Rizatriptan microneedle patch, preparation method therefor, and use thereof

Abstract

A rizatriptan microneedle patch, a preparation method therefor, and use thereof. The rizatriptan microneedle patch comprises a substrate and a needle body arranged on a 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, copovidone, a combination of polyvinyl alcohol and dextran, a combination of hypromellose and dextran, or a combination of sodium carboxymethyl cellulose and dextran. The rizatriptan microneedle patch has high mechanical strength and cumulative drug permeation.

Description

Rizatriptan microneedle patch, its preparation method and application

[0001] Related applications

[0002] This application claims priority to Chinese patent application No. 2024119011656, filed on December 20, 2024, entitled "Rizatriptan Microneedle Patch and Preparation Method and Application Thereof Thereof", the entire contents of which are incorporated herein by reference. Technical Field

[0003] This application relates to the field of pharmaceutical formulation technology, and in particular to a rizatriptan microneedle patch, its preparation method, and its application. Background Technology

[0004] Migraine is a common disabling headache disorder, clinically characterized by recurrent, unilateral throbbing pain, often accompanied by nausea, hearing and olfactory disturbances, which worsen after exertion, leading to physical and psychosocial problems. One in ten people worldwide suffers from migraines. The World Health Organization (WHO) lists migraines as one of the 20 most debilitating diseases. Migraine sufferers have a 3-7 times higher risk of depression, anxiety, and suicide than healthy individuals, and a 1.5-2 times higher risk of cardiovascular disease, heart attack, and stroke.

[0005] Triptans are selective serotonin agonists that bind to serotonin receptors (5-HT1B) in intracranial blood vessels (which dilate during migraine attacks), causing vasoconstriction; they also bind to neurogenic and central serotonin receptors (5-HT1D), inhibiting the release of substance P and CGRP, and blocking pain signals to the brain by inhibiting nociceptors. In this way, triptans have the potential to reverse various steps of trigeminal vascular activation in migraines. Compared to non-selective serotonin agonists like ergot alkaloids, triptans carry a lower risk.

[0006] Rizatriptan is a second-generation triptan drug, characterized by rapid headache relief and fewer side effects compared to other triptans. The US FDA has approved rizatriptan benzoate in tablet and orally disintegrating tablet form. In China, it is available in tablet and capsule forms, with dispersible tablets, granules, chewable tablets, and orally disintegrating tablets undergoing clinical trials. Other formulations include oral films, oral sprays, nasal sprays, and patches. However, oral dosage forms suffer from the first-pass effect in the liver, resulting in low drug bioavailability, slow onset of action, and susceptibility to gastric contents or food intake. Furthermore, migraine attacks are often accompanied by nausea and vomiting, which may cause oral medications to be expelled. While oral instant films and oral sprays avoid the first-pass effect, they are prone to loss during use, reducing bioavailability. Nasal administration, although it can cross the nasobrain barrier and take effect quickly, is prone to accidental ingestion, significantly reducing bioavailability. Moreover, the irritation of the nasal mucosa by the medication is not negligible, reducing medication adherence. Although transdermal patches avoid gastrointestinal side effects, the skin's stratum corneum barrier hinders transdermal absorption, greatly reducing bioavailability and causing a slow onset of action.

[0007] Another method involves a rizatriptan benzoate microneedle, which, while capable of penetrating the stratum corneum barrier to deliver the drug and significantly improving bioavailability and patient compliance, still requires improvement in mechanical strength and cumulative drug penetration. Furthermore, this rizatriptan benzoate microneedle has a relatively long time to peak drug concentration and a slow onset of action, which is not conducive to relieving acute migraine symptoms. Summary of the Invention

[0008] Based on this, this application provides a rizatriptan microneedle patch, its preparation method, and its application.

[0009] A first aspect of this application provides a rizatriptan microneedle patch, comprising a substrate and needles disposed on the surface of the substrate, wherein the needles are composed of rizatriptan benzoate and a matrix material; the matrix material comprises a combination of dextran and trehalose, copovidone, a combination of polyvinyl alcohol and dextran, a combination of hydroxypropyl methylcellulose and dextran, or a combination of sodium carboxymethyl cellulose and dextran.

[0010] In one embodiment, the mass ratio of dextran to trehalose in the combination of dextran and trehalose is (55-65):(25-35).

[0011] In one embodiment, the mass ratio of polyvinyl alcohol to dextran in the combination of polyvinyl alcohol and dextran is (55-65):(15-25).

[0012] In one embodiment, the mass ratio of hydroxypropyl methylcellulose to dextran in the combination of hydroxypropyl methylcellulose and dextran is (20-30):(30-40).

[0013] 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).

[0014] In one embodiment, the skeleton material comprises a combination of dextran and trehalose or a combination of sodium carboxymethyl cellulose and dextran.

[0015] In one embodiment, the skeleton material comprises a combination of dextran and trehalose.

[0016] In one embodiment, the skeleton material comprises 60% to 90% by mass in the composition of the needle body.

[0017] In one embodiment, the mass percentage of rizatriptan benzoate in the needle body is 10% to 40%.

[0018] In one embodiment, the substrate comprises one or more of polyvinylpyrrolidone, polyvinyl alcohol, sodium hyaluronate, sodium carboxymethyl cellulose, and hydroxypropyl methylcellulose.

[0019] A second aspect of this application provides a method for preparing a rizatriptan microneedle patch, comprising the following steps:

[0020] After mixing the matrix material with water, rizatriptan benzoate is added to prepare the injection solution; the matrix material includes a combination of dextran and trehalose, copovidone, a combination of polyvinyl alcohol and dextran, a combination of hydroxypropyl methylcellulose and dextran, or a combination of sodium carboxymethyl cellulose and dextran.

[0021] The substrate composition is mixed with a solvent to swell, thus preparing a substrate swelling solution;

[0022] The needle solution is molded and dried in a mold, and then the base swelling liquid is added to the mold, molded and dried to form a base and needles disposed on the surface of the base, thus preparing a rizatriptan microneedle patch.

[0023] In one embodiment, the mass ratio of dextran to trehalose in the combination of dextran and trehalose is (55-65):(25-35).

[0024] In one embodiment, the mass ratio of polyvinyl alcohol to dextran in the combination of polyvinyl alcohol and dextran is (55-65):(15-25).

[0025] In one embodiment, the mass ratio of hydroxypropyl methylcellulose to dextran in the combination of hydroxypropyl methylcellulose and dextran is (20-30):(30-40).

[0026] 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).

[0027] In one embodiment, the skeleton material comprises a combination of dextran and trehalose or a combination of sodium carboxymethyl cellulose and dextran.

[0028] In one embodiment, the skeleton material comprises a combination of dextran and trehalose.

[0029] In one embodiment, the skeleton material comprises 60% to 90% by mass in the composition of the needle body.

[0030] In one embodiment, the mass percentage of rizatriptan benzoate in the needle body is 10% to 40%.

[0031] In one embodiment, the substrate comprises one or more of polyvinylpyrrolidone, polyvinyl alcohol, sodium hyaluronate, sodium carboxymethyl cellulose, and hydroxypropyl methylcellulose.

[0032] In one embodiment, the drying conditions include: a temperature of room temperature and a time of 20 to 30 hours.

[0033] A third aspect of this application provides the use of the rizatriptan microneedle patch described in the first aspect in the preparation of a medicament for treating migraines. Attached Figure Description

[0034] Figure 1 shows the stress curves of rizatriptan benzoate microneedle patches with different needle tip skeleton materials.

[0035] Figure 2 shows the cumulative permeability of rizatriptan benzoate microneedle patches at different time points using different needle tip skeleton materials.

[0036] Figure 3 shows the pharmacokinetic time curves for rizatriptan benzoate microneedle patch and oral administration. Detailed Implementation

[0037] The following detailed description, in conjunction with specific embodiments, illustrates the rizatriptan microneedle patch, its preparation method, and its application. This application can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a more thorough and complete understanding of the disclosure of this application.

[0038] 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 herein in the specification of this application is for the purpose of describing particular embodiments only and is not intended to be limiting of this application.

[0039] In this article, "one or more" refers to any one, two or more of the listed items.

[0040] In this application, terms such as "first aspect," "second aspect," and "third aspect" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or quantity, nor should they be construed as implicitly indicating the importance or quantity of the indicated technical features. Moreover, terms such as "first," "second," and "third" serve only as a non-exhaustive enumeration and should be understood not to constitute a closed limitation on quantity.

[0041] In this application, the technical features described in an open-ended manner include both closed technical solutions consisting of the listed features and open technical solutions that include the listed features.

[0042] In this application, numerical ranges are referred to as continuous unless otherwise specified, and include the minimum and maximum values ​​of the range, as well as every value between the minimum and maximum values. Furthermore, when the range refers to integers, it includes every integer between the minimum and maximum values ​​of the range. Additionally, when multiple ranges are provided to describe a feature or characteristic, the ranges may be merged. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges to which they are incorporated.

[0043] Unless otherwise specified, the percentage content mentioned in this application refers to mass percentage for solid-liquid mixtures and solid-phase-solid mixtures, and volume percentage for liquid-phase-liquid mixtures.

[0044] Unless otherwise specified, all percentage concentrations mentioned in this application refer to the final concentration. The final concentration refers to the proportion of the added component in the system after the addition of that component.

[0045] Unless otherwise specified, the temperature parameters in this application may be either constant temperature processing or processing within a certain temperature range. The constant temperature processing allows temperature fluctuations within the precision range controlled by the instrument.

[0046] In this application, room temperature generally refers to 4℃~30℃, and preferably 20±5℃.

[0047] Some examples of this application provide a rizatriptan microneedle patch, including a substrate and needles disposed on the surface of the substrate, the needles comprising rizatriptan benzoate and a matrix material; the matrix material comprising a combination of dextran and trehalose, copovidone, a combination of polyvinyl alcohol and dextran, a combination of hydroxypropyl methylcellulose and dextran, or a combination of sodium carboxymethyl cellulose and dextran.

[0048] This 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, enabling it to penetrate the skin's stratum corneum barrier and improve the transdermal drug delivery efficiency of rizatriptan benzoate. It also has a high drug accumulation permeability and a short onset time, which can effectively relieve acute migraine symptoms.

[0049] Furthermore, transdermal drug delivery via microneedle patches allows patients to take medication outside of medical settings, improving medication adherence. Compared to oral formulations, it has higher bioavailability, is not affected by food in the stomach, reduces gastrointestinal side effects, and also reduces irritation and drug loss associated with nasal administration, demonstrating significant clinical advantages.

[0050] Furthermore, by rationally controlling the mass ratio of the skeleton material in each combination, the mechanical strength of the needle and the cumulative drug penetration rate can be optimized.

[0051] In some examples, the mass ratio of dextran to trehalose in the combination of dextran and 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 any range between the two aforementioned.

[0052] In some examples, the mass ratio of polyvinyl alcohol to dextran in the combination of polyvinyl alcohol and 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 any range between the two.

[0053] In some examples, the mass ratio of hydroxypropyl methylcellulose to dextran in the combination of hydroxypropyl methylcellulose and 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 any range between the two aforementioned.

[0054] In some examples, the mass ratio of sodium carboxymethyl cellulose and dextran in the combination 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 any range between the two.

[0055] Furthermore, by using appropriate types of matrix materials, the mechanical strength of the needle and the cumulative drug permeability can be optimized.

[0056] In some examples, the backbone material comprises a combination of dextran and trehalose or a combination of sodium carboxymethyl cellulose and dextran. Further, the backbone material comprises a combination of dextran and trehalose.

[0057] In some examples, the skeleton material comprises 60% to 90% by mass in the needle body. 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 any range between the foregoing.

[0058] In some examples, the mass percentage of rizatriptan benzoate in the composition of the needle body is 10% to 40%. Specifically, the mass percentage of 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 any range between the foregoing.

[0059] In some examples, the substrate comprises one or more of polyvinylpyrrolidone, polyvinyl alcohol, sodium hyaluronate, sodium carboxymethyl cellulose, and hydroxypropyl methylcellulose. Without limitation, the polyvinylpyrrolidone may be, for example, one or more of PVP K90, PVP K30, and PVP K60.

[0060] Other examples of this application provide a method for preparing a rizatriptan microneedle patch, comprising the following steps:

[0061] After mixing the matrix material with water, rizatriptan benzoate is added to prepare the injection solution; the matrix material includes a combination of dextran and trehalose, copovidone, a combination of polyvinyl alcohol and dextran, a combination of hydroxypropyl methylcellulose and dextran, or a combination of sodium carboxymethyl cellulose and dextran.

[0062] The substrate composition is mixed with a solvent to swell, thus preparing a substrate swelling solution;

[0063] The needle solution is molded and dried in a mold, and then the base swelling liquid is added to the mold, molded and dried to form a base and needles disposed on the surface of the base, thus preparing a rizatriptan microneedle patch.

[0064] Understandably, the skeleton material, needle body, substrate, etc. in the above preparation method have similar schemes and effects as the aforementioned rizatriptan microneedle patch, and will not be described in detail here.

[0065] In some of these examples, the drying conditions included a temperature of room temperature and a time of 20 to 30 hours.

[0066] In some of these examples, the solvent used in the preparation of the substrate swelling solution includes anhydrous ethanol.

[0067] In some examples, the step of molding the needle solution in a mold includes:

[0068] Add the needle solution to the microneedle negative mold and centrifuge at 3500 rpm to 4500 rpm at 0℃ to 10℃ for 5 min to 15 min. After centrifugation, rotate the mold 180° and continue centrifuging at 3500 rpm to 4500 rpm at 0℃ to 10℃ for 5 min to 15 min. Remove excess needle solution and continue centrifuging at 3500 rpm to 4500 rpm at 0℃ to 10℃ for 25 min to 35 min.

[0069] In some examples, the base swelling liquid is added to the mold, and the molding step includes:

[0070] The base swelling solution is added to a microneedle mold including the aforementioned dried needle body, and centrifuged at 3500 rpm to 4500 rpm at 0℃ to 10℃ for 1 min to 10 min. Then, vacuum treatment is performed, and centrifuged again at 3500 rpm to 4500 rpm at 0℃ to 10℃ for 1 min to 10 min.

[0071] Understandably, after the needle body and the substrate are formed, the rizatriptan microneedle patch can be prepared by demolding.

[0072] Other examples of this application also provide the use of the rizatriptan microneedle patch, as described above, in the preparation of a medicament for treating migraines.

[0073] Other examples of this application provide the use of the rizatriptan microneedle patch as described above in the treatment of migraines.

[0074] Other examples of this application provide a method for treating migraines, including the step of applying a rizatriptan microneedle patch as described above.

[0075] For experimental parameters not specified in the following specific embodiments, please refer to the guidelines given in this application document first, or refer to experimental manuals or other experimental methods known in the art, or refer to the experimental conditions recommended by the manufacturer.

[0076] The raw materials and reagents involved in the following specific embodiments can be obtained commercially or prepared by those skilled in the art using known methods.

[0077] The preparation methods of the rizatriptan microneedle patches in the examples and comparative examples are as follows:

[0078] (1) Preparation of needle solution: Weigh the appropriate proportion of the skeleton material, add ultrapure water, stir and dissolve to obtain the excipient solution. Weigh rizatriptan and add it to the above excipient solution, stir and dissolve to obtain the needle tip solution.

[0079] (2) Preparation of base solution: Weigh 17.5g of PVP K90 into a centrifuge cup, add 100mL of anhydrous ethanol, stir thoroughly, let stand overnight, and obtain the base solution after full swelling.

[0080] (3) Preparation of needle tips: Add 200 μL of the above needle tip solution to the microneedle negative mold, and centrifuge at 4000 rpm for 10 min at 0℃~10℃. After centrifugation, rotate the mold 180° and continue to centrifuge at 4000 rpm for 10 min at 0℃~10℃. Then remove the microneedle mold and scrape off the residual needle tip solution on the upper layer. Then continue to centrifuge at 4000 rpm for 30 min at 0℃~10℃. Remove the microneedle mold and place it in a dehumidifying cabinet to dry the needle tips.

[0081] (4) Substrate preparation: Add 300 μL of the above substrate solution to the negative mold after needle tip drying, and centrifuge at 4000 rpm for 3 min at 0℃~10℃ to ensure uniform dispersion of the substrate solution on the mold. Remove the mold and place it in a vacuum drying oven, evacuate to a vacuum level close to -0.1 MPa, and then immediately open the gas valve to restore the vacuum chamber to normal pressure. Remove the mold and place it in a centrifuge, centrifuge at 4000 rpm for 5 min at 0℃~10℃ to remove air bubbles from the substrate surface. Remove the mold and place it in a room temperature oven to dry for 24 h.

[0082] (5) Demolding: Peel the microneedles from the mold to obtain the soluble microneedle patch of zatriptane.

[0083] Example 1

[0084] This embodiment is a rizatriptan microneedle patch, which consists of a base and needles disposed on the surface of the base:

[0085] Substrate material: Polyvinylpyrrolidone (PVPK90);

[0086] The materials of the needle body are shown in Table 1 below:

[0087] Table 1

[0088] Example 2

[0089] This embodiment is a rizatriptan microneedle patch, which consists of a base and needles disposed on the surface of the base:

[0090] Substrate material: Polyvinylpyrrolidone (PVPK90);

[0091] The materials of the needle body are shown in Table 2 below:

[0092] Table 2

[0093] Example 3

[0094] This embodiment is a rizatriptan microneedle patch, which consists of a base and needles disposed on the surface of the base:

[0095] Substrate material: Polyvinylpyrrolidone (PVPK90);

[0096] The materials of the needle body are shown in Table 3 below:

[0097] Table 3

[0098] Example 4

[0099] This embodiment is a rizatriptan microneedle patch, which consists of a base and needles disposed on the surface of the base:

[0100] Substrate material: Polyvinylpyrrolidone (PVPK90);

[0101] The materials of the needle body are shown in Table 4 below:

[0102] Table 4

[0103] Example 5

[0104] This embodiment is a rizatriptan microneedle patch, which consists of a base and needles disposed on the surface of the base:

[0105] Substrate material: Polyvinylpyrrolidone (PVPK90);

[0106] The materials of the needle body are shown in Table 5 below:

[0107] Table 5

[0108] Test example:

[0109] (1) Mechanical strength study

[0110] Experimental method: The mechanical strength of the microneedle patch was analyzed using a texture analyzer. The microneedle patch was placed on the test platform with the needle tip facing upwards. The probe was lowered at a speed of 0.1 mm / s. The stress on the needle tip during the probe displacement was measured. The analyzer recorded the mechanical changes during the period from when the probe contacted the needle tip until it reached the preset height (microneedle patch height).

[0111] The test results are shown in Figure 1 and Table 6:

[0112] Table 6

[0113] (2) In vitro transdermal studies

[0114] Experimental Method: Pigskin was fixed on a platform directly below the probe of a tensile testing machine. A microneedle patch was fixed to the probe with the needle tip facing downwards. The tensile testing machine was set to maintain a drug delivery state under a force of 100 N for 3 minutes. After drug delivery, the pigskin was transferred to a Franz diffusion cell for transdermal drug delivery studies. Drug content was measured at 1, 2, 6, 16, and 24 hours to calculate the cumulative release. Each time point was measured in triplicate.

[0115] The test results are shown in Table 7, and the cumulative transmittance at each time point is shown in Figure 2.

[0116] Table 7

[0117] (3) In vivo pharmacokinetic experiments

[0118] 1. Experimental preparation:

[0119] Reagents: Rizatriptan benzoate microneedle patch (Example 1), rizatriptan benzoate tablets.

[0120] Experimental animals: 6 male SD rats, SPF grade, weighing 180-200g.

[0121] 2. Test methods:

[0122] Animals were randomly divided into two groups based on their body weight: a rizatriptan benzoate microneedle group and a rizatriptan benzoate oral administration group.

[0123] 3. Test Procedure:

[0124] The experimental groups are shown in Table 8:

[0125] Table 8

[0126] Microneedle administration method: Before administration, weigh each rat and anesthetize it by intraperitoneal injection of 7% chloral hydrate. After anesthesia, mark the rat. Use a razor to remove long hairs from the back of the rat, then apply depilatory cream to the entire back area for 5 minutes. Shave off the fine hairs on the skin surface, wash off any remaining depilatory cream, and wipe the skin dry. Fix the microneedles to the drug delivery backing of the microneedle applicator and administer the drug using the applicator. After microneedle administration, apply the microneedle patch to the rat's skin surface using medical tape and remove it after 30 minutes.

[0127] Administration method for oral administration group: Hold the gavage syringe in the right hand and grasp the skin of the rat's neck with the left hand, so that the rat's head, neck and trunk are in a straight line. Insert the gavage syringe into the corner of the mouth, press down on the tongue and the palate, and gently push it inward. Slowly insert the gavage syringe along the posterior pharyngeal wall into the esophagus. After aspirating the syringe and finding no air backflow, inject the drug solution (gavage volume is 1 mL).

[0128] Sampling method: For the microneedling group, 0.4 mL of blood was collected from the orbital cavity of rats at 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, and 6 h after drug administration. For the oral administration group, 0.4 mL of blood was collected from the orbital cavity of rats at 10 min, 20 min, 30 min, 45 min, 1 h, 2 h, and 3 h after drug administration. The blood samples were placed in centrifuge tubes coated with sodium heparin. Hemostasis was achieved immediately after blood collection using sterile gauze. The blood samples were immediately centrifuged at 4℃ and 4000 rpm for 10 min, and the supernatant was collected and stored immediately at -80℃. PK plasma samples were analyzed using LC / MS. Drug-time curves were constructed for the microneedling and subcutaneous injection groups, with the drug concentration at each time point as the ordinate and the time point as the abscissa. The Tmax, Cmax, and AUC of each group were compared to calculate the relative bioavailability (Frel).

[0129] 4. The experimental results are shown in Table 9 and Figure 3:

[0130] Table 9

[0131] As shown in Table 9 and Figure 3, the rizatriptan benzoate microneedle group exhibits rapid onset of action, reaching Tmax within 0.25 hours after administration, thus shortening the drug's onset time. Compared to the oral administration group, the relative bioavailability reaches 233.23%, significantly improving drug delivery efficiency.

[0132] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above 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.

[0133] The embodiments described above are merely illustrative of several implementation methods of this application, intended to facilitate a detailed understanding of the technical solutions of this application, but should not be construed as limiting the scope of protection of the patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the scope of protection of this application. It should be understood that technical solutions obtained by those skilled in the art based on the technical solutions provided in this application through logical analysis, reasoning, or limited experimentation are all within the scope of protection of the appended claims. Therefore, the scope of protection of this patent application should be determined by the content of the appended claims, and the specification can be used to interpret the content of the claims.

Claims

1. A rizatriptan microneedle patch, comprising a substrate and needles disposed on the surface of the substrate, wherein the needles are composed of rizatriptan benzoate and a matrix material; the matrix material comprises a combination of dextran and trehalose, copovidone, a combination of 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, wherein, In the combination of dextran and trehalose, the mass ratio of dextran to trehalose is (55-65):(25-35).

3. The rizatriptan microneedle patch according to claim 1, wherein, In the combination of polyvinyl alcohol and dextran, the mass ratio of polyvinyl alcohol to dextran is (55-65):(15-25).

4. The rizatriptan microneedle patch according to claim 1, wherein, In the combination of hydroxypropyl methylcellulose and dextran, the mass ratio of hydroxypropyl methylcellulose to dextran is (20-30):(30-40).

5. The rizatriptan microneedle patch according to claim 1, wherein, In the combination of sodium carboxymethyl cellulose and dextran, the mass ratio of sodium carboxymethyl cellulose to dextran is (30-40):(25-35).

6. The rizatriptan microneedle patch according to any one of claims 1 to 5, wherein, The scaffold material includes a combination of dextran and trehalose or a combination of sodium carboxymethyl cellulose and dextran.

7. The rizatriptan microneedle patch according to claim 6, wherein, The scaffold material comprises a combination of dextran and trehalose.

8. The rizatriptan microneedle patch according to any one of claims 1 to 7, wherein, In the composition of the needle body, the mass percentage of the skeleton material is 60% to 90%.

9. The rizatriptan microneedle patch according to any one of claims 1 to 8, wherein, In the composition of the needle body, the mass percentage of rizatriptan benzoate is 10% to 40%.

10. The rizatriptan microneedle patch according to any one of claims 1 to 9, wherein, The substrate comprises one or more of polyvinylpyrrolidone, polyvinyl alcohol, sodium hyaluronate, sodium carboxymethyl cellulose, and hydroxypropyl methylcellulose.

11. A method for preparing a rizatriptan microneedle patch, comprising the following steps: After mixing the matrix material with water, rizatriptan benzoate is added to prepare the injection solution; the matrix material includes a combination of dextran and trehalose, copovidone, a combination of polyvinyl alcohol and dextran, a combination of hydroxypropyl methylcellulose and dextran, or a combination of sodium carboxymethyl cellulose and dextran. The substrate composition is mixed with a solvent to swell, thus preparing a substrate swelling solution; The needle solution is molded and dried in a mold, and then the base swelling liquid is added to the mold, molded and dried to form a base and needles disposed on the surface of the base, thus preparing a rizatriptan microneedle patch.

12. The method for preparing the rizatriptan microneedle patch according to claim 11, wherein, It 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).

13. The method for preparing the rizatriptan microneedle patch according to claim 11, wherein, The scaffold material includes a combination of dextran and trehalose or a combination of sodium carboxymethyl cellulose and dextran.

14. The method for preparing the rizatriptan microneedle patch according to any one of claims 11 to 13, characterized in that, The drying conditions include: room temperature and time of 20 to 30 hours.

15. The use of the rizatriptan microneedle patch according to any one of claims 1 to 10 or the rizatriptan microneedle patch prepared by the preparation method according to any one of claims 11 to 14 in the preparation of a medicament for treating migraine.

Images