Rizatriptan microneedle patches, methods of making and using the same

Abstract

The application relates to a rizatriptan microneedle patch and a preparation method and application thereof. The rizatriptan microneedle patch comprises a substrate and a needle body arranged on the surface of the substrate, the composition of the needle body comprises rizatriptan benzoate and a skeleton material; the skeleton material comprises a combination of dextran and trehalose, a combination of copolyvidone, polyvinyl alcohol and dextran, a combination of hydroxypropyl methyl cellulose and dextran or a combination of sodium carboxymethyl cellulose and dextran. The rizatriptan microneedle patch has high mechanical strength and drug accumulation permeability.

Description

TECHNICAL FIELD

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

[0002] Migraine is a common disabling headache disorder, characterized by recurrent attacks of unilateral pulsating pain, often accompanied by nausea, visual and olfactory disturbances, and aggravated by exertion, leading to physical and psychosocial morbidity. One in ten people worldwide suffers from migraine, and the World Health Organization (WHO) has listed 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 5-hydroxytryptamine agonists that bind to 5-hydroxytryptamine receptors (5-HT1B) in intracranial blood vessels (dilated during migraine attacks), causing vasoconstriction; bind to neurogenic and central 5-hydroxytryptamine receptors (5-HT1D) to inhibit the release of substance P and CGRP, and block the pain signals sent to the brain by inhibiting nociceptors. In this way, triptans can reverse each step of trigeminal vascular activation in migraine. Compared with non-selective serotonin agonists ergot alkaloids, triptans have lower risk.

[0004] Rizatriptan is a second-generation triptan with the characteristics of rapid relief of headache and fewer side effects compared with other triptans. The FDA has approved rizatriptan benzoate in the form of tablets and orodispersible tablets for marketing in the United States, and tablets, capsules have been marketed in China. Dispersible tablets, granules, chewable tablets, and orodispersible tablets have been reported for clinical trials. In addition, there are methods to provide oral dissolving film, oral spray, nasal spray, and patch. However, oral dosage forms have a first-pass effect in the liver, low drug bioavailability, slow onset, and are easily affected by gastric contents or food intake. In addition, migraine attacks are often accompanied by symptoms of nausea and vomiting, and oral drugs may be vomited out. Oral dissolving film and oral spray can avoid the first-pass effect, but they are easily lost during use, reducing bioavailability. Nasal administration of drugs can quickly cross the nasal-brain barrier and take effect, but the drug solution can easily enter the esophagus during use, greatly reducing the bioavailability of the drug. In addition, the irritation of the drug solution to the nasal mucosa cannot be ignored, reducing drug compliance. Transdermal patches avoid gastrointestinal side effects, but the stratum corneum barrier hinders the transdermal absorption of drugs, greatly reducing bioavailability and slowing the onset.

[0005] There is also a method for providing a rizatriptan benzoate microneedle which, although it can penetrate the stratum corneum barrier to deliver drugs, greatly improves the bioavailability and patient compliance, but its mechanical strength and drug cumulative penetration rate need to be improved. In addition, the peak time of the rizatriptan benzoate microneedle drug is longer, and the effect is slow, which is not conducive to the relief of acute migraine symptoms. SUMMARY

[0006] Based on this, the present application provides a rizatriptan microneedle patch with high mechanical strength and drug cumulative penetration rate, as well as 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, the composition of the needle body comprising rizatriptan benzoate and a matrix material; the matrix material comprises a combination of dextran and trehalose, a combination of copovidone, polyvinyl alcohol and dextran, a combination of hypromellose and dextran, or a combination of sodium carboxymethyl cellulose and dextran.

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

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

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

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

[0012] In one embodiment, the matrix material comprises a combination of dextran and trehalose or a combination of sodium carboxymethyl cellulose and dextran.

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

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

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

[0016] In one embodiment, the base is composed of one or more of polyvinylpyrrolidone, polyvinyl alcohol, sodium hyaluronate, sodium carboxymethyl cellulose, and hypromellose.

[0017] In a second aspect of the present application, a preparation method of the rizatriptan microneedle patch of the first aspect is provided, comprising the following steps:

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

[0019] The composition of the base is mixed with a solvent to swell and prepare a base swelling solution;

[0020] The needle body solution is shaped and dried in a mold, and then the base swelling solution is added to the mold to shape and dry, thereby forming the needle body and the base to prepare the rizatriptan microneedle patch.

[0021] In one embodiment, the drying conditions include a temperature of room temperature and a time of 20-30 hours.

[0022] In a third aspect of the present application, the rizatriptan microneedle patch of the first aspect is provided for use in the preparation of a drug for treating migraine.

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

[0024] In addition, the transdermal administration is achieved by the microneedle patch, which is convenient for patients to take medicine outside medical institutions, improves the medication compliance, has a higher bioavailability compared to oral preparations, is not affected by food in the stomach, reduces the gastrointestinal side effects, and also reduces the irritation and drug loss of nasal administration, etc., and has obvious clinical application advantages. BRIEF DESCRIPTION OF DRAWINGS

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

[0026] Figure 2 Cumulative penetration rates of rizatriptan benzoate microneedle patches with different needle tip skeleton materials at different time points.

[0027] Figure 3 Pharmacokinetic curves of rizatriptan benzoate microneedle patches and oral administration. DETAILED DESCRIPTION

[0028] The rizatriptan microneedle patch, the preparation method and the application thereof of the present application will be further described in detail below in connection with specific embodiments. The present application can be realized 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 thorough and comprehensive.

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in the description of the application herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.

[0030] Herein, "one or more" means any one, any two or any two or more of the listed items.

[0031] In the present application, "first aspect", "second aspect", "third aspect" and the like are only for the purpose of description 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 technical features indicated. Moreover, "first", "second", "third" and the like only serve the purpose of non-exhaustive enumeration and description, and should be understood as not constituting a closed limitation on the quantity.

[0032] In the present application, in the technical features described in an open-ended manner, both the closed technical solution consisting of the listed features and the open technical solution containing the listed features are included.

[0033] In the present application, when referring to a numerical interval, unless otherwise specified, the numerical interval is considered to be continuous and includes the minimum value and the maximum value of the range, as well as every value between the minimum value and the maximum value. Further, when the range refers to integers, every integer between the minimum value and the maximum value of the range is included. In addition, when multiple ranges are provided to describe a feature or a characteristic, the ranges can be combined. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all sub-ranges encompassed therein.

[0034] In the present application, the percentage content, unless otherwise specified, refers to mass percentage for solid-liquid mixing and solid-solid mixing, and refers to volume percentage for liquid-liquid mixing.

[0035] In the present application, the percentage concentration, unless otherwise specified, refers to the final concentration. The final concentration refers to the proportion of the added ingredient in the system after the ingredient is added.

[0036] In the present application, the temperature parameter, unless otherwise specified, allows both constant temperature treatment and treatment within a certain temperature range. The constant temperature treatment allows the temperature to fluctuate within the accuracy range controlled by the instrument.

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

[0038] Some examples of the present application provide a rizatriptan microneedle patch, comprising a substrate and a needle body disposed on the surface of the substrate, the composition of the needle body comprising rizatriptan benzoate and a matrix material; the matrix material comprising a combination of dextran and trehalose, a combination of copovidone, polyvinyl alcohol and dextran, a combination of hypromellose and dextran, or a combination of sodium carboxymethyl cellulose and dextran.

[0039] Further, by reasonably controlling the mass ratio of the matrix material in each combination, the mechanical strength and drug cumulative permeability of the needle body can be optimized.

[0040] In some examples, the mass ratio of dextran and trehalose in the combination of dextran and trehalose is (55-65):(25-35). Specifically, the mass ratio of dextran and 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, the mass ratio of polyvinyl alcohol and dextran in the combination of polyvinyl alcohol and dextran is (55-65):(15-25). Specifically, the mass ratio of polyvinyl alcohol and 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, the mass ratio of hypromellose and dextran in the combination of hypromellose and dextran is (20-30):(30-40). Specifically, the mass ratio of hypromellose and 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, the mass ratio of sodium carboxymethyl cellulose and dextran in the combination of sodium carboxymethyl cellulose and dextran is (30-40):(25-35). Specifically, the mass ratio of sodium carboxymethyl cellulose and 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] Further, by using suitable types of matrix materials, the mechanical strength and drug cumulative permeability of the needle body can be optimized.

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

[0046] In some examples, the needle body comprises the matrix material in a mass percentage of 60% to 90%. Specifically, the mass percentage of the matrix 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 needle body comprises the rizatriptan benzoate in a mass percentage of 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 base comprises one or more of polyvinylpyrrolidone, polyvinyl alcohol, sodium hyaluronate, sodium carboxymethylcellulose, and hydroxypropyl methylcellulose. Without limitation, the polyvinylpyrrolidone can be one or more of PVP K90, PVP K30, and PVP K60.

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

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

[0051] The composition of the base is mixed with a solvent to swell the base to prepare a base swelling solution;

[0052] The needle body solution is shaped in a mold and dried, and then the base swelling solution is added to the mold to shape and dry the needle body and the base to prepare the rizatriptan microneedle patch.

[0053] In some examples, the drying condition comprises a temperature of room temperature and a time of 20 hours to 30 hours.

[0054] In some examples, the solvent used in the preparation of the base swelling solution comprises anhydrous ethanol.

[0055] In some examples, the step of shaping the needle body solution in a mold comprises:

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

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

[0058] The base swelling solution is added to the microneedle negative mold containing the dried needle body, centrifuged at 3500 rpm to 4500 rpm for 1 min to 10 min at 0°C to 10°C, then vacuumized, 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 base are formed, the microneedle patch of the rizatriptan can be prepared by demolding.

[0060] In some examples of the present application, the use of the microneedle patch of the rizatriptan as described above in the preparation of a drug for treating migraine is also provided.

[0061] In the following specific examples, the experimental parameters not written in the examples are preferably referred to the guidance given in the present application, and can also be referred to the experimental manual in the art or other experimental methods known in the art, or to the experimental conditions recommended by the manufacturer.

[0062] In the following specific examples, the raw materials and reagents involved can be obtained by commercial purchase, or can be prepared by known means by those skilled in the art.

[0063] The preparation method of the microneedle patch of rizatriptan in the examples and comparative examples is as follows:

[0064] (1) Preparation of the needle body solution: the corresponding proportion of the skeleton material is weighed, and then added to ultrapure water. After stirring and dissolving, a excipient solution is obtained. The rizatriptan is weighed and added to the excipient solution, and then stirred and dissolved to obtain a needle tip solution.

[0065] (2) Preparation of the base solution: 17.5 g of PVP K90 is weighed into a centrifugal cup, 100 mL of anhydrous ethanol is added, and then stirred thoroughly. After standing overnight, the base solution is obtained after sufficient swelling.

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

[0067] (4) Preparation of the base: 300 μL of the base solution was added to the tip-dried negative mold, and centrifuged at 4000 rpm for 3 min at 0-10°C to evenly distribute the base solution on the mold. The mold was removed and placed in a vacuum drying oven, and vacuumed to a vacuum degree close to -0.1 MPa. The valve was then opened to restore the normal pressure. The mold was removed and centrifuged at 4000 rpm for 5 min at 0-10°C to remove the bubbles on the surface of the base. The mold was removed and placed in a room temperature oven for drying for 24 h.

[0068] (5) Demolding: the microneedle was peeled off from the mold to obtain the rizatriptan soluble microneedle patch.

[0069] Example 1

[0070] The rizatriptan microneedle patch of the present example is composed of a base and a needle body arranged on the surface of the base.

[0071] The material of the base: polyvinylpyrrolidone (PVP K90);

[0072] The material of the needle body is shown in Table 1 below:

[0073] Table 1

[0074] Formulation composition Function Mass fraction Rizatriptan benzoate Active substance 12.5％ Dextran 40 (Dex 40) Needle body skeleton material 58.4％ Trehalose Needle body skeleton material 29.1％

[0075] Example 2

[0076] The rizatriptan microneedle patch of the present example is composed of a base and a needle body arranged on the surface of the base.

[0077] The material of the base: polyvinylpyrrolidone (PVP K90);

[0078] The material of the needle body is shown in Table 2 below:

[0079] Table 2

[0080] Formulation composition Function Mass fraction Rizatriptan benzoate Active substance 28.6％ Copolymer (PVP / VA 64) Needle body skeleton material 71.4％

[0081] Example 3

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

[0083] The material of the substrate: polyvinylpyrrolidone (PVP K90);

[0084] The material of the needle body is shown in Table 3 as follows:

[0085] Table 3

[0086] Formulation composition Function Mass fraction Rizatriptan benzoate Active substance 21.1％ Polyvinyl alcohol (PVA 1788) Needle body skeleton material 59.2％ Dextran 40 (Dex 40) Needle body skeleton material 19.7％

[0087] Example 4

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

[0089] The material of the substrate: polyvinylpyrrolidone (PVP K90);

[0090] The material of the needle body is shown in Table 4 as follows:

[0091] Table 4

[0092] Formulation composition Function Mass fraction Rizatriptan benzoate Active substance 39.0％ Hydroxypropyl methyl cellulose (HPMC K15M) Needle body skeleton material 24.4％ Dextran 40 (Dex 40) Needle body skeleton material 36.6％

[0093] Example 5

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

[0095] The material of the substrate: polyvinylpyrrolidone (PVP K90);

[0096] The material of the needle body is shown in Table 5 as follows:

[0097] Table 5

[0098] Formulation composition Function Mass fraction Rizatriptan benzoate Active substance 36.8％ Sodium carboxymethyl cellulose (CMC-Na) Needle body skeleton material 34.5％ Dextran 40 (Dex 40) Needle body skeleton material 28.7％

[0099] Test Example:

[0100] (1) Mechanical strength study

[0101] Test method: A texture analyzer is used to analyze the mechanical strength of the microneedle patch. The microneedle patch is placed on the test platform with the needle tip facing up. The probe is lowered at a speed of 0.1 mm / s. The stress borne by the needle tip during the displacement of the probe is measured. The analyzer records the mechanical changes during the contact between the probe and the needle tip until the preset height (the height of the microneedle patch) is reached.

[0102] The test results are shown in Figure 1 and Table 6:

[0103] Table 6

[0104]

[0105]

[0106] (2) In vitro transdermal study

[0107] Test method: The pigskin was fixed on the platform under the probe of the tensile tester, and the microneedle patch was fixed on the probe of the tensile tester with the needle tip facing down. The parameters of the tensile tester were set to maintain the drug state for 3 min under the action of 100 N force. After the drug administration was completed, the pigskin was transferred to the Franz diffusion cell for drug transdermal study. The drug content was detected at 1, 2, 6, 16, and 24 h, respectively, and the cumulative release amount was calculated. Each time point was detected in triplicate.

[0108] The test results are shown in Table 7, and the cumulative permeation rate at each time point is shown in Table 8: Figure 2

[0109] Table 7

[0110] Example Needle tip skeleton material type Drug 24h cumulative permeation rate (%) Example 1 Dex 40 + trehalose 69.5 Example 2 PVP / VA 64 32.9 Example 3 Dex 40 + PVA 1788 42.2 Example 4 Dex 40 + HPMC K15M 43.5 Example 5 Dex 40 + CMC-Na 54.5

[0111] (3) In vivo pharmacokinetic experiment

[0112] 1. Test preparation:

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

[0114] Test animals: 6 male SD rats, SPF level, body weight 180-200 g.

[0115] 2. Test method:

[0116] According to the body weight, the animals were randomly divided into 2 groups, namely the rizatriptan benzoate microneedle group and the rizatriptan benzoate oral administration group.

[0117] 3. Test scheme:

[0118] The test grouping is shown in Table 8:

[0119] Table 8

[0120]

[0121]

[0122] ​Micro-needle group administration method: Before administration, the weight of each rat was measured, and 7% chloral hydrate was injected intraperitoneally for anesthesia. After anesthesia, the rats were marked. The long hair on the back skin of the rats was removed with a hair clipper, and the back area was completely covered with depilatory cream for 5 min. Then the fluff on the skin surface was scraped off, and the remaining depilatory cream was washed off. After the skin surface was wiped clean of water, it was ready for use. The micro-needles were fixed on the administration backing of the micro-needle administration device, and the administration device was used for administration. After the micro-needle administration was completed, the micro-needle patch was attached to the skin surface of the rats using medical adhesive tape, and was removed after 30 min.

[0123] Oral administration group administration method: The right hand held a gavage syringe, the left hand held the neck skin of the rat, the head, neck and trunk of the rat were in a straight line, the gavage needle entered from the corner of the mouth, the tongue was pressed, the upper palate was pressed, and the gavage needle was slowly inserted along the posterior pharyngeal wall into the esophagus. After no air backflow was found in the syringe, the drug solution was injected (the gavage volume was 1 mL).

[0124] Sampling method: The rats in the micro-needle group were taken 0.4 mL of blood from the orbit at 5 min, 15 min, 30 min, 1 h, 2 h, 4 h and 6 h after administration. The rats in the oral administration group were taken 0.4 mL of blood from the orbit 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 heparin sodium coated on the inner wall. After the blood was taken, sterile gauze was used to stop the bleeding in time. The blood sample was immediately centrifuged at 4°C and 4000 rpm for 10 min. The supernatant was collected and immediately stored in a-80°C refrigerator. The PK plasma samples were determined by LC / MS method. The blood drug concentration at each time point was taken as the vertical coordinate, and the time point was taken as the horizontal coordinate. The "drug-time curve" of the micro-needle administration group and the subcutaneous injection group was drawn respectively. The Tmax, Cmax and AUC of the curves of each group were compared, and the relative bioavailability (Frel) was calculated.

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

[0126] Table 9

[0127]

[0128] According to Table 9 and Figure 3 , it can be seen that the rizatriptan benzoate micro-needle group has rapid onset, reaches Tmax at 0.25 h after administration, and shortens the drug onset time. Compared with the oral administration group, the relative bioavailability reaches 233.23%, which greatly improves the drug delivery efficiency.

[0129] ​Any combination of the technical features in the above-described embodiments can be made, and for the sake of brevity, not all possible combinations are described, however, it is understood that the scope of the present disclosure encompasses all possible combinations.

[0130] The above-described embodiments only express several implementation manners of the present application, facilitate specific and detailed understanding of the technical solutions of the present application, but should not be understood as a limitation on the patent protection scope of the present application. It should be pointed out that, for ordinary skilled persons in the art, several modifications and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. It should be understood that, on the basis of the technical solutions provided by the present application, the technical solutions obtained by logical analysis, reasoning or limited experiments by those skilled in the art all belong to the protection scope of the appended claims of the present application. Therefore, the protection scope of the patent of the present application should be subject to the content of the appended claims, and the description can be used to explain the content of the claims.

Claims

1. A rizatriptan microneedle patch characterized by, The base and the needle body provided on the surface of the base, the composition of the needle body is rizatriptan benzoate and a skeleton material; the skeleton material is a combination of dextran and trehalose with a mass ratio of (55-65):(25-35); The mass percentage of the skeleton material in the composition of the needle body is 80%-90%.

2. The rizatriptan microneedle patch of claim 1, wherein, The mass ratio of dextran and trehalose in the combination of dextran and trehalose is 58.4:29.

1.

3. The rizatriptan microneedle patch according to claim 1 or 2, characterized by, The mass percentage of rizatriptan benzoate in the composition of the needle body is 10%-15%.

4. The rizatriptan microneedle patch of claim 1 or 2, wherein The composition of the base is selected from one or more of polyvinylpyrrolidone, polyvinyl alcohol, sodium hyaluronate, sodium carboxymethyl cellulose and hydroxypropyl methyl cellulose.

5. The rizatriptan microneedle patch of claim 4, wherein, The composition of the base is polyvinylpyrrolidone.

6. The method of preparing the rizatriptan microneedle patch according to any one of claims 1 to 5, characterized by, The steps include: After mixing the skeleton material with water, the rizatriptan benzoate is added to prepare a needle body solution; The composition of the base is mixed with a solvent to swell the base to prepare a base swelling solution; The needle body solution is formed in a mold, dried, and then the base swelling solution is added to the mold to form and dry to form the needle body and the base, thereby preparing the rizatriptan microneedle patch.

7. The method of claim 6, wherein the rizatriptan microneedle patch is prepared by the steps of: The drying conditions include a temperature of room temperature and a time of 20-30 hours.

8. Use of the rizatriptan microneedle patch of any one of claims 1-5 in the preparation of a drug for treating migraine.

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