Microneedle patch for regulating blood uric acid and preparation method thereof

Abstract

The present invention relates to a microneedle patch for blood uric acid regulation and a preparation method thereof, comprising a microneedle substrate and microneedle tips distributed thereon in an array, wherein the microneedle substrate is a biodegradable water-soluble polymer, and the microneedle tips are blended and hot-pressed by a biodegradable polymer, a water-soluble polymer and a blood uric acid regulation drug. Compared with oral administration, the microneedle patch of the present invention not only avoids the first-pass liver metabolism effect, but also can accelerate the speed at which the drug takes effect. In addition, the microneedle tips are composed of a biodegradable polymer, a water-soluble polymer and a blood uric acid regulation drug, and the slow degradation of the polymer can be utilized to release the remaining drug, so that the drug effect is maintained for a longer time. Moreover, the microneedle tips will not touch nerve endings, and therefore can alleviate the patient's pain and improve the patient's compliance.

Description

Technical Field

[0001] The present invention belongs to the technical field of microneedle transdermal drug delivery, and particularly relates to a microneedle patch for regulating blood uric acid and a preparation method thereof. Background Art

[0002] Hyperuricemia has become the "fourth high" after the "three highs," and its harmful effects cannot be ignored. According to statistics, hyperuricemia has become the second most common metabolic disease after diabetes. Hyperuricemia is not only a major risk factor for gout but can also lead to various types of chronic kidney disease, particularly uric acid nephropathy, and in severe cases, uremia. The need for long-term, stable control of uric acid levels to meet target levels is urgent.

[0003] Currently, the main method for regulating uric acid levels in the human body is through oral medication. However, once oral medications enter the stomach, they are affected by gastric juice and food residue, causing some of the medications to lose their effectiveness. This can lead to some medications not being able to achieve their intended effect. Furthermore, most oral medications require entry into the small intestine to be effective, where the active ingredients are transported throughout the body through the bloodstream. This process takes several hours, making the effects relatively slow.

[0004] Microneedle transdermal drug delivery technology is an emerging transdermal drug delivery system that uses micron-sized needles to penetrate the skin's stratum corneum and deliver drugs. The microneedles range in length from 200 to 1000 μm and can be selected based on individual needs. During microneedle transdermal drug delivery, drugs enter the body directly through capillaries, avoiding first-pass liver metabolism and preventing gastrointestinal problems. Furthermore, microneedles avoid contacting nerve endings, thereby reducing pain and improving patient compliance.

[0005] Therefore, microneedle transdermal drug delivery system shows broad prospects in the treatment of hyperuricemia. Summary of the Invention

[0006] Based on the above-mentioned shortcomings and deficiencies in the prior art, one of the objects of the present invention is to at least solve one or more of the above-mentioned problems in the prior art. In other words, one of the objects of the present invention is to provide a microneedle patch for blood uric acid regulation and a preparation method thereof that meets one or more of the above-mentioned needs.

[0007] In order to achieve the above-mentioned object of the invention, the present invention adopts the following technical solutions:

[0008] A microneedle patch for regulating blood uric acid comprises a microneedle substrate and microneedle tips distributed thereon in an array. The microneedle substrate is a biodegradable water-soluble polymer, and the microneedle tips are formed by blending and hot-pressing the biodegradable polymer, a water-soluble polymer, and a blood uric acid regulating drug.

[0009] As a preferred embodiment, the microneedle tip comprises the following components by weight percentage:

[0010] 10-30 wt% of biodegradable polymer, 20-50 wt% of water-soluble polymer, and 20-50 wt% of blood uric acid regulating drug.

[0011] As a preferred embodiment, the biodegradable polymer is selected from one or more of polycaprolactone, polylactic acid, polyglycolic acid, and poly(lactic acid-glycolic acid) copolymer.

[0012] As a preferred embodiment, the water-soluble polymer is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol, hyaluronic acid, and polyacrylamide.

[0013] As a preferred embodiment, the blood uric acid regulating drug is selected from one or more of allopurinol, colchicine, febuxostat, and benzbromarone.

[0014] As a preferred embodiment, the biodegradable water-soluble polymer is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol, and hyaluronic acid.

[0015] The present invention also provides a method for preparing the microneedle patch as described in any of the above schemes, comprising the following steps:

[0016] Step 1: Evenly mix a biodegradable polymer, a water-soluble polymer, and a blood uric acid regulating drug, and evenly fill them into a cavity array mold using a hot pressing method, then remove excess melt from the mold surface and retain it for 5 to 10 minutes;

[0017] Step 2: Prepare a biodegradable water-soluble polymer solution, and evenly spread it on the surface of the array mold as a microneedle patch substrate using a hot pressing method and retain it for 10 to 15 minutes;

[0018] Step 3: Take out the microneedle patch array mold and peel it off after cooling it at room temperature to obtain a microneedle patch.

[0019] As a preferred solution, in step 1, the process parameters of the hot pressing method include: hot pressing temperature of 120-190° C., and pressure of 0.4-1 MPa.

[0020] As a preferred solution, in step 2, the process parameters of the hot pressing method include: hot pressing temperature of 60 to 120° C., and pressure of 0.2 to 0.6 MPa.

[0021] As a preferred solution, in step 2, the concentration of the biodegradable water-soluble polymer solution is 40-50 wt%.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] The microneedle patch of the present invention delivers drugs transdermally via microneedles, allowing the drug to enter the body directly through capillaries, avoiding first-pass liver metabolism and preventing gastrointestinal problems. Furthermore, the microneedle tips avoid contact with nerve endings, thus alleviating pain and improving patient compliance.

[0024] Compared to oral administration, the microneedle patch of this invention not only avoids first-pass liver metabolism but also accelerates the onset of drug efficacy. Furthermore, the microneedle tips are composed of a biodegradable polymer, a water-soluble polymer, and a blood uric acid-regulating drug. The slow degradation of the polymer allows the release of the remaining drug, maintaining its effectiveness for a longer period of time. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 Schematic diagram of the structure of the microneedle patch for regulating blood uric acid according to Example 1 of the present invention;

[0026] Figure 2 This is a comparison chart of changes in uric acid levels in mice in various experimental groups in Example 1 of the present invention;

[0027] Figure 3 This is a comparison chart of changes in mouse creatinine levels in each experimental group in Example 1 of the present invention;

[0028] Figure 4 This is a comparison chart of changes in nitric oxide (NO) levels in mice in various experimental groups in Example 1 of the present invention;

[0029] Figure 5 This is a comparison chart of changes in adenosine deaminase ADA activity in the liver of mice in each experimental group in Example 1 of the present invention. DETAILED DESCRIPTION

[0030] The technical solution of the present invention is further explained below through specific embodiments.

[0031] Example 1:

[0032] The method for preparing the microneedle patch for regulating blood uric acid in this embodiment comprises the following steps:

[0033] Step 1: Polycarbonate (30 wt%), polyvinyl pyrrolidone (50 wt%), and allopurinol (20 wt%) are uniformly mixed, and the mixture powder is evenly filled into a cavity array mold by hot pressing. Excess melt on the mold surface is then removed and the mixture is retained for 6 minutes; wherein the hot pressing temperature is 180° C. and the pressure is 0.6 MPa.

[0034] Step 2: Using a hot pressing method, a polyvinyl pyrrolidone aqueous solution (40 wt%) is evenly spread on the surface of the array mold as a microneedle patch substrate and retained for 10 minutes; wherein the hot pressing temperature is 110° C. and the pressure is 0.5 MPa;

[0035] Step 3: Take out the prepared microneedle patch array mold and cool it at room temperature for 15 minutes, then peel it off from the mold to obtain a microneedle patch for blood uric acid regulation, the structure of which is as follows: Figure 1 shown.

[0036] The following experimental model uses mice as an experimental model to conduct a comparative test on the therapeutic effect of the microneedle patch for regulating blood uric acid in this embodiment. The specific experimental process is as follows:

[0037] To evaluate the efficacy of the microneedle patch in treating hyperuricemia, mice were divided into the following groups: (1) blank control group: no treatment was performed; (2) model group: hyperuricemia mice were not treated with other treatments; (3) oral group: hyperuricemia mice were treated with oral medication; (4) microneedle group: the microneedle patch of this example was applied to hyperuricemia mice;

[0038] The uric acid levels of each group were measured at time intervals of 1, 2, 3, 4, and 5 hours.

[0039] like Figures 2 to 5 As shown, microneedle transdermal administration can restore serum uric acid, creatinine, and NO levels to normal within 3 hours. It also alleviates and even reverses hyperuricemia-induced kidney damage by effectively improving renal tubular edema and vacuolar degeneration of renal tubular epithelial cells in hyperuricemic mice. The oral administration group not only had a slower onset of effect but also caused significant liver damage, as indicated by ADA activity values. This phenomenon was not observed in the microneedle group.

[0040] The microneedle patch of this embodiment delivers medication transdermally via microneedles, allowing the drug to enter the body directly through capillaries, avoiding first-pass liver metabolism and preventing gastrointestinal problems. Furthermore, the microneedle tips avoid contact with nerve endings, thereby alleviating pain and improving patient compliance. Compared to oral administration, the microneedle patch of this embodiment not only avoids first-pass liver metabolism but also restores serum uric acid, creatinine, and nitric oxide levels to normal in a relatively short period of time.

[0041] Example 2:

[0042] The method for preparing the microneedle patch for regulating blood uric acid in this embodiment comprises the following steps:

[0043] Step 1: Polycaprolactone (30 wt%), polyvinylpyrrolidone (50 wt%), and allopurinol (20 wt%) were uniformly mixed, and the mixture powder was evenly filled into a cavity array mold by hot pressing. Excess melt on the mold surface was then removed and the mixture was retained for 6 minutes; wherein the hot pressing temperature was 180° C. and the pressure was 0.6 MPa;

[0044] Step 2: Using a hot pressing method, a polyvinyl pyrrolidone aqueous solution (40 wt%) is evenly spread on the surface of the array mold as a microneedle patch substrate and retained for 10 minutes; wherein the hot pressing temperature is 110° C. and the pressure is 0.5 MPa;

[0045] Step 3: Take out the prepared microneedle patch array mold and cool it at room temperature for 15 minutes, then peel it off from the mold to obtain the microneedle patch for blood uric acid regulation.

[0046] Example 3:

[0047] The method for preparing the microneedle patch for regulating blood uric acid in this embodiment comprises the following steps:

[0048] Step 1: Polylactic acid (30 wt%), polyvinyl pyrrolidone (50 wt%), and allopurinol (20 wt%) were uniformly mixed and the mixture powder was evenly filled into a cavity array mold using a hot pressing method. Excess melt on the mold surface was then removed and the mixture was retained for 6 minutes. The temperature was 180°C and the pressure was 0.6 MPa.

[0049] Step 2: Using a hot pressing method, a polyvinyl pyrrolidone aqueous solution (40 wt%) was evenly spread on the surface of the array mold as a microneedle patch substrate and retained for 10 minutes; wherein, the temperature was 110° C. and the pressure was 0.5 MPa;

[0050] Step 3: Take out the prepared microneedle patch array mold and cool it at room temperature for 15 minutes, then peel it off from the mold to obtain the microneedle patch for blood uric acid regulation.

[0051] The following is a comparative analysis of the blood uric acid lowering effects of the microneedle patches for blood uric acid regulation of Examples 1-3, as shown in Table 1.

[0052] Table 1 Effects of the microneedle patches of Examples 1-3 on lowering blood uric acid and drug release mechanisms

[0053]

[0054] Hyperuricemia (HUA) is a common biochemical abnormality, typically characterized by a fasting blood uric acid level >420 μmol / L (male) or >360 μmol / L (female). The pH of uric acid measures the concentration of uric acid in the blood, with a normal range of 5.5 to 7.5. The pH of hyperuricemia is lower than 5.5. The carbonate ions in polycarbonate react with uric acid in an acidic environment, promoting sustained release.

[0055] In the above embodiment and its alternatives, 10-30 wt% of biodegradable polymer, 20-50 wt% of water-soluble polymer, and 20-50 wt% of blood uric acid regulating drug can all be determined according to actual needs within the corresponding range of raw materials and dosage.

[0056] In the above embodiment and its alternatives, the biodegradable polymer is selected from one or more of polycaprolactone, polylactic acid, polyglycolic acid, and poly(lactic-co-glycolic acid).

[0057] In the above embodiment and its alternatives, the water-soluble polymer is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol, hyaluronic acid, and polyacrylamide.

[0058] In the above embodiment and its alternatives, the blood uric acid regulating drug is selected from one or more of allopurinol, colchicine, febuxostat, and benzbromarone.

[0059] In the above embodiment and its alternatives, the biodegradable water-soluble polymer is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol, and hyaluronic acid. The concentration of the biodegradable water-soluble polymer solution is within the range of 40-50 wt %, and the concentration is determined according to actual needs.

[0060] In the above embodiment and its alternatives, the residence time in step 1 can be determined at 5 to 10 minutes according to actual conditions, the hot pressing temperature is 120 to 190° C., and the pressure is 0.4 to 1 MPa. The specific temperature and pressure are determined according to the melting point of the raw materials.

[0061] In the above embodiment and its alternatives, the residence time in step 1 can be determined at 10 to 15 minutes according to actual conditions, the hot pressing temperature is 60 to 120° C., and the pressure is 0.2 to 0.6 MPa. The specific temperature and pressure are determined according to the melting point of the raw materials.

[0062] The above description is only a detailed description of the preferred embodiments and principles of the present invention. For ordinary technicians in this field, based on the ideas provided by the present invention, there may be changes in the specific implementation methods, and these changes should also be considered as the scope of protection of the present invention.

Claims

1. A method for preparing a microneedle patch for regulating blood uric acid, characterized in that: The following steps are involved: Step 1: 30 wt% polycarbonate, 50 wt% polyvinylpyrrolidone, and 20 wt% allopurinol were uniformly mixed, and the mixture powder was evenly filled into a cavity array mold by hot pressing. Excess melt on the mold surface was then removed and the mixture was retained for 6 minutes; wherein the hot pressing temperature was 180°C and the pressure was 0.6 MPa; Step 2: Using a hot pressing method, a 40 wt% aqueous solution of polyvinyl pyrrolidone was evenly spread on the surface of the array mold as a microneedle patch substrate and retained for 10 minutes; wherein the hot pressing temperature was 110°C and the pressure was 0.5 MPa; Step 3: Take out the prepared microneedle patch array mold and cool it at room temperature for 15 minutes, then peel it off from the mold to obtain the microneedle patch for blood uric acid regulation.

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