, wherein Said angle is between 10° and 70°, and optionally or preferably, between 20° and 60°.

6. The microneedle according to any one of the preceding claims, wherein The angle is greater than 45°.

7. The microneedle according to any one of the preceding claims, wherein There are a plurality of outlet channels, and the outlet channels are offset relative to each other along the longitudinal axis of the microneedle.

8. A microneedle according to any one of the preceding claims, wherein There are a plurality of outlet channels, and the outlet channels are angularly offset relative to each other about the longitudinal axis of the microneedle, and optionally or preferably, wherein the outlet channels are uniformly angularly offset relative to each other about the longitudinal axis.

9. The microneedle according to any one of the preceding claims, wherein The width of the input channel varies along the longitudinal axis of the microneedle.

10. The microneedle according to any one of the preceding claims, wherein The input channel has a tapered profile, a sinusoidal profile, a staggered profile, a stepped profile, or an irregular profile.

11. The microneedle according to any one of the preceding claims, wherein The microneedle is a cylinder, a tapered cylinder, a pyramid, a tetrahedron or a cone.

12. The microneedle according to any one of the preceding claims, wherein The microneedles are formed of, or include, a polymer material.

13. The microneedle according to claim 12, wherein The microneedle is formed of or includes a high-strength biocompatible polymer material, such as polyglycolide (PGA), polylactic acid (PLA), polymethyl methacrylate (PMMA), cyclic olefin copolymer (COC), polycarbonate (PC) or liquid crystal polymer (LCP).

14. The microneedle according to any one of claims 1 to 11, wherein The microneedle is formed of or includes a metal, a ceramic or a semiconductor material.

15. The microneedle of any one of claims 2-14, wherein the one or more outlet channels comprise a first end formed in the inner surface of the sidewall and a second end formed in the outer surface of the sidewall, and the one or more outlet channels are tapered such that a size of the first end of the one or more outlet channels is not equal to a size of the second end of the outlet channel.

16. A microneedle array device comprising: Pedestal; One or more microneedles according to any one of claims 1 to 15, the one or more microneedles being disposed on a first side of the substrate; a drug inlet, the drug inlet being disposed on the second side of the base; as well as A hollow chamber within the base forms a fluid connection between the one or more microneedles and the drug inlet.

17. The microneedle array device according to claim 16, wherein: The drug inlet includes a connection means for connecting the microneedle array device to a syringe or a container.

18. The microneedle array device according to claim 17, wherein: The connection device is a tapered hole, or the connection device includes a tapered hole.

19. The microneedle array device according to claim 17 or 18, wherein: The connecting device is an elastic sealing ring or other types of sealing components, or the connecting device includes an elastic sealing ring or other types of sealing components.

20. The microneedle array device of any one of claims 16 to 19, wherein the one or more microneedles comprise a first microneedle and a second microneedle, the first microneedle comprising one or more outlet channels, the second microneedle comprising one or more outlet channels, wherein the one or more outlet channels of the first microneedle are distributed in a first pattern, and the one or more outlet channels of the second microneedle are distributed in a second pattern, wherein the first pattern is different from the second pattern.

21. The microneedle array device according to claim 20, wherein: The one or more outlet channels distributed in the first pattern have a different position along the longitudinal axis of the microneedle than the one or more outlet channels distributed in the second pattern.

22. The microneedle array device according to claim 20 or 21, wherein: The one or more outlet channels distributed in the first pattern have a different angular position about the longitudinal axis of the microneedle than the one or more outlet channels distributed in the second pattern.

23. The microneedle array device according to any one of claims 17 to 22, wherein: There are a plurality of microneedles, and at least a first microneedle of the plurality of microneedles has a different length than at least a second microneedle of the plurality of microneedles.

24. A method of manufacturing a microneedle or microneedle array device according to any one of the preceding claims, the method comprising: Provide molds; Providing polymer materials; as well as The polymer material is injection molded using the mold to form the microneedles.

25. The method according to claim 24, wherein: The one or more outlet channels are formed during the step of injection molding.

26. The method according to claim 24, wherein: The method further comprises the step of removing one or more portions of the side wall to form the one or more outlet channels after the step of injection molding; and preferably Wherein removing the one or more portions of the sidewall comprises laser cutting or direct polymer cutting.

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