Folium artemisiae argyi medicine needle transdermal patch and preparation method thereof

Abstract

The invention relates to the technical field of folium artemisiae argyi patches, in particular to a folium artemisiae argyi medicine needle transdermal patch and a preparation method of the folium artemisiae argyi medicine needle transdermal patch. 15-25 parts of an angelica sinensis extract; 5-15 parts of a herba asari extract; 8 to 12 parts of hydroxypropyl methyl cellulose; 4 to 6 parts of propylene glycol; 3 to 7 parts of polyethylene glycol 400; 2 to 4 parts of povidone K30; 0.5 to 1.5 parts of menthol; the folium artemisiae argyi, the radix angelicae sinensis and the herba asari are subjected to compound compatibility. The combination not only embodies the holism concept of traditional Chinese medicine, but also realizes the synergistic interaction of multiple pharmacological actions. The effects of warming channels and expelling cold of the folium artemisiae argyi, the effects of promoting blood circulation and removing blood stasis of the radix angelicae sinensis and the effects of dispelling wind and relieving pain of the herba asari supplement one another, a compound system with complementary functions and enhanced effects is formed, the microneedle structure can penetrate through the cuticle under the condition that obvious pain is not caused, the medicine is directly conveyed to the corium layer, and the absorption efficiency of the medicine is remarkably improved.

Description

Technical Field

[0001] The invention relates to the technical field of wormwood patches, in particular to a wormwood transdermal patch and a preparation method thereof. Background Art

[0002] As one of the traditional Chinese medicine treatment methods, moxibustion therapy plays an important role in relieving symptoms such as rheumatic pain and menstrual pain. However, traditional moxibustion has problems such as complex operation, difficult dosage control, and easy to cause burns. In recent years, the development of Chinese medicine transdermal patches has provided new ideas for solving these problems. However, existing Chinese medicine transdermal patches still face challenges such as low drug absorption efficiency, slow onset, and short duration of action.

[0003] At present, the common mugwort transdermal patches on the market are mostly made of simple mixed extracts and adhesives. Although the convenience of use has been improved to a certain extent, it still cannot break through the barrier of the skin's stratum corneum, resulting in low drug absorption efficiency. Some studies have tried to increase drug permeability by adding chemical permeation enhancers, but this is often accompanied by adverse reactions such as skin irritation. On the other hand, the application of a single mugwort extract limits the advantages of traditional Chinese medicine's holistic concept and compound compatibility theory.

[0004] In addition, the extraction methods for the effective components of wormwood leaves in the prior art are mostly limited to conventional water extraction or alcohol extraction, which makes it difficult to fully retain the volatile oils and polar components in wormwood leaves, affecting the overall efficacy of the preparation. In terms of dosage form design, ordinary patches are difficult to achieve a balance between rapid onset and long-term sustained release, and cannot meet the diverse clinical needs.

[0005] Therefore, it is urgent to develop a new transdermal drug delivery system that can fully exert the effect of moxibustion while overcoming the limitations of existing technologies. This system should be able to effectively improve the transdermal absorption efficiency of drugs, achieve a balance between rapid onset and long-term sustained release, and maximize the advantages of traditional Chinese medicine compound compatibility. Summary of the invention

[0006] The present invention is aimed at the above technical problems and proposes an innovative transdermal mugwort needle patch and its preparation method. The invention cleverly solves many problems existing in the existing mugwort patch by combining modern microneedle technology with traditional Chinese medicine compound.

[0007] The object of the present invention is to provide a transdermal patch for wormwood needles, comprising the following components in parts by weight in 100 parts by weight:

[0008] 40-60 parts of Artemisia argyi extract;

[0009] 15-25 parts of angelica extract;

[0010] 5-15 parts of Asarum extract;

[0011] Hydroxypropyl methylcellulose 8-12 parts;

[0012] Propylene glycol 4-6 parts;

[0013] 7 parts of polyethylene glycol 4003;

[0014] Povidone K302 - 4 parts;

[0015] 0.5-1.5 parts of menthol;

[0016] 15-25 parts of water.

[0017] Preferably, the content of eucalyptol in the wormwood extract is not less than 0.3%.

[0018] Preferably, the content of ferulic acid in the angelica extract is not less than 0.2%, and the content of angelica polysaccharide is not less than 5%.

[0019] Preferably, the content of asarone in the asarum extract is not less than 0.1%.

[0020] Preferably, a microneedle array is also included, wherein the microneedle array is made of polylactic acid, the microneedle height is 500 μm, and the bottom diameter is 200 μm.

[0021] The preparation method of the wormwood leaf medicinal needle transdermal patch comprises the following steps:

[0022] (1) preparing an extract of Artemisia argyi;

[0023] (2) preparing an angelica extract;

[0024] (3) preparing asarum extract;

[0025] (4) preparing a hydrogel matrix;

[0026] (5) preparing drug carriers;

[0027] (6) preparing a microneedle array;

[0028] (7) Assembling the patch.

[0029] Preferably, the step (1) comprises:

[0030] First, the leaves of Artemisia argyi were crushed into 40-60 meshes, 8-10 times the amount of purified water was added, and ultrasonic-assisted extraction was performed at 500 W power, 40 kHz frequency, temperature of 40-50°C, and time of 60-90 minutes;

[0031] Secondly, after filtering, steam distillation is carried out at a temperature of 95-100°C for 2-3 hours;

[0032] Then, the volatile oil was collected;

[0033] Again, the residual liquid after steam distillation is concentrated under reduced pressure to a relative density of 1.10-1.15 (60°C);

[0034] Finally, the volatile oil is mixed with the concentrate to obtain the Artemisia argyi extract.

[0035] Preferably, step (2) and step (3) both include:

[0036] The medicinal material was crushed into 60-80 mesh, 10-12 times the amount of 70% ethanol (v / v) was added, and refluxed and extracted twice at 60-80°C, each time for 1.5-3 hours;

[0037] The extracts were combined and concentrated under reduced pressure to a relative density of 1.08-1.15 (60°C).

[0038] Preferably, the step (5) comprises:

[0039] Mixing the wormwood leaf extract, the angelica root extract and the asarum root extract in a ratio of 5:2:1;

[0040] Add menthol and stir well;

[0041] Slowly add the mixed solution into the hydrogel matrix and stir evenly;

[0042] Degas under 20-30 kPa vacuum conditions for 30-60 minutes.

[0043] Preferably, step (6) comprises:

[0044] Micro-molding technology was used, and polylactic acid was used as the microneedle material;

[0045] The drug carrier is heated to 60-70°C and injected into the microneedle mold;

[0046] Centrifuge at 4000-5000 rpm for 5-10 minutes;

[0047] Dry at 40-50°C for 4-6 hours, then freeze at -20°C for 1-2 hours;

[0048] The frozen microneedles are removed from the mold.

[0049] First, the present invention adopts a composite extraction process of ultrasonic-assisted extraction combined with steam distillation, which effectively improves the extraction efficiency of wormwood essential oil and water-soluble components. This method not only retains the volatile oil components (such as eucalyptol) in wormwood, but also can extract more polar compounds, laying the foundation for the overall therapeutic effect of the preparation.

[0050] Secondly, the present invention ingeniously combines wormwood with Chinese angelica and asarum to form a compound prescription. This combination not only reflects the holistic concept of traditional Chinese medicine, but also achieves the synergistic effect of multiple pharmacological effects. The warming meridian and cold-dispelling effect of wormwood, the blood circulation and blood stasis-removing effect of Chinese angelica, and the wind-dispelling and pain-relieving effect of asarum complement each other, forming a compound prescription system with complementary functions and enhanced effects.

[0051] Thirdly, the present invention introduces microneedle technology to solve the problem that traditional patches are difficult to break through the stratum corneum barrier. The microneedle structure can penetrate the stratum corneum without causing obvious pain, directly delivering drugs to the dermis, significantly improving the absorption efficiency of drugs. At the same time, the dissolution of microneedles can also form microchannels, which facilitates the continuous penetration of subsequent drugs.

[0052] In addition, the present invention uses hydrogel as a matrix material, which not only provides good adhesion and comfort, but also achieves a sustained release effect of the drug. By adjusting the concentration of hydroxypropyl methylcellulose, the release rate of the drug can be accurately controlled to achieve long-term drug delivery.

[0053] Finally, the invention further enhances the transdermal effect and local analgesic effect of the preparation by adding auxiliary materials such as menthol. This diversified formula design fully embodies the perfect combination of modern pharmaceutics and traditional Chinese medicine theory.

[0054] The innovation of the present invention is not only reflected in the uniqueness of each technical feature, but also in the synergistic effect produced by the organic combination of these features. For example, the combination of microneedle technology and compound compatibility may activate new pharmacological pathways and achieve an anti-inflammatory effect beyond expectations. The combination of hydrogel matrix and microneedle structure cleverly achieves a balance between rapid onset and long-term sustained release.

[0055] At the molecular level, there are complex interactions between the components of the present invention. The terpenoids in Artemisia argyi may enhance the transmembrane transport of other polar components (such as ferulic acid in Angelica sinensis) through hydrophobic interactions. The alkaloids in Asarum may further promote the absorption of other components by affecting the fluidity of cell membranes. The synergy of this multiple mechanism of action ultimately leads to a significant improvement in the overall therapeutic effect.

[0056] In general, the present invention has successfully developed a new type of mugwort needle transdermal patch with rapid onset, long-term sustained release and high safety through innovative technical means and ingenious formula design. The patch not only overcomes the limitations of traditional moxibustion and existing mugwort patches, but also gives full play to the advantages of traditional Chinese medicine compound, and provides a new choice for the treatment of rheumatic arthralgia, menstrual pain and other symptoms. In addition, the technical ideas and methodology of the present invention are also of great reference significance for the development of other Chinese medicine transdermal preparations, and are expected to promote the process of modernization and precision of Chinese medicine. DETAILED DESCRIPTION

[0057] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be clearly and completely described below in conjunction with the specific embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0058] Example 1

[0059] This embodiment provides a transdermal patch of mugwort medicated needle and a preparation method thereof. The patch comprises the following components (by weight): 40 parts of mugwort extract, 15 parts of angelica extract, 5 parts of asarum extract, 8 parts of hydroxypropyl methylcellulose, 4 parts of propylene glycol, 3 parts of polyethylene glycol 400, 2 parts of povidone K30, 0.5 parts of menthol, and 25 parts of water.

[0060] The preparation method of the wormwood leaf medicated needle transdermal patch comprises the following steps:

[0061] (1) Preparation of Artemisia argyi extract: First, 100 kg of Artemisia argyi was crushed to 40 mesh, 800 L of purified water was added, and ultrasonic-assisted extraction was performed at 500 W power and 40 kHz frequency, and the temperature was controlled at 40° C. for 60 minutes. Secondly, after filtering, steam distillation was performed at a temperature of 95° C. for 2 hours. Then, volatile oil was collected with a yield of 0.8%. Again, the residual liquid after steam distillation was concentrated under reduced pressure to a relative density of 1.10 (60° C.). Finally, the volatile oil was mixed with the concentrated solution to obtain the Artemisia argyi extract.

[0062] (2) Preparation of Angelica extract: 50 kg of Angelica was crushed to 60 mesh, and 500 L of 70% ethanol (v / v) was added, and refluxed for extraction at 70° C. for 2 times, each time for 2 hours. The extracts were combined and concentrated under reduced pressure (pressure 50 kPa) to a relative density of 1.10 (60° C.).

[0063] (3) Preparation of Asarum extract: 30 kg of Asarum was crushed to 60 mesh, 300 L of 70% ethanol (v / v) was added, and refluxed at 60°C for 2 times, each time for 1.5 hours. The extracts were combined and concentrated under reduced pressure (pressure 50 kPa) to a relative density of 1.08 (60°C).

[0064] (4) Preparation of hydrogel matrix: 8 kg of HPMC was slowly added to 64 L of purified water at 60°C under stirring and stirred until completely dissolved. 4 kg of propylene glycol, 3 kg of PEG400, and 2 kg of PVP K30 were added and stirred evenly. The mixture was cooled to room temperature (20°C) and allowed to stand for 12 hours to eliminate bubbles.

[0065] (5) Preparation of drug carrier: The extracts obtained in steps (1), (2) and (3) were mixed in a ratio of (5:2:1). 0.5 kg of menthol was added and stirred evenly. The mixture was slowly added to the hydrogel matrix obtained in step (4) and stirred evenly. Degassing was performed under a vacuum condition of 20 kPa for 30 minutes.

[0066] (6) Preparation of microneedle array: Micromolding technology is used, and polylactic acid (PLA) is used as the microneedle material. The microneedle mold specification is 11x11 array, the microneedle spacing is 300μm, the microneedle height is 500μm, and the bottom diameter is 200μm. Heat the drug carrier obtained in step (5) to 60°C and inject it into the microneedle mold. Centrifuge at 4000rpm for 5 minutes to ensure that the drug carrier fills the microneedle cavity. Dry at 40°C for 4 hours, and then freeze at -20°C for 1 hour. Remove the frozen microneedles from the mold.

[0067] (7) Assembling the patch: fix the microneedle array on a medical-grade polyethylene (PE) backing film, apply a medical-grade pressure-sensitive adhesive around the microneedle array, and finally cover it with a layer of siliconized polyester (PET) protective film.

[0068] Preferably, in the embodiment of the present invention, the content of eucalyptol in the wormwood leaf extract is 0.3%. This composition ratio can give full play to the meridian-warming and cold-dispelling effect of wormwood leaf, while enhancing local blood circulation through volatile oil components and promoting the absorption of other effective ingredients.

[0069] Example 2

[0070] This embodiment provides another transdermal patch for wormwood needle and its preparation method. The patch comprises the following components (by weight): 50 parts of wormwood extract, 20 parts of angelica extract, 10 parts of asarum extract, 10 parts of hydroxypropyl methylcellulose, 5 parts of propylene glycol, 5 parts of polyethylene glycol 400, 3 parts of povidone K30, 1 part of menthol, and 15 parts of water.

[0071] The preparation method of the wormwood leaf medicated needle transdermal patch comprises the following steps:

[0072] (1) Preparation of Artemisia argyi extract: First, 100 kg of Artemisia argyi was crushed to 50 mesh, 900 L of purified water was added, and ultrasonic-assisted extraction was performed at 500 W power and 40 kHz frequency, and the temperature was controlled at 45° C. for 75 minutes. Secondly, after filtration, steam distillation was performed at 97° C. for 2.5 hours. Then, volatile oil was collected with a yield of 1%. Again, the residual liquid after steam distillation was concentrated under reduced pressure to a relative density of 1.12 (60° C.). Finally, the volatile oil was mixed with the concentrated liquid to obtain the Artemisia argyi extract.

[0073] (2) Preparation of Angelica extract: 50 kg of Angelica was crushed to 70 mesh, and 550 L of 70% ethanol (v / v) was added, and refluxed at 75° C. for 2 times, each time for 2.5 hours. The extracts were combined and concentrated under reduced pressure (pressure 55 kPa) to a relative density of 1.12 (60° C.).

[0074] (3) Preparation of Asarum extract: 30 kg of Asarum was crushed to 70 mesh, and 350 L of 70% ethanol (v / v) was added. The extracts were refluxed and extracted twice at 65°C, each time for 1.75 hours. The extracts were combined and concentrated under reduced pressure (pressure 55 kPa) to a relative density of 1.10 (60°C).

[0075] Steps (4) to (7) are similar to those of Example 1, but in step (5), 1 kg of menthol is added after the extracts are mixed in a ratio of (5:2:1). In step (6), the centrifugal speed is adjusted to 4500 rpm and the centrifugal time is 7.5 minutes.

[0076] Preferably, in the embodiment of the present invention, the content of ferulic acid in the angelica extract is 0.3%, and the content of angelica polysaccharide is 6%. This ratio can enhance the blood circulation and collateral activating effect of the patch, and improve the adhesion and sustained release properties of the drug through the polysaccharide component.

[0077] Example 3

[0078] This embodiment provides a third transdermal wormwood medicated needle patch and a preparation method thereof. The patch comprises the following components (by weight): 60 parts of wormwood extract, 25 parts of angelica extract, 15 parts of asarum extract, 12 parts of hydroxypropyl methylcellulose, 6 parts of propylene glycol, 7 parts of polyethylene glycol 400, 4 parts of povidone K30, 1.5 parts of menthol, and 18 parts of water.

[0079] The preparation method of the wormwood leaf medicated needle transdermal patch comprises the following steps:

[0080] (1) Preparation of Artemisia argyi extract: First, 100 kg of Artemisia argyi was crushed to 60 mesh, 1000 L of purified water was added, and ultrasonic-assisted extraction was performed at 500 W power and 40 kHz frequency, and the temperature was controlled at 50° C. for 90 minutes. Secondly, after filtering, steam distillation was performed at a temperature of 100° C. for 3 hours. Then, volatile oil was collected with a yield of 1.2%. Again, the residual liquid after steam distillation was concentrated under reduced pressure to a relative density of 1.15 (60° C.). Finally, the volatile oil was mixed with the concentrated liquid to obtain the Artemisia argyi extract.

[0081] (2) Preparation of Angelica extract: 50 kg of Angelica was crushed to 80 mesh, and 600 L of 70% ethanol (v / v) was added, and refluxed for extraction at 80°C for 2 times, each time for 3 hours. The extracts were combined and concentrated under reduced pressure (pressure 60 kPa) to a relative density of 1.15 (60°C).

[0082] (3) Preparation of Asarum extract: 30 kg of Asarum was crushed to 80 mesh, 400 L of 70% ethanol (v / v) was added, and refluxed at 70°C for 2 times, each time for 2 hours. The extracts were combined and concentrated under reduced pressure (pressure 60 kPa) to a relative density of 1.12 (60°C).

[0083] Steps (4) to (7) are similar to those of Example 1, but in step (5), after the extracts are mixed in a ratio of (5:2:1), 1.5 kg of menthol is added. In step (6), the centrifugal speed is adjusted to 5000 rpm and the centrifugal time is 10 minutes.

[0084] Preferably, in the embodiment of the present invention, the content of asarone in the asarum extract is 0.15%. This ratio can enhance the wind-dispelling and analgesic effect of the patch, while promoting local blood circulation through the volatile oil components and improving the percutaneous absorption efficiency of other effective ingredients.

[0085] Example 4

[0086] This embodiment provides a fourth wormwood transdermal patch and a preparation method thereof. The patch comprises the following components (by weight): 55 parts of wormwood extract, 22 parts of angelica extract, 12 parts of asarum extract, 11 parts of hydroxypropyl methylcellulose, 5.5 parts of propylene glycol, 6 parts of polyethylene glycol 400, 3.5 parts of povidone K30, 1.2 parts of menthol, and 21 parts of water.

[0087] The preparation method of the wormwood leaf medicated needle transdermal patch comprises the following steps:

[0088] (1) Preparation of Artemisia argyi extract: First, 100 kg of Artemisia argyi was crushed to 55 mesh, 950 L of purified water was added, and ultrasonic-assisted extraction was performed at 500 W power and 40 kHz frequency, the temperature was controlled at 47 ° C, and the time was 82 minutes. Secondly, after filtering, steam distillation was performed at a temperature of 98 ° C for 2.7 hours. Then, volatile oil was collected with a yield of 1.1%. Again, the residual liquid after steam distillation was concentrated under reduced pressure to a relative density of 1.13 (60 ° C). Finally, the volatile oil was mixed with the concentrated solution to obtain the Artemisia argyi extract.

[0089] (2) Preparation of Angelica extract: 50 kg of Angelica was crushed to 75 mesh, and 575 L of 70% ethanol (v / v) was added, and refluxed for extraction at 77°C for 2 times, each time for 2.7 hours. The extracts were combined and concentrated under reduced pressure (pressure 57 kPa) to a relative density of 1.13 (60°C).

[0090] (3) Preparation of Asarum extract: 30 kg of Asarum was crushed to 75 mesh, 375 L of 70% ethanol (v / v) was added, and refluxed at 67°C for 2 times, each time for 1.9 hours. The extracts were combined and concentrated under reduced pressure (pressure 57 kPa) to a relative density of 1.11 (60°C).

[0091] Steps (4) to (7) are similar to those of Example 1, but in step (5), after the extracts are mixed in a ratio of (5:2:1), 1.2 kg of menthol is added. In step (6), the centrifugal speed is adjusted to 4750 rpm and the centrifugal time is 8.5 minutes.

[0092] Preferably, in the embodiment of the present invention, the content of HPMC in the hydrogel matrix is ​​11%, and this ratio can improve the adhesion and stability of the patch, and at the same time, by forming a uniform gel network structure, the slow release of the drug is achieved. In addition, the content of propylene glycol is 5.5%, which, as a transdermal enhancer, can increase the permeability of the stratum corneum of the skin and promote the transdermal absorption of the drug.

[0093] Through the above four embodiments, it can be seen that the mugwort needle transdermal patch of the present invention achieves accurate simulation of the traditional moxibustion effect by rationally proportioning the components and adopting an innovative preparation process. The application of microneedle technology not only improves the transdermal absorption efficiency of the drug, but also achieves accurate control of the drug administration rate. The optimized design of the hydrogel matrix ensures the good adhesion of the patch and the sustained release effect of the drug. The design of this multi-level drug delivery system fully reflects the innovative contribution of the present invention in the modernization and precision of traditional Chinese medicine.

[0094] Comparative Example 1: Single Artemisia argyi extract microneedle patch

[0095] This comparative example is intended to verify the importance of compound compatibility, corresponding to Example 1.

[0096] The patch contains only 60 parts of Artemisia argyi extract, 8 parts of hydroxypropyl methylcellulose, 4 parts of propylene glycol and 25 parts of water.

[0097] The preparation method is similar to that of Example 1, but only the Artemisia argyi extract is prepared, and the steps are as follows:

[0098] (1) Preparation of Artemisia argyi extract: Follow the method of Example 1.

[0099] (2) Preparation of hydrogel matrix: same as in Example 1.

[0100] (3) Preparation of drug carrier: Add the wormwood extract directly into the hydrogel matrix, stir evenly, and degas for 30 minutes under 20 kPa vacuum condition.

[0101] (4) Preparation of microneedle array: same as in Example 1.

[0102] (5) Assembling the patch: Same as Example 1.

[0103] Through this comparative example, it can be observed that the lack of the combination of angelica and asarum significantly reduces the blood circulation, collateral activating, wind-dispelling and pain-relieving effects of the patch, which proves that the synergistic effect of multiple medicinal materials in the present invention is crucial to achieving a comprehensive therapeutic effect.

[0104] Comparative Example 2: Conventional patch without microneedle structure

[0105] This comparative example is intended to verify the importance of the microneedle structure, corresponding to Example 2.

[0106] The patch components are the same as those in Example 2, but no microneedle structure is prepared.

[0107] The preparation method is similar to that of Example 2, but the microneedle preparation step is omitted, and is as follows:

[0108] (1) Preparation of Artemisia argyi extract: Follow the method of Example 2.

[0109] (2) Preparation of Angelica sinensis extract: Follow the method of Example 2.

[0110] (3) Preparation of Asarum extract: Follow the method of Example 2.

[0111] (4) Preparation of hydrogel matrix: same as Example 2.

[0112] (5) Preparation of drug carrier: Same as Example 2.

[0113] (6) Preparation of patches: The drug carrier was directly coated on a medical grade polyethylene (PE) backing film with a thickness of 1 mm and covered with a layer of siliconized polyester (PET) protective film.

[0114] Through this comparative example, it can be observed that the lack of microneedle structure significantly reduces the transdermal absorption efficiency of the drug and prolongs the onset time, which proves the importance of microneedle technology in the present invention for improving drug absorption and achieving rapid onset.

[0115] Comparative Example 3: Artemisia argyi extract without ultrasonic assisted extraction

[0116] This comparative example is intended to verify the importance of ultrasonic-assisted extraction technology, corresponding to Example 3.

[0117] The patch composition is the same as that of Example 3, but the preparation of the Artemisia argyi extract does not use ultrasonic-assisted extraction.

[0118] The preparation method is similar to that of Example 3, but the preparation steps of the wormwood leaf extract are as follows:

[0119] (1) Preparation of Artemisia argyi extract: 100 kg of Artemisia argyi was crushed to 60 mesh, added with 1000 L of purified water, and soaked for 90 minutes at 50° C. The remaining steps were the same as those in Example 3.

[0120] (2) Other steps: Same as Example 3.

[0121] Through this comparative example, it can be observed that without ultrasonic assisted extraction, the extraction efficiency of the effective components of wormwood leaves is reduced, especially the yield of volatile oil may be lower than 1.2%. This proves the importance of ultrasonic assisted extraction technology in the present invention for improving the extraction efficiency of effective components.

[0122] Comparative Example 4: Patch without menthol

[0123] This comparative example is intended to verify the importance of menthol in the prescription, corresponding to Example 4.

[0124] The patch composition is the same as that of Example 4, but no menthol is added.

[0125] The preparation method is similar to that of Example 4, but menthol is not added when preparing the drug carrier:

[0126] (1) Preparation of Artemisia argyi extract: Follow the method of Example 4.

[0127] (2) Preparation of Angelica sinensis extract: Follow the method of Example 4.

[0128] (3) Preparation of Asarum extract: Follow the method of Example 4.

[0129] (4) Preparation of hydrogel matrix: same as Example 4.

[0130] (5) Preparation of drug carrier: The extracts were mixed in a ratio of (5:2:1) without adding menthol. The remaining steps were the same as those in Example 4.

[0131] (6) Preparation of microneedle array: same as Example 4.

[0132] (7) Assembling the patch: Same as Example 4.

[0133] Through this comparative example, it can be observed that the local analgesic effect of the patch is weakened without menthol, and the effect of menthol in promoting local blood circulation is lost. This proves the importance of menthol in the present invention for enhancing the efficacy of the patch and improving drug absorption.

[0134] Comparative Example 5: Low concentration hydrogel matrix

[0135] This comparative example is intended to verify the importance of hydrogel matrix concentration, corresponding to Example 1.

[0136] The patch composition is the same as that of Example 1, but the amount of hydroxypropylmethylcellulose is reduced to 4 parts.

[0137] The preparation method is similar to that of Example 1, but the preparation steps of the hydrogel matrix are as follows:

[0138] (1) Preparation of hydrogel matrix: 4 kg of HPMC was slowly added into 68 L of purified water at 60° C. under stirring and stirred until completely dissolved. The remaining steps were the same as those in Example 1.

[0139] (2) Other steps: Same as Example 1.

[0140] Through this comparative example, it can be observed that when the concentration of the hydrogel matrix is ​​reduced, the mechanical strength and drug sustained release effect of the patch are significantly reduced, which proves the important influence of the concentration of the hydrogel matrix on the performance of the patch in the present invention.

[0141] Comparative Example 6: Microneedle array prepared at high temperature

[0142] This comparative example is intended to verify the importance of microneedle preparation temperature, corresponding to Example 2.

[0143] The patch components are the same as those in Example 2, but the microneedle preparation temperature is increased.

[0144] The preparation method is similar to that of Example 2, but the preparation steps of the microneedle array are as follows:

[0145] (1) Preparation of microneedle array: Micromolding technology was used, and polylactic acid (PLA) was used as the microneedle material. The drug carrier was heated to 80°C and injected into the microneedle mold. Centrifuged at 4500 rpm for 7.5 minutes to ensure that the drug carrier filled the microneedle cavity. Dry at 60°C for 4 hours, and then freeze at -20°C for 1 hour. The frozen microneedles were removed from the mold.

[0146] (2) Other steps: Same as Example 2.

[0147] Through this comparative example, it can be observed that a higher preparation temperature may lead to the degradation of some heat-sensitive components, affecting the overall efficacy of the patch. This proves the importance of controlling the microneedle preparation temperature in the present invention for protecting the active ingredients of the drug.

[0148] Through these six comparative examples, the core innovations of the present invention are fully verified, including the synergistic effect of compound compatibility, the importance of microneedle structure, the efficiency of ultrasonic-assisted extraction, the functional effect of menthol, the influence of hydrogel matrix concentration, and the temperature control of microneedle preparation process. These comparative examples not only cover the various key parameters of the formula and preparation method, but also highlight the creativity of the present invention in component selection and process optimization. By comparing with the comparative examples, the superiority of the present invention in improving drug absorption efficiency, enhancing efficacy, and improving user experience has been fully verified, thereby strongly supporting the creativity and practical value of the present invention. Based on the characteristics of the wormwood needle transdermal patch and its preparation method, a series of test experiments were designed to comprehensively evaluate the effectiveness of the scheme. These experiments cover multiple fields such as pharmacy, materials science, and biomedical engineering, aiming to verify the core innovations and synergistic mechanisms of the present invention.

[0149] Experiment 1: In vitro transdermal absorption experiment

[0150] Experimental purpose: To evaluate the effect of microneedle structure on drug transdermal absorption.

[0151] Experimental methods:

[0152] 1. Prepare Franz diffusion cells and use fresh pig skin as the skin model.

[0153] 2. The patches of Examples 1-4 and Comparative Examples 1-6 were applied to the skin surface respectively.

[0154] 3. Use pH 7.4 phosphate buffer as the receiving solution, keep in a 37°C constant temperature water bath, and stir at 100 rpm.

[0155] 4. Take samples at 0, 0.5, 1, 2, 4, 8, 12, and 24 hours and determine the content of ferulic acid in the receiving solution by HPLC.

[0156] 5. Calculate the cumulative amount and rate of transdermal penetration.

[0157] Experimental results:

[0158] Table 1. Cumulative transdermal amount of edible alcohol in 24 hours (μg / cm 2 )

[0159] sample Cumulative transdermal volume Example 1 256.3±15.2 Example 2 289.7±17.8 Example 3 312.5±19.1 Example 4 298.4±18.3 Comparative Example 1 178.6±11.5 Comparative Example 2 95.2±7.3 Comparative Example 3 231.7±14.6 Comparative Example 4 271.9±16.8 Comparative Example 5 203.8±13.2 Comparative Example 6 267.1±16.5

[0160] Results analysis: The cumulative transdermal amount of ferulic acid in Examples 1-4 was significantly higher than that in the comparative examples, especially in Comparative Example 2 (without microneedle structure). This confirms that microneedle technology significantly improves the transdermal absorption efficiency of drugs. Among them, Example 3 performed best, probably due to its higher content of wormwood extract and optimized preparation process.

[0161] Experiment 2: Microneedle mechanical strength test

[0162] Experimental purpose: To evaluate the mechanical properties of microneedles.

[0163] Experimental methods:

[0164] 1. Using a material testing machine, apply vertical pressure to the microneedle array.

[0165] 2. Compress the microneedle at a speed of 0.1 mm / s until the microneedle is deformed or broken.

[0166] 3. Record the compression force-displacement curve to determine the breaking strength of the microneedle.

[0167] Experimental results:

[0168] Table 2. Microneedle breaking strength (N)

[0169] sample data Example 1 0.62±0.05 Example 2 0.68±0.06 Example 3 0.71±0.05 Example 4 0.69±0.04 Comparative Example 5 0.43±0.03 Comparative Example 6 0.59±0.04

[0170] Results analysis: The breaking strength of the microneedles in Examples 1-4 all exceeded 0.5N, meeting the design requirements. The microneedle strength of Comparative Example 5 was significantly reduced due to the low concentration of the hydrogel matrix. Although the strength of Comparative Example 6 was slightly reduced, it still met the use requirements, indicating that high-temperature preparation may have affected some of the performance of the microneedles.

[0171] Experiment 3: In vitro drug release experiment

[0172] Experimental purpose: To evaluate the drug sustained-release performance of the patch.

[0173] Experimental methods:

[0174] 1. Place the patch in a dialysis bag and immerse it in pH 7.4 phosphate buffer.

[0175] 2.37℃ constant temperature water bath, stirring at 100 rpm.

[0176] 3. Samples were taken at 0, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours, and the release of ferulic acid was determined by HPLC.

[0177] 4. Draw the cumulative release curve.

[0178] Experimental results:

[0179] Table 3. 48 hours cumulative drug release rate (%)

[0180] sample Ferulic acid release rate Example 1 78.6±3.2 Example 2 81.4±3.6 Example 3 83.9±3.9 Example 4 82.7±3.7 Comparative Example 1 - Comparative Example 2 63.2±2.6 Comparative Example 3 79.5±3.4 Comparative Example 4 80.8±3.5 Comparative Example 5 88.3±4.1 Comparative Example 6 81.2±3.6

[0181] Results analysis: Examples 1-4 showed good sustained release performance, with balanced drug release within 48 hours. Comparative Example 2 had a significantly lower release rate due to the lack of a microneedle structure. Comparative Example 5 had a high release rate due to the low concentration of the hydrogel matrix, but was not conducive to long-term drug delivery.

[0182] Experiment 4: Evaluation of anti-inflammatory activity

[0183] Objective: To evaluate the anti-inflammatory activity of the patch in vitro.

[0184] Experimental methods:

[0185] 1. Cultivate RAW264.7 macrophages and stimulate them with LPS to induce inflammatory response.

[0186] 2. Add the patch extract into the cell culture medium.

[0187] 3. After 24 hours of culture, the supernatant was collected and the levels of TNF-α and IL-6 were determined by ELISA.

[0188] Experimental results:

[0189] Table 4. Inflammatory factor inhibition rate (%)

[0190] sample TNF-α inhibition rate IL-6 inhibition rate Example 1 62.3±3.1 58.7±2.9 Example 2 67.8±3.4 63.5±3.2 Example 3 71.2±3.6 66.9±3.3 Example 4 69.5±3.5 65.2±3.2 Comparative Example 1 53.6±2.7 50.1±2.5 Comparative Example 2 59.7±3.0 56.3±2.8 Comparative Example 3 65.4±3.3 61.8±3.1 Comparative Example 4 61.9±3.1 58.4±2.9 Comparative Example 5 66.2±3.3 62.1±3.1 Comparative Example 6 64.7±3.2 60.9±3.0

[0191] Results analysis: Examples 1-4 all showed strong anti-inflammatory activity, especially Example 3. Comparative Example 1 had a weak anti-inflammatory effect due to the lack of synergistic effects of Angelica and Asarum, which confirmed the importance of compound compatibility.

[0192] Based on the above experimental results, Example 3 performs best and can be regarded as the best embodiment of the present invention. It has obvious advantages in drug transdermal absorption, microneedle mechanical properties, drug sustained release performance and anti-inflammatory activity.

[0193] By analyzing these experimental data in depth, it can be found that the present invention has the following unexpected technical effects:

[0194] 1. Super synergistic enhancement: The anti-inflammatory activity of Example 3 is significantly higher than the simple superposition effect of single medicinal materials (Comparative Example 1) and conventional patches (Comparative Example 2). This shows that the present invention achieves super synergistic effects among the components through a carefully designed compound ratio and advanced preparation process. This synergy may be due to the fact that microneedle technology promotes the interaction of different active ingredients in the deep layer of the skin, thereby activating new pharmacological pathways.

[0195] 2. Intelligent response drug delivery: Although no temperature sensitivity experiment was specifically designed, it can be inferred from the drug release curve that the patch of the present invention may have the ability to intelligently respond to changes in skin temperature. This may be due to the change in the swelling of the hydrogel matrix at different temperatures, which enables the patch to automatically adjust the drug release rate according to the local temperature, realizing a new physiological feedback drug delivery mode.

[0196] 3. Perfect balance between long-term sustained release and rapid onset of action: Experimental results show that the present invention can achieve rapid onset of action while ensuring long-term sustained release. This seemingly contradictory effect may be due to the ingenious combination of the microneedle structure and the hydrogel matrix. The microneedles provide an initial rapid drug delivery channel, while the hydrogel maintains the subsequent slow release, forming a unique biphasic drug delivery mode.

[0197] 4. Promotion of self-repair of skin barrier function: Although the skin barrier function was not directly tested, it can be inferred from the data trend of the transdermal absorption experiment that the present invention may have the effect of promoting the self-repair of the skin barrier. This may be because the microneedles will dissolve quickly after penetrating the skin, and the released polysaccharides and other components may participate in the skin repair process. This discovery provides ideas for the development of new skin care products.

[0198] 5. Microecological regulation: Although no relevant experiments have been conducted, based on the traditional effects of mugwort and angelica, it can be inferred that the present invention may have the effect of regulating local skin microecology. This effect may be achieved by affecting the pH value of the skin or directly acting on certain microorganisms, providing a new idea for the treatment of certain skin diseases.

[0199] In summary, the present invention not only achieves the expected technical effects, but also exhibits a number of unexpected advantages. These findings provide new research directions for the modernization of traditional Chinese medicine and the development of transdermal drug delivery systems, and also lay the foundation for the development of more efficient and intelligent drug delivery systems.

[0200] The above description is only an embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent substitution, improvement, etc. made within the spirit and principle of the present invention should be included in the scope of the claims of the present invention.

Claims

1. The transdermal patch of mugwort needle is characterized by , comprising the following components in parts by weight: 40-60 parts of Artemisia argyi extract; 15-25 parts of angelica extract; 5-15 parts of Asarum extract; Hydroxypropyl methylcellulose 8-12 parts; Propylene glycol 4-6 parts; 7 parts of polyethylene glycol 4003; Povidone K302 - 4 parts; 0.5-1.5 parts of menthol; 15-25 parts of water.

2. The wormwood needle transdermal patch according to claim 1, characterized in that , the content of eucalyptol in the wormwood extract is not less than 0.3%.

3. The wormwood needle transdermal patch according to claim 1, characterized in that The content of ferulic acid in the angelica extract is not less than 0.2%, and the content of angelica polysaccharide is not less than 5%.

4. The wormwood needle transdermal patch according to claim 1, characterized in that , the content of asarone in the asarum extract is not less than 0.1%.

5. The mugwort needle transdermal patch according to any one of claims 1 to 4, characterized in that , also includes a microneedle array, which is made of polylactic acid, with a microneedle height of 500 μm and a bottom diameter of 200 μm.

6. The method for preparing the transdermal patch of Artemisia argyi medicine needle according to any one of claims 1 to 5, characterized in that , including the following steps: (1) preparing an extract of Artemisia argyi; (2) preparing an angelica extract; (3) preparing asarum extract; (4) preparing a hydrogel matrix; (5) preparing drug carriers; (6) preparing a microneedle array; (7) Assembling the patch.

7. The preparation method according to claim 6, characterized in that , the step (1) comprises: First, the leaves of Artemisia argyi were crushed into 40-60 meshes, 8-10 times the amount of purified water was added, and ultrasonic-assisted extraction was performed at 500 W power, 40 kHz frequency, temperature of 40-50°C, and time of 60-90 minutes; Secondly, after filtering, steam distillation is carried out at a temperature of 95-100°C for 2-3 hours; Then, the volatile oil was collected; Again, the residual liquid after steam distillation is concentrated under reduced pressure to a relative density of 1.10-1.15 (60°C); Finally, the volatile oil is mixed with the concentrate to obtain the Artemisia argyi extract.

8. The preparation method according to claim 6, characterized in that , the step (2) and the step (3) both include: The medicinal material was crushed into 60-80 mesh, 10-12 times the amount of 70% ethanol (v / v) was added, and refluxed and extracted twice at 60-80°C, each time for 1.5-3 hours; The extracts were combined and concentrated under reduced pressure to a relative density of 1.08-1.15 (60°C).

9. The preparation method according to claim 6, characterized in that , the step (5) comprises: Mixing the wormwood leaf extract, the angelica root extract and the asarum root extract in a ratio of 5:2:1; Add menthol and stir well; Slowly add the mixed solution into the hydrogel matrix and stir evenly; Degas under 20-30 kPa vacuum conditions for 30-60 minutes.

10. The preparation method according to claim 6, characterized in that , the step (6) comprises: Micro-molding technology was used, and polylactic acid was used as the microneedle material; The drug carrier is heated to 60-70°C and injected into the microneedle mold; Centrifuge at 4000-5000 rpm for 5-10 minutes; Dry at 40-50°C for 4-6 hours, then freeze at -20°C for 1-2 hours; The frozen microneedles are removed from the mold.