TRANSDERMAL PATCH FOR NEUROPROTECTIVE DRUG DELIVERY AND RELATED METHODS

Abstract

A transdermal patch for delivering Edaravone to a patient includes a biocompatible polymer matrix with Edaravone encapsulated within it, a backing layer, and permeation enhancers to improve skin permeability. This patch is designed to deliver a controlled and continuous dose of Edaravone through the skin, providing sustained neuroprotective effects and improving patient compliance. The patch can eliminate the need for intravenous infusions while maintaining effective therapeutic levels of Edaravone in the body. Additionally, a method for treating amyotrophic lateral sclerosis (ALS) involves applying this transdermal patch to the patient's skin, which reduces oxidative stress and slows motor neuron degeneration. Reference Fig 1

Specification

Description:DETAILED DESCRIPTION
[0015] In one embodiment, the transdermal patch is configured to deliver a controlled and continuous dose of Edaravone through the skin of the patient. This setup allows the patch to deliver Edaravone over a period of 24 to 48 hours, potentially removing the need for intravenous infusions of Edaravone while maintaining therapeutic levels in the body. The transdermal patch is designed to provide neuroprotective effects and improve patient compliance. The biocompatible polymer matrix within the patch stabilizes Edaravone and ensures its controlled release over time, providing continuous neuroprotection. The permeation enhancers, which include oleic acid and dimethyl sulfoxide (DMSO), are configured to improve the permeability of the skin, allowing Edaravone to pass through the skin barrier and enter the systemic circulation. The backing layer of the patch provides structural support and prevents the loss of Edaravone from the patch into the environment. The adhesive polymer layer ensures that the patch adheres to the skin while controlling the release of Edaravone. This configuration may replace the need for intravenous infusions, which require frequent hospital visits or at-home administration, thus potentially improving patient compliance and providing sustained neuroprotective effects.
[0016] In another embodiment, the permeation enhancers are selected from oleic acid and dimethyl sulfoxide (DMSO) to improve the permeability of the skin. This selection allows Edaravone to pass through the skin barrier and enter the systemic circulation. The permeation enhancers are configured to enhance Edaravone delivery by improving the permeability of the skin. The action of improving skin permeability correlates with allowing Edaravone to pass through the skin barrier and enter the systemic circulation. The permeation enhancers, including DMSO and oleic acid, facilitate this process. The transdermal patch is configured to deliver a controlled and continuous dose of Edaravone through the skin of the patient. This setup provides neuroprotective effects and improves patient compliance. The transdermal patch eliminates the need for intravenous infusions of Edaravone while maintaining therapeutic levels of Edaravone in the body. The biocompatible polymer matrix stabilizes Edaravone and ensures controlled release over time. The adhesive polymer layer ensures that the patch adheres to the skin while controlling the release of Edaravone. The backing layer provides structural support and prevents the loss of Edaravone from the patch into the environment. The transdermal patch is applied to the skin of the patient to treat amyotrophic lateral sclerosis (ALS). The efficacy of the transdermal patch is evaluated using a SOD1-G93A transgenic mouse model. The evaluation assesses motor function using tests such as the rotarod test, grip strength test, and hindlimb extension reflex test. The transdermal patch reduces oxidative stress, which plays a role in motor neuron degeneration in ALS patients.

[0017] The adhesive polymer layer is configured to adhere the transdermal patch to the skin of the patient. This setup ensures that the patch remains in place during the intended period of use. The adhesive polymer also plays a role in controlling the release of Edaravone, which is encapsulated within a biocompatible polymer matrix. This encapsulation allows for a sustained release of Edaravone over time, potentially providing continuous neuroprotection to patients with ALS. The adhesive polymer layer is integral to the overall function of the transdermal patch, as it ensures that the patch adheres properly to the skin, thereby facilitating the controlled and continuous delivery of Edaravone. The adhesive polymer is dissolved in an organic solvent, and permeation enhancers such as oleic acid or DMSO are added to enhance the drug's ability to cross the skin barrier. The encapsulated Edaravone is mixed into the polymer solution, ensuring a homogeneous distribution of the drug within the matrix. The adhesive polymer layer thus serves a dual purpose: ensuring patch adherence and contributing to the controlled release of Edaravone. This dual functionality is important in maintaining therapeutic levels of Edaravone in the body, potentially eliminating the need for intravenous infusions. The adhesive polymer layer is therefore a component in the transdermal patch's ability to deliver a controlled and continuous dose of Edaravone through the skin, providing neuroprotective effects and improving patient compliance.

[0018] The biocompatible polymer matrix is configured to stabilize Edaravone and ensure its controlled release over time. This stabilization and controlled release are achieved through the encapsulation of Edaravone within the polymer matrix, which allows for sustained release, providing continuous neuroprotection. The biocompatible polymer matrix is mixed with an adhesive polymer to form the active layer of the transdermal patch. The adhesive polymer ensures that the patch adheres to the skin while controlling the release of Edaravone. The permeation enhancers, which are selected from oleic acid and dimethyl sulfoxide (DMSO), are configured to improve the permeability of the skin, allowing Edaravone to pass through the skin barrier and enter the systemic circulation. This enhancement of permeability facilitates the delivery of Edaravone, ensuring therapeutic levels in the body. The backing layer provides structural support and prevents the loss of Edaravone from the patch into the environment. This structural support is crucial in maintaining the integrity of the patch and ensuring consistent drug delivery. The transdermal patch is configured to deliver a controlled and continuous dose of Edaravone through the skin of the patient, potentially eliminating the need for intravenous infusions while maintaining therapeutic levels of Edaravone in the body. This setup provides neuroprotective effects and improves patient compliance. The transdermal patch is applied to the skin of the patient, beginning treatment at the onset of motor symptoms and continuing for several weeks, potentially reducing oxidative stress and slowing motor neuron degeneration associated with ALS.

[0019] The backing layer of the transdermal patch is configured to provide structural support and prevent the loss of Edaravone from the transdermal patch into the environment. This action is correlated with providing structural support and preventing the loss of Edaravone from the patch. The backing layer serves as a component in maintaining the integrity of the patch, ensuring that Edaravone remains encapsulated within the biocompatible polymer matrix. The structural support provided by the backing layer is essential in preventing the premature release or degradation of Edaravone, thereby ensuring that the drug is delivered in a controlled and continuous manner through the skin of the patient. The prevention of Edaravone loss into the environment is crucial in maintaining the efficacy of the transdermal patch, as it ensures that the intended dose of Edaravone is delivered to the patient over the specified period. The backing layer also contributes to the overall stability of the transdermal patch, allowing it to adhere effectively to the skin and withstand external factors that could compromise its performance. The integration of the backing layer with other components, such as the biocompatible polymer matrix and adhesive polymer layer, facilitates the seamless operation of the transdermal patch, enhancing its ability to deliver Edaravone efficiently and effectively.

[0020] FIG. 1 is a flowchart illustrating a method in step 100 for applying a transdermal patch to the skin of a patient, according to an embodiment. The transdermal patch is designed to deliver a controlled and continuous dose of Edaravone through the skin, potentially providing neuroprotective effects and improving patient compliance. The patch includes a biocompatible polymer matrix that encapsulates Edaravone, allowing for its stabilization and controlled release over time. The adhesive polymer layer ensures that the patch adheres to the skin while controlling the release of Edaravone. Permeation enhancers, such as oleic acid or dimethyl sulfoxide (DMSO), are incorporated to improve the permeability of the skin, facilitating the passage of Edaravone through the skin barrier and into the systemic circulation. The backing layer provides structural support and prevents the loss of Edaravone from the patch into the environment. The application of the transdermal patch begins at the onset of motor symptoms and continues for several weeks, potentially reducing oxidative stress and slowing motor neuron degeneration associated with ALS. The efficacy of the transdermal patch is evaluated using a SOD1-G93A transgenic mouse model, where motor function is assessed using tests such as the rotarod test, grip strength test, and hindlimb extension reflex test. This method may eliminate the need for intravenous infusions of Edaravone while maintaining therapeutic levels in the body.

[0021] Examples:
Test Data for Edaravone Transdermal Patch


Example 1: Drug Release Profile (In Vitro Release Study)
[0022] The objective of this study was to evaluate the rate of Edaravone release from the transdermal patch over time. In this method, the patch was immersed in a phosphate buffer solution with a pH of 7.4. Samples were collected at specific time intervals, and the amount of Edaravone released from the patch was quantified using high-performance liquid chromatography (HPLC). This technique enabled precise measurement of the drug release profile, providing insight into the patch's ability to deliver Edaravone in a controlled manner. Results are given in table 1.

Table 1: Drug Release Profile (In Vitro Release Study)
Time (hours) Cumulative Drug Release (%)
0 0%
1 10%
2 18%
4 35%
6 50%
8 62%
12 75%
24 95%

[0023] Observation: The patch showed a controlled and sustained release of Edaravone, reaching 95% drug release within 24 hours.

Example 2: Adhesion Performance Test
[0024] Adhesion properties of the Edaravone transdermal patch was evaluated. In this method, the patch was applied to the forearm of healthy volunteers, and its adhesion was assessed at two time points: after 24 hours and after 48 hours. The evaluation included checking the patch's ability to remain securely in place without detachment or lifting, ensuring reliable drug delivery during the intended period of use. Results are given in table 2.

Table 2: Adhesion Performance Test
Volunteer Adhesion at 24h Adhesion at 48h Residual Adhesive
Volunteer 1 Excellent Good None
Volunteer 2 Excellent Good None
Volunteer 3 Good Fair None
Volunteer 4 Excellent Excellent None
Volunteer 5 Good Fair None

The patch exhibited good-to-excellent adhesion for up to 48 hours with no adhesive residue left on the skin.

Example 3: Skin Irritation Test
[0025] Potential skin irritation caused by the Edaravone transdermal patch and its components was evaluated. The method involved applying the patch to the forearm of healthy volunteers, where it remained in place for 48 hours. After removal, skin irritation was assessed using a visual scoring system ranging from 0 to 5, with 0 indicating no irritation and 5 indicating severe irritation. This evaluation helped determine the biocompatibility and safety of the patch for prolonged use.

Table 3: Results of Skin Irritation Test
Volunteer Irritation Score (24h) Irritation Score (48h)
Volunteer 1 0 0
Volunteer 2 1 1
Volunteer 3 0 0
Volunteer 4 0 0
Volunteer 5 0 0

No significant skin irritation was observed in any volunteer, indicating good biocompatibility of the patch.

Example 4: Stability Study (Storage at 25°C/60% RH)
[0026] The objective of this study was to evaluate the long-term stability of the Edaravone transdermal patch under controlled storage conditions. [0028] To achieve this, patches were stored at 25°C with 60% relative humidity (RH) for a period of 6 months. At regular intervals during the storage period, the drug content and physical integrity of the patches were assessed to ensure that the formulation remained stable and effective over time. This study was critical for determining the shelf life and storage requirements of the patch.

Table 4: Stability Study (Storage at 25°C/60% RH)
Time Point (Months) Drug Content (% of Initial) Physical Integrity
Initial (0) 100% No changes
1 99.2% No changes
3 98.7% No changes
6 98.0% No changes

The patch maintained over 98% of its initial drug content after 6 months of storage, with no noticeable physical changes, indicating good stability.
, Claims:CLAIMS
We claim:
1. A transdermal patch for delivering Edaravone to a patient, comprising:
a biocompatible polymer matrix;
Edaravone encapsulated within the biocompatible polymer matrix;
a backing layer; and
one or more permeation enhancers configured to improve the permeability of the skin and allow Edaravone to pass through the skin barrier and enter the systemic circulation;
wherein the transdermal patch is configured to deliver a controlled and continuous dose of Edaravone through the skin of the patient to provide sustained neuroprotective effects and improve patient compliance.

2. The transdermal patch as claimed in claim 1, further comprising an adhesive polymer layer configured to adhere the transdermal patch to the skin of the patient.

3. The transdermal patch as claimed in claim 1, wherein the one or more permeation enhancers are selected from the group consisting of oleic acid and dimethyl sulfoxide (DMSO).

4. The transdermal patch as claimed in claim 1, wherein the biocompatible polymer matrix is configured to stabilize Edaravone and ensure controlled release of Edaravone over time.

5. The transdermal patch as claimed in claim 1, wherein the backing layer is configured to provide structural support and prevent the loss of Edaravone from the transdermal patch into the environment.

6. The transdermal patch as claimed in claim 1, wherein the transdermal patch is configured to deliver Edaravone over a period of 24 to 48 hours.

7. The transdermal patch as claimed in claim 1, wherein the transdermal patch eliminates the need for intravenous infusions of Edaravone while maintaining effective therapeutic levels of Edaravone in the body.
8. A method of treating amyotrophic lateral sclerosis (ALS) in a patient, comprising:
applying a transdermal patch to the skin of the patient, the transdermal patch comprising:
a biocompatible polymer matrix;
Edaravone encapsulated within the biocompatible polymer matrix;
a backing layer; and
one or more permeation enhancers configured to improve the permeability of the skin and allow Edaravone to pass through the skin barrier and enter the systemic circulation;
wherein the transdermal patch delivers a controlled and continuous dose of Edaravone through the skin of the patient to provide sustained neuroprotective effects and improve patient compliance.

9. The method as claimed in claim 8, further comprising evaluating the efficacy of the transdermal patch using a SOD1-G93A transgenic mouse model, wherein evaluating the efficacy of the transdermal patch comprises assessing motor function using at least one of a rotarod test, a grip strength test, and a hindlimb extension reflex test.

10. The method as claimed in claim 8, wherein applying the transdermal patch to the skin of the patient begins at the onset of motor symptoms and continues for several weeks, and wherein the transdermal patch reduces oxidative stress in the patient, thereby slowing motor neuron degeneration associated with ALS.

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