Rizatriptan microneedle patch as well as preparation method and application thereof

Abstract

The invention relates to a rizatriptan microneedle patch as well as a preparation method and application thereof. The rizatriptan microneedle patch comprises a substrate and a needle body arranged on the surface of the substrate, wherein the needle body is prepared from rizatriptan benzoate and a framework material; the framework material comprises a combination of dextran and trehalose, a combination of copovidone, polyvinyl alcohol and dextran, a combination of hydroxypropyl methylcellulose and dextran or a combination of sodium carboxymethyl cellulose and dextran. The rizatriptan microneedle patch disclosed by the invention has relatively high mechanical strength and medicine accumulation transmittance.

Description

Technical Field

[0001] The present application relates to the technical field of pharmaceutical preparations, and in particular to a rizatriptan microneedle patch and a preparation method and application thereof. Background Art

[0002] Migraine is a common and disabling headache disorder characterized by recurrent, unilateral throbbing pain, often accompanied by nausea, hearing and smell disorders, etc., which worsens after exertion, leading to physical and psychosocial illnesses in individuals. One in ten people in the world suffers from migraine, and the World Health Organization (WHO) lists migraine as one of the top 20 debilitating diseases. Migraine patients have a 3-7 times higher risk of depression, anxiety and suicide than healthy people, and a 1.5-2 times higher risk of cardiovascular disease, heart attack and stroke than healthy people.

[0003] Triptans are selective serotonin agonists that bind to serotonin receptors (5-HT1B) in intracranial blood vessels (which dilate during a migraine attack), causing vasoconstriction; they bind to neurogenic and central serotonin receptors (5-HT1D), inhibiting the release of substance P and CGRP, and block pain signals to the brain by inhibiting nociceptors. In this way, triptans have the potential to reverse various steps of trigeminovascular activation in migraine. Triptans have a lower risk profile than nonselective serotonin agonists, ergot alkaloids.

[0004] Rizatriptan is a second-generation triptan drug. Compared with other triptan drugs, it has the characteristics of rapid relief of headaches and fewer side effects. The varieties of rizatriptan benzoate approved by the US FDA for marketing include tablets and orodisintegrating tablets. Tablets and capsules are available in China, and the varieties applied for clinical trials include dispersible tablets, granules, chewable tablets, and orodisintegrating tablets. In addition, there are methods to provide its oral fast-dissolving film, oral spray, nasal spray, patch, etc. However, oral dosage forms have a first-pass effect in the liver, low drug bioavailability, slow onset of action, and are easily affected by gastric contents or food. Migraine attacks are often accompanied by nausea and vomiting, and oral medications may be vomited out. Although oral fast-dissolving films and oral sprays avoid the first-pass effect, they are prone to loss during use, reducing bioavailability. Although nasal preparations can quickly take effect through the naso-brain barrier, the drug solution can easily enter the esophagus during medication, greatly reducing the drug's bioavailability. In addition, the irritation of the drug solution to the nasal mucosa cannot be ignored, reducing medication compliance. Although transdermal patches avoid gastrointestinal side effects, the skin stratum corneum barrier hinders the transdermal absorption of the drug, greatly reducing bioavailability and slow onset of action.

[0005] There is also a method to provide a rizatriptan benzoate microneedle, which can penetrate the stratum corneum barrier to deliver drugs, greatly improve bioavailability, and also improve patient compliance, but its mechanical strength and cumulative drug permeability need to be improved. In addition, the rizatriptan benzoate microneedle drug has a long peak time and slow onset, which is not conducive to the relief of acute migraine symptoms. Summary of the invention

[0006] Based on this, the present application provides a rizatriptan microneedle patch with high mechanical strength and cumulative drug permeability, and a preparation method and application thereof.

[0007] In a first aspect of the present application, a rizatriptan microneedle patch is provided, comprising a substrate and a needle body arranged on the surface of the substrate, wherein the needle body is composed of rizatriptan benzoate and a skeleton material; the skeleton material comprises a combination of dextran and trehalose, a combination of copovidone, a combination of polyvinyl alcohol and dextran, a combination of hydroxypropyl methylcellulose and dextran, or a combination of sodium carboxymethyl cellulose and dextran.

[0008] In one embodiment, in the combination of dextran and trehalose, the mass ratio of dextran to trehalose is (55-65):(25-35).

[0009] In one embodiment, in the combination of polyvinyl alcohol and dextran, the mass ratio of polyvinyl alcohol to dextran is (55-65):(15-25).

[0010] In one embodiment, in the combination of hydroxypropyl methylcellulose and dextran, the mass ratio of hydroxypropyl methylcellulose to dextran is (20-30):(30-40).

[0011] In one embodiment, in the combination of sodium carboxymethyl cellulose and dextran, the mass ratio of sodium carboxymethyl cellulose to dextran is (30-40):(25-35).

[0012] In one embodiment, the skeleton material includes a combination of dextran and trehalose or a combination of sodium carboxymethylcellulose and dextran.

[0013] In one embodiment, the backbone material includes a combination of dextran and trehalose.

[0014] In one of the embodiments, the mass percentage of the skeleton material in the composition of the needle body is 60% to 90%.

[0015] In one embodiment, the mass percentage of the rizatriptan benzoate in the needle body is 10% to 40%.

[0016] In one embodiment, the composition of the base includes one or more of polyvinyl pyrrolidone, polyvinyl alcohol, sodium hyaluronate, sodium carboxymethyl cellulose and hydroxypropyl methylcellulose.

[0017] The second aspect of the present application provides a method for preparing the rizatriptan microneedle patch described in the first aspect, comprising the following steps:

[0018] After mixing the skeleton material with water, the rizatriptan benzoate is added to prepare a needle solution;

[0019] Mixing the components of the substrate with a solvent to swell, to prepare a substrate swelling solution;

[0020] The needle body solution is molded and dried in a mold, and then the substrate swelling solution is added to the mold, molded and dried to form the needle body and the substrate, thereby preparing the rizatriptan microneedle patch.

[0021] In one embodiment, the drying conditions include: the temperature is room temperature, and the time is 20 hours to 30 hours.

[0022] The third aspect of the present application provides use of the rizatriptan microneedle patch described in the first aspect in the preparation of a drug for treating migraine.

[0023] The present application provides a microneedle patch for rizatriptan. By selecting a suitable needle tip skeleton material, the mechanical strength of the microneedle patch can be effectively improved, so that it can penetrate the skin stratum corneum barrier and improve the transdermal drug delivery efficiency of rizatriptan benzoate. At the same time, it also has a high cumulative drug permeability and a short onset time, and can effectively relieve acute migraine symptoms.

[0024] In addition, transdermal drug delivery through microneedle patches makes it easier for patients to take medications outside of medical settings, improving medication compliance. Compared with oral preparations, it has higher bioavailability and is not affected by food in the stomach, reducing gastrointestinal side effects. It also reduces irritation and drug loss such as nasal administration, and has obvious clinical application advantages. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 Stress curves of rizatriptan benzoate microneedle patches with different needle tip skeleton materials.

[0026] Figure 2 Cumulative permeability at each time point of rizatriptan benzoate microneedle patches with different needle tip skeleton materials.

[0027] Figure 3 This is the concentration-time curve of rizatriptan benzoate microneedle patch and oral administration. DETAILED DESCRIPTION

[0028] The following is a further detailed description of the Rizatriptan microneedle patch of the present application and its preparation method and application in conjunction with specific examples. The present application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present application more thoroughly understood.

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application.

[0030] As used herein, "one or more" refers to any one, any two, or any two or more of the listed items.

[0031] In this application, "first aspect", "second aspect", "third aspect", etc. are used only for descriptive purposes and cannot be understood as indicating or implying relative importance or quantity, nor can they be understood as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "first", "second", "third", etc. only serve the purpose of non-exhaustive enumeration and description, and it should be understood that they do not constitute a closed limitation on quantity.

[0032] In the present application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0033] In this application, when it comes to numerical ranges, unless otherwise specified, the above numerical ranges are deemed to be continuous and include the minimum and maximum values ​​of the range, as well as each value between such minimum and maximum values. Further, when a range refers to an integer, each integer between the minimum and maximum values ​​of the range is included. In addition, when multiple ranges are provided to describe features or characteristics, the ranges can be merged. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges included therein.

[0034] The percentage contents involved in this application, unless otherwise specified, refer to mass percentage for solid-liquid mixing and solid-solid mixing, and refer to volume percentage for liquid-liquid mixing.

[0035] The percentage concentrations mentioned in this application, unless otherwise specified, refer to the final concentration, which refers to the percentage of the added component in the system after the addition of the component.

[0036] The temperature parameters in this application, unless otherwise specified, allow for both constant temperature treatment and treatment within a certain temperature range. The constant temperature treatment allows the temperature to fluctuate within the accuracy range of instrument control.

[0037] The room temperature in the present application generally refers to 4°C to 30°C, preferably 20±5°C.

[0038] Some examples of the present application provide a rizatriptan microneedle patch, comprising a substrate and a needle body arranged on the surface of the substrate, wherein the needle body is composed of rizatriptan benzoate and a skeleton material; the skeleton material comprises a combination of dextran and trehalose, a combination of copovidone, a combination of polyvinyl alcohol and dextran, a combination of hydroxypropyl methylcellulose and dextran, or a combination of sodium carboxymethyl cellulose and dextran.

[0039] Furthermore, by rationally controlling the mass ratio of the skeleton materials in each combination, the mechanical strength of the needle body and the cumulative drug permeability can be optimized.

[0040] In some examples, in the combination of dextran and trehalose, the mass ratio of dextran to trehalose is (55-65):(25-35). Specifically, the mass ratio of dextran to trehalose includes but is not limited to: 55:25, 55:35, 65:25, 65:35, 58.4:29.1 or a range between any two of the foregoing.

[0041] In some examples, in the combination of polyvinyl alcohol and dextran, the mass ratio of polyvinyl alcohol to dextran is (55-65):(15-25). Specifically, the mass ratio of polyvinyl alcohol to dextran includes but is not limited to: 55:15, 55:25, 65:15, 65:25, 59.2:19.7 or a range between any two of the foregoing.

[0042] In some examples, in the combination of hydroxypropyl methylcellulose and dextran, the mass ratio of hydroxypropyl methylcellulose to dextran is (20-30):(30-40). Specifically, the mass ratio of hydroxypropyl methylcellulose to dextran includes but is not limited to: 20:30, 20:40, 30:30, 30:40, 24.4:36.6 or a range between any two of the foregoing.

[0043] In some examples, in the combination of sodium carboxymethyl cellulose and dextran, the mass ratio of sodium carboxymethyl cellulose to dextran is (30-40):(25-35). Specifically, the mass ratio of sodium carboxymethyl cellulose to dextran includes but is not limited to: 30:25, 30:35, 40:25, 40:35, 34.5:28.7 or a range between any two of the foregoing.

[0044] Furthermore, by using a suitable type of skeleton material, the mechanical strength of the needle body and the cumulative drug permeability can be optimized.

[0045] In some examples, the skeleton material includes a combination of dextran and trehalose or a combination of sodium carboxymethylcellulose and dextran. Further, the skeleton material includes a combination of dextran and trehalose.

[0046] In some examples, the mass percentage of the skeleton material in the composition of the needle body is 60% to 90%. Specifically, the mass percentage of the skeleton material includes but is not limited to: 60%, 61%, 63.2%, 65%, 68%, 71.4%, 73%, 75%, 78.9%, 80%, 83%, 87.5%, 90% or a range between any two of the foregoing.

[0047] In some examples, the mass percentage of the rizatriptan benzoate in the composition of the needle body is 10% to 40%. Specifically, the mass percentage of the rizatriptan benzoate includes but is not limited to: 10%, 12.5%, 15%, 18%, 21.1%, 23%, 25%, 28.6%, 30%, 36.8%, 39%, 40% or a range between any two of the foregoing.

[0048] In some examples, the composition of the substrate includes one or more of polyvinyl pyrrolidone, polyvinyl alcohol, sodium hyaluronate, sodium carboxymethyl cellulose and hydroxypropyl methylcellulose. Without limitation, the polyvinyl pyrrolidone can be one or more of PVPK90, PVPK30 and PVPK60.

[0049] Some other examples of the present application provide a method for preparing the rizatriptan microneedle patch as described above, comprising the following steps:

[0050] After mixing the skeleton material with water, the rizatriptan benzoate is added to prepare a needle solution;

[0051] Mixing the components of the substrate with a solvent to swell, to prepare a substrate swelling solution;

[0052] The needle body solution is molded and dried in a mold, and then the substrate swelling solution is added to the mold, molded and dried to form the needle body and the substrate, thereby preparing the rizatriptan microneedle patch.

[0053] In some of the examples, the drying conditions include: the temperature is room temperature, and the time is 20 hours to 30 hours.

[0054] In some examples, in the preparation of the substrate swelling solution, the solvent includes anhydrous ethanol.

[0055] In some examples, the step of molding the needle solution in a mold includes:

[0056] The needle body solution is added to the microneedle negative mold, and centrifuged at 3500rpm-4500rpm at 0℃-10℃ for 5min-15min. After the centrifugation, the mold is turned 180°, and the centrifugation is continued at 3500rpm-4500rpm at 0℃-10℃ for 5min-15min; the excess needle body solution is removed, and the centrifugation is continued at 3500rpm-4500rpm at 0℃-10℃ for 25min-35min.

[0057] In some examples, the base swelling liquid is added to the mold, and the molding step includes:

[0058] The substrate swelling liquid is added to the microneedle negative mold including the dried needle body, centrifuged at 3500 rpm to 4500 rpm for 1 min to 10 min at 0°C to 10°C, then vacuumed, and then centrifuged at 3500 rpm to 4500 rpm for 1 min to 10 min at 0°C to 10°C.

[0059] It can be understood that after the needle body and the substrate are formed, the rizatriptan microneedle patch can be prepared by demoulding.

[0060] Some other examples of the present application also provide use of the above-mentioned rizatriptan microneedle patch in the preparation of a drug for treating migraine.

[0061] For experimental parameters not specified in the following specific embodiments, reference is made to the instructions given in the present application document, and reference may also be made to experimental manuals in the art or other experimental methods known in the art, or to experimental conditions recommended by manufacturers.

[0062] The raw materials and reagents involved in the following specific examples can be obtained from commercial sources, or can be prepared by those skilled in the art according to known methods.

[0063] The preparation methods of the rizatriptan microneedle patches of the embodiments and comparative examples are as follows:

[0064] (1) Preparation of needle body solution: Weigh the corresponding proportion of framework material, add ultrapure water, and stir to dissolve to obtain an auxiliary material solution. Weigh rizatriptan and add it to the above auxiliary material solution, stir to dissolve to obtain a needle tip solution.

[0065] (2) Preparation of base solution: Weigh 17.5 g of PVP K90 into a centrifuge cup, add 100 mL of anhydrous ethanol, stir thoroughly, and leave overnight to obtain a base solution after sufficient swelling.

[0066] (3) Preparation of needle tip: 200 μL of the needle tip solution was added to the negative microneedle mold, and centrifuged at 4000 rpm for 10 min at 0°C to 10°C. After the centrifugation, the mold was flipped 180° and centrifuged at 4000 rpm for 10 min at 0°C to 10°C. The microneedle mold was then removed and the residual needle tip solution on the upper layer was scraped off. The microneedle mold was then centrifuged at 4000 rpm for 30 min at 0°C to 10°C. The microneedle mold was removed and placed in a moisture-proof cabinet to dry the needle tip.

[0067] (4) Preparation of substrate: Take 300 μL of the above substrate solution and add it to the negative mold after the needle tip is dried. Centrifuge at 4000 rpm for 3 min at 0℃~10℃ to evenly disperse the substrate solution on the mold. Take out the mold and place it in a vacuum drying oven. Evacuate the vacuum to a vacuum degree close to -0.1 MPa, and then immediately open the air valve to restore the vacuum box to normal pressure. Take out the mold and place it in a centrifuge. Centrifuge at 4000 rpm for 5 min at 0℃~10℃ to remove bubbles on the surface of the substrate. Take out the mold and place it in an oven at room temperature to dry for 24 hours.

[0068] (5) Demolding: peeling the microneedles from the mold to obtain the delizatriptan soluble microneedle patch.

[0069] Example 1

[0070] This embodiment is a rizatriptan microneedle patch, which is composed of a substrate and a needle body arranged on the surface of the substrate:

[0071] Substrate material: polyvinyl pyrrolidone (PVPK90);

[0072] The materials of the needle body are shown in Table 1 below:

[0073] Table 1

[0074] Prescription composition Function Quality score Rizatriptan benzoate Active substances 12.5％ Dextran 40 (Dex40) Needle body skeleton material 58.4％ Trehalose Needle body skeleton material 29.1％

[0075] Example 2

[0076] This embodiment is a rizatriptan microneedle patch, which is composed of a substrate and a needle body arranged on the surface of the substrate:

[0077] Substrate material: polyvinyl pyrrolidone (PVPK90);

[0078] The materials of the needle body are shown in Table 2 below:

[0079] Table 2

[0080] Prescription composition Function Quality score Rizatriptan benzoate Active substances 28.6％ Copolyvidone (PVP / VA64) Needle body skeleton material 71.4％

[0081] Example 3

[0082] This embodiment is a rizatriptan microneedle patch, which is composed of a substrate and a needle body arranged on the surface of the substrate:

[0083] Substrate material: polyvinyl pyrrolidone (PVPK90);

[0084] The materials of the needle body are shown in Table 3 below:

[0085] Table 3

[0086] Prescription composition Function Quality score Rizatriptan benzoate Active substances 21.1％ Polyvinyl alcohol (PVA1788) Needle body skeleton material 59.2％ Dextran 40 (Dex40) Needle body skeleton material 19.7％

[0087] Example 4

[0088] This embodiment is a rizatriptan microneedle patch, which is composed of a substrate and a needle body arranged on the surface of the substrate:

[0089] Substrate material: polyvinyl pyrrolidone (PVPK90);

[0090] The materials of the needle body are shown in Table 4 below:

[0091] Table 4

[0092] Prescription composition Function Quality score Rizatriptan benzoate Active substances 39.0％ Hydroxypropyl methylcellulose (HPMCK15M) Needle body skeleton material 24.4％ Dextran 40 (Dex40) Needle body skeleton material 36.6％

[0093] Example 5

[0094] This embodiment is a rizatriptan microneedle patch, which is composed of a substrate and a needle body arranged on the surface of the substrate:

[0095] Substrate material: polyvinyl pyrrolidone (PVPK90);

[0096] The materials of the needle body are shown in Table 5 below:

[0097] Table 5

[0098] Prescription composition Function Quality score Rizatriptan benzoate Active substances 36.8％ Sodium Carboxymethyl Cellulose (CMC-Na) Needle body skeleton material 34.5％ Dextran 40 (Dex40) Needle body skeleton material 28.7％

[0099] Test example:

[0100] (1) Mechanical strength research

[0101] Test method: A texture analyzer was used to analyze the mechanical strength of the microneedle patch. The microneedle patch was placed on the test platform with the needle tip facing upward. The probe was lowered at a speed of 0.1 mm / s to measure the stress on the needle tip during the displacement of the probe. The analyzer recorded the mechanical changes from the time the probe contacted the needle tip until it reached the preset height (microneedle patch height).

[0102] The test results are as follows Figure 1 As shown in Table 6:

[0103] Table 6

[0104]

[0105]

[0106] (2) In vitro transdermal studies

[0107] Test method: Fix the pigskin on the platform directly below the probe of the tensile tester, and fix the microneedle patch on the probe of the tensile tester with the needle tip facing downward. Set the parameters of the tensile tester to maintain the drug administration state for 3 minutes under a force of 100N. After the drug administration, transfer the pigskin to the Franz diffusion cell for drug transdermal study. Samples were taken at 1, 2, 6, 16, and 24 hours to detect the drug content, and the cumulative release amount was calculated. Each time point was tested three times in parallel.

[0108] The test results are shown in Table 7. The cumulative transmittance at each time point is Figure 2 As shown:

[0109] Table 7

[0110] Example Needle tip skeleton material type 24h cumulative drug penetration rate (%) Example 1 Dex40+Trehalose 69.5 Example 2 PVP / VA64 32.9 Example 3 Dex40+PVA1788 42.2 Example 4 Dex40+HPMCK15M 43.5 Example 5 Dex40+CMC-Na 54.5

[0111] (3) In vivo pharmacokinetic experiments

[0112] 1. Test preparation:

[0113] Reagents: Rizatriptan benzoate microneedle patch (Example 1), Rizatriptan benzoate tablets.

[0114] Experimental animals: 6 male SD rats, SPF grade, weighing 180-200 g.

[0115] 2. Test methods:

[0116] The animals were randomly divided into two groups according to their body weight, namely, the rizatriptan benzoate microneedle group and the rizatriptan benzoate oral administration group.

[0117] 3. Experimental plan:

[0118] The test groups are shown in Table 8:

[0119] Table 8

[0120]

[0121]

[0122] Dosage method for the microneedle group: weigh each rat before administration, and anesthetize it with an intraperitoneal injection of 7% chloral hydrate. After anesthesia, mark it. Use a razor to remove the longer hair on the back skin, and then use a depilatory cream to completely cover the back area for 5 minutes, shave off the fluff on the skin surface, clean the remaining depilatory cream, wipe the skin surface for standby use. Fix the microneedle on the dosing backing of the microneedle applicator, use the applicator to administer the drug, and after the microneedle administration is completed, use medical tape to apply the microneedle patch to the rat skin surface, keep it for 30 minutes, and then remove it.

[0123] Dosing method for the oral administration group: hold the gavage syringe in the right hand and grasp the skin of the rat's neck with the left hand to make the rat's head, neck and trunk in a straight line. Insert the gavage needle from the corner of the mouth, press the tongue, press against the upper palate, and gently push inward. Slowly insert the gavage needle into the esophagus along the posterior wall of the pharynx. After withdrawing the syringe without air backflow, inject the drug solution (the gavage volume is 1 mL).

[0124] Sampling method: 0.4 mL of blood was collected from the orbits of rats in the microneedle group at 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, and 6 h after administration, and 0.4 mL of blood was collected from the orbits of rats in the oral administration group at 10 min, 20 min, 30 min, 45 min, 1 h, 2 h, and 3 h after administration. The blood was placed in a centrifuge tube with sodium heparin coated on the inner wall. After blood collection, sterile gauze was used to stop bleeding in the rat's eyes in time. The blood sample was immediately centrifuged at 4 ° C and 4000 rpm for 10 min, and the supernatant was collected and immediately stored in a -80 ° C refrigerator. PK plasma samples were determined by LC / MS. The blood concentration at each time point was used as the ordinate and the time point was used as the abscissa. The "drug-time curve" of the microneedle administration group and the subcutaneous injection group was prepared respectively. The Tmax, Cmax and AUC of the curves of each group were compared to calculate the relative bioavailability (Frel).

[0125] 4. The test results are shown in Table 9 and Figure 3 As shown:

[0126] Table 9

[0127]

[0128] According to Table 9 and Figure 3 It can be seen that the microneedle group of rizatriptan benzoate has a rapid onset of action, reaching Tmax 0.25h after administration, shortening the drug onset time. Compared with the oral administration group, the relative bioavailability reached 233.23%, greatly improving the drug delivery efficiency.

[0129] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0130] The above-described embodiments only express several implementation methods of the present application, which is convenient for understanding the technical solution of the present application in detail, but it cannot be understood as limiting the scope of protection of the patent application. It should be pointed out that for ordinary technicians in this field, without departing from the concept of the present application, several modifications and improvements can be made, which all belong to the scope of protection of the present application. It should be understood that the technical solutions obtained by those skilled in the art through logical analysis, reasoning or limited experiments on the basis of the technical solutions provided in the present application are all within the scope of protection of the claims attached to the present application. Therefore, the scope of protection of the patent of this application shall be based on the content of the attached claims, and the description can be used to interpret the content of the claims.

Claims

1. A rizatriptan microneedle patch, characterized in that: The invention comprises a substrate and a needle body arranged on the surface of the substrate, wherein the needle body comprises rizatriptan benzoate and a skeleton material; the skeleton material comprises a combination of dextran and trehalose, a combination of copovidone, polyvinyl alcohol and dextran, a combination of hydroxypropyl methylcellulose and dextran, or a combination of sodium carboxymethyl cellulose and dextran.

2. The rizatriptan microneedle patch according to claim 1, characterized in that Has one or more of the following characteristics: (1) In the combination of dextran and trehalose, the mass ratio of dextran to trehalose is (55-65):(25-35); (2) In the combination of polyvinyl alcohol and dextran, the mass ratio of polyvinyl alcohol to dextran is (55-65):(15-25); (3) In the combination of hydroxypropyl methylcellulose and dextran, the mass ratio of hydroxypropyl methylcellulose to dextran is (20-30):(30-40); (4) In the combination of sodium carboxymethyl cellulose and dextran, the mass ratio of sodium carboxymethyl cellulose to dextran is (30-40):(25-35).

3. The rizatriptan microneedle patch according to claim 1 or 2, characterized in that: The skeleton material includes a combination of dextran and trehalose or a combination of sodium carboxymethylcellulose and dextran.

4. The rizatriptan microneedle patch according to claim 3, characterized in that: The backbone material includes a combination of dextran and trehalose.

5. The rizatriptan microneedle patch according to claim 1, 2 or 4, characterized in that: In the composition of the needle body, the mass percentage of the skeleton material is 60% to 90%.

6. The rizatriptan microneedle patch according to claim 1, 2 or 4, characterized in that: In the needle body, the mass percentage of rizatriptan benzoate is 10% to 40%.

7. The rizatriptan microneedle patch according to claim 1, 2 or 4, characterized in that: The composition of the base includes one or more of polyvinyl pyrrolidone, polyvinyl alcohol, sodium hyaluronate, sodium carboxymethyl cellulose and hydroxypropyl methylcellulose.

8. The method for preparing the rizatriptan microneedle patch according to any one of claims 1 to 7, characterized in that: The steps include: After mixing the skeleton material with water, the rizatriptan benzoate is added to prepare a needle solution; Mixing the components of the substrate with a solvent to swell, to prepare a substrate swelling solution; The needle body solution is molded and dried in a mold, and then the substrate swelling solution is added to the mold, molded and dried to form the needle body and the substrate, thereby preparing the rizatriptan microneedle patch.

9. The method for preparing the rizatriptan microneedle patch according to claim 8, characterized in that: The drying conditions include: the temperature is room temperature, and the time is 20h to 30h.

10. Use of the rizatriptan microneedle patch according to any one of claims 1 to 7 in the preparation of a medicament for treating migraine.

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