Salmeterol patch and preparation method thereof

Abstract

The invention discloses a salmeterol patch and a preparation method thereof. The preparation method comprises the following steps: firstly, pre-dispersing salmeterol in an emulsion, coating salmeterol in a polymer while polymerizing a monomer vinyl acetate and polyvinyl alcohol to form degradable oleophylic and hydrophilic polymer nanoparticles, and then adding a penetrant, a pressure-sensitive adhesive and the like to prepare the patch. According to the invention, firstly, salmeterol is encapsulated by adopting a hydrophilic and oleophylic polymer, the amphiphilic polymer has better compatibility with auxiliary materials in the patch, the medicine can be more uniformly distributed in the patch after the medicine is encapsulated, meanwhile, salmeterol has better lipophilicity, and in combination with better lipophilicity and hydrophilicity of the polymer, the medicine can be more uniformly distributed in the patch; therefore, the prepared patch has better permeability to the skin, meanwhile, the problem that the medicine is re-crystallized from a supersaturated state is avoided, and the acting effect of the patch is better.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical preparations and relates to a salmeterol patch and a preparation method thereof. Background Art

[0002] Asthma is a chronic inflammatory disease of the airway characterized by reversible airflow limitation and is recognized as one of the four major intractable diseases by the world medical community. Asthma seriously endangers people's physical and mental health, weakens labor ability, reduces the quality of life, and is prone to repeated attacks. It can cause minor injuries to the body and even death in severe cases. Therefore, the prevention and treatment of asthma is extremely urgent. Unfortunately, non-compliance with asthma treatment remains a problem at present. Some reports show that the compliance rate is as low as 50%. Therefore, it is necessary to develop new drug dosage forms to increase population compliance.

[0003] Salmeterol is a new type of selective long-acting β2-receptor agonist anti-asthmatic drug, derived from salbutamol, which can bind more tightly to the β2-receptor and produce a more lasting agonist effect. Salmeterol was first successfully developed by GlaxoSmithKline in the UK and was first launched in the UK in 1990 under the trade names Serevent, Striverdi, Seretide, and Salmeterol. It has a powerful effect of inhibiting the release of allergic reaction mediators by mast cells in the lungs, can inhibit the early and late-phase reactions induced by inhaled antigens, and reduce airway hyperresponsiveness. Clinical trials have shown that salmeterol is more potent than salbutamol, provides longer protection against histamine-induced bronchoconstriction and exercise-induced asthma, and has the characteristics of a long duration of action, little extrapulmonary effect, and good tolerance. It is an ideal drug for the treatment of nocturnal asthma attacks and asthma maintenance treatment.

[0004] The currently marketed products of salmeterol are mainly powder inhalers. After inhalation, the drug is distributed throughout the body. With the gradual use and research in clinical practice, it has been found that salmeterol should not be used frequently or in large doses, as there is a risk of inducing arrhythmia and death when exceeding the recommended inhalation dose. At the same time, inhalation administration has a rapid onset, frequent dosing, obvious blood drug peak and trough phenomena, and a short duration of action, which is inconvenient for patients to use. Based on the above disadvantages of inhalation administration, transdermal administration can release an effective dose of the drug through the natural barrier of the skin, enabling sustained and controlled release of the drug, reducing the dosing frequency, minimizing the drug peak and trough phenomena and side effects, and is more advantageous. Transdermal administration is particularly suitable for patients who cannot take medicine independently, such as the elderly and children, and patients with difficulty swallowing, thereby improving patient acceptance and compliance. Transdermal administration has the advantages of prolonging the dosing time, reducing the loss of the drug before entering the systemic circulation, thereby enhancing the dose and efficacy, and at the same time reducing systemic side effects.

[0005] The design concept of transdermal drug delivery system products is to maximize the flux of drugs through the skin into the systemic circulation while minimizing the retention and metabolism of drugs in the skin, which is usually achieved by passive diffusion. Passive diffusion is the driving force for promoting the differentiation of drugs from transdermal patches into the skin. Therefore, successful drug delivery through the skin requires the drugs in the transdermal patch to reach a saturated to supersaturated state. However, this system is thermodynamically unstable and has a high risk of drug recrystallization, especially during storage. When the solubility of the drug in the matrix of the carrier system is limited, drug crystallization in transdermal patches is often encountered. Crystallization inhibitors are often added during the patch preparation process to prevent drug precipitation in the patches. However, the addition of crystallization inhibitors may cause the drug to transform into another crystal form during storage, affecting the properties of the patch itself. Salmeterol has poor solubility. During the preparation of the patch, it is not only prone to crystallization but also has poor compatibility with excipients and is difficult to be evenly distributed in the patch. Summary of the Invention

[0006] In view of the above problems, the present invention provides a salmeterol patch and a preparation method thereof. In the present invention, salmeterol is encapsulated in biodegradable polymer nanoparticles, and then a penetrant, a pressure-sensitive adhesive, etc. are added to prepare it into a patch. The present invention first encapsulates salmeterol with a hydrophilic-lipophilic polymer. The amphiphilic polymer has better compatibility with the excipients in the patch. After encapsulating the drug, it can make the drug more evenly distributed in the patch. At the same time, salmeterol has good lipophilicity, combined with the good hydrophilic-lipophilicity of the polymer, so that the prepared patch has better permeability to the skin, and at the same time avoids the problem of drug recrystallization from the supersaturated state, making the effect of the patch better. The polymer used for preparing the polymer nanoparticles of this patch is a biodegradable polymer. After loading the nanoparticles, it can successfully deliver drugs through the skin without producing toxicity and has higher safety.

[0007] The technical solution of the present invention is: a salmeterol patch, characterized in that it is prepared from the following raw materials in parts by weight: 5-10 parts of polymer nanoparticles loaded with salmeterol (drug loading 20-30%), 30-60 parts of penetrant, 40-70 parts of pressure-sensitive adhesive, and 50-80 parts of solvent.

[0008] Among them, the preparation method of the salmeterol-loaded polymer nanoparticles is as follows: salmeterol is pre-dispersed in an emulsion, and while vinyl acetate monomer and polyvinyl alcohol are polymerized, salmeterol is encapsulated in the polymer to form biodegradable amphiphilic polymer nanoparticles; more preferably, it is prepared by the following method: 1) Salmeterol treatment: First, it is prepared into nanoparticles by a vibrating ball mill; 2) Aqueous phase preparation: Under stirring, 0.5 - 2.0 parts of sodium lauryl polyoxyethylene ether sulfate and 10 - 30 parts of polyvinyl alcohol are added to purified water, and 15 parts of salmeterol (after vibrating ball milling) are stirred and mixed as the aqueous phase; 3) Oil phase preparation: 25 - 35 parts of vinyl acetate monomer, 0.5 - 2.0 parts of cetane, and 0.2 - 1.0 parts of 2,2'-azobis(2,4-dimethylvaleronitrile) are stirred and mixed evenly as the oil phase; 4) Preparation of polymer nanoparticle emulsion: The aqueous phase is slowly added to the oil phase under stirring to prepare a pre-emulsion; then it is emulsified at high speed, and the obtained emulsion is reacted at 20 - 30 °C for 10 - 15 h to obtain a polymer nanoparticle emulsion. Finally, after filtration, the filtrate is concentrated under reduced pressure and naturally dried to obtain salmeterol-loaded polymer nanoparticles. The above parts are all parts by weight.

[0009] Furthermore, a dispersing emulsifier, polyglycerol lauryl ether, is added during the high-speed emulsification in step 4).

[0010] Among them, the penetrant is a compound of monoglyceride laurate and another penetrant (isopropyl myristate, ethyl oleate, or 1,2-propanediol).

[0011] Among them, the pressure-sensitive adhesive is a polyacrylate pressure-sensitive adhesive containing a hydroxyl functional group or a carboxyl functional group.

[0012] Preferably, the solvent is ethyl acetate / methanol with a volume ratio of 1:4 - 6.

[0013] The preparation method of the above salmeterol patch is characterized in that

[0014] S1: Dissolve the salmeterol-loaded polymer nanoparticles in a solvent and stir until completely dissolved;

[0015] S2: Add the pressure-sensitive adhesive to the solvent and stir until completely dissolved, then add the penetrant and stir until completely dissolved;

[0016] S3: Add the main drug solution in step S1 to the solution in step S2 under stirring and stir until completely dissolved, then stir at high speed again to ensure thorough mixing;

[0017] S4: Let it stand for degassing, and evenly coat the solution in step S3 on the anti-adhesive layer with a coater to obtain an adhesive layer; after the obtained adhesive layer is dried at room temperature, it is placed in a vacuum drying oven to dry and volatilize the solvent;

[0018] S5: Cover the backing layer and cut it to obtain the salmeterol patch. The thickness of the adhesive layer of the final patch is controlled at (50±5) μm.

[0019] The innovation of the process of the present invention lies in:

[0020] 1. The preparation of the polymer nanoparticles reported in the literature (V Vijayan, KR Reddy, S Sakthivel, C Swetha. Optimization and characterization of repaglinide biodegradable polymeric nanoparticle loaded transdermal patchs: In vitro and in vivo studies [J]. Colloids & Surfaces B Biointerfaces, 2013) directly uses polylactic acid, polycaprolactone or chitosan dispersed in a solvent, and is uniformly mixed with repaglinide under the action of an emulsifier to form a homogeneous phase. Through homogenization, polymer-coated nanoparticles are formed. Its process prepares polymer-coated nanoparticles by solvent evaporation. In this method, the rate of solvent volatilization is difficult to control, and the drug loading of the obtained product is relatively low.

[0021] The preparation method of the polymer nanoparticles adopted in the present invention uses emulsion polymerization to prepare polymer nanoparticles by the "one-pot method". The specific method is as follows: Salmeterol is pre-dispersed in an emulsion, and vinyl acetate monomer and polyvinyl alcohol wrap salmeterol in the polymer during polymerization to form biodegradable amphiphilic polymer nanoparticles. This method prepares polymer nanoparticles with a high solid content without solvent volatilization, and the obtained product has a high drug loading.

[0022] 2. Polyacrylate is a commonly used adhesive for patches. However, this type of adhesive has different functional groups, and the functional groups have a great influence on the raw materials and excipients used. The adhesives with carboxyl functional groups or hydroxyl functional groups have good compatibility with the hydrophilic part of the prepared polymer nanoparticles, increasing the solubility of the polymer nanoparticles in the adhesive and avoiding the crystallization phenomenon of the drug.

[0023] 3. The present invention also examines the influence of different penetration enhancers on the patch. Through the screening of penetration enhancers, especially when monolaurin is used in combination with other penetration enhancers as a penetration enhancer, the penetration effect is better, and the obtained patch has better stability.

[0024] 4. The polymer in the polymer nanoparticles used in the present invention is a biodegradable polymer, which will not produce toxicity in vivo and has better safety. Description of the Drawings

[0025] Figure 1 It is a picture of the polymer nanoparticle emulsion diluted and dispersed with purified water and observed under a microscope;

[0026] Figure 2 It is the in vitro release curve of polymer nanoparticles in PBS buffer at pH 7.4 investigated by the dialysis bag method;

[0027] Figure 3 It is the in vitro permeation curve of different permeants in Example 3;

[0028] Figure 4 It is the in vitro permeation curve of different permeants in Example 4. Detailed implementation manners

[0029] The following is to illustrate its effects in combination with examples and drawings.

[0030] Example 1: Preparation of salmeterol patch

[0031] 1. Preparation of biodegradable lipophilic and hydrophilic polymer nanoparticles

[0032] 1) Treatment of salmeterol: First, it is prepared into nanoscale particles by a vibrating ball mill;

[0033] 2) Preparation of the aqueous phase: Under stirring, 1.0 g of sodium lauryl polyoxyethylene ether sulfate and 20 g of polyvinyl alcohol are added to 120 g of purified water, and 15 g of salmeterol (after vibrating ball milling) is stirred and mixed as the aqueous phase;

[0034] 3) Preparation of the oil phase: 30 g of monomer vinyl acetate, 1 g of cetane and 0.5 g of azobisisoheptonitrile are stirred and mixed evenly as the oil phase;

[0035] 4) Preparation of the polymer nanoparticle emulsion: The aqueous phase is slowly added to the oil phase under stirring and stirred for 30 min to prepare a milky pre-emulsion; then 2.0 g of the dispersing emulsifier polyglycerol lauryl ether is used for high-speed emulsification at a speed of more than 15000 rmp for 10 min, and then the obtained emulsion is reacted at 20 - 30 °C for 12 h to obtain a milky solution, which is the polymer nanoparticle emulsion.

[0036] After the obtained polymer nanoparticle emulsion is diluted and dispersed with purified water and observed under a microscope, the result is as Figure 1 shown, and it can be seen from Figure 1 that the polymer nanoparticles have good dispersibility.

[0037] The in vitro release behavior of polymer nanoparticles in PBS buffer at pH 7.4 is investigated by the dialysis bag method, and the result is as Figure 2 shown, and it can be seen from Figure 2It can be seen that the release rate of the polymer nanoparticles can reach over 80%.

[0038] 2. Determination of encapsulation efficiency and drug loading

[0039] The polymer nanoparticle emulsion was filtered and washed with purified water. The filter cake was salmeterol that was not encapsulated in the polymer. It was dried and the weight was recorded. The milky filtrate was collected, concentrated under reduced pressure. After concentration, a white solid was obtained, and the material was air-dried naturally to obtain free-flowing polymer-loaded nanoparticles.

[0040] The calculation formulas for the encapsulation efficiency and drug loading of the drug in the microspheres are as follows:

[0041] Encapsulation efficiency = ((mass of the drug put in - mass of the drug in the filter cake) / mass of the drug put in) × 100%

[0042] Drug loading = ((mass of the drug put in - mass of the drug in the filter cake) / total mass of the drug-loaded microspheres) × 100%

[0043] After calculation, for the polymer-loaded nanoparticles obtained in this example, the drug encapsulation efficiency was 86.7% and the drug loading was 24.8%.

[0044] 3. Preparation of salmeterol patch

[0045] In Example 1, different types of pressure-sensitive adhesives were screened to prepare salmeterol patches, and the specific prescriptions are shown in Table 1.

[0046] Table 1: Screening prescriptions of different types of pressure-sensitive adhesives

[0047]

[0048]

[0049] Note: 1. 8.4 parts of polymer-loaded nanoparticles are equivalent to 2.0 parts of salmeterol; 2. The silicone pressure-sensitive adhesive is amine-compatible; the polyisobutylene pressure-sensitive adhesive model is Oppanol B 11SFN, and the polyacrylate pressure-sensitive adhesive model (without functional groups) is DURO-TAK87-4098.

[0050] The specific operation process is as follows:

[0051] 1) Dissolve the main drug polymer-loaded nanoparticles in 30 parts of ethyl acetate / methanol (volume ratio 1:5), and stir until completely dissolved;

[0052] 2) Add the pressure-sensitive adhesive to 30 parts of ethyl acetate / methanol (volume ratio 1:5), stir until completely dissolved, and then add the penetrants (isopropyl myristate and 1,2-propanediol), and stir until completely dissolved;

[0053] 3) Add the main drug solution prepared in step 1) to the solution in step 2) under stirring, stir until completely dissolved, and then stir at high speed for another 2 h to ensure thorough mixing and uniformity;

[0054] 4) Let it stand for degassing, and evenly coat the solution in step 3) on the anti-sticking layer (coated with dimethyl silicone oil polyester film, manufacturer: Chuangyue New Materials (Taizhou) Co., Ltd.) using a 0.6 mm coater to obtain an adhesive layer; after the obtained adhesive layer is dried at room temperature for 10 min, place it in a vacuum drying oven and dry it at 40 °C for 5 h to volatilize the solvent;

[0055] 5) Cover the backing layer (aluminum / polyethylene composite film, manufacturer: Guangzhou Guanyu Aluminum Foil Packaging Materials Co., Ltd.), and cut it into 5 cm × 5 cm squares with a mold to obtain the salmeterol patch. The thickness of the adhesive layer of the final patch is controlled at (50 ± 5) μm.

[0056] The appearance, initial adhesiveness, and holding adhesiveness of the salmeterol patches prepared with different types of pressure-sensitive adhesives were investigated. The initial adhesiveness was determined according to GB / T 4852-2022, Test Method for Initial Adhesion of Pressure-Sensitive Adhesive Tapes (Rolling Ball Method); the holding adhesiveness was determined according to GB / T 4851-2014 Test Method for Holding Adhesiveness of Adhesive Tapes. The investigation results are shown in Table 2.

[0057] Table 2: Appearance, initial adhesiveness, and holding adhesiveness of salmeterol patches prepared with different types of pressure-sensitive adhesives

[0058]

[0059] The results are shown in Table 2: The salmeterol patches prepared with different types of pressure-sensitive adhesives did not overflow glue. The initial adhesiveness and holding adhesiveness of the patches were respectively detected. The results showed that the salmeterol patches prepared with polyacrylate pressure-sensitive adhesive had better holding adhesiveness and initial adhesiveness. Therefore, polyacrylate pressure-sensitive adhesive was selected for subsequent use.

[0060] Example 2: Screening of different models of pressure-sensitive adhesives

[0061] In Example 2, different models of pressure-sensitive adhesives were screened to prepare salmeterol patches, and the specific prescriptions are shown in Table 3.

[0062] Table 3: Screening prescriptions of different models of polyacrylate pressure-sensitive adhesives

[0063]

[0064] Note: All models of polyacrylate pressure-sensitive adhesives were purchased from Henkel. Among them, the acrylic pressure-sensitive adhesive containing hydroxyl groups has the model DURO-TAK 387-2510; the acrylic pressure-sensitive adhesive containing carboxyl groups has the model DURO-TAK 387-2054; the acrylic pressure-sensitive adhesive without functional groups has the model DURO-TAK 87-4098.

[0065] The specific preparation method of salmeterol patch is the same as that of Example 1.

[0066] The appearance, tack and holding power of salmeterol patches prepared with different types of pressure-sensitive adhesives were investigated. The detection method was the same as that of Example 1, and the detection results are shown in Table 4.

[0067] Table 4: Appearance, tack and holding power of salmeterol patches prepared with different types of pressure-sensitive adhesives

[0068]

[0069] The stability of salmeterol patches prepared with different types of pressure-sensitive adhesives was detected, and the results are shown in Table 5.

[0070] Table 5: Detection results of the stability of salmeterol patches prepared with different types of pressure-sensitive adhesives

[0071]

[0072]

[0073] Conclusion: When salmeterol patches were prepared with different types of polyacrylate pressure-sensitive adhesives, the results showed that none of the different types of polyacrylate pressure-sensitive adhesives oozed glue, and the differences in tack and holding power were not significant. Therefore, different types of polyacrylate pressure-sensitive adhesives had little effect on tack and holding power. However, according to the stability results, the patches prepared with polyacrylate pressure-sensitive adhesives with hydrophilic functional groups had better stability. The reason might be that the hydrophilic polyacrylate pressure-sensitive adhesives with carboxyl or hydroxyl functional groups had good compatibility with the hydrophilic part of the prepared polymer nanoparticles, increased the solubility of the polymer nanoparticles in the adhesive, and avoided the crystallization of the drug.

[0074] Example 3: Investigation of different penetration enhancers

[0075] In Example 3, different penetration enhancers were screened to prepare salmeterol patches, and the specific formulation is shown in Table 6.

[0076] Table 6: Formulation for screening different penetration enhancers

[0077]

[0078]

[0079] Note: All types of polyacrylate pressure-sensitive adhesives were purchased from Henkel. Among them, the acrylic pressure-sensitive adhesive with hydroxyl group has the model DURO-TAK 387-2510; the acrylic pressure-sensitive adhesive with carboxyl group has the model DURO-TAK 387-2054.

[0080] The specific preparation method of the salmeterol patch is the same as that of Example 1.

[0081] 1. The stability of the salmeterol patches prepared with different penetration enhancers was detected respectively, and the results are shown in Table 7.

[0082] Table 7: Stability results of salmeterol patches prepared with different penetration enhancers

[0083]

[0084] 2. In vitro release test (in vitro transdermal experiment) of salmeterol patches prepared with different penetration enhancers:

[0085] Apparatus: vertical diffusion cell; Temperature: 32 °C; Rotation speed: 600 rpm;

[0086] Sample loading amount: 75 mg (0.5 mm quantitative loop); Release medium: pH 6.8 phosphate buffer solution;

[0087] Skin: skin of Bama pigs (abdomen);

[0088] Volume of medium: 10 ml; Sampling amount: 1.5 ml; Make-up volume: 1.5 ml;

[0089] Diameter of the orifice of the diffusion cell: 15 mm; Area of the orifice of the diffusion cell: 1.77 cm 2 ;

[0090] Sampling time: 0 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h.

[0091] HPLC chromatographic conditions: AgelaVenusil MP C18 chromatographic column (4.6×250 mm, 5 μm); Methanol–water (volume ratio 80:20) as the mobile phase; Flow rate: 1.0 ml per minute; Detection wavelength: 280 nm; Column temperature: 30 °C; Injection volume: 10 μl.

[0092] The salmeterol drug concentration in the receiving solution was detected by HLPC, and the cumulative transdermal amount of the drug in the prescription patch was calculated according to the following formula.

[0093]

[0094] In the formula, Q t is the cumulative release amount per unit area (g / cm 2 ), C n is the drug concentration at the nth time (g / mL), V n is the volume of the receiving solution (mL); V is the sampling volume (mL); A is the effective diffusion area of the drug (cm 2 ).

[0095] The in vitro release data are shown in Table 8 below and Figure 3 as follows.

[0096] Table 8: In vitro cumulative release amount of salmeterol patches prepared with different penetration enhancers (μg / cm 2 )

[0097] Time (h) 0 2 4 6 8 12 24 Prescription 2-1 0.0 42.3 77.0 129.6 153.8 186.9 198.2 Prescription 2-2 0.0 26.5 52.5 106.9 126.3 159.6 182.7 Prescription 3-1 0.0 53.9 95.4 158.5 182.1 238.9 321.6 Prescription 3-2 0.0 52.0 89.0 155.6 178.6 213.4 312.9 Prescription 3-3 0.0 63.2 97.6 148.6 189.5 241.6 334.2 Prescription 3-4 0.0 32.2 78.9 126.7 142.9 178.2 259.8

[0098] Conclusion: Different penetration enhancers have little effect on the stability of the patches. Different penetration enhancers have a greater impact on the cumulative release amount. It can be seen from the results that the in vitro penetration results are better when using a mixture of monoglyceryl laurate and another penetration enhancer such as isopropyl myristate, ethyl oleate or 1,2-propanediol. The in vitro penetration results are not as good as those using a mixture of monoglyceryl laurate and another penetration enhancer when not using monoglyceryl laurate as the penetration enhancer or using a single monoglyceryl laurate as the penetration enhancer.

[0099] Example 4: Preparation of salmeterol patches

[0100] Salmeterol patches with different formulations are shown in Table 9.

[0101] Table 9: Salmeterol patches with different formulations

[0102]

[0103] Note: All types of polyacrylate pressure-sensitive adhesives are purchased from Henkel. Among them, the acrylic pressure-sensitive adhesive containing hydroxyl groups is of the type DURO-TAK 387-2510; the acrylic pressure-sensitive adhesive containing carboxyl groups is of the type DURO-TAK 387-2054.

[0104] The specific preparation method of the salmeterol patch is the same as that in Example 1.

[0105] The appearance, tack, holding power and peel strength of the salmeterol patches with different formulations are detected respectively. The detection methods of tack and holding power are the same as those in Example 1. The peel strength is determined by the test method of adhesive tape peel strength in GB / T 2792-2014. The detection results are shown in Table 10.

[0106] Table 10: Detection results of salmeterol patches with different formulations

[0107]

[0108] The stability detection results of the salmeterol patches with different formulations are shown in Table 11.

[0109] Table 11: Stability detection results of salmeterol patches with different formulations

[0110]

[0111]

[0112] The in vitro release detection method of salmeterol patches with different prescriptions is the same as that in Example 3, and the detection results are shown in Table 12 and Figure 4 as follows.

[0113] Table 12: In vitro cumulative release amount (μg) of different prescriptions

[0114] Time (h) 0 2 4 6 8 12 24 Prescription 4-1 0.0 37.2 79.8 123.6 152.5 216.8 324.3 Prescription 4-2 0.0 42.0 77.1 126.3 150.9 198.1 341.4 Prescription 4-3 0.0 40.4 85.0 128.8 159.2 205.7 333.5 Prescription 4-4 0.0 38.4 80.5 122.1 149.4 200.5 316.6

[0115] According to the stability and in vitro release curve (see Figure 4 ), it can be seen that the patch prepared in Example 4 has good stability and good release effect, and the cumulative release amount in 24 h is greater than 300 μg.

Claims

1. A salmeterol patch, characterized in that, It is prepared from the following raw materials in parts by weight: 5 - 10 parts of salmeterol-loaded polymer nanoparticles, 30 - 60 parts of penetrant, 40 - 70 parts of pressure-sensitive adhesive, and 50 - 80 parts of solvent; The preparation method of the salmeterol-loaded polymer nanoparticles is as follows: salmeterol is pre-dispersed in an emulsion, and while vinyl acetate monomer and polyvinyl alcohol are polymerizing, salmeterol is wrapped in the polymer to form degradable amphiphilic polymer nanoparticles.

2. The salmeterol patch according to claim 1, characterized in that, The preparation method of the salmeterol-loaded polymer nanoparticles is as follows: 1) Salmeterol treatment: First, it is prepared into nanoparticles by a vibrating ball mill; 2) Aqueous phase preparation: Under stirring, 0.5 - 2.0 parts of sodium lauryl polyoxyethylene ether sulfate and 10 - 30 parts of polyvinyl alcohol are added to purified water, and 15 parts of salmeterol after vibrating ball milling are stirred and mixed as the aqueous phase; 3) Oil phase preparation: 25 - 35 parts of vinyl acetate monomer, 0.5 - 2.0 parts of cetane, and 0.2 - 1.0 parts of 2,2'-azobis(2-methylheptanenitrile) are stirred and mixed evenly as the oil phase; 4) Preparation of polymer nanoparticle emulsion: The aqueous phase is slowly added to the oil phase under stirring to prepare a pre-emulsion; then it is emulsified at high speed, and the obtained emulsion reacts at 20 - 30 °C for 10 - 15 h to obtain a polymer nanoparticle emulsion. Finally, after filtration, the filtrate is concentrated under reduced pressure and air-dried naturally to obtain salmeterol-loaded polymer nanoparticles. The above parts are all in parts by weight.

3. The salmeterol patch according to claim 2, characterized in that, In step 4), a dispersing emulsifier, polyglycerol lauryl ether, is added during high-speed emulsification.

4. The salmeterol patch according to claim 1, characterized in that, The penetrant is a compound of monoglyceride laurate and another penetrant, and the other penetrant is one of isopropyl myristate, ethyl oleate, or 1,2-propanediol.

5. The salmeterol patch according to claim 1, characterized in that, The pressure-sensitive adhesive is a polyacrylate pressure-sensitive adhesive containing a hydroxyl functional group or a carboxyl functional group.

6. The salmeterol patch according to claim 1, characterized in that, The solvent is ethyl acetate / methanol with a volume ratio of 1:4 - 6.

7. The salmeterol patch according to claim 1, characterized in that, The drug loading of the salmeterol-loaded polymer nanoparticles is 20 - 30%.

8. The preparation method of the salmeterol patch according to any one of claims 1 - 7, characterized in that S1: Dissolve the salmeterol-loaded polymer nanoparticles in the solvent and stir until completely dissolved; S2: Add the pressure-sensitive adhesive to the solvent and stir until completely dissolved, then add the penetrant and stir until completely dissolved; S3: Add the main drug solution in step S1 to the solution in step S2 under stirring and stir until completely dissolved, then stir at high speed again to ensure thorough mixing; S4: Stand for degassing, and evenly coat the solution in step S3 on the release liner with a coater to obtain an adhesive layer; after the obtained adhesive layer is dried at room temperature, it is placed in a vacuum drying oven to dry and volatilize the solvent; S5: Cover the backing layer and cut to obtain the salmeterol patch.

9. The preparation method of the salmeterol patch according to claim 8, characterized in that, The thickness of the adhesive layer of the patch is controlled at 50 ± 5 μm.

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